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Author(s): The PLOS Medicine Editors * The editors of PLOS Medicine , together with guest editors Timothy Walsh, Ramanan Laxminarayan and Ana Cristina Gales, announce a forthcoming Special Issue dedicated [...]

Author(s): The PLOS Medicine Editors * The editors of PLOS Medicine together with Guest Editors Vikram Patel, Daisy Fancourt, Toshi A Furukawa, and Lola Kola are excited to announce a [...]

Nicola Low and colleagues announce a call for research papers on sexually transmitted infections, to accompany a Collection on the topic.

Little is known about how adverse events are summarised and reported in trials, as detailed information is usually considered confidential. We have acquired clinical study reports (CSRs) from the European Medicines Agency through the Freedom of Information Act. The CSRs describe the results of studies conducted as part of the application for marketing authorisation for the slimming pill orlistat. The purpose of this study was to study how adverse events were summarised and reported in study protocols, CSRs, and published papers of orlistat trials.We received the CSRs from seven randomised placebo controlled orlistat trials (4,225 participants) submitted by Roche. The CSRs consisted of 8,716 pages and included protocols. Two researchers independently extracted data on adverse events from protocols and CSRs. Corresponding published papers were identified on PubMed and adverse event data were extracted from this source as well. All three sources were compared. Individual adverse events from one trial were summed and compared to the totals in the summary report. None of the protocols or CSRs contained instructions for investigators on how to question participants about adverse events. In CSRs, gastrointestinal adverse events were only coded if the participant reported that they were "bothersome," a condition that was not specified in the protocol for two of the trials. Serious adverse events were assessed for relationship to the drug by the sponsor, and all adverse events were coded by the sponsor using a glossary that could be updated by the sponsor. The criteria for withdrawal due to adverse events were in one case related to efficacy (high fasting glucose led to withdrawal), which meant that one trial had more withdrawals due to adverse events in the placebo group. Finally, only between 3% and 33% of the total number of investigator-reported adverse events from the trials were reported in the publications because of post hoc filters, though six of seven papers stated that "all adverse events were recorded." For one trial, we identified an additional 1,318 adverse events that were not listed or mentioned in the CSR itself but could be identified through manually counting individual adverse events reported in an appendix. We discovered that the majority of patients had multiple episodes of the same adverse event that were only counted once, though this was not described in the CSRs. We also discovered that participants treated with orlistat experienced twice as many days with adverse events as participants treated with placebo (22.7 d versus 14.9 d, p-value < 0.0001, Student's t test). Furthermore, compared with the placebo group, adverse events in the orlistat group were more severe. None of this was stated in the CSR or in the published paper. Our analysis was restricted to one drug tested in the mid-1990s; our results might therefore not be applicable for newer drugs.In the orlistat trials, we identified important disparities in the reporting of adverse events between protocols, clinical study reports, and published papers. Reports of these trials seemed to have systematically understated adverse events. Based on these findings, systematic reviews of drugs might be improved by including protocols and CSRs in addition to published articles.

In this months editorial, the PLOS Medicine Editors announce an upcoming Special Issue and call for papers, with Guest Editors Carol Brayne and Bruce Miller, on dementia across the lifespan and around the globe.

The editors issue a call for papers for translational and clinical cancer research papers with strong potential to advance patient care, public policy, or clinical research agendas.

In this month's editorial, the PLOS Medicine Editors announce an upcoming Special Issue, with Guest Editors Elaine Mardis and Marc Ladanyi, on actionable advances in research on the cancer genome.

The Maternal Health Task Force (MHTF) and issue the call for papers for Year 3 of the MHTF-PLOS Collection: Integrating Health Care to Meet the Needs of the Mother–Infant Pair.

The PLOS Medicine editors issue a call for papers on addressing global disparities in non-communicable diseases–CVD, cancer, COPD, asthma, diabetes, mental health disorders, and substance abuse–for 2013.

The editors and the Maternal Health Task Force announce a new call for papers on the theme of “maternal health is women's health.”

The PLoS Medicine Editors and partners from the Maternal Health Task Force at the Harvard School of Public Health announce their partnership and a call for papers on “quality of maternal health care.”

Tikki Pang and Robert Terry from WHO, along with the Editors, issue a call for papers for a joint WHO/PLoS collection on the theme of the 2012 World Health Report on Research for Health.

Author(s): Nicola Low 1,*, Nathalie Broutet 2, Richard Turner 3 Sexually transmitted infections (STIs) are common, diverse, and dangerous to health-extending from bacterial diseases that may be readily treatable once [...]

