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Drug-induced orthostatic hypotension: A systematic review and meta-analysis of randomised controlled trials

Ma, 09/11/2021 - 15:00

by Cini Bhanu, Danielle Nimmons, Irene Petersen, Mine Orlu, Daniel Davis, Hajra Hussain, Sanuri Magammanage, Kate Walters

Background

Drug-induced orthostatic hypotension (OH) is common, and its resulting cerebral hypoperfusion is linked to adverse outcomes including falls, strokes, cognitive impairment, and increased mortality. The extent to which specific medications are associated with OH remains unclear.

Methods and findings

We conducted a systematic review and meta-analysis to evaluate the extent to which specific drug groups are associated with OH. EMBASE, MEDLINE, and Web of Science databases were searched from inception through 23 November 2020. Placebo-controlled randomised controlled trials (RCTs) on any drug reporting on OH as an adverse effect in adults (≥18 years) were eligible. Three authors extracted data on the drug, OH, dose, participant characteristics, and study setting. The revised Cochrane risk-of-bias tool for randomised trials (RoB 2) was used to appraise evidence. Summary odds ratios (ORs) were estimated for OH using fixed effects Mantel–Haenszel statistics. We conducted subgroup analysis on validity of OH measurement, drug dose, risk of bias, age, and comorbidity. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) tool was used to summarise the certainty of evidence. Of 36,940 citations, 69 eligible RCTs were included in the meta-analysis comprising 27,079 participants. Compared with placebo, beta-blockers and tricyclic antidepressants were associated with increased odds of OH (OR 7.76 [95% CI 2.51, 24.03]; OR 6.30 [95% CI 2.86, 13.91]). Alpha-blockers, antipsychotics, and SGLT-2 inhibitors were associated with up to 2-fold increased odds of OH, compared to placebo. There was no statistically significant difference in odds of OH with vasodilators (CCBs, ACE inhibitors/ARBs, SSRIs), compared to placebo. Limitations of this study are as follows: data limited to placebo-controlled studies, (excluding head-to-head trials), many RCTs excluded older participants; therefore results may be amplified in older patients in the clinical setting. The study protocol is publicly available on PROSPERO (CRD42020168697).

Conclusions

Medications prescribed for common conditions (including depression, diabetes, and lower urinary tract symptoms) were associated with significantly increased odds of OH. Drugs causing sympathetic inhibition were associated with significantly increased odds of OH, while most vasodilators were associated with small nonsignificant differences in odds of OH, compared to placebo. Drugs targeting multiple parts of the orthostatic blood pressure (BP) reflex pathway (e.g. sympathetic inhibition, vasodilation, cardio-inhibitory effects) may carry cumulative risk, suggesting that individuals with polypharmacy could benefit from postural BP monitoring.

SARS-CoV-2 vaccine uptake in a multi-ethnic UK healthcare workforce: A cross-sectional study

Ve, 05/11/2021 - 15:00

by Christopher A. Martin, Colette Marshall, Prashanth Patel, Charles Goss, David R. Jenkins, Claire Ellwood, Linda Barton, Arthur Price, Nigel J. Brunskill, Kamlesh Khunti, Manish Pareek

Background

Healthcare workers (HCWs) and ethnic minority groups are at increased risk of COVID-19 infection and adverse outcomes. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination is now available for frontline UK HCWs; however, demographic/occupational associations with vaccine uptake in this cohort are unknown. We sought to establish these associations in a large UK hospital workforce.

Methods and findings

We conducted cross-sectional surveillance examining vaccine uptake amongst all staff at University Hospitals of Leicester NHS Trust. We examined proportions of vaccinated staff stratified by demographic factors, occupation, and previous COVID-19 test results (serology/PCR) and used logistic regression to identify predictors of vaccination status after adjustment for confounders. We included 19,044 HCWs; 12,278 (64.5%) had received SARS-CoV-2 vaccination. Compared to White HCWs (70.9% vaccinated), a significantly smaller proportion of ethnic minority HCWs were vaccinated (South Asian, 58.5%; Black, 36.8%; p < 0.001 for both). After adjustment for age, sex, ethnicity, deprivation, occupation, SARS-CoV-2 serology/PCR results, and COVID-19-related work absences, factors found to be negatively associated with vaccine uptake were younger age, female sex, increased deprivation, pregnancy, and belonging to any non-White ethnic group (Black: adjusted odds ratio [aOR] 0.30, 95% CI 0.26–0.34, p < 0.001; South Asian: aOR 0.67, 95% CI 0.62–0.72, p < 0.001). Those who had previously had confirmed COVID-19 (by PCR) were less likely to be vaccinated than those who had tested negative. Limitations include data being from a single centre, lack of data on staff vaccinated outside the hospital system, and that staff may have taken up vaccination following data extraction.

Conclusions

Ethnic minority HCWs and those from more deprived areas as well as younger staff and female staff are less likely to take up SARS-CoV-2 vaccination. These findings have major implications for the delivery of SARS-CoV-2 vaccination programmes, in HCWs and the wider population, and should inform the national vaccination programme to prevent the disparities of the pandemic from widening.

