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PubMed2026

Probiotic supplementation increases fecal TLR4 agonists without improving disease activity in juvenile idiopathic arthritis: a randomized placebo-controlled trial.

Gut dysbiosis has been implicated in the pathogenesis of juvenile idiopathic arthritis (JIA), suggesting that microbiota-targeted interventions may influence immune signalling during early immune development. We conducted the PERMAJI multicentre randomized, double-blind, placebo-controlled trial to evaluate the effects of probiotic supplementation (VSL#3) on host-microbiota immune interactions and disease activity in children with oligoarticular or RF-negative polyarticular JIA. Participants were randomly assigned (1:1) to receive VSL#3 or placebo for 3 months in addition to standard therapy. Stool and serum samples collected at baseline and month 3 were used to assess gut microbiota composition, fecal innate immune agonists, intestinal permeability, and systemic cytokines. The primary clinical endpoint was the proportion achieving an ACR Pedi 30 response at 3 months. Forty-four children were enrolled between September 2017 and July 2022. Clinical responses did not differ between groups (ACR Pedi 30: 47% with VSL#3 vs 63% with placebo; p = 0.33), and conservative worst-case assumptions for missing data suggested lower response rates with VSL#3 (36% vs 68%; p = 0.03). Probiotic supplementation significantly increased fecal Toll-like receptor 4 (TLR4) agonist activity, whereas gut microbiota diversity, intestinal permeability, and systemic cytokine levels remained unchanged. These findings indicate that probiotic supplementation can modify microbial innate immune signalling without detectable changes in microbial community diversity and may increase exposure to pro-inflammatory microbial stimuli in early-life autoimmune disease. The results highlight the complexity of host-microbiota immune interactions and underscore the need for careful evaluation of microbiome-targeted therapies in paediatric autoimmune disorders.

Humans↗

PubMed2026

Toileting dysfunction in SATB2-associated syndrome: results from a caregiver survey.

BACKGROUND: Toilet training and continence are major developmental milestones, but children with neurogenetic conditions often experience extreme difficulties, sometimes never achieving full continence. These challenges impose ongoing burden on caregivers, especially as children age and require toileting assistance outside the home. SATB2-associated syndrome (SAS) is a rare genetic disorder in which such functional issues have not been systematically studied. We sought to assess bladder and bowel function in individuals with SAS and compare symptoms burden to normative data. METHODS: Caregivers completed a survey that included the Vancouver Symptom Score (VSS) for Dysfunctional Elimination Syndrome. VSS scores were analyzed and compared to published norms. Additional data included toilet training milestones, continence status, urinary tract infections, and bowel treatment history. RESULTS: Of the 32 individuals with SAS represented in the caregiver-reported survey, over half (53%) were not toilet trained, and only 22% were fully trained for both day and night (mean age at toilet training 6.9 years). The SAS group (n = 32) had a median total VSS of 16.0 (range: 6-30), indicating clinically significant dysfunction, while control data (n = 49) reported a median of 5.0 (range: 0-12, p < 0.001), with the greatest differences observed in daytime wetting, nighttime wetting, wetting extent, and fecal soiling. CONCLUSIONS: Individuals with SAS experience markedly elevated elimination symptom burden. Findings support the need for early screening and intervention to promote continence and reduce caregiver strain. A clinical pathway is proposed for screening, evaluation, and management of elimination dysfunction in SAS.

Humans↗

PubMed2025

Comparison of three tracking methods to assess usage of two pediatric powered mobility devices for young children with cerebral palsy.

