Weighting methods for truncation by death in cluster-randomized trials.

While the HVTN 505 trial showed no overall efficacy of the tested vaccine to prevent HIV infection over placebo, markers measuring immune response to vaccination were strongly correlated with infection. This finding generated the hypothesis that some marker-defined vaccinated subgroups were partially protected whereas others had their risk increased. This hypothesis can be assessed using the principal stratification framework (Frangakis and Rubin, 2002) for studying treatment effect modification by an intermediate response variable, using methods in the sub-field of principal surrogate (PS) analysis that studies multiple principal strata. Unfortunately, available methods for PS analysis require an augmented study design not available in HVTN 505, and make untestable structural risk assumptions, motivating a need for more robust PS methods. Fortunately, another sub-field of principal stratification, survivor average causal effect (SACE) analysis (Rubin, 2006) - which studies effects in a single principal stratum - provides many methods not requiring an augmented design and making fewer assumptions. We show how, for a binary intermediate response variable, methods developed for SACE analysis can be adapted to PS analysis, providing new and more robust PS methods. Application to HVTN 505 supports that the vaccine partially protected individuals with vaccine-induced T-cells expressing certain combinations of functions.

In randomized trials with follow-up, outcomes may be undefined for individuals who die before the follow-up is complete. In such settings, Frangakis and Rubin [2002] proposed the “principal stratum effect” or “Survivor Average Causal Effect” (SACE), which is a fair treatment comparison in the subpopulation that would have survived under either treatment arm. Many of the existing results for estimating the SACE are difficult to carry out in practice. In this article, when the outcome is binary, we apply the symbolic Balke-Pearl linear programming method to derive simple formulas for the sharp bounds on the SACE under the monotonicity assumption commonly used by many researchers.

The Causal Effect of Fertility on Female Labor Supply: Evidence from Taiwanese Son Preference

Unequal cluster sizes are common in cluster randomized trials (CRTs). While there are a number of previous investigations studying the impact of unequal cluster sizes on the power for testing the average treatment effect in CRTs, little is known about the impact of unequal cluster sizes on the power for testing the heterogeneous treatment effect (HTE) in CRTs. In this work, we expand the sample size procedures for studying HTE in CRTs to accommodate cluster size variation under the linear mixed model framework. Through analytical derivation and graphical exploration, we show that the sample size for the HTE with an individual-level effect modifier is less affected by unequal cluster sizes than with a cluster-level effect modifier. The impact of cluster size variability jointly depends on the mean and coefficient of variation of cluster sizes, covariate intraclass correlation coefficient (ICC) and the conditional outcome ICC. In addition, we demonstrate that the HTE-motivated analysis of covariance framework can be used for analyzing the average treatment effect, and offer a more efficient sample size procedure for studying the average treatment effect adjusting for the effect modifier. We use simulations to confirm the accuracy of the proposed sample size procedures for both the average treatment effect and HTE in CRTs. Extensions to multivariate effect modifiers are provided and our procedure is illustrated in the context of the Strategies to Reduce Injuries and Develop Confidence in Elders trial.

Consider a case where cause-effect relationships between variables can be described as a directed acylic graph and the corresponding recursive factorization of a joint distribution. In order to provide the bounds on average causal effects in studies with a latent response variable, this paper proposes a graphical criterion for selecting covariates and variables caused by the response variable. The result enables us not only to judge from the graph structure whether the bounds on an average causal effect can be expressed through the observed quantities, but also to provide their closed-form expressions in case where its answer is affirmative. The graphical criterion of this paper is helpful to evaluate the bounds on average causal effects when it is difficult to observe a response variable.

Randomized and natural experiments are commonly used in economics and other social science fields to estimate the effect of programs and interventions. Even when employing experimental data, assessing the impact of a treatment is often complicated by the presence of sample selection (outcomes are only observed for a selected group) and noncompliance (some treatment group individuals do not receive the treatment while some control individuals do). We address both of these identification problems simultaneously and derive nonparametric bounds for average treatment effects within a principal stratification framework. We employ these bounds to empirically assess the wage effects of Job Corps (JC), the most comprehensive and largest federally funded job training program for disadvantaged youth in the United States. Our results strongly suggest positive average effects of JC on wages for individuals who comply with their treatment assignment and would be employed whether or not they enrolled in JC (the “always-employed compliers”). Under relatively weak monotonicity and mean dominance assumptions, we find that this average effect is between 5.7% and 13.9% 4 years after randomization, and between 7.7% and 17.5% for non-Hispanics. Our results are consistent with larger effects of JC on wages than those found without adjusting for noncompliance.

