Investigating the Interplay Between Mental Health Conditions and Social Connectedness on Suicide Risk: Findings from a Clinical Sample of Adolescents.

This study examined whether school and community connectedness buffer the relationships between mental health conditions and suicide risk in a clinical sample of adolescents with histories of substance use disorders. Data from 294 adolescents were examined, with approximately 58% reporting lifetime suicidal ideation and/or prior attempts. Multinomial logistic regression was used to examine main and interaction effects on a three-category measure of suicide risk. Depression severity and panic disorder were associated with elevated suicidal ideation risk, whereas disordered eating was associated with elevated risk of attempts. Higher school-based positive peer interactions, school safety, and neighborhood social connection levels were associated with reduced suicide attempt risk. Moderation analyses revealed that high neighborhood social connection levels may partially mitigate the elevated likelihood of attempting suicide associated with disordered eating. Findings suggest clinical populations of adolescents may benefit from approaches aiming to promote social connectedness, further supporting a comprehensive approach to suicide prevention.

Interpersonal violence and suicide risk: Examining buffering effects of school and community connectedness.

Background: Exposure to interpersonal violence is associated with elevated suicide risk. Preventing suicide among high-risk adolescents is most often discussed from a clinical treatment perspective, resulting in a gap in research examining whether school and community connectedness can buffer the relationships between forms of interpersonal violence and suicide risk in clinical samples of adolescents. Methods: Baseline data from 294 adolescents who received substance use treatment were analyzed to help fill this gap in research. Adolescents in this sample were at greater risk for suicidal thoughts and behaviors given their histories of substance use disorders and high rates of interpersonal violence, with 57% reporting experiencing at least one form of abuse/violence. Independent variables included lifetime exposure to physical abuse, sexual abuse, and weapon violence; moderators included various measures of school and community connectedness. Multinomial logistic regression models were estimated to examine the main and interaction effects predicting a three-category measure of suicide risk: non-suicidal, suicidal ideation only, and prior suicide attempts. Results: Sexual abuse survivors had the highest predicted probability of a prior suicide attempt when reporting lower levels of teacher support, school-based positive peer interactions, or neighborhood social connection, but at higher levels of these protective factors, their predicted probability was similar to those not exposed to sexual abuse. The same protective pattern was observed for physical abuse survivors with high neighborhood social connection. Conclusion: The buffering effects observed in this study identified dimensions of school and community social connectedness as protective factors for youth exposed to abuse. Although promoting social connectedness is often cited as a universal suicide prevention approach, tailored efforts to enhance connectedness within this population may also be a promising secondary prevention strategy. Thus, in addition to clinical treatment, more emphasis should be placed on systems-level approaches to reducing risk among youth most vulnerable to suicide.

Probiotic Supplementation for Promotion of Growth in Undernourished Children: A Systematic Review and Meta-Analysis.

OBJECTIVES: Probiotic supplementation has been proposed as a therapeutic intervention to improve growth outcomes in children with undernutrition. The objective of this review is to synthesize the current evidence on probiotic supplementation for promotion of growth in undernourished children. METHODS: We searched MEDLINE, Cochrane CENTRAL, CINAHL, Embase, LILACS, and Scopus for randomized controlled trials (RCTs) that administered probiotics or eligible comparators to undernourished children below 5 years of age. Our primary outcomes of interest were weight-for-age, height-for-age, and weight-for-height at the longest follow-up points reported. Random-effects meta-analysis was used to calculate standardized mean differences (SMD) for continuous outcomes and risk ratios for dichotomous outcomes. The Grading of Recommendations Assessment, Development and Evaluation criteria were used to assess certainty of the evidence. RESULTS: Nine RCTs with 5295 children in total were included. Durations of treatment ranged from 1 month to 1 year. Pooled analyses from 7 studies showed that probiotics may have little to no effect on weight-for-age (SMD 0.05 standard deviation [SD], 95% CI: -0.04 to 0.13, n = 2115 children; low-certainty evidence) and height-for-age (SMD -0.04 SD, 95% CI: -0.14 to 0.07, n = 1357 children; low-certainty evidence). The evidence was very uncertain about the effect on weight-for-height. CONCLUSIONS: Probiotics may have little to no effect on anthropometry in undernourished children, though there is considerable heterogeneity among the trials reviewed thus far. The interaction between gut microbiota and human nutrition is complex, and further research is needed to determine how the gut microbiome may contribute to undernutrition and how probiotics may affect growth in this vulnerable population.

Fecal transplantation for treatment of inflammatory bowel disease.

