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https://www.cityreal.lv/kamagra/ so that a person with hearing kamagra 24 hour delivery loss can hear sound better. Hearing devices have three components. A microphone, amplifier and speaker. Sound comes through the microphone and is converted into an electrical signal and sent to the kamagra 24 hour delivery amplifier.

The amplifier increases the power of the signals and sends them to the ear through the speaker. Today’s hearing aid is much smaller and more powerful than the hearing devices our parents and grandparents wore even 10 years ago. Advances in kamagra 24 hour delivery digital technology make them better able to distinguish conversation in noisy environments. Many are Bluetooth capable and connect with smartphones and other personal electronic devices we now use on a daily basis.

More. See the different types and styles of hearing aids kamagra 24 hour delivery Can hearing aids improve my hearing?. That depends on what type of hearing loss you have. Sensorineural hearing loss is caused by damage to the sensory hair cells of the inner ear.

This damage can be caused by kamagra 24 hour delivery exposure to loud noise, illness, medication, injury or age. If your hearing healthcare professional determines you have sensorineural hearing loss, you will probably benefit from wearing a hearing aid. Age-related hearing loss, generally a subset of sensorineural, is the loss of hearing that occurs in most people as they age. This condition, known medically as presbycusis, is common and can often be improved kamagra 24 hour delivery with hearing aids.

Conductive hearing loss, however is usually caused by an obstruction in the ear canal, such as swelling due to an ear infection or a benign tumor. If your hearing healthcare professional determines your hearing loss is conductive, your hearing may return to normal once the obstruction has been removed. If your hearing does not return kamagra 24 hour delivery to normal, you may benefit from wearing a hearing aid, cochlear implant or bone-anchored hearing system. What should I look for when choosing a hearing aid?.

That depends on your lifestyle and your budget. An active person who enjoys traveling and athletic activities will most likely need a different model of hearing aid than someone who spends most of their time at home watching television kamagra 24 hour delivery. Your hearing healthcare professional will ask a variety of questions to help you determine what type of amplification you need, then work with you to make sure your hearing device works properly to help you hear the sounds that are most important to you. Remember that friend who told you they keep their hearing aids in the dresser drawer?.

That just might be because they weren’t honest kamagra 24 hour delivery with their hearing healthcare professional about their expectations and lifestyle, or didn’t schedule follow-up visits as requested. How long will it take for me to adjust to wearing hearing aids?. Wondering what to expect from new hearing aids?. Adjusting to hearing aids varies from person to person and depends upon how long you waited to treat kamagra 24 hour delivery your hearing loss as well as its severity.

Although our ears collect noise from our environment, it’s actually our brain that translates it into recognizable sound. If hearing loss is left untreated, the auditory part of your brain can actually atrophy, in which case your rehabilitation may take a while longer. You’ll also want to wear kamagra 24 hour delivery them as recommended. Following your doctor’s orders improves your chances for success.

More. 7 tips for getting used to hearing kamagra 24 hour delivery aids How long do hearing aids last?. With proper use and maintenance, hearing aids typically last between three and five years. Can I return my hearing aids if I’m not satisfied?.

Many hearing centers offer a trial period to ensure you are satisfied kamagra 24 hour delivery. Be sure to ask your hearing healthcare professional about their policies before you purchase any hearing device. How can I find out if I need a hearing aid?. The best way to find out if you need a hearing aid is to kamagra 24 hour delivery have your hearing tested by a hearing healthcare professional.

A thorough hearing test will take approximately an hour of your time during which you will most likely be asked to provide your health history, undergo a series of hearing assessments, and discuss your lifestyle and expectations for better hearing. Afterward, a hearing healthcare professional will discuss the results of your test with you and, if its determined that your hearing can benefit from amplification, discuss next steps. If your hearing has changed recently kamagra 24 hour delivery or you suspect you have hearing loss, make an appointment to see a hearing healthcare professional in your community as soon as possible. There’s a lot to hear in this world – laughing children, music, the sound of someone you love calling your name – and hearing aids may be able to help you hear them.When deciding on a new pair of hearing aids, you should consider how long they will last.

Just like buying a car, the actual mileage may vary.Most modern high-quality hearing aids have a life expectancy on average between three and seven years. However, keep in mind that two people can buy exactly the same hearing aids and have them last vastly kamagra 24 hour delivery different amounts of time. Here's why. New hearing aids generally last aroundfive years, but this depends on a lotof different factors.

Factors impacting how kamagra 24 hour delivery long hearing aids will last There are at least nine factors that impact the average lifespan of a hearing aid. Materials used to make hearing aids Frequency of cleaning Where hearing aids are worn How hearing aids are stored Hearing aid style A person's body physiology Frequency of maintenance Technological advancements Unique hearing needs 1. Materials used to make hearing aids Although they are designed to be durable, hearing aids are made of plastic, metal, silicon, polymers and other materials that may be subject to some degree of structural degradation over time. Most hearing aids sold today have a protective nanocoating on them to resist water, dust and moisture, but you should still treat them gently to protect them from shock and impacts kamagra 24 hour delivery.

2. Frequency of cleaning Most people would never dream of going months without washing their hair, face or body. However, they forget their hearing aids are exposed to the same environment—moisture, dust, skin oils kamagra 24 hour delivery and sweat, extreme temperatures and sunlight. All this occurs in addition to the earwax generated by your ear canal in its natural cleaning process.

Some wearers only have their hearing aids professionally cleaned twice a year or so. This takes a kamagra 24 hour delivery toll on hearing aids and can significantly reduce their life expectancy. To help your hearing aids life expectancy, clean them daily as directed by your hearing care practitioner and have them professionally cleaned in the hearing clinic every three to four months. 3.

Where hearing kamagra 24 hour delivery aids are worn Hearing aids that are consistently in damp or dusty environments often have more performance issues than other hearing aids. If you’re concerned about the environments in which you wear your hearing aids, consult your hearing care professional for ideas about protective measures. You may need to use protective sleeves or schedule more frequent professional cleanings to extend the life of your hearing aids. 4.

How hearing aids are stored The way hearing aids are stored when you’re not wearing them can also be a factor in hearing aid life expectancy. For hearing aids with disposable batteries, storing hearing aids with the battery door open will keep them safer. A case with a dehumidifier will keep them drier as well, which will also help them last longer. Ask your hearing care practitioner what type of storage case or dehumidifier options would work best for your hearing aids.

For rechargeable hearing aids, lithium batteries last about four to five years. Just like with smartphones, the battery lifespan gets shorter the longer you own the device. If you notice your battery draining faster than usual, speak to your hearing care provider about whether new rechargeable batteries will help, or if you should get new devices. 5.

Style of hearing aids Conventional wisdom in the hearing aid industry is that behind-the-ear (BTE) styles tend to have a long lifespan than in-the-ear (ITE) styles. The reason behind this wisdom is more of the electronic components sit in the damp environment of the ear canal with ITE styles. However, recent technical advancements in nanocoatings on internal and external components may soon make this durability difference a thing of the past. 6.

Your body’s physiology Some body chemistries are harder on the plastic and metal components of hearing aids and tend to discolor or degrade parts much faster than others. Some people have very oily skin, produce a lot of earwax or sweat profusely–all of these factors can impact hearing aid life, too. You can’t control these things, of course, but if you have any of these issues you should discuss them with your hearing care practitioner when you’re selecting hearing aids. 7.

Frequency of maintenance Most hearing aids have some readily-replaceable parts, such as wax guards, earmold tubing and silicone dome earpiece tips. These parts are regularly replaced during routine maintenance visits with your hearing care practitioner. There are other parts which can usually be replaced or repaired in the clinic if they become damaged or nonfunctional, like battery doors, earmolds, external speakers and microphone covers. These types of maintenance activities are very important for making your hearing aids last as long as possible.

8. Technological advancements Hearing aid technology changes often.Many new hearing aids can connectto phones via Bluetooth, for example. Obsolescence can become an issue for very old hearing aids. After several years (usually between five and 10), hearing aid manufacturers may stop making replacement parts for a particular aid, which may make repairs on old hearing aids difficult or impossible.

Software used to program hearing aids also changes over time and eventually becomes obsolete. This often makes it difficult to reprogram very old hearing aids. Hearing aid performance and features advance very rapidly. The technology in the most advanced hearing aids available six or seven years ago would be considered basic today.

While some folks are content to stick with what they have if it still performs for them, many people who buy hearing aids find themselves wanting to benefit from the new technology that becomes available four or five years down the road. 9. Changing needs Everything described up to this point focuses on the hearings aids themselves. Changing needs of the wearer can also affect how long hearing aids last.

Sometimes after several years, a person's hearing loss can progress to the point where a more powerful hearing aid would suit them better. A person's lifestyle could change and require a hearing aid with more—or fewer—features. In cases where a hearing aid is replaced while it’s still functional, your hearing care practitioner can assist you in donating the used hearing aids to a worthy cause. How do you determine which factors will affect your hearing aids?.

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SALT LAKE kamagra online uk CITY, Sept https://www.cityreal.lv/kamagra-jelly/. 8, 2020 /PRNewswire/ -- Health Catalyst, Inc. ("Health Catalyst," kamagra online uk Nasdaq.

HCAT), a leading provider of data and analytics technology and services to healthcare organizations, today announced that it has completed its seventh annual and first ever virtual Healthcare Analytics Summit (HAS), with record registration of more than 3,500 attendees. Keynotes included Dr kamagra online uk. Amy Abernethy, Principal Deputy Commissioner and Acting CIO of the U.S.

Food and Drug Administration, kamagra online uk Michael Dowling, CEO of Northwell Health, Vice Admiral Raquel Bono, MD, and many others. Other business updates include:The Vitalware, LLC ("VitalWare"), transaction has closed, and integration is underway of the Yakima, Washington-based provider of revenue workflow optimization and analytics SaaS technology solutions for health organizations. This is another kamagra online uk example of Health Catalyst's ability to scale software on top of its cloud-based Data Operating System (DOS™).

DOS will further enhance the analytics insights made available by Vitalware's technology by combining charge and revenue data with claims, cost, and quality data. Vitalware's flagship offering is a Best in KLAS chargemaster management solution that delivers results for the complex regulatory and compliance functions needed by all healthcare provider systems. "As announced on August 11, 2020, we entered into an kamagra online uk acquisition agreement to acquire Vitalware and expected to close the acquisition in Q3 or Q4 of 2020.

We are pleased to announce that we closed the acquisition on September 1, 2020. We are thrilled to formalize the combination kamagra online uk of our solutions for the benefit of our customers and the industry," said CEO Dan Burton. On its upcoming Q3 2020 earnings call, Health Catalyst will share the impact of Vitalware on its Q3 2020 financial performance, which will not be significant given the timing of the acquisition, as well as update its full year 2020 guidance to include the impact of Vitalware.

Health Catalyst Co-Founder Steve Barlow has kamagra online uk returned from his three-year full-time volunteer mission for the Church of Jesus Christ of Latter-Day Saints, having served as Mission President of the Ecuador Quito Mission. He has rejoined Health Catalyst's companywide Leadership Team as a Senior Vice President, responsible for some of the company's largest customer relationships. Dan kamagra online uk Burton said, "We couldn't be more excited about Steve's return to Health Catalyst.

His energy, dedication and commitment to transforming healthcare launched our journey and will continue to make us better and stronger. Steve is leading and overseeing all aspects of our partnerships with some of our largest and longest-standing customers. Steve's extraordinary experience and capability enable him to be a critical partner and leader in enabling these customers' continued improvement and success." "My experience over the past three years in Ecuador reinforced for me how fortunate I am to be in a country with high-quality kamagra online uk healthcare," said Barlow.

"It has been invigorating to return to Health Catalyst and witness the incredible growth and expansion that has occurred over the past few years. We are better positioned than ever before to achieve our mission of being the catalyst for massive, kamagra online uk measurable, data-informed healthcare improvement. I am grateful to be reunited with our longstanding team members and customers, and I'm thrilled to get to know and work alongside our new customers and teammates in this critical work." Effective October 1, 2020, Chief Technology Officer Dale Sanders will be transitioning to a Senior Advisor role with Health Catalyst, and the company is pleased to announce that one of Dale's longtime protégés and colleagues, Bryan Hinton, will serve as Health Catalyst's next Chief Technology Officer.

Hinton joined Health Catalyst in 2012 and currently serves as the Senior Vice President and General Manager of the kamagra online uk DOS Platform Business. He will continue to lead this business in addition to assuming the responsibilities of CTO. He has been instrumental in the development and integration of DOS and has kamagra online uk been working directly with Dale and other technology leaders at Health Catalyst for many years.

His experience prior to joining Health Catalyst includes four years with the .NET Development Center of Excellence at The Church of Jesus Christ of Latter-Day Saints, where he established the architectural guidance of all .NET projects. Previously, at Intel, he was responsible for the development and implementation of Intel's factory data warehouse product installed at Intel global factories. Hinton graduated from Brigham Young University kamagra online uk with a BS in Computer Science.

"Dale has been central to Health Catalyst's growth and success and we are grateful to him for his many years of service to our company and to the broader healthcare industry," said Dan Burton, CEO of Health Catalyst. "Thanks to Dale's vision, passion, innovative thinking and broad-based industry experience and perspective, Health Catalyst has grown from a handful of clients to a large number of organizations relying on us as their digital transformation partner, helping the healthcare ecosystem to constantly learn and improve kamagra online uk. Dale's technology leadership was critical to the company's overall maturation, and I am convinced that we could not have grown and scaled as we have without Dale's foundational leadership and contributions.

We are grateful to continue our association with kamagra online uk Dale in the months and years ahead in his next role as a Senior Advisor to the company." Burton added, "We are thrilled to see Bryan Hinton take on this added role after having demonstrated his technology leadership prowess during the course of his tenure at Health Catalyst and having been mentored by Dale for many years. Bryan is well-prepared and ready for this additional responsibility, and we extend our congratulations to him." "I feel like a parent saying goodbye to my kids at their college graduation," said Dale Sanders. "Many of the concepts we first developed and applied over 20 years ago at Intermountain and then later refined during my kamagra online uk tenure as CIO at Northwestern had a big influence on our technology and products at Health Catalyst.

The vision of the Data Operating System and its application ecosystem originated in the real-world healthcare operations and research trenches of Northwestern. At Health Catalyst, I had the wonderful opportunity to lead the teams who made that vision a reality for the benefit of the entire industry. None of it would have been possible without Bryan Hinton leading the DOS kamagra online uk team and Eric Just and Dan Unger leading the application development teams.

We've been working side-by-side for many years to make the vision real. Bryan is the consummate modern CTO from outside of healthcare that kamagra online uk healthcare needs. I've always described Eric as having a manufacturing engineer's mindset with a healthcare data and software engineer's skills, with Dan Unger leveraging his deep domain expertise in financial transformation to oversee the development of meaningful applications and solutions so relevant for CFOs.

I'm honored and thrilled to step aside and turn the future over to their very capable hands kamagra online uk. Under their leadership, the best is yet to come for Health Catalyst's technology." About Health CatalystHealth Catalyst is a leading provider of data and analytics technology and services to healthcare organizations, and is committed to being the catalyst for massive, measurable, data-informed healthcare improvement. Its customers leverage the cloud-based data platform—powered by data from more than 100 million patient records kamagra online uk and encompassing trillions of facts—as well as its analytics software and professional services expertise to make data-informed decisions and realize measurable clinical, financial and operational improvements.

Health Catalyst envisions a future in which all healthcare decisions are data informed.Health Catalyst Media Contact:Kristen BerrySenior Vice President, Public Relations+1 (617) 234-4123HealthCatalyst@we-worldwide.com View original content to download multimedia:http://www.prnewswire.com/news-releases/health-catalyst-completes-hosting-of-the-largest-ever-healthcare-analytics-summit-and-announces-the-close-of-the-vitalware-acquisition-301125125.htmlSOURCE Health CatalystNEW YORK and SALT LAKE CITY, Aug. 12, 2020 /PRNewswire/ -- Northwell Health today joined Health Catalyst, Inc. ("Health Catalyst," Nasdaq kamagra online uk.

HCAT), a leading provider of data and analytics technology and services to healthcare organizations, in announcing a long-term strategic partnership to transform the quality of patient care by using data and analytics to better anticipate and respond to the evolving needs of patients, providers and payers in today's rapidly evolving healthcare ecosystem. In this partnership, Health Catalyst will provide solutions kamagra online uk to allow for increased cloud-based reliance on data and analytics, while sharing insights and best practices from a decade of support to hundreds of other healthcare clients. This will accelerate greater efficiency in data mapping and data storage to/with the Electronic Medical Record (EMR) and the affordable emergence of an enterprise solution for meaningful and measurable clinical, financial and operational improvements.

The solutions kamagra online uk will be used across the Northwell Health enterprise, which includes the Feinstein Institute and Donald and Barbara Zucker School of Medicine at Hofstra. "Northwell Health's goal is a simple one that has not changed since our inception. Be better tomorrow than we are today kamagra online uk.

Partnering with Health Catalyst will allow us to accelerate the generation of critical insights for one of the world's most diverse patient populations which includes more than 11 million individuals who will potentially turn to us for care," said Michael Dowling, President and CEO of Northwell Health. "Health Catalyst's Augmented Intelligence (AI) and data science experience and expertise, along with our shared cultural attributes and mission alignment, will allow us to use data-informed decision making to achieve our shared commitment of transforming healthcare for the communities we serve."Northwell Health is New York State's largest health care provider and private employer, with 23 hospitals, nearly 800 outpatient facilities and more than 18,500 affiliated physicians. More than 11,000 COVID-19 patients have received care from Northwell's 16,000-plus nurses and 4,000 employed doctors, including members of Northwell Health Physician Partners, and kamagra online uk using 1,600 additional COVID-19 focused beds."We are honored to have the opportunity to join Northwell Health on its mission-driven journey to transform healthcare," said Dan Burton, CEO of Health Catalyst.

"We have deep respect for our Northwell colleagues and are excited about combining our Solution with Northwell's team members' experience, knowledge and passion for improvement. We are also honored to have Northwell's CEO Michael Dowling as a keynote speaker at Health kamagra online uk Catalyst's upcoming Healthcare Analytics Summit (HAS), where we'll hear his important perspectives on the COVID-19 pandemic and the future of healthcare delivery." This partnership will be built using Health Catalyst's DOS™ technology, a data-first analytics and application platform, to capture and map raw data into meaningful, actionable insights. Northwell Health will also immediately have access to Health Catalyst's growing suite of COVID-19 solutions, including but not limited to a registry, staff and patient tracker and capacity planning tool.

Broadly sharing Northwell Health's data driven insights from its COVID-19 work is another significant opportunity kamagra online uk for transformational care."Health Catalyst will become our data and analytics backbone, as their Solutions will enable our organization to take our current data adoption and transformation to entirely new heights," said John Bosco, Senior Vice President and Chief Information Officer at Northwell Health. "We are looking forward to leaning on DOS to create an affordable, yet innovative enterprise solution that will further enable transformative care to the patients we serve."About Northwell HealthNorthwell Health is New York State's largest health care provider and private employer, with 23 hospitals, 665 outpatient facilities and more than 18,500 affiliated physicians. We care for over two million people annually in the New York metro kamagra online uk area and beyond, thanks to philanthropic support from our communities.

Our 66,000 employees – 16,000-plus nurses and 4,000 employed doctors, including members of Northwell Health Physician Partners – are working to change health care for the better. We are making breakthroughs in medicine at the Feinstein Institute kamagra online uk for Medical Research. We are training the next generation of medical professionals at the visionary Donald and Barbara Zucker School of Medicine at Hofstra/Northwell and the Hofstra Northwell School of Graduate Nursing and Physician Assistant Studies.

For information on our more than 100 medical specialties, visit Northwell.edu.About Health CatalystHealth Catalyst is a leading provider of data and analytics technology and services to healthcare organizations, and is committed to being the catalyst for massive, measurable, data-informed healthcare improvement. Its customers leverage the cloud-based data platform—powered by data from more than 100 million patient kamagra online uk records and encompassing trillions of facts—as well as its analytics software and professional services expertise to make data-informed decisions and realize measurable clinical, financial and operational improvements. Health Catalyst envisions a future in which all healthcare decisions are data informed.

Northwell Health Media Contact:Michelle Pinto516-321-6708mpinto@northwell.edu Health Catalyst Media Contact:Kristen BerrySenior Vice President, Public Relations+1 (617) 234-4123+1 (774) 573-0455 (m)kberry@we-worldwide.com View original content to download multimedia:http://www.prnewswire.com/news-releases/health-catalyst-and-northwell-health-partner-to-transform-patient-care-with-cloud-based-data-and-analytics-enterprise-solution-301110803.htmlSOURCE Health CatalystPeople tried to escape a heat wave baking the West by heading to Castaic Lake in California on Saturday.Credit...Marcio Jose Sanchez/Associated PressFor many Americans, Labor Day kamagra online uk is a goodbye to summer before children go back to school and cold weather arrives. But public health experts are worried that in the midst of a pandemic, the traditional last blast of summer could translate into disaster this fall.After the Memorial Day and Fourth of July weekends, cases of Covid-19 surged around the country after people held family gatherings or congregated in large groups. Dr.

Anthony S. Fauci, the country’s top infectious disease expert, said he wanted people to enjoy Labor Day weekend but urged them to take precautions to avoid a post-holiday spike in cases. Take the fun outdoors.

Avoid crowds, keep gatherings to 10 people or fewer. And even outdoors, where transmission risk is much lower, you still need to wear a mask and practice physical distancing if you’re spending time with people outside your household.“We’ve been through this before,” Dr. Fauci said.

€œWe see what happens over holiday weekends, and we want to make sure we don’t have an uptick. What I have been saying is kind of a plea to the American public, and to the younger people, that they can enjoy themselves over Labor Day weekend, but please be aware of and adhere to public health guidelines.”In terms of daily case counts, the United States over all was in worse shape going into Labor Day weekend than it was for Memorial Day weekend. The nation is now averaging about 40,000 new confirmed cases per day, up from about 22,000 per day ahead of Memorial Day weekend.

Dr. Fauci said that the number of daily cases in the United States was “unacceptably high” and that a spike in Covid-19 infections following Labor Day would make it far tougher to control the spread of the disease in the fall as people head indoors.“We’d like to get a good head start into the fall by getting our daily cases and our test positivity as low as possible,” Dr. Fauci said.

€œIf we get another resurgence of infections after Labor Day, it will make it that much more difficult to get that baseline down and make it much more problematic as we enter the fall season.”Public health experts said it might be even more challenging to persuade people to curtail their Labor Day weekend plans, compared with past holiday weekends, because so many people are suffering from pandemic fatigue after six months of social-distancing restrictions, closures and separation from loved ones.“People are getting tired of taking these precautions and of having their lives upended,” said Eleanor J. Murray, an assistant professor of epidemiology at the Boston University School of Public Health. €œThey’re missing their friends and family, and everyone wishes things were back to normal.

That’s totally understandable, but unfortunately we don’t get a say, really.”Dr. Murray said it was important for people to remember that just one gathering could lead to spikes in cases that would affect kamagra iskustva many more people. She noted that a wedding in Maine with an estimated 65 guests had resulted in 147 infections, including three deaths among people who didn’t even attend the wedding.Dr.

Murray said that if people decided to ignore public health guidelines this weekend, at the very least they should place themselves in quarantine for two weeks after the event. €œIf those people at the wedding had said, ‘This is a risk I’m personally willing to take,’ but after the wedding they had quarantined, then the maximum number of cases would have been the 65 wedding attendees,” she said.Although it’s safer to gather outside than indoors, the virus can still be transmitted in outdoor spaces when people gather in large groups or stand close to one another for long periods of time. Alcohol can loosen inhibitions, prompting people to forget about social distancing.

Loud music can prompt people to stand closer and speak louder, which can spew more viral particles and put you at risk even if you’re wearing a mask, health experts say.Dr. Murray said that whatever plan you have for the holiday weekend, ask yourself how you can make it safer for everyone.“People need to socialize and to see people who are important to them,” Dr. Murray said.

€œIf you were thinking of being indoors, go outdoors. If you were thinking about being outdoors, spread out further. Wear masks.

Think about what you can do to move down the risk continuum.”While many people feel safer socializing with family members, a number of outbreaks have been traced back to family parties that included relatives from more than one household. In Maryland, 44 percent of the state’s new cases were traced back to family gatherings, compared with 23 percent from house parties and 21 percent to outdoor events, according to a tweet posted by Gov. Larry Hogan.After a family gathering of two dozen people in Catawba County, N.C., 14 people who attended became ill, but it didn’t end there.

€œBefore they started to show symptoms, they continued with their daily lives, such as going to work or taking a beach trip with other families,” Jennifer McCracken, Catawba County’s public health director, wrote in a case study of the event. €œThis set into motion a person-to-person contact chain that to date has spread COVID-19 to 41 people in nine different families and eight different workplaces.”Gregg Gonsalves, an assistant professor of epidemiology at the Yale School of Public Health, said the holiday weekend would multiply the number of family gatherings around the country.“A family gathering one weekend in August that sets off cases in a given county or town is one thing,” Dr. Gonsalves said.

€œOne hundred family gatherings in that county on Labor Day weekend makes it a much larger epidemiological impact.”Dr. Gonsalves said concerns about Labor Day celebrations were being compounded by the fact that there are already large outbreaks on college campuses. €œWe’ve had this gigantic migration event over the past few weeks where students are moving all over the country from homes to universities,” Dr.

Gonsalves said. €œThe relative calm of places like New York and Connecticut has to be now thought of in the context of all this big jumble of people crisscrossing the country to get back to college.”ABC News posted a video on Twitter showing crowds of people gathering at a sports bar near the University of South Carolina. The university has reported more than 1,735 cases since Aug.

1, including 1,461 active cases, according to its Covid-19 dashboard.Brian Pace, a 35-year old psychologist in Phoenix, said he and his friends in Salt Lake City had talked about getting together for a socially distanced outdoor barbecue this weekend. He decided it was smarter to stay home, so he will get takeout from a local barbecue restaurant, JL Smokehouse, instead.“I debated with friends,” Mr. Pace said.

€œBut in the end, my decision boiled down to. Will I look back five years from now and say, ‘That was pretty stupid,’ or regret that I didn’t do it?. It probably would be that it was stupid to do that, so we’re pretty much hunkered down here.

When I go out, I wear a mask, and it’s takeout only.”Dr. Fauci said he didn’t want his words of caution about Labor Day celebrations to stop people from enjoying the holiday. He said he personally planned to spend the weekend with his wife, fishing in the Potomac and having dinner with two friends, for a total of four people, on his backyard deck.“You don’t want to tell people on a holiday weekend that even outdoors is bad — they will get completely discouraged,” Dr.

Fauci said. €œWhat we try to say is enjoy outdoors, but you can do it with safe spacing. You can be on a beach, and you don’t have to be falling all over each other.

You can be six, seven, eight, nine or 10 feet apart. You can go on a hike. You can go on a run.

You can go on a picnic with a few people. You don’t have to be in a crowd with 30, 40 or 50 people all breathing on each other.”The medical mistakes that befell the 87-year-old mother of a North Carolina pharmacist should not happen to anyone, and my hope is that this column will keep you and your loved ones from experiencing similar, all-too-common mishaps.As the pharmacist, Kim H. DeRhodes of Charlotte, N.C., recalled, it all began when her mother went to the emergency room two weeks after a fall because she had lingering pain in her back and buttocks.

Told she had sciatica, the elderly woman was prescribed prednisone and a muscle relaxant. Three days later, she became delirious, returned to the E.R., was admitted to the hospital, and was discharged two days later when her drug-induced delirium resolved.A few weeks later, stomach pain prompted a third trip to the E.R. And a prescription for an antibiotic and proton-pump inhibitor.

Within a month, she developed severe diarrhea lasting several days. Back to the E.R., and this time she was given a prescription for dicyclomine to relieve intestinal spasms, which triggered another bout of delirium and three more days in the hospital. She was discharged after lab tests and imaging studies revealed nothing abnormal.“Review of my mother’s case highlights separate but associated problems.

Likely misdiagnosis and inappropriate prescribing of medications,” Ms. DeRhodes wrote in JAMA Internal Medicine. €œDiagnostic errors led to the use of prescription drugs that were not indicated and caused my mother further harm.

The muscle relaxer and prednisone led to her first incidence of delirium. Prednisone likely led to the gastrointestinal issues, and the antibiotic likely led to the diarrhea, which led to the prescribing of dicyclomine, which led to the second incidence of delirium.”The doctors who wrote the woman’s prescriptions apparently never consulted the Beers Criteria, a list created by the American Geriatrics Society of drugs often unsafe for the elderly.In short, Ms. DeRhodes’s mother was a victim of two medical problems that are too often overlooked by examining doctors and unrecognized by families.

The first is giving an 87-year-old medications known to be unsafe for the elderly. The second is a costly and often frightening medically induced condition called “a prescribing cascade” that starts with drug-induced side effects which are then viewed as a new ailment and treated with yet another drug or drugs that can cause still other side effects.I’d like to think that none of this would have happened if instead of going to the E.R. The older woman had seen her primary care doctor.

But experts told me that no matter where patients are treated, they are not immune to getting caught in a prescribing cascade. The problem also can happen to people who self-treat with over-the-counter or herbal remedies. Nor is it limited to the elderly.

Young people can also become victims of a prescribing cascade, Ms. DeRhodes said.“Doctors are often taught to think of everything as a new problem,” Dr. Timothy Anderson, internist at Beth Israel Deaconess Medical Center in Boston, said.

€œThey have to start thinking about whether the patient is on medication and whether the medication is the problem.”“Doctors are very good at prescribing but not so good at deprescribing,” Ms. DeRhodes said. €œAnd a lot of times patients are given a prescription without first trying something else.”A popular treatment for high blood pressure, which afflicts a huge proportion of older people, is a common precipitant of the prescribing cascade, Dr.

Anderson said.He cited a Canadian study of 41,000 older adults with hypertension who were prescribed drugs called calcium channel blockers. Within a year after treatment began, nearly one person in 10 was given a diuretic to treat leg swelling caused by the first drug. Many were inappropriately prescribed a so-called loop diuretic that Dr.

