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cialis pre workout. Eric Stann, 573-882-3346, StannE@missouri.eduCheryl S. Rosenfeld is a professor of biomedical sciences in the College of Veterinary Medicine, investigator cialis cost in the Christopher S. Bond Life Sciences Center and research faculty member in the Thompson Center for Autism and Neurodevelopmental Disorders.Scientists at the University of Missouri have discovered possible biological markers that they hope could one day help identify the presence of an opioid use disorder during human pregnancy.Cheryl S.

Rosenfeld, an author on the study, said women often take opioids for pain regulation during pregnancy, including oxycodone, so cialis cost it’s important to understand the effects of these drugs on the fetal placenta, a temporary organ that is essential in providing nutrients from a mother to her unborn child. Rosenfeld is a professor of biomedical sciences in the College of Veterinary Medicine, investigator in the Christopher S. Bond Life Sciences Center and research faculty member in the Thompson Center for Autism and Neurodevelopmental Disorders.According to the Centers for Disease Control and Prevention, the number of cialis cost pregnant women diagnosed with an opioid use disorder has quadrupled between 1999 and 2014.“Many pregnant women are being prescribed opioids — in particular OxyContin, or oxycodone — to help with the pain they can experience during pregnancy, and this can lead to opioid use disorders,” Rosenfeld said. €œMany women also don’t want to admit to taking these drugs, and we know that children born from mothers who have taken opioids during pregnancy experience post-birth conditions, such as low-birth weight.

But, so far cialis cost no one has studied the potential ramifications of opioid use during fetal life. Thus, we focused on the placenta because it is the main communication organ between the mother and her unborn child.”Previous studies examining these effects have used human cell cultures, but this is one of the first studies to use an animal model to examine how developmental exposure to these drugs affect the conceptus. In the study, Rosenfeld and her colleagues focused on how a mother’s use of oxycodone during her pregnancy can affect a mouse’s placenta. Mouse and human placentas are similar in cialis cost many ways, including having placenta-specific cells in direct contact with a mother’s blood.

They found the use of this drug during pregnancy can negatively affect the placenta’s structure, such as reducing and killing cells that produce by-products needed for normal brain development. In addition, Rosenfeld said their findings show specific differences in genetic expressions between female and male placentas in response to maternal oxycodone exposure.“Our results show when mothers take oxycodone during cialis cost pregnancy, it causes severe placental disruptions, including elevation of certain gene expressions,” Rosenfeld said. €œWe know what the normal levels should be and if there are any changes, then we know something might have triggered such effects. For instance, in response to material oxycodone exposure, female placentas start increasing production of key genes essential cialis cost in regulating material physiology.

However, in male placentas, we see some of these same genes are reduced in expression. These expression patterns could be potential cialis cost biomarkers for detecting exposure to oxycodone use.”Rosenfeld said by studying this in an animal model, it allows scientists to see these changes quicker than if they were completing a comparable study in people, because a pregnant mouse can give birth in 21 days compared to about nine months in people.“This also allows us to easily study other regions of the body, especially the brain of exposed offspring, that would be affected by taking these opioids,” Rosenfeld said. €œWe can then use this information to help epidemiologists identify behaviors that people should be looking at in children whose mothers have taken these opioids.”Rosenfeld suggests that opioids should be added to other widely discussed warning factors during pregnancy, such as smoking and drinking alcohol. She said short-term use of opioids by pregnant women, such as someone who has kidney stones, might not cause much of an effect on their pregnancy, but that likely depends on when the mother is taking the drug cialis cost while pregnant.

Future plans for this study include analyzing how offspring are affected once they are born.Rosenfeld’s research is an example of an early step in translational medicine, or research that aims to improve human health by determining the relevance of animal science discoveries to people. This research can provide the foundation for precision medicine, or personalized human health care. Precision medicine cialis cost will be a key component of the NextGen Precision Health Initiative — the University of Missouri System’s top priority — by helping to accelerate medical breakthroughs for both patients in Missouri and beyond.The study, “Maternal oxycodone treatment causes pathophysiological changes in the mouse placenta,” was published in Placenta, the official journal of the International Federation of Placenta Associations. Other authors include Madison T.

Green, Rachel cialis cost E. Martin, Jessica A. Kinkade, Robert cialis cost R. Schmidt, Nathan J.

Bivens and Jiude cialis cost Mao at MU. And Geetu Tuteja at Iowa State University.Funding was provided by grants from the National Institute of Environmental Health Sciences and the Eunice Kennedy Shriver National Institute of Child Health and Human Development. The content is solely the responsibility of the authors and does not necessarily represent the official views of the funding agencies.First-of-its-kind study, based on a mouse model, finds living in a polluted environment could be comparable to eating a high-fat diet, leading to a pre-diabetic state CLEVELAND—Air pollution is the world’s leading environmental risk factor, and causes more than nine million deaths per year. New research cialis cost published in the Journal of Clinical Investigation shows air pollution may play a role in the development of cardiometabolic diseases, such as diabetes.

Importantly, the effects were reversible with cessation of exposure. Researchers found that air cialis cost pollution was a “risk factor for a risk factor” that contributed to the common soil of other fatal problems like heart attack and stroke. Similar to how an unhealthy diet and lack of exercise can lead to disease, exposure to air pollution could be added to this risk factor list as well. “In this study, we created an environment that mimicked a cialis cost polluted day in New Delhi or Beijing,” said Sanjay Rajagopalan, MD, first author on the study, Chief of Cardiovascular Medicine at University Hospitals Harrington Heart and Vascular Institute, and Director of the Case Western Reserve University Cardiovascular Research Institute.

€œWe concentrated fine particles of air pollution, called PM2.5 (particulate matter component <. 2.5 microns) cialis cost. Concentrated particles like this develop from human impact on the environment, such as automobile exhaust, power generation and other fossil fuels.” These particles have been strongly connected to risk factors for disease. For example, cardiovascular effects of cialis cost air pollution can lead to heart attack and stroke.

The research team has shown exposure to air pollution can increase the likelihood of the same risk factors that lead to heart disease, such as insulin resistance and type 2 diabetes. In the mouse model study, three groups were observed. A control group receiving clean filtered air, a group exposed to polluted air for 24 cialis cost weeks, and a group fed a high-fat diet. Interestingly, the researchers found that being exposed to air pollution was comparable to eating a high-fat diet.

Both the air pollution cialis cost and high-fat diet groups showed insulin resistance and abnormal metabolism – just like one would see in a pre-diabetic state. These changes were associated with changes in the epigenome, a layer of control that can masterfully turn on and turn off thousands of genes, representing a critical buffer in response to environmental factors. This study is the first-of-its-kind to compare genome-wide epigenetic changes in response to air cialis cost pollution, compare and contrast these changes with that of eating an unhealthy diet, and examine the impact of air pollution cessation on these changes.“The good news is that these effects were reversible, at least in our experiments” added Dr. Rajagopalan.

€œOnce the air pollution was removed from the environment, the mice appeared healthier and the pre-diabetic state seemed cialis cost to reverse.” Dr. Rajagopalan explains that if you live in a densely polluted environment, taking actions such as wearing an N95 mask, using portable indoor air cleaners, utilizing air conditioning, closing car windows while commuting, and changing car air filters frequently could all be helpful in staying healthy and limiting air pollution exposure.Next steps in this research involve meeting with a panel of experts, as well as the National Institutes of Health, to discuss conducting clinical trials that compare heart health and the level of air pollution in the environment. For example, if someone has a heart attack, should they be wearing an N95 mask or using a portable air filter at home during recovery?. Dr cialis cost.

Rajagopalan and his team believe that it is important to address the environment as a population health risk factor and continue to diligently research these issues. The authors also note that these findings should encourage policymakers to enact measures aimed at reducing air pollution.Shyam Biswal, PhD, Professor in the Department of Environmental Health and Engineering at Johns Hopkins University School of Public Health, is the joint cialis cost senior author on the study. Drs. Rajagopalan and Biswal are co-PIs on the NIH grant cialis cost that supported this work.###Rajagopalan, S., Biswal, S., et al.

€œMetabolic effects of air pollution exposure and reversibility.” Journal of Clinical Investigation. DOI. 10.1172/JCI137315. This work was supported by the National Institute of Environmental Health Sciences TaRGET II Consortium grant U01ES026721, as well as grants R01ES015146 and R01ES019616..

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The wildfire season is off to a roaring cialis everyday pill start. The hot summer is worsening drought and drying out vegetation—an unfortunately ideal environment for wildfires to rage. But that’s cialis everyday pill just one consequence of global warming. It’s also leading to flooding, torrential rainstorms and heat-related deaths.

In fact, the climate crisis has led to a widespread public health crisis. And as an ear, nose and throat physician, I see the effects more cialis everyday pill and more often. I vividly remember a patient who came in late for her appointment during a July heat wave. When I walked in, she said, “I’m so sorry I’m late, I was up all night walking my grandbaby around the train station.” Without air conditioning at home, the child was sweating through her clothes in the heat of the night, putting her at risk for dehydration.

July 2019 was cialis everyday pill the hottest July on record. September 2019 was the hottest on record. January 2020 was the hottest on record. May 2020 was the hottest on cialis everyday pill record.

This is not a coincidence. It is a pattern. Carbon dioxide, cialis everyday pill an important greenhouse gas contributing to global warming, has increased by 9 percent since 2005 and by 31 percent since 1950. A U.N.

Intergovernmental Panel on Climate Change special cialis everyday pill report pointed out that the world has already warmed about one degree Celsius from pre-industrial levels. It stressed the urgency to act to limit warming to 1.5 degrees, and that a two-degree increase will lead to unprecedented extreme heat, water scarcity and food shortages around the globe. Heat affects every part of our body. It can lead to heat exhaustion, heat stroke, anxiety, impaired cognitive cialis everyday pill function and even premature death from heart and lung disease.

Across the country, the health concerns of the climate crisis are increasingly being recognized, pushing thousands of medical providers—doctors, nurses, pharmacists, therapists, medical students—to become advocates for change. In my own practice, I explain to patients how the climate crisis affects their health. For example, apart from contributing to global warming, rising carbon cialis everyday pill dioxide levels increase the amount of pollen that plants produce as a consequence of higher rates of photosynthesis. This rise in pollen levels can lead to worsening allergy symptoms.

Another example is fine particulate matter (known as PM2.5) associated with air pollution, much of it linked to the burning of fossil fuels that help drive the warming. When we breathe in these particles, they travel down the airway and settle in the tiny air sacs called alveoli of the cialis everyday pill lungs, causing inflammation and potentially worsening asthma symptoms. The explanations are simple, but the health risks are widespread and complex. Ground-level ozone pollution, which is worse in hotter weather, can also harm people with asthma and other respiratory diseases.

And that harm falls disproportionately on the poor cialis everyday pill. Wealthier people living in North America have a per capita carbon footprint that is 25 percent higher than those of lower-income residents, with some affluent suburbs producing emissions 15 times higher than nearby neighborhoods. These carbon emissions contribute cialis everyday pill to global warming, and the subsequent health consequences are felt far beyond the neighborhood that produces them. Older adults, children, low-income communities and communities of color are less resilient on average to the health impacts of climate change.

The climate crisis is thus leading to a disproportionate public health crisis—and worse, it is a threat multiplier. At a time when many Americans are economically challenged, continued heat waves cialis everyday pill and the higher energy bills they trigger threaten access to water and energy security. The economic benefits of a low-carbon economy are clear. Estimates suggest that without climate investments, the United States will face economic damage from climate change equivalent to 1–3 percent of GDP per year by 2100.

The majority of Americans think global warming is cialis everyday pill happening. The climate crisis has unfairly been labeled as political, when in fact, people recognize that something needs to be done about it. Even for those who are seemingly unaffected, there is increasing global recognition that the safeguards of living in a protected community and affording expert medical care will eventually fail if global warming continues unchecked. Unfortunately, there will be no vaccine in six months or cialis everyday pill a year for the climate crisis.

The only treatment is collective climate action in the present. Climate action is required of our elected leaders, and we must mandate it of ourselves. It can be cialis everyday pill as simple as educating family and friends, while making sustainable shopping and traveling choices. It includes eating less meat, unplugging electronics and raising a voice against the fossil fuel industry.

With a rise in demand for absentee ballots for the election this November, it is crucial to request mail-in ballots right away to make sure our cialis everyday pill voices are heard. The United States is the second largest emitter of greenhouse gases, and we must vote for green policy. Legislative action and policy change work, as evidenced by the Clean Air Act and its subsequent amendments, which are projected to save 230,000 lives in 2020. The climate crisis is a public health issue, and we must start healing the planet cialis everyday pill in order to heal each other.

Fighting against the climate crisis is one of the most patriotic things we can do right now. It will protect our health and the health of our neighbors across the country and the globe, and will allow all of us to live on this planet, the only home we have.The items below are highlights from the free newsletter, “Smart, useful, science stuff about COVID-19.” To receive newsletter issues daily in your inbox, sign up here. Please consider a monthly contribution to support cialis everyday pill this newsletter. Women’s immune response to SARS-CoV-2 is stronger than men’s immune response to the virus, according to a study published 8/26/20 in Nature and covered the same day by Apoorva Mandavilli at The New York Times.

The finding could explain why men “are twice as likely to become severely sick and to die [from COVID-19] as women of the same age,” Mandavilli writes. The study also suggests that older men might need multiple shots of a coronavirus vaccine compared perhaps cialis everyday pill with young women, who might need just one shot, according to an immunologist quoted in the story. He's at the Heinrich Pette Institute and the University Medical Center Hamburg-Eppendorf in Germany. The study leader, a Yale University immunologist, is quoted in the story as saying, “Women who are older — even very old, like 90 years — the women are still making pretty good, decent immune response” to SARS-CoV-2.

The U.S cialis everyday pill. Food and Drug Administration (FDA) on 8/26/20 gave emergency-use authorization to Abbott Laboratories' $5, portable nasal-swab SARS-CoV-2 test that returns results in 15 minutes, reports Sheila Kaplan at The New York Times (8/26/20). The test detects viral fragments called antigens. Such tests miss more infections than widely used, slower tests cialis everyday pill that rely on a technology called polymerase chain reaction (PCR).

But the speed of antigen tests, three others of which previously received FDA emergency-use approval, could prove useful in relieving test backlogs. Abbott says its new antigen test will become available in September, cialis everyday pill the story states. Autopsies of 11 people who died of COVID-19 revealed that their spleens and lymph nodes lacked sites called germinal centers where B cells (immune cells) gather to “mature and refine their antibody response to the virus,” writes Jon Cohen at Science (8/25/20). The researchers compared tissue from the people who died of COVID-19 with tissue from 6 people who died of other causes, the story states.

The finding, which confirms an earlier study’s findings in a smaller group, could provide insights into cialis everyday pill the progression of severe cases of COVID-19, the story states. The studies “establish a profound lack of [antibody] responses in the deceased population of COVID-19 patients,” says a Huazhong University of Science and Technology (HUST) researcher who co-authored the smaller study and is quoted in the story. The missing germinal centers in severe COVID-19 patients could be linked to the biochemical “cytokine storms” that often occur in the dangerous, second phase of the disease, the HUST researcher is quoted as saying. Meanwhile, a MGH, MIT and Harvard immunologist who is a co-author of the newer study, published earlier this cialis everyday pill month in the journal Cell, says it won’t be difficult to stop SARS-CoV-2 with a vaccine.

He is quoted as saying, “This is a piece of cake.” The United States, UK, Japan, and the European Union nations all have pre-ordered in bulk doses of vaccines under development to protect against SARS-CoV-2, reports Ewen Callaway at Nature (8/24/20). Some of these candidate vaccines could be approved in late 2020 or early 2021 at the earliest, the story states. But only "1 billion doses will be available by the fourth quarter of 2021,” according to a life-sciences market analytics firm, the story states cialis everyday pill. A different organization estimates 2 billion to 4 billion doses will be available by the end of 2021, the story states.

A chart near the top of the piece illustrates pre-order details by vaccine manufacturer, nation and number of doses. Meanwhile, an international effort to secure vaccine doses for people living in a total of 92 low- and middle-income, as well as some wealthier countries, is “far short of raising the roughly $18 billion that it estimates” will cialis everyday pill be needed to meet its target number of doses, Callaway reports. Lower in the piece, a chart illustrates pre-orders made by several countries and regions worldwide. Callaway writes that “patents and intellectual property are not what’s standing in the way of fair distribution of COVID-19 vaccines…rather, equitable access and affordable prices require cialis everyday pill collaboration between governments and vaccine makers,” according to the head of the International AIDS Vaccine Initiative in New York City, which reportedly is co-developing a COVID-19 vaccine.

In an 8/22/20 essay for The Washington Post, Elizabeth Svoboda writes that many people in the U.S. Have become desensitized to the risks of SARS-CoV-2, which has led to some behavioral backsliding, especially in crowded places. €œThis habituation stems from a principle cialis everyday pill well-known in psychological therapy,” Svoboda writes. €œThe more we’re exposed to a given threat, the less intimidating it seems.” Some researchers recommend a return to stricter distancing, outdoor masking and stay-at-home orders, the essay suggests.

But we also need authorities to “supply in-your-face reminders of those mandates, especially visual cues, so people won’t draw their own erroneous conclusions about what’s safe,” she writes. In any case, we cialis everyday pill should cultivate an awareness of the diminishing effectiveness of our “snap judgments about COVID-19’s dangers,” and make more careful decisions, a la Nobel laureate Daniel Kahneman's “slow thinking,” she advises. Ventilation discussions in public-health circles predate the current pandemic. Infection control theories born of the U.S.

Experience with the Spanish flu pandemic of 1918-1919 inspired engineers of the early 20th century to design steam-heating systems for buildings that could be effective in cold weather even with apartment windows open, reports cialis everyday pill Patrick Sisson for Bloomberg CityLab. That’s right. Steam-heat radiators were designed to be used with the open windows, allowing fresh air to gush in, which “health officials thought (correctly)…would ward off airborne diseases,” Sisson writes. The piece draws from cialis everyday pill a 1992 book “The Lost Art of Steam Heating,” by heating-systems researcher Dan Holohan.

Radiators were designed, according to Holohan the story states, in response to a New York City Board of Health order that windows should remain open for ventilation in the winter. €œAnybody who’s thrown their windows open in January, when their apartment is stifling, is in an odd way, replicating what engineers hoped would happen a cialis everyday pill century ago,” Sisson writes (8/5/20). You might enjoy. €œJerry Seinfeld.

So You Think New York Is ‘Dead’ (It’s not.)” (8/24/20).In four days of speeches lasting more than eight hours at the Republican National Convention, climate change was cialis everyday pill never mentioned as a threat to the country. That silence stands apart from the climate alarm bells that have been sounding since Donald Trump accepted his first nomination for president four years ago. Thousands of Americans have been killed in natural disasters such as hurricanes and wildfires during Trump’s first term in office. Each of those four cialis everyday pill years has been among the world’s hottest on record.

Leaders of other nations have taken action as the United States ignores the issue. Even Wall Street has begun to take notice of how climate change could affect economic growth. None of that cialis everyday pill was apparent during the convention. Instead, Republican speakers insisted that the real concern was the climate ideas presented by Democrats.

Many experts say that if climate change is left unanswered, it could cost trillions of dollars to the U.S. Economy. Republicans said the real costs would come from Democratic plans to restrain the use of fossil fuels. €œBiden has promised to abolish the production of American oil, coal, shale and natural gas—laying waste to the economies of Pennsylvania, Ohio, Texas, North Dakota, Oklahoma, Colorado and New Mexico,” Trump said.

€œMillions of jobs will be lost, and energy prices will soar.” (Biden’s plan does not call for a fracking ban). Those sentiments play well with Trump’s core supporters, but they’re askew from what most voters believe, including younger Republicans, according to polls. They don’t reflect the events that many Americans are either experiencing or seeing online. Uncontrolled wildfires in California and the strongest hurricane to hit Louisiana in 160 years.

Even as an unrelinquishing pandemic has killed more than 180,000 people in the United States and kept millions of children across the country from returning to school, climate change remains on the minds of voters, polls show. Here are five climate themes that have advanced since Trump accepted his first nomination in 2016. Natural disasters More than 3,000 Americans have died in natural catastrophes during the past four years. Most of them were victims of Hurricane Maria in 2017.

The massive Category 5 storm killed an estimated 2,975 people in Puerto Rico and forced thousands to flee the U.S. Territory. The devastation continues to have ripple effects three years later. Tens of thousands of people still live under leaky blue tarps.

The island’s power supply, never reliable to begin with, has become far worse, and some parts of Puerto Rico were without power for a year. That was the same year that Hurricane Harvey dumped 60 inches of rain on parts of Houston, becoming the wettest cyclone on record. Tens of thousands of homes were damaged, and about 70 people were killed. Harvey caused more than $100 billion in damage, making it one of the costliest disasters to strike the United States.

Record wildfires have also burned across the West. The 2018 Camp Fire in California was the deadliest. It killed 85 people and destroyed more than 10,000 homes. It was fueled by drought, an outcome of climate change.

This week, California continued to battle the second- and third-largest wildfires in state history. Officials have connected the fires to climate change. €œAll but three of the Top 20 Largest #Wildfires have occurred since 2000, with 10 of these large and damaging wildfires occurring in the last decade,” the California Department of Forestry and Fire Protection tweeted yesterday. €œAs fire weather continues to become more extreme, California is adjusting to fight these larger and more destructive wildfires.” Heat The Trump years have been some of the hottest since record-keeping began after the Civil War, according to NASA.

After a record-warm July, this year may break the all-time annual heat record set in 2016. That’s a likely outcome, said Gavin Schmidt, director of the NASA Goddard Institute for Space Studies. That’s notable because four years ago, the record warmth was fueled by El Niño, a band of warm water covering the tropical Pacific Ocean. That influence is absent this year, Schmidt said, and long-term trends point to rising heat.

€œWe know that the trend is moving up. On average, every decade is warmer than the last,” he said. €œThe changes we’re seeing now are so far outside what would be possible in an un-globally-warmed world.” Public opinion Polling shows that voter concern about climate change has been growing for years and that it has not diminished as a result of the coronavirus pandemic. Concern among some voters has spiked during Trump’s tenure.

Before the virus, polling showed climate change was the second-most important issue for Democratic primary voters, behind only health care. Now, responding to the virus and restoring the economy top the list. But the public still wants the federal government to address climate change, recent polling shows. More Americans than ever—about 25%—view climate change as “extremely personally important,” according to a poll released last week by Stanford University, Resources for the Future and ReconMR.

That number is twice as large as it was in 2006, said the poll, which surveyed 1,000 adults between May and August. It also found that 82% of respondents want the federal government to act on climate change. And three-quarters of those surveyed said they had personally experienced the effects of global warming. €œThe COVID-19 pandemic has offered a unique opportunity to learn how people feel about climate change when faced with a global crisis,” said Ray Kopp, vice president of research and policy engagement at Resources for the Future.

€œThe claim that we can’t do anything about climate change without crashing the economy, or that we need to focus only on the pandemic and not do anything on climate right now, simply doesn’t resonate with Americans,” he said. The U.S. (and everyone else) Since Trump pledged to withdraw from the Paris climate agreement in 2017, world leaders have pressed him to rejoin and to take the issue seriously. Among them are German Chancellor Angela Merkel and French President Emmanuel Macron.

Last year, Trump said Prince Charles spent 90 minutes talking to him about climate change, trying to convince him to take stronger action and to once again make the United States a world leader. In response, Trump said he wanted “good climate,” but his administration has continued to roll back environmental safeguards meant to reduce emissions. In December, Macron said other governments, including China, Russia and the European Union, would lead the world in reducing emissions. The yearslong process of withdrawing from the Paris Agreement won’t be done until November.

Yesterday, Biden tweeted that if he wins the election, he would rejoin the pact on the first day of his presidency. Climate hits Wall Street This week, it was announced that Exxon Mobil Corp. Would be dropped from the Dow Jones Industrial Average stock index. It’s a significant departure, as Exxon was the longest-tenured company on the Dow, having been listed for almost a century.

It’s also a reflection of how oil companies have taken a financial hit amid growing concerns about climate change and as a result of declining consumption due to the pandemic. At the same time, some solar and wind companies have grown bigger than their fossil fuel competitors. The same factors that have weakened fossil fuel companies, including more aggressive climate targets, helped drive clean energy technologies. On Wall Street, business interests are increasingly warning the Federal Reserve and other regulators that climate change could pose a significant risk to the economy.

Earlier this year, 40 investment firms and organizations that handle more than $1 trillion in assets urged Fed Chairman Jerome Powell to take action. They warned him that climate “threats have the potential to compound in ways we don’t yet understand, with disastrous impacts the likes of which we haven’t seen before.” Reprinted from Climatewire with permission from E&E News. E&E provides daily coverage of essential energy and environmental news at www.eenews.net..

The wildfire cialis cost season is off to a roaring start. The hot summer is worsening drought and drying out vegetation—an unfortunately ideal environment for wildfires to rage. But that’s just one consequence of cialis cost global warming. It’s also leading to flooding, torrential rainstorms and heat-related deaths. In fact, the climate crisis has led to a widespread public health crisis.

And as an ear, nose and throat physician, I see the effects more and more cialis cost often. I vividly remember a patient who came in late for her appointment during a July heat wave. When I walked in, she said, “I’m so sorry I’m late, I was up all night walking my grandbaby around the train station.” Without air conditioning at home, the child was sweating through her clothes in the heat of the night, putting her at risk for dehydration. July 2019 was the cialis cost hottest July on record. September 2019 was the hottest on record.

January 2020 was the hottest on record. May 2020 was cialis cost the hottest on record. This is not a coincidence. It is a pattern. Carbon dioxide, cialis cost an important greenhouse gas contributing to global warming, has increased by 9 percent since 2005 and by 31 percent since 1950.

A U.N. Intergovernmental Panel on Climate Change cialis cost special report pointed out that the world has already warmed about one degree Celsius from pre-industrial levels. It stressed the urgency to act to limit warming to 1.5 degrees, and that a two-degree increase will lead to unprecedented extreme heat, water scarcity and food shortages around the globe. Heat affects every part of our body. It can lead to heat exhaustion, heat cialis cost stroke, anxiety, impaired cognitive function and even premature death from heart and lung disease.

Across the country, the health concerns of the climate crisis are increasingly being recognized, pushing thousands of medical providers—doctors, nurses, pharmacists, therapists, medical students—to become advocates for change. In my own practice, I explain to patients how the climate crisis affects their health. For example, apart from contributing to global warming, rising carbon dioxide levels increase the amount of pollen that plants produce as a consequence of higher rates of cialis cost photosynthesis. This rise in pollen levels can lead to worsening allergy symptoms. Another example is fine particulate matter (known as PM2.5) associated with air pollution, much of it linked to the burning of fossil fuels that help drive the warming.

When we breathe in these particles, they travel down the airway and settle in the tiny air sacs called alveoli of the lungs, causing inflammation and potentially worsening cialis cost asthma symptoms. The explanations are simple, but the health risks are widespread and complex. Ground-level ozone pollution, which is worse in hotter weather, can also harm people with asthma and other respiratory diseases. And that harm cialis cost falls disproportionately on the poor. Wealthier people living in North America have a per capita carbon footprint that is 25 percent higher than those of lower-income residents, with some affluent suburbs producing emissions 15 times higher than nearby neighborhoods.

These carbon emissions contribute to global warming, and the subsequent health consequences are felt far beyond the neighborhood that produces cialis cost them. Older adults, children, low-income communities and communities of color are less resilient on average to the health impacts of climate change. The climate crisis is thus leading to a disproportionate public health crisis—and worse, it is a threat multiplier. At a time when many Americans are economically challenged, continued heat waves and the higher cialis cost energy bills they trigger threaten access to water and energy security. The economic benefits of a low-carbon economy are clear.

Estimates suggest that without climate investments, the United States will face economic damage from climate change equivalent to 1–3 percent of GDP per year by 2100. The majority of Americans think global warming cialis cost is happening. The climate crisis has unfairly been labeled as political, when in fact, people recognize that something needs to be done about it. Even for those who are seemingly unaffected, there is increasing global recognition that the safeguards of living in a protected community and affording expert medical care will eventually fail if global warming continues unchecked. Unfortunately, there will be no vaccine in cialis cost six months or a year for the climate crisis.

The only treatment is collective climate action in the present. Climate action is required of our elected leaders, and we must mandate it of ourselves. It can be as simple as educating family and friends, while making sustainable shopping and cialis cost traveling choices. It includes eating less meat, unplugging electronics and raising a voice against the fossil fuel industry. With a rise in demand for absentee ballots for the election this November, it is crucial to request mail-in ballots right away to make sure our voices are heard cialis cost.

The United States is the second largest emitter of greenhouse gases, and we must vote for green policy. Legislative action and policy change work, as evidenced by the Clean Air Act and its subsequent amendments, which are projected to save 230,000 lives in 2020. The climate crisis is a public health issue, and we must start cialis cost healing the planet in order to heal each other. Fighting against the climate crisis is one of the most patriotic things we can do right now. It will protect our health and the health of our neighbors across the country and the globe, and will allow all of us to live on this planet, the only home we have.The items below are highlights from the free newsletter, “Smart, useful, science stuff about COVID-19.” To receive newsletter issues daily in your inbox, sign up here.

Please consider a monthly contribution to support this newsletter cialis cost. Women’s immune response to SARS-CoV-2 is stronger than men’s immune response to the virus, according to a study published 8/26/20 in Nature and covered the same day by Apoorva Mandavilli at The New York Times. The finding could explain why men “are twice as likely to become severely sick and to die [from COVID-19] as women of the same age,” Mandavilli writes. The study also suggests that older men might need multiple shots of a coronavirus vaccine compared perhaps with young women, cialis cost who might need just one shot, according to an immunologist quoted in the story. He's at the Heinrich Pette Institute and the University Medical Center Hamburg-Eppendorf in Germany.

The study leader, a Yale University immunologist, is quoted in the story as saying, “Women who are older — even very old, like 90 years — the women are still making pretty good, decent immune response” to SARS-CoV-2. The U.S cialis cost. Food and Drug Administration (FDA) on 8/26/20 gave emergency-use authorization to Abbott Laboratories' $5, portable nasal-swab SARS-CoV-2 test that returns results in 15 minutes, reports Sheila Kaplan at The New York Times (8/26/20). The test detects viral fragments called antigens. Such tests miss more infections than widely cialis cost used, slower tests that rely on a technology called polymerase chain reaction (PCR).

But the speed of antigen tests, three others of which previously received FDA emergency-use approval, could prove useful in relieving test backlogs. Abbott says its new antigen test will become available in cialis cost September, the story states. Autopsies of 11 people who died of COVID-19 revealed that their spleens and lymph nodes lacked sites called germinal centers where B cells (immune cells) gather to “mature and refine their antibody response to the virus,” writes Jon Cohen at Science (8/25/20). The researchers compared tissue from the people who died of COVID-19 with tissue from 6 people who died of other causes, the story states. The finding, which confirms an earlier study’s findings in a smaller cialis cost group, could provide insights into the progression of severe cases of COVID-19, the story states.

The studies “establish a profound lack of [antibody] responses in the deceased population of COVID-19 patients,” says a Huazhong University of Science and Technology (HUST) researcher who co-authored the smaller study and is quoted in the story. The missing germinal centers in severe COVID-19 patients could be linked to the biochemical “cytokine storms” that often occur in the dangerous, second phase of the disease, the HUST researcher is quoted as saying. Meanwhile, a MGH, MIT and Harvard immunologist who is a co-author of the newer study, published earlier this month in the journal Cell, says it won’t be difficult cialis cost to stop SARS-CoV-2 with a vaccine. He is quoted as saying, “This is a piece of cake.” The United States, UK, Japan, and the European Union nations all have pre-ordered in bulk doses of vaccines under development to protect against SARS-CoV-2, reports Ewen Callaway at Nature (8/24/20). Some of these candidate vaccines could be approved in late 2020 or early 2021 at the earliest, the story states.

But only cialis cost "1 billion doses will be available by the fourth quarter of 2021,” according to a life-sciences market analytics firm, the story states. A different organization estimates 2 billion to 4 billion doses will be available by the end of 2021, the story states. A chart near the top of the piece illustrates pre-order details by vaccine manufacturer, nation and number of doses. Meanwhile, an international effort to secure vaccine doses for people living in a total of 92 low- and middle-income, as well as some wealthier countries, is cialis cost “far short of raising the roughly $18 billion that it estimates” will be needed to meet its target number of doses, Callaway reports. Lower in the piece, a chart illustrates pre-orders made by several countries and regions worldwide.

Callaway writes that “patents and intellectual property are not what’s standing in the way of fair distribution of COVID-19 vaccines…rather, equitable access and affordable prices require collaboration cialis cost between governments and vaccine makers,” according to the head of the International AIDS Vaccine Initiative in New York City, which reportedly is co-developing a COVID-19 vaccine. In an 8/22/20 essay for The Washington Post, Elizabeth Svoboda writes that many people in the U.S. Have become desensitized to the risks of SARS-CoV-2, which has led to some behavioral backsliding, especially in crowded places. €œThis habituation stems from a principle well-known in psychological therapy,” Svoboda writes cialis cost. €œThe more we’re exposed to a given threat, the less intimidating it seems.” Some researchers recommend a return to stricter distancing, outdoor masking and stay-at-home orders, the essay suggests.

But we also need authorities to “supply in-your-face reminders of those mandates, especially visual cues, so people won’t draw their own erroneous conclusions about what’s safe,” she writes. In any case, cialis cost we should cultivate an awareness of the diminishing effectiveness of our “snap judgments about COVID-19’s dangers,” and make more careful decisions, a la Nobel laureate Daniel Kahneman's “slow thinking,” she advises. Ventilation discussions in public-health circles predate the current pandemic. Infection control theories born of the U.S. Experience with the Spanish flu pandemic of 1918-1919 inspired engineers of the early 20th century to design steam-heating systems for buildings that could be effective in cold weather even with apartment windows open, reports Patrick Sisson for Bloomberg CityLab cialis cost.

That’s right. Steam-heat radiators were designed to be used with the open windows, allowing fresh air to gush in, which “health officials thought (correctly)…would ward off airborne diseases,” Sisson writes. The piece draws from a cialis cost 1992 book “The Lost Art of Steam Heating,” by heating-systems researcher Dan Holohan. Radiators were designed, according to Holohan the story states, in response to a New York City Board of Health order that windows should remain open for ventilation in the winter. €œAnybody who’s thrown their windows open in January, when their apartment is stifling, is in an odd way, replicating what engineers hoped would happen a century cialis cost ago,” Sisson writes (8/5/20).

You might enjoy. €œJerry Seinfeld. So You Think New York Is ‘Dead’ (It’s not.)” (8/24/20).In four days of speeches cialis cost lasting more than eight hours at the Republican National Convention, climate change was never mentioned as a threat to the country. That silence stands apart from the climate alarm bells that have been sounding since Donald Trump accepted his first nomination for president four years ago. Thousands of Americans have been killed in natural disasters such as hurricanes and wildfires during Trump’s first term in office.

Each of those four years has cialis cost been among the world’s hottest on record. Leaders of other nations have taken action as the United States ignores the issue. Even Wall Street has begun to take notice of how climate change could affect economic growth. None of that cialis cost was apparent during the convention. Instead, Republican speakers insisted that the real concern was the climate ideas presented by Democrats.

Many experts say that if climate change is left unanswered, it could cost trillions of dollars to the U.S. Economy. Republicans said the real costs would come from Democratic plans to restrain the use of fossil fuels. €œBiden has promised to abolish the production of American oil, coal, shale and natural gas—laying waste to the economies of Pennsylvania, Ohio, Texas, North Dakota, Oklahoma, Colorado and New Mexico,” Trump said. €œMillions of jobs will be lost, and energy prices will soar.” (Biden’s plan does not call for a fracking ban).

Those sentiments play well with Trump’s core supporters, but they’re askew from what most voters believe, including younger Republicans, according to polls. They don’t reflect the events that many Americans are either experiencing or seeing online. Uncontrolled wildfires in California and the strongest hurricane to hit Louisiana in 160 years. Even as an unrelinquishing pandemic has killed more than 180,000 people in the United States and kept millions of children across the country from returning to school, climate change remains on the minds of voters, polls show. Here are five climate themes that have advanced since Trump accepted his first nomination in 2016.

Natural disasters More than 3,000 Americans have died in natural catastrophes during the past four years. Most of them were victims of Hurricane Maria in 2017. The massive Category 5 storm killed an estimated 2,975 people in Puerto Rico and forced thousands to flee the U.S. Territory. The devastation continues to have ripple effects three years later.

