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PubMed2026

Temporal Trends and Spatial Variation in Preterm Prelabour Rupture of Membranes: A Population-Based Study.

OBJECTIVE: To describe the temporal trends in Preterm prelabour rupture of membranes (PPROM) in metropolitan France and the geographical distribution at the administrative division level. DESIGN: Exploratory population-based study using administrative data of the French National Health Data System. SETTING: Metropolitan France, 2015 to 2023. POPULATION: Pregnancy with a diagnosis of PROM before 37 SA. METHODS: Annual crude incidence of PPROM was calculated by dividing the number of pregnancies with PPROM diagnosis by the number of live births recorded during the same period. Annual trend was estimated by a binomial negative mixed model. Smoothed standardised incidence ratios were estimated based on a BYM2 model, which accounts for spatial variability between departments. MAIN OUTCOME: PPROM cases, defined as pregnancies with first hospitalizations with a diagnosis of PROM before 37 weeks. RESULTS: Over the study period, we included 150 615 PPROM cases representing 16 735 (±596) per year. Incidence of PPROM cases showed an ascending trend over time (incidence rate ratio 1.023 per year; 95% CI: 1.017-1.030) with an annual crude incidence ranging from 2.2% in 2015 to 2.7% in 2023. A decrease in the incidence was observed in 2020 relative to other years (incidence rate ratio 0.903, 95% CI: 0.887-0.920). A map of smoothed SIRs of PPROM cases at the French administrative division level revealed geographical inequalities. CONCLUSIONS: This first population-based study describing PPROM cases in metropolitan France paves the way for further studies to explore environmental hypotheses. Identifying temporal and geographical disparities in PPROM incidence is relevant to public health policy and practice as such disparities argue for the development of targeted prevention strategies in high-risk areas.

French national health data system↗

PubMed2026

Outcomes of Response-Based Watch-and-Wait and Surgical Management After Total Neoadjuvant Therapy for Rectal Cancer: A Systematic Review and Meta-analysis.

BackgroundTotal neoadjuvant therapy (TNT) increases clinical complete response rates in locally advanced rectal cancer (RC), allowing response-based management strategies such as watch-and-wait (WW) as an alternative to total mesorectal excision (TME). Outcomes associated with WW after TNT remain incompletely defined. This study aimed to compare oncologic and organ-preservation outcomes between WW and surgical management following TNT.MethodsA systematic search was conducted in PubMed, Scopus, and Cochrane Central up to April 2025. Observational studies comparing WW and TME following TNT were included. Pooled odds ratios (ORs), hazard ratios (HRs), and 95% confidence intervals (CIs) were calculated using a random-effects model. Heterogeneity was assessed with I2 statistics. Secondary outcomes included tumor regrowth, salvage surgery, and permanent stoma. Risk of bias was evaluated using ROBINS-I.ResultsSix studies comprising 793 patients were analyzed. WW showed no significant difference compared with TME regarding local recurrence (OR 1.36, 95% CI 0.07-26.17; I2 = 80%), distant metastases (OR 0.62, 95% CI 0.29-1.33; I2 = 49%), 5-year disease-free survival (HR 0.97, 95% CI 0.71-1.31; I2 = 51.7%), or overall survival (HR 1.03, 95% CI 0.81-1.30; I2 = 27.9%). Permanent stoma rates were lower with WW (OR 0.12, 95% CI 0.01-1.23; I2 = 71%), becoming significant after sensitivity analysis (OR 0.04, 95% CI 0.01-0.19).ConclusionWW after TNT offers oncologic outcomes comparable to TME, with high organ preservation and reduced surgical morbidity in highly selected patients.

Humans↗

PubMed2026

Patterns and implications of co-use between vaping and hallucinogens: a systematic review and meta-analysis.

