María J. Bravo

Mortality risk during and after opioid substitution treatment: systematic review and meta-analysis of cohort studies

Objective To compare the risk for all cause and overdose mortality in people with opioid dependence during and after substitution treatment with methadone or buprenorphine and to characterise trends in risk of mortality after initiation and cessation of treatment. Design Systematic review and meta-analysis. Data sources Medline, Embase, PsycINFO, and LILACS to September 2016. Study selection Prospective or retrospective cohort studies in people with opioid dependence that reported deaths from all causes or overdose during follow-up periods in and out of opioid substitution treatment with methadone or buprenorphine. Data extraction and synthesis Two independent reviewers performed data extraction and assessed study quality. Mortality rates in and out of treatment were jointly combined across methadone or buprenorphine cohorts by using multivariate random effects meta-analysis. Results There were 19 eligible cohorts, following 122 885 people treated with methadone over 1.3-13.9 years and 15 831 people treated with buprenorphine over 1.1-4.5 years. Pooled all cause mortality rates were 11.3 and 36.1 per 1000 person years in and out of methadone treatment (unadjusted out-to-in rate ratio 3.20, 95% confidence interval 2.65 to 3.86) and reduced to 4.3 and 9.5 in and out of buprenorphine treatment (2.20, 1.34 to 3.61). In pooled trend analysis, all cause mortality dropped sharply over the first four weeks of methadone treatment and decreased gradually two weeks after leaving treatment. All cause mortality remained stable during induction and remaining time on buprenorphine treatment. Overdose mortality evolved similarly, with pooled overdose mortality rates of 2.6 and 12.7 per 1000 person years in and out of methadone treatment (unadjusted out-to-in rate ratio 4.80, 2.90 to 7.96) and 1.4 and 4.6 in and out of buprenorphine treatment. Conclusions Retention in methadone and buprenorphine treatment is associated with substantial reductions in the risk for all cause and overdose mortality in people dependent on opioids. The induction phase onto methadone treatment and the time immediately after leaving treatment with both drugs are periods of particularly increased mortality risk, which should be dealt with by both public health and clinical strategies to mitigate such risk. These findings are potentially important, but further research must be conducted to properly account for potential confounding and selection bias in comparisons of mortality risk between opioid substitution treatments, as well as throughout periods in and out of each treatment.

Has health in Spain been declining since the economic crisis

Background The economic recession starting in 2008 may be having negative effects on health. Purpose We aimed to identify and characterise changes in trends in 15 health indicators in Spain during the recession. Methods Joinpoint regression and average annual percent change (AAPC) were used to compare trends. Results Premature mortality rates from several causes of death, except from cancer, showed statistically significant downward trends during the recession, as did poor self-reported health. HIV incidence was stable. No indicator declined significantly more slowly during the recession than in the preceding 4-year period, and two declined significantly faster. Conclusion Health in Spain has continued to improve during the first four years of the economic recession at a rate equal to or higher than in previous years.

Use of supervised injection facilities and injection risk behaviours among young drug injectors

AIMS To study the use of supervised injection facilities (SIFs) as a predictor of safer injecting practices. DESIGN Cross-sectional study conducted with face-to-face interview using a structured questionnaire with computer-assisted personal interviewing. Dried blood spot samples were collected for human immunodeficiency virus (HIV) and hepatitis C virus (HCV) antibody testing. SETTING All participants were street-recruited by chain referral methods in Madrid and Barcelona. PARTICIPANTS A total of 249 young heroin drug injectors recruited by the ITINERE cohort study in two Spanish cities with SIFs. MEASUREMENTS The main outcome measures were self-reported injecting behaviours and SIFs attendance. RESULTS SIF users were more marginalized socially than non-users. They were also more often regular injectors (weekly or more versus sporadic) [odds ratio (OR) = 4.9, 95% confidence interval (CI): 2.7-8.8], speedball users (OR = 2.5, 95% CI: 1.5-4.3) and anti-HCV-positive (OR = 3.1, 95% CI: 1.4-7.1). In the logistic regression analysis, using SIFs was associated independently with not borrowing used syringes (OR = 3.3, 95% CI: 1.4-7.7). However, no significant association was found between SIF use and not sharing injection equipment indirectly (OR = 1.1, 95% CI: 0.5-2.2). CONCLUSIONS SIFs attract highly disadvantaged drug injectors who engage none the less in less borrowing of used syringes than non-users of these facilities. The risks of indirect sharing should be emphasized when counselling SIF attendees.

