Ninad S. Chaudhary

Alcohol Dependence and Its Relationship With Insomnia and Other Sleep Disorders

Sleep-related complaints are widely prevalent in those with alcohol dependence (AD). AD is associated not only with insomnia, but also with multiple sleep-related disorders as a growing body of literature has demonstrated. This article will review the various aspects of insomnia associated with AD. In addition, the association of AD with other sleep-related disorders will be briefly reviewed. The association of AD with insomnia is bidirectional in nature. The etiopathogenesis of insomnia has demonstrated multiple associations and is an active focus of research. Treatment with cognitive behavioral therapy for insomnia is showing promise as an optimal intervention. In addition, AD may be associated with circadian abnormalities, short sleep duration, obstructive sleep apnea, and sleep-related movement disorder. The burgeoning knowledge on insomnia associated with moderate-to-severe alcohol use disorder has expanded our understanding of its underlying neurobiology, clinical features, and treatment options.

Daytime Sleepiness: Associations with Alcohol Use and Sleep Duration in Americans

The aim of the current analysis was to investigate the relationship of daytime sleepiness with alcohol consumption and sleep duration using a population sample of adult Americans. Data was analyzed from adult respondents of the National Health and Nutritional Examination Survey (NHANES) 2007-2008 (N = 2919) using self-reported variables for sleepiness, sleep duration, and alcohol consumption (quantity and frequency of alcohol use). A heavy drinking episode was defined as the consumption of ≥5 standard alcoholic beverages in a day. Logistic regression models adjusted for sociodemographic variables and insomnia covariates were used to evaluate the relationship between daytime sleepiness and an interaction of alcohol consumption variables with sleep duration. The results showed that daytime sleepiness was reported by 15.07% of the subjects. In univariate analyses adjusted for covariates, an increased probability of daytime sleepiness was predicted by decreased log drinks per day [OR = 0.74 (95% CI, 0.58–0.95)], a decreased log drinking frequency [0.90 (95% CI, 0.83–0.98)], and lower sleep duration [OR = 0.75 (95% CI, 0.67–0.84)]. An interaction between decreased sleep duration and an increased log heavy drinking frequency predicted increased daytime sleepiness (P = 0.004). Thus, the effect of sleep duration should be considered when evaluating the relationship between daytime sleepiness and heavy drinking.

Nocturnal Wakefulness as a Previously Unrecognized Risk Factor for Suicide.

OBJECTIVE Suicide is a major public health problem and the 10th leading cause of death in the United States. The identification of modifiable risk factors is essential for reducing the prevalence of suicide. Recently, it has been shown that insomnia and nightmares significantly increase the risk for suicidal ideation, attempted suicide, and death by suicide. While both forms of sleep disturbance may independently confer risk, and potentially be modifiable risk factors, it is also possible that simply being awake at night represents a specific vulnerability for suicide. The present analysis evaluates the frequency of completed suicide per hour while taking into account the percentage of individuals awake at each hour. METHODS Archival analyses were conducted estimating the time of fatal injury using the National Violent Death Reporting System for 2003-2010 and the proportion of the American population awake per hour across the 24-hour day using the American Time Use Survey. RESULTS The mean ± SD incident rate from 06:00-23:59 was 2.2% ± 0.7%, while the mean ± SD incident rate from 00:00-05:59 was 10.3% ± 4.9%. The maximum incident rate was from 02:00-02:59 (16.3%). Hour-by-hour observed values differed from those that would be expected by chance (P < .001), and when 6-hour blocks were examined, the observed frequency at night was 3.6 times higher than would be expected by chance (P < .001). CONCLUSIONS Being awake at night confers greater risk for suicide than being awake at other times of the day, suggesting that disturbances of sleep or circadian neurobiology may potentiate suicide risk.

