QuestionWhat are the late adverse consequences among survivors of pediatric acute kidney injury (AKI)?FindingsIn this systematic review and meta-analysis of 39 studies involving 16 151 children, AKI was associated with an increased risk of late adverse outcomes. Children with a history of AKI had higher odds of developing chronic kidney disease and higher late mortality, and risk was further elevated in those with more severe AKI.MeaningThese findings underscore the importance of structured, long-term follow-up and kidney health surveillance for children after AKI, particularly for those with moderate or severe injury. This systematic review and meta-analysis estimates the pooled incidence and relative risk of chronic kidney disease, mortality, hypertension, and proteinuria following acute kidney injury in hospitalized children. ImportanceAcute kidney injury (AKI) is a common complication among hospitalized children and may have lasting kidney and cardiovascular consequences. However, the long-term risks after pediatric AKI have not been comprehensively quantified.ObjectiveTo estimate the pooled incidence and relative risk with odds ratio of chronic kidney disease (CKD), mortality, hypertension, and proteinuria following AKI in hospitalized children.Data SourcesPubMed, Embase, and Web of Science were searched from January 2007 through November 2025 without language restrictions.Study SelectionStudies were included if they reported at least 1 long-term outcome (CKD, mortality, hypertension, or proteinuria) following AKI in hospitalized children. Studies limited to children with obstructive lesions, primary vascular disorders (eg, hemolytic uremic syndrome) or solid organ transplant were excluded.Data Extraction and SynthesisTwo reviewers independently extracted data and assessed risk of bias. Random-effects meta-analyses were performed to estimate pooled cumulative incidences and odds ratios (ORs) with 95% CIs.Main Outcomes and MeasuresCumulative incidence and odds of CKD, mortality, hypertension, and proteinuria following pediatric AKI.ResultsOf 17 068 screened records, 39 studies comprising 16 151 participants were included. The pooled cumulative incidences following AKI were 17% (95% CI, 12-22) for CKD, 6% (95% CI, 3-8) for mortality, 20% (95% CI, 12-29) for proteinuria, and 16% (95% CI, 11-23) for hypertension. In 23 studies with non-AKI comparators and follow-up ranging from 3 months to 18 years, AKI was associated with increased odds of CKD (OR, 1.74; 95% CI, 1.02-2.95) and mortality (OR, 1.92; 95% CI, 1.35-2.75) but not proteinuria (OR, 1.18; 95% CI, 0.62-2.25) or hypertension (OR, 1.29; 95% CI, 0.72-2.31). Greater AKI severity was associated with a higher odds of CKD (stages 2-3: OR, 2.84; 95% CI, 1.49-4.15; stage 1: OR, 1.72; 95% CI, 1.11-2.67).Conclusions and RelevanceThe findings in this systematic review and meta-analysis demonstrate that, similar to adults, children experienced increased risk of late adverse outcomes following AKI, particularly CKD and mortality, supporting the need for structured post-AKI follow up.

IntroductionThis paper reports on the first two phases of a three-phase project to develop and evaluate an "integrated" iteration of ENabling VISions And Growing Expectations (ENVISAGE). ENVISAGE is a validated online 5-week program grounded in strengths-based and family-centred approaches to child and family development in the context of neurodevelopmental disability. The two phases included (i) partnership formation and collaborative adaptation of the ENVISAGE programs for families (ENVISAGE-Families) and for service providers (ENVISAGE-SP) to create an "integrated" approach; and (ii) conduction of a feasibility study.MethodsENVISAGE-Integrated was co-developed through an iterative process of revising and combining the original ENVISAGE programs (for families and for service providers). The Framework for Reporting Adaptations and Modification-Expanded (FRAME) was used to report modifications. The feasibility study included 12 participants (7 service providers and 5 parents) from a children's treatment centre. Participants completed a demographic questionnaire and surveys after each workshop, including open-ended and 5-point Likert-scaled questions about their experiences of the program. All data were analyzed descriptively.ResultsProgram modifications were undertaken to ensure relevance to both service providers and parents and to preserve the core ENVISAGE concepts. Key modifications included (i) incorporating weekly icebreaker activities and (ii) tailoring current and creating additional scenarios to prompt discussion and apply concepts. Participants found the integrated format was valuable, meaningful, and relevant. Challenges included recruiting participants and scheduling synchronous group discussions.ConclusionParticipants' feedback informed two program adaptations: (i) allotting more time to apply concepts to scenarios during group discussions and (ii) supporting the use of the platform's discussion board. The findings from the feasibility study justify the ongoing development and evaluation of program outcomes on both service providers and parents.

