Patient Enrolment into HIV Care and Treatment within 90 Days of HIV Diagnosis in Eight Rwandan Health Facilities: A Review of Facility-Based Registers

INTRODUCTION: Access to antiretroviral therapy (ART) has increased greatly in sub-Saharan Africa. However many patients do not enrol timely into HIV care and treatment after HIV diagnosis. We studied enrolment into care and treatment and determinants of non-enrolment in Rwanda. METHODS: Data were obtained from routine clinic registers from eight health facilities in Rwanda on patients who were diagnosed with HIV at the antenatal care, voluntary counselling-and-testing, outpatient or tuberculosis departments between March and May 2009. The proportion of patients enrolled into HIV care and treatment was calculated as the number of HIV infected patients registered in ART clinics for follow-up care and treatment within 90 days of HIV diagnosis divided by the total number of persons diagnosed with HIV in the study period. RESULTS: Out of 482 patients diagnosed with HIV in the study period, 339 (70%) were females, and the median age was 29 years (interquartile range [IQR] 24-37). 201 (42%) enrolled into care and treatment within 90 days of HIV diagnosis. The median time between testing and enrolment was six days (IQR 2-14). Enrolment in care and treatment was not significantly associated with age, sex, or department of testing, but was associated with study site. None of those enrolled were in WHO stage 4. The median CD4 cell count among adult patients was 387 cells/mm(3) (IQR: 242-533 cells/mm(3)); 81 of 170 adult patients (48%) were eligible to start ART (CD4 count<350 cells/mm(3) or WHO stage 4). Among those eligible, 45 (56%) started treatment within 90 days of HIV diagnosis. CONCLUSION: Less than 50% of diagnosed HIV patients from eight Rwandan health facilities had enrolled into care and treatment within 90 days of diagnosis. Improving linkage to care and treatment after HIV diagnosis is needed to harness the full potential of ART

Linkage to HIV care before and after the introduction of provider-initiated testing and counselling in six Rwandan health facilities.

HIV testing and counselling forms the gateway to the HIV care and treatment continuum. Therefore, the World Health Organization recommends provider-initiated testing and counselling (PITC) in countries with a generalized HIV epidemic. Few studies have investigated linkage-to-HIV-care among out-patients after PITC. Our objective was to study timely linkage-to-HIV-care in six Rwandan health facilities (HFs) before and after the introduction of PITC in the out-patient departments (OPDs). Information from patients diagnosed with HIV was abstracted from voluntary counselling and testing, OPD and laboratory registers of six Rwandan HFs during three-month periods before (March-May 2009) and after (December 2009-February 2010) the introduction of PITC in the OPDs of these facilities. Information on patients' subsequent linkage-to-pre-antiretroviral therapy (ART) care and ART was abstracted from ART clinic registers of each HF. To triangulate the findings from HF routine, a survey was held among patients to assess reasons for non-enrolment. Of 635 patients with an HIV diagnosis, 232 (36.5%) enrolled at the ART clinic within 90 days of diagnosis. Enrolment among out-patients decreased after the introduction of PITC (adjusted odds ratio, 2.0; 95% confidence interval, 1.0-4.2; p = .051). Survey findings showed that retesting for HIV among patients already diagnosed and enrolled into care was not uncommon. Patients reported non-acceptance of disease status, stigma and problems with healthcare services as main barriers for enrolment. Timely linkage-to-HIV-care was suboptimal in this Rwandan study before and after the introduction of PITC; the introduction of PITC in the OPD may have had a negative impact on linkage-to-HIV-care. Healthier patients tested through PITC might be less ready to engage in HIV care. Fear of HIV stigma and mistrust of test results appear to be at the root of these problems

Genetic, household and spatial clustering of leprosy on an island in Indonesia: a population-based study

