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kamagra thailand pharmacy DSD.11 14 Several projects have now worked to resolve this variability in care kamagra street price. The European Cooperation in Science and Technology (EU COST) action BM1303 ‘A systematic elucidation of differences of sex development’ has been a platform to achieve European agreement on harmonisation of clinical management and laboratory practices.15–17 Another such initiative involved an update of the 2006 DSD consensus document by an international group of professionals and patient representatives.18 These initiatives have highlighted how cultural and financial aspects and the availability of resources differ significantly between countries and kamagra street price societies, a situation that hampers supranational agreement on common diagnostic protocols. As only a few national guidelines have been published in international journals, comparison of these guidelines is difficult even though such a comparison is necessary to capture the differences and initiate actions to overcome them. Nonetheless, four DSD (expert) centres located in the Netherlands and Flanders (the Dutch-speaking Northern part of Belgium) have collaborated to produce a detailed guideline on diagnostics in DSD.19 This shows that kamagra street price a supranational guideline can be a reasonable approach for countries with similarly structured healthcare systems and similar resources. Within the guideline there is agreement that optimisation of expertise and care can be achieved through centralisation, for example, by limiting analysis of next-generation sequencing (NGS)-based diagnostic panels to only a few centres and by centralising pathological review of gonadal tissues.

International networks such as the European Reference Network for rare endocrine conditions (EndoERN), in which DSD is embedded, may facilitate the expansion of this kind of collaboration across Europe.This paper highlights key discussion points in the Dutch-Flemish guideline that kamagra street price have been insufficiently addressed in the literature thus far because they reflect evolving technologies or less visible stakeholders. For example, prenatal observation of an atypical aspect of the genitalia indicating a possible DSD is becoming increasingly common, and we discuss appropriate counselling and a diagnostic approach for these cases, including the option of using NGS-based genetic testing. So far, little attention has been paid to this process.20 21 Furthermore, informing patients and/or their parents about kamagra street price atypical sex development and why this may warrant referral to a specialised team may be challenging, especially for professionals with limited experience in DSD.22 23 Therefore, a section of the Dutch-Flemish guideline was written for these healthcare providers. Moreover, this enables DSD specialists to refer to the guideline when advising a referral. Transition from the prenatal to the postnatal team and from the paediatric to the adult team requires optimal kamagra street price communication between the specialists involved.

Application of NGS-based techniques may lead to a higher diagnostic yield, providing a molecular genetic diagnosis in previously unsolved cases.16 We address the timing of this testing and the problems associated with this technique such as the interpretation of variants of unknown clinical significance (VUS). Similarly, histopathological interpretation and classification of removed gonadal tissue is challenging and would benefit from international collaboration and centralisation of expertise.MethodsFor the guideline revision, an interdisciplinary kamagra street price multicentre group was formed with all members responsible for updating the literature for a specific part of the guideline. Literature search in PubMed was not systematic, but rather intended to be broad in order to cover all areas and follow expert opinions. This approach is more in line with the Clinical Practice Advisory Document method described by Burke et al24 for guidelines involving genetic practice because it is often kamagra street price troublesome to substantiate such guidelines with sufficient evidence due to the rapid changes in testing methods, for example, gene panels. All input provided by the group was synthesised by the chairperson (YvB), who also reviewed abstracts of papers on DSD published between 2010 and September 2017 for the guideline and up to October 2019 for this paper.

Abstracts had to be written in English and were identified using a kamagra street price broad range of Medical Subject Headings terms (eg, DSD, genetic, review, diagnosis, diagnostics, 46,XX DSD, 46,XY DSD, guideline, multidisciplinary care). Next, potentially relevant papers on diagnostic procedures in DSD were selected. Case reports were excluded, as were articles that were not open access or kamagra street price retrievable through institutional access. Based on this, a draft guideline was produced that was in line with the international principles of good diagnostic care in DSD. This draft was discussed by the writing committee and, kamagra street price after having obtained agreement on remaining points of discussion, revised into a final draft.

This version was sent to a broad group of professionals from academic centres and DSD teams whose members had volunteered to review the draft guideline. After receiving and incorporating their input, the final kamagra street price version was presented to the paediatric and genetic associations for approval. After approval by the members of the paediatric (NVK), clinical genetic (VKGN) and genetic laboratory (VKGL) associations, the guideline was published on their respective websites.19 Although Turner syndrome and Klinefelter syndrome are considered to be part of the DSD spectrum, they are not extensively discussed in this diagnostic guideline as guidelines dedicated to these syndromes already exist.25 26 However, some individuals with Turner syndrome or Klinefelter syndrome may present with ambiguous or atypical genitalia and may therefore initially follow the DSD diagnostic process.Guideline highlightsPrenatal settingPresentationThe most frequent prenatal presentation of a DSD condition is atypical genitalia found on prenatal ultrasound as an isolated finding or in combination with other structural anomalies. This usually occurs after the 20-week routine medical ultrasound for screening of congenital anomalies, but may also occur earlier, for example, when a commercial ultrasound is performed at the request of the parents.Another way DSD can be diagnosed before birth is when invasive prenatal genetic testing carried out for a different reason, for example, due to suspicion of other structural anomalies, reveals kamagra street price a discrepancy between the genotypic sex and the phenotypic sex seen by ultrasound. In certified laboratories, the possibility of a sample switch is extremely low but should be ruled out immediately.

More often, the discrepancy will be due to sex-chromosome mosaicism or a true form of DSD.A situation now occurring with increasing frequency is a discrepancy between the genotypic sex revealed by non-invasive prenatal testing (NIPT), which is now available to high-risk pregnant women in the Netherlands and kamagra street price to all pregnant women in Belgium, and later ultrasound findings. NIPT screens for CNVs in the fetus. However, depending on legal restrictions and/or ethical considerations, the X kamagra street price and Y chromosomes are not always included in NIPT analysis and reports. If the X and Y chromosomes are included, it is important to realise that the presence of a Y-chromosome does not necessarily imply male fetal development. At the time kamagra street price that NIPT is performed (usually 11–13 weeks), genital development cannot be reliably appreciated by ultrasound, so any discrepancy or atypical aspect of the genitalia will only be noticed later in pregnancy and should prompt further evaluation.Counselling and diagnosticsIf a DSD is suspected, first-line sonographers and obstetricians should refer the couple to their colleague prenatal specialists working with or in a DSD team.

After confirming an atypical genital on ultrasound, the specialist team should offer the couple a referral for genetic counselling to discuss the possibility of performing invasive prenatal testing (usually an amniocentesis) to identify an underlying cause that fits the ultrasound findings.22 23 To enable the parents to make a well-informed decision, prenatal counselling should, in our opinion, include. Information on kamagra street price the ultrasound findings and the limitations of this technique. The procedure(s) that can be followed, including the risks associated with an amniocentesis. And the type of information genetic testing kamagra street price can and cannot provide. Knowing which information has been provided and what words have been used by the prenatal specialist is very helpful for those involved in postnatal care.It is important that parents understand that the biological sex of a baby is determined by a complex interplay of chromosomes, genes and hormones, and thus that assessment of the presence or absence of a Y-chromosome alone is insufficient to assign the sex of their unborn child or, as in any unborn child, say anything about the child’s future gender identity.Expecting parents can be counselled by the clinical geneticist and the psychologist from the DSD team, although other DSD specialists can also be involved.

The clinical geneticist should be experienced in prenatal counselling and well informed about the diagnostic possibilities given the limited time span in which test results need to be available to allow parents to make a well-informed decision about whether or not to continue the pregnancy kamagra street price. Termination of pregnancy can be considered, for instance, in a syndromic form of DSD with multiple malformations, but when the DSD occurs as an kamagra street price apparently isolated condition, expecting parents may also consider termination of pregnancy, which, although considered controversial by some, is legal in Belgium and the Netherlands. The psychologist of the DSD team can support parents during and after pregnancy and help them cope with feelings of uncertainty and eventual considerations of a termination of pregnancy, as well as with practical issues, for example, how to inform others. The stress of not knowing exactly what the child’s genitalia will look like and uncertainty about the diagnosis, treatment and kamagra street price prognosis cannot be avoided completely. Parents are informed that if the postnatal phenotype is different from what was prenatally expected, the advice given about diagnostic testing can be adjusted accordingly, for example, if a hypospadias is milder than was expected based on prenatal ultrasound images.

In our experience, parents appreciate having already spoken to some members of the DSD team during pregnancy and having a contact person before birth.After expert prenatal counselling, a significant number of pregnant couples decline prenatal testing (personal experience IALG, MK, kamagra street price ABD, YvB, MC and HC-vdG). At birth, umbilical cord blood is a good source for (molecular) karyotyping and storage of DNA and can be obtained by the obstetrician, midwife or neonatologist. The terminology used in communication with parents should be carefully chosen,22 23 and midwives and staff of neonatal and delivery units should be clearly instructed to use gender-neutral and non-stigmatising vocabulary (eg, ‘your baby’) kamagra street price as long as sex assignment is pending.An algorithm for diagnostic evaluation of a suspected DSD in the prenatal situation is proposed in figure 1. When couples opt for invasive prenatal diagnosis, the genetic analysis usually involves an (SNP)-array. It was recently estimated that >30% of individuals who have a DSD have additional structural anomalies, with cardiac and neurological anomalies and fetal growth restriction being particularly common.27 28 If additional anomalies are seen, the geneticist can consider specific gene defects that may underlie a known genetic syndrome or carry kamagra street price out NGS.

NGS-based techniques have also now made their appearance in prenatal diagnosis of congenital anomalies.29 30 Panels using these techniques can be specific for genes involved in DSD, or be larger panels covering multiple congenital anomalies, and are usually employed with trio-analysis to compare variants identified in the child with the parents’ genetics.29–31 Finding a genetic cause before delivery can help reduce parental stress in the neonatal period and speed up decisions regarding gender assignment. In such cases there is no kamagra street price tight time limit, and we propose completing the analysis well before the expected delivery.Disorders/differences of sex development (DSD) in the prenatal setting. A diagnostic algorithm. *SOX9. Upstream anomalies and balanced translocations at promotor sites!.

Conventional karyotyping can be useful. NGS, next-generation sequencing." data-icon-position data-hide-link-title="0">Figure 1 Disorders/differences of sex development (DSD) in the prenatal setting. A diagnostic algorithm. *SOX9. Upstream anomalies and balanced translocations at promotor sites!.

Conventional karyotyping can be useful. NGS, next-generation sequencing.First contact by a professional less experienced in DSDWhereas most current guidelines start from the point when an individual has been referred to the DSD team,1 15 the Dutch-Flemish guideline dedicates a chapter to healthcare professionals less experienced in DSD as they are often the first to suspect or identify such a condition. Apart from the paper of Indyk,7 little guidance is available for these professionals about how to act in such a situation. The chapter in the Dutch-Flemish guideline summarises the various clinical presentations that a DSD can have and provides information on how to communicate with parents and/or patients about the findings of the physical examination, the first-line investigations and the need for prompt referral to a specialised centre for further evaluation. Clinical examples are offered to illustrate some of these recurring situations.

The medical issues in DSD can be very challenging, and the social and psychological impact is high. For neonates with ambiguous genitalia, sex assignment is an urgent and crucial issue, and it is mandatory that parents are informed that it is possible to postpone registration of their child’s sex. In cases where sex assignment has already taken place, the message that the development of the gonads or genitalia is still atypical is complicated and distressing for patients and parents or carers. A list of contact details for DSD centres and patient organisations in the Netherlands and Flanders is attached to the Dutch-Flemish guideline. Publishing such a list, either in guidelines or online, can help healthcare professionals find the nearest centres for consultations and provide patients and patient organisations with an overview of the centres where expertise is available.Timing and place of genetic testing using NGS-based gene panelsThe diagnostic workup that is proposed for 46,XX and 46,XY DSD is shown in figures 2 and 3, respectively.

Even with the rapidly expanding molecular possibilities, a (family) history and a physical examination remain the essential first steps in the diagnostic process. Biochemical and hormonal screening aim at investigating serum electrolytes, renal function and the hypothalamic-pituitary-gonadal and hypothalamic-pituitary-adrenal axes. Ultrasound screening of kidneys and internal genitalia, as well as establishing genotypic sex, should be accomplished within 48 hours and complete the baseline diagnostic work-up of a child born with ambiguous genitalia.1 16 32 3346,XX disorders/differences of sex development (DSD) in the postnatal setting. A diagnostic algorithm. NGS, next-generation sequencing.

CAH, Congenital adrenal hyperplasia. AMH, Anti-Müllerian Hormone." data-icon-position data-hide-link-title="0">Figure 2 46,XX disorders/differences of sex development (DSD) in the postnatal setting. A diagnostic algorithm. NGS, next-generation sequencing. CAH, Congenital adrenal hyperplasia.

AMH, Anti-Müllerian Hormone.46,XY disorders/differences of sex development (DSD) in the postnatal setting. A diagnostic algorithm. * SOX9. Upstream anomalies and balanced translocations at promotor sites!. Conventional karyotyping can be useful.

NGS, next-generation sequencing." data-icon-position data-hide-link-title="0">Figure 3 46,XY disorders/differences of sex development (DSD) in the postnatal setting. A diagnostic algorithm. *SOX9. Upstream anomalies and balanced translocations at promotor sites!. Conventional karyotyping can be useful.

