Effect Of Treatment Assignment Research Articles

Abstract P399: The Effect of Self-Monitoring of Diet, Weight and Steps and Adherence to Diet, Fat and Physical Activity Goals on Weight Loss at 12 Months: Smarter RCT

Introduction: Self-monitoring (SM) is the core of behavioral weight loss. Efficacy evidence for mHealth to improve SM adherence and impact weight loss outcomes is limited. Purpose: Examine associations among diet, weight, and physical activity (PA) SM and adherence to diet, fat and PA goals on weight loss at 12 mos in adults with overweight or obesity. Methods: SMARTER was a single-site, 2-arm weight loss trial. We randomized adults with (BMI) 27-43 kg/m 2 to diet, weight, and PA SM plus tailored feedback messages (SM+FB, n=251) or SM alone (n=251). The SM+FB group received feedback messages via the SMARTER app on diet daily, PA every other day and weight weekly. The study provided Fitbit Charge 2™ for PA, smart scales for weight and Fitbit app for diet. Participants received individualized daily calorie/fat goals (based on sex & weight) and incremental weekly PA goals to reach ≥300 min/wk of moderate- and vigorous-intensity PA. Staff measured weight at baseline, 6 and 12 mos. Diet SM was the % of days with ≥50% of calorie goal recorded. Weight SM was the % of days with weight recorded. PA SM was % of days with ≥500 steps. Calorie goal adherence was % of days with ≥85% and <115% of calorie goals and fat goals as ≤25% of calorie goals. PA goal adherence was the average % of weekly MVPA meeting the PA goal for ≥4 days/wk. Weight loss at 12 mos was computed as the % of change in weight from baseline to 12 mos relative to baseline weight. We compared diet, weight and PA SM and adherence to calorie, fat and PA goals by treatment assignment using Wilcoxon rank-sum tests. The effect of diet, weight and PA SM and adherence to calorie, fat and PA goals on weight loss at 12 mos was examined using separate linear regression models considering treatment assignment and interaction effects. Results: The sample (N=502) was 82% white (n=414), 79% female (n=399), on average 45.0±14.4 years of age with a mean BMI of 33.7±4.0 kg/m 2 . Treatment arms were similar on % days of weight and PA SM and % days adherent to calorie, fat and PA goals (p≥.05); however, the SM+FB group had greater % days of SM diet than the SM group (58.9 [24.7, 84.9] vs. 41.1 [14.0, 81.9]; P=.01). Weight loss at 12 mos was significantly associated (reported as b [95% CI]) with higher % of days of SM diet (-0.10 [-0.13, -0.08]), weight (-0.12 [-0.14, -0.09]) and PA (-0.10 [-0.13, -0.07]) and % days adherent to calorie (-0.06 [-0.11, -0.01]) and fat goals (-0.11 [-0.20, -0.02]) and average % days adherent to PA goals (-0.04 [-0.06, -0.02]). The effect of treatment assignment and its interactions with SM of diet, weight and PA and adherence to calorie, fat and PA goals on weight loss at 12 mos were not significant. Conclusions: In this study, SM of lifestyle behaviors and adherence to diet and PA goals were associated with better weight loss at 12 months and did not depend on treatment group assignment, suggesting that the mHealth intervention did not enhance adherence sufficiently to affect weight loss outcomes.

How does a social norms-based intervention affect behaviour change? Interim findings from a cluster randomised controlled trial in Odisha, India

BackgroundBehaviour change interventions targeting social norms are burgeoning, but researchers have little guidance on what they look like, and which components affect behaviour change. The Reduction in Anaemia through Normative...

Population intervention effects in observational studies to emulate target trial results: reconciling the effects of improved sanitation on child growth.

