Sheila M. Bird

Meta-analysis of drug-related deaths soon after release from prison

Aims The transition from prison back into the community is particularly hazardous for drug-using offenders whose tolerance for heroin has been reduced by imprisonment. Studies have indicated an increased risk of drug-related death soon after release from prison, particularly in the first 2 weeks. For precise, up-to-date understanding of these risks, a meta-analysis was conducted on the risk of drug-related death in weeks 1 + 2 and 3 + 4 compared with later 2-week periods in the first 12 weeks after release from prison. Methods English-language studies were identified that followed up adult prisoners for mortality from time of index release for at least 12 weeks. Six studies from six prison systems met the inclusion criteria and relevant data were extracted independently. Results These studies contributed a total of 69 093 person-years and 1033 deaths in the first 12 weeks after release, of which 612 were drug-related. A three- to eightfold increased risk of drug-related death was found when comparing weeks 1 + 2 with weeks 3–12, with notable heterogeneity between countries: United Kingdom, 7.5 (95% CI: 5.7–9.9); Australia, 4.0 (95% CI: 3.4–4.8); Washington State, USA, 8.4 (95% CI: 5.0–14.2) and New Mexico State, USA, 3.1 (95% CI: 1.3–7.1). Comparing weeks 3 + 4 with weeks 5–12, the pooled relative risk was: 1.7 (95% CI: 1.3–2.2). Conclusions These findings confirm that there is an increased risk of drug-related death during the first 2 weeks after release from prison and that the risk remains elevated up to at least the fourth week.

The impact of study size on meta-analyses: examination of underpowered studies in Cochrane reviews.

Background Most meta-analyses include data from one or more small studies that, individually, do not have power to detect an intervention effect. The relative influence of adequately powered and underpowered studies in published meta-analyses has not previously been explored. We examine the distribution of power available in studies within meta-analyses published in Cochrane reviews, and investigate the impact of underpowered studies on meta-analysis results. Methods and Findings For 14,886 meta-analyses of binary outcomes from 1,991 Cochrane reviews, we calculated power per study within each meta-analysis. We defined adequate power as ≥50% power to detect a 30% relative risk reduction. In a subset of 1,107 meta-analyses including 5 or more studies with at least two adequately powered and at least one underpowered, results were compared with and without underpowered studies. In 10,492 (70%) of 14,886 meta-analyses, all included studies were underpowered; only 2,588 (17%) included at least two adequately powered studies. 34% of the meta-analyses themselves were adequately powered. The median of summary relative risks was 0.75 across all meta-analyses (inter-quartile range 0.55 to 0.89). In the subset examined, odds ratios in underpowered studies were 15% lower (95% CI 11% to 18%, P<0.0001) than in adequately powered studies, in meta-analyses of controlled pharmacological trials; and 12% lower (95% CI 7% to 17%, P<0.0001) in meta-analyses of controlled non-pharmacological trials. The standard error of the intervention effect increased by a median of 11% (inter-quartile range −1% to 35%) when underpowered studies were omitted; and between-study heterogeneity tended to decrease. Conclusions When at least two adequately powered studies are available in meta-analyses reported by Cochrane reviews, underpowered studies often contribute little information, and could be left out if a rapid review of the evidence is required. However, underpowered studies made up the entirety of the evidence in most Cochrane reviews.

Influence of Alcohol on the Progression of Hepatitis C Virus Infection: A Meta-analysis