Powered mobility devices are underutilized for promoting self-initiated mobility in young children with cerebral palsy due to prioritization of walking, caregiver effort, device characteristics, and environmental factors. Understanding device usage patterns is important to assess the impact of powered mobility interventions on child outcomes. As part of clinical trial (NCT04684576), three objective tracking methods including integrated loggers, Global Positioning System trackers (GPST), and caregiver reported activity logs (CRAL) were compared to provide insights into device usage patterns. Metrics included play session frequency, session duration, total usage minutes, and unique usage days for two powered mobility devices: Modified Ride-on Cars (MROC) and the Permobil Explorer Mini (EM). Twelve children with cerebral palsy used each device for eight consecutive weeks in home and community settings (16 weeks total), with device ordered randomized. Results showed no significant differences among tracking methods for the MROC. For the EM, only session duration differed between GPST and CRAL. Correlation analysis revealed variable relationships amongst tracking methods for both devices. The EM was used more frequently than the MROC, with significantly greater total usage minutes and session duration via CRAL, not GPST. The findings highlight the need for reliable tracking technologies that can be used across powered mobility devices.

Child, Preschool↗

PubMed2026

Effects of hospital planning reforms on access, costs, efficiency, and quality of care in OECD countries: Systematic review and meta-analysis.

BACKGROUND: Many OECD countries have implemented hospital planning reforms to rising healthcare costs, demographic changes, and concerns about access, efficiency, and quality of care. Despite broad implementation, evidence on effectiveness remains fragmented and country-specific. OBJECTIVE: To synthesize evidence on the effects of hospital planning reforms aross four outcome domains: access, costs, efficiency, and quality of care. METHODS: We conducted a systematic review following Cochrane methodology, searching PubMed and Web of Science (January 2000 - September 2025). Studies were categorized into four intervention types - centralization, minimum volume requirements (MVR), performance-based targets, and governance and ownership restructuring. Risk of bias was assessed using Joanna Briggs Institute checklist for quasi-experimental designs. Where data permitted, random-effects meta-analyses pooled standardized mean differences (SMD) for access and efficiency and risk differences (RD) for quality outcomes. RESULTS: 26 studies from 12 countries were included. Centralization increased patient travel distances and reduced length of stay (SMD -0.09, 95% CI -0.17 to -0.01) and complications (RD -14.52 pp, -25.95 to -3.09), and, jointly with performance-based targets, 30-day readmissions (RD -0.43 pp, -0.65 to -0.22). Mortality effects varied by timepoint and intervention: short-term endpoints were largely non-significant, whereas 90-day mortality was reduced under centralization (RD -0.80 pp, -1.25 to -0.35) and 60-day mortality under MVR (RD -2.00 pp, -2.82 to -1.18). Survival was non-significant throughout. No study examined costs. CONCLUSION: The absence of cost evidence is a critical gap. Substantial heterogeneity reflects variation in reform design and context, underscoring the need to interpret findings by intervention and country conditions.

Humans↗

PubMed2026

Vertical distribution of accessory canals in different tooth types: A systematic review and meta-analysis.

OBJECTIVE: To systematically analyze the vertical distribution of accessory canals and propose potential root-end resection levels in different tooth types. DATA: Proportional distribution of accessory canals (PD-AC) in 1 mm intervals, cumulative proportions within 2 mm and 3 mm (CP-AC0-2 and CP-AC0-3), mean distance from accessory foramen to root apex or main foramen (MD-AF), and prevalence of accessory canals in 2D cross-sections (PR-AC-2D). SOURCES: A systematic search of electronic databases was conducted through December 25, 2025. The review was registered in PROSPERO (CRD420251107855). STUDY SELECTION: Two reviewers independently performed study selection, data extraction, and risk of bias assessment using the AQUA tool. Nineteen studies were included for qualitative synthesis, of which eleven provided sufficient data for meta-analysis. A random-effects model was used, and subgroup analyses were stratified by tooth type, accessory canal type, and country. Within 0-1 mm, 1-2 mm, 2-3 mm, and 3-4 mm from the apex, 41.5%, 34.3%, 9.9%, and 4.4% of accessory canals were located, respectively. Molars had significantly higher proportions than anterior teeth both within 2 mm (90.0% vs. 72.4%) and 3 mm (96.9% vs. 87.5%). Of apical ramifications, 86.4% were within 2 mm. The pooled MD-AF was 1.472 mm. PR-AC-2D decreased from 29.3% at 1 mm to 1.3% at 5 mm. All studies presented moderate to high risk of bias. CONCLUSIONS: A 2 mm root-end resection level may be sufficient for molars, whereas anterior teeth may require a higher level. Further randomized controlled trials are needed. CLINICAL SIGNIFICANCE: A 2 mm resection may adequately expose or remove most accessory canals in molars, potentially preserving more root length while maintaining treatment efficacy. In anterior teeth, a traditional 3 mm resection remains advisable until further evidence becomes available.

