A general class of small area estimation using calibrated hierarchical likelihood approach with applications to COVID-19 data.

The direct estimation techniques in small area estimation (SAE) models require sufficiently large sample sizes to provide accurate estimates. Hence, indirect model-based methodologies are developed to incorporate auxiliary information. The most commonly used SAE models, including the Fay-Herriot (FH) model and its extended models, are estimated using marginal likelihood estimation and the Bayesian methods, which rely heavily on the computationally intensive integration of likelihood function. In this article, we propose a Calibrated Hierarchical (CH) likelihood approach to obtain SAE through hierarchical estimation of fixed effects and random effects with the regression calibration method for bias correction. The latent random variables at the domain level are treated as 'parameters' and estimated jointly with other parameters of interest. Then the dispersion parameters are estimated iteratively based on the Laplace approximation of the profile likelihood. The proposed method avoids the intractable integration to estimate the marginal distribution. Hence, it can be applied to a wide class of distributions, including generalized linear mixed models, survival analysis, and joint modeling with distinct distributions. We demonstrate our method using an area-level analysis of publicly available count data from the novel coronavirus (COVID-19) positive cases.

Impact of octreotide on sodium level in cirrhotic inpatients with hyponatremia: a retrospective study.

OBJECTIVE: Octreotide could increase serum sodium in cirrhotics with hyponatremia by counteracting splanchnic vasodilation. Current supporting data is limited to case reports and series. The aim of the study is to assess the effect of octreotide on serum sodium in cirrhotic inpatients with hyponatremia compared with controls. METHODS: This is a retrospective study including adult inpatients with cirrhosis, admitted for ≥5 days with Na <133 at baseline. We excluded those receiving other vasoconstrictor infusions, hypertonic saline, tolvaptan or dialysis. Controls represented an equal number of inpatients with cirrhosis not receiving octreotide. Sodium changes on days 5, 7 and 10 were evaluated with multivariable adjustment. RESULTS: Each group consisted of 156 patients. The octreotide subjects had more cirrhosis complications. Baseline sodium was lower in the octreotide group, and their change in sodium at day 5 was higher (6.6 ± 5.6 vs. 3.5 ± 5.3; P < 0.001). Significant differences were also noted on days 7 and 10 (7.84 ± 6.76 vs. 4.33 ± 6.2 and 7.99 ± 6.72 vs. 5.2 ± 6.56, respectively). The impact of octreotide was lessened but remained significant ( P = 0.019) in a mixed model adjusting for baseline sodium, creatinine, requirement of paracentesis, midodrine, albumin and fresh frozen plasma. More octreotide patients achieved hyponatremia resolution (55.1% vs. 42.3%; P = 0.031), but significance was not preserved in multivariate logistic regression. CONCLUSION: Octreotide administration is associated with an increase in serum sodium among inpatient cirrhotics with hyponatremia, even after accounting for confounders. Prospective randomized controlled trials are warranted.

Recent and lifetime maternal substance use: Rurality and economic distress.

Research on opioid use disorder (OUD) in pregnancy has mainly considered women in urban areas receiving treatment, with less known about women in rural areas. We sought to describe demographics and substance use characteristics of pregnant women with OUD and to compare the women based on urbanicity, in a state (Kentucky) with unfavorable economic conditions in many rural counties; we hypothesized that pregnant women in rural areas would have greater adversity, broadly defined, related to substance use. Using data collected from a larger project between 2017 and 2020, we analyzed characteristics of 93 pregnant women (59 rural and 34 urban) with OUD; we examined data in medical, employment, substance use, legal, family history, relationship, and psychiatric health domains, both overall and within rural (population <50,000) and urban (population ≥50,000) strata. Pregnant women with OUD from rural and urban areas were similar on almost all attributes. Among the few significant differences, 30% from urban areas perceived inadequate prenatal care versus 11% from rural areas (p = 0.024); 21% of urban women used amphetamines/methamphetamines in the month before delivery versus 0% of rural women (p < 0.001); and rural women had longer most recent abstinence from substance use than their urban counterparts (medians 7.0 and 2.8 months, p = 0.049). The few significant differences that were discovered favored rural women. These findings, contrary to our hypothesis, suggest that tailoring interventions may require more than focusing on geography. The participants in this study were pregnant women being treated for OUD, and as such there is patient contribution of data.

