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IntroductionThere has been considerable interest in elucidating the contribution of genetic factors to the development of common diseases and using this information for better prediction online zithromax prescription of disease risk. The common disease common variant hypothesis predicts that variants that are common in the population play a role in disease susceptibility.1 Genome-wide association studies (GWAS) using single nucleotide polymorphism (SNP) arrays were developed as a mechanism by which to investigate these genetic factors and it was hoped this would lead to identification of variants associated with disease risk and subsequent development online zithromax prescription of predictive tests. Variants identified as associated with particular traits by these studies, for the large part, are SNPs that individually have a minor effect on disease risk and hence, by themselves, cannot be reliably used in disease prediction.

Looking at the aggregate impact of these SNPs in the form of a polygenic score (PGS) appeared to be one online zithromax prescription possible means of using this information to predict disease.2 It is thought this will be of benefit as our genetic make-up is largely stable from birth and dictates a ‘baseline risk’ on which external influences act and modulate. Therefore, PGS are a potential mechanism to act as a risk predictor by capturing information on this genetic liability.The use of PGS as a predictive biomarker is being explored in a number of different disease areas, including cancer,3 4 psychiatric disorders,5–7 metabolic disorders (diabetes,8 obesity9) and coronary artery disease (CAD).10 The proposed applications range from aiding disease diagnosis, informing selection of therapeutic interventions, improvement of risk prediction, informing disease screening and, on a personal level, informing life planning. Therefore, genetic risk information in the form of a PGS is considered to have potential in informing both clinical and individual-level decision-making.Recent advances in statistical techniques, improved computational power and the availability of large data sets have led to rapid developments online zithromax prescription in this area over the past few years.

This has resulted in a variety of approaches to construction of models for score calculation and the investigation of these scores for prediction of common diseases.11 Several review articles aimed at researchers with a working knowledge of this field have been produced.6 11–17 In this article, we provide an overview of the key aspects of PGS construction to assist clinicians and researchers in other areas of academia to gain an understanding of the processes involved in score construction. We also consider the implications of evolving methodologies for the development of applications of PGS in healthcare.Evolution in polygenic model construction methodologiesTerminology with respect to PGS has evolved over time, reflecting online zithromax prescription evolving approaches and methodology. Other terms include PGS, polygenic risk score, polygenic load, genotype score, genetic burden, polygenic hazard score, genetic risk score (GRS), metaGRS and allelic risk score.

Throughout this article we use the terms polygenic models to refer to the method used to calculate an online zithromax prescription output in the form of a PGS. Different polygenic models can be used to calculate a PGS and analysis of these scores can be used to examine associations with particular markers or to predict an individuals risk of diseases.12Usual practice in calculating PGS is as a weighted sum of a number of risk alleles carried by an individual, where the risk alleles and their weights are defined by SNPs and their measured effects (figure 1).11 Polygenic models have been constructed using a few, hundreds or thousands of SNPs, and more recently SNPs across the whole genome. Consequently, determining which SNPs to include and the disease-associated weighting to assign to SNPs are important aspects of model construction (figure 2).18 These aspects are influenced by available genotype data and effect size estimates as well as the methodology employed in online zithromax prescription turning this information into model parameters (ie, weighted SNPs).Polygenic score calculation.

This calculation aggregates the SNPs and their weights selected for a polygenic score. Common diseases online zithromax prescription are thought to be influenced by many genetic variants with small individual effect sizes, such that meaningful risk prediction necessitates examining the aggregated impact of these multiple variants including their weightings. PGS, polygenic score." data-icon-position data-hide-link-title="0">Figure 1 Polygenic score calculation.

This calculation aggregates the SNPs online zithromax prescription and their weights selected for a polygenic score. Common diseases are thought to be influenced by many genetic online zithromax prescription variants with small individual effect sizes, such that meaningful risk prediction necessitates examining the aggregated impact of these multiple variants including their weightings. PGS, polygenic score.Construction of a polygenic score.

In the process of developing a polygenic score, online zithromax prescription numerous models are tested and then compared. The model that performs best (as determined by one or more measures) is then selected for validation in the external data set. GWAS, genome-wide association studies." data-icon-position data-hide-link-title="0">Figure 2 Construction online zithromax prescription of a polygenic score.

In the process of developing a polygenic score, numerous models are tested and then compared. The model that online zithromax prescription performs best (as determined by one or more measures) is then selected for validation in the external data set. GWAS, genome-wide association studies.Changes in data availability over time have had an impact on the approach taken in SNP selection and weighting.

Early studies to identify variants associated with common diseases took the form of candidate online zithromax prescription gene studies. The small size of candidate gene studies, the limitation of technologies available for genotyping and stringent significance thresholds meant that these studies investigated fewer variants and those that were identified with disease associations had relatively large effect sizes.19 Taken together, this meant that a relatively small number of variants were available for consideration for inclusion in a polygenic model.20 21 Furthermore, weighting parameters for these few variants were often simplistic, such as counts of the number of risk alleles carried, ignoring their individual effect sizes.16The advent of GWAS enabled assessment of SNPs across the genome, leading to the identification of a larger number of disease-associated variants and therefore more variants suitable for inclusion in a polygenic model. In addition, the increasing number of individuals in the association studies meant that the power of these studies increased, allowing for more precise estimates of effect sizes.19 Furthermore, some theorised online zithromax prescription that lowering stringent significance thresholds set for SNP–trait associations could also identify SNPs that might play a part in disease risk.11 16 This resulted in more options with respect to polygenic model parameters of SNPs to include and weights to assign to them.

However, the inclusion of more SNPs and direct application of GWAS effect sizes as a weighting parameter does not always equate to better predictive performance.4 16 This is because GWAS do not provide perfect information with respect to the causal SNP, the effect sizes or the number of SNPs that contribute to the trait. Therefore, different methods have been developed to address these issues and online zithromax prescription optimise predictive performance of the score. Current common practice is to construct models with different iterations of SNPs and weighting, with assessment of the performance of each to identify the optimum configuration of SNPs and their weights (figure 2).Methods used in SNP selection and weighting assignmentSome methods of model development will initially involve selection of SNPs followed by optimisation of weighting, whereas others may involve optimisation of weightings for all SNPs that have been genotyped using their overall GWAS effect sizes, the linkage disequilibrium (LD) and an estimate of the proportion of SNPs that are expected to contribute to the risk.22LD is the phenomenon where some SNPs are coinherited more frequently with other SNPs due to their close proximity on the genome.

Segments with strong LD between SNPs are referred to as haplotype blocks online zithromax prescription. This phenomenon means that GWAS often identify multiple SNPs in the same haplotype block associated with disease and the true causal SNP is not known. As models have started to assess more SNPs, careful consideration is required to take online zithromax prescription into account possible correlation between SNPs as a result of this phenomenon.

Correlation between SNPs can lead online zithromax prescription to double counting of SNPs and association redundancy, where multiple SNPs in a region of LD are identified as being associated with the outcome. This can lead to reduction in the predictive performance of the model. Therefore, processes for filtering SNPs and using online zithromax prescription one SNP (tag SNP) to act as a marker in an area of high LD, through LD thinning, were developed.

Through these processes SNPs correlated with other SNPs in a block are removed, by either pruning or clumping. Pruning ignores p value thresholds and ‘eliminates’ SNPs by a process of iterative comparison online zithromax prescription between a pair of SNPs to assess if they are correlated, and subsequently could remove SNPs that are deemed to have evidence of association. Clumping (also known as informed pruning) is guided by GWAS p values and chooses the most significant SNP, therefore keeping the most significant SNP within a block.23 This is all done with the aim of pinpointing relatively small areas of the genome that contribute to risk of the trait.

Different significance thresholds may be used to select SNPs from this subgroup for inclusion in models.Poor performance of a model can result from imperfect tagging with the underlying causal SNP.16 This is because the causal online zithromax prescription SNP that is associated with disease might not be in LD with the tag SNP that is in the model but is in LD with another SNP which is not in the model. This particularly occurs where the LD and variant frequency differs between population groups.24 An alternate approach to filter SNPs is stepwise regression where SNPs are selected based on how much the SNPs improve the model’s performance. This is a statistical approach and does not online zithromax prescription consider the impact of LD or effect size.As described above, early studies used simple weighting approaches or directly applied effect sizes from GWAS as weighting parameters for SNPs.

However, application of effect sizes as a weighting parameter directly from a GWAS may not be optimal, due to differences in the population that the GWAS was conducted in and the target population. Also as described above, LD and the online zithromax prescription fact that not all SNPs may contribute to the trait mean that these effect sizes from GWAS are imperfect estimates. Therefore, methods have been developed that adjust effect size estimates from GWAS using statistical techniques which make assumptions about factors such as the number of causal SNPs, level of LD between SNPs or knowledge of their potential function to better reflect their impact on a trait.

Numerous statistical methodologies have been developed to improve weighting with a online zithromax prescription view to enhancing the discriminative power of a PGS.25 26 Examples of some methodological approaches are LDpred,22 winner’s curse correction,23 empirical Bayes estimation,27 shrinkage regression (Lasso),28 linear mixed models,29 with more being developed or tested. An additional improvement on the methods is to embed non-genetic information (eg, age-specific ORs).6 Determination of which methodology or hybrid of methodologies is most appropriate for various settings and conditions is continuously being explored and is evolving with new statistical approaches developing at a rapid pace.In summary, model development has evolved in an attempt to gain the most from available GWAS data and address some of the issues that arise due to working with data sets which cannot be directly translated into parameters for prediction models. The different approaches taken in SNP selection and weighting, and the impact on the predictive online zithromax prescription performance of a model are important to consider when assessing different models.

This is because different approaches to PGS modelling can achieve the same or a similar level of prediction. From a health system implementation perspective, particular approaches online zithromax prescription may be preferred following practical considerations and trade-offs between obtaining genotype data, processes for score construction and model performance. In addition, online zithromax prescription the degree to which these parameters need to be optimised will also be impacted by the input data and validation data set, and the quality control procedures that need to be applied to these data sets.12Sources of input data for score constructionKey to the development of a polygenic model is the availability of data sets that can provide input parameters for model construction.

Genotype data used in model construction can either be available as raw GWAS data or provided as GWAS summary statistics. Data in the raw format are individual-level data from a SNP array and may not have undergone basic quality control such as assessment of missingness, sex discrepancy checks, deviation from Hardy-Weinberg equilibrium, heterozygosity rate, relatedness or assessment for outliers.30 31 Availability online zithromax prescription of raw GWAS data allows for different polygenic models to be developed because of the richness of the data, however computational issues arise because of the size of the data sets. Data based on genome sequencing, as opposed to SNP arrays, could also be used in model construction.

There have been limited studies of PGS developed from this form of data due to limitations in data availability, which is mainly due to cost restraints.15 32 Individual-level genomic data are also often not available to researchers due to privacy concerns.Due to these issues, the focus of polygenic model development has therefore been on using well-powered GWAS summary statistics.33 These are available from open access repositories and contain summary information such as the online zithromax prescription allele positions, ORs, CIs and allele frequency, without containing confidential information on individuals. These data sets have usually been through the basic quality control measures mentioned above. There are, however, no online zithromax prescription standards for publicly available files, meaning some further processing steps may be required, in particular when various data sets are combined for a meta-analysis.

Quality control on summary statistics is only possible if information such as missing genotype rate, minor allele frequency, Hardy-Weinberg equilibrium failures and non-Mendelian transmission rates is provided.12Processing of GWAS data may include additional quality control steps, imputation and filtering of the SNP information, which can be done at the level of genotype or summary statistics data. SNP arrays used in GWAS only have common SNPs represented on them as they rely on LD between SNPs to cover the online zithromax prescription entire genome. As described above, one tag SNP on the array can represent many other SNPs.

Imputation of SNPs is common in GWAS and describes the process of predicting genotypes that have not been directly genotyped but are statistically inferred (imputed) based on online zithromax prescription haplotype blocks from a reference sequence.33–35 Often association tests between the imputed SNPs and trait are repeated. As genotype imputation requires individual-level data, researchers have proposed summary statistics imputation as a mechanism to infer the association between untyped SNPs and a trait. The performance of imputation has been evaluated and shown that, with online zithromax prescription certain limitations, summary statistics imputation is an efficient and cost-effective methodology to identify loci associated with traits when compared with imputation done on genotypes.36An alternative source of input data for the selection of SNPs and their weightings is through literature or in existing databases, where already known trait-associated SNPs and their effect sizes are used as the input parameters in model development.

A number of studies have taken this approach37 38 and it is possible to use multiple sources when developing various polygenic models and establishing the preferred parameters to use.Currently, there does not appear to be one methodology that works across all contexts and traits, each trait will need to be assessed to determine which method is the most suitable for the trait being evaluated. For example, four different polygenic model construction strategies were explored online zithromax prescription for three skin cancer subtypes4 by using data on SNPs and their effect sizes from different sources, such as the latest GWAS meta-analysis results, the National Human Genome Research Institute (NHGRI) EBI GWAS catalogue, UK Biobank GWAS summary statistics with different thresholds and GWAS summary statistics with LDpred. In this setting for basal cell carcinoma and melanoma, the meta-analysis and catalogue-derived models were found to perform similarly but that the latter was ultimately used as it included more SNPs.

For squamous online zithromax prescription cell carcinoma the meta-analysis-derived model performed better than the catalogue-derived model. This demonstrates how each disease subtype, model construction strategy and data set can have their own limitations and advantages.Knowledge of the sources of input data and its subsequent use in model development is important in understanding online zithromax prescription the limitations of available models. Models that are developed using data sets that reflect the population in which prediction is to be carried out will perform better.

For example, data collected from a symptomatic or high-risk population may not be suitable as an input data set for the development of a polygenic model online zithromax prescription that will be used for disease prediction in the general population. Large GWAS studies were previously focused on high-risk individuals, such as patients with breast cancer with a strong family history or known pathogenic variants in BRCA1 or BRCA2. These studies would not be suitable for the development of PGS for use in the general population online zithromax prescription but can inform risk assessment in high-risk individuals.

The source of the data for SNP selection and weighting also has implications for downstream uses and validation. For example, variant online zithromax prescription frequency and LD patterns can vary between populations and this can translate to poor performance of the polygenic model if the external validation population is different from that of the input data set.39–41 Furthermore, the power and validity of polygenic analyses are influenced by the input data sources.12 42From a model to a scorePGS can be calculated using one of the methodologies discussed above. The resulting PGS units of measurement depend on which measurement is used for the weighting.12 For example, the weightings may have been calculated based on logOR for discrete traits or linear regression coefficient (β/beta) in continuous traits from univariate regression tests carried out in the GWAS.

The resulting scores are then usually transformed to a standard normal distribution to give scores ranging from −1 to 1, or 0 to online zithromax prescription 100 for ease of interpretation. This enables further examination of the association between the score and a trait and the predictive ability of different scores generated by different models. Similar to other biomarker analyses, this involves using the PGS as a predictor of a trait with other covariates (eg, age, smoking, and so on) online zithromax prescription added, if appropriate, in a target sample.

Examination of differences in the distribution of scores in cases and controls, or by examining differences in traits between different strata of PGS can enable assessment of predictive ability (figure 3). Common practice is for individual-level PGS values to be used to stratify populations into distinct groups of risk based on percentile cut-off or threshold values (eg, the top 1%).Example distribution of polygenic online zithromax prescription scores across a population. Thresholds can be set to stratify risk as low (some), average (most) and high (some)." data-icon-position data-hide-link-title="0">Figure 3 Example distribution of polygenic scores across a population.

Thresholds can be set to stratify risk as low (some), average (most) and high (some).Model validationPolygenic model development is reliant on further data sets for model testing online zithromax prescription and validation and the composition of these data sets is important in ensuring that the models are appropriate for a particular purpose. The development of a model to calculate a PGS involves refinement of the previously discussed input parameters, and selection of the ‘best’ of online zithromax prescription several models based on performance (figure 2). Therefore, a testing/training data set is often required to assess the model’s ability to accurately predict the trait of interest.

This is often a online zithromax prescription data set that is independent of the base/input/discovery data set. It may comprise a subset of the discovery data set that is only used for testing and was not included in the initial development of the model but should ideally be a separate independent data set.Genotype and phenotype data are needed in these data sets. Polygenic models are used to online zithromax prescription calculate PGS for individuals in the training data set and regression analysis is performed with the PGS as a predictor of a trait.

Other covariates may also be included, if appropriate. This testing phase can be considered a process for identifying models with better online zithromax prescription overall performance and/or informing refinements needed. Hence, this phase often involves comparison of different models that are developed using the same input data set to identify those models that have optimal performance.The primary purpose is to determine which model best discriminates between cases and controls.

The area under the curve (AUC) or the C-statistic is the most commonly used measure in online zithromax prescription assessing discriminative ability. It has been criticised as being an insensitive measure that is not able to fully capture all aspects of predictive ability. For instance, in some instances, AUC can remain unchanged between models but the individuals within are categorised into a different online zithromax prescription risk group.43 Alternative metrics that have been used to evaluate model performance include increase in risk difference, integrated discrimination improvement, R2 (estimate of variance explained by the PGS after covariate adjustment), net classification index and the relative risk (highest percentile vs lowest percentile).