NGS, next-generation sequencing.Very recently, a European position paper has been published focusing on the genetic workup of DSD.16 It highlights the limitations and drawbacks of NGS-based tests, which include the chance of missing subtle structural variants such as CNVs and mosaicism and the fact that NGS cannot detect methylation defects or other epigenetic changes.16 28 31 Targeted DNA analysis is preferred in cases where hormonal investigations suggest a block in steroidogenesis (eg, 11-β-hydroxylase deficiency, 21-hydroxylase deficiency), or in the context of a specific clinical constellation such as the often coincidental finding of Müllerian structures in a boy with normal external genitalia or cryptorchidism, that is, persistent Müllerian duct syndrome.33 34 Alternative tests should also be considered depending on the available information. Sometimes, a simple mouth swab for FISH analysis can detect mosaic XY/X in a male with hypospadias or asymmetric gonadal development or in a female with little or no Turner syndrome stigmata and a normal male molecular karyotyping profile or peripheral blood karyotype. Such targeted testing avoids incidental findings and is cheaper and faster than analysis of a large NGS-based panel, although the cost difference is rapidly declining.However, due to the genetic and phenotypic heterogeneity of DSD conditions, the most cost-effective next steps in the majority of cases are whole exome sequencing followed by panel analysis of genes involved in genital development and function or trio-analysis of a large gene panel (such as a Mendeliome).16 35–38 Pretest genetic counselling involves discussing what kind of information will be reported to patients or parents and the chance of detecting VUS, and the small risk of incidental findings when analysing a DSD panel should be mentioned. Laboratories also differ in what class of variants they report.39 In our experience, the fear of incidental findings is a major reason why some parents refrain from genetic testing.Timing of the DSD gene panel analysis is also important. While some patients or parents prefer that all diagnostic procedures be performed as soon as possible, others need time to reflect on the complex information related to more extensive genetic testing and on its possible consequences.

If parents or patients do not consent to panel-based genetic testing, analysis of specific genes, such as WT1, should be considered when appropriate in view of the clinical consequences if a mutation is present (eg, clinical surveillance of renal function and screening for Wilms’ tumour in the case of WT1 mutations). Genes that are more frequently involved in DSD (eg, SRY, NR5A1) and that match the specific clinical and hormonal features in a given patient could also be considered for sequencing. Targeted gene analysis may also be preferred in centres located in countries that do not have the resources or technical requirements to perform NGS panel-based genetic testing. Alternatively, participation by these centres in international collaborative networks may allow them to outsource the molecular genetic workup abroad.Gene panels differ between centres and are regularly updated based on scientific progress. A comparison of DSD gene panels used in recent studies can be found at https://www.nature.com/articles/s41574-018-0010-8%23Sec46.15 The panels currently used at the coauthors’ institutions can be found on their respective websites.

Given the pace of change, it is important to regularly consider repeating analysis in patients with an unexplained DSD, for example, when they transition into adult care or when they move from one centre to another. This also applies to patients in whom a clinical diagnosis has never been genetically confirmed. Confusion may arise when the diagnosis cannot be confirmed or when a mutation is identified in a different gene, for example, NR5A1 in someone with a clinical diagnosis of CAIS that has other consequences for relatives. Hence, new genetic counselling should always accompany new diagnostic endeavours.Class 3 variants and histopathological examinationsThe rapidly evolving diagnostic possibilities raise new questions. What do laboratories report?.

How should we deal with the frequent findings of mainly unique VUS or class 3 variants (ACMG recommendation) in the many different DSD-related genes in the diagnostic setting?. Reporting VUS can be a source of uncertainty for parents, but not reporting these variants precludes further investigations to determine their possible pathogenicity. It can also be difficult to prove variant pathogenicity, both on gene-level and variant-level.39 Moreover, given the gonad-specific expression of some genes and the variable phenotypic spectrum and reduced penetrance, segregation analysis is not always informative. A class 3 variant that does not fit the clinical presentation may be unrelated to the observed phenotype, but it could also represent a newly emerging phenotype. This was recently demonstrated by the identification of the NR5A1 mutation, R92W, in individuals with 46,XX testicular and ovotesticular DSD.40 This gene had previously been associated with 46,XY DSD.

In diagnostic laboratories, there is usually no capacity or expertise to conduct large-scale functional studies to determine pathogenicity of these unique class 3 VUS in the different genes involved in DSD. Functional validation of variants identified in novel genes may be more attractive in a research context. However, for individual families with VUS in well-established DSD genes such as AR or HSD17B3, functional analysis may provide a confirmed diagnosis that implies for relatives the option of undergoing their own DNA analysis and estimating the genetic risk of their own future offspring. This makes genetic follow-up important in these cases and demonstrates the usefulness of international databases and networks and the centralisation of functional studies of genetic variants in order to reduce costs and maximise expertise.The same is true for histopathological description, germ-cell tumour risk assessment in specific forms of DSD and classification of gonadal samples. Germ-cell tumour risk is related to the type of DSD (among other factors), but it is impossible to make risk estimates in individual cases.41–44 Gonadectomy may be indicated in cases with high-risk dysgenetic abdominal gonads that cannot be brought into a stable superficial (ie, inguinal, labioscrotal) position that allows clinical or radiological surveillance, or to avoid virilisation due to 5-alpha reductase deficiency in a 46,XY girl with a stable female gender identity.45 Pathological examination of DSD gonads requires specific expertise.

For example, the differentiation between benign germ cell abnormalities, such as delayed maturation and (pre)malignant development of germ cells, is crucial for clinical management but can be very troublesome.46 Centralised pathological examination of gonadal biopsy and gonadectomy samples in one centre, or a restricted number of centres, on a national scale can help to overcome the problem of non-uniform classification and has proven feasible in the Netherlands and Belgium. We therefore believe that uniform assessment and classification of gonadal differentiation patterns should also be addressed in guidelines on DSD management.International databases of gonadal tissues are crucial for learning more about the risk of malignancy in different forms of DSD, but they are only reliable if uniform criteria for histological classification are strictly applied.46 These criteria could be incorporated in many existing networks such as the I-DSD consortium, the Disorders of Sex Development Translational Research Network, the European Reference Network on Urogenital Diseases (eUROGEN), the EndoERN and COST actions.15–17 47Communication at the transition from paediatric to adult carePaediatric and adult teams need to collaborate closely to facilitate a well-organised transition from paediatric to adult specialist care.15 48–50 Both teams need to exchange information optimally and should consider transition as a longitudinal process rather than a fixed moment in time. Age-appropriate information is key at all ages, and an overview of topics to be discussed at each stage is described by Cools et al.15 Table 1 shows an example of how transition can be organised.View this table:Table 1 Example of transition table as used in the DSD clinic of the Erasmus Medical CenterPsychological support and the continued provision of information remains important for individuals with a DSD at all ages.15 22 In addition to the information given by the DSD team members, families and patients can benefit from resources such as support groups and information available on the internet.47 Information available online should be checked for accuracy and completeness when referring patients and parents to internet sites.Recommendations for future actionsMost guidelines and articles on the diagnosis and management of DSD are aimed at specialists and are only published in specialist journals or on websites for endocrinologists, urologists or geneticists. Yet there is a need for guidelines directed towards first-line and second-line healthcare workers that summarise the recommendations about the first crucial steps in the management of DSD. These should be published in widely available general medical journals and online, along with a national list of DSD centres.

Furthermore, DSD (expert) centres should provide continuous education to all those who may be involved in the identification of individuals with a DSD in order to enable these healthcare professionals to recognise atypical genitalia, to promptly refer individuals who have a DSD and to inform the patient and parents about this and subsequent diagnostic procedures.As DSD continues to be a rare condition, it will take time to evaluate the effects of having such a guideline on the preparedness of first-line and second-line healthcare workers to recognise DSD conditions. One way to evaluate this might be the development and use of questionnaires asking patients, carers and families and referring physicians how satisfied they were with the initial medical consultation and referral and what could be improved. A helpful addition to existing international databases that collect information on genetic variations would be a list of centres that offer suitable functional studies for certain genes, ideally covering the most frequently mutated genes (at minimum).Patient organisations can also play an important role in informing patients about newly available diagnostic or therapeutic strategies and options, and their influence and specific role has now been recognised and discussed in several publications.17 47 However, it should be kept in mind that these organisations do not represent all patients, as a substantial number of patients and parents are not member of such an organisation.Professionals have to provide optimal medical care based on well-established evidence, or at least on broad consensus. Yet not everything can be regulated by recommendations and guidelines. Options, ideas and wishes should be openly discussed between professionals, patients and families within their confidential relationship.

This will enable highly individualised holistic care tailored to the patient’s needs and expectations. Once they are well-informed of all available options, parents and/or patients can choose what they consider the optimal care for their children or themselves.15 16ConclusionThe Dutch-Flemish guideline uniquely addresses some topics that are under-represented in the literature, thus adding some key aspects to those addressed in recent consensus papers and guidelines.15–17 33 47As more children with a DSD are now being identified prenatally, and the literature on prenatal diagnosis of DSD remains scarce,20 21 we propose a prenatal diagnostic algorithm and emphasise the importance of having a prenatal specialist involved in or collaborating with DSD (expert) centres.We also stress that good communication between all involved parties is essential. Professionals should be well informed about protocols and communication. Collaboration between centres is necessary to optimise aspects of care such as uniform interpretation of gonadal pathology and functional testing of class 3 variants found by genetic testing. Guidelines can provide a framework within which individualised patient care should be discussed with all stakeholders.AcknowledgmentsThe authors would like to thank the colleagues of the DSD teams for their input in and critical reading of the Dutch-Flemish guideline.

Amsterdam University Center (AMC and VU), Maastricht University Medical Center, Erasmus Medical Center Rotterdam, Radboud University Medical Center Nijmegen, University Medical Center Groningen, University Medical Center Utrecht, Ghent University Hospital. The authors would like to thank Kate McIntyre for editing the revised manuscript and Tom de Vries Lentsch for providing the figures as a PDF. Three of the authors of this publication are members of the European Reference Network for rare endocrine diseases—Project ID 739543.IntroductionEndometrial cancer is the most common gynaecological malignancy in the developed world.1 Its incidence has risen over the last two decades as a consequence of the ageing population, fewer hysterectomies for benign disease and the obesity epidemic. In the USA, it is estimated that women have a 1 in 35 lifetime risk of endometrial cancer, and in contrast to cancers of most other sites, cancer-specific mortality has risen by approximately 2% every year since 2008 related to the rapidly rising incidence.2Endometrial cancer has traditionally been classified into type I and type II based on morphology.3 The more common subtype, type I, is mostly comprised of endometrioid tumours and is oestrogen-driven, arises from a hyperplastic endometrium, presents at an early stage and has an excellent 5 year survival rate.4 By contrast, type II includes non-endometrioid tumours, specifically serous, carcinosarcoma and clear cell subtypes, which are biologically aggressive tumours with a poor prognosis that are often diagnosed at an advanced stage.5 Recent efforts have focused on a molecular classification system for more accurate categorisation of endometrial tumours into four groups with distinct prognostic profiles.6 7The majority of endometrial cancers arise through the interplay of familial, genetic and lifestyle factors. Two inherited cancer predisposition syndromes, Lynch syndrome and the much rarer Cowden syndrome, substantially increase the lifetime risk of endometrial cancer, but these only account for around 3–5% of cases.8–10 Having first or second degree relative(s) with endometrial or colorectal cancer increases endometrial cancer risk, although a large European twin study failed to demonstrate a strong heritable link.11 The authors failed to show that there was greater concordance in monozygotic than dizygotic twins, but the study was based on relatively small numbers of endometrial cancers.

Lu and colleagues reported an association between common single nucleotide polymorphisms (SNPs) and endometrial cancer risk, revealing the potential role of SNPs in explaining part of the risk in both the familial and general populations.12 Thus far, many SNPs have been reported to modify susceptibility to endometrial cancer. However, much of this work predated genome wide association studies and is of variable quality. Understanding genetic predisposition to endometrial cancer could facilitate personalised risk assessment with a view to targeted prevention and screening interventions.13 This emerged as the most important unanswered research question in endometrial cancer according to patients, carers and healthcare professionals in our recently completed James Lind Womb Cancer Alliance Priority Setting Partnership.14 It would be particularly useful for non-endometrioid endometrial cancers, for which advancing age is so far the only predictor.15We therefore conducted a comprehensive systematic review of the literature to provide an overview of the relationship between SNPs and endometrial cancer risk. We compiled a list of the most robust endometrial cancer-associated SNPs. We assessed the applicability of this panel of SNPs with a theoretical polygenic risk score (PRS) calculation.

We also critically appraised the meta-analyses investigating the most frequently reported SNPs in MDM2. Finally, we described all SNPs reported within genes and pathways that are likely involved in endometrial carcinogenesis and metastasis.MethodsOur systematic review follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) collaboration 2009 recommendations. The registered protocol is available through PROSPERO (CRD42018091907).16Search strategyWe searched Embase, MEDLINE and Cumulative Index to Nursing and Allied Health Literature (CINAHL) databases via the Healthcare Databases Advanced Search (HDAS) platform, from 2007 to 2018, to identify studies reporting associations between polymorphisms and endometrial cancer risk. Key words including MeSH (Medical Subject Heading) terms and free-text words were searched in both titles and abstracts. The following terms were used.

€œendomet*”,“uter*”, “womb”, “cancer(s)”, “neoplasm(s)”, “endometrium tumour”, “carcinoma”, “adenosarcoma”, “clear cell carcinoma”, “carcinosarcoma”, “SNP”, “single nucleotide polymorphism”, “GWAS”, and “genome-wide association study/ies”. No other restrictions were applied. The search was repeated with time restrictions between 2018 and June 2019 to capture any recent publications.Eligibility criteriaStudies were selected for full-text evaluation if they were primary articles investigating a relationship between endometrial cancer and SNPs. Study outcome was either the increased or decreased risk of endometrial cancer relative to controls reported as an odds ratio (OR) with corresponding 95% confidence intervals (95% CIs).Study selectionThree independent reviewers screened all articles uploaded to a screening spreadsheet developed by Helena VonVille.17 Disagreements were resolved by discussion. Chronbach’s α score was calculated between reviewers and indicated high consistency at 0.92.