Importance:Acute kidney injury (AKI) is a common complication among hospitalized children and may have lasting kidney and cardiovascular consequences. However, the long-term risks after pediatric AKI have not been comprehensively quantified. Objective:To estimate the pooled incidence and relative risk with odds ratio of chronic kidney disease (CKD), mortality, hypertension, and proteinuria following AKI in hospitalized children. Data Sources:PubMed, Embase, and Web of Science were searched from January 2007 through November 2025 without language restrictions. Study Selection:Studies were included if they reported at least 1 long-term outcome (CKD, mortality, hypertension, or proteinuria) following AKI in hospitalized children. Studies limited to children with obstructive lesions, primary vascular disorders (eg, hemolytic uremic syndrome) or solid organ transplant were excluded. Data Extraction and Synthesis:Two reviewers independently extracted data and assessed risk of bias. Random-effects meta-analyses were performed to estimate pooled cumulative incidences and odds ratios (ORs) with 95% CIs. Main Outcomes and Measures:Cumulative incidence and odds of CKD, mortality, hypertension, and proteinuria following pediatric AKI. Results:Of 17 068 screened records, 39 studies comprising 16 151 participants were included. The pooled cumulative incidences following AKI were 17% (95% CI, 12-22) for CKD, 6% (95% CI, 3-8) for mortality, 20% (95% CI, 12-29) for proteinuria, and 16% (95% CI, 11-23) for hypertension. In 23 studies with non-AKI comparators and follow-up ranging from 3 months to 18 years, AKI was associated with increased odds of CKD (OR, 1.74; 95% CI, 1.02-2.95) and mortality (OR, 1.92; 95% CI, 1.35-2.75) but not proteinuria (OR, 1.18; 95% CI, 0.62-2.25) or hypertension (OR, 1.29; 95% CI, 0.72-2.31). Greater AKI severity was associated with a higher odds of CKD (stages 2-3: OR, 2.84; 95% CI, 1.49-4.15; stage 1: OR, 1.72; 95% CI, 1.11-2.67). Conclusions and Relevance:The findings in this systematic review and meta-analysis demonstrate that, similar to adults, children experienced increased risk of late adverse outcomes following AKI, particularly CKD and mortality, supporting the need for structured post-AKI follow up.

Opioid Use Disorder (OUD) is a chronic condition for which Medications for Opioid Use Disorder (MOUD) are crucial. Methadone Maintenance Treatment (MMT) and buprenorphine/naloxone (BN) are MOUD used to decrease opioid cravings and use, however, retention rates for MMT and BN vary. Genetic factors associated with retention in patients with other MOUD are largely unknown. The objective was to investigate the role of the T allele in rs204076 (found within Opioid Receptor Delta 1 gene) as a predictor for treatment retention in MOUD. Data were collected for the Pharmacogenetics of Opioid Substitution Treatment Response (POST) project. Retention time was calculated from the reported time of initiation of MOUD until loss to follow up or completion 12 month follow up using Kaplan-Meier survival analyses. A Cox regression analysis was conducted based on predictor variables for MOUD treatment retention. Of patients on MOUD(n = 1,607), majority were male (57%) and with an average age of 40 years. Survival time did not differ among carriers of the rs204076 T allele (p = 0.24). When controlling for non-genetic factors, individuals with the T allele had a 40% lower hazard of leaving treatment (Hazard Ratio [HR] = 0.60, 95% Confidence Interval [CI] = 0.44, 0.84, p = 0.002). MMT was associated with a 56% lower hazard of leaving treatment compared to BN (HR = 0.44, CI = 0.34, 0.58, p = 1.07 × 10- 9), however the benefit of MMT compared to BN was reduced in T allele carriers (HR = 1.43, 95% CI = 1.02, 2.00, p = 0.038) when controlling for non-genetic predictors of treatment retention. There was no association between sex and treatment retention. Understanding predictors of treatment retention including genetic variants in the OUD contributes to treatment personalized medicine and making informed treatment decisions regarding MOUD.

