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What do we know about medical invalidation and related concepts? - A scoping review and thematic analysis about the definitions, measurements, causes, consequences and potential solutions for medical invalidation.

BACKGROUND: Medical invalidation, medical gaslighting, and related constructs have gained visibility in public discourse but remain inconsistently defined in scientific literature. Despite growing research-often focused on specific diseases- to date, no single review has comprehensively synthesized their definitions, causes, consequences, or methods of measurement. This scoping review addresses this gap by examining medical invalidation and related constructs. METHODS: Using a preregistered protocol, we systematically searched PubMed, CINAHL, Web of Science, Google Scholar, and ProQuest (dissertations) without year restrictions. Eligible sources included peer-reviewed empirical, theoretical, and conceptual work in English addressing invalidation, gaslighting, or closely related notions within healthcare. A total of 158 studies were identified through database searches and citation tracking. Data extraction followed a standardized schema, and findings were synthesized descriptively and through thematic analysis to clarify terminology, map determinants and outcomes, and identify existing measurement approaches. RESULTS: The results showed substantial inconsistency in how "invalidation," "not being taken seriously," and "gaslighting" were defined. Medical invalidation emerged as a multifactorial phenomenon driven by diagnostic challenges, structural and societal factors, provider and patient characteristics, stigma, misattribution, interactional dynamics, academic knowledge gaps, and disease-related complexity. Invalidation was associated with wide-ranging behavioural, emotional, cognitive, physical, relational, and systemic harms, while validation had consistently beneficial effects. Proposed solutions in the summarized studies included communication improvements, clinician training, patient support, targeted research, and structural and systemic changes. DISCUSSIONS: Medical invalidation represents a complex, systemic issue with significant implications for patient safety. The discussion highlights its multifactorial origins, its potential to cause both psychological and physical harm, and the need for clearer conceptualisation within the field. Advancing research requires validated instruments and longitudinal designs to examine underlying mechanisms and consequences. Addressing medical invalidation will demand multi-level interventions to improve communication, reduce structural barriers, and promote equitable, patient-centred care. OSF PREREGISTRATION: https://doi.org/10.17605/OSF.IO/MPE6U.

Humans

Associations between smart infusion pump-electronic health record interoperability and healthcare outcomes: A systematic review.

OBJECTIVE: This study synthesized available evidence on the associations between smart infusion pump-electronic health record (EHR) interoperability and healthcare outcomes. METHODS: A systematic review of PubMed, CINAHL, Embase, and Scopus databases identified 901 records, which were imported into Rayyan® for duplicate removal, independent screening by three reviewers, and resolution of discrepancies. Eligible studies were peer-reviewed, data-driven, and reported associations between smart infusion pump-EHR interoperability and healthcare outcomes. Studies focused solely on technical validation or interoperability prototypes were excluded. A backward citation search identified additional studies. Two reviewers independently extracted and cross-validated study characteristics using standardized templates. Methodological quality was assessed with the Joanna Briggs Institute Critical Appraisal Tools. RESULTS: Twenty records of 14 full-text studies and 6 conference proceedings were included. Most records reported positive associations between smart infusion pump-EHR interoperability and outcomes related to safety (e.g., medication administration errors, safety-reported events, pump alerts, and compliance with interoperability and drug library), operational efficiency (e.g., programming and documentation time and technical issues), financial performance (e.g., charges captured, and cost avoided), and user experience domains. Most studies used observational designs, reflecting real-world interoperability implementations, where controlling confounding factors is challenging. Limited reporting of baseline characteristics, pump type, and sample sizes limited comparability across studies. CONCLUSIONS: Smart infusion pump-EHR interoperability was associated with improvements in patient safety, efficiency, charge capture, and user experience, with variable findings across studies. Future research should use rigorous methodologies and standardized measures, examine relationships across outcome domains, assess limitations of pump-EHR interoperability, and evaluate underexplored outcomes, including team communication, cognitive workload, and AI-enabled pumps. IMPLICATIONS FOR CLINICAL PRACTICE: Interoperability should be viewed as a component of a broader sociotechnical system, in which technology, user, workflow, clinical content, and organizational practices collectively determine overall effectiveness.

Humans

Predictors of transition readiness in adolescents with neurogenic lower urinary tract dysfunction.

PURPOSE: Adolescents with Neurogenic Lower Urinary Tract Dysfunction (NLUTD) face significant challenges in their quality of life and readiness to transition to adult healthcare services. This study examines the impact of various demographic and clinical factors on transition readiness. METHODS: We performed a retrospective review of prospectively collected data from 75 adolescents with NLUTD managed at a specialized tertiary referral pediatric facility. We employed multivariate linear regression analysis to explore the relationship between transition readiness scores collected from the Good2Go questionnaire, including the total transition readiness score and its sub-domains (self-advocacy, knowledge, self-care, and social support), and predictors such as age, sex, reconstructive surgery status, and clean intermittent catheter (CIC) usage. RESULTS: The mean age of participants was 16.74 years (SD 2.44). Reconstructive surgery had been performed in 32 % of patients, and 77.3 % were on CIC. Multivariate regression analysis indicated that age significantly predicted transition readiness across several domains. Each additional year of age was associated with a 4.40-point increase in the total transition readiness score, a 3.66-point increase in knowledge, a 4.26-point increase in self-advocacy and a 5.41-point increase in self-care. Conversely, CIC significantly negatively impacted the social support domain, with scores decreasing by 9.69 points. Reconstructive surgery was significantly associated with lower self-care scores, with an average decrease of 12.12 points among those who had undergone surgery. CONCLUSION: Age significantly improves transition readiness in adolescents with NLUTD, reflecting cognitive and developmental growth. However, the negative effects of CIC on social support and reconstructive surgery on self-care underscore the need for personalized interventions to optimize health outcomes during the transition to adult care.

