Nevin Manimala

Addiction. 2026 Jul 28. doi: 10.1111/add.70558. Online ahead of print.

ABSTRACT

BACKGROUND AND AIMS: Amid ongoing debate on whether low-to-moderate alcohol consumption reduces cardiovascular risk, studies examining the association between alcohol consumption and cognitive function have reported inconsistent results. To quantitatively assess this association, we conducted a dose-response meta-analysis of cohort studies, including stratified analyses by potential modifiers and study-level characteristics.

METHODS: Eligible studies were identified by searching PubMed, Embase and Web of Science for articles published through 13 June 2025. Studies investigating major cognitive impairment were excluded. Pooled standardized mean differences (SMDs) were calculated using a random-effects model.

RESULTS: We identified 20 studies including 78 657 participants. A weak inverted J-shaped association between alcohol consumption and cognitive function was observed, but the test for nonlinearity did not reach statistical significance (P for nonlinearity = 0.06). Compared with no alcohol consumption, heavy alcohol consumption (≥67 g/day) was inversely associated with cognitive function [SMD at 67 g/day = -0.18, 95% confidence interval (CI) = -0.36 to -0.00; 20 studies, 78 657 participants], while the evidence for a protective effect of low-to-moderate alcohol intake remained uncertain. In studies that accounted for baseline cognition, alcohol consumption of ≥28 g/day was associated with lower cognitive function (SMD at 28 g/day = -0.08, 95% CI = -0.15 to -0.01; 9 studies, 23 385 participants), whereas the association remained uncertain in studies that did not account for baseline cognition (SMD at 28 g/day = 0.13, 95% CI = -0.05 to 0.32; 11 studies, 55 272 participants) (P for interaction < 0.01). By region, alcohol consumption of ≥33 g/day was associated with lower cognitive function in studies conducted in the United States (SMD at 33 g/day = -0.11, 95% CI = -0.22 to -0.01; 7 studies, 25 538 participants), whereas the association remained uncertain in studies conducted in Europe (SMD at 33 g/day = 0.07, 95% CI = -0.08 to 0.22; 10 studies, 44 235 participants) (P for interaction = 0.02).

CONCLUSIONS: A review of current evidence shows that heavy alcohol consumption (≥67 g/day) is inversely associated with cognitive function, while the evidence for a protective effect of low-to-moderate alcohol intake remains uncertain. The inverse association is stronger in studies that accounted for baseline cognition, with the alcohol intake threshold (~28 g/day) for lower cognitive function close to the drinking guideline limits, although these findings should be interpreted cautiously because of the limited number of studies.

PMID:42517285 | DOI:10.1111/add.70558

J Sleep Res. 2026 Jul 28:e70411. doi: 10.1111/jsr.70411. Online ahead of print.

ABSTRACT

Sleep-related and chronotype traits have been shown to impact health in observational studies. To identify whether these associations are potentially causal, we conducted phenome-wide Mendelian randomisation analyses of short sleep, insomnia symptoms, total sleep duration, long sleep, snoring, daytime sleepiness and morning chronotype with a broad range of health-related phenotypes. We assessed the association between the genetic predisposition to these traits and the occurrence of 702 health-related phenotypes, using summary statistics of the largest genome-wide association studies in European individuals. Results that were significant (multiple comparisons: False Discovery Rate) and valid (robust genetic instruments, unaffected by horizontal pleiotropy) were validated using data from the second largest European genome-wide association study. Genetically determined short sleep was associated with increased risks of attention-deficit/hyperactivity disorder and neuroticism, musculoskeletal conditions, asthma and gastroesophageal reflux and lower educational attainment. Genetically determined insomnia symptoms showed associations with increased risk of coronary artery disease, major depression and osteoarticular disease. Genetically determined long sleep was linked to higher risk of iron deficiency anaemia and lower bone mineral density. Genetic predisposition to snoring was associated with more falls, greater body mass and higher low-grade inflammation. Genetically determined morning chronotype was related to higher vitamin D levels and lower risk of irritable bowel syndrome. No associations were found for daytime sleepiness. Overall, these findings indicate that genetically determined short sleep duration and insomnia symptoms are associated with mental and neurological problems, cardiovascular disease and musculoskeletal disorders, suggesting a potentially preventive, causal role of healthy sleeping patterns on chronic disease.

PMID:42517234 | DOI:10.1111/jsr.70411

Circ Arrhythm Electrophysiol. 2026 Jul 28:e014755. doi: 10.1161/CIRCEP.125.014755. Online ahead of print.

