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Effectiveness of tobacco cessation interventions delivered in clinical settings in South Asia: a systematic review and meta-analysis.

BACKGROUND: Despite the burden of tobacco use, access to cessation support in South Asia remains scarce. OBJECTIVE: This review evaluates the effectiveness of tobacco cessation interventions delivered in clinical settings in South Asia. METHODS: Five relevant databases were searched from inception to February 2025. Eligibility criteria included randomized and non-randomized studies evaluating behavioral, pharmacotherapy, and multicomponent interventions delivered in clinical settings in South Asia. Data on study setting and design, participant information, intervention, comparator, and outcomes were extracted. Meta-analyses using random-effect models were conducted where possible. Certainty of evidence was assessed using GRADE. RESULTS: Thirty-seven studies were included (22 randomized and 15 non-randomized). Interventions involved pharmacotherapy (n = 6; 16.2%), nicotine replacement therapy (n = 7; 18.9%), behavioral counseling (n = 12; 32.4%), or combined/multicomponent interventions (n = 12; 32.4%). Most studies were conducted in India (n = 26; 70.3%), followed by Pakistan (n = 6; 16.2%), Nepal (n = 3; 8.1%), and two studies (5.4%) were multi-country in India, Pakistan, and Bangladesh. Pooled analyses demonstrated higher quit rates among intervention versus control for continuous abstinence at 0-3 months (RR: 1.21, 95%CI: 1.06 to 1.37) and >3 months (RR: 1.68, 95%CI: 1.1.4 to 2.47), and for point abstinence at >3 months post-intervention (RR: 2.03, 95%CI:1.35 to 3.08). Heterogeneity was high for all analyses (I2 range: 94% to 97%). Combined behavioral and pharmacotherapy interventions were most effective (RR: 1.70, 95%CI: 0.98 to 2.92), although not statistically significant (p = 0.06). CONCLUSION: Tobacco cessation interventions delivered in clinical settings in South Asia are effective, particularly when combining behavioral support with pharmacotherapy. However, evidence is limited by methodological weaknesses.

Humans

Optimizing smoking cessation pharmacotherapy and counseling for adult primary care patients: a factorial randomized controlled trial.

BACKGROUND: Even with the most effective smoking cessation pharmacotherapies (i.e., varenicline or combination nicotine replacement [C-NRT]), the majority of people ultimately return to smoking. This research explored how to optimize the use of varenicline and C-NRT to promote smoking cessation. METHODS: Primary care patients participated in a 2x2x2x2 factorial experiment that evaluated 4 factors: 1) Medication Type (Varenicline vs. C-NRT [patch + mini-lozenge]), 2) Preparation (pre-quit) Medication (4 Weeks vs. Standard); 3) Medication Duration (Extended [24 weeks] vs. Standard [12 weeks]); and 4) Counseling Type (Cessation Counseling [4 sessions] vs. Referral Support [2 sessions focused on use of referral resources]). This study was discontinued prior to reaching the proposed sample size (N = 608) due to pandemic-related budgetary constraints. RESULTS: Participants (N = 496) were 55% women and 45.6% Black individuals. There were no statistically significant main effects of the 4 factors on abstinence at 12, 26 or 52 weeks. There was a 3-way interaction between Medication Type, Preparation Medication, and Counseling Type (p = 0.04) predicting the primary outcome of biochemically confirmed abstinence at 52 weeks; cessation counseling vs. referral support improved varenicline quit rates when 4 weeks versus 1 week of pre-quit medication was offered. For C-NRT, counseling type did not significantly improve quit rates regardless of the use of preparation medication. CONCLUSIONS: There was no robust evidence that enhanced pre-quit or extended duration of varenicline or C-NRT increased abstinence rates. More intensive counseling may support cessation for different pharmacotherapy regimens. Given the lack of consistent findings, this research should be viewed as exploratory to guide future research.

Humans

Affective reactivity to a remote computer-based Trier Social Stress Test during a planned quit attempt: associations with short-term cigarette smoking lapse risk.