Case–control, prospective and retrospective studies, genome-wide association studies (GWAS), and both discovery and validation studies were selected for full-text evaluation. Non-English articles, editorials, conference abstracts and proceedings, letters and correspondence, case reports and review articles were excluded.Candidate-gene studies with at least 100 women and GWAS with at least 1000 women in the case arm were selected to ensure reliability of the results, as explained by Spencer et al.18 To construct a panel of up to 30 SNPs with the strongest evidence of association, those with the strongest p values were selected. For the purpose of an SNP panel, articles utilising broad European or multi-ethnic cohorts were selected. Where overlapping populations were identified, the most comprehensive study was included.Data extraction and synthesisFor each study, the following data were extracted. SNP ID, nearby gene(s)/chromosome location, OR (95% CI), p value, minor or effect allele frequency (MAF/EAF), EA (effect allele) and OA (other allele), adjustment, ethnicity and ancestry, number of cases and controls, endometrial cancer type, and study type including discovery or validation study and meta-analysis.

For risk estimates, a preference towards most adjusted results was applied. For candidate-gene studies, a standard p value of<0.05 was applied and for GWAS a p value of <5×10-8, indicating genome-wide significance, was accepted as statistically significant. However, due to the limited number of SNPs with p values reaching genome-wide significance, this threshold was then lowered to <1×10-5, allowing for marginally significant SNPs to be included. As shown by Mavaddat et al, for breast cancer, SNPs that fall below genome-wide significance may still be useful for generating a PRS and improving the models.19We estimated the potential value of a PRS based on the most significant SNPs by comparing the predicted risk for a woman with a risk score in the top 1% of the distribution to the mean predicted risk. Per-allele ORs and MAFs were taken from the publications and standard errors (SEs) for the lnORs were derived from published 95% CIs.

The PRS was assumed to have a Normal distribution, with mean 2∑βipI and SE, σ, equal to √2∑βi2pI(1−pi), according to the binomial distribution, where the summation is over all SNPs in the risk score. Hence the relative risk (RR) comparing the top 1% of the distribution to the mean is given by exp(Z0.01σ), where Z is the inverse of the standard normal cumulative distribution.ResultsThe flow chart of study selection is illustrated in figure 1. In total, 453 text articles were evaluated and, of those, 149 articles met our inclusion criteria. One study was excluded from table 1, for having an Asian-only population, as this would make it harder to compare with the rest of the results which were all either multi-ethnic or Caucasian cohorts, as stated in our inclusion criteria for the SNP panel.20 Any SNPs without 95% CIs were also excluded from any downstream analysis. Additionally, SNPs in linkage disequilibrium (r2 >0.2) with each other were examined, and of those in linkage disequilibrium, the SNP with strongest association was reported.

Per allele ORs were used unless stated otherwise.View this table:Table 1 List of top SNPs most likely to contribute to endometrial cancer risk identified through systematic review of recent literature21–25Study selection flow diagram. *Reasons. Irrelevant articles, articles focusing on other conditions, non-GWAS/candidate-gene study related articles, technical and duplicate articles. GWAS, genome-wide association study. Adapted from.

Moher D, Liberati A, Tetzlaff J, Altman DG, The PRISMA Group (2009). Preferred Reporting Items for Systematic Reviews and Meta-Analyses. The PRISMA Statement. PLoS Med 6(6). E1000097.

Doi:10.1371/journal.pmed1000097." data-icon-position data-hide-link-title="0">Figure 1 Study selection flow diagram. *Reasons. Irrelevant articles, articles focusing on other conditions, non-GWAS/candidate-gene study related articles, technical and duplicate articles. GWAS, genome-wide association study. Adapted from.

Moher D, Liberati A, Tetzlaff J, Altman DG, The PRISMA Group (2009). Preferred Reporting Items for Systematic Reviews and Meta-Analyses. The PRISMA Statement. PLoS Med 6(6). E1000097.

Doi:10.1371/journal.pmed1000097.Top SNPs associated with endometrial cancer riskFollowing careful interpretation of the data, 24 independent SNPs with the lowest p values that showed the strongest association with endometrial cancer were obtained (table 1).21–25 These SNPs are located in or around genes coding for transcription factors, cell growth and apoptosis regulators, and enzymes involved in the steroidogenesis pathway. All the SNPs presented here were reported on the basis of a GWAS or in one case, an exome-wide association study, and hence no SNPs from candidate-gene studies made it to the list. This is partly due to the nature of larger GWAS providing more comprehensive and powered results as opposed to candidate gene studies. Additionally, a vast majority of SNPs reported by candidate-gene studies were later refuted by large-scale GWAS such as in the case of TERT and MDM2 variants.26 27 The exception to this is the CYP19 gene, where candidate-gene studies reported an association between variants in this gene with endometrial cancer in both Asian and broad European populations, and this association was more recently confirmed by large-scale GWAS.21 28–30 Moreover, a recent article authored by O’Mara and colleagues reviewed the GWAS that identified most of the currently known SNPs associated with endometrial cancer.31Most of the studies represented in table 1 are GWAS and the majority of these involved broad European populations. Those having a multi-ethnic cohort also consisted primarily of broad European populations.

Only four of the variants in table 1 are located in coding regions of a gene, or in regulatory flanking regions around the gene. Thus, most of these variants would not be expected to cause any functional effects on the gene or the resulting protein. An eQTL search using GTEx Portal showed that some of the SNPs are significantly associated (p<0.05) with modified transcription levels of the respective genes in various tissues such as prostate (rs11263761), thyroid (rs9668337), pituitary (rs2747716), breast mammary (rs882380) and testicular (rs2498794) tissue, as summarised in table 2.View this table:Table 2 List of eQTL hits for the selected panel of SNPsThe only variant for which there was an indication of a specific association with non-endometrioid endometrial cancer was rs148261157 near the BCL11A gene. The A allele of this SNP had a moderately higher association in the non-endometrioid arm (OR 1.64, 95% CI 1.32 to 2.04. P=9.6×10-6) compared with the endometrioid arm (OR 1.25, 95% CI 1.14 to 1.38.

P=4.7×10-6).21Oestrogen receptors α and β encoded by ESR1 and ESR2, respectively, have been extensively studied due to the assumed role of oestrogens in the development of endometrial cancer. O’Mara et al reported a lead SNP (rs79575945) in the ESR1 region that was associated with endometrial cancer (p=1.86×10-5).24 However, this SNP did not reach genome-wide significance in a more recent larger GWAS.21 No statistically significant associations have been reported between endometrial cancer and SNPs in the ESR2 gene region.AKT is an oncogene linked to endometrial carcinogenesis. It is involved in the PI3K/AKT/mTOR pro-proliferative signalling pathway to inactivate apoptosis and allow cell survival. The A allele of rs2494737 and G allele of rs2498796 were reported to be associated with increased and decreased risk of endometrial cancer in 2016, respectively.22 30 However, this association was not replicated in a larger GWAS in 2018.21 Nevertheless, given the previous strong indications, and biological basis that could explain endometrial carcinogenesis, we decided to include an AKT1 variant (rs2498794) in our results.PTEN is a multi-functional tumour suppressor gene that regulates the AKT/PKB signalling pathway and is commonly mutated in many cancers including endometrial cancer.32 Loss-of-function germline mutations in PTEN are responsible for Cowden syndrome, which exerts a lifetime risk of endometrial cancer of up to 28%.9 Lacey and colleagues studied SNPs in the PTEN gene region. However, none showed significant differences in frequency between 447 endometrial cancer cases and 439 controls of European ancestry.33KRAS mutations are known to be present in endometrial cancer.

These can be activated by high levels of KLF5 (transcriptional activator). Three SNPs have been identified in or around KLF5 that are associated with endometrial cancer. The G allele of rs11841589 (OR 1.15, 95% CI 1.11 to 1.21. P=4.83×10-11), the A allele of rs9600103 (OR 1.23, 95% CI 1.16 to 1.30. P=3.76×10-12) and C allele of rs7981863 (OR 1.16, 95% CI 1.12 to 1.20.

P=2.70×10-17) have all been found to be associated with an increased likelihood of endometrial cancer in large European cohorts.21 30 34 It is worth noting that these SNPs are not independent, and hence they quite possibly tag the same causal variant.The MYC family of proto-oncogenes encode transcription factors that regulate cell proliferation, which can contribute to cancer development if dysregulated. The recent GWAS by O’Mara et al reported three SNPs within the MYC region that reached genome-wide significance with conditional p values reaching at least 5×10–8.35To test the utility of these SNPs as predictive markers, we devised a theoretical PRS calculation using the log ORs and EAFs per SNP from the published data. The results were very encouraging with an RR of 3.16 for the top 1% versus the mean, using all the top SNPs presented in table 1 and 2.09 when using only the SNPs that reached genome-wide significance (including AKT1).Controversy surrounding MDM2 variant SNP309MDM2 negatively regulates tumour suppressor gene TP53, and as such, has been extensively studied in relation to its potential role in predisposition to endometrial cancer. Our search identified six original studies of the association between MDM2 SNP rs2279744 (also referred to as SNP309) and endometrial cancer, all of which found a statistically significant increased risk per copy of the G allele. Two more original studies were identified through our full-text evaluation.

However, these were not included here as they did not meet our inclusion criteria—one due to small sample size, the other due to studying rs2279744 status dependent on another SNP.36 37 Even so, the two studies were described in multiple meta-analyses that are listed in table 3. Different permutations of these eight original studies appear in at least eight published meta-analyses. However, even the largest meta-analysis contained <2000 cases (table 3)38View this table:Table 3 Characteristics of studies that examined MDM2 SNP rs2279744In comparison, a GWAS including nearly 13 000 cases found no evidence of an association with OR and corresponding 95% CI of 1.00 (0.97 to 1.03) and a p value of 0.93 (personal communication).21 Nevertheless, we cannot completely rule out a role for MDM2 variants in endometrial cancer predisposition as the candidate-gene studies reported larger effects in Asians, whereas the GWAS primarily contained participants of European ancestry. There is also some suggestion that the SNP309 variant is in linkage disequilibrium with another variant, SNP285, which confers an opposite effect.It is worth noting that the SNP285C/SNP309G haplotype frequency was observed in up to 8% of Europeans, thus requiring correction for the confounding effect of SNP285C in European studies.39 However, aside from one study conducted by Knappskog et al, no other study including the meta-analyses corrected for the confounding effect of SNP285.40 Among the studies presented in table 3, Knappskog et al (2012) reported that after correcting for SNP285, the OR for association of this haplotype with endometrial cancer was much lower, though still significant. Unfortunately, the meta-analyses which synthesised Knappskog et al (2012), as part of their analysis, did not correct for SNP285C in the European-based studies they included.38 41 42 It is also concerning that two meta-analyses using the same primary articles failed to report the same result, in two instances.38 42–44DiscussionThis article represents the most comprehensive systematic review to date, regarding critical appraisal of the available evidence of common low-penetrance variants implicated in predisposition to endometrial cancer.

We have identified the most robust SNPs in the context of endometrial cancer risk. Of those, only 19 were significant at genome-wide level and a further five were considered marginally significant. The largest GWAS conducted in this field was the discovery- and meta-GWAS by O’Mara et al, which utilised 12 096 cases and 108 979 controls.21 Despite the inclusion of all published GWAS and around 5000 newly genotyped cases, the total number did not reach anywhere near what is currently available for other common cancers such as breast cancer. For instance, BCAC (Breast Cancer Association Consortium) stands at well over 200 000 individuals with more than half being cases, and resulted in identification of ~170 SNPs in relation to breast cancer.19 45 A total of 313 SNPs including imputations were then used to derive a PRS for breast cancer.19 Therefore, further efforts should be directed to recruit more patients, with deep phenotypic clinical data to allow for relevant adjustments and subgroup analyses to be conducted for better precision.A recent pre-print study by Zhang and colleagues examined the polygenicity and potential for SNP-based risk prediction for 14 common cancers, including endometrial cancer, using available summary-level data from European-ancestry datasets.46 They estimated that there are just over 1000 independent endometrial cancer susceptibility SNPs, and that a PRS comprising all such SNPs would have an area under the receiver-operator curve of 0.64, similar to that predicted for ovarian cancer, but lower than that for the other cancers in the study. The modelling in the paper suggests that an endometrial cancer GWAS double the size of the current largest study would be able to identify susceptibility SNPs together explaining 40% of the genetic variance, but that in order to explain 75% of the genetic variance it would be necessary to have a GWAS comprising close to 150 000 cases and controls, far in excess of what is currently feasible.We found that the literature consists mainly of candidate-gene studies with small sample sizes, meta-analyses reporting conflicting results despite using the same set of primary articles, and multiple reports of significant SNPs that have not been validated by any larger GWAS.

The candidate-gene studies were indeed the most useful and cheaper technique available until the mid to late 2000s. However, a lack of reproducibility (particularly due to population stratification and reporting bias), uncertainty of reported associations, and considerably high false discovery rates make these studies much less appropriate in the post-GWAS era. Unlike the candidate-gene approach, GWAS do not require prior knowledge, selection of genes or SNPs, and provide vast amounts of data. Furthermore, both the genotyping process and data analysis phases have become cheaper, the latter particularly due to faster and open-access pre-phasing and imputation tools being made available.It is clear from table 1 that some SNPs were reported with wide 95% CI, which can be directly attributed to small sample sizes particularly when restricting the cases to non-endometrioid histology only, low EAF or poor imputation quality. Thus, these should be interpreted with caution.

Additionally, most of the SNPs reported by candidate-gene studies were not detected by the largest GWAS to date conducted by O’Mara et al.21 However, this does not necessarily mean that the possibility of those SNPs being relevant should be completely dismissed. Moreover, meta-analyses were attempted for other variants. However, these showed no statistically significant association and many presented with high heterogeneity between the respective studies (data not shown). Furthermore, as many studies utilised the same set of cases and/or controls, conducting a meta-analysis was not possible for a good number of SNPs. It is therefore unequivocal that the literature is crowded with numerous small candidate-gene studies and conflicting data.

