State-of-the-art behavioral and pharmacological treatments for alcohol use disorder

Background: Alcohol use disorder (AUD) and its associated consequences remain significant public health concerns. Given that AUD represents a spectrum of severity, treatment options represent a continuum of care, ranging from single-session brief interventions to more intensive, prolonged, and specialized treatment modalities. Objective: This qualitative literature review seeks to describe the best practices for AUD by placing a particular emphasis on identifying those practices which have received the most empirical support. Method: This review summarizes psychological and pharmacological intervention options for AUD treatment, with a focus on the relapse prevention phase of recovery. Psychological and pharmacological treatments are summarized in terms of the empirical evidence favoring each approach and the level of AUD severity for which they are most indicated. Scientific significance: One of the broad assertions from this review is that while AUD is highly prevalent, seeking treatment for AUD is not. There are a myriad of behavioral and pharmacological treatments that have shown compelling evidence of efficacy for the treatment of AUD. In the behavioral treatment literature, cognitive behavioral therapy has received the most consistent support. Opioid antagonism (via naltrexone) has been the most widely studied pharmacotherapy and has produced moderate effect sizes. While none of the treatments reviewed herein represents a so-called silver bullet for AUD, they each have the potential to significantly improve the odds of recovery. Precision medicine, or the identification of best treatment matches for individual patients, looms as an important overarching goal for the field, although specific matches are not yet sufficiently reliable in their empirical evidence to warrant clinical dissemination.     

A Delta-Opioid Receptor Gene Polymorphism Moderates the Therapeutic Response to Extended-Release Buprenorphine in Opioid Use Disorder

BackgroundBuprenorphine treatment is not equally effective in all patients with opioid use disorder (OUD). Two retrospective studies showed that, among African Americans (AAs), rs678849, a polymorphism in the delta-opioid receptor gene, moderated the therapeutic effect of sublingual buprenorphine. MethodsWe examined rs678849 as a moderator of the response to an extended-release subcutaneous buprenorphine formulation (BUP-XR) in a 24-week OUD treatment study of 127 AAs and 327 European Americans (EAs). Participants were randomly assigned to receive: (1) BUP-XR as 2 monthly injections of 300 mg followed by either 300 mg monthly or 100 mg monthly for 4 months, or (2) monthly volume-matched placebo injections. Generalized estimating equations logistic regression analyses tested, per population group, the main and interaction effects of treatment (BUP-XR vs placebo) and genotype group (rs678849*CC vs CT/TT) on weekly urine drug screens (UDS). ResultsAmong AAs, the placebo group had higher rates of opioid-positive UDS than the BUP-XR group (log odds ratio = 1.67, 95% CI = 0.36, 2.98), but no genotype by treatment effect (P = .80). Among EAs, the placebo group also showed higher rates of opioid-positive UDS than the BUP-XR group (log odds ratio = 1.97, 95% CI = 1.14, 2.79) but a significant genotype by treatment interaction (χ ²₍₁₎ = 4.33, P = .04). ConclusionWe found a moderating effect of rs678849 on the response to buprenorphine treatment of OUD in EAs, but not AAs. These findings require replication in well-powered, prospective studies of both AA and EA OUD patients treated with BUP-XR and stratified on rs678849 genotype.     

Effect of propranolol on myocardial-infarct size in a randomized blinded multicenter trial

A multicenter randomized single-blind study was performed to evaluate the effects of propranolol administered during the evolution of myocardial infarction. Five centers enrolled a total of 269 patients, with 134 receiving propranolol and 135 placebo. Propranolol or placebo was given intravenously upon randomization (0.1 mg per kilogram of body weight) and then orally for nine days to keep the heart rate between 45 and 60 beats per minute. Less than 2 per cent of patients were treated within 4 hours after the onset of symptoms, but 50 per cent received therapy within 8 hours of onset of chest pain, and the remainder between 8 and 18 hours. The heart rates in the propranolol-treated group were significantly lower than those in the placebo group (P less than 0.001). Base-line characteristics, including the mean heart rate (79.6 vs. 81.3) and the left ventricular ejection fraction (49.0 vs. 49.5), were similar in the two groups. The primary end point evaluated--infarct size as estimated from plasma MB creatine kinase activity--was virtually identical in the two groups, averaging 13.3 and 13.6 gram-equivalents of MB creatine kinase per square meter of body-surface area. Peak plasma levels of the enzyme were also similar in the two groups. No significant difference was observed between the propranolol and placebo groups in the change in left ventricular ejection fraction, extent of area involved in pyrophosphate uptake, R-wave loss on electrocardiograms, or mortality (after three years). These results do not support the use of propranolol administered four or more hours after the onset of symptoms to limit infarct size.     

An Intervention to Assist Men Who Have Sex with Men Disclose Their Serostatus to Family Members: Results from a Pilot Study

The purpose of this study was to evaluate the efficacy of an intervention to assist HIV positive men who have sex with men (MSM) in forming and executing strategies for the disclosure of their serostatus to their families of origin. Results indicate that the intervention was successful in assisting men with the primary outcome of disclosure. Participants reported no regret with disclosures occurring during the intervention and follow-up period. Effects on secondary outcomes including family functioning, depression, loneliness, and perceived social support were inconclusive. Implications, refinements of this intervention, and suggestions for future disclosure research are provided.     

