Relapse to opioid use in opioid-dependent individuals released from compulsory drug detention centres compared with those from voluntary methadone treatment centres in Malaysia: a two-arm, prospective observational study

Background Detention of people who use drugs into compulsory drug detention centres (CDDCs) is common throughout East and Southeast Asia. Evidence-based pharmacological therapies for treating substance use disorders, such as opioid agonist treatments with methadone, are generally unavailable in these settings. We used a unique opportunity where CDDCs coexisted with voluntary drug treatment centres (VTCs) providing methadone in Malaysia to compare the timing and occurrence of opioid relapse (measured using urine drug testing) in individuals transitioning from CDDCs versus methadone maintenance in VTCs. Methods We did a parallel, two-arm, prospective observational study of opioid-dependent individuals aged 18 years and older who were treated in Malaysia in the Klang Valley in two settings: CDDCs and VTCs. We used sequential sampling to recruit individuals. Assessed individuals in CDDCs were required to participate in services such as counselling sessions and manual labour. Assessed individuals in VTCs could voluntarily access many of the components available in CDDCs, in addition to methadone therapy. We undertook urinary drug tests and behavioural interviews to assess individuals at baseline and at 1, 3, 6, 9, and 12 months post-release. The primary outcome was time to opioid relapse post-release in the community confi rmed by urinary drug testing in individuals who had undergone baseline interviewing and at least one urine drug test (our analytic sample). Relapse rates between the groups were compared using time-to-event methods. This study is registered at ClinicalTrials.gov (NCT02698098). Findings Between July 17, 2012, and August 21, 2014, we screened 168 CDDC attendees and 113 VTC inpatients; of these, 89 from CDDCs and 95 from VTCs were included in our analytic sample. The baseline characteristics of the two groups were similar. In unadjusted analyses, CDDC participants had signifi cantly more rapid relapse to opioid use post-release compared with VTC participants (median time to relapse 31 days [IQR 26–32] vs 352 days [256–unestimable], log rank test, p<0·0001). VTC participants had an 84% (95% CI 75–90) decreased risk of opioid relapse after adjustment for control variables and inverse propensity of treatment weights. Time-varying eff ect modelling revealed the largest hazard ratio reduction, at 91% (95% CI 83–96), occurs during the fi rst 50 days in the community. Interpretation Opioid-dependent individuals in CDDCs are signifi cantly more likely to relapse to opioid use after release, and sooner, than those treated with evidence-based treatments such as methadone, suggesting that CDDCs have no role in the treatment of opioid-use disorders

Pre-incarceration police harassment, drug addiction and HIV risk behaviours among prisoners in Kyrgyzstan and Azerbaijan: results from a nationally representative cross-sectional study.

INTRODUCTION: The expanding HIV epidemic in Azerbaijan and Kyrgyzstan is concentrated among people who inject drugs (PWID), who comprise a third of prisoners there. Detention of PWID is common but its impact on health has not been previously studied in the region. We aimed to understand the relationship between official and unofficial (police harassment) detention of PWID and HIV risk behaviours. METHODS: In a nationally representative cross-sectional study, soon-to-be released prisoners in Kyrgyzstan (N=368) and Azerbaijan (N=510) completed standardized health assessment surveys. After identifying correlated variables through bivariate testing, we built multi-group path models with pre-incarceration official and unofficial detention as exogenous variables and pre-incarceration composite HIV risk as an endogenous variable, controlling for potential confounders and estimating indirect effects. RESULTS: Overall, 463 (51%) prisoners reported at least one detention in the year before incarceration with an average of 1.3 detentions in that period. Unofficial detentions (13%) were less common than official detentions (41%). Optimal model fit was achieved (X (2)=5.83, p=0.44; Goodness of Fit Index (GFI) GFI=0.99; Comparative Fit Index (CFI) CFI=1.00; Root Mean Square Error of Approximation (RMSEA) RMSEA=0.00; PCLOSE=0.98) when unofficial detention had an indirect effect on HIV risk, mediated by drug addiction severity, with more detentions associated with higher addiction severity, which in turn correlated with increased HIV risk. The final model explained 35% of the variance in the outcome. The effect was maintained for both countries, but stronger for Kyrgyzstan. The model also holds for Kyrgyzstan using unique data on within-prison drug injection as the outcome, which was frequent in prisoners there. CONCLUSIONS: Detention by police is a strong correlate of addiction severity, which mediates its effect on HIV risk behaviour. This pattern suggests that police may target drug users and that such harassment may result in an increase in HIV risk-taking behaviours, primarily because of the continued drug use within prisons. These findings highlight the important negative role that police play in the HIV epidemic response and point to the urgent need for interventions to reduce police harassment, in parallel with interventions to reduce HIV transmission within and outside of prison

