Alexander M. Kaizer

Childhood pneumococcal disease in Africa – A systematic review and meta-analysis of incidence, serotype distribution, and antimicrobial susceptibility

BACKGROUND Determining the incidence, disease-associated serotypes and antimicrobial susceptibility of invasive pneumococcal disease (IPD) among children in Africa is essential in order to monitor the impact of these infections prior to widespread introduction of the pneumococcal conjugate vaccine (PCV). METHODS To provide updated estimates of the incidence, serotype distribution, and antimicrobial susceptibility profile of Streptococcus pneumoniae causing disease in Africa, we performed a systematic review of articles published from 2000 to 2015 using Ovid Medline and Embase. We included prospective and surveillance studies that applied predefined diagnostic criteria. Meta-analysis for all pooled analyses was based on random-effects models. RESULTS We included 38 studies consisting of 386,880 participants in 21 countries over a total of 350,613 person-years. The pooled incidence of IPD was 62.6 (95% CI 16.9, 226.5) per 100,000 person-years, including meningitis which had a pooled incidence of 24.7 (95% CI 11.9, 51.6) per 100,000 person-years. The pooled prevalence of penicillin susceptibility was 78.1% (95% CI 61.9, 89.2). Cumulatively, PCV10 and PCV13 included 66.9% (95% CI 55.9, 76.7) and 80.6% (95% CI 66.3, 90.5) of IPD serotypes, respectively. CONCLUSIONS Our study provides an integrated and robust summary of incidence data, serotype distribution and antimicrobial susceptibility for S. pneumoniae in children ≤5years of age in Africa prior to widespread introduction of PCV on the continent. The heterogeneity of studies and wide range of incidence rates across the continent indicate that surveillance efforts should be intensified in all regions of Africa to improve the integrity of epidemiologic data, vaccine impact and cost benefit. Although the incidence of IPD in young children in Africa is substantial, currently available conjugate vaccines are estimated to cover the majority of invasive disease-causing pneumococcal serotypes. These data provide a reliable baseline from which to monitor the impact of the broad introduction of PCV.

Meal replacements followed by topiramate for the treatment of adolescent severe obesity: A pilot randomized controlled trial.

To assess the safety and efficacy of short‐term meal replacement therapy followed by topiramate for body mass index (BMI) reduction in adolescents with severe obesity.

Factors associated with long-term weight-loss maintenance following bariatric surgery in adolescents with severe obesity.

BACKGROUND/OBJECTIVES:Bariatric surgery produces robust weight loss, however, factors associated with long-term weight-loss maintenance among adolescents undergoing Roux-en-Y gastric bypass surgery are unknown.SUBJECTS/METHODS:Fifty adolescents (mean±s.d. age and body mass index (BMI)=17.1±1.7 years and 59±11 kg m−2) underwent Roux-en-Y gastric bypass surgery, had follow-up visits at 1 year and at a visit between 5 and 12 years following surgery (Follow-up of Adolescent Bariatric Surgery at 5 Plus years (FABS-5+) visit; mean±s.d. 8.1±1.6 years). A non-surgical comparison group (n=30; mean±s.d. age and BMI=15.3±1.7 years and BMI=52±8 kg m−2) was recruited to compare weight trajectories over time. Questionnaires (health-related and eating behaviors, health responsibility, impact of weight on quality of life (QOL), international physical activity questionnaire and dietary habits via surgery guidelines) were administered at the FABS-5+ visit. Post hoc, participants were split into two groups: long-term weight-loss maintainers (n=23; baseline BMI=58.2 kg m−2; 1-year BMI=35.8 kg m−2; FABS-5+ BMI=34.9 kg m−2) and re-gainers (n=27; baseline BMI=59.8 kg m−2; 1-year BMI=36.8 kg m−2; FABS-5+ BMI=48.0 kg m−2) to compare factors which might contribute to differences. Data were analyzed using generalized estimating equations adjusted for age, sex, baseline BMI, baseline diabetes status and length of follow-up.Results:The BMI of the surgical group declined from baseline to 1 year (−38.5±6.9%), which, despite some regain, was largely maintained until FABS-5+ (−29.6±13.9% change). The BMI of the comparison group increased from baseline to the FABS-5+ visit (+10.3±20.6%). When the surgical group was split into maintainers and re-gainers, no differences in weight-related and eating behaviors, health responsibility, physical activity/inactivity, or dietary habits were observed between groups. However, at FABS-5+, maintainers had greater overall QOL scores than re-gainers (87.5±10.5 vs 65.4±20.2, P<0.001) and in each QOL sub-domain (P<0.01 all).Conclusions:Long-term weight outcomes for those who underwent weight-loss surgery were superior to those who did not undergo surgical treatment. While no behavioral factors were identified as predictors of success in long-term weight-loss maintenance, greater QOL was strongly associated with maintenance of weight loss among adolescents who underwent Roux-en-Y gastric bypass surgery surgery.

