Dialogues in clinical neuroscienceNatalia G Docteur, Hayley G P Huston, Avery A Krupa, Brandy L Callahan
Attention-deficit/hyperactivity disorder (ADHD) affects 2.5% of adults and is associated with cognitive decline and dementia. The neurobiological mechanisms contributing to adverse outcomes in ADHD are poorly understood. ADHD-related brain alterations may persist into later life and interact with ageing-related processes, potentially increasing susceptibility to neuropathology. This preregistered systematic review synthesised neuroimaging findings in adults aged 35 years and older with clinical, symptomatic, or genetic risk for ADHD, and summarised cognitive and clinical correlates. A search of five databases produced 13 included studies. Risk of bias was assessed using the Newcastle-Ottawa Scale. Most studies (11/13) had low risk of bias. Compared to controls, ADHD groups exhibited alterations in fronto-striatal, fronto-parietal, and limbic systems implicated in executive control and attention. Middle-aged adults with clinical ADHD showed more widespread cortical structural differences, whereas older adults demonstrated abnormalities primarily in frontal regions, possibly reflecting attenuation of differences through ageing. Two functional studies in those with clinical ADHD reported frontal hypoactivation alongside parietal hyperactivation, consistent with compensatory recruitment. Among undiagnosed samples, there were interactions between genetic risk for ADHD and Alzheimer's disease-related pathology affecting brain and cognitive outcomes. Overall, ADHD-associated neurobiological alterations appear to persist into older age. Longitudinal investigations are needed to clarify these relationships.
Renal failureYue Yuan, Siyuan Lei, Aoyi Duan, Jiansheng Li
Sepsis remains a leading cause of mortality worldwide, and extracorporeal blood purification has been widely implemented despite ongoing uncertainty regarding its survival benefit. We conducted an umbrella review of 42 systematic reviews and meta-analyses evaluating mortality across major extracorporeal blood purification modalities. Mortality estimates generally favored extracorporeal blood purification over conventional care, but effect sizes and consistency varied substantially by modality, and the overall certainty of evidence for mortality was low. At the review level, polymyxin B hemoperfusion showed a relatively consistent direction toward lower mortality, whereas renal replacement therapy-based strategies were typically closer to the null. However, most included reviews were of low or critically low methodological quality, with downgrading driven by risk of bias, inconsistency, and potential publication bias. Therefore, these findings should be interpreted cautiously and should not be considered definitive evidence of survival benefit. They highlight persistent evidentiary fragility and underscore the need for rigorously designed, phenotype-informed trials to clarify modality-specific effects in sepsis.
PulmonologyDavid Jimenez, Behnood Bikdeli, Victor Tapson, Cecilia Becattini, Lisa Moores, Geoffrey D Barnes, Manuel Monreal, Stavros Konstantinides, Gregory Piazza, Raque…
BACKGROUND: For patients with acute pulmonary embolism (PE), assessment of prognosis helps with risk stratification, triage for level of care, management strategy, and communication among healthcare workers and patients. We sought to identify prognostic models and individual factors associated with short-term outcomes after acute symptomatic PE. METHODS: We performed a systematic review of prognostic factors for PE, searching MEDLINE, Embase, and Web of Science for records up to 1 June 2024. Studies of any design evaluating potential prognostic models or individual variables (not contained in the models) associated with short-term mortality after acute PE were included. RESULTS: We identified 314 studies that included 2,495,115 patients. Of these, 225 studies included 2,267,952 patients and evaluated 24 prognostic models for patients with acute PE. The most frequently used validated models were the simplified Pulmonary Embolism Severity Index (sPESI) (127 studies), the original PESI (79 studies), and the European Society of Cardiology risk schema (34 studies). Each model-development study had a c-index ≥ 0.7. Individual factors associated with prognosis included older age, presence of coexisting conditions, abnormal clinical signs and symptoms, clot burden, markers of right‑ventricle dilatation/dysfunction and myocardial injury, altered laboratory results indicating impaired haemodynamics, and tests that assess for systemic inflammation. Pooled odds ratios for variables not contained in any eligible prognostic model ranged from 1.43 (for D-dimer) to 2.65 (for right heart thrombi). CONCLUSIONS: This systematic review identified 24 prognostic models and 18 individual variables distinct from the prognostic models associated with short-term mortality after acute PE.
