Table 1 shows characteristics of the cohort at recruitment. Table 2 shows follow-up outcomes and current drug use and health status of interviewees.
Table 1 Characteristics at recruitment and follow-up in 794 participants in Edinburgh addiction cohort. Figures are numbers (percentages), unless stated otherwise
Table 2 Injecting and health status of interviewees in Edinburgh addiction cohort at follow-up. Figures are numbers (percentages)
Among interviewees, 302 (70%) were currently receiving opiate substitution treatment, primarily methadone; 135 (31%) were currently injecting, of whom 112 (83%) were also receiving opiate substitution treatment; and 165 (38%) had achieved long term cessation, of whom 106 (64%) were currently receiving opiate substitution treatment. Most interviewees were current smokers (403, 93%). For other measures, 20% (87) were problem drinkers, 48% (209) were anxious, 26% (114) were depressed, and 52% (226) had poor health related quality of life. Interviewees who achieved long term cessation had lower levels of morbidity.
Among the 654 with data extracted from primary care case notes, 558 (85%) had a history of opiate substitution treatment: 79% (439) had received methadone, 73% (410) dihydrocodeine, 7% (37) buprenorphine, and 1% (8) other opiates; 314 patients had had multiple forms of opiate substitution treatment. A history of periods in prison was recorded in primary care notes for 360 (55%); 281 (43%) had a history of problem drinking and 237 (36%) had a history of overdose requiring hospital treatment; 199 (30%) had been referred to specialist mental health services; and 196 (30%) had a history of self harm. In total, 189 (29%) participants were HIV antibody positive.
By the study end point, 228 (29%) participants had died (table 3). The leading causes of death were HIV (102, 45%), drug overdose (55, 24%), and liver disease/injury (37, 16%). More than three quarters of deaths from drug overdose were among those who did not achieve long term cessation (78%), and drug overdose deaths accounted for 38% (43) of all deaths in that group. Most deaths could be attributed to injecting drug use (table 3), with many of the remaining deaths due to associated problems with other substance use, particularly tobacco and alcohol, or comorbid mental illness.
Table 3 Primary cause of death in Edinburgh addiction cohort. Figures are numbers (percentages) of participants
Overall survival and competing risks: survival and long term cessation
Figure 1 shows survival by HIV status. Median survival for HIV positive patients was 24 years compared with 41 years for HIV negative patients (for patients set to median exposure to opiate substitution treatment, median age at first injection, onset <1986, no prison history, and no history of overdose).
Fig 1 Overall survival from year of first injection to death by HIV status
Among those who died and interviewees whose first injection had been at least six years before follow-up (n=566), 49% (277) achieved long term cessation, 16% (91) died before achieving long term cessation, and 35% (198) survived but had not achieved long term cessation by follow-up. Of those who died before achieving long term cessation, within 25 years after their first injection, half of HIV positive participants had died compared with 10% (9) of HIV negative participants. Opiate substitution treatment was associated with increased survival (that is, decreased time to death). Table 4 shows that for each year of opiate substitution treatment, the probability of death was reduced by 10%. Without adjustment for other factors, survival was also reduced in those with a prison history and history of overdose and was negatively associated with age at onset of injecting (table 4). There was no difference in survival by sex or history of alcohol problems, self harm, or serious mental illness. Evidence for improved survival with opiate substitution treatment remained after adjustment (for HIV, history of overdose, prison history, age at first injection, calendar period of onset), with the hazard of death reduced by 13% (95% confidence interval 17% to 9%, P<0.001). Figure 2 shows that for patients who do not start opiate substitution treatment (unexposed), a quarter will be dead within 25 years of their first injection compared with 6% of those with more than five cumulative years of exposure to opiate substitution treatment (with other factors set to HIV negative, median age at first injection, onset <1986, no prison history, no history of overdose). After adjustment for opiate substitution treatment and other covariates (see above), the probability of death before long term cessation was increased almost sixfold (3.5 to 10.1) for those infected with HIV and twofold (1.3 to 3.1) for those with a history of heroin overdose and the effect of prison history on survival was diluted. The effect of calendar period (onset of injecting from 1986) on survival switched from insufficient or weak evidence of a protective effect (hazard ratio 0.74, P=0.22) to evidence of a more than twofold increase in the probability of death before long term cessation (1.1 to 4.0, P=0.02) after adjustment for HIV infection in particular and other covariates (opiate substitution treatment, history of overdose, age at first injection, prison history, sex).
Table 4 Competing risk (hazard) from year of first injection to achieving long term cessation or death before long term cessation in participants in Edinburgh addiction cohort whose first injection had been at least six years before follow-up (multinomial (more ...)
Fig 2 Survival: probability of not dying before long term cessation by exposure to opiate substitution to treatment
Opiate substitution treatment was associated with an increased duration of injecting (that is, time to long term cessation): for each year of treatment, before adjustment, duration was increased by 11% (table 4). Table 4 shows also that after adjustment for key covariates (sex, HIV infection, age at first injection, calendar period of onset, prison history, history of overdose) and an interaction between opiate substitution treatment and time, the impact of opiate substitution treatment on duration wanes over time—that is, decreasing the probability of cessation by 0.73 (0.65 to 0.81) in the first year and then, as the interactions are all greater than 1, by 0.89 in years 2-10, 0.95 in years 11-15, and 0.91 in years 16-38. (The latter are generated by multiplying the interaction terms with the effect of opiate substitution treatment.) Figure 3 shows that for patients who did not start opiate substitution treatment, the median duration of injecting was five years (with nearly 30% ceasing within a year) compared with 20 years for those with more than five years of exposure to treatment (with other factors set to HIV negative, median age at first injection, onset <1986, no prison history, no history of overdose). Figure 3 also shows that the difference in the probability of long term cessation between those who do and those who do not receive opiate substitution treatment narrows over time.
Fig 3 Injecting duration: probability of achieving long term cessation by exposure to opiate substitution treatment
Table 4 also shows that the probability of cessation, after adjustment for opiate substitution treatment and other covariates in the model, was lower for injecting drug users with more than one period of prison recorded (0.57, 0.42 to 0.78) and for those injecting from 1986 (0.54, 0.38 to 0.77). There was weak evidence that women had a 30% higher probability of achieving long term cessation, but after adjustment the difference was diluted (1.11, 0.84 to 1.47). Age at onset was associated with a 6% (3% to 9%) higher probability of cessation; and there was weak evidence that HIV infection was also associated with a higher probability of cessation (1.32, 0.99 to 1.75).
Based on data available from the 369 interviewed patients, those exposed to opiate substitution treatment reported injecting less frequently while receiving treatment compared with periods out of treatment (mean 157 v 273 days a year, t=−3.9, df=171, P<0.001). For those who achieved long term cessation, however, the number of total days injecting tended to be lower among those who were not exposed to opiate substitution treatment compared with those who were exposed (878 v 1469 days, t=−0.9, df=140, P=0.36).