Patterns and Correlates of Prescription Opioid Receipt Among US Veterans: A National, 18-Year Observational Cohort Study.

A better understanding of predisposition to transition to high-dose, long-term opioid therapy after initial opioid receipt could facilitate efforts to prevent opioid use disorder (OUD). We extracted data on 69,268 patients in the Veterans Aging Cohort Study who received any opioid prescription between 1998 and 2015. Using latent growth mixture modelling, we identified four distinguishable dose trajectories: low (53%), moderate (29%), escalating (13%), and rapidly escalating (5%). Compared to low dose trajectory, those in the rapidly escalating dose trajectory were proportionately more European-American (59% rapidly escalating vs. 38% low); had a higher prevalence of HIV (31% vs. 29%) and hepatitis C (18% vs. 12%); and during follow-up, had a higher incidence of OUD diagnoses (13% vs. 3%); were hospitalised more often [18.1/100 person-years (PYs) vs. 12.5/100 PY]; and had higher all-cause mortality (4.7/100 PY vs. 1.8/100 PY, all p < 0.0001). These measures can potentially be used in future prevention research, including genetic discovery.

Predictors of Treatment Referral after AUDIT-C Screening for Heavy Drinking.

OBJECTIVES: The Veterans Health Administration has implemented annual screening for heavy drinking during primary care encounters using the 3-item Alcohol Use Disorders Identification Test - Consumption (AUDIT-C) questionnaire and made specialized services available to patients with alcohol use disorders (AUDs). We sought to identify the factors that influence whether a patient who has an elevated AUDIT-C score receives appropriate care in the context of an integrated mental health services program. We focused on higher AUDIT-C scores, as these are seen in individuals who are most likely to have a moderate-to-severe AUD and more severe alcohol-related consequences. METHODS: Utilizing electronic health record data, we conducted a four-year retrospective study of veterans at high-risk for an AUD, based upon an AUDIT-C score >=8 recorded during a primary care encounter at a Veterans Affairs Medical Center and its community-based outpatient clinics. RESULTS: In multivariate analysis, the predictors of treatment referral were younger age, being non-white, higher AUDIT-C score, and main campus location. Among patients referred for treatment, younger age and being white were associated with an increased likelihood of completing a pre-treatment assessment. CONCLUSIONS: Efforts to increase the consistency of treatment referrals, according to established clinical guidelines, could enhance the effectiveness of AUDIT-C screening during primary care visits. Subgroups of patients who may benefit from such efforts include individuals with high-risk but sub-maximal AUDIT-C scores, older patients, and patients who are seen at community-based outpatient clinics.

Comparing 3-month recall to daily reporting of sexual behaviours.

OBJECTIVES: This study aimed to examine discrepancies between self-report methods and methodological issues related to sexual risk taking. We examined sexual behaviour assessed via 3-month electronic recall and by daily electronic reporting among a large cohort of patients attending STI clinics. METHODS: STI clinic attenders (N= 628) aged 15 to 60 years reported on demographic information (at baseline), penile-vaginal sex acts, condom-unprotected penile-vaginal sex and STI history using 3-month recall and daily reports. Additionally, interviewer-participant match related to race and gender, as well as study site were considered as covariates. RESULTS: Concordance between recall and daily reports on penile-vaginal sex was moderately strong (Spearman's r (rs)=0.62; p<0.001). Comparison for reports for condom-unprotected penile-vaginal sex resulted in a correlation coefficient of 0.61 (p<0.001), also indicating moderately strong agreement between the two methods. Two generalised logit models were conducted to explain lack of strong concordance in penile-vaginal sex acts and condom-unprotected penile-vaginal sex. The odds of a female reporting higher frequency of sex in daily reports compared with recall were more than two times that of a male. Every five person increase in the number of lifetime sexual partners was associated with five times the odds of a discrepancy in reporting methods. Age was also significantly associated with unequal daily versus recall sex frequency reporting. CONCLUSIONS: Shifting focus to methodological considerations of technological reports can help ensure better investment of resources into sexual health research due to greater understanding of the methodological properties of data collection methods.

Effects of Recent Alcohol Consumption Level on Neurocognitive Performance in HIV+ Individuals.