BACKGROUND: The co-occurrence use of e-cigarettes and hallucinogens has become increasingly common, particularly among youth and young adults. However, evidence regarding the association between these behaviors remains limited and fragmented. This systematic review and meta-analysis aimed to synthesize current evidence, examining the correlation between hallucinogen use and the likelihood of being an e-cigarette user. METHODS: A comprehensive search was conducted in PubMed, Scopus, Web of Science, EMBASE, and Cochrane CENTRAL up to June 2025. Eligible studies measured both hallucinogen and e-cigarette use and reported quantitative associations between these behaviors. Data extraction and risk-of-bias assessments were performed independently by three reviewers using the Newcastle-Ottawa Scale. Pooled effect sizes were calculated using a random-effects model (REML). Certainty of evidence was evaluated with the GRADE approach. RESULTS: Eleven studies met the inclusion criteria (n = 247,904), and seven were included in the meta-analysis (n = 217,478). The pooled analysis demonstrated that hallucinogen users had 4.47 times higher odds of being e-cigarette users (OR: 4.47, 95% CI 2.72 to 7.34; p < 0.001; I2 = 95.7%, n = 7). The certainty of evidence was rated as low. CONCLUSIONS: Hallucinogen use is directionally and strongly associated with e-cigarette use across diverse populations. Although the direction of association was consistent across studies, the magnitude of effect was heterogeneous. These behaviors likely share psychosocial and environmental determinants, although alternative explanations, including shared genetic liability, recall bias, and residual confounding, cannot be excluded. Further longitudinal studies are needed to clarify the underlying mechanisms of this association and establish temporality. The findings also support integrating hallucinogen-use screening into e-cigarette prevention and harm-reduction programs targeting youth and young adults.

Humans↗

PubMed2026

Current Diagnostic Pathways for Rheumatoid Arthritis-Associated Interstitial Lung Disease Result in Substantial Underdiagnosis and Excess Mortality: A Multicenter Norwegian Quality Assurance Audit.

OBJECTIVE: Recent guidelines suggest risk-stratified screening for rheumatoid arthritis-associated interstitial lung disease (RA-ILD). However, the diagnostic gap between current routine care and this screening approach remains unquantified. We assessed currently detected RA-ILD in Norway, benchmarking findings against recent screening-based estimates of the true disease burden. METHODS: This 10-year quality assurance audit across six centers covered 43% of the Norwegian population. RA-ILD cases identified via ICD-10 codes were confirmed by manual chart review. Prevalence was calculated relative to a registry-derived total RA background population and benchmarked against a 10% expected target derived from recent prospective studies. Mortality was compared to a 3:1 frequency-matched RA control group using Cox proportional hazards regression. RESULTS: Among 17,305 RA patients, 188 (1.1%) had verified ILD; when benchmarked against an expected 10% prevalence, this indicates an 89% diagnostic gap in routine clinical care. Mean age at ILD detection was 67.5 years. Most cases (93.6%) possessed ≥2 established risk factors for RA-ILD: 93.6% were seropositive, 76.1% had smoking histories, while RA onset age ≥60 and persistently increased inflammatory laboratory markers were present in over half of patients. RA-ILD was associated with significantly increased mortality; 66 (4.1/100 person-years) deaths occurred in the RA-ILD group vs. 120 (2.3/100 person-years) among RA controls (HR 1.77; 95% CI: 1.31-2.39, p<0.001). CONCLUSION: When comparing to prevalence expectations, current routine care may leave a substantial proportion of cases undetected, primarily capturing a high-risk phenotype with excess mortality. Systematic, risk-stratified screening is needed to bridge this diagnostic gap, aiming to enable earlier intervention.

Interstitial lung disease↗

PubMed2026

Urinary Small Extracellular Vesicle DNA as a Biomarker for the Non-Invasive Diagnosis of Bladder Cancer.

Existing diagnostic technologies for bladder cancer (BC) suffer from low sensitivity, low specificity, or a lack of validation. Therefore, validated, non-invasive diagnostic biomarkers with high sensitivity and specificity for early detection of BC are needed to complement and improve upon the limitations of existing diagnostic methods. We used low-pass whole genome sequencing (LP-WGS) technology to detect copy number variations (CNVs) in small extracellular vesicle (sEV) DNA isolated from urine samples of patients. Based on these results, we constructed and validated a diagnostic model to differentiate between benign and malignant bladder lesions. We conducted a receiver operating characteristic analysis and calculated the area under the curve (AUC) to evaluate the performance of the diagnostic model. The urine sEV-DNA LP-WGS data revealed CNV differences between benign and malignant samples. The diagnostic model achieved an AUC of 0.953, a sensitivity of 86.7%, and a specificity of 100% in the training cohort and an AUC of 0.985, a sensitivity of 90%, and a specificity of 100% in the validation cohort. Even at the lowest coverage depth of 0.01X, the performance of the diagnostic model remained relatively robust. Notably, the performance of this diagnostic model surpassed that of the biomarker neuron-specific enolase (sensitivity: 85.7% vs. 64.3%; specificity: 100% vs. 87.5%) and urinary cytology (sensitivity: 100% vs. 66.7%; specificity: 100% vs. 94.1%). Our study demonstrates that urine sEV-DNA exhibits high discriminatory power in distinguishing between benign and malignant bladder lesions, making it a promising tool for auxiliary diagnosis of BC.

