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PubMed2026

Association of media use with sleep of children and adolescents: an umbrella review.

Adequate sleep is essential for child and adolescent development, driving extensive research across scientific disciplines. This umbrella review provides a comprehensive overview of existing evidence on media consumption and sleep and thereby lays the foundation for identifying key concepts and gaps. An inclusive systematic search for reviews reporting literature searches was conducted in 02/2021 and updated last in 09/2024. Methodological quality of the included reviews was assessed using AMSTAR-2. We included 84 reviews reporting on the association between media use and sleep in individuals aged 0-18 years. The field is dominated by reviews of low methodological quality, mainly including original cross-sectional studies with subjective measures in older children and adolescents. A total of 475 original articles were covered by the reviews; only 10 of them appeared in at least seven and at most nine reviews. Screen time generally had a negative impact on sleep, though evidence varied from very low to strong. Evidence for effects of conventional books on sleep remains inconclusive. High quality systematic reviews are needed to evaluate robust studies using objective measures of sleep and contemporary media use across all age groups up to adolescence and to explore the impact of non-digital media use on sleep, considering age and gender differences.

Humans↗

PubMed2026

Clinical applications of digital twin technology in In Vitro Fertilisation.

BACKGROUND: Digital twin technology, originating from aerospace and manufacturing industries, has emerged as a transformative tool in healthcare. In vitro fertilisation (IVF) faces persistent challenges including suboptimal embryo selection, unpredictable treatment outcomes, and limited personalisation of protocols. Despite advances in assisted reproductive technology, existing literature exhibits fragmentation: artificial intelligence applications in embryo selection, ovarian stimulation, and endometrial assessment have been developed independently without systematic integration into comprehensive treatment frameworks. Digital twin technology offers unprecedented opportunities to create virtual replicas of biological systems, enabling real-time monitoring, predictive modelling, and personalised treatment strategies. AIM: This narrative review aims to critically examine the current applications of digital twin technology in IVF, evaluate its potential benefits and limitations, synthesize existing evidence into an integrative conceptual model, and identify future directions for implementation in reproductive medicine. METHOD: A comprehensive narrative review was conducted using PubMed, Scopus, Web of Science, and IEEE Xplore databases. A narrative review approach was selected over systematic review to accommodate the heterogeneity of evidence types in this emerging field, including theoretical frameworks, simulation studies, and proof-of-concept implementations that would be excluded from systematic reviews. Search terms included "digital twin," "IVF," "in vitro fertilisation," "assisted reproductive technology," "embryo selection," and "predictive modelling." Studies published between 2015 and 2025 were included, focusing on original research articles, systematic reviews, and proof-of-concept studies describing digital twin applications in reproductive medicine. RESULTS: Digital twin technology in IVF demonstrates significant potential across multiple domains including embryo development simulation, ovarian response prediction, endometrial receptivity modelling, and personalised stimulation protocols. Current applications integrate artificial intelligence, machine learning algorithms, time-lapse imaging, and omics data to create comprehensive virtual models. Early evidence suggests improvements in embryo selection accuracy, ovarian response prediction, and treatment protocol optimization, though large-scale randomized controlled trials remain limited. Implementation challenges include data integration complexity, computational requirements, regulatory considerations, and validation requirements. CONCLUSION: Digital twin technology represents a paradigm shift in IVF practice, offering personalised, predictive, and precision medicine approaches. This review synthesizes existing evidence to propose an integrative conceptual model for digital twin implementation across the IVF treatment spectrum, identifies critical knowledge gaps, and establishes research priorities to advance clinical translation. Despite current limitations, continued advancement promises improved success rates and patient outcomes.

Humans↗

PubMed2026

Co-location of services: an umbrella review to consider how primary care estates could be better used to support disadvantaged groups.

AIM: To examine how co-located community and health services in primary care could support disadvantaged groups. BACKGROUND: Co-locating services is thought to improve access, collaboration, and patient outcomes. There are thousands of primary care premises across the UK. At a time of stagnating or widening health inequalities, they present an ideal opportunity to support communities, especially in disadvantaged areas. METHOD: We conducted a systematic umbrella review. Articles were retrieved from Ovid MEDLINE and Ovid Embase with supplementary snowball and grey literature searches. Reviews of co-located services supporting disadvantaged groups in primary care between 2010 and February 2024 were included. Quality and risk of bias were assessed using the Joanna Briggs Institute checklist. Two reviewers assessed eligibility, extracted data and assessed quality. Outcomes relating to health, welfare, healthcare utilization, and activity and processes were assessed. Data were narratively synthesized using a convergent integrated approach. FINDINGS: 2626 studies were screened, supplemented by snowball and grey literatures searches. Thirteen reviews were included for synthesis. One review included meta-analysis. Three models of care were identified; legal advice, welfare advice, and complementary health care. Data were synthesized according to themes: access and engagement, quality of care, efficiency, improved health, and improved social factors. We found co-located services can improve access to care, engagement in treatment, and quality of care for disadvantaged groups. Improvements to social determinants of health and mental health and well-being outcomes were reported. Findings were inconsistent when considering the impact of co-location on efficiency. We conclude that co-located services in primary care have the potential to improve identification of people most in need and improve their access to high quality health care and social support. Policy makers and practitioners should maximize the use of primary care estates to support disadvantaged groups and communities.

Humans↗

PubMed2026

Circular RNAs in amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by the progressive loss of motor neurons, with most cases lacking a clear genetic basis. Emerging evidence highlights the involvement of non-coding RNAs, particularly circular RNAs (circRNAs), in disease onset and progression. Here, we investigated circRNAs implicated in ALS and related motor neuron diseases (MNDs). Here, we provide a general overview of circular RNA metabolism and cellular functions. We then present our systematic literature review that identified ALS-associated circRNAs, followed by in silico analyses of 15 circular RNA candidates that were selected based on the most compelling data regarding ALS. Our results revealed that several circular RNAs regulate ALS-related genes, such as unfolded protein response, oxidative stress, cell cycle regulation, and apoptosis. Protein-RNA interaction analysis further showed that ALS-related circRNAs can sponge 20 RNA-binding proteins. Additionally, molecular docking analysis demonstrated that ALS-associated FUS variants significantly alter its binding affinity to circular RNAs. RNA-seq data from ALS patients confirmed significant alterations in the expression of host genes of ALS-related circRNAs and hub proteins in ALS-affected CNS tissues. Collectively, our findings identify circRNAs as potential key contributors to ALS pathogenesis.

Amyotrophic Lateral Sclerosis↗

PubMed2026

Trends in demographic and health survey publications based on a bibliometric analysis.

