The meat industry's role in funding and influencing scientific research raises concerns about its impact on evidence used to inform public health policy. Although industry influence on other food and beverage sectors is well-documented, its effects on studies of meat consumption remain understudied. This study aimed to investigate the influence of meat industry involvement on study conclusions of research examining the health impacts of meat consumption. A meta-research review of relevant studies published between 2014 and 2023 was conducted using PubMed and Scopus. Studies investigating the nutritional health impacts of meat consumption were included. Study characteristics, author affiliations, declared funding sources, declared conflicts of interest, and study conclusions were extracted. Association tests were used to assess the relationship between industry ties and study conclusions. Of 500 included studies, 78 (15.6%) reported industry involvement. Studies with industry ties were 16 times more likely to report favorable conclusions regarding meat consumption (odds ratio [OR] = 16.4, 95% CI: 7.5-35.8), and there was a significant association (p < 0.001) between industry involvement and study conclusion. Meat industry involvement significantly increases the likelihood of favorable study conclusions in nutrition research. These findings underscore the need for caution when interpreting research funded or associated with the meat industry and emphasize the importance of minimizing conflicts of interest in nutrition research. Prospero: ID CRD42024526116.
Breast cancer is one of the most prevalent cancers worldwide, with a 5-year survival rate exceeding 90%. Despite advances in treatment, survivors frequently experience persistent cancer- and treatment-related symptoms that negatively impact their quality of life. Body-oriented interventions (BOIs) have demonstrated effectiveness in symptom management; however, systematic reviews focused exclusively on BOIs for women who survived breast cancer (WSBC) remain limited. This systematic review protocol outlines the methodology for evaluating the scientific evidence on the effects of BOIs on cancer- and treatment-related symptoms in WSBC. The aim of this study is to examine the scientific evidence on the effects of BOIs on cancer- and treatment-related symptoms, well-being, and quality of life in WSBC. This protocol follows PRISMA-P (Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols) guidelines. We will conduct searches in 6 electronic databases: PubMed, Cochrane, Web of Science, Scopus, APA PsycNet, and Portal Regional da BVS. Studies will be considered for inclusion if they are written in English, French, Portuguese, or Spanish, with no restrictions on publication date; they consist of WSBC (aged 18 to 64 years); they are randomized controlled trials, quasi-randomized controlled trials, and pilot studies focusing on BOIs; they include a control group receiving no intervention, standard care, or a non-BOI; and the primary outcomes of interest include preintervention and postintervention measures of cancer- and treatment-related symptoms, well-being, and quality of life. The methodological quality of the studies and the risk of bias will be assessed using the PEDro scale and version 2 of the Cochrane risk-of-bias tool, respectively. The synthesis of results will be measured through the Best Evidence Synthesis. Two experienced independent reviewers will conduct study selection, data extraction, methodological quality assessment, and scientific evidence assessment. Disagreements will be resolved by a third reviewer. This protocol describes the prespecified methodology for the systematic review. At the time of publication of this protocol, the corresponding full systematic review manuscript was under peer review. The outcomes will synthesize the scientific evidence on the effects of BOIs on cancer- and treatment-related symptoms in WSBC. It is anticipated that this systematic review will identify benefits and directions for future research to support the integration of BOIs tailored to this population. Considering that previous systematic reviews focused on the effects of BOIs in survivors of all cancer types, challenges related to study risk of bias such as heterogeneity in intervention types, study designs, and outcome measures are anticipated, potentially leading to some inconsistency and imprecision. To mitigate these issues, PRISMA guidelines will be followed, and methodological quality and best evidence strength will be rigorously assessed. This review will systematically synthesize the effects of BOIs on cancer- and treatment-related symptoms in WSBC. These findings will provide health professionals with reliable evidence and methodological guidance for further research. PROSPERO CRD42023452519; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=452519. DERR1-10.2196/76858.
To synthesize evidence on institutional spillover effects of antimicrobial use (AMU) on antimicrobial resistance (AMR) and Clostridioides difficile infections on individuals without direct antimicrobial exposure. Systematic review. Three databases were searched through August 2024 for studies evaluating spillover effects of AMU on unexposed individuals in institutional settings. Study characteristics, AMU, and outcomes were extracted. Study quality was assessed based on underlying methodology to detect spillover effect. A hybrid synthesis, including effect direction and meta-analysis of studies reporting continuous AMU and non-aggregate outcomes was utilized. Reporting followed PRISMA guidelines. Of 5916 screened studies, five observational studies met inclusion criteria. Three were conducted across 68 hospital wards (ward-level exposure), and two across 693 nursing homes (facility-level exposure). Three studies evaluated all antimicrobial classes; two focused on penicillins, fluoroquinolones, and carbapenems. Two studies examined C. difficile, one MRSA, one carbapenem-resistant Enterobacterales, and one reported combined AMR and C. difficile outcomes. Low to moderate quality evidence indicated a positive spillover effect direction with increasing facility AMU. Meta-analysis of three studies yielded a pooled IRR of 1.54 (95% CI 0.85-2.80) per 100 days of therapy per 1,000 patient-days, with significant heterogeneity (I 2 = 97.6%). This review identified five studies suggesting a positive association between institutional AMU and collateral risks of AMR and C. difficile among unexposed individuals. Findings were limited by methodological heterogeneity and potential publication bias. Standardizing terminology, specifying spillover mechanisms, and adopting robust observational designs can enhance future research on spillover effects.
The clinical risk of cognitive disorders linked to various drugs is not well-defined. This study aimed to identify medications with notable signals for drug-related cognitive disorders and evaluate whether their US Food and Drug Administration (FDA)-approved labels include relevant safety warnings. A retrospective disproportionality analysis using FDA Adverse Event Reporting System data (2004-2024) employed four algorithms-Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN) and Multi-Item Gamma Poisson Shrinker (MGPS)-for signal detection. To confirm the results, a cross-database consistency check was performed with the Japanese Adverse Drug Event Report (JADER) and World Health Organization (WHO) VigiAccess databases. An analysis of 41,775 reports on drug-related cognitive disorders found significant signals for 50 medications using four algorithms. Notably, 74% of these drugs, including finasteride, diltiazem, and carbidopa/levodopa, lacked cognitive disorder warnings in FDA labels. Reporting patterns were classified into early or random failure types. Subgroup analyses showed certain drugs were disproportionately reported in vulnerable groups, such as antiepileptics in children and neurologic agents in seniors. The U.S. had the most reports. Multivariate analysis identified 43 factors linked to higher reporting odds, including conditions like depression and the use of specific drugs. Cross-database validation confirmed consistent signals for 92% of primary drug-event pairs. This pharmacovigilance analysis uncovers significant, previously unrecognized signals of drug-related cognitive disorders in various medications, most lacking label warnings. These findings highlight the need for further research, potential label updates, and increased clinical awareness, particularly in high-risk groups. Importantly, these results indicate statistical associations, not causal links, between the drugs and cognitive disorders.