Anderson said can result in dehydration, kidney problems, lightheadedness and falls.Type 2 diabetes is another common condition in which medications are often improperly prescribed to treat drug-induced side effects, said Lisa M. McCarthy, doctor of pharmacy at the University of Toronto who directed the Canadian study. Recognizing a side effect for what it is can be hampered when the effect doesn’t happen for weeks or even months after a drug is started.

While patients taking opioids for pain may readily recognize constipation as a consequence, Dr. McCarthy said that over time, patients taking metformin for diabetes can develop diarrhea and may self-treat with Lomotil, which in turn can cause dizziness and confusion.Dr. Paula Rochon, geriatrician at Women’s College Hospital in Ontario, said patients taking a drug called a cholinesterase inhibitor to treat early dementia can develop urinary incontinence, which is then treated with another drug that can worsen the patient’s confusion.Complicating matters is the large number of drugs some people take.

€œOlder adults frequently take many medications, with two-fifths taking five or more,” Dr. Anderson wrote in JAMA Internal Medicine. In cases of polypharmacy, as this is called, it can be hard to determine which, if any, of the drugs a person is taking is the cause of the current symptom.Dr.

Rochon emphasized that a prescribing cascade can happen to anybody. She said, “Everyone needs to consider the possibility every time a drug is prescribed.”Before accepting a prescription, she recommended that patients or their caregivers should ask the doctor a series of questions, starting with “Am I experiencing a symptom that could be a side effect of a drug I’m taking?. € Follow-up questions should include:Is this new drug being used to treat a side effect?.

Is there a safer drug available than the one I’m taking?. Could I take a lower dose of the prescribed drug?. Most important, Dr.

Rochon said, patients should ask “Do I need to take this drug at all?. €Patients and doctors alike often overlook or resist alternatives to medication that may be more challenging to adopt than swallowing a pill. For example, among well-established nondrug remedies for hypertension are weight loss, increasing physical activity, consuming less salt and other sources of sodium, and eating more potassium-rich foods like bananas and cantaloupe.For some patients, frequent use of a nonsteroidal anti-inflammatory drug sold over-the-counter, like ibuprofen or naproxen, is responsible for their elevated blood pressure.The risk of getting caught in a prescribing cascade is increased when patients are prescribed medications by more than one provider.

It’s up to patients to be sure every doctor they consult is given an up-to-date list of every drug they take, whether prescription or over-the-counter, as well as nondrug remedies and dietary supplements. Dr. Rochon recommended that patients maintain an up-to-date list of when and why they started every new drug, along with its dose and frequency, and show that list to the doctor as well..

SALT LAKE kamagra 24 hour delivery CITY, Sept https://www.cityreal.lv/kamagra-24/. 8, 2020 /PRNewswire/ -- Health Catalyst, Inc. ("Health Catalyst," Nasdaq kamagra 24 hour delivery. HCAT), a leading provider of data and analytics technology and services to healthcare organizations, today announced that it has completed its seventh annual and first ever virtual Healthcare Analytics Summit (HAS), with record registration of more than 3,500 attendees. Keynotes included kamagra 24 hour delivery Dr.

Amy Abernethy, Principal Deputy Commissioner and Acting CIO of the U.S. Food and kamagra 24 hour delivery Drug Administration, Michael Dowling, CEO of Northwell Health, Vice Admiral Raquel Bono, MD, and many others. Other business updates include:The Vitalware, LLC ("VitalWare"), transaction has closed, and integration is underway of the Yakima, Washington-based provider of revenue workflow optimization and analytics SaaS technology solutions for health organizations. This is another example of Health Catalyst's ability to scale kamagra 24 hour delivery software on top of its cloud-based Data Operating System (DOS™). DOS will further enhance the analytics insights made available by Vitalware's technology by combining charge and revenue data with claims, cost, and quality data.

Vitalware's flagship offering is a Best in KLAS chargemaster management solution that delivers results for the complex regulatory and compliance functions needed by all healthcare provider systems. "As announced on August kamagra 24 hour delivery 11, 2020, we entered into an acquisition agreement to acquire Vitalware and expected to close the acquisition in Q3 or Q4 of 2020. We are pleased to announce that we closed the acquisition on September 1, 2020. We are thrilled to kamagra 24 hour delivery formalize the combination of our solutions for the benefit of our customers and the industry," said CEO Dan Burton. On its upcoming Q3 2020 earnings call, Health Catalyst will share the impact of Vitalware on its Q3 2020 financial performance, which will not be significant given the timing of the acquisition, as well as update its full year 2020 guidance to include the impact of Vitalware.

Health Catalyst Co-Founder Steve Barlow has returned from his three-year full-time volunteer mission for the Church of Jesus Christ of Latter-Day kamagra 24 hour delivery Saints, having served as Mission President of the Ecuador Quito Mission. He has rejoined Health Catalyst's companywide Leadership Team as a Senior Vice President, responsible for some of the company's largest customer relationships. Dan Burton said, "We couldn't be more excited about Steve's return kamagra 24 hour delivery to Health Catalyst. His energy, dedication and commitment to transforming healthcare launched our journey and will continue to make us better and stronger. Steve is leading and overseeing all aspects of our partnerships with some of our largest and longest-standing customers.

Steve's extraordinary experience kamagra 24 hour delivery and capability enable him to be a critical partner and leader in enabling these customers' continued improvement and success." "My experience over the past three years in Ecuador reinforced for me how fortunate I am to be in a country with high-quality healthcare," said Barlow. "It has been invigorating to return to Health Catalyst and witness the incredible growth and expansion that has occurred over the past few years. We are kamagra 24 hour delivery better positioned than ever before to achieve our mission of being the catalyst for massive, measurable, data-informed healthcare improvement. I am grateful to be reunited with our longstanding team members and customers, and I'm thrilled to get to know and work alongside our new customers and teammates in this critical work." Effective October 1, 2020, Chief Technology Officer Dale Sanders will be transitioning to a Senior Advisor role with Health Catalyst, and the company is pleased to announce that one of Dale's longtime protégés and colleagues, Bryan Hinton, will serve as Health Catalyst's next Chief Technology Officer. Hinton joined kamagra 24 hour delivery Health Catalyst in 2012 and currently serves as the Senior Vice President and General Manager of the DOS Platform Business.

He will continue to lead this business in addition to assuming the responsibilities of CTO. He has been instrumental in the development and integration of DOS kamagra 24 hour delivery and has been working directly with Dale and other technology leaders at Health Catalyst for many years. His experience prior to joining Health Catalyst includes four years with the .NET Development Center of Excellence at The Church of Jesus Christ of Latter-Day Saints, where he established the architectural guidance of all .NET projects. Previously, at Intel, he was responsible for the development and implementation of Intel's factory data warehouse product installed at Intel global factories. Hinton graduated from Brigham Young University with a BS kamagra 24 hour delivery in Computer Science.

"Dale has been central to Health Catalyst's growth and success and we are grateful to him for his many years of service to our company and to the broader healthcare industry," said Dan Burton, CEO of Health Catalyst. "Thanks to Dale's vision, passion, innovative thinking and broad-based industry experience and perspective, Health Catalyst has grown from a handful of clients to a large number of organizations relying on us as their digital transformation partner, helping the healthcare kamagra 24 hour delivery ecosystem to constantly learn and improve. Dale's technology leadership was critical to the company's overall maturation, and I am convinced that we could not have grown and scaled as we have without Dale's foundational leadership and contributions. We are grateful to continue our association with Dale in the months and years ahead kamagra 24 hour delivery in his next role as a Senior Advisor to the company." Burton added, "We are thrilled to see Bryan Hinton take on this added role after having demonstrated his technology leadership prowess during the course of his tenure at Health Catalyst and having been mentored by Dale for many years. Bryan is well-prepared and ready for this additional responsibility, and we extend our congratulations to him." "I feel like a parent saying goodbye to my kids at their college graduation," said Dale Sanders.

"Many of the concepts we first developed and applied over 20 years ago at Intermountain and then later refined during my tenure as CIO at kamagra 24 hour delivery Northwestern had a big influence on our technology and products at Health Catalyst. The vision of the Data Operating System and its application ecosystem originated in the real-world healthcare operations and research trenches of Northwestern. At Health Catalyst, I had the wonderful opportunity to lead the teams who made that vision a reality for the benefit of the entire industry. None of it would have been possible without Bryan Hinton leading the DOS team and Eric Just and Dan Unger leading kamagra 24 hour delivery the application development teams. We've been working side-by-side for many years to make the vision real.

Bryan is the consummate modern CTO from outside of healthcare that kamagra 24 hour delivery healthcare needs. I've always described Eric as having a manufacturing engineer's mindset with a healthcare data and software engineer's skills, with Dan Unger leveraging his deep domain expertise in financial transformation to oversee the development of meaningful applications and solutions so relevant for CFOs. I'm honored and thrilled to step aside and turn the kamagra 24 hour delivery future over to their very capable hands. Under their leadership, the best is yet to come for Health Catalyst's technology." About Health CatalystHealth Catalyst is a leading provider of data and analytics technology and services to healthcare organizations, and is committed to being the catalyst for massive, measurable, data-informed healthcare improvement. Its customers leverage the cloud-based data platform—powered by data from more than 100 million patient records and encompassing trillions of facts—as kamagra 24 hour delivery well as its analytics software and professional services expertise to make data-informed decisions and realize measurable clinical, financial and operational improvements.

Health Catalyst envisions a future in which all healthcare decisions are data informed.Health Catalyst Media Contact:Kristen BerrySenior Vice President, Public Relations+1 (617) 234-4123HealthCatalyst@we-worldwide.com View original content to download multimedia:http://www.prnewswire.com/news-releases/health-catalyst-completes-hosting-of-the-largest-ever-healthcare-analytics-summit-and-announces-the-close-of-the-vitalware-acquisition-301125125.htmlSOURCE Health CatalystNEW YORK and SALT LAKE CITY, Aug. 12, 2020 /PRNewswire/ -- Northwell Health today joined Health Catalyst, Inc. ("Health Catalyst," Nasdaq kamagra 24 hour delivery. HCAT), a leading provider of data and analytics technology and services to healthcare organizations, in announcing a long-term strategic partnership to transform the quality of patient care by using data and analytics to better anticipate and respond to the evolving needs of patients, providers and payers in today's rapidly evolving healthcare ecosystem. In this partnership, Health Catalyst will provide solutions to allow for increased cloud-based reliance on data and kamagra 24 hour delivery analytics, while sharing insights and best practices from a decade of support to hundreds of other healthcare clients.

This will accelerate greater efficiency in data mapping and data storage to/with the Electronic Medical Record (EMR) and the affordable emergence of an enterprise solution for meaningful and measurable clinical, financial and operational improvements. The solutions will be used across the Northwell Health enterprise, which kamagra 24 hour delivery includes the Feinstein Institute and Donald and Barbara Zucker School of Medicine at Hofstra. "Northwell Health's goal is a simple one that has not changed since our inception. Be better tomorrow kamagra 24 hour delivery than we are today. Partnering with Health Catalyst will allow us to accelerate the generation of critical insights for one of the world's most diverse patient populations which includes more than 11 million individuals who will potentially turn to us for care," said Michael Dowling, President and CEO of Northwell Health.

"Health Catalyst's Augmented Intelligence (AI) and data science experience and expertise, along with our shared cultural attributes and mission alignment, will allow us to use data-informed decision making to achieve our shared commitment of transforming healthcare for the communities we serve."Northwell Health is New York State's largest health care provider and private employer, with 23 hospitals, nearly 800 outpatient facilities and more than 18,500 affiliated physicians. More than 11,000 kamagra 24 hour delivery COVID-19 patients have received care from Northwell's 16,000-plus nurses and 4,000 employed doctors, including members of Northwell Health Physician Partners, and using 1,600 additional COVID-19 focused beds."We are honored to have the opportunity to join Northwell Health on its mission-driven journey to transform healthcare," said Dan Burton, CEO of Health Catalyst. "We have deep respect for our Northwell colleagues and are excited about combining our Solution with Northwell's team members' experience, knowledge and passion for improvement. We are also honored to have Northwell's CEO Michael Dowling as a keynote speaker at Health Catalyst's upcoming Healthcare Analytics Summit (HAS), where we'll hear his important perspectives on the COVID-19 pandemic and the future of healthcare delivery." This partnership will be built using Health Catalyst's DOS™ technology, kamagra 24 hour delivery a data-first analytics and application platform, to capture and map raw data into meaningful, actionable insights. Northwell Health will also immediately have access to Health Catalyst's growing suite of COVID-19 solutions, including but not limited to a registry, staff and patient tracker and capacity planning tool.

Broadly sharing Northwell Health's data driven insights from its COVID-19 work is another significant opportunity for transformational care."Health Catalyst will become our data and analytics backbone, as their Solutions will enable our kamagra 24 hour delivery organization to take our current data adoption and transformation to entirely new heights," said John Bosco, Senior Vice President and Chief Information Officer at Northwell Health. "We are looking forward to leaning on DOS to create an affordable, yet innovative enterprise solution that will further enable transformative care to the patients we serve."About Northwell HealthNorthwell Health is New York State's largest health care provider and private employer, with 23 hospitals, 665 outpatient facilities and more than 18,500 affiliated physicians. We care for over two million people annually in the New kamagra 24 hour delivery York metro area and beyond, thanks to philanthropic support from our communities. Our 66,000 employees – 16,000-plus nurses and 4,000 employed doctors, including members of Northwell Health Physician Partners – are working to change health care for the better. We are making breakthroughs kamagra 24 hour delivery in medicine at the Feinstein Institute for Medical Research.

We are training the next generation of medical professionals at the visionary Donald and Barbara Zucker School of Medicine at Hofstra/Northwell and the Hofstra Northwell School of Graduate Nursing and Physician Assistant Studies. For information on our more than 100 medical specialties, visit Northwell.edu.About Health CatalystHealth Catalyst is a leading provider of data and analytics technology and services to healthcare organizations, and is committed to being the catalyst for massive, measurable, data-informed healthcare improvement. Its customers leverage the cloud-based data platform—powered by data from more than 100 million patient records and encompassing trillions of facts—as well as its analytics software and professional services expertise to make data-informed kamagra 24 hour delivery decisions and realize measurable clinical, financial and operational improvements. Health Catalyst envisions a future in which all healthcare decisions are data informed. Northwell Health Media Contact:Michelle Pinto516-321-6708mpinto@northwell.edu Health Catalyst Media Contact:Kristen BerrySenior Vice President, Public Relations+1 (617) 234-4123+1 (774) 573-0455 (m)kberry@we-worldwide.com View original content to download multimedia:http://www.prnewswire.com/news-releases/health-catalyst-and-northwell-health-partner-to-transform-patient-care-with-cloud-based-data-and-analytics-enterprise-solution-301110803.htmlSOURCE Health CatalystPeople tried to escape a heat wave baking the West by heading to Castaic Lake kamagra 24 hour delivery in California on Saturday.Credit...Marcio Jose Sanchez/Associated PressFor many Americans, Labor Day is a goodbye to summer before children go back to school and cold weather arrives.

But public health experts are worried that in the midst of a pandemic, the traditional last blast of summer could translate into disaster this fall.After the Memorial Day and Fourth of July weekends, cases of Covid-19 surged around the country after people held family gatherings or congregated in large groups. Dr. Anthony S. Fauci, the country’s top infectious disease expert, said he wanted people to enjoy Labor Day weekend but urged them to take precautions to avoid a post-holiday spike in cases. Take the fun outdoors.

Avoid crowds, keep gatherings to 10 people or fewer. And even outdoors, where transmission risk is much lower, you still need to wear a mask and practice physical distancing if you’re spending time with people outside your household.“We’ve been through this before,” Dr. Fauci said. €œWe see what happens over holiday weekends, and we want to make sure we don’t have an uptick. What I have been saying is kind of a plea to the American public, and to the younger people, that they can enjoy themselves over Labor Day weekend, but please be aware of and adhere to public health guidelines.”In terms of daily case counts, the United States over all was in worse shape going into Labor Day weekend than it was for Memorial Day weekend.

The nation is now averaging about 40,000 new confirmed cases per day, up from about 22,000 per day ahead of Memorial Day weekend. Dr. Fauci said that the number of daily cases in the United States was “unacceptably high” and that a spike in Covid-19 infections following Labor Day would make it far tougher to control the spread of the disease in the fall as people head indoors.“We’d like to get a good head start into the fall by getting our daily cases and our test positivity as low as possible,” Dr. Fauci said. €œIf we get another resurgence of infections after Labor Day, it will make it that much more difficult to get that baseline down and make it much more problematic as we enter the fall season.”Public health experts said it might be even more challenging to persuade people to curtail their Labor Day weekend plans, compared with past holiday weekends, because so many people are suffering from pandemic fatigue after six months of social-distancing restrictions, closures and separation from loved ones.“People are getting tired of taking these precautions and of having their lives upended,” said Eleanor J.

Murray, an assistant professor of epidemiology at the Boston University School of Public Health. €œThey’re missing their friends and family, and everyone wishes things were back to normal. That’s totally understandable, but unfortunately we don’t get a say, really.”Dr. Murray said it was important for people to remember that just one gathering could lead to spikes in cases that https://www.cityreal.lv/buy-kamagra-next-day-delivery/ would affect many more people. She noted that a wedding in Maine with an estimated 65 guests had resulted in 147 infections, including three deaths among people who didn’t even attend the wedding.Dr.

Murray said that if people decided to ignore public health guidelines this weekend, at the very least they should place themselves in quarantine for two weeks after the event. €œIf those people at the wedding had said, ‘This is a risk I’m personally willing to take,’ but after the wedding they had quarantined, then the maximum number of cases would have been the 65 wedding attendees,” she said.Although it’s safer to gather outside than indoors, the virus can still be transmitted in outdoor spaces when people gather in large groups or stand close to one another for long periods of time. Alcohol can loosen inhibitions, prompting people to forget about social distancing. Loud music can prompt people to stand closer and speak louder, which can spew more viral particles and put you at risk even if you’re wearing a mask, health experts say.Dr. Murray said that whatever plan you have for the holiday weekend, ask yourself how you can make it safer for everyone.“People need to socialize and to see people who are important to them,” Dr.

Murray said. €œIf you were thinking of being indoors, go outdoors. If you were thinking about being outdoors, spread out further. Wear masks. Think about what you can do to move down the risk continuum.”While many people feel safer socializing with family members, a number of outbreaks have been traced back to family parties that included relatives from more than one household.

In Maryland, 44 percent of the state’s new cases were traced back to family gatherings, compared with 23 percent from house parties and 21 percent to outdoor events, according to a tweet posted by Gov. Larry Hogan.After a family gathering of two dozen people in Catawba County, N.C., 14 people who attended became ill, but it didn’t end there. €œBefore they started to show symptoms, they continued with their daily lives, such as going to work or taking a beach trip with other families,” Jennifer McCracken, Catawba County’s public health director, wrote in a case study of the event. €œThis set into motion a person-to-person contact chain that to date has spread COVID-19 to 41 people in nine different families and eight different workplaces.”Gregg Gonsalves, an assistant professor of epidemiology at the Yale School of Public Health, said the holiday weekend would multiply the number of family gatherings around the country.“A family gathering one weekend in August that sets off cases in a given county or town is one thing,” Dr. Gonsalves said.

€œOne hundred family gatherings in that county on Labor Day weekend makes it a much larger epidemiological impact.”Dr. Gonsalves said concerns about Labor Day celebrations were being compounded by the fact that there are already large outbreaks on college campuses. €œWe’ve had this gigantic migration event over the past few weeks where students are moving all over the country from homes to universities,” Dr. Gonsalves said. €œThe relative calm of places like New York and Connecticut has to be now thought of in the context of all this big jumble of people crisscrossing the country to get back to college.”ABC News posted a video on Twitter showing crowds of people gathering at a sports bar near the University of South Carolina.

The university has reported more than 1,735 cases since Aug. 1, including 1,461 active cases, according to its Covid-19 dashboard.Brian Pace, a 35-year old psychologist in Phoenix, said he and his friends in Salt Lake City had talked about getting together for a socially distanced outdoor barbecue this weekend. He decided it was smarter to stay home, so he will get takeout from a local barbecue restaurant, JL Smokehouse, instead.“I debated with friends,” Mr. Pace said. €œBut in the end, my decision boiled down to.

Will I look back five years from now and say, ‘That was pretty stupid,’ or regret that I didn’t do it?. It probably would be that it was stupid to do that, so we’re pretty much hunkered down here. When I go out, I wear a mask, and it’s takeout only.”Dr. Fauci said he didn’t want his words of caution about Labor Day celebrations to stop people from enjoying the holiday. He said he personally planned to spend the weekend with his wife, fishing in the Potomac and having dinner with two friends, for a total of four people, on his backyard deck.“You don’t want to tell people on a holiday weekend that even outdoors is bad — they will get completely discouraged,” Dr.

Fauci said. €œWhat we try to say is enjoy outdoors, but you can do it with safe spacing. You can be on a beach, and you don’t have to be falling all over each other. You can be six, seven, eight, nine or 10 feet apart. You can go on a hike.

You can go on a run. You can go on a picnic with a few people. You don’t have to be in a crowd with 30, 40 or 50 people all breathing on each other.”The medical mistakes that befell the 87-year-old mother of a North Carolina pharmacist should not happen to anyone, and my hope is that this column will keep you and your loved ones from experiencing similar, all-too-common mishaps.As the pharmacist, Kim H. DeRhodes of Charlotte, N.C., recalled, it all began when her mother went to the emergency room two weeks after a fall because she had lingering pain in her back and buttocks. Told she had sciatica, the elderly woman was prescribed prednisone and a muscle relaxant.

Three days later, she became delirious, returned to the E.R., was admitted to the hospital, and was discharged two days later when her drug-induced delirium resolved.A few weeks later, stomach pain prompted a third trip to the E.R. And a prescription for an antibiotic and proton-pump inhibitor. Within a month, she developed severe diarrhea lasting several days. Back to the E.R., and this time she was given a prescription for dicyclomine to relieve intestinal spasms, which triggered another bout of delirium and three more days in the hospital. She was discharged after lab tests and imaging studies revealed nothing abnormal.“Review of my mother’s case highlights separate but associated problems.

Likely misdiagnosis and inappropriate prescribing of medications,” Ms. DeRhodes wrote in JAMA Internal Medicine. €œDiagnostic errors led to the use of prescription drugs that were not indicated and caused my mother further harm. The muscle relaxer and prednisone led to her first incidence of delirium. Prednisone likely led to the gastrointestinal issues, and the antibiotic likely led to the diarrhea, which led to the prescribing of dicyclomine, which led to the second incidence of delirium.”The doctors who wrote the woman’s prescriptions apparently never consulted the Beers Criteria, a list created by the American Geriatrics Society of drugs often unsafe for the elderly.In short, Ms.

DeRhodes’s mother was a victim of two medical problems that are too often overlooked by examining doctors and unrecognized by families. The first is giving an 87-year-old medications known to be unsafe for the elderly. The second is a costly and often frightening medically induced condition called “a prescribing cascade” that starts with drug-induced side effects which are then viewed as a new ailment and treated with yet another drug or drugs that can cause still other side effects.I’d like to think that none of this would have happened if instead of going to the E.R. The older woman had seen her primary care doctor. But experts told me that no matter where patients are treated, they are not immune to getting caught in a prescribing cascade.

The problem also can happen to people who self-treat with over-the-counter or herbal remedies. Nor is it limited to the elderly. Young people can also become victims of a prescribing cascade, Ms. DeRhodes said.“Doctors are often taught to think of everything as a new problem,” Dr. Timothy Anderson, internist at Beth Israel Deaconess Medical Center in Boston, said.

€œThey have to start thinking about whether the patient is on medication and whether the medication is the problem.”“Doctors are very good at prescribing but not so good at deprescribing,” Ms. DeRhodes said. €œAnd a lot of times patients are given a prescription without first trying something else.”A popular treatment for high blood pressure, which afflicts a huge proportion of older people, is a common precipitant of the prescribing cascade, Dr. Anderson said.He cited a Canadian study of 41,000 older adults with hypertension who were prescribed drugs called calcium channel blockers. Within a year after treatment began, nearly one person in 10 was given a diuretic to treat leg swelling caused by the first drug.

Many were inappropriately prescribed a so-called loop diuretic that Dr. Anderson said can result in dehydration, kidney problems, lightheadedness and falls.Type 2 diabetes is another common condition in which medications are often improperly prescribed to treat drug-induced side effects, said Lisa M. McCarthy, doctor of pharmacy at the University of Toronto who directed the Canadian study. Recognizing a side effect for what it is can be hampered when the effect doesn’t happen for weeks or even months after a drug is started. While patients taking opioids for pain may readily recognize constipation as a consequence, Dr.

McCarthy said that over time, patients taking metformin for diabetes can develop diarrhea and may self-treat with Lomotil, which in turn can cause dizziness and confusion.Dr. Paula Rochon, geriatrician at Women’s College Hospital in Ontario, said patients taking a drug called a cholinesterase inhibitor to treat early dementia can develop urinary incontinence, which is then treated with another drug that can worsen the patient’s confusion.Complicating matters is the large number of drugs some people take. €œOlder adults frequently take many medications, with two-fifths taking five or more,” Dr. Anderson wrote in JAMA Internal Medicine. In cases of polypharmacy, as this is called, it can be hard to determine which, if any, of the drugs a person is taking is the cause of the current symptom.Dr.

Rochon emphasized that a prescribing cascade can happen to anybody. She said, “Everyone needs to consider the possibility every time a drug is prescribed.”Before accepting a prescription, she recommended that patients or their caregivers should ask the doctor a series of questions, starting with “Am I experiencing a symptom that could be a side effect of a drug I’m taking?. € Follow-up questions should include:Is this new drug being used to treat a side effect?. Is there a safer drug available than the one I’m taking?. Could I take a lower dose of the prescribed drug?.

Most important, Dr. Rochon said, patients should ask “Do I need to take this drug at all?. €Patients and doctors alike often overlook or resist alternatives to medication that may be more challenging to adopt than swallowing a pill. For example, among well-established nondrug remedies for hypertension are weight loss, increasing physical activity, consuming less salt and other sources of sodium, and eating more potassium-rich foods like bananas and cantaloupe.For some patients, frequent use of a nonsteroidal anti-inflammatory drug sold over-the-counter, like ibuprofen or naproxen, is responsible for their elevated blood pressure.The risk of getting caught in a prescribing cascade is increased when patients are prescribed medications by more than one provider. It’s up to patients to be sure every doctor they consult is given an up-to-date list of every drug they take, whether prescription or over-the-counter, as well as nondrug remedies and dietary supplements.

Dr. Rochon recommended that patients maintain an up-to-date list of when and why they started every new drug, along with its dose and frequency, and show that list to the doctor as well..

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Take Kamagra by mouth with a glass of water. The dose is usually taken 1 hour before sexual activity. You should not take the dose more than once per day. Do not take your medicine more often than directed. Overdosage: If you think you have taken too much of Kamagra contact a poison control center or emergency room at once. NOTE: Kamagra is only for you. Do not share Kamagra with others.

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18 or kamagra next day delivery review Extra resources <. 19 in school) 138% FPL*** Children <. 5 and pregnant women have HIGHER LIMITS than shown ESSENTIAL PLAN For MAGI-eligible people over MAGI income limit up to 200% FPL No long term care. See info here 1 2 1 2 3 1 2 Income $875 (up from $859 in 201) $1284 (up from $1,267 in 2019) $1,468 $1,983 $2,498 $2,127 $2,873 Resources $15,750 (up from $15,450 in 2019) $23,100 (up from $22,800 in 2019) NO LIMIT** NO LIMIT SOURCE for 2019 figures is GIS kamagra next day delivery review 18 MA/015 - 2019 Medicaid Levels and Other Updates (PDF). All of the attachments with the various levels are posted here.

NEED TO KNOW PAST MEDICAID INCOME AND RESOURCE LEVELS?. Which kamagra next day delivery review household size applies?. The rules are complicated. See rules here. On the kamagra next day delivery review HRA Medicaid Levels chart - Boxes 1 and 2 are NON-MAGI Income and Resource levels -- Age 65+, Blind or Disabled and other adults who need to use "spend-down" because they are over the MAGI income levels.

Box 10 on page 3 are the MAGI income levels -- The Affordable Care Act changed the rules for Medicaid income eligibility for many BUT NOT ALL New Yorkers. People in the "MAGI" category - those NOT on Medicare -- have expanded eligibility up to 138% of the Federal Poverty Line, so may now qualify for Medicaid even if they were not eligible before, or may now be eligible for Medicaid without a "spend-down." They have NO resource limit. Box 3 on page 1 is Spousal Impoverishment levels for Managed kamagra next day delivery review Long Term Care &. Nursing Homes and Box 8 has the Transfer Penalty rates for nursing home eligibility Box 4 has Medicaid Buy-In for Working People with Disabilities Under Age 65 (still 2017 levels til April 2018) Box 6 are Medicare Savings Program levels (will be updated in April 2018) MAGI INCOME LEVEL of 138% FPL applies to most adults who are not disabled and who do not have Medicare, AND can also apply to adults with Medicare if they have a dependent child/relative under age 18 or under 19 if in school. 42 C.F.R.

§ 435.4 kamagra next day delivery review. Certain populations have an even higher income limit - 224% FPL for pregnant women and babies <. Age 1, 154% FPL for children age 1 - 19. CAUTION kamagra next day delivery review. What is counted as income may not be what you think.

For the NON-MAGI Disabled/Aged 65+/Blind, income will still be determined by the same rules as before, explained in this outline and these charts on income disregards. However, for the MAGI population - which is kamagra next day delivery review virtually everyone under age 65 who is not on Medicare - their income will now be determined under new rules, based on federal income tax concepts - called "Modifed Adjusted Gross Income" (MAGI). There are good changes and bad changes. GOOD. Veteran's benefits, Workers compensation, and gifts from family or others no longer count as income kamagra next day delivery review.

BAD. There is no more "spousal" or parental refusal for this population (but there still is for the Disabled/Aged/Blind.) and some other rules. For all of the rules see kamagra next day delivery review. ALSO SEE 2018 Manual on Lump Sums and Impact on Public Benefits - with resource rules The income limits increase with the "household size." In other words, the income limit for a family of 5 may be higher than the income limit for a single person. HOWEVER, Medicaid rules about how to calculate the household size are not intuitive or even logical.