Tens of thousands of people still live under leaky blue tarps. The island’s power supply, never reliable to begin with, has become far worse, and some parts of Puerto Rico were without power for a year. That was the same year that Hurricane Harvey dumped 60 inches of rain on parts of Houston, becoming the wettest cyclone on record. Tens of thousands of homes were damaged, and about 70 people were killed. Harvey caused more than $100 billion in damage, making it one of the costliest disasters to strike the United States.

Record wildfires have also burned across the West. The 2018 Camp Fire in California was the deadliest. It killed 85 people and destroyed more than 10,000 homes. It was fueled by drought, an outcome of climate change. This week, California continued to battle the second- and third-largest wildfires in state history.

Officials have connected the fires to climate change. €œAll but three of the Top 20 Largest #Wildfires have occurred since 2000, with 10 of these large and damaging wildfires occurring in the last decade,” the California Department of Forestry and Fire Protection tweeted yesterday. €œAs fire weather continues to become more extreme, California is adjusting to fight these larger and more destructive wildfires.” Heat The Trump years have been some of the hottest since record-keeping began after the Civil War, according to NASA. After a record-warm July, this year may break the all-time annual heat record set in 2016. That’s a likely outcome, said Gavin Schmidt, director of the NASA Goddard Institute for Space Studies.

That’s notable because four years ago, the record warmth was fueled by El Niño, a band of warm water covering the tropical Pacific Ocean. That influence is absent this year, Schmidt said, and long-term trends point to rising heat. €œWe know that the trend is moving up. On average, every decade is warmer than the last,” he said. €œThe changes we’re seeing now are so far outside what would be possible in an un-globally-warmed world.” Public opinion Polling shows that voter concern about climate change has been growing for years and that it has not diminished as a result of the coronavirus pandemic.

Concern among some voters has spiked during Trump’s tenure. Before the virus, polling showed climate change was the second-most important issue for Democratic primary voters, behind only health care. Now, responding to the virus and restoring the economy top the list. But the public still wants the federal government to address climate change, recent polling shows. More Americans than ever—about 25%—view climate change as “extremely personally important,” according to a poll released last week by Stanford University, Resources for the Future and ReconMR.

That number is twice as large as it was in 2006, said the poll, which surveyed 1,000 adults between May and August. It also found that 82% of respondents want the federal government to act on climate change. And three-quarters of those surveyed said they had personally experienced the effects of global warming. €œThe COVID-19 pandemic has offered a unique opportunity to learn how people feel about climate change when faced with a global crisis,” said Ray Kopp, vice president of research and policy engagement at Resources for the Future. €œThe claim that we can’t do anything about climate change without crashing the economy, or that we need to focus only on the pandemic and not do anything on climate right now, simply doesn’t resonate with Americans,” he said.

The U.S. (and everyone else) Since Trump pledged to withdraw from the Paris climate agreement in 2017, world leaders have pressed him to rejoin and to take the issue seriously. Among them are German Chancellor Angela Merkel and French President Emmanuel Macron. Last year, Trump said Prince Charles spent 90 minutes talking to him about climate change, trying to convince him to take stronger action and to once again make the United States a world leader. In response, Trump said he wanted “good climate,” but his administration has continued to roll back environmental safeguards meant to reduce emissions.

In December, Macron said other governments, including China, Russia and the European Union, would lead the world in reducing emissions. The yearslong process of withdrawing from the Paris Agreement won’t be done until November. Yesterday, Biden tweeted that if he wins the election, he would rejoin the pact on the first day of his presidency. Climate hits Wall Street This week, it was announced that Exxon Mobil Corp. Would be dropped from the Dow Jones Industrial Average stock index.

It’s a significant departure, as Exxon was the longest-tenured company on the Dow, having been listed for almost a century. It’s also a reflection of how oil companies have taken a financial hit amid growing concerns about climate change and as a result of declining consumption due to the pandemic. At the same time, some solar and wind companies have grown bigger than their fossil fuel competitors. The same factors that have weakened fossil fuel companies, including more aggressive climate targets, helped drive clean energy technologies. On Wall Street, business interests are increasingly warning the Federal Reserve and other regulators that climate change could pose a significant risk to the economy.

Earlier this year, 40 investment firms and organizations that handle more than $1 trillion in assets urged Fed Chairman Jerome Powell to take action. They warned him that climate “threats have the potential to compound in ways we don’t yet understand, with disastrous impacts the likes of which we haven’t seen before.” Reprinted from Climatewire with permission from E&E News. E&E provides daily coverage of essential energy and environmental news at www.eenews.net..

What should I tell my health care provider before I take Cialis?

They need to know if you have any of these conditions:

  • eye or vision problems, including a rare inherited eye disease called retinitis pigmentosa
  • heart disease, angina, a history of heart attack, irregular heart beats, or other heart problems
  • high or low blood pressure
  • kidney or liver disease
  • stroke
  • an unusual or allergic reaction to tadalafil, other medicines, foods, dyes, or preservatives

How to get cialis in the us

NONE

Minnesota marketplace highlights and how to get cialis in the us updatesOpen enrollment for 2021 health cialis tablets price in uae plans. November 1, 2020 through December how to get cialis in the us 22, 2020. Residents with qualifying events can still enroll or make changes to their 2020 coverage.Insurers implementing modest rate increases for 2021, after three straight years of average rate decreases.

Quartz has joined the exchange how to get cialis in the us for 2021, bringing total number of insurers to five.117,520 people enrolled for 2020, a new record for MNsure.Insurer participation in MNsure. 2014 to 2021.Reinsurance program received federal approval, began operation in 2018.With reinsurance, rates decreased for 2018 and again, even more significantly, for 2019. But reinsurance also reduced funding for MinnesotaCare.The elimination of CSR funding further reduced MinnesotaCare funding, but this has been partly restored by a court ruling.MN provided premium relief for non-subsidy-eligible enrollees for 2017 only.Governor vetoed a proposed 2019 switch to HealthCare.gov.MNsure’s small business exchange no longer has any participating insurers.Minnesota health exchange overviewMinnesota’s how to get cialis in the us one of the states fighting the hardest to preserve the Affordable Care Act’s gains.

See actions Minnesota has taken.Minnesota’s state-run exchange, MNsure, has five participating insurers for 2021, up from four in 2020. The exchange has more than 117,000 individual market enrollees as of 2020.As a result of the COVID-19 pandemic, MNsure joined most of the other state-run exchanges in offering a special enrollment period during how to get cialis in the us which people who were uninsured could enroll in a health plan. MNsure’s special enrollment period began March 23, and continued through April 21.

Nearly 9,500 Minnesota residents enrolled in private plans through MNsure during this window, as well as another 13,700 who enrolled in MinnesotaCare or Medicaid (enrollment in how to get cialis in the us those programs is open year-round for eligible residents).Allison O’Toole, who led MNsure as CEO for three years, announced her resignation in March 2018, and the exchange named Nate Clark, the MNsure COO, as acting CEO. A few months later, the MNsure board named Clark as the permanent CEO. O’Toole left MNsure to work as director of state affairs for United States of Care, a non-profit created by Andy Slavitt, who was the acting administrator of CMS under the Obama Administration.Throughout 2017, Minnesotans who bought their own health insurance (on or off-exchange) and weren’t eligible for ACA subsidies were provided with 25 percent premium rebates from the state as how to get cialis in the us a result of S.F.1, signed into law by Governor Dayton in early 2017.

The subsidies helped to offset the large premium increases that applied in Minnesota in 2017, and helped to stabilize the individual health insurance market in 2017. But the premium rebate program how to get cialis in the us expired at the end of 2017.Thanks in large part to the new reinsurance program that Minnesota created (details below), premiums decreased in Minnesota’s individual market in 2018, 2019, and again in 2020, although rates are increasing modestly for 2021. In May 2019, Minnesota leaders reached an agreement on a budget that included an extension of the reinsurance program through 2020 and 2021 (it has already been granted federal approval through the end of 2022, but the state has to continue to cover its share of the cost.

Minnesota Governor Tim Walz had hoped to implement how to get cialis in the us a premium subsidy program and a new tax credit in Minnesota starting in 2020. But a compromise in the budget ended up with the state opting to continue the existing reinsurance program for two more years instead.).But the waiver that provides federal pass-through funding for reinsurance also resulted in a sharp and unexpected decrease in federal funding for MinnesotaCare, the Basic Health Program that provides coverage for people with income between 138 percent and 200 percent of the poverty level (between $16,642 and $24,120 for a single person).In addition, the elimination of federal funding for cost-sharing reductions (CSR) in October 2018 resulted in a funding cut for MinnesotaCare, since the program is funded in large part by federal funds that would otherwise have been used to pay for premium subsidies and cost-sharing reductions in the exchange for the population that is instead eligible for MinnesotaCare. After an ensuing legal battle, a judge ordered HHS to restore funding for MinnesotaCare, although a resolution how to get cialis in the us of the situation is ongoing, and the amount that HHS agreed to pay was still less than MinnesotaCare would have received if CSR funding had continued.Open enrollment for 2021 health plans extended through December 22, 2020.

Insurers implementing modest rate increases for 2021, after three years of overall rate decreasesMNsure enabled window shopping for 2021 health plans as of October 12, 2020. This gives residents a few weeks to browse how to get cialis in the us the available plans before open enrollment starts on November 1, 2020. And MNsure has announced that open enrollment will continue through December 22, 2020.

That’s a week longer than the open enrollment period that will apply in states that use the how to get cialis in the us federally-run exchange. The flexibility to extend open enrollment is often cited as one of the benefits of having a fully state-run exchange. (MNsure had a similar extension last December, for 2020 health plans).For 2021, Quartz is joining the Minnesota how to get cialis in the us marketplace.

Quartz currently offers plans in Illinois and Wisconsin, and is expanding into Minnesota for 2021. And two of the existing insurers — HealthPartners and UCare — are expanding their coverage areas for 2021 how to get cialis in the us (BluePlus and Medica offer coverage statewide, and will continue to do so in 2021).The following average rate changes have been approved for MNsure’s insurers:Blue Plus. 4.21 percent how to get cialis in the us increase (down from an initially proposed 7.12 percent increase)Group Health/Health Partners (GHI).

0.67 percent increase (down from an initially proposed 4.15 percent increase)Medica. 2.42 percent increase (down from how to get cialis in the us an initially proposed 7.06 percent increase)UCare. 1.6 percent increase (up from an initially proposed 1.39 percent decrease)Quartz.

New for 2021, so no applicable rate changePreferredOne Insurance Company, which offers plans outside the exchange, is increasing premiums by how to get cialis in the us 1.05 percent (down from an initially proposed average increase of 5.09 percent). Rate changes in previous years2015. Average increase of 4.5 how to get cialis in the us percent.

MNsure critics characterized the official announcement as misleading as it failed to take into account low-cost 2014 plans from PreferredOne. Consumers who how to get cialis in the us bought a PreferredOne plan through MNsure for 2014 could only renew their policies for 2015 by working directly with the insurer, since PreferredOne stopped offering plans in the exchange at the end of 2014. However, PreferredOne rates went up an average of 63 percent, and consumers didn’t qualify for subsidies if they shopped outside the exchange.

2016. Average increase of 41.4 percent for the individual market, and about 38.5 for plans sold in MNsure (ie, not counting PreferredOne). Rates increased significantly in 2016 across the entire individual market in Minnesota — including plans sold through MNsure, the state-run exchange.Approved rates for 2016 were announced on October 1, 2015, ranging from about 15 percent for Medica to 49 percent for Blue Cross Blue Shield of Minnesota.

In general, the carriers cited higher-than-expected claims costs over the past year, along with the impending phase-out of the ACA’s reinsurance program as justification for their 2016 rate requests. But Governor Mark Dayton called some of the higher proposed increases “outrageous,” and promised a rigorous review of the filed rate changes and justifications. Ultimately, regulators were able to limit the highest rate increases to 49 percent — as opposed to the 54 percent that had been requested by Blue Plus and BCBS of MN — but the final weighted average rate increase in the individual market in Minnesota still ended up being the highest in the nation.

But Minnesota still had the lowest overall premiums in the upper midwest (although Minnesota had the highest average rate increase in the country for 2016, they had the lowest overall rates in the country in 2014 and 2015).Minnesota Commerce Commissioner Mike Rothman called the rate increases “unacceptably high,” and Gov. Dayton noted that he was “extremely unhappy” with the rate changes. But Rothman noted that his office “objected to all of the rates across the board,” and “squeezed out everything we could that was not actuarial justified.” In other words, the final rates, although much higher than officials and policyholders would have liked, were justified based on medical claims costs — the population enrolled in individual health plans in Minnesota was sicker than expected, and drug costs had been particularly onerous.Only about 55 percent of people who had 2015 coverage through MNsure received premium subsidies.

But due to the sharp premium increases, that had increased to about 63 percent for the people who had purchased or renewed coverage as of June 2016.2017. When the Minnesota Department of Commerce announced health insurance rates for 2017 for the individual and small group markets, the rate hikes were somewhat reasonable in the small group market (ranging from a decrease of 1 percent to an increase of 17.8 percent), but the individual market was “experiencing serious disruptions in 2017” and “on the verge of collapse.” The four carriers that offered plans through MNsure had the following average rate increases in 2017:Blue Plus = 55 percentHealthPartners/Group Health (GHI) = 50 percent (HealthPartners is only offering plans in 10 of the 67 counties where they offered plans in 2016. Their enrollment cap is 72,000 for 2017)Medica = 57.5 percent (enrollment cap is 50,000 for 2017)UCare = 66.8 percent (UCare capped enrollment at 30,000 for 2017, but only had 16,000 enrollees in 2016)The enrollment caps that HealthPartners, Medica, and UCare employed for 2017 were approved as part of the rate review process, and are designed to protect carriers from further financial losses as they absorb BCBSMN’s enrollees who are shopping for new coverage during open enrollment.In a news release relating to the rate announcement for 2017, the Minnesota Department of Commerce didn’t mince words.

They noted that the individual market in the state was on the brink of collapse, and that they did everything in their power to save the market. While they succeeded in keeping the state’s individual market viable for 2017, with only one carrier exiting (BCBSMN, although their HMO affiliate, Blue Plus, remained in the exchange), they reiterated very clearly that substantial reforms would be needed to keep the market stable in future years, and highlighted the fact that rates would be sharply higher and that carriers would limit enrollment in 2017.2018. Final rates for 2018 were approved in October 2017 (comprehensive information about the approved rates is here), based on the Minnesota Premium Security Plan (MSPS) being implemented but cost-sharing reductions (CSR) not being funded by the federal government (the cost of CSRs was added to on-exchange Silver plans).

Average approved rate changes for MNsure insurers ranged from a 13.3 percent decrease for UCare to a 2.8 percent increase for Blue Plus. Three of the four MNsure insurers decreased their average premiums for 2018.On September 21, MNsure had posted a notice indicating that if the reinsurance program were not approved, rates would be about 20 percent higher than they would otherwise be in 2018. Fortunately for Minnesota residents, the reinsurance program did receive federal approval, and average rates declined slightly for 2018.But some enrollees who don’t get ACA premium subsidies still experienced a rate increase, due to the termination of the one-year, state-funded 25 percent premium rebates at the end of 2017.PreferredOne, which exited MNsure at the end of 2014 and only offers coverage in the off-exchange market, proposed dramatically lower rates for 2018.

A 38 percent average decrease if MSPS were to be approved, and a 23 percent average decrease if not. The 38 percent decrease was implemented, and no adjustments were necessary to account for CSR funding, since PreferredOne does not offer plans in the exchange, and CSRs are only available on silver exchange plans.2019. Average premium decrease of 12.4 percent.

Average premiums dropped for all five insurers in the individual market in 2019. This was the second year in a row of declining rates in Minnesota, but Blue Plus had a small rate increase for 2018, so 2019 was the first year that all five insurers decreased their average rates. Minnesota insurance regulators noted that rates in 2019 were about 20 percent lower than they would have been without the reinsurance program.But most of Minnesota’s insurers charged higher rates in 2019 than they would have if the individual mandate penalty hadn’t been eliminated, and if access to short-term plans and association health plans hadn’t been expanded by the Trump administration.

For example, UCare’s rate filing notes that while average rates were decreasing by about 10 percent, the rate decrease would have been nearly 15 percent if the individual mandate penalty had remained in place.At ACA Signups, Charles Gaba calculated a weighted average rate decrease of 12.4 percent for 2019 in Minnesota, but noted that the average decrease would have been nearly 19 percent without those changes at the federal level.2020. Average premium decrease of 1 percent. Four of the five insurers (including PreferredOne, which only offers coverage off-exchange) in Minnesota’s individual market decreased their average premiums for 2020.

This was the third year in a row that average individual market premiums dropped in Minnesota’s individual market, due in large part to the reinsurance program that the state has established.The following average rate changes were implemented for 2020:Blue Plus. 1.5 percent decrease (Blue Plus had originally proposed a 4.8 percent increase)Group Health/Health Partners (GHI). 1.26 percent decrease (GHI had originally proposed a 2.1 percent increase)Medica.

1.01 percent decrease (Medica had originally proposed an average decrease of 1.4 percent)UCare. 0.18 percent increase (UCare originally proposed a 0.3 percent increase)PreferredOne, which only offers off-exchange coverage, reduced their rates by an average of 20 percent, on the heels of an 11 percent decrease in 2019. MNsure enrollment exceeded 116k in 2018, dropped to 113k for 2019, but grew to more than 1117k in 2020From 2014 through 2018, enrollment in MNsure’s individual market plans increased every year, reaching 116,358 people by 2018.

That was the highest open enrollment total in MNsure’s history, despite the shorter enrollment period, which ended in mid-January instead of the end of January (open enrollment for 2018 coverage ended on December 15, 2017 in states that use HealthCare.gov, but MNsure opted to extend their enrollment window that year, and have also extended subsequent enrollment windows).Enrollment dropped for the first time in 2019, when 113,552 people enrolled in individual market plans through MNsure. In most states that use HealthCare.gov, enrollment peaked in 2016 and has been dropping since then. But MNsure’s drop-off in 2019, which amounted to only a 2.4 percent reduction in enrollment, is the only time year-over-year enrollment has declined.

Notably, the ACA’s individual mandate penalty was eliminated as of 2019, and regulations that the Trump administration implemented in late 2018 now make it more feasible for healthy people to use short-term plans instead of ACA-compliant plans (Minnesota has its own rules for short-term plans, but they’re more relaxed than the Obama-era federal rules that applied in 2017 and most of 2018).And for 2020, enrollment grew again, reaching a record high of 117,520 enrollees.Here’s a look at the number of people who have signed up for individual market plans through MNsure during each year’s open enrollment period. These numbers all represent total enrollment at the end of open enrollment. Effectuated enrollment is always lower, and MNsure provides periodic effectuated enrollment data on their board meeting materials page.

Insurer participation in MNsure. 2014-20212014. Five insurers offered individual policies through MNsure for 2014.

Blue Cross Blue Shield of Minnesota, HealthPartners/Group Health, Medica, PreferredOne, and UCare. Kaiser Health News reported that Minnesota offered some of the lowest premiums for silver (mid-level) plans in the U.S. Four of Minnesota’s nine regions made Kaiser’s list of the 10 least expensive places to buy health insurance.2015.

But PreferredOne, which offered the lowest rates in the nation in 2014 and captured a large portion of 2014 enrollees, withdrew from MNsure for 2015. PreferredOne said remaining on the exchange was “not administratively and financially sustainable.” A Star Tribune business writer attributed PreferredOne’s departure as a market dynamics issue rather than a problem with MNsure.However, Blue Plus (an affiliate of Blue Cross Blue Shield of MN, offering HMO plans) joined the exchange for 2015, so there were still five insurers offering plans for 2015. Blue Cross Blue Shield of Minnesota, Blue Plus, Health Partners/Group Health, Medica, and UCare.

MNsure offered 84 plans statewide, up from 78 for 2014.2016. BCBSMN, Blue Plus, Health Partners/Group Health, Medica, and UCare offered individual market plans through MNsure for 2016.2017. In an effort to recruit more carriers to offer plans through MNsure for 2017 — particularly outside the Twin Cities metro area — state regulators sent out a request for proposals from health insurers on August 15, 2016.

Regulators noted that insurers could propose waivers of regulations in order to make it feasible for them to offer coverage through MNsure, although any such waiver requests would have to be approved by regulators.Steven Parente, a health insurance expert at the University of Minnesota, called the state’s effort to recruit insurers to MNsure a “distress call” and noted that August 15 is awfully late in the year to be putting out a request for insurer participation, given that open enrollment begins November 1. And ultimately, no new insurers opted to join MNsure for 2017.Blue Cross Blue Shield of MN dropped their individual market PPO plans at the end of 2016 due to significant financial losses. That left Blue Plus (which offered HMOs and covered roughly 13,000 people in 2016 in the individual market) as the only BCBSMN affiliate in the exchange.

Roughly 103,000 people had to select new plans during open enrollment.Most of those BCBSMN enrollees had off-exchange coverage, though. There were only about 20,400 MNsure enrollees (a little more than one in five MNsure enrollees) with coverage under BCBSMN who needed to switch to another plan during open enrollment. BCBSMN had individual PPO options available in all 87 counties in Minnesota through MNsure in 2016, while the Blue Plus coverage area — comprised of four separate HMO networks — was available in 77 of the state’s counties.Nationwide, carriers have been shifting away from PPOs and towards HMOs and EPOs.

In Colorado, Anthem Blue Cross Blue Shield also dropped their PPOs at the end of 2016. In Indiana, there were no PPOs available in the individual market by 2017. Blue Cross Blue Shield of New Mexico dropped all of their individual market plans at the end of 2015 except one off-exchange HMO.

Blue Cross Blue Shield of Texas dropped their individual market PPO plans at the end of 2015.The broad network offered by PPOs tends to be attractive to enrollees who have health problems. They’re often willing to pay higher premiums in trade for access to broad network of hospitals and specialists. But PPOs are expensive for carriers, as enrollees don’t need primary care referrals to see specialists, and it’s more challenging for carriers to hold down costs when there are more providers in the network.All of the MNsure carriers except Blue Plus are also limiting their total enrollment for 2017.

By November 11, 2016, less than two weeks into open enrollment for 2017 coverage, Medica had hit their 50,000 member enrollment cap for 2017 (including on and off-exchange enrollments, and also accounting for expected renewals of 2016 Medica plans), and their policies were no longer available in the individual market in Minnesota, on or off-exchange. The only exception was five counties (Benton, Crow Wing, Mille Lacs, Morrison, and Stearns) where Medica agreed not to limit enrollment, as all of the other available carriers in those counties have imposed enrollment caps too. In those five counties, Medica plans continued to be available.At that point, Medica’s market share in MNsure for 2017 stood at 34.2 percent.

By December 14, Medica’s market share had dropped to 27.7 percent, as enrollments had continued to climb for the remaining carriers.On January 31, Medica re-opened enrollment for 2017. This was because a smaller-than-expected number of 2016 Medica enrollees renewed their plans for 2017, meaning that the carrier still had some wiggle room under their 50,000 member cap. At that point, they had room for about 7,000 more enrollees.

Medica plans were thus available throughout the duration of the special enrollment period that was added on at the end of open enrollment, and continue to be available for people with qualifying events.2018. Plans continued to be available from Blue Plus, Health Partners/Group Health (GHI), Medica, UCare. In the months before a decision was reached regarding an extension of the open enrollment window for 2018 plans (the first year that the federal government imposed a shorter, month-and-a-half enrollment window), two of MNsure’s participating insurers had differing positions.

UCare believed the exchange should add an additional two-week special enrollment period, while Medica did not want the exchange to have the option to extend the newly-scheduled six-week enrollment window. Notably, Medica capped their enrollment very early during the 2017 open enrollment period, and while UCare also had an enrollment cap, it was set with a target of nearly doubling their 2016 enrollment. But Medica is the only MNsure insurer that didn’t set an enrollment cap for 2018.As was the case for 2017, enrollment caps were used in the individual market in Minnesota for 2018 by all insurers other than Medica (Medica did have an enrollment cap for 2017, which they hit very early in open enrollment.

However, they resumed enrollments at the end of January 2017). Details about the insurers’ enrollment caps are in the plan binders in SERFF. For 2018, MNsure insurers implemented the following enrollment caps:Blue Plus.

55,000 member cap (aiming for a target of 50,000 effectuated enrollees, but effectuated enrollment is always lower than the number of people who initially enroll)Health Partners/Group Health (GHI). 73,400 member cap (aiming for a target of 70,000 effectuated enrollees)Medica. No enrollment capUCare.

35,000 member cap (aiming for a target of 30,000 effectuated enrollees)MNsure confirmed in May 2018 that none of their insurers had hit their enrollment caps for 2018.Outside the exchange, PreferredOne had an enrollment cap of 3,000 members, although their 2017 membership was only about 300 people.2019 and 2020. Blue Plus, Health Partners/Group Health, UCare, and Medica have continued to offer plans through MNsure, and all of them continued to participate in 2020 as well. Blue Plus expanded to once again offer statewide coverage in 2020, for the first time since 2016.2021.

Quartz joined the exchange for 2021, joining the four existing insurers. HealthPartners and UCare are both expanding their coverage areas for 2021.Minnesota Premium Security Plan. 1332 waiver proposal approved by CMS, but with a significant funding cut for MinnesotaCareIn May 2017, Minnesota Governor Mark Dayton submitted a 1332 waiver proposal to CMS.

The 1332 waiver was based on H.F.5, which was enacted without Dayton’s signature in April 2017 (Dayton had proposed an alternative measure that would have allowed people in Minnesota to buy into MinnesotaCare. That measure was not able to pass the state’s Republican-dominated legislature).[For more than two decades, MinnesotaCare was a state program subsidizing health insurance for low-income residents. As of January 1, 2015, it transitioned to a Basic Health Program under the ACA, becoming the first BHP in the nation.]H.F.5 created the Minnesota Premium Security Plan (MPSP), which is a state-based reinsurance program (similar to the one the ACA implemented on a temporary basis through 2016, and that Alaska created for 2017.

Several other states have since implemented reinsurance programs). The reinsurance program, which took effect in Minnesota in 2018, covers a portion of the claims that insurers face, resulting in lower total claims costs for the insurers, and thus lower premiums (average individual market premiums in Minnesota decreased from 2017 to 2018 as a result of the reinsurance program). The reinsurance kicks in once claims reach $50,000, and covers them at 80 percent up to $250,000 (this is similar to the coverage under the transitional reinsurance program that the ACA provided from 2014 through 2016).H.F.5 was contingent upon approval of the 1332 waiver, because it relies partially on federal funding, in addition to state funding.

Under the federal approval that was granted in September 2017, the federal government is giving Minnesota the money that they save on premium tax credits, and that money is combined with state funds to implement the reinsurance program (lower premiums — as a result of the reinsurance program — result in the federal government having to pay a smaller total amount of premium tax credits, since the tax credits are smaller when premiums are smaller).It was expected that CMS would approve the state’s 1332 waiver proposal, and Governor Dayton requested that the approval process be swift so that the state could move forward with the implementation of the Minnesota Premium Security Plan in time for the 2018 plan year. Dayton indicated that his office had been told that approval would come in August 2017, but CMS didn’t approve the waiver until September 22. And the waiver approval letter noted that the federal savings for MinnesotaCare (the state’s Basic Health Program, or BHP) resulting from the reinsurance program would not be eligible to be passed along to the state — in other words, CMS would keep those savings instead.[Federal BHP funding is equal to 95 percent of the amount that the federal government would have otherwise spent on premium subsidies and cost-sharing reductions for the population that ends up being eligible for the BHP.

So lower premiums — as a result of reinsurance — for qualified health plans in the exchange means that the amount the federal government would have had to spend on premium subsidies for that population is lower. That translates into a smaller amount of funding for the state’s BHP, according to the approach that HHS took for Minnesota’s waiver approval.]And based on the scathing letter that Dayton sent CMS a few days earlier, it appeared at that point that Minnesota could actually lose money on the deal — losing more in federal funding for MinnesotaCare than they gain in reinsurance funding. Dayton noted in his letter that the 1332 waiver approval process had been “nightmarish,” and that Minnesota went to great lengths to follow instructions from CMS at every turn, throughout the process of drafting H.F.5 and the 1332 waiver proposal.

He explains that CMS provided Minnesota with explicit guidance in terms of how to draft the reinsurance program while maintaining full federal funding for MinnesotaCare, and highlighted the fact that the state never deviated from the instructions that were provided.The StarTribune editorial board called out then-Secretary of HHS, Tom Price and the Trump Administration for their lack of clarity on the issue, for apparently misleading the state during the 1332 waiver drafting process, and for effectively punishing the state of Minnesota for taking an innovative approach to ensuring that as many people as possible have health insurance.Insurers filed rates based on reinsurance being available. And by the time the waiver was approved, there was very little time to evaluate the potential impacts of the funding changes, as rates had to be finalized by October 2 in Minnesota. The finalized rates did incorporate the reinsurance program.

The state has accepted the approved waiver, but Gov. Dayton sent a letter to HHS on October 3, asking them to reconsider the MinnesotaCare funding cuts, but the issue has remained unresolved.Elimination of CSR funding results in additional funding cut for MinnesotaCare, but a lawsuit has partially restored that fundingNationwide, 54 percent of exchange enrollees benefit from cost-sharing subsidies. But in Minnesota, only 13 percent of exchange enrollees are receiving cost-sharing subsidies.

This is because of MinnesotaCare, which covers all enrollees with income up to 200 percent of the poverty level. That’s the same group that would otherwise benefit the most from cost-sharing subsidies, so the fact that MinnesotaCare is available means that most of the people who would otherwise be enrolled in cost-sharing subsidy plans are instead enrolled in MinnesotaCare.At first glance, this would appear to have made the uncertainty surrounding cost-sharing subsidy funding in 2017 a little less of a pressing issue in Minnesota than it was in many other states, since private insurers weren’t facing the sort of losses that insurers in other states were facing without federal funding for CSR. But when the Trump Administration eliminated federal funding for CSR in October 2017, HHS took the position tha t since CSR funding had been eliminated, the CSR portion of the federal funding for the BHPs in New York and Minnesota would be reduced to $0.

This was not a cut-and-dried conclusion, however, as explained earlier in 2017 by Michael Kalina.In January 2018, the Attorneys General for New York and Minnesota filed a lawsuit against the US Department of Health and Human Services, seeking to restore funding for their Basic Health Programs. A judge ruled in favor of the states in May 2018, ensuring that MinnesotaCare would continue to receive at least some CSR-based funding. The amount awarded to the state for the first quarter of 2018 was just over half of what the state had initially expected in CSR-related funding, but a larger chuck of the funding was restored later in 2018.

According to the Star Tribune, however, Minnesota still ended up losing $161 million in federal funding for MinnesotaCare due to the CSR funding cuts.In early 2019, the Trump administration proposed yet another funding cut (a third, after the cuts imposed by the reinsurance program and the elimination of CSR funding) as part of a new methodology for calculating BHP funding. This one was much smaller than the other two cuts, but taken together the funding reductions are pushing MinnesotaCare towards a looming budget shortfall. SHOP exchange.

Down to one carrier as of 2016, zero by 2018 (and still zero in 2019)In 2015, there were two carriers in MNsure’s SHOP exchange for small businesses. Blue Cross Blue Shield of Minnesota, and Medica. But Medica announced in 2015 that they would exit the SHOP exchange in Minnesota, North Dakota, and Wisconsin at the end of the year.

That left BCBS as the only small group carrier available through MNsure in 2016, but it didn’t change much from a practical standpoint, since 83 percent of MNsure’s small groups were enrolled in plans through BCBS in 2015. Indeed, Medica’s reason for exiting the small business exchange was based on low enrollment in the first two years.Blue Cross Blue Shield of Minnesota continued to be the only insurer offering SHOP coverage via MNsure in 2017, but announced in July 2017 that they would no longer offer SHOP coverage in 2018, and would instead transition their SHOP enrollees to small business coverage outside the exchange. At that point, there were only 3,287 people enrolled in SHOP coverage in Minnesota — far below the 155,000 people that were originally projected to have coverage through MNsure’s SHOP program by 2016 (this much lower-than-anticipated enrollment has been the case in nearly every state’s SHOP exchange.

This situation is not unique to Minnesota). State law provided 25% premium rebate in 2017. Amendment to allow plans without essential benefits was cut from final legislationThroughout 2016, then-Governor Dayton called for a state-funded premium rebate for people who buy their own insurance but aren’t eligible for the ACA’s premium subsidies (those are only available for people with income up to 400 percent of the poverty level, or $100,400 for a family of four in 2019).Governor Dayton also noted that the government needed to act quickly to stabilize the individual market in Minnesota, and by late November 2016, his patience with lawmakers was wearing thin.

In a November 23 press conference, Dayton said that House Republicans needed to “stop dilly-dallying” and decide whether to move forward with Dayton’s rebate proposal.Dayton had also indicated that he was considering calling a special session of the legislature after election day to address the situation, and that was being negotiated for December 20. But the talks fell through when Dayton and Republican House Speaker Kurt Daudt couldn’t agree on the three bills that would have been addressed in the special session. As a result, there was no special session.Instead, the issue was taken up by lawmakers as soon as the 2017 legislative session began.

On January 5, Minnesota Senators Michelle Benson (R, 31st District) and Gary Dahms (R, 16th District) introduced S.F.1. The bill called for using $300 million in state funding to provide a 25 percent rebate to roughly 125,000 people in Minnesota.S.F.1 passed the Minnesota Senate by a 35-31 vote on January 12. Only one DFL Senator (Melisa Franzen, from Edina) voted with Republicans in favor of the legislation.

It was then sent to the House, where an amendment was added that stripped out the requirement that health plans provide various mandated benefits (see “Journal of the Day” section “Top of page 154” in this version of the bill. Under the terms of the amendment, as long as a carrier offered at least one plan with all the mandated benefits, they would have been allowed to offer others without mandated benefits).The amended bill was sent back to the Senate on January 23. Differences between the bills that the two chambers passed had to be reconciled before being sent to Governor Dayton for his signature.

By that point, the amendment to allow less-robust plans to be sold had garnered national attention, and public outrage helped to push lawmakers away from the provision. S.F.1 had also called for $150 million to be appropriated for fiscal year 2018 (through June 30, 2019) from the state general fund to a state-based reinsurance program to stabilize the individual market (Alaska did something similar in 2016, preventing a market collapse), but that provision was also removed in the final version (Minnesota did ultimately set up a reinsurance program, effective in 2018, which has served to stabilize the market and reduce premiums).A Conference Committee in the Senate recommended that the House “recede from its amendments” and the Conference Committee report passed the Senate on a 47-19 vote. The House passed the bill a few hours later, 108-19.

It was sent to Governor Dayton, who immediately signed it into law. DFLers did have to compromise on one issue during the process. S.F.1 allows for-profit HMOs to begin operating in Minnesota’s individual market, which had long been limited to non-profit HMOs.Consumers were told to expect the premium rebates to show up by April 2017, but they were retroactively effective to January 2017.

So a person who had been paying full price for a plan since January 2017 saw a substantial premium reduction on the April or May invoice. Going forward, for the remainder of the year, a 25 percent rebate applied each month.Since S.F.1 was signed into law with only a few days remaining in open enrollment (it ended January 31 that year), Governor Dayton and exchange officials were worried that there wouldn’t be enough time for people to learn about the rebate and apply for coverage before January 31. In December, Dayton had asked HHS to allow MNsure to extend its enrollment deadline to February 28 (instead of January 31) in order to allow lawmakers more time to work out the details of a state-based premium rebate while still allowing people to enroll after the legislative process is complete.HHS denied the request for a blanket extension, but MNsure used their own authority on January 28 to grant a one-week special enrollment period (February 1 to February 8) due to exceptional circumstances.

Although the state-based 25 percent premium rebate was available on or off the exchange, the one-week extension was only valid through MNsure. Health insurers did not have to accept off-exchange enrollments without a qualifying event after January 31.The 25 percent premium rebate program in Minnesota was only authorized for one year, so the rebates did not continue into 2018. And although almost 100,000 people received premium relief through the program in 2017, it ended up costing less than the legislature had allocated, and about $100 million was returned to the state’s budget at the end of 2017.Protecting Medicaid enrollees from estate liensIn every state, Medicaid is jointly funded by the state and the federal government.

Longstanding federal regulations, which predate the ACA, require states to “seek recovery of payments from the individual’s estate for nursing facility services, home and community-based services, and related hospital and prescription drug services” for any Medicaid enrollee over the age of 55. This applies essentially to long-term care services, but states also have the option to go after the individual’s estate to recover costs for other care that was provided by Medicaid after age 55.Prior to 2014, this wasn’t typically an issue, as Medicaid eligibility was generally restricted by asset tests or requirements that applicants be disabled or pregnant (although Minnesota did have much more generous Medicaid eligibility guidelines than most states prior to 2014). But as of 2014, in states that expanded Medicaid under the ACA, the only eligibility guideline is income.