Association of baseline steroid use with long-term rates of infection and sepsis in the REGARDS cohort

BackgroundPrior studies associate steroid use with infection risk but were limited to select populations and short follow-up periods. The association of steroid use with long-term risk of community-acquired infections is unknown. We sought to determine the association of steroid risk with long-term risks of community- acquired infections and sepsis.MethodsWe used data on 30,239 adults aged ≥ 45 years old from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort. The primary exposure was oral or injectable steroid use, determined from medication inventory obtained at baseline in-home visit. The primary outcome was time to first infection event during 2003–2012, determined through adjudicated review of hospital records. We determined associations between baseline steroid use and first infection hospitalization events using Cox proportional hazards models, adjusting for demographics, health behaviors, chronic medical conditions, and medication adherence. Among the first infection hospitalization events, we also determined the association between baseline steroid use and sepsis.ResultsSteroid use was reported in 2.24% (n = 677) of the study population. There were 2593 incident infection events during the 10-year follow-up period. Infection incidence rates were higher for steroid than non-steroid users (37.99 vs. 13.79 per 1000 person-years). Steroid use was independently associated with increased risk of infection (adjusted HR 2.10, 95% CI: 1.73–2.56). Among first-infection events, steroid use was associated with increased odds of sepsis (adjusted OR 2.11, 95% CI: 1.33–3.36). The associations persisted in propensity matched analyses as well as models stratified by propensity score and medication adherence.ConclusionsIn this population-based cohort study, baseline steroid use was associated with increased long-term risks of community-acquired infections and sepsis.

Home Dialysis Utilization Among Racial and Ethnic Minorities in the United States at the National, Regional, and State Level

♦ Background: United States Renal Data System (USRDS) data from 2014 show that African Americans (AA) are underrepresented in the home dialysis population, with 6.4% versus 9.2% utilization in the general populace. This racial disparity may be inaccurately ascribed to the nation as a whole if regional and inter-state variability exists. This investigation sought to examine home dialysis utilization by minority Medicare beneficiary populations across the US nationally, regionally, and by individual state. ♦ Methods: The 2012 Medicare 100% Outpatient Standard Analytic File was used to identify all Medicare fee-for-service (FFS) patients, with state of residence and race, receiving an outpatient dialysis facility bill type. Peritoneal dialysis (PD) and home hemodialysis (HHD) patients were identified using revenue and condition codes and were defined by having at least one claim during the year that met criteria for the category. Beneficiaries were counted once for each modality used that year. A home dialysis utilization ratio (UR) was calculated as the ratio of the proportion of a minority on PD or HHD within a geographic division to the proportion of Caucasians on PD or HHD within the same geographic division. A UR less than 1.00 indicated under-representation while a UR over 1.00 indicated over-representation. Utilization ratios were compared using a Poisson regression model. ♦ Results: A total of 369,164 Medicare FFS dialysis patients were identified. Within the total cohort, AA were the most underrepresented minority on PD (UR 0.586; 95% confidence interval [CI]: 0.585 – 0.586; p < 0.0001), followed by Hispanics (UR 0.744; 95% CI 0.743 – 0.744; p < 0.0001). The underutilization of PD by AA and Hispanics could not be ascribed to any region of the US, as all regions of the US had UR < 1.00. Only Massachusetts had a UR > 1.00 for AA on PD. Peritoneal dialysis UR values for Asians and those self-identified as Other were 0.954; 95% CI 0.953 – 0.954 and 0.932; 95% CI 0.931 – 0.932, respectively. Nationally, all minorities utilized HHD less than Caucasians. However, more variability existed, with Asians utilizing more HHD than Caucasians in the Midwest. ♦ Conclusions: Although regional and interstate variability exists, there is near universal under-representation of AA and Hispanics in the home dialysis population, while Asians and Other demonstrate more interregional and interstate variability.

Insomnia severity is associated with decreased executive functioning in patients with suicidal ideation and drug abuse.