BACKGROUND: The Trier Social Stress Test (TSST) elicits affective responses and has been linked to smoking behavior. However, its remote use during a planned quit attempt-when stress reactivity may influence early lapse-remains understudied. OBJECTIVE: To quantify affective reactivity to a remotely administered TSST on a planned quit date following overnight abstinence and evaluate associations with cigarette use and lapse within 48 h. METHODS: This secondary analysis used data from a randomized controlled trial of adult smokers completing a remotely administered TSST following overnight nicotine abstinence. Urge, anxiety, and stress were assessed using visual analog scales and summarized using area under the curve (AUC) metrics. Smoking outcomes included cigarette count and lapse within 48 h. Associations were estimated using generalized estimating equations. RESULTS: In adjusted models, anxiety reactivity-but not urge or stress-was associated with cigarette count and lapse. Greater anxiety exposure (AUCtot) and change above baseline (AUCab) were associated with higher cigarette count (IRR=1.0004, 95%CI:1.0002-1.001, p=.002; IRR=1.01, 95%CI: 1.002-1.01, p=.002) and increased odds of lapse (OR=1.001, 95%CI: 1.0001-1.002, p=.03; OR=1.02, 95%CI: 1.001-1.03, p=.03). Effect sizes were small. CONCLUSIONS: Anxiety reactivity under nicotine deprivation was associated with increased cigarette use and lapse 48 h post quit attempt, suggesting individual differences in stress-evoked anxiety may serve as a behavioral marker for early lapse. Remote TSST administration appears feasible for eliciting affective responses on a quit date.

Humans

Effect of flavored on!® nicotine pouch products on smoking behaviors: A sequential, multiple assignment, randomized controlled trial.

PURPOSE: To evaluate whether flavored versus unflavored nicotine pouch (NP) access affects cigarette reduction and smoke exposure among adults who smoke daily, and whether delayed flavor introduction affects these outcomes. METHODS: Adults who smoked ≥ 5 cigarettes/day (CPD) with interest in replacing cigarettes with NPs were enrolled in a remote, six-week, sequential multiple assignment randomized trial (n = 402 randomized; n = 400 analyzed). Participants were randomized to immediate access to seven NP flavors (Flavor), unflavored-only access for six weeks (Original), or unflavored-only for three weeks followed by flavor access (Delayed Flavor). Primary outcomes were ≥ 50% reduction in weekly mean expired-air carbon monoxide (CO) from baseline and mean CO at Week 6. Secondary outcomes included ≥ 50% CPD reduction, mean CPD, CO-verified 7-day abstinence, and incident smoke-free days. RESULTS: At Week 6, Flavor and Original did not differ in ≥ 50% CO reduction (14.3% vs 14.2%; IRR=1.0, 95% CI=0.6-1.8) or mean CO (18.3 vs 16.5 ppm; β=1.9, 95% CI=-1.3-5.0). CPD decreased across groups by Week 6, with no differences between Flavor and Original in ≥ 50% CPD reduction (50.3% vs 51.6%; IRR=1.0, 95% CI=0.8-1.2) or CO-verified abstinence (9.3% vs 8.9%; IRR=1.0, 95% CI=0.5-2.2). Flavor increased smoke-free days early, with attenuation over time. Among Week 3 non-responders, delayed flavor access increased ≥ 50% CPD reduction at Week 6 (33.3% vs 18.6%; IRR=1.8, 95% CI=1.0-3.2). CONCLUSIONS: NP access supported cigarette reduction regardless of flavor availability, but flavors may accelerate smoke-free days and improve response among individuals who do not reduce cigarette consumption with unflavored products alone.

Humans

Brain network alterations underlying cue reactivity and craving in abstinent methamphetamine users: a systematic review of functional MRI findings.

BACKGROUND: Methamphetamine use disorder (MUD) is marked by intense craving and high relapse risk, often triggered by drug-related cues. Functional magnetic resonance imaging (fMRI) provides key insight into the neural basis of this cue reactivity, implicating large-scale brain networks for reward, motivation, and control. Yet, findings remain inconsistent across studies due to differences in task design, abstinence duration, and participant characteristics. OBJECTIVE: This systematic review synthesises evidence on how abstinence influences brain network alterations underlying cue reactivity and craving in methamphetamine users, integrating task-based and resting-state fMRI findings within leading neurobiological models of addiction. METHODS: A systematic search of PubMed, Scopus, Web of Science, and Ovid was conducted up to August 10, 2025, following PRISMA 2020 guidelines. Eligible fMRI studies examined cue reactivity or craving in abstinent methamphetamine users. Data were extracted on activation, connectivity, and brain-behaviour associations, and synthesised narratively. RESULTS: Task-based studies revealed heightened activation across reward, salience, and control networks during cue exposure, which diminished as parietal and executive control systems re-engaged with longer abstinence. Resting-state findings showed disrupted intrinsic connectivity among default mode, salience, and frontoparietal networks, reflecting persistent imbalances linked to craving and use severity. CONCLUSION: fMRI evidence shows that MUD is marked by network-level disruption linking reward, salience, and control systems. Task-based findings reveal strong cue reactivity in reward circuits, while resting-state data show persistent imbalance among default mode and control networks. With abstinence, partial restoration of network integrity emerges, highlighting both vulnerability and opportunities for targeted, recovery-based interventions.