Infant mortality trends in a region of Belarus, 1980–2000

BACKGROUND: The Chernobyl disaster in 1986 and the breakup of the former Soviet Union (FSU) in 1991 challenged the public health infrastructure in the former Soviet republic of Belarus. Because infant mortality is regarded as a sensitive measure of the overall health of a population, patterns of neonatal and postneonatal deaths were examined within the Mogilev region of Belarus between 1980 and 2000. METHODS: Employing administrative death files, this study utilized a regional cohort design that included all infant deaths occurring among persons residing within the Mogilev oblast of Belarus between 1980 and 2000. Patterns of death and death rates were examined across 3 intervals: 1980–1985 (pre-Chernobyl), 1986–1991 (post-Chernobyl & pre-FSU breakup), and 1992–2000 (post-Chernobyl & post-FSU breakup). RESULTS: Annual infant mortality rates declined during the 1980s, increased during the early 1990s, and have remained stable thereafter. While infant mortality rates in Mogilev have decreased since the period 1980–1985 among both males and females, this decrement appears due to decreases in postneonatal mortality. Rates of postneonatal mortality in Mogilev have decreased since the period 1980–1985 among both males and females. Analyses of trends for infant mortality and neonatal mortality demonstrated continuous decreases between 1990, followed by a bell-shaped excess in the 1990's. Compared to rates of infant mortality for other countries, rates in the Mogilev region are generally higher than rates for the United States, but lower than rates in Russia. During the 1990s, rates for both neonatal and postneonatal mortality in Mogilev were two times the comparable rates for East and West Germany. CONCLUSIONS: While neonatal mortality rates in Mogilev have remained stable, rates for postneonatal mortality have decreased among both males and females during the period examined. Infant mortality rates in the Mogilev region of Belarus remain elevated compared to rates for other western countries, but lower than rates in Russia. The public health infrastructure might attempt to assure that prenatal, maternal, and postnatal care is maximized

Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead.

Lifestyle factors are responsible for a considerable portion of cancer incidence worldwide, but credible estimates from the World Health Organization and the International Agency for Research on Cancer (IARC) suggest that the fraction of cancers attributable to toxic environmental exposures is between 7% and 19%. To explore the hypothesis that low-dose exposures to mixtures of chemicals in the environment may be combining to contribute to environmental carcinogenesis, we reviewed 11 hallmark phenotypes of cancer, multiple priority target sites for disruption in each area and prototypical chemical disruptors for all targets, this included dose-response characterizations, evidence of low-dose effects and cross-hallmark effects for all targets and chemicals. In total, 85 examples of chemicals were reviewed for actions on key pathways/mechanisms related to carcinogenesis. Only 15% (13/85) were found to have evidence of a dose-response threshold, whereas 59% (50/85) exerted low-dose effects. No dose-response information was found for the remaining 26% (22/85). Our analysis suggests that the cumulative effects of individual (non-carcinogenic) chemicals acting on different pathways, and a variety of related systems, organs, tissues and cells could plausibly conspire to produce carcinogenic synergies. Additional basic research on carcinogenesis and research focused on low-dose effects of chemical mixtures needs to be rigorously pursued before the merits of this hypothesis can be further advanced. However, the structure of the World Health Organization International Programme on Chemical Safety 'Mode of Action' framework should be revisited as it has inherent weaknesses that are not fully aligned with our current understanding of cancer biology

Self-organization of developing embryo using scale-invariant approach

<p>Abstract</p> <p>Background</p> <p>Self-organization is a fundamental feature of living organisms at all hierarchical levels from molecule to organ. It has also been documented in developing embryos.</p> <p>Methods</p> <p>In this study, a scale-invariant power law (SIPL) method has been used to study self-organization in developing embryos. The SIPL coefficient was calculated using a centro-axial skew symmetrical matrix (CSSM) generated by entering the components of the Cartesian coordinates; for each component, one CSSM was generated. A basic square matrix (BSM) was constructed and the determinant was calculated in order to estimate the SIPL coefficient. This was applied to developing <it>C. elegans </it>during early stages of embryogenesis. The power law property of the method was evaluated using the straight line and Koch curve and the results were consistent with fractal dimensions (fd). Diffusion-limited aggregation (DLA) was used to validate the SIPL method.</p> <p>Results and conclusion</p> <p>The fractal dimensions of both the straight line and Koch curve showed consistency with the SIPL coefficients, which indicated the power law behavior of the SIPL method. The results showed that the ABp sublineage had a higher SIPL coefficient than EMS, indicating that ABp is more organized than EMS. The fd determined using DLA was higher in ABp than in EMS and its value was consistent with type 1 cluster formation, while that in EMS was consistent with type 2.</p

