Africa’s oesophageal cancer corridor: geographic variations in incidence correlate with certain micronutrient deficiencies

Background The aetiology of Africa’s easterly-lying corridor of squamous cell oesophageal cancer is poorly understood. Micronutrient deficiencies have been implicated in this cancer in other areas of the world, but their role in Africa is unclear. Without prospective cohorts, timely insights can instead be gained through ecological studies. Methods Across Africa we assessed associations between a country’s oesophageal cancer incidence rate and food balance sheet-derived estimates of mean national dietary supplies of 7 nutrients: calcium (Ca), copper (Cu), iron (Fe), iodine (I), magnesium (Mg), selenium (Se) and zinc (Zn). We included 32 countries which had estimates of dietary nutrient supplies and of better-quality GLOBCAN 2012 cancer incidence rates. Bayesian hierarchical Poisson lognormal models were used to estimate incidence rate ratios for oesophageal cancer associated with each nutrient, adjusted for age, gender, energy intake, phytate, smoking and alcohol consumption, as well as their 95% posterior credible intervals (CI). Adult dietary deficiencies were quantified using an estimated average requirements (EAR) cut-point approach. Results Adjusted incidence rate ratios for oesophageal cancer associated with a doubling of mean nutrient supply were: for Fe 0.49 (95% CI: 0.29–0.82); Mg 0.58 (0.31–1.08); Se 0.40 (0.18–0.90); and Zn 0.29 (0.11–0.74). There were no associations with Ca, Cu and I. Mean national nutrient supplies exceeded adult EARs for Mg and Fe in most countries. For Se, mean supplies were less than EARs (both sexes) in 7 of the 10 highest oesophageal cancer ranking countries, compared to 23% of remaining countries. For Zn, mean supplies were less than the male EARs in 8 of these 10 highest ranking countries compared to in 36% of other countries

Secondary Distribution of HIV Self-Testing Kits to Social and Sexual Networks of PLWH in KwaZulu-Natal, South Africa. A Brief Report

Background: To reach 95% of persons living with HIV (PLWH) knowing their HIV status, alternative testing approaches such as HIV self-testing (HIVST) and secondary HIVST kit distribution are needed. We investigated if secondary HIVST kit distribution from male and female PLWH in South Africa would successfully lead to their contacts testing for HIV and linking to care if positive. / Methods: Male and female PLWH participating in an HIV treatment trial between July and November 2018 in KwaZulu-Natal, South Africa were offered participation as "HIVST kit distributors" in a pilot of secondary distribution of HIVST kits to give to sexual partners and social networks. Univariate descriptive statistics were used to describe the characteristics of volunteer distributors, proportion of HIVST recipients who reported their results, and linkage to care among those who tested positive using HIVST were assessed. / Results: Sixty-three participant kit distributors accepted kits to disperse to contacts, of whom 52% were female, median age was 34 years (IQR 26-42.5), 84% reported 1 sexual partner and 76% did not know their partner's HIV status. HIVST kit distributors took 218 kits, with 13/218 (6%) of kits reported to be intended to be given to a sexual partner. A total of 143 HIVST recipients reported their HIVST results; 92% reported their results were negative, 11 recipients reported positive results and 1 HIVST-positive recipient was linked to HIV care. / Conclusion: Secondary distribution of HIVST to social networks and sexual partners from South African PLWH is feasible, with two thirds of contacts reporting use of the HIVST kits. Additional support is necessary to facilitate linkage to care

Intra-household agreement of urinary elemental concentrations in Tanzania and Kenya: potential surrogates in case–control studies

Element deficiencies and excesses play important roles in non-communicable disease aetiology. When investigating their roles in epidemiologic studies without prospective designs, reverse-causality limits the utility of transient biomarkers in cases. This study aimed to investigate whether surrogate participants may provide viable proxies by assessing concentration correlations within households. We obtained spot urine samples from 245 Tanzanian and Kenyan adults (including 101 household pairs) to investigate intra-household correlations of urinary elements (As, Ba, Ca, Cd, Co, Cs, Cu, Fe, Li, Mn, Mo, Ni, Pb, Rb, S, Se, Sr, Tl, V and Zn) and concentrations (also available for: Bi, Ce, Sb, Sn and U) relative to external population-levels and health-based values. Moderate-strong correlations were observed for As (r = 0.65), Cs (r = 0.67), Li (r = 0.56), Mo (r = 0.57), Se (r = 0.68) and Tl (r = 0.67). Remaining correlations were <0.41. Median Se concentrations in Tanzania (29 µg/L) and Kenya (24 µg/L) were low relative to 5738 Canadians (59 µg/L). Exceedances (of reference 95th percentiles) were observed for: Co, Mn, Mo, Ni and U. Compared to health-based values, exceedances were present for As, Co, Mo and Se but deficiencies were also present for Mo and Se. For well correlated elements, household members in East African settings provide feasible surrogate cases to investigate element deficiencies/excesses in relation to non-communicable diseases