BACKGROUND: The Demographic and Health Surveys (DHS) Program, launched in 1984, provides high-quality population health data that underpins a vast body of global health research. However, the scale and growth patterns of DHS-based publications remain underexplored, particularly as donor funding uncertainties threaten program sustainability. OBJECTIVE: We examine temporal trends in DHS-based research output from 1984 to 2025, quantifying growth patterns and publication delays to inform understanding of the program's global research expansion. METHODS: A systematic bibliometric review was conducted following PRISMA guidelines across PubMed, Scopus, Web of Science, Dimensions, Wiley, and CINAHL. Eligible peer-reviewed articles using DHS data between 1984 and 2025 were identified. Annual publication counts were analyzed, segmented regression identified growth inflection points, and timeliness was assessed by calculating lag between survey completion and publication. RESULTS: Over 10,000 DHS-based publications were identified. Annual output rose from isolated studies in the 1980s to several hundred annually by the 2010s. Segmentation analysis revealed two rapid growth phases: a 56-publications/year increase from 2004-2012, and a 71-publications/year increase from 2012 to 2024. Despite this growth, median lag from survey completion to publication remained approximately 5 years, with only a modest recent improvement (Kendall's τ =  -0.623, p < 0.001). CONCLUSION: DHS data have fueled exponential growth in global health research over four decades, confirming their vital role in evidence generation. However, persistent publication delays highlight the need to shorten the pathway from data collection to dissemination through strengthened research capacity in low- and middle-income countries. Sustained funding is essential to maintain this critical evidence source.

Bibliometrics↗

PubMed2026

Practical Saudi Guidelines on management of moderate-to-severe psoriasis: 2026 update.

BACKGROUND: Psoriasis is a chronic, immune-mediated inflammatory skin disease that affects approximately 5.3% of the population in the Kingdom of Saudi Arabia (KSA). Thus, we aim to develop updated evidence-based clinical practice guidelines for the management of adults and pediatric patients with moderate-to-severe plaque psoriasis in the KSA. METHODS: These guidelines followed the "Grading of Recommendations, Assessment, Development, and Evaluation" (GRADE) methodology. We conducted a systematic literature review of PubMed, EMBASE, and the Cochrane Library for high-quality evidence published between 2020 and 2026. The panel developed 31 PICO questions that address key treatment considerations for moderate-to-severe psoriasis. RESULTS: We established 27 evidence-based recommendations and 4 good-practice statements addressing key aspects of moderate-to-severe psoriasis management. These guidelines strongly recommend adopting the Psoriasis Area and Severity Index (PASI) 90 as the primary treatment goal over PASI 75. For adult patients, the guidelines recommend biologic therapies, including interleukin (IL)-17 inhibitors, IL-23 inhibitors, IL-12/23 inhibitors, and tumor necrosis factor (TNF)-α inhibitors, for better disease control. For pediatric patients, the guidelines recommend early initiation of biologic therapy, with etanercept, secukinumab, ixekizumab, and adalimumab as preferred options. CONCLUSION: These Saudi national guidelines offer a comprehensive, evidence-based framework for managing moderate-to-severe psoriasis in adults and pediatric patients.

Humans↗

PubMed2026

Facilitators and Barriers to Volunteers' Involvement in Palliative Care: A Qualitative Meta-Synthesis.

OBJECTIVE: This study aims to systematically synthesize qualitative evidence on facilitators and barriers to volunteer involvement in palliative care services, providing insights to inform strategies for strengthening volunteer support systems. METHODS: PubMed, Web of Science, Embase, Cochrane Library, Medline, EBSCO, ProQuest, China National Knowledge Infrastructure, Wanfang, VIP, and Sinomed were searched from inception to December 2025 to identify qualitative studies examining factors influencing volunteer participation in palliative care. Methodological quality was assessed using the Joanna Briggs Institute Critical Appraisal Checklist for Qualitative Research. Data were analyzed using Thomas and Harden's thematic synthesis approach and managed using NVivo 12.0 software, following the Enhancing Transparency in Reporting the Synthesis of Qualitative Research (ENTREQ) guidelines. RESULTS: Thirty-one studies involving 1042 participants were included, yielding 68 findings. Facilitators included intrinsic motivation and meaning-making at the individual level; supportive relationships and teamwork at the interpersonal level; structured support and professional recognition at the organizational level; social recognition and resource integration at the community level; and institutional safeguards and governmental incentives at the policy level. Barriers included emotional burden and limited competencies at the individual level; relationship conflicts and insufficient collaboration at the interpersonal level; management deficiencies at the organizational level; community resource imbalances at the community level; and inadequate regulations and incentives at the policy level. CONCLUSION: Volunteer participation in palliative care is influenced by multiple interacting factors. Strengthening training and support systems, enhancing team collaboration, and improving institutional frameworks may help sustain volunteer engagement and improve the quality of palliative care services.

Palliative Care↗

PubMed2026

GPR3 in neuro-metabolic-immune-reproductive nexus - a potential therapeutic target for Multi-System diseases.

BACKGROUND: GPR3(G-protein-coupled receptor 3), an orphan G-protein-coupled receptor (GPCR) with constitutive Gs activity, is expressed in the brain, liver, ovary, and other tissues, regulating cell proliferation, differentiation, and apoptosis across the nervous, reproductive, immune, and metabolic systems. This review synthesizes evidence on its integrated signaling and physiological functions to address the lack of a comprehensive multisystem pathophysiology overview. METHODS: A systematic literature search was conducted on PubMed and Web of Science, using keywords such as "GPR3", "GPCR", "neurodegeneration", "metabolism", "immune", "reproduction", "agonist", "inhibitor", and "therapeutic target". This search identified GPR3's roles in neurodegenerative diseases, immune inflammation, reproduction, and energy metabolism. The analysis focused on signaling pathways, ligand regulation, and therapeutic potential. RESULTS: The research indicates that GPR3 is involved in neuronal survival, synaptic plasticity, and microglial activity via the cAMP/PKA, PI3K/Akt, and β - arrestin pathways. It promotes amyloid - β formation in Alzheimer's disease (AD), yet provides neuroprotection in Parkinson's disease (PD) models. It may contribute to anxiety/depression - like states, maintain oocyte meiotic arrest in the ovary, and activate thermogenic genes in adipose tissue. GPR3 modulates immune responses. Using oleic acid (OA) and diphenyleneiodonium (DPI) as activators, and AF64394 and cannabidiol (CBD) as antagonists, it shows potential in disease models. CONCLUSION: GPR3 acts as a central molecular hub integrating neural, metabolic, immune, and reproductive signaling, highlighting its potential as a therapeutic target for chronic multisystem disorders. However, its dual roles in certain pathologies and translation challenges necessitate further research.

Humans↗

PubMed2026

Thymosin-ɑ1 for people with chronic hepatitis B.

