<sec id="st1"><title>BACKGROUND</title>The inclusion of adolescents in TB drug trials is essential for the development of safe, child-friendly regimens for the prevention and treatment of TB. TB Trials Consortium Study 31/AIDS Clinical Trials Group A5349 (S31/A5349) enrolled adolescents as young as 12 years old. We assessed investigator and coordinator described facilitators and barriers to adolescent recruitment, enrollment, and retention.</sec><sec id="st2"><title>METHODS</title>Interviews were conducted with six investigators from sites that enrolled adolescent participants and six investigators from non-enrolling sites. Additionally, two focus groups were conducted with study coordinators from enrolling sites and two focus groups with non-enrolling sites. Discussions were transcribed, analyzed, summarized, and summaries were reviewed by Community Research Advisors Group members and research group representatives for content validity.</sec><sec id="st3"><title>RESULTS</title>Investigators and coordinators attributed the successful enrollment of adolescents to the establishment and cultivation of external partnerships, flexibility to accommodate adolescents' schedules, staff engagement, recruitment from multiple locations, dedicated recruitment staff working onsite to access potential participants, creation of youth-friendly environments, and effective communications. Non-enrolling sites were mainly hindered by regulations. Suggestions for improvement in future trials focused on study planning and site preparations.</sec><sec id="st4"><title>CONCLUSION</title>Proactive partnerships and collaboration with institutions serving adolescents helped identify and reduce barriers to their inclusion in this trial.</sec>.

School connectedness is an important factor in the lives of youth and are a leverage point for optimizing youth's social, emotional, and physical health. This study presents a meta-analysis examining the relationship between school connectedness and four health domains that are prevalent in adolescence, have implications for adult health, and often co-occur: mental health, sexual health, violence, and high-risk substance use. Ninety articles published between 2009 and 2019 were included in the analysis. The study found that school connectedness had a protective average effect size across all health domains (Hedges' g = -0.345, p-value<0.001). When examined separately, school connectedness had a significant protective relationship with substance use (g = -0.379, p < 0.001), mental health (Hedges' g = -0.358, p < 0.001), violence (Hedges' g = -0.318, p < 0.001), sexual health (Hedges' g = -0.145, p < 0.001), and with co-occurring risks (Hedges' g = -0.331, p < 0.001). These results provide strong evidence that school connectedness has the potential to prevent and mitigate multiple health risks during adolescence.

BACKGROUND: Cardiopulmonary exercise testing has demonstrated clinical utility in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). However, to what extent exercise responses are independent of, or confounded by, aerobic fitness remains unclear. PURPOSE: To characterize and compare exercise responses in ME/CFS and controls with and without matching for aerobic fitness. METHODS: As part of the Multi-site Clinical Assessment of ME/CFS (MCAM) study, 403 participants (n = 214 ME/CFS; n = 189 controls), across six ME/CFS clinics, completed ramped cycle ergometry to volitional exhaustion. Metabolic, heart rate (HR), and ratings of perceived exertion (RPE) were measured. Ventilatory equivalent ([Formula: see text], [Formula: see text]), metrics of ventilatory efficiency, and chronotropic incompetence (CI) were calculated. Exercise variables were compared using Hedges' g effect size with 95% confidence intervals. Differences in cardiopulmonary and perceptual features during exercise were analyzed using linear mixed effects models with repeated measures for relative exercise intensity (20-100% peak [Formula: see text]). Subgroup analyses were conducted for 198 participants (99 ME/CFS; 99 controls) matched for age (5 years) and peak [Formula: see text] (~1 ml/kg/min-1). RESULTS: Ninety percent of tests (n = 194 ME/CFS, n = 169 controls) met standard criteria for peak effort. ME/CFS responses during exercise (20-100% peak [Formula: see text]) were significantly lower for ventilation, breathing frequency, HR, measures of efficiency, and CI and significantly higher for [Formula: see text], [Formula: see text] and RPE (p<0.05adjusted). For the fitness-matched subgroup, differences remained for breathing frequency, [Formula: see text], [Formula: see text], and RPE (p<0.05adjusted), and higher tidal volumes were identified for ME/CFS (p<0.05adjusted). Exercise responses at the gas exchange threshold, peak, and for measures of ventilatory efficiency (e.g., [Formula: see text]) were generally reflective of those seen throughout exercise (i.e., 20-100%). CONCLUSION: Compared to fitness-matched controls, cardiopulmonary responses to exercise in ME/CFS are characterized by inefficient exercise ventilation and augmented perception of effort. These data highlight the importance of distinguishing confounding fitness effects to identify responses that may be more specifically associated with ME/CFS.