Vaccination uptake amongst older adults from minority ethnic backgrounds: A systematic review

Gi, 04/11/2021 - 15:00

by Cini Bhanu, Dipesh P. Gopal, Kate Walters, Umar A. R. Chaudhry

Background

Older adults from minority ethnic backgrounds are at increased risk of contracting COVID-19 and developing severe infection and have increased risk of mortality. Whilst an age-based vaccination approach prioritising older groups is being implemented worldwide, vaccine hesitancy is high amongst minority ethnic groups.

Methods and findings

We conducted a systematic review and convergent synthesis to systematically examine perceptions of vaccinations amongst older adults from minority ethnic backgrounds. We included studies that reported on perceptions, beliefs, and attitudes towards vaccinations in older adults aged ≥65 years from a minority ethnic background. We excluded studies of vaccinations in investigation or development, studies focused on specific medical conditions, studies where ethnic background or age group was unidentifiable, systematic reviews, editorials, and conference abstracts. We searched MEDLINE, Embase, Virtual Health Library, Web of Science, Cochrane Library, medRxiv, and PROSPERO databases from inception to 15 July 2021. Risk of bias for studies was assessed using the Mixed Methods Appraisal Tool. The quality of evidence of collective outcomes was estimated using the Grading of Recommendations Assessment, Development and Evaluation–Confidence in the Evidence from Reviews of Qualitative research (GRADE–CERQual) framework. A total of 28 eligible studies conducted between 1997 and 2020 were included in the final analysis (17 quantitative surveys, 8 focus group or interview studies, 2 mixed methods studies, and 1 case–control study). The majority were US studies in English or Spanish, except for 6 studies set in Hong Kong, 2 studies in Japan, 1 study in Brazil, and 1 multi-centre study (including China, Indonesia, Turkey, South Korea, Greece, UK, Brazil, and Nigeria). In total, 28,262 individuals with an estimated mean age of 69.8 years were included, 63.2% of whom were female. We summarised the common concepts and themes across studies and populations using a convergent synthesis analysis. Thirteen themes categorised as barriers or facilitators were identified and grouped into structural factors—healthcare provider and system related, patient related, and policy and operational—and were analysed by minority ethnic group. The main limitation of the study was the predominance of studies from the US and East Asia.

Conclusions

In this systematic review, we found that factors influencing vaccination uptake involve healthcare provider and system, patient-related, and governance-level factors that are specific to the older ethnic minority community being served. The evidence included in this review is supported by high or moderate certainty and can be translated to practice and policy. A tailored, multi-level approach combining increased education, access, and culturally competent discussions with trusted healthcare professionals to address health beliefs can maximise the potential impact of widespread vaccination policies.

Epidemiology of type 2 diabetes remission in Scotland in 2019: A cross-sectional population-based study

Ma, 02/11/2021 - 15:00

by Mireille Captieux, Kelly Fleetwood, Brian Kennon, Naveed Sattar, Robert Lindsay, Bruce Guthrie, Sarah H. Wild, on behalf of the Scottish Diabetes Research Network Epidemiology Group

Background

Clinical pathways are changing to incorporate support and appropriate follow-up for people to achieve remission of type 2 diabetes, but there is limited understanding of the prevalence of remission in current practice or patient characteristics associated with remission.

Methods and findings

We carried out a cross-sectional study estimating the prevalence of remission of type 2 diabetes in all adults in Scotland aged ≥30 years diagnosed with type 2 diabetes and alive on December 31, 2019. Remission of type 2 diabetes was assessed between January 1, 2019 and December 31, 2019. We defined remission as all HbA1c values <48 mmol/mol in the absence of glucose-lowering therapy (GLT) for a continuous duration of ≥365 days before the date of the last recorded HbA1c in 2019. Multivariable logistic regression in complete and multiply imputed datasets was used to examine characteristics associated with remission. Our cohort consisted of 162,316 individuals, all of whom had at least 1 HbA1c ≥48 mmol/mol (6.5%) at or after diagnosis of diabetes and at least 1 HbA1c recorded in 2019 (78.5% of the eligible population). Over half (56%) of our cohort was aged 65 years or over in 2019, and 64% had had type 2 diabetes for at least 6 years. Our cohort was predominantly of white ethnicity (74%), and ethnicity data were missing for 19% of the cohort. Median body mass index (BMI) at diagnosis was 32.3 kg/m2. A total of 7,710 people (4.8% [95% confidence interval [CI] 4.7 to 4.9]) were in remission of type 2 diabetes. Factors associated with remission were older age (odds ratio [OR] 1.48 [95% CI 1.34 to 1.62] P < 0.001) for people aged ≥75 years compared to 45 to 54 year group), HbA1c <48 mmol/mol at diagnosis (OR 1.31 [95% CI 1.24 to 1.39] P < 0.001) compared to 48 to 52 mmol/mol), no previous history of GLT (OR 14.6 [95% CI 13.7 to 15.5] P < 0.001), weight loss from diagnosis to 2019 (OR 4.45 [95% CI 3.89 to 5.10] P < 0.001) for ≥15 kg of weight loss compared to 0 to 4.9 kg weight gain), and previous bariatric surgery (OR 11.9 [95% CI 9.41 to 15.1] P < 0.001). Limitations of the study include the use of a limited subset of possible definitions of remission of type 2 diabetes, missing data, and inability to identify self-funded bariatric surgery.