Humans↗

PubMed2026

Robotic assistance in total hip arthroplasty: a systematic review and meta-analysis of leg length, cup orientation, and early outcomes.

This review examined whether robotic assistance alters postoperative leg-length discrepancy (LLD), acetabular cup orientation, or early hip-specific outcomes relative to conventional total hip arthroplasty (THA). We searched PubMed and Web of Science through May 2026 for comparative English-language reports. Study eligibility, data extraction, and methodological appraisal were undertaken independently by two reviewers. Mean differences (MDs) and 95% confidence intervals (CIs) were calculated in Review Manager 5.4. Model selection was based on the target estimand and anticipated clinical and methodological diversity; leave-one-out and alternative-model sensitivity analyses were undertaken for heterogeneous outcomes. The protocol is registered with PROSPERO (CRD420261454043). The review included seven studies and 968 participants. Compared with conventional THA, robot-assisted THA yielded a smaller postoperative LLD (MD = -2.02, 95% CI -3.46 to -0.58; P = 0.006) and a higher Harris Hip Score (MD = 2.96, 95% CI 1.12 to 4.80; P = 0.002). Mean cup anteversion was lower in the robotic group (MD = -1.52, 95% CI -2.29 to -0.76; P < 0.0001), whereas cup inclination did not differ (MD = -0.71, 95% CI -3.26 to 1.83; P = 0.58). The robotic group also had higher Forgotten Joint Score (MD = 14.68, 95% CI 5.02 to 24.33; P = 0.003) and Oxford Hip Score values (MD = 2.61, 95% CI 0.71 to 4.51; P = 0.007). Robotic assistance was linked to a modest improvement in leg-length restoration and to higher scores on several early functional measures. The limited number of studies, predominance of nonrandomized designs, and marked heterogeneity in some analyses temper the certainty of these findings.

Humans↗

PubMed2026

The impact of absolute change in tibiofemoral morphology on patient reported outcome measures post total knee arthroplasty.

BACKGROUND: Reconstructing knee morphology and alignment is important for outcomes post total knee arthroplasty (TKA). Personalised alignment strategies are proposed to improve outcomes by replicating native alignment. However, how change in morphology affects patient outcomes is unclear. This study aimed to investigate the relationship between absolute change in morphological measures post-TKA and patient reported outcome measures (PROMs). METHOD: An observational analysis of a randomised clinical trial was conducted. Participants received preoperative and postoperative CT scans and completed PROMs at six-months post-TKA. Absolute change in hip-knee-ankle angle, medial proximal tibial angle, lateral distal femoral angle, non-weightbearing joint line convergence angle, tibial and femoral rotation, and posterior tibial slope (PTS) were calculated. PROMs included visual analogue scales of pain and satisfaction (0-100), Oxford Knee Score, Forgotten Joint Score, and the Kujala Score. Regression and principal component (PCA) analyses investigated relationships between PROMs and change in morphology. RESULTS: Sixty-one participants were included for analysis (61% women, age 66.9 ± 9.1 [mean ± SD] years, BMI 32.8 ± 6.8 kg/m2). The PCA demonstrated coronal, axial, and sagittal plane measures were interdependent, with over 65% of variability driven by change in tibial rotation (PC1) and the PTS (PC2). The regression analysis showed no relationships between morphological change and PROMs postoperatively. CONCLUSION: Tibiofemoral morphology was interrelated across coronal, axial, and sagittal planes. However, this study suggests absolute morphological change had minimal impact upon PROMs at six-months post-TKA. Future research should clearly distinguish between osteoarthritic versus prearthritic alignment and consider the influence of soft-tissue releases upon PROMs.

Humans↗

PubMed2026

Potential Links Between Physiological and Perceptual Strain in High Heat Stress.