BACKGROUND & AIMS A convincing, yet inconsistent, pattern has emerged that demonstrates increased progression of HCV-related liver disease with heavy alcohol use. The aim was to perform a meta-analysis to quantify the effect of alcohol on cirrhosis risk among persons infected with HCV. METHODS A meta-analysis of 20 articles, involving more than 15,000 HCV chronically infected persons, published between 1995 and 2004 was undertaken to explore the relationship between advanced liver disease and the consumption of alcohol. RESULTS The pooled relative risk of cirrhosis associated with heavy alcohol intake (defined in the range of at least 210-560 g per week) was 2.33 (95% confidence interval, 1.67-3.26) by the random effects model. The risk of HCV-related liver disease associated with heavy alcohol intake increased with severity of the outcome; the lowest (1.63; 95% confidence interval, 1.22-2.17) and highest (3.54; 2.14-5.85) pooled relative risk estimates were obtained for advanced fibrosis and decompensated cirrhosis, respectively. The regression effect of alcohol might, however, be underestimated in studies investigating the risk of HCV-related cirrhosis because they necessarily include patients undergoing liver biopsy and could therefore under-represent heavy alcohol users. CONCLUSIONS The evidence overwhelmingly shows a worsened outcome for those with chronic HCV and concurrent alcohol use. Studies varied widely in their definition of significant alcohol intake, and so the true threshold above which alcohol accelerates HCV disease progression remains uncertain. Alcohol consumption should be minimized as much as possible in those who have chronic HCV until a safe threshold is more definitively determined.

Modeling the current and future disease burden of hepatitis C among injection drug users in Scotland

Quantitative estimates of the current and future burden of hepatitis C virus (HCV) disease are required to plan a public health response to the HCV epidemic with regard to both prevention and treatment. A forward projection model was used to estimate the numbers of both current and former injecting drug users (IDUs) who acquired HCV and progressed to moderate and severe disease in Glasgow and Scotland during 1960‐2030. The model was designed to synthesize information on the incidence and cessation of injecting drug use, the incidence of HCV infection among IDUs, the rate of HCV disease progression, and the annual number of IDUs developing HCV‐related decompensated cirrhosis. During 2003, a total of 17,400 and 42,900 HCV‐infected IDUs were estimated in Glasgow and Scotland, respectively; this compares with approximately 5,000 and 13,900 diagnosed, respectively, and 13,200 and 32,200 with chronic HCV, respectively. The number of IDUs developing HCV‐related decompensated cirrhosis in Scotland is estimated to double between 2000 and 2020. As many as 16% and 27% of former IDUs in 2005 aged 30‐39 and 40‐49 years, respectively, were estimated to have moderate disease, which highlights the potential benefit of targeting HCV testing at former IDUs who belong to these age groups. In conclusion, the identification and treatment of a larger proportion of former IDUs with HCV disease and education about the importance of minimal alcohol consumption are needed to help achieve a greater impact on the future morbidity and mortality of this disease. (HEPATOLOGY 2005;42:711–723.)

Impact of supervision of methadone consumption on deaths related to methadone overdose (1993-2008): analyses using OD4 index in England and Scotland

Objective To evaluate the impact of introduction of supervision of methadone dosing on deaths related to overdose of methadone in Scotland and England between 1993 and 2008 while controlling for increased prescribing of methadone. Design Analysis of annual trends in deaths related to overdose of methadone in relation to defined daily doses of methadone prescribed. Setting Scotland and England. Population Deaths in which methadone was coded as the only drug involved or as one of the drugs implicated. Main outcome measure Annual OD4-methadone index (number of deaths with methadone implicated per million defined daily doses of methadone prescribed in that year). Results OD4-methadone declined substantially over the four epochs of four years between 1993 and 2008. It decreased significantly (P<0.05) in 10 of 12 epoch changes: in Scotland from 19.3 (95% confidence interval 15 to 24) to 4.1 (2.8 to 5.4) and finally to 3.0 (2.4 to 3.5) for methadone only deaths (and from 58 to 29 to 14 for deaths with any mention of methadone); in England from 27.1 (25 to 29) to 24.8 (23 to 27) and finally to 5.8 (5.3 to 6.3) for methadone only deaths (and from 46 to 42 to 12 for deaths with any mention of methadone). The decreases in OD4-methadone were closely related to the introduction of supervised dosing of methadone in both countries, first in Scotland (1995-2000) and later in England (1999-2005). These declines occurred over periods of substantial increases in prescribing of methadone (18-fold increase in defined daily doses per million population annually in Scotland and sevenfold increase in England). Conclusions Introduction of supervised methadone dosing was followed by substantial declines in deaths related to overdose of methadone in both Scotland and England. OD4-methadone index analyses, controlled for substantial increases in methadone prescribing in both countries, identified at least a fourfold reduction in deaths due to methadone related overdose per defined daily dose (OD4-methadone) over this period.