To the Editor: Insomnia has been associated with decreased executive functioning in those without substance use disorders.1 Although numerous studies have linked impulsivity with substance abuse and suicidal ideation, its relationship with insomnia in the substance-abusing population is unclear.2–6 In this preliminary study, we explore the relationship of insomnia severity with objective and subjective impulsivity measured by computerized behavioral tests and a self-report questionnaire, respectively, in patients with suicidal ideation/behavior attending a psychiatric emergency department. We hypothesized that a higher insomnia severity would be associated with increased objective impulsivity (a decrease in executive functioning) and higher subjective impulsivity scores. Method. This investigation involved secondary analyses of cross-sectional data from an ongoing study (N.S., J.L.E., unpublished data, 2012). Subjects were adults (N = 21, ≤ 65 years of age) who presented with suicidal ideation/behavior between July 2012 and December 2012 to the emergency department, where they were observed until their symptoms stabilized. We excluded patients with any motor response, visual or hearing disorders, psychotic symptoms, or inability to read or comprehend English. The instruments used in this study included the following: The Stop-Signal Reaction-Time Task,7 which assesses objective impulsivity through response inhibition (a facet of executive functioning) based on correct responses and reaction times7,8; The UPPS Impulsive Behavior Scale,9 which is a 45-item self-report measure that assesses personality aspects of subjective impulsivity (the “S” sensation-seeking component was excluded in this protocol); The sleep question from the Center for Epidemiology Studies-Depression Scale (CES-D),10 which assesses insomnia by inquiring, “Over last week, my sleep was restless….” with the responses arrayed as “less than a day,” “1–2 days,” “3–4 days,” and “5–7 days.” The responses were categorized into “frequent” (ie, those with restless sleep for ≥ 5 nights/wk) or “infrequent” (those with ≤ 4 nights/wk) insomnia on the basis of the distribution of responses, clinical significance, and similarity to analyses from prior literature11; The remaining CES-D items, which assess depressive symptoms. The institutional review board approved the study, and subjects signed informed consent prior to participation. Results. The demographic variables included the following: the mean age was 38.3 (SD = 10.1) years, 18 (85.7%) identified themselves as African American, 18 (85.7%) were male, 9 (42.9%) were single, 16 (76.2%) were unemployed, 8 (38.1%) had ≥ 12 years of education, and 12 (57.1%) reported being homeless. Urine drug screens at admission were positive in 14 (66.7%) for cocaine, 6 (28.6%) for cannabis, 5 (23.8%) for phencyclidine, 4 (19.0%) for sedative-hypnotic medications, and 3 (14.3%) for opioids. Four subjects (19.0%) reported use of only 1 drug (cocaine). Subjects with frequent insomnia had significantly higher CES-D scores. In analyses adjusted for demographic and mood covariates, those with frequent insomnia (as compared to those with infrequent insomnia) had a significantly decreased number of correct responses and a higher mean reaction time at 160 ms. Similarly, a higher reaction time was seen at 320 ms for this group, although this was not statistically significant. Those with frequent insomnia (in comparison to those with infrequent insomnia) had nonsignificantly lower scores on the UPPS impulsivity scales (see Table 1). Table 1 Measures of Impulsivity Across Insomnia Groups The limitations associated with this preliminary study include the lack of a formal standardized insomnia rating instrument, the small sample size, and its cross-sectional nature. Despite the limitations, we observed that frequent sleep impairment was associated with a lower response inhibition on the Stop Signal Reaction Time Task without any difference in the personality aspects of impulsivity in this complex sample. These results suggest that improving sleep in this population might help improve mood and executive functioning and thus reduce the likelihood of behaviors precipitating visits to the emergency department. Future studies should assess for subjective and objective insomnia using standardized instruments and expand the range of impulsivity facets being assessed.

APOL1 Nephropathy Risk Variants and Incident Cardiovascular Disease Events in Community-Dwelling Black Adults

