Background: Although Heart failure (HF) has similar lifetime risk among both men and women, women are more likely to develop HF with preserved ejection fraction and experience distinct risk factors and outcomes. Despite this, women remain underrepresented in HF clinical trials, particularly in studies of HF with reduced ejection fraction and device-based interventions, with average women participation of 25%. As a result, current guideline recommendations, including those from the leading US cardiology institutes, are predominantly based on evidence derived from male cohorts, compromising the applicability of these recommendations to women. In our study, we examined the the representation of women in the studies used to formulate the current HF management practice guidelines. Methods: We conducted systematic review of all primary studies cited in the 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure that reported the number of women participants and included in the evidence table; those were mainly used to derive the current recommendations. Studies were classified into randomized controlled trials (RCTs) and nonrandomized studies. The average women participation proportion were analyzed to RCTs and non-RCTs and comparison done for the average proportion of women participants by year of publication and the section where was cited in the guidelines. Results: A total of 462 studies (192 RCTs, 270 non-RCTs) were included in the analysis, the mean proportion of women participants was 27.8% in RCTs and 36.2% in non-RCTs. Temporal analysis demonstrated a gradual increase in women representation in both study types; however, the gap between RCTs and non-RCTs persisted. In the most recent period, women representation reached 33.2% in non-RCTs and 26.4% in RCTs. Despite these improvements, women remain consistently underrepresented relative to their disease burden. Conclusion: Women representation in HF studies cited in the current clinical practice guidelines remains suboptimal, particularly within RCTs. Although modest improvements have occurred over time, significant disparities persist. These findings underscore the need to identify the barriers and implement systematic strategies to enhance the inclusion of women in clinical research, especially in studies that inform clinical practice guidelines, to ensure equitable, evidence-based care for all patients with HF.

Studies have shown an underrepresentation of women in clinical research, but little is known about trends over time and factors associated with this underrepresentation. This study aimed to investigate the evolution and the independent factors associated with the proportion of women in the authorship of high-impact critical care randomized controlled trials (RCTs) over 25years. This meta-epidemiological study screened adult critical care RCTs published between 1999 and 2023 in the six highest-impact general and critical care journals. Sex was assessed using a combination of authors' biographies, available photographs, the gender R package, and a native Chinese speaker's assistance to ensure cultural accuracy. The primary outcome was the proportion of women among the authors. Unadjusted and adjusted generalized linear mixed models were performed. Of 1,203 RCTs, the sex of all authors was determined in 1,199 (99.7%). Overall, 4,335 out of 16,057 authors (27%) were women. Women were less frequently first (247/1,199 [21%], p < 0.001) or senior authors (174/1,199 [15%], p < 0.001) compared to other positions. The proportion of women among authors increased by a change rate of 0.7% per year ([0.5%-0.9%]) from 18% in 1999 to 32% in 2023. In multivariable analysis, the proportion of women increased significantly per year of publication (odds ratio [OR] = 1.05, 95% confidence interval [1.02-1.09], p < 0.01) and sample size (OR = 1.007 [1.003-1.012] per 100 patients increase, p = 0.01), and decreased significantly in European RCTs (OR = 0.53 [0.33-0.85], p < 0.01), RCTs on ventilation (OR = 0.50 [0.25-0.97], p = 0.04) but not sepsis (OR = 0.74 [0.37-1.46], p = 0.39), mortality as primary outcome (OR = 0.36 [0.14-0.92], p = 0.03), and with endorsement by a study group (OR = 0.36 [0.18-0.69], p < 0.01). Although the proportion of women in authorship has risen over 25years, women are still widely underrepresented in the authors of high-impact RCTs, especially as first and senior authors. This underrepresentation is exacerbated in Europe, in trials with mortality as primary outcome, on ventilation, or endorsed by a study group. This illustrates the "leaky pipeline" framework: women are still excluded from the highest-level of critical care research.

The position of pregnant women in clinical research remains a topic of international ethical debate. Yet, the reflections of actual and potential trial participants, including pregnant women themselves, often remain absent. Following a policy reversal in 2019, pregnant women were eligible to participate in a second Ebola vaccine trial during an epidemic in the eastern Democratic Republic of the Congo (DRC). This article follows how this decision was perceived in Goma, a city in the DRC, the meanings and functions of the rumors that emerged about reproductive health, and how these rumors influenced pregnant women's experience of the trial. I argue that the womb became a site to discuss broader biopolitical anxieties about collective survival, but that rumors also became a vehicle for ethical debate amid uncertainty. Ethical debates about medical research continue locally through other ethical vernaculars‐ like rumors‐ and center on contested ideas of acceptable risk, shaped by collective historical experiences.