Humans↗

PubMed2026

Effects of dietary interventions on gut microbiota and related cardiometabolic changes in pediatric obesity: a systematic review and meta-analysis.

BACKGROUND: Gut microbiota imbalances may contribute to obesity, yet whether dietary interventions can modulate the microbiota and improve metabolic health in pediatrics has not been thoroughly reviewed. This systematic review and meta-analysis explores the impact of dietary interventions on the gut microbiota of children and adolescents with overweight or obesity, and its association with cardiometabolic improvements. METHODS: A systematic search of clinical trials in Pubmed, Cochrane and EMBASE was conducted following PRISMA guidelines (PROSPERO n°CRD42024505494). Risk of bias was assessed with RoB2 and ROBINS, for randomized and non-randomized intervention studies. RESULTS: Overall, 60 articles were assessed for full-text eligibility, 8 were included, and 4 provided alpha-diversity data for meta-analysis. A total of 200 participants were included (6-16 years). Six studies implemented calorie-restricted diets, one a low free-sugar diet, and one CHILD-1 diet. The meta-analysis revealed a significant increase in Chao1 (48.76 [95%CI 1.81; 95.70]; I2 = 86.8%, p < 0.001) following a balanced calorie-restricted dietary intervention. Although there was heterogeneity in taxa-level changes, several butyrate-producing genera (Clostridium XVIa, Coprococcus, Roseburia, Faecalibacterium, Blautia, Butyricimonas) increased following dietary intervention. CONCLUSIONS: Balanced dietary interventions with calorie-restriction adequate for pediatric age could increase gut microbiota richness and butyrate-producing bacteria abundance. Future trials should clarify diet-driven gut microbiota changes in childhood obesity and related metabolic changes. IMPACT: Balanced calorie restriction diet may increase gut microbiota richness in childhood obesity Butyrate-producer expansion needs long-term dietary intervention Gaps in linking microbiota-metabolism interplay in pediatric obesity.

Journal Article↗

PubMed2026

Effect of transcutaneous auricular vagus nerve stimulation on postoperative pain in patients undergoing thoracoscopic partial lung resection: a randomized, double-blind, controlled clinical trial.

BACKGROUND: Postoperative pain after thoracic surgery remains common and challenging. Transcutaneous auricular vagus nerve stimulation (taVNS) is a noninvasive neuromodulation technique with potential analgesic effects. This study aimed to evaluate the efficacy and safety of taVNS for postoperative pain management in patients undergoing thoracoscopic partial lung resection. METHODS: Adults undergoing thoracoscopic partial lung resection were randomized to active or sham taVNS. The primary outcome was cough pain intensity at 48h post-surgery, assessed by Numeric Rating Scale (NRS). Secondary outcomes included cough pain at 24h and 72h, resting pain, moderate-to-severe pain incidence, opioid consumption, quality of recovery, postoperative pulmonary complications , chest tube duration, hospital stay, postoperative nausea/vomiting, and adverse events. RESULTS: Among 119 analyzed patients (active n = 60, sham n = 59), active taVNS reduced cough pain scores at 24h, 48h, and 72h postoperatively, as well as resting pain (p < 0.05). It also lowered the incidence of moderate-to-severe cough pain at 24h and 48h, reduced cumulative postoperative opioid use at 24h and 72h, and decreased rescue analgesia on postoperative day 3 (p < 0.05). Active taVNS was associated with a lower incidence of postoperative pneumothorax (p < 0.05). No serious adverse events occurred. CONCLUSION: Perioperative taVNS was associated with a modest analgesic benefit and reduced postoperative opioid requirements after thoracoscopic partial lung resection. The observed reduction in postoperative pneumothorax requires cautious interpretation, and further multicenter trials are needed to determine its clinical utility.

