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Cross-sectional approaches to outcome assessment may not adequately capture heterogeneity in recovery after traumatic brain injury (TBI). Using latent class mixed models (LCMM), a data-driven analytic that identifies groups of patients with similar trajectories, we identified distinct 6 month functional recovery trajectories in a large cohort (n = 1046) of adults 18-70 years of age with complicated mild to severe TBI who participated in the Citicoline Brain Injury Treatment Trial (COBRIT). We used multinomial logistic fixed effect models and backward elimination, forward selection, and forward stepwise selection with several stopping rules to explore baseline predictors of functional recovery trajectory. Based on statistical and clinical considerations, the seven-class model was deemed superior. Visualization of these seven functional recovery trajectories revealed that each trajectory class started at one of three recovery levels at 1 month, which, for ease of reference we labeled groups A-C: Group A, good recovery (two classes; A1 and A2); Group B, moderate disability (two classes; B1 and B2); and Group C, severe disability (three classes; C1, C2, and C3). By 6 months, these three groups experienced dramatically divergent trajectories. Group A experienced stable good recovery (A1, n = 115) or dramatic decline (A2, n = 4); Group B experienced rapid complete recovery (B1, n = 71) or gradual recovery (B2, n = 742); Group C experienced dramatic rapid recovery (C1, n = 12), no recovery (C2, n = 91), or death (C3, n = 11). Trajectory class membership was not predicted by citicoline treatment (p = 0.57). The models identified demographic, pre-injury, and injury-related predictors of functional recovery trajectory, including: age, race, education, pre-injury employment, pre-injury diabetes, pre-injury psychiatric disorder, site, Glasgow Coma Scale (GCS) score, post-traumatic amnesia, TBI mechanism, major extracranial injury, hemoglobin, and acute computed tomographic (CT) findings. GCS was the most consistently selected predictor across all models. All models also selected at least one demographic or pre-injury medical predictor. LCMM successfully identified dramatically divergent, clinically meaningful 6 month recovery trajectories with utility to inform clinical trial design.

Increase of peripheral blood CD4 lymphocyte counts is a key goal of combined antiretroviral therapy (cART); most, but not all, recipients respond adequately and promptly. A small number of studies have examined specific genetic factors associated with the extent of CD4 recovery. We report a genome-wide examination of factors that predict CD4 recovery in HIV-infected women. We identified women in in a cohort study who were on cART with viral load below 400 copies, and drew racially and ethnically matched samples of those with good CD4 response over 2 years or poor response. We analyzed the exomes of those women employing next generation sequencing for genes associated with CD4 recovery after controlling for non-genetic factors identified through forward stepwise selection as important. We studied 48 women with good CD4 recovery and 42 with poor CD4 recovery during virologically-suppressive cART. Stepwise logistic regression selected only age as a statistically significant (p

BACKGROUND: The 2017 American College of Cardiology/American Heart Association blood pressure guideline classified 31 million US adults as having stage 1 hypertension and recommended clinicians provide counseling on behavioral change to the low-risk portion of this group. However, nationwide reductions in cardiovascular disease (CVD) and associated health care expenditures achievable by nonpharmacologic therapy remain unquantified. METHODS: We simulated interventions on a target population of US adults aged 35 to 64 years, identified from the 2015-2018 National Health and Nutrition Examination Survey, with low-risk stage 1 systolic hypertension: that is, untreated systolic blood pressure 130 to 139 mm Hg with diastolic BP <90 mm Hg; no history of CVD, diabetes, or chronic kidney disease; and a low 10-year risk of CVD. We used meta-analyses and trials to estimate the effects of population-level behavior modification on systolic blood pressure. We assessed the extent to which restricting intervention to those in regular contact with clinicians might prevent the delivery of nonpharmacologic therapy. RESULTS: Controlling systolic blood pressure to <130 mm Hg among the 8.8 million low-risk US adults with stage 1 hypertension could prevent 26 100 CVD events, avoid 2900 deaths, and save $1.7 billion in total direct health care costs over 10 years. Adoption of the Dietary Approaches to Stop Hypertension diet could prevent 28 000 CVD events. Other nonpharmacologic interventions could avert between 3800 and 19 500 CVD events. However, only 51% of men and 75% of women regularly interacted with clinicians for counseling opportunities. CONCLUSIONS: Among low-risk adults with stage 1 hypertension, substantial benefits to cardiovascular health could be achieved through public policy that promotes the adoption of nonpharmacologic therapy. [ABSTRACT FROM AUTHOR]