OBJECTIVES: Although HIV+ individuals may be at increased risk of alcohol-related cognitive impairment, the relations between drinking level and cognitive performance in these individuals are not well understood. We examined whether higher levels of recent drinking in HIV+ individuals were associated with poorer cognitive performance, particularly in executive functioning (EF) and memory. METHODS: We administered a comprehensive cognitive battery to 120 seropositive subjects (101 men) who reported alcohol consumption in the preceding 90 days. Participants were excluded if they were seeking alcohol treatment or showed evidence of dementia. Using the computerized CogState battery, we measured performance in EF, verbal learning/memory, visual learning/memory, attention, working memory, and psychomotor speed. The computerized Iowa Gambling Task was used to assess decision-making. RESULTS: The HIV+ subjects showed significantly slower psychomotor speed than a normative sample. Although across most domains, neurocognitive performance in our sample was not significantly associated with recent alcohol consumption, performance on the CogState measures of visual memory and attention was significantly poorer with a higher level of drinking in the past 3 months and a current alcohol use disorder, respectively. CONCLUSIONS: Although cognitive weaknesses were detectable among these non-treatment-seeking HIV+ drinkers, the level of alcohol consumption was not a primary determinant of neurocognitive performance in this group. A comprehensive profile analysis may be most valuable for detecting cognitive strengths and weaknesses given the heterogeneity of this population. Longitudinal studies are needed to examine the potential additive or synergistic effects of heavy drinking and HIV seropositivity on cognitive performance.

Enhancing condom use among Black male youths: a randomized controlled trial.

OBJECTIVES: We tested the efficacy of a brief intervention to promote correct and consistent use of condoms among Black male youths attending sexually transmitted infection (STI) clinics in 3 southern US cities. METHODS: In 2010 to 2012, we screened (n = 1102) and enrolled (n = 702) youths aged 15 to 23 years who identified as Black and reported recent (past 2 months) sexual activity and randomized them to a private, brief, interactive intervention (n = 349) or an attention-equivalent control condition (n = 353). Assessments occurred at baseline and 2 and 6 months after the intervention. RESULTS: At 6 months, with adjustment for age and pretest nonequivalence of the outcome variable, an estimated odds ratio (EOR) of 1.63 (95% confidence interval [CI] = 1.07, 2.49; P = .02) indicated efficacy for correct condom use. An adjusted generalized estimating equations model with both 2- and 6-month condom use variables produced an EOR of 1.49 (95% CI = 1.06, 2.08; P = .02). We did not observe significant effects on chlamydia and gonorrhea incidence. CONCLUSIONS: This brief intervention, delivered as part of STI clinical care, could help alleviate the disproportionate STI-HIV burden among young Black men.

Circadian Pattern of Deaths Due to Suicide in Intoxicated Alcohol-Dependent Individuals.

OBJECTIVE: Alcohol intoxication and dependence are risk factors for suicide, a leading cause of death in the United States. We examined the hours of peak and nadir in completed suicides over a 24-hour period among intoxicated, alcohol-dependent individuals. We also evaluated suicide-related factors associated with intoxication at different times of the day. METHODS: We analyzed cross-sectional data from the 2003-2010 National Violent Death Reporting System provided by 16 US states. In the primary database, the deceased individuals' alcohol-dependent status was classified as "yes" or "no or unknown." We restricted the analysis to alcohol-dependent individuals with alcohol level data available (N = 3,661). The primary outcome measure was the reported time of death. Secondary outcome measures were predisposing and injury-related factors. Individuals were classified on the basis of their blood alcohol level (BAL) as heavy drinking (BALH [≥ 80 mg/dL]) or non-heavy drinking (BALO [< 80 mg/dL]). The time of injury was divided into 1-hour bins, which were used to compute the incidence of suicide over 24 hours. We also evaluated the association between clinical factors and BALH for each of six 4-hour time periods beginning at 00:01 hours. RESULTS: The majority (73.4%) of individuals showed evidence of alcohol consumption prior to committing suicide. BALH was observed in 60.7% of all individuals. Peak incidences in suicide were identified at 21:00 for BALH and 12:00 for BALO, with nadirs at 05:00 and 03:00 hours, respectively. In a multivariable analysis, between 20:01 and 00:00 hours, BALH was associated with more risk and protective factors than BALO. CONCLUSIONS: Identifying critical times and associated risk factors for suicidal behavior may contribute to suicide prevention efforts in intoxicated alcohol-dependent individuals.

AUDIT-C and ICD codes as phenotypes for harmful alcohol use: association with ADH1B polymorphisms in two US populations.