Introduction: The effect of Ramadan fasting on the quality of life of older Muslims is a challenging issue. The present study was carried out to examine the effect of Ramadan fasting on elderly Muslims’ quality of life. Methods: This observational correlational study was carried out throughout the natural intervention of Ramadan fasting in 2016 during which the length of fasting days was about sixteen hours. A convenience sample of 100 people older than 60 years who referred to Rafsanjan Health Centers was recruited. The twelve-item Short Form Survey of Quality of Life was used for assessing participants’ quality of life at three measurement time (T) points including before (T1), one day after (T2), and one month after Ramadan (T3). Data was analyzed through the two-way repeated measures ANOVA, using SPSS (v.18) and P<0.05 was considered as significant. Result: There was a significant difference among the three measurement time points (T1=47.02±14.15, T2=50.76±17.06, T3=51.53±16.79) regarding the total sf-12 score of quality of life (P value < 0.0001). Conclusion: Elderly Muslims’ quality of life can be improved through fasting.

IntroductionHyperglycaemia is common in critical illness and associated with poor outcome. Glycaemic control using insulin may decrease morbidity and mortality. Many questions remain about the cause of critical illness hyperglycaemia (CIH). Our objective was to investigate the endocrinological basis of paediatric CIH.MethodsC-peptide and blood glucose (BG) levels were assessed in 41 children aged 2 to 18 years old who were admitted to our paediatric intensive care unit (PICU). Patients who developed CIH, defined as persistent BG above 7.7 mmol/L, were treated with insulin infusion to achieve BG levels between 4.4 and 7.7 mmol/L. C-peptide levels were compared with respect to CIH development and degree of organ failure in all patients. Respiratory and cardiovascular failure were defined as need for mechanical ventilation and need for vasoactive infusions, respectively. Clinical and laboratory parameters, including c-peptide levels, were assessed.ResultsOf 41 children enrolled, 18 had respiratory failure only, 11 had both respiratory and cardiovascular failure, and 12 had neither respiratory or cardiovascular failure. Nine patients with respiratory failure only, 10 with both respiratory and cardiovascular failure, and none with no respiratory or cardiovascular failure developed CIH. Patients with CIH and respiratory and cardiovascular failure (n = 10) had very low c-peptide levels (4.4 ng/mL) despite significantly elevated mean BG levels (10.8 mmol/L), while those with CIH and respiratory failure only had very high c-peptide levels (11.5 ng/mL) with mean BG of 9.9 mmol/L. Low endogenous insulin production in those with respiratory and cardiovascular failure was associated with rapid onset of CIH, illness severity, higher insulin requirement and longer mechanical ventilation days, PICU length of stay and CIH duration.ConclusionsPrimary beta-cell dysfunction as defined by low endogenous c-peptide production appears to be prevalent in critically ill children with both respiratory and cardiovascular failure who develop CIH, whereas elevated insulin resistance appears to be the prominent cause of CIH in children with respiratory failure only. Our finding that beta-cell dysfunction is present in a subset of critically ill children with CIH challenges the assertion from adult studies that CIH is primarily the result of elevated insulin resistance.

Cluster randomized trials (CRTs) have been widely used in field experiments treating a cluster of individuals as the unit of randomization. This study focused particularly on situations where CRTs are accompanied by a common complication, namely, treatment noncompliance or, more generally, intervention nonadherence. In CRTs, compliance may be related not only to individual characteristics but also to the environment of clusters individuals belong to. Therefore, analyses ignoring the connection between compliance and clustering may not provide valid results. Although randomized field experiments often suffer from both noncompliance and clustering of the data, these features have been studied as separate rather than concurrent problems. On the basis of Monte Carlo simulations, this study demonstrated how clustering and noncompliance may affect statistical inferences and how these two complications can be accounted for simultaneously. In particular, the effect of the intervention on individuals who not only were assigned to active intervention but also abided by this intervention assignment (complier average causal effect) was the focus. For estimation of intervention effects considering noncompliance and data clustering, an ML-EM estimation method was employed.