Humans

Premature closure underlies bias in medical diagnosis in students: A randomised controlled experiment.

OBJECTIVE: The purpose of the study reported in this article was to shed light on the cognitive mechanism mediating between biasing information and diagnostic error. The literature suggests at least two different hypotheses: premature closure leading biased participants to spend less time on diagnosis or increased competition between diagnostic hypotheses. The latter hypothesis predicts that biased participants would spend more time reaching a diagnosis. METHOD: Using the salient distracting findings (SDF) experimental paradigm, we biased 58 fourth-year medical students while diagnosing 12 clinical vignettes in a within-group incomplete block design under three conditions: cases presented without SDF, with SDF at the beginning and with SDF at the end. For each of these conditions, diagnostic accuracy, the number of SDF-related mistakes and time per word needed to process the case were recorded. The data were analysed using linear mixed modelling. Estimated marginal mean scores were reported. RESULTS: Participants confronted with salient distracting features (SDFs) at the beginning of a clinical case demonstrated significantly lower diagnostic accuracy (mean 0.11) compared with the No-SDF condition (0.27), representing a 61% reduction (F2,693&#x2009;=&#x2009;11.995, p&#x2009;<&#x2009;0.001), and made more SDF-related mistakes (F2, 693&#x2009;=&#x2009;16.395, p&#x2009;<&#x2009;0.001). When SDFs were presented at the end of the case, diagnostic accuracy was also reduced (mean 0.17; 36% reduction), but processing time did not differ from the No-SDF condition. Only early presentation of SDFs was associated with reduced processing time per word (F2,636&#x2009;=&#x2009;4.799, p&#x2009;<&#x2009;0.01), consistent with premature closure. CONCLUSION: These findings demonstrate that biasing information increases diagnostic error in medical students and that only early bias is associated with reduced information processing. The data do not support the competition hypothesis for early bias, as processing time did not increase under biasing conditions. Premature closure can therefore be directly observed rather than inferred, inviting further research.

Humans

Factors associated with successful integration of pharmacists into residential aged care teams: A qualitative study.

BACKGROUND: Australia's Aged Care Onsite Pharmacist program aims to support quality use of medicines in residential aged care homes. This is a novel role introduced into existing teams in a complex environment. Factors associated with successful integration since implementation are currently unknown. AIM: This study aims to explore the perspectives of pharmacists and other stakeholders within aged care homes regarding successful integration of the novel aged care pharmacist service into healthcare teams. METHODS: A qualitative approach, using interpretive descriptive methodology, was used to explore perspectives. Semi-structured focus groups and interviews with pharmacists, nursing and care staff, allied health professionals, general practitioners, residents, and family members were undertaken. Data were collected via Zoom&#x2122;, audio- and video-recorded, and transcribed verbatim. Two researchers undertook inductive thematic analysis to identify key themes. RESULTS: 30 participants across focus groups, focus-group interviews, interviews, and member-checking processes contributed. An overarching theme of proactivity and showing a genuine interest in others underpinned three key themes. Theme 1: Pharmacists needed to be seen, through physical presence and availability, as well as developing a distinct identity. Theme 2: Pharmacists needed to build trust, through collaboration in real time and demonstrating value. Theme 3: Pharmacists needed to develop an understanding of the aged care home environment, including social and contextual norms, as well as procedures, routines and roles. DISCUSSION: This research complements existing understandings of interprofessional collaboration and teamwork amongst healthcare professionals. Themes were interlinked; we used a sensitising framework, social cognitive theory, to present and explain the findings and interactions that can support pharmacist integration into existing teams. Aged care services should structure onboarding to prioritise early visibility, clarify roles and organisational needs, and foster in-person collaboration. Pharmacists should demonstrate proactivity and an authentic interest in all staff, residents and families.

Humans

Multicenter randomized effectiveness/implementation trial of a digital self-management support tool to improve the quality of life during adjuvant hormonal therapy for patients with early breast cancer: The HOPE trial.

BACKGROUND: For patients with hormone receptor (HR) positive early breast cancer (BC), adjuvant endocrine therapy (ET) represents the cornerstone of treatment. However, 75% of patients experience ET-related symptoms that negatively affect their quality of life (QOL). Despite their high prevalence, these symptoms are often underestimated and under-addressed during consultations. As a result, non-adherence to ET is common and remains a major barrier for optimal disease and survival outcomes. METHODS: National, prospective, randomized, open-label hybrid type 1 effectiveness/implementation trial conducted in France comparing a personalized digital health pathway plus standard of care (SoC) vs. SoC alone in patients with HR+ early BC reporting ET-related symptoms. 180 patients will be randomized 1:1 to receive either 12&#xa0;weeks of the digital health pathway or 12&#xa0;weeks of SoC. The intervention is anchored by the Resilience&#xa9; digital companion including remote symptom and needs assessment, an introductory nurse-navigator phone call, and access to personalized, symptom-specific online educational and self-management programs (physical activity, yoga, meditation or cognitive behavioral therapy). In both arms, patients will be invited to wear a wearable device to objectively monitor behavioral parameters. The primary endpoint is the ET symptoms scale of the European Organization for Research and Treatment of Cancer (EORTC) QLQ-BR45 over 12-weeks. Secondary endpoints include other QOL domains, self-reported ET adherence, eHealth literacy, self-efficacy, and evaluation of the implementation process. DISCUSSION: This study should provide evidence on the effectiveness and real-world implementation of a personalized digital health pathway to improve QOL in patients experiencing ET-related symptoms. TRIAL REGISTRATION: ClinicalTrials.gov NCT06781996; Protocol version 3.0.

