Determinants of successful chronic hepatitis C case finding among patients receiving opioid maintenance treatment in a primary care setting

Aims   Injection drug users are at high risk for chronic hepatitis C virus infection (CHC). Opioid maintenance treatment (OMT) offers a unique opportunity to screen for CHC. This study proposed the hypothesis that a general practitioner (GP) with special interest in addiction medicine can achieve CHC screening rates comparable to specialized centres and aimed to investigate determinants for a successful CHC case finding in a primary care setting.
Design and participants   Retrospective medical record analysis of 387 patients who received opioid maintenance therapy between 1 January 2002 and 31 May 2008 in a general practice in Zurich, Switzerland.
Measurements   Successful CHC assessment was defined as performance of hepatitis C virus (HCV) serology with consecutive polymerase chain reaction-based RNA and genotype recordings. The association between screening success and patient characteristics was assessed using multiple logistic regression.
Findings   Median (interquartile range) age and duration of OMT of the 387 (268 males) patients was 38.5 (33.6–44.5) years and 34 (11.3–68.0) months, respectively. Fourteen patients (3.6%) denied HCV testing and informed consent about screening was missing in 13 patients (3.4%). In 327 of 360 patients (90.8%) with informed consent a successful CHC assessment has been performed. Screening for HCV antibodies was positive in 136 cases (41.6%) and in 86 of them (63.2%) a CHC was present. The duration of OMT was an independent determinant of a successful CHC assessment.
Conclusions   In addicted patients a high CHC assessment rate in a primary care setting in Switzerland is feasible and opioid substitution provides an optimal framework.     

Opiates,cocaine and alcohol combinations in accidental drug overdose deaths in New York City, 1990-98

Aims  Accidental drug overdose contributes substantially to mortality among drug users. Multi-drug use has been documented as a key risk factor in overdose and overdose mortality in several studies. This study investigated the contribution of multiple drug combinations to overdose mortality trends.
Design  We collected data on all overdose deaths in New York City between 1990 and 1998 using records from the Office of the Chief Medical Examiner (OCME). We standardized yearly overdose death rates by age, sex and race to the 1990 census population for NYC to enable comparability between years relevant to this analysis.
Findings  Opiates, cocaine and alcohol were the three drugs most commonly attributed as the cause of accidental overdose death by the OCME, accounting for 97.6% of all deaths; 57.8% of those deaths were attributed to two or more of these three drugs in combination. Accidental overdose deaths increased in 1990–93 and subsequently declined slightly in 1993–98. Changes in the rate of multi-drug combination deaths accounted for most of the change in overdose death rates, whereas single drug overdose death rates remained relatively stable. Trends in accidental overdose death rates within gender and racial/ethnic strata varied by drug combination suggesting different patterns of multi-drug use among different subpopulations.
Conclusions  These data suggest that interventions to prevent accidental overdose mortality should address the use of drugs such as heroin, cocaine and alcohol in combination.     

The effectiveness of opioid maintenance treatment in prison settings: a systematic review

Aims To review evidence on the effectiveness of opioid maintenance treatment (OMT) in prison and post‐release. Methods Systematic review of experimental and observational studies of prisoners receiving OMT regarding treatment retention, opioid use, risk behaviours, human immunodeficiency virus (HIV)/hepatitis C virus (HCV) incidence, criminality, re‐incarceration and mortality. We searched electronic research databases, specialist journals and the EMCDDA library for relevant studies until January 2011. Review conducted according to Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) guidelines. Results Twenty‐one studies were identified: six experimental and 15 observational. OMT was associated significantly with reduced heroin use, injecting and syringe‐sharing in prison if doses were adequate. Pre‐release OMT was associated significantly with increased treatment entry and retention after release if arrangements existed to continue treatment. For other outcomes, associations with pre‐release OMT were weaker. Four of five studies found post‐release reductions in heroin use. Evidence regarding crime and re‐incarceration was equivocal. There was insufficient evidence concerning HIV/HCV incidence. There was limited evidence that pre‐release OMT reduces post‐release mortality. Disruption of OMT continuity, especially due to brief periods of imprisonment, was associated with very significant increases in HCV incidence. Conclusions Benefits of prison OMT are similar to those in community settings. OMT presents an opportunity to recruit problem opioid users into treatment, to reduce illicit opioid use and risk behaviours in prison and potentially minimize overdose risks on release. If liaison with community‐based programmes exists, prison OMT facilitates continuity of treatment and longer‐term benefits can be achieved. For prisoners in OMT before imprisonment, prison OMT provides treatment continuity.     