There are different rules depending on the "category" of the kamagra next day delivery review person seeking Medicaid. Here are the 2 basic categories and the rules for calculating their household size. People who are Disabled, Aged 65+ or Blind - "DAB" or "SSI-Related" Category -- NON-MAGI - See this chart for their household size. These same rules apply to the Medicare Savings Program, with some exceptions explained in this kamagra next day delivery review article. Everyone else -- MAGI - All children and adults under age 65, including people with disabilities who are not yet on Medicare -- this is the new "MAGI" population.

Their household size will be determined using federal income tax rules, which are very complicated. New rule is explained in State's directive 13 ADM-03 - Medicaid Eligibility Changes under the Affordable kamagra next day delivery review Care Act (ACA) of 2010 (PDF) pp. 8-10 of the PDF, This PowerPoint by NYLAG on MAGI Budgeting attempts to explain the new MAGI budgeting, including how to determine the Household Size. See slides 28-49. Also seeLegal Aid Society and Empire Justice Center materials OLD RULE used until end of 2013 -- Count the person(s) applying for Medicaid kamagra next day delivery review who live together, plus any of their legally responsible relatives who do not receive SNA, ADC, or SSI and reside with an applicant/recipient.

Spouses or legally responsible for one another, and parents are legally responsible for their children under age 21 (though if the child is disabled, use the rule in the 1st "DAB" category. Under this rule, a child may be excluded from the household if that child's income causes other family members to lose Medicaid eligibility. See kamagra next day delivery review 18 NYCRR 360-4.2, MRG p. 573, NYS GIS 2000 MA-007 CAUTION. Different people in the same household may be in different "categories" and hence have different household sizes AND Medicaid income and resource limits.

If a man is age 67 and has Medicare and his wife is age 62 and not disabled or blind, the husband's household size for Medicaid is kamagra next day delivery review determined under Category 1/ Non-MAGI above and his wife's is under Category 2/MAGI. The following programs were available prior to 2014, but are now discontinued because they are folded into MAGI Medicaid. Prenatal Care Assistance Program (PCAP) was Medicaid for pregnant women and children under age 19, with higher income limits for pregnant woman and infants under one year (200% FPL for pregnant women receiving perinatal coverage only not full Medicaid) than for children ages 1-18 (133% FPL). Medicaid for adults between ages 21-65 who are not disabled and without children under 21 in kamagra next day delivery review the household. It was sometimes known as "S/CC" category for Singles and Childless Couples.

This category had lower income limits than DAB/ADC-related, but had no asset limits. It did not allow "spend down" of excess kamagra next day delivery review income. This category has now been subsumed under the new MAGI adult group whose limit is now raised to 138% FPL. Family Health Plus - this was an expansion of Medicaid to families with income up to 150% FPL and for childless adults up to 100% FPL. This has kamagra next day delivery review now been folded into the new MAGI adult group whose limit is 138% FPL.

For applicants between 138%-150% FPL, they will be eligible for a new program where Medicaid will subsidize their purchase of Qualified Health Plans on the Exchange. PAST INCOME &. RESOURCE LEVELS -- Past Medicaid income and resource levels in NYS are shown on these oldNYC HRA charts for kamagra next day delivery review 2001 through 2019, in chronological order. These include Medicaid levels for MAGI and non-MAGI populations, Child Health Plus, MBI-WPD, Medicare Savings Programs and other public health programs in NYS. This article was authored by the Evelyn Frank Legal Resources Program of New York Legal Assistance Group.A huge barrier to people returning to the community from nursing homes is the high cost of housing.

One way New York State is trying to address that barrier is with the Special Housing Disregard that allows certain members of Managed Long Term Care or FIDA plans to keep more of their income to pay for rent or kamagra next day delivery review other shelter costs, rather than having to "spend down" their "excess income" or spend-down on the cost of Medicaid home care. The special income standard for housing expenses helps pay for housing expenses to help certain nursing home or adult home residents to safely transition back to the community with MLTC. Originally it was just for former nursing home residents but in 2014 it was expanded to include people who lived in adult homes. GIS 14/MA-017 Since you are allowed to keep more of your income, you may no longer need kamagra next day delivery review to use a pooled trust. KNOW YOUR RIGHTS - FACT SHEET on THREE ways to Reduce Spend-down, including this Special Income Standard.

September 2018 NEWS -- Those already enrolled in MLTC plans before they are admitted to a nursing home or adult home may obtain this budgeting upon discharge, if they meet the other criteria below. "How nursing home administrators, adult home operators and MLTC plans should identify individuals who are eligible for the special kamagra next day delivery review income standard" and explains their duties to identify eligible individuals, and the MLTC plan must notify the local DSS that the individual may qualify. "Nursing home administrators, nursing home discharge planning staff, adult home operators and MLTC health plans are encouraged to identify individuals who may qualify for the special income standard, if they can be safely discharged back to the community from a nursing home and enroll in, or remain enrolled in, an MLTC plan. Once an individual has been accepted into an MLTC plan, the MLTC plan must notify the individual's local district of social services that the transition has occurred and that the individual may qualify for the special income standard. The special income standard will be effective kamagra next day delivery review upon enrollment into the MLTC plan, or, for nursing home residents already enrolled in an MLTC plan, the month of discharge to the community.

Questions regarding the special income standard may be directed to DOH at 518-474-8887. Who is eligible for this special income standard?. must be age 18+, must have been in a nursing home or an adult home for 30 days or more, must have had Medicaid pay toward the nursing home care, and must enroll in or REMAIN ENROLLED IN a Managed Long Term Care (MLTC) plan kamagra next day delivery review or FIDA plan upon leaving the nursing home or adult home must have a housing expense if married, spouse may not receive a "spousal impoverishment" allowance once the individual is enrolled in MLTC. How much is the allowance?. The rates vary by region and change yearly.

Region Counties Deduction (2020) Central Broome, Cayuga, Chenango, Cortland, Herkimer, Jefferson, Lewis, Madison, Oneida, kamagra next day delivery review Onondaga, Oswego, St. Lawrence, Tioga, Tompkins $436 Long Island Nassau, Suffolk $1,361 NYC Bronx, Kings, Manhattan, Queens, Richmond $1,451 (up from 1,300 in 2019) Northeastern Albany, Clinton, Columbia, Delaware, Essex, Franklin, Fulton, Greene, Hamilton, Montgomery, Otsego, Rensselaer, Saratoga, Schenectady, Schoharie, Warren, Washington $483 North Metropolitan Dutchess, Orange, Putnam, Rockland, Sullivan, Ulster, Westchester $930 Rochester Chemung, Livingston, Monroe, Ontario, Schuyler, Seneca, Steuben, Wayne, Yates $444 Western Allegany, Cattaraugus, Chautauqua, Erie, Genesee, Niagara, Orleans, Wyoming $386 Past rates published as follows, available on DOH website 2020 rates published in Attachment I to GIS 19 MA/12 – 2020 Medicaid Levels and Other Updates 2019 rates published in Attachment 1 to GIS 18/MA015 - 2019 Medicaid Levels and Other Updates 2018 rates published in GIS 17 MA/020 - 2018 Medicaid Levels and Other Updates. The guidance on how the standardized amount of the disregard is calculated is found in NYS DOH 12- ADM-05. 2017 rate -- GIS 16 MA/018 - 2016 Medicaid Only Income and Resource Levels and Spousal Impoverishment Standards kamagra next day delivery review Attachment 12016 rate -- GIS 15-MA/0212015 rate -- Were not posted by DOH but were updated in WMS. 2015 Central $382 Long Island $1,147 NYC $1,001 Northeastern $440 N.

Metropolitan $791 Rochester $388 Western $336 2014 rate -- GIS-14-MA/017 HOW DOES IT WORK?. Here is a sample budget for a single person in NYC with Social Security income of $2,386/month paying a Medigap premium of $261/mo. Gross monthly income $2,575.50 DEDUCT Health insurance premiums (Medicare Part B) - 135.50 (Medigap) - 261.00 DEDUCT Unearned income disregard - 20 DEDUCT Shelter deduction (NYC—2019) - 1,300 DEDUCT Income limit for single (2019) - 859 Excess income or Spend-down $0 WITH NO SPEND-DOWN, May NOT NEED POOLED TRUST!. HOW TO OBTAIN THE HOUSING DISREGARD. When you are ready to leave the nursing home or adult home, or soon after you leave, you or your MLTC plan must request that your local Medicaid program change your Medicaid budget to give you the Housing Disregard.

See September 2018 NYS DOH Medicaid Update that requires MLTC plan to help you ask for it. The procedures in NYC are explained in this Troubleshooting guide. NYC Medicaid program prefers that your MLTC plan file the request, using Form MAP-3057E - Special income housing Expenses NH-MLTC.pdf and Form MAP-3047B - MLTC/NHED Cover Sheet Form MAP-259f (revised 7-31-18)(page 7 of PDF)(DIscharge Notice) - NH must file with HRA upon discharge, certifying resident was informed of availability of this disregard. GOVERNMENT DIRECTIVES (beginning with oldest). NYS DOH 12- ADM-05 - Special Income Standard for Housing Expenses for Individuals Discharged from a Nursing Facility who Enroll into the Managed Long Term Care (MLTC) Program Attachment II - OHIP-0057 - Notice of Intent to Change Medicaid Coverage, (Recipient Discharged from a Skilled Nursing Facility and Enrolled in a Managed Long Term Care Plan) Attachment III - Attachment III – OHIP-0058 - Notice of Intent to Change Medicaid Coverage, (Recipient Disenrolled from a Managed Long Term Care Plan, No Special Income Standard) MLTC Policy 13.02.

MLTC Housing Disregard NYC HRA Medicaid Alert Special Income Standard for housing expenses NH-MLTC 2-9-2013.pdf 2018-07-28 HRA MICSA ALERT Special Income Standard for Housing Expenses for Individuals Discharged from a Nursing Facility and who Enroll into the MLTC Program - update on previous policy. References Form MAP-259f (revised 7-31-18)(page 7 of PDF)(Discharge Notice) - NH must file with HRA upon discharge, certifying resident was informed of availability of this disregard. GIS 18 MA/012 - Special Income Standard for Housing Expenses for Certain Managed Long-Term Care Enrollees Who are Discharged from a Nursing Home issued Sept. 28, 2018 - this finally implements the most recent Special Terms &.

18 or kamagra 24 hour delivery < company website. 19 in school) 138% FPL*** Children <. 5 and pregnant women have HIGHER LIMITS than shown ESSENTIAL PLAN For MAGI-eligible people over MAGI income limit up to 200% FPL No long term care.

See info here 1 2 1 2 3 1 2 Income $875 (up from $859 in 201) $1284 (up from $1,267 in 2019) $1,468 $1,983 $2,498 $2,127 $2,873 Resources $15,750 (up from $15,450 in 2019) $23,100 (up from $22,800 in 2019) NO LIMIT** NO LIMIT SOURCE for 2019 figures is GIS 18 MA/015 - 2019 Medicaid Levels and Other Updates kamagra 24 hour delivery (PDF). All of the attachments with the various levels are posted here. NEED TO KNOW PAST MEDICAID INCOME AND RESOURCE LEVELS?.

Which household size kamagra 24 hour delivery applies?. The rules are complicated. See rules here.

On the HRA Medicaid Levels chart - Boxes 1 and 2 are NON-MAGI Income and kamagra 24 hour delivery Resource levels -- Age 65+, Blind or Disabled and other adults who need to use "spend-down" because they are over the MAGI income levels. Box 10 on page 3 are the MAGI income levels -- The Affordable Care Act changed the rules for Medicaid income eligibility for many BUT NOT ALL New Yorkers. People in the "MAGI" category - those NOT on Medicare -- have expanded eligibility up to 138% of the Federal Poverty Line, so may now qualify for Medicaid even if they were not eligible before, or may now be eligible for Medicaid without a "spend-down." They have NO resource limit.

Box 3 on page kamagra 24 hour delivery 1 is Spousal Impoverishment levels for Managed Long Term Care &. Nursing Homes and Box 8 has the Transfer Penalty rates for nursing home eligibility Box 4 has Medicaid Buy-In for Working People with Disabilities Under Age 65 (still 2017 levels til April 2018) Box 6 are Medicare Savings Program levels (will be updated in April 2018) MAGI INCOME LEVEL of 138% FPL applies to most adults who are not disabled and who do not have Medicare, AND can also apply to adults with Medicare if they have a dependent child/relative under age 18 or under 19 if in school. 42 C.F.R.

§ 435.4 kamagra 24 hour delivery. Certain populations have an even higher income limit - 224% FPL for pregnant women and babies <. Age 1, 154% FPL for children age 1 - 19.

CAUTION kamagra 24 hour delivery. What is counted as income may not be what you think. For the NON-MAGI Disabled/Aged 65+/Blind, income will still be determined by the same rules as before, explained in this outline and these charts on income disregards.

However, for the MAGI population - which is virtually everyone under age 65 who is not on Medicare - their income will now be determined under new rules, based on federal income kamagra 24 hour delivery tax concepts - called "Modifed Adjusted Gross Income" (MAGI). There are good changes and bad changes. GOOD.

Veteran's benefits, Workers compensation, and gifts from family or others kamagra 24 hour delivery no longer count as income. BAD. There is no more "spousal" or parental refusal for this population (but there still is for the Disabled/Aged/Blind.) and some other rules.

For all of the rules kamagra 24 hour delivery see. ALSO SEE 2018 Manual on Lump Sums and Impact on Public Benefits - with resource rules The income limits increase with the "household size." In other words, the income limit for a family of 5 may be higher than the income limit for a single person. HOWEVER, Medicaid rules about how to calculate the household size are not intuitive or even logical.

There are different rules depending on the "category" kamagra 24 hour delivery of the person seeking Medicaid. Here are the 2 basic categories and the rules for calculating their household size. People who are Disabled, Aged 65+ or Blind - "DAB" or "SSI-Related" Category -- NON-MAGI - See this chart for their household size.

These same rules apply to the Medicare Savings Program, with some kamagra 24 hour delivery exceptions explained in this article. Everyone else -- MAGI - All children and adults under age 65, including people with disabilities who are not yet on Medicare -- this is the new "MAGI" population. Their household size will be determined using federal income tax rules, which are very complicated.

New rule is explained in State's directive 13 ADM-03 - Medicaid Eligibility Changes under the Affordable Care Act (ACA) of 2010 kamagra 24 hour delivery (PDF) pp. 8-10 of the PDF, This PowerPoint by NYLAG on MAGI Budgeting attempts to explain the new MAGI budgeting, including how to determine the Household Size. See slides 28-49.

Also seeLegal Aid Society and Empire Justice Center materials OLD RULE used until end of 2013 -- Count the person(s) applying for Medicaid kamagra 24 hour delivery who live together, plus any of their legally responsible relatives who do not receive SNA, ADC, or SSI and reside with an applicant/recipient. Spouses or legally responsible for one another, and parents are legally responsible for their children under age 21 (though if the child is disabled, use the rule in the 1st "DAB" category. Under this rule, a child may be excluded from the household if that child's income causes other family members to lose Medicaid eligibility.

See 18 kamagra 24 hour delivery NYCRR 360-4.2, MRG p. 573, NYS GIS 2000 MA-007 CAUTION. Different people in the same household may be in different "categories" and hence have different household sizes AND Medicaid income and resource limits.

If a man is age 67 and has Medicare and his wife is age 62 and not disabled or blind, the husband's household size for kamagra 24 hour delivery Medicaid is determined under Category 1/ Non-MAGI above and his wife's is under Category 2/MAGI. The following programs were available prior to 2014, but are now discontinued because they are folded into MAGI Medicaid. Prenatal Care Assistance Program (PCAP) was Medicaid for pregnant women and children under age 19, with higher income limits for pregnant woman and infants under one year (200% FPL for pregnant women receiving perinatal coverage only not full Medicaid) than for children ages 1-18 (133% FPL).

Medicaid for adults between ages 21-65 who are not disabled and without children kamagra 24 hour delivery under 21 in the household. It was sometimes known as "S/CC" category for Singles and Childless Couples. This category had lower income limits than DAB/ADC-related, but had no asset limits.

It kamagra 24 hour delivery did not allow "spend down" of excess income. This category has now been subsumed under the new MAGI adult group whose limit is now raised to 138% FPL. Family Health Plus - this was an expansion of Medicaid to families with income up to 150% FPL and for childless adults up to 100% FPL.

This has now been folded into the new MAGI adult group whose limit is 138% FPL kamagra 24 hour delivery. For applicants between 138%-150% FPL, they will be eligible for a new program where Medicaid will subsidize their purchase of Qualified Health Plans on the Exchange. PAST INCOME &.

RESOURCE LEVELS -- Past Medicaid income and resource levels in NYS are kamagra 24 hour delivery shown on these oldNYC HRA charts for 2001 through 2019, in chronological order. These include Medicaid levels for MAGI and non-MAGI populations, Child Health Plus, MBI-WPD, Medicare Savings Programs and other public health programs in NYS. This article was authored by the Evelyn Frank Legal Resources Program of New York Legal Assistance Group.A huge barrier to people returning to the community from nursing homes is the high cost of housing.

One way New York State is kamagra 24 hour delivery trying to address that barrier is with the Special Housing Disregard that allows certain members of Managed Long Term Care or FIDA plans to keep more of their income to pay for rent or other shelter costs, rather than having to "spend down" their "excess income" or spend-down on the cost of Medicaid home care. The special income standard for housing expenses helps pay for housing expenses to help certain nursing home or adult home residents to safely transition back to the community with MLTC. Originally it was just for former nursing home residents but in 2014 it was expanded to include people who lived in adult homes.

GIS 14/MA-017 Since you are allowed to keep more of your income, kamagra 24 hour delivery you may no longer need to use a pooled trust. KNOW YOUR RIGHTS - FACT SHEET on THREE ways to Reduce Spend-down, including this Special Income Standard. September 2018 NEWS -- Those already enrolled in MLTC plans before they are admitted to a nursing home or adult home may obtain this budgeting upon discharge, if they meet the other criteria below.

"How nursing home administrators, adult home operators and MLTC plans should identify individuals who are eligible for the special income standard" and explains their duties to identify eligible individuals, and the kamagra 24 hour delivery MLTC plan must notify the local DSS that the individual may qualify. "Nursing home administrators, nursing home discharge planning staff, adult home operators and MLTC health plans are encouraged to identify individuals who may qualify for the special income standard, if they can be safely discharged back to the community from a nursing home and enroll in, or remain enrolled in, an MLTC plan. Once an individual has been accepted into an MLTC plan, the MLTC plan must notify the individual's local district of social services that the transition has occurred and that the individual may qualify for the special income standard.

The special income standard will be effective upon enrollment into the MLTC plan, or, for nursing home residents already enrolled in an MLTC plan, the month of kamagra 24 hour delivery discharge to the community. Questions regarding the special income standard may be directed to DOH at 518-474-8887. Who is eligible for this special income standard?.

must be age 18+, kamagra 24 hour delivery must have been in a nursing home or an adult home for 30 days or more, must have had Medicaid pay toward the nursing home care, and must enroll in or REMAIN ENROLLED IN a Managed Long Term Care (MLTC) plan or FIDA plan upon leaving the nursing home or adult home must have a housing expense if married, spouse may not receive a "spousal impoverishment" allowance once the individual is enrolled in MLTC. How much is the allowance?. The rates vary by region and change yearly.

Region Counties Deduction (2020) Central Broome, Cayuga, Chenango, Cortland, Herkimer, Jefferson, Lewis, Madison, Oneida, Onondaga, Oswego, St. Lawrence, Tioga, Tompkins $436 Long Island Nassau, Suffolk $1,361 NYC Bronx, Kings, Manhattan, Queens, Richmond $1,451 (up from 1,300 in 2019) Northeastern Albany, Clinton, Columbia, Delaware, Essex, Franklin, Fulton, Greene, Hamilton, Montgomery, Otsego, Rensselaer, Saratoga, Schenectady, Schoharie, Warren, Washington $483 North Metropolitan Dutchess, Orange, Putnam, Rockland, Sullivan, Ulster, Westchester $930 Rochester Chemung, Livingston, Monroe, Ontario, Schuyler, Seneca, Steuben, Wayne, Yates $444 Western Allegany, Cattaraugus, Chautauqua, Erie, Genesee, Niagara, Orleans, Wyoming $386 Past rates published as follows, available on DOH website 2020 rates published in Attachment I to GIS 19 MA/12 – 2020 Medicaid Levels and Other Updates 2019 rates published in Attachment 1 to GIS 18/MA015 - 2019 Medicaid Levels and Other Updates 2018 rates published in GIS 17 MA/020 - 2018 Medicaid Levels and Other Updates. The guidance on how the standardized amount of the disregard is calculated is found in NYS DOH 12- ADM-05.

2017 rate -- GIS 16 MA/018 - 2016 Medicaid Only Income and Resource Levels and Spousal Impoverishment Standards Attachment 12016 rate -- GIS 15-MA/0212015 rate -- Were not posted by DOH but were updated in WMS. 2015 Central $382 Long Island $1,147 NYC $1,001 Northeastern $440 N. Metropolitan $791 Rochester $388 Western $336 2014 rate -- GIS-14-MA/017 HOW DOES IT WORK?.

Here is a sample budget for a single person in NYC with Social Security income of $2,386/month paying a Medigap premium of $261/mo. Gross monthly income $2,575.50 DEDUCT Health insurance premiums (Medicare Part B) - 135.50 (Medigap) - 261.00 DEDUCT Unearned income disregard - 20 DEDUCT Shelter deduction (NYC—2019) - 1,300 DEDUCT Income limit for single (2019) - 859 Excess income or Spend-down $0 WITH NO SPEND-DOWN, May NOT NEED POOLED TRUST!. HOW TO OBTAIN THE HOUSING DISREGARD.

When you are ready to leave the nursing home or adult home, or soon after you leave, you or your MLTC plan must request that your local Medicaid program change your Medicaid budget to give you the Housing Disregard. See September 2018 NYS DOH Medicaid Update that requires MLTC plan to help you ask for it. The procedures in NYC are explained in this Troubleshooting guide.

NYC Medicaid program prefers that your MLTC plan file the request, using Form MAP-3057E - Special income housing Expenses NH-MLTC.pdf and Form MAP-3047B - MLTC/NHED Cover Sheet Form MAP-259f (revised 7-31-18)(page 7 of PDF)(DIscharge Notice) - NH must file with HRA upon discharge, certifying resident was informed of availability of this disregard. GOVERNMENT DIRECTIVES (beginning with oldest). NYS DOH 12- ADM-05 - Special Income Standard for Housing Expenses for Individuals Discharged from a Nursing Facility who Enroll into the Managed Long Term Care (MLTC) Program Attachment II - OHIP-0057 - Notice of Intent to Change Medicaid Coverage, (Recipient Discharged from a Skilled Nursing Facility and Enrolled in a Managed Long Term Care Plan) Attachment III - Attachment III – OHIP-0058 - Notice of Intent to Change Medicaid Coverage, (Recipient Disenrolled from a Managed Long Term Care Plan, No Special Income Standard) MLTC Policy 13.02.

MLTC Housing Disregard NYC HRA Medicaid Alert Special Income Standard for housing expenses NH-MLTC 2-9-2013.pdf 2018-07-28 HRA MICSA ALERT Special Income Standard for Housing Expenses for Individuals Discharged from a Nursing Facility and who Enroll into the MLTC Program - update on previous policy. References Form MAP-259f (revised 7-31-18)(page 7 of PDF)(Discharge Notice) - NH must file with HRA upon discharge, certifying resident was informed of availability of this disregard. GIS 18 MA/012 - Special Income Standard for Housing Expenses for Certain Managed Long-Term Care Enrollees Who are Discharged from a Nursing Home issued Sept.

28, 2018 - this finally implements the most recent Special Terms &.

Does kamagra work with alcohol

In her https://www.cityreal.lv/kamagra-prescription/ opening statement before the Senate Judiciary Committee last week, Judge does kamagra work with alcohol Amy Coney Barrett, President Trump's nominee to the Supreme Court, opined that courts are not policymakers.This should not be surprising -- after all, she has also said that the courts' obligation is not to decide what legislators meant in the words used to write laws, only to seek out their clarity. Barrett also criticized Supreme Court Chief Justice John Roberts' majority opinion in a 2012 case upholding the Affordable Care Act (ACA), saying that he failed to follow the clear language of the statute when he decided that the fine imposed under the law for not purchasing health insurance was a "tax" allowed under Congress' taxing authority and not a penalty disallowed by the Commerce Clause.In fact, Trump is before the Supreme Court right now, with a case being argued before the justices on Nov. 10 arguing that does kamagra work with alcohol all of Obamacare is unconstitutional.

Pundits have rightfully conjectured that he chose Barrett to do his bidding and vote to strike down the law. As Barrett's confirmation hearing began last week, Trump tweeted:"We will have Healthcare which is FAR BETTER than ObamaCare, at a FAR LOWER COST – big premium REDUCTION, PEOPLE WITH PRE EXISTING CONDITIONS WILL BE does kamagra work with alcohol PROTECTED AT AN EVEN HIGHER LEVEL THAN NOW. HIGHLY UNPOPULAR AND UNFAIR INDIVIDUAL MANDATE ALREADY TERMINATED.

YOU'RE WELCOME! does kamagra work with alcohol. "He has delivered such a message throughout his presidency, in this year alone starting with his State of the Union address, declaring support for Americans with pre-existing conditions and promising every so often that he will be introducing a spanking new healthcare plan to replace the ACA. Nothing has come forth, does kamagra work with alcohol nor will it.

It's pure bluster and deceit.Trump's Last Chance -- Possibly -- to Destroy the ACABut a struggle now comes to bear between Barrett's views on what courts are limited in doing, and Trump wanting her to be his messenger. Trump knows this may be his last chance to destroy Obama's most prizeworthy legislative achievement, one that has survived 70 attempts by Republicans in does kamagra work with alcohol Congress to kill it. Indeed, Democrats are characterizing Barrett's nomination as an attack on Americans' right to healthcare.Barrett told committee members that her prior published views disagreeing with the Supreme Court's two decisions upholding Obamacare (in another case in 2015, the Supreme Court also found the ACA constitutional) have no bearing on her thinking, because the case before the court in November deals with a different issue.

Whether the individual mandate, if it's unconstitutional, can be easily does kamagra work with alcohol severed from the rest of the 974-page law. That reasoning is questionable because before the court can address severability, it must first decide whether the mandate is constitutional.She concurs that severing an unconstitutional provision from the rest of a statute is always a judge's "presumption" and stressed, "I am not here on a mission to destroy the Affordable Care Act. I'm here to apply the law and adhere to the rule of law." She also gave no commitments to the White House on how she would rule.

(A more complete analysis of the options for what the does kamagra work with alcohol Supreme Court may do with Barrett on the bench is covered here.)Despite Barrett's protestations to the contrary, it's unclear how unbiased she might be if she does get on the high court -- remember that Trump chose her. A more fundamental question lurks. Regardless of how cases are decided, is it ethical to take away a law that has become a legislative embodiment of what many now consider to be their lifeline does kamagra work with alcohol -- their right -- to healthcare?.

The History of the Right to HealthcareBack in 2008 while Obama was on the campaign trail running against the late Sen. John McCain (R-Ariz.), he called healthcare a does kamagra work with alcohol right -- not a privilege or a responsibility. That position has become the description du jour this election cycle by many running for office, but they were not the https://www.cityreal.lv/kamagra-fast-next-day-delivery first.

Various forms for providing healthcare besides the ACA have been floated since, from a Medicare-for-All system, to reducing the age to become Medicare-eligible, to amending ACA with a public option, the latter does kamagra work with alcohol supported by Biden. Opponents of government-run healthcare rail against government interference in their lives and call such systems "socialism," even as they hold tightly to their Medicare cards. And consider who paid for Trump's recent COVID-19 hospital and medical care at does kamagra work with alcohol Walter Reed.

It surely wasn't a private insurer.The idea of healthcare as a right has been around for decades, tracing its roots back to FDR in 1943 when he crafted his proposed "Second Bill of Rights." As more fully explained by authors Jean Carmalt and Sarah Zaidi, FDR declared "freedom from want" to be four essential liberties for human security, including "the right to adequate medical care and the opportunity to achieve and enjoy good health." Carmalt and Zaidi wrote, "The right to health was subsequently enshrined in the Universal Declaration of Human Rights, a 1948 United Nations document." We can even go back to the Declaration of Independence for our inalienable rights to life, liberty, and the pursuit of happiness as words connoting an ability to achieve, maintain, and regain our health.Of course, there is no "right" to healthcare in the Constitution. Instead, it is considered a moral imperative, a human right -- at least, that's how does kamagra work with alcohol every other industrialized country views it except for the U.S., where it's considered a profit-making opportunity. True, other facets of life might also be considered "rights" -- equal treatment for LGBTQ persons, fair housing, civil rights, and the right to vote.

And while each of those is surely a noble cause, healthcare is the only one that affects every one of us from birth to death (including the "right to die" for those terminally ill with a painful disease).Ethical Questions to PonderThe judiciary committee expects to approve Barrett's nomination along party lines later this week, and full Senate approval is expected soon thereafter. In the does kamagra work with alcohol meantime, her nomination has become a symbol for assaulting the ACA, a law that's a prime example of the right to healthcare.This assault on the healthcare law raises many ethical questions. Is it ethical, for example, to decide a seminal law in a way that allows destruction of a moral imperative that millions of Americans have counted on for a decade to preserve and protect health?.

That includes those enrolled in its Medicaid expansion programs, children who are now allowed to remain on their parents' policies until does kamagra work with alcohol age 26, and anyone benefitting from the law's ban on annual or lifetime coverage caps. Not to mention the more than 8 million people infected with COVID-19 who will benefit from the ACA's ban on insurer discrimination against people with preexisting conditions.The justices will have to decide the ACA case using analyses within a legal framework and employing various legal doctrines, notably severability. But another does kamagra work with alcohol dilemma, also of some ethical proportion, awaits their particular analysis.

If they find the entire act unconstitutional, there is currently nothing with which to replace it, nor is a replacement likely to appear any time soon. The court may have to decide the case, but it can't simply throw Obamacare under the bus even does kamagra work with alcohol as the justices know their newest member was chosen through a process that some are calling a sham. Barrett's nomination has proceeded at warp speed while an election is ongoing, with millions of votes for the next president already cast.Not since the days of Abraham Lincoln -- in which a vacancy occurred 27 days before a presidential election -- has a justice been chosen in such haste and with utter disregard for what the people want.

