Using standardized methods for research on HIV and injecting drug use in developing/transitional countries: case study from the WHO Drug Injection Study Phase II

BACKGROUND: Successful cross-national research requires methods that are both standardized across sites and adaptable to local conditions. We report on the development and implementation of the methodology underlying the survey component of the WHO Drug Injection Study Phase II – a multi-site study of risk behavior and HIV seroprevalence among Injecting Drug Users (IDUs). METHODS: Standardized operational guidelines were developed by the Survey Coordinating Center in collaboration with the WHO Project Officer and participating site Investigators. Throughout the duration of the study, survey implementation at the local level was monitored by the Coordinating Center. Surveys were conducted in 12 different cities. Prior rapid assessment conducted in 10 cities provided insight into local context and guided survey implementation. Where possible, subjects were recruited both from drug abuse treatment centers and via street outreach. While emphasis was on IDUs, non-injectors were also recruited in cities with substantial non-injecting use of injectable drugs. A structured interview and HIV counseling/testing were administered. RESULTS: Over 5,000 subjects were recruited. Subjects were recruited from both drug treatment and street outreach in 10 cities. Non-injectors were recruited in nine cities. Prior rapid assessment identified suitable recruitment areas, reduced drug users' distrust of survey staff, and revealed site-specific risk behaviors. Centralized survey coordination facilitated local questionnaire modification within a core structure, standardized data collection protocols, uniform database structure, and cross-site analyses. Major site-specific problems included: questionnaire translation difficulties; locating affordable HIV-testing facilities; recruitment from drug treatment due to limited/selective treatment infrastructure; access to specific sub-groups of drug users in the community, particularly females or higher income groups; security problems for users and interviewers, hostility from local drug dealers; and interference by local service providers. CONCLUSION: Rapid assessment proved invaluable in paving the way for the survey. Central coordination of data collection is crucial. While fully standardized methods may be a research ideal, local circumstances may require substantial adaptation of the methods to achieve meaningful local representation. Allowance for understanding of local context may increase rather than decrease the generalizability of the data

HIV risk behaviors among female IDUs in developing and transitional countries

Abstract Background A number of studies suggest females may be more likely to engage in injection and sex risk behavior than males. Most data on gender differences come from industrialized countries, so data are needed in developing countries to determine how well gender differences generalize to these understudied regions. Methods Between 1999 and 2003, 2512 male and 672 female current injection drug users (IDUs) were surveyed in ten sites in developing countries around the world (Nairobi, Beijing, Hanoi, Kharkiv, Minsk, St. Petersburg, Bogotá, Gran Rosario, Rio, and Santos). The survey included a variety of questions about demographics, injecting practices and sexual behavior. Results Females were more likely to engage in risk behaviors in the context of a sexual relationship with a primary partner while males were more likely to engage in risk behaviors in the context of close friendships and casual sexual relationships. After controlling for injection frequency, and years injecting, these gender differences were fairly consistent across sites. Conclusion Gender differences in risk depend on the relational contexts in which risk behaviors occur. The fact that female and male risk behavior often occurs in different relational contexts suggests that different kinds of prevention interventions which are sensitive to these contexts may be necessary.</p

Genotype-Phenotype Correlation in 153 Adult Patients With Congenital Adrenal Hyperplasia due to 21-Hydroxylase Deficiency: Analysis of the United Kingdom Congenital Adrenal Hyperplasia Adult Study Executive (CaHASE) Cohort

CONTEXT: In congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency, a strong genotype-phenotype correlation exists in childhood. However, similar data in adults are lacking. OBJECTIVE: The objective of the study was to test whether the severity of disease-causing CYP21A2 mutations influences the treatment and health status in adults with CAH. RESEARCH DESIGN AND METHODS: We analyzed the genotype in correlation with treatment and health status in 153 adults with CAH from the United Kingdom Congenital adrenal Hyperplasia Adult Study Executive cohort. RESULTS: CYP21A2 mutations were distributed similarly to previously reported case series. In 7 patients a mutation was identified on only 1 allele. Novel mutations were detected on 1.7% of alleles (5 of 306). Rare mutations were found on 2.3% of alleles (7 of 306). For further analysis, patients were categorized into CYP21A2 mutation groups according to predicted residual enzyme function: null (n = 34), A (n = 42), B (n = 36), C (n = 34), and D (n = 7). Daily glucocorticoid dose was highest in group null and lowest in group C. Fludrocortisone was used more frequently in patients with more severe genotypes. Except for lower female height in group B, no statistically significant associations between genotype and clinical parameters were found. Androgens, blood pressure, lipids, blood glucose, and homeostasis model assessment of insulin resistance were not different between groups. Subjective health status was similarly impaired across groups. CONCLUSIONS: In adults with classic CAH and women with nonclassic CAH, there was a weak association between genotype and treatment, but health outcomes were not associated with genotype. The underrepresentation of males with nonclassic CAH may reflect that milder genotypes result in a milder condition that is neither diagnosed nor followed up in adulthood. Overall, our results suggest that the impaired health status of adults with CAH coming to medical attention is acquired rather than genetically determined and therefore could potentially be improved through modification of treatment

Effect of remote ischaemic conditioning on clinical outcomes in patients with acute myocardial infarction (CONDI-2/ERIC-PPCI): a single-blind randomised controlled trial.