Differences in severity of heroin dependence by route of administration: the importance of length of heroin use

To explore differences in the severity of heroin dependence by route of administration, we interviewed 909 heroin users in three Spanish cities. Dependence was measured with the severity dependence scale (SDS). No major differences in the severity of heroin dependence were detected among users with 5 or more years of heroin use (long-term users), but differences were found among newer users (SDS mean scores, 7.3 in heroin injectors; 7.9 in smokers and 4.6 in sniffers; P = 0.006), especially those with fewer than 3 years of use. Similar differences by route of administration were found when frequency of heroin use (days/month) was considered rather than severity of dependence. However, in the latter case major differences were also found among long-term users. These findings suggest that the route of administration probably influences the rate of progression to dependence but has little influence on the long-run level of dependence. They also help explain some aspects of the transition between routes of heroin administration, which is occurring in different areas.

Cocaine use and risk of stroke: A systematic review

BACKGROUND Both cocaine use and strokes impact public health. Cocaine is a putative cause of strokes, but no systematic review of the scientific evidence has been published. METHODS All relevant bibliographic-databases were searched until January 2014 for articles on the epidemiological association between cocaine use and strokes. Search strings were supervised by expert librarians. Three researchers independently reviewed studies for inclusion and data extraction following STROBE recommendations. Quality appraisal included study validity and bias. Both ischemic and hemorrhagic strokes were considered. RESULTS Of 996 articles, 9 were selected: 7 case-control studies (CCS) and 2 cross-sectional (CSS) studies. One CCS (aOR=6.1; 95% CI: 3.3-11.8) and one CSS (aOR=2.33; 95% CI: 1.74-3.11) showed an association between cocaine and hemorrhagic strokes. The latter study also found a positive relationship with ischemic stroke (aOR=2.03; 95% CI: 1.48-2.79). Another CCS found the exposure to be associated with stroke without distinguishing between types (aOR=13.9; 95% CI: 2.8-69.4). One forensic CCS found that deaths with cocaine-positive toxicology presented a 14.3-fold (95% CI: 5.6-37) and 4.6-fold (95% CI: 2.5-8.5) increased risk of atherosclerosis compared to opioid-related deaths and hanging-deaths respectively. One CCS did not provide an aOR but found a statistically significant association between cocaine and hemorrhagic stroke. Three CCS and one CSS did not find any relationship between cocaine and strokes. Inadequate control for confounding was not uncommon. CONCLUSIONS Epidemiological evidence suggests that cocaine use increases the risk of stroke. Larger, more rigorous observational studies, including cohort approaches, are needed to better quantify this risk, and should consider stroke type, hypertension variation, frequency/length of cocaine use, amphetamines co-use, and other factors.

Más de treinta años de drogas ilegales en España: una amarga historia con algunos consejos para el futuro