Pre-incarceration police harassment, drug addiction and HIV risk behaviours among prisoners in Kyrgyzstan and Azerbaijan: results from a nationally representative cross-sectional study

Introduction: The expanding HIV epidemic in Azerbaijan and Kyrgyzstan is concentrated among people who inject drugs (PWID), who comprise a third of prisoners there. Detention of PWID is common but its impact on health has not been previously studied in the region. We aimed to understand the relationship between official and unofficial (police harassment) detention of PWID and HIV risk behaviours. Methods: In a nationally representative cross-sectional study, soon-to-be released prisoners in Kyrgyzstan (N=368) and Azerbaijan (N=510) completed standardized health assessment surveys. After identifying correlated variables through bivariate testing, we built multi-group path models with pre-incarceration official and unofficial detention as exogenous variables and pre-incarceration composite HIV risk as an endogenous variable, controlling for potential confounders and estimating indirect effects. Results: Overall, 463 (51%) prisoners reported at least one detention in the year before incarceration with an average of 1.3 detentions in that period. Unofficial detentions (13%) were less common than official detentions (41%). Optimal model fit was achieved (X2=5.83, p=0.44; Goodness of Fit Index (GFI) GFI=0.99; Comparative Fit Index (CFI) CFI=1.00; Root Mean Square Error of Approximation (RMSEA) RMSEA=0.00; PCLOSE=0.98) when unofficial detention had an indirect effect on HIV risk, mediated by drug addiction severity, with more detentions associated with higher addiction severity, which in turn correlated with increased HIV risk. The final model explained 35% of the variance in the outcome. The effect was maintained for both countries, but stronger for Kyrgyzstan. The model also holds for Kyrgyzstan using unique data on within-prison drug injection as the outcome, which was frequent in prisoners there. Conclusions: Detention by police is a strong correlate of addiction severity, which mediates its effect on HIV risk behaviour. This pattern suggests that police may target drug users and that such harassment may result in an increase in HIV risk-taking behaviours, primarily because of the continued drug use within prisons. These findings highlight the important negative role that police play in the HIV epidemic response and point to the urgent need for interventions to reduce police harassment, in parallel with interventions to reduce HIV transmission within and outside of prison

Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead

Lifestyle factors are responsible for a considerable portion of cancer incidence worldwide, but credible estimates from the World Health Organization and the International Agency for Research on Cancer (IARC) suggest that the fraction of cancers attributable to toxic environmental exposures is between 7% and 19%. To explore the hypothesis that low-dose exposures to mixtures of chemicals in the environment may be combining to contribute to environmental carcinogenesis, we reviewed 11 hallmark phenotypes of cancer, multiple priority target sites for disruption in each area and prototypical chemical disruptors for all targets, this included dose-response characterizations, evidence of low-dose effects and cross-hallmark effects for all targets and chemicals. In total, 85 examples of chemicals were reviewed for actions on key pathways/mechanisms related to carcinogenesis. Only 15% (13/85) were found to have evidence of a dose-response threshold, whereas 59% (50/85) exerted low-dose effects. No dose-response information was found for the remaining 26% (22/85). Our analysis suggests that the cumulative effects of individual (non-carcinogenic) chemicals acting on different pathways, and a variety of related systems, organs, tissues and cells could plausibly conspire to produce carcinogenic synergies. Additional basic research on carcinogenesis and research focused on low-dose effects of chemical mixtures needs to be rigorously pursued before the merits of this hypothesis can be further advanced. However, the structure of the World Health Organization International Programme on Chemical Safety ‘Mode of Action’ framework should be revisited as it has inherent weaknesses that are not fully aligned with our current understanding of cancer biology

Impact of prerelease methadone on mortality among people with HIV and opioid use disorder after prison release: results from a randomized and participant choice open-label trial in Malaysia