Conclusions

In this study, we found that 4.8% of people with type 2 diabetes who had at least 1 HbA1c ≥48 mmol/mol (6.5%) after diagnosis of diabetes and had at least 1 HbA1c recorded in 2019 had evidence of type 2 diabetes remission. Guidelines are required for management and follow-up of this group and may differ depending on whether weight loss and remission of diabetes were intentional or unintentional. Our findings can be used to evaluate the impact of future initiatives on the prevalence of type 2 diabetes remission.

Liveable residential space, residential density, and hypertension in Hong Kong: A population-based cohort study

Ma, 02/11/2021 - 15:00

by Chinmoy Sarkar, Ka Yan Lai, Michael Y. Ni, Sarika Kumari, Gabriel M. Leung, Chris Webster

Background

Hypertension is a leading preventable risk factor of chronic disease and all-cause mortality. Housing is a fundamental social determinant of health. Yet, little is known about the impacts of liveable residential space and density on hypertension.

Methods and findings

This retrospective observational study (median follow-up of 2.2 years) leveraged the FAMILY Cohort, a large territory-wide cohort in Hong Kong, Special Administrative Region, People’s Republic of China to quantify associations of objectively measured liveable space and residential density with blood pressure outcomes among adults aged ≥16 years. Blood pressure outcomes comprised diastolic blood pressure (DBP), systolic blood pressure (SBP), mean arterial pressure (MAP), and hypertension. Liveable space was measured as residential floor area, and density was assessed using the number of residential units per building block and neighborhood residential unit density within predefined catchments. Multivariable regression models examined associations of liveable floor area and residential density with prevalent and incident hypertension. We investigated effect modifications by age, sex, income, employment status, and housing type. Propensity score matching was further employed to match a subset of participants who moved to smaller residences at follow-up with equivalent controls who did not move, and generalized linear models examined the impact of moving to smaller residences upon blood pressure outcomes. Our fully adjusted models of prevalent hypertension outcomes comprised 30,439 participants at baseline, while 13,895 participants were available for incident models at follow-up. We found that each interquartile range (IQR) increment in liveable floor area was associated with lower DBP (beta [β] = −0.269 mm Hg, 95% confidence interval [CI]: −0.419 to −0.118, p < 0.001), SBP (β = −0.317 mm Hg, −0.551 to −0.084, p = 0.008), MAP (β = −0.285 mm Hg, −0.451 to −0.119 with p < 0.001), and prevalent hypertension (odds ratio [OR] = 0.955, 0.918 to 0.993, p = 0.022) at baseline. Each IQR increment in residential units per building block was associated with higher DBP (β = 0.477 mm Hg, 0.212 to 0.742, p = <0.001), SBP (β = 0.750 mm Hg, 0.322 to 1.177, p = <0.001), MAP (β = 0.568 mm Hg, 0.269 to 0.866, p < 0.001), and prevalent hypertension (OR = 1.091, 1.024 to 1.162, p = 0.007). Each IQR increase in neighborhood residential density within 0.5-mi street catchment was associated with lower DBP (β = −0.289 mm Hg, −0.441 to −0.137, p = <0.001), SBP (β = −0.411 mm Hg, −0.655 to −0.168, p < 0.001), MAP (β = −0.330 mm Hg, −0.501 to −0.159, p = <0.001), and lower prevalent hypertension (OR = 0.933, 0.899 to 0.969, p < 0.001). In the longitudinal analyses, each IQR increment in liveable floor area was associated with lower DBP (β = −0.237 mm Hg, −0.431 to −0.043, p = 0.016), MAP (β = −0.244 mm Hg, −0.444 to −0.043, p = 0.017), and incident hypertension (adjusted OR = 0.909, 0.836 to 0.988, p = 0.025). The inverse associations between larger liveable area and blood pressure outcomes were more pronounced among women and those residing in public housing. In the propensity-matched analysis, participants moving to residences of lower liveable floor area were associated with higher odds of incident hypertension in reference to those who did not move (OR = 1.623, 1.173 to 2.199, p = 0.002). The major limitations of the study are unmeasured residual confounding and loss to follow-up.

Conclusions

We disentangled the association of micro-, meso-, and macrolevel residential densities with hypertension and found that higher liveable floor area and neighborhood scale residential density were associated with lower odds of hypertension. These findings suggest adequate housing in the form of provisioning of sufficient liveable space and optimizing residential density at the building block, and neighborhood levels should be investigated as a potential population-wide preventive strategy for lowering hypertension and associated chronic diseases.

Alcohol abstinence and mortality in a general population sample of adults in Germany: A cohort study

Ma, 02/11/2021 - 15:00

by Ulrich John, Hans-Juergen Rumpf, Monika Hanke, Christian Meyer

Background

Evidence suggests that people who abstain from alcohol have a higher mortality rate than those who drink low to moderate amounts. However, little is known about factors that might be causal for this finding. The objective was to analyze former alcohol or drug use disorders, risky drinking, tobacco smoking, and fair to poor health among persons who reported abstinence from alcohol drinking in the last 12 months before baseline in relation to total, cardiovascular, and cancer mortality 20 years later.