Improved sanitation has been associated with improved child growth in observational studies, but multiple randomized trials that delivered improved sanitation found no effect on child growth. We assessed to what extent differences in the effect estimated in the two study designs (the effect of treatment in observational studies and the effect of treatment assignment in trials) could explain the contradictory results. We used parametric g-computation in five prospective studies (n = 21524) and 59 cross-sectional Demographic and Health Surveys (DHS; n = 158439). We compared the average treatment effect (ATE) for improved sanitation on mean length-for-age z-score (LAZ) among children aged <2 years to population intervention effects (PIEs), which are the observational analogue of the effect estimated in trials in which some participants are already exposed. The ATE was >0.15 z-scores, a clinically meaningful difference, in most prospective studies but in <20% of DHS surveys. The PIE was always smaller than the ATE, and the magnitude of difference depended on the baseline prevalence of the improved sanitation. Interventions with suboptimal coverage and interventions delivered in populations with higher mean LAZ had a smaller effect on population-level LAZ. Estimates of PIEs corresponding to anticipated trial results were often smaller than clinically meaningful effects. Incongruence between observational associations and null trial results may in part be explained by expected differences between the effects estimated. Using observational ATEs to set expectations for trials may overestimate the impact that sanitation interventions can achieve. PIEs predict realistic effects and should be more routinely estimated.

The Effects of Accelerated Brain Aging on the Antidepressant Response in Late-Life Depression

Introduction Late-Life Depression (LLD) is characterized by functional and structural brain alterations and accelerated brain aging. Our past work utilized a brain-based marker of accelerated aging to examine LLD and demonstrated a cross-sectional association between accelerated brain aging and impaired cognitive ability (poor episodic memory, slow processing speed, and poor executive function) as well as disability (measured by WHODAS). However, it is unclear whether or not accelerated brain aging influences the antidepressant response in depressed elders. Methods We examined depressed adults over 60 years-old with current Major Depressive Disorder (MDD) without psychotic features (N=95) randomized to receive either escitalopram up to 20mg daily or identical placebo (2:1 subject ratio) for 8 weeks. Subjects underwent baseline depression assessment (MADRS) and MRI prior to randomization. After using an automated deep learning tool to estimate brain age from cranial MRI, the brain age gap (BAG) was calculated by subtracting the participant's chronological age from his or her calculated brain age estimation. The brain MRI estimating tool uses ROI volumes derived from multiple atlases and the BrainAGE algorithm - the algorithm applies a deep convolutional neural network regression model trained on 5000 healthy controls. For statistical analysis, the dependent outcome variable was change in MADRS over 8 weeks. Initial models examined the effects of BAG with baseline MADRS, age, sex, and treatment assignment as covariates. Subsequent models tested for a statistical interaction between treatment assignment and BAG to observe whether or not the effects of brain aging on change in MADRS differed between arms. Results In the primary effects model examining change in MADRS, although there was a strong effect of treatment assignment (t = -3.75, p = 0.0003), there was no significant relationship between BAG and antidepressant response (t = -0.02, p = 0.9819). In the subsequent model, we observed a statistical interaction between BAG and treatment assignment on change in MADRS (t = -2.38, p = 0.0196). Analysis of subgroup data demonstrated that a larger BAG (indicating an older appearing brain) was associated with less change in MADRS for those who received placebo. In contrast, a larger BAG (indicating an older appearing brain) was associated with greater change in MADRS for those who received escitalopram. Conclusions The effect of accelerated brain aging, measured with the BAG, on change in MADRS have opposite patterns based on treatment assignment. Although a larger BAG is associated with poorer cognitive performance and greater disability, a larger BAG was associated with greater change in MADRS in the active treatment arm of our study. This is somewhat discrepant with prior work that associates poor cognitive performance with worse antidepressant response. As a global brain metric, BAG is not specific to discrete functional and/or structural brain impairments. Therefore, the elements that jointly contribute to the brain age metric may act in discrete, separate ways, with some influencing cognitive performance, and with others having less of a functional impact, serving as a marker of positive response to antidepressant medication. Further work must examine the complex relationships between accelerated brain aging, cognition, and response to antidepressants. Funding R01 MH102246, K24 MH110598