BACKGROUND: Inflammatory bowel disease (IBD) is a chronic, relapsing disease of the gastrointestinal (GI) tract that is thought to be associated with a complex interplay between the immune system, the GI tract lining, the environment, and the gut microbiome, leading to an abnormal inflammatory response in genetically susceptible individuals. An altered composition of the gut's native microbiota, known as dysbiosis, may have a major role in the pathogenesis of ulcerative colitis (UC) and Crohn disease (CD), two subtypes of IBD. There is growing interest in the correction of this underlying dysbiosis using fecal microbiota transplantation (FMT). OBJECTIVES: To evaluate the benefits and safety profile of FMT for treatment of IBD in adults and children versus autologous FMT, placebo, standard medication, or no intervention. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, two clinical trial registries, and the reference sections of published trials through 22 December 2022. SELECTION CRITERIA: We included randomized controlled trials that studied adults and children with UC or CD. Eligible intervention arms used FMT, defined as the delivery of healthy donor stool containing gut microbiota to a recipient's GI tract, to treat UC or CD. DATA COLLECTION AND ANALYSIS: Two review authors independently screened studies for inclusion. Our primary outcomes were: 1. induction of clinical remission, 2. maintenance of clinical remission, and 3. serious adverse events. Our secondary outcomes were: 4. any adverse events, 5. endoscopic remission, 6. quality of life, 7. clinical response, 8. endoscopic response, 9. withdrawals, 10. inflammatory markers, and 11. microbiome outcomes. We used the GRADE approach to assess the certainty of evidence. MAIN RESULTS: We included 12 studies with 550 participants. Three studies were conducted in Australia; two in Canada; and one in each of the following: China, the Czech Republic, France, India, the Netherlands, and the USA. One study was conducted in both Israel and Italy. FMT was administered in the form of capsules or suspensions and delivered by mouth, nasoduodenal tube, enema, or colonoscopy. One study delivered FMT by both oral capsules and colonoscopy. Six studies were at overall low risk of bias, while the others had either unclear or high risk of bias. Ten studies with 468 participants, of which nine studies focused on adults and one focused on children, reported induction of clinical remission in people with UC at longest follow-up (range 6 to 12 weeks) and showed that FMT may increase rates of induction of clinical remission in UC compared to control (risk ratio (RR) 1.79, 95% confidence interval (CI) 1.13 to 2.84; low-certainty evidence). Five studies showed that FMT may increase rates of induction of endoscopic remission in UC at longest follow-up (range 8 to 12 weeks); however, the CIs around the summary estimate were wide and included a possible null effect (RR 1.45, 95% CI 0.64 to 3.29; low-certainty evidence). Nine studies with 417 participants showed that FMT may result in little to no difference in rates of any adverse events (RR 0.99, 95% CI 0.85 to 1.16; low-certainty evidence). The evidence was very uncertain about the risk of serious adverse events (RR 1.77, 95% CI 0.88 to 3.55; very low-certainty evidence) and improvement in quality of life (mean difference (MD) 15.34, 95% CI -3.84 to 34.52; very low-certainty evidence) when FMT was used to induce remission in UC. Two studies, of which one also contributed data for induction of remission in active UC, assessed maintenance of remission in people with controlled UC at longest follow-up (range 48 to 56 weeks). The evidence was very uncertain about the use of FMT for maintenance of clinical remission (RR 2.97, 95% CI 0.26 to 34.42; very low-certainty evidence) and endoscopic remission (RR 3.28, 95% CI 0.73 to 14.74; very low-certainty evidence). The evidence was also very uncertain about the risk of serious adverse events, risk of any adverse events, and improvement in quality of life when FMT was used to maintain remission in UC. None of the included studies assessed use of FMT for induction of remission in people with CD. One study with 21 participants reported data on FMT for maintenance of remission in people with CD. The evidence was very uncertain about the use of FMT for maintenance of clinical remission in CD at 24 weeks (RR 1.21, 95% CI 0.36 to 4.14; very low-certainty evidence). The evidence was also very uncertain about the risk of serious or any adverse events when FMT was used to maintain remission in CD. None of the studies reported data on use of FMT for maintenance of endoscopic remission or improvement in quality of life in people with CD. AUTHORS' CONCLUSIONS: FMT may increase the proportion of people with active UC who achieve clinical and endoscopic remission. The evidence was very uncertain about whether use of FMT in people with active UC impacted the risk of serious adverse events or improvement in quality of life. The evidence was also very uncertain about the use of FMT for maintenance of remission in people with UC, as well as induction and maintenance of remission in people with CD, and no conclusive statements could be made in this regard. Further studies are needed to address the beneficial effects and safety profile of FMT in adults and children with active UC and CD, as well as its potential to promote longer-term maintenance of remission in UC and CD.

Fecal microbiota transplantation for the treatment of recurrent Clostridioides difficile (Clostridium difficile).