Retrospective follow-up of maternal deaths and their associated risk factors in a rural district of Tanzania

Summary
objective   To determine the maternal mortality rate in a rural district of Tanzania and to measure the incidence of causes of maternal mortality, the presence of risk factors and the relationship with social and demographic factors.
method   From January to December 1993 a retrospective recording of maternal deaths was completed using verbal autopsy and networking.
results   A total of 76 deaths were found which is equivalent to a maternal mortality ratio of 961 per 100,000 live births for this 12-month period of time. The leading causes of death were postpartum haemorrhage with retained placenta, anaemia, postpartum haemorrhage without retained placenta, AIDS complex and obstructed labour (in descending order of frequency). Maternal deaths were seen irrespective of group factors such as access to a main road, presence of antenatal risk factors and contact with health care personnel or a nearby facility before death. Mortality was also present both in home and hospital deliveries (excluding hospital referrals). Antenatal care had been received by 97.2% of the mothers who died after the second trimester. The referral rate even in the presence of a known antenatal risk factor was 34.6%. Patient compliance to the referral was only 44.4%. Mothers and their families followed strong cultural beliefs even when they were detrimental to the mother's health. Maternal deaths were proportionately higher among women >40 who were also gravid 5, but there was no significant increase in deaths in women < 19 years of age.
conclusion  Effective antenatal care, appropriate emergency treatment of complications, access to transportation and competent referral level care with adequate equipment encompass the most effective answers to reduction of maternal deaths at a district level.     

Comparing retention in treatment and mortality in people after initial entry to methadone and buprenorphine treatment

Aim   To compare retention in treatment and mortality among people entering methadone and buprenorphine treatment for opioid dependence.
Data sources   The Pharmaceutical Drugs of Abuse System (PHDAS) database records start- and end-dates of all episodes of methadone and buprenorphine treatment in New South Wales, and the National Death Index (NDI) records all reported deaths.
Methods   Data linkage study. First entrants to treatment between June 2002 and June 2006 were identified from the PHDAS database. Retention in treatment was compared between methadone and buprenorphine. Names were linked to the NDI database, and 'good matches' were identified. Deaths were classified as occurring during induction, maintenance and either post-methadone or post-buprenorphine, depending on the latest episode of treatment prior to death. The numbers of inductions into treatment, of total person-years spent in each treatment, and person-years post-methadone or buprenorphine, were calculated. Risk of death in different periods, and different treatments, was analysed using Poisson regression.
Results   A total of 5992 people entered their first episode of treatment—3349 (56%) on buprenorphine, 2643 on methadone. Median retention was significantly longer in methadone (271 days) than buprenorphine (40 days). During induction, the risk of death was lower for buprenorphine (relative risk = 0.114, 95% confidence interval = 0.002–0.938, P  = 0.02, Fisher's exact test). Risk of death was lowest during treatment, significantly higher in the first 12 months after leaving both methadone and buprenorphine. Beyond 12 months after leaving treatment, risk of death was non-significantly higher than during treatment.
Conclusions   Buprenorphine was safer during induction. Despite shorter retention in treatment, buprenorphine maintenance was not associated with higher risk of death.     

A multicentre study on the causes of death among Italian injecting drug users. AIDS has overtaken overdose as the principal cause of death

The causes of death among injecting drug users (IDUs) are still being discussed worldwide. We analysed the causes of death among IDUs attending 26 centres for drug users in North-Eastern Italy from 1985 to 1994. The study of a total number of 1,022 deaths reveals the following: (1) AIDS has become the primary cause of death among IDUs since 1991 and is rising even in an area with a moderate HIV seroprevalence; (2) the mean age of death in AIDS patients proved higher than among patients who died of other causes (which may be due to the long incubation period of AIDS); (3) our data do not reveal higher HIV seroprevalence among IDUs who died of overdose and suicide as opposed to IDUs who died of other causes; (4) the mortality rate in IDUs is significantly higher when compared to that of the general population in the same age group.     