Humans

Clustering patterns of behavioral and metabolic risk factors for noncommunicable diseases in Iran: findings from a national STEPS survey.

BACKGROUND: Noncommunicable diseases (NCDs) are the leading cause of mortality in Iran, driven by behavioral and metabolic risk factors that frequently co-occur. OBJECTIVE: To identify patterns of co-occurring behavioral and metabolic NCD risk factors among Iranian adults and characterize their demographic and socioeconomic correlates. METHODS: This cross-sectional study analyzed data from 16,618 adults aged ≥25 years who participated in Iran's 2021 nationally representative STEPS survey. Thirteen behavioral and metabolic variables, including physical activity, nutrition score, smoking frequency, alcohol intake, salt intake, body mass index, blood pressure, fasting plasma glucose, and lipid markers, were entered into a K-means clustering analysis. Clusters were characterized by their risk profiles and demographic/socioeconomic attributes. Multinomial logistic regression examined associations between cluster membership and sociodemographic factors. RESULTS: Five distinct behavioral-metabolic clusters emerged. The smokers-drinkers (SD) cluster (3.1%) comprised mostly older, less-educated men with high smoking and alcohol use. The healthy-low-risk (HLR) cluster (40.3%) showed favorable profiles and included younger, more educated individuals. The physically active (PA) cluster (6.6%) was characterized mainly by younger men with markedly high physical activity levels. The dyslipidemic (DLP) cluster (26.0%) exhibited high dyslipidemia and overweight prevalence, while the hypertensive-diabetic (HTD) cluster (24.0%) had the highest obesity, hypertension, and diabetes rates, common among older urban adults. CONCLUSION: Behavioral and metabolic NCD risk factors in Iran formed five distinct co-occurrence patterns. Nearly half of adults belonged to metabolically high-risk clusters, highlighting the need for targeted prevention strategies that combine lifestyle interventions with screening and management of obesity, hypertension, diabetes, and dyslipidemia.

Humans

Branded packaging raises likelihood of cigarette purchasing in an experimental retail setting by increasing craving.

INTRODUCTION: Exposure to branded cigarette packaging in retail settings has been shown to be associated with purchasing behavior, but the mechanisms underlying this effect are unclear. This study tested whether cigarette craving and perceived health harms mediate the effect of branded packaging on cigarette purchasing in a simulated retail environment. METHODS: Young adults aged 21-34 who currently smoke cigarettes (n = 290) completed an experimental shopping task in the RAND StoreLab, a life-sized replica of a convenience store. Participants were randomly assigned to one of two conditions: (1) branding present, in which branded cigarette packages were displayed; and (2) branding absent condition, in which branded elements were removed and packages were standardized in a brown-green color and uniform text. Cigarette purchases were recorded, and participants completed post-shopping measures of cigarette craving and perceived health harms. Causal effect decomposition analyses were used to assess whether these variables mediated the effect of study condition on the likelihood of purchasing cigarettes. RESULTS: Craving, but not perceived health harms, partially mediated the effect of branded packaging on cigarette purchasing. Exposure to branded packs increased the likelihood of purchasing by elevating craving (average mediated effect = 2.4%, 95% CI 0.2% - 5.0%, p = .03). CONCLUSIONS: Branded cigarette packaging appears to increase cigarette purchasing at least in part by increasing cigarette craving at point of sale. Interventions that address craving management in retail settings (e.g., just-in-time interventions, prn nicotine replacement therapy) may help mitigate the impact of branding on young adults' cigarette purchasing.

Humans

Driving Under the Influence of Cannabis Among U.S. Young Adults Who Use Cannabis: Evidence From the 2021-2024 National Survey on Drug Use and Health.

PURPOSE: To estimate the prevalence of driving under the influence of cannabis (DUIC) and identify associated factors among U.S. young adult drivers reporting past-year cannabis use. METHODS: This cross-sectional study analyzed pooled 2021-2024 National Survey on Drug Use and Health. The analytic data were restricted to drivers aged 18-25 years who reported past-year cannabis use (N = unweighted 17,141; weighted N = 10,814,381). The outcome was self-reported past-year DUIC. Independent variables included demographics, substance use, mental health, cannabis-related perceptions, and driving behaviors. These relationships were assessed by modified Poisson regression. RESULTS: The weighted prevalence of DUIC was 28.0%, representing approximately over three million young adults. DUIC prevalence increased with cannabis use frequency, from 2.51 times higher among those using cannabis 12-49 days (adjusted prevalence ratio [APR]: 2.51; 95% confidence interval [CI]: 2.29-2.75) to 3.63 times higher among those reporting use on 300-365 days (APR: 3.63; 95% CI: 3.60-3.76), compared with those using cannabis 1-11 days. Cannabis use disorder (APR: 2.34; 95% CI: 2.06-2.65), simultaneous alcohol and cannabis use (APR: 1.29; 95% CI: 1.28-1.30), and perceived easy cannabis availability (APR: 2.36; 95% CI: 2.33-2.39) were also associated with higher prevalence of DUIC. Nonenrollment in school and living in a state with a medical cannabis law were associated with lower DUIC prevalence. DISCUSSION: DUIC is highly prevalent among U.S. young adults who use cannabis, with a clear graded association across categories of cannabis use frequency. Public health interventions should address frequent use, cannabis use disorder, alcohol-cannabis co-use, and perceived cannabis availability.