BACKGROUND: It is generally accepted that genetic factors play a role in susceptibility to both leprosy per se and leprosy type, but only few studies have tempted to quantify this. Estimating the contribution of genetic factors to clustering of leprosy within families is difficult since these persons often share the same environment. The first aim of this study was to test which correlation structure (genetic, household or spatial) gives the best explanation for the distribution of leprosy patients and seropositive persons and second to quantify the role of genetic factors in the occurrence of leprosy and seropositivity. METHODS: The three correlation structures were proposed for population data (n = 560), collected on a geographically isolated island highly endemic for leprosy, to explain the distribution of leprosy per se, leprosy type and persons harbouring Mycobacterium leprae-specific antibodies. Heritability estimates and risk ratios for siblings were calculated to quantify the genetic effect. Leprosy was clinically diagnosed and specific anti-M. leprae antibodies were measured using ELISA. RESULTS: For leprosy per se in the total population the genetic correlation structure fitted best. In the population with relative stable household status (persons under 21 years and above 39 years) all structures were significant. For multibacillary leprosy (MB) genetic factors seemed more important than for paucibacillary leprosy. Seropositivity could be explained best by the spatial model, but the genetic model was also significant. Heritability was 57% for leprosy per se and 31% for seropositivity. CONCLUSION: Genetic factors seem to play an important role in the clustering of patients with a more advanced form of leprosy, and they could explain more than half of the total phenotypic variance

Psychosocial factors and cancer incidence (PSY-CA):Protocol for individual participant data meta-analyses

OBJECTIVES: Psychosocial factors have been hypothesized to increase the risk of cancer. This study aims (1) to test whether psychosocial factors (depression, anxiety, recent loss events, subjective social support, relationship status, general distress, and neuroticism) are associated with the incidence of any cancer (any, breast, lung, prostate, colorectal, smoking-related, and alcohol-related); (2) to test the interaction between psychosocial factors and factors related to cancer risk (smoking, alcohol use, weight, physical activity, sedentary behavior, sleep, age, sex, education, hormone replacement therapy, and menopausal status) with regard to the incidence of cancer; and (3) to test the mediating role of health behaviors (smoking, alcohol use, weight, physical activity, sedentary behavior, and sleep) in the relationship between psychosocial factors and the incidence of cancer.METHODS: The psychosocial factors and cancer incidence (PSY-CA) consortium was established involving experts in the field of (psycho-)oncology, methodology, and epidemiology. Using data collected in 18 cohorts (N = 617,355), a preplanned two-stage individual participant data (IPD) meta-analysis is proposed. Standardized analyses will be conducted on harmonized datasets for each cohort (stage 1), and meta-analyses will be performed on the risk estimates (stage 2).CONCLUSION: PSY-CA aims to elucidate the relationship between psychosocial factors and cancer risk by addressing several shortcomings of prior meta-analyses.</p

'I believe that the staff have reduced their closeness to patients': an exploratory study on the impact of HIV/AIDS on staff in four rural hospitals in Uganda

<p>Abstract</p> <p>Background</p> <p>Staff shortages could harm the provision and quality of health care in Uganda, so staff retention and motivation are crucial. Understanding the impact of HIV/AIDS on staff contributes to designing appropriate retention and motivation strategies. This research aimed 'to identify the influence of HIV/AIDS on staff working in general hospitals at district level in rural areas and to explore support required and offered to deal with HIV/AIDS in the workplace'. Its results were to inform strategies to mitigate the impact of HIV/AIDS on hospital staff.</p> <p>Methods</p> <p>A cross-sectional study with qualitative and quantitative components was implemented during two weeks in September 2005. Data were collected in two government and two faith-based private not-for-profit hospitals purposively selected in rural districts in Uganda's Central Region. Researchers interviewed 237 people using a structured questionnaire and held four focus group discussions and 44 in-depth interviews.</p> <p>Results</p> <p>HIV/AIDS places both physical and, to some extent, emotional demands on health workers. Eighty-six per cent of respondents reported an increased workload, with 48 per cent regularly working overtime, while 83 per cent feared infection at work, and 36 per cent reported suffering an injury in the previous year. HIV-positive staff remained in hiding, and most staff did not want to get tested as they feared stigmatization. Organizational responses were implemented haphazardly and were limited to providing protective materials and the HIV/AIDS-related services offered to patients. Although most staff felt motivated to work, not being motivated was associated with a lack of daily supervision, a lack of awareness on the availability of HIV/AIDS counselling, using antiretrovirals and working overtime. The specific hospital context influenced staff perceptions and experiences.</p> <p>Conclusion</p> <p>HIV/AIDS is a crucially important contextual factor, impacting on working conditions in various ways. Therefore, organizational responses should be integrated into responses to other problematic working conditions and adapted to the local context. Opportunities already exist, such as better use of supervision, educational sessions and staff meetings. However, exchanges on interventions to improve staff motivation and address HIV/AIDS in the health sector are urgently required, including information on results and details of the context and implementation process.</p

Risk Factors of Typhoid Infection in the Indonesian Archipelago.

