Racial and Ethnic Inequities in Buprenorphine and Methadone Utilization Among Reproductive-Age Women with Opioid Use Disorder: an Analysis of Multi-state Medicaid Claims in the USA.

BACKGROUND: Associations between race/ethnicity and medications to treat OUD (MOUD), buprenorphine and methadone, in reproductive-age women have not been thoroughly studied in multi-state samples. OBJECTIVE: To evaluate racial/ethnic variation in buprenorphine and methadone receipt and retention in a multi-state U.S. sample of Medicaid-enrolled, reproductive-age women with opioid use disorder (OUD) at the beginning of OUD treatment. DESIGN: Retrospective cohort study. SUBJECTS: Reproductive-age (18-45 years) women with OUD, in the Merative™ MarketScan® Multi-State Medicaid Database (2011-2016). MAIN MEASURES: Differences by race/ethnicity (non-Hispanic White, non-Hispanic Black, Hispanic, "other" race/ethnicity) in the likelihood of receiving buprenorphine and methadone during the start of OUD treatment (yes/no) were estimated using multivariable logistic regression. Differences in time to medication discontinuation (days) by race/ethnicity were evaluated using multivariable Cox regression. RESULTS: Of 66,550 reproductive-age Medicaid enrollees with OUD (84.1% non-Hispanic White, 5.9% non-Hispanic Black, 1.0% Hispanic, 5.3% "other"), 15,313 (23.0%) received buprenorphine and 6290 (9.5%) methadone. Non-Hispanic Black enrollees were less likely to receive buprenorphine (adjusted odds ratio, aOR = 0.76 [0.68-0.84]) and more likely to be referred to methadone clinics (aOR = 1.78 [1.60-2.00]) compared to non-Hispanic White participants. Across both buprenorphine and methadone in unadjusted analyses, the median discontinuation time for non-Hispanic Black enrollees was 123 days compared to 132 days and 141 days for non-Hispanic White and Hispanic enrollees respectively (χ2 = 10.6; P = .01). In adjusted analyses, non-Hispanic Black enrollees experienced greater discontinuation for buprenorphine and methadone (adjusted hazard ratio, aHR = 1.16 [1.08-1.24] and aHR = 1.16 [1.07-1.30] respectively) compared to non-Hispanic White peers. We did not observe differences in buprenorphine or methadone receipt or retention for Hispanic enrollees compared to the non-Hispanic White enrollees. CONCLUSIONS: Our data illustrate inequities between non-Hispanic Black and non-Hispanic White Medicaid enrollees with regard to buprenorphine and methadone utilization in the USA, consistent with literature on the racialized origins of methadone and buprenorphine treatment.

Benzodiazepine, Z-drug, and sleep medication prescriptions in male and female people with opioid use disorder on buprenorphine and comorbid insomnia: an analysis of multistate insurance claims.

STUDY OBJECTIVES: In adult populations, women are more likely than men to be prescribed benzodiazepines. However, such disparities have not been investigated in people with opioid use disorder (OUD) and insomnia receiving buprenorphine, a population with particularly high sedative/hypnotic receipt. This retrospective cohort study used administrative claims data from Merative MarketScan Commercial and MultiState Medicaid Databases (2006-2016) to investigate sex differences in the receipt of insomnia medication prescriptions among patients in OUD treatment with buprenorphine. METHODS: We included people aged 12-64 years with diagnoses of insomnia and OUD-initiating buprenorphine during the study timeframe. The predictor variable was sex (female versus male). The primary outcome was receipt of insomnia medication prescription within 60 days of buprenorphine start, encompassing benzodiazepines, Z-drugs, or non-sedative/hypnotic insomnia medications (e.g. hydroxyzine, trazodone, and mirtazapine). Associations between sex and benzodiazepine, Z-drug, and other insomnia medication prescription receipt were estimated using Poisson regression models. RESULTS: Our sample included 9510 individuals (female n = 4637; male n = 4873) initiating buprenorphine for OUD who also had insomnia, of whom 6569 (69.1%) received benzodiazepines, 3891 (40.9%) Z-drugs, and 8441 (88.8%) non-sedative/hypnotic medications. Poisson regression models, adjusting for sex differences in psychiatric comorbidities, found female sex to be associated with a slightly increased likelihood of prescription receipt: benzodiazepines (risk ratio [RR], RR = 1.17 [1.11-1.23]), Z-drugs (RR = 1.26 [1.18-1.34]), and non-sedative/hypnotic insomnia medication (RR = 1.07, [1.02-1.12]). CONCLUSIONS: Sleep medications are commonly being prescribed to individuals with insomnia in OUD treatment with buprenorphine, with sex-based disparities indicating a higher prescribing impact among female than male OUD treatment patients.