The physiological strain index (PhSI) is widely used to quantify thermoregulatory and cardiovascular strain during heat stress. However, direct physiological measurements may not always be feasible in occupational or athletic settings. Therefore, this study aimed to examine the relationship and agreement between perceptual strain and integrated physiological strain indices during high heat stress. Ten healthy, physically active, non-heat-acclimated males (29 (7) yr; 1.79 (0.11) m; 77.4 (9.3) kg) completed two randomized crossover exercise trials in hot-dry (HD) and warm-humid (WH) environments with equivalent wet-bulb globe temperatures. Heart rate, rectal temperature, skin temperature, rating of perceived exertion, and thermal sensation were measured at baseline and every 15 minutes during 60 minutes of cycling. Physiological strain index (PhSI), adaptive physiological strain index (aPhSI), and perceptual strain index (PeSI) were calculated using validated equations. Repeated-measures correlation analyses demonstrated very strong associations between PeSI and both PhSI and aPhSI under HD (Rrm = 0.940-0.943) and WH (Rrm = 0.980-0.982; all p < 0.001). Receiver operating characteristic analyses demonstrated good-to-excellent discrimination of physiological strain by PeSI (AUC = 0.895-0.969). Mixed-effects analyses showed that higher PeSI values were associated with increased PhSI (β = 1.325, p < 0.001) and aPhSI (β = 1.459, p < 0.001). However, Bland-Altman analyses demonstrated relatively small mean biases (0.4-0.9 AU) but wide limits of agreement (-2.8 to 4.2 AU), indicating that PeSI and physiological strain indices are not interchangeable. These findings suggest that PeSI may serve as a practical adjunctive or screening indicator of physiological strain when direct physiological measurements are unavailable.

Humans↗

PubMed2026

Effectiveness and moderators of PE and CPT in adult PTSD treatment: a systematic review and meta-analysis.

Background: Posttraumatic Stress Disorder (PTSD) is a prevalent and debilitating condition that challenges mental health services worldwide. Effective psychological interventions are crucial for treatment, among which Prolonged Exposure (PE) and Cognitive Processing Therapy (CPT) are prominent. Comparative analyses of these treatments, considering moderators such as patient demographics and treatment specifics, are necessary to tailor interventions effectively.Objective: This meta-analysis synthesised findings from 175 treatment arms across 163 studies to evaluate the comparative effectiveness of PE and CPT for PTSD. Effect sizes were calculated as Hedges' g for between-group (treatment vs. control) and within-group (pre-post) comparisons.Results: Using a random-effects model, the overall pooled effect size was large (Hedges' g = 1.67, 95% CI [1.56, 1.79]), suggesting substantial treatment-related symptom improvement. Multivariate meta-regression revealed, across the full sample, none of the main effects or interactions was significant. A sensitivity analysis excluding 10 influential outliers reduced the overall effect size (g = 1.55), indicating that PE was associated with larger effects than CPT among non-military samples, and larger effects were observed in studies with a higher proportion of female participants, military samples, and samples with lower proportions of sexual trauma. Treatment-by-sample-characteristic interactions were not significant in the trimmed model.Conclusions: Findings suggest that PE and CPT produce large effects in reducing PTSD symptoms, with some variation across treatment type and sample characteristics. Results underscore the importance of examining contextual moderators such as treatment setting and population type and highlight the need for transparent reporting of key sample features to improve future meta-analytic precision.

Humans↗

PubMed2026

A GRADE-assessed systematic review and meta-analysis of randomized controlled trials evaluating the effects of olive leaf or olive pomace supplementation on cardiometabolic and anthropometric health markers.

AIMS: Cardiometabolic diseases (CMDs) are major contributors to global morbidity and mortality, and dietary bioactives such as polyphenols may modulate key risk factors. Olive by-products, particularly olive leaves (OL) and olive pomace (OP), are rich in phenolic compounds with antioxidant, anti-inflammatory, and cardiometabolic effects demonstrated across in vitro, preclinical, and clinical studies. DATA SYNTHESIS: This GRADE-assessed systematic review and meta-analysis included 30 randomized controlled trials (n = 1726) evaluating OL or OP supplementation on 21 standardized biomarkers, encompassing inflammatory markers, lipid profile, glycemic control, insulin sensitivity, anthropometric measures, and blood pressure. Meta-analyses were conducted using random-effects models, with effect sizes calculated as mean differences (or standardized mean differences for oxLDL). Between-study heterogeneity was assessed with I2 statistics, and sensitivity and subgroup analyses explored potential sources of variability. Publication bias was evaluated using Begg's test and funnel plots where appropriate. OL supplementation significantly improved lipid parameters (total cholesterol, triglycerides, LDL-C, ApoB, oxLDL) and increased ApoA1, while reducing TNF-α, systolic and diastolic blood pressure, body weight, and BMI. No significant effects were observed on glycemic markers. OP supplementation showed no consistent cardiometabolic benefits and was associated with an increase in IL-8. Certainty of evidence ranged from very low to high, with several outcomes downgraded due to imprecision, heterogeneity, or limited study numbers. CONCLUSION: These findings support the targeted use of OL as an adjunctive strategy for cardiometabolic risk management. Evidence for OP supplementation remains limited, underscoring the need for well-powered, high-quality RCTs to clarify its clinical effects.