Associations of potential ADRD plasma biomarkers in cognitively normal volunteers.

INTRODUCTION: This study examined the relationships between 13 novel blood-plasma biomarkers and dementia-related demographic and health factors in a cohort of 237 cognitively normal research volunteers whose average age was ≈82 years and who were 63% female. METHODS: We regressed each biomarker on selected covariates to explore the associations between the biomarkers and selected factors to assess whether they may contribute to biomarker values. Post hoc sensitivity analyses were done with updated data and consistent variable sets for robustness and batch effects. RESULTS: Biomarker concentrations were largely not associated with demographics or health conditions, but some expected associations (e.g., apolipoprotein E [APOE] status with amyloid beta [Aß]42/Aß40) were observed. Post hoc results remained similar to those of the main analysis. DISCUSSION: The absence of strong associations between the biomarkers with age, gender, or medical conditions suggests that changes in these biomarkers, when observed, may be attributable to neuropathological changes. HIGHLIGHTS: Among N = 237 cognitively normal adults, we studied candidate Alzheimer's disease and related dementia (ADRD) plasma biomarkers. Biomarkers were largely not associated with demographic or health factors. Apolipoprotein E (APOE) status was associated with amyloid beta (Aß)42/Aß40 ratio. These results support hypotheses that plasma biomarkers are informative for ADRD.

Ratio of Mixed Venous Oxygen Saturation-to-Pulmonary Capillary Wedge Pressure: Insights From the Veterans Affairs Clinical Assessment, Reporting, and Tracking Program.

BACKGROUND: Hemodynamic values from right heart catheterization aid diagnosis and clinical decision-making but may not predict outcomes. Mixed venous oxygen saturation percentage and pulmonary capillary wedge pressure relate to cardiac output and congestion, respectively. We theorized that a novel, simple ratio of these measurements could estimate cardiovascular prognosis. METHODS: We queried Veterans Affairs' databases for clinical, hemodynamic, and outcome data. Using the index right heart catheterization between 2010 and 2016, we calculated the ratio of mixed venous oxygen saturation-to-pulmonary capillary wedge pressure, termed ratio of saturation-to-wedge (RSW). The primary outcome was time to all-cause mortality; secondary outcome was 1-year urgent heart failure presentation. Patients were stratified into quartiles of RSW, Fick cardiac index (CI), thermodilution CI, and pulmonary capillary wedge pressure alone. Kaplan-Meier curves and Cox proportional hazards models related comparators with outcomes. RESULTS: Of 12 019 patients meeting inclusion criteria, 9826 had values to calculate RSW (median 4.00, interquartile range, 2.67-6.05). Kaplan-Meier curves showed early, sustained separation by RSW strata. Cox modeling estimated that increasing RSW by 50% decreases mortality hazard by 19% (estimated hazard ratio, 0.81 [95% CI, 0.79-0.83], P<0.001) and secondary outcome hazard by 28% (hazard ratio, 0.72 [95% CI, 0.70-0.74], P<0.001). Among the 3793 patients with data for all comparators, Cox models showed RSW best associated with outcomes (by both C statistics and Bayes factors). Furthermore, pulmonary capillary wedge pressure was superior to thermodilution CI and Fick CI. Multivariable adjustment attenuated without eliminating the association of RSW with outcomes. CONCLUSIONS: In a large national database, RSW was superior to conventional right heart catheterization indices at assessing risk of mortality and urgent heart failure presentation. This simple calculation with routine data may contribute to clinical decision-making in this population.

Effects of maternal controlled exercise on offspring adiposity and glucose tolerance.

