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Methadone and buprenorphine have pharmacologic properties that are concerning for a high risk of drug-drug interactions (DDIs). We performed high-throughput screening for clinically relevant DDIs with methadone or buprenorphine by combining pharmacoepidemiologic and pharmacokinetic approaches. We conducted pharmacoepidemiologic screening via a series of self-controlled case series studies (SCCS) in Optum claims data from 2000 to 2019. We included persons 18 years or older who experienced an outcome of interest during target drug treatment. Exposures were all overlapping medications (i.e., the candidate precipitants) during target drug treatment. Outcomes were opioid overdose, non-overdose adverse effects, and cardiac arrest. We used conditional Poisson regression to calculate rate ratios, accounting for multiple comparisons with semi-Bayes shrinkage. We explored the impact of key study design choices in analyses that varied the exposure definitions of the target drugs and the candidate precipitant drugs. Pharmacokinetic screening was conducted by incorporating published data on CYP enzyme metabolism into an equation-based static model. In SCCS analysis, 1,432 events were included from 248,069 new users of methadone or buprenorphine. In the primary analysis, statistically significant DDIs included gabapentinoids with either methadone or buprenorphine; baclofen with methadone; and benzodiazepines with methadone. In sensitivity analysis, additional statistically significant DDIs included methocarbamol, quetiapine, or simvastatin with methadone. Pharmacokinetic screening identified two moderate-to-strong potential DDIs (clonidine and fluconazole with buprenorphine). The combination of clonidine and buprenorphine was also associated with a significantly increased risk of opioid overdose in pharmacoepidemiologic screening. These DDI signals may be the most important targets for future confirmation studies.

"From his work as part of the prosecution in the 1995 O. J. Simpson murder trial to his star billing on TV's America's Most Wanted, former San Diego prosecutor George "Woody" Clarke has been party to some of the justice system's most visible, controversial, and melodramatic moments. He puts that populist knack to work in this nonfiction page turner that should appeal just as much to true crime buffs as those concerned with the workings of the criminal justice system."-Publishers Weekly (starred review) "Clarke's account of the rise of DNA evidence is engaging and well paced, and the author comes across as likable and genuinely humble-a rarity in a book of war stories."-San Francisco Chronicle "As a former prosecutor who specialized in DNA evidence, Woody Clarke has the ability to make the difficult science that sometimes confuses a jury understandable to his reader."-Dominick Dunne Databases of both convicted offenders and no-suspect cases demonstrate the power of DNA testing to solve the unsolvable. George "Woody" Clarke chronicles his experiences in some of the most disturbing and notorious sexual assault and murder court cases in California. He charts the beginnings of DNA testing in police investigations and the fight for its acceptance by courts and juries and illustrates the power of science in cases he personally prosecuted or in which he assisted, including his work with the prosecution team in the trial of O. J. Simpson. As Clarke tells the story of how he came to understand and use this new form of evidence, readers will develop a new appreciation for the role of science in the legal system. George "Woody" Clarke, a judge of the Superior Court in San Diego County for the past several years, lectures internationally on DNA evidence and has cohosted America's Most Wanted.

This study examines the relationship between institutional fiscal strain and the availability of opiate substitution therapy (eg, methadone maintenance), an effective but relatively expensive treatment for heroin addiction. An observational design was used to examine the association of changes in funding and changes in provision for treating opiate addiction at 29 VA Medical Centers (VAMCs). We hypothesized that VAMCs experiencing greater fiscal strain would show reduced availability of opiate substitution treatment. Administrative records from each of 29 VAMCs that provided opiate substitution therapy in both Fiscal Year (FY) 1995 and FY 1999 were used to measure changes in the availability of this service, ie, the percent change in total patients treated, annual visits per patient, and total services delivered. Institutional fiscal strain was measured by the percent decline in per capita funding at four levels at each VAMC: the entire medical center, all mental health programs, all substance abuse programs (inpatient and outpatient), and outpatient substance abuse programs alone. The total number of patients receiving opiate substitution increased from 5,549 in FY 1995 to 6,884 in FY 1999 (24%), annual visits per patient decreased by 16%, and the total number of units of services increased by 4%. There were no significant relationships between changes in the delivery of opiate substitution services and changes in per capita funding at any of the four institutional levels. No new programs were started during these years. Although no new programs were started, the availability of opiate substitution therapy at VA facilities with existing programs was maintained over a five-year period regardless of local funding changes, although at somewhat reduced intensity.