Humans

Prevalence of unruptured intracranial aneurysms according to comorbidities, risk factors, country, and time period: a systematic review and meta-analysis.

BACKGROUND: The incidence of aneurysmal subarachnoid haemorrhage declined between 1980 and 2010, which coincided with a decline in smoking and prevalence of hypertension. We aimed to investigate whether the decrease in subarachnoid haemorrhage incidence is paralleled by declines in unruptured intracranial aneurysm (UIA) prevalence. METHODS: For this systematic review and meta-analysis, we searched Embase, PubMed, and Web of Science for articles published in any language from Jan 1, 2011 to Dec 31, 2025, and reassessed 68 articles published before March 1, 2011 from a 2011 systematic review and meta-analysis. Articles were eligible for inclusion if they used a cross-sectional or case-control design and provided the crude number of participants and those with UIA. We only included studies reporting numbers of UIA separately from ruptured aneurysms and with ten or more patients. Summary data were independently extracted by JD with AZ or CB and conflicts were resolved by GJER. The primary outcome was proportion of participants with UIA. Relative to a hypothetical reference population (mean age 50 years, 50% women, and no comorbidities), age and/or sex-adjusted prevalence ratios (PRs) for regions, comorbidities, and risk ratios (RRs) for female sex, smoking, and hypertension were estimated using generalised linear mixed models. A time trend analysis was done by binomial meta regression using the mid-year of data acquisition. We assessed the certainty of evidence using GRADE. The study was registered with PROSPERO, number CRD420261296728. FINDINGS: Our search screened 4708 studies. 67 reassessed and 95 newly identified articles, reporting on 316 131 participants and 11 822 people with UIAs, were included in our meta-analysis. In the reference population, the estimated prevalence of UIAs was 3·9% (95% CI 3·0-5·1). The prevalence of UIAs in individuals with atherosclerosis was 5·5% (4·7-6·4; 2229 of 40970 participants) and the adjusted PR was 1·3 (95% CI 0·8-2·0) compared with the reference population. For positive family history of aneurysmal subarachnoid haemorrhage (aSAH) or UIA, the UIA prevalence was 7·9% (5·6-11·1; 412 of 4252 participants) and the adjusted PR was 2·4 (0·5-11·2). For connective-tissue disorder, the UIA prevalence was 10·3% (6·5-16·0; 94 of 879 participants) and the adjusted PR was 3·9 (2·0-7·6). For autosomal dominant polycystic kidney disease (ADPKD), the UIA prevalence was 12·8% (9·2-17·6; 293 of 1990 participants) and the adjusted PR was 4·4 (1·5-12·6). RRs were for current smoking 1·4 (1·2-1·6; 798 of 27911 participants), for having hypertension 1·6 (1·5-1·7, 4043 of 83053 participants), and for female sex 1·9 (1·8-2·0; 3415 of 65020 women and 2122 of 76130 men). In studies on healthy individuals with MR angiography or CT angiography as imaging modality, the prevalence in 2016-2022 was 6·6% (6·3-6·8; 2904 of 41191 participants). The adjusted PR was 1·8 (1·1-2·8) for 2016-2022 versus 2002-2015. Prevalence of UIAs of 5 mm or larger was 0·7% (0·6-0·8) in 2002-2015 and 1·4% (1·0-1·9) in 2016-2022. The UIA prevalence did not differ between countries. τ2 showed significant heterogeneity between studies. The certainty of the evidence ranged from very low to moderate. INTERPRETATION: Prevalence of UIA is increasing, particularly over the past two decades. This increase is only in part explained by improved detection of small UIAs and an ageing population, and other factors-such as environmental-are likely involved. Alongside patients with ADPKD and a positive family history of aSAH, patients with connective-tissue disorders had a higher prevalence of UIA than the reference population. Our findings warrant further investigation into the potential benefit of personalised screening and management strategies in groups at high risk for having UIAs. FUNDING: None.

Humans

Lung function after randomization to metformin, lifestyle intervention or placebo in the Diabetes Prevention Program Outcomes Study (DPPOS).

