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.

     

Evaluating Community-Based Translational Interventions Using Historical Controls: Propensity Score vs. Disease Risk Score Approach

Many community-based translations of evidence-based interventions are designed as one-arm studies due to ethical and other considerations. Evaluating the impacts of such programs is challenging. Here, we examine the effectiveness of the lifestyle intervention implemented by the Special Diabetes Program for Indians Diabetes Prevention (SDPI-DP) demonstration project, a translational lifestyle intervention among American Indian and Alaska Native communities. Data from the landmark Diabetes Prevention Program placebo group was used as a historical control. We compared the use of propensity score (PS) and disease risk score (DRS) matching to adjust for potential confounder imbalance between groups. The unadjusted hazard ratio (HR) for diabetes risk was 0.35 for SDPI-DP lifestyle intervention vs. control. However, when relevant diabetes risk factors were considered, the adjusted HR estimates were attenuated toward 1, ranging from 0.56 (95% CI 0.44–0.71) to 0.69 (95% CI 0.56–0.96). The differences in estimated HRs using the PS and DRS approaches were relatively small but DRS matching resulted in more participants being matched and smaller standard errors of effect estimates. Carefully employed, publicly available randomized clinical trial data can be used as a historical control to evaluate the intervention effectiveness of one-arm community translational initiatives. It is critical to use a proper statistical method to balance the distributions of potential confounders between comparison groups in this kind of evaluations.

     

Immediate open reduction and internal fixation in open ankle fractures

In this prospective study, 30 patients (28 men and 2 women) with open ankle fractures were treated with early debridement and immediate stable internal fixation after anatomical reduction to achieve better functional results after early mobilization. The procedure was performed an average of 8 hours (range, 6-15 hours) after injury. According to the classification system of Gustilo and Anderson, 11 fractures (37%) were grade I, 12 (40%) were grade II, 5 (17%) were grade IIIA, and 2 (7%) were grade IIIB. Six complications occurred: four patients had superficial skin necrosis and two had loss of reduction, resulting in residual ankle stiffness. Twenty patients had excellent results, eight had good results, and two had fair results according to the modified criteria of Ketenjian and Shelton. We found that immediate debridement, anatomical reduction, and internal fixation of open ankle fractures leads to better functional results, especially in grade I and grade II injuries.     

Total costs of injury from accidents in the home and during education, sports and leisure activities: estimates for Norway with assessment of uncertainty

Injury accidents occurring in the home, during educational, sports or leisure activities were estimated from samples of hospital data, combined with fatality data from vital statistics. Uncertainty of estimated figures was assessed in simulation-based analysis. Total economic costs to society from injuries and fatalities due to such accidents were estimated at approximately NOK 150 billion per year. The estimated costs reveal the scale of the public health problem and lead to arguments for the establishment of a proper injury register for the identification of preventive measures to reduce the costs to society.

A comparison of four prenatal care indices in birth outcome models: comparable results for predicting small-for-gestational-age outcome but different results for preterm birth or infant mortality

ObjectiveSeveral different indices of prenatal care have been used in birth outcome models to analyze the relationship between the adequacy of prenatal care and low birthweight, preterm birth, and infant mortality. This investigation compared the performance of the Kessner index, the GINDEX, the adequacy of prenatal care utilization (APNCU) and certain variants of the APNCU in such outcome models.Study Design and SettingData from National Center for Health Statistics' (NCHS) Linked Birth and Infant Death Cohort files were used in multivariate logistic regression models to estimate adjusted odds ratios comparing different prenatal care utilization categories for each index.ResultsWhen the indices were used in small-for-gestational-age outcome models, the conclusions suggested by the various indices were similar. In models for preterm birth and infant mortality, by contrast, the various indices gave widely differing results. Unlike the use of other indices, the use of the GINDEX paradoxically suggested that birth outcomes were better in the inadequate, intermediate, and intensive categories than in the adequate category.ConclusionThe conclusions drawn concerning the association between prenatal care utilization and small-for-gestational-age seem relatively robust in the sense of being consistent across indices. In analyzing associations between prenatal care and preterm birth or infant mortality, care must be taken in choosing indices, because results differ substantially across indices.     

Uncemented hips: current status

Total hip replacement (THR) is an established procedure for symptomatic end stage arthritis of the hip to improve function and alleviate pain thereby improving the quality of life of millions of patients. Of the range of possible joint replacements, it is suggested that THR is a landmark surgery. It is one of the most cost effective and predictable operations. Its success in the short term as well as in the long term has led to THR being performed in younger and more active patients. Survival of THR in the young and active patients was suboptimal for many years and management of this group continues to be a challenge. This paper provides an up-to-date review of the relevant history of uncemented hip replacements, key design features, mechanisms of fixation, current status, guidance to use and long-term results of uncemented hips.