No abstract

Longitudinal or repeated measures data with clumping at zero occur in many applications in biometrics, including health policy research, epidemiology, nutrition, and meteorology. These data exhibit correlation because they are measured on the same subject over time or because subjects may be considered repeated measures within a larger unit such as a family. They present special challenges because of the extreme non-normality of the distributions involved. A model for repeated measures data with clumping at zero, using a mixed-effects mixed-distribution model with correlated random effects, is presented. The model contains components to model the probability of a nonzero value and the mean of nonzero values, allowing for repeated measurements using random effects and allowing for correlation between the two components. Methods for describing the effect of predictor variables on the probability of nonzero values, on the mean of nonzero values, and on the overall mean amount are given. This interpretation also applies to the mixed-distribution model for cross-sectional data. The proposed methods are illustrated with analyses of effects of several covariates on medical expenditures in 1996 for subjects clustered within households using data from the Medical Expenditure Panel Survey.

IMPORTANCE Little is known about cardiac adverse events among patients with nonobstructive coronary artery disease (CAD). OBJECTIVE To compare myocardial infarction (MI) and mortality rates between patients with nonobstructive CAD, obstructive CAD, and no apparent CAD in a national cohort. DESIGN, SETTING, AND PARTICIPANTS Retrospective cohort study of all US veterans undergoing elective coronary angiography for CAD between October 2007 and September 2012 in the Veterans Affairs health care system. Patients with prior CAD events were excluded. EXPOSURES Angiographic CAD extent, defined by degree (no apparent CAD: no stenosis >20%; nonobstructive CAD: ≥1 stenosis ≥20% but no stenosis ≥70%; obstructive CAD: any stenosis ≥70% or left main [LM] stenosis ≥50%) and distribution (1,2, or 3 vessel). MAIN OUTCOMES AND MEASURES The primary outcome was 1-year hospitalization for nonfatal MI after the index angiography. Secondary outcomes included 1-year all-cause mortality and combined 1-year MI and mortality. RESULTS Among37 674 patients, 8384 patients (22.3%) had nonobstructive CAD and 20 899 patients (55.4%) had obstructive CAD. Within 1 year, 845 patients died and 385 were rehospitalized for MI. Among patients with no apparent CAD, the 1-year MI rate was 0.11% (n = 8, 95% CI, 0.10%–0.20%) and increased progressively by 1-vessel nonobstructive CAD, 0.24% (n = 10, 95% CI, 0.10%–0.40%); 2-vessel nonobstructive CAD, 0.56% (n = 13, 95% CI, 0.30%–1.00%); 3-vessel nonobstructive CAD, 0.59% (n = 6, 95% CI, 0.30%–1.30%); 1-vessel obstructive CAD, 1.18% (n = 101, 95% CI, 1.00%–1.40%); 2-vessel obstructive CAD, 2.18% (n = 110, 95% CI, 1.80%–2.60%); and 3-vessel or LM obstructive CAD, 2.47% (n = 137, 95% CI, 2.10%–2.90%). After adjustment, 1-year MI rates increased with increasing CAD extent. Relative to patients with no apparent CAD, patients with 1-vessel nonobstructive CAD had a hazard ratio (HR) for 1-year MI of 2.0 (95% CI, 0.8–5.1); 2-vessel nonobstructive HR, 4.6 (95% CI, 2.0–10.5); 3-vessel nonobstructive HR, 4.5 (95% CI, 1.6–12.5); 1-vessel obstructive HR, 9.0 (95% CI, 4.2–19.0); 2-vessel obstructive HR, 16.5 (95% CI, 8.1–33.7); and 3-vessel or LM obstructive HR, 19.5 (95% CI, 9.9–38.2). One-year mortality rates were associated with increasing CAD extent, ranging from 1.38% among patients without apparent CAD to 4.30% with 3-vessel or LM obstructive CAD. After risk adjustment, there was no significant association between 1- or 2-vessel nonobstructive CAD and mortality, but there were significant associations with mortality for 3-vessel nonobstructive CAD (HR, 1.6; 95% CI, 1.1–2.5), 1-vessel obstructive CAD (HR, 1.9; 95% CI, 1.4–2.6), 2-vessel obstructive CAD (HR, 2.8; 95% CI, 2.1–3.7), and 3-vessel or LM obstructive CAD (HR, 3.4; 95% CI, 2.6–4.4). Similar associations were noted with the combined outcome. CONCLUSIONS AND RELEVANCE In this cohort of patients undergoing elective coronary angiography, nonobstructive CAD, compared with no apparent CAD, was associated with a significantly greater 1-year risk of MI...