Methods and findings

A sample of residents aged 18 to 64 years had been drawn at random among the general population in northern Germany and a standardized interview conducted in the years 1996 to 1997. The baseline assessment included 4,093 persons (70.2% of those who had been eligible). Vital status and death certificate data were retrieved in the years 2017 and 2018.We found that among the alcohol-abstinent study participants at baseline (447), there were 405 (90.60%) former alcohol consumers. Of the abstainers, 322 (72.04%) had met one or more criteria for former alcohol or drug dependence or abuse, alcohol risky drinking, or had tried to cut down or to stop drinking, were daily smokers, or self-rated their health as fair to poor. Among the abstainers with one or more of these risk factors, 114 (35.40%) had an alcohol use disorder or risky alcohol consumption in their history. Another 161 (50.00%) did not have such an alcohol-related risk but were daily smokers. The 322 alcohol-abstinent study participants with one or more of the risk factors had a shorter time to death than those with low to moderate alcohol consumption. The Cox proportional hazard ratio (HR) was 2.44 (95% confidence interval (CI), 1.68 to 3.56) for persons who had one or more criteria for an alcohol or drug use disorder fulfilled in their history and after adjustment for age and sex. The 125 alcohol-abstinent persons without these risk factors (27.96% of the abstainers) did not show a statistically significant difference from low to moderate alcohol consumers in total, cardiovascular, and cancer mortality. Those who had stayed alcohol abstinent throughout their life before (42; 9.40% of the alcohol-abstinent study participants at baseline) had an HR 1.64 (CI 0.72 to 3.77) compared to low to moderate alcohol consumers after adjustment for age, sex, and tobacco smoking. Main limitations of this study include its reliance on self-reported data at baseline and the fact that only tobacco smoking was analyzed as a risky behavior alongside alcohol consumption.

Conclusions

The majority of the alcohol abstainers at baseline were former alcohol consumers and had risk factors that increased the likelihood of early death. Former alcohol use disorders, risky alcohol drinking, ever having smoked tobacco daily, and fair to poor health were associated with early death among alcohol abstainers. Those without an obvious history of these risk factors had a life expectancy similar to that of low to moderate alcohol consumers. The findings speak against recommendations to drink alcohol for health reasons.

Opioid prescribing among new users for non-cancer pain in the USA, Canada, UK, and Taiwan: A population-based cohort study

Lu, 01/11/2021 - 15:00

by Meghna Jani, Nadyne Girard, David W. Bates, David L. Buckeridge, Therese Sheppard, Jack Li, Usman Iqbal, Shelly Vik, Colin Weaver, Judy Seidel, William G. Dixon, Robyn Tamblyn

Background

The opioid epidemic in North America has been driven by an increase in the use and potency of prescription opioids, with ensuing excessive opioid-related deaths. Internationally, there are lower rates of opioid-related mortality, possibly because of differences in prescribing and health system policies. Our aim was to compare opioid prescribing rates in patients without cancer, across 5 centers in 4 countries. In addition, we evaluated differences in the type, strength, and starting dose of medication and whether these characteristics changed over time.

Methods and findings

We conducted a retrospective multicenter cohort study of adults who are new users of opioids without prior cancer. Electronic health records and administrative health records from Boston (United States), Quebec and Alberta (Canada), United Kingdom, and Taiwan were used to identify patients between 2006 and 2015. Standard dosages in morphine milligram equivalents (MMEs) were calculated according to The Centers for Disease Control and Prevention. Age- and sex-standardized opioid prescribing rates were calculated for each jurisdiction. Of the 2,542,890 patients included, 44,690 were from Boston (US), 1,420,136 Alberta, 26,871 Quebec (Canada), 1,012,939 UK, and 38,254 Taiwan. The highest standardized opioid prescribing rates in 2014 were observed in Alberta at 66/1,000 persons compared to 52, 51, and 18/1,000 in the UK, US, and Quebec, respectively. The median MME/day (IQR) at initiation was highest in Boston at 38 (20 to 45); followed by Quebec, 27 (18 to 43); Alberta, 23 (9 to 38); UK, 12 (7 to 20); and Taiwan, 8 (4 to 11). Oxycodone was the first prescribed opioid in 65% of patients in the US cohort compared to 14% in Quebec, 4% in Alberta, 0.1% in the UK, and none in Taiwan. One of the limitations was that data were not available from all centers for the entirety of the 10-year period.

Conclusions

In this study, we observed substantial differences in opioid prescribing practices for non-cancer pain between jurisdictions. The preference to start patients on higher MME/day and more potent opioids in North America may be a contributing cause to the opioid epidemic.