Applicants with income that doesn’t exceed 138 percent of the poverty level are directed to Medicaid, regardless of any assets they might have.When applicants use the health insurance exchange — MNsure in Minnesota — they’re automatically funneled into Medical Assistance (Medicaid) if their income is under 138 percent of the poverty level. But what these enrollees didn’t know was that the state also had a program in place to put liens on estates for Medicaid-provided services for people age 55 and older.The combination of these systems caught numerous residents off guard. They were enrolled in Medical Assistance through MNsure based on their income, but were not aware that liens were being placed on their homes so that the state could recoup the costs upon their deaths.State Senator Tony Lourey (DFL, District 11) addressed the issue with language included in HF2749, the Omnibus supplemental budget bill, which was signed into law by Governor Dayton on June 1, 2016.

The legislation limits estate recovery to just what’s required under federal Medicaid rules (ie, essentially, long-term care costs for people age 55 or older), and makes the provision retroactive to January 1, 2014.Early tech strugglesMNsure opened for business in the fall of 2013, but technological issues persisted well into 2015, despite numerous improvements throughout 2014. Given MNsure’s difficult launch, the state conducted a series of audits and reviews. The first audit reviewed how MNsure spent state and federal money.

Auditors concluded that the exchange has generally adequate internal controls and found no fraud or abuse. The review was conducted by the state Office of the Legislative Auditor, and the report was published in October 2014.Another audit, also conducted by the Office of the Legislative Auditor and released in November 2014, found that the MNsure system in some cases incorrectly determined who qualified for public health benefits. The errors occurred during the first open enrollment period, before a series of system fixes were implemented.

The audit did not quantify the total financial impact of the errors. The state Human Services commissioner said a consultant working on technical fixes to MNsure concluded that the eligibility functionality was working correctly as of June 2014.A third audit, a performance evaluation report released in February 2015, said “MNsure’s failures outweighed its achievements.” Among other criticisms, auditors said MNsure staff withheld information from the board of directors and state officials, the enrollment website was seriously flawed and launched without adequate testing, and the first-year enrollment target was unrealistically low.In April 2014, MNsure hired Deloitte Consulting to audit MNsure’s technology and improve the website to make enrolling in coverage and updating life events easier and more streamlined. Deloitte has been involved in successful state-run marketplaces for Connecticut, Kentucky, Rhode Island and Washington.Software upgrades were installed in August 2014, and system testing continued right up until the start of open enrollment.

To reduce wait times for consumers and insurance professionals, MNsure increased its call center and support staff and launched a dedicated service line for agents and brokers.More in-person assisters were available in Minnesota for the 2015 open enrollment period. MNsure encourages residents to utilize the exchange’s assister directory to find local navigators and brokers who can help with the enrollment process.MNsure has improved dramatically in terms of its technology since the early days of ACA implementation, and enrollment increased every year from 2014 through 2019.Lawmakers approved switching to HealthCare.gov as of 2019, but governor vetoedOn May 9, 2017, lawmakers in Minnesota passed SF800, an omnibus health and human services bill. Among many other things, the legislation called for switching from MNsure to the federally-run marketplace (HealthCare.gov) starting in 2019 (see Section 5).

But Governor Dayton vetoed it.Gov. Dayton has long been supportive of MNsure, and had previously clarified that he would veto the bill. In noting his plans to veto the legislation, Dayton made no mention of the transition to HealthCare.gov that was included in the legislation, but focused instead on the sharp budget cuts in the bill.

But his veto ensured that MNsure would remain in place, at least for the time being.The Senate’s original version of SF800 did not call for scrapping MNsure, but the bill went through considerable back-and-forth between the two chambers, and the version that passed was the 4th engrossment of the bill.In March 2015, Dayton had asked the legislature to create a Task Force on Health Care Financing that would study MNsure along with possible future alternatives. Dayton noted in his letter that he supported making MNsure “directly accountable to the governor and subject to the same legislative oversight as other state agencies” and his budget included half a million dollars devoted to the task force. The spending bill was approved by the legislature in May, and the 29-member task force was appointed in the summer.One of the possibilities that the task force considered was the possibility of switching to Healthcare.gov, but it’s clear that there was no cut-and-dried answer to the question of whether Minnesota is better served by having a state-run exchange, switching to a federally-run exchange, or teaming up with the federal government on either a supported state-based marketplace or partnership exchange.In a December 2015 meeting of the task force, the MN Department of Human Services presented a financial analysis of the alternatives available to MNsure.

They determined that switching entirely to Healthcare.gov would cost the state an additional $5.1 million in one-time costs from June 2016 to June 2017. And switching to a supported state-based marketplace would cost an additional $6.6 million during that same time frame. If the state had opted to switch to Healthcare.gov, the soonest it could have happened was 2018, since HHS requires a year’s notice from states wishing to transition to Healthcare.gov, and Minnesota wouldn’t have been in a position to make a decision until sometime in 2016.There were significant reservations about making that switch prior to the Supreme Court’s ruling on King v.

Burwell. The Court ruled in June 2015 that subsidies are legal in every state, including those that use Healthcare.gov. Prior to the decision, a switch to Healthcare.gov could have jeopardized subsidies for tens of thousands of Minnesota residents.

But once it was clear that Healthcare.gov’s subsidies are safe, some stakeholders began calling for Minnesota to scrap its state-run exchange and use Healthcare.gov instead. Because the MNsure task force was included in the 2016 budget, no hasty decisions were made.In January 2016, the task force submitted their recommendations to the legislature. They covered a broad range of issues, but did not recommend that MNsure transition to the federal enrollment platform.

Lawmakers essentially left the exchange alone during the 2016 legislative session.The magnitude of the 2016 rate increases that were announced in October resulted in MNsure opponents renewing their calls to switch to Healthcare.gov. But it’s important to keep in mind that the 41 percent weighted average rate hike in Minnesota was market-wide, and did not just apply to MNsure enrollees. In fact, the off-exchange carrier (PreferredOne) had among the highest rate hikes in the state for 2016, at 39 percent, and the exchange’s weighted average rate increase (38.5 percent) was lower than the weighted average rate increase for the whole individual market (41 percent).Minnesota health insurance exchange linksMNsure855-3MNSURE (855-366-7873)State Exchange Profile.

MinnesotaThe Henry J. Kaiser Family Foundation overview of Minnesota’s progress toward creating a state health insurance exchange.Louise Norris is an individual health insurance broker who has been writing about health insurance and health reform since 2006. She has written dozens of opinions and educational pieces about the Affordable Care Act for healthinsurance.org.

Her state health exchange updates are regularly cited by media who cover health reform and by other health insurance experts.Key takeaways Medicaid expansion in HawaiiHawaii adopted Medicaid expansion through the Affordable Care Act, extending eligibility for Medicaid to adults with income up to 133 percent of the poverty level (138 percent with the automatic 5 percent income disregard). Medicaid expansion took effect in January 2014.According to the Kaiser Family Foundation, about 70,000 Hawaii residents were uninsured in 2015. With Medicaid expansion now covering low-income, nonelderly adults, 50 percent of Hawaii’s remaining uninsured population at that point was eligible for Medicaid – although they may not realize that they’re eligible.

According to U.S. Census data, only 3.5 percent of Hawaii residents were uninsured as of 2016, down from 6.7 percent in 2013. Although the state’s uninsured rate was reduced by nearly half from 2013 to 2016, it was already less than half of the national average uninsured rate even in 2013, before the bulk of the ACA’s provisions had taken effect.

Hawaii’s Prepaid Health Care Act, which has been in place since the 1970s, had already resulted in nearly all of the state’s population having insurance coverage, even before the ACA took effect. However, with the coronavirus outbreak, job losses and the subsequent loss of employer-provided insurance have contributed to a jump in the uninsured rate across the U.S. As of May 2020, Hawaii’s uninsured rate was 10 percent.Medicaid expansion helped cement top-ranking health scores Federalpoverty levelcalculator 0.0% of Federal Poverty Level Hawaii has a long history of supporting initiatives to make health insurance broadly available to residents.

Hawaii was among the first six states that implemented a Medicaid program in January 1966, just six months after federal legislation authorizing the program was enacted. In 1974, Hawaii implemented its Prepaid Health Care Act, which mandated that most employers make health insurance available to employees who work at least 20 hours a week.In conjunction with the Affordable Care Act (ACA), Hawaii initially implemented a state-run health insurance marketplace and adopted Medicaid expansion. The marketplace transitioned to a federally-supported state-run marketplace for 2016, and transitioned again to a fully federally-run exchange for 2017, largely in an effort to take advantage of the economies of scale that the federally-run exchange could bring to a state with low overall enrollment in the individual market (because of Hawaii’s Prepaid Health Care Act, nearly all non-elderly Hawaii residents get coverage from an employer, and relatively few need coverage under individual market plans).

Nothing changed about Medicaid with the switch to Healthcare.gov though. The expanded Medicaid eligibility guidelines are still in effect in Hawaii.Through its efforts, Hawaii consistently has low uninsured rates and high overall health scores. As of 2015, Hawaii was ranked the healthiest state in the nation according to the Gallup Healthways Physical Wellbeing Index, and the state consistently scores near the top in other ranking systems (number 2 the America’s Health Rankings 2017 survey, and number 3 in the Commonwealth Fund’s 2017 Scorecard on State Health System Performance).Who is eligible for Medicaid in Hawaii?.

Hawaii’s Medicaid eligibility levels for children are much higher than the national average and about average for pregnant women and parents.Children ages 0-18 qualify with family income levels up to 308 of the federal poverty level (FPL)Pregnant women qualify with family income up to 191 percent of FPLParents and other adults qualify with family income up to 138 percent of FPLHawaii also uses Medicaid funds to help cover premium costs for Hawaii residents who aren’t U.S. Citizens but who are citizens of nations that have entered into the Compact of Free Association (COFA) with the U.S.How do I enroll in Medicaid in Hawaii?. Hawaii’s Medicaid program is called MED-QUEST (MQD).

QUEST stands for Quality care, Universal access, Efficient utilization, Stabilizing costs, and Transforming the way health care is provided to recipients.You can apply for MED-QUEST. Hawaii Medicaid enrollment numbersMore than 351,000 people were enrolled in Hawaii’s Medicaid and CHIP programs as of June 2020. This figure is a 22% increase over 2013 (pre-ACA) enrollment, when about 288,000 people were enrolled.

Accordingly to the Kaiser Family Foundation, 107,300 of those enrolled in Hawaii Medicaid are part of the ACA-authorized expansion as of June 2019.Hawaii Medicaid historyHawaii implemented its Medicaid program in January 1966.In the early 1990s, Hawaii implemented the State Health Insurance Program (SHIP) to cover people who weren’t eligible for Medicaid. Then, in 1994, CMS approved Hawaii’s section 1115 Medicaid waiver (one of the first in the nation) to wrap SHIP in with Medicaid in an effort to achieve universal insurance coverage (in combination with the state’s Prepaid Health Care Act). The result of the waiver was the creation of Hawaii’s MED-QUEST program, which initially covered low-income women and children, but has since expanded (as of 2009) to cover nearly all of Hawaii’s Medicaid beneficiaries.

The MED-QUEST waiver is subject to renewal every five years.Medicaid in Hawaii is separated into two different methods of providing services. The fee-for-service (FFS) program and the managed care program, called MED-QUEST or MQD. Under the FFS program, doctors and other healthcare providers bill Medicaid directly to be reimbursed for services provided to Medicaid beneficiaries.

Under MED-QUEST, the state contracts with managed care plans who in turn provide healthcare services to Medicaid beneficiaries.As of 2011, more than 98 percent of the people enrolled in Hawaii’s Medicaid program were covered through managed care. By March 2015, Kaiser Family Foundation reported that 335,007 Medicaid enrollees in Hawaii were covered under managed care programs. That’s higher than the August 2015 total Medicaid/CHIP enrollment count, but KFF notes that the managed care number includes people who are covered under Hawaii’s fully-state-funded Medicaid program, in addition to the majority of enrollees who are in regular Medicaid that’s funded partially by the state and partially by the federal government.In August 2017, Hawaii submitted a waiver amendment to CMS in order to gain federal approval to use Medicaid funding to provide housing services to qualified Medicaid enrollees who are homeless and also have behavioral health and/or substance abuse problems.

That waiver request was still pending as of February 2018.Louise Norris is an individual health insurance broker who has been writing about health insurance and health reform since 2006. She has written dozens of opinions and educational pieces about the Affordable Care Act for healthinsurance.org. Her state health exchange updates are regularly cited by media who cover health reform and by other health insurance experts..

Minnesota marketplace how do you take cialis highlights and updatesOpen enrollment for 2021 health cialis cost plans. November 1, cialis cost 2020 through December 22, 2020. Residents with qualifying events can still enroll or make changes to their 2020 coverage.Insurers implementing modest rate increases for 2021, after three straight years of average rate decreases. Quartz has joined the exchange for 2021, bringing total number of insurers to five.117,520 people enrolled for 2020, a new record for cialis cost MNsure.Insurer participation in MNsure.

2014 to 2021.Reinsurance program received federal approval, began operation in 2018.With reinsurance, rates decreased for 2018 and again, even more significantly, for 2019. But reinsurance also reduced funding for MinnesotaCare.The elimination of CSR funding further reduced MinnesotaCare funding, but this has been partly restored by a court ruling.MN provided premium relief cialis cost for non-subsidy-eligible enrollees for 2017 only.Governor vetoed a proposed 2019 switch to HealthCare.gov.MNsure’s small business exchange no longer has any participating insurers.Minnesota health exchange overviewMinnesota’s one of the states fighting the hardest to preserve the Affordable Care Act’s gains. See actions Minnesota has taken.Minnesota’s state-run exchange, MNsure, has five participating insurers for 2021, up from four in 2020. The exchange has more than 117,000 individual market enrollees as of 2020.As a result of the COVID-19 pandemic, MNsure joined most of the other state-run cialis cost exchanges in offering a special enrollment period during which people who were uninsured could enroll in a health plan.

MNsure’s special enrollment period began March 23, and continued through April 21. Nearly 9,500 Minnesota residents enrolled in private plans through MNsure during this window, as well as another 13,700 who enrolled in MinnesotaCare or Medicaid (enrollment in those programs is open year-round for eligible residents).Allison O’Toole, who led MNsure as CEO for three years, announced her resignation in March 2018, and the exchange named Nate cialis cost Clark, the MNsure COO, as acting CEO. A few months later, the MNsure board named Clark as the permanent CEO. O’Toole left MNsure to work as director of state affairs for United States cialis cost of Care, a non-profit created by Andy Slavitt, who was the acting administrator of CMS under the Obama Administration.Throughout 2017, Minnesotans who bought their own health insurance (on or off-exchange) and weren’t eligible for ACA subsidies were provided with 25 percent premium rebates from the state as a result of S.F.1, signed into law by Governor Dayton in early 2017.

The subsidies helped to offset the large premium increases that applied in Minnesota in 2017, and helped to stabilize the individual health insurance market in 2017. But the premium rebate program expired at the end of 2017.Thanks in large part to the new reinsurance program that Minnesota created (details below), premiums decreased cialis cost in Minnesota’s individual market in 2018, 2019, and again in 2020, although rates are increasing modestly for 2021. In May 2019, Minnesota leaders reached an agreement on a budget that included an extension of the reinsurance program through 2020 and 2021 (it has already been granted federal approval through the end of 2022, but the state has to continue to cover its share of the cost. Minnesota Governor Tim Walz had hoped to implement a premium subsidy program and a new cialis cost tax credit in Minnesota starting in 2020.

But a compromise in the budget ended up with the state opting to continue the existing reinsurance program for two more years instead.).But the waiver that provides federal pass-through funding for reinsurance also resulted in a sharp and unexpected decrease in federal funding for MinnesotaCare, the Basic Health Program that provides coverage for people with income between 138 percent and 200 percent of the poverty level (between $16,642 and $24,120 for a single person).In addition, the elimination of federal funding for cost-sharing reductions (CSR) in October 2018 resulted in a funding cut for MinnesotaCare, since the program is funded in large part by federal funds that would otherwise have been used to pay for premium subsidies and cost-sharing reductions in the exchange for the population that is instead eligible for MinnesotaCare. After an ensuing legal battle, a judge ordered HHS to restore funding for MinnesotaCare, although cialis cost a resolution of the situation is ongoing, and the amount that HHS agreed to pay was still less than MinnesotaCare would have received if CSR funding had continued.Open enrollment for 2021 health plans extended through December 22, 2020. Insurers implementing modest rate increases for 2021, after three years of overall rate decreasesMNsure enabled window shopping for 2021 health plans as of October 12, 2020. This gives residents a few weeks cialis cost to browse the available plans before open enrollment starts on November 1, 2020.

And MNsure has announced that open enrollment will continue through December 22, 2020. That’s a week cialis cost longer than the open enrollment period that will apply in states that use the federally-run exchange. The flexibility to extend open enrollment is often cited as one of the benefits of having a fully state-run exchange. (MNsure had cialis cost a similar extension last December, for 2020 health plans).For 2021, Quartz is joining the Minnesota marketplace.

Quartz currently offers plans in Illinois and Wisconsin, and is expanding into Minnesota for 2021. And two of the existing insurers — HealthPartners and UCare — are expanding their coverage areas cialis cost for 2021 (BluePlus and Medica offer coverage statewide, and will continue to do so in 2021).The following average rate changes have been approved for MNsure’s insurers:Blue Plus. 4.21 percent increase (down from an initially proposed cialis cost 7.12 percent increase)Group Health/Health Partners (GHI). 0.67 percent increase (down from an initially proposed 4.15 percent increase)Medica.

2.42 percent increase (down from an initially proposed cialis cost 7.06 percent increase)UCare. 1.6 percent increase (up from an initially proposed 1.39 percent decrease)Quartz. New for 2021, so no applicable rate changePreferredOne Insurance Company, which offers plans outside cialis cost the exchange, is increasing premiums by 1.05 percent (down from an initially proposed average increase of 5.09 percent). Rate changes in previous years2015.

Average increase cialis cost of 4.5 percent. MNsure critics characterized the official announcement as misleading as it failed to take into account low-cost 2014 plans from PreferredOne. Consumers who bought a PreferredOne plan through MNsure for 2014 could only renew their policies for 2015 by working directly with the insurer, since cialis cost PreferredOne stopped offering plans in the exchange at the end of 2014. However, PreferredOne rates went up an average of 63 percent, and consumers didn’t qualify for subsidies if they shopped outside the exchange.

2016. Average increase of 41.4 percent for the individual market, and about 38.5 for plans sold in MNsure (ie, not counting PreferredOne). Rates increased significantly in 2016 across the entire individual market in Minnesota — including plans sold through MNsure, the state-run exchange.Approved rates for 2016 were announced on October 1, 2015, ranging from about 15 percent for Medica to 49 percent for Blue Cross Blue Shield of Minnesota. In general, the carriers cited higher-than-expected claims costs over the past year, along with the impending phase-out of the ACA’s reinsurance program as justification for their 2016 rate requests.

But Governor Mark Dayton called some of the higher proposed increases “outrageous,” and promised a rigorous review of the filed rate changes and justifications. Ultimately, regulators were able to limit the highest rate increases to 49 percent — as opposed to the 54 percent that had been requested by Blue Plus and BCBS of MN — but the final weighted average rate increase in the individual market in Minnesota still ended up being the highest in the nation. But Minnesota still had the lowest overall premiums in the upper midwest (although Minnesota had the highest average rate increase in the country for 2016, they had the lowest overall rates in the country in 2014 and 2015).Minnesota Commerce Commissioner Mike Rothman called the rate increases “unacceptably high,” and Gov. Dayton noted that he was “extremely unhappy” with the rate changes.

But Rothman noted that his office “objected to all of the rates across the board,” and “squeezed out everything we could that was not actuarial justified.” In other words, the final rates, although much higher than officials and policyholders would have liked, were justified based on medical claims costs — the population enrolled in individual health plans in Minnesota was sicker than expected, and drug costs had been particularly onerous.Only about 55 percent of people who had 2015 coverage through MNsure received premium subsidies. But due to the sharp premium increases, that had increased to about 63 percent for the people who had purchased or renewed coverage as of June 2016.2017. When the Minnesota Department of Commerce announced health insurance rates for 2017 for the individual and small group markets, the rate hikes were somewhat reasonable in the small group market (ranging from a decrease of 1 percent to an increase of 17.8 percent), but the individual market was “experiencing serious disruptions in 2017” and “on the verge of collapse.” The four carriers that offered plans through MNsure had the following average rate increases in 2017:Blue Plus = 55 percentHealthPartners/Group Health (GHI) = 50 percent (HealthPartners is only offering plans in 10 of the 67 counties where they offered plans in 2016. Their enrollment cap is 72,000 for 2017)Medica = 57.5 percent (enrollment cap is 50,000 for 2017)UCare = 66.8 percent (UCare capped enrollment at 30,000 for 2017, but only had 16,000 enrollees in 2016)The enrollment caps that HealthPartners, Medica, and UCare employed for 2017 were approved as part of the rate review process, and are designed to protect carriers from further financial losses as they absorb BCBSMN’s enrollees who are shopping for new coverage during open enrollment.In a news release relating to the rate announcement for 2017, the Minnesota Department of Commerce didn’t mince words.

They noted that the individual market in the state was on the brink of collapse, and that they did everything in their power to save the market. While they succeeded in keeping the state’s individual market viable for 2017, with only one carrier exiting (BCBSMN, although their HMO affiliate, Blue Plus, remained in the exchange), they reiterated very clearly that substantial reforms would be needed to keep the market stable in future years, and highlighted the fact that rates would be sharply higher and that carriers would limit enrollment in 2017.2018. Final rates for 2018 were approved in October 2017 (comprehensive information about the approved rates is here), based on the Minnesota Premium Security Plan (MSPS) being implemented but cost-sharing reductions (CSR) not being funded by the federal government (the cost of CSRs was added to on-exchange Silver plans). Average approved rate changes for MNsure insurers ranged from a 13.3 percent decrease for UCare to a 2.8 percent increase for Blue Plus.

Three of the four MNsure insurers decreased their average premiums for 2018.On September 21, MNsure had posted a notice indicating that if the reinsurance program were not approved, rates would be about 20 percent higher than they would otherwise be in 2018. Fortunately for Minnesota residents, the reinsurance program did receive federal approval, and average rates declined slightly for 2018.But some enrollees who don’t get ACA premium subsidies still experienced a rate increase, due to the termination of the one-year, state-funded 25 percent premium rebates at the end of 2017.PreferredOne, which exited MNsure at the end of 2014 and only offers coverage in the off-exchange market, proposed dramatically lower rates for 2018. A 38 percent average decrease if MSPS were to be approved, and a 23 percent average decrease if not. The 38 percent decrease was implemented, and no adjustments were necessary to account for CSR funding, since PreferredOne does not offer plans in the exchange, and CSRs are only available on silver exchange plans.2019.

Average premium decrease of 12.4 percent. Average premiums dropped for all five insurers in the individual market in 2019. This was the second year in a row of declining rates in Minnesota, but Blue Plus had a small rate increase for 2018, so 2019 was the first year that all five insurers decreased their average rates. Minnesota insurance regulators noted that rates in 2019 were about 20 percent lower than they would have been without the reinsurance program.But most of Minnesota’s insurers charged higher rates in 2019 than they would have if the individual mandate penalty hadn’t been eliminated, and if access to short-term plans and association health plans hadn’t been expanded by the Trump administration.

For example, UCare’s rate filing notes that while average rates were decreasing by about 10 percent, the rate decrease would have been nearly 15 percent if the individual mandate penalty had remained in place.At ACA Signups, Charles Gaba calculated a weighted average rate decrease of 12.4 percent for 2019 in Minnesota, but noted that the average decrease would have been nearly 19 percent without those changes at the federal level.2020. Average premium decrease of 1 percent. Four of the five insurers (including PreferredOne, which only offers coverage off-exchange) in Minnesota’s individual market decreased their average premiums for 2020. This was the third year in a row that average individual market premiums dropped in Minnesota’s individual market, due in large part to the reinsurance program that the state has established.The following average rate changes were implemented for 2020:Blue Plus.

1.5 percent decrease (Blue Plus had originally proposed a 4.8 percent increase)Group Health/Health Partners (GHI). 1.26 percent decrease (GHI had originally proposed a 2.1 percent increase)Medica. 1.01 percent decrease (Medica had originally proposed an average decrease of 1.4 percent)UCare. 0.18 percent increase (UCare originally proposed a 0.3 percent increase)PreferredOne, which only offers off-exchange coverage, reduced their rates by an average of 20 percent, on the heels of an 11 percent decrease in 2019.

MNsure enrollment exceeded 116k in 2018, dropped to 113k for 2019, but grew to more than 1117k in 2020From 2014 through 2018, enrollment in MNsure’s individual market plans increased every year, reaching 116,358 people by 2018. That was the highest open enrollment total in MNsure’s history, despite the shorter enrollment period, which ended in mid-January instead of the end of January (open enrollment for 2018 coverage ended on December 15, 2017 in states that use HealthCare.gov, but MNsure opted to extend their enrollment window that year, and have also extended subsequent enrollment windows).Enrollment dropped for the first time in 2019, when 113,552 people enrolled in individual market plans through MNsure. In most states that use HealthCare.gov, enrollment peaked in 2016 and has been dropping since then. But MNsure’s drop-off in 2019, which amounted to only a 2.4 percent reduction in enrollment, is the only time year-over-year enrollment has declined.

Notably, the ACA’s individual mandate penalty was eliminated as of 2019, and regulations that the Trump administration implemented in late 2018 now make it more feasible for healthy people to use short-term plans instead of ACA-compliant plans (Minnesota has its own rules for short-term plans, but they’re more relaxed than the Obama-era federal rules that applied in 2017 and most of 2018).And for 2020, enrollment grew again, reaching a record high of 117,520 enrollees.Here’s a look at the number of people who have signed up for individual market plans through MNsure during each year’s open enrollment period. These numbers all represent total enrollment at the end of open enrollment. Effectuated enrollment is always lower, and MNsure provides periodic effectuated enrollment data on their board meeting materials page. Insurer participation in MNsure.

2014-20212014. Five insurers offered individual policies through MNsure for 2014. Blue Cross Blue Shield of Minnesota, HealthPartners/Group Health, Medica, PreferredOne, and UCare. Kaiser Health News reported that Minnesota offered some of the lowest premiums for silver (mid-level) plans in the U.S.

Four of Minnesota’s nine regions made Kaiser’s list of the 10 least expensive places to buy health insurance.2015. But PreferredOne, which offered the lowest rates in the nation in 2014 and captured a large portion of 2014 enrollees, withdrew from MNsure for 2015. PreferredOne said remaining on the exchange was “not administratively and financially sustainable.” A Star Tribune business writer attributed PreferredOne’s departure as a market dynamics issue rather than a problem with MNsure.However, Blue Plus (an affiliate of Blue Cross Blue Shield of MN, offering HMO plans) joined the exchange for 2015, so there were still five insurers offering plans for 2015. Blue Cross Blue Shield of Minnesota, Blue Plus, Health Partners/Group Health, Medica, and UCare.

MNsure offered 84 plans statewide, up from 78 for 2014.2016. BCBSMN, Blue Plus, Health Partners/Group Health, Medica, and UCare offered individual market plans through MNsure for 2016.2017. In an effort to recruit more carriers to offer plans through MNsure for 2017 — particularly outside the Twin Cities metro area — state regulators sent out a request for proposals from health insurers on August 15, 2016. Regulators noted that insurers could propose waivers of regulations in order to make it feasible for them to offer coverage through MNsure, although any such waiver requests would have to be approved by regulators.Steven Parente, a health insurance expert at the University of Minnesota, called the state’s effort to recruit insurers to MNsure a “distress call” and noted that August 15 is awfully late in the year to be putting out a request for insurer participation, given that open enrollment begins November 1.

And ultimately, no new insurers opted to join MNsure for 2017.Blue Cross Blue Shield of MN dropped their individual market PPO plans at the end of 2016 due to significant financial losses. That left Blue Plus (which offered HMOs and covered roughly 13,000 people in 2016 in the individual market) as the only BCBSMN affiliate in the exchange. Roughly 103,000 people had to select new plans during open enrollment.Most of those BCBSMN enrollees had off-exchange coverage, though. There were only about 20,400 MNsure enrollees (a little more than one in five MNsure enrollees) with coverage under BCBSMN who needed to switch to another plan during open enrollment.

BCBSMN had individual PPO options available in all 87 counties in Minnesota through MNsure in 2016, while the Blue Plus coverage area — comprised of four separate HMO networks — was available in 77 of the state’s counties.Nationwide, carriers have been shifting away from PPOs and towards HMOs and EPOs. In Colorado, Anthem Blue Cross Blue Shield also dropped their PPOs at the end of 2016. In Indiana, there were no PPOs available in the individual market by 2017. Blue Cross Blue Shield of New Mexico dropped all of their individual market plans at the end of 2015 except one off-exchange HMO.

Blue Cross Blue Shield of Texas dropped their individual market PPO plans at the end of 2015.The broad network offered by PPOs tends to be attractive to enrollees who have health problems. They’re often willing to pay higher premiums in trade for access to broad network of hospitals and specialists. But PPOs are expensive for carriers, as enrollees don’t need primary care referrals to see specialists, and it’s more challenging for carriers to hold down costs when there are more providers in the network.All of the MNsure carriers except Blue Plus are also limiting their total enrollment for 2017. By November 11, 2016, less than two weeks into open enrollment for 2017 coverage, Medica had hit their 50,000 member enrollment cap for 2017 (including on and off-exchange enrollments, and also accounting for expected renewals of 2016 Medica plans), and their policies were no longer available in the individual market in Minnesota, on or off-exchange.

The only exception was five counties (Benton, Crow Wing, Mille Lacs, Morrison, and Stearns) where Medica agreed not to limit enrollment, as all of the other available carriers in those counties have imposed enrollment caps too. In those five counties, Medica plans continued to be available.At that point, Medica’s market share in MNsure for 2017 stood at 34.2 percent. By December 14, Medica’s market share had dropped to 27.7 percent, as enrollments had continued to climb for the remaining carriers.On January 31, Medica re-opened enrollment for 2017. This was because a smaller-than-expected number of 2016 Medica enrollees renewed their plans for 2017, meaning that the carrier still had some wiggle room under their 50,000 member cap.

At that point, they had room for about 7,000 more enrollees. Medica plans were thus available throughout the duration of the special enrollment period that was added on at the end of open enrollment, and continue to be available for people with qualifying events.2018. Plans continued to be available from Blue Plus, Health Partners/Group Health (GHI), Medica, UCare. In the months before a decision was reached regarding an extension of the open enrollment window for 2018 plans (the first year that the federal government imposed a shorter, month-and-a-half enrollment window), two of MNsure’s participating insurers had differing positions.

UCare believed the exchange should add an additional two-week special enrollment period, while Medica did not want the exchange to have the option to extend the newly-scheduled six-week enrollment window. Notably, Medica capped their enrollment very early during the 2017 open enrollment period, and while UCare also had an enrollment cap, it was set with a target of nearly doubling their 2016 enrollment. But Medica is the only MNsure insurer that didn’t set an enrollment cap for 2018.As was the case for 2017, enrollment caps were used in the individual market in Minnesota for 2018 by all insurers other than Medica (Medica did have an enrollment cap for 2017, which they hit very early in open enrollment. However, they resumed enrollments at the end of January 2017).

Details about the insurers’ enrollment caps are in the plan binders in SERFF. For 2018, MNsure insurers implemented the following enrollment caps:Blue Plus. 55,000 member cap (aiming for a target of 50,000 effectuated enrollees, but effectuated enrollment is always lower than the number of people who initially enroll)Health Partners/Group Health (GHI). 73,400 member cap (aiming for a target of 70,000 effectuated enrollees)Medica.

No enrollment capUCare. 35,000 member cap (aiming for a target of 30,000 effectuated enrollees)MNsure confirmed in May 2018 that none of their insurers had hit their enrollment caps for 2018.Outside the exchange, PreferredOne had an enrollment cap of 3,000 members, although their 2017 membership was only about 300 people.2019 and 2020. Blue Plus, Health Partners/Group Health, UCare, and Medica have continued to offer plans through MNsure, and all of them continued to participate in 2020 as well. Blue Plus expanded to once again offer statewide coverage in 2020, for the first time since 2016.2021.

Quartz joined the exchange for 2021, joining the four existing insurers. HealthPartners and UCare are both expanding their coverage areas for 2021.Minnesota Premium Security Plan. 1332 waiver proposal approved by CMS, but with a significant funding cut for MinnesotaCareIn May 2017, Minnesota Governor Mark Dayton submitted a 1332 waiver proposal to CMS. The 1332 waiver was based on H.F.5, which was enacted without Dayton’s signature in April 2017 (Dayton had proposed an alternative measure that would have allowed people in Minnesota to buy into MinnesotaCare.

That measure was not able to pass the state’s Republican-dominated legislature).[For more than two decades, MinnesotaCare was a state program subsidizing health insurance for low-income residents. As of January 1, 2015, it transitioned to a Basic Health Program under the ACA, becoming the first BHP in the nation.]H.F.5 created the Minnesota Premium Security Plan (MPSP), which is a state-based reinsurance program (similar to the one the ACA implemented on a temporary basis through 2016, and that Alaska created for 2017. Several other is there a generic brand of cialis states have since implemented reinsurance programs). The reinsurance program, which took effect in Minnesota in 2018, covers a portion of the claims that insurers face, resulting in lower total claims costs for the insurers, and thus lower premiums (average individual market premiums in Minnesota decreased from 2017 to 2018 as a result of the reinsurance program).

The reinsurance kicks in once claims reach $50,000, and covers them at 80 percent up to $250,000 (this is similar to the coverage under the transitional reinsurance program that the ACA provided from 2014 through 2016).H.F.5 was contingent upon approval of the 1332 waiver, because it relies partially on federal funding, in addition to state funding. Under the federal approval that was granted in September 2017, the federal government is giving Minnesota the money that they save on premium tax credits, and that money is combined with state funds to implement the reinsurance program (lower premiums — as a result of the reinsurance program — result in the federal government having to pay a smaller total amount of premium tax credits, since the tax credits are smaller when premiums are smaller).It was expected that CMS would approve the state’s 1332 waiver proposal, and Governor Dayton requested that the approval process be swift so that the state could move forward with the implementation of the Minnesota Premium Security Plan in time for the 2018 plan year. Dayton indicated that his office had been told that approval would come in August 2017, but CMS didn’t approve the waiver until September 22. And the waiver approval letter noted that the federal savings for MinnesotaCare (the state’s Basic Health Program, or BHP) resulting from the reinsurance program would not be eligible to be passed along to the state — in other words, CMS would keep those savings instead.[Federal BHP funding is equal to 95 percent of the amount that the federal government would have otherwise spent on premium subsidies and cost-sharing reductions for the population that ends up being eligible for the BHP.

So lower premiums — as a result of reinsurance — for qualified health plans in the exchange means that the amount the federal government would have had to spend on premium subsidies for that population is lower. That translates into a smaller amount of funding for the state’s BHP, according to the approach that HHS took for Minnesota’s waiver approval.]And based on the scathing letter that Dayton sent CMS a few days earlier, it appeared at that point that Minnesota could actually lose money on the deal — losing more in federal funding for MinnesotaCare than they gain in reinsurance funding. Dayton noted in his letter that the 1332 waiver approval process had been “nightmarish,” and that Minnesota went to great lengths to follow instructions from CMS at every turn, throughout the process of drafting H.F.5 and the 1332 waiver proposal. He explains that CMS provided Minnesota with explicit guidance in terms of how to draft the reinsurance program while maintaining full federal funding for MinnesotaCare, and highlighted the fact that the state never deviated from the instructions that were provided.The StarTribune editorial board called out then-Secretary of HHS, Tom Price and the Trump Administration for their lack of clarity on the issue, for apparently misleading the state during the 1332 waiver drafting process, and for effectively punishing the state of Minnesota for taking an innovative approach to ensuring that as many people as possible have health insurance.Insurers filed rates based on reinsurance being available.