Comparison of Performance of Psychiatrists vs Other Outpatient Physicians in the 2020 US Medicare Merit-Based Incentive Payment System.

Importance: Medicare's Merit-Based Incentive Payment System (MIPS) is a new, mandatory, outpatient value-based payment program that ties reimbursement to performance on cost and quality measures for many US clinicians. However, it is currently unknown how the program measures the performance of psychiatrists, who often treat a different patient case mix with different clinical considerations than do other outpatient clinicians. Objective: To compare performance scores and value-based reimbursement for psychiatrists vs other outpatient physicians in the 2020 MIPS. Design Setting and Participants: In this cross-sectional study, the Centers for Medicare & Medicaid Services Provider Data Catalog was used to identify outpatient Medicare physicians listed in the National Downloadable File between January 1, 2018, and December 31, 2020, who participated in the 2020 MIPS and received a publicly reported final performance score. Data from the 593 863 clinicians participating in the 2020 MIPS were used to compare differences in the 2020 MIPS performance scores and value-based reimbursement (based on performance in 2018) for psychiatrists vs other physicians, adjusting for physician, patient, and practice area characteristics. Exposures: Participation in MIPS. Main Outcomes and Measures: Primary outcomes were final MIPS performance score and negative (penalty), positive, and exceptional performance bonus payment adjustments. Secondary outcomes were scores in the MIPS performance domains: quality, promoting interoperability, improvement activities, and cost. Results: This study included 9356 psychiatrists (3407 [36.4%] female and 5 949 [63.6%] male) and 196 306 other outpatient physicians (69 221 [35.3%] female and 127 085 [64.7%] male) (data on age and race are not available). Compared with other physicians, psychiatrists were less likely to be affiliated with a safety-net hospital (2119 [22.6%] vs 64 997 [33.1%]) or a major teaching hospital (2148 [23.0%] vs 53 321 [27.2%]) and had lower annual Medicare patient volume (181 vs 437 patients) and mean patient risk scores (1.65 vs 1.78) (P < .001 for all). The mean final MIPS performance score for psychiatrists was 84.0 vs 89.7 for other physicians (absolute difference, -5.7; 95% CI, -6.2 to -5.2). A total of 573 psychiatrists (6.1%) received a penalty vs 5739 (2.9%) of other physicians (absolute difference, 3.2%; 95% CI, 2.8%-3.6%); 8664 psychiatrists (92.6%) vs 189 037 other physicians (96.3%) received a positive payment adjustment (absolute difference, -3.7%; 95% CI, -3.3% to -4.1%), and 7672 psychiatrists (82.0%) vs 174 040 other physicians (88.7%) received a bonus payment adjustment (absolute difference, -6.7%; 95% CI, -6.0% to -7.3%). These differences remained significant after adjustment. Conclusions and Relevance: In this cross-sectional study that compared US psychiatrists with other outpatient physicians, psychiatrists had significantly lower 2020 MIPS performance scores, were penalized more frequently, and received fewer bonuses. Policy makers should evaluate whether current MIPS performance measures appropriately assess the performance of psychiatrists.

Underutilization of guideline-concordant smoking cessation treatments in surgical patients: Lessons from a learning health system.

While smoking is a well-established risk factor for surgical complications, it is unclear how frequently guideline-concordant tobacco treatments are prescribed to surgical patients. In this cross-sectional study including 164673 unique patients evaluated in outpatient surgery clinics at a single institution in 2020, despite a relatively high smoking prevalence (14.7%), guideline-concordant treatment rates were very low, with only 12.7% of patients receiving pharmacotherapy and 31.7% receiving any treatment. Addressing disparities in smoking cessation treatments are critical given the disproportionate impact of smoking on surgical outcomes.