ABSTRACT

BACKGROUND: Large left atrial volume (LAV) is a strong predictor of advanced left atrial substrate and is associated with less successful outcomes following pulmonary vein isolation (PVI) alone. Prespecified variables of the aMAZE trial were evaluated to access for the impact of LAV and left atrial appendage ligation on atrial fibrillation (AF) outcomes.

METHODS: The aMAZE trial (REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02513797) was a multicenter, randomized-controlled study evaluating the effects of LAV on freedom from atrial arrhythmias (AA) following PVI-only compared with LARIAT and PVI (LARIAT+PVI). In total, 610 drug-refractory patients with nonparoxysmal AF were randomized 2:1 to LARIAT versus PVI alone. Freedom from AA was assessed 12 months postprocedure. LAV was independently assessed by a core laboratory from cardiac computed tomography performed before ablation.

RESULTS: There were 404 patients in the LARIAT+PVI group and 206 in the PVI-only group. Logistic regression performed within each subgroup for primary effectiveness with LAV demonstrated that the recurrence of AA after PVI was directly related to increasing LAV. Freedom from recurrence of AA in the LARIAT+PVI arm was independent and preserved irrespective of LAV. Similar results were seen with LAV index. A tercile analysis of early persistent AF (perAF) patients (AF >7 days and <6 months) and LARIAT+PVI in the highest (>148 cm³) LAV tercile showed statistically significant freedom from AA compared with PVI-only (69% versus 49%; P=0.02). Significant differences (P<0.04) between groups in the early perAF cohort began at an LAV of 130 cm³ and an LAV index of 65 cm³/m².

CONCLUSIONS: The correlation of LAV with PVI effectiveness in this study demonstrates that AA recurrence after PVI alone is directly related to increasing LAV. Freedom from AA after left atrial appendage ligation in addition to PVI is independent of increasing LAV, and left atrial appendage ligation may therefore provide an adjunctive benefit in patients with nonparoxysmal AF and enlarged LAV.

PMID:42517227 | DOI:10.1161/CIRCEP.125.014755

Circ Arrhythm Electrophysiol. 2026 Jul 28:e014785. doi: 10.1161/CIRCEP.125.014785. Online ahead of print.

ABSTRACT

BACKGROUND: Recent meta-analyses of randomized controlled trials have raised concerns that treatment with omega-3 fatty acids may increase the risk of atrial fibrillation (AF). However, these meta-analyses included at most 8 trials. The aim of this current meta-analysis was to expand the search by including other eligible omega-3 randomized controlled trials with AF incidence data, incorporating both published and unpublished data.

METHODS: Eligible studies were randomized controlled trials investigating daily doses of ≥500 mg/d of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA). Additional inclusion criteria included ≥12 months of treatment with EPA/DHA, participants ≥50 years of age, and, where possible, the absence of known AF/atrial flutter at baseline. The primary outcome was the occurrence of new-onset AF. Our primary hypothesis was that risk for AF would simultaneously depend on both omega-3 dose (above or below 1500 mg/d) and background cardiovascular disease risk status, and that their combined impact on AF risk would be synergistic.

RESULTS: A total of 35 randomized controlled trials (37 data sets; n=114 592) were included in this meta-analysis. Only studies including patients at high-risk for cardiovascular disease who were treated with high-doses of EPA/DHA (>1500 mg/d) showed a statistically significant increase in AF risk with a pooled odds ratio (OR) of 1.43 (95% CI, 1.14-1.79) and an absolute risk difference of 0.8% (0.40%-1.1%). None of the other 3 groups showed statistically significant levels of AF risk (odds ratios, 1.07 [high risk-low dose], 1.06 [low risk-low dose], and 1.03 [low risk-high dose]).

CONCLUSIONS: This meta-analysis suggests that high-dose EPA/DHA treatment is associated with an increased risk of AF in patients at high cardiovascular disease risk, whereas low-dose EPA/DHA does not appear to increase AF risk, even in high-risk populations. Further prospective studies are needed to evaluate any potential increased risk of higher doses balanced against potential benefits.

PMID:42517224 | DOI:10.1161/CIRCEP.125.014785

AIDS. 2026 Jul 28. doi: 10.1097/QAD.0000000000004588. Online ahead of print.