RATIONALE: Chronic hepatitis B is a global public health concern. It is caused by infection with the hepatitis B virus (HBV). The goal of treating chronic HBV infection is to prevent progression to chronic hepatitis, cirrhosis, hepatic decompensation, liver failure, hepatocellular carcinoma, and death. Individual studies have evaluated various immunomodulatory therapies with inconsistent results. Thymosin-ɑ1 is known to have antiviral effects; however, results of randomised clinical trials on the effects of thymosin-α1 as a potential treatment for people with chronic HBV have been inconsistent. OBJECTIVES: To assess the benefits and harms of thymosin-ɑ1 therapy in people with chronic hepatitis B. SEARCH METHODS: We searched the Cochrane Hepato-Biliary Group Controlled Trials Register, CENTRAL, MEDLINE, four other databases and six trials registers, in addition to reference checking, citation searching, and contacting study authors to identify trials for inclusion. The latest search date was 10 June 2026. ELIGIBILITY CRITERIA: We included randomised controlled trials (RCTs) that evaluated thymosin-α1 at any dose, route of administration, or formulation type, in people with chronic hepatitis B regardless of age, sex, or ethnicity. Thymosin-α1 could have been administered as monotherapy, in combination with an additional drug, or in addition to standard medical treatment and compared with placebo, no intervention, the same additional drug, or the same standard medical treatment. OUTCOMES: Our critical outcomes were all-cause mortality, serious adverse events, and health-related quality of life. Among our important outcomes were HBV-related morbidity, HBV-related mortality, non-serious adverse events, and the proportion of people without histological improvements. RISK OF BIAS: We used the Cochrane Risk of bias 2 tool (RoB 2) to assess risk of bias. SYNTHESIS METHODS: We followed Cochrane methods. We conducted meta-analyses for predefined outcomes using data from the longest follow-up period, irrespective of the risk of bias judgements. We presented dichotomous outcome results as risk ratios (RRs) and continuous outcome results as mean differences, with 95% confidence intervals (CIs) at their longest follow-ups. We used the random-effects model for our primary analyses. We used GRADE to assess the certainty of the evidence for each outcome. INCLUDED STUDIES: We included 10 RCTs conducted in Bangladesh, China, Italy, Korea, Singapore, and Taiwan, with 1349 randomised participants (range: 12 to 690; 1045 (77.5%) were male). Among the trials reporting age, none included participants younger than 17 years (age range: 17 to 75 years). The trials were published between 1991 and 2018, and assessed thymosin-ɑ1 in adults with chronic hepatitis B infection, with or without comorbidities. Only two trials mentioned comorbidities (cirrhosis and acute-on-chronic liver failure). The trials compared thymosin-ɑ1, with or without a cointervention, with placebo or no intervention, or with the same cointervention. The control interventions were placebos in two trials and no intervention in two. The remaining six trials administered co-interventions, such as interferon, pegylated interferon, lamivudine, and standard medical therapy (entecavir or tenofovir), and entecavir. Follow-ups ranged from six months to five years after the end of treatment (median: 12 months). Four trials were funded by industry, five by research grants, and one provided no information. All 10 trials (11 records) provided data on at least one outcome in our review. We identified no ongoing trials. Sixteen studies are awaiting assessment due to incomplete reporting. We received no responses to our enquiries. SYNTHESIS OF RESULTS: Thymosin-ɑ1, compared with the control interventions, may reduce all-cause mortality (RR 0.53, 95% CI 0.29 to 0.96; I² = 0%; 3 studies, 907 participants; very low-certainty evidence), serious adverse events (RR 0.72, 95% CI 0.53 to 0.99; I² = 0%; 5 studies, 1056 participants; low-certainty evidence), HBV-related mortality (RR 0.53, 95% CI 0.29 to 0.96; I² = 0%; 3 studies, 907 participants; very low-certainty evidence), non-serious adverse events (RR 0.47, 95% CI 0.27 to 0.83; I² = 0%; 5 studies, 300 participants; very low-certainty evidence), and may have little to no effect on health-related quality of life (MD 0.70, 95% CI -2.55 to 3.95; I² not applicable; 1 study, 161 participants; very low-certainty evidence; score range: 0 to 100; the higher the score, the better) and on histological improvement (RR 0.51, 95% CI 0.13 to 2.06; I² = 74%; 2 studies, 702 participants; very low-certainty evidence). The evidence is very uncertain about the effect of thymosin-ɑ1 on hepatitis B-related morbidity (RR 0.86, 95% CI 0.54 to 1.40; I² = 3%; 3 studies, 854 participants; very low-certainty evidence). We judged the certainty of evidence to be low for serious adverse events and very low for the remaining outcomes. Reasons for downgrading were mainly due to study limitations, including overall high or some concerns for risk of bias; imprecision of the pooled effect estimates (including wide or very wide confidence intervals crossing the line of no effect, and small participant numbers); and inconsistency due to substantial heterogeneity (I² = 74%). The test for subgroup differences provided no evidence of differences in effect according to thymosin‑α1 administration for any outcome (P ≥ 0.05). AUTHORS' CONCLUSIONS: We assessed the certainty of evidence as very low for all outcomes except for serious adverse events (low). Therefore, we are not sure whether thymosin-α1 monotherapy versus placebo or no intervention, or with the same co-interventions, reduces all-cause mortality, serious adverse events, HBV-related mortality, and non-serious adverse events, nor whether it has any effect on quality of life (based on one trial) and histological improvement. The effect of thymosin-ɑ1 on HBV-related morbidity is very uncertain. We observed no statistically significant differences between trials with and without cointerventions. We found no ongoing trials. FUNDING: This Cochrane review had no dedicated funding. REGISTRATION: Protocol available via DOI: 10.1002/14651858.CD014610.

Humans↗

PubMed2026

Holmium laser enucleation of the prostate for the treatment of lower urinary tract symptoms in men with benign prostatic hyperplasia.