(Lincoln, unlike Trump, waited until immediately after the election to nominate a replacement -- both because the Senate wasn't in session does kamagra work with alcohol when the vacancy occurred, and because he could use the opening to his advantage during the campaign.) Even Barrett's colleagues at the University of Notre Dame, in an open letter, are calling on her to put the country ahead of the rush to get her confirmed.Whether she likes it or not, Amy Coney Barrett has become the poster child for whether or not the ACA will remain the sine qua non of healthcare as a right for all.Miles J. Zaremski, JD, has been a healthcare attorney and writer for 47 years. He has written and lectured extensively in the healthcare law space, both nationally and abroad does kamagra work with alcohol.

He has written books and also contributed essays to the Huffington Post and to CNN's Michael Smerconish site. He is past president of the American College of Legal Medicine and for 5 years served as chair of the American Bar Association's Standing Committee on Medical Professional Liability..

In her opening statement before this the Senate Judiciary Committee last week, Judge Amy Coney Barrett, President Trump's nominee to the Supreme Court, opined that courts are not policymakers.This should not be surprising -- after all, she kamagra 24 hour delivery has also said that the courts' obligation is not to decide what legislators meant in the words used to write laws, only to seek out their clarity. Barrett also criticized Supreme Court Chief Justice John Roberts' majority opinion in a 2012 case upholding the Affordable Care Act (ACA), saying that he failed to follow the clear language of the statute when he decided that the fine imposed under the law for not purchasing health insurance was a "tax" allowed under Congress' taxing authority and not a penalty disallowed by the Commerce Clause.In fact, Trump is before the Supreme Court right now, with a case being argued before the justices on Nov. 10 arguing kamagra 24 hour delivery that all of Obamacare is unconstitutional.

Pundits have rightfully conjectured that he chose Barrett to do his bidding and vote to strike down the law. As Barrett's confirmation hearing began last week, Trump tweeted:"We will have Healthcare which is FAR BETTER than ObamaCare, at a FAR LOWER COST – big premium REDUCTION, PEOPLE WITH PRE EXISTING CONDITIONS WILL BE PROTECTED AT AN EVEN HIGHER LEVEL THAN NOW kamagra 24 hour delivery. HIGHLY UNPOPULAR AND UNFAIR INDIVIDUAL MANDATE ALREADY TERMINATED.

YOU'RE WELCOME! kamagra 24 hour delivery. "He has delivered such a message throughout his presidency, in this year alone starting with his State of the Union address, declaring support for Americans with pre-existing conditions and promising every so often that he will be introducing a spanking new healthcare plan to replace the ACA. Nothing has come forth, nor kamagra 24 hour delivery will it.

It's pure bluster and deceit.Trump's Last Chance -- Possibly -- to Destroy the ACABut a struggle now comes to bear between Barrett's views on what courts are limited in doing, and Trump wanting her to be his messenger. Trump knows this may be his last chance to kamagra 24 hour delivery destroy Obama's most prizeworthy legislative achievement, one that has survived 70 attempts by Republicans in Congress to kill it. Indeed, Democrats are characterizing Barrett's nomination as an attack on Americans' right to healthcare.Barrett told committee members that her prior published views disagreeing with the Supreme Court's two decisions upholding Obamacare (in another case in 2015, the Supreme Court also found the ACA constitutional) have no bearing on her thinking, because the case before the court in November deals with a different issue.

Whether the individual mandate, if it's unconstitutional, can be kamagra 24 hour delivery easily severed from the rest of the 974-page law. That reasoning is questionable because before the court can address severability, it must first decide whether the mandate is constitutional.She concurs that severing an unconstitutional provision from the rest of a statute is always a judge's "presumption" and stressed, "I am not here on a mission to destroy the Affordable Care Act. I'm here to apply the law and adhere to the rule of law." She also gave no commitments to the White House on how she would rule.

(A more complete analysis of the options for what the Supreme Court may do with Barrett on the bench is covered here.)Despite Barrett's protestations to the contrary, it's unclear how unbiased she might be if she kamagra 24 hour delivery does get on the high court -- remember that Trump chose her. A more fundamental question lurks. Regardless of how cases are decided, is it ethical to take away a law that has become a legislative embodiment of what kamagra 24 hour delivery many now consider to be their lifeline -- their right -- to healthcare?.

The History of the Right to HealthcareBack in 2008 while Obama was on the campaign trail running against the late Sen. John McCain (R-Ariz.), he called healthcare a right -- not kamagra 24 hour delivery a privilege or a responsibility. That position More hints has become the description du jour this election cycle by many running for office, but they were not the first.

Various forms for providing healthcare besides the ACA have been floated since, from a Medicare-for-All system, to reducing the age to become Medicare-eligible, to amending ACA with kamagra 24 hour delivery a public option, the latter supported by Biden. Opponents of government-run healthcare rail against government interference in their lives and call such systems "socialism," even as they hold tightly to their Medicare cards. And consider who paid for Trump's recent kamagra 24 hour delivery COVID-19 hospital and medical care at Walter Reed.

It surely wasn't a private insurer.The idea of healthcare as a right has been around for decades, tracing its roots back to FDR in 1943 when he crafted his proposed "Second Bill of Rights." As more fully explained by authors Jean Carmalt and Sarah Zaidi, FDR declared "freedom from want" to be four essential liberties for human security, including "the right to adequate medical care and the opportunity to achieve and enjoy good health." Carmalt and Zaidi wrote, "The right to health was subsequently enshrined in the Universal Declaration of Human Rights, a 1948 United Nations document." We can even go back to the Declaration of Independence for our inalienable rights to life, liberty, and the pursuit of happiness as words connoting an ability to achieve, maintain, and regain our health.Of course, there is no "right" to healthcare in the Constitution. Instead, it is considered a kamagra 24 hour delivery moral imperative, a human right -- at least, that's how every other industrialized country views it except for the U.S., where it's considered a profit-making opportunity. True, other facets of life might also be considered "rights" -- equal treatment for LGBTQ persons, fair housing, civil rights, and the right to vote.

And while each of those is surely a noble cause, healthcare is the only one that affects every one of us from birth to death (including the "right to die" for those terminally ill with a painful disease).Ethical Questions to PonderThe judiciary committee expects to approve Barrett's nomination along party lines later this week, and full Senate approval is expected soon thereafter. In the meantime, her nomination has become a symbol for assaulting the ACA, a law that's a prime example of the right kamagra 24 hour delivery to healthcare.This assault on the healthcare law raises many ethical questions. Is it ethical, for example, to decide a seminal law in a way that allows destruction of a moral imperative that millions of Americans have counted on for a decade to preserve and protect health?.

That includes those enrolled in its Medicaid expansion programs, children who are now allowed to remain on their parents' policies until age 26, and anyone benefitting from the law's ban on annual or kamagra 24 hour delivery lifetime coverage caps. Not to mention the more than 8 million people infected with COVID-19 who will benefit from the ACA's ban on insurer discrimination against people with preexisting conditions.The justices will have to decide the ACA case using analyses within a legal framework and employing various legal doctrines, notably severability. But another kamagra 24 hour delivery dilemma, also of some ethical proportion, awaits their particular analysis.

If they find the entire act unconstitutional, there is currently nothing with which to replace it, nor is a replacement likely to appear any time soon. The court may have to decide the case, but it can't simply throw Obamacare under the bus even as the justices know their kamagra 24 hour delivery newest member was chosen through a process that some are calling a sham. Barrett's nomination has proceeded at warp speed while an election is ongoing, with millions of votes for the next president already cast.Not since the days of Abraham Lincoln -- in which a vacancy occurred 27 days before a presidential election -- has a justice been chosen in such haste and with utter disregard for what the people want.

(Lincoln, unlike Trump, waited until immediately after the election to nominate a replacement -- both because the Senate wasn't in session when the vacancy occurred, and because he could use the opening to his advantage during the campaign.) Even Barrett's colleagues at the University of Notre Dame, in an open letter, are calling on her to put the country ahead of the rush to get her confirmed.Whether she likes it or not, Amy Coney Barrett has become the poster child for whether or not the ACA will remain the sine qua non of healthcare as a right for kamagra 24 hour delivery all.Miles J. Zaremski, JD, has been a healthcare attorney and writer for 47 years. He has kamagra 24 hour delivery written and lectured extensively in the healthcare law space, both nationally and abroad.

He has written books and also contributed essays to the Huffington Post and to CNN's Michael Smerconish site. He is past president of the American College of Legal Medicine and for 5 years served as chair of the American Bar Association's Standing Committee on Medical Professional Liability..

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Seven new cases of COVID-19 were diagnosed in the 24 hours to 8pm last night, bringing the total number of cases in NSW to 3,851.Confirmed cases (including interstate residents in NSW health care facilities)3,851Deaths (in NSW from confirm​​ed cases)54Total tests carried out2,157,255There were 19,626 tests reported in the 24-hour reporting period, where can you buy kamagra compared with 24,632 in the previous 24 hours.Of the seven new cases to 8pm last night:One is what is kamagra gold a returned traveller who is in hotel quarantineFive are linked to a known case or clusterOne is locally acquired with their source still under investigationOne of the cases today is a student at St Paul’s Catholic College Greystanes who attended school while infectious. The school will be closed on Monday 31 August. Cleaning and where can you buy kamagra contact tracing is underway. We will keep you updated about when the school will reopen.Five of the new cases are linked to the CBD cluster. One is a household contact of a where can you buy kamagra previous case.

Two new cases attended the City Tattersalls Fitness Centre. The total number of cases linked to this cluster is now 28.Justice Health and Forensic Mental Health Network (the Network) is taking appropriate health and safety measures after a staff where can you buy kamagra member at Surry Hills Police Cells Complex was diagnosed with COVID-19. Contact tracing has been undertaken and the staff member is isolating.NSW Health is treating 66 COVID-19 cases, including six in intensive care and three who are ventilated. 86 per cent of cases being treated by NSW Health are in non-acute, out-of-hospital care.COVID-19 cases have visited the following locations while infectious.Anyone who attended the following venues are considered casual contacts and must monitor for symptoms and where can you buy kamagra get tested immediately if they develop. After testing you must stay isolated until a negative test result is received.Monitor for symptoms:Mater Clinic Wollstonecraft – 28 August from 8.30am to 9amVirgin Active Pitt St Gym, Sydney, - 25 August from 5pm to 6.30pm*Virgin Active Margaret St Gym, Sydney – 26 August from 5.10pm to 6.40pm*House, Broadway, - 24 August 2pm to 2.10pmSt Ives Shopping Centre – 26 August from 5.30pm to 6pmHighfield Caringbah 22 August from 6:00pm to 8:30pm*Caringbah Hotel 22 August from 8:30pm to 11pm*Bus 442, Gladstone Park, Darling St, to Gladstone Park, Darling St on 25 August, 9.18am to 9.31amBus 442, QVB, York St, Stand B to Darling St, at Phillip St, Balmain on 25 August 2.39pm to 2.52pmBus.

Merrylands Park to Parramatta where can you buy kamagra station, on 27 August, approximately 7:10pmTrain. Parramatta station to Lidcombe station, on 27 August, approximately 7:10pmTrain. Lidcombe station to Merrylands station, on 27 where can you buy kamagra August, approximately 7:20pmTrain. Merrylands station to Parramatta station, 24, 25 and 26 August, approximately 3:40pmTrain. Parramatta station to Mount Druitt, 24, 25 and 26 August, approximately 3:45pm to 4pm*If you are contacted by NSW Health and identified as a close contact you must immediately get tested and self-isolate for 14 days.COVID-19 where can you buy kamagra continues to circulate in the community and we must all be vigilant.

It is vital that people get a test as soon as they develop symptoms. People should ensure that they stay at least 1.5m from others and that they wear a mask in situations - especially on public transport - where physical distancing is difficult.Locations linked to known cases, advice on testing and isolation, and areas identified for increased testing can be found at NSW Government - Latest new and updates.​Anyone identified as a close contact and directed to undertake 14 days self-isolation where can you buy kamagra must stay in isolation for the full 14 days, even if they test negative during this time.To help stop the spread of COVID-19:If you are unwell, stay in, get tested and isolate. Wash your hands regularly. Take hand sanitiser with you when where can you buy kamagra you go out.Keep your distance. Leave 1.5 metres between yourself and others.Wear a mask in situations where you cannot physically distance.

A full list of COVID-19 testing clinics is available or people can visit their GP.Confirmed cases to date Overseas2,068Interstate acquired89Locally acquired – contact of a confirmed case and/or in a known cluster1,303Locally acquired – contact not identified391Under investigation​0 Counts where can you buy kamagra reported for a particular day may vary over time with ongoing enhanced surveillance activities. Returned travellers in hotel quarantine to date​​ Symptomatic travellers tested4,766Found positive122 As​ymptomatic travellers screened at a day 218,096Found positive88 Asymptomatic travellers screened at a day 1031,103​Found positive119​Video update​​Fourteen new cases of COVID-19 were diagnosed in the 24 hours to 8pm last night, bringing the total number of cases in NSW to 3,844. Confirmed cases (including interstate residents in NSW health care facilities)3,844Deaths (in NSW from confirm​​ed cases)54Total tests carried out2,137,629 There were 24,632 tests reported in the where can you buy kamagra 24-hour reporting period, compared with 30,282 in the previous 24 hours. Of the fourteen new cases to 8pm last night. One is a re​turned traveller who is in hotel quarantine Ten are linked to a known case or cluster Three are locally acquired with their source still under investigation Eight of the new cases where can you buy kamagra are linked to the Sydney CBD cluster, bringing the total number of cases in this cluster to 23.

Of the new cases, two are household contacts of previously reported cases, three attended the City Tattersalls Club, and three were close contacts of people linked to this cluster. Further investigations where can you buy kamagra have found one case reported yesterday is discount kamagra review also linked to this cluster. NSW Health is investigating whether the CBD cluster originated in the City Tattersalls Club and then spread to workplaces in the city and to households across Sydney and the Central Coast. To assist in identifying earlier and possible undiagnosed cases, NSW Health is asking anyone who attended the Club between 4 August 2020 – 18 August 2020 to get tested for COVID-19 and isolate until a where can you buy kamagra negative test result is received. Genomic sequencing of the virus from cases in this cluster are related to other recent clusters in NSW.

This virus is genetically different to where can you buy kamagra that of the Marriott Hotel security guard, who had a strain that had come from overseas. All identified close contacts of cases linked to this cluster are being contacted and told they must isolate for 14 days, get tested, get another test if any symptoms develop and stay isolated for the full 14 days, even if a negative test result is received within this period. Among the new cases today, two are household contacts of cases where can you buy kamagra linked to Liverpool Hospital. Prior to diagnosis many of the recently confirmed cases have attended a variety of locations and a full list of locations is available on the link below. New COVID-19 cases have visited the following locations in Mosman, St Ives and Rosebery and people attending at the same time where can you buy kamagra must monitor for symptoms, get tested immediately if they develop and stay isolated until a negative test result is received.

Archie Bear café, Mosman Rowers - 24 August 11am to 12 noon and Tuesday 25 August 9:00am to 9.30am Rosebery Post Shop, 371 Gardeners Rd, Rosebery - 26 August 1:30pm-1:40pm St Ives Shopping Centre, 166 Mona Vale Rd, St Ives - 24 August 2:30pm-3:30 pm NSW Health is treating 67 COVID-19 cases, including six in intensive care and four who are ventilated. 85 per cent of cases being treated by where can you buy kamagra NSW Health are in non-acute, out-of-hospital care. Due to the widening spread of the CBD cluster across multiple locations in the Sydney and Central Coast, NSW Health is strongly advising people who live or work in these areas to not visit aged care facilities at this time. This is a precaution while the cluster is investigated, cases are where can you buy kamagra identified and isolated and contact tracing is done. NSW Health will continue to closely monitor the number and location of cases in Sydney and the Central Coast and will adjust the advice regarding visitor restrictions on aged care facilities according to the level of local risk.

NSW Health will provide where can you buy kamagra an update during the next week. COVID-19 continues to circulate in the community and we must all be vigilant. It is vital that people get a test as soon where can you buy kamagra as they develop symptoms. People should ensure that they stay at least 1.5m from others and that they wear a mask in situations - especially on public transport - where physical distancing is difficult. Locations linked to known cases, advice on testing and isolation, where can you buy kamagra and areas identified for increased testing can be found at NSW Government - Latest new and updates.​ Anyone identified as a close contact and directed to undertake 14 days self-isolation must stay in isolation for the full 14 days, even if they test negative during this time.

To help stop the spread of COVID-19. If you where can you buy kamagra are unwell, stay in, get tested and isolate. Wash your hands regularly. Take hand sanitiser with you when you where can you buy kamagra go out.Keep your distance. Leave 1.5 metres between yourself and others.Wear a mask in situations where you cannot physically distance.

A full list of COVID-19 testing clinics is available where can you buy kamagra or people can visit their GP. Confirmed cases to date Overseas2,067Interstate acquired89Locally acquired – contact of a confirmed case and/or in a known cluster1,296Locally acquired – contact not identified391Under investigation​1 Counts reported for a particular day may vary over time with ongoing enhanced surveillance activities. Returned travellers in hotel quarantine to date​​ Symptomatic travellers tested4,765Found positive122 As​ymptomatic travellers screened at a day 217,750Found positive88 Asymptomatic travellers screened at a day 1030,788​Found positive119​Video update​​.

Seven new cases of COVID-19 were diagnosed in the 24 hours to 8pm last night, bringing the total number of cases in NSW to 3,851.Confirmed cases (including interstate residents in NSW health care facilities)3,851Deaths (in NSW from confirm​​ed cases)54Total tests carried out2,157,255There were 19,626 tests reported in the 24-hour reporting period, compared with 24,632 in the previous 24 hours.Of the seven new cases investigate this site to 8pm last night:One is a returned traveller who is in hotel quarantineFive are linked to a known case or clusterOne is locally acquired with their source still under investigationOne of the cases today is a student at St Paul’s Catholic College Greystanes who attended school kamagra 24 hour delivery while infectious. The school will be closed on Monday 31 August. Cleaning and contact kamagra 24 hour delivery tracing is underway.

We will keep you updated about when the school will reopen.Five of the new cases are linked to the CBD cluster. One is kamagra 24 hour delivery a household contact of a previous case. Two new cases attended the City Tattersalls Fitness Centre.

The total number of cases linked to this cluster is now 28.Justice Health and Forensic Mental Health Network (the Network) is taking appropriate health and safety measures after a staff member at Surry Hills Police Cells Complex was kamagra 24 hour delivery diagnosed with COVID-19. Contact tracing has been undertaken and the staff member is isolating.NSW Health is treating 66 COVID-19 cases, including six in intensive care and three who are ventilated. 86 per cent of cases being treated by NSW Health are in non-acute, out-of-hospital care.COVID-19 cases have visited the following locations while infectious.Anyone who attended the following venues are considered casual contacts and must monitor for symptoms and kamagra 24 hour delivery get tested immediately if they develop.

After testing you must stay isolated until a negative test result is received.Monitor for symptoms:Mater Clinic Wollstonecraft – 28 August from 8.30am to 9amVirgin Active Pitt St Gym, Sydney, - 25 August from 5pm to 6.30pm*Virgin Active Margaret St Gym, Sydney – 26 August from 5.10pm to 6.40pm*House, Broadway, - 24 August 2pm to 2.10pmSt Ives Shopping Centre – 26 August from 5.30pm to 6pmHighfield Caringbah 22 August from 6:00pm to 8:30pm*Caringbah Hotel 22 August from 8:30pm to 11pm*Bus 442, Gladstone Park, Darling St, to Gladstone Park, Darling St on 25 August, 9.18am to 9.31amBus 442, QVB, York St, Stand B to Darling St, at Phillip St, Balmain on 25 August 2.39pm to 2.52pmBus. Merrylands Park kamagra 24 hour delivery to Parramatta station, on 27 August, approximately 7:10pmTrain. Parramatta station to Lidcombe station, on 27 August, approximately 7:10pmTrain.

Lidcombe station to Merrylands station, on 27 August, approximately kamagra 24 hour delivery 7:20pmTrain. Merrylands station to Parramatta station, 24, 25 and 26 August, approximately 3:40pmTrain. Parramatta station to Mount Druitt, 24, kamagra 24 hour delivery 25 and 26 August, approximately 3:45pm to 4pm*If you are contacted by NSW Health and identified as a close contact you must immediately get tested and self-isolate for 14 days.COVID-19 continues to circulate in the community and we must all be vigilant.

It is vital that people get a test as soon as they develop symptoms. People should ensure that they stay at least 1.5m from others and that they wear a mask in situations - especially on public transport - where physical distancing is difficult.Locations linked to known cases, advice on testing and isolation, and areas identified for increased testing can be found at NSW Government - Latest new and updates.​Anyone identified as a close contact and directed to undertake 14 days self-isolation must kamagra 24 hour delivery stay in isolation for the full 14 days, even if they test negative during this time.To help stop the spread of COVID-19:If you are unwell, stay in, get tested and isolate. Wash your hands regularly.

Take hand sanitiser with you when you go out.Keep your kamagra 24 hour delivery distance. Leave 1.5 metres between yourself and others.Wear a mask in situations where you cannot physically distance. A full list of COVID-19 testing clinics is available or people can visit their GP.Confirmed cases to date Overseas2,068Interstate acquired89Locally acquired – contact of a confirmed case kamagra 24 hour delivery and/or in a known cluster1,303Locally acquired – contact not identified391Under investigation​0 Counts reported for a particular day may vary over time with ongoing enhanced surveillance activities.

Returned travellers in hotel quarantine to date​​ Symptomatic travellers tested4,766Found positive122 As​ymptomatic travellers screened at a day 218,096Found positive88 Asymptomatic travellers screened at a day 1031,103​Found positive119​Video update​​Fourteen new cases of COVID-19 were diagnosed in the 24 hours to 8pm last night, bringing the total number of cases in NSW to 3,844. Confirmed cases (including interstate residents in NSW health care facilities)3,844Deaths (in NSW from confirm​​ed cases)54Total tests carried out2,137,629 There were 24,632 tests reported in the 24-hour reporting period, compared with kamagra 24 hour delivery 30,282 in the previous 24 hours. Of the fourteen new cases to 8pm last night.

One is a re​turned traveller who is in hotel quarantine Ten are linked to a known case or cluster Three are locally acquired with their source still under investigation Eight of kamagra 24 hour delivery the new cases are linked to the Sydney CBD cluster, bringing the total number of cases in this cluster to 23. Of the new cases, two are household contacts of previously reported cases, three attended the City Tattersalls Club, and three were close contacts of people linked to this cluster. Further investigations have found one case reported kamagra 24 hour delivery yesterday is also linked to this cluster.

NSW Health is investigating whether the CBD cluster originated in the City Tattersalls Club and then spread to workplaces in the city and to households across Sydney and the Central Coast. To assist in identifying earlier and possible undiagnosed cases, NSW Health is asking anyone who attended kamagra 24 hour delivery the Club between 4 August 2020 – 18 August 2020 to get tested for COVID-19 and isolate until a negative test result is received. Genomic sequencing of the virus from cases in this cluster are related to other recent clusters in NSW.

This virus kamagra 24 hour delivery is genetically different to that of the Marriott Hotel security guard, who had a strain that had come from overseas. All identified close contacts of cases linked to this cluster are being contacted and told they must isolate for 14 days, get tested, get another test if any symptoms develop and stay isolated for the full 14 days, even if a negative test result is received within this period. Among the new cases today, two are household contacts of cases linked to kamagra 24 hour delivery Liverpool Hospital.

Prior to diagnosis many of the recently confirmed cases have attended a variety of locations and a full list of locations is available on the link below. New COVID-19 cases have visited the following locations in kamagra 24 hour delivery Mosman, St Ives and Rosebery and people attending at the same time must monitor for symptoms, get tested immediately if they develop and stay isolated until a negative test result is received. Archie Bear café, Mosman Rowers - 24 August 11am to 12 noon and Tuesday 25 August 9:00am to 9.30am Rosebery Post Shop, 371 Gardeners Rd, Rosebery - 26 August 1:30pm-1:40pm St Ives Shopping Centre, 166 Mona Vale Rd, St Ives - 24 August 2:30pm-3:30 pm NSW Health is treating 67 COVID-19 cases, including six in intensive care and four who are ventilated.

85 per cent of cases being treated by NSW Health are in non-acute, kamagra 24 hour delivery out-of-hospital care. Due to the widening spread of the CBD cluster across multiple locations in the Sydney and Central Coast, NSW Health is strongly advising people who live or work in these areas to not visit aged care facilities at this time. This is a precaution while the cluster is investigated, cases are identified and isolated kamagra 24 hour delivery and contact tracing is done.

NSW Health will continue to closely monitor the number and location of cases in Sydney and the Central Coast and will adjust the advice regarding visitor restrictions on aged care facilities according to the level of local risk. NSW Health will provide kamagra 24 hour delivery an update during the next week. COVID-19 continues to circulate in the community and we must all be vigilant.

It is vital that people get a test as soon as they kamagra 24 hour delivery develop symptoms. People should ensure that they stay at least 1.5m from others and that they wear a mask in situations - especially on public transport - where physical distancing is difficult. Locations linked to known cases, advice kamagra 24 hour delivery on testing and isolation, and areas identified for increased testing can be found at NSW Government - Latest new and updates.​ Anyone identified as a close contact and directed to undertake 14 days self-isolation must stay in isolation for the full 14 days, even if they test negative during this time.

To help stop the spread of COVID-19. If you are unwell, kamagra 24 hour delivery stay in, get tested and isolate. Wash your hands regularly.

Take hand sanitiser with kamagra 24 hour delivery you when you go out.Keep your distance. Leave 1.5 metres between yourself and others.Wear a mask in situations where you cannot physically distance. A full kamagra 24 hour delivery list of COVID-19 testing clinics is available or people can visit their GP.

Confirmed cases to date Overseas2,067Interstate acquired89Locally acquired – contact of a confirmed case and/or in a known cluster1,296Locally acquired – contact not identified391Under investigation​1 Counts reported for a particular day may vary over time with ongoing enhanced surveillance activities. Returned travellers in hotel quarantine to date​​ Symptomatic travellers tested4,765Found positive122 As​ymptomatic travellers screened at a day 217,750Found positive88 Asymptomatic travellers screened at a day 1030,788​Found positive119​Video update​​.

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How to https://www.cityreal.lv/kamagra-gel-packs/ cite how can i buy kamagra 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 how can i buy kamagra 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, the media went how can i buy kamagra 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 how can i buy kamagra 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 started getting distress calls from their how can i buy kamagra 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 on Preventing how can i buy kamagra 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 how can i buy kamagra 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 how can i buy kamagra 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 how can i buy kamagra 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 how can i buy kamagra detrimental to the image of psychiatry in addition to doing harm and injustice to our 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 how can i buy kamagra “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 how can i buy kamagra 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, 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 how can i buy kamagra should be justified and limited by the boundaries of scientific knowledge available at the moment. References Correspondence Address:Dr.

O P SinghAA 304, how can i buy kamagra 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.

Electroconvulsive therapy. Part I. A perspective on the evolution and current practice of ECT.

J Psychiatr Pract 2009;15:346-68. 2.Lauber C, Nordt C, Falcato L, Rössler W. Can a seizure help?.

The public's attitude toward electroconvulsive therapy. Psychiatry Res 2005;134:205-9. 3.Stefanazzi M.

Is electroconvulsive therapy (ECT) ever ethically justified?. If so, under what circumstances. HEC Forum 2013;25:79-94.

4.Devanand DP, Dwork AJ, Hutchinson ER, Bolwig TG, Sackeim HA. Does ECT alter brain structure?. Am J Psychiatry 1994;151:957-70.

5.Devanand DP. Does electroconvulsive therapy damage brain cells?. Semin Neurol 1995;15:351-7.

6.Pearsall J, Trumble B, editors. The Oxford English Reference Dictionary. 2nd ed.

Oxford, England. New York. Oxford University Press.

1996. 7.Collin PH. Dictionary of Medical Terms.

2004. 8.Hajdu SI. Entries on laboratory medicine in the first illustrated medical dictionary.

Ann Clin Lab Sci 2005;35:465-8. 9.Mander AJ, Whitfield A, Kean DM, Smith MA, Douglas RH, Kendell RE. Cerebral and brain stem changes after ECT revealed by nuclear magnetic resonance imaging.

Br J Psychiatry 1987;151:69-71. 10.Coffey CE, Weiner RD, Djang WT, Figiel GS, Soady SA, Patterson LJ, et al. Brain anatomic effects of electroconvulsive therapy.

A prospective magnetic resonance imaging study. Arch Gen Psychiatry 1991;48:1013-21. 11.Scott AI, Douglas RH, Whitfield A, Kendell RE.

Time course of cerebral magnetic resonance changes after electroconvulsive therapy. Br J Psychiatry 1990;156:551-3. 12.Pande AC, Grunhaus LJ, Aisen AM, Haskett RF.

A preliminary magnetic resonance imaging study of ECT-treated depressed patients. Biol Psychiatry 1990;27:102-4. 13.Coffey CE, Figiel GS, Djang WT, Sullivan DC, Herfkens RJ, Weiner RD.

Effects of ECT on brain structure. A pilot prospective magnetic resonance imaging study. Am J Psychiatry 1988;145:701-6.

14.Qiu H, Li X, Zhao W, Du L, Huang P, Fu Y, et al. Electroconvulsive therapy-Induced brain structural and functional changes in major depressive https://www.cityreal.lv/buy-kamagra-now/ disorders. A longitudinal study.

Med Sci Monit 2016;22:4577-86. 15.Kunigiri G, Jayakumar PN, Janakiramaiah N, Gangadhar BN. MRI T2 relaxometry of brain regions and cognitive dysfunction following electroconvulsive therapy.

Indian J Psychiatry 2007;49:195-9. [PUBMED] [Full text] 16.Pirnia T, Joshi SH, Leaver AM, Vasavada M, Njau S, Woods RP, et al. Electroconvulsive therapy and structural neuroplasticity in neocortical, limbic and paralimbic cortex.

Transl Psychiatry 2016;6:e832. 17.Szabo K, Hirsch JG, Krause M, Ende G, Henn FA, Sartorius A, et al. Diffusion weighted MRI in the early phase after electroconvulsive therapy.