A clear understanding on how to interpret the performance within various settings is important in determining which model is most suitable.44As per normal practice when developing any prediction model, polygenic models with the optimal performance in a testing/training data set should be further validated in external data sets. External data sets are critical in validation of models and assessment of generalisability, hence must also conform to the desired situations in which a model is to online zithromax prescription be used. The goal is to find a model with suitable parameters of predictive performance in data sets outside of those in which it was developed.

Ideally, external online zithromax prescription validation requires replication in independent data sets. Few existing polygenic models have been validated to this extent, the focus being rather on the development of new models rather than evaluation of existing ones. One example where replication has been carried out is in the field of CAD, where the GPSCAD45 and metaGRSCAD10 polygenic models (both developed using UK Biobank data) were evaluated in a Finnish population cohort.46 Predictive ability was online zithromax prescription found to be lower in the Finnish population.

This is likely to online zithromax prescription be due to the differences in genetic structure of this population and the population of the data set used for polygenic model development. Research is ongoing to evaluate polygenic models in other populations and strategies are being developed to ensure the same performance when used more widely, possibly through reweighting and adjustment of the scores.47Moving towards clinical applicationsPGS are thought to be useful information that could improve risk estimation and provide an avenue for disease prevention and deciding treatment strategies. There are indications from a number of fields that genetic information in the form of PGS can act as online zithromax prescription independent biomarkers and aid stratification.11 16 48 However, the clinical benefits of stratification using a PGS and the implications for clinical practice are only just beginning to be examined.

The use of PGS as part of existing risk prediction tools or as a stand-alone predictor has been suggested. This latter option may online zithromax prescription be true for diseases where knowledge or predictive ability with other risk factors is limited, such as in prostate cancer.49 In either case, polygenic models need to be individually examined to determine suitability and applicability for the specific clinical question.50 Despite some commercial companies developing PGS,51 52 currently PGS are not an established part of clinical practice.Integration into clinical practice requires evaluation of a PGS-based test. An important concept to consider in this regard is the distinction between an assay and a test.

This has been previously discussed with respect to genetic test evaluation.53 54 It is worth examining this concept as applied to PGS, as their evaluation online zithromax prescription is reliant on a clear understanding of the test to be offered. As outlined by Zimmern and Kroese,54 the method used to analyse a substance in a sample is considered the assay, whereas a test is the use of an assay within a specific context. With respect to PGS, the process of developing a model to derive a score can be considered the assay, while the use of this model online zithromax prescription for a particular disease, population and purpose can be considered the test.

This distinction is important when assessing if studies are reporting on assay performance as opposed to test performance. It is our online zithromax prescription view that, with respect to polygenic models, progress has been made with respect to assay development, but PGS-based tests are yet to be developed and evaluated. This can enable a clearer understanding of their potential clinical utility and issues that may arise for clinical implementation.11 18 55 It is clear that this is still an evolving field, and going forward different models may be required for different traits due to their underlying genetic architecture,26 different clinical contexts and needs.Clinical contexts where risk stratification is already established practice are most likely where implementation of PGS will occur first.

Risk prediction models based on non-genetic factors have been developed for many conditions and are used in clinical care, for example, in online zithromax prescription cardiovascular disease over 100 such models exist.56 In such contexts, how a PGS and its ability to predict risk compared with, or improves on, these existing models is being investigated.3 44 57–61 The extent to which PGS improves prediction, as well as the cost implications of including this, is likely to impact on implementation.Integration of PGS into clinical practice, for any application, requires robust and validated mechanisms to generate these scores. Therefore, given the numerous models available, an assessment of their suitability as part of a test is required. Parameters or guidelines with respect to aspects of model performance and metrics that could assist in selecting online zithromax prescription the model to take forward as a PGS-based test are limited and need to be addressed.

Currently, there are different mechanisms to generate PGS and have arisen in response to the challenges in aggregating large-scale genomic data for prediction. For example, a review reported 29 PGS models for breast online zithromax prescription cancer from 22 publications.62 Due to there being a number of different methodologies to generate a score, numerous models may exist for the same condition and each of the resulting models could perform differently. Models may perform differently because the population, measured online zithromax prescription outcome or context of the development data sets used to generate the models is diverse, for example, a score for risk of breast cancer versus a breast cancer subtype.44 63 This diversity, alongside the lack of established best practice and standardised reporting in publications, makes comparison and evaluation of polygenic models for use in clinical settings challenging.

It is clear that moving the field forward is reliant on transparent reporting and evaluation. Recommendations for best online zithromax prescription practices on the reporting of polygenic models in literature have been proposed14 64 as well as a database,65 66 which could allow for such comparisons. Statements and guidelines for risk prediction model development, such as the Genetic Risk Prediction Studies and Transparent Reporting of a Multivariable Prediction Model for Individual Prognosis or Diagnosis (TRIPOD), already exist, but are not consistently used.

TRIPOD explicitly covers the development and validation of prediction models for both diagnosis and prognosis, for all medical domains.One clear issue is generalisability and drop in performance of polygenic models once they are applied in a population group different from the one in which they were developed.22 46 67–70 This is an ongoing challenge in genomics as most GWAS, from which most PGS are being developed, have been conducted in European-Caucasian populations.71 Efforts to improve representation are underway72 and there are attempts to reweight/adjust scores when applied to different population groups which are showing some potential online zithromax prescription but need further research.47 Others have demonstrated that models developed in more diverse population groups have improved performance when applied to external data sets in different populations.24 73 It is important to consider this issue when moving towards clinical applications as it may pose an ethical challenge if the PGS is not generalisable.A greater understanding of different complex traits and the impact of pleiotropy is only beginning to be investigated.74 There is growing appreciation of the role of pleiotropy as multiple variants have been identified to be associated with multiple traits and exert diverse effects, providing insight into overlapping mechanisms.75 76 This, together with the impact of population stratification, genetic relatedness, ascertainment and other sources of heterogeneity leading to spurious signals and reduced power in genetic association studies, all impacting on the predictive ability of PGS in different populations and for different diseases.While many publications report on model development and evaluation, often there is a lack of clarity on intended purpose,50 77 leading to uncertainties as to the clinical pathways in which implementation is envisaged. A clear description of intended use within clinical pathways is a central component in evaluating the use of an application with any form of PGS and in considering practical implications, such as mechanisms of obtaining the score, incorporation into health records, interpretation of scores, relevant cut-offs for intervention initiation, mechanisms for feedback of results and costs, among other issues. These parameters will also be online zithromax prescription impacted by the polygenic model that is taken forward for implementation.

Meaning that there are still some important questions that need to be addressed to determine how and where PGS could work within current healthcare systems, particularly at a population level.78It is widely accepted that genotyping using arrays is a lower cost endeavour in comparison to genome sequencing, making the incorporation of PGS into routine healthcare an attractive proposition. However, we were online zithromax prescription unable to find any studies reporting on the use or associated costs of such technology for population screening. Studies are beginning to examine use case scenarios and model cost-effectiveness, but this has only been in very few, specific investigations.79 80 Costs will also be influenced by the testing technology and by the downstream consequences of testing, which is likely to differ depending on specific applications that are developed and the pathways in which such tests are incorporated.

This is particularly the case in screening or primary care online zithromax prescription settings, where such testing is currently not an established part of care pathways and may require additional resources, not least as a result of the volume of testing that could be expected. Moving forward, the clinical role of PGS needs to be developed further, including defining the clinical applications as well as supporting evidence, for example, on the effect of clinical outcomes, the feasibility for use in routine practice and cost-effectiveness.ConclusionThere is a large amount of diversity in the PGS field with respect to model development approaches, and this continues to evolve. There is rapid progress which is being driven by the availability of larger data sets, primarily from GWAS and concomitant developments in statistical methodologies online zithromax prescription.

As understanding and knowledge develops, the usefulness and appropriateness of polygenic models for different diseases and contexts are being explored. Nevertheless, this is still an emerging field, with a variable evidence base online zithromax prescription demonstrating some potential. The validity of PGS needs to be clearly demonstrated, and their applications evaluated prior to clinical implementation..

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These children often miss school and social activities due to doctors' visits or health restrictions.For the study, the researchers reviewed medical records of close to 119,000 kids, aged 4 to 17, who were treated at Texas Children's Hospital in Houston more than once between 2011 and 2016.Of those, 1,164 had congenital azithromycin zithromax 500mg heart disease. All of those youngsters, including the youngest, were more likely than their peers to have anxiety, depression or ADHD, the records revealed.Slightly more than 18% of those who had been born with heart disease had a diagnosis or medication for anxiety and/or depression, compared to just over 5% of others, the researchers found.The findings were published online Jan. 4 in the journal Pediatrics.Exactly why these children are at higher risk for mental health issues is not azithromycin zithromax 500mg fully understood. But the study's lead author described these kids as "uniquely vulnerable.""They are frequently hospitalized and often undergo multiple invasive procedures or surgeries early in azithromycin zithromax 500mg childhood and throughout their lifetime," said Dr.

Vincent Gonzalez, a pediatric cardiology fellow at Baylor College of Medicine/Texas Children's Hospital in Houston."These factors, along with a higher prevalence of underlying genetic disorders, learning disabilities, increased parental anxiety and social stressors all likely contribute to this increase in mental health disorders," he added.Nonetheless, kids who are born with heart defects are living longer and fuller lives today than ever before, said Dr. David Meyer, a heart surgeon at Cohen's Children's Hospital in New Hyde Park, N.Y., who reviewed the findings."We used to focus solely on survival, but now that these kids are doing so well, we need to take a more holistic approach and monitor them for secondary issues that may arise down the road, such as anxiety, depression and or ADHD," Meyer said.Looking out for signs -- such as extreme sadness, constant worry, irritability or trouble sleeping -- azithromycin zithromax 500mg can help kids get the treatments they need to feel better, the experts agreed.Gonzalez said that the study findings "indicate that providers caring for all patients with any type of [congenital heart disease] should consider screening for symptoms of these disorders earlier in childhood, as opposed to waiting until the typical adolescent time period."The study also found that uninsured children and those from minority groups are diagnosed with anxiety, depression or ADHD at a strikingly lower rate than their white peers."This suggests that these populations are at increased risk for being underdiagnosed and treated for these conditions, and providers should have a higher index of suspicion when seeing these patients," Gonzalez said. IMAGES Heart Illustration Browse through our medical image collection to see illustrations of human anatomy and physiology azithromycin zithromax 500mg See Images Rebecca Berry is a clinical associate professor of child and adolescent psychiatry at Hassenfeld Children's Hospital at NYU Langone Health in New York City. She reviewed the findings and pointed out that a certain degree of fear or worry is to be expected when a child has a serious medical condition."The question is.

Are these symptoms distressing and disruptive to a child's quality of life and disproportionate to azithromycin zithromax 500mg what we would expect for a child with this condition?. " she said.Many pediatric heart surgery teams include a psychologist to help children and their families cope with the heart defect, its treatment and its effect on day-to-day life.Parents can do their part, too, Berry said."Listen to your child and validate what they are saying and feeling," she suggested. "Don't make everything about the illness azithromycin zithromax 500mg. Try and treat them as a child and include them in normal activities whenever you can."More informationThe U.S azithromycin zithromax 500mg.

Centers for Disease Control and Prevention has more about congenital heart defects.SOURCES. Vincent Gonzalez, MD, MS, azithromycin zithromax 500mg pediatric cardiology fellow, Baylor College of Medicine/Texas Children's Hospital, Houston. David Meyer, MD, pediatric cardiothoracic surgeon, Cohen Children's Hospital, New Hyde Park, N.Y., and associate professor, cardiothoracic surgery and pediatrics, Zucker-Hofstra School of azithromycin zithromax 500mg Medicine, Hempstead, N.Y.. Rebecca Berry, PhD, clinical associate professor, child and adolescent psychiatry, Child Study Center, Hassenfeld Children's Hospital at NYU Langone Health, New York City.

Pediatrics, Jan azithromycin zithromax 500mg. 4, 2021, onlineCopyright © azithromycin zithromax 500mg 2020 HealthDay. All rights reserved. From Healthy Heart Resources Featured Centers Health Solutions From Our SponsorsLatest antibiotics azithromycin zithromax 500mg News By Ernie Mundell HealthDay ReporterTUESDAY, Jan.

5, 2021 (HealthDay News)By Nov. 15 of last year, roughly azithromycin zithromax 500mg 47 million Americans -- about 14.5% of the U.S. Population -- had already been infected azithromycin zithromax 500mg with the new antibiotics, a new study finds.That's much higher than the close to 11 million known U.S. Cases of that were recorded by that date, the researchers said, because reported cases "do not represent the full antibiotics disease burden.""Case reports are dependent on patients seeking health care," among other factors, and at least 40% of all s are thought to be asymptomatic, according to a team led by Dr.

Frederick Angulo azithromycin zithromax 500mg. He works in medical development and scientific/clinical affairs at Pfizer treatments, which has an approved buy antibiotics treatment already in distribution in the United States.It's believed azithromycin zithromax 500mg that everyone who becomes infected with the new antibiotics will develop some form of immunity. And if enough of the population (about 70%) were to gain immunity -- either through or vaccination -- so-called "herd immunity" would set in, thwarting the zithromax' ability to spread further.But the numbers for Nov. 15, 2020 show that herd immunity is still far away, the research team said."Findings of this study suggest that azithromycin zithromax 500mg although more than 14% of the U.S.

Population was infected with antibiotics by azithromycin zithromax 500mg mid-November, a substantial gap remains before herd immunity can be reached," they reported Jan. 5 in JAMA Network Open.The Nov. 15 numbers were based on a total azithromycin zithromax 500mg U.S. Count of recorded cases on that date of 10,846,373. rates have exploded across the United States since then, and according to a tally kept daily by The New York azithromycin zithromax 500mg Times, more than 20.8 million verified cases have been recorded as of Tuesday.Even so, Americans remain far away from herd immunity, one expert said, so the rollout of a nationwide vaccination campaign remains imperative."While it has always been the case that a major underestimate of the true disease burden with buy antibiotics has been present, most parts of the country have not reached herd immunity," said Dr.

Amesh Adalja, an infectious disease expert and senior scholar at the Johns Hopkins Center for Health Security, in Baltimore."This underscores the need for vaccination uptake to be optimal to put this zithromax behind us," Adalja said.In their study, Angulo's group analyzed data from four "seroprevalence" (blood test) surveys conducted by the U.S. Centers for azithromycin zithromax 500mg Disease Control and Prevention in April, May, June, July and August. These surveys were conducted in 10 states (California, Connecticut, Florida, Louisiana, Minnesota, Missouri, New York, Pennsylvania, Utah and Washington). A fifth CDC survey was conducted in 47 states nationwide.All of that data helped the researchers estimate the level of "under-reporting" of antibiotics s -- the gap between the number of people recorded as having buy antibiotics and the larger "true" number of cases, reported and unreported.Angulo's team used those calculations to come up with an estimated number of 46,910,006 cases of antibiotics having occurred among Americans by azithromycin zithromax 500mg Nov.

15, 2020.The researchers stressed that the buy antibiotics zithromax is not a static phenomenon, so these calculations "will change over time as the proportion of persons with tested, diagnosed and reported changes." Their calculations may, in fact, be "conservative," the team said.The introduction of an immunization campaign could change the numbers greatly, as well, so additional surveys are needed "to monitor the zithromax, including after the development of safe and efficacious treatments," Angulo and colleagues concluded.More informationFind out more azithromycin zithromax 500mg about the unfolding zithromax at the U.S. Centers for Disease Control and Prevention.SOURCES. Amesh Adalja, MD, senior scholar, Johns Hopkins Center for azithromycin zithromax 500mg Health Security, Baltimore. JAMA Network azithromycin zithromax 500mg Open, Jan.

5, 2021, onlineCopyright © 2020 HealthDay. All rights reserved.Latest antibiotics News By Dennis Thompson HealthDay azithromycin zithromax 500mg ReporterTUESDAY, Jan. 5, 2021 (HealthDay News)Stem cells derived from a baby's umbilical cord can help save the lives of the sickest buy antibiotics patients, results from a small new clinical trial suggest.Severely ill buy antibiotics patients who received two intravenous doses of stem cells three days apart were much azithromycin zithromax 500mg more likely to survive and recover quickly, researchers found."The results are quite spectacular," said senior researcher Dr. Camillo Ricordi, director of the Diabetes Research Institute and Cell Transplant Center at the University of Miami Miller School of Medicine.

"It's probably the best trial ever zithromax capsules buy done for a buy antibiotics cure, because we have 100% survival in subjects less than 85 years of age versus 42% survival in the control group."The clinical trial involved 24 buy antibiotics patients at one of two Miami-area hospitals who had developed severe acute respiratory distress syndrome, a condition in which the body's immune response to a serious causes the lungs to fill with fluid.Half were randomly chosen to receive two separate IV infusions of 100 million stem cells, while the others received a placebo IV.After one month, 91% of patients in azithromycin zithromax 500mg the stem-cell-treated group had survived compared to 42% in the control group. Among patients younger than 85 years old, everyone treated with stem cells survived.The stem cells also sped recovery time. More than half of stem-cell patients were able to leave the hospital within two weeks and more than 80% recovered by day azithromycin zithromax 500mg 30, compared with less than 37% in the control group.The therapy also proved safe, with no infusion-related serious adverse events.Ricordi and his colleagues thought to use stem cells in buy antibiotics treatment because they had already been looking into ways the cells might help people suffering from other diseases in which the immune system causes extreme inflammation.Previous studies have shown that stem cells are a promising therapy to blunt an overactive immune response and excessive inflammation, which damage the body's organs."Our results confirm the powerful anti-inflammatory, immunomodulatory effect of [umbilical stem cells]. These cells have clearly inhibited the 'cytokine storm,' a hallmark of severe buy antibiotics," lead researcher Giacomo Lanzoni said azithromycin zithromax 500mg in a University of Miami news release.

