The Leeds Evaluation of Efficacy of Detoxification Study (LEEDS) project: An open-label pragmatic randomised control trial comparing the efficacy of differing therapeutic agents for primary care detoxification from either street heroin or methadone [ISRCTN07752728]

Background

Heroin is a synthetic opioid with an extensive illicit market leading to large numbers of people becoming addicted. Heroin users often present to community treatment services requesting detoxification and in the UK various agents are used to control symptoms of withdrawal. Dissatisfaction with methadone detoxification [8] has lead to the use of clonidine, lofexidine, buprenorphine and dihydrocodeine; however, there remains limited evaluative research. In Leeds, a city of 700,000 people in the North of England, dihydrocodeine is the detoxification agent of choice. Sublingual buprenorphine, however, is being introduced. The comparative value of these two drugs for helping people successfully and comfortably withdraw from heroin has never been compared in a randomised trial. Additionally, there is a paucity of research evaluating interventions among drug users in the primary care setting. This study seeks to address this by randomising drug users presenting in primary care to receive either dihydrocodeine or buprenorphine.

Methods/design

The Leeds Evaluation of Efficacy of Detoxification Study (LEEDS) project is a pragmatic randomised trial which will compare the open use of buprenorphine with dihydrocodeine for illicit opiate detoxification, in the UK primary care setting. The LEEDS project will involve consenting adults and will be run in specialist general practice surgeries throughout Leeds. The primary outcome will be the results of a urine opiate screening at the end of the detoxification regimen. Adverse effects and limited data to three and six months will be acquired.

     

Treating Opioid Dependence with Buprenorphine in the Safety Net: Critical Learning from Clinical Data

Research has examined the safety, efficacy, feasibility, and cost-effectiveness of buprenorphine for the treatment of opioid dependence, but few studies have examined patient and provider experiences, especially in community health centers. Using de-identified electronic health record system (EHRS) data from 70 OCHIN community health centers (n = 1825), this cross-sectional analysis compared the demographics, comorbidities, and service utilization of patients receiving buprenorphine to those not receiving medication-assisted treatment (MAT). Compared to non-MAT patients, buprenorphine patients were younger and less likely to be Hispanic or live in poverty. Buprenorphine patients were less likely to have Medicaid insurance coverage, more likely to self-pay, and have private insurance coverage. Buprenorphine patients were less likely to have problem medical comorbidities or be coprescribed high-risk medications. It is important for providers, clinic administrators, and patients to understand the clinical application of medications for opioid dependence to ensure safe and effective care within safety net clinics.     

Factors Affecting Buprenorphine Utilization and Spending in Medicaid, 2002-2018

ObjectiveBuprenorphine is an essential medication for the treatment of opioid use disorder (OUD), but studies show it has been underused over the last 2 decades. We sought to evaluate utilization of and spending on buprenorphine formulations in Medicaid and to evaluate the impact of key market and regulatory factors affecting availability of different formulations and generic versions.MethodsWe first identified all buprenorphine formulations approved by the Food and Drug Administration for OUD using Drugs@FDA. We then used National Drug Codes to identify each drug in the Medicaid State Drug Utilization Data and extracted annual utilization rates and spending between 2002 and 2018 by drug and according to whether a brand-name or generic version was dispensed. We compared these trends to market and regulatory factors that affected competition, which we identified through searching the Federal Register, Westlaw, PubMed, and Google News.ResultsBrand-name buprenorphine-naloxone sublingual tablet and film formulations (Suboxone) were dispensed 2.7 times more (n = 634 213 140) and reimbursed 4.4 times more (n = $4 440 556 473) than all other formulations combined (n = 237 769 689; $1 018 988 133). We identified numerous market and regulatory factors that contributed to an estimated 9-year delay in generic versions of the tablet formulation and 6-year delay for generic versions of the film formulation.ConclusionsBrand-name buprenorphine formulations have been widely used in Medicaid, leading to substantial costs, in part because generic versions were delayed by multiple years owing to market and regulatory factors. Timely availability of low-cost generics could have helped encourage OUD treatment with buprenorphine during the height of the opioid crisis.     

Substance Abuse Treatment Organizations as Mediators of Social Policy: Slowing the Adoption of a Congressionally Approved Medication

Most substance abuse treatment occurs in outpatient treatment centers, necessitating an understanding of what motivates organizations to adopt new treatment modalities. Tichy’s framework of organizations as being comprised of three intertwined internal systems (technical, cultural, and political) was used to explain treatment organizations’ slow adoption of buprenorphine, a new medication for opiate dependence. Primary data were collected from substance abuse treatment organizations in four of the ten metropolitan areas with the largest number of heroin users. Only about one fifth offered buprenorphine. All three internal systems were important determinants of buprenorphine adoption in our multivariate model. However, the cultural system, measured by attitude toward medications, was a necessary condition for adoption. Health policies designed to encourage adoption of evidence-based performance measures typically focus on the technical system of organizations. These findings suggest that such policies would be more effective if they incorporate an understanding of all three internal systems.     