Prevalence of, and risk factors for, hepatitis C virus infection among recent initiates to injecting in London and Glasgow: cross sectional analysis.

Summary.  Our aim was to compare the prevalence of antibody to hepatitis C virus (anti‐HCV) among recently initiated injecting drug users (IDUs) in London and Glasgow, and to identify risk factors which could explain differences in prevalence between the cities. Complementary studies of community recruited IDUs who had initiated injection drug use since 1996 were conducted during 2001–2002. Data on HCV risk behaviours were gathered using structured questionnaires with identical core questions and respondents were asked to provide an oral fluid specimen which was tested anonymously for anti‐HCV but was linked to the questionnaire. Sensitivities of the anti‐HCV assays for oral fluid were 92–96%. Prevalence of anti‐HCV was 35% (122/354) in London and 57% (207/366) in Glasgow (P < 0.001). Multifactorially, factors significantly associated with raised odds of anti‐HCV positivity were increasing length of injecting career, daily injection, polydrug use, having had a needlestick injury, and having served a prison sentence. In addition lower odds of anti‐HCV positivity were associated with non‐injection use of crack cocaine and recruitment from drug agencies. After adjustment for these factors, the increased odds of anti‐HCV associated with being a Glasgow IDU were diminished but remained significant. HCV continues to be transmitted among the IDU population of both cities at high rates despite the availability of syringe exchange and methadone maintenance. Effectiveness of harm reduction interventions may be compromised by inadequate coverage and failure to reduce sufficiently the frequency of sharing different types of injecting equipment, as well as the high background prevalence of HCV, and its high infectivity. Comprehensive action is urgently required to reduce the incidence of HCV among injectors.

Effectiveness of Scotland's national naloxone programme for reducing opioid-related deaths: a before (2006-10) versus after (2011-13) comparison.

Abstract Aims To assess the effectiveness for Scotlands National Naloxone Programme (NNP) by comparison between 2006–10 (before) and 2011–13 (after NNP started in January 2011) and to assess cost‐effectiveness. Design This was a pre–post evaluation of a national policy. Cost‐effectiveness was assessed by prescription costs against life‐years gained per opioid‐related death (ORD) averted. Setting Scotland, in community settings and all prisons. Intervention Brief training and standardized naloxone supply became available to individuals at risk of opioid overdose. Measurements ORDs as identified by National Records of Scotland. Look‐back determined the proportion of ORDs who, in the 4 weeks before ORD, had been (i) released from prison (primary outcome) and (ii) released from prison or discharged from hospital (secondary). We report 95% confidence intervals for effectiveness in reducing the primary (and secondary) outcome in 2011–13 versus 2006–10. Prescription costs were assessed against 1 or 10 life‐years gained per averted ORD. Findings In 2006–10, 9.8% of ORDs (193 of 1970) were in people released from prison within 4 weeks of death, whereas only 6.3% of ORDs in 2011–13 followed prison release (76 of 1212, P < 0.001; this represented a difference of 3.5% [95% confidence interval (CI) = 1.6–5.4%)]. This reduction in the proportion of prison release ORDs translates into 42 fewer prison release ORDs (95% CI = 19–65) during 2011–13, when 12 000 naloxone kits were issued at current prescription cost of £225 000. Scotlands secondary outcome reduced from 19.0 to 14.9%, a difference of 4.1% (95% CI = 1.4–6.7%). Conclusions Scotlands National Naloxone Programme, which started in 2011, was associated with a 36% reduction in the proportion of opioid‐related deaths that occurred in the 4 weeks following release from prison.