Humans↗

PubMed2026

Pharmacokinetics and Safety of Nerandomilast in Healthy Volunteers.

BACKGROUND AND OBJECTIVES: Nerandomilast, a preferential phosphodiesterase 4B inhibitor, is approved for idiopathic pulmonary fibrosis and progressive pulmonary fibrosis in some countries. The objective of this study was to evaluate the safety and pharmacokinetics of nerandomilast in healthy volunteers through single- and multiple-rising-dose studies, and a human mass balance study evaluating absorption, distribution, metabolism, and excretion. METHODS: Healthy participants received oral nerandomilast doses ranging from 0.02 mg to 24 mg in the single-rising-dose trial, 1 mg or 6 mg twice daily for 14 days in the multiple-rising-dose trial, and a single oral dose of 18 mg [14C]-labeled nerandomilast in the mass balance trial. In each trial, pharmacokinetic blood samples were collected for determination of nerandomilast plasma concentrations. In the mass balance study, urine, feces, and blood samples were collected, and [14C]-radioactivity was quantified from these matrices. All pharmacokinetic parameters were calculated via noncompartmental analysis. RESULTS: Nerandomilast was rapidly absorbed postadministration, with peak plasma concentrations occurring between 0.5 and 1.25 h postdose before declining in a multiphasic manner. Nerandomilast exposure increased dose proportionally following single- and multiple-dose administrations. Steady state was reached by day 7 after twice-daily dosing with up to 1.69-fold drug accumulation. Following a single oral dose administration of [14C]nerandomilast, 58.0% and 36.4% of radioactivity was excreted in feces and urine, respectively. Of the administered dose, 11.9% was excreted as unchanged parent compound in urine. Nerandomilast safety was acceptable across all three studies and nerandomilast was well tolerated in healthy participants. CONCLUSIONS: Nerandomilast exhibited rapid oral absorption, multiphasic elimination profile, dose-proportional exposure, and was excreted via urine and feces. TRIAL REGISTRATION: NCT01594515 (registered 2012-05-07), NCT01835899 (registered 2013-04-11), and NCT04771286 (registered 2021-02-23).

Humans↗

PubMed2026

Acute mild cold exposure with shivering reduces 24 h glucose levels in individuals with type 2 diabetes but not prediabetes.