Since the rise of freely accessible pornographic streaming websites, pornography consumption has become widespread and normative worldwide. In Flanders, early exposure-before age 13-has tripled over the past decade, and frequent use, particularly among young men, is common. While pornography consumption may support body satisfaction, self-exploration, and self-esteem, evidence on its effects on sexual development and sexual well-being remains limited. Public debates are polarized, swinging between moral panic and denial of potential risks. Care providers and helplines increasingly report young people struggling with pornography-related concerns, such as self-perceived porn-induced sexual dysfunctions. Adolescents and young adults from diverse backgrounds express a clear need for guidance in navigating sexually explicit media, particularly when communication with parents, teachers, or health care providers is difficult. This project aims to generate evidence-based insights into the complex relationships between pornography consumption, sexual development, and sexual well-being among young people. By producing actionable knowledge, it seeks to inform education, prevention, and care practices that help adolescents and young adults navigate sexually explicit media in ways that promote healthy and inclusive sexual well-being within Flanders' ethnically and sexually diverse society. The project consists of four interconnected work packages: (1) examining pornography in relation to societal norms and inequalities, (2) exploring pornography within family-based sexual development, (3) investigating pornography's role in health care contexts, and (4) developing evidence-based pornography literacy tools for education and prevention. A mixed methods approach will combine systematic scoping reviews, a nationally representative survey, laboratory studies, qualitative interviews and focus groups, and co-creation with key societal stakeholders. The project received funding from Research Foundation - Flanders in 2024, and researchers were appointed between September and November 2024. Scoping reviews began in January 2025 and concluded in October 2025. A large-scale survey will be conducted between January and March 2026, followed by subsequent stages of analysis, dissemination, and valorization, concluding in 2028. Although empirical results are not yet available, the project will deliver new evidence on how pornography consumption shapes sexual development and sexual well-being across diverse contexts. It will produce practical outputs for education, health care, and policy, and contribute to reducing stigma and misinformation around pornography use. By addressing pornography as a multifaceted social and sexual phenomenon, this multidisciplinary research will advance scientific understanding and promote more inclusive, evidence-based approaches to sexual health education, care, and policy.
Ecological momentary assessment (EMA) is a tool facilitating the repeated collection of real-time data in naturalistic settings that can be applied to clinical research. Despite established methodological strengths, EMA protocols may be burdensome for participants, potentially leading to problems with adherence. Existing meta-analytic evidence is insufficient to inform the decision making of clinical researchers in using EMA in their work. In the current registered report, we address this need by conducting a systematic review with meta-analysis (1) examining adherence (enrollment, dropout, and compliance) in children and adolescents with psychological disorders and symptoms and (2) identifying aspects of study design that maximize adherence. In January 2023, we searched five databases for empirical EMA studies of youth (8-17 years) with psychological symptoms/diagnoses with data on adherence. We extracted data, assessed study quality, and conducted meta-analyses using random-effects models. We included 130 studies with 14,400 participants. On average, surveys contained 15 items, took over 3 min to complete, and incorporated surveys with multiple response scale types delivered using smartphones/cell phones provided to participants. Meta-analyses revealed that study enrollment was moderate to high (82% in youth with psychopathology, 67% in community youth) and dropout prior to starting EMA protocols was low (<1-2%). Dropout during EMA protocols was 12% for youth with psychopathology and 8% for community youth, underscoring the importance of maintaining participant engagement throughout EMA studies. Compliance approximated the 80% field benchmark for healthy youth but was lower for youth from the community and with psychopathology. Participant characteristics (e.g., younger age) and design factors (e.g., incentive-based compensation) were associated with greater compliance in certain groups. Despite limitations (missing data, methodological constraints), findings have important implications for researchers developing and conducting pediatric EMA protocols. The stage 1 protocol for this Registered Report was accepted in principle on April 19, 2024. The protocol, as accepted by the journal, can be found at: https://doi.org/10.6084/m9.figshare.25732482.v1 . This research was supported by the Intramural Research Program (IRP) of the NIMH and the NIH Library's and Office of Research Service's support of the NIH IRP. Ecological momentary assessment (EMA) is a tool for collecting naturalistic, real-time data. We conducted a systematic review with meta-analysis examining adherence (enrollment, dropout, and compliance) in children and adolescents with psychological disorders and symptoms and aspects of study design that maximize adherence.
Peripherally Inserted Central Catheter (PICC)-associated complications, such as infections and thrombosis, impact significantly upon patients’ experiences and outcomes of care. The purpose of this study was to assess the utility of a patient-reported outcome measure (EuroQol Five Dimension Five Level (EQ5D-5L)), and patient-reported experience measure (Australian Hospital Patient Experience Question Set (AHPEQS)), to discriminate incidence of PICC failure among adults. A secondary analysis was undertaken of two large randomised controlled trials, conducted in two adult tertiary hospitals in Queensland, Australia. The EQ5D-5L and AHPEQS instruments were assessed against incidence of three clinical outcomes likely to impact upon self-reported outcomes and experiences: Central Line Associated Bloodstream Infection (CLABSI), venous thrombosis, and all-cause PICC complication. Partial proportional odds, multinomial logistic, linear regression and generalised linear regression models were used to assess instrument performance. Overall, 984 participants provided baseline EQ5D-5L responses. Subsequently, n=628 completed an EQ5D-5L at study end; n=552 further completed the AHPEQS. EQ5D-5L demonstrated poor discrimination of individual complications (CLABSI, thrombosis), however, there was a significant association (p=<0.05) between all-cause PICC complication and: utility (− 0.1, Confidence Interval (CI) − 0.1 to − 0.1); disutility (0.4, CI 0.2–0.7); and self-reported health (– 4.3, CI − 7.8 to − 0.9). AHPEQS demonstrated poor discrimination; one item (‘both physical and emotional harm’) was significantly associated with all-cause PICC complication (1.0, 95%CI 0.1–1.9); CLABSI (2.4, 95%CI 0.7–4.2); and thrombosis (2.0, 95%CI 0.7–3.4). EQ5D-5L demonstrated moderate suitability for use among patients with PICCs; AHPEQS demonstrated little reliability. The online version contains supplementary material available at 10.1007/s11136-026-04264-2. Patients needing long-term or ‘irritant’ intravenous treatments (like chemotherapy, or antibiotics) often need Peripherally Inserted Central Catheters. One in every four of these devices fail (e., they fall out, or become blocked or infected). As a result, patients can experience both negative physical (discomfort, treatment delay) and psychological (distress) effects. It is important that researchers, doctors, and nurses understand these experiences, to identify where and how care can improve. To do this, special questionnaires called ‘patient-reported outcome measures’ and ‘patient-reported experience measures’ are used to assess health outcomes of patients’ care, and how patients experience this care. These questionnaires can either be very general or relate specifically to a condition (cancer) or intervention (surgery). To date there has been no ‘gold standard’ questionnaire for Peripherally Inserted Central Catheters. Two recent large trials have used general questionnaires as part of their regular data collection. This data was combined and analysed to find out if they were good at picking up whether a patient had experienced Peripherally Inserted Central Catheter complications (i.e., do they do what they are supposed to?). Neither questionnaire was considered ‘gold standard,’ however a few select questions within them appeared useful. The online version contains supplementary material available at 10.1007/s11136-026-04264-2.
To estimate the prevalence of US adults' exposure to point-of-sale corrective statements about the health effects, addictiveness, and deceptive marketing of cigarettes, as well as reactions to these messages. We analysed data from the 2024 Health Information National Trends Survey, a cross-sectional, nationally representative sample of the US civilian non-institutionalised population aged 18+ (March-September 2024, N=7278). Weighted multivariable logistic regression models estimated associations of tobacco use, sociodemographic characteristics and perceptions of conflicting health recommendations with self-reported exposure and reactions. In 2024, 36.5% of US adults reported seeing point-of-sale corrective statements. Individuals who currently smoked (52.9%) were more likely to report exposure compared with those who never (34.7%) or formerly smoked (34.3%). Among those exposed, 53.6% trusted the information, 49.3% supported the court's mandate, 26.5% thought about friends/family who smoke and 7.9% wanted to look for more information about smoking risks. 41.1% of individuals who currently smoked and saw the statements reported thinking about quitting. Multivariable analyses indicated that those who smoked or used non-cigarette tobacco products were more likely to report exposure and less likely to support the mandate, while individuals who believed that health recommendations often conflict were less likely to trust the information. About one in three US adults-and about half of people who smoke-reported noticing point-of-sale corrective statements in 2024. Although exposure rates were relatively consistent across sociodemographic groups, variations in individual reactions point to a need for strategies that enhance the impact of corrective statements, particularly among those who smoke.