Annals of medicineJinglong Li, Qisen Zhu, Mohamad Nabil Mohd Noor, Chan Choong Foong
BACKGROUND: Cerebral Palsy (CP) is the main cause of motor disabilities in childhood, necessitating innovative approaches to rehabilitation and assistive technology (AT). Simultaneously, artificial intelligence (AI) is increasingly being integrated into devices to create more adaptive, personalized, and effective AT. This systematic review aimed to evaluate the effectiveness and usability of AI-powered assistive technologies designed to support daily activities and rehabilitation in children with CP. MATERIALS AND METHODS: Five databases, including Scopus, Web of Science, PubMed, Embase, and IEEE Xplore, were systematically searched, and 23 articles were included in the final analysis. Articles were identified, selected, and categorized into emerging thematic areas based on the primary function and application of the technology. RESULTS: Five key thematic topics were identified: 1) AI-driven motor rehabilitation and gait training for functional mobility; 2) intelligent assessment and monitoring systems for clinical decision support; 3) AI-supported communication, social interaction, and intention recognition tools; 4) gamified and virtual reality-based interventions to enhance engagement and usability; and 5) smart assistive systems supporting daily living and independent mobility. The findings demonstrate a strong trend toward the application of AI technologies in personalized, engaging, and data-driven interventions for children with CP. However, the field is predominantly in the proof-of-concept stage, with limitations including small sample sizes, lack of long-term clinical validation, challenges in user-centered design, and usability for children with CP. CONCLUSION: AI-powered assistive technologies hold significant potential for transforming the care of children with CP by enabling highly personalized and engaging interventions. To actualize this potential, future work must realize that practical application remains challenging owing to limited clinical validation, technological integration, and usability barriers for children with CP. Future research must prioritize user-centered design and multidisciplinary collaboration to ensure that AI and robotic advancements improve the usability and quality of life for children with CP.
Journal of medical economicsToby A Eyre, Leyla Mohseninejad, Lianne Barnieh, Kaijun Wang, Yiran He, Keri Yang, Rhys Williams, Bijal D Shah
OBJECTIVE: No head-to-head trials have compared the efficacy of zanubrutinib versus ibrutinib in relapsed/refractory mantle-cell lymphoma (R/R MCL). METHODS: Following a systematic literature review, individual patient data from trials of zanubrutinib (n = 118) and aggregate data from a pooled analysis of ibrutinib trials (n = 370) were analyzed using an unanchored matching-adjusted indirect comparison (MAIC). RESULTS: After matching selected covariates, statistically significant differences were observed with zanubrutinib versus ibrutinib for progression-free survival (hazard ratio [HR] = 0.63; 95% confidence interval [CI] 0.46-0.87, p = .0044) and overall survival (HR, 0.46; 95% CI 0.30-0.71, p = .0005). CONCLUSION: These MAIC analyses demonstrate that zanubrutinib may be more effective than ibrutinib at delaying disease progression and death in R/R MCL.
International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia GroupHua-Wei Gao, Zhi-Hong Li, Yan Lu, Yi-Gong Fang, Fang-Fang Shen, Ling-Wei Song, Fang-Zhou Yu
OBJECTIVE: To systematically evaluate the efficacy of doxorubicin (DOX)-loaded graphene nanoplatform chemo-photothermal therapy (CPT) compared with photothermal therapy (PTT) alone on relative tumor volume (RTV) in breast cancer xenograft models and to summarize reported secondary safety and translational endpoints. METHODS: PubMed, Embase, Web of Science, and Cochrane Library were searched for animal studies published from January 2010 to December 2025 investigating DOX-loaded graphene nanomaterial-mediated CPT in breast cancer xenograft tumors. Hedges' g was used as the effect size measure, and standardized mean differences (SMDs) were pooled using a random-effects model. Heterogeneity, publication bias, subgroup analyses, sensitivity analyses, and qualitatively reported secondary endpoints were assessed. RESULTS: Nine breast cancer xenograft studies were included, involving 46 animals in the CPT group and 46 in the PTT group. The pooled SMD was -2.20 (95% CI: -2.76 to -1.65, p < 0.0001), with negligible heterogeneity (I2 = 0.0%). Subgroup analyses showed no statistically significant differences by cell line, graphene type, or publication period (all p > 0.05). Leave-one-out sensitivity analyses yielded pooled SMDs from -2.09 to -2.37. Funnel plot inspection and Egger's test suggested mild small-study asymmetry, but Trim-and-Fill correction did not change the direction or significance of the result. Secondary endpoint extraction showed limited survival, toxicity, biodistribution, and clearance reporting, supporting short-term tolerability but not definitive clinical translation. CONCLUSION: DOX-loaded graphene nanoplatform CPT was associated with significantly greater suppression of RTV than PTT alone in breast cancer xenograft models. The evidence supports a robust preclinical antitumor association while highlighting the need for standardized survival, long-term toxicity, biodistribution, and elimination studies before clinical application.