While metabolic disorders such as obesity and diabetes are costly and deadly to the current population, they are also extremely detrimental to the next generation. Much of the current literature focuses on the negative impact of poor maternal choices on offspring disease, while there is little work examining maternal behaviors that may improve offspring health. Research has shown that voluntary maternal exercise in mouse models improves metabolic function in offspring. In this study, we hypothesized that controlled maternal exercise in a mouse model will effect positive change on offspring obesity and glucose homeostasis. Female mice were separated into three groups: home cage, sedentary, and exercise. The sedentary home cage group was not removed from the home cage, while the sedentary wheel group was removed from the cage and placed in an immobile wheel apparatus. The exercise group was removed from the home cage and run on the same wheel apparatus but with the motor activated at 5-10 m/min for 1 h/d prior to and during pregnancy. Offspring were subjected to oral glucose tolerance testing and body composition analysis. There was no significant difference in offspring glucose tolerance or body composition as a consequence of the maternal exercise intervention compared to the sedentary wheel group. There were no marked negative consequences of the maternal controlled exercise intervention. Further research should clarify the potential advantages of the controlled exercise model and improve experimental techniques to facilitate translation of this research to human applications.

A Comparison of Methods for Predicting Future Cognitive Status: Mixture Modeling, Latent Class Analysis, and Competitors.

PURPOSE: The present work compares various methods for using baseline cognitive performance data to predict eventual cognitive status of longitudinal study participants at the University of Kentucky's Alzheimer's Disease Center. METHODS: Cox proportional hazards models examined time to cognitive transition as predicted by risk strata derived from normal mixture modeling, latent class analysis, and a 1-SD thresholding approach. An additional comparator involved prediction directly from a numeric value for baseline cognitive performance. RESULTS: A normal mixture model suggested 3 risk strata based on Consortium to Establish a Registry for Alzheimer's Disease (CERAD) T scores: high, intermediate, and low risk. Cox modeling of time to cognitive decline based on posterior probabilities for risk stratum membership yielded an estimated hazard ratio of 4.00 with 95% confidence interval 1.53-10.44 in comparing high risk membership to low risk; for intermediate risk membership versus low risk, the modeling yielded hazard ratio=2.29 and 95% confidence interval=0.98-5.33. Latent class analysis produced 3 groups, which did not have a clear ordering in terms of risk; however, one group exhibited appreciably greater hazard of cognitive decline. All methods for generating predictors of cognitive transition yielded statistically significant likelihood ratio statistics but modest concordance statistics. CONCLUSION: Posterior probabilities from mixture modeling allow for risk stratification that is data-driven and, in the case of CERAD T scores, modestly predictive of later cognitive decline. Incorporating other covariates may enhance predictions.

Increasing Heart Transplant Volume by Expansion of Donor Heart Selection Criteria: A Single-Center Analysis.

BACKGROUND: Our transplant center recently expanded the acceptance criteria for cardiac donors to increase heart transplant volume. Our purpose was to assess the success of this strategy while maintaining acceptable 1-year survival. METHODS: We retrospectively reviewed patients who underwent heart transplantation at our institution from January 2011 through December 2017. This time period was divided into 2 periods: 2011 to 2014 (Period A) and 2015 to 2017 (Period B) because we implemented our new donor acceptance policy at the onset of 2015. We compared recipient and donor characteristics from the 2 time periods. The primary outcomes were 1-year graft and patient survival. RESULTS: Transplant volume increased in Period B with the expanded donor acceptance policy: 128 heart transplants over 36 months compared to 52 transplants in 48 months in Period A. Mean (± SD) recipient age was significantly higher in Period B (54 ± 12 vs 50 ± 15 years; P = .04) whereas other recipient variables were similar. Donors in Period B were significantly older, more likely to be female, had larger body mass index, were located a greater distance from the transplant center, and had a higher sequence number. Female donor to male recipient occurred more often in Period B than in Period A (27% vs 10%; P = .01). Both 1-year patient survival and graft survival were unchanged between Period B (95% for both) and Period A (96% for both). CONCLUSIONS: Using a more aggressive donor acceptance policy allowed for an increase in heart transplant volume while maintaining acceptable 1-year graft and patient survival.

Implantation of Left Ventricular Assist Device Results in Immediate Improvement of Glucose Metabolism in Patients With and Without Diabetes Mellitus.