BACKGROUND AND AIMS: Longitudinal electronic health record (EHR) data offer a large-scale, untapped source of phenotypical information on harmful alcohol use. Using established, alcohol-associated variants in the gene that encodes the enzyme alcohol dehydrogenase 1B (ADH1B) as criterion standards, we compared the individual and combined validity of three longitudinal EHR-based phenotypes of harmful alcohol use: Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) trajectories; mean age-adjusted AUDIT-C; and diagnoses of alcohol use disorder (AUD). DESIGN: With longitudinal EHR data from the Million Veteran Program (MVP) linked to genetic data, we used two population-specific polymorphisms in ADH1B that are associated strongly with AUD in African Americans (AAs) and European Americans (EAs): rs2066702 (Arg369Cys, AAs) and rs1229984 (Arg48His, EAs) as criterion measures. SETTING: United States Department of Veterans Affairs Healthcare System. PARTICIPANTS: A total of 167 721 veterans (57 677 AAs and 110 044 EAs; 92% male, mean age = 63 years) took part in this study. Data were collected from 1  October 2007 to 1 May 2017. MEASUREMENTS: Using all AUDIT-C scores and AUD diagnostic codes recorded in the EHR, we calculated age-adjusted mean AUDIT-C values, longitudinal statistical trajectories of AUDIT-C scores and ICD-9/10 diagnostic groupings for AUD. FINDINGS: A total of 19 793 AAs (34.3%) had one or two minor alleles at rs2066702 [minor allele frequency (MAF) = 0.190] and 6933 EAs (6.3%) had one or two minor alleles at rs1229984 (MAF = 0.032). In both populations, trajectories and age-adjusted mean AUDIT-C were correlated (r = 0.90) but, when considered separately, highest score (8+ versus 0) of age-adjusted mean AUDIT-C demonstrated a stronger association with the ADH1B variants [adjusted odds ratio (aOR) 0.54 in AAs and 0.37 in AAs] than did the highest trajectory (aOR 0.71 in AAs and 0.53 in EAs); combining AUDIT-C metrics did not improve discrimination. When age-adjusted mean AUDIT-C score and AUD diagnoses were considered together, age-adjusted mean AUDIT-C (8+ versus 0) was associated with lower odds of having the ADH1B minor allele than were AUD diagnostic codes: aOR = 0.59 versus 0.86 in AAs and 0.48 versus 0.68 in EAs. These independent associations combine to yield an even lower aOR of 0.51 for AAs and 0.33 for EAs. CONCLUSIONS: The age-adjusted mean AUDIT-C score is associated more strongly with genetic polymorphisms of known risk for alcohol use disorder than are longitudinal trajectories of AUDIT-C or AUD diagnostic codes. AUD diagnostic codes modestly enhance this association.

The impact of service-connected disability and therapist experience on outcomes from prolonged exposure therapy with veterans.

OBJECTIVE: Although prolonged exposure therapy (PE) has been shown to be effective in treating posttraumatic stress disorder (PTSD), a sizable minority do not benefit. Examining patient and therapist characteristics that impact treatment outcome may improve treatment delivery and identify individuals who are less likely to respond to treatment or are at risk to prematurely discontinue treatment. The current study uses a sample from a large urban Veterans' Affairs (VA) hospital to build on a previous report that identified correlates of treatment outcome for Veterans who received PE. METHOD: Two hundred eighty-seven veterans completed measures of PTSD, depression, and quality of life at the beginning and end of treatment. Veterans' service-connected disability rating, therapist experience, benzodiazepine prescription, and traumatic brain injury diagnosis were investigated as predictors of treatment outcome in linear regression analyses. RESULTS: Results showed that Veterans with a service-connected disability for a mental health condition had smaller treatment gains than those without service connection (p < .01). Additionally, results showed that patients treated by certified PE therapists had larger treatment gains than those treated by noncertified PE therapists (p < .01). Finally, younger age and therapist certification were associated with dropout from treatment (p < .05). CONCLUSION: Veterans treated by PE-certified therapists and Veterans who were not service-connected for a mental health condition fared better in treatment. Results suggest that additional study of both the national effort to train VA clinicians in PE and the impact of service connection on PTSD treatment outcome may be helpful for future research. (PsycINFO Database Record

Individual and Network Correlates of Antisocial Personality Disorder Among Rural Nonmedical Prescription Opioid Users.

PURPOSE: Examination of the association of antisocial personality disorder (ASPD) with substance use and HIV risk behaviors within the social networks of rural people who use drugs. METHODS: Interviewer-administered questionnaires were used to assess substance use, HIV risk behavior, and social network characteristics of drug users (n = 503) living in rural Appalachia. The MINI International Psychiatric Interview was used to determine whether participants met DSM-IV criteria for ASPD and Axis-I psychological comorbidities (eg, major depressive disorder, posttraumatic stress disorder, generalized anxiety disorder). Participants were also tested for herpes simplex 2, hepatitis C, and HIV. Multivariate generalized linear mixed modeling was used to determine the association between ASPD and risk behaviors, substance use, and social network characteristics. RESULTS: Approximately one-third (31%) of participants met DSM-IV criteria for ASPD. In multivariate analysis, distrust and conflict within an individual's social networks, as well as past 30-day use of heroin and crack, male gender, younger age, lesser education, heterosexual orientation, and comorbid MDD were associated with meeting diagnostic criteria for ASPD. CONCLUSIONS: Participants meeting criteria for ASPD were more likely to report recent heroin and crack use, which are far less common drugs of abuse in this population in which the predominant drug of abuse is prescription opioids. Greater discord within relationships was also identified among those with ASPD symptomatology. Given the elevated risk for blood-borne infection (eg, HIV) and other negative social and health consequences conferred by this high-risk subgroup, exploration of tailored network-based interventions with mental health assessment is recommended.

