Systematic Reviews

Importance Non-inferiority trials are becoming increasingly popular in abdominal surgery. The non- inferiority margin is critical in the interpretation and conclusion of these trials. Objective This systematic review aims to assess the methodological and reporting quality of non- inferiority randomized controlled trials in abdominal surgery. Evidence Review Non-inferiority trials were systematically identified by searching Ovid Medline, Embase and the CENTRAL databases from 2006 until December 2025. Randomized controlled trials in adult patients with any type of abdominal surgical intervention in at least one trial arm and a sample size greater than or equal to 100 were eligible for inclusion. The primary outcome was the definition of the non- inferiority margin. Secondary outcomes were the reporting of the non-inferiority margin, the robustness of its estimation, the uncertainty of the point estimate and the adequacy of conclusions. Findings A total of 11 045 trials were identified, of which 101 were eligible, enrolling 44 370 patients. Most trials provided a rationale for the non-inferiority design, while six (5.9%) trials did not. Previous literature was commonly used (n=56; 55.4%), but the non-inferiority margin was most often based on a clinical fixed margin or on historical comparison of the treatment and the active comparator. Based on the margin, investigators tolerated substantially worse outcomes of the treatment compared to the comparator. Conclusions were appropriate based on the confidence interval and the predefined non- inferiority margin in 88 (87.1%) of trials. The clinical judgement of the conclusion was overall adequate. Confidence interval estimations were reported in 16 (15.8%) of trials. Simulation studies were limited by the reporting quality. Conclusions and Relevance Clinical fixed margins are commonly used in abdominal surgery non-inferiority randomized controlled trials, however, substantial shortcomings in reporting limit the interpretability and reproduction of study findings. Based on the findings of this study, guidance on surgical- specific non-inferiority margin definitions is needed.

Importance. Systematic reviews and meta-analyses inform suicide-prevention policy and practice, but broad database searches are difficult to screen manually. This limits capture of upstream interventions, such as economic policies, with indirect effects on suicide. Reliable automated screening could make broader and more comprehensive evidence syntheses feasible. Objective. To develop and validate ScreenAgent, a large language model (LLM) agent for title and abstract screening, and a review-specific method for prospectively estimating screening performance. Design, Setting, and Participants. ScreenAgent was validated internally on a prospective meta-analysis, and externally on two published systematic reviews. The correct include and exclude decisions followed standard systematic-review screening methodology. Exposures. ScreenAgent, an LLM agent returning structured include-or-exclude decisions. Records it marked for inclusion were re-checked by a second, cascade pass using a higher-effort LLM. For the external reviews, the agent's prompt was tuned automatically on a small set of labeled examples. Main Outcomes and Measures. We calculated sensitivity, specificity, workload reduction (the percentage of records removed from human review), and agent-versus-human reliability via Cohen kappa. Sensitivity was estimated by direct comparison (internal) and 5-fold cross-validation (external). Results. In the internal validation, ScreenAgent identified 43 of 44 eligible studies (sensitivity 97.7%; 95% CI, 88.2%-99.6%) with a generic prompt applied without any review-specific optimization, specificity 98.0%, and a measured full-corpus workload reduction of 99.4%. The cost was $855.91 for the full 201,064-record corpus (0.43 US cents per record). Agent-versus-human-consensus agreement exceeded human-versus-human agreement (Cohen kappa 0.75 vs 0.64; percent agreement 97.3% vs 95.4%). For two external validation studies, automatic tuning resulted in a cross-validated sensitivity of 95.9% (95% CI, 90.0%-98.4%) and 97.4% (90.9%-99.3%), with workload reductions of 97.4% and 98.4%. Conclusions and Relevance. Suicide prevention efforts often require rapid consolidation of evidence because of the inherent challenges of single studies trying to prevent rare outcomes. On both internal and external validation sets, ScreenAgent identified nearly all eligible studies with human-level reliability for a fraction of a US cent per record while keeping human reviewers as the final arbiters. By making broad searches feasible and screening performance measurable beforehand, this approach can serve as a transparent methodology to strengthen the speed at which we can inform and advance suicide prevention efforts.