"The results are critically important not only for buy antibiotics but also for other diseases characterized by aberrant and hyperinflammatory immune responses, such as autoimmune Type 1 Diabetes."Lanzoni is an assistant research professor at the university's Diabetes Research Institute.Research out of China and Israel had indicated that stem cells might be used to treat buy antibiotics patients, but those results drew widespread skepticism because none had been randomized, Ricordi noted.Ricordi's team has approval from the U.S. Food and Drug Administration to try stem cells as a treatment for type 1 diabetes, which is much more complicated because the infusion must take place in specific arteries that will steer the cells directly to the pancreas.To treat buy antibiotics, "we could just do azithromycin zithromax 500mg a simple blood transfusion, and all the cells just go automatically to the lungs," Ricordi said.The treatment appears very promising and should be tested in larger trials, said Dr. Amesh Adalja, senior scholar with the Johns Hopkins Center for Health Security in Baltimore."You obviously want to see azithromycin zithromax 500mg bigger studies to make sure your results are sound," said Adalja, who wasn't part of this research. "This positive study provides a path to bigger studies to understand how well this works in larger groups of patients."Adalja expressed some skepticism that umbilical cord stem cells could be a treatment that makes its way out of large academic hospitals and into smaller community medical centers."It's one thing to be able to do it in an academic medical center.

It's another thing to azithromycin zithromax 500mg be able to do it in community hospital," Adalja said. "Is this a scalable azithromycin zithromax 500mg type of intervention?. "Ricordi thinks stem cells could become a widespread treatment, given that one umbilical cord recovered from a healthy newborn can generate more than 10,000 therapeutic doses.The team has just filed paperwork with the FDA for a larger trial involving 120 patients, Ricordi said."In the meantime, we will be able to offer compassionate use to hospitals in North America requesting our assistance, to ship these cells to them," he said. Because the research is supported by a $3 million grant from North America's Building Trades Unions and additional funding from The Cure Alliance, the azithromycin zithromax 500mg therapy can be offered at low cost, Ricordi added.

No pharmaceutical companies are involved.It wouldn't be the first time an academic center made a promising buy antibiotics treatment widely available, Adalja noted."Because of the expanded access programs that were put in place by the Mayo Clinic, for example, many community hospitals that wouldn't ordinarily have access to convalescent plasma did get access to it," Adalja said. "You could envision something azithromycin zithromax 500mg similar to do, but I think the next step would be larger randomized controlled trials before we would go that far."Results from the new trial were published Jan. 5 in the journal Stem Cells azithromycin zithromax 500mg Translational Medicine.More informationThe U.S. Food and Drug Administration has more about cord blood therapies.SOURCES.

Camillo Ricordi, MD, director, Diabetes Research Institute and Cell Transplant Center, University of azithromycin zithromax 500mg Miami Miller School of Medicine. Amesh Adalja, MD, senior scholar, azithromycin zithromax 500mg Johns Hopkins Center for Health Security, Baltimore. University of Miami, news release, Jan. 5, 2021 azithromycin zithromax 500mg.

Stem Cells azithromycin zithromax 500mg Translational Medicine, Jan. 5, 2021Copyright © 2020 HealthDay. All rights azithromycin zithromax 500mg reserved.Latest Pregnancy News By Amy Norton HealthDay ReporterTUESDAY, Jan. 5, 2021 (HealthDay News)For decades, women have commonly azithromycin zithromax 500mg been given oxygen during childbirth, but a new research review finds little evidence it benefits newborns.The American College of Obstetricians and Gynecologists recommends that women be given supplemental oxygen when fetal heart monitoring shows an abnormal heart rate.

That's based on the possibility that oxygen deprivation is causing the problem.Yet there has been little research evidence that the tactic does any good. And the new review, of 16 clinical trials, uncovered no clear benefits for newborns.Overall, infants born to women who received oxygen fared no better than those whose mothers simply breathed "room air." Their breathing, heart rate, reflexes and muscle azithromycin zithromax 500mg tone at birth were similar, and they were no less likely to be admitted to the neonatal intensive care unit (NICU), the analysis found.The practice of giving women oxygen during labor began in the 1960s, said Dr. Nandini Raghuraman, lead researcher on the analysis.There is a theoretical basis for it, she said, but little in the way of scientific proof that it helps.Yet the practice has persisted. One study estimated that in the United States, two out of three women who go into labor receive oxygen at some point."I think part azithromycin zithromax 500mg of this relates to the general myth that the more oxygen, the better," said Raghuraman, an assistant professor of obstetrics and gynecology at Washington University School of Medicine in St.

Louis.But in some medical contexts other than childbirth, she noted, research has shown "over-oxygenation" can be harmful (for example, by producing cell-damaging free radicals).Whether prolonged supplemental oxygen could pose any risk during childbirth is unclear.But based on the existing data, Raghuraman said that, in most cases, oxygen is probably not effective.The findings — published online Jan azithromycin zithromax 500mg. 4 in JAMA Pediatrics — are based on 16 clinical trials where women were randomly assigned to either receive supplemental oxygen or breathe room air. Some trials involved azithromycin zithromax 500mg women in labor. Others focused on women having scheduled or emergency cesarean sections.Raghuraman said researchers pooled results from the azithromycin zithromax 500mg trials, since that larger number of patients can allow more definitive answers than a single, small study can.Overall, the investigators found no evidence that supplemental oxygen made a significant difference in oxygen supply to the umbilical artery.

And there was no effect on newborns' odds of being admitted to the NICU, or on their Apgar scores (a standard measure of breathing, heart rate and other health indicators done right after birth).Dr. Erika Werner is division director of maternal-fetal medicine at azithromycin zithromax 500mg Women &. Infants Hospital of Rhode Island, in Providence.She said that a decrease in azithromycin zithromax 500mg fetal heart rate is sometimes related to lack of oxygen. So "there was biologic plausibility that if you give mom oxygen, it will get to the fetus," Werner said."The problem is, many things that have biologic plausibility turn out to not actually improve outcomes," she added.According to Werner, it's still possible there's some benefit from the approach.

Rarer problems were not assessed in these trials."To determine if supplemental oxygen improves rare outcomes like azithromycin zithromax 500mg neonatal seizures, you would need much larger studies," Werner said. "Ideally, children would also be followed for several years to identify differences in longer-term outcomes, like cerebral palsy."It's not clear why, based on studies so far, that supplemental oxygen hasn't benefited newborns. But one issue, Raghuraman said, is that doctors don't fully understand all the causes of fetal heart rate abnormalities.Still, she said, there are other ways to manage those heart azithromycin zithromax 500mg rate problems, short of rushing to do a C-section. Changing the mother's position and giving IV fluids are common tactics.Raghuraman said that at the hospital azithromycin zithromax 500mg where she delivers babies, Barnes-Jewish Hospital, they have become more judicious about giving supplemental oxygen.

SLIDESHOW Conception. The Amazing Journey from Egg to Embryo See Slideshow More research is needed to see whether there could be any harms azithromycin zithromax 500mg from giving women prolonged oxygen during labor, she said.More informationThe nonprofit initiative Choosing Wisely has more on fetal heart rate monitoring.SOURCES. Nandini Raghuraman, MD, MS, assistant professor, obstetrics and azithromycin zithromax 500mg gynecology, Washington University School of Medicine, St. Louis.

Erika Werner, MD, MS, division director, maternal-fetal medicine, Women azithromycin zithromax 500mg &. Infants Hospital of Rhode Island, and associate azithromycin zithromax 500mg professor, obstetrics and gynecology, Alpert Medical School of Brown University, Providence, R.I.. JAMA Pediatrics, Jan. 4, 2021, azithromycin zithromax 500mg onlineCopyright © 2020 HealthDay.

Latest Heart News By Denise Mann online zithromax prescription HealthDay ReporterTUESDAY, Jan. 5, 2021 (HealthDay News)Kids born with heart defects may be more likely to develop anxiety, depression and/or attention-deficit/hyperactivity disorder (ADHD), online zithromax prescription regardless of the severity of their heart condition.Congenital heart defects are the most common type of birth defect in the United States, affecting about 40,000 babies a year, according to the U.S. Centers for Disease Control and Prevention. The defects range from mild to severe and sometimes require immediate online zithromax prescription or multiple surgeries.

These children often miss school and social activities due to doctors' visits or health restrictions.For the study, the researchers reviewed medical records of online zithromax prescription close to 119,000 kids, aged 4 to 17, who were treated at Texas Children's Hospital in Houston more than once between 2011 and 2016.Of those, 1,164 had congenital heart disease. All of those youngsters, including the youngest, were more likely than their peers to have anxiety, depression or ADHD, the records revealed.Slightly more than 18% of those who had been born with heart disease had a diagnosis or medication for anxiety and/or depression, compared to just over 5% of others, the researchers found.The findings were published online Jan. 4 in the journal online zithromax prescription Pediatrics.Exactly why these children are at higher risk for mental health issues is not fully understood. But the study's lead author described these online zithromax prescription kids as "uniquely vulnerable.""They are frequently hospitalized and often undergo multiple invasive procedures or surgeries early in childhood and throughout their lifetime," said Dr.

Vincent Gonzalez, a pediatric cardiology fellow at Baylor College of Medicine/Texas Children's Hospital in Houston."These factors, along with a higher prevalence of underlying genetic disorders, learning disabilities, increased parental anxiety and social stressors all likely contribute to this increase in mental health disorders," he added.Nonetheless, kids who are born with heart defects are living longer and fuller lives today than ever before, said Dr. David Meyer, a heart surgeon at Cohen's Children's Hospital in New Hyde Park, N.Y., who reviewed the findings."We used to focus solely on survival, but now that these kids are doing so well, we need to take a more holistic approach and monitor them for secondary issues that may arise down the road, such as anxiety, depression and or ADHD," Meyer said.Looking out for signs -- such as extreme sadness, constant worry, irritability or trouble sleeping -- can help kids get the treatments they need to feel better, the experts agreed.Gonzalez said that the study findings "indicate that providers caring for all patients with any type of [congenital heart disease] should consider screening for symptoms of these disorders earlier in childhood, as opposed to waiting until the typical adolescent time period."The study also found that uninsured children and those from minority groups are diagnosed with anxiety, depression or ADHD at a strikingly lower rate than their white peers."This suggests online zithromax prescription that these populations are at increased risk for being underdiagnosed and treated for these conditions, and providers should have a higher index of suspicion when seeing these patients," Gonzalez said. IMAGES Heart Illustration Browse through our medical image collection to see illustrations of human anatomy and physiology See Images Rebecca Berry is a clinical associate professor of child and adolescent psychiatry at Hassenfeld Children's Hospital online zithromax prescription at NYU Langone Health in New York City. She reviewed the findings and pointed out that a certain degree of fear or worry is to be expected when a child has a serious medical condition."The question is.

Are these symptoms distressing and disruptive to a child's quality of life and disproportionate to what we would online zithromax prescription expect for a child with this condition?. " she said.Many pediatric heart surgery teams include a psychologist to help children and their families cope with the heart defect, its treatment and its effect on day-to-day life.Parents can do their part, too, Berry said."Listen to your child and validate what they are saying and feeling," she suggested. "Don't make everything about online zithromax prescription the illness. Try and treat them as online zithromax prescription a child and include them in normal activities whenever you can."More informationThe U.S.

Centers for Disease Control and Prevention has more about congenital heart defects.SOURCES. Vincent Gonzalez, MD, MS, pediatric cardiology fellow, online zithromax prescription Baylor College of Medicine/Texas Children's Hospital, Houston. David Meyer, MD, pediatric cardiothoracic surgeon, Cohen Children's online zithromax prescription Hospital, New Hyde Park, N.Y., and associate professor, cardiothoracic surgery and pediatrics, Zucker-Hofstra School of Medicine, Hempstead, N.Y.. Rebecca Berry, PhD, clinical associate professor, child and adolescent psychiatry, Child Study Center, Hassenfeld Children's Hospital at NYU Langone Health, New York City.

Pediatrics, Jan online zithromax prescription. 4, 2021, onlineCopyright © 2020 online zithromax prescription HealthDay. All rights reserved. From Healthy Heart Resources Featured Centers Health online zithromax prescription Solutions From Our SponsorsLatest antibiotics News By Ernie Mundell HealthDay ReporterTUESDAY, Jan.

5, 2021 (HealthDay News)By Nov. 15 of last year, roughly 47 million Americans -- about online zithromax prescription 14.5% of the U.S. Population -- had already been infected with the online zithromax prescription new antibiotics, a new study finds.That's much higher than the close to 11 million known U.S. Cases of that were recorded by that date, the researchers said, because reported cases "do not represent the full antibiotics disease burden.""Case reports are dependent on patients seeking health care," among other factors, and at least 40% of all s are thought to be asymptomatic, according to a team led by Dr.

Frederick Angulo online zithromax prescription. He works in medical development and scientific/clinical affairs at Pfizer treatments, which has an approved online zithromax prescription buy antibiotics treatment already in distribution in the United States.It's believed that everyone who becomes infected with the new antibiotics will develop some form of immunity. And if enough of the population (about 70%) were to gain immunity -- either through or vaccination -- so-called "herd immunity" would set in, thwarting the zithromax' ability to spread further.But the numbers for Nov. 15, 2020 show that herd immunity is still far away, the research team said."Findings of this study online zithromax prescription suggest that although more than 14% of the U.S.

Population was infected with antibiotics online zithromax prescription by mid-November, a substantial gap remains before herd immunity can be reached," they reported Jan. 5 in JAMA Network Open.The Nov. 15 numbers online zithromax prescription were based on a total U.S. Count of recorded cases on that date of 10,846,373. rates have exploded across the United States since then, and according to online zithromax prescription a tally kept daily by The New York Times, more than 20.8 million verified cases have been recorded as of Tuesday.Even so, Americans remain far away from herd immunity, one expert said, so the rollout of a nationwide vaccination campaign remains imperative."While it has always been the case that a major underestimate of the true disease burden with buy antibiotics has been present, most parts of the country have not reached herd immunity," said Dr.

Amesh Adalja, an infectious disease expert and senior scholar at the Johns Hopkins Center for Health Security, in Baltimore."This underscores the need for vaccination uptake to be optimal to put this zithromax behind us," Adalja said.In their study, Angulo's group analyzed data from four "seroprevalence" (blood test) surveys conducted by the U.S. Centers for Disease Control and Prevention in April, May, June, July and August online zithromax prescription. These surveys were conducted in 10 states (California, Connecticut, Florida, Louisiana, Minnesota, Missouri, New York, Pennsylvania, Utah and Washington). A fifth CDC survey was conducted in 47 states nationwide.All of that data helped the researchers estimate the level of "under-reporting" of antibiotics s -- the gap between the number of people recorded as having buy antibiotics and the larger "true" number of cases, reported and unreported.Angulo's team used online zithromax prescription those calculations to come up with an estimated number of 46,910,006 cases of antibiotics having occurred among Americans by Nov.

15, 2020.The researchers stressed that the buy antibiotics zithromax is not a static phenomenon, so these calculations "will change over time as the proportion of persons with tested, diagnosed and reported changes." Their calculations may, in fact, be "conservative," the online zithromax prescription team said.The introduction of an immunization campaign could change the numbers greatly, as well, so additional surveys are needed "to monitor the zithromax, including after the development of safe and efficacious treatments," Angulo and colleagues concluded.More informationFind out more about the unfolding zithromax at the U.S. Centers for Disease Control and Prevention.SOURCES. Amesh Adalja, MD, online zithromax prescription senior scholar, Johns Hopkins Center for Health Security, Baltimore. JAMA Network Open, Jan online zithromax prescription.

5, 2021, onlineCopyright © 2020 HealthDay. All rights reserved.Latest antibiotics News By Dennis Thompson HealthDay ReporterTUESDAY, online zithromax prescription Jan. 5, 2021 (HealthDay News)Stem cells derived from a baby's umbilical cord can help save the lives of the sickest buy antibiotics patients, results from a small new clinical trial suggest.Severely online zithromax prescription ill buy antibiotics patients who received two intravenous doses of stem cells three days apart were much more likely to survive and recover quickly, researchers found."The results are quite spectacular," said senior researcher Dr. Camillo Ricordi, director of the Diabetes Research Institute and Cell Transplant Center at the University of Miami Miller School of Medicine.