BACKGROUND: Knowledge of risk factors and their relative importance in different settings is essential to develop effective health education material for the prevention of typhoid. In this study, we examine the effect of household level and individual behavioural risk factors on the risk of typhoid in three Indonesian islands (Sulawesi, Kalimantan and Papua) in the Eastern Indonesian archipelago encompassing rural, peri-urban and urban areas. METHODS: We enrolled 933 patients above 10 years of age in a health facility-based case-control study between June 2010 and June 2011. Individuals suspected of typhoid were tested using the typhoid IgM lateral flow assay for the serodiagnosis of typhoid fever followed by blood culture testing. Cases and controls were defined post-recruitment: cases were individuals with a culture or serology positive result (n = 449); controls were individuals negative to both serology and culture, with or without a diagnosis other than typhoid (n = 484). Logistic regression was used to examine the effect of household level and individual level behavioural risk factors and we calculated the population attributable fraction (PAF) of removing each risk significant independent behavioural risk factor. RESULTS: Washing hands at critical moments of the day and washing hands with soap were strong independent protective factors for typhoid (OR = 0.38 95% CI 0.25 to 0.58 for each unit increase in hand washing frequency score with values between 0 = Never and 3 = Always; OR = 3.16 95% CI = 2.09 to 4.79 comparing washing hands with soap sometimes/never vs. often). These effects were independent of levels of access to water and sanitation. Up to two thirds of cases could be prevented by compliance to these practices (hand washing PAF = 66.8 95% CI 61.4 to 71.5; use of soap PAF = 61.9 95%CI 56.7 to 66.5). Eating food out in food stalls or restaurant was an important risk factor (OR = 6.9 95%CI 4.41 to 10.8 for every unit increase in frequency score). CONCLUSIONS: Major gains could potentially be achieved in reducing the incidence of typhoid by ensuring adherence to adequate hand-washing practices alone. This confirms that there is a pivotal role for 'software' related interventions to encourage behavior change and create demand for goods and services, alongside development of water and sanitation infrastructure

Genetic and lifestyle risk factors for MRI-defined brain infarcts in a population-based setting.

OBJECTIVE: To explore genetic and lifestyle risk factors of MRI-defined brain infarcts (BI) in large population-based cohorts. METHODS: We performed meta-analyses of genome-wide association studies (GWAS) and examined associations of vascular risk factors and their genetic risk scores (GRS) with MRI-defined BI and a subset of BI, namely, small subcortical BI (SSBI), in 18 population-based cohorts (n = 20,949) from 5 ethnicities (3,726 with BI, 2,021 with SSBI). Top loci were followed up in 7 population-based cohorts (n = 6,862; 1,483 with BI, 630 with SBBI), and we tested associations with related phenotypes including ischemic stroke and pathologically defined BI. RESULTS: The mean prevalence was 17.7% for BI and 10.5% for SSBI, steeply rising after age 65. Two loci showed genome-wide significant association with BI: FBN2, p = 1.77 × 10-8; and LINC00539/ZDHHC20, p = 5.82 × 10-9. Both have been associated with blood pressure (BP)-related phenotypes, but did not replicate in the smaller follow-up sample or show associations with related phenotypes. Age- and sex-adjusted associations with BI and SSBI were observed for BP traits (p value for BI, p [BI] = 9.38 × 10-25; p [SSBI] = 5.23 × 10-14 for hypertension), smoking (p [BI] = 4.4 × 10-10; p [SSBI] = 1.2 × 10-4), diabetes (p [BI] = 1.7 × 10-8; p [SSBI] = 2.8 × 10-3), previous cardiovascular disease (p [BI] = 1.0 × 10-18; p [SSBI] = 2.3 × 10-7), stroke (p [BI] = 3.9 × 10-69; p [SSBI] = 3.2 × 10-24), and MRI-defined white matter hyperintensity burden (p [BI] = 1.43 × 10-157; p [SSBI] = 3.16 × 10-106), but not with body mass index or cholesterol. GRS of BP traits were associated with BI and SSBI (p ≤ 0.0022), without indication of directional pleiotropy. CONCLUSION: In this multiethnic GWAS meta-analysis, including over 20,000 population-based participants, we identified genetic risk loci for BI requiring validation once additional large datasets become available. High BP, including genetically determined, was the most significant modifiable, causal risk factor for BI