Background Little is known about how adverse events are summarised and reported in trials, as detailed information is usually considered confidential. We have acquired clinical study reports (CSRs) from the European Medicines Agency through the Freedom of Information Act. The CSRs describe the results of studies conducted as part of the application for marketing authorisation for the slimming pill orlistat. The purpose of this study was to study how adverse events were summarised and reported in study protocols, CSRs, and published papers of orlistat trials. Methods and Findings We received the CSRs from seven randomised placebo controlled orlistat trials (4,225 participants) submitted by Roche. The CSRs consisted of 8,716 pages and included protocols. Two researchers independently extracted data on adverse events from protocols and CSRs. Corresponding published papers were identified on PubMed and adverse event data were extracted from this source as well. All three sources were compared. Individual adverse events from one trial were summed and compared to the totals in the summary report. None of the protocols or CSRs contained instructions for investigators on how to question participants about adverse events. In CSRs, gastrointestinal adverse events were only coded if the participant reported that they were 'bothersome,' a condition that was not specified in the protocol for two of the trials. Serious adverse events were assessed for relationship to the drug by the sponsor, and all adverse events were coded by the sponsor using a glossary that could be updated by the sponsor. The criteria for withdrawal due to adverse events were in one case related to efficacy (high fasting glucose led to withdrawal), which meant that one trial had more withdrawals due to adverse events in the placebo group. Finally, only between 3% and 33% of the total number of investigator-reported adverse events from the trials were reported in the publications because of post hoc filters, though six of seven papers stated that 'all adverse events were recorded.' For one trial, we identified an additional 1,318 adverse events that were not listed or mentioned in the CSR itself but could be identified through manually counting individual adverse events reported in an appendix. We discovered that the majority of patients had multiple episodes of the same adverse event that were only counted once, though this was not described in the CSRs. We also discovered that participants treated with orlistat experienced twice as many days with adverse events as participants treated with placebo (22.7 d versus 14.9 d, p-value < 0.0001, Student's t test). Furthermore, compared with the placebo group, adverse events in the orlistat group were more severe. None of this was stated in the CSR or in the published paper. Our analysis was restricted to one drug tested in the mid-1990s; our results might therefore not be applicable for newer drugs. Conclusions In the orlistat trials, we identified important disparities in the reporting of adverse events between protocols, clinical study reports, and published papers. Reports of these trials seemed to have systematically understated adverse events. Based on these findings, systematic reviews of drugs might be improved by including protocols and CSRs in addition to published articles., Author(s): Jeppe Bennekou Schroll *, Elisabeth I. Penninga, Peter C. Gøtzsche Introduction Randomised trials generally underreport harms, which according to Consolidated Standards of Reporting Trials (CONSORT) is the totality of [...]

Author(s): The PLOS Medicine Editors * As part of our continued commitment to disseminating open-access research and commentary on the world's most pressing health challenges, PLOS Medicine is now inviting [...]

Author(s): The PLOS Medicine Editors * PLOS Medicine, the leading open access medical journal, is regularly publishing special issues in order to highlight and encourage progress in especially active and [...]

PLOS Medicine, now in our 12th year, publishes research across the spectrum of translation, from lab to clinic to epidemiology and public health. As editors of a journal with such [...]

In May 2014, PLOS Medicine joined PLOS Neglected Tropical Diseases in launching the Blue Marble Health Collection [1], to which we now invite ongoing manuscript submissions. The collection (available at [...]

PLOS Medicine turns ten years old in October this year. As we approach this milestone, we could dwell on our substantial accomplishments over these first ten years, such as becoming [...]

The Maternal Health Task Force (MHTF) at Harvard School of Public Health and PLOS Medicine are pleased to announce the third year of our Open Access collection of research and [...]

The Maternal Health Task Force (MHTF) and the PLOS Medicine Editors are delighted to announce our continued collaboration to create a freely available, open access collection of outstanding research and [...]

Progress to Build On With four years remaining before the world is held accountable to the Millennium Development Goals (MDGs) and with numerous recent global pledges, it is imperative that [...]

It seems astonishing that in the 21st century decisions on health care can still be made without a solid grounding in research evidence. This is true even in clinical research, [...]

This past month PLoS Medicine published two original analyses on smoking, the single greatest preventable risk for poor health and death in the developed world, and an increasingly important risk [...]

The PLOS Medicine editors issue a call for papers for translational and clinical cancer research papers with strong potential to advance patient care, public policy, or clinical research agendas. [ABSTRACT FROM AUTHOR]

This month's PLoS Medicine publishes a paper describing the results of a very early drug discovery study. The nature of early drug development is to identify many promising compounds, only [...]