ABSTRACT

OBJECTIVE: To compare maternal safety and pregnancy outcomes among women who did and did not use daily oral emtricitabine-tenofovir disoproxil fumarate (FTC/TDF) for preexposure prophylaxis (PrEP) during pregnancy and postpartum.

DESIGN: Parallel cohort design, with follow-up from pregnancy to 6 months postpartum.

SETTING: Seven research clinics in Malawi, South Africa, Uganda, and Zimbabwe.

PARTICIPANTS: Three hundred fifty pregnant women aged 16-24 years at 32 weeks or less gestation, meeting local criteria for PrEP. At entry, PrEP initiators and decliners were enrolled 2 : 1. Participants could start or stop PrEP at any time.

MAIN OUTCOME MEASURES: Maternal adverse events were defined as grade ≥3 signs, symptoms, and diagnoses, and grade ≥2 chemistry abnormalities according to Division of AIDS toxicity tables. Adverse pregnancy outcomes included fetal loss, preterm birth, and small-for-gestational-age.

RESULTS: From March to December 2022, 350 eligible participants enrolled: 229 initiating and 121 declining PrEP at entry. Median duration of PrEP use was 34 weeks (interquartile range [IQR]: 16-40). Sixty maternal adverse events were reported over 230.3 person-years (incidence rate: 25.6, 95% confidence interval [95% CI]: 20.0-32.8). Although those on PrEP had higher rates of adverse events, this was not statistically significant (adjusted incidence rate ratio: 1.84, 95% CI: 0.53-6.30). Most frequent grade ≥3 adverse events were complications of pregnancy or delivery. Five (8%) were considered related to PrEP use. Among those with delivery information, 79 (24%) participants reported adverse pregnancy outcomes, with no differences between PrEP groups. No participants acquired HIV infections during follow-up.

CONCLUSION: Daily oral FTC-TDF remains a well tolerated and essential component of HIV prevention in pregnancy.

PMID:42517223 | DOI:10.1097/QAD.0000000000004588

Circulation. 2026 Jul 28. doi: 10.1161/CIRCULATIONAHA.126.079391. Online ahead of print.

ABSTRACT

BACKGROUND: Screening for atrial fibrillation (AF) on the basis of AF risk may be more effective. We aimed to develop, externally validate, and prospectively test a machine learning prediction model using electronic health records (EHRs) to guide AF screening.

METHODS: We developed and validated a random forest prediction model for new AF within 6 months, using age, sex, and 10 comorbidities (Future Innovations in Novel Detection of Atrial Fibrillation [FIND-AF] 2.0) in EHRs in the United Kingdom (n=2 081 139), Japan (n=7 795 244), Israel (n=2 166 795), Canada (n=627 919), and China (n=149 145). We conducted a prospective study where participants ≥30 years old without AF and with a CHA₂DS₂-VASc score ≥2 in men and ≥3 in women, stratified by FIND-AF 2.0 into high and low risk, undertook 4 ECG recordings per day for 3 weeks using a handheld ECG recorder, with a primary outcome of newly diagnosed AF. We estimated stroke risk associated with nonanticoagulated AF in patients with high FIND-AF 2.0 risk in the FinACAF (Finnish Anticoagulation in Atrial Fibrillation) registry of patients with AF (n=229 565).

RESULTS: FIND-AF 2.0 was applicable to all EHRs and showed good to excellent prediction performance (United Kingdom: area under the receiver operating characteristic curve [AUROC], 0.819 [95% CI, 0.809-0.829]; Israel: AUROC, 0.835 [95% CI, 0.828-0.842]; Japan: AUROC, 0.751 [95% CI, 0.745-0.757]; Canada: AUROC, 0.747 [95% CI, 0.741-0.753]; China: AUROC, 0.753 [95% CI, 0.725-0.771]), with AUROC>0.7 in men and women in all cohorts, and improved performance compared with CHA₂DS₂-VASc and C₂HEST. Of 1923 participants from 15 sites in the prospective study (mean age, 70.2 [SD 9.4] years), with a mean of 74.8 (SD, 19.4) ECG recordings, AF was diagnosed in 5 of 902 (0.6%) with low FIND-AF 2.0 risk and 46 of 1021 (4.5%) with high FIND-AF 2.0 risk (odds ratio, 8.46 [95% CI, 3.35-21.40], P<0.001). Median AF burden among high FIND-AF 2.0 risk-detected cases was 33.4% (interquartile range, 5.1%-91.6%), and 96.1% initiated oral anticoagulants. In the FinACAF registry, the rate of ischemic stroke for patients with high FIND-AF 2.0 risk, AF, and no anticoagulants was 6.0 events per 100 patient-years.