Human vaccines & immunotherapeuticsAshok Kumar Dutta, Rashna Dass Hazarika, K L Ravikumar, Vijay Yewale, Sanjay Niranjan, Jaydeep Choudhury, Gurpreet Singh, Suresh Panuganti, Jeetendra Gavhane, …
Invasive meningococcal disease (IMD) is a significant but under-recognized public health challenge in India, marked by rapid progression, high mortality, and severe sequelae. This consensus document, developed from literature review, outbreak analyses, and deliberations by 14 Indian experts, highlights outbreaks from 1966 (Delhi: 616 cases, case fatality ration: CFR 20.9%) to 2022-2023 (Kolkata). Serogroup A remains predominant, with emerging serogroups C, W, and Y. Systematic review evidence shows 12.1% prevalence in epidemics (CFR 12.8%) and 0.76% in endemic settings (CFR 3.0%), though true burden is underestimated due to weak surveillance. IMD shows bimodal age distribution, highest in children < 5 y (61.8%) and adolescents. MenACWY conjugate vaccines show 95.7-99.5% seroprotection across serogroups. Experts recommend vaccination at 9-12 months with booster at 10-11 y, mandatory reporting, sentinel surveillance, and clinician awareness. The roadmap stresses awareness, short-term surveillance, and long-term data generation toward National Immunization Program inclusion.
Renal failureKyle Backston, Benjamin Buehrer, Defne Ezgü, Pranav Sivaram, Shay Tanna, Riddhima Koka, Sidharth Kumar Sethi, Michael Moritz, Rupesh Raina
Acute Kidney Injury (AKI) is currently diagnosed in pediatric patients by measuring rises in serum creatinine. The objective of this systematic review is to determine the diagnostic accuracy of novel biomarkers for early detection or prediction of pediatric AKI across a variety of high-risk pediatric populations. Relevant studies were searched in PubMed, Cochrane Library, and Web of Science databases. Observational studies and randomized trials assessing diagnostic biomarkers for AKI in high-risk pediatric populations were included, while studies limited to traditional biomarkers, adult populations, or non-original research were excluded. Risk of bias was assessed using the QUADAS-2 tool. The review was prospectively registered in PROSPERO (CRD420261293432). Diagnostic accuracy outcomes included AUC, sensitivity, specificity, and other performance measures. 53 total studies were included and grouped into 1 of 5 categories based on the specific population of pediatric patients studied and the general etiology of their AKI. Of note, neutrophil gelatinase-associated lipocalin, kidney injury molecule-1, and cystatin-C were among the most studied biomarkers and showed significant promise as reliable indicators of kidney injury. The product of tissue inhibitor of metalloproteinase-2 and insulin-like growth factor binding protein-7, interleukin-18, and others showed some evidence of being predictive, early markers of AKI and warrant additional investigation. The review further discusses the integration of novel biomarkers within existing clinical detection frameworks, including validated risk stratification tools and emerging FDA-approved biomarker assays, to contextualize their translational potential in high-risk pediatric populations. Future advances in precision medicine may lead to earlier diagnosis and better prognosis for pediatric patients suffering from AKI.