INTRODUCTION: With the growing use of online study management systems and rapid availability of data, timely data review and quality assessments are necessary to ensure proper clinical trial implementation. In this report we describe central monitoring used to ensure protocol compliance and accurate data reporting, implemented during a large phase 3 clinical trial. MATERIAL AND METHODS: The Tuberculosis Trials Consortium (TBTC) Study 31/AIDS Clinical Trials Group (ACTG) study A5349 (S31) is an international, multi-site, randomized, open-label, controlled, non-inferiority phase 3 clinical trial comparing two 4-month regimens to a standard 6 month regimen for treatment of drug-susceptible tuberculosis (TB) among adolescents and adults with a sample size of 2500 participants. RESULTS: Central monitoring utilized primary study data in a five-tiered approach, including (1) real-time data checks & topic-specific intervention reports, (2) missing forms reports, (3) quality assurance metrics, (4) critical data reports and (5) protocol deviation identification, aimed to detect and resolve quality challenges. Over the course of the study, 240 data checks and reports were programed across the five tiers used. DISCUSSION: This use of primary study data to identify issues rapidly allowed the study sponsor to focus quality assurance and data cleaning activities on prioritized data, related to protocol compliance and accurate reporting of study results. Our approach enabled us to become more efficient and effective as we informed sites about deviations, resolved missing or inconsistent data, provided targeted guidance, and gained a deeper understanding of challenges experienced at clinical trial sites. TRIAL REGISTRATION: This trial was registered with ClinicalTrials.gov (Identifier: NCT02410772) on April 8, 2015.

Introduction: There is a great need for analytic techniques that allow for the synthesis of learning across seemingly idiosyncratic interventions. Objectives: The primary objective of this paper is to introduce taxonomic meta-analysis and explain how it is different from conventional meta-analysis. Results: Conventional meta-analysis has previously been used to examine the effectiveness of childhood obesity prevention interventions. However, these tend to examine narrowly defined sections of obesity prevention initiatives, and as such, do not allow the field to draw conclusions across settings, participants, or subjects. Compared with conventional meta-analysis, taxonomic meta-analysis widens the aperture of what can be examined to synthesize evidence across interventions with diverse topics, goals, research designs, and settings. A component approach is employed to examine interventions at the level of their essential features or activities to identify the concrete aspects of interventions that are used (intervention components), characteristics of the intended populations (target population or intended recipient characteristics), and facets of the environments in which they operate (contextual elements), and the relationship of these components to effect size. In addition, compared with conventional meta-analysis methods, taxonomic meta-analyses can include the results of natural experiments, policy initiatives, program implementation efforts and highly controlled experiments (as examples) regardless of the design of the report being analyzed as long as the intended outcome is the same. It also characterizes the domain of interventions that have been studied. Conclusion: Taxonomic meta-analysis can be a powerful tool for summarizing the evidence that exists and for generating hypotheses that are worthy of more rigorous testing.

Meta-analysis has been used to examine the effectiveness of childhood obesity prevention efforts, yet traditional conventional meta-analytic methods restrict the kinds of studies included, and either narrowly define mechanisms and agents of change, or examine the effectiveness of whole interventions as opposed to the specific actions that comprise interventions. Taxonomic meta-analytic methods widen the aperture of what can be included in a meta-analysis data set, allowing for inclusion of many types of interventions and study designs. The National Collaborative on Childhood Obesity Research Childhood Obesity Evidence Base (COEB) project focuses on interventions intended to prevent childhood obesity in children 2-5 years old who have an outcome measure of BMI. The COEB created taxonomies, anchored in the Social Ecological Model, which catalog specific outcomes, intervention components, intended recipients, and contexts of policies, initiatives, and interventions conducted at the individual, interpersonal, organizational, community, and societal level. Taxonomies were created by discovery from the literature itself using grounded theory. This article describes the process used for a novel taxonomic meta-analysis of childhood obesity prevention studies between the years 2010 and 2019. This method can be applied to other areas of research, including obesity prevention in additional populations.

Objective: To evaluate the efficacy of childhood obesity interventions and conduct a taxonomy of intervention components that are most effective in changing obesity-related health outcomes in children 2-5 years of age. Methods: Comprehensive searches located 51 studies from 18,335 unique records. Eligible studies: (1) assessed children aged 2-5, living in the United States; (2) evaluated an intervention to improve weight status; (3) identified a same-aged comparison group; (4) measured BMI; and (5) were available between January 2005 and August 2019. Coders extracted study, sample, and intervention characteristics. Effect sizes [ESs; and 95% confidence intervals (CIs)] were calculated by using random-effects models. Meta-regression was used to determine which intervention components explain variability in ESs. Results: Included were 51 studies evaluating 58 interventions (N = 29,085; mean age = 4 years; 50% girls). Relative to controls, children receiving an intervention had a lower BMI at the end of the intervention (g = 0.10, 95% CI = 0.02-0.18; k = 55) and at the last follow-up (g = 0.17, 95% CI = 0.04-0.30; k = 14; range = 18-143 weeks). Three intervention components moderated efficacy: engage caregivers in praise/encouragement for positive health-related behavior; provide education about the importance of screen time reduction to caregivers; and engage pediatricians/health care providers. Conclusions: Early childhood obesity interventions are effective in reducing BMI in preschool children. Our findings suggest that facilitating caregiver education about the importance of screen time reduction may be an important strategy in reducing early childhood obesity.

