Addressing Methodologic Challenges and Minimizing Threats to Validity in Synthesizing Findings from Individual-Level Data Across Longitudinal Randomized Trials

Integrative Data Analysis (IDA) encompasses a collection of methods for data synthesis that pools participant-level data across multiple studies. Compared with single-study analyses, IDA provides larger sample sizes, better representation of participant characteristics, and often increased statistical power. Many of the methods currently available for IDA have focused on examining developmental changes using longitudinal observational studies employing different measures across time and study. However, IDA can also be useful in synthesizing across multiple randomized clinical trials to improve our understanding of the comprehensive effectiveness of interventions, as well as mediators and moderators of those effects. The pooling of data from randomized clinical trials presents a number of methodological challenges, and we discuss ways to examine potential threats to internal and external validity. Using as an illustration a synthesis of 19 randomized clinical trials on the prevention of adolescent depression, we articulate IDA methods that can be used to minimize threats to internal validity, including (1) heterogeneity in the outcome measures across trials, (2) heterogeneity in the follow-up assessments across trials, (3) heterogeneity in the sample characteristics across trials, (4) heterogeneity in the comparison conditions across trials, and (5) heterogeneity in the impact trajectories. We also demonstrate a technique for minimizing threats to external validity in synthesis analysis that may result from non-availability of some trial datasets. The proposed methods rely heavily on latent variable modeling extensions of the latent growth curve model, as well as missing data procedures. The goal is to provide strategies for researchers considering IDA.     

Preventing Youth Internalizing Symptoms Through the Familias Unidas Intervention: Examining Variation in Response

Prevention programs that strengthen parenting and family functioning have been found to reduce poor behavioral outcomes in adolescents, including substance use, HIV risk, externalizing and internalizing problems. However, there is evidence that not all youth benefit similarly from these programs. Familias Unidas is a family-focused intervention designed to prevent substance use and sexual risk among Hispanic youth and has recently demonstrated unanticipated reductions in internalizing symptoms for some youth. This paper examines variation in intervention response for internalizing symptoms using individual-level data pooled across four distinct Familias Unidas trials: (1) 266 eighth grade students recruited from the general school population; (2) 160 ninth grade students from the general school population; (3) 213 adolescents with conduct, aggression, and/or attention problems; and (4) 242 adolescents with a delinquency history. Causal inference growth mixture modeling suggests a three-class model. The two largest classes represent youth with low (60 %) and medium (27 %) internalizing symptoms at baseline, and both intervention and control participants show reductions in internalizing symptoms. The third class (13 %) represents youth with high levels of baseline internalizing symptoms who remain at steady levels of internalizing symptoms when exposed to the intervention, but who experience an increase in symptoms under the control condition. Female gender, low baseline levels of parent–adolescent communication, and older age were associated with membership in the high-risk class. These synthesis analyses involving a large sample of youth with varying initial risk levels represent a further step toward strengthening our knowledge of preventive intervention response and improving preventive interventions.     

Predictors of engagement and retention into a parent-centered, ecodevelopmental HIV preventive intervention for Hispanic adolescents and their families

OBJECTIVE: This study examined predictors of engagement and retention into a parent-centered, ecodevelopmental HIV preventive intervention for Hispanic adolescents and their families. The influence of retention on changes in adolescent HIV-risk attitudes was also examined. METHODS: Participants in this study were 91 Hispanic adolescents and their primary parents. Structural equation modeling was used to identify (a) predictors of initial engagement, (b) the effects of group processes on retention, and (c) the effects of retention on change HIV-risk attitudes in adolescents. RESULTS: Although some participant characteristics predicted engagement, the parent-facilitator relationship quality at the initial contact was found to be the strongest predictor of engagement. Furthermore, within-group processes such as group cohesion positively predicted retention. Finally, parent retention predicted decreases in adolescent HIV-risk attitudes. CONCLUSIONS: The results may have important implications for engagement and retention in parent-centered interventions, as well as for reducing risks for HIV transmission in Hispanic adolescents. Implications for services research are also discussed.     

A PERSON-CENTERED AND ECOLOGICAL INVESTIGATION OF ACCULTURATION STRATEGIES IN HISPANIC IMMIGRANT YOUTH

Understanding the processes of acculturation in ethnic minority populations is one of the central tasks of crosscultural research. Addressing challenges of theory, methods, and application in acculturation research requires ongoing advancements in methods and theoretical and model development. The current study was designed to explain a person-centered approach to investigating acculturation and biculturalism and to illustrate this method with a sample of 315 Hispanic youth. Pattern analyses of the Hispanicism and Americanism scores from the Bicultural Involvement Scale yielded four distinct acculturation types, including one characterized by moderate scores on both scales. Relations between acculturation types and indicators of individual, family, and peer adaptation were tested. Results indicated that bicultural youth tended to show the most adaptive pattern of functioning across multiple sociocultural domains. Assimilated youth did not show as strongly negative a pattern as has been reported elsewhere. Implications and benefits of a person-centered approach are discussed.     