HomeCirculationVol. 123, No. 23Standardized Bleeding Definitions for Cardiovascular Clinical Trials Free AccessResearch ArticlePDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissionsDownload Articles + Supplements ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toSupplementary MaterialsFree AccessResearch ArticlePDF/EPUBStandardized Bleeding Definitions for Cardiovascular Clinical TrialsA Consensus Report From the Bleeding Academic Research Consortium Roxana Mehran, MD, Sunil V. Rao, MD, Deepak L. Bhatt, MD, MPH, C. Michael Gibson, MS, MD, Adriano Caixeta, MD, PhD, John Eikelboom, MD, MBBS, Sanjay Kaul, MD, Stephen D. Wiviott, MD, Venu Menon, MD, Eugenia Nikolsky, MD, PhD, Victor Serebruany, MD, PhD, Marco Valgimigli, MD, PhD, Pascal Vranckx, MD, David Taggart, MD, PhD, Joseph F. Sabik, MD, Donald E. Cutlip, MD, Mitchell W. Krucoff, MD, E. Magnus Ohman, MD, Philippe Gabriel Steg, MD and Harvey White, MB, ChB, DSc Roxana MehranRoxana Mehran The BARC represents a collaboration of independent academic research organizations (Cardialysis, Rotterdam, the Netherlands; Cardiovascular Research Foundation, New York City, NY; Duke Clinical Research Institute, Durham, NC; TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA; Harvard Clinical Research Institute, Boston, MA; Green Lane Coordinating Centre, Auckland, New Zealand; Cleveland Clinic Coordinating Center for Clinical Research, Cleveland, OH; and PERFUSE, Boston, MA), professional societies (European Society of Cardiology, and Society of Cardiac Angiography and Intervention), federal agencies (the US FDA, National Institutes of Health), and independent expert scientists and consultants (Appendix). Search for more papers by this author , Sunil V. RaoSunil V. Rao The BARC represents a collaboration of independent academic research organizations (Cardialysis, Rotterdam, the Netherlands; Cardiovascular Research Foundation, New York City, NY; Duke Clinical Research Institute, Durham, NC; TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA; Harvard Clinical Research Institute, Boston, MA; Green Lane Coordinating Centre, Auckland, New Zealand; Cleveland Clinic Coordinating Center for Clinical Research, Cleveland, OH; and PERFUSE, Boston, MA), professional societies (European Society of Cardiology, and Society of Cardiac Angiography and Intervention), federal agencies (the US FDA, National Institutes of Health), and independent expert scientists and consultants (Appendix). Search for more papers by this author , Deepak L. BhattDeepak L. Bhatt The BARC represents a collaboration of independent academic research organizations (Cardialysis, Rotterdam, the Netherlands; Cardiovascular Research Foundation, New York City, NY; Duke Clinical Research Institute, Durham, NC; TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA; Harvard Clinical Research Institute, Boston, MA; Green Lane Coordinating Centre, Auckland, New Zealand; Cleveland Clinic Coordinating Center for Clinical Research, Cleveland, OH; and PERFUSE, Boston, MA), professional societies (European Society of Cardiology, and Society of Cardiac Angiography and Intervention), federal agencies (the US FDA, National Institutes of Health), and independent expert scientists and consultants (Appendix). Search for more papers by this author , C. Michael GibsonC. Michael Gibson The BARC represents a collaboration of independent academic research organizations (Cardialysis, Rotterdam, the Netherlands; Cardiovascular Research Foundation, New York City, NY; Duke Clinical Research Institute, Durham, NC; TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA; Harvard Clinical Research Institute, Boston, MA; Green Lane Coordinating Centre, Auckland, New Zealand; Cleveland Clinic Coordinating Center for Clinical Research, Cleveland, OH; and PERFUSE, Boston, MA), professional societies (European Society of Cardiology, and Society of Cardiac Angiography and Intervention), federal agencies (the US FDA, National Institutes of Health), and independent expert scientists and consultants (Appendix). Search for more papers by this author , Adriano CaixetaAdriano Caixeta The BARC represents a collaboration of independent academic research organizations (Cardialysis, Rotterdam, the Netherlands; Cardiovascular Research Foundation, New York City, NY; Duke Clinical Research Institute, Durham, NC; TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA; Harvard Clinical Research Institute, Boston, MA; Green Lane Coordinating Centre, Auckland, New Zealand; Cleveland Clinic Coordinating Center for Clinical Research, Cleveland, OH; and PERFUSE, Boston, MA), professional societies (European Society of Cardiology, and Society of Cardiac Angiography and Intervention), federal agencies (the US FDA, National Institutes of Health), and independent expert scientists and consultants (Appendix). Search for more papers by this author , John EikelboomJohn Eikelboom The BARC represents a collaboration of independent academic research organizations (Cardialysis, Rotterdam, the Netherlands; Cardiovascular Research Foundation, New York City, NY; Duke Clinical Research Institute, Durham, NC; TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA; Harvard Clinical Research Institute, Boston, MA; Green Lane Coordinating Centre, Auckland, New Zealand; Cleveland Clinic Coordinating Center for Clinical Research, Cleveland, OH; and PERFUSE, Boston, MA), professional societies (European Society of Cardiology, and Society of Cardiac Angiography and Intervention), federal agencies (the US FDA, National Institutes of Health), and independent expert scientists and consultants (Appendix). Search for more papers by this author , Sanjay KaulSanjay Kaul The BARC represents a collaboration of independent academic research organizations (Cardialysis, Rotterdam, the Netherlands; Cardiovascular Research Foundation, New York City, NY; Duke Clinical Research Institute, Durham, NC; TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA; Harvard Clinical Research Institute, Boston, MA; Green Lane Coordinating Centre, Auckland, New Zealand; Cleveland Clinic Coordinating Center for Clinical Research, Cleveland, OH; and PERFUSE, Boston, MA), professional societies (European Society of Cardiology, and Society of Cardiac Angiography and Intervention), federal agencies (the US FDA, National Institutes of Health), and independent expert scientists and consultants (Appendix). Search for more papers by this author , Stephen D. WiviottStephen D. Wiviott The BARC represents a collaboration of independent academic research organizations (Cardialysis, Rotterdam, the Netherlands; Cardiovascular Research Foundation, New York City, NY; Duke Clinical Research Institute, Durham, NC; TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA; Harvard Clinical Research Institute, Boston, MA; Green Lane Coordinating Centre, Auckland, New Zealand; Cleveland Clinic Coordinating Center for Clinical Research, Cleveland, OH; and PERFUSE, Boston, MA), professional societies (European Society of Cardiology, and Society of Cardiac Angiography and Intervention), federal agencies (the US FDA, National Institutes of Health), and independent expert scientists and consultants (Appendix). Search for more papers by this author , Venu MenonVenu Menon The BARC represents a collaboration of independent academic research organizations (Cardialysis, Rotterdam, the Netherlands; Cardiovascular Research Foundation, New York City, NY; Duke Clinical Research Institute, Durham, NC; TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA; Harvard Clinical Research Institute, Boston, MA; Green Lane Coordinating Centre, Auckland, New Zealand; Cleveland Clinic Coordinating Center for Clinical Research, Cleveland, OH; and PERFUSE, Boston, MA), professional societies (European Society of Cardiology, and Society of Cardiac Angiography and Intervention), federal agencies (the US FDA, National Institutes of Health), and independent expert scientists and