"It's probably the best trial ever done for a buy antibiotics cure, because we have 100% survival in subjects less than 85 years of age versus 42% survival in the control group."The clinical trial involved 24 buy antibiotics patients at one of two Miami-area hospitals who had developed severe acute respiratory distress syndrome, a condition in which the body's immune response to a serious causes the online zithromax prescription lungs to fill with fluid.Half were randomly chosen to receive two separate IV infusions of 100 million stem cells, while the others received a placebo IV.After one month, 91% of patients in the stem-cell-treated group had survived compared to 42% in the control group. Among patients younger than 85 years old, everyone treated with stem cells survived.The stem cells also sped recovery time. More than half of stem-cell patients were able to leave online zithromax prescription the hospital within two weeks and more than 80% recovered by day 30, compared with less than 37% in the control group.The therapy also proved safe, with no infusion-related serious adverse events.Ricordi and his colleagues thought to use stem cells in buy antibiotics treatment because they had already been looking into ways the cells might help people suffering from other diseases in which the immune system causes extreme inflammation.Previous studies have shown that stem cells are a promising therapy to blunt an overactive immune response and excessive inflammation, which damage the body's organs."Our results confirm the powerful anti-inflammatory, immunomodulatory effect of [umbilical stem cells]. These cells have clearly inhibited the 'cytokine storm,' online zithromax prescription a hallmark of severe buy antibiotics," lead researcher Giacomo Lanzoni said in a University of Miami news release.

"The results are critically important not only for buy antibiotics but also for other diseases characterized by aberrant and hyperinflammatory immune responses, such as autoimmune Type 1 Diabetes."Lanzoni is an assistant research professor at the university's Diabetes Research Institute.Research out of China and Israel had indicated that stem cells might be used to treat buy antibiotics patients, but those results drew widespread skepticism because none had been randomized, Ricordi noted.Ricordi's team has approval from the U.S. Food and Drug Administration to try stem cells as a online zithromax prescription treatment for type 1 diabetes, which is much more complicated because the infusion must take place in specific arteries that will steer the cells directly to the pancreas.To treat buy antibiotics, "we could just do a simple blood transfusion, and all the cells just go automatically to the lungs," Ricordi said.The treatment appears very promising and should be tested in larger trials, said Dr. Amesh Adalja, senior scholar with the Johns Hopkins Center for Health Security in Baltimore."You obviously want to see bigger studies to make sure your results are sound," said Adalja, who wasn't online zithromax prescription part of this research. "This positive study provides a path to bigger studies to understand how well this works in larger groups of patients."Adalja expressed some skepticism that umbilical cord stem cells could be a treatment that makes its way out of large academic hospitals and into smaller community medical centers."It's one thing to be able to do it in an academic medical center.

It's another thing to be able to do it in community hospital," Adalja said online zithromax prescription. "Is this a scalable type of online zithromax prescription intervention?. "Ricordi thinks stem cells could become a widespread treatment, given that one umbilical cord recovered from a healthy newborn can generate more than 10,000 therapeutic doses.The team has just filed paperwork with the FDA for a larger trial involving 120 patients, Ricordi said."In the meantime, we will be able to offer compassionate use to hospitals in North America requesting our assistance, to ship these cells to them," he said. Because the research online zithromax prescription is supported by a $3 million grant from North America's Building Trades Unions and additional funding from The Cure Alliance, the therapy can be offered at low cost, Ricordi added.

No pharmaceutical companies are involved.It wouldn't be the first time an academic center made a promising buy antibiotics treatment widely available, Adalja noted."Because of the expanded access programs that were put in place by the Mayo Clinic, for example, many community hospitals that wouldn't ordinarily have access to convalescent plasma did get access to it," Adalja said. "You could envision something similar to do, but I online zithromax prescription think the next step would be larger randomized controlled trials before we would go that far."Results from the new trial were published Jan. 5 in the journal Stem Cells Translational Medicine.More informationThe online zithromax prescription U.S. Food and Drug Administration has more about cord blood therapies.SOURCES.

Camillo Ricordi, MD, director, Diabetes Research Institute and Cell Transplant Center, University online zithromax prescription of Miami Miller School of Medicine. Amesh Adalja, MD, senior scholar, Johns Hopkins Center for Health online zithromax prescription Security, Baltimore. University of Miami, news release, Jan. 5, 2021 online zithromax prescription.

Stem Cells online zithromax prescription Translational Medicine, Jan. 5, 2021Copyright © 2020 HealthDay. All rights reserved.Latest Pregnancy News By Amy online zithromax prescription Norton HealthDay ReporterTUESDAY, Jan. 5, 2021 (HealthDay News)For decades, women have commonly been given oxygen during childbirth, but a new research review finds little evidence it benefits newborns.The American College of Obstetricians and Gynecologists recommends that women be given supplemental oxygen when fetal heart monitoring shows an online zithromax prescription abnormal heart rate.

That's based on the possibility that oxygen deprivation is causing the problem.Yet there has been little research evidence that the tactic does any good. And the new review, of 16 clinical trials, uncovered no clear benefits for newborns.Overall, infants born to women who received oxygen fared no better than those whose mothers simply breathed "room air." Their breathing, heart rate, reflexes and muscle tone at birth were similar, and they were no less online zithromax prescription likely to be admitted to the neonatal intensive care unit (NICU), the analysis found.The practice of giving women oxygen during labor began in the 1960s, said Dr. Nandini Raghuraman, lead researcher on the analysis.There is a theoretical basis for it, she said, but little in the way of scientific proof that it helps.Yet the practice has persisted. One study estimated that in the United States, two out of three women who online zithromax prescription go into labor receive oxygen at some point."I think part of this relates to the general myth that the more oxygen, the better," said Raghuraman, an assistant professor of obstetrics and gynecology at Washington University School of Medicine in St.

Louis.But in some medical contexts other than childbirth, she noted, research has shown "over-oxygenation" can be online zithromax prescription harmful (for example, by producing cell-damaging free radicals).Whether prolonged supplemental oxygen could pose any risk during childbirth is unclear.But based on the existing data, Raghuraman said that, in most cases, oxygen is probably not effective.The findings — published online Jan. 4 in JAMA Pediatrics — are based on 16 clinical trials where women were randomly assigned to either receive supplemental oxygen or breathe room air. Some trials online zithromax prescription involved women in labor. Others focused on women having scheduled or emergency cesarean sections.Raghuraman said researchers pooled results from the trials, since that larger number of patients can allow online zithromax prescription more definitive answers than a single, small study can.Overall, the investigators found no evidence that supplemental oxygen made a significant difference in oxygen supply to the umbilical artery.

And there was no effect on newborns' odds of being admitted to the NICU, or on their Apgar scores (a standard measure of breathing, heart rate and other health indicators done right after birth).Dr. Erika Werner is division director online zithromax prescription of maternal-fetal medicine at Women &. Infants Hospital of Rhode Island, in Providence.She said that a decrease in online zithromax prescription fetal heart rate is sometimes related to lack of oxygen. So "there was biologic plausibility that if you give mom oxygen, it will get to the fetus," Werner said."The problem is, many things that have biologic plausibility turn out to not actually improve outcomes," she added.According to Werner, it's still possible there's some benefit from the approach.

Rarer problems were not assessed in these trials."To determine if supplemental online zithromax prescription oxygen improves rare outcomes like neonatal seizures, you would need much larger studies," Werner said. "Ideally, children would also be followed for several years to identify differences in longer-term outcomes, like cerebral palsy."It's not clear why, based on studies so far, that supplemental oxygen hasn't benefited newborns. But one issue, online zithromax prescription Raghuraman said, is that doctors don't fully understand all the causes of fetal heart rate abnormalities.Still, she said, there are other ways to manage those heart rate problems, short of rushing to do a C-section. Changing the mother's position and giving IV fluids are common tactics.Raghuraman said that at the hospital where she delivers babies, Barnes-Jewish Hospital, they have become more judicious about giving supplemental online zithromax prescription oxygen.

SLIDESHOW Conception. The Amazing Journey from Egg to Embryo See Slideshow More research is needed to see whether there could be any harms from giving women prolonged oxygen online zithromax prescription during labor, she said.More informationThe nonprofit initiative Choosing Wisely has more on fetal heart rate monitoring.SOURCES. Nandini Raghuraman, MD, MS, assistant professor, obstetrics and gynecology, Washington University School of Medicine, St online zithromax prescription. Louis.

Erika Werner, MD, MS, division director, maternal-fetal medicine, Women online zithromax prescription &. Infants Hospital of Rhode Island, and associate professor, obstetrics and gynecology, Alpert Medical School of Brown University, Providence, R.I.. JAMA Pediatrics, Jan. 4, 2021, onlineCopyright © 2020 HealthDay.

What is Zithromax?

AZITHROMYCIN is a macrolide antibiotic that interferes with the growth of bacterial cells. It is used to treat bacterial s in many different parts of the body. Azithromycin also treats sexually transmitted vaginal or urinary tract s caused by chlamydia. It will not work for colds, flu, or other zithromax s.

Zithromax a penicillin

How to http://facummings.com/?p=1 cite this article:Singh OP zithromax a penicillin. Mental health in diverse India. Need for zithromax a penicillin advocacy. Indian J Psychiatry 2021;63:315-6”Unity in diversity” - That is the theme of India which we are quite proud of.

We have diversity zithromax a penicillin in terms of geography – From the Himalayas to the deserts to the seas. Every region has its own distinct culture and food. There are so many varieties of dress and language. There is huge difference between the states in terms of development, zithromax a penicillin attitude toward women, health infrastructure, child mortality, and other sociodemographic development indexes.

There is now ample evidence that sociocultural factors influence mental health. Compton and Shim[1] have described in their model of gene environment interaction how public policies and social norms act on the distribution of opportunity leading zithromax a penicillin to social inequality, exclusion, poor environment, discrimination, and unemployment. This in turn leads to reduced options, poor choices, and high-risk behavior. Combining genetic vulnerability and early brain insult with low access to health care leads to poor mental health, disease, and morbidity.When we come to the field of mental health, we find huge differences between different states zithromax a penicillin of India.

The prevalence of psychiatric disorders was markedly different while it was 5.8 and 5.1 for Assam and Uttar Pradesh at the lower end of the spectrum, it was 13.9 and 14.1 for Madhya Pradesh and Maharashtra at the higher end of the spectrum. There was also a huge difference between the rural areas and metros, particularly in terms of psychosis and bipolar disorders.[2] The difference was distinct not only in the prevalence but also in the type of psychiatric disorders. While the more developed southern states had higher prevalence of adult-onset zithromax a penicillin disorders such as depression and anxiety, the less developed northern states had more of childhood onset disorders. This may be due to lead toxicity, nutritional status, and perinatal issues.

Higher rates of depression and zithromax a penicillin anxiety were found in females. Apart from the genetic and hormonal factors, increase was attributed to gender discrimination, violence, sexual abuse, and adverse sociocultural norms. Marriage was found to be a negative prognostic indicator contrary to the zithromax a penicillin western norms.[3]Cultural influences on the presentation of psychiatric disorders are apparent. Being in recessive position in the family is one of the strongest predictors of psychiatric illnesses and psychosomatic disorders.

The presentation of depressive and anxiety disorders with more somatic symptoms results from inability to express due to unequal power equation in the family rather than the lack of expressions. Apart from culture bound syndromes, the role of cultural idioms of distress in manifestations of psychiatric symptoms is well acknowledged.When we look into suicide data, suicide in lower zithromax a penicillin socioeconomic strata (annual income <1 lakh) was 92,083, in annual income group of 1–5 lakhs, it was 41,197, and in higher income group, it was 4726. Among those who committed suicide, 67% were young adults, 34% had family problems, 23.4% of suicides occurred in daily laborers, 10.1% in unemployed persons, and 7.4% in farmers.[4]While there are huge regional differences in mental health issues, the challenges in mental health in India remain stigma reduction, conducting research on efficacy of early intervention, reaching the unreached, gender sensitive services, making quality mental healthcare accessible and available, suicide prevention, reduction of substance abuse, implementing insurance for mental health and reducing out-of-pocket expense, and finally, improving care for homeless mentally ill. All these require sustained advocacy aimed at promoting zithromax a penicillin rights of mentally ill persons and reducing stigma and discriminations.

It consists of various actions aimed at changing the attitudinal barriers in achieving positive mental health outcomes in the general population. Psychiatrists as Mental Health Advocates There is a debate whether psychiatrists who are overburdened with clinical care could or should be involved in the advocacy activities which require skills in other areas, and sometimes, they find themselves at the receiving end of mental health advocates. We must be involved and pathways should be to build technical evidence for mapping out the problem, cost-effective interventions, and their efficacy.Advocacy can be done at institutional level, organizational level, and individual zithromax a penicillin level. There has been huge work done in this regard at institution level.

Important research work done in this regard includes the National Mental Health Survey, National Survey on Extent and Pattern of Substance Use in India, Global Burden of Diseases in Indian States, and Trajectory zithromax a penicillin of Brain Development. Other activities include improving the infrastructure of mental hospitals, telepsychiatry services, provision of free drugs, providing training to increase the number of service providers. Similarly, at organizational level, the Indian Psychiatric Society (IPS) has filed a case for lacunae in zithromax a penicillin Mental Health-care Act, 2017. Another case filed by the IPS lead to change of name of the film from “Mental Hai Kya” to “Judgemental Hai Kya.” In LGBT issue, the IPS statement was quoted in the final judgement on the decriminalization of homosexuality.

The IPS has also started helplines at different levels and media interactions. The Indian Journal of Psychiatry has also come out with editorials highlighting the need of care of marginalized population such as migrant zithromax a penicillin laborers and persons with dementia. At an individual level, we can be involved in ensuring quality treatment, respecting dignity and rights of the patient, sensitization of staff, working with patients and caregivers to plan services, and being involved locally in media and public awareness activities.The recent experience of Brazil is an eye opener where suicide reduction resulted from direct cash transfer pointing at the role of economic decision in suicide.[5] In India where economic inequality is increasing, male-to-female ratio is abysmal in some states (877 in Haryana to 1034 in Kerala), our actions should be sensitive to this regional variation. When the zithromax a penicillin enemy is economic inequality, our weapon is research highlighting the role of these factors on mental health.

References 1.Compton MT, Shim RS. The social determinants of mental health zithromax a penicillin. Focus 2015;13:419-25. 2.Gururaj G, Varghese M, Benegal V, Rao GN, Pathak K, Singh LK, et al.

National Mental zithromax a penicillin Health Survey of India, 2015-16. Prevalence, Patterns and Outcomes. Bengaluru. National Institute of Mental Health and Neuro Sciences, NIMHANS Publication No.

129. 2016. 3.Sagar R, Dandona R, Gururaj G, Dhaliwal RS, Singh A, Ferrari A, et al. The burden of mental disorders across the states of India.

The Global Burden of Disease Study 1990–2017. Lancet Psychiatry 2020;7:148-61. 4.National Crime Records Bureau, 2019. Accidental Deaths and Suicides in India.

2019. Available from. Https://ncrb.gov.in. [Last accessed on 2021 Jun 24].

5.Machado DB, Rasella D, dos Santos DN. Impact of income inequality and other social determinants on suicide rate in Brazil. PLoS One 2015;10:e0124934. Correspondence Address:Om Prakash SinghDepartment of Psychiatry, WBMES, Kolkata, West Bengal.

AMRI Hospitals, Kolkata, West Bengal IndiaSource of Support. None, Conflict of Interest. NoneDOI. 10.4103/indianjpsychiatry.indianjpsychiatry_635_21Abstract Sexual health, an essential component of individual's health, is influenced by many complex issues including sexual behavior, attitudes, societal, and cultural factors on the one hand and while on the other hand, biological aspects, genetic predisposition, and associated mental and physical illnesses.

Sexual health is a neglected area, even though it influences mortality, morbidity, and disability. Dhat syndrome (DS), the term coined by Dr. N. N.

Wig, has been at the forefront of advancements in understanding and misunderstanding. The concept of DS is still evolving being treated as a culture-bound syndrome in the past to a syndrome of depression and treated as “a culturally determined idiom of distress.” It is bound with myths, fallacies, prejudices, secrecy, exaggeration, and value-laden judgments. Although it has been reported from many countries, much of the literature has emanated from Asia, that too mainly from India. The research in India has ranged from the study of a few cases in the past to recent national multicentric studies concerning phenomenology and beliefs of patients.

The epidemiological studies have ranged from being hospital-based to population-based studies in rural and urban settings. There are studies on the management of individual cases by resolving sexual myths, relaxation exercises, supportive psychotherapy, anxiolytics, and antidepressants to broader and deeper research concerning cognitive behavior therapy. The presentation looks into DS as a model case highlighting the importance of exploring sexual health concerns in the Indian population in general and in particular need to reconsider DS in the light of the newly available literature. It makes a fervent appeal for the inclusion of DS in the mainstream diagnostic categories in the upcoming revisions of the diagnostic manuals which can pave the way for a better understanding and management of DS and sexual problems.Keywords.

Culture-bound syndrome, Dhat syndrome, Dhat syndrome management, Dhat syndrome prevalence, psychiatric comorbidity, sexual disordersHow to cite this article:Sathyanarayana Rao T S. History and mystery of Dhat syndrome. A critical look at the current understanding and future directions. Indian J Psychiatry 2021;63:317-25 Introduction Mr.