Assessment of formal tobacco treatment and smoking cessation in dual users of cigarettes and e-cigarettes.

BACKGROUND: The utility of electronic cigarettes ('e-cigarettes') as a smoking cessation adjunct remains unclear. Similarly, it is unclear if formal tobacco treatment (pharmacotherapy and/or behavioural support) augments smoking cessation in individuals who use both cigarettes and e-cigarettes. METHODS: We performed a longitudinal cohort study of adult outpatients evaluated in our tertiary care medical centre (6/2018-6/2020). E-cigarette use, smoking status and formal tobacco treatment (deterrent pharmacotherapy and/or behavioural support) were assessed in 6-month blocks (eg, cohort 1 (C1)=6/2018-12/2018, C2=1/2019-6/2019 and so on) using our electronic health record. We assessed the relationship between e-cigarette use (either with or without formal tobacco treatment) and point prevalence of smoking cessation at 6 and 12 months. RESULTS: 111 823 unique patients were included in the study. The prevalence of dual use of cigarettes and e-cigarettes increased significantly over the study period (C1=0.8%; C2=1.1%; C3=1.8%; C4=2.3%; p<0.001). The prevalence of smoking cessation at 12 months was higher among e-cigarette users (20.8%) compared with non-users (16.8%) (risk difference, 4.0% (95% CI 2.5% to 5.5%); adjusted relative risk (aRR) 1.354, 95% CI 1.252 to 1.464, p<0.0001). Further, among dual users of cigarettes and e-cigarettes, the prevalence of smoking cessation at 12 months was higher among individuals who received tobacco treatment (29.1%) compared with individuals who did not receive tobacco treatment (19.6%) (risk difference, 9.5% (95% CI, 4.6% to 14.4%); aRR 1.238, 95% CI 1.071 to 1.432, p=0.004). INTERPRETATION: These results suggest that dual users of cigarettes and e-cigarettes benefit from formal tobacco treatment. Clinicians should consider offering formal tobacco treatment to such patients, though future trials are needed.

Racial disparities in intensity of smoke exposure and nicotine intake among low-dependence smokers.

BACKGROUND: Compared to white smokers, Black smokers are at disproportionately higher risk for smoking-related disease, despite consuming fewer cigarettes per day (CPD). To examine racial disparities in biobehavioral influences on smoking and disease risk, we analyzed the relationship between self-reported tobacco dependence and intensity of tobacco smoke exposure per cigarette, on the one hand, and intensity of nicotine intake per cigarette, on the other. METHODS: In 270 Black and 516 white smokers, smoke exposure was measured by expired carbon monoxide (CO), and nicotine intake was measured by plasma cotinine (COT) and cotinine+3'-hydroxycotinine ([COT + 3HC]). Using linear regression analyses, we analyzed how the Fagerström Test for Cigarette Dependence (FTCD) predicted intensity of smoke exposure per cigarette (CO/CPD) and intensity of nicotine intake per cigarette (COT/CPD; [COT + 3HC]/CPD), and how race moderated these relations. RESULTS: Overall, Black smokers consumed fewer CPD than white smokers and had higher levels of CO/CPD, COT/CPD, and [COT + 3HC]/CPD. These elevations were most pronounced at lower levels of dependence: amongst Black smokers, FTCD negatively predicted intensity of smoke exposure as measured by CO/CPD (B = -0.12, 95% CI = -0.18, -0.05, p = 0.0003) and intensity of nicotine intake as measured by [COT + 3HC]/CPD (B = -1.31, 95% CI = -2.15, -0.46, p = 0.002). CONCLUSIONS: Low-dependence Black smokers had higher intensities of both smoke exposure and nicotine intake per cigarette compared to similarly dependent white smokers, suggesting that measures of dependence, exposure, and intake underestimate incremental risk of each cigarette to Black smokers.

Age disparities in six-month treatment retention for opioid use disorder.