BACKGROUND: Several studies demonstrated improvement in diabetes mellitus (DM) following left ventricular assist device (LVAD) implantation, but the timing of these changes has not been identified. We sought to determine if favourable metabolic changes occur immediately, within the initial hospitalisation following LVAD implantation. We also wanted to see whether favourable changes in glucose metabolism occur in patients without diabetes. METHODS: This is a retrospective analysis of patients receiving LVADs at our institution. We collected the data on fasting blood glucose (FBG) and total daily insulin requirements before the LVAD implantation and before the discharge. Patients served as their own controls. RESULTS: We studied 70 consecutive patients, half of them diabetic. In both diabetics and non-diabetics there was a significant reduction in FBG after LVAD implantation. In diabetic patients, there was an overall reduction in insulin requirements from the average 29.2 units of insulin per day before the LVAD to 16.2 units per day (p=0.038) before discharge. Specifically, insulin requirement decreased in 16 patients by a median of 25.2 units per day (the interquartile range [IQR)]: -47.8 to -9.2), increased in 10 patients (by 7.3 units/day, IQR 0.7 to 15.3), and remained unchanged in six patients. CONCLUSIONS: Favourable metabolic changes on LVAD support occurred almost immediately, within initial hospitalisation, in diabetics and non-diabetics alike. Decline in insulin requirements should be considered when managing diabetics following LVAD implantation.

Gabapentin drug misuse signals: A pharmacovigilance assessment using the FDA adverse event reporting system.

BACKGROUND: Although there have been increasing reports of intentional gabapentin misuse, epidemiological evidence for the phenomenon is limited. The purpose of this study was to determine whether there are pharmacovigilance abuse signals for gabapentin. METHODS: Using FDA Adverse Events Reporting System reports from January 1, 2005 to December 31, 2015, we calculated pharmacovigilance signal measures (i.e., reporting odds ratio, proportional reporting ratio, information component, and empirical Bayes geometric mean) for abuse-related adverse event (AR-AE)-gabapentin pairs. Loglinear modeling assessed the frequency of concurrent reporting of abuse-related and abuse-specific AEs (AS-AEs) associated with gabapentin. Findings were compared to a positive (pregabalin) and negative (duloxetine) control. RESULTS: From 2005-2015 there were 5,951,229 unique AE reports submitted to the FDA including 99,977 for gabapentin, 73,977 for duloxetine, and 97,813 for pregabalin. Significant drug-AR-AE pair signals involving gabapentin included: drug abuser, multiple drug overdose, and substance-induced psychotic disorder. Significant drug AR-AE signals involving gabapentin and pregabalin, but not duloxetine, were: ataxia, dependence, drug abuse, increased drug tolerance, and overdose. Compared to duloxetine, gabapentin had significantly greater odds of a co-report for an AS-AE with drug withdrawal syndrome (OR: 6.55), auditory hallucinations (OR: 4.57), delusions (OR: 2.36), euphoric mood (OR: 5.45), ataxia (OR: 2.85), drug abuser (OR: 3.01), aggression (OR: 1.98), psychotic disorder (OR: 1.96), and feeling abnormal (OR: 1.31). CONCLUSIONS: We identified abuse-related signals for gabapentin and highlighted several CNS effects that may be associated with its abuse. Gabapentin prescribers should be aware of the drug's abuse liability and effects that may accompany its use.

Influence of enhanced bioavailable curcumin on obesity-associated cardiovascular disease risk factors and arterial function: A double-blinded, randomized, controlled trial.