On March 16, 2020, the day that national social distancing guidelines were released (1), the Arkansas Department of Health (ADH) was notified of two cases of coronavirus disease 2019 (COVID-19) from a rural county of approximately 25,000 persons; these cases were the first identified in this county. The two cases occurred in a husband and wife; the husband is the pastor at a local church (church A). The couple (the index cases) attended church-related events during March 6-8, and developed nonspecific respiratory symptoms and fever on March 10 (wife) and 11 (husband). Before his symptoms had developed, the husband attended a Bible study group on March 11. Including the index cases, 35 confirmed COVID-19 cases occurred among 92 (38%) persons who attended events held at church A during March 6-11; three patients died. The age-specific attack rates among persons aged </=18 years, 19-64 years, and >/=65 years were 6.3%, 59.4%, and 50.0%, respectively. During contact tracing, at least 26 additional persons with confirmed COVID-19 cases were identified among community members who reported contact with church A attendees and likely were infected by them; one of the additional persons was hospitalized and subsequently died. This outbreak highlights the potential for widespread transmission of SARS-CoV-2, the virus that causes COVID-19, both at group gatherings during church events and within the broader community. These findings underscore the opportunity for faith-based organizations to prevent COVID-19 by following local authorities' guidance and the U.S. Government's Guidelines: Opening Up America Again (2) regarding modification of activities to prevent virus transmission during the COVID-19 pandemic.

BACKGROUND/AIMS: Efficient recruitment of eligible participants, optimizing time and sample size, is a crucial component in conducting a successful clinical trial. Inefficient participant recruitment can impede study progress, consume staff time and resources, and limit quality and generalizability or the power to assess outcomes. Recruitment for disease prevention trials poses additional challenges because patients are asymptomatic. We evaluated candidates for a disease prevention trial to determine reasons for nonparticipation and to identify factors that can be addressed to improve recruitment efficiency. METHODS: During 2001-2009, the Tuberculosis Trials Consortium conducted Study 26 (PREVENT TB), a randomized clinical trial at 26 sites in four countries, among persons with latent tuberculosis infection at high risk for tuberculosis disease progression, comparing 3 months of directly observed once-weekly rifapentine plus isoniazid with 9 months of self-administered daily isoniazid. During March 2005-February 2008, non-identifying demographic information, risk factors for experiencing active tuberculosis disease, and reasons for not enrolling were collected from screened patients to facilitate interpretation of trial data, to meet Consolidated Standards of Reporting Trials standards, and to evaluate reasons for nonparticipation. RESULTS: Of the 7452 candidates screened in Brazil, Canada, Spain, and the United States, 3584 (48%) were not enrolled, because of ineligibility (41%), site decision (10%), or patient choice (49%). Among those who did not enroll by own choice, and for whom responses were recorded on whether they would accept treatment outside of the study (n = 1430), 68% reported that they planned to accept non-study latent tuberculosis infection treatment. Among 1305 patients with one or more reported reasons for nonparticipation, study staff recorded a total of 1886 individual reasons (reason count: median = 1/patient; range = 1-9) for why patients chose not to enroll, including grouped concerns about research (24% of 1886), work or school conflicts (20%), medication or health beliefs (16%), latent tuberculosis infection beliefs (11%), and patient lifestyle and family concerns (10%). CONCLUSION: Educational efforts addressing clinical research concerns and beliefs about medication and health, as well as study protocols that accommodate patient-related concerns (e.g. work, school, and lifestyle) might increase willingness to enter clinical trials. Findings from this evaluation can support development of communication and education materials for clinical trial sites at the beginning of a trial to allow study staff to address potential participant concerns during study screening.

Worldwide, infectious diseases continue to emerge at an alarming pace, due to numerous factors including microbial adaptation, increasing human population migration, urbanization, conflict and instability, intensified animal-human interface, and habitat perturbation [1,2,3,4,5,6]. The litmus test for an effective national public health program is its ability to be ready to initiate an effective response for an unknown emerging or re-emerging infectious disease or public health event. The most impactful global health programs are built with the understanding that they must be able to help countries strengthen core public health capacity so that new threats can be detected and contained before they become international crises that increase morbidity and mortality, adversely impact the health and livelihoods of individuals and populations, disrupt travel, interfere with global trade and economies, or even lead to political destabilization [6, 7].