Background: Poor representation of pregnant and lactating women and people in clinical trials has marginalised their health concerns and denied the maternal–fetal/infant dyad benefits of innovation in therapeutic research and development. This mixed-methods systematic review synthesised factors affecting the participation of pregnant and lactating women in clinical trials, across all levels of the research ecosystem. Methods and findings: We searched 8 databases from inception to 14 February 2024 to identify qualitative, quantitative, and mixed-methods studies that described factors affecting participation of pregnant and lactating women in vaccine and therapeutic clinical trials in any setting. We used thematic synthesis to analyse the qualitative literature and assessed confidence in each qualitative review finding using the GRADE-CERQual approach. We compared quantitative data against the thematic synthesis findings to assess areas of convergence or divergence. We mapped review findings to the Theoretical Domains Framework (TDF) and Capability, Opportunity, and Motivation Model of Behaviour (COM-B) to inform future development of behaviour change strategies. We included 60 papers from 27 countries. We grouped 24 review findings under 5 overarching themes: (a) interplay between perceived risks and benefits of participation in women's decision-making; (b) engagement between women and the medical and research ecosystems; (c) gender norms and decision-making autonomy; (d) factors affecting clinical trial recruitment; and (e) upstream factors in the research ecosystem. Women's willingness to participate in trials was affected by: perceived risk of the health condition weighed against an intervention's risks and benefits, therapeutic optimism, intervention acceptability, expectations of receiving higher quality care in a trial, altruistic motivations, intimate relationship dynamics, and power and trust in medicine and research. Health workers supported women's participation in trials when they perceived clinical equipoise, had hope for novel therapeutic applications, and were convinced an intervention was safe. For research staff, developing reciprocal relationships with health workers, having access to resources for trial implementation, ensuring the trial was visible to potential participants and health workers, implementing a woman-centred approach when communicating with potential participants, and emotional orientations towards the trial were factors perceived to affect recruitment. For study investigators and ethics committees, the complexities and subjectivities in risk assessments and trial design, and limited funding of such trials contributed to their reluctance in leading and approving such trials. All included studies focused on factors affecting participation of cisgender pregnant women in clinical trials; future research should consider other pregnancy-capable populations, including transgender and nonbinary people. Conclusions: This systematic review highlights diverse factors across multiple levels and stakeholders affecting the participation of pregnant and lactating women in clinical trials. By linking identified factors to frameworks of behaviour change, we have developed theoretically informed strategies that can help optimise pregnant and lactating women's engagement, participation, and trust in such trials. Using a mixed-methods approach, Mridula Shankar and colleagues investigate the reasons why those who are pregnant and breastfeeding are under-represented in clinical trials. Author summary: Why was this study done?: Pregnant and lactating women and people are routinely excluded from participating in drug and vaccine clinical trials, resulting in limited options for prevention and treatment of medical conditions. Challenges to including pregnant and lactating women and people in clinical research have been identified at multiple levels of the research and health systems, but the full range of barriers and facilitators to participation are not well known. What did the researchers do and find?: We conducted a mixed-methods systematic review and identified 60 research articles from 27 countries on the views and experiences of pregnant and lactating women's participation in clinical research, from the perspectives of cisgender women, family and community members, health workers, and people involved in the conduct of clinical research. Using a thematic synthesis approach, we identified barriers affecting participation including women having a limited appetite for risk during pregnancy and lactation, concerns about women's bodily autonomy during pregnancy, and challenges in obtaining ethical approval for clinical research with pregnant women. We also identified facilitators of participation including the potential for personal health benefits, expectations of higher quality care, trust in the medical and research systems, and strong teamwork between researchers and health workers. What do these findings mean?: Our findings demonstrate the need for multipronged strategies to address barriers and reinforce facilitators across the various levels of the research and health systems. The actions that are needed to overcome these barriers and reinforce facilitators must be discussed, prioritised, and adapted to specific contexts. All included studies focused on factors affecting participation of cisgender pregnant women in clinical trials; future research should consider other pregnancy-capable populations, including transgender and nonbinary people. [ABSTRACT FROM AUTHOR]