consultants (Appendix). Search for more papers by this author , Eugenia NikolskyEugenia Nikolsky The BARC represents a collaboration of independent academic research organizations (Cardialysis, Rotterdam, the Netherlands; Cardiovascular Research Foundation, New York City, NY; Duke Clinical Research Institute, Durham, NC; TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA; Harvard Clinical Research Institute, Boston, MA; Green Lane Coordinating Centre, Auckland, New Zealand; Cleveland Clinic Coordinating Center for Clinical Research, Cleveland, OH; and PERFUSE, Boston, MA), professional societies (European Society of Cardiology, and Society of Cardiac Angiography and Intervention), federal agencies (the US FDA, National Institutes of Health), and independent expert scientists and consultants (Appendix). Search for more papers by this author , Victor SerebruanyVictor Serebruany The BARC represents a collaboration of independent academic research organizations (Cardialysis, Rotterdam, the Netherlands; Cardiovascular Research Foundation, New York City, NY; Duke Clinical Research Institute, Durham, NC; TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA; Harvard Clinical Research Institute, Boston, MA; Green Lane Coordinating Centre, Auckland, New Zealand; Cleveland Clinic Coordinating Center for Clinical Research, Cleveland, OH; and PERFUSE, Boston, MA), professional societies (European Society of Cardiology, and Society of Cardiac Angiography and Intervention), federal agencies (the US FDA, National Institutes of Health), and independent expert scientists and consultants (Appendix). Search for more papers by this author , Marco ValgimigliMarco Valgimigli The BARC represents a collaboration of independent academic research organizations (Cardialysis, Rotterdam, the Netherlands; Cardiovascular Research Foundation, New York City, NY; Duke Clinical Research Institute, Durham, NC; TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA; Harvard Clinical Research Institute, Boston, MA; Green Lane Coordinating Centre, Auckland, New Zealand; Cleveland Clinic Coordinating Center for Clinical Research, Cleveland, OH; and PERFUSE, Boston, MA), professional societies (European Society of Cardiology, and Society of Cardiac Angiography and Intervention), federal agencies (the US FDA, National Institutes of Health), and independent expert scientists and consultants (Appendix). Search for more papers by this author , Pascal VranckxPascal Vranckx The BARC represents a collaboration of independent academic research organizations (Cardialysis, Rotterdam, the Netherlands; Cardiovascular Research Foundation, New York City, NY; Duke Clinical Research Institute, Durham, NC; TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA; Harvard Clinical Research Institute, Boston, MA; Green Lane Coordinating Centre, Auckland, New Zealand; Cleveland Clinic Coordinating Center for Clinical Research, Cleveland, OH; and PERFUSE, Boston, MA), professional societies (European Society of Cardiology, and Society of Cardiac Angiography and Intervention), federal agencies (the US FDA, National Institutes of Health), and independent expert scientists and consultants (Appendix). Search for more papers by this author , David TaggartDavid Taggart The BARC represents a collaboration of independent academic research organizations (Cardialysis, Rotterdam, the Netherlands; Cardiovascular Research Foundation, New York City, NY; Duke Clinical Research Institute, Durham, NC; TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA; Harvard Clinical Research Institute, Boston, MA; Green Lane Coordinating Centre, Auckland, New Zealand; Cleveland Clinic Coordinating Center for Clinical Research, Cleveland, OH; and PERFUSE, Boston, MA), professional societies (European Society of Cardiology, and Society of Cardiac Angiography and Intervention), federal agencies (the US FDA, National Institutes of Health), and independent expert scientists and consultants (Appendix). Search for more papers by this author , Joseph F. SabikJoseph F. Sabik The BARC represents a collaboration of independent academic research organizations (Cardialysis, Rotterdam, the Netherlands; Cardiovascular Research Foundation, New York City, NY; Duke Clinical Research Institute, Durham, NC; TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA; Harvard Clinical Research Institute, Boston, MA; Green Lane Coordinating Centre, Auckland, New Zealand; Cleveland Clinic Coordinating Center for Clinical Research, Cleveland, OH; and PERFUSE, Boston, MA), professional societies (European Society of Cardiology, and Society of Cardiac Angiography and Intervention), federal agencies (the US FDA, National Institutes of Health), and independent expert scientists and consultants (Appendix). Search for more papers by this author , Donald E. CutlipDonald E. Cutlip The BARC represents a collaboration of independent academic research organizations (Cardialysis, Rotterdam, the Netherlands; Cardiovascular Research Foundation, New York City, NY; Duke Clinical Research Institute, Durham, NC; TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA; Harvard Clinical Research Institute, Boston, MA; Green Lane Coordinating Centre, Auckland, New Zealand; Cleveland Clinic Coordinating Center for Clinical Research, Cleveland, OH; and PERFUSE, Boston, MA), professional societies (European Society of Cardiology, and Society of Cardiac Angiography and Intervention), federal agencies (the US FDA, National Institutes of Health), and independent expert scientists and consultants (Appendix). Search for more papers by this author , Mitchell W. KrucoffMitchell W. Krucoff The BARC represents a collaboration of independent academic research organizations (Cardialysis, Rotterdam, the Netherlands; Cardiovascular Research Foundation, New York City, NY; Duke Clinical Research Institute, Durham, NC; TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA; Harvard Clinical Research Institute, Boston, MA; Green Lane Coordinating Centre, Auckland, New Zealand; Cleveland Clinic Coordinating Center for Clinical Research, Cleveland, OH; and PERFUSE, Boston, MA), professional societies (European Society of Cardiology, and Society of Cardiac Angiography and Intervention), federal agencies (the US FDA, National Institutes of Health), and independent expert scientists and consultants (Appendix). Search for more papers by this author , E. Magnus OhmanE. Magnus Ohman The BARC represents a collaboration of independent academic research organizations (Cardialysis, Rotterdam, the Netherlands; Cardiovascular Research Foundation, New York City, NY; Duke Clinical Research Institute, Durham, NC; TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA; Harvard Clinical Research Institute, Boston, MA; Green Lane Coordinating Centre, Auckland, New Zealand; Cleveland Clinic Coordinating Center for Clinical Research, Cleveland, OH; and PERFUSE, Boston, MA), professional societies (European Society of Cardiology, and Society of Cardiac Angiography and Intervention), federal agencies (the US FDA, National Institutes of Health), and independent expert scientists and consultants (Appendix). Search for more papers by this author , Philippe Gabriel StegPhilippe Gabriel Steg The BARC represents a collaboration of independent academic research organizations (Cardialysis, Rotterdam, the Netherlands; Cardiovascular Research Foundation, New York City, NY; Duke Clinical Research Institute, Durham, NC; TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA; Harvard Clinical Research Institute, Boston, MA; Green Lane Coordinating Centre, Auckland, New Zealand; Cleveland Clinic Coordinating Center for Clinical Research, Cleveland, OH; and PERFUSE, Boston, MA), professional societies (European Society of Cardiology, and Society of Cardiac Angiography and Intervention), federal agencies (the US FDA, National Institutes of Health), and independent expert scientists and consultants (Appendix). Search for more papers by this author and Harvey WhiteHarvey White The BARC represents a collaboration of independent academic research organizations (Cardialysis, Rotterdam, the Netherlands; Cardiovascular Research Foundation, New York City, NY; Duke Clinical Research Institute, Durham, NC; TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA; Harvard Clinical Research Institute, Boston, MA; Green Lane Coordinating Centre, Auckland, New Zealand; Cleveland Clinic Coordinating Center for Clinical Research, Cleveland, OH; and PERFUSE, Boston, MA), professional societies (European Society of Cardiology, and Society of Cardiac Angiography and Intervention), federal agencies (the US FDA, National Institutes of Health), and independent expert scientists and consultants (Appendix). Search for more papers by this author Originally published14 Jun 2011https://doi.org/10.1161/CIRCULATIONAHA.110.009449Circulation. 