ABSTRACT Approximately half of the world’s population will transition into menopause during their 5th and 6th decades of life. Despite this inevitability and its impact on individuals, whether and how menopause might be a public, and thus a policy, concern have in some countries been relatively recent debates. We explored the menopause-related national policy discourses of two western industrialized nations, the United States and the United Kingdom, over 40 years. Applying Bacchi’s What is the Problem Represented to Be? framework, we analyze one of the earliest themes to emerge: menopause-related research. We find that the US Congress and UK Parliament both consistently approached menopause research as a biomedical inquiry, parallelling other questions about the historical exclusion of women in clinical research, overall. Menopause’s research ‘problem’ was further characterized as one of the insufficient interest and need to pursue associated risks, all issues legislators portrayed as addressable via policy. Muted in both nations, however, were other lines of inquiry, such as the menopause-impacting impacts of socioeconomic contexts across groups. We discuss legislative ‘medicalization’ of a problem that can, indeed, present symptoms and risks that medicine informs, but which also raises non-clinical questions with implications for how societies organize themselves.

Background/Objectives: Migraines are a common neurological disorder that significantly impact women, especially during their reproductive years. Hormonal, neurological, and lifestyle factors shape migraine patterns, with fluctuations during menstruation, pregnancy, perimenopause, and menopause influencing migraine prevalence and severity. This expert opinion explores current challenges, therapeutic strategies, and future directions for personalized care, addressing the limited inclusion of women in clinical research across different life stages. Methods: In order to focus on hormonal influences, pharmacological and non-pharmacological therapies, including CGRP monoclonal antibodies, neuromodulation, and lifestyle interventions, a comprehensive analysis of literature, in particular on clinical trials, real-world studies, and guidelines on migraine management was performed. Emerging digital tools and AI-based approaches were also evaluated to improve personalized care for women with migraine. Results: Hormonal therapies, including contraceptives and HRTs, present both risks and benefits, particularly for women with migraines with aura, highlighting the need for individualized approaches. Advances in CGRP-targeted therapies have shown effectiveness in preventing refractory migraines. Non-pharmacological treatments, such as neuromodulation, acupuncture, and lifestyle adjustments, further expand the treatment landscape. However, research gaps remain, particularly regarding hormonal influences on migraines during pregnancy and menopause. Conclusions: Future research should prioritize female-specific clinical trials to better understand the impact of hormonal changes on migraines. Tailored therapies combining pharmacological, non-pharmacological, and digital solutions are essential for improving care. A multidisciplinary approach integrating personalized medicine, technological advancements, and patient education is crucial to optimizing outcomes and enhancing quality of life for women with migraine.

Pregnant women had a large demand for diagnosis and treatment, but the clinical research was not sufficient, and there were many barriers for pregnant women to participate in clinical research. This study aimed to systematically identify these barriers and facilitators, map them with Theoretical Domains Framework (TDF) and Behavior Change Techniques (BCTs) to inform the development of interventions promoting pregnant women's involvement in clinical research. This was a mixed-methods systematic review. PubMed, Embase, Cochrane Library, APA PsycInfo, CINAHL, China National Knowledge Infrastructure, WanFang, VIP Database for Chinese Technical Periodicals, Chinese Biomedical Literature Database, and related references were searched. Qualitative, quantitative, and mixed-methods studies exploring barriers and facilitators to pregnant women's participation in clinical trials were included. The barriers and facilitators were extracted, after transforming the quantitative data into qualitative data, all qualitative data were used to thematic synthesis. The identified barriers and facilitators were mapped into TDF and BCTs. A total of 103 studies (66 qualitative, 24 quantitative, and 13 mixed-methods) were included. Three main themes were formed: personal factors, environmental factors and research characteristics, with identified barriers and facilitators within each theme. "Knowledge," "Environmental Context and Resources," and "Beliefs about Consequences" were the main domains where barriers and facilitators identified by pregnant women and researchers were mapped in TDF. Additionally, the barriers and facilitators identified by pregnant women also mapped on "Social Influences" and "Goals." "Instruction on how to perform a behavior," "restructuring the physical environment," "salience of consequences," "social support (unspecified)," "goal setting (outcome)" were the main BCTs identified based on barriers and facilitators. The barriers and facilitators to clinical research participation identified in this study involved three main themes of personal, environmental, and research characteristics, which mainly mapped to five TDF domains. Based on these barriers and facilitators, 23 BCTs were identified. Future research should focus on developing behavior change interventions, assessing their efficacy and implementability.

