Yield of Facility-based Targeted Universal Testing for Tuberculosis With Xpert and Mycobacterial Culture in High-Risk Groups Attending Primary Care Facilities in South Africa.

BACKGROUND: We report the yield of targeted universal tuberculosis (TB) testing of clinic attendees in high-risk groups. METHODS: Clinic attendees in primary healthcare facilities in South Africa with one of the following risk factors underwent sputum testing for TB: human immunodeficiency virus (HIV), contact with a TB patient in the past year, and having had TB in the past 2 years. A single sample was collected for Xpert-Ultra (Xpert) and culture. We report the proportion positive for Mycobacterium tuberculosis. Data were analyzed descriptively. The unadjusted clinical and demographic factors' relative risk of TB detected by culture or Xpert were calculated and concordance between Xpert and culture is described. RESULTS: A total of 30 513 participants had a TB test result. Median age was 39 years, and 11 553 (38%) were men. The majority (n = 21734, 71%) had HIV, 12 492 (41%) reported close contact with a TB patient, and 1573 (5%) reported prior TB. Overall, 8.3% were positive for M. tuberculosis by culture and/or Xpert compared with 6.0% with trace-positive results excluded. In asymptomatic participants, the yield was 6.7% and 10.1% in symptomatic participants (with trace-positives excluded). Only 10% of trace-positive results were culture-positive. We found that 55% of clinic attendees with a sputum result positive for M. tuberculosis did not have a positive TB symptom screen. CONCLUSIONS: A high proportion of clinic attendees with specific risk factors (HIV, close TB contact, history of TB) test positive for M. tuberculosis when universal testing is implemented.

Evaluating systematic targeted universal testing for tuberculosis in primary care clinics of South Africa: A cluster-randomized trial (The TUTT Trial).

BACKGROUND: The World Health Organization (WHO) recommends systematic symptom screening for tuberculosis (TB). However, TB prevalence surveys suggest that this strategy does not identify millions of TB patients, globally. Undiagnosed or delayed diagnosis of TB contribute to TB transmission and exacerbate morbidity and mortality. We conducted a cluster-randomized trial of large urban and rural primary healthcare clinics in 3 provinces of South Africa to evaluate whether a novel intervention of targeted universal testing for TB (TUTT) in high-risk groups diagnosed more patients with TB per month compared to current standard of care (SoC) symptom-directed TB testing. METHODS AND FINDINGS: Sixty-two clinics were randomized; with initiation of the intervention clinics over 6 months from March 2019. The study was prematurely stopped in March 2020 due to clinics restricting access to patients, and then a week later due to the Coronavirus Disease 2019 (COVID-19) national lockdown; by then, we had accrued a similar number of TB diagnoses to that of the power estimates and permanently stopped the trial. In intervention clinics, attendees living with HIV, those self-reporting a recent close contact with TB, or a prior episode of TB were all offered a sputum test for TB, irrespective of whether they reported symptoms of TB. We analyzed data abstracted from the national public sector laboratory database using Poisson regression models and compared the mean number of TB patients diagnosed per clinic per month between the study arms. Intervention clinics diagnosed 6,777 patients with TB, 20.7 patients with TB per clinic month (95% CI 16.7, 24.8) versus 6,750, 18.8 patients with TB per clinic month (95% CI 15.3, 22.2) in control clinics during study months. A direct comparison, adjusting for province and clinic TB case volume strata, did not show a significant difference in the number of TB cases between the 2 arms, incidence rate ratio (IRR) 1.14 (95% CI 0.94, 1.38, p = 0.46). However, prespecified difference-in-differences analyses showed that while the rate of TB diagnoses in control clinics decreased over time, intervention clinics had a 17% relative increase in TB patients diagnosed per month compared to the prior year, interaction IRR 1.17 (95% CI 1.14, 1.19, p < 0.001). Trial limitations were the premature stop due to COVID-19 lockdowns and the absence of between-arm comparisons of initiation and outcomes of TB treatment in those diagnosed with TB. CONCLUSIONS: Our trial suggests that the implementation of TUTT in these 3 groups at extreme risk of TB identified more TB patients than SoC and could assist in reducing undiagnosed TB patients in settings of high TB prevalence. TRIAL REGISTRATION: South African National Clinical Trials Registry DOH-27-092021-4901.

Conditional Cash Transfers to Incentivize Tuberculosis Screening: Description of a Novel Strategy for Contact Investigation in Rural South Africa.