Estimating the impact of identifying and treating HIV-infected male circumcision clients in Uganda, Zambia, and Swaziland: a mathematical modeling analysis

Thesis (Master's)--University of Washington, 2015Introduction: Men represent an underserved population in sub-Saharan Africa with respect to HIV testing and treatment. Identification and treatment of HIV-infected men are vital both to improve their health and prevent onward transmission to their partners, especially for men in sero-discordant partnerships. One means of identifying HIV-infected men is via HIV testing and counseling in conjunction with voluntary medical male circumcision (VMMC) programs. Men in discordant couples could be identified by offering at-home testing to their cohabiting partners. Methods: This analysis utilizes a modified version of the UNAIDS Modes of Transmission (MoT) mathematical model to estimate the number of primary HIV transmissions that could be averted over one year in 2014 and on average from 2015-2025, under two scenarios: 1) identifying and treating HIV-infected VMMC clients in discordant couples as per World Health Organization recommendations; and 2) identifying and treating all HIV-infected VMMC clients. The analysis was applied to three countries with differing magnitudes of HIV prevalence: Uganda, Zambia, and Swaziland. Univariate sensitivity analyses were performed on key model parameters. Results: To meet the WHO/UNAIDS target of 80% coverage of adult male circumcision by 2025, we estimate that each year from 2015 to 2025, an average of 390,945 circumcisions will need to be performed in Uganda, 189,387 in Zambia, and 20,486 in Swaziland. On average over 2015-2025 we estimate that about 2% of men presenting for male circumcision will be HIV-positive and in a discordant couple and that about 40% of those men could be identified and successful treated with ART for at least one year. Using the MoT model we predict that in one year this intervention could successfully identify and treat 2,517 men, preventing 298 new HIV cases in Uganda; 2,232 men, preventing 210 cases in Zambia, and 195 men, preventing 19 cases in Swaziland. Under a scenario in which all HIV-infected men, regardless of relationship status or CD4 count, were offered ART treatment we estimate that about 46% would start and stay on treatment for one year. In one year during 2015-2025, we predict this intervention could successfully identify and treat 9,089 men, preventing 537 new HIV cases in Uganda; 8,893 men, preventing 410 cases in Zambia, and 2,063 men, preventing 68 cases in Swaziland. Discussion and Conclusions: VMMC programs are an important, relatively short-term opportunity to identify HIV-infected men that may not otherwise volunteer for HIV testing. A substantial proportion of the male national population in the 14 VMMC target countries will visit clinics between 2015 and 2025 and large numbers of HIV-infected men will be identified there. We predict that while circumcision programs to date have recruited mostly adolescents, as countries move toward the 80% coverage target, clients will be tend to be older and be more likely to be infected with HIV. If VMMC programs integrate HIV treatment as prevention, even if targeted only at men in discordant couples, thousands of transmissions to partners could be prevented each year

Lower respiratory tract disorder hospitalizations among children born via elective early-term delivery

<p><i>Objective</i>: We evaluated the hypothesis that elective early-term delivery increases the risk of childhood lower respiratory tract disorder hospitalization.</p> <p><i>Methods</i>: Children born via early-term elective inductions were compared to full- or late-term elective inductions in a retrospective cohort study using Washington State birth certificate and hospital discharge data. Outcomes were the odds of lower respiratory disorder hospitalization before age five and cause specific odds ratios for asthma, bronchiolitis, bronchitis, and pneumonia. In addition, a subgroup analysis excluding infants with perinatal complications was conducted.</p> <p><i>Results</i>: Electively induced early-term children were at significantly increased risk of hospitalization before age five for lower respiratory disorders compared to similar full- or late-term children (adjusted OR: 1.31, 95% CI: 1.11–1.55). Bronchiolitis was the only cause-specific outcome with a statistically significant increase in odds of hospitalization, though comparable increases were found for the less common diagnoses of asthma (adjusted OR: 1.39, 95% CI: 0.93–2.08) and pneumonia (adjusted OR: 1.27, 95% CI: 0.99–1.64). Excluding infants with perinatal complications did not alter the results.</p> <p><i>Conclusions</i>: There was an association between electively induced early-term delivery and hospitalization for lower respiratory tract disorders before age five. This reinforces policies discouraging elective early-term delivery.</p

Eastern and western rift valley overlaid on a map of oesophageal cancer incidence rates in Africa, GLOBOCAN 2012.

<p>Countries are only named on the graph for women, to simplify the display.</p

Hydroxychloroquine as Postexposure Prophylaxis to Prevent Severe Acute Respiratory Syndrome Coronavirus 2 Infection : A Randomized Trial.