INTRODUCTION/OBJECTIVES:This systematic review aimed to summarize the evidence on the effect of the fixed-dose combination of tiotropium/olodaterol (Tio/Olo 5/5 μg FDC) on exercise-related outcome measures. METHODS:We included randomized clinical trials (RCTs) from four databases that investigated the effectiveness of Tio/Olo 5/5 μg FDC on exercise tolerance, breathlessness, lung function, and physical activity from inception to October 2024. RESULTS:Findings from eight RCTs indicated that Tio/Olo 5/5 μg FDC was superior to Tio 5 μg or placebo for the following outcomes: exercise tolerance [Tio 5 μg: 3 RCTs, mean difference (MD) = 16.6 m, 95% CI: 5.2-28.1, p < 0.001], exercise endurance time [Placebo: 2 RCTs, SMD = 0.29, 95% CI: 0.19-0.39, p = p < 0.001], inspiratory capacity [Tio 5 μg: 3 RCTs, MD = 0.13 L, 95% CI: 0.07-0.19, p < 0.001], and forced expiratory volume in 1 second (FEV1) [Tio 5 μg: 4 RCTs, MD = 0.12 L, 95% CI: 0.11-0.14, p < 0.001; Placebo: 2 RCTs, MD = 0.33 L, 95% CI: 0.3-0.35, p < 0.001], with no effect on physical activity levels. CONCLUSION:Tio/Olo 5/5 μg FDC compared to Tio 5 μg or placebo may improve exercise tolerance and lung function, but not physical activity levels in COPD. PROTOCOL REGISTRATION:The systematic review protocol is registered on PROSPERO (International Prospective Register of Systematic Reviews): number CRD42024598553.

Objectives:Varied substance use outcomes have been reported among individuals with a hepatitis C viral (HCV) infection on opioid agonist treatment (OAT) for opioid use disorder. Accordingly, the current study sought to evaluate the association between HCV serostatus, among other factors, and opioid-related acute health service utilization (e.g., emergency department [ED] visits and hospitalizations) among individuals prescribed OAT. Methods:Multi-site prospective cohort study data were used to characterize demographic characteristics, substance use patterns, and physical health amongst individuals prescribed OAT. Logistic regression models were built to estimate the association between HCV-seropositivity and opioid-related ED visits and hospitalizations over a three-year follow up period. Results:Among 3430 participants, 10.6 % (n = 365) were HCV-seropositive. In the follow-up period, 21.3 % (n = 730) attended the ED and 8.7 % (n = 298) were hospitalized for opioid related-harms. HCV-seropositivity was associated with an increased incidence of ED visits for opioid poisoning (9.0 % vs 4.9 % for participants who were HCV-seronegative, p < 0.01) and other opioid-related harms (22.5 % vs. 20.8 % for seronegative participants, p = 0.03). However, multiple logistical regression models showed no association between HCV serostatus and opioid-related health service utilization; rather, injection drug use was a significant predictor of opioid-related ED visits (OR 3.39, p < 0.01) and hospitalizations (OR 1.21, p = 0.01). Conclusion:Among individuals prescribed OAT, those with seropositive HCV have increased incidence of ED visits and hospitalizations for opioid-related harms, an association which may be driven by injection use practices. These findings highlight the importance of screening for injection use practices and health symptoms, as well as the potential role for targeting resources (e.g., harm reduction supplies, education regarding transmission) within this vulnerable subgroup.