Neurol Res 2007;29:256-9. 18.Nordanskog P, Dahlstrand U, Larsson MR, Larsson EM, Knutsson L, Johanson A. Increase in hippocampal volume after electroconvulsive therapy in patients with depression.

A volumetric magnetic resonance imaging study. J ECT 2010;26:62-7. 19.Nordanskog P, Larsson MR, Larsson EM, Johanson A.

Hippocampal volume in relation to clinical and cognitive outcome after electroconvulsive therapy in depression. Acta Psychiatr Scand 2014;129:303-11. 20.Tendolkar I, van Beek M, van Oostrom I, Mulder M, Janzing J, Voshaar RO, et al.

Electroconvulsive therapy increases hippocampal and amygdala volume in therapy refractory depression. A longitudinal pilot study. Psychiatry Res 2013;214:197-203.

21.Dukart J, Regen F, Kherif F, Colla M, Bajbouj M, Heuser I, et al. Electroconvulsive therapy-induced brain plasticity determines therapeutic outcome in mood disorders. Proc Natl Acad Sci U S A 2014;111:1156-61.

22.Abbott CC, Jones T, Lemke NT, Gallegos P, McClintock SM, Mayer AR, et al. Hippocampal structural and functional changes associated with electroconvulsive therapy response. Transl Psychiatry 2014;4:e483.

23.Lyden H, Espinoza RT, Pirnia T, Clark K, Joshi SH, Leaver AM, et al. Electroconvulsive therapy mediates neuroplasticity of white matter microstructure in major depression. Transl Psychiatry 2014;4:e380.

24.Bouckaert F, De Winter FL, Emsell L, Dols A, Rhebergen D, Wampers M, et al. Grey matter volume increase following electroconvulsive therapy in patients with late life depression. A longitudinal MRI study.

J Psychiatry Neurosci 2016;41:105-14. 25.Ota M, Noda T, Sato N, Okazaki M, Ishikawa M, Hattori K, et al. Effect of electroconvulsive therapy on gray matter volume in major depressive disorder.

J Affect Disord 2015;186:186-91. 26.Zeng J, Luo Q, Du L, Liao W, Li Y, Liu H, et al. Reorganization of anatomical connectome following electroconvulsive therapy in major depressive disorder.

Neural Plast 2015;2015:271674. 27.van Eijndhoven P, Mulders P, Kwekkeboom L, van Oostrom I, van Beek M, Janzing J, et al. Bilateral ECT induces bilateral increases in regional cortical thickness.

Transl Psychiatry 2016;6:e874. 28.Bouckaert F, Dols A, Emsell L, De Winter FL, Vansteelandt K, Claes L, et al. Relationship between hippocampal volume, serum BDNF, and depression severity following electroconvulsive therapy in late-life depression.

Neuropsychopharmacology 2016;41:2741-8. 29.Depping MS, Nolte HM, Hirjak D, Palm E, Hofer S, Stieltjes B, et al. Cerebellar volume change in response to electroconvulsive therapy in patients with major depression.

Prog Neuropsychopharmacol Biol Psychiatry 2017;73:31-5. 30.Joshi SH, Espinoza RT, Pirnia T, Shi J, Wang Y, Ayers B, et al. Structural plasticity of the hippocampus and amygdala induced by electroconvulsive therapy in major depression.

Biol Psychiatry 2016;79:282-92. 31.Wade BS, Joshi SH, Njau S, Leaver AM, Vasavada M, Woods RP, et al. Effect of electroconvulsive therapy on striatal morphometry in major depressive disorder.

Neuropsychopharmacology 2016;41:2481-91. 32.Wolf RC, Nolte HM, Hirjak D, Hofer S, Seidl U, Depping MS, et al. Structural network changes in patients with major depression and schizophrenia treated with electroconvulsive therapy.

Eur Neuropsychopharmacol 2016;26:1465-74. 33.Ende G, Braus DF, Walter S, Weber-Fahr W, Henn FA. The hippocampus in patients treated with electroconvulsive therapy.

A proton magnetic resonance spectroscopic imaging study. Arch Gen Psychiatry 2000;57:937-43. 34.Michael N, Erfurth A, Ohrmann P, Arolt V, Heindel W, Pfleiderer B.

Metabolic changes within the left dorsolateral prefrontal cortex occurring with electroconvulsive therapy in patients with treatment resistant unipolar depression. Psychol Med 2003;33:1277-84. 35.Michael N, Erfurth A, Ohrmann P, Arolt V, Heindel W, Pfleiderer B.

Neurotrophic effects of electroconvulsive therapy. A proton magnetic resonance study of the left amygdalar region in patients with treatment-resistant depression. Neuropsychopharmacology 2003;28:720-5.

36.Pfleiderer B, Michael N, Erfurth A, Ohrmann P, Hohmann U, Wolgast M, et al. Effective electroconvulsive therapy reverses glutamate/glutamine deficit in the left anterior cingulum of unipolar depressed patients. Psychiatry Res 2003;122:185-92.

37.Merkl A, Schubert F, Quante A, Luborzewski A, Brakemeier EL, Grimm S, et al. Abnormal cingulate and prefrontal cortical neurochemistry in major depression after electroconvulsive therapy. Biol Psychiatry 2011;69:772-9.

38.Jorgensen A, Magnusson P, Hanson LG, Kirkegaard T, Benveniste H, Lee H, et al. Regional brain volumes, diffusivity, and metabolite changes after electroconvulsive therapy for severe depression. Acta Psychiatr Scand 2016;133:154-64.

39.Njau S, Joshi SH, Espinoza R, Leaver AM, Vasavada M, Marquina A, et al. Neurochemical correlates of rapid treatment response to electroconvulsive therapy in patients with major depression. J Psychiatry Neurosci 2017;42:6-16.

40.Cano M, Martínez-Zalacaín I, Bernabéu-Sanz Á, Contreras-Rodríguez O, Hernández-Ribas R, Via E, et al. Brain volumetric and metabolic correlates of electroconvulsive therapy for treatment-resistant depression. A longitudinal neuroimaging study.

Transl Psychiatry 2017;7:e1023. 41.Figiel GS, Krishnan KR, Doraiswamy PM. Subcortical structural changes in ECT-induced delirium.

J Geriatr Psychiatry Neurol 1990;3:172-6. 42.Rotheneichner P, Lange S, O'Sullivan A, Marschallinger J, Zaunmair P, Geretsegger C, et al. Hippocampal neurogenesis and antidepressive therapy.

Shocking relations. Neural Plast 2014;2014:723915. 43.Singh A, Kar SK.

How electroconvulsive therapy works?. Understanding the neurobiological mechanisms. Clin Psychopharmacol Neurosci 2017;15:210-21.

44.Gbyl K, Videbech P. Electroconvulsive therapy increases brain volume in major depression. A systematic review and meta-analysis.

Acta Psychiatr Scand 2018;138:180-95. 45.Oltedal L, Narr KL, Abbott C, Anand A, Argyelan M, Bartsch H, et al. Volume of the human hippocampus and clinical response following electroconvulsive therapy.

Biol Psychiatry 2018;84:574-81. 46.Breggin PR. Brain-Disabling Treatments in Psychiatry.

Drugs, Electroshock, and the Role of the FDA. New York. Springer Pub.

Co.. 1997. 47.Posse S, Otazo R, Dager SR, Alger J.

MR spectroscopic imaging. Principles and recent advances. J Magn Reson Imaging 2013;37:1301-25.

48.Simmons ML, Frondoza CG, Coyle JT. Immunocytochemical localization of N-acetyl-aspartate with monoclonal antibodies. Neuroscience 1991;45:37-45.

49.Obergriesser T, Ende G, Braus DF, Henn FA. Long-term follow-up of magnetic resonance-detectable choline signal changes in the hippocampus of patients treated with electroconvulsive therapy. J Clin Psychiatry 2003;64:775-80.

50.Bramham CR, Messaoudi E. BDNF function in adult synaptic plasticity. The synaptic consolidation hypothesis.

Prog Neurobiol 2005;76:99-125. 51.Duman RS, Monteggia LM. A neurotrophic model for stress-related mood disorders.

Biol Psychiatry 2006;59:1116-27. 52.Bocchio-Chiavetto L, Bagnardi V, Zanardini R, Molteni R, Nielsen MG, Placentino A, et al. Serum and plasma BDNF levels in major depression.

A replication study and meta-analyses. World J Biol Psychiatry 2010;11:763-73. 53.Brunoni AR, Lopes M, Fregni F.

A systematic review and meta-analysis of clinical studies on major depression and BDNF levels. Implications for the role of neuroplasticity in depression. Int J Neuropsychopharmacol 2008;11:1169-80.

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.

J Psychiatr Res 2016;83:47-53. 55.UK ECT Review Group. Efficacy and safety of electroconvulsive therapy in depressive disorders.

A systematic review and meta-analysis. Lancet 2003;361:799-808. 56.57.Semkovska M, McLoughlin DM.

Objective cognitive performance associated with electroconvulsive therapy for depression. A systematic review and meta-analysis. Biol Psychiatry 2010;68:568-77.

58.Tulving E, Madigan SA. Memory and verbal learning. Annu Rev Psychol 1970;21:437-84.

59.Rose D, Fleischmann P, Wykes T, Leese M, Bindman J. Patients' perspectives on electroconvulsive therapy. Systematic review.

BMJ 2003;326:1363. 60.Semkovska M, McLoughlin DM. Measuring retrograde autobiographical amnesia following electroconvulsive therapy.

Historical perspective and current issues. J ECT 2013;29:127-33. 61.Fraser LM, O'Carroll RE, Ebmeier KP.

The effect of electroconvulsive therapy on autobiographical memory. A systematic review. J ECT 2008;24:10-7.

62.Squire LR, Chace PM. Memory functions six to nine months after electroconvulsive therapy. Arch Gen Psychiatry 1975;32:1557-64.

63.Squire LR, Slater PC. Electroconvulsive therapy and complaints of memory dysfunction. A prospective three-year follow-up study.

Br J Psychiatry 1983;142:1-8. 64.Squire LR, Slater PC, Miller PL. Retrograde amnesia and bilateral electroconvulsive therapy.

Long-term follow-up. Arch Gen Psychiatry 1981;38:89-95. 65.Squire LR, Wetzel CD, Slater PC.

Memory complaint after electroconvulsive therapy. Assessment with a new self-rating instrument. Biol Psychiatry 1979;14:791-801.

66.Calev A, Nigal D, Shapira B, Tubi N, Chazan S, Ben-Yehuda Y, et al. Early and long-term effects of electroconvulsive therapy and depression on memory and other cognitive functions. J Nerv Ment Dis 1991;179:526-33.

67.Sackeim HA, Prudic J, Devanand DP, Nobler MS, Lisanby SH, Peyser S, et al. A prospective, randomized, double-blind comparison of bilateral and right unilateral electroconvulsive therapy at different stimulus intensities. Arch Gen Psychiatry 2000;57:425-34.

68.Abrams R. Does brief-pulse ECT cause persistent or permanent memory impairment?. J ECT 2002;18:71-3.

69.Peretti CS, Danion JM, Grangé D, Mobarek N. Bilateral ECT and autobiographical memory of subjective experiences related to melancholia. A pilot study.

J Affect Disord 1996;41:9-15. 70.Weiner RD, Rogers HJ, Davidson JR, Squire LR. Effects of stimulus parameters on cognitive side effects.

Ann N Y Acad Sci 1986;462:315-25. 71.Prudic J, Peyser S, Sackeim HA. Subjective memory complaints.

A review of patient self-assessment of memory after electroconvulsive therapy. J ECT 2000;16:121-32. 72.Sackeim HA, Prudic J, Devanand DP, Kiersky JE, Fitzsimons L, Moody BJ, et al.

Effects of stimulus intensity and electrode placement on the efficacy and cognitive effects of electroconvulsive therapy. N Engl J Med 1993;328:839-46. 73.Frith CD, Stevens M, Johnstone EC, Deakin JF, Lawler P, Crow TJ.

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.

Efficacy and cognitive effects of right unilateral electroconvulsive therapy. J ECT 2000;16:370-9. 75.Coleman EA, Sackeim HA, Prudic J, Devanand DP, McElhiney MC, Moody BJ.

Subjective memory complaints prior to and following electroconvulsive therapy. Biol Psychiatry 1996;39:346-56. 76.Berggren Š, Gustafson L, Höglund P, Johanson A.

A long-term longitudinal follow-up of depressed patients treated with ECT with special focus on development of dementia. J Affect Disord 2016;200:15-24. 77.Brodaty H, Hickie I, Mason C, Prenter L.

A prospective follow-up study of ECT outcome in older depressed patients. J Affect Disord 2000;60:101-11. 78.Osler M, Rozing MP, Christensen GT, Andersen PK, Jørgensen MB.

Electroconvulsive therapy and risk of dementia in patients with affective disorders. A cohort study. Lancet Psychiatry 2018;5:348-56.

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 this kamagra 24 hour delivery article:Singh O P. Aftermath of celebrity suicide – Media coverage and role of psychiatrists. Indian J Psychiatry 2020;62:337-8Celebrity kamagra 24 hour delivery 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, the media went into a frenzy as newspapers, news channels, and social media were full of stories providing minute details of the suicidal kamagra 24 hour delivery 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 kamagra 24 hour delivery 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 started getting distress calls from their patients in kamagra 24 hour delivery 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 on kamagra 24 hour delivery 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 kamagra 24 hour delivery 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 measures to ensure ethics in kamagra 24 hour delivery 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 kamagra 24 hour delivery 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 kamagra 24 hour delivery psychiatry in addition to doing harm and injustice to our 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 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 kamagra 24 hour delivery 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 kamagra 24 hour delivery guidelines and resource books for interacting with media, and psychiatrists 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 kamagra 24 hour delivery 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 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, West Bengal IndiaSource of Support kamagra 24 hour delivery. 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. Electroconvulsive therapy.

Part I. A perspective on the evolution and current practice of ECT. J Psychiatr Pract 2009;15:346-68. 2.Lauber C, Nordt C, Falcato L, Rössler W. Can a seizure help?.

The public's attitude toward electroconvulsive therapy. Psychiatry Res 2005;134:205-9. 3.Stefanazzi M. Is electroconvulsive therapy (ECT) ever ethically justified?. If so, under what circumstances.

HEC Forum 2013;25:79-94. 4.Devanand DP, Dwork AJ, Hutchinson ER, Bolwig TG, Sackeim HA. Does ECT alter brain structure?. Am J Psychiatry 1994;151:957-70. 5.Devanand DP.

Does electroconvulsive therapy damage brain cells?. Semin Neurol 1995;15:351-7. 6.Pearsall J, Trumble B, editors. The Oxford English Reference Dictionary. 2nd ed.

Oxford, England. New York. Oxford University Press. 1996. 7.Collin PH.

Dictionary of Medical Terms. 4th ed. London. Bloomsbury. 2004.

8.Hajdu SI. Entries on laboratory medicine in the first illustrated medical dictionary. Ann Clin Lab Sci 2005;35:465-8. 9.Mander AJ, Whitfield A, Kean DM, Smith MA, Douglas RH, Kendell RE. Cerebral and brain stem changes after ECT revealed by nuclear magnetic resonance imaging.

Br J Psychiatry 1987;151:69-71. 10.Coffey CE, Weiner RD, Djang WT, Figiel GS, Soady SA, Patterson LJ, et al. Brain anatomic effects of electroconvulsive therapy. A prospective magnetic resonance imaging study. Arch Gen Psychiatry 1991;48:1013-21.

11.Scott AI, Douglas RH, Whitfield A, Kendell RE. Time course of cerebral magnetic resonance changes after electroconvulsive therapy. Br J Psychiatry 1990;156:551-3. 12.Pande AC, Grunhaus LJ, Aisen AM, Haskett RF. A preliminary magnetic resonance imaging study of ECT-treated depressed patients.

Biol Psychiatry 1990;27:102-4. 13.Coffey CE, Figiel GS, Djang WT, Sullivan DC, Herfkens RJ, Weiner RD. Effects of ECT on brain structure. A pilot prospective magnetic resonance imaging study. Am J Psychiatry 1988;145:701-6.

14.Qiu H, Li X, Zhao W, Du L, Huang P, Fu Y, et al. Electroconvulsive therapy-Induced brain structural and functional changes in major depressive disorders. A longitudinal study. Med Sci Monit 2016;22:4577-86. 15.Kunigiri G, Jayakumar PN, Janakiramaiah N, Gangadhar BN.

MRI T2 relaxometry of brain regions and cognitive dysfunction following electroconvulsive therapy. Indian J Psychiatry 2007;49:195-9. [PUBMED] [Full text] 16.Pirnia T, Joshi SH, Leaver AM, Vasavada M, Njau S, Woods RP, et al. Electroconvulsive therapy and structural neuroplasticity in neocortical, limbic and paralimbic cortex. Transl Psychiatry 2016;6:e832.

17.Szabo K, Hirsch JG, Krause M, Ende G, Henn FA, Sartorius A, et al. Diffusion weighted MRI in the early phase after electroconvulsive therapy. Neurol Res 2007;29:256-9. 18.Nordanskog P, Dahlstrand U, Larsson MR, Larsson EM, Knutsson L, Johanson A. Increase in hippocampal volume after electroconvulsive therapy in patients with depression.

A volumetric magnetic resonance imaging study. J ECT 2010;26:62-7. 19.Nordanskog P, Larsson MR, Larsson EM, Johanson A. Hippocampal volume in relation to clinical and cognitive outcome after electroconvulsive therapy in depression. Acta Psychiatr Scand 2014;129:303-11.

20.Tendolkar I, van Beek M, van Oostrom I, Mulder M, Janzing J, Voshaar RO, et al. Electroconvulsive therapy increases hippocampal and amygdala volume in therapy refractory depression. A longitudinal pilot study. Psychiatry Res 2013;214:197-203. 21.Dukart J, Regen F, Kherif F, Colla M, Bajbouj M, Heuser I, et al.

Electroconvulsive therapy-induced brain plasticity determines therapeutic outcome in mood disorders. Proc Natl Acad Sci U S A 2014;111:1156-61. 22.Abbott CC, Jones T, Lemke NT, Gallegos P, McClintock SM, Mayer AR, et al. Hippocampal structural and functional changes associated with electroconvulsive therapy response. Transl Psychiatry 2014;4:e483.

23.Lyden H, Espinoza RT, Pirnia T, Clark K, Joshi SH, Leaver AM, et al. Electroconvulsive therapy mediates neuroplasticity of white matter microstructure in major depression. Transl Psychiatry 2014;4:e380. 24.Bouckaert F, De Winter FL, Emsell L, Dols A, Rhebergen D, Wampers M, et al. Grey matter volume increase following electroconvulsive therapy in patients with late life depression.

A longitudinal MRI study. J Psychiatry Neurosci 2016;41:105-14. 25.Ota M, Noda T, Sato N, Okazaki M, Ishikawa M, Hattori K, et al. Effect of electroconvulsive therapy on gray matter volume in major depressive disorder. J Affect Disord 2015;186:186-91.

26.Zeng J, Luo Q, Du L, Liao W, Li Y, Liu H, et al. Reorganization of anatomical connectome following electroconvulsive therapy in major depressive disorder. Neural Plast 2015;2015:271674. 27.van Eijndhoven P, Mulders P, Kwekkeboom L, van Oostrom I, van Beek M, Janzing J, et al. Bilateral ECT induces bilateral increases in regional cortical thickness.

Transl Psychiatry 2016;6:e874. 28.Bouckaert F, Dols A, Emsell L, De Winter FL, Vansteelandt K, Claes L, et al. Relationship between hippocampal volume, serum BDNF, and depression severity following electroconvulsive therapy in late-life depression. Neuropsychopharmacology 2016;41:2741-8. 29.Depping MS, Nolte HM, Hirjak D, Palm E, Hofer S, Stieltjes B, et al.

Cerebellar volume change in response to electroconvulsive therapy in patients with major depression. Prog Neuropsychopharmacol Biol Psychiatry 2017;73:31-5. 30.Joshi SH, Espinoza RT, Pirnia T, Shi J, Wang Y, Ayers B, et al. Structural plasticity of the hippocampus and amygdala induced by electroconvulsive therapy in major depression. Biol Psychiatry 2016;79:282-92.

31.Wade BS, Joshi SH, Njau S, Leaver AM, Vasavada M, Woods RP, et al. Effect of electroconvulsive therapy on striatal morphometry in major depressive disorder. Neuropsychopharmacology 2016;41:2481-91. 32.Wolf RC, Nolte HM, Hirjak D, Hofer S, Seidl U, Depping MS, et al. Structural network changes in patients with major depression and schizophrenia treated with electroconvulsive therapy.

Eur Neuropsychopharmacol 2016;26:1465-74. 33.Ende G, Braus DF, Walter S, Weber-Fahr W, Henn FA. The hippocampus in patients treated with electroconvulsive therapy. A proton magnetic resonance spectroscopic imaging study. Arch Gen Psychiatry 2000;57:937-43.

34.Michael N, Erfurth A, Ohrmann P, Arolt V, Heindel W, Pfleiderer B. Metabolic changes within the left dorsolateral prefrontal cortex occurring with electroconvulsive therapy in patients with treatment resistant unipolar depression. Psychol Med 2003;33:1277-84. 35.Michael N, Erfurth A, Ohrmann P, Arolt V, Heindel W, Pfleiderer B. Neurotrophic effects of electroconvulsive therapy.

A proton magnetic resonance study of the left amygdalar region in patients with treatment-resistant depression. Neuropsychopharmacology 2003;28:720-5. 36.Pfleiderer B, Michael N, Erfurth A, Ohrmann P, Hohmann U, Wolgast M, et al. Effective electroconvulsive therapy reverses glutamate/glutamine deficit in the left anterior cingulum of unipolar depressed patients. Psychiatry Res 2003;122:185-92.

37.Merkl A, Schubert F, Quante A, Luborzewski A, Brakemeier EL, Grimm S, et al. Abnormal cingulate and prefrontal cortical neurochemistry in major depression after electroconvulsive therapy. Biol Psychiatry 2011;69:772-9. 38.Jorgensen A, Magnusson P, Hanson LG, Kirkegaard T, Benveniste H, Lee H, et al. Regional brain volumes, diffusivity, and metabolite changes after electroconvulsive therapy for severe depression.

Acta Psychiatr Scand 2016;133:154-64. 39.Njau S, Joshi SH, Espinoza R, Leaver AM, Vasavada M, Marquina A, et al. Neurochemical correlates of rapid treatment response to electroconvulsive therapy in patients with major depression. J Psychiatry Neurosci 2017;42:6-16. 40.Cano M, Martínez-Zalacaín I, Bernabéu-Sanz Á, Contreras-Rodríguez O, Hernández-Ribas R, Via E, et al.

Brain volumetric and metabolic correlates of electroconvulsive therapy for treatment-resistant depression. A longitudinal neuroimaging study. Transl Psychiatry 2017;7:e1023. 41.Figiel GS, Krishnan KR, Doraiswamy PM. Subcortical structural changes in ECT-induced delirium.

J Geriatr Psychiatry Neurol 1990;3:172-6. 42.Rotheneichner P, Lange S, O'Sullivan A, Marschallinger J, Zaunmair P, Geretsegger C, et al. Hippocampal neurogenesis and antidepressive therapy. Shocking relations. Neural Plast 2014;2014:723915.

43.Singh A, Kar SK. How electroconvulsive therapy works?. Understanding the neurobiological mechanisms. Clin Psychopharmacol Neurosci 2017;15:210-21. 44.Gbyl K, Videbech P.

Electroconvulsive therapy increases brain volume in major depression. A systematic review and meta-analysis. Acta Psychiatr Scand 2018;138:180-95. 45.Oltedal L, Narr KL, Abbott C, Anand A, Argyelan M, Bartsch H, et al. Volume of the human hippocampus and clinical response following electroconvulsive therapy.

Biol Psychiatry 2018;84:574-81. 46.Breggin PR. Brain-Disabling Treatments in Psychiatry. Drugs, Electroshock, and the Role of the FDA. New York.

Springer Pub. Co.. 1997. 47.Posse S, Otazo R, Dager SR, Alger J. MR spectroscopic imaging.

Principles and recent advances. J Magn Reson Imaging 2013;37:1301-25. 48.Simmons ML, Frondoza CG, Coyle JT. Immunocytochemical localization of N-acetyl-aspartate with monoclonal antibodies. Neuroscience 1991;45:37-45.

49.Obergriesser T, Ende G, Braus DF, Henn FA. Long-term follow-up of magnetic resonance-detectable choline signal changes in the hippocampus of patients treated with electroconvulsive therapy. J Clin Psychiatry 2003;64:775-80. 50.Bramham CR, Messaoudi E. BDNF function in adult synaptic plasticity.

The synaptic consolidation hypothesis. Prog Neurobiol 2005;76:99-125. 51.Duman RS, Monteggia LM. A neurotrophic model for stress-related mood disorders. Biol Psychiatry 2006;59:1116-27.

52.Bocchio-Chiavetto L, Bagnardi V, Zanardini R, Molteni R, Nielsen MG, Placentino A, et al. Serum and plasma BDNF levels in major depression. A replication study and meta-analyses. World J Biol Psychiatry 2010;11:763-73. 53.Brunoni AR, Lopes M, Fregni F.

A systematic review and meta-analysis of clinical studies on major depression and BDNF levels. Implications for the role of neuroplasticity in depression. Int J Neuropsychopharmacol 2008;11:1169-80. 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. J Psychiatr Res 2016;83:47-53. 55.UK ECT Review Group. Efficacy and safety of electroconvulsive therapy in depressive disorders. A systematic review and meta-analysis.

Lancet 2003;361:799-808. 56.57.Semkovska M, McLoughlin DM. Objective cognitive performance associated with electroconvulsive therapy for depression. A systematic review and meta-analysis. Biol Psychiatry 2010;68:568-77.

58.Tulving E, Madigan SA. Memory and verbal learning. Annu Rev Psychol 1970;21:437-84. 59.Rose D, Fleischmann P, Wykes T, Leese M, Bindman J. Patients' perspectives on electroconvulsive therapy.

Systematic review. BMJ 2003;326:1363. 60.Semkovska M, McLoughlin DM. Measuring retrograde autobiographical amnesia following electroconvulsive therapy. Historical perspective and current issues.

J ECT 2013;29:127-33. 61.Fraser LM, O'Carroll RE, Ebmeier KP. The effect of electroconvulsive therapy on autobiographical memory. A systematic review. J ECT 2008;24:10-7.

62.Squire LR, Chace PM. Memory functions six to nine months after electroconvulsive therapy. Arch Gen Psychiatry 1975;32:1557-64. 63.Squire LR, Slater PC. Electroconvulsive therapy and complaints of memory dysfunction.

A prospective three-year follow-up study. Br J Psychiatry 1983;142:1-8. 64.Squire LR, Slater PC, Miller PL. Retrograde amnesia and bilateral electroconvulsive therapy. Long-term follow-up.

Arch Gen Psychiatry 1981;38:89-95. 65.Squire LR, Wetzel CD, Slater PC. Memory complaint after electroconvulsive therapy. Assessment with a new self-rating instrument. Biol Psychiatry 1979;14:791-801.

66.Calev A, Nigal D, Shapira B, Tubi N, Chazan S, Ben-Yehuda Y, et al. Early and long-term effects of electroconvulsive therapy and depression on memory and other cognitive functions. J Nerv Ment Dis 1991;179:526-33. 67.Sackeim HA, Prudic J, Devanand DP, Nobler MS, Lisanby SH, Peyser S, et al. A prospective, randomized, double-blind comparison of bilateral and right unilateral electroconvulsive therapy at different stimulus intensities.

Arch Gen Psychiatry 2000;57:425-34. 68.Abrams R. Does brief-pulse ECT cause persistent or permanent memory impairment?. J ECT 2002;18:71-3. 69.Peretti CS, Danion JM, Grangé D, Mobarek N.

Bilateral ECT and autobiographical memory of subjective experiences related to melancholia. A pilot study. J Affect Disord 1996;41:9-15. 70.Weiner RD, Rogers HJ, Davidson JR, Squire LR. Effects of stimulus parameters on cognitive side effects.

Ann N Y Acad Sci 1986;462:315-25. 71.Prudic J, Peyser S, Sackeim HA. Subjective memory complaints. A review of patient self-assessment of memory after electroconvulsive therapy. J ECT 2000;16:121-32.

72.Sackeim HA, Prudic J, Devanand DP, Kiersky JE, Fitzsimons L, Moody BJ, et al. Effects of stimulus intensity and electrode placement on the efficacy and cognitive effects of electroconvulsive therapy. N Engl J Med 1993;328:839-46. 73.Frith CD, Stevens M, Johnstone EC, Deakin JF, Lawler P, Crow TJ. 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. Efficacy and cognitive effects of right unilateral electroconvulsive therapy. J ECT 2000;16:370-9. 75.Coleman EA, Sackeim HA, Prudic J, Devanand DP, McElhiney MC, Moody BJ.

Subjective memory complaints prior to and following electroconvulsive therapy. Biol Psychiatry 1996;39:346-56. 76.Berggren Š, Gustafson L, Höglund P, Johanson A. A long-term longitudinal follow-up of depressed patients treated with ECT with special focus on development of dementia. J Affect Disord 2016;200:15-24.

77.Brodaty H, Hickie I, Mason C, Prenter L. A prospective follow-up study of ECT outcome in older depressed patients. J Affect Disord 2000;60:101-11. 78.Osler M, Rozing MP, Christensen GT, Andersen PK, Jørgensen MB. Electroconvulsive therapy and risk of dementia in patients with affective disorders.

A cohort study. Lancet Psychiatry 2018;5:348-56. 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].

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A multisite kamagra canada pharmacy study led by UC Davis Health found that two prominent early intervention models for autism had a similar impact. The researchers compared developmental and symptom improvements in toddlers with autism who received one year of one-on-one intervention sessions using either the Early Intensive Behavioral Intervention (EIBI) or Early Start Denver Model (ESDM). They found that the effect did not differ significantly whether delivered at 15-hours or 25-hours kamagra canada pharmacy per week. Parents of toddlers with autism ask about the suitable early intervention for their kids“When parents receive the first diagnosis, they typically ask.