Effect of the number of peak expiratory flow readings per day on the estimation of diurnal variation

BACKGROUND: The number of peak expiratory flow (PEF) readings required per day to assess diurnal variation accurately is not known; published studies have used between two and seven PEF readings per day. This study compares the diurnal variation calculated using 2-10 PEF readings per day. METHODS: All days with 10 readings were selected from a database of PEF records. For each day, diurnal variations calculated using 2-9 of the readings available were compared with that calculated using the full 10 PEF readings. Diurnal variation calculated using all 10 readings was taken as the true diurnal variation. When less than 10 readings were used the readings were evenly spaced over waking hours. Diurnal variation was calculated as maximum--minimum/predicted. RESULTS: Two hundred and 25 days with 10 readings per day were selected from PEF records provided by 63 individuals. When only two PEF readings per day were used, the limits of agreement suggested a possible underestimate of true diurnal variation, calculated using all 10 readings, of 1.23-15.10%. The possible underestimate fell to 0.27-3.96% when calculated using four evenly spaced readings. Analysis of the timing of the highest PEF reading of the day was undertaken for rest and work days. This showed a mean (SD) timing of 13:56 (4:56 hours) for rest days and 11:47 (5:59 hours) for work days. CONCLUSIONS: Clinically significant underestimates of true diurnal variation may be seen when only small numbers of PEF readings per day are used in its calculation. At and above four readings the results suggest that the underestimate becomes increasingly insignificant in terms of the diagnosis and treatment of asthma. Analysis of the timing of the highest PEF reading of the day showed a wide variation, precluding the ability to capture the true diurnal variation with just two or three carefully timed PEF readings per day. The authors suggests that at least four readings per day should be performed, evenly spaced during waking hours, to obtain an accurate assessment of diurnal variation in PEF.     

Ferroportin Q248h, dietary iron, and serum ferritin in community African-Americans with low to high alcohol consumption

Background: Alcohol consumption is associated with increased iron stores. In sub‐Saharan Africa, high dietary ionic iron and the ferroportin Q248H allele have also been implicated in iron accumulation. We examined the associations of ferroportin Q248H, alcohol and dietary iron with serum ferritin, aspartate aminotransaminase (AST) and alanine aminotransaminase (ALT) concentrations in African‐Americans. Methods: Inner‐city African‐Americans (103 men, 40 women) were recruited from the community according to reported ingestion of >4 alcoholic drinks/d or <2/wk. Typical daily heme iron, nonheme iron and alcohol were estimated using University of Hawaii’s multiethnic dietary questionnaire. Based on dietary questionnaire estimates we established categories of < versus ≥56 g alcohol/d, equivalent to 4 alcoholic drinks/d assuming 14 g alcohol per drink. Results: Among 143 participants, 77% drank <56 g alcohol/d and 23%≥56 g/d as estimated by the questionnaire. The prevalence of ferroportin Q248H was 23.3% with alcohol >56 g/d versus 7.5% with lower amounts (p = 0.014). Among subjects with no history of HIV disease, serum ferritin concentration had positive relationships with male gender (p = 0.041), alcohol consumption (p = 0.021) and ALT concentration (p = 0.0001) but not with dietary iron intake or ferroportin Q248H. Serum AST and ALT concentrations had significant positive associations with male gender and hepatitis C seropositivity but not with alcohol or dietary iron intake or ferroportin Q248H. Conclusions: Our findings suggest a higher prevalence of ferroportin Q248H with greater alcohol consumption, and this higher prevalence raises the possibility that the allele might ameliorate the toxicity of alcohol. Our results suggest that alcohol but not dietary iron contributes to higher body iron stores in African‐Americans. Studies with larger numbers of participants are needed to further clarify the relationship of ferroportin Q248H with the toxicity of alcohol consumption.     

Acute Kidney Injury in Hematopoietic Cell Transplantation Patients Receiving Vancomycin and Piperacillin/Tazobactam Versus Vancomycin and Cefepime

Empiric antimicrobials are frequently utilized in the pre-engraftment phase after hematopoietic cell transplantation (HCT). Recent evidence suggests an increased risk of acute kidney injury (AKI) from combination of vancomycin with piperacillin/tazobactam; however, this has not specifically been evaluated in the HCT population. A single-center, retrospective review was conducted from 2011 to 2017 on 110 autologous and 60 allogeneic HCT patients with the primary objective of comparing incidence of AKI for those who received vancomycin with piperacillin/tazobactam versus vancomycin with cefepime in the pre-engraftment phase. Demographics and outcomes were compared for all patients who received vancomycin with piperacillin/tazobactam versus vancomycin with cefepime as well as within the autologous and allogeneic subgroups. The primary endpoint of incidence of AKI, defined as increase in serum creatinine by .3?mg/dL or?>50% from baseline (whichever was larger), was significantly higher for those who received vancomycin with piperacillin/tazobactam versus cefepime for the overall cohort (68% versus 27%; P?<?.001) resulting in an odds ratio (OR) of 5.16 (95% confidence interval [CI], 2.5 to 10.5) when adjusting for hypotension. Results were similar within the autologous (59% versus 22%; P?<?.001; OR, 4.63; 95% CI, 1.85 to 11.6) and allogeneic (79% versus 39%; P?=?.0021; OR, 5.41; 95% CI, 1.60 to 18.3) subgroups. Within the overall cohort between those who received vancomycin with piperacillin/tazobactam versus cefepime the time to onset of AKI was more commonly within 48 hours of concomitant antimicrobial use (53% versus 26%; P?=?.012), whereas resolution of AKI by discharge date was not different (39% versus 26%; P?=?.23). No difference in percentage of patients requiring at least 1 session of dialysis, duration of hospital stay, or 30-day mortality was found between overall cohorts. Further studies of HCT patients are warranted to fully elucidate the risk of various combination antimicrobial regimens on renal outcomes.     

eHealth Familias Unidas: Efficacy Trial of an Evidence-Based Intervention Adapted for Use on the Internet with Hispanic Families

Prevention Science - While substance use and sexual risk behaviors among Hispanic youth continue to be public health concerns, few evidence-based preventive interventions are developed for and...