BACKGROUND AND AIMS: Adolescents with opioid use disorder (OUD) are an understudied and vulnerable population. We examined the association between age and six-month treatment retention, and whether any such association was moderated by medication treatment. METHODS: In this retrospective cohort study, we used an insurance database with OUD treatment claims from 2006-2016. We examined 261,356 OUD treatment episodes in three age groups: adolescents (ages 12-17), young adults (18-25) and older adults (26-64). We used logistic regression to estimate prevalence of six-month retention before and after stratification by treatment type (buprenorphine, naltrexone, or psychosocial only). Insurance differences (commercial vs Medicaid) in medication treatment prevalence were also assessed. RESULTS: Adolescents were less likely to be retained compared to adults (17.6 %; 95 % CI 16.5-18.7 % for adolescents; 25.1 %; 95 % CI 24.7-25.4 % for young adults; 33.3 %; 95 % CI 33.0-33.5 % for older adults). This disparity was reduced after adjusting for treatment type. For all ages, buprenorphine was more strongly associated with retention than naltrexone or psychosocial treatment. Adolescents who received buprenorphine were more than four times as likely to be retained in treatment (44.8 %; 95 % CI 40.6-49.0) compared to those who received psychosocial services (9.7 %; 95 % CI 8.8-10.8). Persons with commercial insurance were more likely to receive medication than those with Medicaid (73 % vs 36 %, (χ2 = 38,042.6, p < .001). CONCLUSIONS: Age disparities in six-month treatment retention are strongly related to age disparities in medication treatment. Results point to need for improved implementation of medication treatment for persons with OUD, regardless of age or insurance status.

Low Burden Strategies Are Needed to Reduce Smoking in Rural Healthcare Settings: A Lesson from Cancer Clinics.

Rural populations face significant smoking-related health disparities, such as a higher prevalence of lung cancer and cancer mortality, higher prevalence of smoking, and lower likelihood of receiving cessation treatment than urban counterparts. A significant proportion of health disparities in rural populations could be eliminated with low-barrier, easy-access treatment delivery methods for smoking cessation. In this study, we assessed treatment engagement among patients in rural and urban settings. Then, we examined the effect of an electronic health record-based smoking cessation module on patient receipt of evidence-based cessation care. As part of a quality improvement project, we retrospectively observed 479,798 unique patients accounting for 1,426,089 outpatient clinical encounters from June 2018-March 2019 across 766 clinics in the greater St. Louis, southern Illinois, and mid-Missouri regions. Smoking prevalence was higher in rural versus urban clinics (20.7% vs. 13.9%, 6.7% [6.3, 7.1], odds ratio = 1.6 [1.6, 1.6], p < 0.0001), and yet rural smokers were nearly three times less likely than their urban counterparts to receive any smoking cessation treatment after adjusting for patients clustering within clinics (9.6% vs. 25.8%, -16.2% [-16.9, -15.5], odds ratio = 0.304 [0.28, 0.33], p < 0.0001). Although not yet scaled up in the rural setting, we examined the effects of a low-burden, point-of-care smoking module currently implemented in cancer clinics. After adjusting for patient clustering within clinics, patients were more likely to receive smoking treatment in clinics that implemented the module versus clinics that did not implement the module (31.2% vs. 17.5%, 13.7% [10.8, 16.6], odds ratio = 2.1 [1.8, 2.6], p < 0.0001). The point-of-care treatment approach offers a promising solution for rural settings, both in and outside the context of cancer care.

Trends in Prescribed Central Nervous System Depressant Medications Among Adults Who Regularly Consume Alcohol: United States 1999 to 2014.