International journal of qualitative studies on health and well-beingFayez Abdulrazeq, Chris Gastmans, Nikola Biller-Andorno, Julian März
PURPOSE: Healthcare providers play a critical role in delivering care to undocumented migrants, who face systemic barriers to healthcare access. While research has documented undocumented migrants' legal and policy barriers, less is known about the ethical challenges and moral stressors experienced by providers. This systematic review synthesizes qualitative studies on providers' experiences when delivering care to undocumented migrants. METHODS: The review followed PRISMA guidelines. PubMed, Embase, CINAHL, and the Cochrane Library were searched for relevant qualitative studies. Studies were screened by title, abstract, and full text using predefined inclusion and exclusion criteria. Quality assessment was conducted using the CASP checklist. Data were synthesized using the Qualitative Analysis Guide of Leuven (QUAGOL), integrating Graneheim and Lundman's approach to qualitative content analysis. RESULTS: The systematic search identified 37 qualitative studies. Analysis revealed 58 themes and subthemes, organized under five key concepts: experiences, perceptions, attitudes, practices and coping mechanisms, and ethical challenges. Providers reported moral distress, emotional exhaustion, and professional dilemmas arising from legal constraints, resource limitations, and conflicting obligations. Ethical tensions centered on beneficence vs. non-maleficence, professional duty vs. legal compliance, and the moral dilemma of deservingness. Across these findings, the synthesis identifies ethical burden-shifting as a central analytical contribution: restrictive systems transfer the moral and practical consequences of exclusionary arrangements onto providers and undocumented migrants at the point of care. CONCLUSION: This review shows that providers' ethical challenges are not only individual clinical dilemmas but structurally generated moral stressors. Addressing these challenges requires structural interventions, including policy reforms that reconcile professional ethics with legal constraints and institutional support to mitigate moral distress.
Journal of the International Society of Sports NutritionLulu Guan, Linhang Han, Yu Zou, Dushuo Feng, Pengxuan Xia, Yuxin Peng, Ziqi Fan
BACKGROUND: Exercise-induced fatigue is a complex, non-pathological state that acutely limits physical performance, and the serotonergic (5-HT) system has been proposed as an important modulator of its central components. This systematic review and meta-analysis aimed to clarify the effects of serotonergic pharmacological manipulation on exercise-related outcomes. METHODS: Following PRISMA guidelines, we systematically searched PubMed, Scopus, Web of Science, Cochrane Central, and SportDiscus from inception to August 2025. Randomized controlled trials examining the effects of serotonergic pharmacological manipulation on exercise-related outcomes in healthy adults were included. Study selection, data extraction, and risk-of-bias assessment using RoB 2.0 were conducted independently. Pooled effects were synthesized using three-level random-effects models, and the certainty and robustness of the evidence were examined in additional analyses. RESULTS: Twenty-one randomized controlled trials involving 248 healthy adults were included in the systematic review, of which 19 studies involving 229 participants were included in the meta-analysis. In the primary models, serotonergic pharmacological manipulation was associated with small reductions in evoked motor response (Hedges' g = -0.24, 95% CI -0.46 to -0.02), time-domain EMG (Hedges' g = -0.18, 95% CI -0.33 to -0.02), heart rate (Hedges' g = -0.17, 95% CI -0.34 to -0.01), and blood glucose (Hedges' g = -0.50, 95% CI -0.89 to -0.11). Voluntary activation showed a borderline negative pooled estimate (Hedges' g = -0.20, 95% CI -0.40 to 0), whereas ratings of perceived exertion showed a positive but statistically uncertain pooled estimate (Hedges' g = 0.63, 95% CI -0.01 to 1.28). Resting twitch torque showed a small positive pooled effect (Hedges' g = 0.12, 95% CI 0.04 to 0.19), whereas superimposed twitch torque, maximal voluntary contraction, prolactin, lactic acid, and time to task failure did not show clear overall effects. CONCLUSIONS: Overall, this meta-analysis indicates that serotonergic pharmacological manipulation has outcome-specific effects on exercise-related fatigue rather than a single uniform influence across domains. The most consistent primary-model signals were found for evoked motor response, time-domain EMG, heart rate, and blood glucose, whereas overt performance and perceptual outcomes remained more variable. By integrating evidence across different serotonergic interventions and exercise paradigms, these findings improve our understanding of how 5-HT-related mechanisms may contribute to central fatigue during exercise.