2011;123:2736–2747Advances in antithrombotic therapy, along with an early invasive strategy, have reduced the incidence of recurrent ischemic events and death in patients with acute coronary syndromes (ACS; unstable angina, non–ST-segment–elevation myocardial infarction [MI], and ST-segment–elevation MI).1–4 However, the combination of multiple pharmacotherapies, including aspirin, platelet P2Y12 inhibitors, heparin plus glycoprotein IIb/IIIa inhibitors, direct thrombin inhibitors, and the increasing use of invasive procedures, has also been associated with an increased risk of bleeding.Editorial see p 2664Bleeding complications have been associated with an increased risk of subsequent adverse outcomes, including MI, stroke, stent thrombosis, and death, in patients with ACS and in those undergoing percutaneous coronary intervention (PCI),5–10 as well as in the long-term antithrombotic setting.11,12 Thus, balancing the anti-ischemic benefits against the bleeding risk of antithrombotic agents and interventions is of paramount importance in assessing new therapies and in managing patients. Prior randomized trials comparing antithrombotic agents suggest that a reduction in bleeding events is associated with improved survival.13,14Because prevention of major bleeding may represent an important step in improving outcomes by balancing safety and efficacy in the contemporary treatment of ACS, bleeding events have been systematically identified as a crucial end point for the assessment of the safety of drugs during the course of randomized clinical trials, and are an important aspect of the evaluation of new devices and interventional therapies.15 Unlike ischemic clinical events (eg, cardiac death, MI, stent thrombosis), for which there is now general consensus on end-point definitions,16,17 there is substantial heterogeneity among the many bleeding definitions currently in use. Lack of standardization makes it difficult to optimally organize key clinical trial processes such as adjudication, and even more difficult to interpret relative safety comparisons of different antithrombotic agents across studies, or even within a given trial, because results may vary according to the definition(s) used for bleeding. Finally, as reflected by the various terms used to describe bleeding (serious, severe, catastrophic, major, life-threatening, etc), the heterogeneity of definitions may undermine the ability of clinical trials to meaningfully define the balance of safety and efficacy in vascular interventions.In response to the need to develop, disseminate, and ultimately adopt standardized bleeding end-point definitions for patients receiving antithrombotic therapy, the Bleeding Academic Research Consortium (BARC) convened in February 2010 at the US Food and Drug Administration (FDA) headquarters in White Oak, MD. Modeled after the 2006 Academic Research Consortium, which standardized key ischemic end-point definitions in studies aimed at evaluating coronary stents,17 the BARC effort brought together representatives from academic research organizations, the FDA, the National Institutes of Health, and pharmaceutical and cardiovascular device manufacturers and independent physician thought leaders in the field of cardiovascular disease to develop consensus bleeding definitions that would be useful for cardiovascular clinical trials. Application of these definitions is recommended for both clinical trials and registries.Importance of Bleeding as an End PointHemorrhagic complications occur with a frequency of 1% to 10% during treatment for ACS and after PCI.18–20 This wide variability in the measured incidence is due to several factors, including differences in patient characteristics, concomitant therapies, timing of event reporting, and definitions across data sets. Regardless of the definition used, several studies have demonstrated that bleeding is associated with an increased risk for short- and long-term adverse outcomes, including death,18,20 nonfatal MI,6 stroke,5 and stent thrombosis.9 The exact mechanisms underlying this relationship are not known, but may include the cessation of evidence-based therapies, including antiplatelet agents, β-blockers, and/or statin therapies, in patients who suffer bleeding complications,21,22 the direct effects of blood transfusion used to treat bleeding,20,23 or greater prevalence of comorbidities in patients who bleed,21 as well as a deleterious role of anemia.24The relationship between bleeding and morbidity and mortality is underscored by studies demonstrating that bleeding reduction strategies are associated with improved survival in patients with ACS and those undergoing PCI. The data summarized inTable 1 emphasize the importance of bleeding as a common, clinically relevant safety event. To optimize both the end point and its role in clinical trial designs, a consistent approach to collecting bleeding data and adjudicating events is critical.30 Toward this end, a thoughtful, broadly based consensus definition of what constitutes a bleeding event, similar to what has been done with MI and stent thrombosis, is the objective of BARC efforts.17Table 1. Impact of Major Bleeding on Mortality in Registries and Randomized Trials of Patients With Acute Coronary Syndromes or Undergoing Percutaneous Coronary InterventionsStudySetting, DesignPrimary Definition*PatientsPatients With Bleeding, n (%)Outcomes in Patients With Major or Severe Bleeding vs No BleedingEarly Deaths (In Hospital or at 30 d)Deaths up to 1 yDeath Rates, %Adjusted Risk Ratio for Death (95% CI)Death Rates, %Adjusted Risk Ratio for Death (95% CI)Kinnaird et al,7 2003PCI, registryTIMI10 974588 (5.4)7.5 vs 0.63.5 (1.9–6.7)17.2 vs 5.5Not significant†GRACE,10 2003ACS, registryGRACE24 045933 (3.9)18.6 vs 5.11.6 (1.2–2.3)……GRACE,21 2007ACS, registryGRACE40 0871140 (2.8)20.9 vs 5.61.9 (1.6–2.2)7.9 vs 5.20.8 (0.6–1.0)REPLACE-2,25 2007PCI, RCTREPLACE-2/ISAR-REACT 36001195 (3.2)5.1 vs 0.2…8.7 vs 1.92.7 (1.4–4.9)Rao et al,6 2005NSTE-ACS, meta-analysis of RCTsGUSTO26 452107 (0.4)25.7 vs 2.910.6 (8.3–13.6)35.1 vs 4.27.5 (6.1–9.3)Eikelboom et al,5 2006NSTE-ACS, meta-analysis of RCTs/registryCURE34 146783 (2.3)12.8 vs 2.59.8 (7.5–12.7)4.6 vs 2.9‡1.9 (1.3–2.8)ACUITY,9 2007NSTE-ACS, RCTACUITY13 819644 (4.7)7.3 vs 1.27.6 (4.7–12.2)…3.5 (2.7–4.4)Ndrepepa et al,15 2008PCI, meta-analysis of RCTsTIMI5384215 (4.0; n=59 major/n=156 minor)……12.2 vs 3.34.1 (2.1–8.3)EVENT,26 2009PCI, registryTIMI5961(3.0 overall: 0.7 major, 2.3 minor)……15.6 vs 2.43.8 (2.5–5.9)OASIS-5,27 2009NSTE-ACS, RCTESSENCE20 078990 (4.9): major, 423 (2.1) minor8.4 vs 2.73.5 (2.6–4.6)14.3 vs 5.43.1 (2.6–3.8)Amlani et al,28 2010STEMI, registryProtocol defined1389152 (10.9)19.7 vs 8.22.8 (1.8–4.3)……ISAR-REACT 3,29 2010PCI, RCTREPLACE-2/ISAR-REACT 34570555 (12.1) 174 major/381 minor……5.2 vs 1.34.1 (2.6–6.5)CI indicates confidence interval; PCI, percutaneous coronary intervention; TIMI, Thrombolysis in Myocardial Infarction; ACS, acute coronary syndrome; GRACE, Global Registry of Acute Coronary Events; RCT, randomized controlled trial; REPLACE-2, Randomized Evaluation in PCI Linking Angiomax to Reduced Clinical Events; ISAR-REACT 3, Intracoronary Stenting and Antithrombotic Regimen: Rapid Early Action for Coronary Treatment; NSTE, non–ST-elevation; GUSTO, Global Use of Strategies to Open Occluded Arteries; CURE, Clopidogrel in Unstable Angina to Prevent Recurrent Events; ACUITY, Acute Catheterization and Urgent Intervention Triage Strategy; EVENT, Evaluation of Drug Eluting Stents and Ischemic Events; and OASIS-5, Organization for the Assessment of Strategies for Ischemic Syndromes.