The purpose of this study was to determine the feasibility (recruitment, retention, and adherence rates) and effectiveness of institution-based exercise and self-management (SM) on physical activity (PA) level, exercise knowledge and intention, health status, functional capacity, patient engagement, and lower extremity strength for individuals with breast cancer receiving treatment. We conducted a hybrid implementation-effectiveness trial (type 1), including female participants with a current diagnosis of breast cancer undergoing treatment. Participants were randomized to (1) exercise and SM (EXSM; 8 in person exercise sessions and SM education), (2) SM only (8 sessions of SM), or (3) usual care (UC; no intervention). The RE-AIM model was used to explore the interventions success. The primary outcome was PA level at post-intervention. An ANCOVA determined effectiveness of the intervention at each timepoint. Eighty-five participants were included in the study. Study recruitment was 72%. Both the EXSM and SM interventions had high levels of retention (EXSM: 72%; SM: 93%) and adherence (EXSM: 76%; SM: 93%). A significant effect of group was found between EXSM and UC for PA level at post-intervention timepoint (adjusted mean difference: 9.28 (95% CI 6.45, 12.10); p < 0.001), and was maintained at 6- and 12-month follow-ups (11.78 (8.93, 14.64); p < 0.001; 11.10 (8.28, 13.92); p < 0.001). Exercise and SM using strategies that maximize availability and accessibility of exercise and SM services for survivors of breast cancer can successfully be implemented during treatment within the cancer institution in Canada. Future research should explore implementation of this program at multiple centers, maximizing referral of diverse participants from diverse providers, and consider cost-effectiveness of the interventions provided over the long term in order to facilitate sustained implementation across cancer centers.

BACKGROUND:Individuals with opioid use disorder (OUD) have a high prevalence of co-occurring mental health disorders; however, there exists little information on mental health service use for this population. We aimed to determine the prevalence of non-substance use-related mental health emergency department (ED) visits, hospitalizations, and outpatient physician visits for individuals receiving treatment for OUD over one year. We also explored individual-level characteristics associated with mental health care service use and estimated the costs of this care. METHODS:We linked observational cohort data collected from 3,430 individuals receiving treatment for OUD in Ontario, Canada, with health administrative records available for all individuals enrolled in Ontario's public health insurance program. Eligible participants were receiving medication treatment for OUD and were recruited between 2011 and 2021 Starting on the day of cohort enrolment, we included health service data for up to 12 months. We identified ED visits and hospitalizations for non-substance use-related mental health disorders using ICD-10-CA diagnostic codes. Outpatient mental health visits to primary care providers and psychiatrists were ascertained by examining the diagnostic codes of physician billing claims. We used logistic regression to explore the association between demographic and clinical factors of interest and mental health-related ED visits or hospitalizations. Mean one-year mental healthcare costs, calculated in 2022 Canadian dollars, were estimated. We fit a two-part zero-inflated negative binomial model to explore the association between factors of interest and healthcare costs. FINDINGS:Altogether, 14.9% of individuals had mental health-related acute care ED visits or hospitalizations and 37.3% had outpatient mental health visits during the follow up period. For participants with at least one visit, we determined the mean number of ED visits (1.93, standard deviation [SD] = 2.15), hospitalizations (1.46, SD = 1.05), primary care visits (3.51, SD = 4.31), and psychiatry visits (4.04, SD = 4.73). Lower odds of ED use and hospitalization were associated with older age (46+ compared to less than 25 years: odds ratio [OR] 0.43, 95% confidence interval [CI]: 0.29, 0.63) and being employed (OR 0.48, 95% CI 0.37, 0.61). Higher odds of ED use and hospitalization was associated with positive opioid urine drug screens (50% positive urine drug screens compared to 0%: OR 1.45, 95% CI 1.05, 2.01), having more comorbid conditions (7+ health conditions compared to 0-2 health conditions: OR 3.76, 95% CI 2.60, 5.44), and receipt of outpatient mental healthcare (OR 2.38, 95% CI 1.95, 2.92) were associated with higher odds of ED visits or hospitalizations. Mean one-year mental healthcare costs for individuals receiving ED visits or hospitalizations totaled $9,117.80 (95% CI 7,372.90, 10,862.70) per person. Mean one-year costs for individuals with outpatient mental healthcare alone totaled $382.30 (95% CI 343.20, 421.30) per person. CONCLUSIONS:Individuals receiving treatment for OUD receive care in EDs, inpatient units, and outpatient clinics for mental health conditions other than substance use-related diagnoses. Healthcare costs were considerably higher for those receiving acute care treatment for mental health conditions. Studying integrated mental health and substance use disorder treatment in the outpatient setting should be a priority to bolster care for this population.

