Cost-Effectiveness of Take-Home Naloxone for the Prevention of Overdose Fatalities among Heroin Users in the United Kingdom

Background: Heroin overdose is a major cause of premature death. Naloxone is an opioid antagonist that is effective for the reversal of heroin overdose in emergency situations and can be used by nonmedical responders. Objective: Our aim was to assess the cost-effectiveness of distributing naloxone to adults at risk of heroin overdose for use by nonmedical responders compared with no naloxone distribution in a European healthcare setting (United Kingdom). Methods: A Markov model with an integrated decision tree was developed based on an existing model, using UK data where available. We evaluated an intramuscular naloxone distribution reaching 30% of heroin users. Costs and effects were evaluated over a lifetime and discounted at 3.5%. The results were assessed using deterministic and probabilistic sensitivity analyses. Results: The model estimated that distribution of intramuscular naloxone, would decrease overdose deaths by around 6.6%. In a population of 200,000 heroin users this equates to the prevention of 2,500 premature deaths at an incremental cost per quality-adjusted life year (QALY) gained of £899. The sensitivity analyses confirmed the robustness of the results. Conclusions: Our evaluation suggests that the distribution of take-home naloxone decreased overdose deaths by around 6.6% and was cost-effective with an incremental cost per QALY gained well below a £20,000 willingness-to-pay threshold set by UK decision-makers. The model code has been made available to aid future research. Further study is warranted on the impact of different formulations of naloxone on cost-effectiveness and the impact take-home naloxone has on the wider society.     

Attitudes about prescribing take-home naloxone to injection drug users for the management of heroin overdose: a survey of street-recruited injectors in the San Francisco Bay Area

Naloxone, an injectable opiate antagonist, can immediately reverse an opiate overdose and prevent overdose death. We sought to determine injection drug users’ (IDUs) attitudes about being prescribed take-home naloxone. During November 1999 to February 2000, we surveyed 82 street-recruited IDUs from the San Francisco Bay Area of California who had experienced one or more heroin overdose events. We used a questiomaire that included structured and open-ended questions. Most respondents (89%) had witnessed an overdose, and 90% reported initially attempting lay remedies in an effort to help companions survive. Only 51% reported soliciting emergency assistance (calling 911) for the last witnessed overdose, with most hesitating due to fear of police involvement. Of IDUs surveyed, 87% were strongly in favor of participating in an overdose management training program to receive take-home naloxone and training in resuscitation techniques. Nevertheless, respontdents expressed a variety of concerning attitudes. If provided naloxone, 35% predicted that they might feel comfortable using greater amounts of heroin, 62% might be less inclined to call 911 for an overdose, 30% might leave an overdose victim after naloxone resuscitation, and 46% might not be able to dissuade the victim from using heroin again to alleviate with drawal symptoms induced by naloxone. Prescribing take-home naloxone to IDUs with training in its use and in resuscitation techniques may represent a life-saving, peer-based adjunct to accessing emergency services. Nevertheless, strategies for overcoming potential risks associated with the use of take-home naloxone would need to be emphasized in an overdose management training program.     

Naloxone distribution and cardiopulmonary resuscitation training for injection drug users to prevent heroin overdose death: A pilot intervention study

Fatal heroin overdose has become a leading cause of death among injection drug users (IDUs). Several recent feasibility studies have concluded that naloxone distribution programs for heroin injectors should be implemented to decrease heroin overdose deaths, but there have been no prospective trials of such programs in North America. This pilot study was undertaken to investigate the safety and feasibility of training injection drug using partners to perform cardiopulmonary resuscitation (CPR) and administer naloxone in the event of heroin overdose. During May and June 2001, 24 IDUs (12 pairs of injection partners) were recruited from street settings in San Francisco. Participants took part in 8-hour training in heroin overdose prevention, CPR, and the use of naloxone. Following the intervention, participants were prospectively followed for 6 months to determine the number and outcomes of witnessed heroin overdoses, outcomes of participant interventions, and changes in participants’ knowledge of overdose and drug use behavior. Study participants witnessed 20 heroin overdose events during 6 months follow-up. They performed CPR in 16 (80%) events, administered naloxone in 15 (75%) and did one or the other in 19 (95%). All overdose victims survived. Knowledge about heroin overdose management increased, whereas heroin use decreased. IDUs can be trained to respond to heroin overdose emergencies by performing CPR and administering naloxone. Future research is needed to evaluate the effectiveness of this peer intervention to prevent fatal heroin overdose.     