What kind of treatment should I seek and for how kamagra canada pharmacy many hours per week?. € said Sally J. Rogers, professor emeritus of psychiatry and behavioral sciences at the UC kamagra canada pharmacy Davis MIND Institute and lead author on the study. €œAs clinicians, we had no data from well-controlled experimental studies to answer these questions.

This study is the first to ask these questions experimentally.”Their study, published in the Journal of the American Academy of Child and Adolescent Psychiatry, found that neither the type of intervention nor the intensity of delivery led to significant differences in the children’s rate of progress.EIBI and ESDM interventions for autismThe two interventions vary considerably kamagra canada pharmacy in their delivery style and underlying theories. EIBI is based on applied behavior analysis and uses simple, structured instructions to teach the children. ESDM is naturalistic and based on developmental and behavioral sciences with an interactive style embedded in everyday activities, both play and typical kamagra canada pharmacy routines.Previous studies have documented that both treatment types can result in significant child gains in language understanding and use, learning rates, and cognitive and adaptive skills. However, recommendations for a specific number of hours per week of treatment have been based on assumptions rather than high-quality experimental evidence.“We designed the trial to provide objective answers about the effect of initial child characteristics, treatment styles and treatment intensities on the child’s progress over time,” Rogers said.

€œWe assessed this progress by measuring key developmental and symptom indicators.”Researchers enrolled kamagra canada pharmacy 87 toddlers with autism (between the ages of 12 and 30 months) from three university sites. Based on their age and development level, the children were randomly assigned to one of four intervention groups. 15 or 25 hours of ESDM kamagra canada pharmacy. 15 or 25 hours of EIBI.The researchers delivered one year of one-on-one interventions in homes and childcare settings.

They also provided caregiver coaching to the kamagra canada pharmacy families through two 1.5-hour sessions per month. According to Rogers, the ESDM and EIBI treatments were delivered at the highest quality.“Therapists followed the treatment manuals and maintained high fidelity to the principles of each treatment. They also received frequent supervision and coached parents to use the kamagra canada pharmacy interventions and to generalize child skills from therapy into everyday activities at home and in the community,” Rogers said.The children received four clinic assessments from the time of enrollment, at six-month intervals. Therapists assessed progress daily and updated the intervention frequently to meet children’s changing developmental and behavioral needs.More intervention hours not necessarily betterThe researchers found that neither style nor intensity of intervention had a differing effect overall on the study’s four outcome measures.

Children’s progress in receptive language, expressive communication, nonverbal ability and autism symptom change kamagra canada pharmacy. They also found that the treatment providers in both models used the models flexibly to meet individual children’s needs. Both models tended to provide greater structure and practice for children who needed it, and more child choice and naturalistic teaching for children who were ready for it.“Parents may find it reassuring that even within highly specified treatment approaches like these kamagra canada pharmacy two, therapists still adjust to individual child needs.”The initial severity of developmental delay and autism symptom severity did not influence the impact of treatment style or intensity on any of the outcomes.The current findings apply only to the toddler-aged children who were studied. They need to be validated through replication.

The study approach also needs to be applied to older children to understand their responses to these differing treatments and intensities.###Funding for the study came from National Institute of Child Health and Human Development (NICHD) (R01 MH100030), as part of the Autism Centers of Excellence (ACE) Treatment Network, and from kamagra canada pharmacy the MIND Institute Intellectual and Developmental Disabilities Research Center U54 HD079125. Clinicaltrials.gov identifier NCT02272192.Co-authors on the study are Marie Rocha of UC Davis MIND Institute. Paul Yoder, Zachary Warren, Lisa Wallace and Elizabeth Gardner of kamagra canada pharmacy Vanderbilt University. Annette Estes, Jeff Munson and Jessica Greenson of University of Washington.

John McEachin of Autism kamagra canada pharmacy Partnership Foundation. Geraldine Dawson of Duke University. Catherine Sugar, Gerhard Hellemann and Fiona Whelan of University of California Los Angeles.Article. Rogers et kamagra canada pharmacy al.

(2020). A multisite randomized controlled kamagra canada pharmacy trial comparing the effects of intervention intensity and intervention style on outcomes of young children with autism, Journal of the American Academy of Child and Adolescent Psychiatry. DOI. Https://doi.org/10.1016/j.jaac.2020.06.013Jim Robinson has one word for anyone kamagra canada pharmacy living near a wildfire.

Leave. Jim Robinson (pictured with Karen Fiscus) wants others to know about his experiences with the most recent wine country kamagra canada pharmacy fire. (Courtesy Jim Robinson.)He wishes he had done that sooner. Like so many others, he underestimated the intensity and speed of a fire that ended up trapping him and his girlfriend, Karen Fiscus kamagra canada pharmacy.

For them, it was the LNU Lightning Complex fire that devastated wine country beginning in mid-August.The costs of waiting have been much too high. He and Fiscus had to hide in a drainage pipe as fire surrounded them twice before emergency responders were able to reach them.Today, kamagra canada pharmacy Robinson is still recovering from second- and third-degree burns on 27% of his body following seven weeks in the UC Davis Burn Center. He also is grieving, as his girlfriend died from her injuries. His Napa hog farm is now an eerie moonscape and his animals are gone.Still, he wants to talk about what kamagra canada pharmacy happened, and offer advice to those in wildfire zones.“In the past, we’ve been able to wait out the fires,” Robinson said.

€œIt kind of goes with living where I live. But this fire was different kamagra canada pharmacy. Way different. It had its own atmosphere.”UC Davis surgeon Tina Palmieri kamagra canada pharmacy is a nationally recognized expert on treating and improving outcomes for burn patients.Two bright spots for Robinson as he recovers have been his family and the Burn Center, where a specially trained team treated his injuries and helped him accept his survival.

The weeks he spent there were, he said, “One of the best experiences I ever had. The doctors and nurses were phenomenal.”The Burn Center treats adults in Northern California and Western Nevada who need kamagra canada pharmacy intensive burn care. Tina Palmieri, a burn surgeon and director of the center, said the number of wildfire-injured patients her team treats has steadily increased over the past few years.“Wildfire-related burns can be particularly challenging because they are often severe, and because transportation to a hospital for care can be delayed by the fire itself,” Palmieri said.Palmieri echoes Robinson’s guidance about leaving quickly once a fire breaks out in your area. She also suggests covering up from head to toe, despite the heat of a kamagra canada pharmacy fire, and bringing a flashlight.

Both helped Robinson. His clothes offered some protection for his skin and the flashlight guided emergency responders to him.As wildfires in Northern California increase so do the number of patients in UC Davis’ Burn Center with wildfire-related injuries.If you do get burned, Palmieri said, rinse the burn injury kamagra canada pharmacy with cool water for up to 20 minutes if you can, as this may decrease the extent of the injury. However, keep the rest of your skin covered and dry. And, as soon as possible, get emergency care.Robinson said that while protecting your property may be your first instinct in a fire, you should ignore that instinct.“Give yourself enough kamagra canada pharmacy time to get your belongings together and just go,” he said.

€œYou can start over, but you can’t bring a life back.” A Center of Excellence, the Firefighters Burn Institute Regional Burn Center at UC Davis Medical Center unites the exceptional surgical, critical care and rehabilitation resources of UC Davis Health to care for the unique needs of adult burn patients. The team also treats pediatric burn patients through a partnership with Shriners Hospitals for Children kamagra canada pharmacy – Northern California. In addition to a comprehensive clinical program, the burn center conducts research aimed at improving patient outcomes, leads community outreach to support burn survivors, and provides education to reduce burn injuries. More information is on the Burn Center website.The kamagra canada pharmacy Burn Center also hosts a support group for all burn survivors in the region.

For information about joining, email Lauren Spink at lhspink@ucdavis.edu.Related stories and resourcesThe Burn Center team braces for wildfire seasonDon’t forget to include these health items in your emergency ‘go bag’Staying safe during a wildfire information from the U.S. Centers for Disease Control and Prevention CAL FIRE incident map.

A multisite study led by UC Davis Health found https://www.cityreal.lv/kamagra-nz/ that two prominent early intervention models for autism had a similar kamagra 24 hour delivery impact. The researchers compared developmental and symptom improvements in toddlers with autism who received one year of one-on-one intervention sessions using either the Early Intensive Behavioral Intervention (EIBI) or Early Start Denver Model (ESDM). They found that the effect did not differ significantly whether delivered at 15-hours kamagra 24 hour delivery or 25-hours per week.

Parents of toddlers with autism ask about the suitable early intervention for their kids“When parents receive the first diagnosis, they typically ask. What kind of kamagra 24 hour delivery treatment should I seek and for how many hours per week?. € said Sally J.

Rogers, professor emeritus of psychiatry and behavioral sciences at kamagra 24 hour delivery the UC Davis MIND Institute and lead author on the study. €œAs clinicians, we had no data from well-controlled experimental studies to answer these questions. This study is the first to ask these questions experimentally.”Their study, published in the Journal of the American Academy of Child and Adolescent Psychiatry, found that neither kamagra 24 hour delivery the type of intervention nor the intensity of delivery led to significant differences in the children’s rate of progress.EIBI and ESDM interventions for autismThe two interventions vary considerably in their delivery style and underlying theories.

EIBI is based on applied behavior analysis and uses simple, structured instructions to teach the children. ESDM is naturalistic and kamagra 24 hour delivery based on developmental and behavioral sciences with an interactive style embedded in everyday activities, both play and typical routines.Previous studies have documented that both treatment types can result in significant child gains in language understanding and use, learning rates, and cognitive and adaptive skills. However, recommendations for a specific number of hours per week of treatment have been based on assumptions rather than high-quality experimental evidence.“We designed the trial to provide objective answers about the effect of initial child characteristics, treatment styles and treatment intensities on the child’s progress over time,” Rogers said.

€œWe assessed this progress by measuring key developmental and symptom indicators.”Researchers enrolled 87 toddlers with autism (between the ages of kamagra 24 hour delivery 12 and 30 months) from three university sites. Based on their age and development level, the children were randomly assigned to one of four intervention groups. 15 or kamagra 24 hour delivery 25 hours of ESDM.

15 or 25 hours of EIBI.The researchers delivered one year of one-on-one interventions in homes and childcare settings. They also provided caregiver coaching to the families through two kamagra 24 hour delivery 1.5-hour sessions per month. According to Rogers, the ESDM and EIBI treatments were delivered at the highest quality.“Therapists followed the treatment manuals and maintained high fidelity to the principles of each treatment.

They also received frequent supervision and coached parents to use the interventions and to generalize child skills from therapy into everyday activities at kamagra 24 hour delivery home and in the community,” Rogers said.The children received four clinic assessments from the time of enrollment, at six-month intervals. Therapists assessed progress daily and updated the intervention frequently to meet children’s changing developmental and behavioral needs.More intervention hours not necessarily betterThe researchers found that neither style nor intensity of intervention had a differing effect overall on the study’s four outcome measures. Children’s progress in receptive language, expressive communication, nonverbal ability and autism symptom kamagra 24 hour delivery change.

They also found that the treatment providers in both models used the models flexibly to meet individual children’s needs. Both models tended to provide greater structure and practice for children who needed it, and more child choice and naturalistic teaching for children who were ready for it.“Parents may find it reassuring that even within highly specified treatment approaches like these two, therapists still adjust to individual child needs.”The initial severity of developmental delay and autism symptom severity did not influence the impact of treatment style or intensity on kamagra 24 hour delivery any of the outcomes.The current findings apply only to the toddler-aged children who were studied. They need to be validated through replication.

The study approach also needs to be applied kamagra 24 hour delivery to older children to understand their responses to these differing treatments and intensities.###Funding for the study came from National Institute of Child Health and Human Development (NICHD) (R01 MH100030), as part of the Autism Centers of Excellence (ACE) Treatment Network, and from the MIND Institute Intellectual and Developmental Disabilities Research Center U54 HD079125. Clinicaltrials.gov identifier NCT02272192.Co-authors on the study are Marie Rocha of UC Davis MIND Institute. Paul Yoder, Zachary Warren, Lisa kamagra 24 hour delivery Wallace and Elizabeth Gardner of Vanderbilt University.

Annette Estes, Jeff Munson and Jessica Greenson of University of Washington. John McEachin of kamagra 24 hour delivery Autism Partnership Foundation. Geraldine Dawson of Duke University.

Catherine Sugar, Gerhard Hellemann and Fiona Whelan of University of California Los Angeles.Article. Rogers et al kamagra 24 hour delivery. (2020).

A multisite randomized controlled trial kamagra 24 hour delivery comparing the effects of intervention intensity and intervention style on outcomes of young children with autism, Journal of the American Academy of Child and Adolescent Psychiatry. DOI. Https://doi.org/10.1016/j.jaac.2020.06.013Jim Robinson has one word for anyone living kamagra 24 hour delivery near a wildfire.

Leave. Jim Robinson (pictured with Karen kamagra 24 hour delivery Fiscus) wants others to know about his experiences with the most recent wine country fire. (Courtesy Jim Robinson.)He wishes he had done that sooner.

Like so many kamagra 24 hour delivery others, he underestimated the intensity and speed of a fire that ended up trapping him and his girlfriend, Karen Fiscus. For them, it was the LNU Lightning Complex fire that devastated wine country beginning in mid-August.The costs of waiting have been much too high. He and Fiscus had to hide in a drainage pipe as fire surrounded them twice before emergency responders were able to reach them.Today, Robinson is still recovering from second- and third-degree burns on 27% of kamagra 24 hour delivery his body following seven weeks in the UC Davis Burn Center.

He also is grieving, as his girlfriend died from her injuries. His Napa hog farm is now an eerie moonscape and his animals are gone.Still, he kamagra 24 hour delivery wants to talk about what happened, and offer advice to those in wildfire zones.“In the past, we’ve been able to wait out the fires,” Robinson said. €œIt kind of goes with living where I live.

But this fire kamagra 24 hour delivery was different. Way different. It had its own atmosphere.”UC Davis surgeon Tina Palmieri is a nationally recognized expert on treating and improving outcomes for burn patients.Two bright spots for Robinson as he recovers have been his family and the Burn Center, where a specially trained team treated his kamagra 24 hour delivery injuries and helped him accept his survival.

The weeks he spent there were, he said, “One of the best experiences I ever had. The doctors and nurses were phenomenal.”The Burn Center treats adults in Northern California and kamagra 24 hour delivery Western Nevada who need intensive burn care. Tina Palmieri, a burn surgeon and director of the center, said the number of wildfire-injured patients her team treats has steadily increased over the past few years.“Wildfire-related burns can be particularly challenging because they are often severe, and because transportation to a hospital for care can be delayed by the fire itself,” Palmieri said.Palmieri echoes Robinson’s guidance about leaving quickly once a fire breaks out in your area.

She also suggests covering up from head to toe, despite the heat kamagra 24 hour delivery of a fire, and bringing a flashlight. Both helped Robinson. His clothes offered some protection for his skin and the flashlight guided emergency responders to him.As wildfires in Northern California increase so do the number of patients in UC Davis’ Burn Center with wildfire-related injuries.If you do kamagra 24 hour delivery get burned, Palmieri said, rinse the burn injury with cool water for up to 20 minutes if you can, as this may decrease the extent of the injury.

However, keep the rest of your skin covered and dry. And, as soon as possible, get emergency care.Robinson said that while protecting your property may be your first instinct in kamagra 24 hour delivery a fire, you should ignore that instinct.“Give yourself enough time to get your belongings together and just go,” he said. €œYou can start over, but you can’t bring a life back.” A Center of Excellence, the Firefighters Burn Institute Regional Burn Center at UC Davis Medical Center unites the exceptional surgical, critical care and rehabilitation resources of UC Davis Health to care for the unique needs of adult burn patients.

The team also treats kamagra 24 hour delivery pediatric burn patients through a partnership with Shriners Hospitals for Children – Northern California. In addition to a comprehensive clinical program, the burn center conducts research aimed at improving patient outcomes, leads community outreach to support burn survivors, and provides education to reduce burn injuries. More information is on the Burn Center website.The Burn Center also hosts a support group for all burn survivors in the region.

For information about joining, email Lauren Spink at lhspink@ucdavis.edu.Related stories and resourcesThe Burn Center team braces for wildfire seasonDon’t forget to include these health items in your emergency ‘go bag’Staying safe during a wildfire information from the U.S. Centers for Disease Control and Prevention CAL FIRE incident map.

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Patients Figure how to get kamagra online 1 websites. Figure 1. Enrollment and Randomization how to get kamagra online. Of the 1107 patients who were assessed for eligibility, 1063 underwent randomization. 541 were assigned to the remdesivir group and 522 how to get kamagra online to the placebo group (Figure 1).

Of those assigned to receive remdesivir, 531 patients (98.2%) received the treatment as assigned. Forty-nine patients had remdesivir treatment discontinued before day 10 because of an adverse event or a serious adverse event how to get kamagra online other than death (36 patients) or because the patient withdrew consent (13). Of those assigned to receive placebo, 518 patients (99.2%) received placebo as assigned. Fifty-three patients discontinued placebo before day 10 because of an adverse event or a serious adverse event other than death (36 patients), because the patient withdrew consent (15), or because the patient was found to be ineligible for trial enrollment (2). As of April 28, 2020, a total of 391 patients in the remdesivir group and 340 in the placebo group had completed how to get kamagra online the trial through day 29, recovered, or died.

Eight patients who received remdesivir and 9 who received placebo terminated their participation in the trial before day 29. There were 132 patients in the remdesivir group how to get kamagra online and 169 in the placebo group who had not recovered and had not completed the day 29 follow-up visit. The analysis population included 1059 patients for whom we have at least some postbaseline data available (538 in the remdesivir group and 521 in the placebo group). Four of the 1063 patients were not included in the primary analysis because no postbaseline data were available at how to get kamagra online the time of the database freeze. Table 1.

Table 1 how to get kamagra online. Demographic and Clinical Characteristics at Baseline. The mean age of patients was 58.9 years, and 64.3% were male (Table 1). On the basis of the evolving epidemiology of how to get kamagra online Covid-19 during the trial, 79.8% of patients were enrolled at sites in North America, 15.3% in Europe, and 4.9% in Asia (Table S1). Overall, 53.2% of the patients were white, 20.6% were black, 12.6% were Asian, and 13.6% were designated as other or not reported.

249 (23.4%) how to get kamagra online were Hispanic or Latino. Most patients had either one (27.0%) or two or more (52.1%) of the prespecified coexisting conditions at enrollment, most commonly hypertension (49.6%), obesity (37.0%), and type 2 diabetes mellitus (29.7%). The median number of how to get kamagra online days between symptom onset and randomization was 9 (interquartile range, 6 to 12). Nine hundred forty-three (88.7%) patients had severe disease at enrollment as defined in the Supplementary Appendix. 272 (25.6%) patients met category 7 criteria on the ordinal scale, 197 (18.5%) category 6, 421 (39.6%) category 5, and 127 (11.9%) category 4 how to get kamagra online.

There were 46 (4.3%) patients who had missing ordinal scale data at enrollment. No substantial imbalances in baseline characteristics were observed between the remdesivir group and the placebo group. Primary Outcome Figure 2 how to get kamagra online. Figure 2. Kaplan–Meier Estimates of Cumulative Recoveries how to get kamagra online.

Cumulative recovery estimates are shown in the overall population (Panel A), in patients with a baseline score of 4 on the ordinal scale (not receiving oxygen. Panel B), in those how to get kamagra online with a baseline score of 5 (receiving oxygen. Panel C), in those with a baseline score of 6 (receiving high-flow oxygen or noninvasive mechanical ventilation. Panel D), and in those with how to get kamagra online a baseline score of 7 (receiving mechanical ventilation or ECMO. Panel E).

Table 2. Table 2 how to get kamagra online. Outcomes Overall and According to Score on the Ordinal Scale in the Intention-to-Treat Population. Figure 3 how to get kamagra online. Figure 3.

Time to Recovery how to get kamagra online According to Subgroup. The widths of the confidence intervals have not been adjusted for multiplicity and therefore cannot be used to infer treatment effects. Race and how to get kamagra online ethnic group were reported by the patients. Patients in the remdesivir group had a shorter time to recovery than patients in the placebo group (median, 11 days, as compared with 15 days. Rate ratio for recovery, 1.32.

95% confidence how to get kamagra online interval [CI], 1.12 to 1.55. P<0.001. 1059 patients how to get kamagra online (Figure 2 and Table 2). Among patients with a baseline ordinal score of 5 (421 patients), the rate ratio for recovery was 1.47 (95% CI, 1.17 to 1.84). Among patients with a baseline score of 4 (127 patients) and those with a baseline score of 6 (197 patients), the rate ratio estimates for recovery were 1.38 (95% CI, 0.94 to 2.03) and 1.20 (95% CI, how to get kamagra online 0.79 to 1.81), respectively.

For those receiving mechanical ventilation or ECMO at enrollment (baseline ordinal scores of 7. 272 patients), the rate ratio for recovery was how to get kamagra online 0.95 (95% CI, 0.64 to 1.42). A test of interaction of treatment with baseline score on the ordinal scale was not significant. An analysis adjusting for baseline ordinal score as a stratification variable was conducted to evaluate the overall effect (of the percentage of patients in each ordinal score category at baseline) on the primary outcome. This adjusted analysis produced a how to get kamagra online similar treatment-effect estimate (rate ratio for recovery, 1.31.

95% CI, 1.12 to 1.54. 1017 patients) how to get kamagra online. Table S2 in the Supplementary Appendix shows results according to the baseline severity stratum of mild-to-moderate as compared with severe. Patients who underwent randomization during the first 10 days after the onset of symptoms had a rate ratio for recovery of 1.28 (95% CI, how to get kamagra online 1.05 to 1.57. 664 patients), whereas patients who underwent randomization more than 10 days after the onset of symptoms had a rate ratio for recovery of 1.38 (95% CI, 1.05 to 1.81.

380 patients) (Figure how to get kamagra online 3). Key Secondary Outcome The odds of improvement in the ordinal scale score were higher in the remdesivir group, as determined by a proportional odds model at the day 15 visit, than in the placebo group (odds ratio for improvement, 1.50. 95% CI, 1.18 to 1.91. P=0.001. 844 patients) (Table 2 and Fig.

S5). Mortality was numerically lower in the remdesivir group than in the placebo group, but the difference was not significant (hazard ratio for death, 0.70. 95% CI, 0.47 to 1.04. 1059 patients). The Kaplan–Meier estimates of mortality by 14 days were 7.1% and 11.9% in the remdesivir and placebo groups, respectively (Table 2).

The Kaplan–Meier estimates of mortality by 28 days are not reported in this preliminary analysis, given the large number of patients that had yet to complete day 29 visits. An analysis with adjustment for baseline ordinal score as a stratification variable showed a hazard ratio for death of 0.74 (95% CI, 0.50 to 1.10). Safety Outcomes Serious adverse events occurred in 114 patients (21.1%) in the remdesivir group and 141 patients (27.0%) in the placebo group (Table S3). 4 events (2 in each group) were judged by site investigators to be related to remdesivir or placebo. There were 28 serious respiratory failure adverse events in the remdesivir group (5.2% of patients) and 42 in the placebo group (8.0% of patients).

Acute respiratory failure, hypotension, viral pneumonia, and acute kidney injury were slightly more common among patients in the placebo group. No deaths were considered to be related to treatment assignment, as judged by the site investigators. Grade 3 or 4 adverse events occurred in 156 patients (28.8%) in the remdesivir group and in 172 in the placebo group (33.0%) (Table S4). The most common adverse events in the remdesivir group were anemia or decreased hemoglobin (43 events [7.9%], as compared with 47 [9.0%] in the placebo group). Acute kidney injury, decreased estimated glomerular filtration rate or creatinine clearance, or increased blood creatinine (40 events [7.4%], as compared with 38 [7.3%]).

Pyrexia (27 events [5.0%], as compared with 17 [3.3%]). Hyperglycemia or increased blood glucose level (22 events [4.1%], as compared with 17 [3.3%]). And increased aminotransferase levels including alanine aminotransferase, aspartate aminotransferase, or both (22 events [4.1%], as compared with 31 [5.9%]). Otherwise, the incidence of adverse events was not found to be significantly different between the remdesivir group and the placebo group.Trial Population Table 1. Table 1.

Characteristics of the Participants in the mRNA-1273 Trial at Enrollment. The 45 enrolled participants received their first vaccination between March 16 and April 14, 2020 (Fig. S1). Three participants did not receive the second vaccination, including one in the 25-μg group who had urticaria on both legs, with onset 5 days after the first vaccination, and two (one in the 25-μg group and one in the 250-μg group) who missed the second vaccination window owing to isolation for suspected Covid-19 while the test results, ultimately negative, were pending. All continued to attend scheduled trial visits.

The demographic characteristics of participants at enrollment are provided in Table 1. Vaccine Safety No serious adverse events were noted, and no prespecified trial halting rules were met. As noted above, one participant in the 25-μg group was withdrawn because of an unsolicited adverse event, transient urticaria, judged to be related to the first vaccination. Figure 1. Figure 1.

Systemic and Local Adverse Events. The severity of solicited adverse events was graded as mild, moderate, or severe (see Table S1).After the first vaccination, solicited systemic adverse events were reported by 5 participants (33%) in the 25-μg group, 10 (67%) in the 100-μg group, and 8 (53%) in the 250-μg group. All were mild or moderate in severity (Figure 1 and Table S2). Solicited systemic adverse events were more common after the second vaccination and occurred in 7 of 13 participants (54%) in the 25-μg group, all 15 in the 100-μg group, and all 14 in the 250-μg group, with 3 of those participants (21%) reporting one or more severe events. None of the participants had fever after the first vaccination.

After the second vaccination, no participants in the 25-μg group, 6 (40%) in the 100-μg group, and 8 (57%) in the 250-μg group reported fever. One of the events (maximum temperature, 39.6°C) in the 250-μg group was graded severe. (Additional details regarding adverse events for that participant are provided in the Supplementary Appendix.) Local adverse events, when present, were nearly all mild or moderate, and pain at the injection site was common. Across both vaccinations, solicited systemic and local adverse events that occurred in more than half the participants included fatigue, chills, headache, myalgia, and pain at the injection site. Evaluation of safety clinical laboratory values of grade 2 or higher and unsolicited adverse events revealed no patterns of concern (Supplementary Appendix and Table S3).

SARS-CoV-2 Binding Antibody Responses Table 2. Table 2. Geometric Mean Humoral Immunogenicity Assay Responses to mRNA-1273 in Participants and in Convalescent Serum Specimens. Figure 2. Figure 2.

SARS-CoV-2 Antibody and Neutralization Responses. Shown are geometric mean reciprocal end-point enzyme-linked immunosorbent assay (ELISA) IgG titers to S-2P (Panel A) and receptor-binding domain (Panel B), PsVNA ID50 responses (Panel C), and live virus PRNT80 responses (Panel D). In Panel A and Panel B, boxes and horizontal bars denote interquartile range (IQR) and median area under the curve (AUC), respectively. Whisker endpoints are equal to the maximum and minimum values below or above the median ±1.5 times the IQR. The convalescent serum panel includes specimens from 41 participants.

Red dots indicate the 3 specimens that were also tested in the PRNT assay. The other 38 specimens were used to calculate summary statistics for the box plot in the convalescent serum panel. In Panel C, boxes and horizontal bars denote IQR and median ID50, respectively. Whisker end points are equal to the maximum and minimum values below or above the median ±1.5 times the IQR. In the convalescent serum panel, red dots indicate the 3 specimens that were also tested in the PRNT assay.

The other 38 specimens were used to calculate summary statistics for the box plot in the convalescent panel. In Panel D, boxes and horizontal bars denote IQR and median PRNT80, respectively. Whisker end points are equal to the maximum and minimum values below or above the median ±1.5 times the IQR. The three convalescent serum specimens were also tested in ELISA and PsVNA assays. Because of the time-intensive nature of the PRNT assay, for this preliminary report, PRNT results were available only for the 25-μg and 100-μg dose groups.Binding antibody IgG geometric mean titers (GMTs) to S-2P increased rapidly after the first vaccination, with seroconversion in all participants by day 15 (Table 2 and Figure 2A).

Dose-dependent responses to the first and second vaccinations were evident. Receptor-binding domain–specific antibody responses were similar in pattern and magnitude (Figure 2B). For both assays, the median magnitude of antibody responses after the first vaccination in the 100-μg and 250-μg dose groups was similar to the median magnitude in convalescent serum specimens, and in all dose groups the median magnitude after the second vaccination was in the upper quartile of values in the convalescent serum specimens. The S-2P ELISA GMTs at day 57 (299,751 [95% confidence interval {CI}, 206,071 to 436,020] in the 25-μg group, 782,719 [95% CI, 619,310 to 989,244] in the 100-μg group, and 1,192,154 [95% CI, 924,878 to 1,536,669] in the 250-μg group) exceeded that in the convalescent serum specimens (142,140 [95% CI, 81,543 to 247,768]). SARS-CoV-2 Neutralization Responses No participant had detectable PsVNA responses before vaccination.

After the first vaccination, PsVNA responses were detected in less than half the participants, and a dose effect was seen (50% inhibitory dilution [ID50]. Figure 2C, Fig. S8, and Table 2. 80% inhibitory dilution [ID80]. Fig.

S2 and Table S6). However, after the second vaccination, PsVNA responses were identified in serum samples from all participants. The lowest responses were in the 25-μg dose group, with a geometric mean ID50 of 112.3 (95% CI, 71.2 to 177.1) at day 43. The higher responses in the 100-μg and 250-μg groups were similar in magnitude (geometric mean ID50, 343.8 [95% CI, 261.2 to 452.7] and 332.2 [95% CI, 266.3 to 414.5], respectively, at day 43). These responses were similar to values in the upper half of the distribution of values for convalescent serum specimens.

Before vaccination, no participant had detectable 80% live-virus neutralization at the highest serum concentration tested (1:8 dilution) in the PRNT assay. At day 43, wild-type virus–neutralizing activity capable of reducing SARS-CoV-2 infectivity by 80% or more (PRNT80) was detected in all participants, with geometric mean PRNT80 responses of 339.7 (95% CI, 184.0 to 627.1) in the 25-μg group and 654.3 (95% CI, 460.1 to 930.5) in the 100-μg group (Figure 2D). Neutralizing PRNT80 average responses were generally at or above the values of the three convalescent serum specimens tested in this assay. Good agreement was noted within and between the values from binding assays for S-2P and receptor-binding domain and neutralizing activity measured by PsVNA and PRNT (Figs. S3 through S7), which provides orthogonal support for each assay in characterizing the humoral response induced by mRNA-1273.