BACKGROUND: Although the risks of using central nervous system depressant (CNS-D) medications with alcohol are well documented, little is known about trends in prescribed use of these medications among individuals who regularly consume alcohol (i.e., trends in "concurrent use"). We examined changes in the prevalence of prescribed CNS-D medications among individuals who drank alcohol on 52 or more occasions in the past year ("regular drinking"). CNS-D medications included sedative-hypnotics (subclassified as anxiolytics or sleep medications) and opioids. METHODS: We used 8 cross-sectional cycles of the National Health and Nutrition Examination Survey (1999-2000 to 2013-2014) from participants aged 20 and older (n = 37,709). We used log-binomial regression to examine (i) prevalence trends of prescribed CNS-D medication use, (ii) trend differences by drinking status, and (iii) correlates of CNS-D medication use. RESULTS: Among those who drink regularly, the relative annual increase in prevalence of sedative-hypnotic use was 5.3% (95% CI: 2.7 to 7.9): Anxiolytic and sleep medication use increased annually by 3.7% (95% CI: 0.8 to 6.7) and 11.2% (95% CI: 6.5 to 16.0), respectively. Opioid use trends among those who drink regularly were not statistically significant but were nonlinear. Differences in CNS-D medication trends between those who drink regularly and those who drink infrequently/abstain were not statistically significant. Those who drink regularly were less likely than those who drink infrequently/abstain to use opioids (adjusted relative risk [ARR]: 0.69, 95% CI: 0.60 to 0.78) and anxiolytics (ARR: 0.71, 95% CI: 0.61 to 0.81), but not sleep medications (ARR: 1.04, 95% CI: 0.80 to 1.35). Those aged 40 and older were 2 to 5 times as likely as those aged 20 to 29 to use sedative-hypnotics. CONCLUSIONS: Among those who drink regularly, the prevalence of prescribed sedative-hypnotic use increased and prescribed opioid use remained common. These trends indicate that a substantial portion of the population is at risk of alcohol-related adverse drug reactions-particularly those aged 40 and older.

Using genomic profiling for understanding and improving response to smoking cessation treatment.

Purpose of Review: This review focuses on the implementation of genomic discoveries associated with smoking behaviors and smoking-related illnesses to improve prevention efforts and smoking cessation. Recent Findings: Large-scale studies have discovered genomic variation that contributes to smoking heaviness and smoking cessation. Variation in the α5 nicotinic acetylcholine receptor subunit (CHRNA5) and the primary nicotine metabolizing gene (CYP2A6) strongly contribute to smoking behaviors, lung cancer, and chronic obstructive pulmonary disease. The analytic and clinical validity of these genes is clearly established, and evidence of clinical utility for risk stratification is growing. Equity will be a critical issue facing the translation of genomic findings into improved health because the majority of genomic studies have been conducted in European ancestry populations. Summary: Now is the time to increase the state of readiness for implementation of genomic profiling and we must address issues of increasing healthcare disparities that may arise with this new genomic technology.

Daily Drinking Is Associated with Increased Mortality.

BACKGROUND: There is evidence that low-level alcohol use, drinking 1 to 2 drinks on occasion, is protective for cardiovascular disease, but increases the risk of cancer. Synthesizing the overall impact of low-level alcohol use on health is therefore complex. The objective of this paper was to examine the association between frequency of low-level drinking and mortality. METHODS: Two data sets with self-reported alcohol use and mortality follow-up were analyzed: 340,668 individuals from the National Health Interview Survey (NHIS) and 93,653 individuals from the Veterans Health Administration (VA) outpatient medical records. Survival analyses were conducted to evaluate the association between low-level drinking frequency and mortality. RESULTS: The minimum risk drinking frequency among those who drink 1 to 2 drinks per occasion was found to be 3.2 times weekly in the NHIS data, based on a continuous measure of drinking frequency, and 2 to 3 times weekly in the VA data. Relative to these individuals with minimum risk, individuals who drink 7 times weekly had an adjusted hazard ratio (HR) of all-cause mortality of 1.23 (p < 0.0001) in the NHIS data, and individuals who drink 4 to 7 times weekly in the VA data also had an adjusted HR of 1.23 (p = 0.01). Secondary analyses in the NHIS data showed that the minimum risk was drinking 4 times weekly for cardiovascular mortality, and drinking monthly or less for cancer mortality. The associations were consistent in stratified analyses of men, women, and never smokers. CONCLUSIONS: The minimum risk of low-level drinking frequency for all-cause mortality appears to be approximately 3 occasions weekly. The robustness of this finding is highlighted in 2 distinctly different data sets: a large epidemiological data set and a data set of veterans sampled from an outpatient clinic. Daily drinking, even at low levels, is detrimental to one's health.