Attitudes of emergency medical service providers toward naloxone distribution programs

Training and distributing naloxone to drug users is a promising method for reducing deaths associated with heroin overdose. Emergency Medical Service (EMS) providers have experience responding to overdose, administering naloxone, and performing clinical management of the patient. Little is known about the attitudes of EMS providers toward training drug users to use naloxone. We conducted an anonymous survey of 327 EMS providers to assess their attitudes toward a pilot naloxone program. Of 176 who completed the survey, the majority were male (79%) and Caucasian (75%). The average number of years working as an EMS provider was 7 (SD=6). Overall attitudes toward training drug users to administer naloxone were negative with 56% responding that this training would not be effective in reducing overdose deaths. Differences in attitudes did not vary by gender, level of training, or age. Providers with greater number of years working in EMS were more likely to view naloxone trainings as effective in reducing overdose death. Provider concerns included drug users’ inability to properly administer the drug, program condoning and promoting drug use, and unsafe disposal of used needles. Incorporating information about substance abuse and harm reduction approaches in continuing education classes may improve the attitudes of provider toward naloxone training programs.     

Acceptability of prison-based take-home naloxone programmes among a cohort of incarcerated men with a history of regular injecting drug use

Background

Take-home naloxone (THN) programmes are an evidence-based opioid overdose prevention initiative. Elevated opioid overdose risk following prison release means release from custody provides an ideal opportunity for THN initiatives. However, whether Australian prisoners would utilise such programmes is unknown. We examined the acceptability of THN in a cohort of male prisoners with histories of regular injecting drug use (IDU) in Victoria, Australia.

Methods

The sample comprised 380 men from the Prison and Transition Health (PATH) Cohort Study; all of whom reported regular IDU in the 6 months prior to incarceration. We asked four questions regarding THN during the pre-release baseline interview, including whether participants would be willing to participate in prison-based THN. We describe responses to these questions along with relationships between before- and during-incarceration factors and willingness to participate in THN training prior to release from prison.

Results

Most participants (81%) reported willingness to undertake THN training prior to release. Most were willing to resuscitate a friend using THN if they were trained (94%) and to be revived by a trained peer (91%) using THN. More than 10 years since first injection (adjusted odds ratio [AOR] 2.22, 95%CI 1.03–4.77), having witnessed an opioid overdose in the last 5 years (AOR 2.53, 95%CI 1.32–4.82), having ever received alcohol or other drug treatment in prison (AOR 2.41, 95%CI 1.14–5.07) and injecting drugs during the current prison sentence (AOR 4.45, 95%CI 1.73–11.43) were significantly associated with increased odds of willingness to participate in a prison THN programme. Not specifying whether they had injected during their prison sentence (AOR 0.37, 95%CI 0.18–0.77) was associated with decreased odds of willingness to participate in a prison THN training.

Conclusion

Our findings suggest that male prisoners in Victoria with a history of regular IDU are overwhelmingly willing to participate in THN training prior to release. Factors associated with willingness to participate in prison THN programmes offer insights to help support the implementation and uptake of THN programmes to reduce opioid-overdose deaths in the post-release period.

     

Risk of death in prisoners after release from jail

OBJECTIVE: To compare the risk of death in a cohort of Western Australian released prisoners with the risk experienced by the general population of Western Australia. METHODS: A cohort study of prisoners in Western Australia whose last date of release ranged from 1 January 1994 to 1 January 1999. Overall mortality and cause of death were determined by data linkage to the Registrar General's record of deaths. RESULTS: Aboriginal prisoners had a significantly lower survival rate after release than non-Aboriginal prisoners (p < 0.0001). When compared with their peers in the Western Australian community, both Aboriginal and non-Aboriginal prisoners were found to have an increased relative risk of death. Female non-Aboriginal released prisoners aged between 20 and 40 years were 17.8 (95% CI 8.1-27.5) times more likely to die than other female non-Aboriginals in Western Australia in the same age range. Male non-Aboriginal prisoners aged 20-40 years were 6.3 (95% CI 5.2-7.4) times more likely to die than their counterparts in the WA community. Female Aboriginal released prisoners were 3.4 (95% CI 1.2-5.6) times more likely to die than their peers, while male Aboriginal released prisoners were 2.9 (95% CI 2.2-3.5) times more likely to die. In their first six months after release, female non-Aboriginal prisoners aged 20 to 40 years were 69.1 (95% CI 17.9-120.3) times more likely to die than their counterparts in the WA community. The main causes of excess death were related to drug and alcohol abuse. CONCLUSION: All prisoners were at greater than expected relative risk of death after release from prison, with female non-Aboriginal prisoners at particularly high relative risk.     