President, Chairpersons, my respected teachers and seniors, my professional colleagues and friends, ladies and gentlemen:I deem it a proud privilege and pleasure to receive and to deliver DLN Murti Rao Oration Award for 2020. I am humbled at this great honor and remain grateful to the Indian Psychiatric Society (IPS) in general and the awards committee in particular. I would like to begin my presentation with my homage to Professor DLN Murti Rao, who was a Doyen of Psychiatry.[1] I have a special connection to the name as Dr. Doddaballapura Laxmi Narasimha Murti Rao, apart from a family name, obtained his medical degree from Mysore Medical College, Mysuru, India, the same city where I have served last 33 years in JSS Medical College and JSS Academy of Higher Education and Research.

His name carries the reverence in the corridors of the current National Institute of Mental Health and Neuro Sciences (NIMHANS) at Bangalore which was All India Institute of Mental Health, when he served as Head and the Medical Superintendent. Another coincidence was his untimely demise in 1962, the same year another Doyen Dr. Wig[2],[3] published the article on a common but peculiar syndrome in the Indian context and gave the name Dhat syndrome (DS). Even though Dr.

Wig is no more, his legacy of profound contribution to psychiatry and psychiatric education in general and service to the society and Mental Health, in particular, is well documented. His keen observation and study culminated in synthesizing many aspects and developments in DS.I would also like to place on record my humble pranams to my teachers from Christian Medical College, Vellore – Dr. Abraham Varghese, the first Editor of the Indian Journal of Psychological Medicine and Dr. K.

Kuruvilla, Past Editor of Indian Journal of Psychiatry whose legacies I carried forward for both the journals. I must place on record that my journey in the field of Sexual Medicine was sown by Dr. K. Kuruvilla and subsequent influence of Dr.

Ajit Avasthi from Postgraduate Institute of Medical Education and Research from Chandigarh as my role model in the field. There are many more who have shaped and nurtured my interest in the field of sex and sexuality.The term “Dhat” was taken from the Sanskrit language, which is an important word “Dhatu” and has known several meanings such as “metal,” a “medicinal constituent,” which can be considered as most powerful material within the human body.[4] The Dhat disorder is mainly known for “loss of semen”, and the DS is a well-known “culture-bound syndrome (CBS).”[4] The DS leads to several psychosexual disorders such as physical weakness, tiredness, anxiety, appetite loss, and guilt related to the loss of semen through nocturnal emission, in urine and by masturbation as mentioned in many studies.[4],[5],[6] Conventionally, Charaka Samhita mentions “waste of bodily humors” being linked to the “loss of Dhatus.”[5] Semen has even been mentioned by Aristotle as a “soul substance” and weakness associated with its loss.[6] This has led to a plethora of beliefs about “food-blood-semen” relationship where the loss of semen is considered to reduce vitality, potency, and psychophysiological strength. People have variously attributed DS to excessive masturbation, premarital sex, promiscuity, and nocturnal emissions. Several past studies have emphasized that CBS leads to “anxiety for loss of semen” is not only prevalent in the Indian subcontinent but also a global phenomenon.[7],[8],[9],[10],[11],[12],[13],[14],[15],[16],[17],[18],[19],[20]It is important to note that DS manifestation and the psychosexual features are based on the impact of culture, demographic profiles, and the socioeconomic status of the patients.[7],[8],[9],[10],[11],[12],[13],[14],[15],[16],[17],[18],[19],[20] According to Leff,[21] culture depends upon norms, values, and myths, based on a specific area, and is also shared by the indigenous individuals of that area.

Tiwari et al.[22] mentioned in their study that “culture is closely associated with mental disorders through social and psychological activities.” With this background, the paper attempts to highlight the multidimensional construct of DS for a better clinical understanding in routine practice. Dhat Syndrome. A Separate Entity or a “Cultural Variant” of Depression Even though DS has been studied for years now, a consensus on the definition is yet to be achieved. It has mostly been conceptualized as a multidimensional psychosomatic entity consisting of anxiety, depressive, somatic, and sexual phenomenology.

Most importantly, abnormal and erroneous attributions are considered to be responsible for the genesis of DS. The most important debate is, however, related to the nosological status of DS. Although considered to a CBS unique to India, it has also been increasingly reported in China, Europe, Japan, Malaysia, Russia, and America.[11] The consistency and validity of its diagnosis have been consistently debated, and one of the most vital questions that emerged was. Can there be another way to conceptualize DS?.

There is no single answer to that question. Apart from an independent entity, the diagnostic validity of which has been limited in longitudinal studies,[23] it has also been a cultural variant of depressive and somatization disorders. Mumford[11] in his study of Asian patients with DS found a significant association with depressed mood, anxiety, and fatigue. Around the same time, another study by Chadha[24] reported comorbidities in DS at a rate of 50%, 32%, and 18% related to depression, somatoform disorders, and anxiety, respectively.

Depression continued to be reported as the most common association of DS in many studies.[25],[26] This “cause-effect” dilemma can never be fully resolved. Whether “loss of semen” and the cultural attributions to it leads to the affective symptoms or whether low mood and neuroticism can lead to DS in appropriate cultural context are two sides of the argument. However, the cognitive biases resulting in the attributional errors of DS and the subsequently maintained attitudes with relation to sexuality can be explained by the depressive cognitions and concepts of learned helplessness. Balhara[27] has argued that since DS is not really culture specific as thought of earlier, it should not be solely categorized as a functional somatic syndrome, as that can have detrimental effects on its understanding and management.

He also mentions that the underlying “emotional distress and cultural contexts” are not unique to DS but can be related to any psychiatric syndrome for that matter. On the contrary, other researchers have warned that subsuming DS and other CBS under the broader rubric of “mood disorders” can lead to neglect and reductionism in disorder like DS that can have unique cultural connotations.[28] Over the years, there have been multiple propositions to relook and relabel CBS like DS. Considering it as a variant of depression or somatization can make it a “cultural phenotype” of these disorders in certain regions, thus making it easier for the classificatory systems. This dichotomous debate seems never-ending, but clinically, it is always better to err on over-diagnosing and over-treating depression and anxiety in DS, which can improve the well-being of the distressed patients.

Why Discuss Dhat Syndrome. Implications in Clinical Practice DS might occur independently or associated with multiple comorbidities. It has been a widely recognized clinical condition in various parts of the world, though considered specific to the Indian subcontinent. The presentation can often be polymorphic with symptom clusters of affective, somatic, behavioral, and cognitive manifestations.[29] Being common in rural areas, the first contacts of the patients are frequently traditional faith healers and less often, the general practitioners.

A psychiatric referral occurs much later, if at all. This leads to underdetection and faulty treatments, which can strengthen the already existing misattributions and misinformation responsible for maintaining the disorder. Furthermore, depression and sexual dysfunction can be the important comorbidities that if untreated, lead to significant psychosocial dysfunction and impaired quality of life.[30] Besides many patients of DS believe that their symptoms are due to failure of interpersonal relationships, s, and heredity, which might cause early death and infertility. This contributes to the vicious cycle of fear and panic.[31] Doctor shopping is another challenge and failure to detect and address the concern of DS might lead to dropping out from the care.[15] Rao[17] in their epidemiological study reported 12.5% prevalence in the general population, with 20.5% and 50% suffering from comorbid depression and sexual disorders.

The authors stressed upon the importance of early detection of DS for the psychosexual and social well-being. Most importantly, the multidimensional presentation of DS can at certain times be a facade overshadowing underlying neurotic disorders (anxiety, depression, somatoform, hypochondriasis, and phobias), obsessive-compulsive spectrum disorders and body dysmorphic disorders, delusional disorders, sexual disorders (premature ejaculation and erectile dysfunction) and infectious disorders (urinary tract s, sexually transmitted diseases), and even stress-related manifestations in otherwise healthy individuals.[4],[14],[15] This significant overlap of symptomatology, increased prevalence, and marked comorbidity make it all the more important for physicians to make sense out of the construct of DS. That can facilitate prompt detection and management of DS in routine clinical practice.In an earlier review study, it was observed that few studies are undertaken to update the research works from published articles as an updated review, systemic review, world literature review, etc., on DS and its management approach.[29],[32],[33],[34],[35] The present paper attempts to compile the evidence till date on DS related to its nosology, critique, manifestations, and management plan. The various empirical studies on DS all over the world will be briefly discussed along with the implications and importance of the syndrome.

The Construct of Dhat Syndrome. Summary of Current Evidence DS is a well-known CBS, which is defined as undue concern about the weakening effects after the passage of semen in urine or through nocturnal emission that has been stated by the International Statistical Classification of Diseases and Related Health Problems (ICD-10).[36] It is also known as “semen loss syndrome” by Shakya,[20] which is prevalent mainly in the Indian subcontinent[37] and has also been reported in the South-Eastern and western population.[15],[16],[20],[32],[38],[39],[40],[41] Individuals with “semen loss anxiety” suffer from a myriad of psychosexual symptoms, which have been attributed to “loss of vital essence through semen” (common in South Asia).[7],[15],[16],[17],[32],[37],[41],[42],[43] The various studies related to attributes of DS and their findings are summarized further.Prakash et al.[5] studied 100 DS patients through 139 symptoms of the Associated Symptoms Scale. They studied sociodemographic profile, Hamilton Depression Rating Scale, Hamilton Anxiety Rating Scale, Mini-International Neuropsychiatric Interview, and Postgraduate Institute Neuroticism Scale. The study found a wide range of physical, anxiety, depression, sexual, and cognitive symptoms.

Most commonly associated symptoms were found as per score ≥1. This study reported several parameters such as the “sense of being unhealthy” (99%), worry (99%), feeling “no improvement despite treatment” (97%), tension (97%), tiredness (95%), fatigue (95%), weakness (95%), and anxiety (95%). The common sexual disorders were observed as loss of masculinity (83%), erectile dysfunction (54%), and premature ejaculation (53%). Majority of patients had faced mild or moderate level of symptoms in which 47% of the patients reported severe weakness.

Overall distress and dysfunction were observed as 64% and 81% in the studied subjects, respectively.A study in Taiwan involved 87 participants from a Urology clinic. Most of them have sexual neurosis (Shen-K'uei syndrome).[7] More than one-third of the patients belonged to lower social class and symptoms of depression, somatization, anxiety, masturbation, and nocturnal emissions. Other bodily complaints as reported were sleep disturbances, fatigue, dizziness, backache, and weakness. Nearly 80% of them considered that all of their problems were due to masturbatory practices.De Silva and Dissanayake[8] investigated several manifestations on semen loss syndrome in the psychiatric clinic of Colombo General Hospital, Sri Lanka.

Beliefs regarding effects of semen loss and help-seeking sought for DS were explored. 38 patients were studied after psychiatrically ill individuals and those with organic disorders were excluded. Duration of semen loss varied from 1 to 20 years. Every participant reported excessive loss of semen and was preoccupied with it.

The common forms of semen loss were through nocturnal emission, masturbation, urinary loss, and through sexual activities. Most of them reported multiple modes of semen loss. Masturbatory frequency and that of nocturnal emissions varied significantly. More than half of the patients reported all types of complaints (psychological, sexual, somatic, and genital).In the study by Chadda and Ahuja,[9] 52 psychiatric patients (mostly adolescents and young adults) complained of passing “Dhat” in urine.

They were assessed for a period of 6 months. More than 80% of them complained of body weakness, aches, and pains. More than 50% of the patients suffered from depression and anxiety. All the participants felt that their symptoms were due to loss of “dhat” in urine, attributed to excessive masturbation, extramarital and premarital sex.

Half of those who faced sexual dysfunctions attributed them to semen loss.Mumford[11] proposed a controversial explanation of DS arguing that it might be a part of other psychiatric disorders, like depression. A total of 1000 literate patients were recruited from a medical outdoor in a public sector hospital in Lahore, Pakistan. About 600 educated patients were included as per Bradford Somatic Inventory (BSI). Men with DS reported greater symptoms on BSI than those without DS.

60 psychiatric patients were also recruited from the same hospital and diagnosed using Diagnostic and Statistical Manual (DSM)-III-R. Among them, 33% of the patients qualified for “Dhat” items on BSI. The symptoms persisted for more than 15 days. It was observed that symptoms of DS highly correlated with BSI items, namely erectile dysfunction, burning sensation during urination, fatigue, energy loss, and weakness.

This comparative study indicated that patients with DS suffered more from depressive disorders than without DS and the age group affected by DS was mostly the young.Grover et al.[15] conducted a study on 780 male patients aged >16 years in five centers (Chandigarh, Jaipur, Faridkot, Mewat, and New Delhi) of Northern India, 4 centers (2 from Kolkata, 1 each in Kalyani and Bhubaneswar) of Eastern India, 2 centers (Agra and Lucknow) of Central India, 2 centers (Ahmedabad and Wardha) of Western India, and 2 centers of Southern India (both located at Mysore) spread across the country by using DS questionnaire. Nearly one-third of the patients were passing “Dhat” multiple times a week. Among them, nearly 60% passed almost a spoonful of “Dhat” each time during a loss. This work on sexual disorders reported that the passage of “Dhat” was mostly attributed to masturbation (55.1%), dreams on sex (47.3%), sexual desire (42.8%), and high energy foods consumption (36.7%).

Mostly, the participants experienced passage of Dhat as “night falls” (60.1%) and “while passing stools” (59.5%). About 75.6% showed weakness in sexual ability as a common consequence of the “loss of Dhat.” The associated symptoms were depression, hopelessness, feeling low, decreased energy levels, weakness, and lack of pleasure. Erectile problems and premature ejaculation were also present.Rao[17] in his first epidemiological study done in Karnataka, India, showed the prevalence rate of DS in general male population as 12.5%. It was found that 57.5% were suffering either from comorbid depression or anxiety disorders.

The prevalence of psychiatric and sexual disorders was about three times higher with DS compared to non-DS subjects. One-third of the cases (32.8%) had no comorbidity in hospital (urban). One-fifth (20.5%) and 50% subjects (51.3%) had comorbid depressive disorders and sexual dysfunction. The psychosexual symptoms were found among 113 patients who had DS.

The most common psychological symptoms reported by the subjects with DS were low self-esteem (100%), loss of interest in any activity (95.60%), feeling of guilt (92.00%), and decreased social interaction (90.30%). In case of sexual disorders, beliefs were held commonly about testes becoming smaller (92.00%), thinness of semen (86.70%), decreased sexual capabilities (83.20%), and tilting of penis (70.80%).Shakya[20] studied a clinicodemographic profile of DS patients in psychiatry outpatient clinic of B. P. Koirala Institute of Health Sciences, Dharan, Nepal.

A total of 50 subjects were included in this study, and the psychiatric diagnoses as well as comorbidities were investigated as per the ICD-10 criteria. Among the subjects, most of the cases had symptoms of depression and anxiety, and all the subjects were worried about semen loss. Somehow these subjects had heard or read that semen loss or masturbation is unhealthy practice. The view of participants was that semen is very “precious,” needs preservation, and masturbation is a malpractice.

Beside DS, two-thirds of the subjects had comorbid depression.In another Indian study, Chadda et al.[24] compared patients with DS with those affected with neurotic/depressive disorders. Among 100 patients, 50%, 32%, and 18% reported depression, somatic problems, and anxiety, respectively. The authors argued that cases of DS have similar symptom dimensions as mood and anxiety disorders.Dhikav et al.[31] examined prevalence and management depression comorbid with DS. DSM-IV and Hamilton Depression Rating Scale were used for assessments.

About 66% of the patients met the DSM-IV diagnostic criteria of depression. They concluded that depression was a frequent comorbidity in DS patients.In a study by Perme et al.[37] from South India that included 32 DS patients, the control group consisted of 33 people from the same clinic without DS, depression, and anxiety. The researchers followed the guidelines of Bhatia and Malik's for the assessment of primary complaints of semen loss through “nocturnal emissions, masturbation, sexual intercourse, and passing of semen before and after urine.” The assessment was done based on several indices, namely “Somatization Screening Index, Illness Behavior Questionnaire, Somatosensory Amplification Scale, Whitley Index, and Revised Chalder Fatigue Scale.” Several complaints such as somatic complaints, hypochondriacal beliefs, and fatigue were observed to be significantly higher among patients with DS compared to the control group.A study conducted in South Hall (an industrial area in the borough of Middlesex, London) included Indian and Pakistani immigrants. Young men living separately from their wives reported promiscuity, some being infected with gonorrhea and syphilis.

Like other studies, nocturnal emission, weakness, and impotency were the other reported complaints. Semen was considered to be responsible for strength and vigor by most patients. Compared to the sexual problems of Indians, the British residents complained of pelvic issues and backache.In another work, Bhatia et al.[42] undertook a study on culture-bound syndromes and reported that 76.7% of the sample had DS followed by possession syndrome and Koro (a genital-related anxiety among males in South-East Asia). Priyadarshi and Verma[43] performed a study in Urology Department of S M S Hospital, Jaipur, India.

They conducted the study among 110 male patients who complained of DS and majority of them were living alone (54.5%) or in nuclear family (30%) as compared to joint family. Furthermore, 60% of them reported of never having experienced sex.Nakra et al.[44] investigated incidence and clinical features of 150 consecutive patients who presented with potency complaints in their clinic. Clinical assessments were done apart from detailed sexual history. The patients were 15–50 years of age, educated up to mid-school and mostly from a rural background.