OBJECTIVES:Equitable representation in research leadership is essential across all areas of medical science. In the context of HIV-where women are disproportionately affected-examining gender distribution in the leadership of HIV trials is essential to assess progress towards equity and identify persisting barriers. METHODS:We conducted a methodological study of trials from the CASCADE database, which evaluates interventions to improve the HIV care cascade. We extracted first and last authors' names and used Genderize.io to determine their gender, classifying authors as 'women' if the probability was 60% or greater. The primary outcome was the proportion of trials with women in leadership (first or last author), with secondary outcomes examining the proportions of trials with women as: first authors, last authors and in both roles. We also assessed associations with country income level, focus on women participants, study setting, pragmatism and team size. RESULTS:Gender for both authorship roles could be determined in 332 trials, of which 233/332 (70.2%) had a woman first or last author; 169/334 (50.6%) had a woman first author; 143/337 (42.4%) had a woman last author and 74/332 (22.3%) featured women in both roles. Women's leadership increased over time but was not associated with country income level, gender focus, study setting or impact factor. Effectiveness trials and those with fewer authors were more likely to have women in leadership. CONCLUSIONS:Women's leadership in HIV trials has increased, reflecting progress in gender equity. However, smaller author teams appear to facilitate women's leadership, suggesting barriers in larger collaborations. Continued efforts are needed to ensure sustained progress and equitable representation.

Background: The substance use crisis continues to progress. Medication for Opioid Use Disorder (MOUD) prescribed to reduce opioid use and related harms; however, many individuals continue to use substances while on treatment. The objective of this study was to describe the temporal and demographic trends of the agreement between self-reported and urine tested substances. Methods: The current study is a retrospective secondary analysis of three phases of a prospective cohort study (Pilot 2011, Genetics of opioid addiction (GENOA) 2013-2017, and Pharmacogenetics of opioid substitution treatment (POST)) 2018-2022) spanning 2011-2022. We compared the self-reported substance use data opioids, benzodiazepines, amphetamine/methamphetamine (AMP/MET), and cocaine with urine drug results. We compared the positive predictive value (PPV), false omission rate (FOR), sensitivity, and specificity between (i) different drugs; (ii) by sex, and (iii) age group at enrollment in each phase of the study using self-reported substance use at baseline and retrospective electronic health record data on urine drug screenings collected over the same time period. Results: Overall, the average PPV and FOR for any drug across all phases was 80.7 % and 37.9 %, respectively. Sensitivity and specificity were highest for cocaine and lowest for benzodiazepines. We found no specific trend by sex. Lastly, we found a higher sensitivity for opioids and AMP/MET in those under 25 years of age compared to other age groups. PPV increased over time for benzodiazepines, AMP/MET and cocaine and FOR was higher during the pilot and POST phases than the GENOA phase. Conclusion: Our study highlights the unique challenges associated with ascertaining substance use behaviour individuals receiving MOUD, indicating many patients will accurately report substance use while others do not. is therefore important to consider the context of the patient, and the type of the co-substance used to select patient-centred testing as indicated. Therefore, the answer to the question of do we need urine drug screen is yes in some cases.

Background Multimorbidity, the presence of two or more (2+) chronic conditions, presents significant challenges for healthcare delivery, particularly among populations with opioid use disorder (OUD). Multimorbidity patterns among individuals with OUD are not well established, and minimal research exists examining the impact of clustering methods on identifying these patterns.Objective Our study aimed to assess multimorbidity prevalence, explore associated sociodemographic and clinical characteristics, and determine multimorbidity patterns using hierarchical cluster analysis (HCA) and K-means clustering among people receiving treatment for OUD in Ontario, Canada between 2011 and 2021.Methods Data from two prospective cohort studies were merged and linked to Ontario provincial health administrative databases. We identified 16 chronic conditions, used in prior research examining multimorbidity in Ontario, using ICD-10-CA diagnostic codes and the diagnostic codes of physician billing claims using a 2-year lookback. Multimorbidity was defined as the presence of 2+ of the above conditions, excluding the diagnosis of OUD. We conducted a retrospective cohort study, following the participants for eight years in the data holdings to ascertain the prevalence of multimorbidity. Sociodemographic and clinical characteristics were analyzed using modified Poisson regression models, and multimorbidity patterns were identified through HCA and K-means clustering.Results Among 3,430 people with OUD, 32.5% (n = 1,114, 95% confidence interval (CI)=30.9, 34.1) experienced multimorbidity over an eight-year period, with older age (Prevalence Ratio (PR)=3.39, 95% CI = 2.36, 4.87) and unemployment (PR = 1.31, 95% CI = 1.13, 1.54) associated with increased prevalence. HCA identified six distinct disease clusters, whereas K-means clustering identified four clusters. Both methods identified groupings of cardiovascular (coronary syndrome), cardiometabolic (diabetes, hypertension), and respiratory (chronic obstructive pulmonary disease) diseases, reflecting shared comorbidities among people with OUD.Discussion Our findings highlight the substantial burden of multimorbidity among populations with OUD, and the importance of considering sociodemographic factors in understanding multimorbidity prevalence. Moreover, the choice of clustering method significantly influences the identification and interpretation of multimorbidity patterns, with HCA providing more clinically meaningful groupings compared to K-means clustering. Our findings highlight the need for clinicians to tailor care plans and for policymakers to prioritize integrated healthcare delivery strategies to address the complex health needs of people with OUD.