ObjectiveCoinfection with hepatitis C virus (HCV) is a major cause of morbidity and mortality among individuals with HIV. Our objective was to assess the prognostic performance of noninvasive measures of liver fibrosis in predicting all-cause mortality in women with HIV/HCV coinfection.DesignWe studied HCV/HIV coinfected women enrolled in the prospective, multicenter Women's Interagency HIV Study. Aspartate aminotransferase to platelet ratio and FIB-4 were used to identify women without fibrosis at all visits and women who progressed to severe fibrosis.MethodsEnhanced liver fibrosis (ELF), which utilizes direct measures of fibrosis, hyaluronic acid, procollagen III aminoterminal peptide and tissue inhibitor of matrix metalloproteinase was performed.ResultsIncluded were 381 women with 2296 ELF measurements, with mean follow-up 8.3 ± 3.3 years. There were 134 deaths (60% with severe liver fibrosis). Receiver operator characteristic curves at fixed time windows prior to death or at end of follow-up showed that ELF was best at predicting mortality when tested within a year of death (area under the curve for ELF 0.85 vs. APRI 0.69, P

The deleterious effects of racism on a wide range of health outcomes, including HIV risk, are well documented among racial/ethnic minority groups in the United States. However, little is known about how men of color who have sex with men (MSM) cope with stress from racism and whether the coping strategies they employ buffer against the impact of racism on sexual risk for HIV transmission. We examined associations of stress and coping with racism with unprotected anal intercourse (UAI) in a sample of African American (N = 403), Asian/Pacific Islander (N = 393), and Latino (N = 400) MSM recruited in Los Angeles County, CA during 2008-2009. Almost two-thirds (65 %) of the sample reported being stressed as a consequence of racism experienced within the gay community. Overall, 51 % of the sample reported having UAI in the prior 6 months. After controlling for race/ethnicity, age, nativity, marital status, sexual orientation, education, HIV serostatus, and lifetime history of incarceration, the multivariate analysis found statistically significant main effects of stress from racism and avoidance coping on UAI; no statistically significant main effects of dismissal, education/confrontation, and social-support seeking were observed. None of the interactions of stress with the four coping measures were statistically significant. Although stress from racism within the gay community increased the likelihood of engaging in UAI among MSM of color, we found little evidence that coping responses to racism buffered stress from racism. Instead, avoidance coping appears to suggest an increase in UAI.

Research has documented deleterious effects of racism among ethnic minorities and of homophobia among men who have sex with men (MSM). Less is known about the impact of multiple forms of stigmatization on ethnic minority MSM. This study examined substance use by African American, Asian/Pacific Islander and Latino MSM, and the associations of experienced racism and homophobia from various sources with polydrug use and stimulant drug use. Experienced racism within the general community was associated with higher levels of use; other forms of discrimination were either not associated with polydrug or stimulant use or had more complex relationships with use. Implications for further research and interventions are discussed.

Investigators commonly gather longitudinal data to assess changes in responses over time and to relate these changes to within-subject changes in predictors. With rare or expensive outcomes such as uncommon diseases and costly radiologic measurements, outcome-dependent, and more generally outcome-related, sampling plans can improve estimation efficiency and reduce cost. Longitudinal follow up of subjects gathered in an initial outcome-related sample can then be used to study the trajectories of responses over time and to assess the association of changes in predictors within subjects with change in response. In this article, we develop two likelihood-based approaches for fitting generalized linear mixed models (GLMMs) to longitudinal data from a wide variety of outcome-related sampling designs. The first is an extension of the semi-parametric maximum likelihood approach developed in Neuhaus, Scott and Wild (2002, Biometrika 89, 23-37) and Neuhaus, Scott and Wild (2006, Biometrics 62, 488-494) and applies quite generally. The second approach is an adaptation of standard conditional likelihood methods and is limited to random intercept models with a canonical link. Data from a study of attention deficit hyperactivity disorder in children motivates the work and illustrates the findings.