Remission, relapse, and risk of major cardiovascular events after metabolic surgery in persons with hypertension: A Swedish nationwide registry-based cohort study

Lu, 01/11/2021 - 15:00

by Erik Stenberg, Richard Marsk, Magnus Sundbom, Johan Ottosson, Tomas Jernberg, Ingmar Näslund, Erik Näslund

Background

Several studies have shown that metabolic surgery is associated with remission of diabetes and hypertension. In terms of diabetes, factors such as duration, insulin use, weight loss, and age have been shown to contribute to the likelihood of remission. Such factors have not been determined for hypertension. The aim of this study was to evaluate factors associated with the remission and relapse of hypertension after metabolic surgery, as well as the risk for major adverse cardiovascular event (MACE) and mortality in patients with and without remission.

Methods and findings

All adults who underwent metabolic surgery between January 2007 and June 2016 were identified in the nationwide Scandinavian Obesity Surgery Registry (SOReg). Through cross-linkage with the Swedish Prescribed Drug Register, Patient Register, and Statistics Sweden, individual data on prescriptions, inpatient and outpatient diagnoses, and mortality were retrieved. Of the 15,984 patients with pharmacologically treated hypertension, 6,286 (39.3%) were in remission at 2 years. High weight loss and male sex were associated with higher chance of remission, while duration, number of antihypertensive drugs, age, body mass index (BMI), cardiovascular disease, and dyslipidemia were associated with lower chance. After adjustment for age, sex, BMI, comorbidities, and education, the cumulative probabilities of MACEs (2.8% versus 5.7%, adjusted odds ratio (OR) 0.60, 95% confidence interval (CI) 0.47 to 0.77, p < 0.001) and all-cause mortality (4.0% versus 8.0%, adjusted OR 0.71, 95% CI 0.57 to 0.88, p = 0.002) were lower for patients being in remission at 2 years compared with patients not in remission, despite relapse of hypertension in 2,089 patients (cumulative probability 56.3%) during 10-year follow-up. The main limitations of the study were missing information on nonpharmacological treatment for hypertension and the observational study design.

Conclusions

In this study, we observed an association between high postoperative weight loss and male sex with better chance of remission, while we observed a lower chance of remission depending on disease severity and presence of other metabolic comorbidities. Patients who achieved remission had a halved risk of MACE and death compared with those who did not. The results suggest that in patients with severe obesity and hypertension, metabolic surgery should not be delayed.

Safety and immunogenicity of 2-dose heterologous Ad26.ZEBOV, MVA-BN-Filo Ebola vaccination in healthy and HIV-infected adults: A randomised, placebo-controlled Phase II clinical trial in Africa

Ve, 29/10/2021 - 15:00

by Houreratou Barry, Gaudensia Mutua, Hannah Kibuuka, Zacchaeus Anywaine, Sodiomon B. Sirima, Nicolas Meda, Omu Anzala, Serge Eholie, Christine Bétard, Laura Richert, Christine Lacabaratz, M. Juliana McElrath, Stephen De Rosa, Kristen W. Cohen, Georgi Shukarev, Cynthia Robinson, Auguste Gaddah, Dirk Heerwegh, Viki Bockstal, Kerstin Luhn, Maarten Leyssen, Macaya Douoguih, Rodolphe Thiébaut, the EBL2002 Study group

Background

We investigated safety, tolerability, and immunogenicity of the heterologous 2-dose Ebola vaccination regimen in healthy and HIV-infected adults with different intervals between Ebola vaccinations.

Methods and findings

In this randomised, observer-blind, placebo-controlled Phase II trial, 668 healthy 18- to 70-year-olds and 142 HIV-infected 18- to 50-year-olds were enrolled from 1 site in Kenya and 2 sites each in Burkina Faso, Cote d’Ivoire, and Uganda. Participants received intramuscular Ad26.ZEBOV followed by MVA-BN-Filo at 28-, 56-, or 84-day intervals, or saline. Females represented 31.4% of the healthy adult cohort in contrast to 69.7% of the HIV-infected cohort. A subset of healthy adults received booster vaccination with Ad26.ZEBOV or saline at Day 365. Following vaccinations, adverse events (AEs) were collected until 42 days post last vaccination and serious AEs (SAEs) were recorded from signing of the ICF until the end of the study. The primary endpoint was safety, and the secondary endpoint was immunogenicity. Anti-Ebola virus glycoprotein (EBOV GP) binding and neutralising antibodies were measured at baseline and at predefined time points throughout the study.The first participant was enrolled on 9 November 2015, and the date of last participant’s last visit was 12 February 2019. No vaccine-related SAEs and mainly mild-to-moderate AEs were observed among the participants. The most frequent solicited AEs were injection-site pain (local), and fatigue, headache, and myalgia (systemic), respectively. Twenty-one days post-MVA-BN-Filo vaccination, geometric mean concentrations (GMCs) with 95% confidence intervals (CIs) of EBOV GP binding antibodies in healthy adults in 28-, 56-, and 84-day interval groups were 3,085 EU/mL (2,648 to 3,594), 7,518 EU/mL (6,468 to 8,740), and 7,300 EU/mL (5,116 to 10,417), respectively. In HIV-infected adults in 28- and 56-day interval groups, GMCs were 4,207 EU/mL (3,233 to 5,474) and 5,283 EU/mL (4,094 to 6,817), respectively. Antibody responses were observed until Day 365. Ad26.ZEBOV booster vaccination after 1 year induced an anamnestic response.Study limitations include that some healthy adult participants either did not receive dose 2 or received dose 2 outside of their protocol-defined interval and that the follow-up period was limited to 365 days for most participants.