Bayesian analyses offer a robust framework for integrating data from multiple sources to better inform population-level estimates of disease prevalence. This methodological approach is particularly suited to instances where data from observational studies is linked to administrative health records, with the capacity to advance our understanding of psychiatric disorders. The objective of our paper was to provide an introductory overview and tutorial on Bayesian analysis for primary observational studies in mental health research. We provided: (i) an overview of Bayesian statistics, (ii) the utility of Bayesian methods for psychiatric epidemiology, (iii) a tutorial example of a Bayesian approach to estimating the prevalence of mood and/or anxiety disorders in observational research, and (iv) suggestions for reporting Bayesian analyses in health research.

OBJECTIVES:Despite significant rises in unregulated stimulant use across North America, little is known about the characteristics of stimulant use among individuals with opioid use disorder (OUD). This study sought to describe patterns of stimulant use among a cohort of patients receiving opioid agonist therapy (OAT) from 2013 to 2020. METHODS:A multi-center prospective cohort study (2013-2020) was undertaken to recruit patients > 16 years of age or older with OUD receiving OAT from 57 outpatient treatment centers in Ontario, Canada. Baseline data collected upon enrollment included demographics, medical history, current OAT prescription, and substance use patterns. Participants were followed for 1 year, with regular urine drug screens (UDS). The primary outcome was temporal change in baseline stimulant use reported at a cohort level, including type and frequency, over the study period. Multivariable logistic regressions were used to identify patient factors associated with higher likelihood of stimulant use. RESULTS:A total of 3476 participants were recruited between 2013 and 2020. The percentage of respondents reporting stimulant use increased from 18.0 % to 32.9 % (p-value 0.06) during this time. The observed increase was driven by a significant rise in crystal methamphetamine use from 2.0 % to 17.7 % (p-value 0.002). The proportion of patients using stimulants daily also increased, from 0.4 % in 2013 to 7.6 % in 2020 (p-value 0.002). The reported increase in use was corroborated by UDS findings. Overall, higher likelihood of stimulant use was associated with lower rates of employment (Odds ratio [OR] = 0.72, 95 % Confidence Interval [CI]: 0.61, 0.86), daily fentanyl consumption (OR = 3.49, 95 % CI: 1.87, 6.51) and injection drug use (OR = 7.95, 95 % CI: 6.38, 9.91). CONCLUSIONS:Among individuals receiving OAT for OUD, an increasing trend in stimulant use was observed from 2013 to 2020, driven primarily by the significant rise in crystal methamphetamine use. Understanding the evolving patterns of concurrent substance use in patients on OAT is essential for public health responses, harm reduction programs and treatment planning.