Risk of death for young ex‐prisoners in the year following release from adult prison

Background : In the community, all‐cause mortality rates among those younger than 25 years are considerably lower than those of older adults and are largely attributable to risk‐taking behaviours. However, given the unique health profiles of prisoners, this pattern may not be replicated among those leaving prison. We compared rates and patterns of mortality among young and older ex‐prisoners in Queensland, Australia. Methods : We linked the identities of 42,015 persons (n=14,920 aged <25 years) released from adult prisons in Queensland, Australia with the Australian National Death Index. Observations were censored at death or 365 days from release. We used Cox proportional hazards regression to explore associations between mortality and demographic and criminographic characteristics. We used indirect standardisation to compare rates of all‐cause mortality for both age groups with those for the general population. We calculated proportion of deaths across specific causes for each age group and relative risks for each cause for young versus older ex‐prisoners. Results : Being young was protective against death from all causes (AHR=0.7, 95% CI 0.5–0.8); however, the elevation in risk of all‐cause death relative to the general population was greater for those aged less than 25 years (SMR=6.5, 95% CI 5.3–8.1) than for older ex‐prisoners (SMR=4.0, 95% CI 3.5–4.5). Almost all deaths in young ex‐prisoners and the majority of those in older ex‐prisoners were caused by injury or poisoning. Conclusions : Young people are at markedly increased risk of death after release from prison and the majority of deaths are preventable.     

Fatal heroin-related overdose in San Francisco, 1997–2000: a case for targeted intervention

Heroin-related overdose is the single largest cause of accidental death in San Francisco. We examined demographic, location, nontoxicological, and toxicological characteristics of opiate overdose deaths in San Francisco, California. Medical examiner’s case files for every opioid-positive death from July 1, 1997, to June 30, 2000, were reviewed and classified as overdose deaths or other. Demographic variables were compared to two street-based studies of heroin users and to census data. From 1997 to 2000, of all heroin-related overdoses in San Francisco 47% occurred in low-income residential hotels; 36% occurred in one small central area of the city. In 68% of deaths, the victim was reportedly alone. When others were present between last ingestion of heroin and death, appropriate responses were rare. In three cases, police arrested the person who called emergency services or others present on the scene. We recommend the development of overdose response training targeted at heroin users and those close to them, including the staff of residential hotels.     

Inpatient hospital use in the first year after release from prison: a Western Australian population-based record linkage study

Objective: To describe three aspects of inpatient use for ex‐prisoners within the first 12 months of release from prison: the proportion of released prisoners who were hospitalised; the amount of resources used (bed days, separations and cost); and the most common reasons for hospitalisation. Methods: Secondary analysis of whole‐population linked prison and inpatient data from the Western Australian Data Linkage System. The main outcome measure was first inpatient admission within 12 months of release from prison between 2000 and 2002 and related resource use. Results: One in five adults released from Western Australian prisons between 2000 and 2002 were hospitalised in the 12 months that followed, which translated into 12,074 inpatient bed days, 3,426 separations and costs of $10.4 million. Aboriginals, females and those released to freedom were most at risk of hospitalisation. Mental health disorders such as schizophrenia and depression, and injuries involving the head or face and/or fractures, accounted for 58.9% of all bed days. Ex‐prisoners were 1.7 times more likely to be hospitalised during a year than Western Australia's general adult population of roughly the same age. Conclusions: Using whole‐population administrative linked health and justice data, our findings show that prisoners are vulnerable to hospitalisation in the 12‐month period following their release from prison, particularly Aboriginals, females and those with known mental health problems. Implications: Further research is needed to assess whether contemporary services to support community re‐entry following incarceration have led to a measurable reduction in hospital contacts, especially for the subgroups identified in this study.     