OBJECTIVES: This study aimed to determine whether an enhanced bioavailable curcumin formulation, CurQfen®, would improve circulating cardiovascular disease-related blood biomarkers and arterial function in young (age 18-35 y), obese (body mass index ≥ 30.0 kg/m2) men. METHODS: This double-blinded, placebo-controlled trial evaluated 22 men. The participants were matched based on body mass index and randomized to the intervention (curcumin formulated with fenugreek soluble fiber, for enhanced absorption) or control (fenugreek soluble fiber) group for 12 wk at 500mg/d without dietary modification or exercise. Blood samples and endothelial function measures were acquired at 0 and 12 wk, and blood samples were analyzed for cardiovascular disease-related blood biomarkers. Furthermore, central (aortic) blood pressure and augmentation index were monitored at 0, 4, 8, and 12 wk. RESULTS: After 12 wk of intervention, homocysteine levels were lower (curcumin before: 12.22 ± 2.29 µg/mL, after: 8.62 ± 1.02 µg/mL versus placebo before: 9.45 ± 0.84 µg/mL, after: 11.84 ± 1.63 µg/mL; P = 0.04) and high-density lipoprotein levels were higher (curcumin before: 40.77 ± 5.37 mg/dL, after: 54.56 ± 11.72 mg/dL versus placebo before: 61.20 ± 5.76 mg/dL, after: 48.82 ± 5.49 mg/dL; P = 0.04) in the curcumin group relative to the placebo group. However, there was no significant difference in changes between the circulating concentrations of glucose, insulin, leptin, adiponectin, or oxidative stress biomarkers in the curcumin group compared with the placebo group (P > 0.05). No changes were found with endothelial function, augmentation index, or central blood pressure in the curcumin group compared with the placebo group (P > 0.05). CONCLUSIONS: Our data provide evidence for an enhanced bioavailable curcumin to improve homocysteine and high-density lipoprotein concentrations, which may promote favorable cardiovascular health in young, obese men. Improvements in endothelial function or blood pressure were not observed with curcumin supplementation, thus further investigation is warranted.

Evaluating trajectories of episodic memory in normal cognition and mild cognitive impairment: Results from ADNI.

BACKGROUND: Memory assessment is a key factor for the diagnosis of cognitive impairment. However, memory performance over time may be quite heterogeneous within diagnostic groups. METHOD: To identify latent trajectories in memory performance and their associated risk factors, we analyzed data from Alzheimer's Disease Neuroimaging Initiative (ADNI) participants who were classified either as cognitively normal or as Mild Cognitive Impairment (MCI) at baseline and were administered the Rey Auditory Verbal Learning test (RAVLT) for up to 9 years. Group-based trajectory modeling on the 30-minute RAVLT delayed recall score was applied separately to the two baseline diagnostic groups. RESULTS: There were 219 normal subjects with mean age 75.9 (range from 59.9 to 89.6) and 52.5% male participants, and 372 MCI subjects with mean age 74.8 (range from 55.1 to 89.3) and 63.7% male participants included in the analysis. For normal subjects, six trajectories were identified. Trajectories were classified into three types, determined by the shape, each of which may comprise more than one trajectory: stable (~30% of subjects), curvilinear decline (~ 28%), and linear decline (~ 42%). Notably, none of the normal subjects assigned to the stable stratum progressed to dementia during the study period. In contrast, all trajectories identified for the MCI group tended to decline, although some participants were later re-diagnosed with normal cognition. Age, sex, and education were significantly associated with trajectory membership for both diagnostic groups, while APOE ɛ4 was only significantly associated with trajectories among MCI participants. CONCLUSION: Memory trajectory is a strong indicator of dementia risk. If likely trajectory of memory performance can be identified early, such work may allow clinicians to monitor or predict progression of individual patient cognition. This work also shows the importance of longitudinal cognitive testing and monitoring.

Left ventricular assist device-related infections: does the time of onset matter?

A frequent complication of left ventricular assist devices (LVAD) is the LVAD-associated infections (LVADIs). Contamination may occur during initial surgery/admission or at a later time. We studied the clinical manifestations and outcomes of LVADIs depending on the time of the onset. Patients implanted with LVADs at our institution between August 2009 and December 2014 were included. Patients were stratified into 2 groups based on whether the infection occurred early (< 180 days) or late (≥ 180 days) after LVAD implantation. Out of 37 overall LVADI episodes, 16 (43%) and 21 (57%) occurred early or late after device implantation, respectively. Median time to first LVADI was 88 ± 35 vs. 456 ± 187 days between groups. While superficial driveline-related infection was the most common LVADI type for both groups (56 vs. 71%, p = 0.489), driveline drainage was more prevalent in the late group (24 vs. 69%; p = 0.009). Early LVADIs involved more gram-positive flora, mostly Staphylococcus aureus (69 vs. 33%, p = 0.049), whereas late LVADIs involved more gram-negative pathogens, mostly Pseudomonas aueroginosa (25 vs. 57%; p = 0.045). High rates of treatment failure were consistent between groups (88 vs. 71%, p = 0.384). Compared with superficial LVADI, deeper infections were associated with an increase in mortality (13 vs 46%, p = 0.046). We concluded that early onset with likely in-hospital contamination involved more gram-positive flora, whereas late infection involved more gram-negative flora. Regardless of timing, success of antibacterial treatment was dismal, and infection depth correlated with poorer outcomes.