*For Definitions, please seeTable 2.†Data not provided.‡Events between 30 days and 6 months.Bleeding Academic Research Consortium Composition and GoalsAn informal collaboration among academic research organizations from the United States and Europe, joined by representatives from the FDA and device manufacturers, led to a consensus document to standardize clinical end points for coronary stent trials.17 This Academic Research Consortium developed a rapid, scholarly, and clinically relevant process resulting in a portfolio of clinical end-point definitions that were endorsed by the FDA and broadly incorporated into clinical trial end points.31,32 The Academic Research Consortium process was a demonstration of effective collaboration among the academic community, FDA, and industry to respond to safety concerns over drug-eluting stents and to improve the conduct of clinical research. This initiative has since been expanded to other clinical domains, including percutaneous valves and peripheral arterial disease, and the effort to establish standardized bleeding definitions presented in this consensus document. These standardized definitions are intended to allow the clinical community to determine the relative safety of different antithrombotic strategies, to provide the industry with a framework in which to evaluate the safety of emerging antithrombotic therapies, and potentially to enhance the regulatory review of new anticoagulant and antiplatelet drugs.Heterogeneity of Bleeding Definitions Across TrialsSeveral definitions of bleeding have been used in published clinical trials and registries.33–35Table 2 highlights the lack of uniformity in bleeding definitions among recent ACS and PCI clinical trials. Current bleeding definitions consist of both laboratory parameters, such as decreases in hemoglobin and hematocrit scores, and clinical events, including the need for transfusion or surgery, cardiac tamponade, hematomas, and various degrees of bleeding. Each definition incorporates a different combination of these data elements and then rank orders these combinations into severity categories, which vary widely between definitions.Table 2. Heterogeneity in Bleeding Definitions Used in Acute Coronary Syndrome TrialsTrialBleeding DefinitionTIMI6,37,38Non-CABG related bleeding Major Any intracranial bleeding (excluding microhemorrhages <10 mm evident only on gradient-echo MRI)Clinically overt signs of hemorrhage associated with a drop in hemoglobin of ≥5 g/dLFatal bleeding (bleeding that directly results in death within 7 d)Minor Clinically overt (including imaging), resulting in hemoglobin drop of 3 to <5 g/dLRequiring medical attention Any overt sign of hemorrhage that meets one of the following criteria and does not meet criteria for a major or minor bleeding event, as defined aboveRequiring intervention (medical practitioner-guided medical or surgical treatment to stop or treat bleeding, including temporarily or permanently discontinuing or changing the dose of a medication or study drug)Leading to or prolonging hospitalizationPrompting evaluation (leading to an unscheduled visit to a healthcare professional and diagnostic testing, either laboratory or imaging)Minimal Any overt bleeding event that does not meet the criteria aboveBleeding in the setting of CABG Fatal bleeding (bleeding that directly results in death)Perioperative intracranial bleedingReoperation after closure of the sternotomy incision for the purpose of controlling bleedingTransfusion of ≥5 U PRBCs or whole blood within a 48-h period; cell saver transfusion will not be counted in calculations of blood products.Chest tube output >2 L within a 24-h periodGUSTO24Severe or life-threatening Intracerebral hemorrhageResulting in substantial hemodynamic compromise requiring treatmentModerate Requiring blood transfusion but not resulting in hemodynamic compromiseMild Bleeding that does not meet above criteriaCURE5Major bleeding Life-threatening (fatal, intracranial, requiring surgical intervention, results in substantial hypotension requiring the use of intravenous inotropic agents) Hemoglobin decrease ≥5 g/dL or required ≥4 U of bloodOther major bleed
OBJECTIVE: The "Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)" disease has caused a worldwide challenging and threatening pandemic (COVID-19), with huge health and economic losses. The US Food and Drug Administration, (FDA) has granted emergency use authorization for treatment with the Pfizer/BioNTech and Moderna COVID-19 vaccines. Many people have a history of a significant allergic reaction to a specific food, medicine, or vaccine; hence, people all over the world have great concerns about these two authorized vaccines. This article compares the pharmacology, indications, contraindications, and adverse effects of the Pfizer/BioNTech and Moderna vaccines. MATERIALS AND METHODS: The required documents and information were collected from the relevant databases, including Web of Science (Clarivate Analytics), PubMed, EMBASE, World Health Organization (WHO), Food and Drug Authorities (FDA) USA, Local Ministries, Health Institutes, and Google Scholar. The key terms used were: Coronavirus, SARS-COV-2, COVID-19 pandemic, vaccines, Pfizer/BioNTech vaccine, Moderna vaccine, pharmacology, benefits, allergic responses, indications, contraindications, and adverse effects. The descriptive information was recorded, and we eventually included 12 documents including research articles, clinical trials, and websites to record the required information. RESULTS: Based on the currently available literature, both vaccines are beneficial to provide immunity against SARS-CoV-2 infection. Pfizer/BioNTech Vaccine has been recommended to people 16 years of age and older, with a dose of 30 μg (0.3 m) at a cost of $19.50. It provides immunogenicity for at least 119 days after the first vaccination and is 95% effective in preventing the SARS-COV-2 infection. However, Moderna Vaccine has been recommended to people 18 years of age and older, with a dose of 50 μg (0.5 mL) at a cost of $32-37. It provides immunogenicity for at least 119 days after the first vaccination and is 94.5% effective in preventing the SARS-CoV-2 infection. However, some associated allergic symptoms have been reported for both vaccines. The COVID-19 vaccines can cause mild adverse effects after the first or second doses, including pain, redness or swelling at the site of vaccine shot, fever, fatigue, headache, muscle pain, nausea, vomiting, itching, chills, and joint pain, and can also rarely cause anaphylactic shock. The occurrence of adverse effects is reported to be lower in the Pfizer/BioNTech vaccine compared to the Moderna vaccine; however, the Moderna vaccine compared to the Pfizer vaccine is easier to transport and store because it is less temperature sensitive. CONCLUSIONS: The FDA has granted emergency use authorization for the Pfizer/BioNTech and Moderna COVID-19 vaccines. These vaccines can protect recipients from a SARS-CoV- 2 infection by formation of antibodies and provide immunity against a SARS-CoV-2 infection. Both vaccines can cause various adverse effects, but these reactions are reported to be less frequent in the Pfizer/BioNTech vaccine compared to the Moderna COVID-19 vaccine; however, the Moderna vaccine compared to the Pfizer vaccine is easier to transport and store because it is less temperature sensitive.