INTRODUCTION: Metformin and physical activity have been suggested as beneficial for chronic lung disease; however, there are no prior randomized trials. METHODS: The Diabetes Prevention Program (DPP) was a 3-year trial that randomized 3234 individuals at risk for diabetes to metformin, lifestyle intervention or placebo. After the DPP, 88% of participants enrolled in the DPP Outcomes Study that offered lifestyle intervention to all and open-label continuation of metformin. Spirometry was performed at approximately 19 and 22 years post-randomization. Lung function measures were compared in an intention-to-treat (ITT) analysis by original randomization group. Models were unadjusted and adjusted for demographics, body size, smoking and sitting/standing at spirometry. Additional analyses tested prevalence of obstruction (FEV1/FVC <70%), restrictive pattern (FVC&#x202f;<&#x202f;LLN and FEV1/FVC &#x2265;70%), preserved ratio impaired spirometry (PRISm: FEV1 <80% predicted, FEV1/FVC &#x2265;70%) and symptoms (COPD Assessment Test [CAT] score &#x2265;10). RESULTS: The 1888 participants with spirometry were a mean (&#xb1;SD) age of 68.2&#x202f;&#xb1;&#x202f;9.3 years, 70% female and 6% currently smoked and 33% had previously smoked cigarettes. Mean follow-up time was 19.0&#x202f;&#xb1;&#x202f;0.8 years. The mean FEV1 was 2.14&#x202f;&#xb1;&#x202f;0.60&#x202f;L, FVC 2.74&#x202f;&#xb1;&#x202f;0.74&#x202f;L, FEV1/FVC 78.4&#x202f;&#xb1;&#x202f;6.4%, mean BMI was 32.4&#x202f;&#xb1;&#x202f;6.7&#x202f;kg/m2 and 58% had diabetes. In both unadjusted and adjusted ITT analyses, randomization group was not associated with FEV1, FVC or FEV1/FVC. Likewise, rates of obstruction, restrictive pattern, PRISm or symptoms did not differ by randomization group. CONCLUSIONS: In this long-term follow-up after a randomized trial, we found no significant associations between randomization to metformin or lifestyle intervention and lung function or respiratory symptoms.

Humans

Machine learning-based prediction of unplanned readmission and construction of an online calculator for elderly patients with mild ischemic stroke.

OBJECTIVE: To screen for independent risk factors for unplanned readmission in elderly patients with mild ischemic stroke, and to construct and validate an online risk prediction calculator based on an interpretable machine learning model, thereby providing a promising practical tool for accurate clinical assessment of 30&#x2011;day all&#x2011;cause unplanned readmission risk in this population. METHODS: A prospective cohort study was conducted, including 1050 patients aged&#xa0;&#x2265;&#xa0;60&#xa0;years with mild ischemic stroke admitted between August 2023 and September 2024. Participants were randomly divided into a training set (840 cases) and a test set (210 cases) at a ratio of 8:2. Risk factors were screened by univariate analysis and multivariable Logistic regression. Four machine learning models, namely LightGBM, XGBoost, Random Forest, and K&#x2011;Nearest Neighbors (KNN), were developed and their performance was evaluated using AUC, accuracy, sensitivity, and specificity as metrics. The SHAP framework was used for interpretability analysis, and an online calculator was subsequently developed based on the optimal model. RESULTS: Univariate analysis showed significant differences (P&#xa0;<&#xa0;0.05) in 13 factors including age, smoking, AIP, TyG index, HALP score, etc. Multivariable Logistic regression identified age (OR&#xa0;=&#xa0;9.752), smoking (OR&#xa0;=&#xa0;5.171), AIP (OR&#xa0;=&#xa0;6.691), TyG index (OR&#xa0;=&#xa0;4.393), HALP score (OR&#xa0;=&#xa0;2.831), and&#xa0;&#x2265;&#xa0;2 comorbidities (OR&#xa0;=&#xa0;3.664) as independent risk factors. All four machine learning models demonstrated good predictive performance. Based on a comprehensive evaluation of multiple metrics and computational efficiency, the LightGBM model exhibited the best predictive performance (AUC&#xa0;=&#xa0;0.884, accuracy&#xa0;=&#xa0;0.829, sensitivity&#xa0;=&#xa0;0.812, specificity&#xa0;=&#xa0;0.875). SHAP analysis showed that age, AIP, TyG index, smoking, and HALP score were key predictors. An online calculator developed based on this model enables individualized risk predictions. CONCLUSION: Key risk factors associated with 30&#x2011;day unplanned readmission in elderly patients with mild ischemic stroke were identified. The LightGBM model demonstrated high predictive accuracy, and together with the interpretability analysis and online calculator, offers a practical tool to support clinical risk assessment. However, this tool requires future external validation.