Humans

Use of Wearable Sensors in Angelman Syndrome: A Systematic Review.

BACKGROUND: Wearable sensors are a promising method for collecting clinical trial outcome data for people with Angelman syndrome (AS). However, there has yet to be a systematic probe into the ways in which wearable sensors have been successfully used in AS. The current study aims to provide a quantitative summary of wearable sensors used in AS, including contexts of use and psychometric properties, and to present key narrative highlights. METHOD: Literature searches were performed in three electronic databases: APA PsycInfo, PubMed and Web of Science Core Collection. Data items were categorized into four categories: sample characteristics, study methodological details, wearable sensor characteristics and psychometric properties assessed. Sample characteristics included sample size, age, biological sex, race/ethnicity and cognitive/developmental functioning. Study methodological details were subdivided into study design and setting. Wearable sensor characteristics included sensor type, placement site, means of attachment, assessed construct and sensor-related data loss. Psychometric properties assessed included reliability and validity of sensor-derived data. RESULTS: We identified 16 articles through our systematic review. Wearable sensors were used to study sleep (n&#x2009;=&#x2009;10, 62.5%), language (n&#x2009;=&#x2009;2, 12.5%), gait (n&#x2009;=&#x2009;2, 12.5%), caregiver proximity (n&#x2009;=&#x2009;1, 6.3%), EEG power (n = 1, 6.3%),&#xa0;and arousal (n&#x2009;=&#x2009;1, 6.3%) in AS through actigraphs, vocalization recorders, inertial sensors, radio-frequency identification watches, wireless EEG caps,&#xa0;and functional near-infrared spectroscopy caps, respectively. Findings from these studies broadly indicate that wearable sensors are feasible, reliable and valid for assessing a range of behaviours relevant to AS. CONCLUSIONS: Wearable sensors are a promising solution to enhance assessments in AS. However, with the small extant literature characterized by small sample sizes and restricted focus on a few relevant features in AS, there remains ample opportunities to explore the use of wearable sensors in people with AS. Additional studies will better inform clinical decision-making and ultimately improve the lives of people with AS and their families.

Humans

From prediction to mechanism: Explainable AI uncovers plasma and CSF proteomic signatures of Alzheimer's disease.

Alzheimer's disease (AD) plasma and cerebrospinal fluid (CSF) proteomics can distinguish AD from cognitively normal controls, but the generalizability of machine learning performance and the recurrence of biological signals across datasets require cautious interpretation. We developed an explainable artificial intelligence framework spanning two fluids and four ADNI proteomic datasets, covering 2082 modality specific samples, all analysed internally within ADNI. Phase 1 analysed plasma using a 119 analyte NULISA and targeted UPENN panel (n&#xa0;=&#xa0;727; 216&#xa0;CE, 511 controls). Phase 2 extended the analysis to CSF using SOMAscan7k, TMT-MS and targeted SET2, with Elecsys A&#x3b2;42, A&#x3b2;40, total tau and p-tau181 as anchor biomarkers. Only SOMAscan was subject-independent relative to Phase 1 plasma; TMT-MS and SET2 overlapped with Phase 1 for 96.0% and 97.7% of subjects and therefore are not independent replication cohorts. Under subject-level splits with fold internal preprocessing, we compared Elastic Net, Explainable Boosting Machines and gradient boosted trees with SHAP-based explanations. Among the candidate pipelines, we selected the pipeline with the highest held-out test ROC AUC for each platform; the selected values were 0.927 in plasma and 0.954-0.973 across the three CSF datasets. Because the same held out test performance was used for pipeline selection and headline reporting, these are optimistically selected single-holdout estimates, not unbiased estimates of generalizable or clinical performance. Explanations identified five recurring biological axes within ADNI: cholinergic (ACHE), tau/14-3-3 (YWHAG, YWHAZ, YWHAB, YWHAE), neuro-axonal (NEFL, NEFH), microglial/complement (CHIT1, SMOC1, CHI3L1, C7, CFH) and synaptic (NPTXR, NPTX2, DLG4, SYT5, VSNL1, ELAVL2). CSF analyses showed synaptic vesicle-cycle enrichment (q&#xa0;=&#xa0;2&#xa0;&#xd7;&#xa0;10-6), and CSF YWHAG correlated strongly with total tau (&#x3c1;&#xa0;=&#xa0;0.87). Cross-fluid directional concordance was modest overall (54-57%) but increased to 73-80% among mapped analyte/protein rows reaching q&#xa0;<&#xa0;0.05 in CSF. These findings provide hypothesis-generating, internally supported evidence within ADNI. Independent external cohorts with locked pipelines are required to evaluate generalizable performance and biological reproducibility; the overlapping TMT-MS and SET2 analyses should not be interpreted as independent replication.

Alzheimer Disease

Toward personalized interventions for preventing depression in primary care: Qualitative and quantitative findings from the e-predictD pilot study.