AIMS/HYPOTHESIS: Repeated cold exposure with shivering has been proposed as a potential strategy to enhance glucose metabolism by increasing energy expenditure and substrate utilisation. However, acute effects/benefits of cold-induced shivering on glucose homeostasis in metabolically compromised individuals are unknown. Here, we aimed to determine whether cold exposure at two different intensities improves 24 h glucose homeostasis in individuals with prediabetes and type 2 diabetes. METHODS: In a randomised crossover trial conducted in the South Limburg/Maastricht region of the Netherlands, men and postmenopausal women with prediabetes (n=12) and stable type 2 diabetes (n=12), aged 40-75 years, body mass index ≥27 and ≤35 kg/m2, non-smoking and sedentary, underwent two whole-body cold exposure sessions using a water-perfused suit. Session order was randomised using an online randomisation tool (randomizer.org); participants were masked to the cold exposure intensity received, but investigators were not. Sessions were designed to elicit ~1.5-fold (mild, 15°C) and ~2.5-fold (moderate, 4°C) increases in resting metabolic rate (RMR). Continuous glucose monitoring assessed interstitial glucose concentrations over 24 h periods before and after each intervention, with controlled diet and activity. Shivering was confirmed via indirect calorimetry and electromyography. RESULTS: In both study groups and periods, RMR increased significantly vs baseline (p<0.001 for all). In prediabetes, the increase in the final 1 h of cold was 1.53 × RMR in mild and 1.94 × RMR in moderate cold. In type 2 diabetes, the increase was 1.57 × RMR and 2.09 × RMR in the final 1 h of mild and moderate cold, respectively. In prediabetes, neither mild nor moderate cold exposure altered mean 24 h glucose levels. In contrast, after mild cold exposure the type 2 diabetes group exhibited a significant reduction in mean 24 h glucose levels (-0.6 ± 0.5 mmol/l, p=0.003) and fasting glucose (-0.6 ± 0.8 mmol/l, p=0.019), as well as an increase in time in normal range (+8.8 ± 10.3%, p=0.013) and reduced time in hyperglycaemia (-10.9 ± 12.9%, p=0.014). Moderate cold did not significantly affect any of the glucose outcomes in type 2 diabetes. Baseline fasting glucose, age and ALT levels were predictors of the glucose-lowering response, suggesting greater benefits in individuals who have higher baseline glucose levels, are younger and/or have more optimal liver health, i.e. lower ALT. CONCLUSIONS/INTERPRETATION: Acute mild cold exposure with shivering reduced 24 h glucose levels in individuals with type 2 diabetes. No changes were observed in prediabetes. The observed effects appear to depend on baseline metabolic status rather than acute substrate utilisation during cold exposure. These findings support the potential of cold exposure as an adjunct non-pharmacological therapy for type 2 diabetes, although further mechanistic studies and validation in larger cohorts are warranted. TRIAL REGISTRATION: ClinicalTrials.gov NCT05576025 FUNDING: Dutch Organisation for Knowledge and Innovation in Health, Healthcare and Well-being (ZonMw): 09120012010062.

Humans↗

PubMed2026

Postoperative complications and outcomes after surgical treatment for tophaceous gout: A systematic review and meta-analysis.

BACKGROUND: Surgical treatment remains necessary for selected patients with tophaceous gout, particularly when mechanical limitation, nerve compression, ulceration, infection, deformity, or failure of conservative treatment is present. However, postoperative outcomes after surgery for tophaceous gout have not been comprehensively quantified. This systematic review and meta-analysis evaluated postoperative complication profiles and recurrence burden after surgical treatment for tophaceous gout. METHODS: A systematic search of PubMed, Embase, Web of Science, and the Cochrane Library was conducted from database inception to March 25, 2026. Original studies reporting postoperative outcomes after surgical treatment for tophaceous gout were included. Pooled event rates with 95% confidence intervals (CIs) were calculated using a random-effects single-arm meta-analytic approach. Primary outcomes were postoperative infection, delayed wound healing, and recurrence. Secondary outcomes were reoperation, amputation, and overall complications. Functional outcomes were summarized descriptively. RESULTS: 18 retrospective studies were included. The pooled postoperative infection rate was 11.3% (95% CI 8.0%-15.7%), delayed wound healing 9.9% (95% CI 5.1%-18.2%), and recurrence 8.5% (95% CI 4.7%-14.9%). Secondary pooled rates were 9.7% (95% CI 5.5%-16.7%) for reoperation, 3.7% (95% CI 2.0%-6.8%) for amputation, and 24.0% (95% CI 14.0%-38.1%) for overall complications. Significant subgroup differences were identified only for infection according to anatomic site and intervention type. Sensitivity analyses showed that pooled estimates were robust. The certainty of evidence was very low for all outcomes. CONCLUSIONS: Surgical treatment for tophaceous gout is associated with measurable postoperative risks, particularly infection and overall complications. These findings support careful perioperative counseling, structured postoperative surveillance, integrated long-term urate-lowering management, and more standardized reporting of perioperative risk factors and postoperative outcomes in future surgical studies of tophaceous gout.

Humans↗

PubMed2026

Prognostic value of early changes in the frontal QRS-T angle in patients with heart failure and left bundle branch block undergoing cardiac resynchronization therapy.