OBJECTIVE:We systematically reviewed the existing literature on the efficacy of the ketogenic diet (KD) in patients with epileptic spasms (ES) and analyzed predictors of seizure outcomes. METHODS:The Preferred Report Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines were followed. The primary outcome was the proportion of patients achieving 50-99 % spasm reduction at 3 months following KD initiation. Additional outcomes included the proportion of patients achieving complete spasm freedom at 1, 3, and 6 months. Meta-regression was employed to examine clinical determinants of seizure outcomes. RESULTS:Twenty-two studies (n = 1077 individuals) were included. There were 607 males (62.2 %) and 369 females (37.8 %) (k = 16 studies). The mean age of KD initiation was 16 months (SD: 5.4, range: 8.4-23 months) (k = 11 studies). Epilepsy etiology was reported in 453 individuals (k = 15 studies), 297 (65.6 %) had a known etiology and 156 (34.4 %) were unknown. Structural (n = 178, 59.9 %) and genetic/metabolic (n = 80, 26.9 %) causes were common. Most received the classic ketogenic diet (n = 975/1077, 90.5 %) and 102 patients (9.5 %) received the modified Atkins diet (MAD). At 3 months, 48 % (95 % CI: 40 %, 57 %) achieved a 50-99 % spasm reduction and 25 % (95 % CI: 17 %, 34 %), achieved spasm freedom. At 6 months, 41 % (95 % CI: 32 %, 50 %) achieved 50-99 % spasm reduction and 25 % (95 % CI: 17 %,35 %), achieved spasm freedom. Meta-regression did not identify predictors of treatment response. CONCLUSION:KD may be an effective treatment option for ES. However, predictors of clinical response were not identified, highlighting the need for larger studies to better understand them and long-term outcomes.

Background The fragility index is a statistical measure of the robustness or "stability" of a statistically significant result. It has been adapted to assess the robustness of statistically significant outcomes from randomized controlled trials. By hypothetically switching some non-responders to responders, for instance, this metric measures how many individuals would need to have responded for a statistically significant finding to become non-statistically significant. The purpose of this study is to assess the fragility index of randomized controlled trials evaluating opioid substitution and antagonist therapies for opioid use disorder. This will provide an indication as to the robustness of trials in the field and the confidence that should be placed in the trials' outcomes, potentially identifying ways to improve clinical research in the field. This is especially important as opioid use disorder has become a global epidemic, and the incidence of opioid related fatalities have climbed 500% in the past two decades.Methods Six databases were searched from inception to September 25, 2021, for randomized controlled trials evaluating opioid substitution and antagonist therapies for opioid use disorder, and meeting the necessary requirements for fragility index calculation. Specifically, we included all parallel arm or two-by-two factorial design RCTs that assessed the effectiveness of any opioid substitution and antagonist therapies using a binary primary outcome and reported a statistically significant result. The fragility index of each study was calculated using methods described by Walsh and colleagues. The risk of bias of included studies was assessed using the Revised Cochrane Risk of Bias tool for randomized trials.Results Ten studies with a median sample size of 82.5 (interquartile range (IQR) 58, 179, range 52-226) were eligible for inclusion. Overall risk of bias was deemed to be low in seven studies, have some concerns in two studies, and be high in one study. The median fragility index was 7.5 (IQR 4, 12, range 1-26).Conclusions Our results suggest that approximately eight participants are needed to overturn the conclusions of the majority of trials in opioid use disorder. Future work should focus on maximizing transparency in reporting of study results, by reporting confidence intervals, fragility indexes, and emphasizing the clinical relevance of findings.Trial registration PROSPERO CRD42013006507. Registered on November 25, 2013.

Introduction:Atopic dermatitis (AD) is a chronic inflammatory skin disease with multifactorial pathophysiology. Biologic therapies, including dupilumab (IL-4/IL-13 inhibitor) and tralokinumab (IL-13 inhibitor), as well as selective Janus kinase-1 (JAK-1) inhibitors such as upadacitinib and abrocitinib, have been approved for the treatment of moderate to severe AD. However, their association with the incidence of malignancy in AD patients remains uncertain. Aim:We conducted a systematic review and network meta-analysis (NMA) to investigate and compare the indidence and risk of malignancy in individuals with moderate-to-severe AD treated with abrocitinib, upadacitinib, tralokinumab, or dupilumab. Material and methods:Systematic searches were conducted in Ovid MEDLINE and EMBASE that included AD, malignancy, biologic and advanced therapies. The primary outcome was incidence of malignancy in AD patients receiving placebo or at least one of the following advanced therapies: dupilumab, tralokinumab, abrocitinib or upadacitinib. A random-effects NMA was conducted with odds ratios and a frequentist model. Results:Our search identified 11 trials comprising 10097 patients. The NMA did not show any statistically significant association between dupilumab or selective JAK-1 inhibitors and the incidence of malignancy up to an average of 41 weeks of treatment. Conclusions:Our analysis revealed no statistically significant increased risk of malignancy and no significant difference in the incidence of malignancy between selective JAK-1 inhibitors and dupilumab for the treatment of AD up to an average follow-up of 41 weeks. Nevertheless, further prospective studies with longer follow-up periods are warranted to confirm the safety of these therapies and their impact on the risk of malignancy.