Most of them were married and reported premarital sexual practices, while nearly 67% of them practiced masturbation from early age. There was significant guilt associated with nocturnal emissions and masturbation. Nearly 27% of the cases reported DS-like symptoms attributing their health problems to semen loss.Behere and Nataraj[45] reported that majority of the patients with DS presented with comorbidities of physical weakness, anxiety, headache, sad mood, loss of appetite, impotence, and premature ejaculation. The authors stated that DS in India is a symptom complex commonly found in younger age groups (16–23 years).

The study subjects presented with complaints of whitish discharge in urine and believed that the loss of semen through masturbation was the reason for DS and weakness.Singh et al.[46] studied 50 cases with DS and sexual problems (premature ejaculation and impotence) from Punjab, India, after exclusion of those who were psychiatrically ill. It was assumed in the study that semen loss is considered synonymous to “loss of something precious”, hence its loss would be associated with low mood and grief. Impotency (24%), premature ejaculation (14%), and “Dhat” in urine (40%) were the common complaints observed. Patients reported variety of symptoms including anxiety, depression, appetite loss, sleep problems, bodily pains, and headache.

More than half of the patients were independently diagnosed with depression, and hence, the authors argued that DS may be a manifestation of depressive disorders.Bhatia and Malik[47] reported that the most common complaints associated with DS were physical weakness, fatigue and palpitation, insomnia, sad mood, headache, guilt feeling and suicidal ideation, impotence, and premature ejaculation. Psychiatric disorders were found in 69% of the patients, out of which the most common was depression followed by anxiety, psychosis, and phobia. About 15% of the patients were found to have premature ejaculation and 8% had impotence.Bhatia et al.[48] examined several biological variables of DS after enrolment of 40 patients in a psychosexual clinic in Delhi. Patients had a history of impotence, premature ejaculation, and loss of semen (after exclusion of substance abuse and other psychiatric disorders).

Twenty years was the mean age of onset and semen loss was mainly through masturbation and sexual intercourse. 67.5% and 75% of them reported sexual disorders and psychiatric comorbidity while 25%, 12.5%, and 37.5% were recorded to suffer from ejaculatory impotence, premature ejaculation, and depression (with anxiety), respectively.Bhatia[49] conducted a study on CBS among 60 patients attending psychiatric outdoor in a teaching hospital. The study revealed that among all patients with CBSs, DS was the most common (76.7%) followed by possession syndrome (13.3%) and Koro (5%). Hypochondriasis, sexually transmitted diseases, and depression were the associated comorbidities.

Morrone et al.[50] studied 18 male patients with DS in the Dermatology department who were from Bangladesh and India. The symptoms observed were mainly fatigue and nonspecific somatic symptoms. DS patients manifested several symptoms in psychosocial, religious, somatic, and other domains. The reasons provided by the patients for semen loss were urinary loss, nocturnal emission, and masturbation.

Dhat Syndrome. The Epidemiology The typical demographic profile of a DS patient has been reported to be a less educated, young male from lower socioeconomic status and usually from rural areas. In the earlier Indian studies by Carstairs,[51],[52],[53] it was observed that majority of the cases (52%–66.7%) were from rural areas, belonged to “conservative families and posed rigid views about sex” (69%-73%). De Silva and Dissanayake[8] in their study on semen loss syndrome reported the average age of onset of DS to be 25 years with most of them from lower-middle socioeconomic class.

Chadda and Ahuja[9] studied young psychiatric patients who complained of semen loss. They were mainly manual laborers, farmers, and clerks from low socioeconomic status. More than half were married and mostly uneducated. Khan[13] studied DS patients in Pakistan and reported that majority of the patients visited Hakims (50%) and Homeopaths (24%) for treatment.

The age range was wide between 12 and 65 years with an average age of 24 years. Among those studied, majority were unmarried (75%), literacy was up to matriculation and they belonged to lower socioeconomic class. Grover et al.[15] in their study of 780 male subjects showed the average age of onset to be 28.14 years and the age ranged between 21 and 30 years (55.3%). The subjects were single or unmarried (51.0%) and married (46.7%).

About 23.5% of the subjects had graduated and most were unemployed (73.5%). Majority of subjects were lower-middle class (34%) and had lower incomes. Rao[17] studied 907 subjects, in which majority were from 18 to 30 years (44.5%). About 45.80% of the study subjects were illiterates and very few had completed postgraduation.

The subjects were both married and single. Majority of the subjects were residing in nuclear family (61.30%) and only 0.30% subjects were residing alone. Most of the patients did not have comorbid addictive disorders. The subjects were mainly engaged in agriculture (43.40%).

Majority of the subjects were from lower middle and upper lower socioeconomic class.Shakya[20] had studied the sociodemographic profile of 50 patients with DS. The average age of the studied patients was 25.4 years. The age ranges in decreasing order of frequency were 16–20 years (34%) followed by 21–25 years (28%), greater than 30 years (26%), 26–30 years (10%), and 11–15 years (2%). Further, the subjects were mostly students (50%) and rest were in service (26%), farmers (14%), laborers (6%), and business (4%), respectively.

Dhikav et al.[31] conducted a study on 30 patients who had attended the Psychiatry Outpatient Clinic of a tertiary care hospital with complaints of frequently passing semen in urine. In the studied patients, the age ranged between 20 and 40 years with an average age of 29 years and average age of onset of 19 years. The average duration of illness was that of 11 months. Most of the studied patients were unmarried (64.2%) and educated till middle or high school (70%).

Priyadarshi and Verma[43] performed a study in 110 male patients with DS. The average age of the patients was 23.53 years and it ranged between 15 and 68 years. The most affected age group of patients was of 18–25 years, which comprised about 60% of patients. On the other hand, about 25% ranged between 25 and 35 years, 10% were lesser than 18 years of age, and 5.5% patients were aged >35 years.

Higher percentage of the patients were unmarried (70%). Interestingly, high prevalence of DS was found in educated patients and about 50% of patients were graduate or above but most of the patients were either unemployed or student (49.1%). About 55% and 24.5% patients showed monthly family income of <10,000 and 5000 Indian Rupees (INR), respectively. Two-third patients belonged to rural areas of residence.

Behere and Nataraj[45] found majority of the patients with DS (68%) to be between 16 and 25 years age. About 52% patients were married while 48% were unmarried and from lower socioeconomic strata. The duration of DS symptoms varied widely. Singh[46] studied patients those who reported with DS, impotence, and premature ejaculation and reported the average age of the affected to be 21.8 years with a younger age of onset.

Only a few patients received higher education. Bhatia and Malik[47] as mentioned earlier reported that age at the time of onset of DS ranged from 16 to 24 years. More than half of them were single. It was observed that most patients had some territorial education (91.67%) but few (8.33%) had postgraduate education or professional training.

Finally, Bhatia et al.[48] studied cases of sexual dysfunctions and reported an average age of 21.6 years among the affected, majority being unmarried (80%). Most of those who had comorbid DS symptoms received minimal formal education. Management. A Multimodal Approach As mentioned before, individuals affected with DS often seek initial treatment with traditional healers, practitioners of alternative medicine, and local quacks.

As a consequence, varied treatment strategies have been popularized. Dietary supplements, protein and iron-rich diet, Vitamin B and C-complexes, antibiotics, multivitamin injections, herbal “supplements,” etc., have all been used in the treatment though scientific evidence related to them is sparse.[33] Frequent change of doctors, irregular compliance to treatment, and high dropout from health care are the major challenges, as the attributional beliefs toward DS persist in the majority even after repeated reassurance.[54] A multidisciplinary approach (involving psychiatrists, clinical psychologists, psychiatric social workers) is recommended and close liaison with the general physicians, the Ayurveda, Yoga, Unani, Siddha, Homeopathy practitioners, dermatologists, venereologists, and neurologists often help. The role of faith healers and local counselors is vital, and it is important to integrate them into the care of DS patients, rather than side-tracking them from the system. Community awareness needs to be increased especially in primary health care for early detection and appropriate referrals.

Follow-up data show two-thirds of patients affected with DS recovering with psychoeducation and low-dose sedatives.[45] Bhatia[49] studied 60 cases of DS and reported better response to anti-anxiety and antidepressant medications compared to psychotherapy alone. Classically, the correction of attributional biases through empathy, reflective, and nonjudgmental approaches has been proposed.[38] Over the years, sex education, psychotherapy, psychoeducation, relaxation techniques, and medications have been advocated in the management of DS.[9],[55] In psychotherapy, cognitive behavioral and brief solution-focused approaches are useful to target the dysfunctional assumptions and beliefs in DS. The role of sex education is vital involving the basic understanding of sexual anatomy and physiology of sexuality. This needs to be tailored to the local terminology and beliefs.

Biofeedback has also been proposed as a treatment modality.[4] Individual stress factors that might have precipitated DS need to be addressed. A detailed outline of assessment, evaluation, and management of DS is beyond the scope of this article and has already been reported in the IPS Clinical Practice Guidelines.[56] The readers are referred to these important guidelines for a comprehensive read on management. Probably, the most important factor is to understand and resolve the sociocultural contexts in the genesis of DS in each individual. Adequate debunking of the myths related to sexuality and culturally appropriate sexual education is vital both for the prevention and treatment of DS.[56] Adequate treatment of comorbidities such as depression and anxiety often helps in reduction of symptoms, more so when the DS is considered to be a manifestation of the same.

Future of Dhat Syndrome. The Way Forward Classifications in psychiatry have always been fraught with debates and discussion such as categorical versus dimensional, biological versus evolutionary. CBS like DS forms a major area of this nosological controversy. Longitudinal stability of a diagnosis is considered to be an important part of its independent categorization.

Sameer et al.[23] followed up DS patients for 6.0 ± 3.5 years and concluded that the “pure” variety of DS is not a stable diagnostic entity. The authors rather proposed DS as a variant of somatoform disorder, with cultural explanations. The right “place” for DS in classification systems has mostly been debated and theoretically fluctuant.[14] Sridhar et al.[57] mentioned the importance of reclassifying DS from a clinically, phenomenologically, psycho-pathologically, and diagnostically valid standpoint. Although both ICD and DSM have been culturally sensitive to classification, their approach to DS has been different.

While ICD-10 considers DS under “other nonpsychotic mental disorders” (F48), DSM-V mentions it only in appendix section as “cultural concepts of distress” not assigning the condition any particular number.[12],[58] Fundamental questions have actually been raised about its separate existence altogether,[35] which further puts its diagnostic position in doubt. As discussed in the earlier sections, an alternate hypothesization of DS is a cultural variant of depression, rather than a “true syndrome.”[27] Over decades, various schools of thought have considered DS either to be a global phenomenon or a cultural “idiom” of distress in specific geographical regions or a manifestation of other primary psychiatric disorders.[59] Qualitative studies in doctors have led to marked discordance in their opinion about the validity and classificatory area of DS.[60] The upcoming ICD-11 targets to pay more importance to cultural contexts for a valid and reliable classification. However, separating the phenomenological boundaries of diseases might lead to subsetting the cultural and contextual variants in broader rubrics.[61],[62] In that way, ICD-11 might propose alternate models for distinction of CBS like DS at nosological levels.[62] It is evident that various factors include socioeconomics, acceptability, and sustainability influence global classificatory systems, and this might influence the “niche” of DS in the near future. It will be interesting to see whether it retains its diagnostic independence or gets subsumed under the broader “narrative” of depression.

In any case, uniformity of diagnosing this culturally relevant yet distressing and highly prevalent condition will remain a major area related to psychiatric research and treatment. Conclusion DS is a multidimensional psychiatric “construct” which is equally interesting and controversial. Historically relevant and symptomatically mysterious, this disorder provides unique insights into cultural contexts of human behavior and the role of misattributions, beliefs, and misinformation in sexuality. Beyond the traditional debate about its “separate” existence, the high prevalence of DS, associated comorbidities, and resultant dysfunction make it relevant for emotional and psychosexual health.

It is also treatable, and hence, the detection, understanding, and awareness become vital to its management. This oration attempts a “bird's eye” view of this CBS taking into account a holistic perspective of the available evidence so far. The clinical manifestations, diagnostic and epidemiological attributes, management, and nosological controversies are highlighted to provide a comprehensive account of DS and its relevance to mental health. More systematic and mixed methods research are warranted to unravel the enigma of this controversial yet distressing psychiatric disorder.AcknowledgmentI sincerely thank Dr.

Debanjan Banerjee (Senior Resident, Department of Psychiatry, NIMHANS, Bangalore) for his constant selfless support, rich academic discourse, and continued collaboration that helped me condense years of research and ideas into this paper.Financial support and sponsorshipNil.Conflicts of interestThere are no conflicts of interest. References 1.2.3.Srinivasa Murthy R, Wig NN. A man ahead of his time. In.

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62.Sharan P, Keeley J. Cultural perspectives related to international classification of diseases-11. Indian J Soc Psychiatry 2018;34 Suppl S1:1-4. Correspondence Address:T S Sathyanarayana RaoDepartment of Psychiatry, JSS Medical College and Hospital, JSS Academy of Higher Education and Research, Mysore - 570 004, Karnataka IndiaSource of Support.

None, Conflict of Interest. NoneDOI. 10.4103/psychiatry.IndianJPsychiatry_791_20.

How to buy zithromax azithromycin cite online zithromax prescription this article:Singh OP. Mental health in diverse India. Need for online zithromax prescription advocacy. Indian J Psychiatry 2021;63:315-6”Unity in diversity” - That is the theme of India which we are quite proud of. We have diversity in terms of geography – From the Himalayas to the online zithromax prescription deserts to the seas.

Every region has its own distinct culture and food. There are so many varieties of dress and language. There is huge difference between the states in terms of development, attitude toward women, health infrastructure, child mortality, and online zithromax prescription other sociodemographic development indexes. There is now ample evidence that sociocultural factors influence mental health. Compton and Shim[1] have described in their model of gene environment interaction how public policies and social norms act on the distribution online zithromax prescription of opportunity leading to social inequality, exclusion, poor environment, discrimination, and unemployment.

This in turn leads to reduced options, poor choices, and high-risk behavior. Combining genetic vulnerability and early brain insult with low access to health online zithromax prescription care leads to poor mental health, disease, and morbidity.When we come to the field of mental health, we find huge differences between different states of India. The prevalence of psychiatric disorders was markedly different while it was 5.8 and 5.1 for Assam and Uttar Pradesh at the lower end of the spectrum, it was 13.9 and 14.1 for Madhya Pradesh and Maharashtra at the higher end of the spectrum. There was also a huge difference between the rural areas and metros, particularly in terms of psychosis and bipolar disorders.[2] The difference was distinct not only in the prevalence but also in the type of psychiatric disorders. While the more developed southern states online zithromax prescription had higher prevalence of adult-onset disorders such as depression and anxiety, the less developed northern states had more of childhood onset disorders.

This may be due to lead toxicity, nutritional status, and perinatal issues. Higher rates of depression and online zithromax prescription anxiety were found in females. Apart from the genetic and hormonal factors, increase was attributed to gender discrimination, violence, sexual abuse, and adverse sociocultural norms. Marriage was found to be a negative prognostic indicator contrary online zithromax prescription to the western norms.[3]Cultural influences on the presentation of psychiatric disorders are apparent. Being in recessive position in the family is one of the strongest predictors of psychiatric illnesses and psychosomatic disorders.

The presentation of depressive and anxiety disorders with more somatic symptoms results from inability to express due to unequal power equation in the family rather than the lack of expressions. Apart from culture bound syndromes, the role of cultural idioms of distress in manifestations of psychiatric symptoms is well acknowledged.When we look into suicide data, suicide in lower socioeconomic strata (annual income <1 lakh) was 92,083, in online zithromax prescription annual income group of 1–5 lakhs, it was 41,197, and in higher income group, it was 4726. Among those who committed suicide, 67% were young adults, 34% had family problems, 23.4% of suicides occurred in daily laborers, 10.1% in unemployed persons, and 7.4% in farmers.[4]While there are huge regional differences in mental health issues, the challenges in mental health in India remain stigma reduction, conducting research on efficacy of early intervention, reaching the unreached, gender sensitive services, making quality mental healthcare accessible and available, suicide prevention, reduction of substance abuse, implementing insurance for mental health and reducing out-of-pocket expense, and finally, improving care for homeless mentally ill. All these require sustained advocacy aimed at online zithromax prescription promoting rights of mentally ill persons and reducing stigma and discriminations. It consists of various actions aimed at changing the attitudinal barriers in achieving positive mental health outcomes in the general population.

Psychiatrists as Mental Health Advocates There is a debate whether psychiatrists who are overburdened with clinical care could or should be involved in the advocacy activities which require skills in other areas, and sometimes, they find themselves at the receiving end of mental health advocates. We must be involved and pathways should be to build technical evidence for mapping out the problem, cost-effective interventions, online zithromax prescription and their efficacy.Advocacy can be done at institutional level, organizational level, and individual level. There has been huge work done in this regard at institution level. Important research work done in this regard includes the National Mental Health Survey, National Survey on Extent and Pattern of Substance Use in India, Global Burden of Diseases in Indian States, and Trajectory of Brain Development online zithromax prescription. Other activities include improving the infrastructure of mental hospitals, telepsychiatry services, provision of free drugs, providing training to increase the number of service providers.