This makes it particularly hard to detect novel SNPs and conduct meaningful meta-analyses.We found convincing evidence for 19 variants that indicated the strongest association with endometrial cancer, as shown in table 1. The associations between endometrial cancer and variants in or around HNF1B, CYP19A1, SOX4, MYC, KLF and EIF2AK found in earlier GWAS were then replicated in the latest and largest GWAS. These SNPs showed promising potential in a theoretical PRS we devised based on published data. Using all 24 or genome-wide significant SNPs only, women with a PRS in the top 1% of the distribution would be predicted to have a risk of endometrial cancer 3.16 and 2.09 times higher than the mean risk, respectively.However, the importance of these variants and relevance of the proximate genes in a functional or biological context is challenging to evaluate. Long distance promoter regulation by enhancers may disguise the genuine target gene.

In addition, enhancers often do not loop to the nearest gene, further complicating the relevance of nearby gene(s) to a GWAS hit. In order to elucidate biologically relevant candidate target genes in endometrial cancer, O’Mara et al looked into promoter-associated chromatin looping using a modern HiChIP approach.47 The authors utilised normal and tumoural endometrial cell lines for this analysis which showed significant enrichment for endometrial cancer heritability, with 103 candidate target genes identified across the 13 risk loci identified by the largest ECAC GWAS. Notable genes identified here were CDKN2A and WT1, and their antisense counterparts. The former was reported to be nearby of rs1679014 and the latter of rs10835920, as shown in table 1. Moreover, of the 36 candidate target genes, 17 were found to be downregulated while 19 were upregulated in endometrial tumours.The authors also investigated overlap between the 13 endometrial cancer risk loci and top eQTL variants for each target gene.47 In whole blood, of the two particular lead SNPs, rs8822380 at 17q21.32 was a top eQTL for SNX11 and HOXB2, whereas rs937213 at 15q15.1 was a top eQTL for SRP14.

In endometrial tumour, rs7579014 at 2p16.1 was found to be a top eQTL for BCL11A. This is particularly interesting because BCL11A was the only nearby/candidate gene that had a GWAS association reported in both endometrioid and non-endometrioid subtypes. The study looked at protein–protein interactions between endometrial cancer drivers and candidate target gene products. Significant interactions were observed with TP53 (most significant), AKT, PTEN, ESR1 and KRAS, among others. Finally, when 103 target candidate genes and 387 proteins were combined together, 462 pathways were found to be significantly enriched.

Many of these are related to gene regulation, cancer, obesity, insulinaemia and oestrogen exposure. This study clearly showed a potential biological relevance for some of the SNPs reported by ECAC GWAS in 2018.Most of the larger included studies used cohorts primarily composed of women of broad European descent. Hence, there are negligible data available for other ethnicities, particularly African women. This is compounded by the lack of reference genotype data available for comparative analysis, making it harder for research to be conducted in ethnicities other than Europeans. This poses a problem for developing risk prediction models that are equally valuable and predictive across populations.

Thus, our results also are of limited applicability to non-European populations.Furthermore, considering that non-endometrioid cases comprise a small proportion (~20%) of all endometrial cancer cases, much larger cohort sizes are needed to detect any genuine signals for non-endometrioid tumours. Most of the evaluated studies looked at either overall/mixed endometrial cancer subtypes or endometrioid histology, and those that looked at variant associations with non-endometrioid histology were unlikely to have enough power to detect any signal with statistical significance. This is particularly concerning because non-endometrioid subtypes are biologically aggressive tumours with a much poorer prognosis that contribute disproportionately to mortality from endometrial cancer. It is particularly important that attempts to improve early detection and prevention of endometrial cancer focus primarily on improving outcomes from these subtypes. It is also worth noting that, despite the current shift towards a molecular classification of endometrial cancer, most studies used the overarching classical Bokhman’s classification system, type I versus type II, or no histological classification system at all.

Therefore, it is important to create and follow a standardised and comprehensive classification system for reporting tumour subtypes for future studies.This study compiled and presented available information for an extensively studied, yet unproven in large datasets, SNP309 variant in MDM2. Currently, there is no convincing evidence for an association between this variant and endometrial cancer risk. Additionally, of all the studies, only one accounted for the opposing effect of a nearby variant SNP285 in their analyses. Thus, we conclude that until confirmed by a sufficiently large GWAS, this variant should not be considered significant in influencing the risk of endometrial cancer and therefore not included in a PRS. This is also true for the majority of the SNPs reported in candidate-gene studies, as the numbers fall far short of being able to detect genuine signals.This systematic review presents the most up-to-date evidence for endometrial cancer susceptibility variants, emphasising the need for further large-scale studies to identify more variants of importance, and validation of these associations.

Until data from larger and more diverse cohorts are available, the top 24 SNPs presented here are the most robust common genetic variants that affect endometrial cancer risk. The multiplicative effects of these SNPs could be used in a PRS to allow personalised risk prediction models to be developed for targeted screening and prevention interventions for women at greatest risk of endometrial cancer..

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Telehealth has been gaining buy kamagra over the counter ground as a breakout star of the COVID-19 pandemic. But while much of the recent attention has focused on using it to treat patients at home, the practice has also been vital to keeping clinical staff members safer as providers revamp emergency departments to curb the buy kamagra over the counter risk of infection.Telehealth played a major role when Renown Health set up a medical tent during the early days of the pandemic to expand its ED’s triage capacity for patients with COVID-19 symptoms.After getting their vital signs taken by a nurse in-person, patients would speak with an emergency medicine physician via video, who would determine whether they needed testing, treatment or another next step.The Reno, Nev.-based system took down its alternate care site in June, but has kept aspects of that virtual component alive in its ED. €œOur first priority is patient safety and patient care,” said Dr.

Paul Sierzenski, buy kamagra over the counter an emergency medicine physician and chief medical officer for acute-care services at Renown. €œRight next to that is our staff safety and staff care.”When patients present at the ED, they’re immediately screened for COVID-19. Those with symptoms are sent to an individual room, where they’ll typically use a tablet or telehealth cart—which includes internet-connected devices, such as digital stethoscopes—to complete a virtual evaluation and assessment with a physician, depending on their acuity.Renown uses software and hardware from a few different companies for its telehealth program.It’s the first time the health system has used telehealth to connect its buy kamagra over the counter on-site physicians to ED patients, though it has provided telehealth consultations for specialty services like stroke care and behavioral health to EDs for years.Some health systems were adding telehealth to their EDs before COVID-19 hit.

Those with high ED visit volumes in particular had been rolling out processes for physician assistants or physicians—often based at a central station, but managing patients at multiple facilities—to help triage patients via telehealth, in an effort to reduce long wait times, said Arielle Trzcinski, a senior analyst at market research firm Forrester.That type of “tele-triage” can help a facility manage capacity, since a remote physician assistant or physician can redirect patients who might be a better fit for urgent or primary care. For patients with more buy kamagra over the counter pressing cases, staff can start ordering lab tests and X-rays before a patient even gets to an exam room. It’s become more common to see telehealth in EDs since March, as health systems have wanted to address patient surges quickly and use portable video equipment in new ways to decrease clinicians’ COVID-19 exposure, Trzcinski said.

She believes buy kamagra over the counter many health systems will keep the new processes in place, at least for busy times of the year, such as flu season.Emergency medicine staff at Aurora St. Luke’s Medical Center, a Milwaukee hospital that’s part of Advocate Aurora Health, had been thinking about using remote physician assistants to help triage patients, but the practice didn’t catch on until COVID cases started mounting. Since the spring, patients who present at Aurora St buy kamagra over the counter.

Luke’s ED with COVID-19 symptoms are directed to a so-called “hot zone” buy kamagra over the counter. Those without symptoms are sent to the “cold zone.” A telehealth cart with a tablet is rolled over, so a physician assistant—located elsewhere in the hospital—can remotely triage patients in both areas.The tele-triage system lets remote physician assistants assess any patient without having to change personal protective equipment, said Dr. Bill Lieber, buy kamagra over the counter an emergency medicine physician who has practiced at the hospital for more than 15 years.The tele-triage system is likely to remain at Aurora St.

Luke’s after the pandemic subsides, Lieber said. Aurora St buy kamagra over the counter. Luke’s uses virtual care technology from EmOpti for tele-triage.Aside from reducing risk of exposure, Lieber said it has helped with efficiency, since the physician assistant can remotely triage patients at other facilities while at Aurora St.

Luke’s.EmOpti bases its software fees on a facility’s annual ED visit buy kamagra over the counter volumes, according to Dr. Edward Barthell, an emergency medicine physician and the company’s founder and CEO.It’s too early to share outcomes from Aurora St. Luke’s tele-triage buy kamagra over the counter use, but a sister hospital saw its typical patient wait time drop from 40 minutes to 10 minutes after implementing tele-triage, according to Barthell.

The hospital’s length of stay for patients discharged from the ED decreased by 45 minutes..

Telehealth has look at this website been gaining ground as a kamagra street price breakout star of the COVID-19 pandemic. But while much of the recent attention has focused on using it to treat patients at home, the practice has also been vital to keeping clinical staff members safer as providers revamp emergency departments to curb the risk of infection.Telehealth played a major role when Renown Health set up a medical tent during the early days of the pandemic kamagra street price to expand its ED’s triage capacity for patients with COVID-19 symptoms.After getting their vital signs taken by a nurse in-person, patients would speak with an emergency medicine physician via video, who would determine whether they needed testing, treatment or another next step.The Reno, Nev.-based system took down its alternate care site in June, but has kept aspects of that virtual component alive in its ED. €œOur first priority is patient safety and patient care,” said Dr. Paul Sierzenski, an emergency medicine kamagra street price physician and chief medical officer for acute-care services at Renown. €œRight next to that is our staff safety and staff care.”When patients present at the ED, they’re immediately screened for COVID-19.

Those with symptoms are sent to an individual room, where they’ll typically use a tablet or telehealth cart—which includes internet-connected devices, such as digital stethoscopes—to complete a virtual evaluation and assessment with a physician, depending on their acuity.Renown uses software and hardware from a few different companies for its telehealth program.It’s the first time the health system has used telehealth to connect its on-site physicians to ED patients, though it has provided telehealth consultations for specialty services like stroke care and behavioral health to EDs for years.Some health systems were kamagra street price adding telehealth to their EDs before COVID-19 hit. Those with high ED visit volumes in particular had been rolling out processes for physician assistants or physicians—often based at a central station, but managing patients at multiple facilities—to help triage patients via telehealth, in an effort to reduce long wait times, said Arielle Trzcinski, a senior analyst at market research firm Forrester.That type of “tele-triage” can help a facility manage capacity, since a remote physician assistant or physician can redirect patients who might be a better fit for urgent or primary care. For patients with kamagra street price more pressing cases, staff can start ordering lab tests and X-rays before a patient even gets to an exam room. It’s become more common to see telehealth in EDs since March, as health systems have wanted to address patient surges quickly and use portable video equipment in new ways to decrease clinicians’ COVID-19 exposure, Trzcinski said. She believes many health systems will keep the new processes in place, at least for busy kamagra street price times of the year, such as flu season.Emergency medicine staff at Aurora St.

Luke’s Medical Center, a Milwaukee hospital that’s part of Advocate Aurora Health, had been thinking about using remote physician assistants to help triage patients, but the practice didn’t catch on until COVID cases started mounting. Since the spring, patients navigate to this web-site who kamagra street price present at Aurora St. Luke’s ED with COVID-19 symptoms are kamagra street price directed to a so-called “hot zone”. Those without symptoms are sent to the “cold zone.” A telehealth cart with a tablet is rolled over, so a physician assistant—located elsewhere in the hospital—can remotely triage patients in both areas.The tele-triage system lets remote physician assistants assess any patient without having to change personal protective equipment, said Dr. Bill Lieber, an emergency medicine physician who has practiced at kamagra street price the hospital for more than 15 years.The tele-triage system is likely to remain at Aurora St.

Luke’s after the pandemic subsides, Lieber said. Aurora St kamagra street price. Luke’s uses virtual care technology from EmOpti for tele-triage.Aside from reducing risk of exposure, Lieber said it has helped with efficiency, since the physician assistant can remotely triage patients at other facilities while at Aurora St. Luke’s.EmOpti bases its software fees on a facility’s annual ED visit volumes, according kamagra street price to Dr. Edward Barthell, an emergency medicine physician and the company’s founder and CEO.It’s too early to share outcomes from Aurora St.

Luke’s tele-triage use, but a sister hospital saw its typical kamagra street price patient wait time drop from 40 minutes to 10 minutes after implementing tele-triage, according to Barthell. The hospital’s length of stay for patients discharged from the ED decreased by 45 minutes..

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COVID-19 has kamagra viagra jelly evolved rapidly into a pandemic order kamagra gel with global impacts. However, as the pandemic has developed, it has become increasingly evident that the order kamagra gel risks of COVID-19, both in terms of infection rates and particularly of severe complications, are not equal across all members of society. While general risk factors for hospital admission with COVID-19 infection include age, male sex and specific comorbidities (eg, cardiovascular disease, hypertension and diabetes), there is increasing evidence that people identifying with Black, Asian and Minority Ethnic (BAME) groupsi have disproportionately higher risks of being adversely affected by COVID-19 in the UK and the USA. The ethnic disparities include overall numbers of cases, as well as the relative numbers of critical care admissions and deaths.1In the area of mental health, for people from BAME groups, even before the current pandemic there were already significant mental order kamagra gel health inequalities.2 These inequalities have been increased by the pandemic in several ways. The constraints of quarantine have made access to traditional face-to-face support from mental health services more difficult in general.

This difficulty order kamagra gel will increase pre-existing inequalities where there are challenges to engaging people in care and in providing early access to services. The restrictions may also reduce the flexibility of care offers, given the need for social isolation, limiting non-essential travel and closure of routine clinics. The service impacts are compounded by constraints on the use of non-traditional or alternative routes to care and support.In addition, there is growing evidence of order kamagra gel specific mental health consequences from significant COVID-19 infection, with increased rates of not only post-traumatic stress disorder, anxiety and depression, but also specific neuropsychiatric symptoms.3 Given the higher risks of mental illnesses and complex care needs among ethnic minorities and also in deprived inner city areas, COVID-19 seems to deliver a double blow. Physical and mental health vulnerabilities are inextricably linked, especially as a significant proportion of healthcare workers (including in mental health services) in the UK are from BAME groups.Focusing on mental health, there is very little COVID-19-specific guidance on the needs of patients in the BAME group. The risk to staff in general healthcare (including mental healthcare) is a particular concern, and in response, the Royal College order kamagra gel of Psychiatrists and NHS England have produced a report on the impact of COVID-19 on BAME staff in mental healthcare settings, with guidance on assessment and management of risk using an associated risk assessment tool for staff.4 5However, there is little formal guidance for the busy clinician in balancing different risks for individual mental health patients and treating appropriately.