Effects of Bronchopulmonary Dysplasia on Swallow:Breath Interaction and Phase of Respiration with Swallow During Non-nutritive Suck.

OBJECTIVES: The objective of this study is to describe swallow:breath interaction (SwBr) and phase of respiration incident to swallow (POR) during non-nutritive suck in infants with bronchopulmonary dysplasia and determine if speech-language intervention can modify the characteristics of non-nutritive suck in these infants. METHODS: Logistic regression models were used to describe SwBr and POR in 16 low-risk preterm (LRP) infants and 43 infants with bronchopulmonary dysplasia. Infants with bronchopulmonary dysplasia were randomized to receive individualized intervention from a speech-language pathologist (BPDwithTX) or standard care (BPDnoTX). RESULTS: No significant differences were noted between low-risk infants and either group of BPD infants for the distribution of SwBr types. Infants with bronchopulmonary dysplasia showed minor differences in the progression of POR. Speech-Language intervention did not change the progression of SwBr or POR in infants with bronchopulmonary dysplasia. CONCLUSION: Infants with bronchopulmonary dysplasia can improve the progression of SwBr through practice as effectively as low-risk preterm infants can. The minor differences in POR in infants with bronchopulmonary dysplasia are consistent with dysmature development as seen with other feeding studies of infants with this disease. Speech-Language intervention did not modify the developmental progression of swallow:breath interaction or phase of respiration incident to swallow.

Ticagrelor Reduces Thromboinflammatory Markers in Patients With Pneumonia.

Despite treatment advances for sepsis and pneumonia, significant improvements in outcome have not been realized. Antiplatelet therapy may improve outcome in pneumonia and sepsis. In this study, the authors show that ticagrelor reduced leukocytes with attached platelets as well as the inflammatory biomarker interleukin (IL)-6. Pneumonia patients receiving ticagrelor required less supplemental oxygen and lung function tests trended toward improvement. Disruption of the P2Y12 receptor in a murine model protected against inflammatory response, lung permeability, and mortality. Results indicate a mechanistic link between platelets, leukocytes, and lung injury in settings of pneumonia and sepsis, and suggest possible therapeutic approaches to reduce complications.(Targeting Platelet-Leukocyte Aggregates in Pneumonia With Ticagrelor [XANTHIPPE]; NCT01883869).

Comparison of Complications of Catheter Ablation for Ventricular Arrhythmias in Adults With Versus Without Structural Heart Disease.

Catheter ablation (CA) is an effective treatment for ventricular arrhythmias (VA), with a potential for complications. The presence of structural heart disease (SHD) is associated with a higher complication rate although there is no data comparing CA of VA between patients with SHD and those without. We aimed to compare trends, morbidity, and mortality associated with real world practice of CA for VA (ventricular tachycardia and premature ventricular contraction) based on the presence of SHD. Using weighted sampling in the National Inpatient Sample database, we collected and compared characteristics and outcomes of patients with or without SHD that underwent CA of VA. Among 34,907 patients that underwent CA for VA (1999-2013), 18,014 (51.6%) had SHD. Major and all complications occurred among 1,135/18,014 (6.3%) and 2139/18,014 (11.9%) patients with SHD respectively compared with 355/16,893 (2.1%) and 739/16,893 (4.4%) for patients without SHD, p < 0.001 for both comparisons. Furthermore, 452/18,014 (2.51%) with SHD died versus 20/16,893 (0.12%) without SHD, p < 0.001. Heart failure was associated with an odds ratio (OR) of 3.09 for major complications (95%CI: 1.53-6.27, p = 0.002) for patients with SHD while coronary artery disease OR for major complications was 2.47 (95%CI: 1.44-4.23, p = 0.001) for patients without SHD. There was a significant increase in major complications over the 15-year study period in patients with SHD, p < 0.001. In conclusion, the presence of SHD during CA for VA increased the complication rate of major and any complications by approximately threefold for both and the hospital mortality by >20-fold compared with patients without SHD.