BACKGROUND: The predictD intervention, delivered by family physicians (FPs), has demonstrated effectiveness and cost-efficiency in preventing depression and anxiety. The e-predictD study aims to design, develop, and evaluate a novel personalized intervention for depression prevention by integrating information and communication technologies (ICTs), risk prediction algorithms, and decision support systems (DSS) for both patients and FPs. OBJECTIVE: To evaluate the satisfaction, usability, and acceptability, of a beta version of the e-predictD intervention in primary care settings. METHODS: The e-predictD intervention follows a biopsychosocial approach, including an initial patient-FP interview, specific FP training, and an app. A &#x3b2;-version was tested in a pilot study without a control group over three months. The app integrates a validated depression risk prediction algorithm, decision algorithms, and a monitoring system supporting the DSS. The DSS generates a personalized prevention plan (PPP) from eight intervention modules: physical exercise, social relationships, problem-solving, communication skills, decision-making, assertiveness, sleep improvement, and cognitive restructuring. Patients and FPs discussed the PPP in a 15-minute baseline interview, selecting modules for implementation over three months. Semi-structured interviews gathered feedback. Assessments included depression (PHQ-9), anxiety (GAD-7), quality of life (SF-12), and major depression risk (predictD algorithm). RESULTS: Six FPs from six Spanish cities enrolled 56 non-depressed patients at moderate-to-high risk of depression; 47 (84%) completed follow-up. The app was used for a median of six days (interquartile range: 1-30). Both FPs and patients expressed satisfaction, leading to incorporated improvements. After three months, significant reductions in major depression risk and anxiety symptoms were observed, alongside improved mental quality of life. However, no significant changes were found in depressive symptoms or physical quality of life. CONCLUSION: This pilot study supports the feasibility and acceptability of the e-predictD &#x3b2;-version, despite lower-than-expected app usability. Health improvements were observed, warranting confirmation in a randomized controlled trial. TRIAL REGISTRATION: ClinicalTrials.gov NCT03990792.

Adult

Efficacy and safety of add-on topiramate vs. metformin on cardiometabolic profile in patients of schizophrenia on atypical antipsychotics with metabolic syndrome: an active-controlled, rater-blinded, parallel-design randomized controlled trial.

BACKGROUND: Metabolic syndrome is common among patients with schizophrenia, but current treatment options are limited, with metformin being the most studied. While placebo-controlled studies suggest potential benefits of topiramate, comparative efficacy and safety data are lacking. This study aimed to compare the efficacy and safety of topiramate versus metformin for treating metabolic syndrome and reducing cardiovascular risks among patients with schizophrenia. METHODS: A randomised, open-label, parallel-group clinical trial was conducted on 60 patients of schizophrenia with metabolic syndrome, randomised equally to receive either topiramate (50&#xa0;mg/day) or metformin (1000&#xa0;mg/day) for eight weeks. Primary outcome was cardiovascular risk score (QRISK3), and secondary outcomes were LDL&#x2236;HDL ratio, insulin resistance (HOMA-IR), positive and negative syndrome scale (PANSS), Montreal Cognitive Assessment (MoCA) and clinical global impression-Schizophrenia scale (CGI-SCH) scores. RESULTS: Over the study period, QRISK3 scores improved significantly in both groups [topiramate: MD&#x2009;=&#x2009;0.61 (0.02 to 1.21), p&#x2009;=&#x2009;0.04; metformin: MD&#x2009;=&#x2009;0.45 (0.07 to 0.83), p&#x2009;=&#x2009;0.02], with no significant between-group difference in unadjusted analysis (p&#x2009;=&#x2009;0.648). However, ANCOVA adjusting for baseline QRISK3 revealed a significantly greater improvement in the topiramate group (&#x3b2; = -0.324, p&#x2009;=&#x2009;0.043). Metformin showed significant within-group improvements in LDL: HDL ratio and HOMA-IR; however, ANCOVA adjusting for baseline HOMA-IR showed the between-group difference remained non-significant (&#x3b2; = -1.209, p&#x2009;=&#x2009;0.078). Both groups showed significant improvements in PANSS and CGI-SCH scores, with no significant between-group differences in MoCA scores. A moderate correlation between the QRISK3 change, the PANSS change, and the CGI-SCH-I scores was observed in the topiramate group and the total population. Regression analysis identified PANSS change as a predictor of QRISK3 improvement. CONCLUSION: Topiramate demonstrated comparable, and on adjusted analysis superior, cardiovascular risk reduction compared to metformin, supporting its use as a viable alternative in the management of metabolic syndrome in patients with schizophrenia on atypical antipsychotics, particularly where metformin is contraindicated.

Humans

Gene-environment interaction between perinatal oxytocin exposure and Pten mutation shapes epigenetic reprogramming of oxytocin signaling and behavior in mice.

Synthetic oxytocin (Pitocin) is the most commonly used pharmacologic agent for induction and augmentation of labor. Beyond its uterotonic effects, oxytocin plays a critical role in neurodevelopment and social behavior. Dysregulated oxytocin signaling has been implicated in autism spectrum disorder (ASD), raising concern that perinatal exposure to exogenous oxytocin may have lasting neurodevelopmental consequences. This study aimed to determine whether offspring harboring a genetic predisposition for ASD are differentially impacted by perinatal oxytocin exposures, with a focus on long-term oxytocin signaling and autism-like behavior. Pregnant mice carrying offspring with heterozygous mutations in phosphatase and tensin homolog deleted on chromosome ten (Pten), a well-established monogenic risk factor for ASD, received continuous oxytocin versus phosphate-buffered saline (PBS) control via micro-osmotic pumps during late gestation. Wild-type (WT) offspring exposed to each treatment served as a secondary control. Adult offspring were assessed for oxytocin receptor (Oxtr) methylation in the frontal cortex and hippocampus, oxytocin expression in the hypothalamus, serum oxytocin levels, and were subject to a battery of social and anxiety-related behavior tests. Perinatal oxytocin exposure produced genotype-dependent effects in offspring. Epigenetic analyses revealed bidirectional remodeling of Oxtr methylation in the frontal cortex and hippocampus, with increased exon 1 methylation in WT mice and decreased methylation in Pten-mutant mice, resulting in significant genotype-treatment interactions. Hypothalamic oxytocin expression increased following treatment regardless of genotype, though baseline levels were higher in Pten-mutant mice. Neither oxytocin treatment nor genotype impacted long-term serum oxytocin levels. Behavioral outcomes were modest but context-specific: repetitive behaviors and cognition performance were unchanged, but oxytocin-treated Pten-mutant mice exhibited increased anxiety-like behavior alongside improved social memory. In contrast, oxytocin-treated WT mice showed reduced social novelty preference. Exploratory analyses suggested potential sex-dependent trends. Our findings support a model in which genetic susceptibility shapes the epigenetic encoding of early-life hormonal signals, thereby recalibrating oxytocin system function and downstream behavioral outcomes. Together, these data highlight the context-dependent effects of perinatal oxytocin exposure and argue against uniformly beneficial or detrimental effects, emphasizing the importance of gene-environment interactions in neurodevelopmental trajectories.