Humans↗

PubMed2026

Life-course stress exposure and cognitive decline in middle-aged and older Chinese adults: The role of sex differences and educational protection.

BACKGROUND: Stressful life events (SLEs) across the life course have been associated with cognitive decline, but evidence on their cumulative impact and potential modifiers remains limited. We aimed to examine the associations between SLE exposure in childhood, adulthood, or both life stages and cognitive trajectories, and to investigate whether these associations vary by sex and education. METHODS: We used data from the China Health and Retirement Longitudinal Study, a nationally representative cohort of adults aged ≥45 years. Participants with complete data on SLEs, cognition, and covariates were included (n = 5922). SLEs were retrospectively assessed for childhood and adulthood. Cognitive function was measured using a composite score (range 0-21) across three waves (2011-2015). Linear mixed-effects models examined longitudinal associations, adjusting for sociodemographic factors, health behaviors, and chronic conditions, with interaction analyses for sex and education. RESULTS: Compared with participants reporting no SLEs, cumulative exposure showed the strongest association with cognitive decline (β = -0.52, 95% CI -0.69 to -0.35), followed by childhood-only (β = -0.34, -0.48 to -0.20) and adulthood-only exposure (β = -0.22, -0.37 to -0.07). Sex significantly moderated the associations for childhood and cumulative exposure, with women exhibiting greater cognitive vulnerability. Higher educational attainment attenuated the associations between single-period stress and cognitive decline, with only partial protection observed against cumulative adversity. CONCLUSION: Cumulative life-course stress is associated with accelerated cognitive decline in Chinese middle-aged and older adults. Women appear more vulnerable to stress-related cognitive effects, whereas higher education confers partial resilience, highlighting the need for sex-sensitive and education-informed prevention strategies.

Humans↗

PubMed2025

Online Risk Behavior in Adolescents: A Systematic Review.

Identifying and categorizing online risk behaviors is crucial for assessing their impact on adolescents. Despite extensive research, previous studies have not provided a clear classification of these behaviors. This systematic review synthesizes the quantitative literature on adolescent online risk behaviors from the inception of research to September 2023, aiming to: (a) offer a comprehensive overview of the types of online risk behaviors and the specific actions encompassed within each category among adolescents; (b) summarize the adverse outcomes associated with these behaviors; and (c) discuss the implications and future research directions. Utilizing key terms, this study sourced studies from four electronic databases (Scopus, PubMed, Web of Science, and EMBASE), ultimately including 22 English-language quantitative studies. The review reveals that online risk behaviors are primarily categorized into content risk behaviors, contact risk behaviors, and conduct risk behaviors. Adolescents engaging in these behaviors are at an increased risk of experiencing physical health issues, mental health problems, externalizing behaviors, and even self-harm and suicidal thoughts or actions. Further research is needed to develop and validate an online risk behavior scale and conduct longitudinal and experimental studies to establish causal relationships and examine the long-term effects of these behaviors on adolescent well-being. The review concludes with implications for future research and potential prevention, intervention, and policy strategies to mitigate online risk behaviors in adolescents.

Humans↗

PubMed2026

Depressive Symptoms and Smoking Cessation Among Adolescents and Young Adults Who Smoke: A Prospective Cohort Study.