Stroke genetics informs drug discovery and risk prediction across ancestries

Previous genome-wide association studies (GWASs) of stroke - the second leading cause of death worldwide - were conducted predominantly in populations of European ancestry(1,2). Here, in cross-ancestry GWAS meta-analyses of 110,182 patients who have had a stroke (five ancestries, 33% non-European) and 1,503,898 control individuals, we identify association signals for stroke and its subtypes at 89 (61 new) independent loci: 60 in primary inverse-variance-weighted analyses and 29 in secondary meta-regression and multitrait analyses. On the basis of internal cross-ancestry validation and an independent follow-up in 89,084 additional cases of stroke (30% non-European) and 1,013,843 control individuals, 87% of the primary stroke risk loci and 60% of the secondary stroke risk loci were replicated (P < 0.05). Effect sizes were highly correlated across ancestries. Cross-ancestry fine-mapping, in silico mutagenesis analysis(3), and transcriptome-wide and proteome-wide association analyses revealed putative causal genes (such as SH3PXD2A and FURIN) and variants (such as at GRK5 and NOS3). Using a three-pronged approach(4), we provide genetic evidence for putative drug effects, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as possible targets, with drugs already under investigation for stroke for F11 and PROC. A polygenic score integrating cross-ancestry and ancestry-specific stroke GWASs with vascular-risk factor GWASs (integrative polygenic scores) strongly predicted ischaemic stroke in populations of European, East Asian and African ancestry(5). Stroke genetic risk scores were predictive of ischaemic stroke independent of clinical risk factors in 52,600 clinical-trial participants with cardiometabolic disease. Our results provide insights to inform biology, reveal potential drug targets and derive genetic risk prediction tools across ancestries.</p

Stroke genetics informs drug discovery and risk prediction across ancestries

Previous genome-wide association studies (GWASs) of stroke — the second leading cause of death worldwide — were conducted predominantly in populations of European ancestry1,2. Here, in cross-ancestry GWAS meta-analyses of 110,182 patients who have had a stroke (five ancestries, 33% non-European) and 1,503,898 control individuals, we identify association signals for stroke and its subtypes at 89 (61 new) independent loci: 60 in primary inverse-variance-weighted analyses and 29 in secondary meta-regression and multitrait analyses. On the basis of internal cross-ancestry validation and an independent follow-up in 89,084 additional cases of stroke (30% non-European) and 1,013,843 control individuals, 87% of the primary stroke risk loci and 60% of the secondary stroke risk loci were replicated (P < 0.05). Effect sizes were highly correlated across ancestries. Cross-ancestry fine-mapping, in silico mutagenesis analysis3, and transcriptome-wide and proteome-wide association analyses revealed putative causal genes (such as SH3PXD2A and FURIN) and variants (such as at GRK5 and NOS3). Using a three-pronged approach4, we provide genetic evidence for putative drug effects, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as possible targets, with drugs already under investigation for stroke for F11 and PROC. A polygenic score integrating cross-ancestry and ancestry-specific stroke GWASs with vascular-risk factor GWASs (integrative polygenic scores) strongly predicted ischaemic stroke in populations of European, East Asian and African ancestry5. Stroke genetic risk scores were predictive of ischaemic stroke independent of clinical risk factors in 52,600 clinical-trial participants with cardiometabolic disease. Our results provide insights to inform biology, reveal potential drug targets and derive genetic risk prediction tools across ancestries