An observational prospective cohort study of naloxone use at witnessed overdoses,Kazakhstan, Kyrgyzstan,Tajikistan, Ukraine

ObjectiveTo determine whether participation in the United Nations Office on Drugs and Crime (UNODC) and the World Health Organization’s (WHO) Stop Overdose Safely (S-O-S) take-home naloxone training project in Kazakhstan, Kyrgyzstan, Tajikistan and Ukraine resulted in naloxone use at witnessed opioid overdoses.MethodsAn observational prospective cohort study was performed by recruiting participants in the implementation of the S-O-S project, which was developed as part of the broader S-O-S initiative. Training included instruction on overdose responses and naloxone use. Study participants were followed for 6 months after completing training. The primary study outcome was participants’ naloxone use at witnessed overdoses, reported at follow-up.FindingsBetween 400 and 417 S-O-S project participants were recruited in each country. Overall, 84% (1388/1646) of participants were interviewed at 6-month follow-up. The percentage who reported witnessing an overdose between baseline and follow-up was 20% (71/356) in Tajikistan, 33% (113/349) in Kyrgyzstan, 37% (125/342) in Ukraine and 50% (170/341) in Kazakhstan. The percentage who reported using naloxone at their most recently witnessed overdose was 82% (103/125) in Ukraine, 89% (152/170) in Kazakhstan, 89% (101/113) in Kyrgyzstan and 100% (71/71) in Tajikistan.ConclusionImplementation of the UNODC–WHO S-O-S training project in four low- to middle-income countries resulted in the reported use of take-home naloxone at around 90% of witnessed opioid overdoses. The percentage varied between countries but was generally higher than found in previous studies. Take-home naloxone is particularly important in countries where emergency medical responses to opioid overdoses may be limited.     

A Comparison of Liver Disease Mortality With HIV and Overdose Mortality Among Georgia Prisoners and Releasees: A 2-Decade Cohort Study of Prisoners Incarcerated in 1991