RATIONALE: A range of surgical options is available for the treatment of benign prostatic hyperplasia (BPH), including holmium laser enucleation of the prostate (HoLEP). The evidence is unclear regarding differences in functional, perioperative, and morbidity outcomes between these modalities. OBJECTIVES: To assess the effects of holmium laser enucleation of the prostate compared with other surgical treatments for lower urinary tract symptoms in men with benign prostatic hyperplasia. SEARCH METHODS: We searched multiple databases (including MEDLINE, Embase, CENTRAL, Web of Science, LILACS, and the International HTA database), trial registries, and conference abstracts through April 08, 2026. ELIGIBILITY CRITERIA: We only included randomized trials of men over 40 years of age with a prostate volume of at least 20 mL (assessed by digital rectal examination, ultrasound, or conventional imaging) who exhibited lower urinary tract symptoms (LUTS) defined by an International Prostate Symptom Score (IPSS) of eight or greater undergoing surgical interventions for BPH. OUTCOMES: The critical outcomes measured were the urologic symptoms score, the quality-of-life score, and major adverse events. The important outcomes measured were: re-treatment, erectile function, ejaculatory function, transfusions, acute urinary retention, indwelling urinary catheter duration, and hospital stay duration. RISK OF BIAS: We used the Cochrane risk of bias tool (RoB 1) to assess for potential sources of bias on a study and outcome level basis. SYNTHESIS METHODS: We pooled outcome data using the random-effects model and performed meta-analyses using the Mantel-Haenszel method. We assessed statistical heterogeneity in the pooled data by visually inspecting forest plots and using the I2 statistic to quantify it. We used the GRADE framework to assess the certainty of evidence. INCLUDED STUDIES: We included 52 trials that included 6242 participants that compared HoLEP to other surgical interventions for benign prostatic hyperplasia. The median age of participants across the studies ranged from 65 to 74 years. The baseline prostate volume ranged from 30 cc to 142 cc. Baseline IPSS scores ranged from 19.6 to 28.6 (range 0-35). SYNTHESIS OF RESULTS: We prioritized comparing HoLEP with transurethral resection of the prostate (TURP) at short-term follow-up (up to 12 months), because TURP is the long-standing reference standard and the predominant comparator in randomized surgical trials. Findings for the four remaining comparisons (laser ablation, alternative energy source enucleation, other minimally invasive therapies, and simple prostatectomy), for long-term follow-up, and for all remaining outcomes are reported in full in the review. Compared to TURP, at short-term follow-up: Critical outcomes - HoLEP may result in little to no difference in short-term urologic symptom scores measured using the IPSS (range 0 to 35; lower values reflect fewer symptoms) (MD -0.67, 95% CI -1.20 to -0.14; I² = 93%; 14 studies, 1666 participants, low-certainty evidence). - HoLEP may result in little to no difference in short-term quality of life (range 0 to 6; lower values reflect better quality of life) (MD -0.04, 95% CI -0.23 to 0.15; I² = 73%; 6 studies, 876 participants, low-certainty evidence). - HoLEP may result in little to no difference in short-term major adverse events (RR 0.75, 95% CI 0.35 to 1.58; I² = 0%; 10 studies, 1147 participants, low-certainty evidence). Important outcomes - HoLEP likely results in little to no difference in re-treatment (RR 0.45, 95% CI 0.14 to 1.50; I² = 0%; 8 studies, 813 participants, moderate-certainty evidence). - HoLEP likely results in little to no difference in erectile function (MD -0.03, 95% CI -0.47 to 0.42; I² = 0%; 3 studies, 518 participants, moderate-certainty evidence). - Ejaculatory function: we did not find any data for this outcome. - HoLEP likely reduces the need for blood transfusion (RR 0.19, 95% CI 0.09 to 0.42; I² = 0%; 15 studies, 1755 participants, moderate-certainty evidence). AUTHORS' CONCLUSIONS: Compared with TURP, HoLEP may achieve similar relief of urologic symptoms, similar quality of life, and similar rates of major adverse events in the first 12 months after surgery, and probably similar re-treatment rates and erectile function. HoLEP likely reduces the need for blood transfusion; this is the only advantage of HoLEP that the randomized evidence, as summarized here, supports as clinically important. There was insufficient evidence to assess outcomes in the subset of individuals with larger prostates or on anticoagulation. Future research should prioritize long-term trials reporting sexual function and urinary incontinence outcomes, recruit men with very large prostates (≥ 150 cc) or on anticoagulation therapy, and evaluate cost-effectiveness and training requirements. FUNDING: No external funding was received for this review. REGISTRATION: The protocol for this review was published in the Cochrane Database 2019 (https://doi.org/10.1002/14651858.CD013291).

Humans↗

PubMed2026

Pharmacological therapies for the prevention of fractures in men.

RATIONALE: Pharmacological therapies for fracture prevention usually target osteoporosis, a skeletal disorder characterised by compromised bone mass or quality (or both). As most participants in osteoporosis trials are women, a review of pharmacological therapies for fracture prevention in men was warranted. OBJECTIVES: To determine the benefits and harms of bisphosphonates, parathyroid (PTH) or parathyroid-related protein (PTHrP) analogues, denosumab, and romosozumab therapy for the prevention of fractures in men. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, and two trial registries (ClinicalTrials.gov and WHO ICTRP) until 14 October 2025, with no restrictions on date or language of publication. ELIGIBILITY CRITERIA: We included randomised controlled trials that compared bisphosphonates, PTH or PTHrP analogues, denosumab, or romosozumab (alone or with calcium or vitamin D, or both) with placebo, other drugs, or non-pharmacological therapies in men aged 50 years or older. Our primary comparison was bisphosphonates versus placebo. OUTCOMES: Critical outcomes were incidence of hip fractures, symptomatic vertebral fractures, other (not hip or vertebral) fractures, disability, participants with adverse events, study withdrawals due to adverse events, and participants with serious adverse events. Our primary time point was the final time point reported in the trials. RISK OF BIAS: We used Cochrane's RoB 2 tool to assess risk of bias. SYNTHESIS METHODS: We used a random-effects model for meta-analysis employing the Mantel-Haenszel approach, and the DerSimonian and Laird method to estimate between-trial variance. We assessed the certainty of evidence using GRADE. INCLUDED STUDIES: Seventeen trials (4132 participants) met our inclusion criteria. The average age of participants ranged from 52 to 73 years. Twelve trials used a placebo comparator versus bisphosphonate (7 trials, 2548 participants), PTH or PTHrP analogues (4 trials, 569 participants), denosumab (1 trial, 240 participants), and romosozumab (1 trial, 244 participants). For the other planned comparisons, a bisphosphonate was compared to vitamin D/vitamin D analogues (2 trials, 434 participants), to calcitonin (1 trial, 32 participants), to PTH or PTHrP analogues (1 trial, 19 participants), or to another bisphosphonate (1 trial, 301 participants), and one trial compared a bisphosphonate plus calcium to calcium tablets alone (46 participants). SYNTHESIS OF RESULTS: Placebo-controlled trials were largely susceptible to bias in selection of the reported result (83%), while most trials without a placebo control were also susceptible to bias arising from the randomisation process (100%) and in measurement of the outcome (80%). We are very uncertain about the effect of bisphosphonates on the incidence of hip fractures, symptomatic vertebral fractures, or other (non-hip non-vertebral) fractures compared to placebo at the final follow-up (up to two years). We downgraded the certainty of evidence once for risk of bias, twice for imprecision (very low event rates), and once for suspected publication bias. The certainty of evidence for incidence of other fractures was further downgraded for indirectness, as it was unclear if hip fractures were also included in the outcome. At up to two years, 2/875 participants (2 per 1000) in the bisphosphonate group reported hip fractures compared with 2/760 (3 per 1000) in the placebo group (risk ratio (RR) 0.73, 95% confidence interval (CI) 0.06 to 8.51; I² = 36%; 4 trials, 1635 participants); 5/1021 (4/1000) participants in the bisphosphonate group had a symptomatic vertebral fracture compared to 7/855 (8/1000) participants in the placebo group (RR 0.49, 95% CI 0.14 to 1.74; I² = 0%; 5 trials, 1876 participants); 25/1130 participants (16/1000) in the bisphosphonate group reported other (non-hip non-vertebral) fractures compared to 19/913 participants (21/1000) in the placebo group (RR 0.78, 95% CI 0.42 to 1.45; I² = 0%; 6 trials, 2043 participants). Bisphosphonates probably do not increase the risk of adverse events: 1024/1374 participants (746/1000) receiving bisphosphonates reported adverse events compared to 826/1174 participants (704/1000) receiving placebo (RR 1.06, 95% CI 0.93 to 1.19; I² = 75%; 7 trials, 2548 participants; moderate-certainty evidence) or serious adverse events: 329/1329 participants (272/1000) receiving bisphosphonate reported serious adverse events compared to 323/1128 participants (286/1000) receiving placebo (RR 0.95, 95% CI 0.84 to 1.08; I² = 0%; 6 trials, 2457 participants; moderate-certainty evidence). We downgraded the certainty of evidence once due to potential bias for adverse events and serious adverse events. We are very uncertain if bisphosphonates result in more withdrawals due to adverse events: 41/1374 participants (25/1000) in the bisphosphonate group withdrew due to adverse events compared with 43/1174 participants (37/1000) in the placebo group (RR 0.68, 95% CI 0.39 to 1.18; I² = 37%; 7 trials, 2548 participants; very low-certainty evidence). We downgraded the certainty of evidence once for risk of bias, once for indirectness, and once for imprecision. No trial reported disability. We are very uncertain about the effects of PTH or PTHrP analogues, denosumab, or romosozumab compared to placebo on fracture outcomes. We are very uncertain about the effects of PTH/PTHrP analogues on total adverse events, withdrawals due to adverse events, and serious adverse events. Denosumab may not increase the risk of adverse events or serious adverse events compared to placebo, while the evidence for withdrawals due to adverse events is very uncertain. Romosozumab probably does not increase the risk of adverse events and may not increase the risk of serious adverse events or result in more withdrawals due to adverse events. AUTHORS' CONCLUSIONS: We are very uncertain about the effects of bisphosphonates compared to placebo on the incidence of hip fractures, symptomatic vertebral fractures, or other (non-hip non-vertebral) fractures in men at up to two years of use. Bisphosphonates probably do not increase the risk of adverse events or serious adverse events, and we are very uncertain if they result in more withdrawals due to adverse events. We downgraded the certainty of evidence for indirectness, imprecision (low event rate), and serious risk of bias in selection of the reported result, as it was unclear if all studies fully reported every fracture. We found similar results for PTH or PTHrP analogues, denosumab, or romosozumab versus placebo. Larger, longer placebo-controlled studies are needed to determine whether pharmacological therapies are beneficial for reducing fractures in men. FUNDING: This Cochrane review had no dedicated funding. REGISTRATION: Protocol (2021): https://doi.org/10.1002/14651858.CD014707.