The Use of a Variable Representing Compliance Improves Accuracy of Estimation of the Effect of Treatment Allocation Regardless of Discontinuation in Trials with Incomplete Follow-up

–In Clinical Trials, not all randomized patients follow the course of treatment they are allocated to. The potential impact of such deviations is increasingly recognized, and it has been one of the reasons for a redefinition of the targets of estimation (“Estimands”) in the ICH E9 draft Addendum. Among others, the effect of treatment assignment, regardless of the adherence, appears an Estimand of practical interest, in line with the intention-to-treat principle. This study aims at evaluating the performance of different estimation techniques in trials with incomplete post-discontinuation follow-up when a “treatment-policy” strategy is implemented. To achieve that, we have (i) modeled and visualized as directed acyclic diagram a reasonable data-generating model; (ii) investigated which set of variables allows identification and estimation of such effect; (iii) simulated 10,000 trials in Major Depressive Disorder, with varying real treatment effects, proportions of patients discontinuing the treatment, and incomplete follow-up. Our results suggest that, at least in a “Missing at Random” setting, all studied estimation methods increase their performance when a variable representing compliance is used. This effect is more pronounced the higher the proportion of post-discontinuation follow-up is.

Clinical Outcomes by Race and Ethnicity in the Systolic Blood Pressure Intervention Trial (SPRINT): A Randomized Clinical Trial.

BACKGROUNDThe Systolic Blood Pressure Intervention Trial (SPRINT) showed that targeting a systolic blood pressure (SBP) of ≤ 120 mm Hg (intensive treatment) reduced cardiovascular disease (CVD) events compared to SBP of ≤ 140 mm Hg (standard treatment); however, it is unclear if this effect is similar in all racial/ethnic groups.METHODSWe analyzed SPRINT data within non-Hispanic White (NHW), non-Hispanic Black (NHB), and Hispanic subgroups to address this question. High-risk nondiabetic hypertensive patients (N = 9,361; 30% NHB; 11% Hispanic) 50 years and older were randomly assigned to intensive or standard treatment. Primary outcome was a composite of the first occurrence of a myocardial infarction, acute coronary syndrome, stroke, decompensated heart failure, or CVD death.RESULTSAverage postbaseline SBP was similar among NHW, NHB, and Hispanics in both treatment arms. Hazard ratios (HRs) (95% confidence interval) (intensive vs. standard treatment groups) for primary outcome were 0.70 (0.57–0.86), 0.71 (0.51–0.98), 0.62 (0.33–1.15) (interaction P value = 0.85) in NHW, NHB, and Hispanics. CVD mortality HRs were 0.49 (0.29–0.81), 0.77 (0.37–1.57), and 0.17 (0.01–1.08). All-cause mortality HRs were 0.61 (0.47–0.80), 0.92 (0.63–1.35), and 1.58 (0.73–3.62), respectively. A test for differences among racial/ethnic groups in the effect of treatment assignment on all-cause mortality was not significant (Hommel-adjusted P value = 0.062) after adjustment for multiple comparisons.CONCLUSIONTargeting a SBP goal of ≤ 120 mm Hg compared to ≤ 140 mm Hg led to similar SBP control and was associated with similar benefits and risks among all racial ethnic groups, though NHBs required an average of ~0.3 more medications.CLINICAL TRIALS REGISTRATIONTrial Number NCT01206062, ClinicalTrials.gov Identifier at https://clinicaltrials.gov/ct2/show/NCT01206062.