Thus, for example, an inpatient clinician may want to know whether a patient who is older, has additional comorbidities and is from an ethnic background, should be started on one antipsychotic medication or another, or whether treatments such as vitamin D prophylaxis or treatment and venous thromboembolism prevention should be started earlier in the context of the COVID-19 pandemic. While syntheses of the existing guidelines are available about COVID-19 and mental health,6 7 there is nothing specific about the healthcare needs of patients from ethnic minorities during the pandemic.To fill this gap, we propose three core actions that may help:Ensure good information and psychoeducation packages are made available to those with English as a second language, and ensure health beliefs and knowledge are based on order kamagra gel the best evidence available. Address culturally grounded explanatory models and illness perceptions to allay fears and worry, and ensure timely access to testing and care if needed.Maintain levels of service, flexibility in care packages, and personal relationships with patients and carers from ethnic minority backgrounds in order to continue existing care and to identify changes needed order kamagra gel to respond to worsening of mental health.Consider modifications to existing interventions such as psychological therapies and pharmacotherapy. Have a high index of suspicion to take into account emerging physical health problems and the greater risk of serious consequences of COVID-19 in ethnic minority people with pre-existing chronic conditions and vulnerability factors.These actions are based on clinical common sense, but guidance in this area should be provided on the basis of good evidence. There has already been a call for urgent research in the area of COVID-19 and mental health8 and also a clear need for order kamagra gel specific research focusing on the post-COVID-19 mental health needs of people from the BAME group.

Research also needs to recognise the diverse range of different people, with different needs and vulnerabilities, who are grouped under the multidimensional term BAME, including people from different generations, first-time migrants, people from Africa, India, the Caribbean and, more recently, migrants from Eastern Europe. Application of a race equality impact assessment to all research questions and methodology has recently been proposed as a first step in this process.2 At this early stage, the guidance for assessing risks of COVID-19 for health professionals is also useful for patients, until more refined order kamagra gel decision support and prediction tools are developed. A recent Public Health England report on ethnic minorities and COVID-199 recommends better recording of ethnicity data in health and social care, and goes further to suggest this should also apply to death certificates. Furthermore, the report recommends more participatory and experience-based research to understand causes and consequences of pre-existing multimorbidity and COVID-19 infection, integrated care systems that work well for susceptible and marginalised groups, culturally competent health promotion, prevention and occupational risk assessments, and recovery strategies to mitigate the risks of widening inequalities as we come out of restrictions.Primary data collection will need to cover not only hospital admissions but also data from primary care, linking information on mental health, COVID-19 order kamagra gel and ethnicity. We already have research and specific guidance emerging on other risk factors, such as age and gender.

Now we also need to focus on order kamagra gel an equally important aspect of vulnerability. As clinicians, we need to balance the relative risks for each of our patients, so that we can act promptly and proactively in response to their individual needs.10 For this, we need evidence-based guidance to ensure we are balancing every risk appropriately and without bias.Footnotei While we have used the term ‘people identifying with BAME groups’, we recognise that this is a multidimensional group and includes vast differences in culture, identity, heritage and histories contained within this abbreviated term..

COVID-19 has evolved rapidly into a pandemic with global kamagra street price impacts. However, as the pandemic has developed, it has become increasingly kamagra street price evident that the risks of COVID-19, both in terms of infection rates and particularly of severe complications, are not equal across all members of society. While general risk factors for hospital admission with COVID-19 infection include age, male sex and specific comorbidities (eg, cardiovascular disease, hypertension and diabetes), there is increasing evidence that people identifying with Black, Asian and Minority Ethnic (BAME) groupsi have disproportionately higher risks of being adversely affected by COVID-19 in the UK and the USA.

The ethnic disparities include overall numbers of kamagra street price cases, as well as the relative numbers of critical care admissions and deaths.1In the area of mental health, for people from BAME groups, even before the current pandemic there were already significant mental health inequalities.2 These inequalities have been increased by the pandemic in several ways. The constraints of quarantine have made access to traditional face-to-face support from mental health services more difficult in general. This difficulty will increase pre-existing inequalities where there are challenges kamagra street price to engaging people in care and in providing early access to services.

The restrictions may also reduce the flexibility of care offers, given the need for social isolation, limiting non-essential travel and closure of routine clinics. The service impacts are compounded by constraints on the use of non-traditional or alternative routes to care and support.In addition, there is growing evidence of specific mental health consequences from significant COVID-19 infection, with increased rates of not only post-traumatic stress kamagra street price disorder, anxiety and depression, but also specific neuropsychiatric symptoms.3 Given the higher risks of mental illnesses and complex care needs among ethnic minorities and also in deprived inner city areas, COVID-19 seems to deliver a double blow. Physical and mental health vulnerabilities are inextricably linked, especially as a significant proportion of healthcare workers (including in mental health services) in the UK are from BAME groups.Focusing on mental health, there is very little COVID-19-specific guidance on the needs of patients in the BAME group.

The risk to staff in general healthcare (including mental healthcare) is a particular concern, and in response, the Royal College of Psychiatrists and NHS England have produced a report on the impact of COVID-19 on BAME staff in mental healthcare settings, with guidance on assessment and management of risk using an associated risk assessment tool for staff.4 5However, there is little formal guidance for the busy clinician in balancing kamagra street price different risks for individual mental health patients and treating appropriately. Thus, for example, an inpatient clinician may want to know whether a patient who is older, has additional comorbidities and is from an ethnic background, should be started on one antipsychotic medication or another, or whether treatments such as vitamin D prophylaxis or treatment and venous thromboembolism prevention should be started earlier in the context of the COVID-19 pandemic. While syntheses kamagra street price of the existing guidelines are available about COVID-19 and mental health,6 7 there is nothing specific about the healthcare needs of patients from ethnic minorities during the pandemic.To fill this gap, we propose three core actions that may help:Ensure good information and psychoeducation packages are made available to those with English as a second language, and ensure health beliefs and knowledge are based on the best evidence available.

Address culturally grounded explanatory models and illness perceptions to allay fears and worry, and ensure timely access to testing and care if needed.Maintain levels of service, flexibility in care packages, and personal relationships with patients and carers from ethnic minority backgrounds in order to continue existing care and to identify changes needed to respond to worsening of mental health.Consider modifications to existing interventions such as psychological therapies and kamagra street price pharmacotherapy. Have a high index of suspicion to take into account emerging physical health problems and the greater risk of serious consequences of COVID-19 in ethnic minority people with pre-existing chronic conditions and vulnerability factors.These actions are based on clinical common sense, but guidance in this area should be provided on the basis of good evidence. There has already been a call for urgent research in the area of COVID-19 and mental health8 and also a clear need for specific research focusing on the post-COVID-19 mental health needs of people from the BAME kamagra street price group.

Research also needs to recognise the diverse range of different people, with different needs and vulnerabilities, who are grouped under the multidimensional term BAME, including people from different generations, first-time migrants, people from Africa, India, the Caribbean and, more recently, migrants from Eastern Europe. Application of a race equality impact assessment to all research questions and methodology has recently been proposed as a first step in this process.2 At this early stage, the guidance for assessing risks of kamagra street price COVID-19 for health professionals is also useful for patients, until more refined decision support and prediction tools are developed. A recent Public Health England report on ethnic minorities and COVID-199 recommends better recording of ethnicity data in health and social care, and goes further to suggest this should also apply to death certificates.

Furthermore, the report recommends more participatory and experience-based research to understand causes and consequences of pre-existing multimorbidity and COVID-19 infection, integrated care systems that work well for susceptible and marginalised groups, culturally competent health promotion, prevention and occupational risk assessments, and recovery strategies to mitigate the risks of widening inequalities as we come out kamagra street price of restrictions.Primary data collection will need to cover not only hospital admissions but also data from primary care, linking information on mental health, COVID-19 and ethnicity. We already have research and specific guidance emerging on other risk factors, such as age and gender. Now we also need to focus on an equally kamagra street price important aspect of vulnerability.

As clinicians, we need to balance the relative risks for each of our patients, so that we can act promptly and proactively in response to their individual needs.10 For this, we need evidence-based guidance to ensure we are balancing every risk appropriately and without bias.Footnotei While we have used the term ‘people identifying with BAME groups’, we recognise that this is a multidimensional group and includes vast differences in culture, identity, heritage and histories contained within this abbreviated term..

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High burden of antibiotic-resistant Mycoplasma genitalium in symptomatic urethritisMycoplasma genitalium where to get kamagra is an kamagra 50mg aetiological agent of sexually transmitted urethritis. A cohort study investigated M. Genitalium prevalence, antibiotic resistance and association with previous macrolide exposure among 1816 Chinese men who presented with symptomatic urethritis where to get kamagra between 2011 and 2015.

Infection was diagnosed by PCR, and sequencing was used to detect mutations that confer resistance to macrolides and fluoroquinolones. In 11% of men, where to get kamagra M. Genitalium was the sole pathogen identified.

Nearly 90% of infections were resistant where to get kamagra to macrolides and fluoroquinolones. Previous macrolide exposure was associated with higher prevalence of resistance (97%). The findings point to where to get kamagra the need for routine screening for M.

Genitalium in symptomatic men with urethritis. Treatment strategies to overcome where to get kamagra antibiotic resistance in M. Genitalium are needed.Yang L, Xiaohong S, Wenjing L, et al.

Mycoplasma genitalium where to get kamagra in symptomatic male urethritis. Macrolide use is associated with increased resistance. Clin Infect Dis 2020;5:805–10.

Doi:10.1093/cid/ciz294.A new entry inhibitor offers promise for treatment-experienced patients with multidrug-resistant HIVFostemsavir, the prodrug of temsavir, is an where to get kamagra attachment inhibitor. By targeting the gp120 protein on the HIV-1 envelope, it prevents viral interaction with the CD4 receptor. No cross-resistance has been described with other antiretroviral agents, including those that where to get kamagra target viral entry by other modalities.

In the phase III BRIGHTE trial, 371 highly treatment-experienced patients who had exhausted ≥4 classes of antiretrovirals received fostemsavir with an optimised regimen. After 48 weeks, where to get kamagra 54% of those with 1–2 additional active drugs achieved viral load suppression <40 copies/mL. Response rates were 38% among patients lacking other active agents.

Drug-related adverse events included nausea (4%) and diarrhoea (3%) where to get kamagra. As gp120 substitutions reduced fostemsavir susceptibility in up to 70% of patients with virological failure, fostemsavir offers the most valuable salvage option in partnership with other active drugs.Kozal M, Aberg J, Pialoux G, et al. Fostemsavir in where to get kamagra adults with multidrug-resistant HIV-1 infection.

N Engl J Med 2020;382:1232–43. Doi. 10.1056/NEJMoa1902493Novel tools to aid identification of hepatitis C in primary careHepatitis C can now be cured with oral antiviral treatment, and improving diagnosis is a key element of elimination strategies.1 A cluster randomised controlled trial in South West England tested performance and cost-effectiveness of an electronic algorithm that identified at-risk patients in primary care according to national recommendations,2 coupled with educational activities and interventions to increase patients’ awareness.

Outcomes were testing uptake, diagnosis and referral to specialist care. Practices in the intervention arm had an increase in all outcome measures, with adjusted risk ratios of 1.59 (1.21–2.08) for uptake, 2.24 (1.47–3.42) for diagnosis and 5.78 (1.60–21.6) for referral. The intervention was highly cost-effective.

Electronic algorithms applied to practice systems could enhance testing and diagnosis of hepatitis C in primary care, contributing to global elimination goals.Roberts K, Macleod J, Metcalfe C, et al. Cost-effectiveness of an intervention to increase uptake of hepatitis C virus testing and treatment (HepCATT). Cluster randomised controlled trial in primary care.

BMJ 2020;368:m322. Doi:10.1136/bmj.m322Low completion rates for antiretroviral postexposure prophylaxis (PEP) after sexual assaultA 4-week course of triple-agent postexposure prophylaxis (PEP) is recommended following a high-risk sexual assault.3 4 A retrospective study in Barcelona identified 1695 victims attending an emergency room (ER) between 2006 and 2015. Overall, 883 (52%) started prophylaxis in ER, which was mostly (43%) lopinavir/ritonavir based.

Follow-up appointments were arranged for those living in Catalonia (631, 71.5%), and of these, only 183 (29%) completed treatment. Loss to follow-up was more prevalent in those residing outside Barcelona. PEP non-completion was associated with a low perceived risk, previous assaults, a known aggressor and a positive cocaine test.

Side effects were common, occurring in up to 65% of those taking lopinavir/ritonavir and accounting for 15% of all discontinuations. More tolerable PEP regimens, accessible follow-up and provision of 1-month supply may improve completion rates.Inciarte A, Leal L, Masfarre L, et al. Postexposure prophylaxis for HIV infection in sexual assault victims.

HIV Med 2020;21:43–52. Doi:10.1111/hiv.12797.Effective antiretroviral therapy reduces anal high-risk HPV infection and cancer riskAmong people with HIV, effective antiretroviral therapy (ART) is expected to improve control of anal infection with high-risk human papillomavirus (HR-HPV) and reduce https://www.cityreal.lv/kamagra-cost/ the progression of HPV-associated anal lesions. The magnitude of the effect is not well established.

By meta-analysis, people on established ART (vs ART-naive) had a 35% lower prevalence of HR-HPV infection, and those with undetectable viral load (vs detectable viral load) had a 27% and 16% reduced risk of low and high-grade anal lesions, respectively. Sustained virological suppression on ART reduced by 44% the risk of anal cancer. The role of effective ART in reducing anal HR-HPV infection and cancer risks is especially salient given current limitations in anal cancer screening, high rates of anal lesion recurrence and access to vaccination.Kelly H, Chikandiwa A, Alemany Vilches L, et al.