One-to-one peer support is widely used in mental health services, but the components associated with better outcomes remain unclear. We systematically reviewed randomised controlled trials and conducted additive component network meta-analyses to identify which components of one-to-one peer support worker interventions were associated with outcomes for adults using mental health services. CINAHL Ultimate, Embase, MEDLINE, PsycINFO, CENTRAL, ClinicalTrials.gov and ISRCTN were searched, supplemented by citation tracking, previous reviews and expert consultation. Interventions were coded for seven components: Training and development, Maintaining peer support worker wellbeing, Relationship-building, Social support, Emotional support, Practical support and Cultural adaptation. The review followed PRISMA-NMA reporting guidance and was registered with PROSPERO (CRD42022355291). Thirty-six trials randomised 6,645 participants across nine countries. Only quality of life and recovery yielded estimable component effects at one or more follow-up points. For quality of life, Practical support had a positive incremental estimate at 3 months (standardised mean difference 0.52, 95% confidence interval 0.17 to 0.87); no component showed clear evidence of benefit at 6 months; and at 12 months Social support had a positive estimate (1.57, 0.12 to 3.01), whereas Maintaining peer support worker wellbeing had a negative estimate (-1.66, -3.05 to -0.28). These estimates were not consistent across follow-up points. For recovery, Relationship-building had positive estimates at 6 months (0.90, 0.03 to 1.78) and 12 months (0.50, 0.29 to 0.72). Networks were sparse and often disconnected, and additivity could not be tested in disconnected networks. Current trials do not permit definitive prioritisation of peer-support components. Relationship-building was the most consistent candidate component, but all findings remain provisional. Future trials should prospectively specify, manipulate and measure component delivery.

Background Virtual hospital (VH) pathways support early discharge through remote monitoring, but limited evidence has hindered implementation in colorectal surgery. This study aimed to define patient- and carer-relevant outcomes and experiences of VH following colorectal surgery. Methodology A patient and public involvement and engagement (PPIE) consultation was conducted with 8 participants (7 patients, 1 carer; 4 women, 4 men) who had experienced VH following bowel resection at a high-volume robotic unit. Purposive sampling ensured that 50% of participants had experienced readmission. The 90-minute session was delivered via Microsoft Teams. Data were analysed using reflexive thematic analysis. Results Seven themes were identified: readmission, remote monitoring, carer burden, recovery, equity, readiness for discharge, and information delivery. Patients supported early discharge when remote monitoring enabled timely detection of complications and readmission pathways were efficient. Readmission was not perceived as failure but as appropriate escalation. Dissatisfaction with readmission was related to delays in emergency care. Remote monitoring provided psychological safety, with patients feeling held at home. Carers assumed substantial, often unrecognised, quasi-clinical roles. Recovery was defined by return to function rather than length of stay. Equity concerns were evident, with VH favouring those with adequate support at home, digital literacy, and language proficiency. Discharge readiness was both clinical and psychological. Information delivery at discharge was often poorly retained and requires reinforcement preoperatively at every encounter with patients and carers. Conclusions VH pathways are acceptable and valued. Readmission is a marker of system responsiveness rather than failure of early discharge on VH. Psychological preparedness, carer support, and equitable access are critical to successful and scalable implementation of early discharge using a virtual hospital.

BACKGROUND Safe and effective antidepressant deprescribing strategies are needed in general practice where most antidepressant prescribing occurs. METHODS We conducted a pragmatic, cluster-randomised controlled trial in general practice to test invitation to general practitioner (GP) review combined with resources to inform shared decision-making and guide hyperbolic tapering for stopping antidepressants compared to usual care. Adults taking antidepressants for longer than 12 months were recruited from 26 Australian GP practices between March 2023 and November 2024, irrespective of their intention to stop or depression or anxiety symptom scores. The primary outcome was cessation at 12 months. Secondary outcomes included cessation at 6 months, and >75% dose reduction and depression, anxiety and withdrawal symptom scores at 6 and 12 months. RESULTS Overall, 483 patients were randomised. Mean age was 50 years; 73% were women; mean duration of antidepressant use was 14.1 years. Cessation at 12 months was observed in 32 of 215 (14.9%) intervention and 16 of 187 (8.6%) usual care patients (odds ratio (OR) = 1.95 [95%CI, 1.00 to 3.81]; p=0.050). Cessation at 6 months was observed in 11.7% intervention vs 4.8% usual care (OR = 2.68; 95%CI, 1.18 to 6.05), and >75% dose reduction at 12 months in 19.6% intervention vs 9.9% usual care (OR = 2.28; 95%CI, 1.20 to 4.31). Symptom scores were similar between groups. No adverse events were attributable to the intervention. CONCLUSIONS In general practice, invitation to GP antidepressant review combined with information and guidance on hyperbolic tapering can support cessation or dose reduction without causing adverse effects or relapse. Absolute cessation rates were modest but still meaningful given the high prevalence of long term antidepressant use. TRIAL REGISTRATION ANZCT registry identifier, ACTRN12622001379707p.