BACKGROUND: Providing incentives to screen close contacts for tuberculosis (TB) is an alternative to household-based contact investigation. We aimed to characterize patients and contexts where this incentive-based strategy might be preferred. METHODS: This is a secondary analysis of a cluster randomized trial of TB contact investigation in Limpopo District, South Africa, conducted between 2016 and 2020. Twenty-eight clinics were randomly allocated to household-based vs incentive-based contact investigation. In the incentive-based arm, index participants and contacts received transport reimbursement and incentives for TB screening and microbiological diagnosis of contacts. We estimated differences in mean number of contacts per index participant with household-based vs incentive-based contact investigation overall and within subgroups of index participants. RESULTS: A total of 3776 contacts (1903 in the incentive-based and 1873 in the household-based arm) were referred by 2501 index participants. A higher proportion of contacts in the incentive-based than household-based arm were adults (72% vs 59%), reported chronic TB symptoms (25% vs 16%) or ever smoking (23% vs 11%). Index participants who walked or bicycled to a clinic referred 1.03 more contacts per index (95% confidence interval [CI], .48 to 1.57) through incentive-based than household-based investigation. Index participants living with >5 household members referred 0.48 more contacts per index (95% CI, .03 to .94) through household-based than incentive-based investigation. CONCLUSIONS: Relative to household-based investigation, incentive-based investigation identifies contacts likely at higher risk for active TB. Incentive-based investigation may be more appropriate for index participants who can easily access clinics, versus household-based investigation for patients with large households. Clinical Trials Registration. NCT02808507.

Relationship of circulating immune cells with lifestyle factors and cancer recurrence in early-stage breast cancer.

PURPOSE: To evaluate the relationship of circulating immune cells with recurrence and metabolic/lifestyle factors in patients with early-stage breast cancer. METHODS: Patients with early-stage breast cancer were identified from the electronic record and institutional registry. Lymphocyte and monocyte counts were obtained from blood samples at time of diagnosis prior to any chemotherapy. Correlations between lymphocyte and monocyte and recurrence were assessed in the entire cohort and among obese patients, those reporting alcohol consumption and smoking. Competing risk regression was used to analyze time to recurrence. RESULTS: A total of 950 patients with ≥ 5 years of follow-up were identified; 433 had complete data and were eligible for analysis. 293 (68%) had hormone receptor-positive breast cancer, 82 (19%) HER2 positive, and 53 (13%) triple negative. Patients in the highest quintile of lymphocytes compared to the lowest quintile had lower risk of recurrence (subhazard ratio (SHR) = 0.17, 95% CI [0.03-0.93], p = 0.041) while patients in the highest quintile of monocytes had lower risk for recurrence (SHR = 0.19, 95% CI [0.04, 0.92], p = 0.039). Higher monocytes were more strongly associated with lower recurrence among those reporting alcohol consumption (HR = 0.10, 95% CI [0.01, 0.91], p = 0.04). In obese patients, higher lymphocytes were associated with lower risk of recurrence (p = 0.046); in non-obese patients, higher monocytes were associated with lower risk of recurrence (p = 0.02). There were no correlations among patients who reported tobacco use. CONCLUSIONS: High lymphocyte and monocyte counts are associated with lower recurrence rate in early-stage breast cancer, particularly in obese patients and those reporting alcohol consumption.

Daratumumab-lenalidomide-dexamethasone vs standard-of-care regimens: Efficacy in transplant-ineligible untreated myeloma.

Daratumumab in combination with lenalidomide-dexamethasone (D-Rd) recently received FDA approval for the treatment of transplant-ineligible patients with newly diagnosed multiple myeloma (NDMM). The present PEGASUS study compared progression-free survival (PFS) in patients treated with D-Rd in the MAIA trial and patients treated with common standard-of-care regimens from the Flatiron Health electronic health record-derived deidentified database, which has data from patients treated primarily at community-based oncology practices in the United States. Individual-level patient data from both data sources were used to perform an anchored indirect treatment comparison (ITC) of D-Rd to bortezomib-lenalidomide-dexamethasone (VRd) and bortezomib-dexamethasone (Vd); lenalidomide-dexamethasone (Rd) was the common anchor for the ITC. Hazard ratios (HRs) reflecting direct comparisons of PFS within MAIA (D-Rd vs Rd) and Flatiron Health (VRd vs Rd; Vd vs Rd) were used to make ITCs for D-Rd vs VRd and Vd, respectively. After application of MAIA inclusion/exclusion criteria and propensity-score weighting, the Flatiron Health patients resembled the MAIA trial population on measured baseline characteristics. Based on the direct comparison within MAIA, treatment with D-Rd was associated with a significantly lower risk of progression or death compared to Rd (HR 0.54; 95% CI 0.42, 0.71). Based on the ITCs, D-Rd was associated with a significantly lower risk of progression or death compared to VRd (HR 0.68; 95% CI 0.48, 0.98) and Vd (HR 0.48; 95% CI 0.33, 0.69). In the absence of head-to-head trials comparing D-Rd to VRd or Vd, the present ITC may help inform treatment selection in transplant-ineligible patients with NDMM.

Contact tracing versus facility-based screening for active TB case finding in rural South Africa: A pragmatic cluster-randomized trial (Kharitode TB).