A reexamination of medical marijuana policies in relation to suicide risk.

OBJECTIVES: Previous research has suggested that medical marijuana policies lead to reductions in suicide rates. In this study, we further investigate the association between these policies and within-state changes in suicide risk. METHODS: Data on suicide deaths (n=662,993) from the National Vital Statistics System Multiple Cause of Death files were combined with living population data. Fixed-effects regression methods were employed to control for state differences in suicide rates and national and state secular trends. Analyses extended prior research that suggested a protective effect of medical marijuana policies by incorporating newer data and additional covariates. RESULTS: After adjustment for race/ethnicity, tobacco control policies, and other covariates, we found no association between medical marijuana policy and suicide risk in the population ages 15 and older (OR=1.000; 95% CI: 0.956, 1.045; p=0.98), among men overall (OR=0.996; 95% CI: 0.951, 1.043; p=0.87) or for any other age-by-sex groups. CONCLUSION: We find no statistically significant association between medical marijuana policy and suicide risk. These results contradict prior analyses which did not control for race/ethnicity and certain state characteristics such as tobacco control policies. Failure to control for these factors in future analyses would likely bias estimates of the associations between medical marijuana policy and health outcomes.

Effects of state cigarette excise taxes and smoke-free air policies on state per capita alcohol consumption in the United States, 1980 to 2009.

BACKGROUND: Increasing state cigarette excise taxes and strengthening smoke-free air (SFA) laws are known to reduce smoking prevalence. Some studies suggest that such policies may also reduce alcohol use, but results for cigarette taxes have been mixed, and associations with smoke-free air policies have been limited to some demographic subgroups. To shed further light on the potential secondary effects of tobacco control policy, we examined whether increases in cigarette taxes and strengthening of SFA laws were associated with reductions of per capita alcohol consumption and whether any reductions were specific to certain beverage types. METHODS: State per capita alcohol consumption from 1980 to 2009 was modeled as a function of state price per pack of cigarettes and SFA policy scores while controlling for secular trends and salient state covariates. Both policy measures also accounted for local policies. Total alcohol, beer, wine, and spirits consumption per capita were modeled separately. For each type of beverage, we used a nested models approach to determine whether the 2 policies together were associated with reduced consumption. RESULTS: For total alcohol consumption, and for beer or spirits (but not wine), one or both tobacco policies were associated with reductions in consumption. A 1% increase in cigarette price per pack was associated with a 0.083% decrease in per capita total alcohol consumption (95% confidence interval [CI] 0.0002 to 0.166, p = 0.0495), and a 1-point increase in SFA policy score, measured on a 6-point scale, was associated with a 1.1% decrease in per capita total alcohol consumption (95% CI 0.4 to 1.7, p = 0.001; p < 0.001 for the hypothesis that the 2 policies are jointly associated with reduced alcohol consumption). CONCLUSIONS: The public health benefits of increasing cigarette taxes and smoke-free policies may go beyond the reduction of smoking and extend to alcohol consumption, specifically beer and spirits.

Probing the smoking-suicide association: do smoking policy interventions affect suicide risk?

INTRODUCTION: Smokers exhibit elevated risk for suicide, but it is unknown whether smoking interventions reduce suicide risk. We examined whether state-level policy interventions-increases in cigarette excise taxes and strengthening of smoke-free air laws-corresponded to a reduction in suicide risk during the 1990s and the early 2000s. We also examined whether the magnitude of such reductions correlated with individuals' predicted probability of smoking, which would be expected if the associations stemmed from changes in smoking behavior. METHODS: We paired individual-level data on suicide deaths from the U.S. Multiple Cause of Death files, years 1990-2004, with living population data from the same period. These were linked with state data on cigarette excise taxes and smoke-free air policies. Utilizing a quasiexperimental analytical approach, we estimated the association between changes in policy and suicide risk. To examine whether associations correlated with individuals' probability of smoking, we used external survey data to derive a predicted probability of smoking function from demographic variables, which was then used to stratify the population by predicted smoking prevalence. RESULTS: Cigarette excise taxes, smoke-free air policies, and an index combining the two policies all exhibited protective associations with suicide. The associations were strongest in segments of the population where predicted smoking prevalence was the highest and weaker in segments of the population where predicted smoking prevalence was the lowest, suggesting that the protective associations were related to changes in smoking behavior. CONCLUSION: These results provide support for the proposition that population interventions for smoking could reduce risk for suicide.