Animals

Associations of Illness Perception, Resignation Coping, and Social Support With Self-Regulatory Fatigue in Patients With Type 2 Diabetes: A Cross-Sectional Study.

AIMS: To examine the associations among illness perception, resignation coping, social support, and self-regulatory fatigue (SRF) in patients with Type 2 diabetes mellitus. The study specifically explores whether resignation coping and social support exhibit indirect associations with SRF in the context of illness perception. DESIGN: A cross-sectional study. METHODS: From November 2024 to October 2025, a convenience sample of 302 adult patients with T2DM was recruited from a tertiary general hospital in China. Participants completed validated instruments with established psychometric properties, namely the Brief Illness Perception Questionnaire, the Medical Coping Modes Questionnaire, the Perceived Social Support Scale, and the Self-Regulatory Fatigue Scale. Statistical analyses included Spearman correlation and serial mediation analysis using the PROCESS Macro (Model 6) with bias-corrected bootstrapping. RESULTS: SRF was positively correlated with negative illness perception (r&#x2009;=&#x2009;0.579, p&#x2009;<&#x2009;0.01) and resignation coping (r&#x2009;=&#x2009;0.612, p&#x2009;<&#x2009;0.01), and negatively correlated with social support (r&#x2009;=&#x2009;-0.598, p&#x2009;<&#x2009;0.01). Serial mediation analysis revealed that illness perception was associated with SRF through indirect pathways involving resignation coping and social support. Resignation coping and social support mediated the association between illness perception and self-regulatory fatigue, both individually and sequentially. CONCLUSIONS: Negative illness perception correlates with higher SRF. This observed correlation is additionally linked to indirect pathways involving resignation coping and lower social support. Collectively, these findings highlight a pattern of interrelated cognitive (illness perception), behavioural (resignation coping), and resource (social support) factors that are associated with self-regulatory fatigue in this cross-sectional study. IMPLICATIONS FOR THE PROFESSION: The findings offer a clear, evidence-based framework for nursing practice. They highlight the potential value of integrated assessment and intervention that simultaneously addresses patients' illness beliefs, maladaptive coping strategies, and social support systems, which are associated with lower SRF and better diabetes self-management. REPORTING METHOD: This study adheres to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines for cross-sectional studies. PATIENT OR PUBLIC CONTRIBUTION: Patients participated solely as research participants by providing survey data. They were not involved in the study design, implementation, data analysis, interpretation, or manuscript preparation. All patients provided written informed consent prior to questionnaire completion.

Humans

Cardiovascular risks in psychiatric disorders and psychiatric risks in cardiovascular disorders: implications for prevention and clinical management - a large-scale umbrella review encompassing 76 meta-analyses.

OBJECTIVE: Psychiatric and cardiovascular disorders often co-occur, complicating their assessment and management. No umbrella review(UR) has summarized the meta-analytic evidence on the co-occurrence of psychiatric and cardiovascular disorders and assessed its credibility. METHODS: Meta-analytic systematic reviews of observational studies documenting the prevalence, risk factors, and outcomes associated with the co-occurrence of cardiovascular and psychiatric disorders, indexed from inception through March.16.2026, and meeting established diagnostic criteria, were included. Meta-analytic association and prevalence estimates were recalculated and graded based on established or adapted criteria. The AMSTAR-2 assessed the quality of the meta-analyses, while several subgroup analyses and meta-regressions aimed to explain the heterogeneity. RESULTS: We included 76 meta-analyses yielding 131 meta-analytic estimates. Based on pre-existing meta-analytic evidence, 22/24 prevalence estimates (91.7%) met moderate/strong credibility criteria. Strong credibility emerged for: orthostatic hypotension in Lewy body(58%;95%C.I.&#xa0;=&#xa0;50-66%) and Alzheimer's dementias(28.0%&#xa0;=&#xa0;95%C.I.&#xa0;=&#xa0;17.0-40.0%); pericardial effusion in anorexia nervosa(25.0%;95%C.I.&#xa0;=&#xa0;17.0-34.0%); in heart failure(HF): major depressive disorder(MDD)(41.9%;95%C.I.&#xa0;=&#xa0;36.7-47.1%), mild cognitive impairment(MCI)(41.4%;95%C.I.&#xa0;=&#xa0;38.3-45.6%), anxiety(32.0%;95%C.I.&#xa0;=&#xa0;26.5-37.6%), MDD&#xa0;+&#xa0;anxiety(24.7%;95%C.I.&#xa0;=&#xa0;17.9-34.3%), and dementia(19.8%;95%C.I.&#xa0;=&#xa0;12.9-27.8%); in atrial fibrillation(AF): MCI(26.0%;95%C.I.&#xa0;=&#xa0;21.0-30.0%), anxiety in patients undergoing pulmonary vein isolation(PVI)(25.0%;95%C.I.&#xa0;=&#xa0;12.0-46.0%), MDD in PVI patients (20.0%;95%C.I.&#xa0;=&#xa0;13.0-29.0%); in coronary artery disease: MDD&#xa0;+&#xa0;anxiety(19.8%;95%C.I.&#xa0;=&#xa0;16.0-24.6%): in schizophrenia spectrum disorders: clozapine-associated-cardiomyopathy(0.6%;95%C.I.&#xa0;=&#xa0;0.2-2.3%); clozapine-associated-cardiomyopathy absolute death rates (0.0003;95%C.I.&#xa0;=&#xa0;0.0001-0.0012); clozapine-associated-cardiomyopathy case fatality rate (0.078;95%C.I.&#xa0;=&#xa0;0.018-0.285). Several additional disorders were multimorbid in>5% of people, yet with a lower credibility rating. No re-pooled risk factors/outcomes reached strong credibility criteria. CONCLUSIONS: The present study provides an atlas of cardiovascular and psychiatric multimorbidity across varying levels of credibility, reinforcing the need for an integrated, multidisciplinary approach to patient care and for more research on actionable risk/protective factors and outcomes.