BACKGROUND: Clostridioides difficile (formerly known as Clostridium difficile) is a bacterium that can cause potentially life-threatening diarrheal illness in individuals with an unhealthy mixture of gut bacteria, known as dysbiosis, and can cause recurrent infections in nearly a third of infected individuals. The traditional treatment of recurrent C difficile infection (rCDI) includes antibiotics, which may further exacerbate dysbiosis. There is growing interest in correcting the underlying dysbiosis in rCDI using of fecal microbiota transplantation (FMT); and there is a need to establish the benefits and harms of FMT for the treatment of rCDI based on data from randomized controlled trials. OBJECTIVES: To evaluate the benefits and harms of donor-based fecal microbiota transplantation for the treatment of recurrent Clostridioides difficile infection in immunocompetent people. SEARCH METHODS: We used standard, extensive Cochrane search methods. The latest search date was 31 March 2022. SELECTION CRITERIA: We considered randomized trials of adults or children with rCDI for inclusion. Eligible interventions must have met the definition of FMT, which is the administration of fecal material containing distal gut microbiota from a healthy donor to the gastrointestinal tract of a person with rCDI. The comparison group included participants who did not receive FMT and were given placebo, autologous FMT, no intervention, or antibiotics with activity against C difficile. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were 1. proportion of participants with resolution of rCDI and 2. serious adverse events. Our secondary outcomes were 3. treatment failure, 4. all-cause mortality, 5. withdrawal from study, 6. rate of new CDI infection after a successful FMT, 7. any adverse event, 8. quality of life, and 9. colectomy. We used the GRADE criteria to assess certainty of evidence for each outcome. MAIN RESULTS: We included six studies with 320 participants. Two studies were conducted in Denmark, and one each in the Netherlands, Canada, Italy, and the US. Four were single-center and two were multicenter studies. All studies included only adults. Five studies excluded people who were severely immunocompromised, with only one study including 10 participants who were receiving immunosuppressive therapy out of the 64 enrolled; these were similarly distributed between the FMT arm (4/24 or 17%) and comparison arms (6/40 or 15%). The route of administration was the upper gastrointestinal tract via a nasoduodenal tube in one study, two studies used enema only, two used colonoscopic only delivery, and one used either nasojejunal or colonoscopic delivery, depending on a clinical determination of whether the recipient could tolerate a colonoscopy. Five studies had at least one comparison group that received vancomycin. The risk of bias (RoB 2) assessments did not find an overall high risk of bias for any outcome. All six studies assessed the efficacy and safety of FMT for the treatment of rCDI. Pooled results from six studies showed that the use of FMT in immunocompetent participants with rCDI likely leads to a large increase in resolution of rCDI in the FMT group compared to control (risk ratio (RR) 1.92, 95% confidence interval (CI) 1.36 to 2.71; P = 0.02, I2 = 63%; 6 studies, 320 participants; number needed to treat for an additional beneficial outcome (NNTB) 3; moderate-certainty evidence). Fecal microbiota transplantation probably results in a slight reduction in serious adverse events; however, the CIs around the summary estimate were wide (RR 0.73, 95% CI 0.38 to 1.41; P = 0.24, I² = 26%; 6 studies, 320 participants; NNTB 12; moderate-certainty evidence). Fecal microbiota transplantation may result in a reduction in all-cause mortality; however, the number of events was small, and the CIs of the summary estimate were wide (RR 0.57, 95% CI 0.22 to 1.45; P = 0.48, I2 = 0%; 6 studies, 320 participants; NNTB 20; low-certainty evidence). None of the included studies reported colectomy rates. AUTHORS' CONCLUSIONS: In immunocompetent adults with rCDI, FMT likely leads to a large increase in the resolution of recurrent Clostridioides difficile infection compared to alternative treatments such as antibiotics. There was no conclusive evidence regarding the safety of FMT for the treatment of rCDI as the number of events was small for serious adverse events and all-cause mortality. Additional data from large national registry databases might be required to assess any short-term or long-term risks with using FMT for the treatment of rCDI. Elimination of the single study that included some immunocompromised people did not alter these conclusions. Due to the low number of immunocompromised participants enrolled, conclusions cannot be drawn about the risks or benefits of FMT for rCDI in the immunocompromised population.

Investigating for Whom Brief Substance Use Interventions Are Most Effective: An Individual Participant Data Meta-analysis.

Prior research suggests that brief interventions (BIs) for alcohol and other drug use may vary in effectiveness across patient sociodemographic factors. The objective of this individual participant data (IPD) meta-analysis was to explore for whom BIs delivered in general healthcare settings are more or less effective. We examined variability in BI effects by patient age, sex, employment, education, relationship status, and baseline severity of substance use using a two-stage IPD meta-analysis approach. All trials included in a parent aggregate data meta-analysis (k = 116) were invited to contribute IPD, and 29 trials provided patient-level data (12,074 participants). Among females, BIs led to significant reductions in binge alcohol consumption ([Formula: see text] = 0.09, 95% CI [0.03, 0.14]), frequency of alcohol consumption ([Formula: see text] = 0.10, 95% CI [0.03, 0.17]), and alcohol-related consequences ([Formula: see text] = 0.16, 95% CI [0.08, 0.25]), as well as greater substance use treatment utilization ([Formula: see text] = 0.25, 95% CI [0.21, 0.30]). BIs yielded larger reductions in frequency of alcohol consumption at 3-month follow-up for individuals with less than a high school level education ([Formula: see text] = 0.16, 95% CI [0.09, 0.22]). Given evidence demonstrating modest BI effects on alcohol use and mixed or null findings for BI effects on other drug use, BI research should continue to investigate potential drivers of effect magnitude and variation.  PROTOCOL REGISTRATION DETAILS: The protocol for this review was pre-registered in PROSPERO #CRD42018086832 and the analysis plan was pre-registered in OSF: osf.io/m48g6.

Brief Alcohol Interventions are Effective through 6 Months: Findings from Marginalized Zero-inflated Poisson and Negative Binomial Models in a Two-step IPD Meta-analysis.