Conclusions

Ad26.ZEBOV, MVA-BN-Filo vaccination was well tolerated and immunogenic in healthy and HIV-infected African adults. Increasing the interval between vaccinations from 28 to 56 days improved the magnitude of humoral immune responses. Antibody levels persisted to at least 1 year, and Ad26.ZEBOV booster vaccination demonstrated the presence of vaccination-induced immune memory. These data supported the approval by the European Union for prophylaxis against EBOV disease in adults and children ≥1 year of age.

Trial registration

ClinicalTrials.gov NCT02564523

Early childhood undernutrition, preadolescent physical growth, and cognitive achievement in India: A population-based cohort study

Me, 27/10/2021 - 15:00

by Apurv Soni, Nisha Fahey, Zulfiqar A. Bhutta, Wenjun Li, Jean A. Frazier, Tiffany Moore Simas, Somashekhar M. Nimbalkar, Jeroan J. Allison

Background

There is a lack of nationally representative estimates for the consequences of early childhood undernutrition on preadolescent outcomes in India. Understanding this relationship is helpful to develop interventions that not only prevent child undernutrition but also mitigate its consequences.

Methods and findings

In this cohort study, we analyzed prospectively gathered data from 2 waves of the India Human Development Survey (IHDS) to investigate the association of undernutrition during early childhood (0 to 5 years) in 2004 to 2005 with physical and cognitive outcomes during preadolescent (8 to 11 years) years in 2011 to 2012. These surveys interviewed 41,554 households across all 33 states and union territories in India in 2004 to 2005 and reinterviewed 83% of the households in 2011 to 2012. Primary exposure was assessed using the Composite Index of Anthropometric Failure (CIAF) based on 2004 to 2005 survey. Primary outcomes were short stature (height-for-age z-score [HAZ] <−2), thinness (body mass index [BMI] <18.5 kg/m2), reading, and arithmetic skills during preadolescence based on the 2011 to 2012 survey. Survey-weighted generalized linear models were used, and effect modification based on child sex and sociodemographic variables were evaluated using 3-way interaction terms. Of the 7,868 children included in this analysis, 4,334 (57.3%) were undernourished. Being undernourished was associated with increased odds of short stature (odds ratio [OR] 1.73, 95% confidence interval [CI] 1.45 to 2.06) and thinness (OR 1.52, 95% CI 1.33 to 1.73) during the preadolescent period, while it was associated with decreased odds of achieving a higher reading (cumulative odds ratio [cumOR]: 0.76, 0.66 to 0.87) and arithmetic (cumOR: 0.72, 0.63 to 0.82) outcomes. The disparity in outcomes based on CIAF increased with age, especially for female children. Increased level of female education within the household reduced the disadvantages of undernutrition among female children. Study limitations include observational and missing data, which limit our ability to draw strong causal inferences.

Conclusions

In this study, we found that early child undernutrition was associated with several adverse preadolescent physical and cognitive outcomes, especially among female children. Improved female education mitigates this association. Female education promotion should assume a central role in Indian public health policy making.

The estimated health impact of sodium reduction through food reformulation in Australia: A modeling study

Ma, 26/10/2021 - 15:00

by Kathy Trieu, Daisy H. Coyle, Ashkan Afshin, Bruce Neal, Matti Marklund, Jason H. Y. Wu

Background

The Australian Government recently established sodium targets for packaged foods to encourage voluntary reformulation to reduce population sodium consumption and related diseases. We modeled the health impact of Australia’s sodium reformulation targets and additional likely health gains if more ambitious, yet feasible sodium targets had been adopted instead.

Methods and findings

Using comparative risk assessment models, we estimated the averted deaths, incidence, and disability-adjusted life years (DALYs) from cardiovascular disease (CVD), chronic kidney disease (CKD) and stomach cancer after implementation of (a) Australia’s sodium targets (overall and by individual companies); (b) United Kingdom’s targets (that covers more product categories); and (c) an optimistic scenario (sales-weighted 25th percentile sodium content for each food category included in the UK program). We used nationally representative data to estimate pre- and post-intervention sodium intake, and other key data sources from the Global Burden of Disease study. Full compliance with the Australian government’s sodium targets could prevent approximately 510 deaths/year (95% UI, 335 to 757), corresponding to about 1% of CVD, CKD, and stomach cancer deaths, and prevent some 1,920 (1,274 to 2,600) new cases and 7,240 (5,138 to 10,008) DALYs/year attributable to these diseases. Over half (59%) of deaths prevented is attributed to reformulation by 5 market-dominant companies. Compliance with the UK and optimistic scenario could avert approximately an additional 660 (207 to 1,227) and 1,070 (511 to 1,856) deaths/year, respectively, compared to Australia’s targets. The main limitation of this study (like other modeling studies) is that it does not prove that sodium reformulation programs will prevent deaths and disease events; rather, it provides the best quantitative estimates and the corresponding uncertainty of the potential effect of the different programs to guide the design of policies.