Study of 2708 heroin-related deaths in north-eastern Italy 1985-98 to establish the main causes of death

Aims . To ascertain the causes of deaths among a very large cohort of heroin injecting drug users (IDUs) who, from 1985 to 1998, attended 36 Public Health Authority Centres for Drug Users (PCDUs) in north-eastern Italy.
Design . Retrospective analysis of data, obtained from the Annual Register of each Centre and the Municipal Registry Office of each local health district.
Setting . Thirty-six PCDUs in north-eastern Italy and Medical Service for Addictive Disorders of the University of Verona.
Participants . All IDUs who had sought medical care at least once in the PCDUs during the study period.
Findings . Of 2708 deaths, overdose was found to be the major cause (37%), followed by AIDS (32.5%) and road accidents (9.4%). The percentage of deaths due to AIDS increased steadily from 2.7% in 1985 to 42.2% in 1996, and then decreased to 16.9% in 1998. Deaths due to overdose remained almost constant. The average age of death per year rose from 26 in the mid eighties to 34 in 1998. The mortality rate among IDUs proved much higher compared to the general population of the same age (13-fold, 95% CI, 11.3-14.6). The proportion of all deaths attributable to regular use of illegal opiates in the 15-34 age group in the general population in 1991 was 16%. HIV prevalence was not a significant factor in suicides and deaths by overdose.
Conclusions . The mortality rate was 13 times greater than in the general population. To be female and to have dropped out of any kind of treatment proved an important risk factor for overdose. The fall in deaths from AIDS enhances the problem to prevent and treat HCV infection. Decisions in drug projects, in research and in training should be influenced by the strikingly high percentage of deaths due to drug use.     

Dental status and mortality in institutionalized elderly people

Background:   Inadequate dentition for mastication is one of the major issues associated with systemic health for institutionalized elderly people, but its prognostic value and related deaths have not been fully examined.
Methods:   Four hundred and three patients aged 65 and older were recruited from nine nursing homes and were prospectively followed up for morbidity and mortality for 5 years in Japan. These patients were classified into three groups according to dental status: patients who had adequate dentition with natural teeth only or natural teeth with partial dentures (Group A); those who were edentulous but wearing full dentures (Group B); and those who had inadequate dentition without dentures (Group C).
Results:   Dental status was strongly related to age, cognitive function and activities of daily living. After allowing for confounding effects, the 2-year risk of mortality among those in Group C was 1.84 times that of Group A (95% confidence interval 1.01–3.36, P  = 0.047). Furthermore, the 5-year mortality rate in Group C was higher than that in Group A, whereas that was not significant with a hazard ratio of 1.30 (0.90–1.88, P  = 0.168). The main causes of death were respiratory infections, which explained 14.1% of all causes of death in Group A, 14.3% in Group B and 18.3% in Group C. Any associations between a specific cause of death and the different dental status did not reach a significant level.
Conclusion:   Inadequate dental status is associated with high overall mortality. Our findings suggest that systemic attention to dental status should be recommended in institutionalized elderly people.     

Risk factors for in-hospital mortality of visceral leishmaniasis patients in eastern Uganda

Objective  To identify risk factors for in-hospital mortality in patients treated for visceral leishmaniasis (VL) in Uganda.
Methods  Retrospective analysis of VL patients' clinical data collected for project monitoring by Médecins Sans Frontières in Amudat, eastern Uganda.
Results  Between 2000 and 2005, of 3483 clinically suspect patients, 53% were confirmed with primary VL. Sixty-two per cent were children <16 years of age with a male/female ratio of 2.2. The overall case-fatality rate during pentavalent antimonial ( n  = 1641) or conventional amphotericin B treatment ( n  = 217) was 3.7%. There was no difference in the case-fatality rate between treatment groups ( P  > 0.20). The main risk factors for in-hospital death identified by a multivariate analysis were age <6 years and >15 years, concomitant tuberculosis or hepatopathy, and drug-related adverse events. The case-fatality rate among patients >45 years of age was strikingly high (29.0%).
Conclusion  Subgroups of VL patients at higher risk of death during treatment with drugs currently available in Uganda were identified. Less toxic drugs should be evaluated and used in these patients.     