Imputation across genotyping arrays for genome-wide association studies: assessment of bias and a correction strategy.

A great promise of publicly sharing genome-wide association data is the potential to create composite sets of controls. However, studies often use different genotyping arrays, and imputation to a common set of SNPs has shown substantial bias: a problem which has no broadly applicable solution. Based on the idea that using differing genotyped SNP sets as inputs creates differential imputation errors and thus bias in the composite set of controls, we examined the degree to which each of the following occurs: (1) imputation based on the union of genotyped SNPs (i.e., SNPs available on one or more arrays) results in bias, as evidenced by spurious associations (type 1 error) between imputed genotypes and arbitrarily assigned case/control status; (2) imputation based on the intersection of genotyped SNPs (i.e., SNPs available on all arrays) does not evidence such bias; and (3) imputation quality varies by the size of the intersection of genotyped SNP sets. Imputations were conducted in European Americans and African Americans with reference to HapMap phase II and III data. Imputation based on the union of genotyped SNPs across the Illumina 1M and 550v3 arrays showed spurious associations for 0.2 % of SNPs: ~2,000 false positives per million SNPs imputed. Biases remained problematic for very similar arrays (550v1 vs. 550v3) and were substantial for dissimilar arrays (Illumina 1M vs. Affymetrix 6.0). In all instances, imputing based on the intersection of genotyped SNPs (as few as 30 % of the total SNPs genotyped) eliminated such bias while still achieving good imputation quality.

The persistent effects of minimum legal drinking age laws on drinking patterns later in life.

BACKGROUND: Exposure to permissive minimum legal drinking age (MLDA) laws not only affects young adults in the short term, but also later in life; for example, individuals who could legally purchase alcohol before the age of 21 are more likely to suffer from drinking problems as older adults, long after the laws had been changed. However, it is not known how permissive MLDA exposure affects specific drinking behavior. This present study uses changes in MLDA laws during the 1970s and 1980s as a natural experiment to investigate the potential impact of permissive MLDA exposure on average alcohol consumption, frequency of drinking, and patterns of binging and more moderate, nonheavy drinking. METHODS: Policy exposure data were paired with alcohol use data from the 1991 to 1992 National Longitudinal Alcohol Epidemiologic Survey and the 2001 to 2002 National Epidemiologic Survey on Alcohol and Related Conditions. Past-year drinkers born between 1949 and 1972 (n = 24,088) were included. Average daily intake, overall drinking frequency, and frequency of both binge episodes (5+ drinks) and days without a binge episode (nonheavy drinking) for the previous year at the time of interview were tracked for each respondent. RESULTS: Exposure to permissive MLDAs was associated with higher odds to report frequent binging and lower odds to report any moderate drinking; these associations were largely driven by men and those who did not attend college. Overall drinking frequency and average alcohol consumption were not affected by MLDA exposure. CONCLUSIONS: The ability to legally purchase alcohol before the age of 21 does not seem to increase overall drinking frequency, but our findings suggest that it is associated with certain types of problematic drinking behaviors that persist into later adulthood: more frequent binge episodes and less frequent nonheavy drinking. We also propose that policymakers and critics should not focus on college drinking when evaluating the effectiveness of MLDAs.

Assessment of genotype imputation performance using 1000 Genomes in African American studies.