To evaluate and optimize brief alcohol interventions (BAIs), it is critical to have a credible overall effect size estimate as a benchmark. Estimating such an effect size has been challenging because alcohol outcomes often represent responses from a mixture of individuals: those at high risk for alcohol misuse, occasional nondrinkers, and abstainers. Moreover, some BAIs exclusively focus on heavy drinkers, whereas others take a universal prevention approach. Depending on sample characteristics, the outcome distribution might have many zeros or very few zeros and overdispersion; consequently, the most appropriate statistical model may differ across studies. We synthesized individual participant data (IPD) from 19 studies in Project INTEGRATE (Mun et al., 2015b) that randomly allocated participants to intervention and control groups (N = 7,704 participants, 38.4% men, 74.7% White, 58.5% first-year students). We sequentially estimated marginalized zero-inflated Poisson (Long et al., 2014) or negative binomial regression models to obtain covariate-adjusted, study-specific intervention effect estimates in the first step, which were subsequently combined in a random-effects meta-analysis model in the second step. BAIs produced a statistically significant 8% advantage in the mean number of drinks at both 1-3 months (RR = 0.92, 95% CI = [0.85, 0.98]) and 6 months (RR = 0.92, 95% CI = [0.85, 0.99]) compared to controls. At 9-12 months, there was no statistically significant difference in the mean number of drinks between BAIs and controls. In conclusion, BAIs are effective at reducing the mean number of drinks through at least 6 months post intervention. IPD can play a critical role in deriving findings that could not be obtained in original individual studies or standard aggregate data meta-analyses.

Using Machine Learning to Identify and Investigate Moderators of Alcohol Use Intervention Effects in Meta-Analyses.

AIMS: To illustrate a machine learning-based approach for identifying and investigating moderators of alcohol use intervention effects in aggregate-data meta-analysis. METHODS: We illustrated the machine learning technique of random forest modeling using data from an ongoing meta-analysis of brief substance use interventions implemented in general healthcare settings. A subset of 40 trials testing brief alcohol interventions (BAIs) was used; these trials provided 344 estimates of post-intervention effects on participants' alcohol use as well as data on 20 potential moderators of intervention effects. These candidate moderators included characteristics of trial methodology and implementation, intervention design and participant samples. RESULTS: The best-fitting random forest model identified 10 important moderators from the pool of 20 candidate moderators. Meta-regression utilizing the selected moderators found that inclusion of prescriptive advice in a BAI session significantly moderated BAI effects on alcohol use. Observed effects were also significantly moderated by several methodological characteristics of trials, including the type of comparison group used, the overall level of attrition and the strategy used to address missing data. In a meta-regression model that included all candidate moderators, fewer coefficients were found to be significant, indicating that the use of a preliminary data reduction technique to identify only important moderators for inclusion in final analyses may have yielded improved statistical power to detect moderation. CONCLUSIONS: Machine learning methods can be valuable tools for clarifying the influence of trial, intervention and sample characteristics on alcohol use intervention effects, in particular when numerous candidate moderators are available.

Modern Meta-Analytic Methods in Prevention Science: Introduction to the Special Issue.

Meta-analyses that statistically synthesize evidence from multiple research studies can play an important role in advancing evidence-informed prevention science. When done in the context of a well-conducted systematic review, meta-analysis is a powerful tool for synthesizing evidence and exploring research questions that are difficult to address in individual studies, such as the association of individual study limitations on intervention effect estimates, replicability of empirical findings, and variation of effect estimates across populations and settings. Alongside the rapid growth in the number of published reviews and meta-analyses, there has been a parallel growth in the development of meta-analytic techniques to handle the increasingly complex types of questions and types of evidence relevant to prevention science. Despite this rapid evolution of meta-analytic techniques and approaches, there is still a lag between the development of new techniques and their uptake by researchers in the field. This paper serves as a brief introduction to this special issue of Prevention Science, entitled "Modern Meta-Analytic Methods in Prevention Science," which highlights recent developments in meta-analytic methods and demonstrates their application to prevention research. This special issue makes an important contribution to the field by ensuring these methodological advances are widely accessible to prevention science researchers, thereby improving their uptake and utilization, and ultimately improving the utility and rigor of research syntheses for informing evidence-based decision making in prevention.

Differential Predictors of Suicidal Ideation and Suicide Attempts: Internalizing Disorders and Substance Use in a Clinical Sample of Adolescents.

Objective: Dually diagnosed adolescents are a high-risk population for experiencing suicidal thoughts and behavior. Given that research suggests risk factors for suicidal ideation and suicide attempts may be different, this study examined whether internalizing disorder severity, frequency of substance use, and the interaction between them differentiated adolescents who attempted suicide from those who ideated. Methods: Baseline data from 287 adolescents who received formal substance use disorder (SUD) treatment were used in this analysis. Major depressive disorder (MDD) and generalized anxiety disorder (GAD) severity as well as past-3 month use of alcohol, cannabis, and other illicit drugs were considered. The outcome of interest was a three-category measure of suicide risk: no reported suicidal ideation or attempts, suicidal ideation only, and suicide attempts. Results: Over half of the sample disclosed prior suicidal ideation (30.0%) or attempts (27.9%). Multinomial logistic regression models indicated more severe MDD and GAD symptomology differentiated ideators from non-suicidal adolescents, but internalizing disorder severity did not differ between ideators and attempters. Substance use frequency did not differ between suicide risk groups. MDD severity and frequency of alcohol use interacted to increase the risk of attempts, yet the effects were minimal. Instead, prior weapon violence victimization and sexual abuse were the largest differentiators between attempters and ideators. Conclusions: Findings suggest that internalizing disorder severity and prior traumatic experiences put adolescents with SUD histories at higher risk of suicidal thoughts and behaviors. Thus, integrating evidence-based suicide prevention and intervention efforts into SUD treatment is critical, particularly for dually diagnosed adolescents who meet these risk profiles. Psychotherapy and medication may help curtail the development of ideation by reducing symptoms of MDD and GAD, whereas adolescents with prior traumatic experiences may benefit from additional treatments shown to lower risk of suicide attempts.