The total value to society of eliminating all life expectancy disparities attributable to the underrepresentation of minorities for the three common conditions of diabetes, heart disease, and hypertension was approximately $11 trillion based on a commissioned analysis that applied the Future Elderly Model for the National Academies of Sciences, Engineering, and Medicine (NASEM) Committee on Improving the Representation of Women and Underrepresented Minorities in Clinical Trials and Research.1 While older adults experience higher rates of these comorbidities2 and polypharmacy3 than the general population and are the major utilizers of medications,4 they are considerably underrepresented in clinical trials and clinical research overall.5 The prioritization of COVID-19 vaccines for older adults as part of phase 1 by the Centers for Disease Control and Prevention (CDC) Advisory Committee on Immunization Practices was a prominent example of the importance of studying older adults and, particularly, older adults with chronic disease in clinical trials.6 To address the societally pressing challenge of the lack of older adults, women, and minorities in clinical trials and medical research in general, NASEM hosted a virtual workshop titled "Drug Research and Development for Adults Across the Older Age Span" in 2020. The following year through 2022, NASEM performed a Congressionally mandated consensus study with culminating report titled "Improving Representation in Clinical Trials and Research: Building Research Equity for Women and Underrepresented Groups." The goal of these NASEM activities was to examine and shed light on the challenges and opportunities in drug research and development for older adults, women, and underrepresented groups and explore hurdles that impair clinical studies in these populations. The NASEM events described the array of consequences due to the underrepresentation of women and minoritized populations as well as the salient conclusions based on the evidence (Table 1). 1. Lack of representation compromises generalizability and relevance of clinical research findings to the whole U.S. population. 2. Lack of representation translates to hundreds of billions of dollars in medical costs in the United States. 3. Lack of representation may hinder innovation and new discoveries. 4. Lack of representation may compound low accrual that causes many trials to fail. 5. Lack of representation may lead to a lack of access to effective medical interventions. 6. Lack of representation may undermine the trust of the clinical research enterprise and the medical establishment. 7. Lack of representation may lead to the absence of determination and measurement of outcomes meaningful to these populations. 8. Lack of representation precludes ascertaining important variations in medication absorption and metabolism, which may be altered by age, sex/gender, and race/ethnicity. 1. Improving representation in clinical research is urgent. 2. Improving representation in clinical research requires substantial investment that must include education and dialogue with patients and communities who may be unfamiliar with clinical trials and may have concerns about potential risks as well as benefits. 3. Improving representation requires transparency and accountability. 4. Improving representation in clinical research is the responsibility of everyone involved in the clinical research enterprise. 5. Creating a more equitable future entails a paradigm shift. Barriers to the necessary representation of underrepresented and excluded populations in clinical research in the current research system have reduced participation by a diverse population in clinical trials and clinical research at multiple levels. Individual research studies, the institutions that conduct research, funders of studies, institutional review boards (IRBs), medical journals, and the broader landscape of national policies and practices that govern research all contribute to barriers of populations historically excluded from clinical research. At the level of an individual research study, the factors and problems that lead to the underrepresentation and exclusion of certain populations in clinical trials and research begin with and follow the life cycle of a project. Understanding and resolving the underrepresentation and exclusion of these populations in research require careful examination of almost every stage in the research process itself. This includes at the time research questions are developed. The composition, training, and attitudes of the research team must also be considered to foster the thoughtful dialogue and insight necessary to maximize representation of needed populations. Research site selection is also a key facet in bolstering access to priority populations for increasing representativeness. Intentionality in "meeting people where they are" has been identified as a key pillar in improving the representativeness and validity of studies. Consideration on participant selection and study protocols in general that includes determination of sampling approaches, recruitment methods, inclusion, and exclusion criteria must also be carefully evaluated. Appropriately performed this includes review of informed consent processes, remuneration for study participants, as well as development and inclusion of multilingual recruitment and consent documents. For older adults, it has been noted that while most older adults with the most common chronic conditions that result in hospitalization in the United States occur in older people with multiple conditions, having multiple conditions was often an exclusion criterion in the National Institutes of Health (NIH) trials. This approach effectively ensured that the representative older population was systematically excluded from the studies. Deliberate considerations of the consequences of inclusion and exclusion criteria decisions on representativeness must be prioritized as fundamental to the research. Institutional structures are also a barrier to appropriate inclusivity. Medical institutions of different types face a range of structural barriers to inclusion in clinical trials. For example, although academic medical centers conduct 55% of the extramural medical research supported by the NIH and operate 98% of the nation's 41 comprehensive cancer centers as of 2019, sustainably and meaningfully engaging underrepresented and excluded populations often does not align with the traditional incentive structures for researchers at these institutions. Recruiting diverse population groups and properly engaging with community members, which is time-consuming and requires investments to build and sustain trust, are only minimally considered in promotion and tenure decisions at academic medical centers. While community health centers serve a much more diverse community than academic medical centers, these institutions also face barriers to clinical trials and research recruitment, which include limited provider knowledge about available research opportunities and challenges with electronic health record (EHR) infrastructure, that can limit providers' ability to query the EHR using study inclusion and exclusion criteria. IRBs can also present barriers to diverse participation in clinical trials by limiting the types and amount of compensation given to research participants to avoid the impression of coercion or undue influence. However, limiting incentives may ultimately compromise beneficence and justice, two of the ethical principles for research with human subjects detailed in the Belmont Report.7 Research funders also have several roles and responsibilities, which can influence the diversity of clinical trials. These include setting funding priorities, deciding which projects ultimately get funded, providing adequate funding to recruit and retain participants, requiring transparent reporting, and evaluating research outputs. Most clinical trials are funded by pharmaceutical firms. These trials present barriers, including out-of-pocket costs for participants, which are often not discussed in the informed consent process, industry pressures to gather data quickly, and the selection of easy-to-recruit samples often being incentivized. It should be noted that some of these barriers are not solely unique to industry-sponsored trials. Peer-reviewed medical journals serve as the gatekeepers to scientific advancements in clinical practice and health. Their editors wield great power for what is, and is not, published in their pages. Lack of representation on editorial boards and other journal leadership positions may contribute to biases in publication. Recent focused efforts have been formalized to improve representation on journal editorial boards. This included the release of The Journal of the American Medical Association priorities to strive for and promote diversity, equity, and inclusion (DEI) that included the following key approaches: update journal mission statements to include inclusivity aims, appoint an editorial director of equity, improve editorial diversity, promote awareness of and responsibility for DEI, formalize process for assessment and reporting, expand editorial fellowship program, hold seminars on excellence in scientific writing, continue to publish articles on DEI, identify and invite peer reviewers and authors of opinion articles with DEI expertise, encourage authors to address systemic and structural problems to advance DEI, review and update inclusive language guidance for authors and editors update statistical analysis guidance, and participate in International Collaboration on Standards and Policies.8 While the JAMA effort is a necessary step, many more journals must plan, execute, and monitor their efforts to ensure representativeness regarding inclusivity. These activities from NASEM developed an array of policy considerations and recommendations to narrow the inclusiveness gap for minorities, women, and older adults in clinical research. In terms of bolstering reporting, transparency, and accountability, the NASEM report recommended that The Department of Health and Human Services (HHS) create a research equity task force within HHS charged with coordinating data collection and designing study subject