Objectives. We investigated whether eventual causes of death among a cohort of inmates imprisoned in the southeastern United States differed from those in previous prisoner studies.Methods. We matched 23 510 prisoners in Georgia, a state with historically low levels of heroin consumption but moderate amounts of injection drug use, who were incarcerated on June 30, 1991, to death registries through 2010. Main exposure was 4-year time intervals over 2 decades of observation; main outcome was mortality from liver disease, HIV, and overdose.Results. Although the HIV-related mortality rate exceeded that from liver-related conditions before 2003, liver disease subsequently surpassed HIV as a cause of death. Among 3863 deaths, 22 (0.6%) occurred within 2 weeks after release from prison. Of these, only 2 were caused by accidental poisoning (likely drug overdose). Cardiovascular disease and cancer were the most frequent causes of death in this aging cohort.Conclusions. Our study design deemphasized immediate deaths but highlighted long-term sequelae of exposure to viral hepatitis and alcohol. Treating hepatitis C and implementing interventions to manage alcohol use disorders may improve survival among prisoners in the Southeast.Drug use, incarceration, and mortality are intertwined: the use of illicit drugs can result in both incarceration and premature death. A 2010 international meta-analysis of prisoners'' survival after their release into the community emphasized mortality from overdose in the 2 weeks following discharge, possibly attributable to loss of opiate tolerance after forced sobriety in prison,1 but a more recent publication illustrates how this pattern may vary among subpopulations.2Long-term consequences of injection drug use include hepatitis C and HIV infection. In the United States, sexual exposure is the most common mode of HIV transmission, but the hepatitis C epidemic is mainly driven by the injection of drugs, even if the drug use is not sustained.3 HIV prevalence is 3 times as common among prisoners as among the general population,4 but hepatitis C prevalence is 13 times as high.5,6 Sequelae that could lead to death from hepatitis C typically occur 2 to 4 decades after injection drug use was initiated. Little is known about the long-term survival of inmates, particularly in the southeastern United States, where historical and recent patterns of drug use may differ from those in other regions.In contrast with other studies that have examined cohorts of released inmates, we sought to assess long-term prisoner survival by retrospectively following a cohort composed of a cross section of all imprisoned persons in the state of Georgia on a single day in 1991. In a previous study, we did not observe significantly higher mortality among members of this cohort immediately after release from prison than in the subsequent postrelease period.7 Multiple sources suggest that heroin use is less common in Georgia than in other states. Between 2002 and 2012, consistently fewer than 6.5% of men jailed in Atlanta, the capital of and largest city in Georgia, had evidence of heroin in their urine samples.8,9 The prevalence of opiate use in Atlanta was among the lowest for any city studied in the past decade by the Office of the National Drug Control Policy.8–10 In particular, heroin use was lower than in Washington State, site of a previous study of former inmate mortality.11 According to the Treatment Episode Data Set–Admissions for 1992 to 2010 from the Substance Abuse and Mental Health Services Administration, heroin addiction accounted for only 1.6% of admissions for drug rehabilitation in Georgia, but 9.7% in Washington State and 14.2% nationally.12In assessment of risk for hepatitis C, needle use—whether for heroin, cocaine, or another drug—is more important than what is injected. Needle use in Georgia is not uncommon. According to population-wide National Survey on Drug Use and Health data for 2002 to 2009, 1.1% of Georgians have ever used a needle to inject drugs, including cocaine—a moderate rate compared with the frequency in Washington State, where lifetime prevalence is 2.7%, and nationally, where prevalence is 1.6%.13 State-level data on needle use prior to 2002 are not publically available from the Substance Abuse and Mental Health Services Administration.The prevalence of hepatitis C in the Georgia general population is moderately high, especially in Atlanta. At Grady Memorial Hospital, the safety net charity hospital for Atlanta, the prevalence of hepatitis C among ambulatory primary care patients is 7%. A liver clinic established at this hospital saw 807 unique patients in its first 5 years of existence and was still receiving 60 new patient referrals each month through 2010.14 Three quarters of the patients were African American, and most patients were born between 1945 and 1965; 64% were former drug users, and only 4% were currently using.14 High prevalence of hepatitis C in this baby boomer birth cohort probably reflects time-limited parenteral drug use decades ago, perhaps as early as the Vietnam war era.15 Despite relatively low levels of heroin use in the state, we hypothesized that the prevalence of hepatitis C would be high among inmates in the Georgia prison system who were born between 1945 and 1965.We sought to describe the leading causes of death over 2 decades in a large cohort of all Georgians who were in state prisons on June 30, 1991, and to evaluate whether the immediate mortality following prison discharge was low, because Georgia is a state with low heroin use. In light of the moderate background rates of injection drug use in Georgia, we hypothesized that mortality from liver-related causes would rise over time as the cohort aged. Our first aim was to rank the causes of death and categorize which deaths occurred in prison, immediately after release, and subsequently. Second, we compared deaths from liver disease to those from HIV in 4-year intervals between 1991 and 2010.     

Drug-related mortality and fatal overdose risk: Pilot cohort study of heroin users recruited from specialist drug treatment sites in London

Fatal overdose and drug-related mortality are key harms associated with heroin use, especially injecting drug use (IDU), and are a significant contribution to premature mortality among young adults. Routine mortality statistics tend to underreport the number of overdose deaths and do not reflect the wider causes of death associated with heroin use. Cohort studies could provide evidence for interpreting trends in routine mortality statistics and monitoring the effectiveness of strategies that aim to reduce drug-related deaths. We aimed to conduct a retrospective mortality cohort study of heroin users recruited from an anonymous reporting system from specialist drug clinics. Our focus was to test whether (1) specialist agencies would agree to participate with a mortality cohort study, (2) a sample could be recruited to achieve credible estimates of the mortality rate, and (3) ethical considerations could be met. In total, 881 heroin users were recruited from 15 specialist drug agencies. The overall mortality rate of the cohort of heroin users was 1.6 (95% confidence interval [CI], 1.1 to 2.2.) per 100 person-years. Mortality was higher among males, heroin users older than 30 years, and injectors, but not significantly higher after adjustment in a Cox proportional hazard model. Among the 33 deaths, 17 (52%) were certified from a heroin/methadone or opiate overdose, 4 (12%) from drug misuse, 4 (12%) unascertained, and 8 (24%) unrelated to acute toxic effects of drug use. Overall, the overdose mortality rate was estimated to be at least 1.0 per 100 person-years. The standardized mortality ratio (SMR) was 17 times higher for female and male heroin users in the cohort compared to mortality in the non-heroin-using London population aged 15–59 years. The pilot study showed that these studies are feasible and ethical, and that specialist drug agencies could have a vital role to play in the monitoring of drug-related mortality.