Humans↗

PubMed2026

Long-term consequences of childhood sexual abuse: An umbrella review of diagnostic meta-analyses.

BACKGROUND: Childhood sexual abuse (CSA) is a public health issue with an estimated worldwide prevalence of 12.7%, potentially leading to a host of lifelong and significant mental, physical, and behavioral health. The aim of this study was to comprehensively map the long-term consequences of childhood sexual abuse on physical, psychiatric, and behavioral health outcomes. METHODS: An umbrella review of meta-analyses of observational studies, registered on PROSPERO, was conducted to examine the diverse repercussions of childhood sexual abuse on adult health. Three bibliographic databases (PsycINFO, PubMed and Scopus) were searched from the inception of the respective databases to November 1st, 2022. Thirty-eight meta-analyses representing about 20 million individuals were analyzed, revealing a range of long-lasting consequences associated with CSA. RESULTS: Among physical pathologies, cervical cancer and functional neurological syndromes emerged as the most prominent, exhibiting significantly elevated odds ratios (ORs) of 4.18 IC95% and 3.30 IC95%, respectively. Sleep disorders and borderline personality disorders were the most prevalent mental health disorders associated with CSA, with respective ORs of 16.17 IC95% and 5.96 IC95%. Early sexual initiation (OR=3.59 IC95%, sexual assault (OR=3.36 IC95%, and prostitution (OR=3.24 IC95%) emerged as the most common behavioral consequences. Notably, no significant differences in the consequences of CSA were observed between men and women, except for reproductive health outcomes. DISCUSSION: When faced with certain pathologies, clinicians should consider and discuss sexual abuse with their patients. The consequences of abuse have a multifactorial origin, which is a weakness, as are the problems of defining abuse. The strength of our study is that it lists the consequences published in high-quality studies. CONCLUSION: This umbrella review provides compelling evidence of the profound and far-reaching impact of childhood sexual abuse on a broad spectrum of physical, mental, and behavioral health issues.

Humans↗

PubMed2026

Strategies to improve recruitment to randomised trials.