A Comparison of Coverage Restrictions for Biopharmaceuticals and Medical Procedures

Background

Differences in payer evaluation and coverage of pharmaceuticals and medical procedures suggest that coverage may differ for medications and procedures independent of their clinical benefit. We hypothesized that coverage for medications is more restricted than corresponding coverage for nonmedication interventions.

Rabies-free status of the Czech Republic after 15 years of oral vaccination

Rabies in foxes was widespread in the Czech Republic after World War II, reaching its highest incidence in the 1980s. Applied control measures had only a limited effect and rabies incidence in wildlife continuously endangered both domestic animals and human beings. A significant improvement was noticed after the introduction of oral vaccination of foxes in 1989. The original manual distribution of vaccine baits has been replaced by aerial distribution, leading to the total elimination of rabies throughout the country. The last case of rabies was diagnosed in a fox in the district of Trutnov in April 2002. Since that time no case of rabies has been registered in the Czech Republic, and it therefore fulfils the requirements for the status of a 'rabies-free country'. Effective epidemiological surveillance and preventive oral vaccination of foxes will be necessary to maintain this status, especially in the endangered border regions.     

Monitoring of the dietary exposure of the population of chemical substances in the Czech Republic: design and history

The basic objective of the programme of monitoring the dietary exposure in the Czech Republic is to describe the character of the health risk based on the exposure of the Czech population to chemical substances in food. The conception of the monitoring programme is based on the methods of the Total Diet Study, established on the principle of defining the consumption of the most important foodstuffs, their purchase in the network of stores in selected shops on fixed dates, their transport to the central laboratory, cooking and consequent chemical analyses in the central laboratories. In the Czech Republic monitoring has been conducted since 1991/1992 and routine activities have been ongoing since 1994. The programme is fully sponsored by the government. Monitoring carried out in 1994-2001 provided a considerable amount of information, which was applied when drawing programmes of health protection and promotion, in regulatory work and when solving problems of the international food trade.     

Smoking attributable hospital treatment, treatment costs and smoking attributable mortality in the Czech Republic in 2002

OBJECTIVES: The main objective of this work is to quantify the number of hospitalizations caused by smoking, estimate the costs of hospital treatment and to estimate contribution of smoking to mortality in the Czech Republic (CR) in 2002. METHODS: The estimate of the proportion by which smoking contributed to hospitalizations and to mortality in the CR was computed using the method of smoking-attributable fractions (SAF). The SAF was computed from relative risks established in the American study Cancer Prevention Study II and from estimates of the prevalence of smoking in the CR from a nationwide study conducted in 2002. RESULTS: In 2002, based on data provided by the General Health Insurance Company, there were 145,336 hospitalizations, and the total cost of hospital treatment was estimated as 4.727,612 (in thousands) CZK. The total number of deaths caused by smoking was 20,550 (95% CI: 18,851-22,262), 14,525 in men and 6,025 in women. Deaths caused by smoking represented 19% of the total nationwide mortality for 2002. Earlier estimates were published by Peto and Lopez for 1995 (22,300 deaths caused by smoking) and 2000 (17,746 deaths). The estimate arrived by authors using the SAF method for 2002 corresponds quite well with that by Peto and Lopez for 2000. CONCLUSIONS: The high morbidity and mortality rate related to smoking is directly connected to high prevalence of smoking in the Czech Republic. An effective tobacco control policy, including restrictive measures on availability of tobacco products combined with preventive programmes and smoking cessation programmes, could contribute to the reduction of smoking and save lives and treatment costs caused by smoking.     

Drug use and opioid substitution treatment for prisoners

Drug use is prevalent throughout prison populations, and, despite advances in drug treatment programmes for inmates, access to and the quality of these programmes remain substantially poorer than those available for non-incarcerated drug users. Because prisoners may be at greater risk for some of the harms associated with drug use, they deserve therapeutic modalities and attitudes that are at least equal to those available for drug users outside prison. This article discusses drug use by inmates and its associated harms. In addition, this article provides a survey of studies conducted in prisons of opioid substitution therapy (OST), a clinically effective and cost-effective drug treatment strategy. The findings from this overview indicate why treatment efforts for drug users in prison are often poorer than those available for drug users in the non-prison community and demonstrate how the implementation of OST programmes benefits not only prisoners but also prison staff and the community at large. Finally, the article outlines strategies that have been found effective for implementing OST in prisons and offers suggestions for applying these strategies more broadly.     