Insomnia is a transdiagnostic risk factor for depression and anxiety and frequently co-occurs with both conditions. Sleep restriction therapy (SRT) is considered a key active component of cognitive behavioural therapy for insomnia (CBT-I), is now delivered without therapist involvement via digital platforms such as SleepFix. Existing meta-analytic evidence suggests that digital behavioural therapy for insomnia (dBT-I) may improve anxiety and depression, but participant-level evidence remains limited. This individual participant data meta-analysis pooled data from two Australian randomised controlled trials (dBT-I n=220; control n=270; 78.3% female; mean age 66.0 years) to examine whether dBT-I, with SRT as the central component and delivered through the SleepFix program, reduces depressive and anxiety symptoms in adults with insomnia disorder, who were not specifically selected for anxiety and depression. We measured anxiety using the Generalised Anxiety Disorder 7-item scale and depression using the Patient Health Questionnaire-9 or Geriatric Depression Scale-15, with depression scores standardised to a common scale assuming a shared standard deviation of 4. We fitted linear mixed-effects models with random intercepts for participants and trials at Weeks 8 and 16, including baseline GAD-7 (mean 6.1, SD 4.8) in the anxiety model. dBT-I significantly reduced anxiety at Week 8 (mean difference -0.94 GAD-7 points, 95% CI -1.80 to -0.09, p=.030) and Week 16 (-0.94 GAD-7 points, 95% CI -1.86 to -0.02, p=.044), and depression at Week 8 (-0.40 SDs, 95% CI -0.66 to -0.14, p=.003) and Week 16 (-0.44 SDs, 95% CI -0.72 to -0.17, p=.002), with no evidence effects diminished between timepoints. However, the reductions were less than the smallest detectable difference for these questionnaires (i.e., 1 point). These findings support dBT-I as a scalable intervention with modest mental health benefits extending beyond insomnia.

Background: Placebo responding involves the reduction of symptoms in response to contextual features of an intervention (e.g., verbal suggestions), yet it is characterized by pronounced heterogeneity. Although verbal suggestions are widely recognised as a hallmark method for inducing placebo responses, an open question is whether variability in placebo responding can be partly attributed to individual differences in trait responsiveness to verbal suggestions (REVS). We conducted a pre-registered meta-analysis (PROSPERO registration number CRD420250654692) to quantitatively synthesize available research on the association between trait REVS and placebo responding. Methods: PsycInfo, PubMed, MEDLINE, and Embase were searched up to June 2026 for original clinical or experimental studies involving both the assessment of REVS and symptom measures (self-report, behavioural, and/or physiological) in response to an inactive intervention (placebo). Results: Of 1,512 search results, 24 articles presenting 66 correlations between REVS and placebo responding were analysed (N = 1,137). A multi-level meta-analysis revealed a significant, albeit weak, positive correlation between REVS and placebo responses, r = 0.18 [95% CI: 0.13, 0.24], such that individuals with higher REVS reported greater symptom relief in response to the placebo. Meta-regression analyses did not identify any significant moderators of the correlation between REVS and placebo responding and sensitivity analyses based on Bayesian subgroup estimates indicated that the aggregate correlation was stable across methodological quality indicators and study features. Conclusion: These findings suggest that individual differences in REVS may partly explain variability in symptom reduction in response to placebos, with implications for the sources of variance in placebo effects in experimental and applied contexts.

Background: Systematic reviews of clinical prediction models increasingly include studies using artificial intelligence (AI) and machine learning (ML) methods alongside traditional multivariable regression approaches. A previously published Excel tool enabled standardised data extraction using the CHARMS checklist and risk of bias assessment using PROBAST. The recent publication of the PROBAST+AI framework, which distinguishes the assessment of model development quality from the assessment of model evaluation risk of bias and assesses applicability in both parts, necessitates an updated digital instrument applicable across prediction modelling methods. Methods: We updated an open-access Excel tool to incorporate the full PROBAST+AI framework. The updated template incorporates structural separation between assessment of model development quality and model evaluation risk of bias, with applicability assessed in both parts. It also incorporates updated signalling questions, including those addressing methodological issues particularly relevant to AI/ML, and automates the generation of summary tables and graphical displays. Results: The updated tool (CHARMS & PROBAST+AI Template) contains 11 worksheets and supports data extraction and appraisal for up to 30 prediction models. Dedicated, linked worksheets enable separate assessment of model development and model evaluation, with Domain 4 distinguishing among Apparent, Internal, and External evaluation settings. Key updates include dedicated assessments for predictor pre-processing, class imbalance handling and recalibration, data leakage prevention, and replication of the full model development pipeline within resampling procedures. Automated sheets dynamically format tables and summary charts covering PROBAST+AI parts. Conclusions: The CHARMS & PROBAST+AI Excel template provides a standardised, user-friendly, and rigorous digital framework for systematic reviewers appraising traditional statistical and AI-driven clinical prediction models.