Science, Medicine, and the Anesthesiologist

Noninvasive Positive Pressure Ventilation Via Face Mask: First-Line Intervention in Patients With Acute Hypercapnic and Hypoxemic Respiratory Failure

BackgroundBenefits of cash transfers (CTs) for HIV prevention have been demonstrated largely in purposively designed trials, commonly focusing on young women. It is less clear if CT interventions not designed for HIV prevention can have HIV-specific effects, including adverse effects. The cluster-randomised Manicaland Cash Transfer Trial (2010–11) evaluated effects of CTs on children’s (2–17 years) development in eastern Zimbabwe. We evaluated whether this CT intervention with no HIV-specific objectives had unintended HIV prevention spillover effects (externalities).MethodsData on 2909 individuals (15–54 years) living in trial households were taken from a general-population survey, conducted simultaneously in the same communities as the Manicaland Trial. Average treatment effects (ATEs) of CTs on sexual behaviour (any recent sex, condom use, multiple partners) and secondary outcomes (mental distress, school enrolment, and alcohol/cigarette/drug consumption) were estimated using mixed-effects logistic regressions (random effects for study site and intervention cluster), by sex and age group (15–29; 30–54 years). Outcomes were also evaluated with a larger synthetic comparison group created through propensity score matching.ResultsCTs did not affect sexual debut but reduced having any recent sex (past 30 days) among young males (ATE: − 11.7 percentage points [PP] [95% confidence interval: -26.0PP, 2.61PP]) and females (− 5.68PP [− 15.7PP, 4.34PP]), with similar but less uncertain estimates when compared against the synthetic comparison group (males: -9.68PP [− 13.1PP, − 6.30PP]; females: -8.77PP [− 16.3PP, − 1.23PP]). There were no effects among older individuals. Young (but not older) males receiving CTs reported increased multiple partnerships (8.49PP [− 5.40PP, 22.4PP]; synthetic comparison: 10.3PP (1.27PP, 19.2PP). No impact on alcohol, cigarette, or drug consumption was found. There are indications that CTs reduced psychological distress among young people, although impacts were small. CTs increased school enrolment in males (11.5PP [3.05PP, 19.9PP]). Analyses with the synthetic comparison group (but not the original control group) further indicated increased school enrolment among females (5.50PP [1.62PP, 9.37PP]) and condom use among younger and older women receiving CTs (9.38PP [5.90PP, 12.9PP]; 5.95PP [1.46PP, 10.4PP]).ConclusionsNon-HIV-prevention CT interventions can have HIV prevention outcomes, including reduced sexual activity among young people and increased multiple partnerships among young men. No effects on sexual debut or alcohol, cigarette, or drug consumption were observed. A broad approach is necessary to evaluate CT interventions to capture unintended outcomes, particularly in economic evaluations.Trial registrationClinicalTrials.gov, NCT00966849. Registered August 27, 2009.

Evaluating the E ffects of Having Friends on Sales with Observational Data

ABSTRACTSuppose we are interested in estimating the average causal effect (ACE) for the population mean from observational study. Because of simplicity and ease of interpretation, stratification by a propensity score (PS) is widely used to adjust for influence of confounding factors in estimation of the ACE. Appropriateness of the estimation by the PS stratification relies on correct specification of the PS. We propose an estimator based on stratification with multiple PS models by clustering techniques instead of model selection. If one of them correctly specifies, the proposed estimator removes bias and thus is more robust than the standard PS stratification.

High-intensity interval training (HIIT) has emerged as a time-efficient approach to improve aerobic capacity, cardiovascular health, and cognitive functioning in children and adolescents. However, evidence regarding the impact of school-based HIIT programs on motor competence and health-related quality of life in children is limited. This study evaluated the effectiveness of a HIIT intervention, based on playground games on gross motor competence and health-related quality of life in schoolchildren aged 9-11years. A cluster-randomized controlled trial was conducted with 562 participants. The intervention involved four weekly 60 minsessions of extracurricular physical activity using traditional games adapted to a HIIT protocol. Gross motor competence and health-related quality of life were assessed using the Movement Assessment Battery for Children-Second Edition (MABC-2) and the KIDSCREEN-27 questionnaire, respectively. Analyzes were conducted on an intention-to-treat basis using mixed linear regression models to compare changes from baseline to postintervention between the intervention and control groups. No significant improvements in gross motor competence or health-related quality of life were observed after adjusting for baseline variables, age, sex, and school. The results suggest that this HIIT-based program was not effective in enhancing gross motor competence or in improving health-related quality of life. Future programs could improve effectiveness by optimizing the balance between movement intensity and quality, aligning activities with gross motor competence assessment tools, emphasizing health-related quality of life components, training educators to enhance quality of life, extending intervention duration to impact self-esteem and psychological well-being, and improving adherence rates.