Discrepant Parent-Adolescent Reports of Parenting Practices: Associations with Adolescent Internalizing and Externalizing Symptoms.

Discrepancies in multi-informant reports of parenting practices represent a meaningful clinical construct that can be harnessed to predict adolescent mental health outcomes and shed light on the nature of parent-adolescent relationships. To date, however, no research has sought to examine discrepancies in perceptions of parenting practices among adolescents with histories of substance use disorders, a population for whom supportive parenting is a critical protective factor during the recovery process. This study examined parent-adolescent informant discrepancies of parenting practices and their associations with externalizing and internalizing symptomology among a sample of adolescents with substance use disorder histories. Data were analyzed from 294 adolescents (M adolescent age = 16 years; 45% female, 72% white) and their parents (87% female, 83% white) from a larger longitudinal study. Parenting practices of interest were positive parenting, inconsistent discipline, and poor monitoring. Polynomial regression analyses were used to test the discrepancy hypotheses. The results generally suggested null associations between single informant reports and internalizing and externalizing symptoms. Discrepancies were noted, however, in multi-informant reports of positive parenting, such that higher levels of adolescent-reported positive parenting were associated with higher levels of internalizing symptoms at high (but not low) levels of parent-reported positive parenting. Similarly, discrepancies were noted in multi-informant reports of poor monitoring, such that lower levels of adolescent-poor monitoring were associated with higher externalizing symptoms at low levels of parent-reported poor monitoring. The findings are discussed in terms of research and clinical implications of collecting and utilizing multi-informant data among clinical samples of adolescents with unique risk profiles.

Interventions for preventing diarrhoea-associated haemolytic uraemic syndrome.

BACKGROUND: Haemolytic uraemic syndrome (HUS) is a common cause of acquired kidney failure in children and rarely in adults. The most important risk factor for development of HUS is a gastrointestinal infection by Shiga toxin-producing Escherichia coli (STEC). This review addressed the interventions aimed at secondary prevention of HUS in patients with diarrhoea who were infected with a bacteria that increase the risk of HUS. OBJECTIVES: Our objective was to evaluate evidence regarding secondary preventative strategies for HUS associated with STEC infections. In doing so, we sought to assess the effectiveness and safety of interventions as well as their potential to impact the morbidity and death associated with this condition. SEARCH METHODS: We searched the Cochrane Kidney and Transplant Register of Studies up to 12 November 2020 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov. SELECTION CRITERIA: Studies were considered based on the methods, participants, and research goals. Only randomised controlled trials were considered eligible for inclusion. The participants of the studies were paediatric and adult patients with diarrhoeal illnesses due to STEC. The primary outcome of interest was incidence of HUS. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures as recommended by Cochrane. Summary estimates of effect were obtained using a random-effects model, and results were expressed as risk ratios (RR) and their 95% confidence intervals (CI) for dichotomous outcomes. Confidence in the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. MAIN RESULTS: We identified four studies (536 participants) for inclusion that investigated four different interventions including antibiotics (trimethoprim-sulfamethoxazole), anti-Shiga toxin antibody-containing bovine colostrum, Shiga toxin binding agent (Synsorb Pk: a silicon dioxide-based agent), and a monoclonal antibody against Shiga toxin (urtoxazumab). The overall risk of bias was unclear for selection, performance and detection bias and low for attrition, reporting and other sources of bias. It was uncertain if trimethoprim-sulfamethoxazole reduced the incidence of HUS compared to no treatment (47 participants: RR 0.57, 95% CI 0.11-2.81, very low certainty evidence). Adverse events relative to this review, need for acute dialysis, neurological complication and death were not reported. There were no incidences of HUS in either the bovine colostrum group or the placebo group. It was uncertain if bovine colostrum caused more adverse events (27 participants: RR 0.92, 95% CI 0.42 to 2.03; very low certainty evidence). The need for acute dialysis, neurological complications or death were not reported. It is uncertain whether Synsorb Pk reduces the incidence of HUS compared to placebo (353 participants: RR 0.93, 95% CI 0.39 to 2.22; very low certainty evidence). Adverse events relevant to this review, need for acute dialysis, neurological complications or death were not reported. One study compared two doses of urtoxazumab (3.0 mg/kg and 1.0 mg/kg) to placebo. It is uncertain if either 3.0 mg/kg urtoxazumab (71 participants: RR 0.34, 95% CI 0.01 to 8.14) or 1.0 mg/kg urtoxazumab (74 participants: RR 0.95, 95% CI 0.79 to 1.13) reduced the incidence of HUS compared to placebo (very low certainty evidence). Low certainty evidence showed there may be little or no difference in the number of treatment-emergent adverse events with either 3.0 mg/kg urtoxazumab (71 participants: RR 1.00, 95% CI 0.84 to 1.18) or 1.0 mg/kg urtoxazumab (74 participants: RR 0.95, 95% CI 0.79 to 1.13) compared to placebo. There were 25 serious adverse events reported in 18 patients: 10 in the placebo group, and 9 and 6 serious adverse events in the 1.0 mg/kg and 3.0 mg/kg urtoxazumab groups, respectively. It is unclear how many patients experienced these adverse events in each group, and how many patients experienced more than one event. It is uncertain if either dose of urtoxazumab increased the risk of neurological complications or death (very low certainty evidence). Need for acute dialysis was not reported. AUTHORS' CONCLUSIONS: The included studies assessed antibiotics, bovine milk, and Shiga toxin inhibitor (Synsorb Pk) and monoclonal antibodies (Urtoxazumab) against Shiga toxin for secondary prevention of HUS in patients with diarrhoea due to STEC. However, no firm conclusions about the efficacy of these interventions can be drawn given the small number of included studies and the small sample sizes of those included studies. Additional studies, including larger multicentre studies, are needed to assess the efficacy of interventions to prevent development of HUS in patients with diarrhoea due to STEC infection.