Prevalence and clinical relevance of corrected QT interval prolongation during methadone and buprenorphine treatment: a mortality assessment study

Aims To determine the prevalence of corrected QT interval (QTc) prolongation among patients in opioid maintenance treatment (OMT) and to investigate mortality potentially attributable to QTc prolongation in the Norwegian OMT programme. Participants and setting Two hundred OMT patients in Oslo were recruited to the QTc assessment study between October 2006 and August 2007. The Norwegian register of all patients receiving OMT in Norway (January 1997–December 2003) and the national death certificate register were used to assess mortality. Mortality records were examined for the 90 deaths that had occurred among 2382 patients with 6450 total years in OMT. Design and measures The QTc interval was assessed by electrocardiography (ECG). All ECGs were examined by the same cardiologist, who was blind to patient history and medication. Mortality was calculated by cross‐matching the OMT register and the national death certificate register: deaths that were possibly attributable to QTc prolongation were divided by the number of patient‐years in OMT. Findings In the QTc assessment sample (n = 200), 173 patients (86.5%) received methadone and 27 (13.5%) received buprenorphine. In the methadone group, 4.6% (n = 8) had a QTc above 500 milliseconds; 15% (n = 26) had a QTc interval above 470 milliseconds; and 28.9% (n = 50) had a QTc above 450 milliseconds. All patients receiving buprenorphine (n = 27) had QTc results <450 milliseconds. A positive dose‐dependent association was identified between QTc length and dose of methadone, and all patients with a QTc above 500 milliseconds were taking methadone doses of 120 mg or more. OMT patient mortality, where QTc prolongation could not be excluded as the cause of death, was 0.06/100 patient‐years. Only one death among 3850 OMT initiations occurred within the first month of treatment. Conclusion Of the methadone patients, 4.6% had QTc intervals above 500 milliseconds. The maximum mortality attributable to QTc prolongation was low: 0.06 per 100 patient‐years.     

Mortality risk up to 25 years after initiation of treatment among 420 Swedish women with alcohol addiction

Aims   Women treated for alcohol addiction have mortality rates three to five times those of women from the general population (GP). However, these figures may be inflated because socially disadvantaged women with advanced drinking careers are over-represented in previous studies. Our aim was to study the long-term mortality of socially relatively well-functioning patients coming to their first treatment, compared to matched GP controls.
Design   The mortality rates and causes of death were compared between patients and their matched GP controls, using data from the Causes of Death Register throughout the follow-up period (0–25 years).
Setting   A specialized treatment programme for women only, called 'Early treatment for Women with Alcohol Addiction' (EWA) at the Karolinska Hospital, Stockholm, Sweden.
Participants   Subjects ( n  = 420) receiving their first treatment at the EWA programme, compared to a group of matched GP women ( n  = 2037).
Findings   The women patients had significantly higher mortality than matched GP controls throughout the whole follow-up period, with a relative risk of 2.4. However, the younger women had four times higher mortality than their matched controls. The peak of deaths occurred during the first 5 years, and alcohol-related causes of death were highly over-represented, as were uncertain suicides and accidents.
Conclusions   First-time-treated women with alcohol addiction have a substantially lower mortality than reported previously from clinical samples, except for the youngest group. Our figures were corrected for confounding factors such as socio-demographic status. We believe our results could apply to broader groups of heavy drinking women, inside or outside specialized treatment settings.     