Abstract 1: Dual Antiplatelet Therapy is More Effective for Multiple Acute Infarcts: Subgroup Analysis of Chance

Background and Purpose: TIAregistry.org project showed that TIA and minor stroke patients with multiple acute infarctions (MAIs), which represent mechanisms of embolism, are at higher risk of recurrent stroke as compared to those with none or single acute infarction (SAI). We hypothesis that patient with MAIs may be more susceptible to dual antiplatelet therapy. Methods: We compared clopidogrel plus aspirin with aspirin alone with regard to their effectiveness and safety for prevention of stroke recurrence among non-cardiac TIA and minor ischemic stroke patients with different infarction patterns (no acute infarction, SAI, or MAIs) in the imaging subgroup from the Clopidogrel in High-Risk Patients with Acute Non-disabling Cerebrovascular Events (CHANCE) trial. The efficacy and safety outcome were stroke recurrence and moderate-to-severe bleeding event at 90 days respectively. Results: Overall, 1089 patients at 45 centers in CHANCE trial were included. The rate of recurrent stroke was 14.2%, 8.7%, and 2.0% in patients with MAIs, SAI and no infarction respectively at 90 days. Increased risk of stroke recurrence was observed in patients with MAIs (HR, 5.9; 95% CI, 2.3-15.2) and SAI (HR, 4.1; 95% CI, 1.6-10.7) (Figure A) as compared to those without infarction. The dual antiplatelet treatment was superior to aspirin alone for reducing the risk of recurrent stroke in patients with MAIs (HR 0.48; 95% CI, 0.25- 0.92; P = 0.03) but not in patients with SAI and without acute infarction with P=0.046 for interaction (Figure B-D). The effect of treatment assignment on bleeding did not vary among groups with different infarction patterns ( P &gt;0.05 for all). Conclusions: Patients with MAIs had the highest risk for stroke recurrence among patients with different infarction patterns. Patients with MAIs may benefit the most clinically from dual antiplatelet therapy and dual antiplatelet therapy does not increase the risk of hemorrhage among any groups.

Association Between CYP2C19 Loss-of-Function Allele Status and Efficacy of Clopidogrel for Risk Reduction Among Patients With Minor Stroke or Transient Ischemic Attack.

Data are limited regarding the association between CYP2C19 genetic variants and clinical outcomes of patients with minor stroke or transient ischemic attack treated with clopidogrel. To estimate the association between CYP2C19 genetic variants and clinical outcomes of clopidogrel-treated patients with minor stroke or transient ischemic attack. Three CYP2C19 major alleles (*2, *3, *17) were genotyped among 2933 Chinese patients from 73 sites who were enrolled in the Clopidogrel in High-Risk Patients with Acute Nondisabling Cerebrovascular Events (CHANCE) randomized trial conducted from January 2, 2010, to March 20, 2012. Patients with acute minor ischemic stroke or transient ischemic attack in the trial were randomized to treatment with clopidogrel combined with aspirin or to aspirin alone. The primary efficacy outcome was new stroke. The secondary efficacy outcome was a composite of new composite vascular events (ischemic stroke, hemorrhagic stroke, myocardial infarction, or vascular death). Bleeding was the safety outcome. Among 2933 patients, 1948 (66.4%) were men, with a mean age of 62.4 years. Overall, 1207 patients (41.2%) were noncarriers and 1726 patients (58.8%) were carriers of loss-of-function alleles (*2, *3). After day 90 follow-up, clopidogrel-aspirin reduced the rate of new stroke in the noncarriers but not in the carriers of the loss-of-function alleles (P = .02 for interaction; events among noncarriers, 41 [6.7%] with clopidogrel-aspirin vs 74 [12.4%] with aspirin; hazard ratio [HR], 0.51 [95% CI, 0.35-0.75]; events among carriers, 80 [9.4%] with clopidogrel-aspirin vs 94 [10.8%] with aspirin; HR, 0.93 [95% CI, 0.69 to 1.26]). Similar results were observed for the secondary composite efficacy outcome (noncarriers: 41 [6.7%] with clopidogrel-aspirin vs 75 [12.5%] with aspirin; HR, 0.50 [95% CI, 0.34-0.74]; carriers: 80 [9.4%] with clopidogrel-aspirin vs 95 [10.9%] with aspirin; HR, 0.92 [95% CI, 0.68-1.24]; P = .02 for interaction). The effect of treatment assignment on bleeding did not vary significantly between the carriers and the noncarriers of the loss-of-function alleles (2.3% for carriers and 2.5% for noncarriers in the clopidogrel-aspirin group vs 1.4% for carriers and 1.7% for noncarriers in the aspirin only group; P = .78 for interaction). Among patients with minor ischemic stroke or transient ischemic attack, the use of clopidogrel plus aspirin compared with aspirin alone reduced the risk of a new stroke only in the subgroup of patients who were not carriers of the CYP2C19 loss-of-function alleles. These findings support a role of CYP2C19 genotype in the efficacy of this treatment. clinicaltrials.gov Identifier: NCT00979589.