And by the time the waiver was approved, there was very little time to evaluate the potential impacts of the funding changes, as rates had to be finalized by October 2 in Minnesota. The finalized rates did incorporate the reinsurance program. The state has accepted the approved waiver, but Gov. Dayton sent a letter to HHS on October 3, asking them to reconsider the MinnesotaCare funding cuts, but the issue has remained unresolved.Elimination of CSR funding results in additional funding cut for MinnesotaCare, but a lawsuit has partially restored that fundingNationwide, 54 percent of exchange enrollees benefit from cost-sharing subsidies.

But in Minnesota, only 13 percent of exchange enrollees are receiving cost-sharing subsidies. This is because of MinnesotaCare, which covers all enrollees with income up to 200 percent of the poverty level. That’s the same group that would otherwise benefit the most from cost-sharing subsidies, so the fact that MinnesotaCare is available means that most of the people who would otherwise be enrolled in cost-sharing subsidy plans are instead enrolled in MinnesotaCare.At first glance, this would appear to have made the uncertainty surrounding cost-sharing subsidy funding in 2017 a little less of a pressing issue in Minnesota than it was in many other states, since private insurers weren’t facing the sort of losses that insurers in other states were facing without federal funding for CSR. But when the Trump Administration eliminated federal funding for CSR in October 2017, HHS took the position tha t since CSR funding had been eliminated, the CSR portion of the federal funding for the BHPs in New York and Minnesota would be reduced to $0.

This was not a cut-and-dried conclusion, however, as explained earlier in 2017 by Michael Kalina.In January 2018, the Attorneys General for New York and Minnesota filed a lawsuit against the US Department of Health and Human Services, seeking to restore funding for their Basic Health Programs. A judge ruled in favor of the states in May 2018, ensuring that MinnesotaCare would continue to receive at least some CSR-based funding. The amount awarded to the state for the first quarter of 2018 was just over half of what the state had initially expected in CSR-related funding, but a larger chuck of the funding was restored later in 2018. According to the Star Tribune, however, Minnesota still ended up losing $161 million in federal funding for MinnesotaCare due to the CSR funding cuts.In early 2019, the Trump administration proposed yet another funding cut (a third, after the cuts imposed by the reinsurance program and the elimination of CSR funding) as part of a new methodology for calculating BHP funding.

This one was much smaller than the other two cuts, but taken together the funding reductions are pushing MinnesotaCare towards a looming budget shortfall. SHOP exchange. Down to one carrier as of 2016, zero by 2018 (and still zero in 2019)In 2015, there were two carriers in MNsure’s SHOP exchange for small businesses. Blue Cross Blue Shield of Minnesota, and Medica.

But Medica announced in 2015 that they would exit the SHOP exchange in Minnesota, North Dakota, and Wisconsin at the end of the year. That left BCBS as the only small group carrier available through MNsure in 2016, but it didn’t change much from a practical standpoint, since 83 percent of MNsure’s small groups were enrolled in plans through BCBS in 2015. Indeed, Medica’s reason for exiting the small business exchange was based on low enrollment in the first two years.Blue Cross Blue Shield of Minnesota continued to be the only insurer offering SHOP coverage via MNsure in 2017, but announced in July 2017 that they would no longer offer SHOP coverage in 2018, and would instead transition their SHOP enrollees to small business coverage outside the exchange. At that point, there were only 3,287 people enrolled in SHOP coverage in Minnesota — far below the 155,000 people that were originally projected to have coverage through MNsure’s SHOP program by 2016 (this much lower-than-anticipated enrollment has been the case in nearly every state’s SHOP exchange.

This situation is not unique to Minnesota). State law provided 25% premium rebate in 2017. Amendment to allow plans without essential benefits was cut from final legislationThroughout 2016, then-Governor Dayton called for a state-funded premium rebate for people who buy their own insurance but aren’t eligible for the ACA’s premium subsidies (those are only available for people with income up to 400 percent of the poverty level, or $100,400 for a family of four in 2019).Governor Dayton also noted that the government needed to act quickly to stabilize the individual market in Minnesota, and by late November 2016, his patience with lawmakers was wearing thin. In a November 23 press conference, Dayton said that House Republicans needed to “stop dilly-dallying” and decide whether to move forward with Dayton’s rebate proposal.Dayton had also indicated that he was considering calling a special session of the legislature after election day to address the situation, and that was being negotiated for December 20.

But the talks fell through when Dayton and Republican House Speaker Kurt Daudt couldn’t agree on the three bills that would have been addressed in the special session. As a result, there was no special session.Instead, the issue was taken up by lawmakers as soon as the 2017 legislative session began. On January 5, Minnesota Senators Michelle Benson (R, 31st District) and Gary Dahms (R, 16th District) introduced S.F.1. The bill called for using $300 million in state funding to provide a 25 percent rebate to roughly 125,000 people in Minnesota.S.F.1 passed the Minnesota Senate by a 35-31 vote on January 12.

Only one DFL Senator (Melisa Franzen, from Edina) voted with Republicans in favor of the legislation. It was then sent to the House, where an amendment was added that stripped out the requirement that health plans provide various mandated benefits (see “Journal of the Day” section “Top of page 154” in this version of the bill. Under the terms of the amendment, as long as a carrier offered at least one plan with all the mandated benefits, they would have been allowed to offer others without mandated benefits).The amended bill was sent back to the Senate on January 23. Differences between the bills that the two chambers passed had to be reconciled before being sent to Governor Dayton for his signature.

By that point, the amendment to allow less-robust plans to be sold had garnered national attention, and public outrage helped to push lawmakers away from the provision. S.F.1 had also called for $150 million to be appropriated for fiscal year 2018 (through June 30, 2019) from the state general fund to a state-based reinsurance program to stabilize the individual market (Alaska did something similar in 2016, preventing a market collapse), but that provision was also removed in the final version (Minnesota did ultimately set up a reinsurance program, effective in 2018, which has served to stabilize the market and reduce premiums).A Conference Committee in the Senate recommended that the House “recede from its amendments” and the Conference Committee report passed the Senate on a 47-19 vote. The House passed the bill a few hours later, 108-19. It was sent to Governor Dayton, who immediately signed it into law.

DFLers did have to compromise on one issue during the process. S.F.1 allows for-profit HMOs to begin operating in Minnesota’s individual market, which had long been limited to non-profit HMOs.Consumers were told to expect the premium rebates to show up by April 2017, but they were retroactively effective to January 2017. So a person who had been paying full price for a plan since January 2017 saw a substantial premium reduction on the April or May invoice. Going forward, for the remainder of the year, a 25 percent rebate applied each month.Since S.F.1 was signed into law with only a few days remaining in open enrollment (it ended January 31 that year), Governor Dayton and exchange officials were worried that there wouldn’t be enough time for people to learn about the rebate and apply for coverage before January 31.

In December, Dayton had asked HHS to allow MNsure to extend its enrollment deadline to February 28 (instead of January 31) in order to allow lawmakers more time to work out the details of a state-based premium rebate while still allowing people to enroll after the legislative process is complete.HHS denied the request for a blanket extension, but MNsure used their own authority on January 28 to grant a one-week special enrollment period (February 1 to February 8) due to exceptional circumstances. Although the state-based 25 percent premium rebate was available on or off the exchange, the one-week extension was only valid through MNsure. Health insurers did not have to accept off-exchange enrollments without a qualifying event after January 31.The 25 percent premium rebate program in Minnesota was only authorized for one year, so the rebates did not continue into 2018. And although almost 100,000 people received premium relief through the program in 2017, it ended up costing less than the legislature had allocated, and about $100 million was returned to the state’s budget at the end of 2017.Protecting Medicaid enrollees from estate liensIn every state, Medicaid is jointly funded by the state and the federal government.

Longstanding federal regulations, which predate the ACA, require states to “seek recovery of payments from the individual’s estate for nursing facility services, home and community-based services, and related hospital and prescription drug services” for any Medicaid enrollee over the age of 55. This applies essentially to long-term care services, but states also have the option to go after the individual’s estate to recover costs for other care that was provided by Medicaid after age 55.Prior to 2014, this wasn’t typically an issue, as Medicaid eligibility was generally restricted by asset tests or requirements that applicants be disabled or pregnant (although Minnesota did have much more generous Medicaid eligibility guidelines than most states prior to 2014). But as of 2014, in states that expanded Medicaid under the ACA, the only eligibility guideline is income. Applicants with income that doesn’t exceed 138 percent of the poverty level are directed to Medicaid, regardless of any assets they might have.When applicants use the health insurance exchange — MNsure in Minnesota — they’re automatically funneled into Medical Assistance (Medicaid) if their income is under 138 percent of the poverty level.

But what these enrollees didn’t know was that the state also had a program in place to put liens on estates for Medicaid-provided services for people age 55 and older.The combination of these systems caught numerous residents off guard. They were enrolled in Medical Assistance through MNsure based on their income, but were not aware that liens were being placed on their homes so that the state could recoup the costs upon their deaths.State Senator Tony Lourey (DFL, District 11) addressed the issue with language included in HF2749, the Omnibus supplemental budget bill, which was signed into law by Governor Dayton on June 1, 2016. The legislation limits estate recovery to just what’s required under federal Medicaid rules (ie, essentially, long-term care costs for people age 55 or older), and makes the provision retroactive to January 1, 2014.Early tech strugglesMNsure opened for business in the fall of 2013, but technological issues persisted well into 2015, despite numerous improvements throughout 2014. Given MNsure’s difficult launch, the state conducted a series of audits and reviews.

The first audit reviewed how MNsure spent state and federal money. Auditors concluded that the exchange has generally adequate internal controls and found no fraud or abuse. The review was conducted by the state Office of the Legislative Auditor, and the report was published in October 2014.Another audit, also conducted by the Office of the Legislative Auditor and released in November 2014, found that the MNsure system in some cases incorrectly determined who qualified for public health benefits. The errors occurred during the first open enrollment period, before a series of system fixes were implemented.

The audit did not quantify the total financial impact of the errors. The state Human Services commissioner said a consultant working on technical fixes to MNsure concluded that the eligibility functionality was working correctly as of June 2014.A third audit, a performance evaluation report released in February 2015, said “MNsure’s failures outweighed its achievements.” Among other criticisms, auditors said MNsure staff withheld information from the board of directors and state officials, the enrollment website was seriously flawed and launched without adequate testing, and the first-year enrollment target was unrealistically low.In April 2014, MNsure hired Deloitte Consulting to audit MNsure’s technology and improve the website to make enrolling in coverage and updating life events easier and more streamlined. Deloitte has been involved in successful state-run marketplaces for Connecticut, Kentucky, Rhode Island and Washington.Software upgrades were installed in August 2014, and system testing continued right up until the start of open enrollment. To reduce wait times for consumers and insurance professionals, MNsure increased its call center and support staff and launched a dedicated service line for agents and brokers.More in-person assisters were available in Minnesota for the 2015 open enrollment period.

MNsure encourages residents to utilize the exchange’s assister directory to find local navigators and brokers who can help with the enrollment process.MNsure has improved dramatically in terms of its technology since the early days of ACA implementation, and enrollment increased every year from 2014 through 2019.Lawmakers approved switching to HealthCare.gov as of 2019, but governor vetoedOn May 9, 2017, lawmakers in Minnesota passed SF800, an omnibus health and human services bill. Among many other things, the legislation called for switching from MNsure to the federally-run marketplace (HealthCare.gov) starting in 2019 (see Section 5). But Governor Dayton vetoed it.Gov. Dayton has long been supportive of MNsure, and had previously clarified that he would veto the bill.

In noting his plans to veto the legislation, Dayton made no mention of the transition to HealthCare.gov that was included in the legislation, but focused instead on the sharp budget cuts in the bill. But his veto ensured that MNsure would remain in place, at least for the time being.The Senate’s original version of SF800 did not call for scrapping MNsure, but the bill went through considerable back-and-forth between the two chambers, and the version that passed was the 4th engrossment of the bill.In March 2015, Dayton had asked the legislature to create a Task Force on Health Care Financing that would study MNsure along with possible future alternatives. Dayton noted in his letter that he supported making MNsure “directly accountable to the governor and subject to the same legislative oversight as other state agencies” and his budget included half a million dollars devoted to the task force. The spending bill was approved by the legislature in May, and the 29-member task force was appointed in the summer.One of the possibilities that the task force considered was the possibility of switching to Healthcare.gov, but it’s clear that there was no cut-and-dried answer to the question of whether Minnesota is better served by having a state-run exchange, switching to a federally-run exchange, or teaming up with the federal government on either a supported state-based marketplace or partnership exchange.In a December 2015 meeting of the task force, the MN Department of Human Services presented a financial analysis of the alternatives available to MNsure.

They determined that switching entirely to Healthcare.gov would cost the state an additional $5.1 million in one-time costs from June 2016 to June 2017. And switching to a supported state-based marketplace would cost an additional $6.6 million during that same time frame. If the state had opted to switch to Healthcare.gov, the soonest it could have happened was 2018, since HHS requires a year’s notice from states wishing to transition to Healthcare.gov, and Minnesota wouldn’t have been in a position to make a decision until sometime in 2016.There were significant reservations about making that switch prior to the Supreme Court’s ruling on King v. Burwell.

The Court ruled in June 2015 that subsidies are legal in every state, including those that use Healthcare.gov. Prior to the decision, a switch to Healthcare.gov could have jeopardized subsidies for tens of thousands of Minnesota residents. But once it was clear that Healthcare.gov’s subsidies are safe, some stakeholders began calling for Minnesota to scrap its state-run exchange and use Healthcare.gov instead. Because the MNsure task force was included in the 2016 budget, no hasty decisions were made.In January 2016, the task force submitted their recommendations to the legislature.

They covered a broad range of issues, but did not recommend that MNsure transition to the federal enrollment platform. Lawmakers essentially left the exchange alone during the 2016 legislative session.The magnitude of the 2016 rate increases that were announced in October resulted in MNsure opponents renewing their calls to switch to Healthcare.gov. But it’s important to keep in mind that the 41 percent weighted average rate hike in Minnesota was market-wide, and did not just apply to MNsure enrollees. In fact, the off-exchange carrier (PreferredOne) had among the highest rate hikes in the state for 2016, at 39 percent, and the exchange’s weighted average rate increase (38.5 percent) was lower than the weighted average rate increase for the whole individual market (41 percent).Minnesota health insurance exchange linksMNsure855-3MNSURE (855-366-7873)State Exchange Profile.

MinnesotaThe Henry J. Kaiser Family Foundation overview of Minnesota’s progress toward creating a state health insurance exchange.Louise Norris is an individual health insurance broker who has been writing about health insurance and health reform since 2006. She has written dozens of opinions and educational pieces about the Affordable Care Act for healthinsurance.org. Her state health exchange updates are regularly cited by media who cover health reform and by other health insurance experts.Key takeaways Medicaid expansion in HawaiiHawaii adopted Medicaid expansion through the Affordable Care Act, extending eligibility for Medicaid to adults with income up to 133 percent of the poverty level (138 percent with the automatic 5 percent income disregard).

Medicaid expansion took effect in January 2014.According to the Kaiser Family Foundation, about 70,000 Hawaii residents were uninsured in 2015. With Medicaid expansion now covering low-income, nonelderly adults, 50 percent of Hawaii’s remaining uninsured population at that point was eligible for Medicaid – although they may not realize that they’re eligible. According to U.S. Census data, only 3.5 percent of Hawaii residents were uninsured as of 2016, down from 6.7 percent in 2013.

Although the state’s uninsured rate was reduced by nearly half from 2013 to 2016, it was already less than half of the national average uninsured rate even in 2013, before the bulk of the ACA’s provisions had taken effect. Hawaii’s Prepaid Health Care Act, which has been in place since the 1970s, had already resulted in nearly all of the state’s population having insurance coverage, even before the ACA took effect. However, with the coronavirus outbreak, job losses and the subsequent loss of employer-provided insurance have contributed to a jump in the uninsured rate across the U.S. As of May 2020, Hawaii’s uninsured rate was 10 percent.Medicaid expansion helped cement top-ranking health scores Federalpoverty levelcalculator 0.0% of Federal Poverty Level Hawaii has a long history of supporting initiatives to make health insurance broadly available to residents.

Hawaii was among the first six states that implemented a Medicaid program in January 1966, just six months after federal legislation authorizing the program was enacted. In 1974, Hawaii implemented its Prepaid Health Care Act, which mandated that most employers make health insurance available to employees who work at least 20 hours a week.In conjunction with the Affordable Care Act (ACA), Hawaii initially implemented a state-run health insurance marketplace and adopted Medicaid expansion. The marketplace transitioned to a federally-supported state-run marketplace for 2016, and transitioned again to a fully federally-run exchange for 2017, largely in an effort to take advantage of the economies of scale that the federally-run exchange could bring to a state with low overall enrollment in the individual market (because of Hawaii’s Prepaid Health Care Act, nearly all non-elderly Hawaii residents get coverage from an employer, and relatively few need coverage under individual market plans). Nothing changed about Medicaid with the switch to Healthcare.gov though.

The expanded Medicaid eligibility guidelines are still in effect in Hawaii.Through its efforts, Hawaii consistently has low uninsured rates and high overall health scores. As of 2015, Hawaii was ranked the healthiest state in the nation according to the Gallup Healthways Physical Wellbeing Index, and the state consistently scores near the top in other ranking systems (number 2 the America’s Health Rankings 2017 survey, and number 3 in the Commonwealth Fund’s 2017 Scorecard on State Health System Performance).Who is eligible for Medicaid in Hawaii?. Hawaii’s Medicaid eligibility levels for children are much higher than the national average and about average for pregnant women and parents.Children ages 0-18 qualify with family income levels up to 308 of the federal poverty level (FPL)Pregnant women qualify with family income up to 191 percent of FPLParents and other adults qualify with family income up to 138 percent of FPLHawaii also uses Medicaid funds to help cover premium costs for Hawaii residents who aren’t U.S. Citizens but who are citizens of nations that have entered into the Compact of Free Association (COFA) with the U.S.How do I enroll in Medicaid in Hawaii?.

Hawaii’s Medicaid program is called MED-QUEST (MQD). QUEST stands for Quality care, Universal access, Efficient utilization, Stabilizing costs, and Transforming the way health care is provided to recipients.You can apply for MED-QUEST. Hawaii Medicaid enrollment numbersMore than 351,000 people were enrolled in Hawaii’s Medicaid and CHIP programs as of June 2020. This figure is a 22% increase over 2013 (pre-ACA) enrollment, when about 288,000 people were enrolled.

Accordingly to the Kaiser Family Foundation, 107,300 of those enrolled in Hawaii Medicaid are part of the ACA-authorized expansion as of June 2019.Hawaii Medicaid historyHawaii implemented its Medicaid program in January 1966.In the early 1990s, Hawaii implemented the State Health Insurance Program (SHIP) to cover people who weren’t eligible for Medicaid. Then, in 1994, CMS approved Hawaii’s section 1115 Medicaid waiver (one of the first in the nation) to wrap SHIP in with Medicaid in an effort to achieve universal insurance coverage (in combination with the state’s Prepaid Health Care Act). The result of the waiver was the creation of Hawaii’s MED-QUEST program, which initially covered low-income women and children, but has since expanded (as of 2009) to cover nearly all of Hawaii’s Medicaid beneficiaries. The MED-QUEST waiver is subject to renewal every five years.Medicaid in Hawaii is separated into two different methods of providing services.

The fee-for-service (FFS) program and the managed care program, called MED-QUEST or MQD. Under the FFS program, doctors and other healthcare providers bill Medicaid directly to be reimbursed for services provided to Medicaid beneficiaries. Under MED-QUEST, the state contracts with managed care plans who in turn provide healthcare services to Medicaid beneficiaries.As of 2011, more than 98 percent of the people enrolled in Hawaii’s Medicaid program were covered through managed care. By March 2015, Kaiser Family Foundation reported that 335,007 Medicaid enrollees in Hawaii were covered under managed care programs.

That’s higher than the August 2015 total Medicaid/CHIP enrollment count, but KFF notes that the managed care number includes people who are covered under Hawaii’s fully-state-funded Medicaid program, in addition to the majority of enrollees who are in regular Medicaid that’s funded partially by the state and partially by the federal government.In August 2017, Hawaii submitted a waiver amendment to CMS in order to gain federal approval to use Medicaid funding to provide housing services to qualified Medicaid enrollees who are homeless and also have behavioral health and/or substance abuse problems. That waiver request was still pending as of February 2018.Louise Norris is an individual health insurance broker who has been writing about health insurance and health reform since 2006. She has written dozens of opinions and educational pieces about the Affordable Care Act for healthinsurance.org. Her state health exchange updates are regularly cited by media who cover health reform and by other health insurance experts..

How long before cialis works

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NCHS Data how long before cialis works Brief No. 286, September 2017PDF Versionpdf icon (374 KB)Anjel Vahratian, Ph.D.Key findingsData from the National Health Interview Survey, 2015Among those aged 40–59, perimenopausal women (56.0%) were more likely than postmenopausal (40.5%) and premenopausal (32.5%) women to sleep less than 7 hours, on average, in a 24-hour period.Postmenopausal women aged 40–59 were more likely than premenopausal women aged 40–59 to have trouble falling asleep (27.1% compared with 16.8%, respectively), and staying asleep (35.9% compared with 23.7%), four times or more in the past week.Postmenopausal women aged 40–59 (55.1%) were more likely than premenopausal women aged 40–59 (47.0%) to not wake up feeling well rested 4 days or more in the past week.Sleep duration and quality are important contributors to health and wellness. Insufficient sleep how long before cialis works is associated with an increased risk for chronic conditions such as cardiovascular disease (1) and diabetes (2). Women may be particularly vulnerable to sleep problems during times of reproductive hormonal change, such as after the menopausal transition. Menopause is “the permanent cessation of menstruation that occurs after the loss of ovarian activity” (3) how long before cialis works.

This data brief describes sleep duration and sleep quality among nonpregnant women aged 40–59 by menopausal status. The age range selected for this analysis reflects the focus on midlife sleep health. In this analysis, 74.2% of women are how long before cialis works premenopausal, 3.7% are perimenopausal, and 22.1% are postmenopausal. Keywords. Insufficient sleep, menopause, National Health Interview Survey Perimenopausal women were more likely than premenopausal and postmenopausal how long before cialis works women to sleep less than 7 hours, on average, in a 24-hour period.More than one in three nonpregnant women aged 40–59 slept less than 7 hours, on average, in a 24-hour period (35.1%) (Figure 1).

Perimenopausal women were most likely to sleep less than 7 hours, on average, in a 24-hour period (56.0%), compared with 32.5% of premenopausal and 40.5% of postmenopausal women. Postmenopausal women were significantly more likely than premenopausal women to sleep less than 7 hours, on average, in a 24-hour period. Figure 1 how long before cialis works. Percentage of nonpregnant women aged 40–59 who slept less than 7 hours, on average, in a 24-hour period, by menopausal status. United States, 2015image icon1Significant quadratic trend by menopausal status how long before cialis works (p <.

0.05).NOTES. Women were postmenopausal if they had gone without a menstrual cycle for more than 1 year or were in surgical menopause after the removal of their ovaries. Women were perimenopausal if they no longer had a menstrual cycle and their last menstrual cycle was 1 year how long before cialis works ago or less. Women were premenopausal if they still had a menstrual cycle. Access data table how long before cialis works for Figure 1pdf icon.SOURCE.

NCHS, National Health Interview Survey, 2015. The percentage how long before cialis works of women aged 40–59 who had trouble falling asleep four times or more in the past week varied by menopausal status.Nearly one in five nonpregnant women aged 40–59 had trouble falling asleep four times or more in the past week (19.4%) (Figure 2). The percentage of women in this age group who had trouble falling asleep four times or more in the past week increased from 16.8% among premenopausal women to 24.7% among perimenopausal and 27.1% among postmenopausal women. Postmenopausal women were significantly more likely than premenopausal women to have trouble falling asleep four times or more in the past week. Figure 2 how long before cialis works.

Percentage of nonpregnant women aged 40–59 who had trouble falling asleep four times or more in the past week, by menopausal status. United States, 2015image icon1Significant how long before cialis works linear trend by menopausal status (p <. 0.05).NOTES. Women were postmenopausal if they had gone without a menstrual cycle for more than 1 year or were in surgical menopause after the removal of their ovaries. Women were perimenopausal if they no longer had a menstrual cycle and their how long before cialis works last menstrual cycle was 1 year ago or less.

Women were premenopausal if they still had a menstrual cycle. Access data table for Figure 2pdf icon.SOURCE how long before cialis works. NCHS, National Health Interview Survey, 2015. The percentage of women aged 40–59 who had trouble staying asleep four times or more in the past week varied by menopausal status.More than one in four nonpregnant women aged 40–59 had trouble staying asleep four times or more in the past how long before cialis works week (26.7%) (Figure 3). The percentage of women aged 40–59 who had trouble staying asleep four times or more in the past week increased from 23.7% among premenopausal, to 30.8% among perimenopausal, and to 35.9% among postmenopausal women.

Postmenopausal women were significantly more likely than premenopausal women to have trouble staying asleep four times or more in the past week. Figure 3 how long before cialis works. Percentage of nonpregnant women aged 40–59 who had trouble staying asleep four times or more in the past week, by menopausal status. United States, how long before cialis works 2015image icon1Significant linear trend by menopausal status (p <. 0.05).NOTES.

Women were postmenopausal if they had gone without a menstrual cycle for more than 1 year or were in surgical menopause after the removal of their ovaries. Women were perimenopausal if they no longer had a menstrual cycle and their how long before cialis works last menstrual cycle was 1 year ago or less. Women were premenopausal if they still had a menstrual cycle. Access data how long before cialis works table for Figure 3pdf icon.SOURCE. NCHS, National Health Interview Survey, 2015.

The percentage of women aged 40–59 who did not wake up feeling well rested 4 days or more in the past week varied by menopausal status.Nearly one in two nonpregnant women aged 40–59 did not wake up feeling well rested 4 days or more in the past week (48.9%) (Figure 4). The percentage of women in this age group who did not wake up feeling well rested 4 days or more in the past week increased from 47.0% among premenopausal women to 49.9% among perimenopausal and 55.1% among postmenopausal women how long before cialis works. Postmenopausal women were significantly more likely than premenopausal women to not wake up feeling well rested 4 days or more in the past week. Figure 4 how long before cialis works. Percentage of nonpregnant women aged 40–59 who did not wake up feeling well rested 4 days or more in the past week, by menopausal status.

United States, 2015image icon1Significant linear trend by menopausal status (p <. 0.05).NOTES. Women were postmenopausal if they had gone without a menstrual cycle for more than 1 year or were in surgical menopause after the removal of their ovaries. Women were perimenopausal if they no longer had a menstrual cycle and their last menstrual cycle was 1 year ago or less. Women were premenopausal if they still had a menstrual cycle.

Access data table for Figure 4pdf icon.SOURCE. NCHS, National Health Interview Survey, 2015. SummaryThis report describes sleep duration and sleep quality among U.S. Nonpregnant women aged 40–59 by menopausal status. Perimenopausal women were most likely to sleep less than 7 hours, on average, in a 24-hour period compared with premenopausal and postmenopausal women.

In contrast, postmenopausal women were most likely to have poor-quality sleep. A greater percentage of postmenopausal women had frequent trouble falling asleep, staying asleep, and not waking well rested compared with premenopausal women. The percentage of perimenopausal women with poor-quality sleep was between the percentages for the other two groups in all three categories. Sleep duration changes with advancing age (4), but sleep duration and quality are also influenced by concurrent changes in women’s reproductive hormone levels (5). Because sleep is critical for optimal health and well-being (6), the findings in this report highlight areas for further research and targeted health promotion.

DefinitionsMenopausal status. A three-level categorical variable was created from a series of questions that asked women. 1) “How old were you when your periods or menstrual cycles started?. €. 2) “Do you still have periods or menstrual cycles?.

€. 3) “When did you have your last period or menstrual cycle?. €. And 4) “Have you ever had both ovaries removed, either as part of a hysterectomy or as one or more separate surgeries?. € Women were postmenopausal if they a) had gone without a menstrual cycle for more than 1 year or b) were in surgical menopause after the removal of their ovaries.

Women were perimenopausal if they a) no longer had a menstrual cycle and b) their last menstrual cycle was 1 year ago or less. Premenopausal women still had a menstrual cycle.Not waking feeling well rested. Determined by respondents who answered 3 days or less on the questionnaire item asking, “In the past week, on how many days did you wake up feeling well rested?. €Short sleep duration. Determined by respondents who answered 6 hours or less on the questionnaire item asking, “On average, how many hours of sleep do you get in a 24-hour period?.

€Trouble falling asleep. Determined by respondents who answered four times or more on the questionnaire item asking, “In the past week, how many times did you have trouble falling asleep?. €Trouble staying asleep. Determined by respondents who answered four times or more on the questionnaire item asking, “In the past week, how many times did you have trouble staying asleep?. € Data source and methodsData from the 2015 National Health Interview Survey (NHIS) were used for this analysis.

NHIS is a multipurpose health survey conducted continuously throughout the year by the National Center for Health Statistics. Interviews are conducted in person in respondents’ homes, but follow-ups to complete interviews may be conducted over the telephone. Data for this analysis came from the Sample Adult core and cancer supplement sections of the 2015 NHIS. For more information about NHIS, including the questionnaire, visit the NHIS website.All analyses used weights to produce national estimates. Estimates on sleep duration and quality in this report are nationally representative of the civilian, noninstitutionalized nonpregnant female population aged 40–59 living in households across the United States.

The sample design is described in more detail elsewhere (7). Point estimates and their estimated variances were calculated using SUDAAN software (8) to account for the complex sample design of NHIS. Linear and quadratic trend tests of the estimated proportions across menopausal status were tested in SUDAAN via PROC DESCRIPT using the POLY option. Differences between percentages were evaluated using two-sided significance tests at the 0.05 level. About the authorAnjel Vahratian is with the National Center for Health Statistics, Division of Health Interview Statistics.

The author gratefully acknowledges the assistance of Lindsey Black in the preparation of this report. ReferencesFord ES. Habitual sleep duration and predicted 10-year cardiovascular risk using the pooled cohort risk equations among US adults. J Am Heart Assoc 3(6):e001454. 2014.Ford ES, Wheaton AG, Chapman DP, Li C, Perry GS, Croft JB.

Associations between self-reported sleep duration and sleeping disorder with concentrations of fasting and 2-h glucose, insulin, and glycosylated hemoglobin among adults without diagnosed diabetes. J Diabetes 6(4):338–50. 2014.American College of Obstetrics and Gynecology. ACOG Practice Bulletin No. 141.

Management of menopausal symptoms. Obstet Gynecol 123(1):202–16. 2014.Black LI, Nugent CN, Adams PF. Tables of adult health behaviors, sleep. National Health Interview Survey, 2011–2014pdf icon.

2016.Santoro N. Perimenopause. From research to practice. J Women’s Health (Larchmt) 25(4):332–9. 2016.Watson NF, Badr MS, Belenky G, Bliwise DL, Buxton OM, Buysse D, et al.

Recommended amount of sleep for a healthy adult. A joint consensus statement of the American Academy of Sleep Medicine and Sleep Research Society. J Clin Sleep Med 11(6):591–2. 2015.Parsons VL, Moriarity C, Jonas K, et al. Design and estimation for the National Health Interview Survey, 2006–2015.

National Center for Health Statistics. Vital Health Stat 2(165). 2014.RTI International. SUDAAN (Release 11.0.0) [computer software]. 2012.

Suggested citationVahratian A. Sleep duration and quality among women aged 40–59, by menopausal status. NCHS data brief, no 286. Hyattsville, MD. National Center for Health Statistics.

2017.Copyright informationAll material appearing in this report is in the public domain and may be reproduced or copied without permission. Citation as to source, however, is appreciated.National Center for Health StatisticsCharles J. Rothwell, M.S., M.B.A., DirectorJennifer H. Madans, Ph.D., Associate Director for ScienceDivision of Health Interview StatisticsMarcie L. Cynamon, DirectorStephen J.

Blumberg, Ph.D., Associate Director for Science.

NCHS Data cialis cost Brief No. 286, September 2017PDF Versionpdf icon (374 KB)Anjel Vahratian, Ph.D.Key findingsData from the National Health Interview Survey, 2015Among those aged 40–59, perimenopausal women (56.0%) were more likely than postmenopausal (40.5%) and premenopausal (32.5%) women to sleep less than 7 hours, on average, in a 24-hour period.Postmenopausal women aged 40–59 were more likely than premenopausal women aged 40–59 to have trouble falling asleep (27.1% compared with 16.8%, respectively), and staying asleep (35.9% compared with 23.7%), four times or more in the past week.Postmenopausal women aged 40–59 (55.1%) were more likely than premenopausal women aged 40–59 (47.0%) to not wake up feeling well rested 4 days or more in the past week.Sleep duration and quality are important contributors to health and wellness. Insufficient sleep is associated with an increased risk for chronic conditions such as cardiovascular disease cialis cost (1) and diabetes (2). Women may be particularly vulnerable to sleep problems during times of reproductive hormonal change, such as after the menopausal transition.

Menopause is “the permanent cessation of menstruation that occurs after the loss of ovarian activity” (3) cialis cost. This data brief describes sleep duration and sleep quality among nonpregnant women aged 40–59 by menopausal status. The age range selected for this analysis reflects the focus on midlife sleep health. In this cialis cost analysis, 74.2% of women are premenopausal, 3.7% are perimenopausal, and 22.1% are postmenopausal.

Keywords. Insufficient sleep, menopause, National Health Interview Survey Perimenopausal women were more likely than premenopausal and postmenopausal women to sleep less than 7 hours, on average, in a 24-hour period.More than one in three nonpregnant women aged 40–59 slept less than cialis cost 7 hours, on average, in a 24-hour period (35.1%) (Figure 1). Perimenopausal women were most likely to sleep less than 7 hours, on average, in a 24-hour period (56.0%), compared with 32.5% of premenopausal and 40.5% of postmenopausal women. Postmenopausal women were significantly more likely than premenopausal women to sleep less than 7 hours, on average, in a 24-hour period.

Figure 1 cialis cost. Percentage of nonpregnant women aged 40–59 who slept less than 7 hours, on average, in a 24-hour period, by menopausal status. United States, 2015image icon1Significant cialis cost quadratic trend by menopausal status (p <. 0.05).NOTES.

Women were postmenopausal if they had gone without a menstrual cycle for more than 1 year or were in surgical menopause after the removal of their ovaries. Women were perimenopausal if they no longer had a menstrual cycle and their last menstrual cycle was 1 year ago or less cialis cost. Women were premenopausal if they still had a menstrual cycle. Access data cialis cost table for Figure 1pdf icon.SOURCE.

NCHS, National Health Interview Survey, 2015. The percentage of women aged 40–59 who had cialis cost trouble falling asleep four times or more in the past week varied by menopausal status.Nearly one in five nonpregnant women aged 40–59 had trouble falling asleep four times or more in the past week (19.4%) (Figure 2). The percentage of women in this age group who had trouble falling asleep four times or more in the past week increased from 16.8% among premenopausal women to 24.7% among perimenopausal and 27.1% among postmenopausal women. Postmenopausal women were significantly more likely than premenopausal women to have trouble falling asleep four times or more in the past week.

Figure 2 cialis cost. Percentage of nonpregnant women aged 40–59 who had trouble falling asleep four times or more in the past week, by menopausal status. United States, 2015image icon1Significant linear trend by cialis cost menopausal status (p <. 0.05).NOTES.

Women were postmenopausal if they had gone without a menstrual cycle for more than 1 year or were in surgical menopause after the removal of their ovaries. Women were cialis cost perimenopausal if they no longer had a menstrual cycle and their last menstrual cycle was 1 year ago or less. Women were premenopausal if they still had a menstrual cycle. Access data cialis cost table for Figure 2pdf icon.SOURCE.

NCHS, National Health Interview Survey, 2015. The percentage of women aged 40–59 who had trouble staying asleep four times or more in the past week varied by menopausal status.More than one in four nonpregnant women aged 40–59 had trouble staying cialis cost asleep four times or more in the past week (26.7%) (Figure 3). The percentage of women aged 40–59 who had trouble staying asleep four times or more in the past week increased from 23.7% among premenopausal, to 30.8% among perimenopausal, and to 35.9% among postmenopausal women. Postmenopausal women were significantly more likely than premenopausal women to have trouble staying asleep four times or more in the past week.

Figure 3 cialis cost. Percentage of nonpregnant women aged 40–59 who had trouble staying asleep four times or more in the past week, by menopausal status. United States, 2015image cialis cost icon1Significant linear trend by menopausal status (p <. 0.05).NOTES.

Women were postmenopausal if they had gone without a menstrual cycle for more than 1 year or were in surgical menopause after the removal of their ovaries. Women were perimenopausal if they no longer had a menstrual cycle and their last menstrual cycle was 1 cialis cost year ago or less. Women were premenopausal if they still had a menstrual cycle. Access data table for Figure cialis cost 3pdf icon.SOURCE.

