Background Smoking has been identified as a modifiable dementia risk factor by three Lancet Commissions, yet dementia remains absent from most tobacco control strategies. The magnitude of the association across dementia subtypes, smoking categories, and population characteristics has not been comprehensively synthesised since 2015. Methods PubMed, Embase, CENTRAL, and PsycINFO were searched from January 2013 to 31 August 2026, updating the 2015 review, which contributed 34 studies. Random-effects meta-analyses (Restricted Maximum Likelihood (REML) with Hartung–Knapp–Sidik–Jonkman adjustment) estimated pooled relative risks (RRs) with 95% confidence intervals (CIs). Subgroup analyses with tests for interaction and meta-regression examined effect modification by baseline age, ethnicity, follow-up duration, and adjustment for sex, education and Apolipoprotein E ε4 (APOE ε4) genotype. Risk of bias was assessed using Risk Of Bias In Non-randomized Studies of Exposures (ROBINS-E). Heterogeneity was assessed using Cochran’s Q, I2 and τ2 and publication bias using funnel plots and Egger’s test. Dose–response analysis of smoking and dementia risk was performed. Smoking population attributable fractions (PAF, unweighted and communality-weighted) for the risk of dementia were calculated. This study is registered with PROSPERO, CRD42025644539. Findings Sixty-one cohort studies (approximately 2.8 million participants) were included. Current smoking was associated with increased risk of all-cause dementia (RR 1.31 [95% CI 1.23–1.39]; number of studies (k) = 39), Alzheimer’s disease (1.40 [1.08–1.80]; k = 15), and vascular dementia (1.52 [1.20–1.93]; k = 9). Former smoking was not associated with any outcome, and former smokers had a lower risk of all-cause dementia than current smokers (RR 0.81 [0.75–0.88]). I2 ranged from 0% to 80%. Egger’s test suggested small-study effects only for current smoking and all-cause dementia (P = 0.09). The communality-weighted PAF for smoking and dementia was 2.2% (95% CI 1.7–2.8). Dementia risk increased with smoking intensity as the pooled RR was 1.16 (95% CI 1.09–1.23) at 10 cigarettes per day and rose to 1.34 (95% CI 1.18–1.51) at 20 cigarettes per day. Interpretation Current smoking is consistently associated with higher risk of all dementia outcomes and increases with smoking intensity. Estimates refer to clinically diagnosed dementia syndromes [Diagnostic and Statistical Manual of Mental Disorders/International Classification of Diseases (DSM/ICD)] and not to biologically defined disease. Although causality cannot be established from observational data, these findings support considering dementia and brain health outcomes in national tobacco control strategies and associated campaigns. Future work using objectively verified smoking histories is needed to clarify how age at cessation and time since quitting influence dementia risk and whether these effects interact with total years of active smoking. Funding None.
Background Mobile health (mHealth) applications are needed for key populations of people with HIV who experience persistent difficulties with achieving and maintaining undetectable viral load (VL). Methods This remote randomised controlled trial (RCT) tested the efficacy of Supporting Treatment Adherence for Resilience and Thriving (START)—an mHealth application integrating self-monitoring of anti-retroviral therapy (ART) adherence with positive psychological skills (www.clinicaltrials.gov identifier NCT05140876). From 2022 to 2024, 286 sexual minority men with HIV residing in the continental United States who reported recent ART non-adherence and screened positive for a stimulant use disorder (i.e., 92% methamphetamine use disorder) were randomised (1:1) to START (n = 143) or a website control with referrals (n = 143). The primary outcome was detectable VL (>300 copies/mL) at six months (76% retention), measured via remote blood samples. Findings Participants randomised to START had 58% lower odds of detectable VL at six months (adjusted odds ratio [AOR] = 0.42; 95% confidence interval [CI]: 0.19–0.93; p = 0.032). Among the 155 participants with undetectable VL at enrolment (54%), virologic rebound at six months was nearly two-fold greater in the website control versus START (48% versus 25%; p = 0.019). The number needed to treat was 4.75 (95% CI: 2.52–42.00) to prevent one instance of detectable VL. START effects on these VL outcomes were not maintained at 12 months. Interpretation A scalable, mHealth application significantly reduced odds of detectable VL in the short-term, primarily by preventing virologic rebound. Funding National Institute on Drug Abuse (R01-DA049843; UH3-DA058304).