Bayesian hierarchical modeling based on multisource exchangeability

&NA; Bayesian hierarchical models produce shrinkage estimators that can be used as the basis for integrating supplementary data into the analysis of a primary data source. Established approaches should be considered limited, however, because posterior estimation either requires prespecification of a shrinkage weight for each source or relies on the data to inform a single parameter, which determines the extent of influence or shrinkage from all sources, risking considerable bias or minimal borrowing. We introduce multisource exchangeability models (MEMs), a general Bayesian approach for integrating multiple, potentially non‐exchangeable, supplemental data sources into the analysis of a primary data source. Our proposed modeling framework yields source‐specific smoothing parameters that can be estimated in the presence of the data to facilitate a dynamic multi‐resolution smoothed estimator that is asymptotically consistent while reducing the dimensionality of the prior space. When compared with competing Bayesian hierarchical modeling strategies, we demonstrate that MEMs achieve approximately 2.2 times larger median effective supplemental sample size when the supplemental data sources are exchangeable as well as a 56% reduction in bias when there is heterogeneity among the supplemental sources. We illustrate the application of MEMs using a recently completed randomized trial of very low nicotine content cigarettes, which resulted in a 30% improvement in efficiency compared with the standard analysis.

Effect of phentermine on weight reduction in a pediatric weight management clinic

Phentermine is the most widely prescribed obesity medication in adults, yet studies of its use in the pediatric population are limited. We conducted a retrospective chart review of adolescents with obesity treated in a pediatric weight management clinic to examine the weight loss effectiveness of phentermine added to standard of care (SOC) lifestyle modification therapy versus SOC alone. All patients receiving phentermine plus SOC (n=25) were matched with a comparison group receiving only SOC (n=274). Differences at 1, 3 and 6 months were evaluated using generalized estimated equations adjusting for age, sex and baseline body mass index (BMI) and robust variance standard error estimates for confidence intervals and P-values. Phentermine use was associated with a greater percent change in BMI at 1 month (−1.6%; 95% confidence interval (CI): −2.6, −0.6%; P=0.001), 3 months (−2.9%; 95% CI: −4.5, −1.4%; P<0.001) and 6 months (−4.1%; 95% CI: −7.1, −1.0%; P=0.009) compared with SOC alone, with no differences in systolic or diastolic blood pressure between groups. Heart rate was higher at all time-points in the phentermine plus SOC compared with SOC-only group. These data suggest that short-term use of phentermine added to SOC may enhance weight loss in adolescents with obesity in the clinical setting.

A multi-source adaptive platform design for testing sequential combinatorial therapeutic strategies: Multi-Source Adaptive Platform Design

Traditional paradigms for clinical translation are challenged in settings where multiple contemporaneous therapeutic strategies have been identified as potentially beneficial. Platform trials have emerged as an approach for sequentially comparing multiple trials using a single protocol. The Ebola virus disease outbreak in West Africa represents one recent example which utilized a platform design. Specifically, the PREVAIL II master protocol sequentially tested new combinations of therapies against the concurrent, optimal standard of care (oSOC) strategy. Once a treatment demonstrated sufficient evidence of benefit, the treatment was added to the oSOC for all future comparisons (denoted as segments throughout the manuscript). In the interest of avoiding bias stemming from population drift, PREVAIL II considered only within-segment comparisons between the oSOC and novel treatments and failed to leverage data from oSOC patients in prior segments. This article describes adaptive design methodology aimed at boosting statistical power through Bayesian modeling and adaptive randomization. Specifically, the design uses multi-source exchangeability models to combine data from multiple segments and adaptive randomization to achieve information balance within a segment. When compared to the PREVAIL II design, we demonstrate that our proposed adaptive platform design improves power by as much as 51% with limited type-I error inflation. Further, the adaptive platform effectuates more balance with respect to the distribution of acquired information among study arms, with more patients randomized to experimental regimens.

Relationships of Anxiety and Depression with Cardiovascular Health in Youth with Normal Weight to Severe Obesity

Objective To evaluate the relationships of depression and anxiety symptoms with cardiovascular disease (CVD) risk factors and measures of vascular health in youth. Study design Participants (n = 202) were 8‐ to 18‐year‐olds from a cross‐sectional study evaluating cardiovascular health across a wide range of body mass index values (normal weight to severe obesity). CVD risk measurement included blood pressure, fasting lipids, glucose, insulin, carotid artery intima‐media thickness, compliance and distensibility, brachial artery flow‐mediated dilation, carotid‐radial artery pulse wave velocity, body fat percentage, and a metabolic syndrome cluster score. Anxiety and depression symptoms were self‐reported on the Screen for Child Anxiety Related Disorders and Center for Epidemiological Studies Depression Scale for Children. Two sets of adjustment variables were used in evaluation of differences between those with and without anxiety or depression symptomatology for the CVD risk factor and vascular outcomes. The first set included adjustment for Tanner stage, sex, and race; the second was additionally adjusted for percent body fat. Results Anxiety was not significantly associated with CVD risk factors or vascular health in either model. Depression was associated with high‐density lipoprotein cholesterol, triglycerides, and metabolic syndrome cluster score; these relationships were attenuated when accounting for percent body fat. Conclusions When accounting for body fat, we found no clear relationship of self‐reported depression or anxiety symptoms with CVD risk factors or vascular health in youth.

Cardiometabolic risk factors in treatment-seeking youth versus population youth with obesity: Cardiometabolic profiles of youth

Although obesity affects approximately one in five youths, only a fraction is treated in pediatric weight management clinics. Characteristics distinguishing youth with obesity who seek weight management treatment from those who do not are largely unknown. Yet identification of specific health characteristics which differentiate treatment‐seeking from non‐treatment seeking youth with obesity may shed light on underlying motivations for pursuing treatment.