Background: Rapid diagnostic tests (RDTs) for coronavirus disease (COVID) are used in low- and middle-income countries (LMICs) to inform treatment decisions. However, to date, it is unclear when this use is cost-effective. Existing analyses are limited to a narrow set of countries and uses. The aim of this study is to assess the cost-effectiveness of COVID RDTs to inform the treatment of patients with severe illness in LMICs, considering real world practice. Methods and findings: We assessed the cost-effectiveness of COVID testing across LMICs using a decision tree model, differentiating results by country income level, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) prevalence, and testing scenario (none, RDTs, polymerase chain reaction tests—PCRs and combinations). LMIC experts defined realistic care pathways and treatment options. Using a healthcare provider perspective and net monetary benefit approach, we assessed both intended (COVID symptom alleviation) and unintended (treatment side effects) health and economic impacts for each testing scenario. We included the side effects of corticosteroids, which are often the only available treatment for COVID. Because side effects depend both on the treatment and the patient's underlying illness (COVID or COVID-like illnesses, such as influenza), we considered the prevalence of COVID-like illnesses in our analyses. We found that SARS-CoV-2 testing of patients with severe COVID-like illness can be cost-effective in all LMICs, though only in some circumstances. High influenza prevalence among suspected COVID cases improves cost-effectiveness, since incorrectly provided corticosteroids may worsen influenza outcomes. In low- and some lower-middle-income countries, only patients with a high index of suspicion for COVID should be tested with RDTs, while other patients should be presumed to not have COVID. In some lower-middle-income and upper-middle-income countries, suspected severe COVID cases should almost always be tested. Further, in these settings, negative test results in patients with a high initial index of suspicion should be confirmed through PCR and, during influenza outbreaks, positive results in patients with a low initial index of suspicion should also be confirmed with a PCR. The use of interleukin-6 receptor blockers, when supported by testing, may also be cost-effective in higher-income LMICs. The cost at which they would be cost-effective in low-income countries ($162 to $406 per treatment course) is below current prices. The primary limitation of our analysis is substantial uncertainty around some of the parameters in our model due to limited data, most notably on current COVID mortality with standard of care, and insufficient evidence on the impact of corticosteroids on patients with severe influenza. Conclusions: COVID testing can be cost-effective to inform treatment of LMIC patients with severe COVID-like disease. The optimal algorithm is driven by country income level and health budgets, the level of suspicion that the patient may have COVID, and influenza prevalence. Further research to better characterize the unintended effects of corticosteroids, particularly on influenza cases, could improve decision making around the treatment of those with COVID-like symptoms in LMICs. Gabrielle Bonnet and team assess the cost-effectiveness of COVID testing across low-and-middle-income countries, differentiating results by country income level, SARS-CoV-2 prevalence and different testing scenarios. Author summary: Why was this study done?: The main role of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) testing has evolved from transmission reduction to informing the treatment of patients with most vulnerability or most severe illness. SARS-CoV-2 testing availability and use remains inconsistent in some low- and middle-income countries (LMICs), and understanding the cost-effectiveness of testing in such contexts may help guide priority setting and inform guidelines for health professionals. Research on the cost-effectiveness of SARS-CoV-2 testing in LMICs is limited. To our knowledge, no paper has considered both presumptive and symptomatic coronavirus disease (COVID) treatment as alternatives to testing, or has considered a range of treatment options reflective of LMIC contexts. What did the researchers do and find?: We used a decision tree model, health payer provider perspective and net monetary benefit approach to assess the cost-effectiveness of testing to support treatment for patients with severe/critical COVID-like illness in 129 LMICs, based on treatment pathways reported by experts working in LMICs. In low-income and the poorest of lower-middle-income countries, only patients with a high index of suspicion for COVID should be tested with rapid diagnostic tests. In the wealthiest among lower-middle-income countries and in upper-middle-income countries, testing of suspected severe COVID cases is almost always recommended. Polymerase chain reaction (PCR) confirmation of negative test results in patients with a high index of suspicion and, during influenza epidemics/outbreaks, of positive test results in patients with a low index of suspicion, is recommended. What do these findings mean?: COVID testing of patients with severe, COVID-like symptoms in LMICs can be cost-effective, provided sufficiently specific clinical screening algorithms can be used. Policymakers should consider both our study's results regarding variability between countries at a similar income level and its sensitivity analysis, particularly regarding country-specific factors, alongside other considerations such as local feasibility and equity, to inform national level decision-making. The main limitation of the study is uncertainty on some parameters, including current COVID case fatality risks and the impact of corticosteroids on patients with influenza. [ABSTRACT FROM AUTHOR]

Background: India accounts for about one-quarter of people contracting tuberculosis (TB) disease annually and nearly one-third of TB deaths globally. Many Indians do not navigate all care cascade stages to receive TB treatment and achieve recurrence-free survival. Guided by a population/exposure/comparison/outcomes (PECO) framework, we report findings of a systematic review to identify factors contributing to unfavorable outcomes across each care cascade gap for TB disease in India. Methods and findings: We defined care cascade gaps as comprising people with confirmed or presumptive TB who did not: start the TB diagnostic workup (Gap 1), complete the workup (Gap 2), start treatment (Gap 3), achieve treatment success (Gap 4), or achieve TB recurrence-free survival (Gap 5). Three systematic searches of PubMed, Embase, and Web of Science from January 1, 2000 to August 14, 2023 were conducted. We identified articles evaluating factors associated with unfavorable outcomes for each gap (reported as adjusted odds, relative risk, or hazard ratios) and, among people experiencing unfavorable outcomes, reasons for these outcomes (reported as proportions), with specific quality or risk of bias criteria for each gap. Findings were organized into person-, family-, and society-, or health system-related factors, using a social-ecological framework. Factors associated with unfavorable outcomes across multiple cascade stages included: male sex, older age, poverty-related factors, lower symptom severity or duration, undernutrition, alcohol use, smoking, and distrust of (or dissatisfaction with) health services. People previously treated for TB were more likely to seek care and engage in the diagnostic workup (Gaps 1 and 2) but more likely to suffer pretreatment loss to follow-up (Gap 3) and unfavorable treatment outcomes (Gap 4), especially those who were lost to follow-up during their prior treatment. For individual care cascade gaps, multiple studies highlighted lack of TB knowledge and structural barriers (e.g., transportation challenges) as contributing to lack of care-seeking for TB symptoms (Gap 1, 14 studies); lack of access to diagnostics (e.g., X-ray), non-identification of eligible people for testing, and failure of providers to communicate concern for TB as contributing to non-completion of the diagnostic workup (Gap 2, 17 studies); stigma, poor recording of patient contact information by providers, and early death from diagnostic delays as contributing to pretreatment loss to follow-up (Gap 3, 15 studies); and lack of TB knowledge, stigma, depression, and medication adverse effects as contributing to unfavorable treatment outcomes (Gap 4, 86 studies). Medication nonadherence contributed to unfavorable treatment outcomes (Gap 4) and TB recurrence (Gap 5, 14 studies). Limitations include lack of meta-analyses due to the heterogeneity of findings and limited generalizability to some Indian regions, given the country's diverse population. Conclusions: This systematic review illuminates common patterns of risk that shape outcomes for Indians with TB, while highlighting knowledge gaps—particularly regarding TB care for children or in the private sector—to guide future research. Findings may inform targeting of support services to people with TB who have higher risk of poor outcomes and inform multicomponent interventions to close gaps in the care cascade. Tulip A. Jhaveri and team report findings of a systematic review to identify factors contributing to unfavorable outcomes across each care cascade gap for tuberculosis disease in India. Author summary: Why was this study done?: India has the highest tuberculosis (TB) incidence, accounting for about one-quarter of people with TB disease and nearly one-third of TB deaths globally. Many Indians with TB do not traverse all care stages needed to receive treatment and achieve an optimal long-term outcome, with serial losses of people across these stages referred to as the "care cascade." Understanding why losses of people with TB disease occur across the care cascade is crucial to inform interventions to prevent unfavorable outcomes. What did the researchers do and find?: We conducted 3 systematic searches to identify papers published from 2000 to 2023. We extracted information from these studies on risk factors for unfavorable outcomes for each care cascade gap, as well as reasons reported by people with TB who experienced unfavorable outcomes and were surveyed by researchers. Some factors contributed to losses at multiple care cascade stages, including male sex, older age, poverty-related factors, history of prior TB treatment, lower symptom severity or duration, undernutrition, alcohol use, smoking, and dissatisfaction with health services. Other barriers included: lack of TB knowledge and transportation barriers to clinic contributing to lack of care-seeking (Gap 1), poor accessibility of testing and failure to identify people eligible for testing contributing to non-completion of the diagnostic workup (Gap 2), early deaths from diagnostic delays and poor recording of contact information contributing to losses of people before treatment (Gap 3), lack of TB knowledge and depression contributing to unfavorable treatment outcomes (Gap 4), and medication nonadherence contributing to unfavorable treatment outcomes and TB recurrence (Gaps 4 and 5). What do these findings mean?: Reasons for losses of people with TB disease across the care cascade are complex, vary by care cascade gap, and involve patient- and health system-related barriers. India's TB program should target additional services to people with higher risk of poor outcomes and develop multicomponent interventions to address the diverse challenges faced by people with TB. Study limitations include lack of meta-analyses (i.e., estimation of the average effect of each risk factor by combining findings across studies), and caution is required when applying findings across India's diverse population. [ABSTRACT FROM AUTHOR]

