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.
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.
METHODS: This 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.
RESULTS: Overall, 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).
CONCLUSIONS: Postrelease 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 REGISTRATION: NCT02396979. Retrospectively registered 24/03/2015.
METHODS: Data were collected on travellers evaluated at GeoSentinel Network sites who reported healthcare during travel. Both unplanned and planned healthcare were analysed, including the reason and nature of healthcare sought, characteristics of the treatment provided and outcomes. Travellers that presented for rabies post-exposure prophylaxis were described elsewhere and were excluded from detailed analysis.
RESULTS: From May 2017 through June 2020, after excluding travellers obtaining rabies post-exposure prophylaxis (n= 415), 1093 travellers reported care for a medical or dental issue that was an unanticipated part of the travellers' planned itinerary (unplanned healthcare). Travellers who sought unplanned healthcare abroad had frequent diagnoses of acute diarrhoea, dengue, falciparum malaria and unspecified viral syndrome, and obtained care in 131 countries. Thirty-four (3%) reported subsequent deterioration and 230 (21%) reported no change in condition; a third (n = 405; 37%) had a pre-travel health encounter. Forty-one travellers had sufficient data on planned healthcare abroad for analysis. The most common destinations were the US, France, Dominican Republic, Belgium and Mexico. The top reasons for their planned healthcare abroad were unavailability of procedure at home (n = 9; 19%), expertise abroad (n = 9; 19%), lower cost (n = 8; 17%) and convenience (n = 7; 15%); a third (n = 13; 32%) reported cosmetic or surgical procedures. Early and late complications occurred in 14 (33%) and 4 (10%) travellers, respectively. Four travellers (10%) had a pre-travel health encounter.
CONCLUSIONS: International travellers encounter health problems during travel that often could be prevented by pre-travel consultation. Travellers obtaining planned healthcare abroad can experience negative health consequences associated with treatments abroad, for which pre-travel consultations could provide advice and potentially help to prevent complications.
METHODS: We performed a systematic literature review of articles published until May 2022 that reported HZ epidemiology, clinical management, and health economic data in six Southeast Asian countries: Indonesia, Malaysia, the Philippines, Singapore, Thailand, and Vietnam. Literature searches were conducted in Medline, Scopus, Embase, and gray literature. Articles written in English or local languages were considered for inclusion.
RESULTS: In total, 72 publications were included in the study; 22 were case studies and over 60% originated in Singapore and Thailand. Only two studies (data from Thailand) reported incidence of HZ. The proportion of patients reported with HZ was 0.68-0.7% among dermatology clinics, 0.14% at one emergency department (5.3% of dermatology cases) in Singapore, and 3% of admissions at another hospital in Singapore. Pain was the most common symptom associated with HZ, reported in 74.21-100% of patients. HZ complications were reported in 10.2-21.2% of patients, and the proportions with postherpetic neuralgia and HZ ophthalmicus were 6.3-50% and 4.98-28.57%, respectively. Additionally, there is a lack of comprehensive, up-to-date HZ economic data, with only six studies identified for the Philippines, Singapore, and Thailand.
CONCLUSIONS: Overall, there are limited data reporting incidence and prevalence of HZ in Southeast Asia at a national level. High rates of complications, symptoms, and abundance of case reports suggest substantial healthcare resource utilization for patients with HZ and highlight the need for further research in Southeast Asia assessing the societal impact.
METHODS: For each country, we adapted a static multicohort Markov model developed with a 1-year cycle length and lifetime horizon. Demographics were obtained from the World Health Organization, HZ incidence from a worldwide meta-regression reporting Asian-specific values, proportions of postherpetic neuralgia (PHN) and non-PHN complications from local/regional studies, and vaccine efficacy from a long-term follow-up trial. First-dose coverage and second-dose compliance were assumed to be 30% and 70%, respectively. A one-way deterministic sensitivity analysis (OWSA) and probabilistic sensitivity analysis (PSA) were performed to assess the robustness and uncertainty of inputs for each country.
RESULTS: Without RZV, it was estimated that there would be a total of approximately 10 million HZ cases, 2.1 million PHN cases, and 1.4 million non-PHN complications in individuals aged ≥ 50 years included in the model. Introducing RZV under 30% coverage could avoid approximately 2.2 million (22%) HZ cases, almost 500,000 (21%) PHN cases, and around 300,000 (22%) non-PHN complications. OWSA showed that first-dose coverage and initial HZ incidence had the largest impact on the estimated number of HZ cases avoided. The number needed to vaccinate ranged from 15 to 21 to prevent one case of HZ and from 68 to 104 to prevent one case of PHN across each country.
CONCLUSIONS: This study demonstrated that there is substantial HZ disease burden in older adults for the five selected countries in Southeast Asia, negatively impacting national healthcare systems. Introducing RZV could potentially reduce this burden. A graphical abstract is available with this article.