NCHS, National Health Interview Survey, 2015. The percentage of women aged 40–59 who did not wake up feeling well rested 4 days or more in the past week varied by menopausal status.Nearly one in two nonpregnant women aged 40–59 did not wake up feeling well rested 4 days or more in the past week (48.9%) (Figure 4). The percentage of women in this age group who did not wake up feeling cialis cost well rested 4 days or more in the past week increased from 47.0% among premenopausal women to 49.9% among perimenopausal and 55.1% among postmenopausal women. Postmenopausal women were significantly more likely than premenopausal women to not wake up feeling well rested 4 days or more in the past week.

Figure 4 cialis cost. Percentage of nonpregnant women aged 40–59 who did not wake up feeling well rested 4 days or more in the past week, by menopausal status. United States, 2015image icon1Significant linear trend by menopausal status (p <. 0.05).NOTES.

Women were postmenopausal if they had gone without a menstrual cycle for more than 1 year or were in surgical menopause after the removal of their ovaries. Women were perimenopausal if they no longer had a menstrual cycle and their last menstrual cycle was 1 year ago or less. Women were premenopausal if they still had a menstrual cycle. Access data table for Figure 4pdf icon.SOURCE.

NCHS, National Health Interview Survey, 2015. SummaryThis report describes sleep duration and sleep quality among U.S. Nonpregnant women aged 40–59 by menopausal status. Perimenopausal women were most likely to sleep less than 7 hours, on average, in a 24-hour period compared with premenopausal and postmenopausal women.

In contrast, postmenopausal women were most likely to have poor-quality sleep. A greater percentage of postmenopausal women had frequent trouble falling asleep, staying asleep, and not waking well rested compared with premenopausal women. The percentage of perimenopausal women with poor-quality sleep was between the percentages for the other two groups in all three categories. Sleep duration changes with advancing age (4), but sleep duration and quality are also influenced by concurrent changes in women’s reproductive hormone levels (5).

Because sleep is critical for optimal health and well-being (6), the findings in this report highlight areas for further research and targeted health promotion. DefinitionsMenopausal status. A three-level categorical variable was created from a series of questions that asked women. 1) “How old were you when your periods or menstrual cycles started?.

€. 2) “Do you still have periods or menstrual cycles?. €. 3) “When did you have your last period or menstrual cycle?.

€. And 4) “Have you ever had both ovaries removed, either as part of a hysterectomy or as one or more separate surgeries?. € Women were postmenopausal if they a) had gone without a menstrual cycle for more than 1 year or b) were in surgical menopause after the removal of their ovaries. Women were perimenopausal if they a) no longer had a menstrual cycle and b) their last menstrual cycle was 1 year ago or less.

Premenopausal women still had a menstrual cycle.Not waking feeling well rested. Determined by respondents who answered 3 days or less on the questionnaire item asking, “In the past week, on how many days did you wake up feeling well rested?. €Short sleep duration. Determined by respondents who answered 6 hours or less on the questionnaire item asking, “On average, how many hours of sleep do you get in a 24-hour period?.

€Trouble falling asleep. Determined by respondents who answered four times or more on the questionnaire item asking, “In the past week, how many times did you have trouble falling asleep?. €Trouble staying asleep. Determined by respondents who answered four times or more on the questionnaire item asking, “In the past week, how many times did you have trouble staying asleep?.

€ Data source and methodsData from the 2015 National Health Interview Survey (NHIS) were used for this analysis. NHIS is a multipurpose health survey conducted continuously throughout the year by the National Center for Health Statistics. Interviews are conducted in person in respondents’ homes, but follow-ups to complete interviews may be conducted over the telephone. Data for this analysis came from the Sample Adult core and cancer supplement sections of the 2015 NHIS.

For more information about NHIS, including the questionnaire, visit the NHIS website.All analyses used weights to produce national estimates. Estimates on sleep duration and quality in this report are nationally representative of the civilian, noninstitutionalized nonpregnant female population aged 40–59 living in households across the United States. The sample design is described in more detail elsewhere (7). Point estimates and their estimated variances were calculated using SUDAAN software (8) to account for the complex sample design of NHIS.

Linear and quadratic trend tests of the estimated proportions across menopausal status were tested in SUDAAN via PROC DESCRIPT using the POLY option. Differences between percentages were evaluated using two-sided significance tests at the 0.05 level. About the authorAnjel Vahratian is with the National Center for Health Statistics, Division of Health Interview Statistics. The author gratefully acknowledges the assistance of Lindsey Black in the preparation of this report.

ReferencesFord ES. Habitual sleep duration and predicted 10-year cardiovascular risk using the pooled cohort risk equations among US adults. J Am Heart Assoc 3(6):e001454. 2014.Ford ES, Wheaton AG, Chapman DP, Li C, Perry GS, Croft JB.

Associations between self-reported sleep duration and sleeping disorder with concentrations of fasting and 2-h glucose, insulin, and glycosylated hemoglobin among adults without diagnosed diabetes. J Diabetes 6(4):338–50. 2014.American College of Obstetrics and Gynecology. ACOG Practice Bulletin No.

141. Management of menopausal symptoms. Obstet Gynecol 123(1):202–16. 2014.Black LI, Nugent CN, Adams PF.

Tables of adult health behaviors, sleep. National Health Interview Survey, 2011–2014pdf icon. 2016.Santoro N. Perimenopause.

From research to practice. J Women’s Health (Larchmt) 25(4):332–9. 2016.Watson NF, Badr MS, Belenky G, Bliwise DL, Buxton OM, Buysse D, et al. Recommended amount of sleep for a healthy adult.

A joint consensus statement of the American Academy of Sleep Medicine and Sleep Research Society. J Clin Sleep Med 11(6):591–2. 2015.Parsons VL, Moriarity C, Jonas K, et al. Design and estimation for the National Health Interview Survey, 2006–2015.

National Center for Health Statistics. Vital Health Stat 2(165). 2014.RTI International. SUDAAN (Release 11.0.0) [computer software].

2012. Suggested citationVahratian A. Sleep duration and quality among women aged 40–59, by menopausal status. NCHS data brief, no 286.

Hyattsville, MD. National Center for Health Statistics. 2017.Copyright informationAll material appearing in this report is in the public domain and may be reproduced or copied without permission. Citation as to source, however, is appreciated.National Center for Health StatisticsCharles J.

Rothwell, M.S., M.B.A., DirectorJennifer H. Madans, Ph.D., Associate Director for ScienceDivision of Health Interview StatisticsMarcie L. Cynamon, DirectorStephen J. Blumberg, Ph.D., Associate Director for Science.

Can you mix viagra with cialis

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Influenza affects millions of people each year, and because of the COVID-19 pandemic, many physicians and health experts are can you mix viagra with cialis concerned that this year’s flu season will hit with full force. In the Lone Star State, it’s important for Texans to be proactive about their health by getting the yearly flu vaccination. One of the can you mix viagra with cialis worst things that could happen would be having many people sick with the flu while many are ill with coronavirus.Flu vaccination is the best way to reduce the risk of getting and spreading the flu. This year, it also will help keep hospitalizations down as physicians, nurses, and other medical staff continue to care for COVID-19 patients. Traditionally, Texas falls behind on can you mix viagra with cialis flu vaccination.

According to the Centers for Disease Control and Prevention (CDC), only 43.3% of Texas adults got a flu shot in 2018-2019, compared to the national average of 45.3%.Although influenza viruses circulate throughout the year, flu season usually starts in the fall and winter, and peaks between December and February.Like COVID-19, the flu is contagious. Both have some similar symptoms, can you mix viagra with cialis including fever, chills, cough, fatigue, body aches, vomiting, and diarrhea. People with the flu may not experience symptoms until one to four days after catching the virus. The CDC outlines key similarities and differences between influenza and COVID-19 here.While most people recover from the flu, many can experience complications, especially older adults, people with pre-existing can you mix viagra with cialis medical conditions, young children, and pregnant women. If left untreated, infected patients can develop pneumonia, inflammation of the heart, brain, or muscle tissues, organ failure, sepsis, or they could even die.

In Texas, can you mix viagra with cialis more than 21,000 people died from the flu in the past two years. To put that into perspective, that is the population of Katy!. Everyone 6 months or older is encouraged to get the flu vaccine each year – especially adults aged 65 and can you mix viagra with cialis older, pregnant women, young children, and people who have chronic illnesses such as diabetes, asthma, and heart disease. The CDC is urging the public to get the flu vaccine while maintaining social distancing, wearing a mask in public, and practicing good hygiene.People who receive the flu shot may experience some mild side effects like aches and a mild fever, but they can’t get the flu from the shot. Those who get the flu after being vaccinated might have been exposed to the virus beforehand.

The flu vaccination can help lessen flu symptoms and severity, helping reduce the amount of time spent away from can you mix viagra with cialis work and school.In a time when community health is front and center, getting a flu shot is more important than ever. The Texas Medical Association’s Be Wise Immunize℠ program recently created a downloadable poster below in English and Spanish with key takeaways about the flu vaccination. You can print the poster, or save it and share it on can you mix viagra with cialis social media. Be Wise – Immunize is funded in 2020 by the TMA Foundation, thanks to major support from H-E-B and Permian Basin Youth Chavarim.Be Wise – Immunize is a service mark of the Texas Medical Association.Lauren Gambill, MDPediatrician, AustinMember, Texas Medical Association (TMA) Committee on Child and Adolescent HealthExecutive Board Member, Texas Pediatric SocietyDoctors are community leaders. This role can you mix viagra with cialis has become even more important during the COVID-19 pandemic.

As patients navigate our new reality, they are looking to us to determine what is safe, how to protect their families, and the future of their health care. As more Texans lose their jobs, their health insurance, or even their homes, it is crucial that Texas receives the resources it needs to uphold our social safety can you mix viagra with cialis net. The U.S. Census helps determine funding for those resources, and that is why it is of the upmost importance that each and every Texan, no matter address, immigration status, or age, can you mix viagra with cialis respond to the 2020 U.S. Census.

The deadline has been cut short one month and now can you mix viagra with cialis closes Sept. 30.COVID-19 has only increased the importance of completing the census to help our local communities and economies recover. The novel coronavirus has inflicted unprecedented strain on patients and exacerbated inequality as more people are out of work and are many in need of help with food, health care, housing, and more. Schools also have been stretched thin, with teachers scrambling to teach students can you mix viagra with cialis online. Yet, the amount of federal funding Texas has available today to help weather this emergency was driven in part by the census responses made a decade ago.

Getting an can you mix viagra with cialis accurate count in 2020 will help Texans prepare for the decade to follow, the first few years of which most certainly will be spent rebuilding from the pandemic’s fallout. Therefore, it is vital that all Texans be counted.The federal dollars Texas receives generally depends on our population. A George Washington University study recently can you mix viagra with cialis found that even a 1% undercount can lead to a $300 million loss in funding.Take Medicaid, for example. Federal funds pay for 60% of the state’s program, which provides health coverage for two out of five Texas children, one in three individuals with disabilities, and 53% of all births. The complicated formula used to can you mix viagra with cialis calculate the federal portion of this funding depends on accurate census data.

If Texas’ population is undercounted, Texans may appear better off financially than they really are, resulting in Texas getting fewer federal Medicaid dollars. If that happens, lawmakers will have to make up the difference, with cuts in services, program eligibility, or physician and provider payments, any of which are potentially detrimental.The census data also is key to funding other aspects of a community’s social safety net:Health careThe can you mix viagra with cialis Children’s Health Insurance Program (CHIP) provides low-cost health insurance to children whose parents make too much to qualify for Medicaid, but not enough to afford quality coverage. Like Medicaid, how much money the federal government reimburses the state for the program depends in part on the census.Maternal and child health programs that promote public health and help ensure children are vaccinated relies on data from the census. Texas also uses this federal funding to study and respond to maternal mortality and perinatal depression.Food and housing As unemployment rises and families struggle financially, can you mix viagra with cialis many live with uncertainty as to where they will find their next meal. Already, one in seven Texans experiences food insecurity, and 20% of Texas children experience hunger.

Food insecurity is rising in Texas as the pandemic continues. The Central Texas Food Bank saw a 206% rise can you mix viagra with cialis in clients in March. Funding for the Supplemental Nutrition Assistance Program and school lunch programs are both determined by the census. Funding for local housing programs also is calculated can you mix viagra with cialis via the census. An accurate count will help ensure that people who lose their homes during this economic crisis have better hope of finding shelter while our communities recover.

Homelessness is closely connected with declines in overall physical and mental can you mix viagra with cialis health.Childcare and educationAs we navigate the new reality brought on by coronavirus, more parents are taking on roles as breadwinner, parent, teacher, and caretaker. This stress highlights the desperate need for affordable childcare. The census determines funding for programs like Head can you mix viagra with cialis Start that provide comprehensive early childhood education to low-income families. The good news is you still have time to complete the census. Visit 2020census.gov to take can you mix viagra with cialis it.

It takes less than five minutes to complete. Then talk to your family, neighbors, and colleagues can you mix viagra with cialis about doing the same. If you are wondering who counts, the answer is everyone, whether it’s a newborn baby, child in foster care, undocumented immigrant, or an individual experiencing homelessness.Completing the census is one of the best things that you can do for the health of your community, especially during the pandemic. Thank you for helping Texas heal and for supporting these essential safety net programs..

Influenza affects millions of people each year, and because of the COVID-19 cialis cost pandemic, many physicians and health experts are concerned that this year’s flu season will hit with full force. In the Lone Star State, it’s important for Texans to be proactive about their health by getting the yearly flu vaccination. One of cialis cost the worst things that could happen would be having many people sick with the flu while many are ill with coronavirus.Flu vaccination is the best way to reduce the risk of getting and spreading the flu. This year, it also will help keep hospitalizations down as physicians, nurses, and other medical staff continue to care for COVID-19 patients. Traditionally, Texas falls behind on flu vaccination cialis cost.

According to the Centers for Disease Control and Prevention (CDC), only 43.3% of Texas adults got a flu shot in 2018-2019, compared to the national average of 45.3%.Although influenza viruses circulate throughout the year, flu season usually starts in the fall and winter, and peaks between December and February.Like COVID-19, the flu is contagious. Both have some similar symptoms, including fever, chills, cough, fatigue, body cialis cost aches, vomiting, and diarrhea. People with the flu may not experience symptoms until one to four days after catching the virus. The CDC outlines key similarities cialis cost and differences between influenza and COVID-19 here.While most people recover from the flu, many can experience complications, especially older adults, people with pre-existing medical conditions, young children, and pregnant women. If left untreated, infected patients can develop pneumonia, inflammation of the heart, brain, or muscle tissues, organ failure, sepsis, or they could even die.

In Texas, more cialis cost than 21,000 people died from the flu in the past two years. To put that into perspective, that is the population of Katy!. Everyone 6 months or older is encouraged to get the flu vaccine each year – especially adults aged 65 and older, pregnant women, young children, and people who have chronic illnesses such as diabetes, asthma, and heart cialis cost disease. The CDC is urging the public to get the flu vaccine while maintaining social distancing, wearing a mask in public, and practicing good hygiene.People who receive the flu shot may experience some mild side effects like aches and a mild fever, but they can’t get the flu from the shot. Those who get the flu after being vaccinated might have been exposed to the virus beforehand.

The flu vaccination can help lessen flu symptoms and severity, helping reduce the amount of time spent away from work and school.In a time when community cialis cost health is front and center, getting a flu shot is more important than ever. The Texas Medical Association’s Be Wise Immunize℠ program recently created a downloadable poster below in English and Spanish with key takeaways about the flu vaccination. You can print the cialis cost poster, or save it and share it on social media. Be Wise – Immunize is funded in 2020 by the TMA Foundation, thanks to major support from H-E-B and Permian Basin Youth Chavarim.Be Wise – Immunize is a service mark of the Texas Medical Association.Lauren Gambill, MDPediatrician, AustinMember, Texas Medical Association (TMA) Committee on Child and Adolescent HealthExecutive Board Member, Texas Pediatric SocietyDoctors are community leaders. This role has become even more important cialis cost during the COVID-19 pandemic.

As patients navigate our new reality, they are looking to us to determine what is safe, how to protect their families, and the future of their health care. As more Texans lose their jobs, their health insurance, cialis cost or even their homes, it is crucial that Texas receives the resources it needs to uphold our social safety net. The U.S. Census helps determine funding for those resources, and that is why it is of the upmost importance that each and every Texan, no cialis cost matter address, immigration status, or age, respond to the 2020 U.S. Census.

The deadline has been cut short one month cialis cost and now closes Sept. 30.COVID-19 has only increased the importance of completing the census to help our local communities and economies recover. The novel coronavirus has inflicted unprecedented strain on patients and exacerbated inequality as more people are out of work and are many in need of help with food, health care, housing, and more. Schools also have been stretched thin, with teachers scrambling to cialis cost teach students online. Yet, the amount of federal funding Texas has available today to help weather this emergency was driven in part by the census responses made a decade ago.

Getting an accurate count in 2020 will help Texans prepare for the decade to follow, the first few years of which cialis cost most certainly will be spent rebuilding from the pandemic’s fallout. Therefore, it is vital that all Texans be counted.The federal dollars Texas receives generally depends on our population. A George Washington University study recently found that even a 1% undercount can cialis cost lead to a $300 million loss in funding.Take Medicaid, for example. Federal funds pay for 60% of the state’s program, which provides health coverage for two out of five Texas children, one in three individuals with disabilities, and 53% of all births. The complicated formula used to calculate the federal portion of this funding depends cialis cost on accurate census data.

If Texas’ population is undercounted, Texans may appear better off financially than they really are, resulting in Texas getting fewer federal Medicaid dollars. If that happens, lawmakers will have to make up the difference, with cuts in services, program eligibility, or physician and provider cialis cost payments, any of which are potentially detrimental.The census data also is key to funding other aspects of a community’s social safety net:Health careThe Children’s Health Insurance Program (CHIP) provides low-cost health insurance to children whose parents make too much to qualify for Medicaid, but not enough to afford quality coverage. Like Medicaid, how much money the federal government reimburses the state for the program depends in part on the census.Maternal and child health programs that promote public health and help ensure children are vaccinated relies on data from the census. Texas also uses this federal funding to study and respond to maternal mortality and perinatal depression.Food and housing As unemployment rises and families struggle financially, many cialis cost live with uncertainty as to where they will find their next meal. Already, one in seven Texans experiences food insecurity, and 20% of Texas children experience hunger.

Food insecurity is rising in Texas as the pandemic continues. The Central Texas Food Bank saw a 206% rise in clients in March cialis cost. Funding for the Supplemental Nutrition Assistance Program and school lunch programs are both determined by the census. Funding for local housing programs cialis cost also is calculated via the census. An accurate count will help ensure that people who lose their homes during this economic crisis have better hope of finding shelter while our communities recover.

Homelessness is closely connected with declines in overall physical and mental health.Childcare and educationAs we navigate the new reality brought on by coronavirus, more parents are taking on roles as breadwinner, parent, teacher, and caretaker cialis cost. This stress highlights the desperate need for affordable childcare. The census determines funding for programs like cialis cost Head Start that provide comprehensive early childhood education to low-income families. The good news is you still have time to complete the census. Visit 2020census.gov cialis cost to take it.

It takes less than five minutes to complete. Then talk to your family, neighbors, and colleagues about cialis cost doing the same. If you are wondering who counts, the answer is everyone, whether it’s a newborn baby, child in foster care, undocumented immigrant, or an individual experiencing homelessness.Completing the census is one of the best things that you can do for the health of your community, especially during the pandemic. Thank you for helping Texas heal and for supporting these essential safety net programs..

Cialis results

NONE

IntroductionThe lymphatic system is a network of vessels cialis results important for whole body fluid homeostasis, lipid absorption and https://www.cityreal.lv/cialis-coupon/ immune cell trafficking.1 2 Lymphoedema is caused by lymphatic dysfunction, which leads to a build-up of interstitial fluid within the tissues. This manifests with swelling of the extremities, usually of the legs but may involve other regions or segments of the body such as the upper limbs, face, trunk or genital area. There is an increased risk of infection due to disturbances in immune cell trafficking within the segment of compromised lymph drainage.3 Lymphatic dysfunction within the thorax and abdomen, here referred to as systemic/internal involvement (but can be referred to as visceral or central involvement), may present with pleural or pericardial effusions or ascites, any of which may be chylous, as well as intestinal or pulmonary lymphangiectasia, cialis results protein losing enteropathy or chylous reflux.The International Society for the Study of Vascular Anomalies (ISSVA) updated their classification for vascular anomalies in 2018.4 The vascular malformations are subgrouped into ‘combined’, which include more than one type of vessel, ‘simple’ (only involving one vessel type), and those ‘associated with other anomalies’.Lymphoedema due to a presumed genetic developmental fault in the structure or function of lymph conducting pathways is called primary lymphoedema.5 Some developmental faults can lead to overt structural defects of the lymph conducting pathways and are called lymphatic malformations. Such malformations if interfering with lymph drainage cause lymphoedema (truncal malformations) but some lymphatic malformations remain as isolated anomalies with no connection to main lymph drainage pathways and do not cause lymphoedema (non-truncal malformations).6 A primary lymphatic anomaly is an umbrella term referring to all lymphatic abnormalities arising from a developmental fault.For a long time, the diagnosis of primary lymphoedema was based largely on the age of presentation of the swelling, congenital, pubertal and late onset, with limited differentiation between the phenotypes.

The discovery of the first causal gene, vascular endothelial growth factor receptor 3 for Milroy disease, indicated that a molecular diagnosis was possible.7 The first St George’s classification algorithm of primary lymphoedema and other primary lymphatic disorders was an attempt to guide a cialis results clearer categorisation of phenotypes and enable the discovery of further causal genes.8 Age of onset remained a key criterion, but the sites affected and associated features, for example, dysmorphology, distichiasis (aberrant eyelashes), varicose veins, vascular malformations and limb overgrowth were also considered, as was internal or systemic involvement, for example, fetal hydrops, intestinal lymphangiectasia, pleural and pericardial effusions and chylous reflux. A family history of lymphoedema with determination of the mode of inheritance was considered useful.More rigorous phenotyping facilitated the identification of subgroups of patients with the same broad category of primary lymphatic anomaly. These cohorts were then used for molecular studies to cialis results identify more causal genes. Once the genotype was known then crosschecking of the clinical characteristics, natural history and inheritance patterns was possible and an accurate phenotype defined.

Investigations such cialis results as lymphoscintigraphy helped to refine the phenotype further and give insight into the mechanisms for the development of the lymphatic disorder. A first update of the classification was published in 2013.9The St George’s classification algorithm is intended to help clinicians categorise their patients and guide testing towards, where possible, a molecular diagnosis. This algorithm is criteria matching, that is, using certain key findings for classification through a multistep process of history taking, examination findings, mutation testing, cialis results etc. The next step using the information gathered is to advise on natural history, prognosis and risk (including genetic counselling) and to guide management.

While a molecular diagnosis should provide the most specific and accurate diagnosis, it can be seen particularly with the postzygotic mosaic disorders that one genotype can be clinically very heterogenous so there will probably always be a place for good clinical phenotyping supported by investigation to guide management.Here, we present a second update of the St George’s classification algorithm to include newly discovered genes and to bring it in-line with the 2018 ISSVA classification for vascular anomalies.4 The results of an audit, the purpose of which was to determine how well the algorithm was performing as a diagnostic aid to classify patients with primary lymphatic anomalies and guide molecular testing are also presented.MethodsSt George’s classification algorithm of primary lymphatic anomaliesThe St George’s classification algorithm was updated (figure 1) and then applied, retrospectively, to all patients presenting to the national multidisciplinary ‘Primary and Paediatric Lymphoedema’ Clinic held at St George’s Hospital over a 1-year period cialis results. Careful phenotyping was undertaken both on clinical grounds and after selective investigations, for example, lymphoscintigraphy. Where possible and appropriate, targeted genetic testing was performed (this was prior to the introduction of a lymphoedema gene panel in our unit) for some of the genes listed in table 1.St George’s classification algorithm for primary lymphatic anomalies cialis results. The five main groupings (colour coded) with their various clinical subtypes of disease.

Primary lymphoedema is the cialis results major clinical feature in the green, pink and purple sections. Text in red indicates the suggested genetic test and/or differential diagnosis for the subgroup, however, the indicated genes do not explain the cause of disease in all patients in each grouping. For example, only 70% of patients with Milroy disease are explained by mutations in FLT4/VEGFR3.33 FH, cialis results family history. +ve, positive.

ˆ’ve, negative cialis results. (Image shared by St George’s Lymphovascular Research Group under the CC BY-SA 4.0 International licence on Wikimedia Commons)." data-icon-position data-hide-link-title="0">Figure 1 St George’s classification algorithm for primary lymphatic anomalies. The five cialis results main groupings (colour coded) with their various clinical subtypes of disease. Primary lymphoedema is the major clinical feature in the green, pink and purple sections.

Text in red indicates the suggested genetic test and/or differential diagnosis for the subgroup, however, the indicated genes do not explain the cause of disease in cialis results all patients in each grouping. For example, only 70% of patients with Milroy disease are explained by mutations in FLT4/VEGFR3.33 FH, family history. +ve, positive cialis results. ˆ’ve, negative.

(Image shared by St George’s Lymphovascular Research Group under the CC BY-SA 4.0 International licence on Wikimedia Commons).View this table:Table 1 An overview of genetic disorders with primary lymphoedema as a frequent and dominant feature, categorised by inheritance and age of onsetWithin the St George’s classification algorithm (figure 1), there are five main categories of primary lymphatic anomalies. These are presented in the form of colour-coded sections with the individual subtypes (including genotypes) cialis results within the categories. For definitions of some of the terms used, see Glossary of Terms (see online supplementary section).Supplemental materialFirst, the yellow section includes the ‘vascular malformations associated with other anomalies’ and the ‘lymphatic malformations’ (as defined in the ‘Introduction’ section).Second, the patient is assessed for syndromes that have lymphoedema as a non-dominant feature (blue section), for example, the patient is dysmorphic with learning difficulties and possibly has other abnormalities.Then if not obviously syndromic, and the lymphatic problems are the dominant feature, further assessment and investigations for systemic/internal lymphatic dysfunction or central conducting anomalies (eg, chylothoraces, chylopericardial effusions, ascites or protein losing enteropathy) are undertaken (pink section). These include cialis results a careful medical history asking specifically about prenatal history (eg, hydrothoraces, fetal hydrops), chronic diarrhoea, abdominal bloating or discomfort with fatty foods, weight loss or faltering growth (in a child) or shortness of breath on exertion.

Blood investigations (including serum albumin, immunoglobulins, lymphocyte subsets, faecal levels of calprotectin or alpha-1-antitrysin), echocardiograms and chest radiographs are helpful if central lymphatic dysfunction is suspected.Where none of the above features is present, then the age of onset is used to determine the grouping. The green section deals with congenital-onset primary lymphoedema (includes syndromes where lymphoedema is the dominant clinical problem, and which is present at birth or develops within the first year of life but cialis results is not associated with systemic/internal lymphatic dysfunction). The purple section addresses late-onset primary lymphoedema (ie, lymphoedema that is the dominant clinical problem, and which develops after the first year of life but is not associated with systemic/internal lymphatic dysfunction). It was decided not to differentiate between pubertal onset (praecox) and later cialis results onset in life (tarda) when it was discovered that one genotype such as FOXC2 can cause both.It is important to note that the specific diagnosis may be difficult in a neonate presenting with isolated congenital primary lymphoedema.

A baby born with lymphoedema may later present with developmental delay, systemic involvement, progressive segmental overgrowth or a vascular malformation, which could suggest a diagnosis in one of the other categories. It should also be emphasised that cialis results each colour-coded section is not exclusive. Some somatic overgrowth anomalies may possess significant internal involvement. Also, lymphoedema distichiasis syndrome is allocated to the purple late-onset cialis results lymphoedema section because the dominant feature is the late-onset lymphoedema not the associated features, which make it a syndrome.

The blue ‘syndromic’ section refers to conditions with a collection of features where lymphoedema is not the main characteristic. The algorithm is intended to guide a clinical diagnosis and target gene testing.Genetic methodologyFor the purposes of the audit, targeted genetic testing of FOXC2, VEGFR3, CCBE1, SOX18, RASopathy genes and PIK3CA was performed by Sanger sequencing of DNA extracted from lymphocytes or skin fibroblasts in patients in whom a specific genetic diagnosis cialis results was suspected. This was before the introduction of a lymphoedema gene panel. Some patients, who were either negative for the targeted genes or did not fit the relevant phenotypes of those genes, were included in Whole Exome Sequencing (WES) cohorts after classification, which then led to the identification of new disease genes such as EPHB4, GATA2, PIEZO1, GJC2 and FAT4.Retrospective audit of the St George’s Clinic for 2016A 12-month retrospective audit for the cialis results year 2016 (1 January 2016–31 December 2016) was performed.

The aim of the audit was to look at the proportion of patients in each category of the classification algorithm and to look at the success of making a molecular diagnosis through use of the algorithm. The audit criteria required the patients to be seen in our specialist clinic, at any age, with a diagnosis of a primary lymphatic anomaly with data collected from cialis results medical records and laboratory results.ResultsResults of the retrospective auditOver a 12-month period in 2016, 227 patients were seen (age range 2 weeks to 70 years), 25.6% (n=58/227) of which were new patients. Over one-third (38%) of patients seen in the clinic had a family history of primary lymphoedema.Few patients had received genetic testing prior to referral to the clinic. Targeted genetic cialis results testing was completed in 63% (n=143) of the patients seen.

At that time, a lymphoedema gene panel was not available, patients were only tested if the clinician felt there was a reasonable chance of finding a molecular cause, that is, testing was targeted.Of those tested, the underlying genetic cause was identified in 41% (n=59/143). Overall, a molecular diagnosis was made in 26% (59/227) of all the patients seen in 2016.Vascular malformations with associated anomalies and lymphatic cialis results malformations (yellow)This group presents with malformations in the structure and organisation of blood and lymphatic vessels with a patchy, segmental distribution. Lymphoedema may develop in combination with vascular malformations and segmental overgrowth (or occasionally, undergrowth) of tissues within the swollen limb, for example, muscle, skeletal or adipose tissues (figure 2A). The combination of lymphatic and vascular malformations in this group reflects the mutual embryological origins of the two vascular systems.A graphic representation cialis results of the 227 audited patients seen in clinic in 2016 and their distribution across the five categories from figure 1 (pie chart).

(A–G) Images show features of each category. (A) Patients with postzygotic mutations often present with asymmetrical swelling and segmental overgrowth as this patient, who cialis results is mosaic for a mutation in KRAS. (B) Webbed neck in Noonan syndrome. (C) In rare cases, swellings can be widespread affecting all segments of the body such as in this child with biallelic CCBE1 mutations.

(D) In milder forms, often just the dorsum of the foot is affected as in this baby with a VEGFR3 cialis results mutation. (E, F) Lower limb swelling and distichiasis (arrowheads in F) in a patient with a FOXC2 mutation. (G) Lymphoedema is a major cause of skin disease and affected patients suffer from cialis results severe and recurrent episodes of cutaneous infection, especially HPV-associated warts as seen in patients with GATA2 mutations. GLD, generalised lymphatic dysplasia." data-icon-position data-hide-link-title="0">Figure 2 A graphic representation of the 227 audited patients seen in clinic in 2016 and their distribution across the five categories from figure 1 (pie chart).

(A–G) Images show features of each cialis results category. (A) Patients with postzygotic mutations often present with asymmetrical swelling and segmental overgrowth as this patient, who is mosaic for a mutation in KRAS. (B) Webbed cialis results neck in Noonan syndrome. (C) In rare cases, swellings can be widespread affecting all segments of the body such as in this child with biallelic CCBE1 mutations.

(D) In milder forms, often just the dorsum of cialis results the foot is affected as in this baby with a VEGFR3 mutation. (E, F) Lower limb swelling and distichiasis (arrowheads in F) in a patient with a FOXC2 mutation. (G) Lymphoedema is a major cause of skin disease and affected patients suffer from severe and recurrent episodes of cutaneous infection, especially HPV-associated warts cialis results as seen in patients with GATA2 mutations. GLD, generalised lymphatic dysplasia.These conditions are usually due to postzygotic mutations, for example, PIK3CA-related overgrowth spectrum (PROS)).

Exceptions to this are capillary malformation-arteriovenous malformation (MIM 608354) such as Parkes-Weber syndrome, which may be caused by heterozygous, germline mutations in RASA1.10Of the cialis results 227 patients seen in 2016, 17% (n=39) had lymphoedema associated with vascular malformations and/or segmental overgrowth (or undergrowth) (figure 2, pie chart) in comparison with 15% in 2010.8 It has been shown that postzygotic, gain of function mutations in PIK3CA may be responsible for many of the mosaic segmental overgrowth spectrum disorders.11 Postzygotic mutations are rarely identified in blood samples and therefore require a skin biopsy of the affected region. In the 2016 cohort, only 10 patients (26%) provided skin biopsies for genetic analysis, producing just one molecular diagnosis. More research cialis results in this field is required to identify the genetic basis for some of the conditions in this category. However, since the last revision, we have gained a much better understanding of the classification of some of these postzygotic mosaic conditions, therefore a brief review of the latest developments in this area is given in the online supplementary section.Syndromic lymphoedema (blue)Syndromes associated with primary lymphatic anomalies are listed in table 2 and include chromosomal abnormalities, single gene disorders and imprinting disorders.

Patients attending cialis results the clinic with syndromic primary lymphoedema made up 13% (n=29) (figure 2, pie chart), similar to the 15% reported by Connell et al.8 Nearly three-quarters (72%, n=21) of this cohort had a molecular or chromosomal diagnosis. The most frequently seen syndromes were Noonan syndrome (n=8) (figure 2B), Turner syndrome (n=4) and Phelan McDermid syndrome (n=3).View this table:Table 2 An overview of ‘Known Syndromes’ with primary lymphoedema as a non-dominant association as referred to in the St George’s classification algorithm (figure 1, blue section)Lymphoedema with prenatal or postnatal systemic involvement (pink)In some conditions, lymphoedema may be associated with internal (systemic or visceral) disturbances of the lymphatic system within thorax or abdomen, for example, fetal hydrops, intestinal lymphangiectasia (presenting as protein-losing enteropathy), pulmonary lymphangiectasia or with pericardial and/or pleural effusions (often chylous), or chylous reflux (often into the genitalia). Broadly, there cialis results are two types of lymphoedema with systemic involvement. (A) ‘widespread’ swelling affecting all segments of the body (figure 2C), such as that seen in generalised lymphatic dysplasia (GLD).

Due to faulty cialis results development, the structural or functional abnormality of the lymphatic system is affecting the whole body. One type is Hennekam-lymphangiectasia-lymphoedema syndrome12. (B) ‘patchy’ areas of swelling, for example, left arm and right leg, which have been named ‘multisegmental lymphatic dysplasia’ (MLD) cialis results (figure 1).Prenatally, these conditions may present with pleural effusions (hydrothoraces), or as non-immune fetal hydrops (the accumulation of fluid in at least two compartments of a fetus such as the abdominal cavity, pleura or subcutaneous oedema). Fifteen per cent of non-immune cases of hydrops are the result of lymphatic disorders, and approximately 20% are idiopathic, some of which may be due to, as yet, unidentified lymphatic abnormalities.13In our audit, this cohort accounted for 12% (n=27) of patients (figure 2, pie chart), slightly higher than the 8% reported in 2010.8 Molecular testing was carried out in 17 patients.

Nine of cialis results those tested had GLD, and pathogenic variants were identified in seven (78%). Five had biallelic variants in the PIEZO1 gene and one each with biallelic variants in FAT4 and SOX18. Interestingly, two of the families described by Connell et al, cases 3 and 4, have subsequently been found to be caused by biallelic variants in the PIEZO1 gene.8 14None of the eight patients, who presented with ‘patchy’ distribution of lymphoedema (MLD), had an identifiable molecular diagnosis. It is suspected that these patients could have cialis results a postzygotic mosaic mutation or WILD syndrome.15Since the last revision of the St George’s classification algorithm was published,9 five new causal genes associated with GLD and/or non-immune fetal hydrops have been identified.

ADAMTS3,16 EPHB4,17 FAT4,18 FBXL719 and PIEZO114 20 and are reviewed in the online supplementary section.Congenital onset lymphoedema (green)In this category, congenital onset is defined as lymphoedema that is present at birth or develops within the first year of life. Bilateral lower limb swelling is the most frequent presentation (figure 2D), but the swelling cialis results may be unilateral and/or involve the arms, genitalia and/or face, depending on the underlying cause. There are a number of different genetic disorders presenting with congenital lymphoedema (table 1). Milroy disease cialis results (ORPHA79452.