European journal of psychotraumatologyAlexandra J Vogt, Markus A Landolt, Ingeborg Skjærvø, Rahel M Hermann, Elisa Pfeiffer, Cedric Sachser, Lasse Bartels
Background: Post-traumatic stress disorder (PTSD) often impairs children's and adolescents' functioning across different life domains. Significant functional impairment is a diagnostic criterion for PTSD in both the DSM-5 and the ICD-11, but the methods in terms of domains covered and scoring rules to assess functional impairments are quite inconsistent.Objective: This systematic review evaluates instruments specifically designed to assess post-traumatic stress symptoms (PTSS), PTSS modules within diagnostic interviews, and generic functional impairment measures used to capture PTSS-related functional impairment in children and adolescents.Method: A systematic search was conducted across six databases for studies published between January 2010 and November 2025. Eligible papers included the development or psychometric evaluation of PTSS-specific measures, PTSS modules in diagnostic interview, and generic functional impairment measures validated in samples exposed to trauma or adverse childhood experiences. Data were extracted and categorized based on assessed content domains, scoring methods, and psychometric properties, with results stratified by age group (6 years and younger versus 7 years and older).Results: From 3519 records, 30 papers met the inclusion criteria. Thirteen PTSS-specific instruments, one diagnostic interview module, and one generic functional impairment measure were identified. Together, these instruments assessed 11 different life domains, although considerable variation existed in the domains covered across tools. Scoring methods also varied, with approximately half using dichotomous response formats and the remainder using multi-categorical scales. Psychometric properties of the functional impairment scales were reported in only 20.7% of publications.Conclusion: Current tools for assessing PTSS-related functional impairment in youth lack standardization. There is a critical need for well-validated instruments that comprehensively capture the presence and severity of PTSS-related functional impairment.
Journal of medical economicsTendai Mugwagwa, José Marcano Belisario, Louise Hartley, Nguyen Thi Nhan Phan, Ruth Mokgokong
AIMS: Nirmatrelvir/ritonavir (NMV/r)i is an antiviral drug indicated for the treatment of patients with mild to moderate coronavirus disease 2019 (COVID-19) who are at high risk of progressing to severe disease. We performed an updated economic systematic literature review (eSLR) of NMV/r to build upon evidence reported in our previous eSLR and additionally examine the health-related outcomes associated with NMV/r and any potential effect of long COVID. METHODS: A systematic search of Embase, PubMed, Cochrane, and EconLit and of conference and health technology assessment agency websites was performed to identify economic analyses published between January 2022 and October 2025. RESULTS: Of the 33 included economic evaluations, most were cost-utility analyses (n = 16) and used an analysis of a short-term decision tree with a long-term Markov model (n = 11). Several types of health-related endpoints were reported by studies, with most including hospital-related endpoints (n = 20), quality-adjusted life-years (QALYs) (n = 18), and death-related endpoints (n = 18). Positive health-related outcomes were associated with NMV/r treatment, including reductions in hospitalizations and deaths and an increase in QALYs. NMV/r treatment was also associated with a reduced number of patients with long COVID complications. LIMITATIONS: Most studies were conducted in high-income countries, were based on different COVID-19 variants, and were limited in data on the long COVID population. CONCLUSION: In addition to monetary benefits, NMV/r provides short-term and long-term health-related benefits to patients with mild to moderate COVID-19. This study provides further support for NMV/r as a cost-effective treatment option.