The phenomenon of illicit drug use in Spain during the last thirty years has been marked by the extremely serious consequences of heroin use (mainly injecting). More than 300.000 persons were treated for heroin dependence, 20.000-25.000 died from overdose, 100.000 became infected with HIV through drug injection and quite more with hepatitis virus. Some of these consequences can be attributed to the delay in the implementation of effective interventions, such as methadone maintenance treatment (MMT). Currently, the decreasing number of injectors and the positive effects of interventions, mainly MMT, have led to an important decline of the mentioned health problems. However, overdose mortality remains very high (more than 700 deceased per year), prevalence of both HIV and HCV are still high among injectors, and consequences of chronic liver diseases are emerging. In the last years the use of cocaine and associated problems have increased a lot. Nowadays there are more than 100.000 weekly cocaine users, 25.000 persons are annually treated from cocaine abuse or dependence, and cocaine has an important impact on medical emergency services, while its impact on mortality is unknown. Both cannabis use and related problems are increasing too (there are half a million of daily users). We propose to maintain and to strengthen harm reduction programs (MMT, syringe exchange, save-use and injection rooms, hepatitis A and B vaccination, etc.), to urgently develop specific strategies targeted to reduce overdose mortality and cocaine related problems, and to re-evaluate the effectiveness of preventive and supply control strategies.

Injecting and HIV prevalence among young heroin users in three Spanish cities and their association with the delayed implementation of harm reduction programmes

Objectives: To evaluate changes in the prevalence of HIV infection among young heroin users in three Spanish cities, and their association with harm reduction programmes (HRPs). Methods: Two cross sectional studies. The 1995 study included 596 users; half were street recruited and half were recruited at drug treatment centres. The 2001–03 study included 981 street recruited users. Face to face interviews were conducted using a structured questionnaire. Samples for HIV testing (saliva in 1995 and dried blood spot in 2001–03) were collected. Results: The proportion who had ever injected (IDUs) decreased in all three cities. HIV prevalence in IDUs decreased by half in Barcelona (44.1% to 20.8%) and Seville (44.2% to 22.2%), but remained constant in Madrid (36.8% and 34.9%). This difference was attributable to a decrease in HIV prevalence in long term IDUs in Barcelona and Seville, but not in Madrid. The crude odds ratio for HIV prevalence in Madrid compared with Barcelona in long term IDUs was 2.3 (95%CI 1.4 to 3.7), increasing to 3.1 (95%CI 1.5 to 6.2) after adjusting for sociodemographic and risk factors. HIV prevalence in short term IDUs was similar in all cities. In 1992 Barcelona already had 20 heroin users in methadone maintenance programmes (MMPs) per 10 000 population aged 15–49 years; Seville reached this rate in 1994, and Madrid, not until 1998. Conclusions: The prevalence of HIV infection did not decrease in long term injectors in Madrid. The delayed implementation of HRPs, especially MMPs, may be the most plausible hypothesis. This finding should shed light on decision making in countries in a similar epidemiological and sociological situation.

Are Participants in a Street-Based HIV Testing Program Able to Perform Their Own Rapid Test and Interpret the Results?

Objective Availability of over-the-counter rapid HIV tests could improve access to testing those reluctant or unable to use current services. We aimed to evaluate the feasibility of HIV self-testing using a finger-stick whole-blood rapid test (Determine™ HIV Combo) to detect both antigen and antibody. Methods Before being tested, 313 participants in a street-based testing program were given adapted instructions and a test kit, and performed the self-test without supervision. These participants, together with another 207 who performed supervised self-testing, received additional instructions on how to interpret the test results shown in six colour photos and filled out a questionnaire. Logistic regression and generalized estimating equations (GEE) were used in the statistical analysis. Results About 8.0% (95%CI:4.8%–11.2%) obtained an invalid self-test. An invalid result was inversely associated with male participants who had sex with men (OR = 0.3;95%CI:0.1–1.0). Of the 3111 photos interpreted,4.9% (95%CI:4.1–5.7) were incorrect. Only 1.1% (95%CI:0.3–1.8) of the positive results were interpreted as negative. Age 30 or older (OR = 2.1; 95%CI:1.2–3.7), having been born in Latin America (OR = 1.6; 95%CI:1.1–2.2),and not having university education (OR = 2.1;95%CI:1.2–3.7) were associated with misinterpreting test results in the GEE. Participants perceptions of both their proficiency when conducting the test and interpretation were related with actual outcomes. Most participants (83.9%) were more motivated than before to use the self-test in the future, and 51.7% would pay >10 Euros for the test if it was sold in pharmacies. Conclusions This is the first study showing that blood-based self-testing with current technology is feasible in HIV-negative participants demanding the test and without prior training or supervision. Bearing in mind that it was conducted under difficult weather conditions and using a complex kit, over-the-counter tests could be a feasible option to complement current diagnostic strategies. More studies are needed to accommodate technology, minimise interpretation mistakes and provide on-line support.