Back-projection estimates of the number of dependent heroin users in Australia

Aims. To plan an appropriate response to heroin use in Australia, good estimates are needed of the numbers of dependent heroin users, the group who are most in need of treatment, most at risk of fatal opioid overdose and most at risk of contracting and transmitting blood-borne viruses. Methods. Back-projection methods were used to estimate the numbers of people starting dependent heroin injecting in Australia between 1960 and 1997. Separate analyses were based on national opioid overdose deaths and numbers of new entrants to methadone treatment in New South Wales (NSW). Estimates of the rates at which dependent heroin users cease heroin use, commence methadone treatment or die from opioid overdoses were estimated from external data sources. Results. Back-projection estimates derived from opioid overdose deaths indicated that there were 104 000 (lower limit of 72 000 and upper limit of 157 000) people who were heroin dependent in Australia between 1960 and 1997. Of these it was estimated that 67 000 (39 000-120 000) were still heroin dependent at the end of 1997. Back-projection estimates based on numbers of new entrants to methadone treatment in NSW indicated that there were 108 000 (82 000-141 000) heroin-dependent people in Australia between 1960 and 1997, of whom 71 000 (47 000-109 000) were estimated to be heroin dependent at the end of 1997. Both analyses indicated that the number of heroin-dependent people in Australia has increased substantially from the early 1970s onwards. Conclusions. Back-projection estimates based on analyses of treatment entries and opioid overdose deaths provide an additional method for estimating the numbers of heroin-dependent people in the population. The addition of these methods to existing methods, using different data sources and statistical methods, should improve consensus estimates of the numbers of heroin-dependent people.     

Serious adverse events in the Australian National Evaluation of Pharmacotherapies for Opioid Dependence (NEPOD)

Aims The study estimated serious adverse event (SAE) rates among entrants to pharmacotherapies for opioid dependence, during treatment and after leaving treatment. Design A longitudinal study based on data from 12 trials included in the Australian National Evaluation of Pharmacotherapies for Opioid Dependence (NEPOD). Participants and settings A total of 1244 heroin users and methadone patients treated in hospital, community and GP settings. Intervention Six trials included detoxification; all included treatment with methadone, buprenorphine, levo‐alpha‐acetyl‐methadol (LAAM) or naltrexone. Findings During 394 person‐years of observation, 79 SAEs of 28 types were recorded. Naltrexone participants experienced 39 overdoses per 100 person‐years after leaving treatment (44% occurred within 2 weeks after stopping naltrexone). This was eight times the rate recorded among participants who left agonist treatment. Rates of all other SAEs were similar during treatment versus out of treatment, for both naltrexone‐treated and agonist‐treated participants. Five deaths occurred, all among participants who had left treatment, at a rate of six per 100 person‐years. Total SAE rates during naltrexone and agonist treatments were similar (20, 14 per 100 person‐years, respectively). Total SAE and death rates observed among participants who had left treatment were three and 19 times the corresponding rates during treatment. Conclusions Individuals who leave pharmacotherapies for opioid dependence experience higher overdose and death rates compared with those in treatment. This may be due partly to a participant self‐selection effect rather than entirely to pharmacotherapy being protective. Clinicians should alert naltrexone treatment patients in particular about heroin overdose risks. Duty of care may extend beyond cessation of dosing.     

Factors associated with death among HIV-uninfected TB patients in Thailand, 2004–2006

Objectives  In countries with both TB and human immunodeficiency virus (HIV) epidemics, HIV is known to be the most powerful risk factor for death during tuberculosis (TB) treatment. Few recent studies have evaluated risk factors for death among HIV-uninfected TB patients in these countries. We analysed data from a multi-province demonstration project in Thailand to answer this question.
Method  We prospectively collected data from HIV-uninfected TB patients treated for TB in four provinces and the national infectious diseases hospital in Thailand from 2004–2006. Standard WHO definitions were used to classify treatment outcomes. We used log-binomial multivariate regression to calculate adjusted relative risk (aRR) and 95% confidence intervals (CI) for factors associated with death.
Results  Of 5318 cases, 441 (8%) died during TB treatment. The mean age was 47 years (range 8 months–97 years). Multidrug-resistant (MDR)-TB was diagnosed in 62 (1%). In multivariate analysis, patients older than 44 years were significantly more likely to die than patients aged 15–44 years [age 45–64, aRR 2.9 (CI 2.2–3.8)] [age > 64 years, aRR 5.0 (CI 3.9–6.6)]. Other independent risk factors for death included Thai nationality [aRR 3.9 (CI 1.6–9.5)], MDR-TB [aRR 2.8 (CI 1.7–4.8)], not being married [aRR 1.4 (CI 1.2–1.7)], and living in Chiang Rai province [aRR 2.7 (CI 1.7–4.4)].
Conclusions  The death rate was high among HIV-uninfected TB patients in Thailand. Efforts to improve TB diagnosis and treatment in the elderly and to improve MDR-TB treatment may help reduce mortality.     