Background Pulmonary hypertension (PH) is associated with increased morbidity across the cardiopulmonary disease spectrum. Based largely on expert consensus opinion, PH is defined by a mean pulmonary artery pressure (mPAP) ≥25 mmHg. Although mPAP levels below this threshold are common among populations at risk for PH, the relevance of mPAP <25 mmHg to clinical outcome is unknown. Methods and Results We analyzed retrospectively all US veterans undergoing right heart catheterization (RHC)(2007–2012) in the Veterans Affairs health care system (N=21,727; 908 day median follow-up). Cox proportional hazards models were used to evaluate the association between mPAP and outcomes of all-cause mortality and hospitalization, adjusted for clinical covariates. When treating mPAP as a continuous variable, the mortality hazard increased beginning at 19 mmHg (HR=1.183, 95% CI [1.004–1.393]) relative to 10 mmHg. Therefore, patients were stratified into three groups: referent (≤18 mmHg; N=4,207), borderline PH (19–24 mmHg; N=5,030), and PH (≥25 mmHg; N=12,490). The adjusted mortality hazard was increased for borderline PH (HR=1.23, 95% CI [1.12–1.36], P<0.0001) and PH (HR=2.16, 95% CI [1.96–2.38], P<0.0001) compared to the referent group. The adjusted hazard for hospitalization was also increased in borderline PH (HR=1.07, 95% CI [1.01–1.12], P=0.0149) and PH (HR=1.15, 95% CI [1.09–1.22], P<0.0001). The borderline PH cohort remained at increased risk for mortality after excluding the following high-risk subgroups: patients with pulmonary artery wedge pressure >15 mmHg, pulmonary vascular resistance ≥3.0 Wood units, or inpatient status at the time of RHC. Conclusions These data illustrate a continuum of risk according to mPAP level, and that borderline PH is associated with increased mortality and hospitalization. Future investigations are needed to test the generalizability of our findings to other populations and study the effect of treatment on outcome in borderline PH.

OBJECTIVES: Low-fat high-carbohydrate diets are recommended to prevent weight gain in normal weight subjects and reduce body weight in overweight and obese. However, their ef®cacy is controversial. We evaluated the ef®cacy of ad libitum low-fat diets in reducing body weight in non-diabetic individuals from the results of intervention trials. DESIGN: Studies were identi®ed from a computerized search of the Medline database from January 1966 to July 1999 and other sources. Inclusion criteria were: controlled trials lasting more than 2 months comparing ad libitum low-fat diets as the sole intervention with a control group consuming habitual diet or a medium-fat diet ad libitum. MAIN OUTCOME MEASURES: Differences in changes in dietary fat intake, energy intake and body weight. Weighted mean differences for continuous data and 95% con®dence intervals (CIs) were calculated. RESULTS: Two authors independently selected the studies meeting the inclusion criteria and extracted data from 16 trials (duration of 2 ± 12 months) with 19 intervention groups, enrolling 1910 individuals. Fourteen were randomized. Weight loss was not the primary aim in 11 studies. Before the interventions the mean proportions of dietary energy from fat in the studies were 37.7% (95% CI, 36.9 ± 38.5) in the low-fat groups, and 37.4% (36.4 ± 38.4) in the control groups. The low-fat intervention produced a mean fat reduction of 10.2% (8.1 ± 12.3). Low-fat intervention groups showed a greater weight loss than control groups (3.2 kg, 95% con®dence interval 1.9 ± 4.5 kg; P`0.0001), and a greater reduction in energy intake (1138 kJaday, 95% con®dence interval 564 ± 1712 kJaday, P 0.002). Having a body weight 10 kg higher than the average pre-treatment body weight was associated with a 2.6 AE 0.8 kg (P 0.011) greater difference in weight loss. CONCLUSION: A reduction in dietary fat without intentional restriction of energy intake causes weight loss, which is more substantial in heavier subjects.

Visually determined disease extent on CT images is a strong independent predictor of mortality in IPF. Serial evaluation of quantitative CT measures can show disease progression in these patients.

Background Dabigatran is a novel oral anti-coagulant (NOAC) that reduces risk of stroke in patients with non-valvular atrial fibrillation (NVAF). It does not require routine monitoring with laboratory testing which may have an adverse impact on adherence. We aimed to describe adherence to dabigatran in the first year after initiation and assess the association between non-adherence to dabigatran and clinical outcomes in a large integrated healthcare system. Methods We studied a national cohort of 5,376 patients with NVAF, initiated on dabigatran between October-2010 and September-2012 at all Veterans Affairs hospitals. Adherence to dabigatran was calculated as proportion of days covered (PDC) and association between PDC and outcomes was assessed using standard regression techniques. Results Mean age of the study cohort was 71.3 ± 9.7 years; 98.3% were men and mean CHADS2 score was 2.4 ± 1.2 (mean CHA2DS2VASc score 3.2 ± 1.4). Median PDC was 94% (IQR 76%-100%; mean PDC 84% ± 22%) over a median follow-up of 244 days (IQR 140-351). A total of 1,494 (27.8%) patients had a PDC <80% and were classified as non-adherent. After multivariable adjustment, lower adherence was associated with increased risk for combined all-cause mortality and stroke (HR 1.13, 95% CI 1.07–1.19 per 10% decrease in PDC). Adherence to dabigatran was not associated with non-fatal bleeding or myocardial infarction. Conclusions In the year after initiation, adherence to dabigatran for a majority of patients is very good. However, 28% of patients in our cohort had poor adherence. Furthermore, lower adherence to dabigatran was associated with increased adverse outcomes. Concerted efforts are needed to optimize adherence to NOACs.

JSTOR is a not-for-profit service that helps scholars, researchers, and students discover, use, and build upon a wide range of content in a trusted digital archive. We use information technology and tools to increase productivity and facilitate new forms of scholarship.We consider the kernel estimator of conditional density and derive its asymptotic bias, variance, and mean-square error. Optimal bandwidths (with respect to integrated mean-square error) are found and it is shown that the convergence rate of the density estimator is order n-2/3. We also note that the conditional mean function obtained from the estimator is equivalent to a kernel smoother. Given the undesirable bias properties of kernel smoothers, we seek a modified conditional density estimator that has mean equivalent to some other nonparametric regression smoother with better bias properties. It is also shown that our modified estimator has smaller mean square error than the standard estimator in some commonly occurring situations. Finally, three graphical methods for visualizing conditional density estimators are discussed and applied to a data set consisting of maximum daily temperatures in Melbourne, Australia.