A population-based record linkage study of mortality in hepatitis C-diagnosed persons with or without HIV coinfection in Scotland

Infection with the hepatitis C virus (HCV) is known to increase the risk of death from severe liver disease and, because HCV status is strongly associated with a history of injecting drug use, the effect of a key disease progression cofactor, infection with human immunodeficiency virus (HIV), is of interest. We examined all-cause, liver-related and drug-related mortality and excess risk of death from these causes in a large cohort of HCV-monoinfected and HIV-coinfected persons in Scotland. The study population consisted of 20,163 persons confirmed to be infected with hepatitis C through laboratory testing in Scotland between 1991 and 2005. Records with sufficient identifiers were linked to the General Register Office for Scotland death register to retrieve associated mortality data, and were further linked to a national database of HIV-positive individuals to determine coinfection status. A total of 1715 HCV monoinfected and 305 HIV coinfected persons died of any cause during the follow-up period (mean of 5.4 and 6.4 years, respectively). Significant excess mortality was observed in both HCV monoinfected and HIV coinfected populations from liver-related underlying causes (standardised mortality ratios of 25, 95% CI = 23—27; and 37, 95% CI = 26—52 for the two groups, respectively) and drug-related causes (25, 95% CI = 23—27; 39, 95% CI = 28—53. The risk of death from hepatocellular carcinoma, alcoholic or non-alcoholic liver disease, or from a drug-related cause, was greatly increased compared with the general Scottish population, with the highest standardised mortality ratio observed for hepatocellular carcinoma in the monoinfected group (70, 95% CI = 57—85). This study has revealed considerable excess mortality from liver- and drug-related causes in the Scottish HCV-diagnosed population; these data are crucial to inform on the clinical management, and projected future public health burden, of HCV infection.

Time to move to presumed consent for organ donation

Given the UK’s modest 60% consent rate for donation of organs from brain stem dead donors, Sheila Bird and John Harris argue that allowing donation unless the donor has explicitly opted out would substantially increase the number of organs available

Mortality of those who attended drug services in Scotland 1996-2006: record-linkage study.

Background We examine major causes of death amongst persons in contact with drug-treatment services across Scotland during April 1996–March 2006, hereafter Scottish Drug Misuse Database (SDMD) cohort. Methods Drug-treatment records were linked to national registers of deaths and hepatitis C virus (HCV) diagnoses. For eras 1996/97–2000/01 and 2001/02–2005/06, we calculated cause-specific death-rates and standardised mortality ratios (SMRs) using age-, sex- and calendar-rates of the general Scottish population. Major causes of death were identified by high SMRs (>5 across eras) or rates (>50 per 100,000 person-years in either era), and their time-specific influences characterised by proportional hazards analyses. Results The SDMD cohort comprised 69,456 individuals, 350,315 person-years and 2590 deaths. The overall SMR reduced from 6.4 (95% CI: 6.0–6.9) to 4.8 (95% CI: 4.6–5.0) between eras. We identified five major causes of death: drug-related (1383 deaths), homicide (118) and infectious diseases (90) with high SMRs; suicide (269) and digestive system disease (168) with high rates. HCV diagnosis marked individuals with at least double the risk of cause-specific mortality, including adjusted hazard ratio (HR) for no HCV diagnosis of 0.46 (95% CI: 0.41–0.53) for drug-related deaths (DRDs) and 0.15 (95% CI: 0.10–0.22) for death from digestive system disease. Increased DRD risk at older age (>34 years) appeared specific to HCV-diagnosed individuals (interaction: χ12=7.7, p = 0.01). Alcohol misuse increased HRs: for DRD (1.76, 95% CI: 1.50–2.06), suicide (1.88, 95% CI: 1.35–2.60), deaths from digestive system disease (3.19, 95% CI: 2.21–4.60) and non-major causes (1.87, 95% CI: 1.49–2.35). Stimulant misuse increased suicide risk: adjusted HR 1.91 (95% CI: 1.43–2.54). Conclusions Drug-users in Scotland are exposed to variously increased mortality risks. HCV-diagnosed individuals are particularly vulnerable, and may need additional support.