ObjectivesTo examine how social networks influence HIV risk among US racial/ethnic minority men who have sex with men (MSM) and whether the associations of social network characteristics with risk vary by race/ethnicity.MethodsA chain-referral sample of 403 African American, 393 Asian/Pacific Islander, and 400 Latino MSM recruited in Los Angeles County, California, completed a questionnaire, which asked about their egocentric social networks, safer sex peer norms, and male anal intercourse partners. HIV-nonconcordant partnerships were those reported by respondents as serodisconcordant or where self and/or partner serostatus was unknown.ResultsOverall, 26% of the sample reported HIV-nonconcordant unprotected anal intercourse (UAI) with a nonprimary male partner in the previous 6 months. In a generalized estimating equation (GEE) logistic model that controlled for race/ethnicity, age, nativity, incarceration history, and HIV status, being in a more dense network was associated with less HIV-nonconcordant UAI [adjusted odds ratio (AOR) = 0.92, 95% confidence interval (CI): 0.86 to 0.99, P = 0.0467]. In addition, the effect of safer sex peer norms on HIV-nonconcordant UAI was moderated by ego-alter closeness (P = 0.0021). Safer sex peer norms were protective among those reporting "medium" or "high" ego-alter closeness (AOR = 0.70, 95% CI: 0.52 to 0.95, P = 0.0213 and AOR = 0.48, 95% CI: 0.35 to 0.66, P < 0.0001, respectively), but not among those reporting "low" ego-alter closeness (AOR = 0.96, 95% CI: 0.63 to 1.46, P = 0.8333). The effects of density, closeness, and norms on HIV-nonconcordant UAI did not differ by race/ethnicity.ConclusionsThe significant association of social network characteristics with UAI point to network-level factors as important loci for both ongoing research and HIV prevention interventions among US MSM of color.

ObjectivesWe examined the associations between specific types and sources of discrimination and mental health outcomes among US racial/ethnic minority men who have sex with men (MSM) and how these associations varied by race/ethnicity.MethodsA chain-referral sample of 403 African American, 393 Asian and Pacific Islander (API), and 400 Latino MSM recruited in Los Angeles County, California completed a standardized questionnaire. Data were obtained from the Ethnic Minority Men's Health Study from May 2008 to October 2009.ResultsPast-year experiences of racism within the general community and perceived homophobia among heterosexual friends were positively associated with depression and anxiety. Past-year homophobia experienced within the general community was also positively associated with anxiety. These statistically significant associations did not vary across racial/ethnic groups. The positive association of perceived racism within the gay community with anxiety differed by race/ethnicity, and was statistically significant only for APIs. Perceived homophobia within the family was not associated with either depression or anxiety.ConclusionsHigher levels of experiences of discrimination were associated with psychological distress among MSM of color. However, specific types and sources of discrimination were differentially linked to negative mental health outcomes among African American, API, and Latino MSM.

BackgroundFibrosis stages from liver biopsies reflect liver damage from hepatitis C infection, but analysis is challenging due to their ordered but non-numeric nature, infrequent measurement, misclassification, and unknown infection times.MethodsWe used a non-Markov multistate model, accounting for misclassification, with multiple imputation of unknown infection times, applied to 1062 participants of whom 159 had multiple biopsies. Odds ratios (OR) quantified the estimated effects of covariates on progression risk at any given time.ResultsModels estimated that progression risk decreased the more time participants had already spent in the current stage, African American race was protective (OR 0.75, 95% confidence interval 0.60 to 0.95, p = 0.018), and older current age increased risk (OR 1.33 per decade, 95% confidence interval 1.15 to 1.54, p = 0.0002). When controlled for current age, older age at infection did not appear to increase risk (OR 0.92 per decade, 95% confidence interval 0.47 to 1.79, p = 0.80). There was a suggestion that co-infection with human immunodeficiency virus increased risk of progression in the era of highly active antiretroviral treatment beginning in 1996 (OR 2.1, 95% confidence interval 0.97 to 4.4, p = 0.059). Other examined risk factors may influence progression risk, but evidence for or against this was weak due to wide confidence intervals. The main results were essentially unchanged using different assumed misclassification rates or imputation of age of infection.DiscussionThe analysis avoided problems inherent in simpler methods, supported the previously suspected protective effect of African American race, and suggested that current age rather than age of infection increases risk. Decreasing risk of progression with longer time already spent in a stage was also previously found for post-transplant progression. This could reflect varying disease activity, with recent progression indicating active disease and high risk, while longer time already spent in a stage indicates quiescent disease and low risk.