OMIM 153100) is the most common form, occurring as a result of pathogenic variants in FLT4/VEGFR3.21 22 The mutation may occur de novo, so a family history is not essential for this diagnosis. The lymphoedema cialis results is always confined to the lower limbs but may be unilateral, and may (rarely) involve the genitalia. Approximately 10% of mutation carriers do not have lymphoedema. Fetuses with Milroy disease may present antenatally with pedal oedema in the third trimester, and, in a few cases, with bilateral hydrothoraces, which resolve before birth.Pathogenic variants in VEGFC, the ligand for VEGFR3, have also been identified in association with congenital primary lymphoedema of Gordon (OMIM 615907), also affecting the lower cialis results limbs.23–26The congenital category represents 21% (n=47) of the patients seen in 2016 (figure 2, pie chart) compared with 24% in 2010.8 A pathogenic variant was identified in 19 of the 47 (40%) patients genetically tested in this category.

The majority (n=18) had pathogenic variants identified in FLT4/VEGFR3 and, in one patient, a pathogenic variant in the GJC2 gene. A GJC2 mutation in a patient presenting with lymphoedema at birth is unusual but shows the variability of the phenotype.Many of the conditions listed under the other categories in the classification algorithm may initially present with congenital lymphoedema but systemic involvement, progressive overgrowth or vascular malformation may present cialis results later and are so reclassified. Likewise, some syndromic forms may present with congenital lymphoedema before any other manifestations, making diagnosis difficult at times. Thus, the cialis results diagnosis of ‘isolated’ congenital primary lymphoedema may be difficult in a neonate presenting with pedal oedema.

Therefore, a molecular diagnosis in the neonatal period is clinically very useful in the management of these patients.Late-onset lymphoedema (purple)‘Late-onset’ lymphoedema is defined as presenting after the first year of life. Swelling can range from being unilateral, bilateral or can involve cialis results all four limbs and can present from early childhood up to adulthood (figures 1 and 2E). Some may present with unilateral swelling, but the contralateral limb may become involved later or show abnormalities on lymphoscintigram even when clinically uninvolved. The phenotypes cialis results also range from mild to severe.

There are currently five genes known to be associated with late-onset lymphoedema. FOXC2 (figure 2F),27 GJC2,28 29 GATA2 (figure cialis results 2G),30 HGF31 and CELSR132 (table 1). For many patients the molecular cause remains elusive, particularly in those patients with Meige disease and late-onset (usually pubertal) unilateral lower limb lymphoedema.Late-onset primary lymphoedema accounted for 37% (n=85) in 2016 (figure 2, pie chart) comparable to the 36% reported in 2010.8 This category has a low number of molecular diagnoses (n=12. 14%) as there are currently no causative genes for Meige disease, which made up 36% (n=31) of patients in this category.DiscussionThis review presents an updated St George’s classification algorithm of primary cialis results lymphatic anomalies and brings it in-line with the ISSVA classification for vascular anomalies.

It cites eight new causative genes since the last publication and highlights the areas where the genetic basis is still not known. This rapidly evolving field cialis results demonstrates that primary lymphoedema and vascular malformations are highly heterogenous.The audit reports an overall successful molecular diagnosis in 26% of patients seen in the clinic, but 41% of those patients selected for molecular testing. This is a considerable improvement on the rate of a molecular diagnosis since the algorithm was first published in 2010. Only two causal genes cialis results were known at that time.

We can conclude from the audit that the algorithm works well in targeting mutation testing. Furthermore, use of the algorithm has led to the discovery of a number of causal genes. While it could be argued that the introduction of the lymphoedema gene panel obviates any need cialis results for targeted gene tests, we believe that matching a phenotype to a likely gene reduces wasteful testing and helps enormously in the interpretation of variants of unknown significance, which are becoming an increasing problem in the era of next-generation sequencing.Although providing a molecular diagnosis in one-quarter of all the patients with primary lymphoedema represents a considerable improvement from when the algorithm was last reviewed, the molecular diagnosis is still not identified in the majority of patients seen in the St George’s Clinic. In the diagnostic setting, the introduction of next-generation sequencing with a targeted (virtual) ‘lymphoedema gene panel’ may improve the diagnostic rate and broaden the phenotypic spectrum of many of the known genetic disorders.

Understanding of the natural history of the cialis results disorder will enable appropriate surveillance of, for example, leukaemia in Emberger syndrome (GATA2), and allow investigations for known associated problems, for example, congenital heart disease in patients with lymphoedema distichiasis syndrome (FOXC2). Prenatal diagnosis for the more serious conditions also becomes possible. Knowledge of causal genes, and mechanisms of pathophysiology, provide an opportunity for new, improved treatments (personalised medicine) (eg, mammalian target of rapamycin inhibitors for progressive overgrowth disorders).In conclusion, the St George’s classification algorithm for primary cialis results lymphatic anomalies has been further refined. With this review, we have provided insight into the most recently discovered genotypes and how this algorithm can be used in the clinic to guide management of patients with primary lymphoedema.IntroductionTriphalangeal thumb (TPT) is a rare congenital hand anomaly in which the thumb has three phalanges instead of two.

TPT is usually inherited in an autosomal dominant trait and is therefore cialis results commonly seen in affected families. In 1994, Heutink et al located the pathogenic locus of TPT at chromosome 7q36.1 Subsequently, Lettice et al determined that point mutations in the zone of polarising activity regulatory sequence (ZRS) causes TPT and preaxial polydactyly.2 The ZRS is a long-range regulatory element residing in intron 5 of LMBR1 and regulates Sonic Hedgehog (SHH) expression in the embryonic limb bud. Since the identification of the ZRS region, 18 different point mutations in the ZRS have been reported in TPT families.3There is broad phenotypical variability among different point cialis results mutations in the ZRS. For example, variants on locations 323 and 739 in the ZRS cause mild presentations of isolated TPT.2 4 Alternatively, severe anomalies such as TPT accompanied with tibial hypoplasia have been observed in families with variants on position 404 and 406 in the ZRS.2 5–9 In mildly affected phenotypes, reduced penetrance is regularly observed.

In families who are more severely affected however, no reports of reduced penetrance have been made.Identifying and reporting new variants in the ZRS is important cialis results for genotype-phenotype correlations in TPT families. Additionally, it will also help to further elucidate the exact molecular mechanism of the role of the ZRS in the regulation of SHH expression in the embryonic limb.We therefore report two families with variants in the ZRS. These variants cialis results were identified in Dutch families with isolated TPT. Additionally, unaffected family members shared these variants with affected family members.

Although this observation suggests that the genotype is not fully penetrant, minor anomalies within these presumed unaffected family members indicate subclinical cialis results expression of a TPT phenotype rather than reduced penetrance of the genotype. We define subclinical phenotypes as anomalies that are not recognised by affected family members since they do not cause functional constraints in daily life, but can be recognised during clinical workup by experienced physicians.MethodsClinical evaluationFamilies 1 and 2 were identified at the outpatient clinic for Congenital Hand and Upper Limb Anomalies at the Sophia Children’s Hospital in Rotterdam, The Netherlands. The family members were clinically examined and consulted by a clinical cialis results geneticist. In family 1, peripheral blood samples were collected from the index patient, the mother and the grandfather of the index patient (figure 1).

No blood samples were obtained from the brother of this patient as he cialis results was clinically unaffected and was below adult age.Overview of Dutch TPT family 1. (A) Pedigree of the Dutch TPT family 1. The index patient cialis results is patient III-2. (B) X-ray image of the hand of the index patient.

An additional cialis results deltaphalanx is present in both thumbs. (C) X-ray image of the thumbs of patient III-2. Although there is no triphalangism present, the cialis results thumbs are remarkably broad. TPT, triphalangeal thumb." data-icon-position data-hide-link-title="0">Figure 1 Overview of Dutch TPT family 1.

(A) Pedigree of the Dutch TPT family 1. The index patient cialis results is patient III-2. (B) X-ray image of the hand of the index patient. An additional deltaphalanx cialis results is present in both thumbs.

(C) X-ray image of the thumbs of patient III-2. Although there is no triphalangism present, the thumbs cialis results are remarkably broad. TPT, triphalangeal thumb.In family 2, the index patient (III-2) visited the outpatient clinic for Congenital Hand and Upper Limb Anomalies at the Sophia Children’s Hospital in Rotterdam with his parents. The other family members were visited as part of a cialis results field study.

Included family members were clinically evaluated by a clinical geneticist, photographs were obtained and peripheral blood samples were collected (Figure 2, online supplementary figure 1). No radiographs were obtained during cialis results the field study.Supplemental materialOverview of Dutch TPT family 2. (A) Outtake of pedigree of the Dutch TPT family 2. (B) Images of patient III-2 and his father (II-2), showing triphalangism of both thumbs with one additional ray on the cialis results left hand.

(C) Images of patients II-4 and I-1, showing no triphalangism but lack of thumb opposition and mild thenar hypoplasia. TPT, triphalangeal thumb." cialis results data-icon-position data-hide-link-title="0">Figure 2 Overview of Dutch TPT family 2. (A) Outtake of pedigree of the Dutch TPT family 2. (B) Images of patient III-2 and his father (II-2), showing cialis results triphalangism of both thumbs with one additional ray on the left hand.

(C) Images of patients II-4 and I-1, showing no triphalangism but lack of thumb opposition and mild thenar hypoplasia. TPT, triphalangeal thumb.ZRS sequencingDNA samples were isolated from peripheral blood cialis results. The fragments were amplified using standard PCR. An 834 bp fragment covering the ZRS (774 bp) was sequenced in family members of both families (UCSC Genome cialis results Browser, hg19, chr7:156583766–156584600).

Sequencing of PCR products was executed using Big Dye Terminator 3.1. Fragments were loaded on an ABI 3130 Sequence analyser and genetic cialis results analysis was performed with SeqScape Software (V.3.0).ResultsClinical report​Family 1Family 1 (figure 1A) consists of a nuclear family containing two affected patients with TPT. The index patient had a bilateral isolated TPT with an additional deltaphalanx (figure 1B). No other congenital hand or other anomalies were present cialis results.

The mother of the index patient was born with a TPT accompanied with a rudimentary additional thumb on both hands, without any other hand or congenital anomaly (data not shown). The maternal grandfather cialis results of the index patient did not have a TPT or preaxial polydactyly. However, clinical examination of the hands revealed remarkable broadness of both thumbs and mild thenar hypoplasia. Although the X-ray image of the grandfather shows no duplication of the thumb or triphalangism, the broadness of the distal phalanges is striking (figure 1C).​Family 2Family 2 comprises a large seven-generation family (Figure 2A, online supplementary figure 1).

The index patient (III-2) had bilateral cialis results TPT with preaxial polydactyly on the left hand. The father of the index patient (II-1) had bilateral TPT without preaxial polydactyly (figure 2B). All other family members cialis results reported they were not affected. Although the thumbs of family members I-1 and II-2 did not show clear features of triphalangism, further examination revealed that both family members had mild thenar hypoplasia and were unable to oppose both thumbs (figure 2C).

No other congenital anomalies were present in family 2.Mutation analysisSequence analysis of the 774 bp ZRS, in intron 5 of LMBR1, revealed the presence of a heterozygous A to G transition in members of cialis results family 1 (g.156584405A>G, GRCh37/Hg19). Following the more commonly used nomenclature for loci of ZRS variants, introduced by Lettice et al,2 this variant can be defined as a 165A>G variant.2 This variant was present in the affected family members. Patient I-1 of family one also carried a 165A>G variant in cialis results the ZRS, despite not having TPT on either hand. This variant was not present in public databases dbSNP, Clinvar and HGMD.

Additionally, this variant was not present in locally available WGS data sets (GoNL, Wellderly, Public54).10–12In family 2, we identified a cialis results 295T>variant in the ZRS (g.156584535T>C, GRCh37/Hg19). Two family members who did not have TPT carried the 295T>C variant. This variant cialis results has previously been reported in a British family with mild cases of TPT and reduced penetrance of the genotype.13 Additionally, transgenic enhancer assays in mice showed that the 295T>C variant causes ectopic expression in the embryonic limb and therefore confirms the pathogenicity of this variant.DiscussionIn this brief report, we describe two TPT families with either a 165A>G or 295T>C variant in the ZRS. The aim of this paper was to show that these observations of reduced penetrance in TPT families are in retrospect caused by mild and subclinical limb phenotypes without the presence of triphalangism and therefore raise awareness for thorough clinical examination in members of TPT families who are presumed to be unaffected.Ever since the identification of ZRS by Lettice et al in 2003, 18 variants in ZRS have been published in the literature.2 4 6–9 13–20 These variants are generally fully penetrant and have been found in families with either TPT or TPT with preaxial polydactyly.

Exceptions to the above are point mutations on positions 105, 404 and 406 in ZRS, which cause more severe phenotypes like tibial hypoplasia and polysyndactyly.2 5–9 21Although most variants in ZRS are considered fully penetrant, reduced penetrance has been reported in several TPT families with variants on positions 295, 334, 463 and 739 in ZRS.13 14 16 17The first aim of cialis results this paper is to hypothesise that some of these observations might not be caused by reduced penetrance of the genotype, but by a subclinical expression of the phenotype. We base our hypothesis on two arguments. First, family members who were initially presumed unaffected do show minor anomalies cialis results or altered hand function when examined appropriately. In family 1 of this study, the grandfather did not have TPT but had evident broadness of the thumb.

In family 2, patients with initially normal thumbs lacked the ability of opposition, which is caused cialis results by abnormal developmental patterning of the thumb. Although this observation is based on three patients from two families, we believe that these examples clearly illustrate our postulated hypothesis.Second, reports of non-penetrance are consistently associated with mild phenotypes in TPT families and not with severe TPT phenotypes, like tibial hypoplasia and polysyndactyly. This indicates that these observations only occur in TPT families cialis results where SHH expression is only slightly disrupted. In these families, the variability in the phenotypical spectrum is apparently broad enough that family members with variants in ZRS can present with subclinical phenotypes instead of TPT.

However, it remains unclear why the disruption of cialis results SHH causes TPT in one family member and a subclinical phenotype in another. One example of how intrafamilial variability can be explained is based on a reported family, where different degrees of somatic mosaicism were associated with various phenotypes in affected family members.22 As the regulatory function of ZRS on SHH is extremely delicate and affected by timing, location and level of activity, it is plausible that the slightest alteration of one of these factors can cause this interindividual phenotypical variation.The second aim of this paper is to underline the importance of two aspects when clinically examining and counselling patients with an inherited type of TPT. First, it is important to clinically investigate the presumed unaffected family members, as these patients might not encounter functional problems in their daily cialis results life and will report they are unaffected. However, a distinct broadness of the thumb, a double flexion fold in the thumb or a duplicated lunula might indicate a discrete inclination for duplication of the thumb or the presence of an additional phalanx.

Additionally, functional limitations cialis results regarding thumb strength or lack of opposition should be evaluated as well. Second, presumed unaffected family members should only be informed that their future offspring have a population-wide probability of having TPT or polydactyly after genetic evaluation. For complete reassurance, genetic evaluation of ZRS is also indicated for unaffected family members of mildly affected patients to verify whether they share the same disease-causing variant with their affected family members..

IntroductionThe lymphatic system is a network of vessels important for whole body fluid homeostasis, lipid absorption and immune cell cialis cost trafficking.1 2 Lymphoedema is caused by lymphatic dysfunction, which leads Recommended Reading to a build-up of interstitial fluid within the tissues. This manifests with swelling of the extremities, usually of the legs but may involve other regions or segments of the body such as the upper limbs, face, trunk or genital area. There is an increased risk of infection due to disturbances in immune cell trafficking within the segment of compromised lymph drainage.3 Lymphatic dysfunction within the thorax and abdomen, here referred to as systemic/internal involvement (but can be referred to as visceral or central involvement), may present with pleural or pericardial effusions or ascites, any of which may be chylous, as well as intestinal or pulmonary lymphangiectasia, protein losing enteropathy or chylous reflux.The International Society for the Study of Vascular Anomalies (ISSVA) updated their classification for vascular anomalies in 2018.4 The vascular malformations are subgrouped into ‘combined’, which include more than one type of vessel, ‘simple’ (only involving one vessel type), and those ‘associated with other anomalies’.Lymphoedema due to a presumed genetic developmental fault in the structure or function of lymph conducting pathways is called primary lymphoedema.5 Some developmental faults can lead to overt cialis cost structural defects of the lymph conducting pathways and are called lymphatic malformations.

Such malformations if interfering with lymph drainage cause lymphoedema (truncal malformations) but some lymphatic malformations remain as isolated anomalies with no connection to main lymph drainage pathways and do not cause lymphoedema (non-truncal malformations).6 A primary lymphatic anomaly is an umbrella term referring to all lymphatic abnormalities arising from a developmental fault.For a long time, the diagnosis of primary lymphoedema was based largely on the age of presentation of the swelling, congenital, pubertal and late onset, with limited differentiation between the phenotypes. The discovery of the first causal gene, vascular endothelial growth factor receptor 3 for Milroy disease, indicated that a molecular diagnosis was possible.7 The first St George’s classification algorithm of primary lymphoedema and other primary lymphatic disorders was an attempt to guide a clearer categorisation of phenotypes and enable the discovery of further causal genes.8 Age of onset remained a key criterion, but the sites affected and associated features, cialis cost for example, dysmorphology, distichiasis (aberrant eyelashes), varicose veins, vascular malformations and limb overgrowth were also considered, as was internal or systemic involvement, for example, fetal hydrops, intestinal lymphangiectasia, pleural and pericardial effusions and chylous reflux. A family history of lymphoedema with determination of the mode of inheritance was considered useful.More rigorous phenotyping facilitated the identification of subgroups of patients with the same broad category of primary lymphatic anomaly.

These cohorts were cialis cost then used for molecular studies to identify more causal genes. Once the genotype was known then crosschecking of the clinical characteristics, natural history and inheritance patterns was possible and an accurate phenotype defined. Investigations such as lymphoscintigraphy helped to refine the phenotype further and give insight into the mechanisms for the development of the lymphatic disorder cialis cost.

A first update of the classification was published in 2013.9The St George’s classification algorithm is intended to help clinicians categorise their patients and guide testing towards, where possible, a molecular diagnosis. This algorithm cialis cost is criteria matching, that is, using certain key findings for classification through a multistep process of history taking, examination findings, mutation testing, etc. The next step using the information gathered is to advise on natural history, prognosis and risk (including genetic counselling) and to guide management.

While a molecular diagnosis should provide the most specific and accurate diagnosis, it can be seen particularly with the postzygotic mosaic disorders that one genotype can be clinically very heterogenous so there will probably always be a place for good clinical phenotyping supported by investigation to guide management.Here, we present a second update of the St George’s classification algorithm to include newly discovered genes and to bring it in-line with the 2018 ISSVA classification cialis cost for vascular anomalies.4 The results of an audit, the purpose of which was to determine how well the algorithm was performing as a diagnostic aid to classify patients with primary lymphatic anomalies and guide molecular testing are also presented.MethodsSt George’s classification algorithm of primary lymphatic anomaliesThe St George’s classification algorithm was updated (figure 1) and then applied, retrospectively, to all patients presenting to the national multidisciplinary ‘Primary and Paediatric Lymphoedema’ Clinic held at St George’s Hospital over a 1-year period. Careful phenotyping was undertaken both on clinical grounds and after selective investigations, for example, lymphoscintigraphy. Where possible and appropriate, targeted genetic testing was performed (this was prior to the introduction of a lymphoedema gene panel in our unit) for some of the genes listed in table 1.St George’s classification algorithm for primary lymphatic cialis cost anomalies.

The five main groupings (colour coded) with their various clinical subtypes of disease. Primary lymphoedema is the major clinical feature in the green, pink and cialis cost purple sections. Text in red indicates the suggested genetic test and/or differential diagnosis for the subgroup, however, the indicated genes do not explain the cause of disease in all patients in each grouping.

For example, cialis cost only 70% of patients with Milroy disease are explained by mutations in FLT4/VEGFR3.33 FH, family history. +ve, positive. ˆ’ve, negative cialis cost.

(Image shared by St George’s Lymphovascular Research Group under the CC BY-SA 4.0 International licence on Wikimedia Commons)." data-icon-position data-hide-link-title="0">Figure 1 St George’s classification algorithm for primary lymphatic anomalies. The five main groupings (colour coded) with their various clinical cialis cost subtypes of disease. Primary lymphoedema is the major clinical feature in the green, pink and purple sections.

Text in red cialis cost indicates the suggested genetic test and/or differential diagnosis for the subgroup, however, the indicated genes do not explain the cause of disease in all patients in each grouping. For example, only 70% of patients with Milroy disease are explained by mutations in FLT4/VEGFR3.33 FH, family history. +ve, positive cialis cost.

ˆ’ve, negative. (Image shared by St George’s Lymphovascular Research Group under the CC BY-SA 4.0 International licence on Wikimedia Commons).View this table:Table 1 An overview of genetic disorders with primary lymphoedema as a frequent and dominant feature, categorised by inheritance and age of onsetWithin the St George’s classification algorithm (figure 1), there are five main categories of primary lymphatic anomalies. These are presented in the form of colour-coded sections with the individual cialis cost subtypes (including genotypes) within the categories.

For definitions of some of the terms used, see Glossary of Terms (see online supplementary section).Supplemental materialFirst, the yellow section includes the ‘vascular malformations associated with other anomalies’ and the ‘lymphatic malformations’ (as defined in the ‘Introduction’ section).Second, the patient is assessed for syndromes that have lymphoedema as a non-dominant feature (blue section), for example, the patient is dysmorphic with learning difficulties and possibly has other abnormalities.Then if not obviously syndromic, and the lymphatic problems are the dominant feature, further assessment and investigations for systemic/internal lymphatic dysfunction or central conducting anomalies (eg, chylothoraces, chylopericardial effusions, ascites or protein losing enteropathy) are undertaken (pink section). These include a careful medical history asking specifically about prenatal history (eg, hydrothoraces, fetal hydrops), chronic diarrhoea, abdominal bloating or discomfort with fatty foods, weight loss or faltering growth (in a cialis cost child) or shortness of breath on exertion. Blood investigations (including serum albumin, immunoglobulins, lymphocyte subsets, faecal levels of calprotectin or alpha-1-antitrysin), echocardiograms and chest radiographs are helpful if central lymphatic dysfunction is suspected.Where none of the above features is present, then the age of onset is used to determine the grouping.

The green section deals with congenital-onset primary lymphoedema (includes syndromes where lymphoedema is the dominant clinical problem, and which cialis cost is present at birth or develops within the first year of life but is not associated with systemic/internal lymphatic dysfunction). The purple section addresses late-onset primary lymphoedema (ie, lymphoedema that is the dominant clinical problem, and which develops after the first year of life but is not associated with systemic/internal lymphatic dysfunction). It was decided not to differentiate between pubertal onset (praecox) and later onset in life (tarda) when it was discovered that one genotype such as FOXC2 can cause both.It is important to note that the specific diagnosis may be cialis cost difficult in a neonate presenting with isolated congenital primary lymphoedema.

A baby born with lymphoedema may later present with developmental delay, systemic involvement, progressive segmental overgrowth or a vascular malformation, which could suggest a diagnosis in one of the other categories. It should also be emphasised cialis cost that each colour-coded section is not exclusive. Some somatic overgrowth anomalies may possess significant internal involvement.

Also, lymphoedema distichiasis syndrome is allocated to the purple late-onset lymphoedema section because the dominant feature is the late-onset lymphoedema not the associated features, which cialis cost make it a syndrome. The blue ‘syndromic’ section refers to conditions with a collection of features where lymphoedema is not the main characteristic. The algorithm is intended to guide a clinical diagnosis and target gene testing.Genetic methodologyFor cialis cost the purposes of the audit, targeted genetic testing of FOXC2, VEGFR3, CCBE1, SOX18, RASopathy genes and PIK3CA was performed by Sanger sequencing of DNA extracted from lymphocytes or skin fibroblasts in patients in whom a specific genetic diagnosis was suspected.

This was before the introduction of a lymphoedema gene panel. Some patients, who were either negative cialis cost for the targeted genes or did not fit the relevant phenotypes of those genes, were included in Whole Exome Sequencing (WES) cohorts after classification, which then led to the identification of new disease genes such as EPHB4, GATA2, PIEZO1, GJC2 and FAT4.Retrospective audit of the St George’s Clinic for 2016A 12-month retrospective audit for the year 2016 (1 January 2016–31 December 2016) was performed. The aim of the audit was to look at the proportion of patients in each category of the classification algorithm and to look at the success of making a molecular diagnosis through use of the algorithm.

The audit criteria required the patients to be seen in our specialist clinic, at any age, with a diagnosis of a primary lymphatic anomaly with data collected from medical records and laboratory results.ResultsResults of the retrospective auditOver a 12-month period cialis cost in 2016, 227 patients were seen (age range 2 weeks to 70 years), 25.6% (n=58/227) of which were new patients. Over one-third (38%) of patients seen in the clinic had a family history of primary lymphoedema.Few patients had received genetic testing prior to referral to the clinic. Targeted genetic cialis cost testing was completed in 63% (n=143) of the patients seen.

At that time, a lymphoedema gene panel was not available, patients were only tested if the clinician felt there was a reasonable chance of finding a molecular cause, that is, testing was targeted.Of those tested, the underlying genetic cause was identified in 41% (n=59/143). Overall, a molecular diagnosis was cialis cost made in 26% (59/227) of all the patients seen in 2016.Vascular malformations with associated anomalies and lymphatic malformations (yellow)This group presents with malformations in the structure and organisation of blood and lymphatic vessels with a patchy, segmental distribution. Lymphoedema may develop in combination with vascular malformations and segmental overgrowth (or occasionally, undergrowth) of tissues within the swollen limb, for example, muscle, skeletal or adipose tissues (figure 2A).

The combination of lymphatic and vascular malformations in this group reflects the mutual embryological origins of the two vascular systems.A graphic representation of the 227 audited patients seen in clinic in 2016 and their distribution cialis cost across the five categories from figure 1 (pie chart). (A–G) Images show features of each category. (A) Patients with postzygotic mutations often present with asymmetrical swelling and segmental overgrowth as this patient, who cialis cost is mosaic for a mutation in KRAS.

(B) Webbed neck in Noonan syndrome. (C) In rare cases, swellings can be widespread affecting all segments of the body such as in this child with biallelic CCBE1 mutations. (D) In milder forms, often just the dorsum of the foot is affected as in this baby with a cialis cost VEGFR3 mutation.

(E, F) Lower limb swelling and distichiasis (arrowheads in F) in a patient with a FOXC2 mutation. (G) Lymphoedema is a major cause of skin disease and affected patients suffer from severe cialis cost and recurrent episodes of cutaneous infection, especially HPV-associated warts as seen in patients with GATA2 mutations. GLD, generalised lymphatic dysplasia." data-icon-position data-hide-link-title="0">Figure 2 A graphic representation of the 227 audited patients seen in clinic in 2016 and their distribution across the five categories from figure 1 (pie chart).

(A–G) Images show features of each category cialis cost. (A) Patients with postzygotic mutations often present with asymmetrical swelling and segmental overgrowth as this patient, who is mosaic for a mutation in KRAS. (B) Webbed neck cialis cost in Noonan syndrome.

(C) In rare cases, swellings can be widespread affecting all segments of the body such as in this child with biallelic CCBE1 mutations. (D) In milder forms, often just the dorsum of the foot is cialis cost affected as in this baby with a VEGFR3 mutation. (E, F) Lower limb swelling and distichiasis (arrowheads in F) in a patient with a FOXC2 mutation.

(G) Lymphoedema is a major cause of skin disease and affected patients suffer from severe and recurrent episodes of cutaneous cialis cost infection, especially HPV-associated warts as seen in patients with GATA2 mutations. GLD, generalised lymphatic dysplasia.These conditions are usually due to postzygotic mutations, for example, PIK3CA-related overgrowth spectrum (PROS)). Exceptions to cialis cost this are capillary malformation-arteriovenous malformation (MIM 608354) such as Parkes-Weber syndrome, which may be caused by heterozygous, germline mutations in RASA1.10Of the 227 patients seen in 2016, 17% (n=39) had lymphoedema associated with vascular malformations and/or segmental overgrowth (or undergrowth) (figure 2, pie chart) in comparison with 15% in 2010.8 It has been shown that postzygotic, gain of function mutations in PIK3CA may be responsible for many of the mosaic segmental overgrowth spectrum disorders.11 Postzygotic mutations are rarely identified in blood samples and therefore require a skin biopsy of the affected region.

In the 2016 cohort, only 10 patients (26%) provided skin biopsies for genetic analysis, producing just one molecular diagnosis. More research cialis cost in this field is required to identify the genetic basis for some of the conditions in this category. However, since the last revision, we have gained a much better understanding of the classification of some of these postzygotic mosaic conditions, therefore a brief review of the latest developments in this area is given in the online supplementary section.Syndromic lymphoedema (blue)Syndromes associated with primary lymphatic anomalies are listed in table 2 and include chromosomal abnormalities, single gene disorders and imprinting disorders.

Patients attending the clinic with syndromic primary lymphoedema made cialis cost up 13% (n=29) (figure 2, pie chart), similar to the 15% reported by Connell et al.8 Nearly three-quarters (72%, n=21) of this cohort had a molecular or chromosomal diagnosis. The most frequently seen syndromes were Noonan syndrome (n=8) (figure 2B), Turner syndrome (n=4) and Phelan McDermid syndrome (n=3).View this table:Table 2 An overview of ‘Known Syndromes’ with primary lymphoedema as a non-dominant association as referred to in the St George’s classification algorithm (figure 1, blue section)Lymphoedema with prenatal or postnatal systemic involvement (pink)In some conditions, lymphoedema may be associated with internal (systemic or visceral) disturbances of the lymphatic system within thorax or abdomen, for example, fetal hydrops, intestinal lymphangiectasia (presenting as protein-losing enteropathy), pulmonary lymphangiectasia or with pericardial and/or pleural effusions (often chylous), or chylous reflux (often into the genitalia). Broadly, there are cialis cost two types of lymphoedema with systemic involvement.

(A) ‘widespread’ swelling affecting all segments of the body (figure 2C), such as that seen in generalised lymphatic dysplasia (GLD). Due to faulty development, the structural or functional abnormality of the lymphatic system is affecting the cialis cost whole body. One type is Hennekam-lymphangiectasia-lymphoedema syndrome12.

(B) ‘patchy’ cialis cost areas of swelling, for example, left arm and right leg, which have been named ‘multisegmental lymphatic dysplasia’ (MLD) (figure 1).Prenatally, these conditions may present with pleural effusions (hydrothoraces), or as non-immune fetal hydrops (the accumulation of fluid in at least two compartments of a fetus such as the abdominal cavity, pleura or subcutaneous oedema). Fifteen per cent of non-immune cases of hydrops are the result of lymphatic disorders, and approximately 20% are idiopathic, some of which may be due to, as yet, unidentified lymphatic abnormalities.13In our audit, this cohort accounted for 12% (n=27) of patients (figure 2, pie chart), slightly higher than the 8% reported in 2010.8 Molecular testing was carried out in 17 patients. Nine of those tested had GLD, and pathogenic variants were identified cialis cost in seven (78%).

Five had biallelic variants in the PIEZO1 gene and one each with biallelic variants in FAT4 and SOX18. Interestingly, two of the families described by Connell et al, cases 3 and 4, have subsequently been found to be caused by biallelic variants in the PIEZO1 gene.8 14None of the eight patients, who presented with ‘patchy’ distribution of lymphoedema (MLD), had an identifiable molecular diagnosis. It is suspected that these patients could have a postzygotic mosaic mutation or WILD syndrome.15Since the last revision of the St George’s classification algorithm was published,9 five cialis cost new causal genes associated with GLD and/or non-immune fetal hydrops have been identified.

ADAMTS3,16 EPHB4,17 FAT4,18 FBXL719 and PIEZO114 20 and are reviewed in the online supplementary section.Congenital onset lymphoedema (green)In this category, congenital onset is defined as lymphoedema that is present at birth or develops within the first year of life. Bilateral lower limb swelling is the most frequent presentation (figure 2D), but the swelling may be cialis cost unilateral and/or involve the arms, genitalia and/or face, depending on the underlying cause. There are a number of different genetic disorders presenting with congenital lymphoedema (table 1).

Milroy disease cialis cost (ORPHA79452. OMIM 153100) is the most common form, occurring as a result of pathogenic variants in FLT4/VEGFR3.21 22 The mutation may occur de novo, so a family history is not essential for this diagnosis. The lymphoedema is always confined to the lower limbs but cialis cost may be unilateral, and may (rarely) involve the genitalia.

Approximately 10% of mutation carriers do not have lymphoedema. Fetuses with Milroy disease may present antenatally with pedal oedema in the third trimester, and, in a few cases, with bilateral hydrothoraces, which resolve before birth.Pathogenic variants in VEGFC, the ligand for VEGFR3, have also been identified in association with congenital primary lymphoedema of Gordon (OMIM 615907), also affecting the lower limbs.23–26The congenital category represents 21% (n=47) of the patients seen in 2016 (figure 2, pie chart) compared with 24% in 2010.8 A pathogenic variant was identified in 19 of the 47 (40%) patients cialis cost genetically tested in this category. The majority (n=18) had pathogenic variants identified in FLT4/VEGFR3 and, in one patient, a pathogenic variant in the GJC2 gene.

A GJC2 mutation in a patient presenting with lymphoedema at birth is unusual but shows the variability of the phenotype.Many of the conditions listed under the other categories in the classification algorithm may initially present with congenital lymphoedema but systemic involvement, progressive overgrowth or vascular malformation may present later cialis cost and are so reclassified. Likewise, some syndromic forms may present with congenital lymphoedema before any other manifestations, making diagnosis difficult at times. Thus, the diagnosis of ‘isolated’ congenital primary lymphoedema may be difficult site here in a neonate cialis cost presenting with pedal oedema.

Therefore, a molecular diagnosis in the neonatal period is clinically very useful in the management of these patients.Late-onset lymphoedema (purple)‘Late-onset’ lymphoedema is defined as presenting after the first year of life. Swelling can range from being unilateral, bilateral or can involve all four limbs and can present from early childhood up to adulthood cialis cost (figures 1 and 2E). Some may present with unilateral swelling, but the contralateral limb may become involved later or show abnormalities on lymphoscintigram even when clinically uninvolved.

The phenotypes also range from mild to cialis cost severe. There are currently five genes known to be associated with late-onset lymphoedema. FOXC2 (figure cialis cost 2F),27 GJC2,28 29 GATA2 (figure 2G),30 HGF31 and CELSR132 (table 1).

For many patients the molecular cause remains elusive, particularly in those patients with Meige disease and late-onset (usually pubertal) unilateral lower limb lymphoedema.Late-onset primary lymphoedema accounted for 37% (n=85) in 2016 (figure 2, pie chart) comparable to the 36% reported in 2010.8 This category has a low number of molecular diagnoses (n=12. 14%) as there are currently no causative genes for Meige disease, which made up 36% (n=31) of patients in this category.DiscussionThis review presents an updated St George’s classification algorithm of primary lymphatic cialis cost anomalies and brings it in-line with the ISSVA classification for vascular anomalies. It cites eight new causative genes since the last publication and highlights the areas where the genetic basis is still not known.

This rapidly evolving field demonstrates that primary lymphoedema and vascular malformations are highly heterogenous.The audit reports cialis cost an overall successful molecular diagnosis in 26% of patients seen in the clinic, but 41% of those patients selected for molecular testing. This is a considerable improvement on the rate of a molecular diagnosis since the algorithm was first published in 2010. Only two cialis cost causal genes were known at that time.

We can conclude from the audit that the algorithm works well in targeting mutation testing. Furthermore, use of the algorithm has led to the discovery of a number of causal genes. While it could be argued that the introduction of the lymphoedema gene panel obviates any need for targeted gene tests, we believe that matching a phenotype to a likely gene reduces wasteful testing and helps enormously in the cialis cost interpretation of variants of unknown significance, which are becoming an increasing problem in the era of next-generation sequencing.Although providing a molecular diagnosis in one-quarter of all the patients with primary lymphoedema represents a considerable improvement from when the algorithm was last reviewed, the molecular diagnosis is still not identified in the majority of patients seen in the St George’s Clinic.