PURPOSE: This study examined the bidirectional prospective associations between depressive symptoms and smoking cessation among adolescent and young adults who smoke. METHODS: Data on 1,151 participants aged ≤25 years who smoke and receive peer-led quitline counseling in Hong Kong (2016-2022) were analyzed. Exposures included baseline depressive symptoms and smoking cessation (self-reported 7-day abstinence) at 1, 3, and 6 months; Outcome measures included smoking cessation at 1, 3, and 6 months and depressive symptoms at 6 months. Depressive symptoms were assessed using the Center for Epidemiologic Studies Depression Scale, with a score ≥16 indicating at risk for depression. RESULTS: More severe baseline depressive symptoms were associated with lower odds of smoking cessation at 1, 3, and 6 months, which reversely was associated with lower depressive symptoms at 6 months (all p < .05). Similarly, being at risk for depression at baseline was associated with lower odds of smoking cessation at 1 (adjusted odds ratio [aOR] .66, 95% confidential interval [CI] .47-.93) and 3 months (aOR .71, 95% CI .52-.97). Conversely, smoking cessation at 1 (aOR .40, 95% CI .23-.69), 3 (aOR .58, 95% CI .37-.92), and 6 months (aOR .44, 95% CI .29-.69) was associated with lower odds of at risk for depression at 6 months. DISCUSSION: More severe depressive symptoms were prospectively associated with lower odds of smoking cessation, while smoking cessation was associated with lower depressive symptoms and risk for depression. Integrated interventions simultaneously addressing psychological needs and smoking are warranted, when delivered in smoking cessation programs or embedded within mental health services for youth who smoke.

Humans↗

PubMed2026

Understanding FDA's reasons for nonapproval: A systematic review of complete response letters in cell and gene therapy.

BACKGROUND AIMS: Cell and gene therapy products face unique regulatory challenges due to their biological complexity and the stringent expectations for manufacturing control, analytical testing, and clinical assessment. As the pipeline grows, understanding the drivers of FDA non‑approval is increasingly important for improving first‑cycle success and reducing development delays. In this study, we aimed to characterize the frequency and impact of refuse‑to‑file actions, major amendments, and complete response letters issued for biologics licensing applications; and to identify recurring patterns of deficiencies contributing to delayed approval. METHODS: Publicly available documents were extracted from the FDA website. Data from each approved cell and gene therapy product's regulatory history-including complete responses, major amendments, inspection timing, and cited deficiencies-were compiled and categorized across clinical, quality, and labeling domains. RESULTS: Analysis showed that informational deficiencies were common across modalities. Major amendments occurred in roughly half of applications, and complete responses had the most significant impact. Quality deficiencies appeared in all complete responses and were the predominant barrier, while clinical and labeling issues were less frequent but meaningful when present. CONCLUSION: Overall, these findings highlight the need for proactive FDA engagement, comprehensive readiness, and early inspection preparation to reduce regulatory risk and improve first cycle approval outcomes.

Humans↗

PubMed2026

Educational interventions to improve medical students' bad news communication skills: A systematic review and meta-analysis.

OBJECTIVES: This systematic review aimed to both determine whether educational interventions improve medical students' ability and/or confidence in Bad News Communication (BNC), as well as assess the relative efficacy of instructional formats. METHODS: Performed according to the PRISMA guidelines, four databases were searched for articles describing education-based interventions to improve medical student's BNC ability and/or confidence, published in English between 2001 and 2024. Data on students' self-reported or observer-assessed level of competence/ability in BNC (primary outcome), and students' self-assessed confidence in BNC skills (secondary outcomes), were analysed. Meta regression explained the influence of several categorical moderators on heterogeneity in relation to intervention effects on competence/ability. RESULTS: 27 studies met the criteria for inclusion in the systematic review and 17 studies for the meta-analysis. Interventions described in controlled studies were associated with a moderate and significant increase in BNC ability (13 data sets; standardized mean difference [SMD] = 1.09, 95% CI = 0.52 - 1.66). Interventions detailed in pre-post design studies were associated with a significant increase in BNC ability (20 data sets; SMD = 0.92, 95% CI = 0.52 - 1.32), and student confidence/comfort in their BNC skills (12 data sets; SMD = 1.16, 95% CI = 0.57 - 1.75). Subgroup analysis demonstrated better skills/competence outcomes in studies that included simulation-based training (SBT). CONCLUSIONS: Educational interventions improve the BNC ability and confidence of medical students. Interventions should include an SBT element as this leads to greater improvements in BNC ability. Further research is needed to determine to what extent these interventions translate to positive patient outcomes. PRACTICE IMPLICATIONS: Diverse educational programme, especially those including simulation-based training, are effective in improving BNC skills, although the longetivity of these improvements is at present unclear. Therefore, we recommend that refresher courses or practice opportunities should be scheduled throughout students' medical education to ensure retention of BNC skills.