Background: Traumatic brain injury (TBI) is disproportionately prevalent among individuals who intersect or are involved with the criminal justice system (CJS). In the absence of appropriate care, TBI-related impairments, intersecting social determinants of health, and the lack of TBI awareness in CJS settings can lead to lengthened sentences, serious disciplinary charges, and recidivism. However, evidence suggests that most clinical practice guidelines (CPGs) overlook equity and consequently, the needs of disadvantaged groups. As such, this review addressed the research question "To what extent are (1) intersections with the CJS considered in CPGs for TBI, (2) TBI considered in CPGs for CJS, and (3) equity considered in CPGs for CJS?". Methods and findings: CPGs were identified from electronic databases (MEDLINE, Embase, CINAHL, PsycINFO), targeted websites, Google Search, and reference lists of identified CPGs on November 2021 and March 2023 (CPGs for TBI) and May 2022 and March 2023 (CPGs for CJS). Only CPGs for TBI or CPGs for CJS were included. We calculated the proportion of CPGs that included TBI- or CJS-specific content, conducted a qualitative content analysis to understand how evidence regarding TBI and the CJS was integrated in the CPGs, and utilised equity assessment tools to understand if and how equity was considered. Fifty-seven CPGs for TBI and 6 CPGs for CJS were included in this review. Fourteen CPGs for TBI included information relevant to the CJS, but only 1 made a concrete recommendation to consider legal implications during vocational evaluation in the forensic context. Two CPGs for CJS acknowledged the prevalence of TBI among individuals in prison and one specifically recommended considering TBI during health assessments. Both CPGs for TBI and CPGs for CJS provided evidence specific to a single facet of the CJS, predominantly in policing and corrections. The use of equity best practices and the involvement of disadvantaged groups in the development process were lacking among CPGs for CJS. We acknowledge limitations of the review, including that our searches were conducted in English language and thus, we may have missed other non-English language CPGs in this review. We further recognise that we are unable to comment on evidence that is not integrated in the CPGs, as we did not systematically search for research on individuals with TBI who intersect with the CJS, outside of CPGs. Conclusions: Findings from this review provide the foundation to consider CJS involvement in CPGs for TBI and to advance equity in CPGs for CJS. Conducting research, including investigating the process of screening for TBI with individuals who intersect with all facets of the CJS, and utilizing equity assessment tools in guideline development are critical steps to enhance equity in healthcare for this disadvantaged group. Zoe Colclough and co-authors examine how equity is considered in the development of clinical practice guidelines for traumatic brain injury for individuals within the criminal justice system. Author summary: Why was this study done?: Traumatic brain injury (TBI) is more common among individuals involved with the criminal justice system (CJS) than the general population, often resulting in longer prison sentences, serious disciplinary charges, and repeated future conflicts with the CJS. Although individuals with TBI who are involved with the CJS must receive care that meets their needs, studies show that most clinical practice guidelines (CPGs)—designed to guide care—tend to overlook equity and disadvantaged groups, instead focussing on the effectiveness or cost-effectiveness of care. As a first step to improving equitable care, this study assessed existing CPGs for TBI and CPGs for CJS to see if and how (1) evidence regarding individuals who intersect with the CJS is included in CPGs for TBI and evidence regarding TBI is integrated in CPGs for CJS; and (2) equity is considered in CPGs for CJS. What did the researchers do and find?: We used available electronic databases (MEDLINE, Embase, CINAHL, PsycINFO), targeted websites, Google search, and reference lists for CPGs for TBI and CPGs for CJS. We documented their characteristics, reviewed their content, and assessed whether equity was considered using checklists focused on equity and disadvantaged groups. We found that 14 out of 57 CPGs for TBI referenced individuals who are involved with the CJS and 2 out of 6 CPGs for CJS referenced TBI. Practices to ensure that equity is considered, such as the involvement of disadvantaged groups when developing CPGs were lacking in CPGs for CJS. What do these findings mean?: Findings from this review suggest that consideration of equity is lacking in the development of CPGs for TBI for those within the CJS and provide the foundation to consider CJS involvement in CPGs for TBI and to advance equity in CPGs for CJS. There is a critical need for further research into screening processes for TBI with individuals who intersect with all facets of the CJS, and into the benefits of equity assessment tools in guideline development to enhance equity in healthcare for this disadvantaged group Unfortunately, we cannot comment on how much of the existing evidence regarding TBI or individuals who are involved with the CJS remains unintegrated in existing CPGs, as our search did not include research papers on TBI and the CJS, outside of CPGs. [ABSTRACT FROM AUTHOR]