Causal inference methods to assess safety upper bounds in randomized trials with noncompliance.

BackgroundPremature discontinuation and other forms of noncompliance with treatment assignment can complicate causal inference of treatment effects in randomized trials. The intent-to-treat analysis gives unbiased estimates for causal effects of treatment assignment on outcome, but may understate potential benefit or harm of actual treatment. The corresponding upper confidence limit can also be underestimated.PurposeTo compare estimates of the hazard ratio and upper bound of the two-sided 95% confidence interval from causal inference methods that account for noncompliance with those from the intent-to-treat analysis.MethodsWe used simulations with parameters chosen to reflect cardiovascular safety trials of diabetes drugs, with a focus on upper bound estimates relative to 1.3, based on regulatory guidelines. A total of 1000 simulations were run under each parameter combination for a hypothetical trial of 10,000 total subjects randomly assigned to active treatment or control at 1:1 ratio. Noncompliance was considered in the form of treatment discontinuation and cross-over at specified proportions, with an assumed true hazard ratio of 0.9, 1, and 1.3, respectively. Various levels of risk associated with being a non-complier (independent of treatment status) were evaluated. Hazard ratio and upper bound estimates from causal survival analysis and intent-to-treat were obtained from each simulation and summarized under each parameter setting.ResultsCausal analysis estimated the true hazard ratio with little bias in almost all settings examined. Intent-to-treat was unbiased only when the true hazard ratio = 1; otherwise it underestimated both benefit and harm. When upper bound estimates from intent-to-treat were ≥1.3, corresponding estimates from causal analysis were also ≥1.3 in almost 100% of the simulations, regardless of the true hazard ratio. When upper bound estimates from intent-to-treat were <1.3 and the true hazard ratio = 1, corresponding upper bound estimates from causal analysis were ≥1.3 in up to 66% of the simulations under some settings.LimitationsSimulations cannot cover all scenarios for noncompliance in real randomized trials.ConclusionCausal survival analysis was superior to intent-to-treat in estimating the true hazard ratio with respect to bias in the presence of noncompliance. However, its large variance should be considered for safety upper bound exclusion especially when the true hazard ratio = 1. Our simulations provided a broad reference for practical considerations of bias–variance trade-off in dealing with noncompliance in cardiovascular safety trials of diabetes drugs. Further research is warranted for the development and application of causal inference methods in the evaluation of safety upper bounds.

Effect of Late Revascularization of a Totally Occluded Coronary Artery After Myocardial Infarction on Mortality Rates in Patients With Renal Impairment

Renal dysfunction is an independent predictor of cardiovascular events and a negative prognostic indicator after myocardial infarction (MI). Randomized data comparing percutaneous coronary intervention to medical therapy in patients with MI with renal insufficiency are needed. The Occluded Artery Trial (OAT) compared optimal medical therapy alone to percutaneous coronary intervention with optimal medical therapy in 2,201 high-risk patients with occluded infarct arteries >24 hours after MI with serum creatinine levels ≤2.5 mg/dl. The primary end point was a composite of death, MI, and class IV heart failure (HF). Analyses were carried out using estimated glomerular filtration rate (eGFR) as a continuous variable and by eGFR categories. Long-term follow-up data (maximum 9 years) were used for this analysis. Lower eGFR was associated with development of the primary outcome (6-year life-table rates of 16.9% for eGFR >90 ml/min/1.73 m(2), 19.2% for eGFR 60 to 89 ml/min/1.73 m(2), and 34.9% for eGFR <60 ml/min/1.73 m(2); p <0.0001), death, and class IV HF, with no difference in rates of reinfarction. On multivariate analysis, eGFR was an independent predictor of death and HF. There was no effect of treatment assignment on the primary end point regardless of eGFR, and there was no significant interaction between eGFR and treatment assignment on any outcome. In conclusion, lower eGFR at enrollment was independently associated with death and HF in OAT participants. Despite this increased risk, the lack of benefit from percutaneous coronary intervention in the overall trial was also seen in patients with renal dysfunction and persistent occlusion of the infarct artery in the subacute phase after MI.