Multiplex Real-time Polymerase Chain Reaction: A Practical Approach for Rapid Diagnosis of Tuberculous and Brucellar Vertebral Osteomyelitis

Study Design. Case-control study for assessing a diagnostic test. Objective. The aim of this study was to analyze the diagnostic yield of a multiplex real-time polymerase chain reaction (PCR) assay in the differential diagnosis of tuberculous vertebral osteomyelitis (TVO) and brucellar vertebral osteomyelitis (BVO). Summary of Background Data. Vertebral osteomyelitis (VO) is one of commonest osteoarticular complications of tuberculosis and brucellosis. However, the very similar clinical, radiologic, and histologic characteristics of these entities mean that diagnosis requires etiological confirmation, but conventional microbiologic methods have important limitations. Methods. Fifteen vertebral samples from patients with TVO or BVO and 9 from pyogenic and nontuberculous mycobacteria VO were studied by multiplex PCR and conventional microbiologic techniques. To identify Brucella DNA, we used a fragment of 207 bp from the conserved region of the gene coding for an immunogenic membrane protein of 31 kDa of B. abortus (BCSP31) and for Mycobacterium tuberculosis complex, a fragment of 164 bp from the intergenic region SenX3-RegX3. Results. The histopathologic findings were inconclusive in 4 of 14 cases (28.6%) with TVO or BVO and cultures were positive in 11 of 15 cases (73.3%). Multiplex PCR correctly identified 14 of the 15 samples from patients with TVO and BVO and was negative in all the control samples. Thus, the overall sensitivity and specificity of the multiplex PCR were 93.3% and 90%, respectively, with an accuracy of 92% (95% CI, 81.4%–100%). Conclusion. These results suggest that multiplex real-time PCR is far more sensitive than conventional cultures, and this, together with its speed, makes this technique a very practical approach for the differential diagnosis between TVO and BVO.

Harm reduction interventions for drug injectors or heroin users in Spain: expanding coverage as the storm abates

AIMS To show the utility of analysing time trends of need and coverage of needle-exchange programmes (NEPs) and opioid substitution treatment (OST) to assess harm reduction policies targeting drug injectors or heroin users. DESIGN Multiple methods applied to secondary data. SETTING Spain. PARTICIPANTS Thousands of drug injectors or heroin users included in administrative registers, surveys and published studies during 1987-2010. MEASUREMENTS Coverage for the general population was calculated as the ratio between interventions provided (obtained directly from the sources) and interventions needed (estimated by multiple methods), and as the difference between the two. Timeliness was estimated by time elapsed between year of highest need and year in which coverage reached a reference level. FINDINGS In 2010 NEPs provided 138 syringes per drug injector [95% confidence interval (CI) 100-223], covering 25.7% (95% CI 18.3-43.3) of their need. OST coverage was 60.3% (95% CI 44.3-94.2). Syringe and OST provision increased between 1991 and 2001 and then declined. Syringe and OST coverage also increased substantially during this period and then stabilized, due mainly to decreases in drug injection or heroin use. Medium-level coverage for both syringes and OST was not achieved until 2000, 8 years after the peak in need (1992). CONCLUSIONS In Spain, the expansion of harm reduction interventions was greatly delayed, although the concomitant decrease in heroin and injecting drug use led to reasonable coverage after 2000. A longitudinal measurement of need and coverage provides insight into the timeliness and potential population impact of interventions, enabling better assessment of their adequacy.