Similarly, at organizational level, the Indian online zithromax prescription Psychiatric Society (IPS) has filed a case for lacunae in Mental Health-care Act, 2017. Another case filed by the IPS lead to change of name of the film from “Mental Hai Kya” to “Judgemental Hai Kya.” In LGBT issue, the IPS statement was quoted in the final judgement on the decriminalization of homosexuality. The IPS has also started helplines at different levels and media interactions. The Indian Journal of Psychiatry has also come out with editorials highlighting the need of care of marginalized population such as migrant online zithromax prescription laborers and persons with dementia. At an individual level, we can be involved in ensuring quality treatment, respecting dignity and rights of the patient, sensitization of staff, working with patients and caregivers to plan services, and being involved locally in media and public awareness activities.The recent experience of Brazil is an eye opener where suicide reduction resulted from direct cash transfer pointing at the role of economic decision in suicide.[5] In India where economic inequality is increasing, male-to-female ratio is abysmal in some states (877 in Haryana to 1034 in Kerala), our actions should be sensitive to this regional variation.

When the enemy is economic inequality, our weapon is research highlighting online zithromax prescription the role of these factors on mental health. References 1.Compton MT, Shim RS. The social online zithromax prescription determinants of mental health. Focus 2015;13:419-25. 2.Gururaj G, Varghese M, Benegal V, Rao GN, Pathak K, Singh LK, et al.

National Mental online zithromax prescription Health Survey of India, 2015-16. Prevalence, Patterns and Outcomes. Bengaluru. National Institute of Mental Health and Neuro Sciences, NIMHANS Publication No. 129.

2016. 3.Sagar R, Dandona R, Gururaj G, Dhaliwal RS, Singh A, Ferrari A, et al. The burden of mental disorders across the states of India. The Global Burden of Disease Study 1990–2017. Lancet Psychiatry 2020;7:148-61.

4.National Crime Records Bureau, 2019. Accidental Deaths and Suicides in India. 2019. Available from. Https://ncrb.gov.in.

[Last accessed on 2021 Jun 24]. 5.Machado DB, Rasella D, dos Santos DN. Impact of income inequality and other social determinants on suicide rate in Brazil. PLoS One 2015;10:e0124934. Correspondence Address:Om Prakash SinghDepartment of Psychiatry, WBMES, Kolkata, West Bengal.

AMRI Hospitals, Kolkata, West Bengal IndiaSource of Support. None, Conflict of Interest. NoneDOI. 10.4103/indianjpsychiatry.indianjpsychiatry_635_21Abstract Sexual health, an essential component of individual's health, is influenced by many complex issues including sexual behavior, attitudes, societal, and cultural factors on the one hand and while on the other hand, biological aspects, genetic predisposition, and associated mental and physical illnesses. Sexual health is a neglected area, even though it influences mortality, morbidity, and disability.

Dhat syndrome (DS), the term coined by Dr. N. N. Wig, has been at the forefront of advancements in understanding and misunderstanding. The concept of DS is still evolving being treated as a culture-bound syndrome in the past to a syndrome of depression and treated as “a culturally determined idiom of distress.” It is bound with myths, fallacies, prejudices, secrecy, exaggeration, and value-laden judgments.

Although it has been reported from many countries, much of the literature has emanated from Asia, that too mainly from India. The research in India has ranged from the study of a few cases in the past to recent national multicentric studies concerning phenomenology and beliefs of patients. The epidemiological studies have ranged from being hospital-based to population-based studies in rural and urban settings. There are studies on the management of individual cases by resolving sexual myths, relaxation exercises, supportive psychotherapy, anxiolytics, and antidepressants to broader and deeper research concerning cognitive behavior therapy. The presentation looks into DS as a model case highlighting the importance of exploring sexual health concerns in the Indian population in general and in particular need to reconsider DS in the light of the newly available literature.

It makes a fervent appeal for the inclusion of DS in the mainstream diagnostic categories in the upcoming revisions of the diagnostic manuals which can pave the way for a better understanding and management of DS and sexual problems.Keywords. Culture-bound syndrome, Dhat syndrome, Dhat syndrome management, Dhat syndrome prevalence, psychiatric comorbidity, sexual disordersHow to cite this article:Sathyanarayana Rao T S. History and mystery of Dhat syndrome. A critical look at the current understanding and future directions. Indian J Psychiatry 2021;63:317-25 Introduction Mr.

President, Chairpersons, my respected teachers and seniors, my professional colleagues and friends, ladies and gentlemen:I deem it a proud privilege and pleasure to receive and to deliver DLN Murti Rao Oration Award for 2020. I am humbled at this great honor and remain grateful to the Indian Psychiatric Society (IPS) in general and the awards committee in particular. I would like to begin my presentation with my homage to Professor DLN Murti Rao, who was a Doyen of Psychiatry.[1] I have a special connection to the name as Dr. Doddaballapura Laxmi Narasimha Murti Rao, apart from a family name, obtained his medical degree from Mysore Medical College, Mysuru, India, the same city where I have served last 33 years in JSS Medical College and JSS Academy of Higher Education and Research. His name carries the reverence in the corridors of the current National Institute of Mental Health and Neuro Sciences (NIMHANS) at Bangalore which was All India Institute of Mental Health, when he served as Head and the Medical Superintendent.

Another coincidence was his untimely demise in 1962, the same year another Doyen Dr. Wig[2],[3] published the article on a common but peculiar syndrome in the Indian context and gave the name Dhat syndrome (DS). Even though Dr. Wig is no more, his legacy of profound contribution to psychiatry and psychiatric education in general and service to the society and Mental Health, in particular, is well documented. His keen observation and study culminated in synthesizing many aspects and developments in DS.I would also like to place on record my humble pranams to my teachers from Christian Medical College, Vellore – Dr.

Abraham Varghese, the first Editor of the Indian Journal of Psychological Medicine and Dr. K. Kuruvilla, Past Editor of Indian Journal of Psychiatry whose legacies I carried forward for both the journals. I must place on record that my journey in the field of Sexual Medicine was sown by Dr. K.

Kuruvilla and subsequent influence of Dr. Ajit Avasthi from Postgraduate Institute of Medical Education and Research from Chandigarh as my role model in the field. There are many more who have shaped and nurtured my interest in the field of sex and sexuality.The term “Dhat” was taken from the Sanskrit language, which is an important word “Dhatu” and has known several meanings such as “metal,” a “medicinal constituent,” which can be considered as most powerful material within the human body.[4] The Dhat disorder is mainly known for “loss of semen”, and the DS is a well-known “culture-bound syndrome (CBS).”[4] The DS leads to several psychosexual disorders such as physical weakness, tiredness, anxiety, appetite loss, and guilt related to the loss of semen through nocturnal emission, in urine and by masturbation as mentioned in many studies.[4],[5],[6] Conventionally, Charaka Samhita mentions “waste of bodily humors” being linked to the “loss of Dhatus.”[5] Semen has even been mentioned by Aristotle as a “soul substance” and weakness associated with its loss.[6] This has led to a plethora of beliefs about “food-blood-semen” relationship where the loss of semen is considered to reduce vitality, potency, and psychophysiological strength. People have variously attributed DS to excessive masturbation, premarital sex, promiscuity, and nocturnal emissions. Several past studies have emphasized that CBS leads to “anxiety for loss of semen” is not only prevalent in the Indian subcontinent but also a global phenomenon.[7],[8],[9],[10],[11],[12],[13],[14],[15],[16],[17],[18],[19],[20]It is important to note that DS manifestation and the psychosexual features are based on the impact of culture, demographic profiles, and the socioeconomic status of the patients.[7],[8],[9],[10],[11],[12],[13],[14],[15],[16],[17],[18],[19],[20] According to Leff,[21] culture depends upon norms, values, and myths, based on a specific area, and is also shared by the indigenous individuals of that area.

Tiwari et al.[22] mentioned in their study that “culture is closely associated with mental disorders through social and psychological activities.” With this background, the paper attempts to highlight the multidimensional construct of DS for a better clinical understanding in routine practice. Dhat Syndrome. A Separate Entity or a “Cultural Variant” of Depression Even though DS has been studied for years now, a consensus on the definition is yet to be achieved. It has mostly been conceptualized as a multidimensional psychosomatic entity consisting of anxiety, depressive, somatic, and sexual phenomenology. Most importantly, abnormal and erroneous attributions are considered to be responsible for the genesis of DS.

The most important debate is, however, related to the nosological status of DS. Although considered to a CBS unique to India, it has also been increasingly reported in China, Europe, Japan, Malaysia, Russia, and America.[11] The consistency and validity of its diagnosis have been consistently debated, and one of the most vital questions that emerged was. Can there be another way to conceptualize DS?. There is no single answer to that question. Apart from an independent entity, the diagnostic validity of which has been limited in longitudinal studies,[23] it has also been a cultural variant of depressive and somatization disorders.

Mumford[11] in his study of Asian patients with DS found a significant association with depressed mood, anxiety, and fatigue. Around the same time, another study by Chadha[24] reported comorbidities in DS at a rate of 50%, 32%, and 18% related to depression, somatoform disorders, and anxiety, respectively. Depression continued to be reported as the most common association of DS in many studies.[25],[26] This “cause-effect” dilemma can never be fully resolved. Whether “loss of semen” and the cultural attributions to it leads to the affective symptoms or whether low mood and neuroticism can lead to DS in appropriate cultural context are two sides of the argument. However, the cognitive biases resulting in the attributional errors of DS and the subsequently maintained attitudes with relation to sexuality can be explained by the depressive cognitions and concepts of learned helplessness.

Balhara[27] has argued that since DS is not really culture specific as thought of earlier, it should not be solely categorized as a functional somatic syndrome, as that can have detrimental effects on its understanding and management. He also mentions that the underlying “emotional distress and cultural contexts” are not unique to DS but can be related to any psychiatric syndrome for that matter. On the contrary, other researchers have warned that subsuming DS and other CBS under the broader rubric of “mood disorders” can lead to neglect and reductionism in disorder like DS that can have unique cultural connotations.[28] Over the years, there have been multiple propositions to relook and relabel CBS like DS. Considering it as a variant of depression or somatization can make it a “cultural phenotype” of these disorders in certain regions, thus making it easier for the classificatory systems. This dichotomous debate seems never-ending, but clinically, it is always better to err on over-diagnosing and over-treating depression and anxiety in DS, which can improve the well-being of the distressed patients.

Why Discuss Dhat Syndrome. Implications in Clinical Practice DS might occur independently or associated with multiple comorbidities. It has been a widely recognized clinical condition in various parts of the world, though considered specific to the Indian subcontinent. The presentation can often be polymorphic with symptom clusters of affective, somatic, behavioral, and cognitive manifestations.[29] Being common in rural areas, the first contacts of the patients are frequently traditional faith healers and less often, the general practitioners. A psychiatric referral occurs much later, if at all.

This leads to underdetection and faulty treatments, which can strengthen the already existing misattributions and misinformation responsible for maintaining the disorder. Furthermore, depression and sexual dysfunction can be the important comorbidities that if untreated, lead to significant psychosocial dysfunction and impaired quality of life.[30] Besides many patients of DS believe that their symptoms are due to failure of interpersonal relationships, s, and heredity, which might cause early death and infertility. This contributes to the vicious cycle of fear and panic.[31] Doctor shopping is another challenge and failure to detect and address the concern of DS might lead to dropping out from the care.[15] Rao[17] in their epidemiological study reported 12.5% prevalence in the general population, with 20.5% and 50% suffering from comorbid depression and sexual disorders. The authors stressed upon the importance of early detection of DS for the psychosexual and social well-being. Most importantly, the multidimensional presentation of DS can at certain times be a facade overshadowing underlying neurotic disorders (anxiety, depression, somatoform, hypochondriasis, and phobias), obsessive-compulsive spectrum disorders and body dysmorphic disorders, delusional disorders, sexual disorders (premature ejaculation and erectile dysfunction) and infectious disorders (urinary tract s, sexually transmitted diseases), and even stress-related manifestations in otherwise healthy individuals.[4],[14],[15] This significant overlap of symptomatology, increased prevalence, and marked comorbidity make it all the more important for physicians to make sense out of the construct of DS.

That can facilitate prompt detection and management of DS in routine clinical practice.In an earlier review study, it was observed that few studies are undertaken to update the research works from published articles as an updated review, systemic review, world literature review, etc., on DS and its management approach.[29],[32],[33],[34],[35] The present paper attempts to compile the evidence till date on DS related to its nosology, critique, manifestations, and management plan. The various empirical studies on DS all over the world will be briefly discussed along with the implications and importance of the syndrome. The Construct of Dhat Syndrome. Summary of Current Evidence DS is a well-known CBS, which is defined as undue concern about the weakening effects after the passage of semen in urine or through nocturnal emission that has been stated by the International Statistical Classification of Diseases and Related Health Problems (ICD-10).[36] It is also known as “semen loss syndrome” by Shakya,[20] which is prevalent mainly in the Indian subcontinent[37] and has also been reported in the South-Eastern and western population.[15],[16],[20],[32],[38],[39],[40],[41] Individuals with “semen loss anxiety” suffer from a myriad of psychosexual symptoms, which have been attributed to “loss of vital essence through semen” (common in South Asia).[7],[15],[16],[17],[32],[37],[41],[42],[43] The various studies related to attributes of DS and their findings are summarized further.Prakash et al.[5] studied 100 DS patients through 139 symptoms of the Associated Symptoms Scale. They studied sociodemographic profile, Hamilton Depression Rating Scale, Hamilton Anxiety Rating Scale, Mini-International Neuropsychiatric Interview, and Postgraduate Institute Neuroticism Scale.

The study found a wide range of physical, anxiety, depression, sexual, and cognitive symptoms. Most commonly associated symptoms were found as per score ≥1. This study reported several parameters such as the “sense of being unhealthy” (99%), worry (99%), feeling “no improvement despite treatment” (97%), tension (97%), tiredness (95%), fatigue (95%), weakness (95%), and anxiety (95%). The common sexual disorders were observed as loss of masculinity (83%), erectile dysfunction (54%), and premature ejaculation (53%). Majority of patients had faced mild or moderate level of symptoms in which 47% of the patients reported severe weakness.

Overall distress and dysfunction were observed as 64% and 81% in the studied subjects, respectively.A study in Taiwan involved 87 participants from a Urology clinic. Most of them have sexual neurosis (Shen-K'uei syndrome).[7] More than one-third of the patients belonged to lower social class and symptoms of depression, somatization, anxiety, masturbation, and nocturnal emissions. Other bodily complaints as reported were sleep disturbances, fatigue, dizziness, backache, and weakness. Nearly 80% of them considered that all of their problems were due to masturbatory practices.De Silva and Dissanayake[8] investigated several manifestations on semen loss syndrome in the psychiatric clinic of Colombo General Hospital, Sri Lanka. Beliefs regarding effects of semen loss and help-seeking sought for DS were explored.

38 patients were studied after psychiatrically ill individuals and those with organic disorders were excluded. Duration of semen loss varied from 1 to 20 years. Every participant reported excessive loss of semen and was preoccupied with it. The common forms of semen loss were through nocturnal emission, masturbation, urinary loss, and through sexual activities. Most of them reported multiple modes of semen loss.

Masturbatory frequency and that of nocturnal emissions varied significantly. More than half of the patients reported all types of complaints (psychological, sexual, somatic, and genital).In the study by Chadda and Ahuja,[9] 52 psychiatric patients (mostly adolescents and young adults) complained of passing “Dhat” in urine. They were assessed for a period of 6 months. More than 80% of them complained of body weakness, aches, and pains. More than 50% of the patients suffered from depression and anxiety.

All the participants felt that their symptoms were due to loss of “dhat” in urine, attributed to excessive masturbation, extramarital and premarital sex. Half of those who faced sexual dysfunctions attributed them to semen loss.Mumford[11] proposed a controversial explanation of DS arguing that it might be a part of other psychiatric disorders, like depression. A total of 1000 literate patients were recruited from a medical outdoor in a public sector hospital in Lahore, Pakistan. About 600 educated patients were included as per Bradford Somatic Inventory (BSI). Men with DS reported greater symptoms on BSI than those without DS.

60 psychiatric patients were also recruited from the same hospital and diagnosed using Diagnostic and Statistical Manual (DSM)-III-R. Among them, 33% of the patients qualified for “Dhat” items on BSI. The symptoms persisted for more than 15 days. It was observed that symptoms of DS highly correlated with BSI items, namely erectile dysfunction, burning sensation during urination, fatigue, energy loss, and weakness. This comparative study indicated that patients with DS suffered more from depressive disorders than without DS and the age group affected by DS was mostly the young.Grover et al.[15] conducted a study on 780 male patients aged >16 years in five centers (Chandigarh, Jaipur, Faridkot, Mewat, and New Delhi) of Northern India, 4 centers (2 from Kolkata, 1 each in Kalyani and Bhubaneswar) of Eastern India, 2 centers (Agra and Lucknow) of Central India, 2 centers (Ahmedabad and Wardha) of Western India, and 2 centers of Southern India (both located at Mysore) spread across the country by using DS questionnaire.