Humans↗

PubMed2026

Do adherence-focused interventions in low back pain have an impact on rehabilitation outcomes? A systematic review with meta-analysis.

BACKGROUND: Low back pain (LBP) is the leading cause of disability worldwide. Exercise-based interventions are effective, but adherence remains suboptimal. This systematic review and meta-analysis evaluated the effectiveness of strategies designed to enhance adherence to exercise-based interventions in individuals with LBP in terms of adherence as well as pain and functionality. METHODS: Randomized controlled trials including adults with non-specific LBP were eligible if they compared exercise-based interventions incorporating adherence-enhancing strategies versus exercise alone or usual care. Primary outcome was adherence; secondary outcomes were pain and functionality. Searches were conducted in PubMed, Embase, Web of Science, Cochrane Library, CINAHL, Scopus, and PEDro up to May 2026. Two reviewers independently screened studies, extracted data, and assessed risk of bias using the Cochrane RoB 2 tool. Random-effects meta-analyses were performed using standardized mean differences. Certainty of evidence was evaluated using the GRADE approach. RESULTS: Fourteen randomized controlled trials including 1233 participants were included. Risk of bias was low in six studies, with the remainder showing some concerns or high risk. For adherence outcomes, evidence showed no clear effect of adherence-enhancing strategies on either device-measured physical activity (SMD = 0.21, 95% CI -0.01 to 0.43; 3 trials, 320 participants; moderate-certainty evidence) or questionnaire-based adherence (SMD = 0.33, 95% CI -0.23 to 0.89; 4 trials, 377 participants; very low-certainty evidence). For pain and functionality, moderate certainty of evidence indicated small improvements favoring intervention groups in the medium term. CONCLUSIONS: Strategies to enhance adherence to exercise in LBP show uncertain effects on adherence but may provide small improvements in clinical outcomes in the medium term. Higher-quality trials are needed to strengthen the evidence base.

Adult↗

PubMed2026

Association between prenatal exposure to tetrachloroethylene and adverse birth outcomes: Systematic review and meta-analysis.

BACKGROUND: Tetrachloroethylene (PCE) is a ubiquitous chlorinated solvent with documented placental transfer. Despite widespread environmental and occupational exposure, no prior systematic review has synthesized evidence on prenatal PCE exposure and adverse birth outcomes. METHODS: We conducted a systematic review and meta-analysis of observational studies. PubMed, Web of Science, PsycINFO, EMBASE, and CINAHL were searched from inception to July 13, 2026. Eligible studies reported associations between prenatal PCE exposure (drinking water or inhalation) and adverse birth outcomes. Study quality was assessed using the Newcastle-Ottawa Scale (NOS) and Agency for Healthcare Research and Quality (AHRQ) criteria. Random-effects meta-analyses were performed using risk ratios (RRs) with 95% confidence intervals (CIs), with Knapp-Hartung adjustments and Paule-Mandel τ2 estimation. RESULTS: Twenty one studies (1987-2023) met inclusion criteria. Prenatal PCE exposure was associated with spontaneous abortion (8 studies; RR = 1.28, 95% CI 1.00-1.63; I2 = 64.2%). Analyses of stillbirth, central nervous system defects, oral clefts, neural tube defects, preterm birth, low birthweight, and small-for-gestational-age (SGA) yielded positive but statistically non-significant pooled estimates. The certainty of evidence ranged from very low to low across outcomes (GRADE). CONCLUSIONS: Prenatal PCE exposure may be associated with spontaneous abortion, particularly at higher exposure levels, and with SGA. Findings support ongoing regulatory efforts to limit PCE in occupational and environmental settings, particularly for pregnant individuals. Future prospective studies with biological monitoring and confounder-adjusted designs are needed.