BACKGROUND: There is a dearth of comparative effectiveness research examining the implementation of different strategies for active tuberculosis (TB) case finding, particularly in rural settings, which represent 60% of the population of sub-Saharan Africa. METHODS AND FINDINGS: We conducted a pragmatic, cluster-randomized comparative effectiveness trial of two TB case finding strategies (facility-based screening and contact tracing) in 56 public primary care clinics in two largely rural districts of Limpopo Province, South Africa. In the facility-based screening arm, sputum Xpert MTB/RIF was performed on all patients presenting (for any reason) with TB symptoms to 28 study clinics, and no contact tracing was performed. In the contact-tracing arm, contacts of patients with active TB were identified (via household tracing in 14 clinics and using small monetary incentives in the other 14 clinics), screened for TB symptoms, and offered Xpert MTB/RIF testing. The primary outcome was the number of newly identified patients with TB started on treatment. The analysis used multivariable Poisson regression adjusted for historical clinic-level TB case volumes and district. The trial was registered with ClinicalTrials.gov (NCT02808507). From July 18, 2017, to January 17, 2019, a total of 3,755 individuals started TB treatment across 56 study clinics in the 18-month period. Clinic characteristics and clinic-level averages of patient characteristics were similar across the two arms: 40/56 (71%) clinics were in a rural location, 2,136/3,655 (58%) patients were male, and 2,243 (61%) were HIV positive. The treatment initiation ratio comparing the yield of TB patients started on treatment in the facility-based arm compared to that from the contact-tracing arm was 1.04 (95% confidence interval [CI] 0.83-1.30, p = 0. 73). In the contact-tracing arm, 1,677 contacts of 788 new TB index patients were screened, yielding 12 new patients with TB. Prespecified subgroup analyses resulted in similar results, with estimated treatment initiation ratios of 0.96 (95% CI 0.64-1.27; p = 0.78) and 1.23 (95% CI 0.87-1.59; p = 0.29) among historically smaller and historically larger clinics, respectively. This ratio was 1.02 (95% CI 0.66-1.37; p = 0.93) and 1.08 (95% CI 0.74-1.42; p = 0.68) in the Vhembe and Waterberg districts, respectively. The estimated treatment initiation ratio was unchanged in sensitivity analyses excluding 24 records whose TB registration numbers could not be verified (1.03, 95% CI 0.82-1.29; p = 0.78) and excluding transfers-in (1.02, 95% CI 0.80-1.29; p = 0.71). Study limitations include the possibility of imbalance on cluster size owing to changes in catchment population over time and the inability to distinguish the independent effects of the two contact investigation strategies. CONCLUSIONS: Contact tracing based on symptom screening and Xpert MTB/RIF testing did not increase the rate of treatment initiation for TB relative to the less resource-intensive approach of facility-based screening in this rural sub-Saharan setting. TRIAL REGISTRATION: ClinicalTrials.gov NCT02808507.

Pregnancy intervals after stillbirth, neonatal death and spontaneous abortion and the risk of an adverse outcome in the next pregnancy in rural Bangladesh.

BACKGROUND: Studies have revealed associations between preceding short and long birth-to-birth or birth-to-pregnancy intervals and poor pregnancy outcomes. Most of these studies, however, have examined the effect of intervals that began with live births. Using data from Bangladesh, we examined the effect of inter-outcome intervals (IOI) starting with a non-live birth or neonatal death, on outcomes in the next pregnancy. Pregnancy spacing behaviors in rural northeast Bangladesh have changed little since 2004. METHODS: We analyzed pregnancy histories for married women aged 15-49 years who had outcomes between 2000 and 2006 in Sylhet, Bangladesh. We examined the effects of the preceding outcome and the IOI length on the risk of stillbirth, neonatal death and spontaneous abortion using multinomial logistic regression models. RESULTS: Data included 64,897 pregnancy outcomes from 33,495 mothers. Inter-outcome intervals of 27-50 months and live births were baseline comparators. Stillbirths followed by IOI's <=6 months, 7-14 months or overall <=14 months had increased risks for spontaneous abortion with adjusted relative risk ratios (aRRR) and 95% confidence intervals = 29.6 (8.09, 108.26), 1.84 (0.84, 4.02) and 2.53 (1.19, 5.36), respectively. Stillbirths followed by IOIs 7-14 months had aRRR 2.00 (1.39, 2.88) for stillbirths. Neonatal deaths followed by IOIs <=6 months had aRRR 28.2 (8.59, 92.63) for spontaneous abortion. Neonatal deaths followed by IOIs 7-14 and 15-26 months had aRRRs 3.08 (1.82, 5.22) and 2.32 (1.38, 3.91), respectively, for stillbirths; and aRRRs 2.81 (2.06, 3.84) and 1.70 (1.24, 3.84), respectively, for neonatal deaths. Spontaneous abortions followed by IOIs <=6 months and 7-14 months had, respectively, aRRRs 23.21 (10.34, 52.13) and 1.80 (0.98, 3.33) for spontaneous abortion. CONCLUSION: In rural northeast Bangladesh, short inter-outcome intervals after stillbirth, neonatal death and spontaneous abortion were associated with a high risk of a similar outcome in the next pregnancy. These findings are aligned with other studies from Bangladesh. Two studies from similar settings have found benefits of waiting six months before conceiving again, suggesting that incorporating this advice into programs should be considered. Further research is warranted to confirm these findings.