Humans

Adolescent health across Asia Pacific, 2000-23: a systematic analysis for the Global Burden of Disease Study 2023.

BACKGROUND: The Asia Pacific region is home to more than half of the world's 1&#xb7;93 billion adolescents (aged 10-24 years). Addressing adolescent health in this region is of global importance, but to date a systematic analysis of key contributors to disease in adolescents has not been done, which is a barrier to responsive action. This systematic analysis of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2023 aims to provide a comprehensive assessment of adolescent health across the Asia Pacific region, at both the subregional and national levels, encompassing burden of disease, mortality, and prevalence of adolescent risk factors. METHODS: As part of GBD 2023, we obtained estimates for cause-specific mortality, disability-adjusted life-years (DALYs), and risk factor prevalence by sex for adolescents aged 10-24 years and 5-year age groups (10-14 years, 15-19 years, and 20-24 years) across 44 countries and territories (hereafter referred to collectively as Asia Pacific), grouped by seven UN subregions, from 2000 to 2023. We extracted GBD 2023 population counts and estimates of number and rate (per 100&#x2008;000 population) for mortality and disease burden (DALYs). Risk prevalence estimates were obtained directly from the Institute for Health Metrics and Evaluation, and binge drinking estimates were sourced from WHO. Estimates are reported with 95% uncertainty intervals (UIs) where possible. UIs were estimated by running 250 draws of the posterior distribution, ordering the draws, and selecting the 2&#xb7;5th and 97&#xb7;5th percentiles for each metric. FINDINGS: In 2023, in adolescents across Asia Pacific, there were 637&#x2008;496 deaths and a total disease burden of 115&#xb7;8 million DALYs, representing 34&#xb7;1% of global adolescent deaths and 40&#xb7;6% of the global adolescent burden of disease. Non-communicable diseases (NCDs; particularly mental disorders) were the leading causes of disease burden and mortality (64&#xb7;8% of DALYs and 43&#xb7;9% of deaths). Unintentional and transport injuries were also leading causes of death (14&#xb7;7% of deaths due to transport injury and 13&#xb7;3% of deaths due to unintentional injury) and leading causes of disease burden particularly among males in south-eastern Asia. In Melanesia, Micronesia, and some parts of south-eastern Asia (Cambodia, Indonesia, Laos, the Philippines, and Timor-Leste), respiratory infections and tuberculosis remained important contributors. Southern Asia had the largest reduction (1&#xb7;5% per year) in all-cause DALYs over the study period, and Australia and New Zealand (0&#xb7;2% per year) had the smallest, with females in Australia and New Zealand showing a slight increase contrary to regional trends. Eastern Asia had the largest reduction (2&#xb7;8% per year) in all-cause mortality rate and Melanesia (0&#xb7;8% per year) the smallest. Risk factors generally had between-subregion and within-subregion variation; however, some regional trends stood out, with overweight and obesity increasing in all countries across the region, and binge drinking increasing in more countries than not. In 2023, prevalence of smoking in males exceeded that in females in every country, from 40% difference in Timor-Leste to less than 1% difference in Australia. Anaemia prevalence is decreasing in all countries, but female prevalence was higher and reducing at a slower rate than in males. Bullying prevalence was slightly higher in Polynesia, Micronesia, and Melanesia combined, Australia and New Zealand, and eastern Asia compared with southern and south-eastern Asian subregions. INTERPRETATION: Several patterns were consistent across the region: the dominance of mental disorders and NCDs, the universal rise in overweight and obesity (particularly high in Oceanic countries but increasing rapidly in south and south-eastern Asia), and persistent sex-specific challenges across subregions: unintentional injuries and smoking in males, and anaemia in females. Actions to tackle shared risk factors (while accounting for context-specific local health profiles, workforce deficits, cultural factors, and health system capacity) should not be forgone due to local variation. Future research could focus on subnational variation, intersecting inequalities, and multi-sectoral interventions targeting shared risk factors. Priority actions should include regional investment in adolescent mental health services and obesity prevention, targeted injury reduction strategies for high-risk populations, and sex-specific approaches to smoking cessation and anaemia reduction, delivered through local health systems with the capacity and cultural responsiveness to meet local needs. FUNDING: Gates Foundation and Australian Government.

Humans

Prevention of postpartum methamphetamine use with micronized progesterone trial (PROMPT): A pilot randomized controlled trial.