recruitment and accrual monitoring that would track across federal agencies, including the Food and Drug Administration (FDA), NIH, CDC, Agency for Healthcare Research and Quality (AHRQ), Health Resources Services Administration (HRSA), Indian Health Services (IHS), and the Centers for Medicare & Medicaid Services (CMS). This task force would submit an annual report to Congress on the status of clinical trial and clinical research enrollment in the United States, which would include patient counts recruited into clinical studies by phase and condition. Mandated data would include the study patients' age, sex, gender, race, ethnicity, study location, and recruitment site. The annual report would also describe to what degree the study population was representative of the conditions studied as well as the sponsors of the research. Creating a real-time, data dashboard was offered as an example of a tool to make data more accessible and transparent continuously. The report also recommended clarifying how "representativeness" was determined and evaluated for protocols and product development plans.1 This would serve to not only help discern the older adult representation but allow for stratification of the older adult categories by minority, gender, and location to ensure that studies line up with actual disease prevalence for older adult subpopulations. This was coordinated with a frequent comment that the heterogeneity of older adults must be better tracked with improved tools and technology to enhance knowledge and treatment outcomes to increase the proportion of heterogeneous older adults in clinical trials. The improved use of modern tools was also broached in terms of better use of technology such as social media to improve recruitment of older adults from diverse backgrounds into trials.9 For a path toward equitable compensation to research participants and their caregivers, the NASEM report recommended developing specific guidance that would include systematically modified compensation for those who will experience a financial burden when participating in research activities. Receipt of a detailed recruitment plan should be required by the FDA no later than at the time of Investigational New Drug and Investigational Device Exemption application submission. To facilitate that trial characteristics are consistently labeled throughout the database and can be easily disaggregated, exported, and analyzed by the public, NIH should standardize the submission of demographic characteristics to ClinicalTrials.gov beyond current guidelines. A theme across the NASEM activities was that NIH can better leverage its role as a funder to motivate improved inclusiveness of older adults and minorities. The score-driving criteria that measure the scientific integrity and overall impact of a NIH grant proposal should formally include participant representativeness data. Patient representativeness data should be components of the assessment of the scientific approach, including whether it is appropriate for concluding insights for the populations to whom the results are intended to generalize. In the 2020 NASEM workshop, Alzheimer's disease research was referenced as an area in which representation of older adults would be expected. The concept of requiring a justification for not including older adults was described on several occasions.9 The NIH should also assess in its annual review of progress reports of funded studies whether a given study has met the proposed enrollment goals of representativeness by race/ethnicity, sex, and gender and should establish a plan for remediation that includes criteria for pausing funding that has not met predefined recruitment goals. Journal publisher, editors, and the International Committee on Medical Journal Editors should (1) require information on the representativeness of studies for submissions to their journals in context to the affected population; (2) consider this information in acceptance decisions; and (3) publish this information for manuscripts that are accepted. The overall representativeness of the trial, including how well the study population aligns with the target population, should be evident in the publication. The Office of Human Research Protections (OHRP) and the FDA should advise local IRBs determine and report the representativeness of clinical trials as one measure of sound research design. Study protocols in which the pre-specified enrollment departs markedly from the disease prevalence would trigger a request for a justification statement or possible remediation. The commitment to and value of educating review bodies across the clinical development continuum to incorporate considerations of age, gender, and minority status dimensions was a prevailing theme. In terms of coverage and payment, CMS should revise its guidance for coverage with evidence development to require that study protocols include a plan for recruiting and retaining participants who are representative of the affected beneficiary population in age, race, ethnicity, sex, and gender. Congress should direct the FDA to enforce accountability measures already present, as well as establish a taskforce to study new incentives for new drug applications for trials that achieve representative enrollment. This recommendation has in fact been enacted in the Food and Drug Omnibus Reform Act of 2022 (FDORA)10 that requires sponsors of phase 3 or other pivotal medication studies to submit diversity action plans by the time the study protocol is submitted. A synthesis of the current environment was recently detailed in the special article "Current status of inclusion of older groups in evaluations of new medications: Gaps and implementation needs to fill them" in this journal.11 Incentive programs should be designed to improve representativeness in clinical research and ensure they do not impede access to new therapies. Expedited coverage decisions should be considered for therapies based on clinical programs that achieve representativeness of the populations most affected. To incentivize community providers to enroll participants in trials, CMS should develop reimbursement approaches for the time and infrastructure that is required. Development of new payment codes would allow CMS to reimburse activities associated with clinical trial participation including data collection and personnel to support research education and recruitment endeavors. The Government Accountability Office (GAO) should assess the impact of previously enacted policies reimbursing routine care costs associated with CMS trials. To foster equitable compensation to research participants and their caregivers, federal agencies, including the OHRP, NIH, and FDA, should develop guidance to direct IRBs on appropriate remuneration for study participation. This new guidance should encourage and allow for variable compensation to research participants and their caregivers commensurate with the time commitment and financial burden of participating. There are trial designs tested that offer the prospect of increasing enrollment of older adults, including adaptive platform trial designs, home-based trials, mechanistic modeling, simulations, real-world data, and pragmatic clinical trials. Clinical trials can now be successfully completed in many non-traditional clinical trial environments that have included barber shops and pharmacies.9 Similarly, all sponsors of clinical trials and clinical research (e.g., federal, foundation, private, and/or industry) should ensure that trials provide adequate compensation for research participants. A diverse, inclusive, and representative workforce, particularly in leadership circles, should be maintained for all organizations involved in clinical research. Recognition of research, training, and professional activities to promote community-engaged scholarly efforts and other research to enhance clinical trial representativeness should be included as areas of excellence for promotion or tenure considerations. The HHS should substantially invest in research infrastructure in the community. To bolster the capacity of community health centers and safety net hospitals to participate in clinical research, funding should be directed to agencies such as the HRSA, NIH, AHRQ, CDC, and IHS. These recommendations and recent advances to date in each area are summarized in Table 2. Progress has been made at the government level with the passage of FDORA as well as coordinated efforts to improve representativeness in clinical research by other agencies, academic institutions, foundations, and non-governmental organizations. Yet, recommendations on changing the composition of the workforce and individual academic entities will require a longer timeframe and concerted effort as will building trust across all communities. Bridging the inclusion gaps for older adults, minorities, and women in clinical research is achievable and necessary. However, it will demand intentional and committed policy efforts with coordination from an array of stakeholders. Fortunately, informed guidance now exists that we must immediately harness and apply to reverse our flagging population health outcomes and move us closer to peer nations. Dr. Jonathan H. Watanabe contributed to the concept, design, and preparation of the manuscript. Dr. Jonathan H. Watanabe credits his involvement as a Member of the Forum on Drug Discovery, Development, and Translation of the National Academies of Sciences, Engineering, and Medicine (NASEM), a planning committee member for the Drug Research and Development for Older Adults Across the Older Age Span NASEM Workshop, and a prior National Academy of Medicine Emerging Leader in Health and Medicine Scholar. He would like to thank Dr. Janice Schwartz for her insightful feedback that strengthened this manuscript. The information or contents are those of the author and should not be construed as the official position or policy of, nor should any endorsements be inferred by NASEM or NAM. Jonathan H. Watanabe has received research funding from the National Institutes of Health and the National Academies of Sciences, Engineering, and Medicine. These organizations played no role in the design, development, writing, or review of this manuscript. None. None.