Medication for Adolescents and Young Adults With Opioid Use Disorder

Opioid-related morbidity and mortality have risen in many settings globally. It is critical that practitioners who work with adolescents and young adults (AYAs) provide timely, evidence-based treatment for opioid use disorder (OUD). Such treatment should include medications for opioid use disorder (MOUD), including buprenorphine, naltrexone, and methadone. Medication treatment is associated with reduced mortality, fewer relapses to opioid use, and enhanced recovery and retention in addiction care, among other positive health outcomes. Unfortunately, the vast majority of AYAs with OUD do not receive medication. The Society for Adolescent Health and Medicine recommends that AYAs be offered MOUD as a critical component of an integrated treatment approach. Barriers to receipt of medications are widespread; many are common to high-, middle-, and low-income countries alike, whereas others differ. Such barriers should be minimized to ensure equitable access to youth-friendly, affirming, and confidential addiction treatment that includes MOUD. Robust education on OUD and medication treatment should be provided to all practitioners who work with AYAs. Strategies to reduce stigma surrounding medication—and stigma experienced by individuals with substance use disorders more generally—should be widely implemented. A broad research agenda is proposed with the goal of expanding the evidence base for the use and delivery of MOUD for AYAs.     

State Medicaid coverage for tobacco-dependence treatments--United States, 2005

In 2005, approximately 41 million persons in the United States had health insurance coverage through Medicaid, a federally and state-funded health-care program, managed at the state level, for persons with limited incomes. An estimated 29% of adult Medicaid recipients were current smokers in 2004. The 2000 Public Health Service (PHS) clinical practice guideline recommends that insurance coverage be provided for tobacco-dependence treatments, including both medication (i.e., bupropion hydrochloride or nicotine patch, gum, inhaler, or nasal spray) and counseling (i.e., individual, group, or telephone). A national health objective for 2010 is to increase insurance coverage of evidence-based treatments for tobacco dependence among all 51 Medicaid programs (objective 27-8). The type of coverage for tobacco-dependence treatments offered by Medicaid has been reported since 1998, and most recently for 2003, from state surveys conducted by the Center for Health and Public Policy Studies at the University of California, Berkeley. All states and the District of Columbia (collectively referred to as states in this report) were resurveyed in 2005 regarding types of coverage and limitations in coverage since 1994. This report summarizes the results of that survey, which indicated that as of December 31, 2005, 1) 38 state Medicaid programs covered some tobacco-dependence treatment (i.e., counseling or medication) for all Medicaid recipients; 2) four states offered coverage only for pregnant women; 3) one state (Oregon) offered coverage for all medication and counseling treatments recommended by the 2000 PHS guideline; and 4) seven states (including Oregon) covered all recommended medications and at least one form of counseling. If the 2010 national health objective is to be achieved, states should offer or increase Medicaid coverage for treatment of tobacco dependence.     

Sex work involvement among women with long-term opioid injection drug dependence who enter opioid agonist treatment

Background  

Substitution with opioid-agonists (e.g., methadone) has shown to be an effective treatment for chronic long-term opioid dependency. Survival sex work, very common among injection drug users, has been associated with poor Opioid Agonist Treatment (OAT) engagement, retention and response. Therefore, this study was undertaken to determine factors associated with engaging in sex work among long-term opioid dependent women receiving OAT.     

Economic Evaluations of Pharmacologic Treatment for Opioid Use Disorder: A Systematic Literature Review

ObjectiveThe crisis of opioid use puts a strain on resources in the United States and worldwide. There are 3 US Food and Drug Administration–approved medications for treatment of opioid use disorder: methadone, buprenorphine, and injectable extended-release naltrexone (XR-NTX). The comparative effectiveness and cost vary considerably among these 3 medications. Economic evaluations provide evidence that help stakeholders efficiently allocate scarce resources. Our objective was to summarize recent health economic evidence of pharmacologic treatment of opioid use disorder interventions.MethodsWe searched PubMed for peer-reviewed studies in English from August 2015 through December 2019 as an update to a 2015 review. We used the Drummond checklist to evaluate and categorize economic evaluation study quality. We summarized results by economic evaluation methodology and pharmacologic treatment modality.ResultsWe identified 105 articles as potentially relevant and included 21 (4 cost-offset studies and 17 cost-effectiveness/cost-benefit studies). We found strengthened evidence on buprenorphine and methadone, indicating that these treatments are economically advantageous compared with no pharmacotherapy, but found limited evidence on XR-NTX. Only half of the cost-effectiveness studies used a generic preference-based measure of effectiveness, limiting broad comparison across diseases/disorders. The disease/disorder-specific cost-effectiveness measures vary widely, suggesting a lack of consensus on the value of substance use disorder treatment.ConclusionWe found studies that provide new evidence supporting the cost-effectiveness of buprenorphine compared with no pharmacotherapy. We found a lack of evidence supporting superior economic value for buprenorphine versus methadone, suggesting that both are attractive alternatives. Further economic research is needed on XR-NTX, as well as other emerging pharmacotherapies, treatment modalities, and dosage forms.