Conclusions

There is significant potential to strengthen Australia’s sodium reformulation targets to improve its health impact. Promoting compliance by market-dominant food companies will be critical to achieving the potential health gains.

Medical journal requirements for clinical trial data sharing: Ripe for improvement

Lu, 25/10/2021 - 15:00

by Florian Naudet, Maximilian Siebert, Claude Pellen, Jeanne Gaba, Cathrine Axfors, Ioana Cristea, Valentin Danchev, Ulrich Mansmann, Christian Ohmann, Joshua D. Wallach, David Moher, John P. A. Ioannidis

Florian Naudet and co-authors discuss strengthening requirements for sharing clinical trial data.

Association of race and health insurance in treatment disparities of colon cancer: A retrospective analysis utilizing a national population database in the United States

Lu, 25/10/2021 - 15:00

by Scarlett Hao, Rebecca A. Snyder, William Irish, Alexander A. Parikh

Background

Both health insurance status and race independently impact colon cancer (CC) care delivery and outcomes. The relative importance of these factors in explaining racial and insurance disparities is less clear, however. This study aimed to determine the association and interaction of race and insurance with CC treatment disparities.

Study setting

Retrospective cohort review of a prospective hospital-based database.

Methods and findings

In this cross-sectional study, patients diagnosed with stage I to III CC in the United States were identified from the National Cancer Database (NCDB; 2006 to 2016). Multivariable regression with generalized estimating equations (GEEs) were performed to evaluate the association of insurance and race/ethnicity with odds of receipt of surgery (stage I to III) and adjuvant chemotherapy (stage III), with an additional 2-way interaction term to evaluate for effect modification. Confounders included sex, age, median income, rurality, comorbidity, and nodes and margin status for the model for chemotherapy. Of 353,998 patients included, 73.8% (n = 261,349) were non-Hispanic White (NHW) and 11.7% (n = 41,511) were non-Hispanic Black (NHB). NHB patients were less likely to undergo resection [odds ratio (OR) 0.66, 95% confidence interval [CI] 0.61 to 0.72, p < 0.001] or to receive adjuvant chemotherapy [OR 0.83, 95% CI 0.78 to 0.87, p < 0.001] compared to NHW patients. NHB patients with private or Medicare insurance were less likely to undergo resection [OR 0.76, 95% CI 0.63 to 0.91, p = 0.004 (private insurance); OR 0.59, 95% CI 0.53 to 0.66, p < 0.001 (Medicare)] and to receive adjuvant chemotherapy [0.77, 95% CI 0.68 to 0.87, p < 0.001 (private insurance); OR 0.86, 95% CI 0.80 to 0.91, p < 0.001 (Medicare)] compared to similarly insured NHW patients. Although Hispanic patients with private and Medicare insurance were also less likely to undergo surgical resection, this was not the case with adjuvant chemotherapy. This study is mainly limited by the retrospective nature and by the variables provided in the dataset; granular details such as continuity or disruption of insurance coverage or specific chemotherapy agents or dosing cannot be assessed within NCDB.

Conclusions

This study suggests that racial disparities in receipt of treatment for CC persist even among patients with similar health insurance coverage and that different disparities exist for different racial/ethnic groups. Changes in health policy must therefore recognize that provision of insurance alone may not eliminate cancer treatment racial disparities.

Unmet need for hypercholesterolemia care in 35 low- and middle-income countries: A cross-sectional study of nationally representative surveys

Lu, 25/10/2021 - 15:00

by Maja E. Marcus, Cara Ebert, Pascal Geldsetzer, Michaela Theilmann, Brice Wilfried Bicaba, Glennis Andall-Brereton, Pascal Bovet, Farshad Farzadfar, Mongal Singh Gurung, Corine Houehanou, Mohammad-Reza Malekpour, Joao S. Martins, Sahar Saeedi Moghaddam, Esmaeil Mohammadi, Bolormaa Norov, Sarah Quesnel-Crooks, Roy Wong-McClure, Justine I. Davies, Mark A. Hlatky, Rifat Atun, Till W. Bärnighausen, Lindsay M. Jaacks, Jennifer Manne-Goehler, Sebastian Vollmer

Background

As the prevalence of hypercholesterolemia is increasing in low- and middle-income countries (LMICs), detailed evidence is urgently needed to guide the response of health systems to this epidemic. This study sought to quantify unmet need for hypercholesterolemia care among adults in 35 LMICs.