BACKGROUND: Recruiting participants to randomised controlled trials (RCTs) is challenging. Identifying effective recruitment strategies would benefit health research: poor recruitment leads to underpowered trials, reducing the reliability of findings and increasing the risk of wasted resources, ethical concerns, and trial failure. Evidence to inform recruitment strategies is increasingly generated through Studies Within A Trial (SWATs), which are methodological studies embedded within host RCTs. This is an update of a review last published in 2018. OBJECTIVES: Primary: to quantify the effects of strategies to improve recruitment of participants to RCTs. Secondary: to evaluate recruitment strategies' cost-effectiveness and impact on retention, and the equity, diversity, and inclusion (EDI) characteristics of recruited participants. SEARCH METHODS: We used MEDLINE, Embase, and six other databases to identify the studies included in the review. We also sought unpublished recruitment SWATs through social media and targeted email dissemination to trial methodology networks. The latest search date was 16 February 2023. SELECTION CRITERIA: We included randomised SWATs evaluating trial recruitment strategies embedded in healthcare and non-healthcare trials. We excluded quasi-randomised, hypothetical, questionnaire-only, retention-only, or clinician incentive studies. DATA COLLECTION AND ANALYSIS: Primary outcome: proportion of eligible participants or centres recruited. SECONDARY OUTCOMES: cost-effectiveness, retention rates, and EDI characteristics of included participants. We conducted random-effects meta-analysis for strategies evaluated in at least two studies; otherwise, we synthesised results narratively. We reported effects as risk differences (RDs) with 95% confidence intervals (CIs), and assessed between-trial heterogeneity. We used GRADE to assess the certainty of evidence for the primary outcome. We expressed cost-effectiveness as the incremental cost per additional participant recruited in pounds sterling (GBP). MAIN RESULTS: We identified 91 eligible studies (53 new to this update), providing 94 comparisons and involving at least 176,747 participants. Eighty-one studies involved strategies aimed at trial participants, while 10 evaluated strategies aimed at recruiters. All were healthcare studies. We found 65 recruitment strategies; 49 were evaluated in a single study. Only five strategies were supported by high-certainty evidence according to GRADE criteria, and we focus on these strategies in the summary below. Open-label trials versus blinded, placebo trials. Open-label trials recruited more participants than blinded trials (RD 10%, 95% CI 8% to 12%; 3 studies, 9004 participants), corresponding to approximately 10 additional participants per 100 approached. The studies involved mostly women in the UK and Estonia. No cost or retention data were reported. Telephone reminder versus no telephone reminder. Telephone reminders to people who did not respond to an initial postal invitation boosted recruitment by 6% (95% CI 3% to 9%; 2 studies, 1450 participants), in trials with low underlying recruitment (we are less certain for trials with over 10% recruitment). The studies involved people with a mean age of 58 years in Canada and Norway. No cost or retention data were reported. Recruitment primer letter versus no letter. Pre-recruitment letters and leaflets designed to encourage participation made little or no difference to recruitment (absolute improvement 1%, 95% CI -1% to 2%; 2 studies, 5376 participants), and were associated with increased costs compared to not sending a primer (incremental cost: GBP 2.08). The studies involved mostly older white people in the UK and Ireland. Multimedia information via a digital link/QR code plus paper participant information leaflet (PIL) versus paper PIL alone. This made little or no difference to recruitment (absolute improvement 0%, 95% CI -1% to 1%; 7 studies, 11,612 participants) and retention (absolute improvement 0%, 95% CI -2% to 3%; 5 studies, 7403 participants), and increased costs compared to not including multimedia information (incremental cost: GBP 0.78). The studies involved people in the UK. Optimised, user-tested PIL versus standard PIL. Optimising participant information leaflets (e.g. through user-testing the leaflet with the target population to shape its content, format, and appearance) made little or no difference to recruitment: absolute improvement was 0% (95% CI 0% to 1%; 6 studies, 27,805 participants). The studies involved people in the UK. Only one study reported EDI data; participants were mostly older women. No cost or retention data were reported. We had moderate-certainty evidence for 13 other strategies; confidence was often reduced because the results came from single studies. Seven strategies involved changes to how potential participants received information; four involved changes to trial conduct; one targeted the recruiter or recruitment site; and one tested non-monetary incentives. We had much less confidence in the other 47 comparisons because the studies had design flaws, were single studies, or had very uncertain results. Costs were reported in only 17 of 91 studies. Strategy impact on retention was reported in 15 studies. All but one study (99%) were from high-income countries. The most reported demographics were age (49 studies), sex (32 studies), gender (27 studies), and education level (16 studies). AUTHORS' CONCLUSIONS: The evidence on strategies to improve trial recruitment remains broad but lacks depth. Of 65 strategies evaluated, only five were supported by high-certainty evidence. Open-label trial designs and telephone reminders to non-responders increased recruitment, while optimised participant information leaflets, recruitment primer letters, and multimedia information provided alongside a paper participant information leaflet had little or no effect. Reporting of participant characteristics was poor, limiting assessment of equity, diversity, and inclusion across most studies. Evidence is heavily skewed toward high-income countries. Future research must prioritise evaluations in low-to-middle-income settings and consistently report cost, retention, and EDI outcomes. We strongly urge the methodology research community to strengthen the evidence base by prioritising replications of existing strategies over the development and testing of new ones. FUNDING: National Institute for Health and Care Research (Advanced Fellowship, Adwoa Parker, reference:NIHR302256). Health Research Board, Republic of Ireland, Evidence Synthesis Ireland (grant ESI-2021-001) REGISTRATION: This review updates an earlier Cochrane review, which was first published in 2002 and subsequently updated in 2007, 2010, and 2018. Previous versions of the review and their protocols are available at: https://doi.org/10.1002/14651858.MR000013.pub2 https://doi.org/10.1002/14651858.MR000013.pub3 https://doi.org/10.1002/14651858.MR000013.pub4 https://doi.org/10.1002/14651858.MR000013.pub5 https://doi.org/10.1002/14651858.MR000013.pub6.

Randomized Controlled Trials as Topic↗

PubMed2026

Metabolic engineering of Candida yeasts for biotechnological applications.

Candida yeasts represent a versatile yet underexploited platform for industrial biotechnology. These yeasts utilize a remarkably broad range of carbon sources, particularly for hydrophobic carbon sources, coupled with robust growth and diverse biosynthetic capacities, making them promising hosts for sustainable production of chemicals, fuels, and proteins. Despite these advantages, industrial deployment of Candida species has been hindered by concerns regarding opportunistic pathogenicity and the historical lack of efficient genetic manipulation tools, leading to a substantial gap between metabolic potential and practical utilization. Recent advances in functional genomics, genome editing, and systems metabolic engineering are rapidly overcoming these barriers, enabling more precise and efficient strain development. In this review, we systematically summarize recent progress in the metabolic engineering of Candida species as microbial cell factories, with particular emphasis on expanding genetic toolkits, utilizting renewable and non-conventional carbon sources, and biosynthesizing high-value compounds. In addition, we propose a biosafety-oriented classification framework to support their safe industrial deployment. Finally, we discuss current challenges and emerging opportunities, emphasizing that the synergy of synthetic biology and artificial intelligence-driven design holds the key to unlocking the biotechnological potential of Candida yeasts.

Candida↗

PubMed2025

Diagnostic and clinical utility of exome sequencing and chromosomal microarray in children with GDD/iD: a meta-analysis.

BACKGROUND: Global developmental delay/intellectual disability (GDD/ID) is among the most common neurodevelopmental disorders, with up to half of cases are attributed to genetic factors. Chromosome microarray (CMA) has traditionally been the primary genetic test for idiopathic GDD/ID. However, whole exome sequencing (WES) and whole genome sequencing (WGS) have recently emerged, substantially increasing diagnostic yields in these populations. METHODS: We conducted a comprehensive literature search of PubMed, Scopus, EMBASE, and the Cochrane Library from inception to April 29, 2025. Studies reporting the diagnostic utility of these tests in children with GDD/ID were included and analyzed. RESULTS: A total of 102 studies, comprising 55,752 children, were reviewed. The pooled diagnostic yield of WES was 0.37 (95% CI: 0.33-0.41; I2 = 93%), significantly higher than that of CMA at 0.19 (95% CI: 0.16-0.21; I2 = 95%). Subgroup analyses showed that WES yielded significantly higher diagnostic rates than CMA in both same-sample comparisons (OR = 2.27, 95% CI: 1.08-4.78) and different-sample comparisons (OR = 1.65, 95% CI: 1.15-2.37). Only one study evaluated WGS, reporting a diagnostic yield of 0.27. Meta-regression revealed a significant association between CMA diagnostic yield and the proportion of male participants (p < 0.01), but not with WES. No significant difference in diagnostic utility was observed between isolated GDD/ID and GDD/ID with comorbidities. CONCLUSION: In children with unexplained GDD/ID, WES demonstrates superior diagnostic and clinical utility compared to CMA. Incorporating WES as a first-line investigation in the diagnostic evaluation of GDD/ID may be warranted.