Intimate partner violence, HIV and sexually transmitted infections in fishing, trading and agrarian communities in Rakai, Uganda.

BACKGROUND: Intimate partner violence (IPV), HIV and sexually transmitted infections (STI) can contribute to disparities in population health, depending on the individual, social and environmental factors characterizing a setting. To better understand the place-based determinants and patterns of these key interrelated public health problems in Uganda, we compared risk factors for IPV, HIV and STI in fishing, trading and agrarian communities in Rakai, Uganda by gender. METHOD: This study used cross-sectional data collected from 14,464 sexually active men (n = 6531) and women (n = 7933) as part of the Rakai Community Cohort Study, a population-based open cohort study of men and women aged 15-49 years. We used multilevel modified poisson regression models, which incorporated random intercepts for community and households. Factors associated with IPV, HIV and STI were assessed separately for men and women in fishing, trading and agrarian communities. RESULTS: A larger proportion of participants in the fishing communities than those in trading and agrarian communities were HIV positive, engaged in HIV risk behaviors, had STI symptoms and reported perpetration of or victimization by IPV. Female gender was a shared correlate of IPV, HIV and STI in the fishing communities. Engagement in multiple sexual relationships or partner's engagement in multiple relationships were shared correlates of IPV, and HIV in agrarian communities and IPV and STI in trading communities. CONCLUSION: Programs should target factors at multiple levels to reduce risk for syndemic conditions of HIV, STI and IPV in Rakai, Uganda particularly among men and women in fishing communities.

Postoperative Enteral Nutrition Guidelines Reduce the Risk of Intestinal Failure-Associated Liver Disease in Surgical Infants.

OBJECTIVE: To assess the effectiveness of postoperative feeding guidelines in reducing the incidence and severity of intestinal failure-associated liver disease (IFALD) among infants. STUDY DESIGN: Two cohorts of infants <6 months old undergoing intestinal surgery were compared: preguideline (retrospective data from 2007 to 2013; n = 83) and postguideline (prospective data from 2013 to 2016; n = 81). The guidelines included greater initial enteral nutrition volumes of 20 mL/kg/d and daily feeding advancement if tolerated. The primary outcomes were incidence of IFALD (peak direct bilirubin [DB] >2 mg/dL) and severity (DB >5 mg/dL for moderate-severe). Multiple logistic regression was used to determine the odds of developing IFALD. Other outcomes were time to reach 50% and 100% goal calories from enteral nutrition and the incidence of necrotizing enterocolitis after feeding. RESULTS: The incidence of IFALD decreased from 71% to 51% (P = .031), and median peak DB decreased from 5.7 to 2.4 mg/dL (P = .001). After adjusting for diagnosis and prematurity, the odds of developing IFALD of any severity were reduced by 60% (OR 0.40, 95% CI 0.20-0.85), and the odds of developing moderate-to-severe IFALD were reduced by 72% (OR 0.28, 95% CI 0.13-0.58) with guideline use. Time to reach 50% enteral nutrition decreased from a median of 10 to 6 days (P = .020) and time to reach 100% enteral nutrition decreased from 35 to 21 days (P = .035) with guideline use. The incidence of necrotizing enterocolitis after initiating enteral nutrition did not change (5% vs 9%, P = .346). CONCLUSIONS: Implementation of feeding guidelines reduced time to reach feeding goals, significantly reducing IFALD incidence and severity.

Plasma proteins associated with circulating carotenoids in Nepalese school-aged children.

Carotenoids are naturally occurring pigments that function as vitamin A precursors, antioxidants, anti-inflammatory agents or biomarkers of recent vegetable and fruit intake, and are thus important for population health and nutritional assessment. An assay approach that measures proteins could be more technologically feasible than chromatography, thus enabling more frequent carotenoid status assessment. We explored associations between proteomic biomarkers and concentrations of 6 common dietary carotenoids (α-carotene, ß-carotene, lutein/zeaxanthin, ß-cryptoxanthin, and lycopene) in plasma from 500 6-8 year old Nepalese children. Samples were depleted of 6 high-abundance proteins. Plasma proteins were quantified using tandem mass spectrometry and expressed as relative abundance. Linear mixed effects models were used to determine the carotenoid:protein associations, accepting a false discovery rate of q < 0.10. We quantified 982 plasma proteins in >10% of all child samples. Among these, relative abundance of 4 were associated with ß-carotene, 11 with lutein/zeaxanthin and 51 with ß-cryptoxanthin. Carotenoid-associated proteins are notably involved in lipid and vitamin A transport, antioxidant function and anti-inflammatory processes. No protein biomarkers met criteria for association with α-carotene or lycopene. Plasma proteomics may offer an approach to assess functional biomarkers of carotenoid status, intake and biological function for public health application. Original maternal micronutrient trial from which data were derived as a follow-up activity was registered at ClinicalTrials.gov: NCT00115271.