Generalized linear mixed models with random intercepts and slopes provide useful analyses of clustered and longitudinal data and typically require the specification of the distribution of the random effects. Previous work for models with only random intercepts has shown that misspecifying the shape of this distribution may bias estimates of the intercept, but typically leads to little bias in estimates of covariate effects. Very few papers have examined the effects of misspecifying the joint distribution of random intercepts and slopes. However, simulation results in a recent paper suggest that misspecifying the shape of the random slope distribution can yield severely biased estimates of all model parameters. Using analytic results, simulation studies and fits to example data, this paper examines the bias in parameter estimates due to misspecification of the shape of the joint distribution of random intercepts and slopes. Consistent with results for models with only random intercepts, and contrary to the claims of severe bias in a recent paper, we show that misspecification of the joint distribution typically yields little bias in estimates of covariate effects and is restricted to covariates associated with the misspecified random effects distributions. We also show that misspecification of the distribution of random effects has little effect on confidence interval performance. Coverage rates based on the model-based standard errors from fitted likelihoods were generally quite close to nominal. Copyright © 2012 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

In this rejoinder, we discuss the impact of misspecifying the random effects distribution on inferences obtained from generalized linear mixed models (GLMMs). Special attention is paid to the power of the tests for the fixed-effect parameters. To study this misspecification, researchers often use simulation designs in which several choices for the true underlying random-effects distribution are considered, while the assumed distribution is kept fixed. Neuhaus, McCulloch, and Boylan (2010, Biometrics , 000-000) argue that a logically correct approach should consist of varying the assumed, fitted distribution, while holding the true fixed. We argue that both simulation designs can bring valuable insights into the impact of the misspecification. Furthermore, using both designs, we illustrate that the power associated with the tests for the fixed-effect parameters in GLMM may be affected by misspecifying the random-effects distribution. [ABSTRACT FROM AUTHOR]

The article presents information related to a research conducted on external labor market. Structural researchers have usually tended to focus on internal labor markets, those markets under the administrative control of a single organization. In this paper, the author argues that movement in external labor markets, those involved in initial hiring from outside the organization, is also structured, because some positions help their incumbents make moves between employers. Such positions confer skills, permit signaling of ability, provide contacts, or offer credentials. The result is a process of channeled mobility analogous to that in internal labor markets. This paper develops procedures for determining if a position offers advantage in external or internal markets, and shows that the resulting structure does channel mobility between employers. Results also show substantial effects of market position on income and income growth, net of all time-invariant personal characteristics. The results thus confirm key structural claims that labor market structure affects income and mobility, even as the analysis emphasizes the need to broaden the concerns of structural theory beyond internal labor markets.

A letter to the editor is presented in response to the article by Baicker and colleagues which discusses the negative effect of Medicaid coverage in measured physical health.

Objectives: To examine how social networks influence HIV risk among US racial/ethnic minority men who have sex with men (MSM) and whether the associations of social network characteristics with risk vary by race/ethnicity., Methods: A chain-referral sample of 403 African American, 393 Asian/Pacific Islander, and 400 Latino MSM recruited in Los Angeles County, California, completed a questionnaire, which asked about their egocentric social networks, safer sex peer norms, and male anal intercourse partners. HIV-nonconcordant partnerships were those reported by respondents as serodisconcordant or where self and/or partner serostatus was unknown., Results: Overall, 26% of the sample reported HIV-nonconcordant unprotected anal intercourse (UAI) with a nonprimary male partner in the previous 6 months. In a generalized estimating equation (GEE) logistic model that controlled for race/ethnicity, age, nativity, incarceration history, and HIV status, being in a more dense network was associated with less HIV-nonconcordant UAI [adjusted odds ratio (AOR) = 0.92, 95% confidence interval (CI): 0.86 to 0.99, P = 0.0467]. In addition, the effect of safer sex peer norms on HIV-nonconcordant UAI was moderated by ego-alter closeness (P = 0.0021). Safer sex peer norms were protective among those reporting "medium" or "high" ego-alter closeness (AOR = 0.70, 95% CI: 0.52 to 0.95, P = 0.0213 and AOR = 0.48, 95% CI: 0.35 to 0.66, P < 0.0001, respectively), but not among those reporting "low" ego-alter closeness (AOR = 0.96, 95% CI: 0.63 to 1.46, P = 0.8333). The effects of density, closeness, and norms on HIV-nonconcordant UAI did not differ by race/ethnicity., Conclusions: The significant association of social network characteristics with UAI point to network-level factors as important loci for both ongoing research and HIV prevention interventions among US MSM of color.