Association of antiretroviral therapy with anal high-risk human papillomavirus, anal intraepithelial neoplasia and anal cancer in people living with HIV. A systematic review and meta-analysis. Lancet HIV.

2020;7:e262–78. Doi:10.1016/S2352-3018(19)30434-5.The impact of sex work laws and stigma on HIV prevention among female sex workersSex work laws and stigma have been established as structural risk factors for HIV acquisition among female sex workers (FSWs). However, individual-level data assessing these relationships are limited.

A study examined individual-level data collected in 2011–2018 from 7259 FSWs across 10 sub-Saharan African countries. An association emerged between HIV prevalence and increasingly punitive and non-protective laws. HIV prevalence among FSWs was 11.6%, 19.6% and 39.4% in contexts where sex work was partly legalised, not recognised or criminalised, respectively.

Stigma measures such as fear of seeking health services, mistreatment in healthcare settings, lack of police protection, blackmail and violence were associated with higher HIV prevalence and more punitive settings. Sex work laws that protect sex workers and reduce structural risks are needed.Lyons CE, Schwartz SR, Murray SM, et al. The role of sex work laws and stigmas in increasing HIV risks among sex workers.

Nat Commun 2020;11:773. Doi:10.1038/s41467-020-14593-6.BackgroundCumbria Sexual Health Services (CSHS) in collaboration with Cumbria Public Health and local authorities have established a COVID-19 contact tracing pathway for Cumbria. The local system was live 10 days prior to the national system on 18 May 2020.

It was designed to interface and dovetail with the government’s track and trace programme.Our involvement in this initiative was due to a chance meeting between Professor Matt Phillips, Consultant in Sexual Health and HIV, and the Director of Public Health Cumbria, Colin Cox. Colin knew that Cumbria needed to act fast to prevent the transmission of COVID-19 and Matt knew that sexual health had the skills to help.ProcessDespite over 90% of the staff from CSHS being redeployed in March 2020, CSHS maintained urgent sexual healthcare for the county and a phone line for advice and guidance. As staff began to return to the service in May 2020 we had capacity to spare seven staff members, whose hours were the equivalent of four full-time staff.

We had one system administrator, three healthcare assistants, one nurse, Health Advisor Helen Musker and myself.CSHS were paramount to the speed with which the local system began. Following approval from the Trust’s chief executive officer we had adapted our electronic patient records (EPR) system, developed a standard operating procedure and trained staff, using a stepwise competency model, within just 1 day.In collaboration with the local laboratories we developed methods for the input of positive COVID-19 results into our EPR derivative. We ensured that labs would be able to cope with the increase in testing and that testing hubs had additional capacity.

Testing sites and occupational health were asked to inform patients that if they tested positive they would be contacted by our teams.This initiative involved a multiagency system including local public health (PH) teams, local authority, North Cumbria and Morecambe Bay CCGs, Public Health England (PHE) and the military. If CSHS recognise more than one positive result in the same area/organisation, they flag this with PH at the daily incident management meeting and environmental health officers (EHOs) provide advice and guidance for the organisation. We have had an active role in the contact tracing for clusters in local general practices, providing essential information to PH to enable them to initiate outbreak control and provide accurate advice to the practices.

We are an integral part in recognising cases in large organisations and ensuring prompt action is taken to stem the spread of the disease. The team have provided out-of-hours work to ensure timely and efficient action is taken for all contacts.The local contact tracing pilot has evolved and a database was established by local authorities. Our data fed directly into this from the end of May 2020.

This enables the multiagency team to record data in one place, improving recognition of patterns of transmission.DiscussionCumbria is covered by three National Health Service Trusts, which meant accessing data outside of our Trust was challenging and took more time to establish. There are two CCGs for Cumbria, which meant discussions regarding testing were needed with both North and South CCGs and variations in provision had to be accounted for. There are six boroughs in Cumbria with different teams of EHOs working in each.

With so many people involved, not only is there need for large-scale frequent communication across a multisystem team, there is also inevitable duplication of work.Lockdown is easing and sexual health clinics are increasing capacity in a new world of virtual appointments and reduced face-to-face consultations. Staff within the contact tracing team are now balancing their commitments across both teams to maintain their skills and keep abreast of the rapid developments within our service due to COVID-19. We are currently applying for funding from PH in order to second staff and backfill posts in sexual health.ConclusionCSHS have been able to lend our skills effectively to the local contact tracing efforts.

We have expedited the contact tracing in Cumbria and provided crucial information to help contain outbreaks. It has had a positive effect on staff morale within the service and we have gained national recognition for our work. We have developed excellent relationships with our local PH team, PHE, Cumbria Council, EHOs and both CCGs.Cumbria has the infrastructure to meet the demands of a second wave of COVID-19.

The beauty of this model is that if we are faced with a second lockdown, sexual health staff will inevitably be available to help with the increased demand for contact tracing. Our ambition is that this model will be replicated nationally..

High burden of antibiotic-resistant Mycoplasma genitalium in symptomatic urethritisMycoplasma kamagra online without prescription genitalium kamagra street price is an aetiological agent of sexually transmitted urethritis. A cohort study investigated M. Genitalium prevalence, antibiotic resistance and association with kamagra street price previous macrolide exposure among 1816 Chinese men who presented with symptomatic urethritis between 2011 and 2015. Infection was diagnosed by PCR, and sequencing was used to detect mutations that confer resistance to macrolides and fluoroquinolones. In 11% of men, kamagra street price M.

Genitalium was the sole pathogen identified. Nearly 90% of infections were resistant to kamagra street price macrolides and fluoroquinolones. Previous macrolide exposure was associated with higher prevalence of resistance (97%). The findings point kamagra street price to the need for routine screening for M. Genitalium in symptomatic men with urethritis.

Treatment strategies kamagra street price to overcome antibiotic resistance in M. Genitalium are needed.Yang L, Xiaohong S, Wenjing L, et al. Mycoplasma genitalium in symptomatic male urethritis kamagra street price. Macrolide use is associated with increased resistance. Clin Infect Dis 2020;5:805–10.

Doi:10.1093/cid/ciz294.A new entry inhibitor offers promise for treatment-experienced patients with multidrug-resistant HIVFostemsavir, the prodrug of temsavir, is an attachment inhibitor kamagra street price. By targeting the gp120 protein on the HIV-1 envelope, it prevents viral interaction with the CD4 receptor. No cross-resistance kamagra street price has been described with other antiretroviral agents, including those that target viral entry by other modalities. In the phase III BRIGHTE trial, 371 highly treatment-experienced patients who had exhausted ≥4 classes of antiretrovirals received fostemsavir with an optimised regimen. After 48 weeks, 54% of those with 1–2 additional active drugs kamagra street price achieved viral load suppression <40 copies/mL.

Response rates were 38% among patients lacking other active agents. Drug-related adverse events included nausea (4%) and diarrhoea kamagra street price (3%). As gp120 substitutions reduced fostemsavir susceptibility in up to 70% of patients with virological failure, fostemsavir offers the most valuable salvage option in partnership with other active drugs.Kozal M, Aberg J, Pialoux G, et al. Fostemsavir in adults with kamagra street price multidrug-resistant HIV-1 infection. N Engl J Med 2020;382:1232–43.

Doi. 10.1056/NEJMoa1902493Novel tools to aid identification of hepatitis C in primary careHepatitis C can now be cured with oral antiviral treatment, and improving diagnosis is a key element of elimination strategies.1 A cluster randomised controlled trial in South West England tested performance and cost-effectiveness of an electronic algorithm that identified at-risk patients in primary care according to national recommendations,2 coupled with educational activities and interventions to increase patients’ awareness. Outcomes were testing uptake, diagnosis and referral to specialist care. Practices in the intervention arm had an increase in all outcome measures, with adjusted risk ratios of 1.59 (1.21–2.08) for uptake, 2.24 (1.47–3.42) for diagnosis and 5.78 (1.60–21.6) for referral. The intervention was highly cost-effective.

Electronic algorithms applied to practice systems could enhance testing and diagnosis of hepatitis C in primary care, contributing to global elimination goals.Roberts K, Macleod J, Metcalfe C, et al. Cost-effectiveness of an intervention to increase uptake of hepatitis C virus testing and treatment (HepCATT). Cluster randomised controlled trial in primary care. BMJ 2020;368:m322. Doi:10.1136/bmj.m322Low completion rates for antiretroviral postexposure prophylaxis (PEP) after sexual assaultA 4-week course of triple-agent postexposure prophylaxis (PEP) is recommended following a high-risk sexual assault.3 4 A retrospective study in Barcelona identified 1695 victims attending an emergency room (ER) between 2006 and 2015.

Overall, 883 (52%) started prophylaxis in ER, which was mostly (43%) lopinavir/ritonavir based. Follow-up appointments were arranged for those living in Catalonia (631, 71.5%), and of these, only 183 (29%) completed treatment. Loss to follow-up was more prevalent in those residing outside Barcelona. PEP non-completion was associated with a low perceived risk, previous assaults, a known aggressor and a positive cocaine test. Side effects were common, occurring in up to 65% of those taking lopinavir/ritonavir and accounting for 15% of all discontinuations.

More tolerable PEP regimens, accessible follow-up and provision of 1-month supply may improve completion rates.Inciarte A, Leal L, Masfarre L, et al. Postexposure prophylaxis for HIV infection in sexual assault victims. HIV Med 2020;21:43–52. Doi:10.1111/hiv.12797.Effective antiretroviral therapy reduces anal high-risk HPV infection and cancer riskAmong people with HIV, effective antiretroviral therapy (ART) is expected https://www.cityreal.lv/kamagra-sildenafil-32-pills/ to improve control of anal infection with high-risk human papillomavirus (HR-HPV) and reduce the progression of HPV-associated anal lesions. The magnitude of the effect is not well established.

By meta-analysis, people on established ART (vs ART-naive) had a 35% lower prevalence of HR-HPV infection, and those with undetectable viral load (vs detectable viral load) had a 27% and 16% reduced risk of low and high-grade anal lesions, respectively. Sustained virological suppression on ART reduced by 44% the risk of anal cancer. The role of effective ART in reducing anal HR-HPV infection and cancer risks is especially salient given current limitations in anal cancer screening, high rates of anal lesion recurrence and access to vaccination.Kelly H, Chikandiwa A, Alemany Vilches L, et al. Association of antiretroviral therapy with anal high-risk human papillomavirus, anal intraepithelial neoplasia and anal cancer in people living with HIV. A systematic review and meta-analysis.

Lancet HIV. 2020;7:e262–78. Doi:10.1016/S2352-3018(19)30434-5.The impact of sex work laws and stigma on HIV prevention among female sex workersSex work laws and stigma have been established as structural risk factors for HIV acquisition among female sex workers (FSWs). However, individual-level data assessing these relationships are limited. A study examined individual-level data collected in 2011–2018 from 7259 FSWs across 10 sub-Saharan African countries.

An association emerged between HIV prevalence and increasingly punitive and non-protective laws. HIV prevalence among FSWs was 11.6%, 19.6% and 39.4% in contexts where sex work was partly legalised, not recognised or criminalised, respectively. Stigma measures such as fear of seeking health services, mistreatment in healthcare settings, lack of police protection, blackmail and violence were associated with higher HIV prevalence and more punitive settings. Sex work laws that protect sex workers and reduce structural risks are needed.Lyons CE, Schwartz SR, Murray SM, et al. The role of sex work laws and stigmas in increasing HIV risks among sex workers.

Nat Commun 2020;11:773. Doi:10.1038/s41467-020-14593-6.BackgroundCumbria Sexual Health Services (CSHS) in collaboration with Cumbria Public Health and local authorities have established a COVID-19 contact tracing pathway for Cumbria. The local system was live 10 days prior to the national system on 18 May 2020. It was designed to interface and dovetail with the government’s track and trace programme.Our involvement in this initiative was due to a chance meeting between Professor Matt Phillips, Consultant in Sexual Health and HIV, and the Director of Public Health Cumbria, Colin Cox. Colin knew that Cumbria needed to act fast to prevent the transmission of COVID-19 and Matt knew that sexual health had the skills to help.ProcessDespite over 90% of the staff from CSHS being redeployed in March 2020, CSHS maintained urgent sexual healthcare for the county and a phone line for advice and guidance.

As staff began to return to the service in May 2020 we had capacity to spare seven staff members, whose hours were the equivalent of four full-time staff. We had one system administrator, three healthcare assistants, one nurse, Health Advisor Helen Musker and myself.CSHS were paramount to the speed with which the local system began. Following approval from the Trust’s chief executive officer we had adapted our electronic patient records (EPR) system, developed a standard operating procedure and trained staff, using a stepwise competency model, within just 1 day.In collaboration with the local laboratories we developed methods for the input of positive COVID-19 results into our EPR derivative. We ensured that labs would be able to cope with the increase in testing and that testing hubs had additional capacity. Testing sites and occupational health were asked to inform patients that if they tested positive they would be contacted by our teams.This initiative involved a multiagency system including local public health (PH) teams, local authority, North Cumbria and Morecambe Bay CCGs, Public Health England (PHE) and the military.

If CSHS recognise more than one positive result in the same area/organisation, they flag this with PH at the daily incident management meeting and environmental health officers (EHOs) provide advice and guidance for the organisation. We have had an active role in the contact tracing for clusters in local general practices, providing essential information to PH to enable them to initiate outbreak control and provide accurate advice to the practices. We are an integral part in recognising cases in large organisations and ensuring prompt action is taken to stem the spread of the disease. The team have provided out-of-hours work to ensure timely and efficient action is taken for all contacts.The local contact tracing pilot has evolved and a database was established by local authorities. Our data fed directly into this from the end of May 2020.