OBJECTIVES: Methamphetamine use disorder (MUD) contributes to postpartum morbidity and mortality. Postpartum progesterone decline may destabilize &#x3b3;-aminobutyric acid pathways, increasing craving and return to use. We assessed the feasibility and safety of micronized progesterone, generating efficacy estimates for preventing postpartum methamphetamine use. METHODS: We conducted a double-blind, randomized, placebo-controlled feasibility trial (November 2021-January 2024) at an academic center with a perinatal addiction clinic. Participants &#x2264;&#x2009;12 weeks postpartum with &#x2265;&#x2009;4 weeks of abstinence were randomized 1:1, stratified by opioid use disorder (OUD), to micronized progesterone 400mg (200mg twice daily) or identical placebo for 12 weeks. The primary outcome was feasibility, defined as achieving &#x2265;&#x2009;80% of planned enrollment. Safety outcomes included adverse events (AEs) and serious adverse events (SAEs). Efficacy outcomes were return to methamphetamine use (weekly self-report and every two weeks urine toxicology) and methamphetamine craving. Analyses included intent-to-treat and per-protocol approaches, with loss to follow-up imputed as return to use. Craving trajectories were modeled using adjusted regression with interaction terms for medication for OUD (MOUD). RESULTS: Of 253 screened individuals, 43 were eligible and 34 were enrolled (91.8%; 18 progesterone, 16 placebo). Retention at 12 weeks was 88%. AE frequency was similar between groups (78% vs 81%; p&#x2009;>&#x2009;0.05), and no maternal SAEs occurred. Four infant SAEs were deemed unrelated to treatment. Return to methamphetamine use did not differ between groups. Craving trajectories differed by MOUD type. CONCLUSIONS: Micronized progesterone was feasible and safe for postpartum individuals with MUD. MOUD-specific craving effects support evaluation in larger, multicenter efficacy trials. GOV REGISTRATION NUMBER: NCT05128071 NCT REGISTRATION: Prevention of postpartum methamphetamine use with micronized progesterone trial https://clinicaltrials.gov/study/NCT05128071.

Humans

Transcranial Photobiomodulation Variables Assessment Battery: Development and Validation.

Transcranial photobiomodulation (tPBM) response variability is partly driven by biophysical characteristics such as skin tone and hair properties that attenuate photon penetration, and by lifestyle factors including sleep quality, alcohol use, and nicotine consumption that disrupt the mitochondrial and vascular pathways on which tPBM acts. To date, no validated self-report tool exists to capture these moderators systematically. To address this gap, the tPBM Variables Assessment Battery was developed and psychometrically evaluated. It integrates adapted versions of established measures (Brief Pittsburgh Sleep Quality Index, E-cigarette Dependence Scale, Hair Scale Assessment PRO, Monk Skin Tone Scale, and Heaviness of Smoking Index), validated wellbeing evaluators (Ryff's Psychological Wellbeing), and custom measures (Hairstyle Classification, Hair Color Classification). Face and content validity met recommended expert thresholds, internal consistency was acceptable across adapted subscales, and criterion validity analyses confirmed meaningful associations between the lifestyle components and PROMIS-10 global health outcomes. The battery is low-burden, digitally deployable, and psychometrically defensible, offering a practical tool for characterizing the variables most likely to moderate tPBM response in home-use studies.

Humans

HPV Testing Versus Cytology for Cervical Cancer Screening&#xa0;Among Women 50&#x2009;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 &#x2265;&#x2009;50&#x2009;years who are approaching screening cessation remains limited. This analysis included 6471 women aged &#x2265;&#x2009;50 at baseline screening in the HPV FOCAL randomized clinical trial. Women were randomly allocated to receive cytology (Control Group, n&#x2009;=&#x2009;3248, 50.19%) or HPV testing (Intervention Group, n&#x2009;=&#x2009;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&#x2009;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 &#x2265;&#x2009;50&#x2009;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

Uric Acid-to-HDL Cholesterol Ratio is Associated with Hepatic Steatosis but Not Fibrosis in Nonobese Adults: A NHANES 2017-2020 Study.