In moderate‑to‑severe chronic obstructive pulmonary disease (COPD), the number needed to treat (NNT) quantifies therapeutic benefit but remains underused for type-2-targeted biologics. This meta-analysis quantified the NNT for type-2-targeted biologics in moderate-to-severe COPD and incorporated the recent evidence on exacerbations, lung function, symptoms, health status, and responder outcomes. We searched PubMed, Embase and Web of Science through July 2025 for phase 2 or 3 RCTs of type-2targeted biologics in adults with COPD. The primary outcome was NNT for moderate-to-severe exacerbations; secondary outcomes included pre-bronchodilator forced expiratory volume in 1 s (FEV1), St. George's Respiratory Questionnaire (SGRQ), Evaluating Respiratory Symptoms in COPD (E-RS-COPD), and responder proportions. Pooled ratios and mean differences were synthesized using fixed‑ or random‑effects models. Patient-based NNT was derived from cumulative incidence, event‑based NNT was derived from annualized exacerbation rates. Pooled NNTs were estimated under selected baseline‑risk scenarios. Under three baseline‑risk scenarios, pooled patient‑based NNTs for reducing moderate‑to‑severe COPD exacerbations were 12-17 for dupilumab and 11-16 for mepolizumab, benralizumab showed no clear reduction. Event-based NNTs at a baseline annual exacerbation rate of 1.055 per year were 3 for dupilumab and 5 for mepolizumab. Dupilumab was associated with improvements in pre-bronchodilator FEV1, SGRQ, and E-RS-COPD. For mepolizumab, evidence across these non‑exacerbation outcomes was not consistently observed. In conclusion, pooled patient-based and event-based analyses suggest that both dupilumab and mepolizumab consistently reduce moderate-to-severe exacerbations in eosinophilic or type 2 inflammatory COPD, while improvements in lung function and patient-reported outcomes remain less consistent across biologics and warrant further validation. These findings derive from separate placebo‑controlled trials and should not be interpreted as establishing a comparative efficacy hierarchy among biologics.
Human vaccines & immunotherapeuticsFakher Rahim, Ümit Atasever
Despite widespread HPV vaccination, a comprehensive synthesis across populations and cancer outcomes is lacking. This umbrella review evaluates HPV vaccination's population impact on infection, precancerous lesions, and invasive cancers. We searched five databases for meta-analyses reporting prophylactic HPV vaccine outcomes up to Jan 2026. Two reviewers performed selection, data extraction, AMSTAR-2, and GRADE. From 34 meta-analyses, RCTs in HPV-naïve women showed 99% efficacy (95% CI: 98-99%) against HPV16/18 infection, 96% against CIN2+, and 89% against anogenital warts. Observational studies found relative risks of 0.12-0.36 (HPV16/18) and 0.48-0.68 (CIN2+). In men, effectiveness against warts was 74-90%. Ecological studies reported reductions in cervical cancer of 57-88%. GRADE certainty was high for infection/warts, moderate for precancer, and low for invasive cancer. HPV vaccination is highly effective. Invasive cancer prevention evidence is promising but emerging. Further research in immunocompromised populations is needed.
HIV research & clinical practiceHamzah M Alghzawi, Syed Zohad Shah, Zain Ul Abideen, Muhammad Farhan Ashraf
BACKGROUND: The combination of doravirine and islatravir (DOR/ISL) is a novel two-drug regimen for HIV-1. Early development faced challenges due to dose-dependent immunological signals. We aimed to synthesize the evidence on the efficacy and safety of DOR/ISL across all treatment-experience categories, specifically evaluating the impact of islatravir dosage (0.25 mg vs 0.75 mg) on clinical and immunological outcomes. METHODS: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) following PRISMA guidelines. We searched PubMed, Embase, Cochrane Library, and Google Scholar from inception through April 2026. Primary outcomes were virological suppression (<50 copies/mL) and mean change in CD4+ T-cell count at week 48. Data were pooled using random-effects models. Islatravir dose was evaluated as a pre-specified moderator. Quality was assessed using Cochrane RoB 2.0 and certainty of evidence was graded using the GRADE approach. RESULTS: Seven RCTs (n = 3,600 participants) were included. At Week 48, DOR/ISL showed non-inferior suppression rates (RR 1.01 [95% CI 0.99-1.02]; p = 0.516; moderate-certainty evidence) and a statistically significant reduction in virological failure risk (RR 0.55 [0.33-0.92]; p = 0.022) compared to active control. Overall CD4+ gain was lower with DOR/ISL (MD -34.55 cells/μL; low-certainty evidence); however, a profound moderator effect of dose was observed (p < 0.0001). The 0.75 mg dose was associated with significant CD4+ and lymphocyte declines, whereas the approved 0.25 mg dose was immunologically neutral. DOR/ISL was weight-neutral compared to bictegravir/emtricitabine/tenofovir alafenamide (MD -0.25 kg [-0.66 to 0.16]; low-certainty evidence). CONCLUSION: DOR/ISL 100/0.25 mg once daily achieved virological suppression comparable to standard-of-care ART regimens and was associated with lower rates of virological failure compared with active comparators. The immunological safety concerns observed in early trials were successfully resolved by dose optimization. These findings support the use of DOR/ISL (IDVYNSO) as a potential treatment option for both treatment-naïve and virologically suppressed adults while emphasizing long-term safety surveillance.