Background: The consumption of sugar-sweetened beverages (SSBs) is associated with obesity, metabolic diseases, and incremental healthcare costs. Given their health consequences, the World Health Organization (WHO) recommended that countries implement taxes on SSB. Over the last 10 years, obesity prevalence has almost doubled in Brazil, yet, in 2016, the Brazilian government cut the existing federal SSB taxes to their current 4%. Since 2022, a bill to impose a 20% tax on SSB has been under discussion in the Brazilian Senate. To simulate the potential impact of increasing taxes on SSB in Brazil, we aimed to estimate the price-elasticity of SSB and the potential impact of a new 20% or 30% excise SSB tax on consumption, obesity prevalence, and cost savings. Methods and findings: Using household purchases data from the Brazilian Household Budget Survey (POF) from 2017/2018, we estimated constant elasticity regressions. We used a log-log specification by income level for all beverage categories: (1) sugar-sweetened beverages; (2) alcoholic beverages; (3) unsweetened beverages; and (4) low-calorie or artificially sweetened beverages. We estimated the adult nationwide baseline intake for each beverage category using 24-h dietary recall data collected in 2017/2018. Taking group one as the taxed beverages, we applied the price and cross-price elasticities to the baseline intake data, we obtained changes in caloric intake. The caloric reduction was introduced into an individual dynamic model to estimate changes in weight and obesity prevalence. No benefits on cost savings were modeled during the first 3 years of intervention to account for the time lag in obesity cases to reduce costs. We multiplied the reduction in obesity cases during 7 years by the obesity costs per capita to predict the costs savings attributable to the sweetened beverage tax. SSB price elasticities were higher among the lowest tertile of income (−1.24) than in the highest income tertile (−1.13), and cross-price elasticities suggest SSB were weakly substituted by milk, water, and 100% fruit juices. We estimated a caloric change of −17.3 kcal/day/person under a 20% excise tax and −25.9 kcal/day/person under a 30% tax. Ten years after implementation, a 20% tax is expected to reduce obesity prevalence by 6.7%; 9.1% for a 30% tax. These reductions translate into a −2.8 million and −3.8 million obesity cases for a 20% and 30% tax, respectively, and a reduction of $US 13.3 billion and $US 17.9 billion in obesity costs over 10 years for a 20% and 30% tax, respectively. Study limitations include using a quantile distribution method to adjust self-reported baseline weight and height, which could be insufficient to correct for reporting bias; also, weight, height, and physical activity were assumed to be steady over time. Conclusions: Adding a 20% to 30% excise tax on top of Brazil's current federal tax could help to reduce the consumption of ultra-processed beverages, empty calories, and body weight while avoiding large health-related costs. Given the recent cuts to SSB taxes in Brazil, a program to revise and implement excise taxes could prove beneficial for the Brazilian population. Using the context of the proposed Sugar-Sweetened-Beverages tax in Brazil, Ana Basto-Abreu and colleagues model the estimated reduction in obesity prevalence and savings in health-related costs. Author summary: Why was this study done?: The consumption of sugar-sweetened beverages (SSBs) is associated with obesity, metabolic diseases, and incremental healthcare costs. The World Health Organization (WHO) recommends governments to tax SSB to improve diet and reduce chronic diseases. Since 2022, a bill to impose a 20% tax on SSB is under discussion in the Brazilian Senate. What did the researchers do and find?: We estimated SSB own- and cross-price elasticities by socioeconomic status and simulated the potential effects of introducing a 20% excise tax to SSB in consumption. If a 20% tax is introduced, we would expect a 16.9 kcal/day/person caloric reduction among Brazilian adults. We used an individual dynamic weight change model to translate caloric reductions into obesity reductions. We estimated an expected 6.7% reduction in obesity, which could lead to USD 13.3 billion healthcare cost savings over 10 years. Larger benefits of the tax are expected to be experienced by younger adults and by people from high-income groups. What do these findings mean?: The implementation of the SSB tax is expected to produce important reductions in population weight and obesity prevalence, while saving health-related costs. Limitations of our analysis include assuming no change in weight under the no-intervention scenario and using a quantile distribution method to adjust self-reported baseline weight and height. [ABSTRACT FROM AUTHOR]