BACKGROUND: Although metabolic dysfunction-associated steatotic liver disease (MASLD) has traditionally been regarded as a disease closely related to obesity, its prevalence is gradually rising in nonobese populations. The uric acid-to-high-density lipoprotein cholesterol ratio (UHR) is a novel metabolic biomarker that has been shown to be associated with MASLD. However, its role in nonobese individuals remains unclear. This study aimed to investigate the association between UHR and nonobese MASLD. METHODS: Data from the 2017 to 2020 National Health and Nutrition Examination Survey (NHANES) were analyzed. UHR was calculated as the serum uric acid (UA) divided by the high-density lipoprotein cholesterol (HDL). Liver steatosis (using controlled attenuation parameters, CAP) and fibrosis (using liver stiffness measurement, LSM) were evaluated through vibration-controlled transient elastography (VCTE). Multivariate linear regression was employed to evaluate associations. Nonlinear relationships were examined using smoothed curve fitting. RESULTS: This analysis included 3573 participants (47.41% male; aged 20-80 years). Log2-UHR was positively associated with CAP (&#x3b2; = 9.96, 95% CI: 6.93-12.98, P < 0.001) and MASLD prevalence (OR = 1.64, 95% CI: 1.38-1.95, P < 0.001). Subgroup analyses revealed significant interactions by sex, age, ethnicity, and smoking status (all P for interaction < 0.05), with stronger associations in females, adults aged 40-59 years, individuals of other Hispanic ethnicity, and never-smokers. Moreover, the association between log2-UHR and CAP was linear and positive (P < 0.01). No significant association was found between log2-UHR and LSM (P > 0.05). CONCLUSIONS: UHR is independently associated with hepatic steatosis but not fibrosis in nonobese US adults, suggesting its potential utility as an early risk assessment to tool. Large scale prospective studies are needed in the future to further validate the conclusions of this study.

Humans

The impact of body mass index classification on operative characteristics and perioperative outcomes in lumbar microdiscectomy.

INTRODUCTION: Body mass index (BMI) stratification helps classify obesity severity. In patients undergoing microdiscectomy for symptomatic lumbar disc herniation, the effect of obesity on perioperative risk remains incompletely understood. This retrospective single-institution study evaluated whether BMI class influences perioperative risk in a large surgical cohort. METHODS: Adults older than 18&#xa0;years who underwent primary, elective single-level lumbar microdiscectomy between June 2018 and March 2025 with at least 3&#xa0;months of follow-up were included. Patients were grouped by BMI: without obesity (WO, BMI&#xa0;<&#xa0;30), class I (CI, 30-34.9), class II (CII, 35-39.9), and class III (CIII, &#x2265;40). Outcomes were analyzed separately for open microdiscectomy (OM), tubular microdiscectomy (TM), and endoscopic discectomy (ED). Continuous variables were compared using Kruskal-Wallis testing with Dunn post hoc analysis; categorical variables were compared with chi-square tests. Significance was set at p&#xa0;<&#xa0;0.05. RESULTS: A total of 757 patients were included (OM 422, TM 190, ED 145). Higher obesity classes underwent ED more frequently (p&#xa0;=&#xa0;0.038). In the OM cohort (WO 258, CI 97, CII 50, CIII 17), CI had a higher proportion of males and CII a lower proportion (p&#xa0;=&#xa0;0.007). Operative time, length of stay, and estimated blood loss were greatest in CII and CIII patients (all p&#xa0;<&#xa0;0.001). CII patients also had more emergency department visits within 1&#xa0;year than other classes (p&#xa0;=&#xa0;0.026). No differences were found in age, smoking status, disc herniation type, dural tears, intraoperative or postoperative complications, or revision presence/time. In the TM cohort (WO 117, CI 47, CII 21, CIII 5), WO patients were oldest and CIII youngest (p&#xa0;<&#xa0;0.001), with no other significant differences. In the ED cohort (WO 79, CI 31, CII 20, CIII 15), WO patients were oldest and CIII youngest (p&#xa0;=&#xa0;0.004). CIII patients had higher estimated blood loss (p&#xa0;=&#xa0;0.028) and shorter time to revision (p&#xa0;<&#xa0;0.001), while other variables were similar. CONCLUSIONS: ED was used more often in higher obesity classes. In OM, CII and CIII obesity were associated with longer operative time, longer hospital stay, and greater blood loss, likely due to increased exposure requirements. TM and ED showed few obesity-related differences in complications, suggesting minimally invasive approaches may mitigate obesity-related perioperative risk. However, the retrospective design and small number of CIII patients warrant further study.

Humans

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 &#x2265;27 and &#x2264;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&#xb0;C) and ~2.5-fold (moderate, 4&#xb0;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&#xa0;&#xd7;&#xa0;RMR in mild and 1.94&#xa0;&#xd7;&#xa0;RMR in moderate cold. In type 2 diabetes, the increase was 1.57&#xa0;&#xd7;&#xa0;RMR and 2.09&#xa0;&#xd7;&#xa0;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&#xa0;&#xb1;&#xa0;0.5 mmol/l, p=0.003) and fasting glucose (-0.6&#xa0;&#xb1;&#xa0;0.8 mmol/l, p=0.019), as well as an increase in time in normal range (+8.8&#xa0;&#xb1;&#xa0;10.3%, p=0.013) and reduced time in hyperglycaemia (-10.9&#xa0;&#xb1;&#xa0;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