A long history of policymaking and regulation constructed for the purpose of ensuring adequate fetal and infant protections has inadvertently sanctioned the widespread exclusion of pregnant and lactating patients from biomedical research, leaving a paucity of high quality data necessary for clinical decision-making. Although well-intended, the regulatory classification of pregnant women as "vulnerable," in conjunction with burdensome enrollment criteria and other factors weighing against broad inclusion, have ultimately placed the health and safety of these women and their babies in jeopardy. Robust measures are urgently needed to overcome patient and physician reluctance, address substantial evidence gaps, and rectify long-standing disparities which precipitate disproportionately poor health outcomes among this population. In February 2023, the Advancing Safe Medications for Moms and Babies Act of 2023 (the Act) was introduced in the United States House of Representatives with the overarching goal of enabling pregnant and lactating women to achieve equitable participation in clinical research and contribute to developing important biomedical knowledge to guide and improve health care delivered to these patients. This review discusses the historical influence of federal human subject protection regulations on the health and clinical treatment of pregnant and lactating women, outlines and critically analyzes the provisions incorporated into the Act, and reflects on the potential long-term impact the Act would have should it be successful in becoming law. KEY POINTS: · Pregnant and lactating patients are widely excluded from clinical research.. · Evidence guiding the treatment of these patients is limited and of unacceptably low quality.. · Proposed legislation seeks to rectify disparities and empower these patients through improved representation in research..