Precision medicine and pharmacogenetics: what does oncology have that addiction medicine does not?

BACKGROUND AND AIMS: Precision, personalized or stratified medicine, which promises to deliver the right treatment to the right patient, is a topic of international interest in both the lay press and the scientific literature. A key aspect of precision medicine is the identification of biomarkers that predict the response to medications (i.e. pharmacogenetics). We examined why, despite the great strides that have been made in biomarker identification in many areas of medicine, only in oncology has there been substantial progress in their clinical implementation. We also considered why progress in this effort has lagged in addiction medicine. METHODS: We compared the development of pharmacogenetic biomarkers in oncology, cardiovascular medicine (where developments are also promising) and addictive disorders. RESULTS: The first major reason for the success of oncologic pharmacogenetics is ready access to tumor tissue, which allows in-vitro testing and insights into cancer biology. The second major reason is funding, with cancer research receiving, by far, the largest allocation by the National Institutes of Health (NIH) during the past two decades. The second largest allocation of research funding has gone to cardiovascular disease research. Addictions research received a much smaller NIH funding allocation, despite the major impact that tobacco use, alcohol consumption and illicit drug use have on the public health and healthcare costs. CONCLUSIONS: Greater support for research on the personalized treatment of addictive disorders can be expected to yield disproportionately large benefits to the public health and substantial reductions in healthcare costs.

Meta-Analysis of the Antidepressant Effects of Acute Sleep Deprivation.

OBJECTIVE: To provide a quantitative meta-analysis of the antidepressant effects of sleep deprivation to complement qualitative reviews addressing response rates. DATA SOURCES: English-language studies from 1974 to 2016 using the keywords sleep deprivation and depression searched through PubMed and PsycINFO databases. STUDY SELECTION: A total of 66 independent studies met criteria for inclusion: conducted experimental sleep deprivation, reported the percentage of the sample that responded to sleep deprivation, provided a priori definition of antidepressant response, and did not seamlessly combine sleep deprivation with other therapies (eg, chronotherapeutics, repetitive transcranial magnetic stimulation). DATA EXTRACTION: Data extracted included percentage of responders, type of sample (eg, bipolar, unipolar), type of sleep deprivation (eg, total, partial), demographics, medication use, type of outcome measure used, and definition of response (eg, 30% reduction in depression ratings). Data were analyzed with meta-analysis of proportions and a Poisson mixed-effects regression model. RESULTS: The overall response rate to sleep deprivation was 45% among studies that utilized a randomized control group and 50% among studies that did not. The response to sleep deprivation was not affected significantly by the type of sleep deprivation performed, the nature of the clinical sample, medication status, the definition of response used, or age and gender of the sample. CONCLUSIONS: These findings support a significant effect of sleep deprivation and suggest the need for future studies on the phenotypic nature of the antidepressant response to sleep deprivation, on the neurobiological mechanisms of action, and on moderators of the sleep deprivation treatment response in depression.

Gabapentin misuse, abuse and diversion: a systematic review.

BACKGROUND AND AIMS: Since its market release, gabapentin has been presumed to have no abuse potential and subsequently has been prescribed widely off-label, despite increasing reports of gabapentin misuse. This review estimates and describes the prevalence and effects of, motivations behind and risk factors for gabapentin misuse, abuse and diversion. METHODS: Databases were searched for peer-reviewed papers demonstrating gabapentin misuse, characterized by taking a larger dosage than prescribed or taking gabapentin without a prescription, and diversion. All types of studies were considered; grey literature was excluded. Thirty-three papers met inclusion criteria, consisting of 23 case studies and 11 epidemiological reports. Published reports came from the United States, the United Kingdom, Germany, Finland, India, South Africa and France, and two analyzed websites not specific to a particular country. RESULTS: Prevalence of gabapentin misuse in the general population was reported to be 1%, 40-65% among individuals with prescriptions and between 15 and 22% within populations of people who abuse opioids. An array of subjective experiences reminiscent of opioids, benzodiazepines and psychedelics were reported over a range of doses, including those within clinical recommendations. Gabapentin was misused primarily for recreational purposes, self-medication or intentional self-harm and was misused alone or in combination with other substances, especially opioids, benzodiazepines and/or alcohol. Individuals with histories of drug abuse were most often involved in its misuse. CONCLUSIONS: Epidemiological and case report evidence suggests that the anti-epileptic and analgesic medication gabapentin is being misused internationally, with substance abuse populations at special risk for misuse/abuse.