Background: Adverse drug withdrawal events (ADWEs) are a key safety concern during deprescribing but remain poorly explored in pharmacovigilance systems. Objectives: To identify and compare ADWE signals across drug classes, different drugs within drug classes, and across patient characteristics, countries, and over time. Methods: A case/non-case disproportionality analysis was conducted in FDA-FAERS and EMA-EudraVigilance pharmacovigilance databases, with stratification by age (adults: 18-64, older adults: [≥]65), sex (male/female), reporting time (2004-2023 in 5-year intervals), and country (for EMA data). Disproportionality analysis (quantitative signal detection) was used to detect signals between ADWEs and drugs using the proportional reporting rate (PRR[≥]2), reporting odds ratio (ROR>1), and information component (IC>0) with case count [≥]5. Results: Overall, 158,501 reports (FDA-FAERS 145,514; EMA-EudraVigilance 12,987) included drug-event pairs related to ADWEs. In FDA-FAERS, clobetasone (IC=5.58; PRR=79.18; ROR=176.90) showed the strongest ADWE signals, followed by hydromorphone (4.85; 29.94; 37.37), hydrocodone, and paroxetine. In EMA-EudraVigilance, ethyl loflazepate (IC=6.01; PRR=119.80; ROR=197.53), clobetasone (5.39; 102.73; 155.10), veralipride, and levomethadone had the strongest signals. Most drugs maintained positive ADWE signals in analysis stratified into adults and older adults. However, among the top 10 drugs (based on highest IC values), buprenorphine/naloxone, desvenlafaxine, and baclofen in FDA-FAERS (ICs 4.95-6.05) showed stronger signals in older adults. A sex-based difference was observed, with paroxetine, venlafaxine, and buprenorphine/naloxone showing a stronger positive signal in females in both databases, whereas several opioids had stronger signals in males versus females across both databases. Conclusion: This study suggests ADWE signals for some medications differ by age and sex, potentially indicating different risks for withdrawal effects.

Background Treatment of Raynaud phenomenon(RP) with oral vasodilators(calcium channel block-ers and phosphodiesterase type 5 inhibitors) has shown moderate efficacy, may not benefit to all patients, and adverse effects often compromise long-term treatment. In addition, a large placebo effect may jeopardize the assessment of treatment benefits. Pharmaconutritional strategies aiming at increasing nitric oxide bioavailability (beet-root juice and L-citrulline) may be promising alternatives, and we further hypothesized that patient preference for a treatment could be a driver of the response. Methods This study consisted of a series of randomized, double-blind, N-of-1 trials conducted in outpa-tients with primary or secondary RP. Each patient underwent a multiple crossover design with repeated blocks of randomized treatments periods: 2 weeks of placebo, 2 weeks of active treat-ments, and 1 week of washout. Outcomes included the Raynaud Condition Score(RCS), fre-quency and daily duration of attacks. Each patient prespecified its preferred primary outcome, efficacy threshold and preferred treatment, which was used for stratified randomization. Gener-alized linear mixed-effects models were used to determine individual and aggregated efficacy. Results Twenty-one patients completed 2 to 8 treatment blocks. Seventeen patients tested L-citrulline, 17 beetroot juice and 13 both treatments. Ten patients selected RCS as a primary outcome, 6 patients the number of attacks and 5 the duration of attacks. Me-dian threshold for considering treatment efficacy chosen by patients was 50% (min-max 20% to 75%) reduction of symptoms. Using individual criteria to define efficacy neither L-citrulline nor beetroot juice showed significant efficacy compared to baseline. Based on the aggregated data, our results show no significant difference between L-citrulline and the L-citrulline-based placebo, nor between beetroot juice and nitrate-depleted beetroot juice, with the exception of the daily duration of RP attacks with beetroot juice (p=0.002). Finally, there was a marked placebo response, notably when patients received their preferred treatment. Conclusions: Our study did not show significant beetroot juice or L-citrulline efficacy in RP. However, we found that individual preference for one treatment over another maximizes responses to both placebo and active treatments, particularly with regard to the frequency and duration of RP attacks, thus suggesting that a real and modifiable placebo effect exists in RP.