Alzheimer's disease (AD) is a prevalent degenerative neurological disorder with limited treatment options. Prior studies reported specific metabolites and inflammatory proteins to be related to AD risk. However, the intricate relationship between inflammatory proteins, blood metabolites, and AD risk in European population remains unclear. Genetic instruments for 1,091 metabolites and 736 inflammatory proteins were derived from two recent comprehensive genome-wide association studies. Univariable Mendelian Randomization was employed to assess potential causal effects of metabolites on AD risk, potential effects of inflammatory proteins on metabolites, and effects of inflammatory proteins on AD risk. Multivariable MR (MVMR) was further applied to disentangle direct effects of proteins and metabolites on AD. Twelve metabolites were identified to be associated with AD risk, and 226 inflammatory proteins demonstrated likely to be causal effects on these 12 metabolites. Further examining the associations between such inflammatory proteins and AD risk revealed 22 associations for which the effect directions from inflammatory proteins to metabolites, from metabolites to AD risk, and from inflammatory proteins to AD risk were aligned, suggesting inflammatory protein - metabolite - AD risk pathway. MVMR further highlighted four trios in which the effect directions were consistent with the UVMR results, supporting a metabolite‑mediated pattern. This large‑scale genetic analysis highlights specific metabolites as direct contributors to AD risk and suggests that certain inflammatory proteins may influence AD primarily through downstream metabolic pathways. Our findings offer potential novel therapeutic targets for AD intervention.
The amount of time previously spent awake or asleep strongly impacts the sleep electroencephalogram (EEG), especially slow waves during nonrapid-eye-movement (NREM) sleep. These effects on the sleep EEG meaningfully interact with age and to a lesser extent developmental disorders such as attention-deficit hyperactivity disorder (ADHD). We aimed to determine whether EEG oscillations during wakefulness were likewise affected by the interaction of sleep and development, using data collected from 163 participants aged 3-25 years old (62 female). We analyzed age- and sleep-dependent changes in two measures of oscillatory activity (amplitudes and density) and aperiodic activity (offsets and exponents). Finally, we compared wake EEG in children with ADHD (N = 58) to neurotypical controls, with habitual good sleep quality required for inclusion. We found that oscillation amplitudes exhibited the same dynamics as sleep slow waves: decreasing with age, decreasing after sleep, and the overnight decrease decreasing with age. Strikingly, wake oscillation densities in the alpha band decreased overnight in children but increased overnight in adolescents and adults. Aperiodic measures were affected by both sleep and age albeit with minimal interaction. No wake measure showed significant effects of ADHD, suggesting that previously reported differences in patients may reflect uncontrolled variability in sleep quality rather than disorder-specific effects. While these results do not disentangle homeostatic from circadian effects, they underscore the need to control for sleep/wake history and measurement scheduling in all EEG experiments, especially when focusing on children and adolescents.
Suicidal ideation is a strong predictor of suicide attempts making it a major public health concern. While long-term risk factors have been well-established, understanding short-term fluctuations in suicidal ideation is crucial for developing timely interventions. This meta-analysis examined whether sleep disturbances represent a within-person risk factor for next-day suicidal ideation among at-risk populations. Five databases (MEDLINE, PsycINFO, CINAHL, Embase, and Web of Science) were searched from inception to November 2025 for studies using intensive longitudinal designs to assess within-person associations between sleep and suicidal ideation in at-risk populations. A correlated and hierarchical random effects meta-analysis was used to synthesize results, while cluster wild bootstrapping examined subgroup differences. Fifteen reports representing 12 unique studies (67 effect sizes, 959 participants) were included. A significant positive within-person association emerged between sleep disturbances and next-day suicidal ideation (r = .128, 95% CI = .075-.191, p < .001). Results were robust to publication bias. Subgroup analyses revealed no significant differences between sleep dimensions, assessment methods (self-report vs. device-based), or participant age groups (adolescents vs. adults). Sleep disturbances constitute a modest but significant short-term risk factor for suicidal ideation in at-risk populations. Though individual night-to-night effects are small, cumulative impacts over time may meaningfully contribute to suicide risk. These findings support integrating sleep monitoring into digital suicide prevention interventions and highlight the need for research examining specific within-person patterns of sleep disturbances and underlying mechanisms.
Background: Meibomian gland dysfunction (MGD) is a major contributor to evaporative dry eye disease, yet reported prevalence estimates vary widely across studies, largely due to differences in diagnostic criteria, study populations, and settings. We conducted a systematic review and meta-analysis to synthesize available evidence on the prevalence of MGD in adults aged ≥40 years and to examine sources of heterogeneity across studies. Methods: We systematically searched PubMed, Web of Science, Scopus, and Google Scholar from inception to November 2025 for observational studies reporting the prevalence of MGD in adult populations. Random-effects meta-analysis of proportions was performed. Subgroup analyses were conducted by study setting and diagnostic approach. Between-study heterogeneity was quantified using the I2 statistic. Results: Eight observational studies from Singapore, Spain, Russia, Iran, China, Japan, and New Zealand, comprising 20,518 participants, met inclusion criteria. Reported prevalence of MGD varied substantially across studies. The pooled prevalence estimate was 87.08% (95% CI: 65.32-96.02%); however, heterogeneity was extreme (I2 > 99%), indicating substantial variability across populations and study methods. This pooled estimate should be interpreted with caution and not as a single representative global prevalence. Studies using clinical signs alone tended to report higher prevalence than those incorporating both signs and symptoms. Differences in study setting and diagnostic definitions accounted for a significant proportion of heterogeneity. Conclusions: MGD appears to be commonly detected in adults aged ≥40 years; however, prevalence estimates vary markedly depending on diagnostic criteria and study design. Given the extreme heterogeneity, pooled prevalence estimates should be interpreted with caution and not as a single global prevalence value. Standardized diagnostic definitions and population-based studies using harmonized methodologies are needed to generate more comparable and clinically interpretable estimates of MGD burden.
Climate anxiety describes emotional responses such as worry or distress related to climate change. While it is common and linked to mental health in the general population, little is known about its relevance for individuals with pre-existing mental disorders. A nationwide cross-sectional online survey was conducted in Germany between March and July 2025 among adults with at least one self-reported mental disorder. Participants provided socio-demographic and clinical information and completed four items assessing dimensions of climate-related distress: general concern, perceived impact on mental well-being, perceived effects of climatic events on psychological symptoms, and interference with everyday functioning. Group differences were examined using non-parametric tests, and associations with age were analyzed using Spearman correlations with Bonferroni correction. The sample included 427 participants (mean age 36.5 years; 73% female). Reported climate-related distress levels were relatively low across all dimensions within this sample, with minimal interference with daily functioning. Gender differences were found only for perceived effects of climatic events on psychological symptoms, with women reporting higher impact. Associations with age were weak and not significant after correction. Exploratory analyses indicated some variation across diagnostic groups, but most differences were small and did not remain significant after correction. Climate-related distress among individuals with mental disorders appears present but generally modest and rarely functionally impairing. Weak and inconsistent associations with sociodemographic and diagnostic factors suggest that climate-related distress is not strongly structured by specific diagnoses, supporting its consideration within broader clinical and psychological contexts.