Humans↗

PubMed2026

Comparing the Efficacy of Mechanochemical Ablation Versus Radiofrequency Ablation for Treating Great Saphenous Vein Incompetence: A Meta-Analysis.

BACKGROUND: The objective of this meta-analysis was to compare the efficacy of mechanochemical ablation (MOCA) and radiofrequency ablation (RFA) in the treatment of great saphenous vein (GSV) incompetence. METHODS: Online databases including PubMed, Cochrane Library, Embase, and Web of Science were searched to collect randomized controlled trials (RCTs) and cohort studies comparing MOCA and RFA in the treatment of varicose veins in lower extremities from database inception to October 2025. Primary outcome was anatomic success. Secondary outcomes were visual analog scale (VAS), Aberdeen Varicose Vein Questionnaire score (AVVQ), and complications. Two reviewers independently screened the retrieved literature, extracted data, and assessed the risk of bias in the included studies. Subsequent analysis was performed using RevMan 5.3. RESULTS: A total of four RCTs, one cohort study and retrospective cross-sectional study involving 737 patients (380 MOCA patients and 357 RFA patients) were included. The meta-analysis results showed that the RFA group was significantly better than the MOCA group in short term and long term of anatomical success rate [(odds ratio [OR] = 0.38; 95% confidence interval [CI] (0.20, 0.71), P = 0.003), (OR = 0.17, 95% CI (0.06, 0.45), P = 0.0003)], but patients in the MOCA group had significantly lower perioperative period pain (mean difference [MD] = -4.48, 95% CI (-7.58, -1.37), P = 0.005] and required fewer days to return to normal activities (MD = -0.76, 95% CI, (-0.95, -0.57), P < 0.001). No significant differences were observed between the two groups in minor and major complications [(OR = 0.93, 95% CI (0.66, 1.33), P = 0.70), (OR = 1.30, 95% CI (0.32, 5.28), P = 0.72)] or quality of life scores (MD = -0.45, 95% CI (-2.53 to 1.63), P = 0.67). CONCLUSION: MOCA of GSV incompetence is an effective and safe method. Compared with RFA, it has lower postoperative pain score and faster recovery time. However, the anatomical success rates were significantly lower with MOCA than with RFA. Therefore, long-term follow-up to evaluate the impact on clinical results is required.

Humans↗

PubMed2026

Long-term hormone therapy for perimenopausal and postmenopausal women.

BACKGROUND: Hormone therapy is widely provided to control menopausal symptoms and has been used for the management and prevention of cardiovascular disease, osteoporosis and dementia in older women. This is an updated version of a Cochrane review first published in 2005. OBJECTIVES: To assess the long-term effects of prolonged use (at least one year) of hormone therapy on mortality, cardiovascular outcomes, cancer, gallbladder disease, fractures and cognition in perimenopausal and postmenopausal women. SEARCH METHODS: We used the Cochrane Gynaecology and Fertility Group Specialised Register, CENTRAL, MEDLINE, three other databases and two trial registers, together with reference checking, citation searching and contact with study authors to identify the studies included in the review. The latest search date was 26 September 2024. SELECTION CRITERIA: We included randomised, double-blind trials in which peri- or postmenopausal women took hormone therapy or placebo for at least one year. We included various oestrogen formulations, with or without progestogens. We focused on studies assessing hormone therapy's effects on long-term clinical outcomes, including death, coronary events and cancer. Hormone therapy's efficacy in managing menopausal symptoms was beyond the scope of this review, and is assessed in other Cochrane reviews. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies, assessed risk of bias and extracted data. We calculated risk ratios (RRs) for dichotomous data and mean differences (MDs) for continuous data, along with 95% confidence intervals (CIs). We assessed the certainty of the evidence using GRADE. MAIN RESULTS: We included 24 studies - with two newly added in this update - involving 45,660 participants. We derived nearly 70% of the data from two well-conducted studies: the Heart and Estrogen/progestin Replacement Study (HERS 1998) and the large, multi-component Women's Health Initiative research programme, which included two hormone therapy arms (WHI 1998). Across all the studies, most participants were postmenopausal American women with one or more comorbidities. The mean participant age in most studies was over 60 years. Only one included study focused on perimenopausal women. We present full results for all included studies with available data in the main review. The results presented below are drawn from WHI 1998, in which the combined hormone therapy arm and the oestrogen-only arm were run concurrently, with women assigned to the appropriate trial based on their uterus status. One study with 16,608 postmenopausal women with an intact uterus compared combined continuous hormone therapy (conjugated equine oestrogen and medroxyprogesterone acetate) to placebo, and measured outcomes at an average of 5.6 years of follow-up. Based on this study, combined continuous hormone therapy probably makes little to no difference to the risk of a coronary event (RR 1.17, 95% CI 0.95 to 1.44; moderate-certainty evidence). It may increase the risk of stroke (RR 1.39, 95% CI 1.09 to 2.09; low-certainty evidence) and venous thromboembolism (RR 2.03, 95% CI 1.55 to 6.64; low-certainty evidence). Compared to placebo, combined continuous hormone therapy probably increases the risk of breast cancer (RR 1.27, 95% CI 1.03 to 1.56; moderate-certainty evidence) and probably makes little to no difference to the risk of lung cancer (RR 1.06, 95% CI 0.77 to 1.46; moderate-certainty evidence). It may increase gallbladder disease requiring surgery (RR 1.64, 95% CI 1.30 to 2.06; 14,203 participants; low-certainty evidence), and probably reduces the risk of all clinical fractures (RR 0.78, 95% CI 0.71 to 0.86; moderate-certainty evidence). One study including 10,739 postmenopausal women who had undergone a hysterectomy compared oestrogen-only (conjugated equine oestrogen) hormone therapy to placebo, and measured outcomes at an average of seven years' follow-up. Based on this study, oestrogen-only hormone therapy probably makes little to no difference to the risk of coronary events (RR 0.94, 95% CI 0.78 to 1.13), venous thromboembolism (RR 1.32, 95% CI 1.00 to 1.74) and breast cancer (RR 0.79, 95% CI 0.61 to 1.01), all with moderate-certainty evidence. It may make little to no difference to the risk of lung cancer (RR 1.04, 95% CI 0.73 to 1.48; low-certainty evidence). Oestrogen-only hormone therapy probably increases the risk of stroke (RR 1.33, 95% CI 1.06 to 1.67) and gallbladder disease requiring surgery (RR 1.78, 95% CI 1.42 to 2.24), and probably reduces the risk of all clinical fractures (RR 0.73, 95% CI 0.65 to 0.80), all with moderate-certainty evidence. We judged most included studies to have a low risk of bias for most domains. The overall certainty of evidence for the main comparisons was moderate. The main limitation was that only about 30% of women were 50 to 59 years old at baseline, the age group most likely to consider hormone therapy for vasomotor symptoms. AUTHORS' CONCLUSIONS: Long-term follow-up of women using hormone therapy suggests that the risk profiles vary between combined hormone therapy and oestrogen-only therapy. Oestrogen-only hormone therapy probably makes little to no difference to coronary events, and probably increases the risk of stroke and gallbladder disease. It probably makes little to no difference in the risk of breast cancer, and probably reduces the risk of all fractures. Combined hormone therapy may increase the risk of thromboembolism and probably increases the risk of breast cancer. These results should be interpreted with caution as they are based on one study using oral hormone therapy, which may not represent the risks of the hormone therapy currently used in clinical practice.