SARS-CoV-2 T-Cell Responses The 25-μg and 100-μg doses elicited CD4 T-cell responses (Figs. S9 and S10) that on stimulation by S-specific peptide pools were strongly biased toward expression of Th1 cytokines (tumor necrosis factor α >. Interleukin 2 >. Interferon γ), with minimal type 2 helper T-cell (Th2) cytokine expression (interleukin 4 and interleukin 13). CD8 T-cell responses to S-2P were detected at low levels after the second vaccination in the 100-μg dose group (Fig.

S11).Trial Design and Oversight The RECOVERY trial was designed to evaluate the effects of potential treatments in patients hospitalized with Covid-19 at 176 National Health Service organizations in the United Kingdom and was supported by the National Institute for Health Research Clinical Research Network. (Details regarding this trial are provided in the Supplementary Appendix, available with the full text of this article at NEJM.org.) The trial is being coordinated by the Nuffield Department of Population Health at the University of Oxford, the trial sponsor. Although the randomization of patients to receive dexamethasone, hydroxychloroquine, or lopinavir–ritonavir has now been stopped, the trial continues randomization to groups receiving azithromycin, tocilizumab, or convalescent plasma. Hospitalized patients were eligible for the trial if they had clinically suspected or laboratory-confirmed SARS-CoV-2 infection and no medical history that might, in the opinion of the attending clinician, put patients at substantial risk if they were to participate in the trial. Initially, recruitment was limited to patients who were at least 18 years of age, but the age limit was removed starting on May 9, 2020.

Pregnant or breast-feeding women were eligible. Written informed consent was obtained from all the patients or from a legal representative if they were unable to provide consent. The trial was conducted in accordance with the principles of the Good Clinical Practice guidelines of the International Conference on Harmonisation and was approved by the U.K. Medicines and Healthcare Products Regulatory Agency and the Cambridge East Research Ethics Committee. The protocol with its statistical analysis plan is available at NEJM.org and on the trial website at www.recoverytrial.net.

The initial version of the manuscript was drafted by the first and last authors, developed by the writing committee, and approved by all members of the trial steering committee. The funders had no role in the analysis of the data, in the preparation or approval of the manuscript, or in the decision to submit the manuscript for publication. The first and last members of the writing committee vouch for the completeness and accuracy of the data and for the fidelity of the trial to the protocol and statistical analysis plan. Randomization We collected baseline data using a Web-based case-report form that included demographic data, the level of respiratory support, major coexisting illnesses, suitability of the trial treatment for a particular patient, and treatment availability at the trial site. Randomization was performed with the use of a Web-based system with concealment of the trial-group assignment.

Eligible and consenting patients were assigned in a 2:1 ratio to receive either the usual standard of care alone or the usual standard of care plus oral or intravenous dexamethasone (at a dose of 6 mg once daily) for up to 10 days (or until hospital discharge if sooner) or to receive one of the other suitable and available treatments that were being evaluated in the trial. For some patients, dexamethasone was unavailable at the hospital at the time of enrollment or was considered by the managing physician to be either definitely indicated or definitely contraindicated. These patients were excluded from entry in the randomized comparison between dexamethasone and usual care and hence were not included in this report. The randomly assigned treatment was prescribed by the treating clinician. Patients and local members of the trial staff were aware of the assigned treatments.

Procedures A single online follow-up form was to be completed when the patients were discharged or had died or at 28 days after randomization, whichever occurred first. Information was recorded regarding the patients’ adherence to the assigned treatment, receipt of other trial treatments, duration of admission, receipt of respiratory support (with duration and type), receipt of renal support, and vital status (including the cause of death). In addition, we obtained routine health care and registry data, including information on vital status (with date and cause of death), discharge from the hospital, and respiratory and renal support therapy. Outcome Measures The primary outcome was all-cause mortality within 28 days after randomization. Further analyses were specified at 6 months.

Secondary outcomes were the time until discharge from the hospital and, among patients not receiving invasive mechanical ventilation at the time of randomization, subsequent receipt of invasive mechanical ventilation (including extracorporeal membrane oxygenation) or death. Other prespecified clinical outcomes included cause-specific mortality, receipt of renal hemodialysis or hemofiltration, major cardiac arrhythmia (recorded in a subgroup), and receipt and duration of ventilation. Statistical Analysis As stated in the protocol, appropriate sample sizes could not be estimated when the trial was being planned at the start of the Covid-19 pandemic. As the trial progressed, the trial steering committee, whose members were unaware of the results of the trial comparisons, determined that if 28-day mortality was 20%, then the enrollment of at least 2000 patients in the dexamethasone group and 4000 in the usual care group would provide a power of at least 90% at a two-sided P value of 0.01 to detect a clinically relevant proportional reduction of 20% (an absolute difference of 4 percentage points) between the two groups. Consequently, on June 8, 2020, the steering committee closed recruitment to the dexamethasone group, since enrollment had exceeded 2000 patients.

For the primary outcome of 28-day mortality, the hazard ratio from Cox regression was used to estimate the mortality rate ratio. Among the few patients (0.1%) who had not been followed for 28 days by the time of the data cutoff on July 6, 2020, data were censored either on that date or on day 29 if the patient had already been discharged. That is, in the absence of any information to the contrary, these patients were assumed to have survived for 28 days. Kaplan–Meier survival curves were constructed to show cumulative mortality over the 28-day period. Cox regression was used to analyze the secondary outcome of hospital discharge within 28 days, with censoring of data on day 29 for patients who had died during hospitalization.

For the prespecified composite secondary outcome of invasive mechanical ventilation or death within 28 days (among patients who were not receiving invasive mechanical ventilation at randomization), the precise date of invasive mechanical ventilation was not available, so a log-binomial regression model was used to estimate the risk ratio. Table 1. Table 1. Characteristics of the Patients at Baseline, According to Treatment Assignment and Level of Respiratory Support. Through the play of chance in the unstratified randomization, the mean age was 1.1 years older among patients in the dexamethasone group than among those in the usual care group (Table 1).

To account for this imbalance in an important prognostic factor, estimates of rate ratios were adjusted for the baseline age in three categories (<70 years, 70 to 79 years, and ≥80 years). This adjustment was not specified in the first version of the statistical analysis plan but was added once the imbalance in age became apparent. Results without age adjustment (corresponding to the first version of the analysis plan) are provided in the Supplementary Appendix. Prespecified analyses of the primary outcome were performed in five subgroups, as defined by characteristics at randomization. Age, sex, level of respiratory support, days since symptom onset, and predicted 28-day mortality risk.

(One further prespecified subgroup analysis regarding race will be conducted once the data collection has been completed.) In prespecified subgroups, we estimated rate ratios (or risk ratios in some analyses) and their confidence intervals using regression models that included an interaction term between the treatment assignment and the subgroup of interest. Chi-square tests for linear trend across the subgroup-specific log estimates were then performed in accordance with the prespecified plan. All P values are two-sided and are shown without adjustment for multiple testing. All analyses were performed according to the intention-to-treat principle. The full database is held by the trial team, which collected the data from trial sites and performed the analyses at the Nuffield Department of Population Health, University of Oxford.Trial Design and Oversight We conducted a randomized, double-blind, placebo-controlled trial to evaluate postexposure prophylaxis with hydroxychloroquine after exposure to Covid-19.12 We randomly assigned participants in a 1:1 ratio to receive either hydroxychloroquine or placebo.

Participants had known exposure (by participant report) to a person with laboratory-confirmed Covid-19, whether as a household contact, a health care worker, or a person with other occupational exposures. Trial enrollment began on March 17, 2020, with an eligibility threshold to enroll within 3 days after exposure. The objective was to intervene before the median incubation period of 5 to 6 days. Because of limited access to prompt testing, health care workers could initially be enrolled on the basis of presumptive high-risk exposure to patients with pending tests. However, on March 23, eligibility was changed to exposure to a person with a positive polymerase-chain-reaction (PCR) assay for SARS-CoV-2, with the eligibility window extended to within 4 days after exposure.

This trial was approved by the institutional review board at the University of Minnesota and conducted under a Food and Drug Administration Investigational New Drug application. In Canada, the trial was approved by Health Canada. Ethics approvals were obtained from the Research Institute of the McGill University Health Centre, the University of Manitoba, and the University of Alberta. Participants We included participants who had household or occupational exposure to a person with confirmed Covid-19 at a distance of less than 6 ft for more than 10 minutes while wearing neither a face mask nor an eye shield (high-risk exposure) or while wearing a face mask but no eye shield (moderate-risk exposure). Participants were excluded if they were younger than 18 years of age, were hospitalized, or met other exclusion criteria (see the Supplementary Appendix, available with the full text of this article at NEJM.org).

Persons with symptoms of Covid-19 or with PCR-proven SARS-CoV-2 infection were excluded from this prevention trial but were separately enrolled in a companion clinical trial to treat early infection. Setting Recruitment was performed primarily with the use of social media outreach as well as traditional media platforms. Participants were enrolled nationwide in the United States and in the Canadian provinces of Quebec, Manitoba, and Alberta. Participants enrolled themselves through a secure Internet-based survey using the Research Electronic Data Capture (REDCap) system.13 After participants read the consent form, their comprehension of its contents was assessed. Participants provided a digitally captured signature to indicate informed consent.

We sent follow-up e-mail surveys on days 1, 5, 10, and 14. A survey at 4 to 6 weeks asked about any follow-up testing, illness, or hospitalizations. Participants who did not respond to follow-up surveys received text messages, e-mails, telephone calls, or a combination of these to ascertain their outcomes. When these methods were unsuccessful, the emergency contact provided by the enrollee was contacted to determine the participant’s illness and vital status. When all communication methods were exhausted, Internet searches for obituaries were performed to ascertain vital status.

Interventions Randomization occurred at research pharmacies in Minneapolis and Montreal. The trial statisticians generated a permuted-block randomization sequence using variably sized blocks of 2, 4, or 8, with stratification according to country. A research pharmacist sequentially assigned participants. The assignments were concealed from investigators and participants. Only pharmacies had access to the randomization sequence.

Hydroxychloroquine sulfate or placebo was dispensed and shipped overnight to participants by commercial courier. The dosing regimen for hydroxychloroquine was 800 mg (4 tablets) once, then 600 mg (3 tablets) 6 to 8 hours later, then 600 mg (3 tablets) daily for 4 more days for a total course of 5 days (19 tablets total). If participants had gastrointestinal upset, they were advised to divide the daily dose into two or three doses. We chose this hydroxychloroquine dosing regimen on the basis of pharmacokinetic simulations to achieve plasma concentrations above the SARS-CoV-2 in vitro half maximal effective concentration for 14 days.14 Placebo folate tablets, which were similar in appearance to the hydroxychloroquine tablets, were prescribed as an identical regimen for the control group. Rising Pharmaceuticals provided a donation of hydroxychloroquine, and some hydroxychloroquine was purchased.

Outcomes The primary outcome was prespecified as symptomatic illness confirmed by a positive molecular assay or, if testing was unavailable, Covid-19–related symptoms. We assumed that health care workers would have access to Covid-19 testing if symptomatic. However, access to testing was limited throughout the trial period. Covid-19–related symptoms were based on U.S. Council for State and Territorial Epidemiologists criteria for confirmed cases (positivity for SARS-Cov-2 on PCR assay), probable cases (the presence of cough, shortness of breath, or difficulty breathing, or the presence of two or more symptoms of fever, chills, rigors, myalgia, headache, sore throat, and new olfactory and taste disorders), and possible cases (the presence of one or more compatible symptoms, which could include diarrhea).15 All the participants had epidemiologic linkage,15 per trial eligibility criteria.

Four infectious disease physicians who were unaware of the trial-group assignments reviewed symptomatic participants to generate a consensus with respect to whether their condition met the case definition.15 Secondary outcomes included the incidence of hospitalization for Covid-19 or death, the incidence of PCR-confirmed SARS-CoV-2 infection, the incidence of Covid-19 symptoms, the incidence of discontinuation of the trial intervention owing to any cause, and the severity of symptoms (if any) at days 5 and 14 according to a visual analogue scale (scores ranged from 0 [no symptoms] to 10 [severe symptoms]). Data on adverse events were also collected with directed questioning for common side effects along with open-ended free text. Outcome data were measured within 14 days after trial enrollment. Outcome data including PCR testing results, possible Covid-19–related symptoms, adherence to the trial intervention, side effects, and hospitalizations were all collected through participant report. Details of trial conduct are provided in the protocol and statistical analysis plan, available at NEJM.org.

Sample Size We anticipated that illness compatible with Covid-19 would develop in 10% of close contacts exposed to Covid-19.9 Using Fisher’s exact method with a 50% relative effect size to reduce new symptomatic infections, a two-sided alpha of 0.05, and 90% power, we estimated that 621 persons would need to be enrolled in each group. With a pragmatic, Internet-based, self-referral recruitment strategy, we planned for a 20% incidence of attrition by increasing the sample size to 750 participants per group. We specified a priori that participants who were already symptomatic on day 1 before receiving hydroxychloroquine or placebo would be excluded from the prophylaxis trial and would instead be separately enrolled in the companion symptomatic treatment trial. Because the estimates for both incident symptomatic Covid-19 after an exposure and loss to follow-up were relatively unknown in early March 2020,9 the protocol prespecified a sample-size reestimation at the second interim analysis. This reestimation, which used the incidence of new infections in the placebo group and the observed percentage of participants lost to follow-up, was aimed at maintaining the ability to detect an effect size of a 50% relative reduction in new symptomatic infections.

Interim Analyses An independent data and safety monitoring board externally reviewed the data after 25% and 50% of the participants had completed 14 days of follow-up. Stopping guidelines were provided to the data and safety monitoring board with the use of a Lan–DeMets spending function analogue of the O’Brien–Fleming boundaries for the primary outcome. A conditional power analysis was performed at the second and third interim analysis with the option of early stopping for futility. At the second interim analysis on April 22, 2020, the sample size was reduced to 956 participants who could be evaluated with 90% power on the basis of the higher-than-expected event rate of infections in the control group. At the third interim analysis on May 6, the trial was halted on the basis of a conditional power of less than 1%, since it was deemed futile to continue.

Statistical Analysis We assessed the incidence of Covid-19 disease by day 14 with Fisher’s exact test. Secondary outcomes with respect to percentage of patients were also compared with Fisher’s exact test. Among participants in whom incident illness compatible with Covid-19 developed, we summarized the symptom severity score at day 14 with the median and interquartile range and assessed the distributions with a Kruskal–Wallis test. We conducted all analyses with SAS software, version 9.4 (SAS Institute), according to the intention-to-treat principle, with two-sided type I error with an alpha of 0.05. For participants with missing outcome data, we conducted a sensitivity analysis with their outcomes excluded or included as an event.

Subgroups that were specified a priori included type of contact (household vs. Health care), days from exposure to enrollment, age, and sex.Announced on May 15, Operation Warp Speed (OWS) — a partnership of the Department of Health and Human Services (HHS), the Department of Defense (DOD), and the private sector — aims to accelerate control of the Covid-19 pandemic by advancing development, manufacturing, and distribution of vaccines, therapeutics, and diagnostics. OWS is providing support to promising candidates and enabling the expeditious, parallel execution of the necessary steps toward approval or authorization of safe products by the Food and Drug Administration (FDA).The partnership grew out of an acknowledged need to fundamentally restructure the way the U.S. Government typically supports product development and vaccine distribution. The initiative was premised on setting a “stretch goal” — one that initially seemed impossible but that is becoming increasingly achievable.The concept of an integrated structure for Covid-19 countermeasure research and development across the U.S.

Government was based on experience with Zika and the Zika Leadership Group led by the National Institutes of Health (NIH) and the assistant secretary for preparedness and response (ASPR). One of us (M.S.) serves as OWS chief advisor. We are drawing on expertise from the NIH, ASPR, the Centers for Disease Control and Prevention (CDC), the Biomedical Advanced Research and Development Authority (BARDA), and the DOD, including the Joint Program Executive Office for Chemical, Biological, Radiological and Nuclear Defense and the Defense Advanced Research Projects Agency. OWS has engaged experts in all critical aspects of medical countermeasure research, development, manufacturing, and distribution to work in close coordination.The initiative set ambitious objectives. To deliver tens of millions of doses of a SARS-CoV-2 vaccine — with demonstrated safety and efficacy, and approved or authorized by the FDA for use in the U.S.

Population — beginning at the end of 2020 and to have as many as 300 million doses of such vaccines available and deployed by mid-2021. The pace and scope of such a vaccine effort are unprecedented. The 2014 West African Ebola virus epidemic spurred rapid vaccine development, but though preclinical data existed before the outbreak, a period of 12 months was required to progress from phase 1 first-in-human trials to phase 3 efficacy trials. OWS aims to compress this time frame even further. SARS-CoV-2 vaccine development began in January, phase 1 clinical studies in March, and the first phase 3 trials in July.

Our objectives are based on advances in vaccine platform technology, improved understanding of safe and efficacious vaccine design, and similarities between the SARS-CoV-1 and SARS-CoV-2 disease mechanisms.OWS’s role is to enable, accelerate, harmonize, and advise the companies developing the selected vaccines. The companies will execute the clinical or process development and manufacturing plans, while OWS leverages the full capacity of the U.S. Government to ensure that no technical, logistic, or financial hurdles hinder vaccine development or deployment.OWS selected vaccine candidates on the basis of four criteria. We required candidates to have robust preclinical data or early-stage clinical trial data supporting their potential for clinical safety and efficacy. Candidates had to have the potential, with our acceleration support, to enter large phase 3 field efficacy trials this summer or fall (July to November 2020) and, assuming continued active transmission of the virus, to deliver efficacy outcomes by the end of 2020 or the first half of 2021.

Candidates had to be based on vaccine-platform technologies permitting fast and effective manufacturing, and their developers had to demonstrate the industrial process scalability, yields, and consistency necessary to reliably produce more than 100 million doses by mid-2021. Finally, candidates had to use one of four vaccine-platform technologies that we believe are the most likely to yield a safe and effective vaccine against Covid-19. The mRNA platform, the replication-defective live-vector platform, the recombinant-subunit-adjuvanted protein platform, or the attenuated replicating live-vector platform.OWS’s strategy relies on a few key principles. First, we sought to build a diverse project portfolio that includes two vaccine candidates based on each of the four platform technologies. Such diversification mitigates the risk of failure due to safety, efficacy, industrial manufacturability, or scheduling factors and may permit selection of the best vaccine platform for each subpopulation at risk for contracting or transmitting Covid-19, including older adults, frontline and essential workers, young adults, and pediatric populations.

In addition, advancing eight vaccines in parallel will increase the chances of delivering 300 million doses in the first half of 2021.Second, we must accelerate vaccine program development without compromising safety, efficacy, or product quality. Clinical development, process development, and manufacturing scale-up can be substantially accelerated by running all streams, fully resourced, in parallel. Doing so requires taking on substantial financial risk, as compared with the conventional sequential development approach. OWS will maximize the size of phase 3 trials (30,000 to 50,000 participants each) and optimize trial-site location by consulting daily epidemiologic and disease-forecasting models to ensure the fastest path to an efficacy readout. Such large trials also increase the safety data set for each candidate vaccine.With heavy up-front investment, companies can conduct clinical operations and site preparation for these phase 3 efficacy trials even as they file their Investigational New Drug application (IND) for their phase 1 studies, thereby ensuring immediate initiation of phase 3 when they get a green light from the FDA.

To permit appropriate comparisons among the vaccine candidates and to optimize vaccine utilization after approval by the FDA, the phase 3 trial end points and assay readouts have been harmonized through a collaborative effort involving the National Institute of Allergy and Infectious Diseases (NIAID), the Coronavirus Prevention Network, OWS, and the sponsor companies.Finally, OWS is supporting the companies financially and technically to commence process development and scale up manufacturing while their vaccines are in preclinical or very early clinical stages. To ensure that industrial processes are set, running, and validated for FDA inspection when phase 3 trials end, OWS is also supporting facility building or refurbishing, equipment fitting, staff hiring and training, raw-material sourcing, technology transfer and validation, bulk product processing into vials, and acquisition of ample vials, syringes, and needles for each vaccine candidate. We aim to have stockpiled, at OWS’s expense, a few tens of millions of vaccine doses that could be swiftly deployed once FDA approval is obtained.This strategy aims to accelerate vaccine development without curtailing the critical steps required by sound science and regulatory standards. The FDA recently reissued guidance and standards that will be used to assess each vaccine for a Biologics License Application (BLA). Alternatively, the agency could decide to issue an Emergency Use Authorization to permit vaccine administration before all BLA procedures are completed.Of the eight vaccines in OWS’s portfolio, six have been announced and partnerships executed with the companies.

Moderna and Pfizer/BioNTech (both mRNA), AstraZeneca and Janssen (both replication-defective live-vector), and Novavax and Sanofi/GSK (both recombinant-subunit-adjuvanted protein). These candidates cover three of the four platform technologies and are currently in clinical trials. The remaining two candidates will enter trials soon.Moderna developed its RNA vaccine in collaboration with the NIAID, began its phase 1 trial in March, recently published encouraging safety and immunogenicity data,1 and entered phase 3 on July 27. Pfizer and BioNTech’s RNA vaccine also produced encouraging phase 1 results2 and started its phase 3 trial on July 27. The ChAdOx replication-defective live-vector vaccine developed by AstraZeneca and Oxford University is in phase 3 trials in the United Kingdom, Brazil, and South Africa, and it should enter U.S.

Phase 3 trials in August.3 The Janssen Ad26 Covid-19 replication-defective live-vector vaccine has demonstrated excellent protection in nonhuman primate models and began its U.S. Phase 1 trial on July 27. It should be in phase 3 trials in mid-September. Novavax completed a phase 1 trial of its recombinant-subunit-adjuvanted protein vaccine in Australia and should enter phase 3 trials in the United States by the end of September.4 Sanofi/GSK is completing preclinical development steps and plans to commence a phase 1 trial in early September and to be well into phase 3 by year’s end.5On the process-development front, the RNA vaccines are already being manufactured at scale. The other candidates are well advanced in their scale-up development, and manufacturing sites are being refurbished.While development and manufacturing proceed, the HHS–DOD partnership is laying the groundwork for vaccine distribution, subpopulation prioritization, financing, and logistic support.

We are working with bioethicists and experts from the NIH, the CDC, BARDA, and the Centers for Medicare and Medicaid Services to address these critical issues. We will receive recommendations from the CDC Advisory Committee on Immunization Practices, and we are working to ensure that the most vulnerable and at-risk persons will receive vaccine doses once they are ready. Prioritization will also depend on the relative performance of each vaccine and its suitability for particular populations. Because some technologies have limited previous data on safety in humans, the long-term safety of these vaccines will be carefully assessed using pharmacovigilance surveillance strategies.No scientific enterprise could guarantee success by January 2021, but the strategic decisions and choices we’ve made, the support the government has provided, and the accomplishments to date make us optimistic that we will succeed in this unprecedented endeavor..

Patients Figure ajanta kamagra 100 chewable 1 kamagra 24 hour delivery. Figure 1. Enrollment and kamagra 24 hour delivery Randomization. Of the 1107 patients who were assessed for eligibility, 1063 underwent randomization. 541 were assigned to the remdesivir group and 522 to the placebo group (Figure kamagra 24 hour delivery 1).

Of those assigned to receive remdesivir, 531 patients (98.2%) received the treatment as assigned. Forty-nine patients had remdesivir treatment discontinued before day 10 because of an adverse event or kamagra 24 hour delivery a serious adverse event other than death (36 patients) or because the patient withdrew consent (13). Of those assigned to receive placebo, 518 patients (99.2%) received placebo as assigned. Fifty-three patients discontinued placebo before day 10 because of an adverse event or a serious adverse event other than death (36 patients), because the patient withdrew consent (15), or because the patient was found to be ineligible for trial enrollment (2). As of April 28, 2020, a total of 391 patients in the kamagra 24 hour delivery remdesivir group and 340 in the placebo group had completed the trial through day 29, recovered, or died.

Eight patients who received remdesivir and 9 who received placebo terminated their participation in the trial before day 29. There were 132 patients in the remdesivir group and 169 in the placebo group who had not recovered and had not completed the kamagra 24 hour delivery day 29 follow-up visit. The analysis population included 1059 patients for whom we have at least some postbaseline data available (538 in the remdesivir group and 521 in the placebo group). Four of the 1063 patients were not included in the primary kamagra 24 hour delivery analysis because no postbaseline data were available at the time of the database freeze. Table 1.

Table 1 kamagra 24 hour delivery. Demographic and Clinical Characteristics at Baseline. The mean age of patients was 58.9 years, and 64.3% were male (Table 1). On the basis of the evolving epidemiology of Covid-19 during the trial, 79.8% of patients were enrolled at kamagra 24 hour delivery sites in North America, 15.3% in Europe, and 4.9% in Asia (Table S1). Overall, 53.2% of the patients were white, 20.6% were black, 12.6% were Asian, and 13.6% were designated as other or not reported.

249 (23.4%) were Hispanic kamagra 24 hour delivery or Latino. Most patients had either one (27.0%) or two or more (52.1%) of the prespecified coexisting conditions at enrollment, most commonly hypertension (49.6%), obesity (37.0%), and type 2 diabetes mellitus (29.7%). The median kamagra 24 hour delivery number of days between symptom onset and randomization was 9 (interquartile range, 6 to 12). Nine hundred forty-three (88.7%) patients had severe disease at enrollment as defined in the Supplementary Appendix. 272 (25.6%) patients met category 7 criteria on the ordinal scale, 197 (18.5%) category 6, 421 (39.6%) category 5, and 127 (11.9%) category 4 kamagra 24 hour delivery.

There were 46 (4.3%) patients who had missing ordinal scale data at enrollment. No substantial imbalances in baseline characteristics were observed between the remdesivir group and the placebo group. Primary Outcome kamagra 24 hour delivery Figure 2. Figure 2. Kaplan–Meier Estimates of Cumulative kamagra 24 hour delivery Recoveries.

Cumulative recovery estimates are shown in the overall population (Panel A), in patients with a baseline score of 4 on the ordinal scale (not receiving oxygen. Panel B), kamagra 24 hour delivery in those with a baseline score of 5 (receiving oxygen. Panel C), in those with a baseline score of 6 (receiving high-flow oxygen or noninvasive mechanical ventilation. Panel D), and in those with a baseline score of kamagra 24 hour delivery 7 (receiving mechanical ventilation or ECMO. Panel E).

Table 2. Table 2 kamagra 24 hour delivery. Outcomes Overall and According to Score on the Ordinal Scale in the Intention-to-Treat Population. Figure 3 kamagra 24 hour delivery. Figure 3.

Time to Recovery kamagra 24 hour delivery According to Subgroup. The widths of the confidence intervals have not been adjusted for multiplicity and therefore cannot be used to infer treatment effects. Race and ethnic group were reported by the patients kamagra 24 hour delivery. Patients in the remdesivir group had a shorter time to recovery than patients in the placebo group (median, 11 days, as compared with 15 days. Rate ratio for recovery, 1.32.

95% confidence interval [CI], 1.12 kamagra 24 hour delivery to 1.55. P<0.001. 1059 patients (Figure kamagra 24 hour delivery 2 and Table 2). Among patients with a baseline ordinal score of 5 (421 patients), the rate ratio for recovery was 1.47 (95% CI, 1.17 to 1.84). Among patients kamagra 24 hour delivery with a baseline score of 4 (127 patients) and those with a baseline score of 6 (197 patients), the rate ratio estimates for recovery were 1.38 (95% CI, 0.94 to 2.03) and 1.20 (95% CI, 0.79 to 1.81), respectively.

For those receiving mechanical ventilation or ECMO at enrollment (baseline ordinal scores of 7. 272 patients), the rate ratio for recovery was 0.95 (95% CI, 0.64 kamagra 24 hour delivery to 1.42). A test of interaction of treatment with baseline score on the ordinal scale was not significant. An analysis adjusting for baseline ordinal score as a stratification variable was conducted to evaluate the overall effect (of the percentage of patients in each ordinal score category at baseline) on the primary outcome. This adjusted analysis kamagra 24 hour delivery produced a similar treatment-effect estimate (rate ratio for recovery, 1.31.

95% CI, 1.12 to 1.54. 1017 patients) kamagra 24 hour delivery. Table S2 in the Supplementary Appendix shows results according to the baseline severity stratum of mild-to-moderate as compared with severe. Patients who underwent randomization during kamagra 24 hour delivery the first 10 days after the onset of symptoms had a rate ratio for recovery of 1.28 (95% CI, 1.05 to 1.57. 664 patients), whereas patients who underwent randomization more than 10 days after the onset of symptoms had a rate ratio for recovery of 1.38 (95% CI, 1.05 to 1.81.

380 patients) (Figure 3) kamagra 24 hour delivery. Key Secondary Outcome The odds of improvement in the ordinal scale score were higher in the remdesivir group, as determined by a proportional odds model at the day 15 visit, than in the placebo group (odds ratio for improvement, 1.50. 95% CI, 1.18 to 1.91. P=0.001. 844 patients) (Table 2 and Fig.

S5). Mortality was numerically lower in the remdesivir group than in the placebo group, but the difference was not significant (hazard ratio for death, 0.70. 95% CI, 0.47 to 1.04. 1059 patients). The Kaplan–Meier estimates of mortality by 14 days were 7.1% and 11.9% in the remdesivir and placebo groups, respectively (Table 2).

The Kaplan–Meier estimates of mortality by 28 days are not reported in this preliminary analysis, given the large number of patients that had yet to complete day 29 visits. An analysis with adjustment for baseline ordinal score as a stratification variable showed a hazard ratio for death of 0.74 (95% CI, 0.50 to 1.10). Safety Outcomes Serious adverse events occurred in 114 patients (21.1%) in the remdesivir group and 141 patients (27.0%) in the placebo group (Table S3). 4 events (2 in each group) were judged by site investigators to be related to remdesivir or placebo. There were 28 serious respiratory failure adverse events in the remdesivir group (5.2% of patients) and 42 in the placebo group (8.0% of patients).