BackgroundEffective prevention against coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is currently limited to nonpharmaceutical strategies. Laboratory and observational data suggested that hydroxychloroquine had biological activity against SARS-CoV-2, potentially permitting its use for prevention.ObjectiveTo test hydroxychloroquine as postexposure prophylaxis for SARS-CoV-2 infection.DesignHousehold-randomized, double-blind, controlled trial of hydroxychloroquine postexposure prophylaxis. (ClinicalTrials.gov: NCT04328961).SettingNational U.S. multicenter study.ParticipantsClose contacts recently exposed (&lt;96 hours) to persons with diagnosed SARS-CoV-2 infection.InterventionHydroxychloroquine (400 mg/d for 3 days followed by 200 mg/d for 11 days) or ascorbic acid (500 mg/d followed by 250 mg/d) as a placebo-equivalent control.MeasurementsParticipants self-collected mid-turbinate swabs daily (days 1 to 14) for SARS-CoV-2 polymerase chain reaction (PCR) testing. The primary outcome was PCR-confirmed incident SARS-CoV-2 infection among persons who were SARS-CoV-2 negative at enrollment.ResultsBetween March and August 2020, 671 households were randomly assigned: 337 (407 participants) to the hydroxychloroquine group and 334 (422 participants) to the control group. Retention at day 14 was 91%, and 10 724 of 11 606 (92%) expected swabs were tested. Among the 689 (89%) participants who were SARS-CoV-2 negative at baseline, there was no difference between the hydroxychloroquine and control groups in SARS-CoV-2 acquisition by day 14 (53 versus 45 events; adjusted hazard ratio, 1.10 [95% CI, 0.73 to 1.66]; P &gt; 0.20). The frequency of participants experiencing adverse events was higher in the hydroxychloroquine group than the control group (66 [16.2%] versus 46 [10.9%], respectively; P = 0.026).LimitationThe delay between exposure, and then baseline testing and the first dose of hydroxychloroquine or ascorbic acid, was a median of 2 days.ConclusionThis rigorous randomized controlled trial among persons with recent exposure excluded a clinically meaningful effect of hydroxychloroquine as postexposure prophylaxis to prevent SARS-CoV-2 infection.Primary funding sourceBill &amp; Melinda Gates Foundation

Hydroxychloroquine as Postexposure Prophylaxis to Prevent Severe Acute Respiratory Syndrome Coronavirus 2 Infection : A Randomized Trial.

BackgroundEffective prevention against coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is currently limited to nonpharmaceutical strategies. Laboratory and observational data suggested that hydroxychloroquine had biological activity against SARS-CoV-2, potentially permitting its use for prevention.ObjectiveTo test hydroxychloroquine as postexposure prophylaxis for SARS-CoV-2 infection.DesignHousehold-randomized, double-blind, controlled trial of hydroxychloroquine postexposure prophylaxis. (ClinicalTrials.gov: NCT04328961).SettingNational U.S. multicenter study.ParticipantsClose contacts recently exposed (&lt;96 hours) to persons with diagnosed SARS-CoV-2 infection.InterventionHydroxychloroquine (400 mg/d for 3 days followed by 200 mg/d for 11 days) or ascorbic acid (500 mg/d followed by 250 mg/d) as a placebo-equivalent control.MeasurementsParticipants self-collected mid-turbinate swabs daily (days 1 to 14) for SARS-CoV-2 polymerase chain reaction (PCR) testing. The primary outcome was PCR-confirmed incident SARS-CoV-2 infection among persons who were SARS-CoV-2 negative at enrollment.ResultsBetween March and August 2020, 671 households were randomly assigned: 337 (407 participants) to the hydroxychloroquine group and 334 (422 participants) to the control group. Retention at day 14 was 91%, and 10 724 of 11 606 (92%) expected swabs were tested. Among the 689 (89%) participants who were SARS-CoV-2 negative at baseline, there was no difference between the hydroxychloroquine and control groups in SARS-CoV-2 acquisition by day 14 (53 versus 45 events; adjusted hazard ratio, 1.10 [95% CI, 0.73 to 1.66]; P &gt; 0.20). The frequency of participants experiencing adverse events was higher in the hydroxychloroquine group than the control group (66 [16.2%] versus 46 [10.9%], respectively; P = 0.026).LimitationThe delay between exposure, and then baseline testing and the first dose of hydroxychloroquine or ascorbic acid, was a median of 2 days.ConclusionThis rigorous randomized controlled trial among persons with recent exposure excluded a clinically meaningful effect of hydroxychloroquine as postexposure prophylaxis to prevent SARS-CoV-2 infection.Primary funding sourceBill &amp; Melinda Gates Foundation