Humans↗

PubMed2026

Magnesium sulphate for women at risk of preterm birth for neuroprotection of the fetus.

BACKGROUND: Magnesium sulphate is a common therapy in perinatal care. Its benefits when given to women at risk of preterm birth for fetal neuroprotection (prevention of cerebral palsy for children) were shown in a 2009 Cochrane review. Internationally, use of magnesium sulphate for preterm cerebral palsy prevention is now recommended practice. As new randomised controlled trials (RCTs) and longer-term follow-up of prior RCTs have since been conducted, this review updates the previously published version. OBJECTIVES: To assess the effectiveness and safety of magnesium sulphate as a fetal neuroprotective agent when given to women considered to be at risk of preterm birth. SEARCH METHODS: We searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) on 17 March 2023, as well as reference lists of retrieved studies. SELECTION CRITERIA: We included RCTs and cluster-RCTs of women at risk of preterm birth that assessed prenatal magnesium sulphate for fetal neuroprotection compared with placebo or no treatment. All methods of administration (intravenous, intramuscular, and oral) were eligible. We did not include studies where magnesium sulphate was used with the primary aim of preterm labour tocolysis, or the prevention and/or treatment of eclampsia. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed RCTs for inclusion, extracted data, and assessed risk of bias and trustworthiness. Dichotomous data were presented as summary risk ratios (RR) with 95% confidence intervals (CI), and continuous data were presented as mean differences with 95% CI. We assessed the certainty of the evidence using the GRADE approach. MAIN RESULTS: We included six RCTs (5917 women and their 6759 fetuses alive at randomisation). All RCTs were conducted in high-income countries. The RCTs compared magnesium sulphate with placebo in women at risk of preterm birth at less than 34 weeks' gestation; however, treatment regimens and inclusion/exclusion criteria varied. Though the RCTs were at an overall low risk of bias, the certainty of evidence ranged from high to very low, due to concerns regarding study limitations, imprecision, and inconsistency. Primary outcomes for infants/children: Up to two years' corrected age, magnesium sulphate compared with placebo reduced cerebral palsy (RR 0.71, 95% CI 0.57 to 0.89; 6 RCTs, 6107 children; number needed to treat for additional beneficial outcome (NNTB) 60, 95% CI 41 to 158) and death or cerebral palsy (RR 0.87, 95% CI 0.77 to 0.98; 6 RCTs, 6481 children; NNTB 56, 95% CI 32 to 363) (both high-certainty evidence). Magnesium sulphate probably resulted in little to no difference in death (fetal, neonatal, or later) (RR 0.96, 95% CI 0.82 to 1.13; 6 RCTs, 6759 children); major neurodevelopmental disability (RR 1.09, 95% CI 0.83 to 1.44; 1 RCT, 987 children); or death or major neurodevelopmental disability (RR 0.95, 95% CI 0.85 to 1.07; 3 RCTs, 4279 children) (all moderate-certainty evidence). At early school age, magnesium sulphate may have resulted in little to no difference in death (fetal, neonatal, or later) (RR 0.82, 95% CI 0.66 to 1.02; 2 RCTs, 1758 children); cerebral palsy (RR 0.99, 95% CI 0.69 to 1.41; 2 RCTs, 1038 children); death or cerebral palsy (RR 0.90, 95% CI 0.67 to 1.20; 1 RCT, 503 children); and death or major neurodevelopmental disability (RR 0.81, 95% CI 0.59 to 1.12; 1 RCT, 503 children) (all low-certainty evidence). Magnesium sulphate may also have resulted in little to no difference in major neurodevelopmental disability, but the evidence is very uncertain (average RR 0.92, 95% CI 0.53 to 1.62; 2 RCTs, 940 children; very low-certainty evidence). Secondary outcomes for infants/children: Magnesium sulphate probably resulted in little to no difference in severe intraventricular haemorrhage (grade 3 or 4) (RR 0.81, 95% CI 0.64 to 1.04; 6 RCTs, 6542 infants; moderate-certainty evidence) and may have resulted in little to no difference in chronic lung disease/bronchopulmonary dysplasia (average RR 0.92, 95% CI 0.77 to 1.10; 5 RCTs, 6689 infants; low-certainty evidence). Primary outcomes for women: Magnesium sulphate may have resulted in little or no difference in severe maternal outcomes potentially related to treatment (death, cardiac arrest, respiratory arrest) (RR 0.32, 95% CI 0.01 to 7.92; 4 RCTs, 5300 women; low-certainty evidence). However, magnesium sulphate probably increased maternal adverse effects severe enough to stop treatment (average RR 3.21, 95% CI 1.88 to 5.48; 3 RCTs, 4736 women; moderate-certainty evidence). Secondary outcomes for women: Magnesium sulphate probably resulted in little to no difference in caesarean section (RR 0.96, 95% CI 0.91 to 1.02; 5 RCTs, 5861 women) and postpartum haemorrhage (RR 0.94, 95% CI 0.80 to 1.09; 2 RCTs, 2495 women) (both moderate-certainty evidence). Breastfeeding at hospital discharge and women's views of treatment were not reported. AUTHORS' CONCLUSIONS: The currently available evidence indicates that magnesium sulphate for women at risk of preterm birth for neuroprotection of the fetus, compared with placebo, reduces cerebral palsy, and death or cerebral palsy, in children up to two years' corrected age. Magnesium sulphate may result in little to no difference in outcomes in children at school age. While magnesium sulphate may result in little to no difference in severe maternal outcomes (death, cardiac arrest, respiratory arrest), it probably increases maternal adverse effects severe enough to stop treatment. Further research is needed on the longer-term benefits and harms for children, into adolescence and adulthood. Additional studies to determine variation in effects by characteristics of women treated and magnesium sulphate regimens used, along with the generalisability of findings to low- and middle-income countries, should be considered.

Humans↗