Background Among patients with opioid use disorder (OUD), high rates of overdose and death have been reported in subgroups with Hepatitis C Virus (HCV). Evidence on the comorbid effect of HCV on clinical and substance use trajectories has been limited by small sample sizes, short follow-up, and heavy reliance on administrative data which lacks granularity on important prognostic factors. Additionally, few studies include populations on substance use treatment. Aim To establish the impact of HCV exposure (antibody positivity) on health care utilization patterns, substance use treatment response, and death in a cohort of patients with OUD on opioid agonist therapy (OAT). Methods This multi-center prospective cohort study recruited adult patients with OUD on OAT from 57 substance use treatment centers in Ontario, Canada. The study collected substance use outcomes, and classified patients with ≥50 % positive opioid urine screens over one year of follow-up as having poor treatment response. Additional data obtained via linkage with ICES administrative databases evaluated the relationship between HCV status, healthcare service utilization, and death over 3 years of follow-up. Multiple logistic regression models established the adjusted impact of HCV on various outcomes. Results Among recruited participants (n = 3430), 44.10 % were female with a mean age of 38.64 years (Standard deviation: 10.96). HCV was prevalent in 10.6 % of the cohort (n = 365). Methadone was used most often (83.9 %, n = 2876), followed by sublingual buprenorphine (16.2 %, n = 554). Over the three-year follow-up, 5.3 % of patients died (n = 181). Unadjusted results reveal rates of hospitalization (all-cause, mental-health related, critical care) and emergency department visits (mental health-related), were significantly higher among HCV patients. Associations diminished in adjusted models. Active injection drug use exhibited the highest predictive risk for all outcomes. Conclusion A high degree of acute physical and mental illness and its resulting health service utilization burden is concentrated among patients with OUD and comorbid HCV. Future research should explore the role for targeted interventions and how best to implement integrated healthcare models to better address the complex health needs of HCV populations who inject drugs.

Objective To characterise sex and gender-based analysis (SGBA) and diversity metric reporting, representation of female/women participants in acute care trials and temporal changes in reporting before and after publication of the 2016 Sex and Gender Equity in Research guideline.Design Systematic review.Data sources We searched MEDLINE for trials published in five leading medical journals in 2014, 2018 and 2020.Study selection Trials that enrolled acutely ill adults, compared two or more interventions and reported at least one clinical outcome.Data abstraction and synthesis 4 reviewers screened citations and 22 reviewers abstracted data, in duplicate. We compared reporting differences between intensive care unit (ICU) and cardiology trials.Results We included 88 trials (75 (85.2%) ICU and 13 (14.8%) cardiology) (n=111 428; 38 140 (34.2%) females/women). Of 23 (26.1%) trials that reported an SGBA, most used a forest plot (22 (95.7%)), were prespecified (21 (91.3%)) and reported a sex-by-intervention interaction with a significance test (19 (82.6%)). Discordant sex and gender terminology were found between headings and subheadings within baseline characteristics tables (17/32 (53.1%)) and between baseline characteristics tables and SGBA (4/23 (17.4%)). Only 25 acute care trials (28.4%) reported race or ethnicity. Participants were predominantly white (78.8%) and male/men (65.8%). No trial reported gendered-social factors. SGBA reporting and female/women representation did not improve temporally. Compared with ICU trials, cardiology trials reported significantly more SGBA (15/75 (20%) vs 8/13 (61.5%) p=0.005).Conclusions Acute care trials in leading medical journals infrequently included SGBA, female/women and non-white trial participants, reported race or ethnicity and never reported gender-related factors. Substantial opportunity exists to improve SGBA and diversity metric reporting and recruitment of female/women participants in acute care trials.PROSPERO registration number CRD42022282565.