Plasma Selenium Protein P Isoform 1 (SEPP1): A Predictor of Selenium Status in Nepalese Children Detected by Plasma Proteomics.

Selenium deficiency or excess may have public health consequences, yet selenium status is infrequently characterized in populations, perhaps due to challenges in methodology. We are seeking to identify plasma proteins, using proteomics discovery and validation approaches, to serve as proxies for micronutrient status, including selenium, which may in the future be more readily assessed by robust, affordable field methods. In a sample of rural Nepalese children 6 - 8 years old (n = 500), the prevalence of selenium deficiency was 13.6 and 60.9 % at plasma selenium concentrations < 0.60 and < 0.89 µmol/L, respectively, assessed by atomic absorption spectroscopy. Relative abundance of selenoprotein P isoform 1 (SEPP1), glutathione reductase-3, and apolipoprotein A2 from discovery-based experiments was correlated with plasma selenium with a false discovery rate < 10 % (i. e., q < 0.10), all with p < 0.001. In linear mixed effects regression models to predict plasma selenium, only SEPP1 was significant (R2 = 0.63), estimating 8.2 % (95 % CI: 3.9 - 12.6) and 65.5(61.4 - 69.7)% of the in-sample population as deficient at each respective cut-off. Targeted quantification of SEPP1 in a preliminary series of specimens (n = 19) as a validation of the discovery approach revealed a high correlation with plasma selenium (r = 0.757, p = 0.0002). Plasma proteomics can identify valid plasma protein indicators of micronutrient status, as shown with selenium, comprising a step toward making population assessment of selenium status in vulnerable groups more accessible.

Analytical and Clinical Evaluation of the Epistem Genedrive Assay for Detection of Mycobacterium tuberculosis.

The Epistem Genedrive assay rapidly detects the Mycobacterium tuberculosis omplex from sputum and is currently available for clinical use. However, the analytical and clinical performance of this test has not been fully evaluated. The analytical limit of detection (LOD) of the Genedrive PCR amplification was tested with genomic DNA; the performance of the complete (sample processing plus amplification) system was tested by spiking M. tuberculosismc(2)6030 cells into distilled water andM. tuberculosis-negative sputum. Specificity was tested using common respiratory pathogens and nontuberculosis mycobacteria. A clinical evaluation enrolled adults with suspected pulmonary tuberculosis, obtained three sputum samples from each participant, and compared the accuracy of the Gene drive to that of the Xpert MTB/RIF assay using M. tuberculosiscultures as the reference standard. The Genedrive assay had an LOD of 1 pg/µl (100 genomic DNA copies/reaction). The LODs of the system were 2.5 × 10(4)CFU/ml and 2.5 × 10(5)CFU/ml for cells spiked into water and sputum, respectively. False-positiverpoBprobe signals were observed in 3/32 (9.4%) of the negative controls and also in few samples containing Mycobacterium abscessus,Mycobacterium gordonae, o rMycobacterium thermoresistibile In the clinical study, among 336 analyzed participants, the overall sensitivities for the tuberculosis case detection of Gene drive, Xpert, and smear microscopy were 45.4% (95% confidence interval [CI], 35.2% to 55.8%), 91.8% (95% CI, 84.4% to 96.4%), and 77.3% (95% CI, 67.7% to 85.2%), respectively. The sensitivities of Gene drive and Xpert for the detection of smear-microscopy-negative tuberculosis were 0% (95% CI, 0% to 15.4%) and 68.2% (95% CI, 45.1% to 86.1%), respectively. The Genedrive assay did not meet performance standards recommended by the World Health Organization for a smear microscopy replacement tuberculosis test. Epistem is working on modifications to improve the assay.

Arsenic exposure is associated with pediatric pneumonia in rural Bangladesh: a case control study.