Humans

Nurse-led attribution remodeling training based on the Neuman systems model to enhance resilience, adaptive coping, and attributional style in women newly diagnosed with breast cancer: A randomized controlled trial.

BACKGROUND: Psychological interventions for patients with breast cancer often overlook the critical role of maladaptive attributional style in shaping their adjustment. Therefore, the need for theory-driven, scalable interventions that target cognitive restructuring, particularly during the vulnerable post-diagnosis period, is clear. OBJECTIVE: To evaluate the effectiveness of a nurse-led attribution remodeling training intervention grounded in the Neuman systems model for improving resilience, adaptive coping, and attributional style among women newly diagnosed with breast cancer. DESIGN: A randomized controlled trial. SETTING: A tertiary general hospital. PARTICIPANTS: A total of 130 eligible women newly diagnosed with breast cancer were recruited between March and November 2024. METHODS: A two-arm parallel-group randomized controlled trial was conducted. Participants were randomly assigned to receive either attribution remodeling training plus routine nursing (n&#xa0;=&#xa0;65) or routine nursing only (n&#xa0;=&#xa0;65). The nurse-led attribution remodeling training intervention, delivered via a blended model of in-person sessions and continued support through the WeChat mobile platform, was designed to systematically reshape maladaptive attributions into more adaptive ones. Resilience (primary indicator), coping strategy (i.e., confrontation, avoidance, resignation), and attributional style (secondary indicators) were assessed at baseline and at 1, 3, and 6&#xa0;months post-baseline. A linear mixed model was used to analyze the effects of group, time, and group-by-time interactions. Effect sizes (Cohen's D) were calculated based on the means and standard deviations. RESULTS: At the 6-month follow-up, the intervention group had better outcomes than the control group in terms of resilience (mean difference: 1.49, 95% confidence interval: 0.37, 2.61), confrontation coping (3.35 [2.33, 4.37]), and adaptive attributional style (4.16 [3.87, 4.45]). Avoidance coping showed a small increase (0.82 [0.22, 1.42]), whereas resignation coping decreased (-1.66 [-2.49, -0.83]). Group effects and group-by-time interactions were statistically significant for all outcomes. Effect sizes at 6&#xa0;months ranged from small for resilience (D&#xa0;=&#xa0;0.28) and avoidance coping (D&#xa0;=&#xa0;0.26) to moderate for confrontation coping (D&#xa0;=&#xa0;0.60) and resignation coping reduction (D&#xa0;=&#xa0;-0.51), and large for attributional style (D&#xa0;=&#xa0;0.94). CONCLUSIONS: Attribution remodeling training is a promising and effective theory-based intervention that can enhance psychological adaptation in women newly diagnosed with breast cancer. By strengthening key defense mechanisms, as conceptualized by the Neuman systems model, the program is effective, scalable, and nurse-deliverable for psycho-oncology care, bridging a critical gap in supportive cancer care and empowering nurses as primary psychological support providers. REGISTRATION: ChiCTR2000031827, registered prospectively on April 11, 2020, www.Chictr.or.cn.

Humans

A narrative systematic review of definitions and diagnostic criteria for disordered eating and eating disorders in type 1 diabetes.