CONCLUSIONS: The EHR-based machine learning model, FIND-AF 2.0, identifies a high-risk subpopulation for AF diagnosis among patients at elevated risk of stroke and could enable scalable, EHR-driven, risk-guided AF screening.

PMID:42517218 | DOI:10.1161/CIRCULATIONAHA.126.079391

J Inj Violence Res. 2026 Jul 28;18(1). Online ahead of print.

ABSTRACT

BACKGROUND: This exploratory study aimed to describe characteristics associated with pediatric drowning and to examine the socioeconomic context, rather than to establish socioeconomic effects, by conducting a retrospective analysis at the sole tertiary facility with a pediatric intensive care unit in Okinawa Prefecture, Japan.

METHODS: Information from electronic medical records was collated for 75 drowning-related hospitalizations involving individuals aged less than 20 years at the Okinawa Prefectural Nanbu Medical Center and Children’s Medical Center from April 1, 2006, to May 31, 2021. Data on patient gender, drowning or hospitalization duration, drowning timing and settings, pre-existing medical conditions, and zip code were extracted from electronic medical records.

RESULTS: Among the 75 hospitalized patients, 64 were discharged without any morbidity, whereas 11 either perished or sustained severe morbidity. The submersion time (2.9 min, standard deviation [SD]: 4.6, in the no morbidity group vs. 44.1 min, SD: 87.0 in the severe group) and length of stay (4.1 days, SD: 3.7 vs. 46.4 days, SD: 64.9, respectively) were markedly extended in the severe group. Additionally, in patients under four years of age, drownings frequently occurred in bathrooms (p = 0.008), with incidents predominantly taking place between 17:00 and 23:00 (p = 0.021). Among hospitalized pediatric drowning patients, supervision was associated with lower odds of severe morbidity (odds ratio 0.17 (95% confidence interval 0.03-0.81)). This association persisted after adjustment for potential confounders such as the Area Deprivation Index and time of day. The interaction between supervision and the Area Deprivation Index was of borderline statistical significance (p = 0.050) and is considered hypothesis-generating.

CONCLUSIONS: Within this cohort of hospitalized pediatric drowning patients, the presence of supervision was associated with less severe outcomes. These exploratory findings highlight the potential value of preventive strategies tailored to regional attributes, but do not establish socioeconomic or causal effects.

PMID:42517211

J Esthet Restor Dent. 2026 Jul 28. doi: 10.1111/jerd.70246. Online ahead of print.

ABSTRACT

OBJECTIVE: The aim of this in vitro study was to evaluate the effects of different surface treatments on the shear bond strength of repaired milled and 3D-printed resin restorations.

MATERIALS AND METHODS: A total of 84 resin specimens (8 mm diameter, 5 mm height) fabricated using two different methods such as milling (Grandio Disc) and 3D-printing (Saremco Crowntec) were subjected to three surface treatments: silane (control), air abrasion + silane, and laser irradiation + silane. All specimens were subjected to thermocycling (5000 cycles each) before and after the repair protocol which was conducted with a flowable composite, and the shear bond strengths were measured. SEM images were obtained to evaluate the type of failures. Data were analyzed using IBM SPSS V23, and two-way ANOVA analysis was used for comparisons between surface treatments and samples (p < 0.05).

RESULTS: Laser irradiation yielded the highest bond strength (7.61 ± 1.94 MPa), showing a statistically significant difference (p = 0.001). The 3D-printed resin group exhibited significantly higher bond strengths after all surface treatments compared to the milled group (p = 0.028). Representative SEM observations revealed increased surface irregularity and fracture-surface complexity in laser-treated specimens.

CONCLUSION: Laser irradiation is an effective method for improving the bond strength in the repair of both milled and 3D-printed resin restorations. Particularly, 3D-printed resins showed superior repair bond strengths. Silane alone is insufficient; additional micromechanical surface treatments are required for reliable adhesion.

CLINICAL SIGNIFICANCE: Mechanical complications can occur with milled and 3D-printed resin restorations, which are increasingly used in indirect restorations, and intraoral repair protocols are becoming a crucial consideration. Determining the most appropriate repair protocol and surface treatment is crucial for the successful repair of these new-generation resin restorations.