Tetrachloroethylene↗

PubMed2026

Psychedelic-induced hypomania and mania: a systematic review and meta-analysis.

Serotonergic psychedelics are increasingly investigated as treatments for affective disorders. Concerns persist regarding their potential to induce hypomania or mania, particularly in individuals with bipolar spectrum vulnerability. Whether these substances precipitate transient mood switches or contribute to persistent bipolar illness or diagnostic transition remains unclear. We conducted a systematic review of human studies examining manic or hypomanic symptoms following exposure to serotonergic psychedelics (psilocybin, LSD, mescaline, DMT/ayahuasca) or MDMA (CRD420251160656). Databases and trial registries were searched through January 26, 2026. Eligible designs included randomized and non-randomized clinical studies, registry-based cohorts, cross-sectional surveys, and longitudinal observational studies. Outcomes included dysphoria/euphoria, manic or hypomanic symptoms and transition to bipolar disorder. Risk of bias was assessed using ROBINS-I, ROB2 or NIH tools. Twenty-three studies met inclusion criteria, four contributing to meta-analysis. Rates of psychedelic-associated dysphoria/euphoria, hypomania or mania ranged from 5.8% in controlled trials of psilocybin-assisted psychotherapy for major depressive disorders to 30% in naturalistic studies of individuals with bipolar disorder. When present, manic symptoms were typically acute and self-limited. Observational studies identified higher risks among individuals with bipolar I disorder, familial vulnerability, polysubstance use, and unsupervised or illegal use. Registry-based cohorts examining diagnostic transitions showed a prevalence of subsequent transition to bipolar disorder of 4% (95% CI 2-8%; N = 7478; I² = 32.1%), with little evidence for a hallucinogen-specific signal. Overall, serotonergic psychedelics appear to pose a low but clinically meaningful relative risk of transient mood-related symptoms in susceptible individuals while remaining relatively safe in controlled clinical settings. Long-term outcomes and repeated exposure remain insufficiently studied, underscoring the need for rigorous longitudinal research.

Humans↗

PubMed2026

Reproductive Intentions and Fertility Preservation Among Transgender and Nonbinary Individuals: A Cross-Sectional Study in Brazil.

PURPOSE: This study evaluated reproductive intentions, fertility-related knowledge, prior fertility counseling, and factors associated with reproductive intentions among transgender and nonbinary individuals receiving care at a Brazilian public reference center. METHODS: This cross-sectional study with a qualitative component was conducted between July and November 2025 in a specialized gender-affirming care clinic in Brazil. Quantitative data included sociodemographic characteristics, reproductive history, gender-affirming hormone therapy (GAHT), and fertility-related variables. Logistic regression was used to assess factors associated with desire for future parenthood. Responses to a single open-ended question regarding perceived effects of GAHT on fertility were analyzed using thematic content analysis. RESULTS: Eighty-two participants were included (mean age 27.5 ± 7.4 years). Most identified as transgender men (65.9%), followed by transgender women (26.8%) and nonbinary individuals (7.3%); 79.3% were receiving GAHT. Although 63.4% expressed a desire for future parenthood, only 7.3% had children. Current interest in fertility preservation was reported by 20.8% (15/72). Having children (adjusted odds ratio [aOR] = 0.03; 95% confidence interval [CI]: 0.001-0.62; p = 0.023) and each additional year of GAHT duration (aOR = 0.83; 95% CI: 0.70-0.99; p = 0.038) were associated with lower odds of desiring future parenthood. Sex assigned at birth was not independently associated with reproductive intentions. Qualitative analysis revealed misconceptions, uncertainty, and conditional beliefs regarding fertility. CONCLUSIONS: Desire for future parenthood was common among transgender and nonbinary individuals, whereas engagement with fertility preservation remained limited. These findings highlight the need for longitudinal, patient-centered reproductive counseling integrated into gender-affirming care.

fertility preservation↗

PubMed2026

Corticosteroids as adjunctive therapy to standard treatment in Kawasaki disease: a GRADE-assessed systematic review and meta-analysis of randomized controlled trials.