BACKGROUND: Pneumonia is the leading cause of death for children under 5 years of age globally, making research on modifiable risk factors for childhood pneumonia important for reducing this disease burden. Millions of children globally are exposed to elevated levels of arsenic in drinking water. However, there is limited data on the association between arsenic exposure and respiratory infections, particularly among pediatric populations. METHODS: This case control study of 153 pneumonia cases and 296 controls 28 days to 59 months of age in rural Bangladesh is the first to assess whether arsenic exposure is a risk factor for pneumonia in a pediatric population. Cases had physician diagnosed World Health Organization defined severe or very severe pneumonia. Urine collected during hospitalization (hospital admission time point) and 30 days later (convalescent time point) from cases and a single specimen from community controls was tested for urinary arsenic by graphite furnace atomic absorption. RESULTS: The odds for pneumonia was nearly double for children with urinary arsenic concentrations higher than the first quartile (≥6 µg/L) at the hospital admission time point (Odd Ratio (OR):1.88 (95% Confidence Interval (CI): 1.01, 3.53)), after adjustment for urinary creatinine, weight for height, breastfeeding, paternal education, age, and number of people in the household. This was consistent with findings at the convalescent time point where the adjusted OR for children with urinary arsenic concentrations greater than the first quartile (≥6 µg/L) was 2.32 (95% CI: 1.33, 4.02). CONCLUSION: We observed a nearly two times higher odds of pneumonia for children with creatinine adjusted urinary arsenic concentrations greater than the first quartile (≥6 µg/L) at the hospital admission time point. This novel finding suggests that low to moderate arsenic exposure may be a risk factor for pneumonia in children under 5 years of age.

Clustering of neonatal deaths in Bangladesh: results from the Projahnmo studies.

BACKGROUND: Neonatal mortality (NM) tends to be clustered within a small subset of mothers, households and/or geographical areas. Knowledge of the maternal and newborn factors associated with NM can help identify high-risk mothers and guide the targeting of intervention programmes. METHOD: Data from pregnancy history surveys conducted as part of the Project for Advancing the Health of Newborns and Mothers (Projahnmo) in Sylhet and Mirzapur districts of Bangladesh were used to investigate risk factors for NM. We analysed data from babies born between 2001 and 2005 in the control clusters of the Projahnmo trials. Generalised linear mixed models were applied to quantify the heterogeneity among mothers and to investigate factors that contribute to this heterogeneity. RESULTS: There was an indication of correlation among siblings' outcomes. Neonates whose preceding sibling had died as a neonate in the mothers' lifetime pregnancy history were more likely (up to 1.9 times) to die than those with a living sibling. Factors that varied at the child and mother levels as well as the preceding siblings' outcome explained a large proportion (60% in Sylhet and 70% in Mirzapur) of the between-mother variation in NM. CONCLUSION: The preceding sibling's outcome may be a surrogate for genetic and other maternal health factors such as nutrition, infection or environmental factors that were not measured within Projahnmo. Further research into these factors is required in order to explain the variation in the risk for NM.

Contribution of community-based newborn health promotion to reducing inequities in healthy newborn care practices and knowledge: evidence of improvement from a three-district pilot program in Malawi.

BACKGROUND: Inequities in both health status and coverage of health services are considered important barriers to achieving Millennium Development Goal 4. Community-based health promotion is a strategy that is believed to reduce inequities in rural low-income settings. This paper examines the contributions of community-based programming to improving the equity of newborn health in three districts in Malawi. METHODS: This study is a before-and-after evaluation of Malawi's Community-Based Maternal and Newborn Care (CBMNC) program, a package of facility and community-based interventions to improve newborn health. Health Surveillance Assistants (HSAs) within the catchment area of 14 health facilities were trained to make pregnancy and postnatal home visits to promote healthy behaviors and assess women and newborns for danger signs requiring referral to a facility. "Core groups" of community volunteers were also trained to raise awareness about recommended newborn care practices. Baseline and endline household surveys measured the coverage of the intervention and targeted health behaviors for this before-and-after evaluation. Wealth indices were constructed using household asset data and concentration indices were compared between baseline and endline for each indicator. RESULTS: The HSAs trained in the intervention reached 36.7% of women with a pregnancy home visit and 10.9% of women with a postnatal home visit within three days of delivery. Coverage of the intervention was slightly inequitable, with richer households more likely to receive one or two pregnancy home visits (concentration indices (CI) of 0.0786 and 0.0960), but not significantly more likely to receive a postnatal visit or know of a core group. Despite modest coverage levels for the intervention, health equity improved significantly over the study period for several indicators. Greater improvements in inequities were observed for knowledge indicators than for coverage of routine health services. At endline, a greater proportion of women from the poorest quintile knew three or more danger signs for pregnancy, delivery, and postpartum mothers than did women from the least poor quintile (change in CI: -0.1704, -0.2464, and -0.4166, respectively; p < 0.05). Equity also significantly improved for coverage of some health behaviors, including delivery at a health facility (change in CI: -0.0591), breastfeeding within the first hour (-0.0379), and delayed bathing (-0.0405). CONCLUSIONS: Although these results indicate promising improvements for newborn health in Malawi, the extent to which the CBMNC program contributed to these improvements in coverage and equity are not known. The strategies through which community-based programs are implemented likely play an important role in their ability to improve equity, and further research and program monitoring are needed to ensure that the poorest households are reached by community-based health programs.