Effect of Treatment Assignment on Intravaginal Cleansing in a Randomized Study of the Diaphragm with Candidate Microbicide

Effect of Treatment Assignment on Intravaginal Cleansing in a Randomized Study of the Diaphragm with Candidate Microbicide

Sensitivity Analyses Comparing Time-to-Event Outcomes Only Existing in a Subset Selected Postrandomization and Relaxing Monotonicity

In randomized studies researchers may be interested in the effect of treatment assignment on a time-to-event outcome that only exists in a subset selected after randomization. For example, in preventative HIV vaccine trials, it is of interest to determine whether randomization to vaccine affects the time from infection diagnosis until initiation of antiretroviral therapy. Earlier work assessed the effect of treatment on outcome among the principal stratum of individuals who would have been selected regardless of treatment assignment. These studies assumed monotonicity, that one of the principal strata was empty (e.g., every person infected in the vaccine arm would have been infected if randomized to placebo). Here, we present a sensitivity analysis approach for relaxing monotonicity with a time-to-event outcome. We also consider scenarios where selection is unknown for some subjects because of noninformative censoring (e.g., infection status k years after randomization is unknown for some because of staggered study entry). We illustrate our method using data from an HIV vaccine trial.

Evolution of hepatic steatosis in patients with advanced hepatitis C: Results from the hepatitis C antiviral long-term treatment against cirrhosis (HALT-C) trial

Hepatic steatosis is a common histologic feature in patients with chronic hepatitis C (CHC) but there are no large longitudinal studies describing the progression of steatosis in CHC. We examined changes in steatosis on serial biopsies among CHC patients participating in the Hepatitis C Antiviral Long-term Treatment against Cirrhosis (HALT-C) Trial. All 1050 patients in the trial had advanced fibrosis at baseline biopsy and were documented not to have had a sustained virological response to peginterferon and ribavirin. Most (94%) patients had genotype 1 infection. At least one protocol follow-up biopsy was read on 892 patients, and 699 had the last biopsy performed 3.5 years after randomization. At enrollment, 39% had cirrhosis and 61% had bridging fibrosis; 18%, 41%, 31%, and 10% had steatosis scores of 0, 1, 2, and 3 or 4, respectively. The mean steatosis score decreased in the follow-up biopsies in both the interferon-treated patients and controls with no effect of treatment assignment (P = 0.66). A decrease in steatosis score by > or =1 point was observed in 30% of patients and was associated with both progression to cirrhosis and continued presence of cirrhosis (P = 0.02). Compared to patients without a decrease in steatosis, those with a decrease in steatosis had worse metabolic parameters at enrollment, and were more likely to have a decrease in alcohol intake, improvement in metabolic parameters, and worsening liver disease (cirrhosis, esophageal varices, and deterioration in liver function).Serial biopsies demonstrated that in patients with CHC, steatosis recedes during progression from advanced fibrosis to cirrhosis. Decreased alcohol intake and improved metabolic parameters are associated with a decline in steatosis and may modulate hepatitis C progression.