Genotype imputation, used in genome-wide association studies to expand coverage of single nucleotide polymorphisms (SNPs), has performed poorly in African Americans compared to less admixed populations. Overall, imputation has typically relied on HapMap reference haplotype panels from Africans (YRI), European Americans (CEU), and Asians (CHB/JPT). The 1000 Genomes project offers a wider range of reference populations, such as African Americans (ASW), but their imputation performance has had limited evaluation. Using 595 African Americans genotyped on Illumina's HumanHap550v3 BeadChip, we compared imputation results from four software programs (IMPUTE2, BEAGLE, MaCH, and MaCH-Admix) and three reference panels consisting of different combinations of 1000 Genomes populations (February 2012 release): (1) 3 specifically selected populations (YRI, CEU, and ASW); (2) 8 populations of diverse African (AFR) or European (AFR) descent; and (3) all 14 available populations (ALL). Based on chromosome 22, we calculated three performance metrics: (1) concordance (percentage of masked genotyped SNPs with imputed and true genotype agreement); (2) imputation quality score (IQS; concordance adjusted for chance agreement, which is particularly informative for low minor allele frequency [MAF] SNPs); and (3) average r2hat (estimated correlation between the imputed and true genotypes, for all imputed SNPs). Across the reference panels, IMPUTE2 and MaCH had the highest concordance (91%-93%), but IMPUTE2 had the highest IQS (81%-83%) and average r2hat (0.68 using YRI+ASW+CEU, 0.62 using AFR+EUR, and 0.55 using ALL). Imputation quality for most programs was reduced by the addition of more distantly related reference populations, due entirely to the introduction of low frequency SNPs (MAF≤2%) that are monomorphic in the more closely related panels. While imputation was optimized by using IMPUTE2 with reference to the ALL panel (average r2hat = 0.86 for SNPs with MAF>2%), use of the ALL panel for African American studies requires careful interpretation of the population specificity and imputation quality of low frequency SNPs.

The legacy of minimum legal drinking age law changes: long-term effects on suicide and homicide deaths among women.

BACKGROUND: Prior to the establishment of the uniform drinking age of 21 in the United States, many states permitted legal purchase of alcohol at younger ages. Lower drinking ages were associated with several adverse outcomes, including elevated rates of suicide and homicide among youth. The objective of this study is to examine whether individuals who were legally permitted to drink prior to age 21 remained at elevated risk in adulthood. METHODS: Analysis of data from the U.S. Multiple Cause of Death files, 1990 to 2004, combined with data on the living population from the U.S. Census and American Community Survey. The assembled data contained records on over 200,000 suicides and 130,000 homicides for individuals born between 1949 and 1972, the years during which the drinking age was in flux. Logistic regression models were used to evaluate whether adults who were legally permitted to drink prior to age 21 were at elevated risk for death by these causes. A quasi-experimental analytical approach was employed, which incorporated state and birth-year fixed effects to account for unobserved covariates associated with policy exposure. RESULTS: In the population as a whole, we found no association between minimum drinking age and homicide or suicide. However, significant policy-by-sex interactions were observed for both outcomes, such that women exposed to permissive drinking age laws were at higher risk for both suicide (OR = 1.12, 95% CI: 1.05, 1.18, p = 0.0003) and homicide (OR = 1.15, 95% CI: 1.04, 1.25, p = 0.0028). Effect sizes were stronger for the portion of the cohort born after 1960, whereas no significant effects were observed for women born prior to 1960. CONCLUSIONS: Lower drinking ages may result in persistent elevated risk for suicide and homicide among women born after 1960. The national drinking age of 21 may be preventing about 600 suicides and 600 homicides annually.

Inclusion of African Americans in genetic studies: what is the barrier?

To facilitate an increase in the amount of data on minority subjects collected for genetic databases, the authors attempted to clarify barriers to African-American participation in genetic studies. They randomly sampled 78,072 subjects from the community (Missouri Family Registry, 2002-2007). Of these, 28,658 participated in a telephone screening interview, 3,179 were eligible to participate in the genetic study, and 1,919 participated in the genetic study. Response rates were examined in relation to the proportion of subjects in the area who were African-American according to US Census 2000 zip code demographic data. Compared with zip codes with fewer than 5% African Americans (average = 2% African-American), zip codes with at least 60% African Americans (average = 87% African-American) had higher proportions of subjects with an incorrect address or telephone number but lower proportions of subjects who did not answer the telephone and subjects who refused the telephone interview (P < 0.0001). Based on reported race from the telephone screening, 71% of eligible African Americans and 57% of eligible European Americans participated in the genetic study (P < 0.0001). The results of this study suggest that increasing the number of African Americans in genetic databases may be achieved by increasing efforts to locate and contact them.