In the diagnostic setting, the introduction of next-generation sequencing with a targeted (virtual) ‘lymphoedema gene panel’ may improve the diagnostic rate and broaden the phenotypic spectrum of many of the known genetic disorders. Understanding of the natural history of the disorder will enable appropriate surveillance of, for example, leukaemia in Emberger syndrome cialis cost (GATA2), and allow investigations for known associated problems, for example, congenital heart disease in patients with lymphoedema distichiasis syndrome (FOXC2). Prenatal diagnosis for the more serious conditions also becomes possible.

Knowledge of causal genes, and mechanisms of pathophysiology, cialis cost provide an opportunity for new, improved treatments (personalised medicine) (eg, mammalian target of rapamycin inhibitors for progressive overgrowth disorders).In conclusion, the St George’s classification algorithm for primary lymphatic anomalies has been further refined. With this review, we have provided insight into the most recently discovered genotypes and how this algorithm can be used in the clinic to guide management of patients with primary lymphoedema.IntroductionTriphalangeal thumb (TPT) is a rare congenital hand anomaly in which the thumb has three phalanges instead of two. TPT is usually cialis cost inherited in an autosomal dominant trait and is therefore commonly seen in affected families.

In 1994, Heutink et al located the pathogenic locus of TPT at chromosome 7q36.1 Subsequently, Lettice et al determined that point mutations in the zone of polarising activity regulatory sequence (ZRS) causes TPT and preaxial polydactyly.2 The ZRS is a long-range regulatory element residing in intron 5 of LMBR1 and regulates Sonic Hedgehog (SHH) expression in the embryonic limb bud. Since the identification of the ZRS cialis cost region, 18 different point mutations in the ZRS have been reported in TPT families.3There is broad phenotypical variability among different point mutations in the ZRS. For example, variants on locations 323 and 739 in the ZRS cause mild presentations of isolated TPT.2 4 Alternatively, severe anomalies such as TPT accompanied with tibial hypoplasia have been observed in families with variants on position 404 and 406 in the ZRS.2 5–9 In mildly affected phenotypes, reduced penetrance is regularly observed.

In families who cialis cost are more severely affected however, no reports of reduced penetrance have been made.Identifying and reporting new variants in the ZRS is important for genotype-phenotype correlations in TPT families. Additionally, it will also help to further elucidate the exact molecular mechanism of the role of the ZRS in the regulation of SHH expression in the embryonic limb.We therefore report two families with variants in the ZRS. These variants were identified in Dutch families cialis cost with isolated TPT.

Additionally, unaffected family members shared these variants with affected family members. Although this observation cialis cost suggests that the genotype is not fully penetrant, minor anomalies within these presumed unaffected family members indicate subclinical expression of a TPT phenotype rather than reduced penetrance of the genotype. We define subclinical phenotypes as anomalies that are not recognised by affected family members since they do not cause functional constraints in daily life, but can be recognised during clinical workup by experienced physicians.MethodsClinical evaluationFamilies 1 and 2 were identified at the outpatient clinic for Congenital Hand and Upper Limb Anomalies at the Sophia Children’s Hospital in Rotterdam, The Netherlands.

The family members were clinically examined cialis cost and consulted by a clinical geneticist. In family 1, peripheral blood samples were collected from the index patient, the mother and the grandfather of the index patient (figure 1). No blood samples were obtained from cialis cost the brother of this patient as he was clinically unaffected and was below adult age.Overview of Dutch TPT family 1.

(A) Pedigree of the Dutch TPT family 1. The index patient is patient cialis cost III-2. (B) X-ray image of the hand of the index patient.

An additional deltaphalanx is present cialis cost in both thumbs. (C) X-ray image of the thumbs of patient III-2. Although there is cialis cost no triphalangism present, the thumbs are remarkably broad.

TPT, triphalangeal thumb." data-icon-position data-hide-link-title="0">Figure 1 Overview of Dutch TPT family 1. (A) Pedigree of the Dutch TPT family 1. The index patient is patient III-2 cialis cost.

(B) X-ray image of the hand of the index patient. An additional deltaphalanx is present in both cialis cost thumbs. (C) X-ray image of the thumbs of patient III-2.

Although there cialis cost is no triphalangism present, the thumbs are remarkably broad. TPT, triphalangeal thumb.In family 2, the index patient (III-2) visited the outpatient clinic for Congenital Hand and Upper Limb Anomalies at the Sophia Children’s Hospital in Rotterdam with his parents. The other family members were visited as part of a field study cialis cost.

Included family members were clinically evaluated by a clinical geneticist, photographs were obtained and peripheral blood samples were collected (Figure 2, online supplementary figure 1). No radiographs were obtained during the field study.Supplemental cialis cost materialOverview of Dutch TPT family 2. (A) Outtake of pedigree of the Dutch TPT family 2.

(B) Images of patient III-2 and his father (II-2), showing triphalangism of both thumbs with one additional ray on cialis cost the left hand. (C) Images of patients II-4 and I-1, showing no triphalangism but lack of thumb opposition and mild thenar hypoplasia. TPT, triphalangeal thumb." data-icon-position data-hide-link-title="0">Figure 2 Overview cialis cost of Dutch TPT family 2.

(A) Outtake of pedigree of the Dutch TPT family 2. (B) Images cialis cost of patient III-2 and his father (II-2), showing triphalangism of both thumbs with one additional ray on the left hand. (C) Images of patients II-4 and I-1, showing no triphalangism but lack of thumb opposition and mild thenar hypoplasia.

TPT, triphalangeal thumb.ZRS sequencingDNA cialis cost samples were isolated from peripheral blood. The fragments were amplified using standard PCR. An 834 bp fragment covering the ZRS (774 bp) was sequenced cialis cost in family members of both families (UCSC Genome Browser, hg19, chr7:156583766–156584600).

Sequencing of PCR products was executed using Big Dye Terminator 3.1. Fragments were loaded on an ABI 3130 Sequence analyser and genetic analysis was performed with SeqScape Software (V.3.0).ResultsClinical report​Family 1Family 1 (figure 1A) consists of a nuclear family containing two affected patients with cialis cost TPT. The index patient had a bilateral isolated TPT with an additional deltaphalanx (figure 1B).

No other cialis cost congenital hand or other anomalies were present. The mother of the index patient was born with a TPT accompanied with a rudimentary additional thumb on both hands, without any other hand or congenital anomaly (data not shown). The maternal grandfather of the cialis cost index patient did not have a TPT or preaxial polydactyly.

However, clinical examination of the hands revealed remarkable broadness of both thumbs and mild thenar hypoplasia. Although the X-ray image of the grandfather shows no duplication of the thumb or triphalangism, the broadness of the distal phalanges is striking (figure 1C).​Family 2Family 2 comprises a large seven-generation family (Figure 2A, online supplementary figure 1). The index patient (III-2) had bilateral TPT with preaxial polydactyly cialis cost on the left hand.

The father of the index patient (II-1) had bilateral TPT without preaxial polydactyly (figure 2B). All other cialis cost family members reported they were not affected. Although the thumbs of family members I-1 and II-2 did not show clear features of triphalangism, further examination revealed that both family members had mild thenar hypoplasia and were unable to oppose both thumbs (figure 2C).

No other congenital anomalies were present in family 2.Mutation analysisSequence analysis of the 774 bp ZRS, in intron 5 of LMBR1, revealed the presence of a heterozygous A to G transition in members of family 1 (g.156584405A>G, GRCh37/Hg19) cialis cost. Following the more commonly used nomenclature for loci of ZRS variants, introduced by Lettice et al,2 this variant can be defined as a 165A>G variant.2 This variant was present in the affected family members. Patient I-1 of cialis cost family one also carried a 165A>G variant in the ZRS, despite not having TPT on either hand.

This variant was not present in public databases dbSNP, Clinvar and HGMD. Additionally, this variant was not present cialis cost in locally available WGS data sets (GoNL, Wellderly, Public54).10–12In family 2, we identified a 295T>variant in the ZRS (g.156584535T>C, GRCh37/Hg19). Two family members who did not have TPT carried the 295T>C variant.

This variant has previously been reported in a British family with mild cases of TPT and reduced penetrance of the genotype.13 Additionally, transgenic enhancer assays cialis cost in mice showed that the 295T>C variant causes ectopic expression in the embryonic limb and therefore confirms the pathogenicity of this variant.DiscussionIn this brief report, we describe two TPT families with either a 165A>G or 295T>C variant in the ZRS. The aim of this paper was to show that these observations of reduced penetrance in TPT families are in retrospect caused by mild and subclinical limb phenotypes without the presence of triphalangism and therefore raise awareness for thorough clinical examination in members of TPT families who are presumed to be unaffected.Ever since the identification of ZRS by Lettice et al in 2003, 18 variants in ZRS have been published in the literature.2 4 6–9 13–20 These variants are generally fully penetrant and have been found in families with either TPT or TPT with preaxial polydactyly. Exceptions to the above are point mutations on positions 105, 404 and 406 in ZRS, which cause more severe phenotypes like tibial hypoplasia and polysyndactyly.2 5–9 21Although most variants in ZRS are considered fully penetrant, reduced penetrance has been reported in several TPT families with variants on positions 295, 334, 463 and 739 in cialis cost ZRS.13 14 16 17The first aim of this paper is to hypothesise that some of these observations might not be caused by reduced penetrance of the genotype, but by a subclinical expression of the phenotype.

We base our hypothesis on two arguments. First, family members who were initially presumed unaffected cialis cost do show minor anomalies or altered hand function when examined appropriately. In family 1 of this study, the grandfather did not have TPT but had evident broadness of the thumb.

In family 2, patients with initially normal thumbs lacked the ability of opposition, cialis cost which is caused by abnormal developmental patterning of the thumb. Although this observation is based on three patients from two families, we believe that these examples clearly illustrate our postulated hypothesis.Second, reports of non-penetrance are consistently associated with mild phenotypes in TPT families and not with severe TPT phenotypes, like tibial hypoplasia and polysyndactyly. This indicates that these observations only occur in TPT families where SHH expression is cialis cost only slightly disrupted.

In these families, the variability in the phenotypical spectrum is apparently broad enough that family members with variants in ZRS can present with subclinical phenotypes instead of TPT. However, it remains unclear why the disruption of SHH causes cialis cost TPT in one family member and a subclinical phenotype in another. One example of how intrafamilial variability can be explained is based on a reported family, where different degrees of somatic mosaicism were associated with various phenotypes in affected family members.22 As the regulatory function of ZRS on SHH is extremely delicate and affected by timing, location and level of activity, it is plausible that the slightest alteration of one of these factors can cause this interindividual phenotypical variation.The second aim of this paper is to underline the importance of two aspects when clinically examining and counselling patients with an inherited type of TPT.

First, it is important to clinically cialis cost investigate the presumed unaffected family members, as these patients might not encounter functional problems in their daily life and will report they are unaffected. However, a distinct broadness of the thumb, a double flexion fold in the thumb or a duplicated lunula might indicate a discrete inclination for duplication of the thumb or the presence of an additional phalanx. Additionally, functional limitations regarding thumb strength or lack of opposition should be evaluated cialis cost as well.

Second, presumed unaffected family members should only be informed that their future offspring have a population-wide probability of having TPT or polydactyly after genetic evaluation. For complete reassurance, genetic evaluation of ZRS is also indicated for unaffected family members of mildly affected patients to verify whether they share the same disease-causing variant with their affected family members..

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How to cite this where can you buy cialis article:Singh generic cialis 10mg online O P. Aftermath of celebrity suicide – Media coverage and role of psychiatrists. Indian J generic cialis 10mg online Psychiatry 2020;62:337-8Celebrity suicide is one of the highly publicized events in our country.

Indians got a glimpse of this following an unfortunate incident where a popular Hindi film actor died of suicide. As expected, generic cialis 10mg online the media went into a frenzy as newspapers, news channels, and social media were full of stories providing minute details of the suicidal act. Some even going as far as highlighting the color of the cloth used in the suicide as well as showing the lifeless body of the actor.

All kinds of personal details were dug up, and speculations and hypotheses became the order of the day in the next few days that followed. In the process, reputations of generic cialis 10mg online many people associated with the actor were besmirched and their private and personal details were freely and blatantly broadcast and discussed on electronic, print, and social media. We understand that media houses have their own need and duty to report and sensationalize news for increasing their visibility (aka TRP), but such reporting has huge impacts on the mental health of the vulnerable population.The impact of this was soon realized when many incidents of copycat suicide were reported from all over the country within a few days of the incident.

Psychiatrists suddenly generic cialis 10mg online started getting distress calls from their patients in despair with increased suicidal ideation. This has become a major area of concern for the psychiatry community.The Indian Psychiatric Society has been consistently trying to engage with media to promote ethical reporting of suicide. Section 24 (1) of Mental Health Care Act, 2017, forbids publication of photograph of mentally ill person without his consent.[1] The Press Council of India has adopted the guidelines of World Health Organization report generic cialis 10mg online on Preventing Suicide.

A resource for media professionals, which came out with an advisory to be followed by media in reporting cases of suicide. It includes points forbidding them from putting stories in prominent positions and unduly repeating them, explicitly describing the method used, providing details about the site/location, using sensational headlines, or using photographs and video footage of the incident.[2] Unfortunately, the advisory seems to have little effect in the aftermath of celebrity suicides. Channels were generic cialis 10mg online full of speculations about the person's mental condition and illness and also his relationships and finances.

Many fictional accounts of his symptoms and illness were touted, which is not only against the ethics but is also contrary to MHCA, 2017.[1]It went to the extent that the name of his psychiatrist was mentioned and quotes were attributed to him without taking any account from him. The Indian Psychiatric Society has written to the Press Council of India underlining this concern and asking for generic cialis 10mg online measures to ensure ethics in reporting suicide.While there is a need for engagement with media to make them aware of the grave impact of negative suicide reporting on the lives of many vulnerable persons, there is even a more urgent need for training of psychiatrists regarding the proper way of interaction with media. This has been amply brought out in the aftermath of this incident.

Many psychiatrists and mental generic cialis 10mg online health professionals were called by media houses to comment on the episode. Many psychiatrists were quoted, or “misquoted,” or “quoted out of context,” commenting on the life of a person whom they had never examined and had no “professional authority” to do so. There were even stories with byline of a psychiatrist where the content provided was not only unscientific but also way beyond the expertise of a psychiatrist.

These types of viewpoints perpetuate stigma, myths, and “misleading concepts” about psychiatry and are detrimental to the image of psychiatry in addition to doing harm and injustice to our generic cialis 10mg online patients. Hence, the need to formulate a guideline for interaction of psychiatrists with the media is imperative.In the infamous Goldwater episode, 12,356 psychiatrists were asked to cast opinion about the fitness of Barry Goldwater for presidential candidature. Out of 2417 respondents, 1189 psychiatrists reported him to be mentally unfit while none had actually examined him.[3] This led to the formulation of “The Goldwater Rule” by the American Psychiatric Association generic cialis 10mg online in 1973,[4] but we have witnessed the same phenomenon at the time of presidential candidature of Donald Trump.Psychiatrists should be encouraged to interact with media to provide scientific information about mental illnesses and reduction of stigma, but “statements to the media” can be a double-edged sword, and we should know about the rules of engagements and boundaries of interactions.

Methods and principles of interaction with media should form a part of our training curriculum. Many professional societies have guidelines and resource books for interacting with media, and psychiatrists should familiarize themselves with these generic cialis 10mg online documents. The Press Council guideline is likely to prompt reporters to seek psychiatrists for their expert opinion.

It is useful for them to have a template ready with suicide rates, emphasizing multicausality of suicide, role of mental disorders, as well as help available.[5]It is about time that the Indian Psychiatric Society formulated its own guidelines laying down the broad principles and boundaries governing the interaction of Indian psychiatrists with the media. Till then, it is desirable to be guided by the following broad principles:It should be assumed that no statement goes “off the record” as the media person is most likely recording the interview, and we should also record any such conversation from our endIt should be clarified in which capacity comments are being made – professional, personal, or as a representative of an organizationOne should not comment on any person generic cialis 10mg online whom he has not examinedPsychiatrists should take any such opportunity to educate the public about mental health issuesThe comments should be justified and limited by the boundaries of scientific knowledge available at the moment. References Correspondence Address:Dr.

O P generic cialis 10mg online SinghAA 304, Ashabari Apartments, O/31, Baishnabghata, Patuli Township, Kolkata - 700 094, West Bengal IndiaSource of Support. None, Conflict of Interest. NoneDOI.

10.4103/psychiatry.IndianJPsychiatry_816_20Abstract Electroconvulsive therapy (ECT) is an effective modality of treatment for a variety of psychiatric disorders. However, it has always been accused of being a coercive, unethical, and dangerous modality of treatment. The dangerousness of ECT has been mainly attributed to its claimed ability to cause brain damage.

This narrative review aims to provide an update of the evidence with regard to whether the practice of ECT is associated with damage to the brain. An accepted definition of brain damage remains elusive. There are also ethical and technical problems in designing studies that look at this question specifically.

Thus, even though there are newer technological tools and innovations, any review attempting to answer this question would have to take recourse to indirect methods. These include structural, functional, and metabolic neuroimaging. Body fluid biochemical marker studies.

And follow-up studies of cognitive impairment and incidence of dementia in people who have received ECT among others. The review of literature and present evidence suggests that ECT has a demonstrable impact on the structure and function of the brain. However, there is a lack of evidence at present to suggest that ECT causes brain damage.Keywords.

Adverse effect, brain damage, electroconvulsive therapyHow to cite this article:Jolly AJ, Singh SM. Does electroconvulsive therapy cause brain damage. An update.

Indian J Psychiatry 2020;62:339-53 Introduction Electroconvulsive therapy (ECT) as a modality of treatment for psychiatric disorders has existed at least since 1938.[1] ECT is an effective modality of treatment for various psychiatric disorders. However, from the very beginning, the practice of ECT has also faced resistance from various groups who claim that it is coercive and harmful.[2] While the ethical aspects of the practice of ECT have been dealt with elsewhere, the question of harmfulness or brain damage consequent upon the passage of electric current needs to be examined afresh in light of technological advances and new knowledge.[3]The question whether ECT causes brain damage was reviewed in a holistic fashion by Devanand et al. In the mid-1990s.[4],[5] The authors had attempted to answer this question by reviewing the effect of ECT on the brain in various areas – cognitive side effects, structural neuroimaging studies, neuropathologic studies of patients who had received ECT, autopsy studies of epileptic patients, and finally animal ECS studies.

The authors had concluded that ECT does not produce brain damage.This narrative review aims to update the evidence with regard to whether ECT causes brain damage by reviewing relevant literature from 1994 to the present time. Framing the Question The Oxford Dictionary defines damage as physical harm that impairs the value, usefulness, or normal function of something.[6] Among medical dictionaries, the Peter Collins Dictionary defines damage as harm done to things (noun) or to harm something (verb).[7] Brain damage is defined by the British Medical Association Medical Dictionary as degeneration or death of nerve cells and tracts within the brain that may be localized to a particular area of the brain or diffuse.[8] Going by such a definition, brain damage in the context of ECT should refer to death or degeneration of brain tissue, which results in the impairment of functioning of the brain. The importance of precisely defining brain damage shall become evident subsequently in this review.There are now many more tools available to investigate the structure and function of brain in health and illness.

However, there are obvious ethical issues in designing human studies that are designed to answer this specific question. Therefore, one must necessarily take recourse to indirect evidences available through studies that have been designed to answer other research questions. These studies have employed the following methods:Structural neuroimaging studiesFunctional neuroimaging studiesMetabolic neuroimaging studiesBody fluid biochemical marker studiesCognitive impairment studies.While the early studies tended to focus more on establishing the safety of ECT and finding out whether ECT causes gross microscopic brain damage, the later studies especially since the advent of advanced neuroimaging techniques have been focusing more on a mechanistic understanding of ECT.

Hence, the primary objective of the later neuroimaging studies has been to look for structural and functional brain changes which might explain how ECT acts rather than evidence of gross structural damage per se. However, put together, all these studies would enable us to answer our titular question to some satisfaction. [Table 1] and [Table 2] provide an overview of the evidence base in this area.

Structural and Functional Neuroimaging Studies Devanand et al. Reviewed 16 structural neuroimaging studies on the effect of ECT on the brain.[4] Of these, two were pneumoencephalography studies, nine were computed tomography (CT) scan studies, and five were magnetic resonance imaging (MRI) studies. However, most of these studies were retrospective in design, with neuroimaging being done in patients who had received ECT in the past.

In the absence of baseline neuroimaging, it would be very difficult to attribute any structural brain changes to ECT. In addition, pneumoencephalography, CT scan, and even early 0.3 T MRI provided images with much lower spatial resolution than what is available today. The authors concluded that there was no evidence to show that ECT caused any structural damage to the brain.[4] Since then, at least twenty more MRI-based structural neuroimaging studies have studied the effect of ECT on the brain.

The earliest MRI studies in the early 1990s focused on detecting structural damage following ECT. All of these studies were prospective in design, with the first MRI scan done at baseline and a second MRI scan performed post ECT.[9],[11],[12],[13],[41] While most of the studies imaged the patient once around 24 h after receiving ECT, some studies performed multiple post ECT neuroimaging in the first 24 h after ECT to better capture the acute changes. A single study by Coffey et al.

Followed up the patients for a duration of 6 months and repeated neuroimaging again at 6 months in order to capture any long-term changes following ECT.[10]The most important conclusion which emerged from this early series of studies was that there was no evidence of cortical atrophy, change in ventricle size, or increase in white matter hyperintensities.[4] The next major conclusion was that there appeared to be an increase in the T1 and T2 relaxation time immediately following ECT, which returned to normal within 24 h. This supported the theory that immediately following ECT, there appears to be a temporary breakdown of the blood–brain barrier, leading to water influx into the brain tissue.[11] The last significant observation by Coffey et al. In 1991 was that there was no significant temporal changes in the total volumes of the frontal lobes, temporal lobes, or amygdala–hippocampal complex.[10] This was, however, something which would later be refuted by high-resolution MRI studies.

Nonetheless, one inescapable conclusion of these early studies was that there was no evidence of any gross structural brain changes following administration of ECT. Much later in 2007, Szabo et al. Used diffusion-weighted MRI to image patients in the immediate post ECT period and failed to observe any obvious brain tissue changes following ECT.[17]The next major breakthrough came in 2010 when Nordanskog et al.

Demonstrated that there was a significant increase in the volume of the hippocampus bilaterally following a course of ECT in a cohort of patients with depressive illness.[18] This contradicted the earlier observations by Coffey et al. That there was no volume increase in any part of the brain following ECT.[10] This was quite an exciting finding and was followed by several similar studies. However, the perspective of these studies was quite different from the early studies.

In contrast to the early studies looking for the evidence of ECT-related brain damage, the newer studies were focused more on elucidating the mechanism of action of ECT. Further on in 2014, Nordanskog et al. In a follow-up study showed that though there was a significant increase in the volume of the hippocampus 1 week after a course of ECT, the hippocampal volume returned to the baseline after 6 months.[19] Two other studies in 2013 showed that in addition to the hippocampus, the amygdala also showed significant volume increase following ECT.[20],[21] A series of structural neuroimaging studies after that have expanded on these findings and as of now, gray matter volume increase following ECT has been demonstrated in the hippocampus, amygdala, anterior temporal pole, subgenual cortex,[21] right caudate nucleus, and the whole of the medial temporal lobe (MTL) consisting of the hippocampus, amygdala, insula, and the posterosuperior temporal cortex,[24] para hippocampi, right subgenual anterior cingulate gyrus, and right anterior cingulate gyrus,[25] left cerebellar area VIIa crus I,[29] putamen, caudate nucleus, and nucleus acumbens [31] and clusters of increased cortical thickness involving the temporal pole, middle and superior temporal cortex, insula, and inferior temporal cortex.[27] However, the most consistently reported and replicated finding has been the bilateral increase in the volume of the hippocampus and amygdala.

In light of these findings, it has been tentatively suggested that ECT acts by inducing neuronal regeneration in the hippocampus – amygdala complex.[42],[43] However, there are certain inconsistencies to this hypothesis. Till date, only one study – Nordanskog et al., 2014 – has followed study patients for a long term – 6 months in their case. And significantly, the authors found out that after increasing immediately following ECT, the hippocampal volume returns back to baseline by 6 months.[19] This, however, was not associated with the relapse of depressive symptoms.

Another area of significant confusion has been the correlation of hippocampal volume increase with improvement of depressive symptoms. Though almost all studies demonstrate a significant increase in hippocampal volume following ECT, a majority of studies failed to demonstrate a correlation between symptom improvement and hippocampal volume increase.[19],[20],[22],[24],[28] However, a significant minority of volumetric studies have demonstrated correlation between increase in hippocampal and/or amygdala volume and improvement of symptoms.[21],[25],[30]Another set of studies have used diffusion tensor imaging, functional MRI (fMRI), anatomical connectome, and structural network analysis to study the effect of ECT on the brain. The first of these studies by Abbott et al.

In 2014 demonstrated that on fMRI, the connectivity between right and left hippocampus was significantly reduced in patients with severe depression. It was also shown that the connectivity was normalized following ECT, and symptom improvement was correlated with an increase in connectivity.[22] In a first of its kind DTI study, Lyden et al. In 2014 demonstrated that fractional anisotropy which is a measure of white matter tract or fiber density is increased post ECT in patients with severe depression in the anterior cingulum, forceps minor, and the dorsal aspect of the left superior longitudinal fasciculus.

The authors suggested that ECT acts to normalize major depressive disorder-related abnormalities in the structural connectivity of the dorsal fronto-limbic pathways.[23] Another DTI study in 2015 constructed large-scale anatomical networks of the human brain – connectomes, based on white matter fiber tractography. The authors found significant reorganization in the anatomical connections involving the limbic structure, temporal lobe, and frontal lobe. It was also found that connection changes between amygdala and para hippocampus correlated with reduction in depressive symptoms.[26] In 2016, Wolf et al.

Used a source-based morphometry approach to study the structural networks in patients with depression and schizophrenia and the effect of ECT on the same. It was found that the medial prefrontal cortex/anterior cingulate cortex (ACC/MPFC) network, MTL network, bilateral thalamus, and left cerebellar regions/precuneus exhibited significant difference between healthy controls and the patient population. It was also demonstrated that administration of ECT leads to significant increase in the network strength of the ACC/MPFC network and the MTL network though the increase in network strength and symptom amelioration were not correlated.[32]Building on these studies, a recently published meta-analysis has attempted a quantitative synthesis of brain volume changes – focusing on hippocampal volume increase following ECT in patients with major depressive disorder and bipolar disorder.

The authors initially selected 32 original articles from which six articles met the criteria for quantitative synthesis. The results showed significant increase in the volume of the right and left hippocampus following ECT. For the rest of the brain regions, the heterogeneity in protocols and imaging techniques did not permit a quantitative analysis, and the authors have resorted to a narrative review similar to the present one with similar conclusions.[44] Focusing exclusively on hippocampal volume change in ECT, Oltedal et al.

In 2018 conducted a mega-analysis of 281 patients with major depressive disorder treated with ECT enrolled at ten different global sites of the Global ECT-MRI Research Collaboration.[45] Similar to previous studies, there was a significant increase in hippocampal volume bilaterally with a dose–response relationship with the number of ECTs administered. Furthermore, bilateral (B/L) ECT was associated with an equal increase in volume in both right and left hippocampus, whereas right unilateral ECT was associated with greater volume increase in the right hippocampus. Finally, contrary to expectation, clinical improvement was found to be negatively correlated with hippocampal volume.Thus, a review of the current evidence amply demonstrates that from looking for ECT-related brain damage – and finding none, we have now moved ahead to looking for a mechanistic understanding of the effect of ECT.

In this regard, it has been found that ECT does induce structural changes in the brain – a fact which has been seized upon by some to claim that ECT causes brain damage.[46] Such statements should, however, be weighed against the definition of damage as understood by the scientific medical community and patient population. Neuroanatomical changes associated with effective ECT can be better described as ECT-induced brain neuroplasticity or ECT-induced brain neuromodulation rather than ECT-induced brain damage. Metabolic Neuroimaging Studies.

Magnetic Resonance Spectroscopic Imaging Magnetic resonance spectroscopic imaging (MRSI) uses a phase-encoding procedure to map the spatial distribution of magnetic resonance (MR) signals of different molecules. The crucial difference, however, is that while MRI maps the MR signals of water molecules, MRSI maps the MR signals generated by different metabolites – such as N-acetyl aspartate (NAA) and choline-containing compounds. However, the concentration of these metabolites is at least 10,000 times lower than water molecules and hence the signal strength generated would also be correspondingly lower.

However, MRSI offers us the unique advantage of studying in vivo the change in the concentration of brain metabolites, which has been of great significance in fields such as psychiatry, neurology, and basic neuroscience research.[47]MRSI studies on ECT in patients with depression have focused largely on four metabolites in the human brain – NAA, choline-containing compounds (Cho) which include majorly cell membrane compounds such as glycerophosphocholine, phosphocholine and a miniscule contribution from acetylcholine, creatinine (Cr) and glutamine and glutamate together (Glx). NAA is located exclusively in the neurons, and is suggested to be a marker of neuronal viability and functionality.[48] Choline-containing compounds (Cho) mainly include the membrane compounds, and an increase in Cho would be suggestive of increased membrane turnover. Cr serves as a marker of cellular energy metabolism, and its levels are usually expected to remain stable.

The regions which have been most widely studied in MRSI studies include the bilateral hippocampus and amygdala, dorsolateral prefrontal cortex (DLPFC), and ACC.Till date, five MRSI studies have measured NAA concentration in the hippocampus before and after ECT. Of these, three studies showed that there is no significant change in the NAA concentration in the hippocampus following ECT.[33],[38],[49] On the other hand, two recent studies have demonstrated a statistically significant reduction in NAA concentration in the hippocampus following ECT.[39],[40] The implications of these results are of significant interest to us in answering our titular question. A normal level of NAA following ECT could signify that there is no significant neuronal death or damage following ECT, while a reduction would signal the opposite.

However, a direct comparison between these studies is complicated chiefly due to the different ECT protocols, which has been used in these studies. It must, however, be acknowledged that the three older studies used 1.5 T MRI, whereas the two newer studies used a higher 3 T MRI which offers betters signal-to-noise ratio and hence lesser risk of errors in the measurement of metabolite concentrations. The authors of a study by Njau et al.[39] argue that a change in NAA levels might reflect reversible changes in neural metabolism rather than a permanent change in the number or density of neurons and also that reduced NAA might point to a change in the ratio of mature to immature neurons, which, in fact, might reflect enhanced adult neurogenesis.

Thus, the authors warn that to conclude whether a reduction in NAA concentration is beneficial or harmful would take a simultaneous measurement of cognitive functioning, which was lacking in their study. In 2017, Cano et al. Also demonstrated a significant reduction in NAA/Cr ratio in the hippocampus post ECT.

More significantly, the authors also showed a significant increase in Glx levels in the hippocampus following ECT, which was also associated with an increase in hippocampal volume.[40] To explain these three findings, the authors proposed that ECT produces a neuroinflammatory response in the hippocampus – likely mediated by Glx, which has been known to cause inflammation at higher concentrations, thereby accounting for the increase in hippocampal volume with a reduction in NAA concentration. The cause for the volume increase remains unclear – with the authors speculating that it might be due to neuronal swelling or due to angiogenesis. However, the same study and multiple other past studies [21],[25],[30] have demonstrated that hippocampal volume increase was correlated with clinical improvement following ECT.

Thus, we are led to the hypothesis that the same mechanism which drives clinical improvement with ECT is also responsible for the cognitive impairment following ECT. Whether this is a purely neuroinflammatory response or a neuroplastic response or a neuroinflammatory response leading to some form of neuroplasticity is a critical question, which remains to be answered.[40]Studies which have analyzed NAA concentration change in other brain areas have also produced conflicting results. The ACC is another area which has been studied in some detail utilizing the MRSI technique.

In 2003, Pfleiderer et al. Demonstrated that there was no significant change in the NAA and Cho levels in the ACC following ECT. This would seem to suggest that there was no neurogenesis or membrane turnover in the ACC post ECT.[36] However, this finding was contested by Merkl et al.

In 2011, who demonstrated that NAA levels were significantly reduced in the left ACC in patients with depression and that these levels were significantly elevated following ECT.[37] This again is contested by Njau et al. Who showed that NAA levels are significantly reduced following ECT in the left dorsal ACC.[39] A direct comparison of these three studies is complicated by the different ECT and imaging parameters used and hence, no firm conclusion can be made on this point at this stage. In addition to this, one study had demonstrated increased NAA levels in the amygdala following administration of ECT,[34] with a trend level increase in Cho levels, which again is suggestive of neurogenesis and/or neuroplasticity.

A review of studies on the DLPFC reveals a similarly confusing picture with one study, each showing no change, reduction, and elevation of concentration of NAA following ECT.[35],[37],[39] Here, again, a direct comparison of the three studies is made difficult by the heterogeneous imaging and ECT protocols followed by them.A total of five studies have analyzed the concentration of choline-containing compounds (Cho) in patients undergoing ECT. Conceptually, an increase in Cho signals is indicative of increased membrane turnover, which is postulated to be associated with synaptogenesis, neurogenesis, and maturation of neurons.[31] Of these, two studies measured Cho concentration in the B/L hippocampus, with contrasting results. Ende et al.

In 2000 demonstrated a significant elevation in Cho levels in B/L hippocampus after ECT, while Jorgensen et al. In 2015 failed to replicate the same finding.[33],[38] Cho levels have also been studied in the amygdala, ACC, and the DLPFC. However, none of these studies showed a significant increase or decrease in Cho levels before and after ECT in the respective brain regions studied.

In addition, no significant difference was seen in the pre-ECT Cho levels of patients compared to healthy controls.[34],[36],[37]In review, we must admit that MRSI studies are still at a preliminary stage with significant heterogeneity in ECT protocols, patient population, and regions of the brain studied. At this stage, it is difficult to draw any firm conclusions except to acknowledge the fact that the more recent studies – Njau et al., 2017, Cano, 2017, and Jorgensen et al., 2015 – have shown decrease in NAA concentration and no increase in Cho levels [38],[39],[40] – as opposed to the earlier studies by Ende et al.[33] The view offered by the more recent studies is one of a neuroinflammatory models of action of ECT, probably driving neuroplasticity in the hippocampus. This would offer a mechanistic understanding of both clinical response and the phenomenon of cognitive impairment associated with ECT.

However, this conclusion is based on conjecture, and more work needs to be done in this area. Body Fluid Biochemical Marker Studies Another line of evidence for analyzing the effect of ECT on the human brain is the study of concentration of neurotrophins in the plasma or serum. Neurotrophins are small protein molecules which mediate neuronal survival and development.

The most prominent among these is brain-derived neurotrophic factor (BDNF) which plays an important role in neuronal survival, plasticity, and migration.[50] A neurotrophic theory of mood disorders was suggested which hypothesized that depressive disorders are associated with a decreased expression of BDNF in the limbic structures, resulting in the atrophy of these structures.[51] It was also postulated that antidepressant treatment has a neurotrophic effect which reverses the neuronal cell loss, thereby producing a therapeutic effect. It has been well established that BDNF is decreased in mood disorders.[52] It has also been shown that clinical improvement of depression is associated with increase in BDNF levels.[53] Thus, serum BDNF levels have been tentatively proposed as a biomarker for treatment response in depression. Recent meta-analytic evidence has shown that ECT is associated with significant increase in serum BDNF levels in patients with major depressive disorder.[54] Considering that BDNF is a potent stimulator of neurogenesis, the elevation of serum BDNF levels following ECT lends further credence to the theory that ECT leads to neurogenesis in the hippocampus and other limbic structures, which, in turn, mediates the therapeutic action of ECT.

Cognitive Impairment Studies Cognitive impairment has always been the single-most important side effect associated with ECT.[55] Concerns regarding long-term cognitive impairment surfaced soon after the introduction of ECT and since then has grown to become one of the most controversial aspects of ECT.[56] Anti-ECT groups have frequently pointed out to cognitive impairment following ECT as evidence of ECT causing brain damage.[56] A meta-analysis by Semkovska and McLoughlin in 2010 is one of the most detailed studies which had attempted to settle this long-standing debate.[57] The authors reviewed 84 studies (2981 participants), which had used a combined total of 22 standardized neuropsychological tests assessing various cognitive functions before and after ECT in patients diagnosed with major depressive disorder. The different cognitive domains reviewed included processing speed, attention/working memory, verbal episodic memory, visual episodic memory, spatial problem-solving, executive functioning, and intellectual ability. The authors concluded that administration of ECT for depression is associated with significant cognitive impairment in the first few days after ECT administration.