Recovery High School Attendance Effects on Student Delinquency and Substance Use: the Moderating Role of Social Problem Solving Styles.

Recovery high schools (RHSs) provide educational programming and therapeutic support services for young people in recovery from substance use disorders (SUDs). The objectives of this study were to examine whether students with SUDs who attended RHSs report less delinquency and substance use than students with SUDs who attended non-RHSs, and how students' social problem solving styles might moderate those associations. Participants were students from a longitudinal quasi-experimental study of adolescents who enrolled in high schools after receiving treatment for SUDs. The propensity-score balanced sample included 260 adolescents (143 in RHSs, 117 in non-RHSs) enrolled in schools in Minnesota, Wisconsin, or Texas (M age = 16; 83% White; 44% female). Negative binomial regression models were used to compare delinquency and substance use outcomes for RHS and non-RHS students at 6-month and 12-month follow-ups. The results indicated that students attending RHSs after discharge from SUD treatment reported less frequent delinquent behavior while intoxicated, and fewer days of substance use relative to students attending non-RHSs. Negative problem solving styles moderated the effect of RHS attendance on substance use outcomes, with RHSs providing minimal beneficial effects for those students endorsing maladaptive problem solving styles. We conclude that RHSs offer a promising continuing care approach for adolescents in recovery from SUD problems, but may vary in their effectiveness for students with impulsive, careless, or avoidant problem solving styles.

The impact of afterschool program attendance on academic outcomes of middle school students.

This evaluation examined the effects of afterschool programs-supported by an afterschool system intermediary organization (ASIO)-on middle school students' academic performance and examined how those effects varied by student characteristics and program engagement. In this longitudinal, quasi-experimental matched comparison group evaluation, propensity score matching was used to create demographically balanced samples of ASIO-supported afterschool program participants and nonparticipants. Students enrolled in the afterschool programs did not differ from non-participants in growth over time on most academic outcomes. Students attending the afterschool programs showed less growth on certain state test scores compared to nonparticipants. Student demographic characteristics did not consistently influence participant outcomes. Among program participants only, students who were enrolled more than 1 year demonstrated a 7-percentile-point increase in state test scores per year of program engagement. There was no consistent evidence that ASIO-supported afterschool program participation was associated with improved student academic outcomes. However, study results support increased emphasis on afterschool program retention, given that longer duration of participation in the afterschool programs was associated with more growth on multiple academic outcomes.

Net Benefits of Recovery High Schools: Higher Cost but Increased Sobriety and Educational Attainment.

BACKGROUND: Recovery high schools (RHS) provide a supportive educational and therapeutic environment for students subsequent to treatment for substance use disorders (SUDs). Most students served by RHSs have concurrent mental health disorders and are at risk for school failure or dropout and substance use relapse. AIMS OF THE STUDY: The central question addressed is whether RHSs are economically efficient alternatives to other high school settings for students in recovery. The aim is to estimate the incremental cost-benefit of RHSs. METHODS: A quasi-experimental non-equivalent pretest-posttest comparison group design was used. We compared substance use and educational outcomes for adolescents who had received specialty SUD treatment; 143 who enrolled in an RHS were compared to 117 who enrolled in a non-RHS school. Groups were balanced by use of a propensity score to drop students who were not similar to those in the other group. The propensity score was also used as a covariate in multiple regression to estimate cost and outcome parameters and standard errors. To take account of uncertainties in impacts and shadow prices, we used Monte Carlo simulations to estimate the distribution of incremental benefits of RHS relative to non-RHS schooling. RESULTS: Two beneficial impacts of statistical and substantive importance were identified: increased probability of high school graduation and increased sobriety. RHS students had significantly (p<.05) less substance use during the study period -- at 12-month follow-up, 55% of RHS and 26% of comparison students reported 3 month abstinence from alcohol and drugs. Urinalysis confirmed abstinence from THC (cannabis) for 68% of RHS versus 37% of comparison students. RHS students' high school graduation rates were 21 to 25 percentage points higher than comparison students. Adopting a societal perspective, incremental benefits of RHSs were estimated by monetizing the increased probability of high school graduation and comparing it to incremental costs. Mean net benefits ranged from USD16.1 thousand to USD51.9 thousand per participant; benefit-to-cost ratios ranged from 3.0 to 7.2. DISCUSSION: Monetizing the benefits and the incremental costs of RHS relative to conventional schooling show substantial positive net benefits from RHS participation. Two factors lend credibility to the results. First, the RHS improvement in substance use indicates a mechanism through which the increased probability of high school graduation can plausibly occur. Second, the estimated increases in the probability of high school graduation were large and statistically significant. As the productivity gains from high school graduation are also large, the dominant benefit category is very plausible. Limitations include the non-randomized design; selection bias into the study conditions not fully controlled by the propensity scores; generalizability only to young people with treated behavioral health disorders; lack of estimates for direct monetization of reduced substance use among adolescents; possible attenuation of the value of education among individuals with behavioral health issues; and uncertainty in calculation of school costs. IMPLICATIONS FOR BEHAVIORAL HEALTH POLICIES: This research provides evidence that the recovery high school model provides cost beneficial support for high school students after primary SUD treatment. The students who enroll in RHSs typically have co-occurring mental health and substance use disorders, adding complexity to their continuing care. Funding policies recognizing the multiple systems of care (behavioral health, education, child and family services, juvenile justice) responsible for these young people are called for.