Factors related to return to play after knee injury in high school football athletes.

PURPOSE: American football is played by over 1 million high school athletes in the United States, and knee injuries are the third most common injury. The purpose of this study is to identify factors that influence return to play after knee injuries in high school football athletes and whether return to play differs for varsity and nonvarsity football players. METHODS: We used academic year 2006-2007 through 2009-2010 data from the National High School Sports-Related Injury Surveillance Study. Polytomous logistic regression was used to assess factors influencing return to play. RESULTS: Thirty-one percent returned to play in more than 3 weeks or not at all. After adjusting for injury severity, a difference in time to return to play persisted for injuries occurring in the regular or postseason compared to pre-season (OR 0.5, CI: 0.3-0.9), and injuries occurring to varsity players compared with nonvarsity players (OR 0.7, CI: 0.4-1.0). CONCLUSIONS: Time in season, method of injury assessment, and the need for surgery were the main predictors of return to play for football athletes. As more factors were influential for varsity athletes than nonvarsity athletes, future studies should separate the groups of athletes to better identify their specific factors for time to return.

Bidirectional Relations of Impulsive Personality and Alcohol Use Across Three Waves of Data Collection.

OBJECTIVE: To explore the bidirectional relations between alcohol use and three impulsive personality traits, to advance understanding of risk processes. PARTICIPANTS: 525 college students (mean age = 18.95 years) recruited in August 2008 and 2009 and followed up annually for three years. METHODS: Personality and past/current substance use were assessed. RESULTS: T2 sensation seeking mediated the predictive relationship between T1 and T3 alcohol use, and T2 alcohol use mediated the predictive relationship between T1 and T3 sensation seeking. In addition, T2 alcohol problems mediated the predictive relationship between T1 alcohol use and T3 negative urgency. CONCLUSIONS: Findings support a bidirectional relationship between sensation seeking and alcohol use, and drinking anticipates drinking problems, which predict increases in negative urgency. For some individuals, there appears to be an ongoing process of increased risk in the form of increases in both drinking and high-risk personality traits.

Use of digoxin in atrial fibrillation: One step further in the mortality controversy from the AFFIRM study.

BACKGROUND: Whether there is a causal association between digoxin and mortality among patients with atrial fibrillation (AF), with or without congestive heart failure (HF), has been controversial; in particular, two prior analyses of data from the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) trial have yielded conflicting results. We sought to investigate how digoxin impacts mortality, in the full AFFIRM cohort and for various subgroups, by applying marginal structural modeling (MSM) to AFFIRM data. METHODS: MSM is a newer statistical approach, which estimates causal association in the absence of randomization. MSM more effectively accounts for time-varying treatment and mitigates potential biases, in contrast to the two statistical approaches used in prior analyses of the AFFIRM data. RESULTS: Among 4,060 patients in AFFIRM, 660 (16.3%) died during follow-up. Digoxin was associated with significantly higher mortality in the full cohort (estimated hazard ratio [HR] 1.33, 95% confidence interval [CI] 1.11-1.60, P  =  0.002) and in 3,121 patients without HF (HR 1.36, 95% CI 1.07-1.72, P  =  0.011). There was a trend toward higher mortality with digoxin in 939 patients with HF (HR 1.29, 95% CI 0.96-1.72, P  =  0.090). Associations were nonsignificant in 463 patients with HF and left ventricular ejection fraction (EF) ≥40% and in 155 patients with EF ≤30%. CONCLUSIONS: Digoxin is associated with significantly increased mortality among AFFIRM patients collectively, as determined by MSM statistical methodology. However, the impact of digoxin among AFFIRM patients with coexisting HF is inconclusive.