However, it was also seen that impairment in cognitive functioning resolved within a span of 2 weeks and thereafter, a majority of cognitive domains even showed mild improvement compared to the baseline performance. It was also demonstrated that not a single cognitive domain showed persistence of impairment beyond 15 days after ECT.Memory impairment following ECT can be analyzed broadly under two conceptual schemes – one that classifies memory impairment as objective memory impairment and subjective memory impairment and the other that classifies it as impairment in anterograde memory versus impairment in retrograde memory. Objective memory can be roughly defined as the ability to retrieve stored information and can be measured by various standardized neuropsychological tests.

Subjective memory or meta-memory, on the other hand, refers to the ability to make judgments about one's ability to retrieve stored information.[58] As described previously, it has been conclusively demonstrated that anterograde memory impairment does not persist beyond 2 weeks after ECT.[57] However, one of the major limitations of this meta-analysis was the lack of evidence on retrograde amnesia following ECT. This is particularly unfortunate considering that it is memory impairment – particularly retrograde amnesia which has received the most attention.[59] In addition, reports of catastrophic retrograde amnesia have been repeatedly held up as sensational evidence of the lasting brain damage produced by ECT.[59] Admittedly, studies on retrograde amnesia are fewer and less conclusive than on anterograde amnesia.[60],[61] At present, the results are conflicting, with some studies finding some impairment in retrograde memory – particularly autobiographical retrograde memory up to 6 months after ECT.[62],[63],[64],[65] However, more recent studies have failed to support this finding.[66],[67] While they do demonstrate an impairment in retrograde memory immediately after ECT, it was seen that this deficit returned to pre-ECT levels within a span of 1–2 months and improved beyond baseline performance at 6 months post ECT.[66] Adding to the confusion are numerous factors which confound the assessment of retrograde amnesia. It has been shown that depressive symptoms can produce significant impairment of retrograde memory.[68],[69] It has also been demonstrated that sine-wave ECT produces significantly more impairment of retrograde memory as compared to brief-pulse ECT.[70] However, from the 1990s onward, sine-wave ECT has been completely replaced by brief-pulse ECT, and it is unclear as to the implications of cognitive impairment from the sine-wave era in contemporary ECT practice.Another area of concern are reports of subjective memory impairment following ECT.

One of the pioneers of research into subjective memory impairment were Squire and Chace who published a series of studies in the 1970s demonstrating the adverse effect of bilateral ECT on subjective assessment of memory.[62],[63],[64],[65] However, most of the studies conducted post 1980 – from when sine-wave ECT was replaced by brief-pulse ECT report a general improvement in subjective memory assessments following ECT.[71] In addition, most of the recent studies have failed to find a significant association between measures of subjective and objective memory.[63],[66],[70],[72],[73],[74] It has also been shown that subjective memory impairment is strongly associated with the severity of depressive symptoms.[75] In light of these facts, the validity and value of measures of subjective memory impairment as a marker of cognitive impairment and brain damage following ECT have been questioned. However, concerns regarding subjective memory impairment and catastrophic retrograde amnesia continue to persist, with significant dissonance between the findings of different research groups and patient self-reports in various media.[57]Some studies reported the possibility of ECT being associated with the development of subsequent dementia.[76],[77] However, a recent large, well-controlled prospective Danish study found that the use of ECT was not associated with elevated incidence of dementia.[78] Conclusion Our titular question is whether ECT leads to brain damage, where damage indicates destruction or degeneration of nerves or nerve tracts in the brain, which leads to loss of function. This issue was last addressed by Devanand et al.

In 1994 since which time our understanding of ECT has grown substantially, helped particularly by the advent of modern-day neuroimaging techniques which we have reviewed in detail. And, what these studies reveal is rather than damaging the brain, ECT has a neuromodulatory effect on the brain. The various lines of evidence – structural neuroimaging studies, functional neuroimaging studies, neurochemical and metabolic studies, and serum BDNF studies all point toward this.

These neuromodulatory changes have been localized to the hippocampus, amygdala, and certain other parts of the limbic system. How exactly these changes mediate the improvement of depressive symptoms is a question that remains unanswered. However, there is little by way of evidence from neuroimaging studies which indicates that ECT causes destruction or degeneration of neurons.

Though cognitive impairment studies do show that there is objective impairment of certain functions – particularly memory immediately after ECT, these impairments are transient with full recovery within a span of 2 weeks. Perhaps, the single-most important unaddressed concern is retrograde amnesia, which has been shown to persist for up to 2 months post ECT. In this regard, the recent neurometabolic studies have offered a tentative mechanism of action of ECT, producing a transient inflammation in the limbic cortex, which, in turn, drives neurogenesis, thereby exerting a neuromodulatory effect.

This hypothesis would explain both the cognitive adverse effects of ECT – due to the transient inflammation – and the long-term improvement in mood – neurogenesis in the hippocampus. Although unproven at present, such a hypothesis would imply that cognitive impairment is tied in with the mechanism of action of ECT and not an indicator of damage to the brain produced by ECT.The review of literature suggests that ECT does cause at least structural and functional changes in the brain, and these are in all probability related to the effects of the ECT. However, these cannot be construed as brain damage as is usually understood.

Due to the relative scarcity of data that directly examines the question of whether ECT causes brain damage, it is not possible to conclusively answer this question. However, in light of enduring ECT survivor accounts, there is a need to design studies that specifically answer this question.Financial support and sponsorshipNil.Conflicts of interestThere are no conflicts of interest. References 1.Payne NA, Prudic J.

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54.Rocha RB, Dondossola ER, Grande AJ, Colonetti T, Ceretta LB, Passos IC, et al. Increased BDNF levels after electroconvulsive therapy in patients with major depressive disorder. A meta-analysis study.

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Effects of ECT and depression on various aspects of memory. Br J Psychiatry 1983;142:610-7. 74.Ng C, Schweitzer I, Alexopoulos P, Celi E, Wong L, Tuckwell V, et al.

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Correspondence Address:Dr. Shubh Mohan SinghDepartment of Psychiatry, Postgraduate Institute of Medical Education and Research, Chandigarh IndiaSource of Support. None, Conflict of Interest.

NoneDOI. 10.4103/psychiatry.IndianJPsychiatry_239_19 Tables [Table 1], [Table 2].

How to cite cialis cost this article:Singh O P. Aftermath of celebrity suicide – Media coverage and role of psychiatrists. Indian J Psychiatry 2020;62:337-8Celebrity suicide is one of the highly publicized events in our cialis cost country. Indians got a glimpse of this following an unfortunate incident where a popular Hindi film actor died of suicide.

As expected, the media went into a frenzy as newspapers, news channels, and social cialis cost media were full of stories providing minute details of the suicidal act. Some even going as far as highlighting the color of the cloth used in the suicide as well as showing the lifeless body of the actor. All kinds of personal details were dug up, and speculations and hypotheses became the order of the day in the next few days that followed. In the process, reputations of many people associated with the actor were besmirched and cialis cost their private and personal details were freely and blatantly broadcast and discussed on electronic, print, and social media.

We understand that media houses have their own need and duty to report and sensationalize news for increasing their visibility (aka TRP), but such reporting has huge impacts on the mental health of the vulnerable population.The impact of this was soon realized when many incidents of copycat suicide were reported from all over the country within a few days of the incident. Psychiatrists suddenly started getting distress calls from their patients cialis cost in despair with increased suicidal ideation. This has become a major area of concern for the psychiatry community.The Indian Psychiatric Society has been consistently trying to engage with media to promote ethical reporting of suicide. Section 24 (1) of Mental Health Care Act, 2017, forbids publication of photograph of mentally ill person without his consent.[1] The Press Council of India has adopted the guidelines of World cialis cost Health Organization report on Preventing Suicide.

A resource for media professionals, which came out with an advisory to be followed by media in reporting cases of suicide. It includes points forbidding them from putting stories in prominent positions and unduly repeating them, explicitly describing the method used, providing details about the site/location, using sensational headlines, or using photographs and video footage of the incident.[2] Unfortunately, the advisory seems to have little effect in the aftermath of celebrity suicides. Channels were full of speculations about the person's mental condition and cialis cost illness and also his relationships and finances. Many fictional accounts of his symptoms and illness were touted, which is not only against the ethics but is also contrary to MHCA, 2017.[1]It went to the extent that the name of his psychiatrist was mentioned and quotes were attributed to him without taking any account from him.

The Indian cialis cost Psychiatric Society has written to the Press Council of India underlining this concern and asking for measures to ensure ethics in reporting suicide.While there is a need for engagement with media to make them aware of the grave impact of negative suicide reporting on the lives of many vulnerable persons, there is even a more urgent need for training of psychiatrists regarding the proper way of interaction with media. This has been amply brought out in the aftermath of this incident. Many psychiatrists and mental health professionals were called cialis cost by media houses to comment on the episode. Many psychiatrists were quoted, or “misquoted,” or “quoted out of context,” commenting on the life of a person whom they had never examined and had no “professional authority” to do so.

There were even stories with byline of a psychiatrist where the content provided was not only unscientific but also way beyond the expertise of a psychiatrist. These types of viewpoints perpetuate stigma, myths, and “misleading concepts” about psychiatry and are detrimental to the image of psychiatry in addition to doing harm and injustice to our cialis cost patients. Hence, the need to formulate a guideline for interaction of psychiatrists with the media is imperative.In the infamous Goldwater episode, 12,356 psychiatrists were asked to cast opinion about the fitness of Barry Goldwater for presidential candidature. Out of 2417 respondents, 1189 psychiatrists reported him to be mentally unfit cialis cost while none had actually examined him.[3] This led to the formulation of “The Goldwater Rule” by the American Psychiatric Association in 1973,[4] but we have witnessed the same phenomenon at the time of presidential candidature of Donald Trump.Psychiatrists should be encouraged to interact with media to provide scientific information about mental illnesses and reduction of stigma, but “statements to the media” can be a double-edged sword, and we should know about the rules of engagements and boundaries of interactions.

Methods and principles of interaction with media should form a part of our training curriculum. Many professional societies have guidelines and resource books for interacting with media, and psychiatrists cialis cost should familiarize themselves with these documents. The Press Council guideline is likely to prompt reporters to seek psychiatrists for their expert opinion. It is useful for them to have a template ready with suicide rates, emphasizing multicausality of suicide, role of mental disorders, as well as help available.[5]It is about time that the Indian Psychiatric Society formulated its own guidelines laying down the broad principles and boundaries governing the interaction of Indian psychiatrists with the media.

Till then, it is desirable to be guided by the following broad principles:It should be assumed that no statement goes “off the record” as the media person is most likely recording the interview, cialis cost and we should also record any such conversation from our endIt should be clarified in which capacity comments are being made – professional, personal, or as a representative of an organizationOne should not comment on any person whom he has not examinedPsychiatrists should take any such opportunity to educate the public about mental health issuesThe comments should be justified and limited by the boundaries of scientific knowledge available at the moment. References Correspondence Address:Dr. O P SinghAA 304, Ashabari Apartments, O/31, Baishnabghata, Patuli Township, Kolkata - 700 094, cialis cost West Bengal IndiaSource of Support. None, Conflict of Interest.

NoneDOI. 10.4103/psychiatry.IndianJPsychiatry_816_20Abstract Electroconvulsive therapy (ECT) is an effective modality of treatment for a variety of psychiatric disorders. However, it has always been accused of being a coercive, unethical, and dangerous modality of treatment. The dangerousness of ECT has been mainly attributed to its claimed ability to cause brain damage.

This narrative review aims to provide an update of the evidence with regard to whether the practice of ECT is associated with damage to the brain. An accepted definition of brain damage remains elusive. There are also ethical and technical problems in designing studies that look at this question specifically. Thus, even though there are newer technological tools and innovations, any review attempting to answer this question would have to take recourse to indirect methods.

These include structural, functional, and metabolic neuroimaging. Body fluid biochemical marker studies. And follow-up studies of cognitive impairment and incidence of dementia in people who have received ECT among others. The review of literature and present evidence suggests that ECT has a demonstrable impact on the structure and function of the brain.

However, there is a lack of evidence at present to suggest that ECT causes brain damage.Keywords. Adverse effect, brain damage, electroconvulsive therapyHow to cite this article:Jolly AJ, Singh SM. Does electroconvulsive therapy cause brain damage. An update.

Indian J Psychiatry 2020;62:339-53 Introduction Electroconvulsive therapy (ECT) as a modality of treatment for psychiatric disorders has existed at least since 1938.[1] ECT is an effective modality of treatment for various psychiatric disorders. However, from the very beginning, the practice of ECT has also faced resistance from various groups who claim that it is coercive and harmful.[2] While the ethical aspects of the practice of ECT have been dealt with elsewhere, the question of harmfulness or brain damage consequent upon the passage of electric current needs to be examined afresh in light of technological advances and new knowledge.[3]The question whether ECT causes brain damage was reviewed in a holistic fashion by Devanand et al. In the mid-1990s.[4],[5] The authors had attempted to answer this question by reviewing the effect of ECT on the brain in various areas – cognitive side effects, structural neuroimaging studies, neuropathologic studies of patients who had received ECT, autopsy studies of epileptic patients, and finally animal ECS studies. The authors had concluded that ECT does not produce brain damage.This narrative review aims to update the evidence with regard to whether ECT causes brain damage by reviewing relevant literature from 1994 to the present time.

Framing the Question The Oxford Dictionary defines damage as physical harm that impairs the value, usefulness, or normal function of something.[6] Among medical dictionaries, the Peter Collins Dictionary defines damage as harm done to things (noun) or to harm something (verb).[7] Brain damage is defined by the British Medical Association Medical Dictionary as degeneration or death of nerve cells and tracts within the brain that may be localized to a particular area of the brain or diffuse.[8] Going by such a definition, brain damage in the context of ECT should refer to death or degeneration of brain tissue, which results in the impairment of functioning of the brain. The importance of precisely defining brain damage shall become evident subsequently in this review.There are now many more tools available to investigate the structure and function of brain in health and illness. However, there are obvious ethical issues in designing human studies that are designed to answer this specific question. Therefore, one must necessarily take recourse to indirect evidences available through studies that have been designed to answer other research questions.

These studies have employed the following methods:Structural neuroimaging studiesFunctional neuroimaging studiesMetabolic neuroimaging studiesBody fluid biochemical marker studiesCognitive impairment studies.While the early studies tended to focus more on establishing the safety of ECT and finding out whether ECT causes gross microscopic brain damage, the later studies especially since the advent of advanced neuroimaging techniques have been focusing more on a mechanistic understanding of ECT. Hence, the primary objective of the later neuroimaging studies has been to look for structural and functional brain changes which might explain how ECT acts rather than evidence of gross structural damage per se. However, put together, all these studies would enable us to answer our titular question to some satisfaction. [Table 1] and [Table 2] provide an overview of the evidence base in this area.

Structural and Functional Neuroimaging Studies Devanand et al. Reviewed 16 structural neuroimaging studies on the effect of ECT on the brain.[4] Of these, two were pneumoencephalography studies, nine were computed tomography (CT) scan studies, and five were magnetic resonance imaging (MRI) studies. However, most of these studies were retrospective in design, with neuroimaging being done in patients who had received ECT in the past. In the absence of baseline neuroimaging, it would be very difficult to attribute any structural brain changes to ECT.

In addition, pneumoencephalography, CT scan, and even early 0.3 T MRI provided images with much lower spatial resolution than what is available today. The authors concluded that there was no evidence to show that ECT caused any structural damage to the brain.[4] Since then, at least twenty more MRI-based structural neuroimaging studies have studied the effect of ECT on the brain. The earliest MRI studies in the early 1990s focused on detecting structural damage following ECT. All of these studies were prospective in design, with the first MRI scan done at baseline and a second MRI scan performed post ECT.[9],[11],[12],[13],[41] While most of the studies imaged the patient once around 24 h after receiving ECT, some studies performed multiple post ECT neuroimaging in the first 24 h after ECT to better capture the acute changes.

A single study by Coffey et al. Followed up the patients for a duration of 6 months and repeated neuroimaging again at 6 months in order to capture any long-term changes following ECT.[10]The most important conclusion which emerged from this early series of studies was that there was no evidence of cortical atrophy, change in ventricle size, or increase in white matter hyperintensities.[4] The next major conclusion was that there appeared to be an increase in the T1 and T2 relaxation time immediately following ECT, which returned to normal within 24 h. This supported the theory that immediately following ECT, there appears to be a temporary breakdown of the blood–brain barrier, leading to water influx into the brain tissue.[11] The last significant observation by Coffey et al. In 1991 was that there was no significant temporal changes in the total volumes of the frontal lobes, temporal lobes, or amygdala–hippocampal complex.[10] This was, however, something which would later be refuted by high-resolution MRI studies.

Nonetheless, one inescapable conclusion of these early studies was that there was no evidence of any gross structural brain changes following administration of ECT. Much later in 2007, Szabo et al. Used diffusion-weighted MRI to image patients in the immediate post ECT period and failed to observe any obvious brain tissue changes following ECT.[17]The next major breakthrough came in 2010 when Nordanskog et al. Demonstrated that there was a significant increase in the volume of the hippocampus bilaterally following a course of ECT in a cohort of patients with depressive illness.[18] This contradicted the earlier observations by Coffey et al.

That there was no volume increase in any part of the brain following ECT.[10] This was quite an exciting finding and was followed by several similar studies. However, the perspective of these studies was quite different from the early studies. In contrast to the early studies looking for the evidence of ECT-related brain damage, the newer studies were focused more on elucidating the mechanism of action of ECT. Further on in 2014, Nordanskog et al.

In a follow-up study showed that though there was a significant increase in the volume of the hippocampus 1 week after a course of ECT, the hippocampal volume returned to the baseline after 6 months.[19] Two other studies in 2013 showed that in addition to the hippocampus, the amygdala also showed significant volume increase following ECT.[20],[21] A series of structural neuroimaging studies after that have expanded on these findings and as of now, gray matter volume increase following ECT has been demonstrated in the hippocampus, amygdala, anterior temporal pole, subgenual cortex,[21] right caudate nucleus, and the whole of the medial temporal lobe (MTL) consisting of the hippocampus, amygdala, insula, and the posterosuperior temporal cortex,[24] para hippocampi, right subgenual anterior cingulate gyrus, and right anterior cingulate gyrus,[25] left cerebellar area VIIa crus I,[29] putamen, caudate nucleus, and nucleus acumbens [31] and clusters of increased cortical thickness involving the temporal pole, middle and superior temporal cortex, insula, and inferior temporal cortex.[27] However, the most consistently reported and replicated finding has been the bilateral increase in the volume of the hippocampus and amygdala. In light of these findings, it has been tentatively suggested that ECT acts by inducing neuronal regeneration in the hippocampus – amygdala complex.[42],[43] However, there are certain inconsistencies to this hypothesis. Till date, only one study – Nordanskog et al., 2014 – has followed study patients for a long term – 6 months in their case. And significantly, the authors found out that after increasing immediately following ECT, the hippocampal volume returns back to baseline by 6 months.[19] This, however, was not associated with the relapse of depressive symptoms.

Another area of significant confusion has been the correlation of hippocampal volume increase with improvement of depressive symptoms. Though almost all studies demonstrate a significant increase in hippocampal volume following ECT, a majority of studies failed to demonstrate a correlation between symptom improvement and hippocampal volume increase.[19],[20],[22],[24],[28] However, a significant minority of volumetric studies have demonstrated correlation between increase in hippocampal and/or amygdala volume and improvement of symptoms.[21],[25],[30]Another set of studies have used diffusion tensor imaging, functional MRI (fMRI), anatomical connectome, and structural network analysis to study the effect of ECT on the brain. The first of these studies by Abbott et al. In 2014 demonstrated that on fMRI, the connectivity between right and left hippocampus was significantly reduced in patients with severe depression.

It was also shown that the connectivity was normalized following ECT, and symptom improvement was correlated with an increase in connectivity.[22] In a first of its kind DTI study, Lyden et al. In 2014 demonstrated that fractional anisotropy which is a measure of white matter tract or fiber density is increased post ECT in patients with severe depression in the anterior cingulum, forceps minor, and the dorsal aspect of the left superior longitudinal fasciculus. The authors suggested that ECT acts to normalize major depressive disorder-related abnormalities in the structural connectivity of the dorsal fronto-limbic pathways.[23] Another DTI study in 2015 constructed large-scale anatomical networks of the human brain – connectomes, based on white matter fiber tractography. The authors found significant reorganization in the anatomical connections involving the limbic structure, temporal lobe, and frontal lobe.

It was also found that connection changes between amygdala and para hippocampus correlated with reduction in depressive symptoms.[26] In 2016, Wolf et al. Used a source-based morphometry approach to study the structural networks in patients with depression and schizophrenia and the effect of ECT on the same. It was found that the medial prefrontal cortex/anterior cingulate cortex (ACC/MPFC) network, MTL network, bilateral thalamus, and left cerebellar regions/precuneus exhibited significant difference between healthy controls and the patient population. It was also demonstrated that administration of ECT leads to significant increase in the network strength of the ACC/MPFC network and the MTL network though the increase in network strength and symptom amelioration were not correlated.[32]Building on these studies, a recently published meta-analysis has attempted a quantitative synthesis of brain volume changes – focusing on hippocampal volume increase following ECT in patients with major depressive disorder and bipolar disorder.

The authors initially selected 32 original articles from which six articles met the criteria for quantitative synthesis. The results showed significant increase in the volume of the right and left hippocampus following ECT. For the rest of the brain regions, the heterogeneity in protocols and imaging techniques did not permit a quantitative analysis, and the authors have resorted to a narrative review similar to the present one with similar conclusions.[44] Focusing exclusively on hippocampal volume change in ECT, Oltedal et al. In 2018 conducted a mega-analysis of 281 patients with major depressive disorder treated with ECT enrolled at ten different global sites of the Global ECT-MRI Research Collaboration.[45] Similar to previous studies, there was a significant increase in hippocampal volume bilaterally with a dose–response relationship with the number of ECTs administered.

Furthermore, bilateral (B/L) ECT was associated with an equal increase in volume in both right and left hippocampus, whereas right unilateral ECT was associated with greater volume increase in the right hippocampus. Finally, contrary to expectation, clinical improvement was found to be negatively correlated with hippocampal volume.Thus, a review of the current evidence amply demonstrates that from looking for ECT-related brain damage – and finding none, we have now moved ahead to looking for a mechanistic understanding of the effect of ECT. In this regard, it has been found that ECT does induce structural changes in the brain – a fact which has been seized upon by some to claim that ECT causes brain damage.[46] Such statements should, however, be weighed against the definition of damage as understood by the scientific medical community and patient population. Neuroanatomical changes associated with effective ECT can be better described as ECT-induced brain neuroplasticity or ECT-induced brain neuromodulation rather than ECT-induced brain damage.

Metabolic Neuroimaging Studies. Magnetic Resonance Spectroscopic Imaging Magnetic resonance spectroscopic imaging (MRSI) uses a phase-encoding procedure to map the spatial distribution of magnetic resonance (MR) signals of different molecules. The crucial difference, however, is that while MRI maps the MR signals of water molecules, MRSI maps the MR signals generated by different metabolites – such as N-acetyl aspartate (NAA) and choline-containing compounds. However, the concentration of these metabolites is at least 10,000 times lower than water molecules and hence the signal strength generated would also be correspondingly lower.

However, MRSI offers us the unique advantage of studying in vivo the change in the concentration of brain metabolites, which has been of great significance in fields such as psychiatry, neurology, and basic neuroscience research.[47]MRSI studies on ECT in patients with depression have focused largely on four metabolites in the human brain – NAA, choline-containing compounds (Cho) which include majorly cell membrane compounds such as glycerophosphocholine, phosphocholine and a miniscule contribution from acetylcholine, creatinine (Cr) and glutamine and glutamate together (Glx). NAA is located exclusively in the neurons, and is suggested to be a marker of neuronal viability and functionality.[48] Choline-containing compounds (Cho) mainly include the membrane compounds, and an increase in Cho would be suggestive of increased membrane turnover. Cr serves as a marker of cellular energy metabolism, and its levels are usually expected to remain stable. The regions which have been most widely studied in MRSI studies include the bilateral hippocampus and amygdala, dorsolateral prefrontal cortex (DLPFC), and ACC.Till date, five MRSI studies have measured NAA concentration in the hippocampus before and after ECT.

Of these, three studies showed that there is no significant change in the NAA concentration in the hippocampus following ECT.[33],[38],[49] On the other hand, two recent studies have demonstrated a statistically significant reduction in NAA concentration in the hippocampus following ECT.[39],[40] The implications of these results are of significant interest to us in answering our titular question. A normal level of NAA following ECT could signify that there is no significant neuronal death or damage following ECT, while a reduction would signal the opposite. However, a direct comparison between these studies is complicated chiefly due to the different ECT protocols, which has been used in these studies. It must, however, be acknowledged that the three older studies used 1.5 T MRI, whereas the two newer studies used a higher 3 T MRI which offers betters signal-to-noise ratio and hence lesser risk of errors in the measurement of metabolite concentrations.

The authors of a study by Njau et al.[39] argue that a change in NAA levels might reflect reversible changes in neural metabolism rather than a permanent change in the number or density of neurons and also that reduced NAA might point to a change in the ratio of mature to immature neurons, which, in fact, might reflect enhanced adult neurogenesis. Thus, the authors warn that to conclude whether a reduction in NAA concentration is beneficial or harmful would take a simultaneous measurement of cognitive functioning, which was lacking in their study. In 2017, Cano et al. Also demonstrated a significant reduction in NAA/Cr ratio in the hippocampus post ECT.

More significantly, the authors also showed a significant increase in Glx levels in the hippocampus following ECT, which was also associated with an increase in hippocampal volume.[40] To explain these three findings, the authors proposed that ECT produces a neuroinflammatory response in the hippocampus – likely mediated by Glx, which has been known to cause inflammation at higher concentrations, thereby accounting for the increase in hippocampal volume with a reduction in NAA concentration. The cause for the volume increase remains unclear – with the authors speculating that it might be due to neuronal swelling or due to angiogenesis. However, the same study and multiple other past studies [21],[25],[30] have demonstrated that hippocampal volume increase was correlated with clinical improvement following ECT. Thus, we are led to the hypothesis that the same mechanism which drives clinical improvement with ECT is also responsible for the cognitive impairment following ECT.

Whether this is a purely neuroinflammatory response or a neuroplastic response or a neuroinflammatory response leading to some form of neuroplasticity is a critical question, which remains to be answered.[40]Studies which have analyzed NAA concentration change in other brain areas have also produced conflicting results. The ACC is another area which has been studied in some detail utilizing the MRSI technique. In 2003, Pfleiderer et al. Demonstrated that there was no significant change in the NAA and Cho levels in the ACC following ECT.

This would seem to suggest that there was no neurogenesis or membrane turnover in the ACC post ECT.[36] However, this finding was contested by Merkl et al. In 2011, who demonstrated that NAA levels were significantly reduced in the left ACC in patients with depression and that these levels were significantly elevated following ECT.[37] This again is contested by Njau et al. Who showed that NAA levels are significantly reduced following ECT in the left dorsal ACC.[39] A direct comparison of these three studies is complicated by the different ECT and imaging parameters used and hence, no firm conclusion can be made on this point at this stage. In addition to this, one study had demonstrated increased NAA levels in the amygdala following administration of ECT,[34] with a trend level increase in Cho levels, which again is suggestive of neurogenesis and/or neuroplasticity.

A review of studies on the DLPFC reveals a similarly confusing picture with one study, each showing no change, reduction, and elevation of concentration of NAA following ECT.[35],[37],[39] Here, again, a direct comparison of the three studies is made difficult by the heterogeneous imaging and ECT protocols followed by them.A total of five studies have analyzed the concentration of choline-containing compounds (Cho) in patients undergoing ECT. Conceptually, an increase in Cho signals is indicative of increased membrane turnover, which is postulated to be associated with synaptogenesis, neurogenesis, and maturation of neurons.[31] Of these, two studies measured Cho concentration in the B/L hippocampus, with contrasting results. Ende et al. In 2000 demonstrated a significant elevation in Cho levels in B/L hippocampus after ECT, while Jorgensen et al.

In 2015 failed to replicate the same finding.[33],[38] Cho levels have also been studied in the amygdala, ACC, and the DLPFC. However, none of these studies showed a significant increase or decrease in Cho levels before and after ECT in the respective brain regions studied. In addition, no significant difference was seen in the pre-ECT Cho levels of patients compared to healthy controls.[34],[36],[37]In review, we must admit that MRSI studies are still at a preliminary stage with significant heterogeneity in ECT protocols, patient population, and regions of the brain studied. At this stage, it is difficult to draw any firm conclusions except to acknowledge the fact that the more recent studies – Njau et al., 2017, Cano, 2017, and Jorgensen et al., 2015 – have shown decrease in NAA concentration and no increase in Cho levels [38],[39],[40] – as opposed to the earlier studies by Ende et al.[33] The view offered by the more recent studies is one of a neuroinflammatory models of action of ECT, probably driving neuroplasticity in the hippocampus.

This would offer a mechanistic understanding of both clinical response and the phenomenon of cognitive impairment associated with ECT. However, this conclusion is based on conjecture, and more work needs to be done in this area. Body Fluid Biochemical Marker Studies Another line of evidence for analyzing the effect of ECT on the human brain is the study of concentration of neurotrophins in the plasma or serum. Neurotrophins are small protein molecules which mediate neuronal survival and development.

The most prominent among these is brain-derived neurotrophic factor (BDNF) which plays an important role in neuronal survival, plasticity, and migration.[50] A neurotrophic theory of mood disorders was suggested which hypothesized that depressive disorders are associated with a decreased expression of BDNF in the limbic structures, resulting in the atrophy of these structures.[51] It was also postulated that antidepressant treatment has a neurotrophic effect which reverses the neuronal cell loss, thereby producing a therapeutic effect. It has been well established that BDNF is decreased in mood disorders.[52] It has also been shown that clinical improvement of depression is associated with increase in BDNF levels.[53] Thus, serum BDNF levels have been tentatively proposed as a biomarker for treatment response in depression. Recent meta-analytic evidence has shown that ECT is associated with significant increase in serum BDNF levels in patients with major depressive disorder.[54] Considering that BDNF is a potent stimulator of neurogenesis, the elevation of serum BDNF levels following ECT lends further credence to the theory that ECT leads to neurogenesis in the hippocampus and other limbic structures, which, in turn, mediates the therapeutic action of ECT. Cognitive Impairment Studies Cognitive impairment has always been the single-most important side effect associated with ECT.[55] Concerns regarding long-term cognitive impairment surfaced soon after the introduction of ECT and since then has grown to become one of the most controversial aspects of ECT.[56] Anti-ECT groups have frequently pointed out to cognitive impairment following ECT as evidence of ECT causing brain damage.[56] A meta-analysis by Semkovska and McLoughlin in 2010 is one of the most detailed studies which had attempted to settle this long-standing debate.[57] The authors reviewed 84 studies (2981 participants), which had used a combined total of 22 standardized neuropsychological tests assessing various cognitive functions before and after ECT in patients diagnosed with major depressive disorder.

The different cognitive domains reviewed included processing speed, attention/working memory, verbal episodic memory, visual episodic memory, spatial problem-solving, executive functioning, and intellectual ability. The authors concluded that administration of ECT for depression is associated with significant cognitive impairment in the first few days after ECT administration. However, it was also seen that impairment in cognitive functioning resolved within a span of 2 weeks and thereafter, a majority of cognitive domains even showed mild improvement compared to the baseline performance. It was also demonstrated that not a single cognitive domain showed persistence of impairment beyond 15 days after ECT.Memory impairment following ECT can be analyzed broadly under two conceptual schemes – one that classifies memory impairment as objective memory impairment and subjective memory impairment and the other that classifies it as impairment in anterograde memory versus impairment in retrograde memory.

Objective memory can be roughly defined as the ability to retrieve stored information and can be measured by various standardized neuropsychological tests. Subjective memory or meta-memory, on the other hand, refers to the ability to make judgments about one's ability to retrieve stored information.[58] As described previously, it has been conclusively demonstrated that anterograde memory impairment does not persist beyond 2 weeks after ECT.[57] However, one of the major limitations of this meta-analysis was the lack of evidence on retrograde amnesia following ECT. This is particularly unfortunate considering that it is memory impairment – particularly retrograde amnesia which has received the most attention.[59] In addition, reports of catastrophic retrograde amnesia have been repeatedly held up as sensational evidence of the lasting brain damage produced by ECT.[59] Admittedly, studies on retrograde amnesia are fewer and less conclusive than on anterograde amnesia.[60],[61] At present, the results are conflicting, with some studies finding some impairment in retrograde memory – particularly autobiographical retrograde memory up to 6 months after ECT.[62],[63],[64],[65] However, more recent studies have failed to support this finding.[66],[67] While they do demonstrate an impairment in retrograde memory immediately after ECT, it was seen that this deficit returned to pre-ECT levels within a span of 1–2 months and improved beyond baseline performance at 6 months post ECT.[66] Adding to the confusion are numerous factors which confound the assessment of retrograde amnesia. It has been shown that depressive symptoms can produce significant impairment of retrograde memory.[68],[69] It has also been demonstrated that sine-wave ECT produces significantly more impairment of retrograde memory as compared to brief-pulse ECT.[70] However, from the 1990s onward, sine-wave ECT has been completely replaced by brief-pulse ECT, and it is unclear as to the implications of cognitive impairment from the sine-wave era in contemporary ECT practice.Another area of concern are reports of subjective memory impairment following ECT.

One of the pioneers of research into subjective memory impairment were Squire and Chace who published a series of studies in the 1970s demonstrating the adverse effect of bilateral ECT on subjective assessment of memory.[62],[63],[64],[65] However, most of the studies conducted post 1980 – from when sine-wave ECT was replaced by brief-pulse ECT report a general improvement in subjective memory assessments following ECT.[71] In addition, most of the recent studies have failed to find a significant association between measures of subjective and objective memory.[63],[66],[70],[72],[73],[74] It has also been shown that subjective memory impairment is strongly associated with the severity of depressive symptoms.[75] In light of these facts, the validity and value of measures of subjective memory impairment as a marker of cognitive impairment and brain damage following ECT have been questioned. However, concerns regarding subjective memory impairment and catastrophic retrograde amnesia continue to persist, with significant dissonance between the findings of different research groups and patient self-reports in various media.[57]Some studies reported the possibility of ECT being associated with the development of subsequent dementia.[76],[77] However, a recent large, well-controlled prospective Danish study found that the use of ECT was not associated with elevated incidence of dementia.[78] Conclusion Our titular question is whether ECT leads to brain damage, where damage indicates destruction or degeneration of nerves or nerve tracts in the brain, which leads to loss of function. This issue was last addressed by Devanand et al. In 1994 since which time our understanding of ECT has grown substantially, helped particularly by the advent of modern-day neuroimaging techniques which we have reviewed in detail.

And, what these studies reveal is rather than damaging the brain, ECT has a neuromodulatory effect on the brain. The various lines of evidence – structural neuroimaging studies, functional neuroimaging studies, neurochemical and metabolic studies, and serum BDNF studies all point toward this. These neuromodulatory changes have been localized to the hippocampus, amygdala, and certain other parts of the limbic system. How exactly these changes mediate the improvement of depressive symptoms is a question that remains unanswered.

However, there is little by way of evidence from neuroimaging studies which indicates that ECT causes destruction or degeneration of neurons. Though cognitive impairment studies do show that there is objective impairment of certain functions – particularly memory immediately after ECT, these impairments are transient with full recovery within a span of 2 weeks. Perhaps, the single-most important unaddressed concern is retrograde amnesia, which has been shown to persist for up to 2 months post ECT. In this regard, the recent neurometabolic studies have offered a tentative mechanism of action of ECT, producing a transient inflammation in the limbic cortex, which, in turn, drives neurogenesis, thereby exerting a neuromodulatory effect.

This hypothesis would explain both the cognitive adverse effects of ECT – due to the transient inflammation – and the long-term improvement in mood – neurogenesis in the hippocampus. Although unproven at present, such a hypothesis would imply that cognitive impairment is tied in with the mechanism of action of ECT and not an indicator of damage to the brain produced by ECT.The review of literature suggests that ECT does cause at least structural and functional changes in the brain, and these are in all probability related to the effects of the ECT. However, these cannot be construed as brain damage as is usually understood. Due to the relative scarcity of data that directly examines the question of whether ECT causes brain damage, it is not possible to conclusively answer this question.

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Shubh Mohan SinghDepartment of Psychiatry, Postgraduate Institute of Medical Education and Research, Chandigarh IndiaSource of Support. None, Conflict of Interest. NoneDOI. 10.4103/psychiatry.IndianJPsychiatry_239_19 Tables [Table 1], [Table 2].


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