Comparative Effectiveness of Brief Alcohol Interventions for College Students: Results from a Network Meta-Analysis.

Late adolescence is a time of increased drinking, and alcohol plays a predominant role in college social experiences. Colleges seeking to prevent students' hazardous drinking may elect to implement brief alcohol interventions (BAIs). However, numerous manualized BAIs exist, so an important question remains regarding the comparative effectiveness of these different types of BAIs for college students. This study uses network meta-analyses (NMA) to compare seven manualized BAIs for reducing problematic alcohol use among college students. We systematically searched multiple sources for literature, and we screened studies and extracted data in duplicate. For the quantitative synthesis, we employed a random-effects frequentist NMA to determine the effectiveness of different BAIs compared to controls and estimated the relative effectiveness ranking of each BAI. A systematic literature search resulted in 52 included studies: On average, 58% of participants were male, 75% were binge drinkers, and 20% were fraternity/sorority-affiliated students. Consistency models demonstrated that BASICS was consistently effective in reducing students' problematic alcohol use (ES range: g = - 0.23, 95%CI [- 0.36, - 0.16] to g = - 0.36, 95% CI [- 0.55, - 0.18]), but AlcoholEDU (g = - 0.13, 95%CI [- 0.22, - 0.04]), e-CHUG (g = - 0.35, 95%CI [- 0.45, - 0.05]), and THRIVE (g = - 0.47, 95%CI [- 0.60, - 0.33]) were also effective for some outcomes. Intervention rankings indicated that BASICS, THRIVE, and AlcoholEDU hold the most promise for future trials. Several BAIs appear effective for college students. BASICS was the most effective but is resource intensive and may be better suited for higher risk students; THRIVE and e-CHUG are less resource intensive and show promise for universal prevention efforts.

Meta-analytic approaches for examining complexity and heterogeneity in studies of adolescent development.

INTRODUCTION: In the field of adolescent development, meta-analysis offers valuable tools for synthesizing and assessing cumulative research evidence on the effectiveness of programs, practices, and policies intended to promote healthy adolescent development. When examining the impact of a program implemented across multiple primary studies, variation is often observed in the methodological attributes of those primary studies, such as their implementation methods, program components, participant characteristics, outcome measurement, and the systems in which programs are deployed. Differences in methodological attributes of primary studies represented in a meta-analysis, referred to as complexity, can yield variation in true effects across primary studies, which is described as heterogeneity. METHODS: We discuss heterogeneity as a parameter of interest in meta-analysis, introducing and demonstrating both graphical and statistical methods for evaluating the magnitude and impact of heterogeneity. We discuss approaches for presenting characteristics of heterogeneity in meta-analytic findings, and methods for identifying and statistically controlling for aspects of methodological complexity that may contribute to variation in effects across primary studies. RESULTS: Topics and methods related to assessing and explaining heterogeneity were contextualized in the field of adolescent development using a sample of primary studies from a large meta-analysis examining the effectiveness of brief alcohol interventions for youth. We highlighted approaches currently underutilized in the field and provided R code for key methods to broaden their use. CONCLUSIONS: By discussing various heterogeneity statistics, visualizations, and explanatory methods, this article provides the applied developmental researcher a foundational understanding of complexity and heterogeneity in meta-analysis.

Meta-Analysis of Complex Interventions.

Meta-analysis is a prominent method for estimating the effects of public health interventions, yet these interventions are often complex in ways that pose challenges to using conventional meta-analytic methods. This article discusses meta-analytic techniques that can be used in research syntheses on the effects of complex public health interventions. We first introduce the use of complexity frameworks to conceptualize public health interventions. We then present a menu of meta-analytic procedures for addressing various sources of complexity when answering questions about the effects of public health interventions in research syntheses. We conclude with a review of important practices and key resources for conducting meta-analyses on complex interventions, as well as future directions for research synthesis more generally. Overall, we argue that it is possible to conduct meaningful quantitative syntheses of research on the effects of public health interventions, though these meta-analyses may require the use of advanced techniques to properly consider and attend to issues of complexity.

Fecal transplantation for treatment of inflammatory bowel disease.