METHODS: Clinicians reporting patients with suspected AMS to GeoSentinel submitted demographic, clinical, itinerary, and exposure data. We defined a probable case as travel to Tioman Island after 1 March 2011, eosinophilia (>5%), clinical or laboratory-supported myositis, and negative trichinellosis serology. Case confirmation required histologic observation of sarcocysts or isolation of Sarcocystis species DNA from muscle biopsy.
RESULTS: Sixty-eight patients met the case definition (62 probable and 6 confirmed). All but 2 resided in Europe; all were tourists and traveled mostly during the summer months. The most frequent symptoms reported were myalgia (100%), fatigue (91%), fever (82%), headache (59%), and arthralgia (29%); onset clustered during 2 distinct periods: "early" during the second and "late" during the sixth week after departure from the island. Blood eosinophilia and elevated serum creatinine phosphokinase (CPK) levels were observed beginning during the fifth week after departure. Sarcocystis nesbitti DNA was recovered from 1 muscle biopsy.
CONCLUSIONS: Clinicians evaluating travelers returning ill from Malaysia with myalgia, with or without fever, should consider AMS, noting the apparent biphasic aspect of the disease, the later onset of elevated CPK and eosinophilia, and the possibility for relapses. The exact source of infection among travelers to Tioman Island remains unclear but needs to be determined to prevent future illnesses.
OBJECTIVE: To determine whether genetic variants in and around SPINK5 are associated with IgE-mediated food allergy.
METHOD: We genotyped 71 "tag" single nucleotide polymorphisms (tag-SNPs) within a region spanning ~263 kb including SPINK5 (~61 kb) in n=722 (n=367 food-allergic, n=199 food-sensitized-tolerant and n=156 non-food-allergic controls) 12-month-old infants (discovery sample) phenotyped for food allergy with the gold standard oral food challenge. Transepidermal water loss (TEWL) measures were collected at 12 months from a subset (n=150) of these individuals. SNPs were tested for association with food allergy using the Cochran-Mantel-Haenszel test adjusting for ancestry strata. Association analyses were replicated in an independent sample group derived from four paediatric cohorts, total n=533 (n=203 food-allergic, n=330 non-food-allergic), mean age 2.5 years, with food allergy defined by either clinical history of reactivity, 95% positive predictive value (PPV) or challenge, corrected for ancestry by principal components.
RESULTS: SPINK5 variant rs9325071 (A⟶G) was associated with challenge-proven food allergy in the discovery sample (P=.001, OR=2.95, CI=1.49-5.83). This association was further supported by replication (P=.007, OR=1.58, CI=1.13-2.20) and by meta-analysis (P=.0004, OR=1.65). Variant rs9325071 is associated with decreased SPINK5 gene expression in the skin in publicly available genotype-tissue expression data, and we generated preliminary evidence for association of this SNP with elevated TEWL also.
CONCLUSIONS: We report, for the first time, association between SPINK5 variant rs9325071 and challenge-proven IgE-mediated food allergy.
METHODS: We prospectively characterized the clinical features and disease burden in a consecutively-recruited multi-ethnic Asian PSP cohort. Patients were extensively phenotyped using the Movement Disorder Society (MDS-PSP) clinical diagnostic criteria and the PSP-Clinical Deficits Scale (PSP-CDS). Caregiver burden was measured using the modified Zarit Burden Interview (ZBI). Investigations (neuroimaging and genetic tests) were reviewed.
RESULTS: There were 104 patients (64.4% male; 67.3% Chinese, 21.2% Indians, 9.6% Malays), consisting of 48.1% Richardson syndrome (PSP-RS), 37.5% parkinsonian phenotype (PSP-P), and 10.6% progressive gait freezing phenotype (PSP-PGF). Mean age at motor onset was 66.3 ± 7.7 years, with no significant differences between the PSP phenotypes. Interestingly, REM-sleep behaviour disorder (RBD) symptoms and visual hallucinations (considered rare in PSP) were reported in 23.5% and 22.8% of patients, respectively, and a family history of possible neurodegenerative or movement disorder in 20.4%. PSP-CDS scores were highest (worst) in PSP-RS; and correlated moderately with disease duration (rs = 0.45, P P = 0.029) in the overall cohort. Three of 48 (6.3%) patients who had whole-exome sequencing harboured pathogenic/likely pathogenic GBA variants.
CONCLUSIONS: Significant heterogeneity in clinical features and disease burden, and high rates of RBD symptoms, visual hallucinations, and familial involvement were observed in this relatively large cohort. Our findings highlight important considerations when assessing Asian patients, and provide further support for the notion of overlapping neurobiology between PSP and Lewy body disorders.