IntroductionMortality is elevated after prison release and may be higher in people with HIV and opioid use disorder (OUD). Maintenance with&nbsp;opioid agonist therapy (OAT) like methadone or buprenorphine reduces mortality in people with OUD and may confer benefits to people with OUD and HIV leaving prison. Survival benefits of OAT, however, have not been evaluated prospectively in people with OUD and HIV leaving prison.MethodsThis study prospectively evaluated mortality after prison release and whether methadone initiated before release increased survival after release in a sample of men with HIV and OUD (n = 291). We linked national death records to data from a controlled trial of prerelease methadone initiation conducted from 2010 to 2014 with men with HIV and OUD imprisoned in Malaysia. Vital statistics were collected through 2015. Allocation to prerelease methadone was by randomization (n = 64) and participant choice (n = 246). Cox proportional hazards models were used to estimate treatment effects of prerelease methadone on postrelease survival.ResultsOverall, 62 deaths occurred over 872.5 person-years (PY) of postrelease follow-up, a crude mortality rate of 71.1 deaths per 1000 PY (95% confidence interval [CI] 54.5-89.4). Most deaths were of infectious etiology, mostly related to HIV. In a modified intention-to-treat analysis, the impact of prerelease methadone on postrelease mortality was consistent with a null effect in unadjusted (hazard ratio [HR] 1.3, 95% CI 0.6-3.1) and covariate-adjusted (HR 1.2, 95% CI 0.5-2.8) models. Predictors of mortality were educational level (HR 1.4, 95% CI 1.0-1.8), pre-incarceration alcohol use (HR 2.0, 95% CI 1.1-3.9), and lower CD4+ T-lymphocyte count (HR 0.8 per 100-cell/mL increase, 95% CI 0.7-1.0).ConclusionsPostrelease mortality in this sample of men with HIV and OUD was extraordinarily high, and most deaths were likely of infectious etiology. No effect of prerelease methadone on postrelease mortality was observed, which may be due to study limitations or an epidemiological context in which inadequately treated HIV, and not inadequately treated OUD, is the main cause of death after prison release.Trial registrationNCT02396979. Retrospectively registered 24/03/2015

Relapse to opioid use in opioid-dependent individuals released from compulsory drug detention centres compared with those from voluntary methadone treatment centres in Malaysia: a two-arm, prospective observational study

Background: Detention of people who use drugs into compulsory drug detention centres (CDDCs) is common throughout East and Southeast Asia. Evidence-based pharmacological therapies for treating substance use disorders, such as opioid agonist treatments with methadone, are generally unavailable in these settings. We used a unique opportunity where CDDCs coexisted with voluntary drug treatment centres (VTCs) providing methadone in Malaysia to compare the timing and occurrence of opioid relapse (measured using urine drug testing) in individuals transitioning from CDDCs versus methadone maintenance in VTCs. Methods: We did a parallel, two-arm, prospective observational study of opioid-dependent individuals aged 18 years and older who were treated in Malaysia in the Klang Valley in two settings: CDDCs and VTCs. We used sequential sampling to recruit individuals. Assessed individuals in CDDCs were required to participate in services such as counselling sessions and manual labour. Assessed individuals in VTCs could voluntarily access many of the components available in CDDCs, in addition to methadone therapy. We undertook urinary drug tests and behavioural interviews to assess individuals at baseline and at 1, 3, 6, 9, and 12 months post-release. The primary outcome was time to opioid relapse post-release in the community confirmed by urinary drug testing in individuals who had undergone baseline interviewing and at least one urine drug test (our analytic sample). Relapse rates between the groups were compared using time-to-event methods. This study is registered at ClinicalTrials.gov (NCT02698098). Findings: Between July 17, 2012, and August 21, 2014, we screened 168 CDDC attendees and 113 VTC inpatients; of these, 89 from CDDCs and 95 from VTCs were included in our analytic sample. The baseline characteristics of the two groups were similar. In unadjusted analyses, CDDC participants had significantly more rapid relapse to opioid use post-release compared with VTC participants (median time to relapse 31 days [IQR 26–32] vs 352 days [256–unestimable], log rank test, p<0·0001). VTC participants had an 84% (95% CI 75–90) decreased risk of opioid relapse after adjustment for control variables and inverse propensity of treatment weights. Time-varying effect modelling revealed the largest hazard ratio reduction, at 91% (95% CI 83–96), occurs during the first 50 days in the community. Interpretation: Opioid-dependent individuals in CDDCs are significantly more likely to relapse to opioid use after release, and sooner, than those treated with evidence-based treatments such as methadone, suggesting that CDDCs have no role in the treatment of opioid-use disorders. Funding: The World Bank Group, Doris Duke Charitable Foundation, National Institute on Drug Abuse, Australian National Health & Medical Research Council, National Institute of Mental Health, and the University of Malaya-Malaysian Ministry of Higher Education High Impact Research Grant