PMID:42517210 | DOI:10.1111/jerd.70246

Knee Surg Sports Traumatol Arthrosc. 2026 Jul 28. doi: 10.1002/ksa.70548. Online ahead of print.

ABSTRACT

PURPOSE: This study aimed to compare implant survivorship and patient-relevant outcomes associated with the constraint level used at first-time aseptic revision total knee arthroplasty (rTKA).

METHODS: This retrospective cohort study used data from the National Joint Registry for England, Wales, Northern Ireland, the Isle of Man, Guernsey and Jersey, linked to Hospital Episode Statistics and national patient-reported outcome measures (PROMs). Patients undergoing first-time aseptic rTKA between 1 January 2009 and 30 September 2023 were included. Constraint was categorized as unconstrained, posterior-stabilized (PS), condylar-constrained (CCK) or hinge. The primary outcome was 10-year cumulative incidence of re-revision. Prespecified subgroups included patients at high risk of re-revision and those revised for aseptic loosening or instability. Secondary outcomes included 6-month PROMs; 90-day mortality and medical complications; and length of stay. Competing risk regression was used to estimate re-revision risk, treating death as a competing event.

RESULTS: After exclusions, 12,950 cases were analysed (median follow-up 7.4 years [95% confidence interval, CI 7.3-7.5]. CCK prostheses were associated with the lowest unadjusted 10-year cumulative incidence of re-revision overall (9.2% [95% CI 8.4-10.1]) and in all subgroups. In the primary adjusted analysis, unconstrained (subdistribution hazard ratio [sHR] 1.46 [1.23-1.74], p < 0.001), PS (sHR 1.23 [1.04-1.44], p = 0.013) and hinged prostheses (sHR 1.66 [1.38-2.01], p < 0.001) were associated with higher re-revision risk than CCK constructs. There was weak evidence that the association between PS implants and re-revision was greater among low-volume than high-volume surgeons (interaction sHR 1.30 [1.00-1.70], p = 0.053). After further adjustment for implant-related factors, re-revision risk was similar for unconstrained (sHR 0.97 [0.78-1.21], p = 0.792) and PS implants (sHR 1.00 [0.83-1.19], p = 0.972) versus CCK, whilst increased risk associated with hinges persisted (sHR 1.67 [1.36-2.05], p < 0.001).

CONCLUSION: CCK constructs were consistently associated with favourable implant survivorship across a range of clinical scenarios. These findings provide reassurance that clinically indicated use of CCK constraint is not associated with compromised implant survival.

LEVEL OF EVIDENCE: Level III.

PMID:42517199 | DOI:10.1002/ksa.70548

Eur J Phys Rehabil Med. 2026 Aug;62(4):432-440. doi: 10.23736/S1973-9087.26.09267-1.

ABSTRACT

BACKGROUND: A recent definition of clinical obesity emphasises the presence of age-adjusted limitations in activities of daily living (ADLs). Early identification of ADL limitations and factors negatively influencing the development of disability is needed to enhance the effectiveness of rehabilitation programs.

AIM: To investigate the relationship between functional limitations in ADLs, body composition parameters, and comorbid conditions in a large cohort of adults with different degrees of obesity.

DESIGN: Retrospective observational cross-sectional study.

SETTING: Hospital-based rehabilitation setting.

POPULATION: Adult inpatients with different degree of obesity, from mild to severe obesity.

METHODS: Patients were enrolled at hospital admission. Collected data included demographic/anthropometric measures, functional status (by modified Katz ADL Index), comorbidities, body composition, and muscle strength.

RESULTS: Out of 3229 enrolled patients, 193 (6.0%) resulted fully dependent, while 2115 (65.5%) were fully independent. The most frequently observed disabilities were in urine/fecal continence (24.7%) and toileting (15.5%). ADL impairments were significantly associated with older age, higher BMI, higher waist circumference, excess of fat mass, reduced fat-free mass and lower values of HGS. The logistic model identified 5 variables statistically associated with the probability to be a fully dependent patient: age, weight and waist circumference increased this probability, while Muscle Mass and Hand Grip strength lowered it. Osteoarthritis was present in 52% of patient with severe limitations.

CONCLUSIONS: The severity in ADLs is influenced by both body composition and comorbid conditions.

CLINICAL REHABILITATION IMPACT: Rehabilitation should focus on functional limitations and presence of comorbidities and risk factors in patients with obesity, and particularly on preventing muscle mass loss during weight management.

PMID:42517169 | DOI:10.23736/S1973-9087.26.09267-1