This enables the multiagency team to record data in one place, improving recognition of patterns of transmission.DiscussionCumbria is covered by three National Health Service Trusts, which meant accessing data outside of our Trust was challenging and took more time to establish. There are two CCGs for Cumbria, which meant discussions regarding testing were needed with both North and South CCGs and variations in provision had to be accounted for. There are six boroughs in Cumbria with different teams of EHOs working in each. With so many people involved, not only is there need for large-scale frequent communication across a multisystem team, there is also inevitable duplication of work.Lockdown is easing and sexual health clinics are increasing capacity in a new world of virtual appointments and reduced face-to-face consultations. Staff within the contact tracing team are now balancing their commitments across both teams to maintain their skills and keep abreast of the rapid developments within our service due to COVID-19.

We are currently applying for funding from PH in order to second staff and backfill posts in sexual health.ConclusionCSHS have been able to lend our skills effectively to the local contact tracing efforts. We have expedited the contact tracing in Cumbria and provided crucial information to help contain outbreaks. It has had a positive effect on staff morale within the service and we have gained national recognition for our work. We have developed excellent relationships with our local PH team, PHE, Cumbria Council, EHOs and both CCGs.Cumbria has the infrastructure to meet the demands of a second wave of COVID-19. The beauty of this model is that if we are faced with a second lockdown, sexual health staff will inevitably be available to help with the increased demand for contact tracing.

Our ambition is that this model will be replicated nationally..

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Antibodies to SARS-CoV-2 infection lasted for at least 4 months after initial infection, a large serosurvey in Iceland found.Nearly all people who tested positive for SARS-CoV-2 via quantitative PCR (qPCR) tests also tested positive with two pan-immunoglobulin (pan-Ig) SARS-CoV-2 antibody assays and remained seropositive after 120 days, reported Kari Stefansson, MD, PhD, of deCODE Genetics-Amgen in Reykjavik, and colleagues.Moreover, antibody titers as measured by the two assays increased during 2 months after diagnosis, and showed no further decline over the last 2 months, the news authors wrote in the New England Journal of Medicine, although whether the antibodies were adequate to prevent reinfection was not addressed in the study.About 56% of COVID-19 infections were diagnosed via qPCR, 14% occurred in quarantine without a qPCR diagnosis and 30% order kamagra jelly occurred outside quarantine without being detected by qPCR, the researchers found."We therefore conclude that, despite extensive screening via qPCR, a substantial fraction of infections were not detected, which indicates many infected persons did not have substantial symptoms," Stefansson and colleagues wrote.Determining immunity to COVID-19 is an open question, complicated by the wide range of antibody tests providing mixed results, as well as recent media coverage that seems to prove reinfection is possible. Stefansson's group also noted prior research suggesting a "substantial fraction" order kamagra jelly of patients, especially those with mild or no COVID-19 symptoms, may become "antibody-negative" in the early stages of recovery from infection.An accompanying editorial by Galit Alter, PhD, of the Ragon Institute of MGH, MIT and Harvard in Cambridge, Massachusetts, and Robert Seder, MD, of the NIH's Vaccine Research Center in Bethesda, Maryland, said the study "provides hope that immunity" to COVID-19 "may not be fleeting and may be similar to that elicited by most other viral infections.""Unlike previous studies, this study suggested stability of SARS-CoV-2 humoral immunity," the editorialists wrote. "Whether antibodies that persist confer protection and retain neutralizing or other protective effector functions that are required to block reinfection remains unclear."They also praised antibody assays as "highly effective alternatives to PCR testing" in terms of population-level order kamagra jelly surveillance required for "safe reopening" of cities and schools while the world waits for a vaccine to end the pandemic.Stefansson and colleagues measured antibodies in serum samples from 30,576 people, including a subset of 1,237 people followed for up to 4 months after diagnosis.The qPCR testing identified 1,797 COVID-19 cases in Iceland. Of 1,215 who had recovered and were tested for order kamagra jelly antibodies, 91.1% (95% CI 89.4%-92.6%) were seropositive.

The authors determined this order kamagra jelly was the "lower bound of sensitivity of the combined pan-Ig tests "since some of the diagnoses may have been made on the basis of false positive qPCR results."In addition, 2.3% of 4,222 quarantined people were seropositive. In samples from 18,609 other people who had contact with the Icelandic healthcare system for reasons other than COVID-19, 0.3% were order kamagra jelly seropositive.Antibody levels were higher in older and hospitalized people. After adjustment, BMI correlated positively with antibody titers, while smoking and use of anti-inflammatory medication had lower titers.Alter and Seder said the study showed that order kamagra jelly antibody testing "captured a larger percentage of exposures" than the qPCR testing. They also highlighted the finding that asymptomatic cases accounted for nearly one-third of all infections.Based on this data, and the 10 deaths in Iceland, order kamagra jelly Stefansson and colleagues calculated a 0.3% infection-fatality risk.Alter and Seder pointed to the study's focus on "a homogenous population largely from a single ethnic origin and geographic region" as an important limitation.

They called for future extended longitudinal order kamagra jelly studies to "more accurately determine the half-life of SARS-CoV-2 antibodies." Molly Walker is an associate editor, who covers infectious diseases for MedPage Today. She has a passion for evidence, data order kamagra jelly and public health. Follow Disclosures Stefansson disclosed no conflicts of order kamagra jelly interest. One co-author disclosed support from order kamagra jelly GlaxoSmithKline.Alter disclosed support from SeromYx Systems.

Antibodies to kamagra street price SARS-CoV-2 infection lasted for at least 4 months after initial infection, a large serosurvey in Iceland found.Nearly all people who tested positive for SARS-CoV-2 via quantitative PCR (qPCR) tests also tested positive with two pan-immunoglobulin (pan-Ig) SARS-CoV-2 antibody assays and remained kamagra next day delivery seropositive after 120 days, reported Kari Stefansson, MD, PhD, of deCODE Genetics-Amgen in Reykjavik, and colleagues.Moreover, antibody titers as measured by the two assays increased during 2 months after diagnosis, and showed no further decline over the last 2 months, the authors wrote in the New England Journal of Medicine, although whether the antibodies were adequate to prevent reinfection was not addressed in the study.About 56% of COVID-19 infections were diagnosed via qPCR, 14% occurred in quarantine without a qPCR diagnosis and 30% occurred outside quarantine without being detected by qPCR, the researchers found."We therefore conclude that, despite extensive screening via qPCR, a substantial fraction of infections were not detected, which indicates many infected persons did not have substantial symptoms," Stefansson and colleagues wrote.Determining immunity to COVID-19 is an open question, complicated by the wide range of antibody tests providing mixed results, as well as recent media coverage that seems to prove reinfection is possible. Stefansson's group also noted kamagra street price prior research suggesting a "substantial fraction" of patients, especially those with mild or no COVID-19 symptoms, may become "antibody-negative" in the early stages of recovery from infection.An accompanying editorial by Galit Alter, PhD, of the Ragon Institute of MGH, MIT and Harvard in Cambridge, Massachusetts, and Robert Seder, MD, of the NIH's Vaccine Research Center in Bethesda, Maryland, said the study "provides hope that immunity" to COVID-19 "may not be fleeting and may be similar to that elicited by most other viral infections.""Unlike previous studies, this study suggested stability of SARS-CoV-2 humoral immunity," the editorialists wrote. "Whether antibodies that persist confer protection and retain neutralizing or other protective effector functions that are required to block reinfection remains unclear."They also praised antibody assays as "highly effective alternatives to PCR testing" in terms of population-level surveillance required for "safe reopening" of cities and schools while the world waits for a vaccine to end the pandemic.Stefansson and colleagues measured antibodies in kamagra street price serum samples from 30,576 people, including a subset of 1,237 people followed for up to 4 months after diagnosis.The qPCR testing identified 1,797 COVID-19 cases in Iceland. Of 1,215 who had recovered and were kamagra street price tested for antibodies, 91.1% (95% CI 89.4%-92.6%) were seropositive. The authors determined this was the "lower bound of sensitivity of the combined pan-Ig tests "since some of the diagnoses may have been made on the basis of false positive qPCR results."In addition, kamagra street price 2.3% of 4,222 quarantined people were seropositive.

In samples from 18,609 other people who had contact with the Icelandic healthcare system for reasons other than COVID-19, 0.3% were seropositive.Antibody levels were higher kamagra street price in older and hospitalized people. After adjustment, BMI correlated positively with antibody titers, while smoking and use of anti-inflammatory medication had lower titers.Alter kamagra street price and Seder said the study showed that antibody testing "captured a larger percentage of exposures" than the qPCR testing. They also highlighted the finding that asymptomatic cases accounted for nearly one-third of all infections.Based on this data, and the 10 deaths in Iceland, Stefansson and colleagues kamagra street price calculated a 0.3% infection-fatality risk.Alter and Seder pointed to the study's focus on "a homogenous population largely from a single ethnic origin and geographic region" as an important limitation. They called for future extended longitudinal studies to "more accurately determine the half-life of SARS-CoV-2 antibodies." Molly Walker is an associate editor, who covers infectious kamagra street price diseases for MedPage Today. She has kamagra street price a passion for evidence, data and public health.

Follow Disclosures Stefansson disclosed kamagra street price no conflicts of interest. One co-author disclosed support from GlaxoSmithKline.Alter disclosed support from SeromYx Systems. Seder disclosed no conflicts of interest..

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Latest Sleep News By is kamagra safe Dennis ThompsonHealthDay https://www.cityreal.lv/where-to-get-kamagra/ ReporterTHURSDAY, Aug. 27, 2020A frequent need to nap could be a red flag for future heart problems and a is kamagra safe higher risk of early death, a new analysis concludes.Long naps lasting more than an hour are associated with a 34% elevated risk of heart disease and a 30% greater risk of death, according to the combined results of 20 previous studies.Overall, naps of any length were associated with a 19% increased risk of premature death, a Chinese research team found. The study results were released Wednesday for presentation at the virtual annual meeting of the European Society of Cardiology."If you want to take a siesta, our study indicates it's safest to keep it under an hour," lead researcher Zhe Pan of Guangzhou Medical University said in a society news release. "For those of us not in the habit of a daytime slumber, there is no convincing evidence to start."For their study, the researchers analyzed data from 20 is kamagra safe studies involving more than 313,000 participants. About two in five people in the studies said they nap.The investigators found that the connection was more pronounced in people aged 65 and is kamagra safe older.

These older folks had a 27% higher risk of death associated with napping and a 36% greater risk of heart disease. Women also had a is kamagra safe stronger association between napping and poor health, with a 22% greater risk of death and a 31% greater risk of heart problems.Interestingly, long naps were linked with an increased risk of death in people who sleep more than six hours a night. That would seem to rule out poor sleep as an explanation for the increased risk of death and heart health issues.Adults who get less than seven hours of sleep each night are more likely to say they've had a heart attack, according to the U.S. Centers for is kamagra safe Disease Control and Prevention. Poor sleep also has been linked to high blood pressure, type 2 diabetes and obesity, all of which increase the risk of heart disease, heart attack and stroke.Pan is kamagra safe speculated that long naps might affect the body because they are associated with higher levels of inflammation.But heart health experts said that just because you're sleeping through the night doesn't mean you've gotten a good night's sleep -- something for which this study doesn't account.Regarding how well you're resting at night, napping "might be a sign that there's something else going on," said Dr.

Nieca Goldberg, a cardiologist and director of the NYU Langone Center for Women's Health, in New York City."What kind of sleep were these individuals getting?. " Goldberg said of the study participants is kamagra safe. "Were they waking up at night?. Did they have sleep is kamagra safe apnea?. "Dr.

Matthew Tomey, a cardiologist with Mount Sinai Morningside in New York City, agreed that these folks might be suffering from poor sleep."Some people take naps as a matter of habit, or they take a power nap," Tomey said. "For others, they're taking potentially longer naps during the daytime because of too little or too poor quality sleep at night."People should take a nap when they feel like it, but if they regularly need naps that could be a sign of trouble, Tomey said."If they notice that they feel excessively sleepy during the daytime, needing multiple or long naps, that's a wake-up call to pay attention to the quality and quantity of their nighttime sleep," he added.People who frequently nap should talk with their doctor about their sleep issues, since they might be suffering from sleep apnea or some other issue that disrupts quality sleep, Tomey and Goldberg said.Good sleep habits, according to the CDC, include:Sticking to a regular sleep schedule.Getting enough natural light during the day, to positively influence brain chemicals related to sleep.Exercising regularly, but not within a few hours of bedtime.Avoiding artificial light near bedtime.Keeping your bedroom cool, dark and quiet.Copyright © 2020 HealthDay. All rights reserved. SLIDESHOW Sleep Disorders. Foods That Help Sleep or Keep You Awake See Slideshow References SOURCES.

Nieca Goldberg, MD, cardiologist and director, NYU Langone Center for Women's Health, New York City. Matthew Tomey, MD, cardiologist, Mount Sinai Morningside, New York City. European Society of Cardiology, annual meeting.Latest Heart News By Serena McNiffHealthDay ReporterWEDNESDAY, Aug. 26, 2020 (HealthDay News)Most strokes strike when an artery in the brain suddenly becomes blocked, but new research shows a rarer cause of strokes is becoming more common.It's called cerebral venous thrombosis (CVT), and it happens when a vein in the brain is clogged. While CVT is estimated to cause less than 1% of all strokes, scientists discovered it is now more prevalent and affecting a different demographic than previously thought.Study author Dr.

Fadar Otite and his colleagues pored over years of hospital records from New York and Florida to find out how many cases of CVT occurred in these states between 2006 and 2016. Otite is an assistant professor of neurology at SUNY Upstate Medical University in Syracuse, N.Y.Based on the data they analyzed, the researchers estimated that the number of CVT cases in the United States rose from around 14 cases per million in 2006 to 20 cases per million in 2014."We still find that the incidence of CVT is less than 1% of all strokes, even across our study period, but the incidence increased by 70% over time," Otite said. "In 2006, the proportion of all strokes that were CVT was 0.47%. At the end of our study, which was in 2016, that proportion increased to 0.80%."CVT causes blood clots to form in the veins of the brain https://www.cityreal.lv/kamagra-thailand-price/. These veins drain blood that has already been used by brain cells, sending it back to the heart to be replenished with oxygen.