In this months editorial, the PLOS Medicine Editors announce an upcoming Special Issue and call for papers, with Guest Editors Carol Brayne and Bruce Miller, on dementia across the lifespan and around the globe. [ABSTRACT FROM AUTHOR]

Background: The Danish cardiovascular screening (DANCAVAS) trial, a nationwide trial designed to investigate the impact of cardiovascular screening in men, did not decrease all-cause mortality, an outcome decided by the investigators. However, the target group may have varied preferences. In this study, we aimed to evaluate whether men aged 65 to 74 years requested a CT-based cardiovascular screening examination and to assess its impact on outcomes determined by their preferences. Methods and findings: This is a post hoc study of the randomised DANCAVAS trial. All men 65 to 74 years of age residing in specific areas of Denmark were randomised (1:2) to invitation-to-screening (16,736 men, of which 10,471 underwent screening) or usual-care (29,790 men). The examination included among others a non-contrast CT scan (to assess the coronary artery calcium score and aortic aneurysms). Positive findings prompted preventive treatment with atorvastatin, aspirin, and surveillance/surgical evaluation. The usual-care group remained unaware of the trial and the assignments. The user-defined outcome was based on patient preferences and determined through a survey sent in January 2023 to a random sample of 9,095 men from the target group, with a 68.0% response rate (6,182 respondents). Safety outcomes included severe bleeding and mortality within 30 days after cardiovascular surgery. Analyses were performed on an intention-to-screen basis. Prevention of stroke and myocardial infarction was the primary motivation for participating in the screening examination. After a median follow-up of 6.4 years, 1,800 of 16,736 men (10.8%) in the invited-to-screening group and 3,420 of 29,790 (11.5%) in the usual-care group experienced an event (hazard ratio (HR), 0.93 (95% confidence interval (CI), 0.88 to 0.98; p = 0.010); number needed to invite at 6 years, 148 (95% CI, 80 to 986)). A total of 324 men (1.9%) in the invited-to-screening group and 491 (1.7%) in the usual-care group had an intracranial bleeding (HR, 1.17; 95% CI, 1.02 to 1.35; p = 0.029). Additionally, 994 (5.9%) in the invited-to-screening group and 1,722 (5.8%) in the usual-care group experienced severe gastrointestinal bleeding (HR, 1.02; 95% CI, 0.95 to 1.11; p = 0.583). No differences were found in mortality after cardiovascular surgery. The primary limitation of the study is that exclusive enrolment of men aged 65 to 74 renders the findings non-generalisable to women or men of other age groups. Conclusion: In this comprehensive population-based cardiovascular screening and intervention program, we observed a reduction in the user-defined outcome, stroke and myocardial infarction, but entail a small increased risk of intracranial bleeding. Trial registration: ISRCTN Registry number, ISRCTN12157806https://www.isrctn.com/ISRCTN12157806. In this post-hoc analysis of the DANCAVAS trial, Axel Diederichsen and colleagues explore how cardiovascular screening impacts on outcomes as defined by patients themselves. Author summary: Why was this study done?: Stroke and heart attack remain a prevalent cause of decreased quality of life and premature death. Coronary atherosclerosis serves as an important risk modifier and is easily identifiable by cardiac imaging. Despite this, screening for cardiovascular disease by cardiac CT in the Danish cardiovascular screening (DANCAVAS) trial did not lead to a decrease in death from cardiovascular causes. However, it is essential to recognise that patients may have preferences other than death, and these preferences play a critically important role in informed and shared decision-making between caregivers and patients. What did the researchers do and find?: The DANCAVAS trial included men aged 65 to 74 from specific areas of Denmark, with some receiving invitations to screening (16,736 men) and others receiving usual care (29,790 men). Patients with significant atherosclerosis were treated with atorvastatin, aspirin, and underwent surveillance or surgery in case of aneurysms. Here, the study outcomes were determined based on patient preferences, which were assessed through a survey of a random sample of 9,095 men aged 65 to 74. The surveyed men expressed a preference for preventing stroke and heart attack over death. Screening reduced the absolute risk of stroke and heart attack by 0.7%, but it also increased the risk of intracranial haemorrhage by 0.2%. What do these findings mean?: The DANCAVAS trial met patient preferences, but the benefits were modest and accompanied by a slight increase in the risk of intracranial haemorrhage. These data suggest that there is limited benefit to the widespread implementation of cardiovascular screening programmes. The trial specifically targeted men aged 65 to 74, meaning the findings cannot be generalised to women or men outside this age group. Future cardiovascular screening programs should encompass both sexes and accommodate patient preferences. Additionally, they might consider excluding aspirin from the intervention arm. [ABSTRACT FROM AUTHOR]