Viral encephalitis, meningitis, and myelitis are rare but life-threatening complications after autologous or allogeneic hematopoietic cell transplantation (HSCT) and chimeric antigen receptor (CAR) T-cell therapy, associated with 30–60% mortality and frequent neurological sequelae. The absence of harmonised definitions and diagnostic criteria contributes to delayed diagnosis, underreporting, and substantial heterogeneity across centres. This EBMT Practice Harmonization and Guidelines Committee expert consensus provides practical recommendations for the definition, diagnosis, treatment, response assessment, and prevention of viral encephalitis/meningitis and viral myelitis, developed through systematic literature review and multidisciplinary expert consensus following EBMT methodology. We propose standardised diagnostic categories for proven and probable viral encephalitis/meningitis and myelitis, alongside a unified diagnostic algorithm integrating clinical assessment, neuroimaging, electroencephalography, cerebrospinal fluid analysis, and targeted virological testing. We highlight key neurotropic viruses for inclusion in initial cerebrospinal fluid multiplex PCR panels, including human herpesvirus 6, herpes simplex virus 1/2, varicella zoster virus, cytomegalovirus, Epstein-Barr virus, adenovirus, polyomaviruses BK/JC, and selected community-acquired respiratory viruses, such as EV71, and recommend prompt, risk-based empirical antiviral therapy in suspected cases. These recommendations aim to standardise clinical practice, facilitate multicenter research, and improve outcomes. However, many rely on limited observational evidence or expert opinion, underscoring the need for prospective studies.
Background PREVENT-PE showed that screening for preeclampsia risk at 35–36 weeks followed by risk-stratified timed birth reduced birth with preeclampsia overall. We aimed to assess possible benefit and harm within each risk stratum. Methods This post hoc Bayesian analysis included 4734 participants recruited at King's College Hospital, London, UK, in PREVENT-PE. The parent trial included women aged 16 years or older with a live singleton pregnancy, no major fetal abnormality or preeclampsia, and no conflicting trial participation. We included all 2871 intervention participants and 1863 control participants with stored serum and haemodynamic measurements that allowed retrospective calculation of 35–36-week preeclampsia risk. We estimated incidence proportions, ratios, and differences using independent Beta(1, 1) priors and binomial likelihoods. PREVENT-PE is registered with ISRCTN, ISRCTN41632964. Findings PREVENT-PE recruited between May 9, 2023, and June 7, 2024. Birth with preeclampsia occurred in 117/2871 (4.1%; 95% credible interval [CrI] 3.4–4.9) intervention participants and 106/1863 (5.7%; 4.7–6.8) controls; the posterior median incidence ratio was 0.72 (95% CrI 0.56–0.93), with probability of benefit 0.995. Estimates at 39 and 40 weeks favoured intervention and were more precise; estimates at 37 and 38 weeks were much less precise. Heterogeneity of treatment effect was not established. Overall incidence ratios were 1.03 (0.92–1.15) for emergency caesarean and 0.97 (0.76–1.25) for neonatal unit admission for at least 48 h. Interpretation The overall PREVENT-PE strategy is supported by randomised evidence, but these post hoc data do not establish different treatment effects across risk strata. The balance of benefit and harm of routine planned birth at 37–38 weeks remains uncertain and needs further evaluation. Funding Fetal Medicine Foundation.
Central nervous system (CNS) infections in patients after haematopoietic stem cell transplantation (HSCT) and CAR T-cell therapy are caused by a broad range of pathogens and associated with high morbidity and mortality. Lack of standardised definitions and uniform diagnostic approach contributes to underdiagnosis and heterogeneity in reporting. This EBMT Practice Harmonization and Guidelines Committee consensus document provides harmonised definition and recommendations on diagnostics, treatment, and response assessment for focal CNS infections and meningitis of bacterial, fungal and parasitic origin in cellular therapy recipients. Focal brain infections are predominantly caused by Aspergillus spp, Toxoplasma gondii, and Nocardia spp, whereas common bacteria are rare. Bacterial or fungal meningitis is rare and typically occurs late post-HSCT. Rapid diagnosis and treatment are crucial to improving outcomes. Benefits of corticosteroids in bacterial meningitis have not been evaluated in this population. Standardised definitions and outcome reporting should be adopted in registries and studies to improve comparability and strengthen the evidence base for management.