BACKGROUND: Cardiac resynchronization therapy (CRT) reduces morbidity and mortality in selected patients with heart failure (HF). The frontal QRS-T angle (FQTA), reflecting ventricular depolarization-repolarization heterogeneity, has been associated with major adverse cardiovascular events (MACE). We aimed to assess the prognostic value of changes in the FQTA after CRT in predicting long-term MACE. METHODS: A total of 223 consecutive HF patients with left bundle branch block who underwent CRT between 2018 and 2022 were retrospectively analyzed. The FQTA was measured before and after CRT, and the change (ΔFQTA) was calculated. Receiver operating characteristic (ROC) analysis was performed to determine the optimal cutoff value for predicting the primary outcome, MACE. Patients were subsequently stratified according to this cutoff value. Independent predictors were identified using multivariable Cox proportional hazards regression analysis. RESULTS: ROC analysis identified 22.5° as the optimal cutoff value for predicting MACE (AUC: 0.711; 95% CI: 0.642-0.781; p < 0.001). During a mean follow-up of 34.6 ± 17.6 months, patients with ΔFQTA <22.5° had a significantly higher incidence of MACE compared with those with greater angle reduction (44.7% vs. 11.9%; p < 0.001). In multivariable Cox regression analysis, chronic kidney disease (HR: 2.517; p = 0.002) and ΔFQTA <22.5° (HR: 4.56; p < 0.001) were independently associated with MACE. CONCLUSION: A greater reduction in FQTA after CRT is associated with improved long-term outcomes and may serve as a practical electrocardiographic marker for risk stratification.

Humans↗

PubMed2026

Meta-analysis and pharmacoeconomic study of rasagiline versus selegiline in the treatment of Parkinson's disease.

OBJECTIVE: Given the persistent absence of direct head-to-head trials, this study aimed to evaluate the comparative efficacy, safety, and cost-effectiveness of rasagiline versus selegiline as early-stage monotherapy for Parkinson's disease (PD), informing clinical selection and healthcare policies in China. METHODS: A systematic search of PubMed, Embase, and the Cochrane Library identified randomized controlled trials (RCTs) up to April 2026. Focusing on short-term outcomes (10-16 weeks), an adjusted indirect treatment comparison (ITC) using placebo as a common anchor evaluated symptom improvement (UPDRS total scores) and adverse event (AE) incidence. For economic evaluation, a 2-year Markov model was constructed from a Chinese healthcare-system perspective. The incremental cost-effectiveness ratio (ICER) was calculated alongside robust sensitivity analyses. RESULTS: Ten RCTs (rasagiline: 6; selegiline: 4) were included. The ITC revealed no statistically significant differences between rasagiline and selegiline in short-term symptomatic relief (Mean Difference = -0.82, 95% CI [-2.08, 0.44], p = 0.203) or AE risk (Odds Ratio = 0.83, 95% CI [0.50, 1.38], p = 0.475). The overall evidence certainty was rated as moderate. Economically, the base-case simulation indicated rasagiline yielded a marginal benefit of 0.0088 QALYs over selegiline but incurred an additional 17,111.10 Yuan. This resulted in an ICER of 1,951,505.55 Yuan/QALY, substantially exceeding the conventional willingness-to-pay threshold. CONCLUSION: Supported by moderate-certainty evidence, rasagiline and selegiline provide comparable short-term efficacy and safety for early-stage PD monotherapy. However, at its current pricing, rasagiline is not cost-effective. Significant price reductions or definitive proof of long-term superiority are required to justify its economic value.

Humans↗

PubMed2026

HPV Testing Versus Cytology for Cervical Cancer Screening Among Women 50 Years and Older: Evidence From the HPV FOCAL Randomized Controlled Trial.

Evidence on the comparative effectiveness of HPV testing versus cytology specifically in women aged ≥ 50 years who are approaching screening cessation remains limited. This analysis included 6471 women aged ≥ 50 at baseline screening in the HPV FOCAL randomized clinical trial. Women were randomly allocated to receive cytology (Control Group, n = 3248, 50.19%) or HPV testing (Intervention Group, n = 3223, 49.81%) at baseline, with co-testing at 48-month exit. We calculated incidence rates and risk ratios for CIN2+ detection over follow-up and compared missed lesions at exit by screening method. At the 48-month exit, CIN2+ detection was lower among HPV baseline-negative women than among those in the cytology group (1.61/1000 [95% CI, 0.52-3.76] vs. 3.15/1000 [95% CI, 1.51-5.78]; risk ratio, 0.51 [95% CI, 0.11-0.91]), reflecting higher baseline detection with HPV testing and fewer prevalent lesions at exit. Even with cytology re-screening at 2 years, 50% of CIN2+ cases were missed compared to 30% with HPV testing. After adjusting for age, education, smoking status, and lifetime sexual partners, the hazard ratio for CIN2+ comparing HPV to cytology was 0.44 (95% CI, 0.22-0.88). Among women aged ≥ 50 years, HPV primary screening was more effective than cytology at detecting CIN2+ lesions and was associated with a continued lower subsequent risk following a negative HPV test, supporting its use in cervical cancer screening programs in this age cohort.