PURPOSE OF REVIEW: This study was to present meta-analysis findings across selected clinical trials for the effect of health information technologies (HITs) on glycemic control among patients with type 2 diabetes. RECENT FINDINGS: HITs may be promising in diabetes management. However, findings on effect size of glycated hemoglobin level (HbA1c) yielded from HITs varied across previous studies. This is likely due to heterogeneity in sample size, adherence to standard quantitative method, and/or searching criteria (e.g., type of HITs, type of diabetes, specification of patient population, randomized vs. nonrandomized trials). We systematically searched Medline, Cumulative Index of Nursing and Allied Health Literature (CINAHL), and the Cochrane Library for peer-reviewed randomized control trials that studied the effect of HITs on HbA1c reduction. We also used Google Scholar and a hand search to identify additional studies. Thirty-four studies (40 estimates) met the criteria and were included in the analysis. Overall, introduction of HITs to standard diabetes treatment resulted in a statistically and clinically reduced HbA1c. The bias adjusted HbA1c reduction due to the combined HIT interventions was - 0.56 [Hedges' g = - 0.56 (- 0.70, - 0.43)]. The reduction was significant across each of the four types of HIT intervention under review, with mobile phone-based approaches generating the largest effects [Hedges' g was - 0.67 (- 0.90, - 0.45)]. HITs can be an effective tool for glycemic control among patients with type 2 diabetes. Future studies should examine long-term effects of HITs and explore factors that influence their effectiveness.

HIV testing among persons with tuberculosis (TB) results in high-yield identification of persons infected with HIV. To evaluate differences in HIV testing among children versus adults with TB in Vietnam, we collected and analyzed age-disaggregated facility and aggregated provincial data from the National Tuberculosis Program. HIV testing was incompletely documented for >70% of children, whereas adult testing data were >90% complete. Standardized training of personnel for universal HIV testing and documentation for children with TB could improve HIV case-detection and permit linking of children with HIV to antiretroviral treatment to prevent morbidity and mortality.

Many antineoplastic drugs used to treat cancer, particularly alkylating agents and topoisomerase inhibitors, are known to induce genetic damage in patients. Elevated levels of chromosomal aberrations, micronuclei, and DNA damage have been documented in cancer patients. Elevations in these same biomarkers of genetic damage have been reported in numerous studies of healthcare workers, such as nurses and pharmacists, who routinely handle these drugs, but results vary across studies. To obtain an overall assessment of the exposure effect, we performed a meta-analysis on data obtained from peer-reviewed publications reporting chromosomal aberration levels in healthcare workers exposed to antineoplastic drugs. A literature search identified 39 studies reporting on occupational exposure to antineoplastic drugs and measurement of chromosomal aberrations in healthcare workers. After applying strict inclusion criteria for data quality and presentation, data from 17 studies included in 16 publications underwent meta-analysis using Hedges' bias-corrected g and a random-effects model. Results showed the level of chromosomal aberrations in healthcare workers exposed to antineoplastic drugs was significantly higher than in controls. The standardized mean differences (difference of means divided by within sd) from all studies were pooled, yielding a value 1.006 (unitless) with p< 0.001. Thus, in addition to the documented genotoxic effects of antineoplastic drugs in cancer patients, this meta-analysis confirmed a significant association between occupational exposure to antineoplastics during the course of a normal work day and increases in chromosomal aberrations in healthcare workers. Based on the studies reviewed, we were unable to accurately assess whether appropriate use of protective measures might reduce the incidence of genetic damage in healthcare workers. However, given the potential for increased cancer risk linked to increases in chromosomal aberrations, the results of this study support the need to limit occupational exposure of healthcare workers to antineoplastic drugs as much as possible.

In the second of two companion papers, we conducted a meta-analysis of sexual health interventions in three domains. The interventions chosen for the meta-analysis were a subset of studies presented in a narrative review (the first of the two companion papers); these in turn were selected on the basis of fit to principles derived from the World Health Organization (WHO) and other definitions of sexual health. Studies (n = 20) were drawn from Medline and PsycINFO databases (English language, adult populations, 1996-2011) and fell into three domains: knowledge, attitudes, and sexual behaviors. We estimated intervention effects via Hedges' g, using the random-effects approach. Initial estimates revealed a large effect for knowledge, g = 1.32 (95% CI = 0.51-2.14), and smaller effects for attitude change, g = 0.17 (0.11-0.24) and behavior, g = 0.21 (0.13-0.29). After removing outliers to produce more precise estimates, the final effect sizes for knowledge, attitudes, and sexual behavior were, respectively, 0.25 (0.03-0.48), 0.18 (0.12-0.24), and 0.18 (0.11-0.24). Interventions yielded positive effects across populations and in all the domains studied.