Objective. To determine the publication rate of abstracts presented at the American Diabetes Association Scientific Sessions and to evaluate the association between statistical significance of study results and subsequent publication. Research Design and Methods. We conducted a retrospective cohort study of abstracts presented at the 2018 American Diabetes Association Scientific Sessions. The primary exposure was study result category (statistically significant vs. non-statistically significant findings), and the primary outcome was publication in an indexed journal within 5 years after conference presentation. Publication status was determined through PubMed/MEDLINE and Scopus searches. Adjusted relative risks (RRs) and 95% CIs were estimated using generalized linear models with Poisson distribution and robust variance. Results. Among 541 included abstracts, 321 (59.3%) were subsequently published in indexed journals. Abstracts reporting statistically significant findings had a higher publication rate than those reporting non-statistically significant findings (61.9% vs. 42.3%; p=0.002). In the adjusted analysis, abstracts with non-statistically significant findings had a lower likelihood of publication compared with those reporting statistically significant findings (adjusted RR 0.71 [95% CI 0.55-0.93]; p=0.013). Conclusions. Approximately four in ten abstracts presented at the ADA Scientific Sessions were not published within 5 years. Abstracts reporting non-statistically significant findings had a lower likelihood of subsequent publication, suggesting persistent publication bias in diabetology research. Future initiatives promoting the interpretation of effect estimates, confidence intervals and clinical relevance, rather than statistical significance alone, may help reduce selective dissemination of evidence

Background: Although the acute phase of the COVID-19 pandemic has passed, SARS-CoV-2 continues to cause outpatient morbidity. Antioxidant micronutrients support immune regulation and may offer a low-cost, scalable adjunctive treatment in early infection. Objective: To evaluate a pilot combination antioxidant therapy within CanTreatCOVID. Methods: This pilot sub-protocol enrolled non-hospitalized adults across five Canadian provinces (September 5th, 2024-March 31st, 2025) with mild-to-moderate SARS-CoV-2 infection within five days of symptom onset. Participants were randomized to usual care plus a 10-day antioxidant regimen (selenium 300 g, zinc 40 mg, lycopene 45 mg, vitamin C 1.5 g) or usual care alone. Pilot objectives assessed feasibility, retention, adherence, and safety. The primary outcome was hospitalization or death within 28 days; exploratory outcomes included recovery and symptom measures by day 14. Results: Eighty-one participants were randomized (41 antioxidant; 40 usual care). Retention was high 85.4% antioxidant; 82.5% usual care), and 90.2% of antioxidant participants completed the intervention course. Adverse events were infrequent (9.8% vs 2.5%), with no serious adverse events reported. No deaths occurred in either group; no hospitalizations occurred in the antioxidant arm versus 2/40 (5%) in usual care. By day 14, recovery was reported in 32/40 (80.0%) participants receiving antioxidants versus 23/36 (63.9%) in usual care (OR 2.128; 95% CI 0.7474.871). Sustained alleviation of all symptoms occurred in 38/40 (95.0%) versus 29/36 (80.6%), respectively (OR 3.498; 95% CI 0.872 --10.017). Return to usual activity by day 14 occurred in 38/40 (95.0%) versus 30/36 (83.3%) (OR 3.113; 95% CI 0.762--9.022). Adjusted between-group differences in dietary intake were not statistically significant. Conclusions: Combination antioxidant therapy was feasible to deliver in a decentralized outpatient setting, with high adherence and tolerability. While the trial was not powered for definitive efficacy conclusions, consistent directional improvements across symptom outcomes support evaluation of this host-directed antioxidant strategy in larger trials. Keywords: Adaptive Platform Trial; Antioxidant Therapy; SARS-CoV-2 ; Outpatient Therapeutics; Micronutrient Supplementation Trial registration number: https://clinicaltrials.gov/study/NCT05614349