Brief Report: Changing Characteristics Among In-Hospital HIV Deaths: An 11-Year Retrospective Review of a Regional Hospital in South Africa.

BACKGROUND: Elevated HIV-associated mortality persists, despite a notable decline with the expansion of antiretroviral therapy (ART). In South Africa, the relative majority of deaths occur in health facilities, providing an opportunity to track decedent characteristics. SETTING: We analyzed data from 14,870 adult patients who died between 2008 and 2018 at Klerksdorp/Tshepong Hospital Complex in South Africa. METHODS: Recorded data included demographics, causes of death, HIV status, ART, and tuberculosis (TB) history. We present summary statistics and results from linear, log-binomial, and multinomial regressions to quantify changes over time. RESULTS: Over the study period, the median age of decedents with HIV in the hospital increased from 39.3 to 43.4 years, and there was a switch to male predominance (46%-54%). Those who died at a younger age (<40 years) remained more likely to be HIV-positive than the older age group, despite the overall proportion of HIV-positivity decreasing over time. The proportion of decedents with HIV ever started on ART increased from 21% to 67%. The proportion of HIV patients dying from TB and AIDS-defining illnesses decreased from 31% to 22%. CONCLUSIONS: We noted a shift in deaths over time to more men and older individuals, whereas the burden of HIV was heaviest on the younger age groups. Advanced HIV disease remained an important cause of mortality. We also observed an increase in less-traditional opportunistic illnesses among those with HIV, including malignancy, cardiovascular disease, and kidney disease. The high proportion of patients on ART who died prematurely requires further research and interventions.

HIV and viremia prevalence in non-migrating members of migrant households in Rakai region, Uganda: A cross-sectional population-based study.

Introduction: In sub-Saharan Africa, migrants are more likely to be HIV seropositive and viremic than non-migrants. However, little is known about HIV prevalence and viremia in non-migrants living in households with in- or out-migration events. We compared HIV outcomes in non-migrating persons in households with and without migration events using data from the Rakai Community Cohort Study (RCCS), an open population-based cohort in Uganda. Methods: We analyzed RCCS survey data from one survey round collected between August 2016 and May 2018 from non-migrating participants aged 15-49. Migrant households were classified as those reporting ≥1 member moving into or out of the household since the prior survey. A validated rapid test algorithm determined HIV serostatus. HIV viremia was defined as >1,000 copies/mL. Modified Poisson regression was used to estimate associations between household migration and HIV outcomes, with results reported as adjusted prevalence ratios (adjPR) with 95% confidence intervals (95%CI). Analyses were stratified by gender, direction of migration (into/out of the household), and relationship between non-migrants and migrants (e.g., spouse). Results: There were 14,599 non-migrants (7,654, 52% women) identified in 9,299 households. 4,415 (30%) lived in a household with ≥1 recent migrant; of these, 972(22%) had migrant spouses, 1,102(25%) migrant children, and 875(20%) migrant siblings. Overall, HIV prevalence and viremia did not differ between non-migrants in migrant and non-migrant households. However, in stratified analyses, non-migrant women with migrant spouses were significantly more likely to be HIV seropositive compared to non-migrant women with non-migrant spouses (adjPR:1.44, 95%CI:1.21-1.71). Conversely, non-migrant mothers living with HIV who had migrant children were less likely to be viremic (adjPR:0.34, 95%CI:0.13-0.86). Among non-migrant men living with HIV, spousal migration was associated with a non-significant increased risk of viremia (adjPR:1.37, 95%CI:0.94-1.99). Associations did not typically differ for migration into or out of the household. Conclusions: Household migration was associated with HIV outcomes for certain non-migrants, suggesting that the context of household migration influences the observed association with HIV outcomes. In particular, non-migrating women with migrating spouses were more likely to have substantially higher HIV burden. Non-migrants with migrant spouses may benefit from additional support when accessing HIV services.

Arrhythmogenic Right Ventricular Cardiomyopathy Prevalence and Arrhythmic Outcomes in At-Risk Family Members: A Systematic Review and Meta-Analysis.