Risk of fatal overdose during and after specialist drug treatment: the VEdeTTE study, a national multi-site prospective cohort study

BACKGROUND: Specialist drug treatment is critical to overdose prevention; methadone maintenance is effective, but we lack evidence for other modalities. We evaluate the impact of a range of treatments for opiate dependence on overdose mortality. METHODS: Prospective cohort study of 10,454 heroin users entering treatment 1998-2001 in Italy followed-up for 10,208 person-years in treatment and 2,914 person-years out of treatment. Standardized overall mortality ratios (SMR) estimate excess mortality risk for heroin users in and out of treatment compared to the general population. Cox models compare the hazard ratio (HR) of overdose between heroin users in treatment and out of treatment. RESULTS: There were 41 overdose deaths, 10 during treatment and 31 out of treatment, generating annual mortality rates of 0.1% and 1.1% and SMRs of 3.9 [95% confidence interval (CI) 2.8-5.4] and 21.4 (16.7-27.4), respectively. Retention in any treatment was protective against overdose mortality (HR 0.09 95% CI 0.04-0.19) compared to the risk of mortality out of treatment, independent of treatment type and potential confounders. The risk of a fatal overdose was 2.3% in the month immediately after treatment and 0.77% in the subsequent period; compared to the risk of overdose during treatment the HR was 26.6 (95% CI 11.6-61.1) in the month immediately following treatment and 7.3 (3.3-16.2) in the subsequent period. CONCLUSIONS: We demonstrate that a range of treatments for heroin dependence reduces overdose mortality risk. However, the considerable excess mortality risk in the month following treatment indicates the need for greater health education of drug users and implementation of relapse and overdose death prevention programmes. Further investigation is needed to measure and weigh the potential benefits and harms of short-term therapies for opiate use.     

Randomized controlled trial comparing the effectiveness and safety of intranasal and intramuscular naloxone for the treatment of suspected heroin overdose

Aims   Traditionally, the opiate antagonist naloxone has been administered parenterally; however, intranasal (i.n.) administration has the potential to reduce the risk of needlestick injury. This is important when working with populations known to have a high prevalence of blood-borne viruses. Preliminary research suggests that i.n. administration might be effective, but suboptimal naloxone solutions were used. This study compared the effectiveness of concentrated (2 mg/ml) i.n. naloxone to intramuscular (i.m.) naloxone for suspected opiate overdose.
Methods   This randomized controlled trial included patients treated for suspected opiate overdose in the pre-hospital setting. Patients received 2 mg of either i.n. or i.m. naloxone. The primary outcome was the proportion of patients who responded within 10 minutes of naloxone treatment. Secondary outcomes included time to adequate response and requirement for supplementary naloxone. Data were analysed using multivariate statistical techniques.
Results   A total of 172 patients were enrolled into the study. Median age was 29 years and 74% were male. Rates of response within 10 minutes were similar: i.n. naloxone (60/83, 72.3%) compared with i.m. naloxone (69/89, 77.5%) [difference: −5.2%, 95% confidence interval (CI) −18.2 to 7.7]. No difference was observed in mean response time (i.n.: 8.0, i.m.: 7.9 minutes; difference 0.1, 95% CI −1.3 to 1.5). Supplementary naloxone was administered to fewer patients who received i.m. naloxone (i.n.: 18.1%; i.m.: 4.5%) (difference: 13.6%, 95% CI 4.2–22.9).
Conclusions   Concentrated intranasal naloxone reversed heroin overdose successfully in 82% of patients. Time to adequate response was the same for both routes, suggesting that the i.n. route of administration is of similar effectiveness to the i.m. route as a first-line treatment for heroin overdose.