Background: The relative merits of infrainguinal bypass and primary major lower limb amputation (MLLA) for chronic limb-threatening ischaemia (CLTI) remain uncertain, and the baseline profiles of patients selected for each strategy are poorly described. Methods: A systematic review and meta-analysis were undertaken in accordance with PRISMA 2020 and prospectively registered (PROSPERO: CRD42022356094). MEDLINE, Embase, CENTRAL, and CINAHL were searched from inception to March 2025. Prospective studies of adults with CLTI undergoing primary infrainguinal bypass or primary MLLA were eligible. Mortality, major adverse cardiovascular events (MACE) and subsequent amputation outcomes were synthesised using random-effects meta-analysis of proportions. Baseline comorbidity profiles were also extracted. Results: Twenty-seven studies involving 6,576 patients were included: 5,779 underwent infrainguinal bypass and 797 underwent MLLA. After bypass, pooled mortality was 3.7% at 30 days (95% CI 2.8%-4.9%, I2 = 49.4%), 18.5% at 1 year (95% CI 15.6%-21.9%, I2 = 62.3%), and 54.3% at 5 years (95% CI 50.5%-58.0%, I2 = 0%). After MLLA, pooled mortality was 9.2% at 30 days (95% CI 4.1%-19.3%, I2 = 73.5%), 28.5% at 1 year (95% CI 13.3%-51.0, I2 = 70.8%), and 39.9% at 2 years (95% CI 0.3%-99.3, I2 = 90.5%), although longer-term estimates were limited by sparse data and marked heterogeneity. Thirty-day MACE was 6.5% (95% CI 4.3%-9.7, I2 = 63.5%) after bypass and 2.8% after MLLA (95% CI 0.1%-37.6%, I2 = 0%). Early subsequent major amputation after bypass occurred in 3.9% of patients (95% CI 2.0%-7.7%, I2 = 91.2%), rising to 16.2% at 1 year (95% CI 12.6%-20.5%, I2 = 82.0%) and 33.3% at 3 years (95% CI 20.1%-49.8%, I2 = 0%). Early re-amputation after MLLA occurred in 10.9% of patients (95% CI 4.5%-24.4%, I2 = 40.3%). Baseline comorbidity burden was high in both groups, with substantial heterogeneity across studies. Conclusions: CLTI carries a poor prognosis regardless of treatment strategy. Infrainguinal bypass is associated with lower early mortality and better early limb preservation than primary MLLA, but long-term survival remains poor and later limb failure is common. Primary MLLA is not a low-risk alternative. Better contemporary comparative evidence utilising modern causal inference approaches is needed to support individualised decision-making.

Preventive health is a crucial health systems component for managing disease burden and achieving health promotion policy goals. However, effective prevention relies on the modification of relevant risks, often requiring systemic health behaviour change. Australia's National Preventive Health Strategy (NPHS) prioritises seven focus areas: tobacco and nicotine, healthy diet, physical activity, cancer screening, immunisation, alcohol and other drugs, and mental health. The readiness of community members in Australia to address health behaviours relating to these areas has not been fully examined. In response, six focus groups were conducted with 27 adults from the Australian general population to explore their perspectives and experiences of preventive health information and behaviours relating to the seven NPHS focus areas. Themes and sub-themes were identified using an applied descriptive framework. Participants described motivations, barriers and experiences surrounding preventive health through the themes of 'Making informed health choices', 'Facilitating behaviour change and the role of support systems' and 'Spreading the preventive health word'. Sub-themes detailed processes of prioritisation, risk-benefit assessment, critical appraisal, sociocultural influence and support-seeking to understand and personalise preventive health information, implement behavioural change, and share information with others. The focus areas participants engaged with most strongly were healthy eating and physical activity, while cancer screening was discussed less often. These findings indicate high preventive health engagement in the Australian community, alongside challenges navigating and adapting relevant information to personal needs. These insights can support policymakers, healthcare providers and others to effectively enact the NPHS through more targeted preventive health information and care delivery.