Aged↗

PubMed2026

Nasopharyngeal Carriage Rate, Risk Factors, and Co-Resistance Patterns of Methicillin-Resistant Staphylococcus aureus in Ethiopia: Systematic Review and Meta-Analysis.

Methicillin-resistant Staphylococcus aureus (MRSA) nasopharyngeal carriage is a major global health concern linked to severe infections and transmission. However, comprehensive evidence on the burden of MRSA carriage, antimicrobial resistance, and associated risk factors in Ethiopia remains limited. This study aimed to estimate pooled prevalence, resistance pattern, and determinants of nasopharyngeal MRSA carriage. PubMed, ScienceDirect, Scopus, Web of Science, Google Scholar, and gray literature were searched for cross-sectional studies published between January 2015 and December 2025. Two groups of reviewers screened studies based on predefined criteria. The risk of bias was assessed using the Joanna Briggs Institute tool. Pooled prevalence and resistance proportions were estimated using a random-effects model, and pooled odds ratios (ORs) were calculated using the Mantel-Haenszel method. Heterogeneity and publication bias were assessed, and a sensitivity analysis was conducted. A total of 1040 records were identified, and 20 studies (6869 participants) were included. The pooled carriage prevalence was 7.3% (95% CI, 5.0-10.8), with substantial heterogeneity (I2 = 95.5%). Resistance was highest to tetracycline (55.75%) and lowest to clindamycin (12.66%). Increased odds of carriage were associated with prior hospitalization (OR, 3.49) and antibiotic use (OR, 2.35). Inconsistent variable coding across included studies limited the inclusion of other potential risk factors. Evidence of publication bias was detected, suggesting that the pooled prevalence should be interpreted with appropriate caution. The findings indicate a considerable burden of MRSA and highlight the need for strengthened antimicrobial stewardship, improved surveillance, and targeted prevention efforts in higher-risk populations. This review was registered in PROSPERO (CRD420251047192).

Ethiopia↗

PubMed2026

Physical reconfiguration of limb electrodes for Precordial Bipolar Lead acquisition: Morphological validation against digital subtraction.

BACKGROUND: The V2 - V1 Precordial Bipolar Lead (PBL) selectively evaluates the right-to-left retrosternal axis and has shown diagnostic value beyond the standard 12‑lead electrocardiogram. However, its use has been limited by the need for raw electrocardiographic data and post-processing software. This study evaluated whether a simple physical reconfiguration of limb electrodes could reproduce the digitally derived V2 - V1 morphology with sufficient accuracy for clinical application. METHODS: Thirty-seven subjects underwent two sequential 10-s 12‑lead recordings using a Cardiovit FT-1 electrocardiograph sampled at 1000 Hz. In the standard recording, the digital PBL was calculated as V2 - V1. In the second recording, the right-arm and left-arm electrodes were repositioned to the V1 and V2 sites so that Lead I directly recorded the retrosternal dipole. Signals were filtered, synchronized, and analyzed using median beats. Morphological agreement was assessed with Pearson correlation on Z-normalized signals, while absolute agreement was evaluated using Lin's concordance correlation coefficient (CCC), intraclass correlation coefficient (ICC (Lewis, 1931; Nehb, 1938 [1,2])), root mean square error (RMSE), and Bland-Altman analysis. RESULTS: Mean Pearson correlation between digital and physical PBL was 0.955 (SD 0.043), with segment-specific correlations of 0.953 (SD 0.054) for QRS and 0.967 (SD 0.052) for ST-T. Lin's CCC and ICC(2,1) were both 0.871 (SD 0.110), and RMSE was 0.091 (SD 0.049) mV. Bland-Altman analysis showed minimal bias (-0.008 mV). CONCLUSIONS: Physical acquisition of the V2 - V1 PBL achieved high agreement with the digitally derived signal, supporting a simplified analog method for broader clinical implementation.

Humans↗