If a clot forms in one of these veins, it may leak into the surrounding brain tissue and could cause a stroke, the researchers explained.While CVT is still most common in young women -- about two-thirds of all CVT hospitalizations included in the study were in females -- the researchers found that the number of cases among this demographic did not increase over the 10-year study period. Instead, they saw increases in CVT among men and older women."Part of the message is that we agree that CVT is still more common in women, but because of the diverse clinical presentation of CVT, when other symptoms that may be attributable to CVT are present in other demographics, we should take them with more seriousness," Otite said.Another major finding was that CVT incidence in Black people was significantly higher than in other races. But why that is the case remains unknown. "We have no clear explanation, because this is truly the first study to ever relate the incidence of CVT between races," he added.Several factors may put one at a higher risk of developing CVT, including pregnancy and taking hormonal birth control pills, which may be why it is more common in younger women, the researchers noted.And many of the risk factors for CVT -- like blood clotting disorders or medications that cause clotting, severe dehydration, infections of the ear, face or neck, head trauma, obesity and cancer -- are somewhat different from the triggers typically associated with stroke.It is important for clinicians to be aware of this rise in CVT incidence because the condition can easily be confused as something else, Otite said. Patients with CVT may have unspecific complaints such as headaches, blurry vision or seizures.Around 3% of patients in a prior study who had CVT and went to the hospital were diagnosed with something else and sent home, according to Otite.

"So, it's important to recognize this from the start, because by the next time the clinical condition may be worse," he said.CVT can be treated with medication to thin the blood and help prevent further clotting, which may not be prescribed if the condition isn't properly diagnosed, he added.Dr. Jose Biller, chair of the neurology department at Loyola University Medical Center in Hines, Ill., said the takeaway from this study is that more attention should be paid to CVT."I think that there should be an increased awareness of cerebral venous thrombosis because, by and large, when people think about stroke, they don't think about it," Biller said. "There should be an increasing level of awareness because this is a condition that has a specific treatment."The study was published online Aug. 26 in the journal Neurology.Copyright © 2020 HealthDay. All rights reserved.

SLIDESHOW Stroke Causes, Symptoms, and Recovery See Slideshow References SOURCES. Fadar Oliver Otite, MD, assistant professor, neurology, State University of New York (SUNY) Upstate Medical University, Syracuse, N.Y.. Jose Biller, MD, chair, department of neurology, Loyola University Medical Center, Hines, Ill.. Neurology, Aug. 26, 2020, onlineLatest Hearing News WEDNESDAY, Aug.

26, 2020 (HealthDay News)Even if they appear unresponsive, dying people may still be able to hear.That's the takeaway from a Canadian analysis of hospice patients in Vancouver.Researchers compared electroencephalography (EEG) data -- a measure of electrical activity in the brain -- collected when patients were conscious and when they became unresponsive at the end of life. Those patients were compared to a healthy control group.The study looked at brain response to various patterns of common and rare sounds that changed frequency, and found that responses of some of the dying patients were similar to those of healthy people -- even hours before death."In the last hours before an expected natural death, many people enter a period of unresponsiveness," said lead author Elizabeth Blundon, a doctoral student in psychology at the University of British Columbia at the time of the study."Our data shows that a dying brain can respond to sound, even in an unconscious state, up to the last hours of life," she said in a university news release.Co-author Lawrence Ward, a professor of psychology, said researchers were able to identify specific mental processes in both groups of participants."We had to look very carefully at the individual control participants' data, to see if each one of them showed a particular type of brain response before we felt confident that the unresponsive patient's brain reacted similarly," he said in the release.The findings were recently published in the journal Scientific Reports."This research gives credence to the fact that hospice nurses and physicians noticed that the sounds of loved ones helped comfort people when they were dying," said study co-author Dr. Romayne Gallagher, a now-retired palliative care physician at St. John Hospice in Vancouver."And to me, it adds significant meaning to the last days and hours of life and shows that being present, in person or by phone, is meaningful," she said. "It is a comfort to be able to say goodbye and express love."While the evidence of brain activity supports the idea that dying people might hear, it's not known if they're aware of what they're hearing, Blundon noted."Their brains responded to the auditory stimuli, but we can't possibly know if they're remembering, identifying voices, or understanding language," she said.

"There are all these other questions that have yet to be answered. This first glimpse supports the idea that we have to keep talking to people when they are dying because something is happening in their brain."-- Robert PreidtCopyright © 2020 HealthDay. All rights reserved. QUESTION What is hearing loss?. See Answer References SOURCE.

University of British Columbia, news release, July 8, 2020.

Latest Sleep sites News kamagra street price By Dennis ThompsonHealthDay ReporterTHURSDAY, Aug. 27, 2020A frequent need to nap could be a red flag for future heart kamagra street price problems and a higher risk of early death, a new analysis concludes.Long naps lasting more than an hour are associated with a 34% elevated risk of heart disease and a 30% greater risk of death, according to the combined results of 20 previous studies.Overall, naps of any length were associated with a 19% increased risk of premature death, a Chinese research team found. The study results were released Wednesday for presentation at the virtual annual meeting of the European Society of Cardiology."If you want to take a siesta, our study indicates it's safest to keep it under an hour," lead researcher Zhe Pan of Guangzhou Medical University said in a society news release. "For those of us not in the habit of a daytime slumber, there is no convincing evidence to start."For their study, the researchers analyzed data from 20 studies involving kamagra street price more than 313,000 participants. About two in five people in the studies said they nap.The investigators found that the connection was more pronounced in kamagra street price people aged 65 and older.

These older folks had a 27% higher risk of death associated with napping and a 36% greater risk of heart disease. Women also had a stronger association between napping and poor health, with a 22% greater risk of death and a 31% greater risk of heart problems.Interestingly, long naps were linked with an increased risk of kamagra street price death in people who sleep more than six hours a night. That would seem to rule out poor sleep as an explanation for the increased risk of death and heart health issues.Adults who get less than seven hours of sleep each night are more likely to say they've had a heart attack, according to the U.S. Centers for Disease Control and kamagra street price Prevention. Poor sleep also has been linked to high blood pressure, type 2 diabetes and obesity, all of which increase the risk of heart disease, heart attack and stroke.Pan speculated that long naps might affect the body because they are associated with higher levels of inflammation.But heart health experts said that just because you're sleeping through the night doesn't mean you've gotten a good night's sleep -- something for which this study doesn't account.Regarding how well you're resting at night, napping "might be a sign that there's kamagra street price something else going on," said Dr.

Nieca Goldberg, a cardiologist and director of the NYU Langone Center for Women's Health, in New York City."What kind of sleep were these individuals getting?. " Goldberg kamagra street price said of the study participants. "Were they waking up at night?. Did they kamagra street price have sleep apnea?. "Dr.

Matthew Tomey, a cardiologist with Mount Sinai Morningside in New York City, agreed that these folks might be suffering from poor sleep."Some people take naps as a matter of habit, or they take a power nap," Tomey said. "For others, they're taking potentially longer naps during the daytime because of too little or too poor quality sleep at night."People should take a nap when they feel like it, but if they regularly need naps that could be a sign of trouble, Tomey said."If they notice that they feel excessively sleepy during the daytime, needing multiple or long naps, that's a wake-up call to pay attention to the quality and quantity of their nighttime sleep," he added.People who frequently nap should talk with their doctor about their sleep issues, since they might be suffering from sleep apnea or some other issue that disrupts quality sleep, Tomey and Goldberg said.Good sleep habits, according to the CDC, include:Sticking to a regular sleep schedule.Getting enough natural light during the day, to positively influence brain chemicals related to sleep.Exercising regularly, but not within a few hours of bedtime.Avoiding artificial light near bedtime.Keeping your bedroom cool, dark and quiet.Copyright © 2020 HealthDay. All rights reserved. SLIDESHOW Sleep Disorders. Foods That Help Sleep or Keep You Awake See Slideshow References SOURCES.

Nieca Goldberg, MD, cardiologist and director, NYU Langone Center for Women's Health, New York City. Matthew Tomey, MD, cardiologist, Mount Sinai Morningside, New York City. European Society of Cardiology, annual meeting.Latest Heart News By Serena McNiffHealthDay ReporterWEDNESDAY, Aug. 26, 2020 (HealthDay News)Most strokes strike when an artery in the brain suddenly becomes blocked, but new research shows a rarer cause of strokes is becoming more common.It's called cerebral venous thrombosis (CVT), and it happens when a vein in the brain is clogged. While CVT is estimated to cause less than 1% of all strokes, scientists discovered it is now more prevalent and affecting a different demographic than previously thought.Study author Dr.

Fadar Otite and his colleagues pored over years of hospital records from New York and Florida to find out how many cases of CVT occurred in these states between 2006 and 2016. Otite is an assistant professor of neurology at SUNY Upstate Medical University in Syracuse, N.Y.Based on the data they analyzed, the researchers estimated that the number of CVT cases in the United States rose from around 14 cases per million in 2006 to 20 cases per million in 2014."We still find that the incidence of CVT is less than 1% of all strokes, even across our study period, but the incidence increased by 70% over time," Otite said. "In 2006, the proportion of all strokes that were CVT was 0.47%. At the end of our study, which was in 2016, that proportion increased to 0.80%."CVT causes blood clots to form in the veins of the brain. These veins drain blood that has already been used by brain cells, sending it back to the heart to be replenished with oxygen.

If a clot forms in one of these veins, it may leak into the surrounding brain tissue and could cause a stroke, the researchers explained.While CVT is still most common in young women -- about two-thirds of all CVT hospitalizations included in the study were in females -- the researchers found that the number of cases among this demographic did not increase over the 10-year study period. Instead, they saw increases in CVT among men and older women."Part of the message is that we agree that CVT is still more common in women, but because of the diverse clinical presentation of CVT, when other symptoms that may be attributable to CVT are present in other demographics, we should take them with more seriousness," Otite said.Another major finding was that CVT incidence in Black people was significantly higher than in other races. But why that is the case remains unknown. "We have no clear explanation, because this is truly the first study to ever relate the incidence of CVT between races," he added.Several factors may put one at a higher risk of developing CVT, including pregnancy and taking hormonal birth control pills, which may be why it is more common in younger women, the researchers noted.And many of the risk factors for CVT -- like blood clotting disorders or medications that cause clotting, severe dehydration, infections of the ear, face or neck, head trauma, obesity and cancer -- are somewhat different from the triggers typically associated with stroke.It is important for clinicians to be aware of this rise in CVT incidence because the condition can easily be confused as something else, Otite said. Patients with CVT may have unspecific complaints such as headaches, blurry vision or seizures.Around 3% of patients in a prior study who had CVT and went to the hospital were diagnosed with something else and sent home, according to Otite.

"So, it's important to recognize this from the start, because by the next time the clinical condition may be worse," he said.CVT can be treated with medication to thin the blood and help prevent further clotting, which may not be prescribed if the condition isn't properly diagnosed, he added.Dr. Jose Biller, chair of the neurology department at Loyola University Medical Center in Hines, Ill., said the takeaway from this study is that more attention should be paid to CVT."I think that there should be an increased awareness of cerebral venous thrombosis because, by and large, when people think about stroke, they don't think about it," Biller said. "There should be an increasing level of awareness because this is a condition that has a specific treatment."The study was published online Aug. 26 in the journal Neurology.Copyright © 2020 HealthDay. All rights reserved.

SLIDESHOW Stroke Causes, Symptoms, and Recovery See Slideshow References SOURCES. Fadar Oliver Otite, MD, assistant professor, neurology, State University of New York (SUNY) Upstate Medical University, Syracuse, N.Y.. Jose Biller, MD, chair, department of neurology, Loyola University Medical Center, Hines, Ill.. Neurology, Aug. 26, 2020, onlineLatest Hearing News WEDNESDAY, Aug.

26, 2020 (HealthDay News)Even if they appear unresponsive, dying people may still be able to hear.That's the takeaway from a Canadian analysis of hospice patients in Vancouver.Researchers compared electroencephalography (EEG) data -- a measure of electrical activity in the brain -- collected when patients were conscious and when they became unresponsive at the end of life. Those patients were compared to a healthy control group.The study looked at brain response to various patterns of common and rare sounds that changed frequency, and found that responses of some of the dying patients were similar to those of healthy people -- even hours before death."In the last hours before an expected natural death, many people enter a period of unresponsiveness," said lead author Elizabeth Blundon, a doctoral student in psychology at the University of British Columbia at the time of the study."Our data shows that a dying brain can respond to sound, even in an unconscious state, up to the last hours of life," she said in a university news release.Co-author Lawrence Ward, a professor of psychology, said researchers were able to identify specific mental processes in both groups of participants."We had to look very carefully at the individual control participants' data, to see if each one of them showed a particular type of brain response before we felt confident that the unresponsive patient's brain reacted similarly," he said in the release.The findings were recently published in the journal Scientific Reports."This research gives credence to the fact that hospice nurses and physicians noticed that the sounds of loved ones helped comfort people when they were dying," said study co-author Dr. Romayne Gallagher, a now-retired palliative care physician at St. John Hospice in Vancouver."And to me, it adds significant meaning to the last days and hours of life and shows that being present, in person or by phone, is meaningful," she said. "It is a comfort to be able to say goodbye and express love."While the evidence of brain activity supports the idea that dying people might hear, it's not known if they're aware of what they're hearing, Blundon noted."Their brains responded to the auditory stimuli, but we can't possibly know if they're remembering, identifying voices, or understanding language," she said.

"There are all these other questions that have yet to be answered. This first glimpse supports the idea that we have to keep talking to people when they are dying because something is happening in their brain."-- Robert PreidtCopyright © 2020 HealthDay. All rights reserved. QUESTION What is hearing loss?. See Answer References SOURCE.

University of British Columbia, news release, July 8, 2020.


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