Global health actionPranil Man Singh Pradhan, Mark P Funnell, Reshu Agrawal Sagtani, Nikita Bhattarai, Biraj Karmacharya, Abhinav Vaidya, Kamlesh Khunti, Patrick J Highton
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.
The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal ObstetriciansLvping Gu, Jie Shen
BACKGROUND: Intrahepatic cholestasis of pregnancy (ICP) is linked with adverse perinatal outcomes; however, its impact in twin pregnancies remains unclear. This systematic review and meta-analysis aimed to evaluate maternal and neonatal outcomes in twin pregnancies complicated by ICP. METHODS: A comprehensive search of PubMed, Embase, Web of Science, and Scopus was conducted from inception to 14 February 2026. Cohort studies comparing twin pregnancies with and without ICP were included. Random-effects meta-analyses were performed to assess maternal and neonatal outcomes reported by at least three studies. RESULTS: Seven retrospective cohort studies were included. ICP in twin pregnancies was associated with increased risk of cesarean delivery, preeclampsia, and gestational diabetes mellitus. Preterm birth (PTB) <37 weeks was significantly increased with ICP in both crude and adjusted analysis. Mean gestational age was significantly reduced, and birthweight was lower in ICP. ICP was strongly associated with meconium-stained amniotic fluid and increased neonatal intensive care unit (NICU) admission. However, no significant association was noted between ICP and stillbirth, small-for-gestational age and postpartum hemorrhage. CONCLUSIONS: ICP in twin pregnancies is associated with PTB and increased maternal and neonatal morbidity. Current evidence is derived mostly from crude data and from a limited number of studies with high inter-study heterogeneity.
Journal of the International Society of Sports NutritionXuebing Bai, Tailong Xu
BACKGROUND: Creatine (Cr) and β-alanine (BA) are among the most studied ergogenic supplements, acting on distinct physiological pathways-Cr facilitates phosphocreatine resynthesis and rapid ATP turnover, while BA elevates intramuscular carnosine to enhance acid-base buffering. Although both compounds improve high-intensity performance independently, the ergogenic potential of their combined use remains uncertain. OBJECTIVE: To systematically evaluate and compare the isolated and combined effects of Cr and BA supplementation on aerobic and anaerobic performance indices using a network meta-analytic approach. METHODS: Following PRISMA guidelines, a comprehensive search of PubMed, Scopus, and Web of Science (to August 2025) identified randomized controlled trials (RCTs) examining Cr, BA, or Cr + BA supplementation (≥2 weeks) in healthy adult athletes. Fifty-two RCTs (PEDro ≥ 6) met the inclusion criteria. Standardized mean differences (SMD) and 95% confidence intervals (CI) were computed within random effects models. Performance outcomes included sprint, jump, agility, upper- and lower-body muscular endurance (UME, LME), and repeated-sprint ability (RSA). RESULTS: Cr supplementation significantly improved sprint performance (SMD = -0.64; p = 0.04), jump performance (SMD = 0.33; p = 0.002), RSA (SMD = -0.78; p = 0.01), and UME (SMD = 0.43; p = 0.01) versus placebo, with P scores ≥ 0.90 across these domains. In contrast, BA supplementation produced non-significant or context-specific effects, and combined Cr + BA showed no synergistic benefits. Agility and LME outcomes remained unaffected (p > 0.05). Heterogeneity ranged from low to moderate (I2 = 0-73%), with no global inconsistency or substantive publication bias. CONCLUSION: Evidence indicates Cr supplementation alone yields the most consistent improvements in high-intensity and anaerobic performance by enhancing phosphocreatine recovery and neuromuscular output. BA's buffering advantage appears task-specific and insufficient to augment Cr's ergogenic efficacy. Co-supplementation of Cr and BA offers no additional advantage beyond Cr monotherapy. Standardized, long-term, multi-arm RCTs are warranted to further clarify potential interactive mechanisms and sex or sport-specific responses.