Worster-Drought syndrome: poorly recognized despite severe and persistent difficulties with feeding and speech

Aim  Worster-Drought syndrome (WDS), or congenital suprabulbar paresis, is a permanent movement disorder of the bulbar muscles causing persistent difficulties with swallowing, feeding, speech, and saliva control owing to a non-progressive disturbance in early brain development. As such, it falls within the cerebral palsies. The aim of this study was to describe the physical and neuropsychological profiles of children with WDS.
Method  Forty-two children with WDS (26 males, 16 females; mean age 7y 10mo, SD 3y 1mo; range 2y 6mo to 16y 5mo) were studied prospectively using a standard protocol.
Results  All of the children had severe bulbar dysfunction; 36 out of 42 had feeding difficulties and 23 of 38 had unintelligible speech, which was poorly compensated for by augmentative communication. There were accompanying disturbances in cognition (mean non-verbal IQ 59), behaviour (12/40 attention-deficit–hyperactivity disorder [ADHD]), social communication (8/42 autism), and epilepsy (12/39). The severity of bulbar dysfunction and impact of additional impairments made it difficult to use formal assessments.
Interpretation  WDS causes severe and persistent bulbar dysfunction that is often accompanied by additional impairments, as in other cerebral palsies. Speech prognosis is particularly poor. Early diagnosis with appreciation of the underlying neurology would encourage critical evaluation of interventions and long-term planning to improve outcome.     

Local expression of indoleamine 2,3‐dioxygenase suppresses T‐cell‐mediated rejection of an engineered bilayer skin substitute

Engineered skin substitutes (ESSs) comprising both keratinocytes and fibroblasts can afford many advantages over the use of autologous keratinocyte grafts for the treatment of full‐thickness and partial‐thickness burns. In this study, we investigated the efficacy of a novel ESS containing both genetically altered fibroblasts that express the immunosuppressive factor indoleamine 2,3‐dioxygenase (IDO) and primary keratinocytes from a nonautologous source to confer immune protection of xenogeneic cells cultured in a bilayer ESS. The results show that engraftment of IDO expressing skin substitutes on the back of rats significantly improves healing progression over 7 days compared with both nontreated and non‐IDO‐expressing skin substitutes (p<0.001). Immuno‐staining of CD3 and CD31 suggests that IDO‐expressing skin substitutes significantly suppress T cell infiltration (p<0.001) and improve neovascularization by four‐fold (12.6±1.2 vs. 3.0±1.0 vessel‐like structure/high power field), respectively. In conclusion, we found that IDO expression can improve the efficacy of nonautologous ESS for the purpose of wound healing by mitigating T‐cell infiltration as well as promoting vascularization of the graft.     

Tobacco use and secondhand smoke exposure during pregnancy: an investigative survey of women in 9 developing nations

Objectives. We examined pregnant women''s use of cigarettes and other tobacco products and the exposure of pregnant women and their young children to secondhand smoke (SHS) in 9 nations in Latin America, Asia, and Africa.Methods. Face-to-face surveys were administered to 7961 pregnant women (more than 700 per site) between October 2004 and September 2005.Results. At all Latin American sites, pregnant women commonly reported that they had ever tried cigarette smoking (range: 78.3% [Uruguay] to 35.0% [Guatemala]). The highest levels of current smoking were found in Uruguay (18.3%), Argentina (10.3%), and Brazil (6.1%). Experimentation with smokeless tobacco occurred in the Democratic Republic of the Congo and India; one third of all respondents in Orissa, India, were current smokeless tobacco users. SHS exposure was common: between 91.6% (Pakistan) and 17.1% (Democratic Republic of the Congo) of pregnant women reported that smoking was permitted in their home.Conclusions. Pregnant women''s tobacco use and SHS exposure are current or emerging problems in several low- and middle-income nations, jeopardizing ongoing efforts to improve maternal and child health.Tobacco use is widely recognized as one of the leading threats to global health.¹ Historically, the prevalence of smoking among women in the developing world has been very low, in part because of strong cultural constraints against women''s smoking; approximately 50% of men in developing nations smoke cigarettes, compared with 9% of women.² Averting an increase in the prevalence of smoking among women in developing nations is widely recognized as a significant public health opportunity.^3,4Pregnant women are a priority population for tobacco control efforts because both cigarette smoking and smokeless tobacco use during pregnancy pose serious risks to fetal health. Smoking during pregnancy may cause preterm delivery, low birthweight, and sudden infant death syndrome; smokeless tobacco use during pregnancy has been associated with stillbirth, preterm birth, and reduced birthweight.^5–8 Maternal tobacco use is also likely to expose infants and children to secondhand smoke (SHS) and to provide a role model for children''s use of tobacco. Intervening during pregnancy is also important because of the health risks to the woman, who potentially has many years of remaining life. For cigarette smoking, these health risks include lung and other cancers, coronary heart disease and stroke, and chronic obstructive pulmonary disease; health risks from smokeless tobacco products include oral and pancreatic cancer.^9,10The US National Institute of Child Health and Human Development''s Global Network for Women''s and Children''s Health Research consists of 10 research units chosen for scientific merit that are focused on improving maternal and children''s health in the developing world. To determine whether pregnant women''s tobacco use and SHS exposure are emerging public health issues, the Global Network undertook an investigative survey of pregnant women''s knowledge, attitudes, and behaviors regarding tobacco use and SHS exposure. Here we report findings on pregnant women''s experimentation with and use of tobacco products, their perceptions of the social acceptability of tobacco use by women, and their and their young children''s exposure to SHS.