BACKGROUND: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a complex cardiomyopathy with autosomal dominant inheritance and age-related incomplete penetrance, characterized by a high risk of sudden cardiac death. Recent professional consensus guidelines recommend clinical cardiac lifelong serial screening for at-risk family members refined only by age, but family genotype might influence necessary screening. Although numerous studies report prevalence of disease and arrhythmia in family members and explore predictors of penetrance and arrhythmic risk, a systematic review consolidating this evidence is lacking. METHODS: We searched Medline (PubMed), Embase, The Cochrane Library, and Web of Science for studies that reported prevalence of (1) diagnosis of ARVC per 2010 Task Force Criteria and/or (2) sustained ventricular arrhythmias (VA) in at least 10 family members of definite patients with ARVC. RESULTS: We identified 41 studies, including 36 that reported diagnosis by Task Force Criteria and 22 VA. Meta-analysis of 1359 family members, from 13 unique cohorts showed an average prevalence estimate of 25% for diagnosis as per Task Force Criteria (95% CI, 0.15-0.35, I2=96.44%). Overall prevalence of VA among gene-positive family members was 18% (95% CI, 0.13-0.23, I2=33.25%) in 7 independent studies (n=597). Family genotype was a significant risk factor for diagnosis of both ARVC (odds ratio, 6.91 [95% CI, 1.27-37.70]; P=0.0005) and VA (odds ratio, 13.62 [95% CI, 0.91-204.13]; P=0.06). Male gender was not associated with disease prevalence (odds ratio, 1.18 [95% CI, 0.72-1.95]; P=0.42) or VA (odds ratio, 0.81 [95% CI, 0.51-1.29]; P=0.91). CONCLUSIONS: The prevalence of ARVC and VA in at-risk family members differs significantly based on family genotype. Although recent recommendations provide a guideline based only on age, we propose screening every 1 to 2 years for gene-positive family members and every 3 to 5 years for first-degree relatives of gene-elusive cases, as long as they are asymptomatic and not athletes.

CKD and hospitalization in the elderly: a community-based cohort study in the United Kingdom.

BACKGROUND: We previously have shown that chronic kidney disease (CKD) is associated with cardiovascular and all-cause mortality in community-dwelling people 75 years and older. The present study addresses the hypothesis that CKD is associated with a higher rate of hospital admission at an older age. STUDY DESIGN: Cohort study. SETTING & PARTICIPANTS: 15,336 participants from 53 UK general practices underwent comprehensive health assessment between 1994 and 1999. PREDICTOR: Data for estimated glomerular filtration rate (eGFR, derived from creatinine levels using the CKD Epidemiology Collaboration [CKD-EPI] study equation) and dipstick proteinuria were available for 12,371 participants. OUTCOMES: Hospital admissions collected from hospital discharge letters for 2 years after assessment. MEASUREMENTS: Age, sex, cardiovascular risk factors, possible biochemical and health consequences of kidney disease (hemoglobin, phosphate, and albumin levels; physical and mental health problems). RESULTS: 2,310 (17%) participants had 1 hospital admission, and 981 (7%) had 2 or more. After adjusting for age, sex, and cardiovascular risk factors, HRs were 1.66 (95% CI, 1.21-2.27), 1.17 (95% CI, 0.95-1.43), 1.08 (95% CI, 0.90-1.30), and 1.11 (95% CI, 0.91-1.35) for eGFRs <30, 30-44, 45-59, and ≥75 mL/min/1.73 m(2), respectively, compared with eGFRs of 60-74 mL/min/1.73 m(2) for hospitalizations during <6 months of follow-up. HRs were weaker for follow-up of 6-18 months. Dipstick-positive proteinuria was associated with an increased HR throughout follow-up (HR, 1.29 [95% CI, 1.11-1.49], adjusting for cardiovascular risk factors). Dipstick-positive proteinuria and eGFR <30 mL/min/1.73 m(2) were independently associated with 2 or more hospital admissions during the 2-year follow-up. Adjustment for other health factors and laboratory measurements attenuated the effect of eGFR, but not the effect of proteinuria. LIMITATIONS: Follow-up limited to 2 years, selection bias due to nonparticipation in study, missing data for potential covariates, and single noncalibrated measurements from multiple laboratories. CONCLUSIONS: The study indicates that community-dwelling older people who have dipstick-positive proteinuria and/or eGFR <30 mL/min/1.73 m(2) are at increased risk of hospitalization.

High occurrence of witnessing an opioid overdose in a sample of women who use heroin in Tanzania: Implications for overdose prevention.

BACKGROUND: Opioid overdose is preventable and reversible. To target overdose prevention training and naloxone distribution, it is important to understand characteristics of those people who use drugs most likely to witness an overdose. In this paper we report the proportion and characteristics of women who use heroin that have witnessed an opioid overdose in Dar es Salaam, Tanzania. METHODS: We conducted a cross-sectional survey with 200 women who use heroin. We fitted unadjusted and adjusted logistic regression models with witnessing an opioid overdose as the dependent variable and sociodemographic and drug use-related variables as independent variables. RESULTS: The majority of participants (85%) reported having ever witnessed an opioid overdose. Age (adjusted Odds Ratio [aOR] = 1.09; 95% CI: 1.02-1.12), having ever attempted to stop heroin use (aOR = 11.27; 95% CI: 2.25-56.46), history of arrest (aOR = 3.75; 95% CI: 1.32-10.63), and spending time daily in places where people use drugs (aOR = 3.72; 95% CI: 1.43-9.64) were found to be independently associated with ever witnessing an overdose. CONCLUSIONS: Findings suggest the need for expanded access to naloxone to lay people and community and peer-based overdose prevention training in Tanzania, including the distribution of naloxone in settings with high drug use.