BACKGROUND: Inflammatory bowel disease (IBD) is a chronic, relapsing disease of the gastrointestinal tract that is thought to be associated with a complex interplay between microbes and the immune system, leading to an abnormal inflammatory response in genetically susceptible individuals. Dysbiosis, characterized by the alteration of the composition of the resident commensal bacteria in a host compared to healthy individuals, is thought to play a major role in the pathogenesis of ulcerative colitis (UC) and Crohn's disease (CD), two subtypes of IBD. There is growing interest to correct the underlying dysbiosis through the use of fecal microbiota transplantation (FMT) for the treatment of IBD. OBJECTIVES: The objective of this systematic review was to assess the efficacy and safety of FMT for the treatment of IBD. SEARCH METHODS: We searched the MEDLINE, Embase, Cochrane Library, and Cochrane IBD Group Specialized Register databases from inception to 19 March 2018. We also searched ClinicalTrials.gov, ISRCTN metaRegister of Controlled Trials, and the Conference Proceedings Citation Index. SELECTION CRITERIA: Only randomized trials or non-randomized studies with a control arm were considered for inclusion. Adults or pediatric participants with UC or CD were eligible for inclusion. Eligible interventions were FMT defined as the administration of fecal material containing distal gut microbiota from a healthy donor to the gastrointestinal tract of a someone with UC or CD. The comparison group included participants who did not receive FMT and were given placebo, autologous FMT, or no intervention. DATA COLLECTION AND ANALYSIS: Two authors independently screened the titles and extracted data from the included studies. We used the Cochrane risk of bias tool to assess study bias. The primary outcomes were induction of clinical remission, clinical relapse, and serious adverse events. Secondary outcomes included clinical response, endoscopic remission and endoscopic response, quality of life scores, laboratory measures of inflammation, withdrawals, and microbiome outcomes. We calculated the risk ratio (RR) and corresponding 95% confidence interval (95% CI) for dichotomous outcomes and the mean difference and 95% CI for continuous outcomes. Random-effects meta-analysis models were used to synthesize effect sizes across trials. The overall certainty of the evidence supporting the primary and selected secondary outcomes was rated using the GRADE criteria. MAIN RESULTS: Four studies with a total of 277 participants were included. These studies assessed the efficacy of FMT for treatment of UC in adults; no eligible trials were found for the treatment of CD. Most participants had mild to moderate UC. Two studies were conducted in Australia, one study was conducted in Canada, and another in the Netherlands. Three of the included studies administered FMT via the rectal route and one study administered FMT via the nasoduodenal route. Three studies were rated as low risk of bias. One study (abstract publication) was rated as unclear risk of bias. Combined results from four studies (277 participants) suggest that FMT increases rates of clinical remission by two-fold in patients with UC compared to controls. At 8 weeks, 37% (52/140) of FMT participants achieved remission compared to 18% (24/137) of control participants (RR 2.03, 95 % CI, 1.07 to 3.86; I² = 50%; low certainty evidence). One study reported data on relapse at 12 weeks among participants who achieved remission. None of the FMT participants (0/7) relapsed at 12 weeks compared to 20% of control participants (RR 0.28, 95% CI 0.02 to 4.98, 17 participants, very low certainty evidence). It is unclear whether there is a difference in serious adverse event rates between the intervention and control groups. Seven per cent (10/140) of FMT participants had a serious adverse event compared to 5% (7/137) of control participants (RR 1.40, 95% CI 0.55 to 3.58; 4 studies; I² = 0%; low certainty evidence). Serious adverse events included worsening of UC necessitating intravenous steroids or surgery; infection such as Clostridium difficile and cytomegalovirus, small bowel perforation and pneumonia. Adverse events were reported by two studies and the pooled data did not show any difference between the study groups. Seventy-eight per cent (50/64) of FMT participants had an adverse event compared to 75% (49/65) of control participants (RR 1.03, 95% CI 0.81 to 1.31; I² = 31%; moderate certainty evidence). Common adverse events included abdominal pain, nausea, flatulence, bloating, upper respiratory tract infection, headaches, dizziness, and fever. Four studies reported on clinical response at 8 weeks. Forty-nine per cent (68/140) of FMT participants had a clinical response compared to 28% (38/137) of control participants (RR 1.70, 95% CI 0.98 to 2.95, I² = 50%, low certainty evidence). Endoscopic remission at 8 weeks was reported by three studies and the combined results favored FMT over the control group. Thirty per cent (35/117) of FMT participants achieved endoscopic remission compared to 10% (11/112) of control participants (RR 2.96, 95 % CI 1.60 to 5.48, I² = 0%; low certainty evidence). AUTHORS' CONCLUSIONS: Fecal microbiota transplantation may increase the proportion of participants achieving clinical remission in UC. However, the number of identified studies was small and the quality of evidence was low. There is uncertainty about the rate of serious adverse events. As a result, no solid conclusions can be drawn at this time. Additional high-quality studies are needed to further define the optimal parameters of FMT in terms of route, frequency, volume, preparation, type of donor and the type and disease severity. No studies assessed efficacy of FMT for induction of remission in CD or in pediatric participants. In addition, no studies assessed long-term maintenance of remission in UC or CD. Future studies are needed to address the therapeutic benefit of FMT in CD and the long-term FMT-mediated maintenance of remission in UC or CD.

Empirically Based Mean Effect Size Distributions for Universal Prevention Programs Targeting School-Aged Youth: A Review of Meta-Analyses.

This review of reviews presents an empirically based set of mean effect size distributions for judging the relative impact of the effects of universal mental health promotion and prevention programs for school-age youth (ages 5 through 18) across a range of program targets and types of outcomes. Mean effect size distributions were established by examining the findings from 74 meta-analyses of universal prevention and promotion programs that included more than 1100 controlled outcome studies involving over 490,000 school-age youth. The distributions of mean effect sizes from these meta-analyses indicated considerable variability across program targets and outcomes that differed substantially from Cohen's (1988, Statistical power analysis for the behavioral sciences (2nd ed.)) widely used set of conventions for assessing if effects are small, medium, or large. These updated mean effect size distributions will provide researchers, practitioners, and funders with more appropriate evidence-based standards for judging the relative effects of universal prevention programs for youth. Limitations in current data and directions for future work are also discussed.