This Viewpoint summarizes a new report from the National Academies of Sciences, Engineering, and Medicine that encourages the inclusion of pregnant and lactating individuals in clinical research.

Outcome measurement is a crucial component of contemporary professional practice. Many Indian rehabilitation facilities employ the King's Health Questionnaire (KHQ), but there has never been an official Marathi translation with its reliability and validity. As per the recommendations for cross-cultural validation of an outcome assessment, KHQ was translated into the Marathi language at a tertiary hospital in Pune, India. A study was conducted to assess the dependability of 123 patients from tertiary hospitals in India. The reliability of the study was assessed by two competent physiotherapists. The interrater reliability of the KHQ total scores and each item was evaluated using Cronbach's alpha coefficient. To compare the interrater dependability with the findings of other investigations, the intraclass correlation (ICC) coefficient was determined. When evaluated by domain, the KHQ's standardized Cronbach's alpha ranged from 0.49-0.92. All domains had reliability that was rated as moderate to strong by ICC, and the severity rating scale varied from 0.53 to 0.81. The Pearson correlation coefficient between KHQ and short form-36 (SF-36) in the majority of related areas was found to be weak to moderate, with values ranging from -0.27 to -0.53. The Marathi version of the KHQ was translated and adapted for use in Marathi language-speaking Indian women with urinary incontinence complaints. It represents an important instrument for the evaluation of incontinent women in clinical research with good interrater reliability and validity with SF-36 quality-of-life measure.