Background Agenda-setting is a fundamental patient-centered communication practice in which a clinician works with a patient to elicit, propose, and organize topics for discussion during a clinical encounter. Various agenda-setting interventions have been developed, including patient-facing tools and clinician training, but their effects have not been systematically evaluated. We aimed to determine the effects of these interventions on encounter, patient, care partner, and clinician outcomes. Methods We searched grey literature and seven databases, including PubMed, from inception through July 2025 for randomized and non-randomized comparative studies of interventions designed to promote or improve clinical visit agenda-setting. Two reviewers independently screened articles and extracted data, with a third reviewer resolving conflicts. We assessed risk of bias using RoB 2 for randomized studies and ROBINS-I for non-randomized studies. We conducted random effects meta-analyses when outcomes were sufficiently comparable, assessed heterogeneity using I2, and rated certainty of evidence using GRADE. Post hoc exploratory subgroup analyses examined study design, adjustment status, and intervention structure. Results Twenty-nine articles describing 22 unique studies met the inclusion criteria, including 13 randomized and nine non-randomized studies. Agenda-setting interventions increased the occurrence of agenda-setting (risk ratio 5.43, 95% confidence interval (CI) 2.06 to 14.28, I2=34.6%) and favored the intervention for concerns addressed when measured as a continuous outcome (standardized mean difference (SMD) 0.37, 95% CI 0.16 to 0.57, I2=65.3%) and overall clinician satisfaction (SMD 0.50, 95% CI 0.23 to 0.78, I2=0.0%). There were no clear differences in the number of concerns raised (mean difference (MD) 0.21, 95% CI -0.19 to 0.61, I2=59.6%), visit duration (MD 0.64 minutes, 95% CI -0.83 to 2.12, I2=51.4%), or overall patient satisfaction (SMD 0.05, 95% CI -0.05 to 0.15, I2=47.0%). Potentially important heterogeneity was present for four of these six outcomes. Post hoc exploratory subgroup analyses did not provide clear evidence that effects varied by study design, adjustment status, or intervention structure. Risk of bias was often high, serious, or critical, and certainty of evidence was low or very low for all pooled outcomes. Conclusions To our knowledge, this is the first comprehensive synthesis of clinical visit agenda-setting interventions. Such interventions may increase the occurrence of agenda-setting and the extent to which patient concerns are addressed without increasing visit length. However, the certainty of evidence was low or very low, and the available evidence does not establish a superior intervention structure.

Mobile clinical-support applications can facilitate access to evidence-based information at the point of care, but evidence on their usability and perceived usefulness among newly graduated physicians working in health facilities with limited capacity is scarce. We assessed physicians experiences with BMJ Best Practice using a convergent mixed-methods study. All 81 eligible physicians assigned to rural facilities were invited; 32 enrolled and received application access and training. After three months, participants completed an online survey, and 23 reported using the application. Ten physicians reporting the highest consultation frequency were purposively selected for semi-structured interviews. Survey findings showed a predominantly favorable perception of usability: for most items, 70%-90% of participants agreed or strongly agreed with the statements assessed. Among users, 14 of 23 (60.9%) used the mobile application and 9 (39.1%) used the web version. Interviews indicated that participants valued rapid searches, organized and evidence-based information, and support for diagnostic reasoning, referral decisions, learning, and clinical confidence. Barriers included limited connectivity, difficulties searching in Spanish, automatic updates, challenges locating or using some calculators, and treatment information that was sometimes insufficiently specific. Most importantly, participants could not always implement recommendations because suggested medicines, diagnostic tests, or other resources were unavailable in their facilities. Mobile clinical-support applications may complement decision-making and learning among early-career physicians in rural primary care. However, their practical value depends not only on usability and evidence quality, but also on adaptation to users language, workflow, connectivity, and local service capacity.

Background. Guidelines recommend surgery for moderate and severe cervical spondylotic myelopathy (CSM) but support either surgery or nonoperative care for mild disease. How patients weigh the adverse events associated with each pathway is not well characterized. Methods. We conducted a three-arm randomized vignette experiment among United States adults aged 40 years and older recruited through an online research panel. All participants read an identical description of mild CSM and were randomized to one of three scenarios: surgery that improved symptoms, surgery that halted progression without improvement, or nonoperative management with symptom progression. Participants in the surgical scenarios rated 12 possible complications and those in the nonoperative scenario rated 8 progression outcomes. For each item, participants rated how strongly it would influence their decision (0-10) and whether they would still choose the same treatment. Items for which participants would no longer choose the same treatment were termed dominant decision factors. Results. Of 276 respondents, 263 (95.2%) were analyzed. Dominant factor rates ranged from 13.5% to 87.8% across complications. Complications described as persisting at one year produced substantially higher rates than the same complications described as resolving by three months. Adverse events more frequently constituted dominant factors when surgery was framed as offering less benefit, although differences between scenarios were not statistically significant. In the nonoperative scenario, worsening bladder control (56.6%) and neck pain interfering with sleep (53.0%) were the strongest influences, exceeding needing a cane to walk (32.1%). Conclusions. Treatment decisions for mild CSM are driven primarily by the expected permanence of adverse events and their anticipated impact on daily quality of life, rather than by conventional neurological metrics or surgical benefit framing.