Real-world randomized controlled trials (RCTs) evaluating multifaceted interventions often employ multiple study outcomes to measure treatment effects on a small set of underlying constructs. Motivated by a longitudinal RCT evaluating a behavioural intervention, the Arthritis Health Journal (AHJ), we propose a latent-factor multivariate complier average causal effects (MCACE) model for multidimensional longitudinal outcomes with principal strata of compliance types for parsimonious estimation of intervention effects in RCTs with treatment noncompliance. Within each compliance type, a factor regression model relates multiple outcomes to latent constructs, which follow hierarchical regression models. Under the model, high dimensional outcomes are reduced to low dimensional latent factors. This dimension reduction leads to a parsimonious and efficient test of overall CACEs on multiple outcomes, mitigating the multiple testing issues associated with multidimensional outcomes and weak instrumental variable problems associated with low compliance rates. Simulation studies demonstrate that the latent-factor MCACE model outperforms univariate CACE analysis in terms of both statistical power and Type I error control. The application to the AHJ study selects two underlying factors (self-efficacy and interaction with health care providers). Significant and beneficial treatment effects are detected on both factors. Overall, our analysis directly answers the main scientific questions posed by the RCT and yields novel findings not discovered previously.
Host genetic resistance can be improved through selective breeding, yet underlying immune mechanisms often remain unknown due to varying pathogen burden. In previous research, rainbow trout lines, ARS-Fp-R (resistant, R-line) and ARS-Fp-S (susceptible, S-line), were bred for differential resistance to Flavobacterium psychrophilum, but mechanisms remain unclear and study has been confounded by the higher F. psychrophilum load in the susceptible line. Here, we separate line-specific traits from pathogen-load driven effects, by challenging with Weissella tructae, a pathogen for which both lines exhibit equivalent susceptibility. After 3 to 6 days post-challenge with W. tructae, we report the divergent and shared cellular and cytokine profiles. The infected R-line fish exhibited higher granulocyte levels post-challenge, a trait also observed in its response to F. psychrophilum, while S-line fish had a more severe depletion of circulating leukocytes and IgM+ B cells. Proteomic analysis identified 50 infection-induced blood proteins. Using novel salmonid biomarker assays, the S-line exhibited a 6-fold higher tumor necrosis factor-alpha (TNFα) and elevated precerebellin (PCB). In contrast, the R-line showed 3-fold higher baseline complement factor H-like-1 protein (CFHL-1), and a trend toward elevated serum amyloid A (SAA). Other biomarkers, including Cath2, GDF-15, haptoglobin, and C1q-LP3 increased post-infection but did not differ between lines. Both lines exhibited similar granulomatous epicarditis and decreased plasma fibrinogen. Despite equivalent susceptibility to W. tructae, these lines demonstrate divergent cellular and cytokine responses, suggesting a shift in immune architecture due to selective breeding. The novel biomarker assays provide valuable tools for monitoring immune health and precision breeding in salmonid aquaculture.
This longitudinal study concerns initial levels, trajectories of growth, and associations of positive youth development (PYD) with parental warmth and behavioral control from early adolescence to young adulthood. Participants included 1338 adolescents (M = 13.25, SD = 1.04, years; 50% girls) from nine countries trichotomized by income level based on World Bank groupings of economies as well as cultural, sociological, and psychological considerations. Composite measures of PYD at ages 13, 15, 16, 18, and 21 were created from adolescent-report EPOCH dimensions of engagement, perseverance, optimism, connectedness, and happiness. Adolescents reported a high average initial level of PYD (3.50 on a 4-point scale) at 13 years of age; however, developmental trajectories of each income-level group differed with little within-group variation across age. Multigroup latent growth curve models examined associations of family-level and parent-specific dimensions of warmth and control with intercepts and trajectories of PYD. Parental warmth was consistently associated with higher PYD intercepts in all three country income levels, whereas control showed varied effects. PYD followed similar trajectory slopes across the three country income levels; parental warmth was consistently associated with growth, whereas parental control showed nuanced associations with parent and country. Warmth appears to act as a common protective correlate of adolescent PYD, whereas control appears to constitute a protective correlate in some cultural contexts but a risk correlate in other cultural contexts.
Human exposure to micro- and nanoplastics (MP/NPs) is increasingly recognized as a potential environmental health concern, although their role in reproductive carcinogenesis remains unclear. This narrative review aims to evaluate current evidence linking MP/NP exposure to reproductive cancers and to explore the potential chemoprotective effects of bioactive compounds derived from ginger, garlic, and turmeric. A structured literature search was conducted using PubMed, Scopus, Web of Science, and Google Scholar for studies published between 2008 and 2026. Relevant in vitro, in vivo, and human biomonitoring studies were included to assess mechanisms of toxicity, while preclinical and clinical studies were reviewed to examine the anticancer properties of selected dietary phytochemicals. Available evidence suggests that MP/NPs can accumulate in human biological systems, including reproductive tissues, where they induce oxidative stress, chronic inflammation, endocrine disruption, and DNA damage, processes closely associated with carcinogenesis. Although epidemiological data remain limited and do not establish cancer, emerging biomonitoring and experimental findings support a biologically plausible link between MP/NP exposure and hormone-related cancers. Concurrently, bioactive compounds such as curcuminoids, gingerols, and organosulfur compounds demonstrate the ability to modulate key molecular pathways involved in oxidative stress, inflammation, and cell proliferation. Preclinical studies consistently report anticancer effects, while early clinical evidence suggests improvements in oxidative and inflammatory biomarkers, though definitive therapeutic benefits remain uncertain. Overall, this review highlights important mechanistic links and identifies dietary phytochemicals as potential modulators of MP/NP-induced carcinogenic pathways. However, further well-designed epidemiological and clinical studies are needed to clarify causal relationships and validate their protective role.
While pre-exposure prophylaxis (PrEP) can prevent HIV acquisition, associated behavioral changes may increase risk of acquiring other sexually transmitted infections (STIs). The prospective multicenter BRAHMS study enrolled men who were HIV negative, had sex with men, and were aged 18 to 55 years and reported an increased risk to acquire STI. At 3-month intervals for up to 12 months, participants answered questionnaires and underwent site-specific screening for Chlamydia trachomatis (CT), Mycoplasma genitalium (MG), Neisseria gonorrhoeae (NG), and syphilis. We computed 3-month incidence rates and rate ratios, and we employed multilevel mixed effects logistic regression to determine odds ratios (ORs) and 95% CIs for factors associated with any incident STI. The mean age of 1017 participants was 33 years, 54.7% used PrEP at enrollment, and 83.7% reported PrEP use overall. Any STI was diagnosed in 71.8% (CT, 40.4%; MG, 38.5%; NG, 36.0%; syphilis, 10.1%; HIV, 0.5%). PrEP users exhibited a higher prevalence for anorectal infections with CT (35.3% vs 20.5%, P < .05), MG (31.4% vs 23.5%, P < .05), and NG (26.1% vs 16.9%, P < .05). CT incidence decreased from 46.8 cases per 100 person-years to 35.7 (-23.7%, P < .05), and NG incidence decreased from 41.6 cases per 100 person-years to 30.7 (-26.2%, P < .05). MG and syphilis incidence remained stable. Factors independently associated with STI incidence were as follows: symptoms (OR, 1.85; 95% CI, 1.46-2.34), condomless anal sex with >5 casual partners (OR, 1.79; 95% CI, 1.49-2.14), recreational drug use (OR, 1.76; 95% CI, 1.46-2.12), being born abroad (OR, 1.49; 95% CI, 1.19-1.87), PrEP use (OR, 1.29; 95% CI, 1.05-1.58), and having a moderately or largely increased self-perceived risk of HIV (OR, 1.26 [95% CI, 1.03-1.53]; OR, 1.33 [95% CI, 1.02-1.74], respectively). PrEP use was associated with increased STI risk in our cohort. CT and NG incidence decreased in a structured test-and-treat setting.