UNLABELLED: Kawasaki disease (KD) is an acute systemic vasculitis and the leading cause of acquired heart disease in children in developed countries. While IVIG plus aspirin remains standard treatment, 10-20% of patients are IVIG-resistant and face an elevated risk of coronary artery abnormalities. Corticosteroids have been explored as adjunctive therapy, though evidence on their benefit remains inconsistent. To assess the efficacy and safety of adjunctive corticosteroids in Kawasaki disease across key clinical outcomes. This PRISMA 2020-compliant systematic review and meta-analysis included RCTs identified through database searches up to April 2026. Risk of bias was assessed using Cochrane RoB 2.0. Data were pooled using random-effects models to estimate risk ratios (RRs) and mean differences (MDs) with 95% CIs. Subgroup analyses, leave-one-out sensitivity analyses, and GRADE certainty appraisal were also performed. Eight studies (n = 4106) were included. No significant differences were found in coronary artery abnormalities (CAA) within 1 month (RR 0.49, 95% CI 0.17-1.42), after 1 month (RR 0.81, 95% CI 0.43-1.55), fever duration (MD - 1.75, 95% CI - 3.71 to 0.21), or adverse events (RR 1.08, 95% CI 0.57-2.07). Hospital stay was modestly shorter with corticosteroids (MD - 0.99, 95% CI - 1.86 to - 0.11). Exploratory subgroup analyses suggested potential benefits with prednisolone-based and prolonged corticosteroid regimens for selected outcomes; however, these findings should be interpreted cautiously given multiple subgroup comparisons. Overall certainty of evidence was very low. CONCLUSION:  Adjunctive corticosteroids did not significantly improve major outcomes in KD. Prednisolone-based regimens showed some promise, but high-quality trials are still needed before any firm conclusions can be drawn. WHAT IS KNOWN: • Corticosteroids have been studied as adjunctive therapy for Kawasaki disease, but their effects on coronary outcomes and other clinical outcomes remain inconsistent. WHAT IS NEW: • This meta-analysis found no significant improvement in major outcomes with adjunctive corticosteroids, although prednisolone-based and prolonged regimens may provide benefits for selected outcomes.

Humans↗

PubMed2026

Effects of exercise snacking on neuromuscular performance in insufficiently active adults: A systematic review and meta-analysis.

OBJECTIVE: To examine the effects of exercise snacking (ES) on neuromuscular performance in insufficiently active adults. METHODS: Six databases were searched from inception to July 17, 2026. Randomized controlled trials and non-randomized studies of interventions involving insufficiently active adults undertaking ES interventions were included. Outcomes were functional performance, muscular strength, and muscular power. A three-level random-effects meta-analysis was performed. Risk of bias was assessed with RoB 2 or ROBINS-I, and certainty of evidence was evaluated using GRADE. RESULTS: Nine studies (13 reports) involving 313 participants were included. In the primary three-level model, ES showed a small positive overall effect on neuromuscular performance (g = 0.37, 95% CI 0.16-0.58, p = 0.001), which remained supported under trial-clustered robust inference with small-sample adjustment. Domain-specific estimates for muscular power/velocity, functional performance, and muscular strength were positive but imprecise and were not statistically supported after small-sample robust adjustment. Robust moderator tests provided no evidence of between-subgroup differences, and the certainty of evidence was low for all outcomes. CONCLUSION: Current low-certainty evidence suggests that ES may produce a small improvement in overall neuromuscular performance. However, domain-specific effects remain uncertain because of the limited number of independent trials, and the overall prediction interval crossed zero, indicating uncertainty across future populations and settings. Larger, preregistered randomized controlled trials are needed to confirm these preliminary findings.

Adult↗