Hypertension in pregnancyAdili Adilan, Haoran Zhan, Yanan Hu, Lana McClements, Emily J Callander
OBJECTIVE: Preeclampsia is a serious pregnancy complication associated with substantial maternal and infant morbidity worldwide. The adverse outcomes related to preeclampsia increase healthcare costs, highlighting the importance of quantifying its economic burden to inform healthcare policy and resource allocation. This systematic review aimed to synthesize evidence on the economic burden of preeclampsia and identify key cost drivers. METHODS: MEDLINE, PubMed, Web of Science, and the Cochrane Library were searched for English-language studies published between 2014 and 2024. Studies reporting healthcare resource utilization or costs associated with preeclampsia were included. The review followed PRISMA 2020 guidelines and was registered in PROSPERO (CRD42025650091). RESULTS: Of 3,107 records identified, 12 studies were included; most were conducted in high-income countries. All cost estimates were converted to 2024 US dollars for comparability. Direct medical costs ranged from US$109.84 to US$87,339.71, with a mean cost of US$33,585.48 per patient. National healthcare system costs were estimated at €6.5-€9.1 million in Ireland and US$2.18 billion in the United States. CONCLUSION: Preterm birth was identified as a major driver of economic burden, with earlier gestational age significantly increasing maternal and infant costs. Indirect costs and regional disparities remain underexplored, highlighting important gaps for future research.
Journal of the International Society of Sports NutritionZiyu Wang, Bopeng Qiu, Jinxuan Bao, Penglin Diao, Michael Hamlin, Juan Del Coso, Jozo Grgic, Carl Petersen
BACKGROUND: Evidence for acute caffeine supplementation in swimming remains inconsistent across reviews, likely due to between-study heterogeneity and methodological differences. METHODS: Five databases were searched for randomized placebo-controlled crossover trials exploring the effects of caffeine on swimming performance in competitive swimmers. Performance outcomes were pooled as standardized mean differences (SMD; Hedges' g), with time outcomes sign-reversed so that positive values indicated improved performance. Dependence among multiple outcomes within studies was addressed using three-level random-effects models (REML). As a supplementary, interpretable metric, log ratios of means (lnRoM) were meta-analysed and expressed as percentage change. Post-exercise blood lactate (mmol/L) was pooled as mean differences (MD). Risk of bias was assessed using RoB 2 and certainty of evidence using GRADE. Prespecified exploratory moderator analyses examined potential effect modification (dose, timing, distance, administration form, stroke, gender, and athlete level). RESULTS: Thirteen studies were included (144 men and 48 women), which contributed 28 performance effect sizes. Caffeine improved swimming performance (SMD = 0.57, 95% CI: 0.20 to 0.94; p = 0.005), corresponding to a +1.71% improvement in lnRoM (95% CI: +1.01% to +2.41%; p < 0.001). Heterogeneity was substantial (I²total = 64.7%) and primarily between studies. Eight studies contributed 24 blood lactate effect sizes. In the meta-analysis, caffeine increased post-test lactate (MD = 0.85 mmol/L, 95% CI: 0.22 to 1.49; p = 0.016) with high heterogeneity (I²total = 76.5%). Exploratory moderator analyses suggested a possible dose-related pattern for swimming performance, with larger pooled effects at ≥6 mg/kg (SMD = 0.95, 95% CI: 0.52 to 1.38) than at <6 mg/kg (SMD = 0.22, 95% CI: -0.15 to 0.60; p difference = 0.017). Other performance moderators did not show clear between-subgroup differences. For lactate, exploratory subgroup analyses suggested larger increases in freestyle and short-distance events, although these patterns were more sensitive to modelling assumptions and should be interpreted cautiously. CONCLUSION: Acute caffeine ingestion confers a moderate ergogenic benefit for swimming performance (SMD = 0.57, 1.7% improvement) and is associated with higher post-test blood lactate (MD = 0.85 mmol/L). Dose (≥6 mg/kg) may be associated with larger performance benefits, whereas lactate responses appear more pronounced in freestyle and shorter events. However, these subgroup findings are hypothesis-generating and require exploration.