Acute respiratory failure, hypotension, viral pneumonia, and acute kidney injury were slightly more common among patients in the placebo group. No deaths were considered to be related to treatment assignment, as judged by the site investigators. Grade 3 or 4 adverse events occurred in 156 patients (28.8%) in the remdesivir group and in 172 in the placebo group (33.0%) (Table S4). The most common adverse events in the remdesivir group were anemia or decreased hemoglobin (43 events [7.9%], as compared with 47 [9.0%] in the placebo group). Acute kidney injury, decreased estimated glomerular filtration rate or creatinine clearance, or increased blood creatinine (40 events [7.4%], as compared with 38 [7.3%]).

Pyrexia (27 events [5.0%], as compared with 17 [3.3%]). Hyperglycemia or increased blood glucose level (22 events [4.1%], as compared with 17 [3.3%]). And increased aminotransferase levels including alanine aminotransferase, aspartate aminotransferase, or both (22 events [4.1%], as compared with 31 [5.9%]). Otherwise, the incidence of adverse events was not found to be significantly different between the remdesivir group and the placebo group.Trial Population Table 1. Table 1.

Characteristics of the Participants in the mRNA-1273 Trial at Enrollment. The 45 enrolled participants received their first vaccination between March 16 and April 14, 2020 (Fig. S1). Three participants did not receive the second vaccination, including one in the 25-μg group who had urticaria on both legs, with onset 5 days after the first vaccination, and two (one in the 25-μg group and one in the 250-μg group) who missed the second vaccination window owing to isolation for suspected Covid-19 while the test results, ultimately negative, were pending. All continued to attend scheduled trial visits.

The demographic characteristics of participants at enrollment are provided in Table 1. Vaccine Safety No serious adverse events were noted, and no prespecified trial halting rules were met. As noted above, one participant in the 25-μg group was withdrawn because of an unsolicited adverse event, transient urticaria, judged to be related to the first vaccination. Figure 1. Figure 1.

Systemic and Local Adverse Events. The severity of solicited adverse events was graded as mild, moderate, or severe (see Table S1).After the first vaccination, solicited systemic adverse events were reported by 5 participants (33%) in the 25-μg group, 10 (67%) in the 100-μg group, and 8 (53%) in the 250-μg group. All were mild or moderate in severity (Figure 1 and Table S2). Solicited systemic adverse events were more common after the second vaccination and occurred in 7 of 13 participants (54%) in the 25-μg group, all 15 in the 100-μg group, and all 14 in the 250-μg group, with 3 of those participants (21%) reporting one or more severe events. None of the participants had fever after the first vaccination.

After the second vaccination, no participants in the 25-μg group, 6 (40%) in the 100-μg group, and 8 (57%) in the 250-μg group reported fever. One of the events (maximum temperature, 39.6°C) in the 250-μg group was graded severe. (Additional details regarding adverse events for that participant are provided in the Supplementary Appendix.) Local adverse events, when present, were nearly all mild or moderate, and pain at the injection site was common. Across both vaccinations, solicited systemic and local adverse events that occurred in more than half the participants included fatigue, chills, headache, myalgia, and pain at the injection site. Evaluation of safety clinical laboratory values of grade 2 or higher and unsolicited adverse events revealed no patterns of concern (Supplementary Appendix and Table S3).

SARS-CoV-2 Binding Antibody Responses Table 2. Table 2. Geometric Mean Humoral Immunogenicity Assay Responses to mRNA-1273 in Participants and in Convalescent Serum Specimens. Figure 2. Figure 2.

SARS-CoV-2 Antibody and Neutralization Responses. Shown are geometric mean reciprocal end-point enzyme-linked immunosorbent assay (ELISA) IgG titers to S-2P (Panel A) and receptor-binding domain (Panel B), PsVNA ID50 responses (Panel C), and live virus PRNT80 responses (Panel D). In Panel A and Panel B, boxes and horizontal bars denote interquartile range (IQR) and median area under the curve (AUC), respectively. Whisker endpoints are equal to the maximum and minimum values below or above the median ±1.5 times the IQR. The convalescent serum panel includes specimens from 41 participants.

Red dots indicate the 3 specimens that were also tested in the PRNT assay. The other 38 specimens were used to calculate summary statistics for the box plot in the convalescent serum panel. In Panel C, boxes and horizontal bars denote IQR and median ID50, respectively. Whisker end points are equal to the maximum and minimum values below or above the median ±1.5 times the IQR. In the convalescent serum panel, red dots indicate the 3 specimens that were also tested in the PRNT assay.

The other 38 specimens were used to calculate summary statistics for the box plot in the convalescent panel. In Panel D, boxes and horizontal bars denote IQR and median PRNT80, respectively. Whisker end points are equal to the maximum and minimum values below or above the median ±1.5 times the IQR. The three convalescent serum specimens were also tested in ELISA and PsVNA assays. Because of the time-intensive nature of the PRNT assay, for this preliminary report, PRNT results were available only for the 25-μg and 100-μg dose groups.Binding antibody IgG geometric mean titers (GMTs) to S-2P increased rapidly after the first vaccination, with seroconversion in all participants by day 15 (Table 2 and Figure 2A).

Dose-dependent responses to the first and second vaccinations were evident. Receptor-binding domain–specific antibody responses were similar in pattern and magnitude (Figure 2B). For both assays, the median magnitude of antibody responses after the first vaccination in the 100-μg and 250-μg dose groups was similar to the median magnitude in convalescent serum specimens, and in all dose groups the median magnitude after the second vaccination was in the upper quartile of values in the convalescent serum specimens. The S-2P ELISA GMTs at day 57 (299,751 [95% confidence interval {CI}, 206,071 to 436,020] in the 25-μg group, 782,719 [95% CI, 619,310 to 989,244] in the 100-μg group, and 1,192,154 [95% CI, 924,878 to 1,536,669] in the 250-μg group) exceeded that in the convalescent serum specimens (142,140 [95% CI, 81,543 to 247,768]). SARS-CoV-2 Neutralization Responses No participant had detectable PsVNA responses before vaccination.

After the first vaccination, PsVNA responses were detected in less than half the participants, and a dose effect was seen (50% inhibitory dilution [ID50]. Figure 2C, Fig. S8, and Table 2. 80% inhibitory dilution [ID80]. Fig.

S2 and Table S6). However, after the second vaccination, PsVNA responses were identified in serum samples from all participants. The lowest responses were in the 25-μg dose group, with a geometric mean ID50 of 112.3 (95% CI, 71.2 to 177.1) at day 43. The higher responses in the 100-μg and 250-μg groups were similar in magnitude (geometric mean ID50, 343.8 [95% CI, 261.2 to 452.7] and 332.2 [95% CI, 266.3 to 414.5], respectively, at day 43). These responses were similar to values in the upper half of the distribution of values for convalescent serum specimens.

Before vaccination, no participant had detectable 80% live-virus neutralization at the highest serum concentration tested (1:8 dilution) in the PRNT assay. At day 43, wild-type virus–neutralizing activity capable of reducing SARS-CoV-2 infectivity by 80% or more (PRNT80) was detected in all participants, with geometric mean PRNT80 responses of 339.7 (95% CI, 184.0 to 627.1) in the 25-μg group and 654.3 (95% CI, 460.1 to 930.5) in the 100-μg group (Figure 2D). Neutralizing PRNT80 average responses were generally at or above the values of the three convalescent serum specimens tested in this assay. Good agreement was noted within and between the values from binding assays for S-2P and receptor-binding domain and neutralizing activity measured by PsVNA and PRNT (Figs. S3 through S7), which provides orthogonal support for each assay in characterizing the humoral response induced by mRNA-1273.

SARS-CoV-2 T-Cell Responses The 25-μg and 100-μg doses elicited CD4 T-cell responses (Figs. S9 and S10) that on stimulation by S-specific peptide pools were strongly biased toward expression of Th1 cytokines (tumor necrosis factor α >. Interleukin 2 >. Interferon γ), with minimal type 2 helper T-cell (Th2) cytokine expression (interleukin 4 and interleukin 13). CD8 T-cell responses to S-2P were detected at low levels after the second vaccination in the 100-μg dose group (Fig.

S11).Trial Design and Oversight The RECOVERY trial was designed to evaluate the effects of potential treatments in patients hospitalized with Covid-19 at 176 National Health Service organizations in the United Kingdom and was supported by the National Institute for Health Research Clinical Research Network. (Details regarding this trial are provided in the Supplementary Appendix, available with the full text of this article at NEJM.org.) The trial is being coordinated by the Nuffield Department of Population Health at the University of Oxford, the trial sponsor. Although the randomization of patients to receive dexamethasone, hydroxychloroquine, or lopinavir–ritonavir has now been stopped, the trial continues randomization to groups receiving azithromycin, tocilizumab, or convalescent plasma why not try this out. Hospitalized patients were eligible for the trial if they had clinically suspected or laboratory-confirmed SARS-CoV-2 infection and no medical history that might, in the opinion of the attending clinician, put patients at substantial risk if they were to participate in the trial. Initially, recruitment was limited to patients who were at least 18 years of age, but the age limit was removed starting on May 9, 2020.

Pregnant or breast-feeding women were eligible. Written informed consent was obtained from all the patients or from a legal representative if they were unable to provide consent. The trial was conducted in accordance with the principles of the Good Clinical Practice guidelines of the International Conference on Harmonisation and was approved by the U.K. Medicines and Healthcare Products Regulatory Agency and the Cambridge East Research Ethics Committee. The protocol with its statistical analysis plan is available at NEJM.org and on the trial website at www.recoverytrial.net.

The initial version of the manuscript was drafted by the first and last authors, developed by the writing committee, and approved by all members of the trial steering committee. The funders had no role in the analysis of the data, in the preparation or approval of the manuscript, or in the decision to submit the manuscript for publication. The first and last members of the writing committee vouch for the completeness and accuracy of the data and for the fidelity of the trial to the protocol and statistical analysis plan. Randomization We collected baseline data using a Web-based case-report form that included demographic data, the level of respiratory support, major coexisting illnesses, suitability of the trial treatment for a particular patient, and treatment availability at the trial site. Randomization was performed with the use of a Web-based system with concealment of the trial-group assignment.

Eligible and consenting patients were assigned in a 2:1 ratio to receive either the usual standard of care alone or the usual standard of care plus oral or intravenous dexamethasone (at a dose of 6 mg once daily) for up to 10 days (or until hospital discharge if sooner) or to receive one of the other suitable and available treatments that were being evaluated in the trial. For some patients, dexamethasone was unavailable at the hospital at the time of enrollment or was considered by the managing physician to be either definitely indicated or definitely contraindicated. These patients were excluded from entry in the randomized comparison between dexamethasone and usual care and hence were not included in this report. The randomly assigned treatment was prescribed by the treating clinician. Patients and local members of the trial staff were aware of the assigned treatments.

Procedures A single online follow-up form was to be completed when the patients were discharged or had died or at 28 days after randomization, whichever occurred first. Information was recorded regarding the patients’ adherence to the assigned treatment, receipt of other trial treatments, duration of admission, receipt of respiratory support (with duration and type), receipt of renal support, and vital status (including the cause of death). In addition, we obtained routine health care and registry data, including information on vital status (with date and cause of death), discharge from the hospital, and respiratory and renal support therapy. Outcome Measures The primary outcome was all-cause mortality within 28 days after randomization. Further analyses were specified at 6 months.

Secondary outcomes were the time until discharge from the hospital and, among patients not receiving invasive mechanical ventilation at the time of randomization, subsequent receipt of invasive mechanical ventilation (including extracorporeal membrane oxygenation) or death. Other prespecified clinical outcomes included cause-specific mortality, receipt of renal hemodialysis or hemofiltration, major cardiac arrhythmia (recorded in a subgroup), and receipt and duration of ventilation. Statistical Analysis As stated in the protocol, appropriate sample sizes could not be estimated when the trial was being planned at the start of the Covid-19 pandemic. As the trial progressed, the trial steering committee, whose members were unaware of the results of the trial comparisons, determined that if 28-day mortality was 20%, then the enrollment of at least 2000 patients in the dexamethasone group and 4000 in the usual care group would provide a power of at least 90% at a two-sided P value of 0.01 to detect a clinically relevant proportional reduction of 20% (an absolute difference of 4 percentage points) between the two groups. Consequently, on June 8, 2020, the steering committee closed recruitment to the dexamethasone group, since enrollment had exceeded 2000 patients.

For the primary outcome of 28-day mortality, the hazard ratio from Cox regression was used to estimate the mortality rate ratio. Among the few patients (0.1%) who had not been followed for 28 days by the time of the data cutoff on July 6, 2020, data were censored either on that date or on day 29 if the patient had already been discharged. That is, in the absence of any information to the contrary, these patients were assumed to have survived for 28 days. Kaplan–Meier survival curves were constructed to show cumulative mortality over the 28-day period. Cox regression was used to analyze the secondary outcome of hospital discharge within 28 days, with censoring of data on day 29 for patients who had died during hospitalization.

For the prespecified composite secondary outcome of invasive mechanical ventilation or death within 28 days (among patients who were not receiving invasive mechanical ventilation at randomization), the precise date of invasive mechanical ventilation was not available, so a log-binomial regression model was used to estimate the risk ratio. Table 1. Table 1. Characteristics of the Patients at Baseline, According to Treatment Assignment and Level of Respiratory Support. Through the play of chance in the unstratified randomization, the mean age was 1.1 years older among patients in the dexamethasone group than among those in the usual care group (Table 1).

To account for this imbalance in an important prognostic factor, estimates of rate ratios were adjusted for the baseline age in three categories (<70 years, 70 to 79 years, and ≥80 years). This adjustment was not specified in the first version of the statistical analysis plan but was added once the imbalance in age became apparent. Results without age adjustment (corresponding to the first version of the analysis plan) are provided in the Supplementary Appendix. Prespecified analyses of the primary outcome were performed in five subgroups, as defined by characteristics at randomization. Age, sex, level of respiratory support, days since symptom onset, and predicted 28-day mortality risk.

(One further prespecified subgroup analysis regarding race will be conducted once the data collection has been completed.) In prespecified subgroups, we estimated rate ratios (or risk ratios in some analyses) and their confidence intervals using regression models that included an interaction term between the treatment assignment and the subgroup of interest. Chi-square tests for linear trend across the subgroup-specific log estimates were then performed in accordance with the prespecified plan. All P values are two-sided and are shown without adjustment for multiple testing. All analyses were performed according to the intention-to-treat principle. The full database is held by the trial team, which collected the data from trial sites and performed the analyses at the Nuffield Department of Population Health, University of Oxford.Trial Design and Oversight We conducted a randomized, double-blind, placebo-controlled trial to evaluate postexposure prophylaxis with hydroxychloroquine after exposure to Covid-19.12 We randomly assigned participants in a 1:1 ratio to receive either hydroxychloroquine or placebo.

Participants had known exposure (by participant report) to a person with laboratory-confirmed Covid-19, whether as a household contact, a health care worker, or a person with other occupational exposures. Trial enrollment began on March 17, 2020, with an eligibility threshold to enroll within 3 days after exposure. The objective was to intervene before the median incubation period of 5 to 6 days. Because of limited access to prompt testing, health care workers could initially be enrolled on the basis of presumptive high-risk exposure to patients with pending tests. However, on March 23, eligibility was changed to exposure to a person with a positive polymerase-chain-reaction (PCR) assay for SARS-CoV-2, with the eligibility window extended to within 4 days after exposure.

This trial was approved by the institutional review board at the University of Minnesota and conducted under a Food and Drug Administration Investigational New Drug application. In Canada, the trial was approved by Health Canada. Ethics approvals were obtained from the Research Institute of the McGill University Health Centre, the University of Manitoba, and the University of Alberta. Participants We included participants who had household or occupational exposure to a person with confirmed Covid-19 at a distance of less than 6 ft for more than 10 minutes while wearing neither a face mask nor an eye shield (high-risk exposure) or while wearing a face mask but no eye shield (moderate-risk exposure). Participants were excluded if they were younger than 18 years of age, were hospitalized, or met other exclusion criteria (see the Supplementary Appendix, available with the full text of this article at NEJM.org).

Persons with symptoms of Covid-19 or with PCR-proven SARS-CoV-2 infection were excluded from this prevention trial but were separately enrolled in a companion clinical trial to treat early infection. Setting Recruitment was performed primarily with the use of social media outreach as well as traditional media platforms. Participants were enrolled nationwide in the United States and in the Canadian provinces of Quebec, Manitoba, and Alberta. Participants enrolled themselves through a secure Internet-based survey using the Research Electronic Data Capture (REDCap) system.13 After participants read the consent form, their comprehension of its contents was assessed. Participants provided a digitally captured signature to indicate informed consent.

We sent follow-up e-mail surveys on days 1, 5, 10, and 14. A survey at 4 to 6 weeks asked about any follow-up testing, illness, or hospitalizations. Participants who did not respond to follow-up surveys received text messages, e-mails, telephone calls, or a combination of these to ascertain their outcomes. When these methods were unsuccessful, the emergency contact provided by the enrollee was contacted to determine the participant’s illness and vital status. When all communication methods were exhausted, Internet searches for obituaries were performed to ascertain vital status.

Interventions Randomization occurred at research pharmacies in Minneapolis and Montreal. The trial statisticians generated a permuted-block randomization sequence using variably sized blocks of 2, 4, or 8, with stratification according to country. A research pharmacist sequentially assigned participants. The assignments were concealed from investigators and participants. Only pharmacies had access to the randomization sequence.

Hydroxychloroquine sulfate or placebo was dispensed and shipped overnight to participants by commercial courier. The dosing regimen for hydroxychloroquine was 800 mg (4 tablets) once, then 600 mg (3 tablets) 6 to 8 hours later, then 600 mg (3 tablets) daily for 4 more days for a total course of 5 days (19 tablets total). If participants had gastrointestinal upset, they were advised to divide the daily dose into two or three doses. We chose this hydroxychloroquine dosing regimen on the basis of pharmacokinetic simulations to achieve plasma concentrations above the SARS-CoV-2 in vitro half maximal effective concentration for 14 days.14 Placebo folate tablets, which were similar in appearance to the hydroxychloroquine tablets, were prescribed as an identical regimen for the control group. Rising Pharmaceuticals provided a donation of hydroxychloroquine, and some hydroxychloroquine was purchased.

Outcomes The primary outcome was prespecified as symptomatic illness confirmed by a positive molecular assay or, if testing was unavailable, Covid-19–related symptoms. We assumed that health care workers would have access to Covid-19 testing if symptomatic. However, access to testing was limited throughout the trial period. Covid-19–related symptoms were based on U.S. Council for State and Territorial Epidemiologists criteria for confirmed cases (positivity for SARS-Cov-2 on PCR assay), probable cases (the presence of cough, shortness of breath, or difficulty breathing, or the presence of two or more symptoms of fever, chills, rigors, myalgia, headache, sore throat, and new olfactory and taste disorders), and possible cases (the presence of one or more compatible symptoms, which could include diarrhea).15 All the participants had epidemiologic linkage,15 per trial eligibility criteria.

Four infectious disease physicians who were unaware of the trial-group assignments reviewed symptomatic participants to generate a consensus with respect to whether their condition met the case definition.15 Secondary outcomes included the incidence of hospitalization for Covid-19 or death, the incidence of PCR-confirmed SARS-CoV-2 infection, the incidence of Covid-19 symptoms, the incidence of discontinuation of the trial intervention owing to any cause, and the severity of symptoms (if any) at days 5 and 14 according to a visual analogue scale (scores ranged from 0 [no symptoms] to 10 [severe symptoms]). Data on adverse events were also collected with directed questioning for common side effects along with open-ended free text. Outcome data were measured within 14 days after trial enrollment. Outcome data including PCR testing results, possible Covid-19–related symptoms, adherence to the trial intervention, side effects, and hospitalizations were all collected through participant report. Details of trial conduct are provided in the protocol and statistical analysis plan, available at NEJM.org.

Sample Size We anticipated that illness compatible with Covid-19 would develop in 10% of close contacts exposed to Covid-19.9 Using Fisher’s exact method with a 50% relative effect size to reduce new symptomatic infections, a two-sided alpha of 0.05, and 90% power, we estimated that 621 persons would need to be enrolled in each group. With a pragmatic, Internet-based, self-referral recruitment strategy, we planned for a 20% incidence of attrition by increasing the sample size to 750 participants per group. We specified a priori that participants who were already symptomatic on day 1 before receiving hydroxychloroquine or placebo would be excluded from the prophylaxis trial and would instead be separately enrolled in the companion symptomatic treatment trial. Because the estimates for both incident symptomatic Covid-19 after an exposure and loss to follow-up were relatively unknown in early March 2020,9 the protocol prespecified a sample-size reestimation at the second interim analysis. This reestimation, which used the incidence of new infections in the placebo group and the observed percentage of participants lost to follow-up, was aimed at maintaining the ability to detect an effect size of a 50% relative reduction in new symptomatic infections.

Interim Analyses An independent data and safety monitoring board externally reviewed the data after 25% and 50% of the participants had completed 14 days of follow-up. Stopping guidelines were provided to the data and safety monitoring board with the use of a Lan–DeMets spending function analogue of the O’Brien–Fleming boundaries for the primary outcome. A conditional power analysis was performed at the second and third interim analysis with the option of early stopping for futility. At the second interim analysis on April 22, 2020, the sample size was reduced to 956 participants who could be evaluated with 90% power on the basis of the higher-than-expected event rate of infections in the control group. At the third interim analysis on May 6, the trial was halted on the basis of a conditional power of less than 1%, since it was deemed futile to continue.

Statistical Analysis We assessed the incidence of Covid-19 disease by day 14 with Fisher’s exact test. Secondary outcomes with respect to percentage of patients were also compared with Fisher’s exact test. Among participants in whom incident illness compatible with Covid-19 developed, we summarized the symptom severity score at day 14 with the median and interquartile range and assessed the distributions with a Kruskal–Wallis test. We conducted all analyses with SAS software, version 9.4 (SAS Institute), according to the intention-to-treat principle, with two-sided type I error with an alpha of 0.05. For participants with missing outcome data, we conducted a sensitivity analysis with their outcomes excluded or included as an event.

Subgroups that were specified a priori included type of contact (household vs. Health care), days from exposure to enrollment, age, and sex.Announced on May 15, Operation Warp Speed (OWS) — a partnership of the Department of Health and Human Services (HHS), the Department of Defense (DOD), and the private sector — aims to accelerate control of the Covid-19 pandemic by advancing development, manufacturing, and distribution of vaccines, therapeutics, and diagnostics. OWS is providing support to promising candidates and enabling the expeditious, parallel execution of the necessary steps toward approval or authorization of safe products by the Food and Drug Administration (FDA).The partnership grew out of an acknowledged need to fundamentally restructure the way the U.S. Government typically supports product development and vaccine distribution. The initiative was premised on setting a “stretch goal” — one that initially seemed impossible but that is becoming increasingly achievable.The concept of an integrated structure for Covid-19 countermeasure research and development across the U.S.

Government was based on experience with Zika and the Zika Leadership Group led by the National Institutes of Health (NIH) and the assistant secretary for preparedness and response (ASPR). One of us (M.S.) serves as OWS chief advisor. We are drawing on expertise from the NIH, ASPR, the Centers for Disease Control and Prevention (CDC), the Biomedical Advanced Research and Development Authority (BARDA), and the DOD, including the Joint Program Executive Office for Chemical, Biological, Radiological and Nuclear Defense and the Defense Advanced Research Projects Agency. OWS has engaged experts in all critical aspects of medical countermeasure research, development, manufacturing, and distribution to work in close coordination.The initiative set ambitious objectives. To deliver tens of millions of doses of a SARS-CoV-2 vaccine — with demonstrated safety and efficacy, and approved or authorized by the FDA for use in the U.S.

Population — beginning at the end of 2020 and to have as many as 300 million doses of such vaccines available and deployed by mid-2021. The pace and scope of such a vaccine effort are unprecedented. The 2014 West African Ebola virus epidemic spurred rapid vaccine development, but though preclinical data existed before the outbreak, a period of 12 months was required to progress from phase 1 first-in-human trials to phase 3 efficacy trials. OWS aims to compress this time frame even further. SARS-CoV-2 vaccine development began in January, phase 1 clinical studies in March, and the first phase 3 trials in July.

Our objectives are based on advances in vaccine platform technology, improved understanding of safe and efficacious vaccine design, and similarities between the SARS-CoV-1 and SARS-CoV-2 disease mechanisms.OWS’s role is to enable, accelerate, harmonize, and advise the companies developing the selected vaccines. The companies will execute the clinical or process development and manufacturing plans, while OWS leverages the full capacity of the U.S. Government to ensure that no technical, logistic, or financial hurdles hinder vaccine development or deployment.OWS selected vaccine candidates on the basis of four criteria. We required candidates to have robust preclinical data or early-stage clinical trial data supporting their potential for clinical safety and efficacy. Candidates had to have the potential, with our acceleration support, to enter large phase 3 field efficacy trials this summer or fall (July to November 2020) and, assuming continued active transmission of the virus, to deliver efficacy outcomes by the end of 2020 or the first half of 2021.

Candidates had to be based on vaccine-platform technologies permitting fast and effective manufacturing, and their developers had to demonstrate the industrial process scalability, yields, and consistency necessary to reliably produce more than 100 million doses by mid-2021. Finally, candidates had to use one of four vaccine-platform technologies that we believe are the most likely to yield a safe and effective vaccine against Covid-19. The mRNA platform, the replication-defective live-vector platform, the recombinant-subunit-adjuvanted protein platform, or the attenuated replicating live-vector platform.OWS’s strategy relies on a few key principles. First, we sought to build a diverse project portfolio that includes two vaccine candidates based on each of the four platform technologies. Such diversification mitigates the risk of failure due to safety, efficacy, industrial manufacturability, or scheduling factors and may permit selection of the best vaccine platform for each subpopulation at risk for contracting or transmitting Covid-19, including older adults, frontline and essential workers, young adults, and pediatric populations.

In addition, advancing eight vaccines in parallel will increase the chances of delivering 300 million doses in the first half of 2021.Second, we must accelerate vaccine program development without compromising safety, efficacy, or product quality. Clinical development, process development, and manufacturing scale-up can be substantially accelerated by running all streams, fully resourced, in parallel. Doing so requires taking on substantial financial risk, as compared with the conventional sequential development approach. OWS will maximize the size of phase 3 trials (30,000 to 50,000 participants each) and optimize trial-site location by consulting daily epidemiologic and disease-forecasting models to ensure the fastest path to an efficacy readout. Such large trials also increase the safety data set for each candidate vaccine.With heavy up-front investment, companies can conduct clinical operations and site preparation for these phase 3 efficacy trials even as they file their Investigational New Drug application (IND) for their phase 1 studies, thereby ensuring immediate initiation of phase 3 when they get a green light from the FDA.

To permit appropriate comparisons among the vaccine candidates and to optimize vaccine utilization after approval by the FDA, the phase 3 trial end points and assay readouts have been harmonized through a collaborative effort involving the National Institute of Allergy and Infectious Diseases (NIAID), the Coronavirus Prevention Network, OWS, and the sponsor companies.Finally, OWS is supporting the companies financially and technically to commence process development and scale up manufacturing while their vaccines are in preclinical or very early clinical stages. To ensure that industrial processes are set, running, and validated for FDA inspection when phase 3 trials end, OWS is also supporting facility building or refurbishing, equipment fitting, staff hiring and training, raw-material sourcing, technology transfer and validation, bulk product processing into vials, and acquisition of ample vials, syringes, and needles for each vaccine candidate. We aim to have stockpiled, at OWS’s expense, a few tens of millions of vaccine doses that could be swiftly deployed once FDA approval is obtained.This strategy aims to accelerate vaccine development without curtailing the critical steps required by sound science and regulatory standards. The FDA recently reissued guidance and standards that will be used to assess each vaccine for a Biologics License Application (BLA). Alternatively, the agency could decide to issue an Emergency Use Authorization to permit vaccine administration before all BLA procedures are completed.Of the eight vaccines in OWS’s portfolio, six have been announced and partnerships executed with the companies.

Moderna and Pfizer/BioNTech (both mRNA), AstraZeneca and Janssen (both replication-defective live-vector), and Novavax and Sanofi/GSK (both recombinant-subunit-adjuvanted protein). These candidates cover three of the four platform technologies and are currently in clinical trials. The remaining two candidates will enter trials soon.Moderna developed its RNA vaccine in collaboration with the NIAID, began its phase 1 trial in March, recently published encouraging safety and immunogenicity data,1 and entered phase 3 on July 27. Pfizer and BioNTech’s RNA vaccine also produced encouraging phase 1 results2 and started its phase 3 trial on July 27. The ChAdOx replication-defective live-vector vaccine developed by AstraZeneca and Oxford University is in phase 3 trials in the United Kingdom, Brazil, and South Africa, and it should enter U.S.

Phase 3 trials in August.3 The Janssen Ad26 Covid-19 replication-defective live-vector vaccine has demonstrated excellent protection in nonhuman primate models and began its U.S. Phase 1 trial on July 27. It should be in phase 3 trials in mid-September. Novavax completed a phase 1 trial of its recombinant-subunit-adjuvanted protein vaccine in Australia and should enter phase 3 trials in the United States by the end of September.4 Sanofi/GSK is completing preclinical development steps and plans to commence a phase 1 trial in early September and to be well into phase 3 by year’s end.5On the process-development front, the RNA vaccines are already being manufactured at scale. The other candidates are well advanced in their scale-up development, and manufacturing sites are being refurbished.While development and manufacturing proceed, the HHS–DOD partnership is laying the groundwork for vaccine distribution, subpopulation prioritization, financing, and logistic support.

We are working with bioethicists and experts from the NIH, the CDC, BARDA, and the Centers for Medicare and Medicaid Services to address these critical issues. We will receive recommendations from the CDC Advisory Committee on Immunization Practices, and we are working to ensure that the most vulnerable and at-risk persons will receive vaccine doses once they are ready. Prioritization will also depend on the relative performance of each vaccine and its suitability for particular populations. Because some technologies have limited previous data on safety in humans, the long-term safety of these vaccines will be carefully assessed using pharmacovigilance surveillance strategies.No scientific enterprise could guarantee success by January 2021, but the strategic decisions and choices we’ve made, the support the government has provided, and the accomplishments to date make us optimistic that we will succeed in this unprecedented endeavor..


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