Nearly one-third of the patients were passing “Dhat” multiple times a week. Among them, nearly 60% passed almost a spoonful of “Dhat” each time during a loss. This work on sexual disorders reported that the passage of “Dhat” was mostly attributed to masturbation (55.1%), dreams on sex (47.3%), sexual desire (42.8%), and high energy foods consumption (36.7%). Mostly, the participants experienced passage of Dhat as “night falls” (60.1%) and “while passing stools” (59.5%). About 75.6% showed weakness in sexual ability as a common consequence of the “loss of Dhat.” The associated symptoms were depression, hopelessness, feeling low, decreased energy levels, weakness, and lack of pleasure.

Erectile problems and premature ejaculation were also present.Rao[17] in his first epidemiological study done in Karnataka, India, showed the prevalence rate of DS in general male population as 12.5%. It was found that 57.5% were suffering either from comorbid depression or anxiety disorders. The prevalence of psychiatric and sexual disorders was about three times higher with DS compared to non-DS subjects. One-third of the cases (32.8%) had no comorbidity in hospital (urban). One-fifth (20.5%) and 50% subjects (51.3%) had comorbid depressive disorders and sexual dysfunction.

The psychosexual symptoms were found among 113 patients who had DS. The most common psychological symptoms reported by the subjects with DS were low self-esteem (100%), loss of interest in any activity (95.60%), feeling of guilt (92.00%), and decreased social interaction (90.30%). In case of sexual disorders, beliefs were held commonly about testes becoming smaller (92.00%), thinness of semen (86.70%), decreased sexual capabilities (83.20%), and tilting of penis (70.80%).Shakya[20] studied a clinicodemographic profile of DS patients in psychiatry outpatient clinic of B. P. Koirala Institute of Health Sciences, Dharan, Nepal.

A total of 50 subjects were included in this study, and the psychiatric diagnoses as well as comorbidities were investigated as per the ICD-10 criteria. Among the subjects, most of the cases had symptoms of depression and anxiety, and all the subjects were worried about semen loss. Somehow these subjects had heard or read that semen loss or masturbation is unhealthy practice. The view of participants was that semen is very “precious,” needs preservation, and masturbation is a malpractice. Beside DS, two-thirds of the subjects had comorbid depression.In another Indian study, Chadda et al.[24] compared patients with DS with those affected with neurotic/depressive disorders.

Among 100 patients, 50%, 32%, and 18% reported depression, somatic problems, and anxiety, respectively. The authors argued that cases of DS have similar symptom dimensions as mood and anxiety disorders.Dhikav et al.[31] examined prevalence and management depression comorbid with DS. DSM-IV and Hamilton Depression Rating Scale were used for assessments. About 66% of the patients met the DSM-IV diagnostic criteria of depression. They concluded that depression was a frequent comorbidity in DS patients.In a study by Perme et al.[37] from South India that included 32 DS patients, the control group consisted of 33 people from the same clinic without DS, depression, and anxiety.

The researchers followed the guidelines of Bhatia and Malik's for the assessment of primary complaints of semen loss through “nocturnal emissions, masturbation, sexual intercourse, and passing of semen before and after urine.” The assessment was done based on several indices, namely “Somatization Screening Index, Illness Behavior Questionnaire, Somatosensory Amplification Scale, Whitley Index, and Revised Chalder Fatigue Scale.” Several complaints such as somatic complaints, hypochondriacal beliefs, and fatigue were observed to be significantly higher among patients with DS compared to the control group.A study conducted in South Hall (an industrial area in the borough of Middlesex, London) included Indian and Pakistani immigrants. Young men living separately from their wives reported promiscuity, some being infected with gonorrhea and syphilis. Like other studies, nocturnal emission, weakness, and impotency were the other reported complaints. Semen was considered to be responsible for strength and vigor by most patients. Compared to the sexual problems of Indians, the British residents complained of pelvic issues and backache.In another work, Bhatia et al.[42] undertook a study on culture-bound syndromes and reported that 76.7% of the sample had DS followed by possession syndrome and Koro (a genital-related anxiety among males in South-East Asia).

Priyadarshi and Verma[43] performed a study in Urology Department of S M S Hospital, Jaipur, India. They conducted the study among 110 male patients who complained of DS and majority of them were living alone (54.5%) or in nuclear family (30%) as compared to joint family. Furthermore, 60% of them reported of never having experienced sex.Nakra et al.[44] investigated incidence and clinical features of 150 consecutive patients who presented with potency complaints in their clinic. Clinical assessments were done apart from detailed sexual history. The patients were 15–50 years of age, educated up to mid-school and mostly from a rural background.

Most of them were married and reported premarital sexual practices, while nearly 67% of them practiced masturbation from early age. There was significant guilt associated with nocturnal emissions and masturbation. Nearly 27% of the cases reported DS-like symptoms attributing their health problems to semen loss.Behere and Nataraj[45] reported that majority of the patients with DS presented with comorbidities of physical weakness, anxiety, headache, sad mood, loss of appetite, impotence, and premature ejaculation. The authors stated that DS in India is a symptom complex commonly found in younger age groups (16–23 years). The study subjects presented with complaints of whitish discharge in urine and believed that the loss of semen through masturbation was the reason for DS and weakness.Singh et al.[46] studied 50 cases with DS and sexual problems (premature ejaculation and impotence) from Punjab, India, after exclusion of those who were psychiatrically ill.

It was assumed in the study that semen loss is considered synonymous to “loss of something precious”, hence its loss would be associated with low mood and grief. Impotency (24%), premature ejaculation (14%), and “Dhat” in urine (40%) were the common complaints observed. Patients reported variety of symptoms including anxiety, depression, appetite loss, sleep problems, bodily pains, and headache. More than half of the patients were independently diagnosed with depression, and hence, the authors argued that DS may be a manifestation of depressive disorders.Bhatia and Malik[47] reported that the most common complaints associated with DS were physical weakness, fatigue and palpitation, insomnia, sad mood, headache, guilt feeling and suicidal ideation, impotence, and premature ejaculation. Psychiatric disorders were found in 69% of the patients, out of which the most common was depression followed by anxiety, psychosis, and phobia.

About 15% of the patients were found to have premature ejaculation and 8% had impotence.Bhatia et al.[48] examined several biological variables of DS after enrolment of 40 patients in a psychosexual clinic in Delhi. Patients had a history of impotence, premature ejaculation, and loss of semen (after exclusion of substance abuse and other psychiatric disorders). Twenty years was the mean age of onset and semen loss was mainly through masturbation and sexual intercourse. 67.5% and 75% of them reported sexual disorders and psychiatric comorbidity while 25%, 12.5%, and 37.5% were recorded to suffer from ejaculatory impotence, premature ejaculation, and depression (with anxiety), respectively.Bhatia[49] conducted a study on CBS among 60 patients attending psychiatric outdoor in a teaching hospital. The study revealed that among all patients with CBSs, DS was the most common (76.7%) followed by possession syndrome (13.3%) and Koro (5%).

Hypochondriasis, sexually transmitted diseases, and depression were the associated comorbidities. Morrone et al.[50] studied 18 male patients with DS in the Dermatology department who were from Bangladesh and India. The symptoms observed were mainly fatigue and nonspecific somatic symptoms. DS patients manifested several symptoms in psychosocial, religious, somatic, and other domains. The reasons provided by the patients for semen loss were urinary loss, nocturnal emission, and masturbation.

Dhat Syndrome. The Epidemiology The typical demographic profile of a DS patient has been reported to be a less educated, young male from lower socioeconomic status and usually from rural areas. In the earlier Indian studies by Carstairs,[51],[52],[53] it was observed that majority of the cases (52%–66.7%) were from rural areas, belonged to “conservative families and posed rigid views about sex” (69%-73%). De Silva and Dissanayake[8] in their study on semen loss syndrome reported the average age of onset of DS to be 25 years with most of them from lower-middle socioeconomic class. Chadda and Ahuja[9] studied young psychiatric patients who complained of semen loss.

They were mainly manual laborers, farmers, and clerks from low socioeconomic status. More than half were married and mostly uneducated. Khan[13] studied DS patients in Pakistan and reported that majority of the patients visited Hakims (50%) and Homeopaths (24%) for treatment. The age range was wide between 12 and 65 years with an average age of 24 years. Among those studied, majority were unmarried (75%), literacy was up to matriculation and they belonged to lower socioeconomic class.

Grover et al.[15] in their study of 780 male subjects showed the average age of onset to be 28.14 years and the age ranged between 21 and 30 years (55.3%). The subjects were single or unmarried (51.0%) and married (46.7%). About 23.5% of the subjects had graduated and most were unemployed (73.5%). Majority of subjects were lower-middle class (34%) and had lower incomes. Rao[17] studied 907 subjects, in which majority were from 18 to 30 years (44.5%).

About 45.80% of the study subjects were illiterates and very few had completed postgraduation. The subjects were both married and single. Majority of the subjects were residing in nuclear family (61.30%) and only 0.30% subjects were residing alone. Most of the patients did not have comorbid addictive disorders. The subjects were mainly engaged in agriculture (43.40%).

Majority of the subjects were from lower middle and upper lower socioeconomic class.Shakya[20] had studied the sociodemographic profile of 50 patients with DS. The average age of the studied patients was 25.4 years. The age ranges in decreasing order of frequency were 16–20 years (34%) followed by 21–25 years (28%), greater than 30 years (26%), 26–30 years (10%), and 11–15 years (2%). Further, the subjects were mostly students (50%) and rest were in service (26%), farmers (14%), laborers (6%), and business (4%), respectively. Dhikav et al.[31] conducted a study on 30 patients who had attended the Psychiatry Outpatient Clinic of a tertiary care hospital with complaints of frequently passing semen in urine.

In the studied patients, the age ranged between 20 and 40 years with an average age of 29 years and average age of onset of 19 years. The average duration of illness was that of 11 months. Most of the studied patients were unmarried (64.2%) and educated till middle or high school (70%). Priyadarshi and Verma[43] performed a study in 110 male patients with DS. The average age of the patients was 23.53 years and it ranged between 15 and 68 years.

The most affected age group of patients was of 18–25 years, which comprised about 60% of patients. On the other hand, about 25% ranged between 25 and 35 years, 10% were lesser than 18 years of age, and 5.5% patients were aged >35 years. Higher percentage of the patients were unmarried (70%). Interestingly, high prevalence of DS was found in educated patients and about 50% of patients were graduate or above but most of the patients were either unemployed or student (49.1%). About 55% and 24.5% patients showed monthly family income of <10,000 and 5000 Indian Rupees (INR), respectively.

Two-third patients belonged to rural areas of residence. Behere and Nataraj[45] found majority of the patients with DS (68%) to be between 16 and 25 years age. About 52% patients were married while 48% were unmarried and from lower socioeconomic strata. The duration of DS symptoms varied widely. Singh[46] studied patients those who reported with DS, impotence, and premature ejaculation and reported the average age of the affected to be 21.8 years with a younger age of onset.

Only a few patients received higher education. Bhatia and Malik[47] as mentioned earlier reported that age at the time of onset of DS ranged from 16 to 24 years. More than half of them were single. It was observed that most patients had some territorial education (91.67%) but few (8.33%) had postgraduate education or professional training. Finally, Bhatia et al.[48] studied cases of sexual dysfunctions and reported an average age of 21.6 years among the affected, majority being unmarried (80%).

Most of those who had comorbid DS symptoms received minimal formal education. Management. A Multimodal Approach As mentioned before, individuals affected with DS often seek initial treatment with traditional healers, practitioners of alternative medicine, and local quacks. As a consequence, varied treatment strategies have been popularized. Dietary supplements, protein and iron-rich diet, Vitamin B and C-complexes, antibiotics, multivitamin injections, herbal “supplements,” etc., have all been used in the treatment though scientific evidence related to them is sparse.[33] Frequent change of doctors, irregular compliance to treatment, and high dropout from health care are the major challenges, as the attributional beliefs toward DS persist in the majority even after repeated reassurance.[54] A multidisciplinary approach (involving psychiatrists, clinical psychologists, psychiatric social workers) is recommended and close liaison with the general physicians, the Ayurveda, Yoga, Unani, Siddha, Homeopathy practitioners, dermatologists, venereologists, and neurologists often help.

The role of faith healers and local counselors is vital, and it is important to integrate them into the care of DS patients, rather than side-tracking them from the system. Community awareness needs to be increased especially in primary health care for early detection and appropriate referrals. Follow-up data show two-thirds of patients affected with DS recovering with psychoeducation and low-dose sedatives.[45] Bhatia[49] studied 60 cases of DS and reported better response to anti-anxiety and antidepressant medications compared to psychotherapy alone. Classically, the correction of attributional biases through empathy, reflective, and nonjudgmental approaches has been proposed.[38] Over the years, sex education, psychotherapy, psychoeducation, relaxation techniques, and medications have been advocated in the management of DS.[9],[55] In psychotherapy, cognitive behavioral and brief solution-focused approaches are useful to target the dysfunctional assumptions and beliefs in DS. The role of sex education is vital involving the basic understanding of sexual anatomy and physiology of sexuality.

This needs to be article tailored to the local terminology and beliefs. Biofeedback has also been proposed as a treatment modality.[4] Individual stress factors that might have precipitated DS need to be addressed. A detailed outline of assessment, evaluation, and management of DS is beyond the scope of this article and has already been reported in the IPS Clinical Practice Guidelines.[56] The readers are referred to these important guidelines for a comprehensive read on management. Probably, the most important factor is to understand and resolve the sociocultural contexts in the genesis of DS in each individual. Adequate debunking of the myths related to sexuality and culturally appropriate sexual education is vital both for the prevention and treatment of DS.[56] Adequate treatment of comorbidities such as depression and anxiety often helps in reduction of symptoms, more so when the DS is considered to be a manifestation of the same.

Future of Dhat Syndrome. The Way Forward Classifications in psychiatry have always been fraught with debates and discussion such as categorical versus dimensional, biological versus evolutionary. CBS like DS forms a major area of this nosological controversy. Longitudinal stability of a diagnosis is considered to be an important part of its independent categorization. Sameer et al.[23] followed up DS patients for 6.0 ± 3.5 years and concluded that the “pure” variety of DS is not a stable diagnostic entity.

The authors rather proposed DS as a variant of somatoform disorder, with cultural explanations. The right “place” for DS in classification systems has mostly been debated and theoretically fluctuant.[14] Sridhar et al.[57] mentioned the importance of reclassifying DS from a clinically, phenomenologically, psycho-pathologically, and diagnostically valid standpoint. Although both ICD and DSM have been culturally sensitive to classification, their approach to DS has been different. While ICD-10 considers DS under “other nonpsychotic mental disorders” (F48), DSM-V mentions it only in appendix section as “cultural concepts of distress” not assigning the condition any particular number.[12],[58] Fundamental questions have actually been raised about its separate existence altogether,[35] which further puts its diagnostic position in doubt. As discussed in the earlier sections, an alternate hypothesization of DS is a cultural variant of depression, rather than a “true syndrome.”[27] Over decades, various schools of thought have considered DS either to be a global phenomenon or a cultural “idiom” of distress in specific geographical regions or a manifestation of other primary psychiatric disorders.[59] Qualitative studies in doctors have led to marked discordance in their opinion about the validity and classificatory area of DS.[60] The upcoming ICD-11 targets to pay more importance to cultural contexts for a valid and reliable classification.

However, separating the phenomenological boundaries of diseases might lead to subsetting the cultural and contextual variants in broader rubrics.[61],[62] In that way, ICD-11 might propose alternate models for distinction of CBS like DS at nosological levels.[62] It is evident that various factors include socioeconomics, acceptability, and sustainability influence global classificatory systems, and this might influence the “niche” of DS in the near future. It will be interesting to see whether it retains its diagnostic independence or gets subsumed under the broader “narrative” of depression. In any case, uniformity of diagnosing this culturally relevant yet distressing and highly prevalent condition will remain a major area related to psychiatric research and treatment. Conclusion DS is a multidimensional psychiatric “construct” which is equally interesting and controversial. Historically relevant and symptomatically mysterious, this disorder provides unique insights into cultural contexts of human behavior and the role of misattributions, beliefs, and misinformation in sexuality.

Beyond the traditional debate about its “separate” existence, the high prevalence of DS, associated comorbidities, and resultant dysfunction make it relevant for emotional and psychosexual health. It is also treatable, and hence, the detection, understanding, and awareness become vital to its management. This oration attempts a “bird's eye” view of this CBS taking into account a holistic perspective of the available evidence so far. The clinical manifestations, diagnostic and epidemiological attributes, management, and nosological controversies are highlighted to provide a comprehensive account of DS and its relevance to mental health. More systematic and mixed methods research are warranted to unravel the enigma of this controversial yet distressing psychiatric disorder.AcknowledgmentI sincerely thank Dr.

Debanjan Banerjee (Senior Resident, Department of Psychiatry, NIMHANS, Bangalore) for his constant selfless support, rich academic discourse, and continued collaboration that helped me condense years of research and ideas into this paper.Financial support and sponsorshipNil.Conflicts of interestThere are no conflicts of interest. References 1.2.3.Srinivasa Murthy R, Wig NN. A man ahead of his time. In. Sathyanarayana Rao TS, Tandon A, editors.

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