Despite a higher risk of cardiovascular disease (CVD) events in women cancer survivors than their male counterparts, importance of female sex has been underestimated due to under-representation of women in clinical research and male dominant CVD risk models. This study examined ten-year Atherosclerosis Cardiovascular Disease (ASCVD) risk trajectories in women veterans diagnosed with the ten most common cancers—bladder, breast, colorectal, endometrial/uterine/cervix, leukemia, liver, lung and bronchium, Non-Hodgkin’s lymphoma, melanoma, and thyroid cancer—using United States (US) Veterans Affairs (VA) Electronic Health Records data. The study included 78,556 women veterans aged between 30 and 80 years from diverse backgrounds treated at VA hospitals with ≥2 complete outpatient visit records in the VA health care system between January 01, 2007 and December 31, 2017. A steep rise in ASCVD risk score trajectories post-cancer diagnosis was observed among women diagnosed with bladder, breast, liver, lung and thyroid cancer, melanoma, and Non-Hodgkin’s lymphoma, compared to pre-cancer diagnosis periods, as well as significantly elevated pre-cancer ASCVD risk among all patients with cancer, other than thyroid cancer, compared to the no cancer group (p < 0.0001). ASCVD risk monitoring is highly recommended to reduce adverse cardiovascular events for women diagnosed with cancer, survivors, and for women at risk of future cancer incidences.

The article deals with the need of compulsory participation of pregnant women in clinical research of drugs. By the beginning of the 90‑s of the last century, the majority of drugs prescribed to women was characterized by unsubstantial evidence of effectiveness and safety for women. Moreover, pregnant women almost did not participate in clinical research. Though pregnancy is a dynamic condition that can be compared with itself only. Then supervisory bodies created some documents regulating compulsory participation of the population in the research of drugs. However, until now, women are not sufficiently involved in the research of new original drugs, and pregnant women do the same very rarely. Possible scenarios of participation of pregnant women in clinical research have been reviewed. In particular, research of drugs used in therapy of abnormal conditions associated with pregnancy; drugs to treat chronic and acute pathological processes not related to pregnancy, and when a woman gets pregnant during the research have been distinguished. The importance of inclusion of pregnant women into the trials of effectiveness and safety of drugs in the presence of socially significant diseases, including the ones found during COVID‑19 pandemics, is postulated.

More women have Alzheimer disease (AD) than men, but the reasons for this phenomenon are still unknown. Including women in clinical research and studying their biology is key to understand not just their increased risk but also their resilience against the disease. In this sense, women are more affected by AD than men, but their reserve or resilience mechanisms might delay symptom onset. The aim of this review was to explore what is known about mechanisms underlying women's risk and resilience in AD and identify emerging themes in this area that merit further research. We conducted a review of studies analyzing molecular mechanisms that may induce neuroplasticity in women, as well as cognitive and brain reserve. We also analyzed how the loss of steroid hormones in aging may be linked to AD. We included empirical studies with human and animal models, literature reviews as well as meta-analyses. Our search identified the importance of 17-b-estradiol (E2) as a mechanism driving cognitive and brain reserve in women. More broadly, our analysis revealed the following emerging perspectives: (1) the importance of steroid hormones and their effects on both neurons and glia for the study of risk and resilience in AD, (2) E2's crucial role in women's brain reserve, (3) women's verbal memory advantage as a cognitive reserve factor, and (4) E2's potential role in linguistic experiences such as multilingualism and hearing loss. Future directions for research include analyzing the reserve mechanisms of steroid hormones on neuronal and glial plasticity, as well as identifying the links between steroid hormone loss in aging and risk for AD.