Likelihood methods in randomized trials with noncompliance and subsequent nonresponse

This article considers likelihood methods for estimating the causal effect of treatment assignment for a two-armed randomized trial assuming all-or-none treatment noncompliance and allowing for subsequent nonresponse. We first derive the observed data likelihood function as a closed form expression of the parameter given the observed data where both response and compliance state are treated as variables with missing values. Then we describe an iterative procedure which maximizes the observed data likelihood function directly to compute a maximum likelihood estimator (MLE) of the causal effect of treatment assignment. Closed form expressions at each iterative step are provided. Finally we compare the MLE with an alternative estimator where the probability distribution of the compliance state is estimated independent of the response and its missingness mechanism. Our work indicates that direct maximum likelihood inference is straightforward for this problem. Extensive simulation studies are provided to examine the finite sample performance of the proposed methods.

Low Perceived Social Support and Post–Myocardial Infarction Prognosis in the Enhancing Recovery in Coronary Heart Disease Clinical Trial: The Effects of Treatment

In post hoc analyses, to examine in low perceived social support (LPSS) patients enrolled in the Enhancing Recovery in Coronary Heart Disease (ENRICHD) clinical trial (n = 1503), the pattern of social support following myocardial infarction (MI), the impact of psychosocial intervention on perceived support, the relationship of perceived support at the time of MI to subsequent death and recurrent MI, and the relationship of change in perceived support 6 months after MI to subsequent mortality. Partner status (partner, no partner) and score (<12 = low support; >12 = moderate support) on the ENRICHD Social Support Instrument (ESSI) were used post hoc to define four levels of risk. The resulting 4 LPSS risk groups were compared on baseline characteristics, changes in social support, and medical outcomes to a group of concurrently enrolled acute myocardial infarction patients without depression or LPSS (MI comparison group, n = 408). Effects of treatment assignment on LPSS and death/recurrent MI were also examined. All 4 LPSS risk groups demonstrated improvement in perceived support, regardless of treatment assignment, with a significant treatment effect only seen in the LPSS risk group with no partner and moderate support at baseline. During an average 29-month follow-up, the combined end point of death/nonfatal MI was 10% in the MI comparison group and 23% in the ENRICHD LPSS patients; LPSS conferred a greater risk in unadjusted and adjusted models (HR = 1.74-2.39). Change in ESSI score and/or improvement in perceived social support were not found to predict subsequent mortality. Baseline LPSS predicted death/recurrent MI in the ENRICHD cohort, independent of treatment assignment. Intervention effects indicated a partner surrogacy role for the interventionist and the need for a moderate level of support at baseline for the intervention to be effective.

Cigarette Smoking and Risk of Cataracts-Reply

In Reply. —Dr Harding mentions an apparent discrepancy in the number of cataracts in our recent study of cigarette smoking and our earlier aspirin study. 1 In the cigarette smoking study we analyzed eyes with cataract, whereas in the aspirin study we analyzed people with cataract. In addition, we were able to identify additional incident cases since the publication of the aspirin results. Dr Salchert questions whether the study medications may have affected the results. All analyses were adjusted for the potential confounding effects of treatment assignment so the relationship of cigarette smoking with cataract was independent of study treatment. Questions concerning cataract and macular degeneration were asked of study participants because of scientific evidence that study medications might lower the risk of these diseases. Finally, Drs Ravenholt, Roy, and Harding propose mechanisms that require further study.

State anxiety and abortion

This study evaluated the negative emotional reactions of 113 women before and after abortion. A Swedish form of the STAI State Anxiety scale was used. The patients had consented to be randomly assigned to treatment by vacuum aspiration or a medical alternative, prostaglandin in vaginal suppositories. The medical treatment was administered in a nursing ward or self-administered by the patient at home. Psychometric and validity findings for the State Anxiety scale were reported. Post abortion state anxiety had significantly decreased. The effects of treatment assignment, of preference before abortion, and of previous abortion on state anxiety were analyzed. Only preference had an effect. Women who preferred the medical-at-home treatment were lower in anxiety on both occasions than the other groups. The significantly higher level of state anxiety when assessed by anxiety-absent items (scoring reversed) in the context of abortion was discussed.