BACKGROUND: Remote ischaemic conditioning with transient ischaemia and reperfusion applied to the arm has been shown to reduce myocardial infarct size in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI). We investigated whether remote ischaemic conditioning could reduce the incidence of cardiac death and hospitalisation for heart failure at 12 months. METHODS: We did an international investigator-initiated, prospective, single-blind, randomised controlled trial (CONDI-2/ERIC-PPCI) at 33 centres across the UK, Denmark, Spain, and Serbia. Patients (age >18 years) with suspected STEMI and who were eligible for PPCI were randomly allocated (1:1, stratified by centre with a permuted block method) to receive standard treatment (including a sham simulated remote ischaemic conditioning intervention at UK sites only) or remote ischaemic conditioning treatment (intermittent ischaemia and reperfusion applied to the arm through four cycles of 5-min inflation and 5-min deflation of an automated cuff device) before PPCI. Investigators responsible for data collection and outcome assessment were masked to treatment allocation. The primary combined endpoint was cardiac death or hospitalisation for heart failure at 12 months in the intention-to-treat population. This trial is registered with ClinicalTrials.gov (NCT02342522) and is completed. FINDINGS: Between Nov 6, 2013, and March 31, 2018, 5401 patients were randomly allocated to either the control group (n=2701) or the remote ischaemic conditioning group (n=2700). After exclusion of patients upon hospital arrival or loss to follow-up, 2569 patients in the control group and 2546 in the intervention group were included in the intention-to-treat analysis. At 12 months post-PPCI, the Kaplan-Meier-estimated frequencies of cardiac death or hospitalisation for heart failure (the primary endpoint) were 220 (8·6%) patients in the control group and 239 (9·4%) in the remote ischaemic conditioning group (hazard ratio 1·10 [95% CI 0·91-1·32], p=0·32 for intervention versus control). No important unexpected adverse events or side effects of remote ischaemic conditioning were observed. INTERPRETATION: Remote ischaemic conditioning does not improve clinical outcomes (cardiac death or hospitalisation for heart failure) at 12 months in patients with STEMI undergoing PPCI. FUNDING: British Heart Foundation, University College London Hospitals/University College London Biomedical Research Centre, Danish Innovation Foundation, Novo Nordisk Foundation, TrygFonden

Prescribing heroin: what is the evidence?

Prescribing heroin is the first overview of how and why heroin is prescribed in the UK. It brings together research evidence from the UK and elsewhere to provide a comprehensive review of the benefits and drawbacks of heroin prescription. Currently only a small number of UK doctors prescribe heroin. The government is planning a cautious and modest expansion of this treatment. This study considers whether heroin prescription is effective in the short and the long term. It covers: • Reasons given for prescribing heroin and for expanding such treatment; • The history of prescribing heroin and how practice has developed; • The manufacture and use of illicit heroin and its associated risks; • Current approaches to heroin problems in the UK; • The range of services available for heroin users. The study concludes with a summary of the research, clinical, political and practical challenges for expanding heroin prescription

AIDS and injecting drug use in the United Kingdom, 1987–93: the policy response and the prevention of the epidemic

Abstract--This paper assesses policy development, service changes and trends in HIV infection and risk behaviour among injecting drug users (IDUs) in the United Kingdom. In 1986, the U.K. was faced with the possible rapid spread of HIV infection among IDUs. The combination of an outbreak of HIV infection with prevalence levels of 50 % or more in Edinburgh, the recent diffusion of drug injecting, and high levels of syringe-sharing risk behaviour, suggested that HIV infection might spread rapidly through IDU populations. HIV prevention activities commenced in 1986 and developed in 1987. The first report on AIDS and Drugs Misuse by the Advisory Council on the Misuse of Drugs in 1988 was a major catalyst for change. It supported and legitimized emergent views on new ways of working with drug users. Between 1988 and 1993 innovative public health projects increased the ability to target vulnerable populations through syringe distribution, expansion of methadone treatment and outreach to hard-to-reach populations. There were major changes in service philosophy and practices, as ideas of harm minimization, accessibility, flexibility and multiple and intermediate goals were developed. There is evidence that these public health projects encouraged extensive changes in the health behaviour of IDUs. There have been major reductions in syringe-sharing risk behaviour and sharing syringes is no longer the norm. Evaluation of specific interventions (e.g. syringe-exchange) shows their importance in encouraging reductions in risk behaviour