Background: When research evidence is limited, inconsistent, or absent, healthcare decisions and policies need to be based on consensus among interested stakeholders. In these processes, the knowledge, experience, and expertise of health professionals, researchers, policymakers, and the public are systematically collected and synthesised to reach agreed clinical recommendations and/or priorities. However, despite the influence of consensus exercises, the methods used to achieve agreement are often poorly reported. The ACCORD (ACcurate COnsensus Reporting Document) guideline was developed to help report any consensus methods used in biomedical research, regardless of the health field, techniques used, or application. This explanatory document facilitates the use of the ACCORD checklist. Methods and findings: This paper was built collaboratively based on classic and contemporary literature on consensus methods and publications reporting their use. For each ACCORD checklist item, this explanation and elaboration document unpacks the pieces of information that should be reported and provides a rationale on why it is essential to describe them in detail. Furthermore, this document offers a glossary of terms used in consensus exercises to clarify the meaning of common terms used across consensus methods, to promote uniformity, and to support understanding for consumers who read consensus statements, position statements, or clinical practice guidelines (CPGs). The items are followed by examples of reporting items from the ACCORD guideline, in text, tables, and figures. Conclusions: The ACCORD materials—including the reporting guideline and this explanation and elaboration document—can be used by anyone reporting a consensus exercise used in the context of health research. As a reporting guideline, ACCORD helps researchers to be transparent about the materials, resources (both human and financial), and procedures used in their investigations so readers can judge the trustworthiness and applicability of their results/recommendations. Patricia Logullo and colleagues created an explanatory document that facilitates the use of the ACCORD checklist. [ABSTRACT FROM AUTHOR]

Background: Women with mental illness experience an increased risk of cervical cancer. The excess risk is partly due to low participation in cervical screening; however, it remains unknown whether it is also attributable to an increased risk of infection with human papillomavirus (HPV). We aimed to examine whether women with mental illness had an increased infection rate of HPV compared to women without mental illness. Methods and findings: Using a cohort design, we analyzed all 337,116 women aged 30 to 64 and living in Stockholm, who had a negative test result of 14 high-risk HPV subtypes in HPV-based screening, during August 2014 to December 2019. We defined women as exposed to mental illness if they had a specialist diagnosis of mental disorder or had a filled prescription of psychotropic medication. We identified incident infection of any high-risk HPV during follow-up and fitted multivariable Cox models to estimate hazard ratios (HR) with 95% confidence intervals (CI) for HPV infection. A total of 3,263 women were tested positive for high-risk HPV during follow-up (median: 2.21 years; range: 0 to 5.42 years). The absolute infection rate of HPV was higher among women with a specialist diagnosis of mental disorder (HR = 1.45; 95% CI [1.34, 1.57]; p < 0.001) or a filled prescription of psychotropic medication (HR = 1.67; 95% CI [1.55, 1.79]; p < 0.001), compared to women without such. The increment in absolute infection rate was noted for depression, anxiety, stress-related disorder, substance-related disorder, and ADHD, and for use of antidepressants, anxiolytics, sedatives, and hypnotics, and was consistent across age groups. The main limitations included selection of the female population in Stockholm as they must have at least 1 negative test result of HPV, and relatively short follow-up as HPV-based screening was only introduced in 2014 in Stockholm. Conclusions: Mental illness is associated with an increased infection rate of high-risk HPV in women. Our findings motivate refined approaches to facilitate the WHO elimination agenda of cervical cancer among these marginalized women worldwide. Author summary: Why was this study done?: Mental illness has been associated with a higher risk of cervical cancer and precancerous lesions as well as a lower degree of participation in cervical screening. Little is known, however, regarding disparities in HPV infection between women with and without mental illness. What did the researchers do and find?: In a cohort study, we followed all 337,116 women who were at age 30 to 64, living in Stockholm, and had a negative test result of high-risk HPV during August 2014 to December 2019, to assess the link between mental illness and risk of infection with high-risk HPV. The absolute infection rate of HPV was 45% higher among women with a specialist diagnosis of mental disorder and 67% higher among women with a filled prescription of psychotropic medications, compared to women without such. What do these findings mean?: Mental illness is associated with an increased infection rate of oncogenic HPV in women. Refined approaches are needed to facilitate the elimination agenda of cervical cancer among women with mental illness. [ABSTRACT FROM AUTHOR]

The article discusses various reports published within the issue, including one on identifying a novel compound against the liver stage of malarial parasites and another on the methodology for screening compounds active against the liver stages of Plasmodium falciparum.