AIMS/HYPOTHESIS: Type 1 diabetes and disordered eating (T1DE) affects 8-37.1% of adults and is associated with high rates of morbidity and mortality. The absence of a standardised case definition of T1DE and its severity hinders effective screening, diagnosis and treatment. This systematic review aimed to (1) synthesise existing case definitions and diagnostic criteria for T1DE in adults and (2) identify key characteristics to inform consensus for future diagnostic criteria. METHODS: A systematic review was conducted following the Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) guidelines. Eligible studies involved adults (&#x2265;18 years) with type 1 diabetes assessing disordered eating; paediatric studies, mixed samples without disaggregated data, non-empirical designs and non-English publications were excluded. PubMed, MEDLINE, EMBASE, CINAHL and PsycINFO were searched up to November 2025 for peer-reviewed studies involving adults with T1DE. Qualitative and quantitative data on definitions, diagnostic criteria and assessment tools were extracted. Study quality was appraised using a modified Graphical Appraisal Tool for Epidemiological studies (GATE) checklist. Due to heterogeneity of data, a narrative synthesis of findings was performed to describe current definitions of T1DE. RESULTS: Sixty-one studies met the inclusion criteria, with a pooled sample of 111,208 participants (76% women) from over 22 countries. T1DE was defined using a heterogeneous array of terms, diagnostic frameworks and assessment tools (29 distinct methods). The Diabetes Eating Problem Survey-Revised (DEPS-R) was the most used questionnaire, but many studies relied on criteria adapted from general eating disorder classifications or generic questionnaires. Approximately three-quarters of the studies assessed insulin omission behaviours, but the operationalisation of the cognitions for insulin omission varied widely. Beyond physiological markers such as HbA1c and BMI, studies explored various diabetes-related and psychological constructs, although often considering diabetes and disordered eating separately rather than as an integrated condition. CONCLUSIONS/INTERPRETATION: This systematic review highlights the lack of a unified, evidence-based definition of T1DE, resulting in inconsistent screening, diagnostic and reporting practices. Establishing clear, consistent, evidence-based diagnostic criteria and screening questionnaires for T1DE is critical to improving early detection and developing targeted interventions. These findings provide a foundation for refining T1DE definitions as a stepping stone to an international consensus definition. STUDY REGISTRATION: PROSPERO registration no. CRD420250223622 FUNDING: King's College London and King's College Hospital through the KMRT KCH Joint Research Committee studentship. This work was also conducted as part of the National Institute for Health Research (NIHR; CS-2017-17-023)-funded STEADY project (Safe management of people with Type 1 diabetes and EAting Disorders studY). NZ's salary was part-funded by the NIHR via the NIHR Clinician Scientist award to MS; JT and KI are part-funded by the NIHR Mental Health Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London. MS was funded through her NIHR Clinician Scientist Fellowship (CS-2017-17-023).

Humans

Remotely Supervised, Home-Based Transcranial Direct Current Stimulation for Major Depressive Disorder: Systematic Review and Meta-Analysis.

BACKGROUND: Major depressive disorder affects over 280 million people worldwide, and access to effective treatment remains limited. Transcranial direct current stimulation (tDCS) is a noninvasive option, and portable devices now allow for home-based delivery under varying degrees of remote supervision. OBJECTIVE: This study aimed to systematically review and meta-analyze the efficacy, safety, feasibility, and acceptability of home-based and remotely supervised tDCS for depressive disorders. METHODS: Following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) 2020 and PRISMA-S (Preferred Reporting Items for Systematic Reviews and Meta-Analyses literature search extension) guidelines, we searched MEDLINE, Embase, Web of Science, the Cochrane databases, ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry Platform up to July 2025, with backward and forward citation searching. Two reviewers independently screened records, extracted data, and assessed risk of bias (version 2 of the Cochrane risk-of-bias tool for randomized trials, Newcastle-Ottawa Scale for observational studies, and Critical Appraisal Skills Programme for qualitative studies) and certainty of evidence (Grading of Recommendations Assessment, Development, and Evaluation; GRADE). RESULTS: This review included 12 distinct studies (16 reports), of which 6 (50%) were randomized sham-controlled trials forming the meta-analytic pool. Active home-based tDCS produced a small, statistically significant improvement over sham (pooled Hedges g=0.36, 95% CI 0.06-0.66; P=.03; I2=34.3%). The effect was not robust to removal of the single largest positive trial (omitting the one study from 2025: g=0.39, 95% CI -0.12 to 0.91), and trial-level results were mixed: the 2 largest trials (one unsupervised [n=210] and one self-administered [n=141]) were negative on their primary depression outcomes, whereas the largest real-time supervised trial (n=174) was positive (between-group 95% CI 0.51-4.01; P=.01). This estimate was concordant in direction with an independent peer-reviewed meta-analysis of overlapping trials, which reported a pooled Montgomery-&#xc5;sberg Depression Rating Scale reduction (weighted mean difference -2.74, 95% CI -4.19 to -1.29) and Hamilton Depression Rating Scale reduction (weighted mean difference -2.24, 95% CI -4.16 to -1.49), attenuating to nonsignificance (P>.05) in major depressive disorder without comorbid cognitive impairment. The pooled effect fell at or near the minimal clinically important difference. GRADE certainty was moderate. Adverse events were predominantly mild: one pilot study was terminated early for skin lesions, and one nonfatal suicide attempt occurred in an unsupervised trial. CONCLUSIONS: Home-based and remotely supervised tDCS produces a small, statistically significant but clinically modest antidepressant effect that is sensitive to the inclusion of the largest positive trial, with the 2 largest trials being negative. The available controlled evidence does not establish supervision intensity as a determinant of efficacy. Current data are insufficient to recommend routine clinical adoption; adequately powered trials with standardized supervision and longer follow-up are needed.

