Publications

OBJECTIVE

 To investigate the relation between alcohol consumption and heart disease by using differences in county level alcohol sales laws as a natural experiment.

DESIGN

 Observational cohort study using differences in alcohol sales laws.

SETTING

 Hospital based healthcare encounters in Texas, USA.

POPULATION

 1 106 968 patients aged 21 or older who were residents of "wet" (no alcohol restrictions) and "dry" (complete prohibition of alcohol sales) counties and admitted to hospital between 2005 and 2010, identified using the Texas Inpatient Research Data File.

OUTCOME MEASURES

 Prevalent and incident alcohol misuse and alcoholic liver disease were used for validation analyses. The main cardiovascular outcomes were atrial fibrillation, acute myocardial infarction, and congestive heart failure.

RESULTS

 Residents of wet counties had a greater prevalence and incidence of alcohol misuse and alcoholic liver disease. After multivariable adjustment, wet county residents had a greater prevalence (odds ratio 1.05, 95% confidence interval 1.01 to 1.09; P=0.007) and incidence (hazard ratio 1.07, 1.01 to 1.13; P=0.014) of atrial fibrillation, a lower prevalence (odds ratio 0.83, 0.79 to 0.87; P<0.001) and incidence (hazard ratio 0.91, 0.87 to 0.99; P=0.019) of myocardial infarction, and a lower prevalence (odds ratio 0.87, 0.84 to 0.90; P<0.001) of congestive heart failure. Conversion of counties from dry to wet resulted in statistically significantly higher rates of alcohol misuse, alcoholic liver disease, atrial fibrillation, and congestive heart failure, with no detectable difference in myocardial infarction.

CONCLUSIONS

 Greater access to alcohol was associated with more atrial fibrillation and less myocardial infarction and congestive heart failure, although an increased risk of congestive heart failure was seen shortly after alcohol sales were liberalized.

The persistence of latent HIV proviruses in long-lived CD4(+) T cells despite antiretroviral therapy (ART) is a major obstacle to viral eradication. Because current candidate latency-reversing agents (LRAs) induce HIV transcription, but fail to clear these cellular reservoirs, new approaches for killing these reactivated latent HIV reservoir cells are urgently needed. HIV latency depends upon the transcriptional quiescence of the integrated provirus and the circumvention of immune defense mechanisms. These defenses include cell-intrinsic innate responses that use pattern-recognition receptors (PRRs) to detect viral pathogens, and that subsequently induce apoptosis of the infected cell. Retinoic acid (RA)-inducible gene I (RIG-I, encoded by DDX58) forms one class of PRRs that mediates apoptosis and the elimination of infected cells after recognition of viral RNA. Here we show that acitretin, an RA derivative approved by the US Food and Drug Administration (FDA), enhances RIG-I signaling ex vivo, increases HIV transcription, and induces preferential apoptosis of HIV-infected cells. These effects are abrogated by DDX58 knockdown. Acitretin also decreases proviral DNA levels in CD4(+) T cells from HIV-positive subjects on suppressive ART, an effect that is amplified when combined with suberoylanilide hydroxamic acid (SAHA), a histone deacetylase inhibitor. Pharmacological enhancement of an innate cellular-defense network could provide a means by which to eliminate reactivated cells in the latent HIV reservoir.

OBJECTIVES

To develop a prediction index for 1-year mortality after hip fracture in older adults that includes predictors from a wide range of domains.

DESIGN

Retrospective cohort study.

SETTINGS

Health and Retirement Study (HRS).

PARTICIPANTS

HRS participants who experienced hip fracture between 1992 and 2010 as identified according to Medicare claims data (N = 857).

MEASUREMENTS

Outcome measure was death within 1 year of hip fracture. Predictor measures were participant demographic characteristics, socioeconomic status, social support, health, geriatric symptoms, and function. Variables independently associated with 1-year mortality were identified, and best-subsets regression was used to identify the final model. The selected variables were weighted to create a risk index. The index was internally validated using bootstrapping to estimate model optimism.

RESULTS

Mean age at time of hip fracture was 84, and 76% of the participants were women. There were 235 deaths (27%) during the 1-year follow up. Five predictors of mortality were included in the final model: aged 90 and older (2 points), male sex (2 points), congestive heart failure (2 points), difficulty preparing meals (2 points), and not being able to drive (1 point). The point scores of the index were associated with 1-year mortality, with 0 points predicting 10% risk and 7 to 9 points predicting 66% risk. The c-statistic for the final model was 0.73, with an estimated optimism penalty of 0.01, indicating very little evidence of overfitting.

CONCLUSION

The prognostic index combines demographic, comorbidity, and function variables and can be used to differentiate between individuals at low and high risk of 1-year mortality after hip fracture.