Plastic products have greatly improved convenience in daily life. However, diverse pollutants released from these materials pose substantial risks to human health. Lactiplantibacillus plantarum PD01 has previously been demonstrated to reduce microplastic (MP) bioaccumulation and toxicity in murine model. In this study, we conducted a randomized, double-blind, placebo-controlled trial to further evaluate the efficacy of L. plantarum PD01 in reducing MPs and MP-associated chemicals in humans. A total of 106 participants were recruited in November 2025. Eligible participants were randomly assigned to either the placebo or intervention group, and orally received placebo or 1.0x1010 colony-forming units (CFU) L. plantarum PD01 after meals three times a day, respectively. Fecal, urinary, and blood samples were collected to determine the MPs contents, plasticizer levels, gut microbiota composition, blood metabolic profiles and biochemical indicators. Among these measurements, the analysis of urinary phthalate metabolites was completed first and revealed a significant reduction after the probiotic intervention. Compared with the placebo group, 6-week L. plantarum PD01 supplementation resulted in significant relative reductions in urinary levels of MCMHP by 60.2% (P = 0.0343), MMP by 51.2% (P < 0.001), MEHP by 49.6% (P = 0.0058), MiBP by 45.7% (P = 0.0085), MnBP by 35.8% (P = 0.0478), and {Sigma}DEHP by 46.2% (P = 0.0461). The interim results presented here provide the first clinical evidence that the probiotic strain PD01 can significantly reduce residual MP-associated chemicals in human body. To the best of our knowledge, this is the first randomized controlled trial (RCT) to evaluate probiotic intervention targeting MPs and MP-associated chemicals in humans.

Objectives: To describe age-group differences in inability to afford dental treatment and cost related dental delay, among the US community-dwelling population. Study design: Descriptive analysis of nationally representative survey data. Methods: Using nationally representative Medical Expenditure Panel Survey data (2018-2021), we examined trends in inability to afford dental treatment and cost-related dental treatment delays across four age groups (2-17, 18-39, 40-64, [&ge;]65 years). Weighted analyses accounted for the complex survey design; statistical significance was set at p<0.001. Results: Cost-related delays declined modestly from 2018 to 2021 but remained most prevalent among adults aged 40-64 (4.8% for ages 40-64, 3.4% for ages 18- 64, 2.2% for ages>65 in 2021; p<0.001). Conclusion: Middle-aged adults seem to experience delays due to cost, underscoring the need for dental coverage to expand dental coverage for this group and to reduce their out-of-pocket costs.

Background: Complementary and Alternative Medicine (CAM) therapies, such as massage, meditation, and yoga, are widely used to promote wellness, including sleep improvement. Although some CAM therapies may improve sleep through stress reduction, relaxation, and relief of physical discomfort, little is known about associations between individual CAM modalities and sleep health at the population level. Therefore, we investigated the associations between CAM therapies and short sleep duration as well as insomnia symptoms. Methods: Participants from the nationally-representative 2012 National Health Interview Survey (NHIS) self-reported the use of CAM therapies and short sleep duration (<7 hours vs. 7-9 hours) as well as insomnia symptoms (yes vs. no). Poisson regression with robust variance was used to estimate adjusted prevalence ratios (aPRs) and 95% confidence intervals (CIs) for cross-sectional associations between CAM therapy use and sleep outcomes. Results: Among 30,405 participants, the average age was 46.1 +/- 0.2 years and 51% were women. Adults reporting any vs. no CAM therapy use had a higher prevalence of short sleep duration (aPR: 1.11; 95% CI: 1.05-1.16) and insomnia symptoms (aPR: 1.56; 95% CI: 1.47-1.65) after adjustment for sociodemographic and clinical characteristics. Herbal supplements (aPR: 1.13; 95% CI: 1.07-1.19) and massage (aPR: 1.14; 95% CI: 1.05-1.23) were associated with higher prevalence of short sleep duration. Most CAM therapies were associated with higher prevalence of insomnia symptoms, with the strongest associations observed for meditation/guided imagery/progressive relaxation (aPR: 1.84; 95% CI: 1.68-2.02). Conclusion: The higher prevalence of short sleep duration and insomnia symptoms among CAM users may reflect reverse causation, as adults with more severe or persistent sleep disturbances may be more likely to seek CAM therapies. Longitudinal studies are needed to clarify directionality.