Humans

Effectiveness of Wearable Digital Therapeutics in Improving Sleep Outcomes Among Individuals With Insomnia: Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Wearable devices are increasingly used for sleep monitoring and as adjunctive treatment. Existing meta-analyses mostly pool composite digital therapies and rarely isolate stand-alone wearables or distinguish between objective and subjective end points. Whether stand-alone wearable interventions improve sleep outcomes in adults with insomnia, and which factors moderate treatment heterogeneity, remains unclear. OBJECTIVE: This study aims to evaluate the effectiveness of wearable digital interventions on sleep outcomes in adults with insomnia versus control strategies and explore moderators of effectiveness, including device-wearing position, intervention duration, and control type, using meta-regression. METHODS: This systematic review and meta-analysis was conducted in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta&#x2011;Analyses) 2020 statement and the PRISMA-S (Preferred Reporting Items for Systematic Reviews and Meta&#x2011;Analyses Literature Search Extension) guideline. Five electronic databases and clinical trial registries were searched from inception to May 18, 2026. Eligible studies were randomized controlled trials (RCTs) evaluating wearable digital interventions in adults with insomnia compared with sham, waitlist, usual care, or active control conditions and had an intervention duration of at least 1 week. Study screening, data extraction, and risk-of-bias assessment were carried out independently by 2 reviewers. Pooled estimates were calculated using a restricted maximum likelihood random-effects model with the Hartung-Knapp-Sidik-Jonkman correction. Heterogeneity was assessed using the I&#xb2; statistic, and 95% prediction intervals (PIs) were calculated for the primary analyses. The certainty of evidence was rated using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach. RESULTS: Sixteen RCTs (N=910) were included. Wearable digital interventions were associated with a significant reduction in objective sleep-onset latency (SOL; mean difference [MD] -4.52, 95% CI -8.38 to -0.67, PI -9.52 to 0.47 min) and a significant improvement in subjective sleep efficiency (SE; MD 2.00%, 95% CI 1.90%-2.11%, PI 1.85%-2.15%). Subjective total sleep time (TST) also showed a significant increase (MD 19.11, 95% CI 2.98-35.24, PI -16.20 to 54.43 minutes). Meta-regression showed that control type, intervention duration, and device location did not explain the heterogeneity of the insomnia severity index (ISI) (R&#xb2;=0). Sensitivity analysis confirmed the robustness of pooled ISI estimates, and an Egger test indicated no small-study effects (P=.07). Certainty of evidence ranged from moderate to high. CONCLUSIONS: Wearable digital interventions provide selective benefits for objective SOL, subjective SE, and subjective TST in adults with insomnia, with no improvement in overall ISI. Despite statistically significant effects on several sleep parameters, wide PIs, substantial heterogeneity, and limited study numbers indicate preliminary, nonconclusive findings. Wearables should be viewed as affordable adjunctive tools requiring further validation, not substitutes for first-line cognitive behavioral therapy for insomnia. Large-scale, long-term RCTs with standardized protocols and patient-level external validation are required to consolidate the evidence base.

Humans

Premenarche risk factors for future dysmenorrhoea: a prospective cohort study.

BACKGROUND: Dysmenorrhoea, or pain during menstruation, is common in adolescence and is often dismissed or left untreated. Dysmenorrhoea can interfere with daily functioning and can lead to other chronic pain conditions; however, little is known about the risk factors for dysmenorrhoea. We aimed to characterise premenarche risk factors for the presence and severity of future dysmenorrhoea. METHODS: In this prospective cohort study, we obtained data for female adolescents from the population-based Adolescent Brain Cognitive Development Study (USA) who were premenarchal at baseline (age 9-10 years) and had both reached menarche and completed the Menstrual Cycle Survey at 3-year follow-up (age 12-13 years). Parents or guardians provided sociodemographic information and completed the Child Behavior Checklist, the Sleep Disturbance Scale for Children, and the Pubertal Development Scale, which captured data on non-painful somatic symptoms, attention problems, anxiety, depression, sleep disturbances, and pubertal development at baseline. Our primary objective was to analyse associations between dysmenorrhoea at 3-year follow-up (status and severity) with select symptom domains (sleep problems, attention problems, somatic symptoms, anxious or depressive symptoms, and baseline pain status) at baseline. We also investigated associations between dysmenorrhoea and participant characteristics (pubertal status, race or ethnicity, and income-to-needs ratio) that underlie social determinants of health. Differences by race were tested using Fisher exact tests. Differences by ethnicity and baseline pain status were tested using &#x3c7;2 tests. Differences in continuous variables were assessed using ANOVA. Wilcoxon-Rank Sum tests were used in analyses of sleep problems, attention problems, and somatic symptoms, and ANOVA was used for pubertal status and income-to-needs ratio. Multinomial logistic regression was used to test associations with dysmenorrhoea severity, and linear regression was used to test associations with dysmenorrhoea status and menstrual pain interference. FINDINGS: 2254 female adolescents were included in this study. 1299 (57&#xb7;6%) participants developed dysmenorrhoea at age 12-13 years, and 247 (19&#xb7;0% of those with dysmenorrhoea) reported severe dysmenorrhoea. Non-painful somatic symptoms were prospectively associated with future dysmenorrhoea (odds ratio [OR] 1&#xb7;17 [95% CI 1&#xb7;04-1&#xb7;32]; p=0&#xb7;0070), whereas anxiety or depression, sleep disturbances, and attention problems were not. Sleep disturbances were prospectively associated with menstrual pain interference (&#x3b2; coefficient 0&#xb7;16 [95% CI 0&#xb7;01-0&#xb7;31]). Advanced pubertal status at ages 9-10 years was prospectively associated with risk of dysmenorrhoea 3 years later (OR 1&#xb7;79 [95% CI 1&#xb7;47-2&#xb7;17]; p<0&#xb7;0001), as was lower income-to-needs ratio (0&#xb7;96 [0&#xb7;93-1&#xb7;00]; p=0&#xb7;031). Black (1&#xb7;38 [1&#xb7;05-1&#xb7;83]; p=0&#xb7;024) and Hispanic (1&#xb7;34 [1&#xb7;03-1&#xb7;68]; p=0&#xb7;010) young females were at a significantly greater risk of experiencing dysmenorrhoea than were White and non-Hispanic young females, respectively. INTERPRETATION: Sociodemographic characteristics and clinical symptoms present before menarche might help to identify at-risk individuals for dysmenorrhoea before pain becomes a lifelong issue. FUNDING: The National Institute of Nursing Research, the National Institute of Diabetes and Digestive and Kidney Diseases, and the Eunice Kennedy Shriver National Institute for Child Health and Human Development.

Humans