Background: APOL1 renal risk variants are strongly associated with chronic kidney disease in Black adults, but reported associations with cardiovascular disease (CVD) have been conflicting. Methods: We examined associations of APOL1 with incident coronary heart disease (n=323), ischemic stroke (n=331), and the composite CVD outcome (n=500) in 10 605 Black participants of the REGARDS study (Reasons for Geographic and Racial Differences in Stroke). Primary analyses compared individuals with APOL1 high-risk genotypes to APOL1 low-risk genotypes in Cox proportional hazards models adjusted for CVD risk factors and African ancestry. Results: APOL1 high-risk participants were younger and more likely to have albuminuria at baseline than APOL1 low-risk participants. The risk of incident stroke, coronary heart disease, or composite CVD end point did not significantly differ by APOL1 genotype status in multivariable models. The association of APOL1 genotype with incident composite CVD differed by diabetes mellitus status (Pinteraction=0.004). In those without diabetes mellitus, APOL1 high-risk genotypes associated with greater risk of incident composite CVD (hazard ratio, 1.67; 95% confidence interval, 1.12–2.47) compared with those with APOL1 low-risk genotypes in multivariable adjusted models. This latter association was driven by ischemic strokes (hazard ratio, 2.32; 95% confidence interval, 1.33–4.07), in particular, those related to small vessel disease (hazard ratio, 5.10; 95% confidence interval, 1.55–16.56). There was no statistically significant association of APOL1 genotypes with incident CVD in subjects with diabetes mellitus. The APOL1 high-risk genotype was associated with higher stroke risk in individuals without but not those with chronic kidney disease in fully adjusted models. Conclusions: APOL1 high-risk status is associated with CVD events in community-dwelling Black adults without diabetes mellitus.

Aspirin use and long-term rates of sepsis: A population-based cohort study

Objective Sepsis is the syndrome of life-threatening organ dysfunction resulting from dysregulated host response to infection. Aspirin, an anti-inflammatory agent, may play a role in attenuating the inflammatory response during infection. We evaluated the association between aspirin use and long-term rates of sepsis as well as sepsis outcomes. Methods We analyzed data from 30,239 adults ≥45 years old in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort. The primary exposure was aspirin use, identified via patient interview. The primary outcome was sepsis hospitalization, defined as admission for infection with two or more systemic inflammatory response syndrome criteria. We fit Cox proportional hazards models assessing the association between aspirin use and rates of sepsis, adjusted for participant demographics, health behaviors, chronic medical conditions, medication adherence, and biomarkers. We used a propensity-matched analysis and a series of sensitivity analyses to assess the robustness of our results. We also examined risk of organ dysfunction and hospital mortality during hospitalization for sepsis. Results Among 29,690 REGARDS participants with follow-up data available, 43% reported aspirin use (n = 12,869). Aspirin users had higher sepsis rates (hazard ratio 1.35; 95% CI: 1.22–1.49) but this association was attenuated following adjustment for potential confounders (adjusted HR 0.99; 95% CI: 0.88–1.12). We obtained similar results in propensity-matched and sensitivity analyses. Among sepsis hospitalizations, aspirin use was not associated with organ dysfunction or hospital death. Conclusions In the REGARDS cohort, baseline aspirin use was not associated with long-term rates of sepsis.

Is family history of alcohol dependence a risk factor for disturbed sleep in alcohol dependent subjects

BACKGROUND Disturbed sleep and a family history of alcohol dependence (AD) are risk factors for developing AD, yet the underlying relationship between them is unclear among individuals with AD. Understanding these inherited associations will help us not only identify risk for development of these comorbid disorders, but also individualize treatment at this interface. We evaluated whether a first-degree family history of AD (FH+) was a risk factor for sleep continuity disturbance in patients with AD. We also evaluated whether alcohol use or mood disturbance moderated the relationship between FH and sleep. METHODS We analyzed cross-sectional baseline data from an alcohol clinical trial in a sample of individuals with AD (N = 280). Their family history of AD among nuclear family members, sleep complaints, alcohol use (over the last 90 days), and mood disturbance were assessed using the Family History Interview for Substance and Mood Disorders, Medical Outcomes Study Sleep Scale, Time Line Follow-Back Interview, and Profile of Mood States-Short Form, respectively. RESULTS A FH + status (65% of subjects) was significantly associated with lower model estimated mean sleep adequacy (β = - 7.05, p = 0.02) and sleep duration (β = - 0.38, p = 0.04) scale scores. FH was not associated with sleep disturbance scale. No significant moderating effect involving alcohol use or mood disturbance was seen. CONCLUSION Family history of AD is a unique risk factor for sleep complaints in AD. Non-restorative sleep and sleep duration may be noteworthy phenotypes to help probe for underlying genotypic polymorphisms in these comorbid disorders.