Sportiello L and Capuano A (2023), It is the time to change the paradigms of pregnant and breastfeeding women in clinical research!.

ResumoFundamento:Apesar da importância das mulheres na pesquisa clínica, não existe uma avaliação da fração de mulheres em posições de autoria nos periódicos de cardiologia da SBC.Objetivos:Avaliar a fração de mulheres autoras na International Journal of Cardiovascular Sciences (IJCS) e nos Arquivos Brasileiros de Cardiologia (ABC Cardiol) nas últimas décadas.Métodos:Realizamos busca dos artigos originais dos ABC Cardiol, entre 2000 e 2019, e da IJCS, entre 2010 e 2019. Foi feito levantamento do número de primeiras e últimas autoras e do total de artigos originais de 2010 a 2019. Calculamos as proporções totais de autorias femininas e comparamos o primeiro quinquênio com o segundo. Para avaliar a evolução temporal das duas décadas, analisamos apenas dados dos ABC Cardiol. Utilizamos o teste Qui-quadrado para analisar as diferenças dentro de cada revista e entre ambas. O software IBM® SPSS® foi utilizado nas análises. O nível de significância adotado foi de 5%.Resultados:De 2010 a 2019, foram publicados 1157 artigos originais nos ABC Cardiol e 398 na IJCS. Observamos que as mulheres têm maior predominância como primeiras autoras na IJCS em relação aos ABC Cardiol, mas os homens predominam como últimos autores em ambos. De 2010 a 2019, não houve modificação significativa na proporção de autorias femininas. Ao longo das décadas analisadas para os ABC Cardiol, houve projeção de crescimento linear de autorias femininas, sendo que a inclinação da reta é maior na projeção da primeira autoria que na autoria sênior.Conclusões:Há disparidade de gênero com menor representatividade feminina nas autorias dos artigos dos periódicos cardiológicos brasileiros analisados: Arquivos Brasileiros de Cardiologia e International Journal of Cardiovascular Sciences. Acreditamos que a partir destes resultados mais esforços devam ser implementados em busca de equidade de gênero na produção científica cardiológica veiculada por estes periódicos.

ABSTRACT Introduction Left ventricular assist device (LVAD) and heart transplantation (HT) are the two life-sustaining therapies that have revolutionized the management of end-stage heart failure (HF). Yet, significant sex differences exist with respect to their use and effects. Areas Covered This review summarizes sex differences in the utilization, outcomes, and complications of LVAD and HT. Particular emphasis is placed on leading clinical trials in the field, historical and recent large registries-based analyses, as well as contemporary technological and policy changes affecting these differences. Expert Opinion Women with advanced HF remain under-treated with guideline-directed medical therapy and are less likely to be referred for consideration for LVAD and HT. This remains true despite newer LVAD technology and the new heart transplant allocation system. Community outreach, education, as well as increased representation of women in clinical research may reduce inequities.

Race, ethnicity, and gender reporting in North American clinical trials for BCG-unresponsive non-muscle invasive bladder cancer.

Advancing the inclusion of underrepresented women in clinical research

Sex and gender gaps in medicine and the androcentric history of medical research

The precautionary principle is often invoked in relation to pregnant women and may be one of the underlying reasons for their continuous underrepresentation in clinical research. The principle is appealing, because potential fetal harm as a result of research participation is considered to be serious and irreversible. In our paper, we explore through conceptual analysis whether and if so how the precautionary principle should apply to pregnant women. We argue that the principle is a decision-making strategy underlying risk-benefit decisions in clinical research, which can be applied to pregnant women. However, the current application is a strong one, leading to the promotion of absolute exclusion or, less often, absolute inclusion of pregnant women. In order to change this paralyzing situation, a shift toward weak precautionary thinking is necessary. Instead of automatic extreme precaution, a balance will be found between harms and potential benefits of including pregnant women in clinical research.