Substance use disorder in patients with cancer has implications for outcomes. The objective of this study was to analyze the effects of the type and timing of substance use on outcomes in elderly Medicare recipients with advanced prostate cancer.This was an observational cohort study using Surveillance, Epidemiology, and End Results (SEER)-Medicare linked data from 2000 to 2009. Among men who were diagnosed with advanced prostate cancer between 2001 and 2004, we identified those who had a claim for substance use disorder in the year before cancer diagnosis, 1 year after cancer diagnosis, and an additional 4 years after diagnosis. The outcomes investigated were use of health services, costs, and mortality.The prevalence of substance use disorder was 10.6%. The category drug psychoses and related had greater odds of inpatient hospitalizations (odds ratio [OR], 2.3; 95% confidence interval [CI], 1.9-2.8), outpatient hospital visits (OR, 2.6; 95% CI, 1.9-3.6), and emergency room visits (OR, 1.7; 95% CI, 1.2-2.4). Substance use disorder in the follow-up phase was associated with greater odds of inpatient hospitalizations (OR, 2.0; 95% CI, 1.8-2.2), outpatient hospital visits (OR, 2.0; 95% CI, 1.7-2.4), and emergency room visits (OR, 1.7; 95% CI, 1.5-2.1). Compared with men who did not have substance use disorder, those in the category drug psychoses and related had 70% higher costs, and those who had substance use disorder during the follow-up phase had 60% higher costs. The hazard of all-cause mortality was highest for patients in the drug psychoses and related category (hazard ratio, 1.3; 95% CI, 1.1-1.7) and the substance use disorder in treatment phase category (hazard ratio, 1.5; 95% CI, 1.3-1.7).The intersection of advanced prostate cancer and substance use disorder may adversely affect outcomes. Incorporating substance use screening and treatments into prostate cancer care guidelines and coordination of care is desirable.

Researchers have made great strides in understanding and treating alcoholics with co-occurring psychiatric disorders. Improved diagnostic criteria are available, and research has demonstrated that both disorders must be addressed if the dually diagnosed patient is to have the best chance for a good outcome. The best type of treatment program is an integrated approach, assuring that treatments will be coordinated for best effect. Additional research is needed to match optimum treatment approaches with cost-effective reimbursement practices.

FROM: Kowalczyk WJ, Phillips KA, Jobes ML, et al. Lonidine maintenance prolongs opioid abstinence and decouples stress from craving in daily life: a randomized controlled trial with ecological momentary assessment. Am J Psychiatry 2015;172:760–7. Alcohol, marijuana and opioids can reduce anxiety, elevate one's mood and people sometimes turn to them for relief from stress.1 This self-medication can lead to a substance use disorder in someone that has never had one; precipitate a relapse; compromise treatment response; or result in a fatal overdose. Relief is typically short-lived and continued use can result in a new disorder. For example, heavy alcohol use can increase anxiety and depression; and stimulants increase anxiety, precipitate psychotic symptoms or cause depression (crashing). These issues are described in the substance use section of the Diagnostic and Statistical Manual (DSM).2 The study was a randomised trial to see if clonidine decouples stress-related cocaine and heroin administration in patients maintained on buprenorphine. The investigators …

Adolescent substance use disorders are common illnesses that will be encountered in the primary care setting. Though they have been decreasing in prevalence recently, they still manifest in significant public health costs and increase the chance for negative life outcomes. When identification and intervention occur at an early stage, many of the long-term consequences may be mitigated. Thus, identifying, preliminarily treating, and referring to subspecialty treatment when necessary are an important skillset for the primary care provider.