Methods and findings

We pooled individual-level data from 129,040 respondents aged 15 years and older from 35 nationally representative surveys conducted between 2009 and 2018. Hypercholesterolemia care was quantified using cascade of care analyses in the pooled sample and by region, country income group, and country. Hypercholesterolemia was defined as (i) total cholesterol (TC) ≥240 mg/dL or self-reported lipid-lowering medication use and, alternatively, as (ii) low-density lipoprotein cholesterol (LDL-C) ≥160 mg/dL or self-reported lipid-lowering medication use. Stages of the care cascade for hypercholesterolemia were defined as follows: screened (prior to the survey), aware of diagnosis, treated (lifestyle advice and/or medication), and controlled (TC <200 mg/dL or LDL-C <130 mg/dL). We further estimated how age, sex, education, body mass index (BMI), current smoking, having diabetes, and having hypertension are associated with cascade progression using modified Poisson regression models with survey fixed effects.High TC prevalence was 7.1% (95% CI: 6.8% to 7.4%), and high LDL-C prevalence was 7.5% (95% CI: 7.1% to 7.9%). The cascade analysis showed that 43% (95% CI: 40% to 45%) of study participants with high TC and 47% (95% CI: 44% to 50%) with high LDL-C ever had their cholesterol measured prior to the survey. About 31% (95% CI: 29% to 33%) and 36% (95% CI: 33% to 38%) were aware of their diagnosis; 29% (95% CI: 28% to 31%) and 33% (95% CI: 31% to 36%) were treated; 7% (95% CI: 6% to 9%) and 19% (95% CI: 18% to 21%) were controlled. We found substantial heterogeneity in cascade performance across countries and higher performances in upper-middle-income countries and the Eastern Mediterranean, Europe, and Americas. Lipid screening was significantly associated with older age, female sex, higher education, higher BMI, comorbid diagnosis of diabetes, and comorbid diagnosis of hypertension. Awareness of diagnosis was significantly associated with older age, higher BMI, comorbid diagnosis of diabetes, and comorbid diagnosis of hypertension. Lastly, treatment of hypercholesterolemia was significantly associated with comorbid hypertension and diabetes, and control of lipid measures with comorbid diabetes. The main limitations of this study are a potential recall bias in self-reported information on received health services as well as diminished comparability due to varying survey years and varying lipid guideline application across country and clinical settings.

Conclusions

Cascade performance was poor across all stages, indicating large unmet need for hypercholesterolemia care in this sample of LMICs—calling for greater policy and research attention toward this cardiovascular disease (CVD) risk factor and highlighting opportunities for improved prevention of CVD.

Evaluating the impact of DREAMS on HIV incidence among adolescent girls and young women: A population-based cohort study in Kenya and South Africa

Lu, 25/10/2021 - 15:00

by Isolde Birdthistle, Daniel Kwaro, Maryam Shahmanesh, Kathy Baisley, Sammy Khagayi, Natsayi Chimbindi, Vivienne Kamire, Nondumiso Mthiyane, Annabelle Gourlay, Jaco Dreyer, Penelope Phillips-Howard, Judith Glynn, Sian Floyd

Background

Through a multisectoral approach, the DREAMS Partnership aimed to reduce HIV incidence among adolescent girls and young women (AGYW) by 40% over 2 years in high-burden districts across sub-Saharan Africa. DREAMS promotes a combination package of evidence-based interventions to reduce individual, family, partner, and community-based drivers of young women’s heightened HIV risk. We evaluated the impact of DREAMS on HIV incidence among AGYW and young men in 2 settings.

Methods and findings

We directly estimated HIV incidence rates among open population-based cohorts participating in demographic and HIV serological surveys from 2006 to 2018 annually in uMkhanyakude (KwaZulu-Natal, South Africa) and over 6 rounds from 2010 to 2019 in Gem (Siaya, Kenya). We compared HIV incidence among AGYW aged 15 to 24 years before DREAMS and up to 3 years after DREAMS implementation began in 2016. We investigated the timing of any change in HIV incidence and whether the rate of any change accelerated during DREAMS implementation. Comparable analyses were also conducted for young men (20 to 29/34 years).In uMkhanyakude, between 5,000 and 6,000 AGYW were eligible for the serological survey each year, an average of 85% were contacted, and consent rates varied from 37% to 67%. During 26,395 person-years (py), HIV incidence was lower during DREAMS implementation (2016 to 2018) than in the previous 5-year period among 15- to 19-year-old females (4.5 new infections per 100 py as compared with 2.8; age-adjusted rate ratio (aRR) = 0.62, 95% confidence interval [CI] 0.48 to 0.82), and lower among 20- to 24-year-olds (7.1/100 py as compared with 5.8; aRR = 0.82, 95% CI 0.65 to 1.04). Declines preceded DREAMS introduction, beginning from 2012 to 2013 among the younger and 2014 for the older women, with no evidence of more rapid decline during DREAMS implementation. In Gem, between 8,515 and 11,428 AGYW were eligible each survey round, an average of 34% were contacted and offered an HIV test, and consent rates ranged from 84% to 99%. During 10,382 py, declines in HIV incidence among 15- to 19-year-olds began before DREAMS and did not change after DREAMS introduction. Among 20- to 24-year-olds in Gem, HIV incidence estimates were lower during DREAMS implementation (0.64/100 py) compared with the pre-DREAMS period (0.94/100 py), with no statistical evidence of a decline (aRR = 0.69, 95% CI 0.53 to 2.18). Among young men, declines in HIV incidence were greater than those observed among AGYW and also began prior to DREAMS investments. Study limitations include low study power in Kenya and the introduction of other interventions such as universal treatment for HIV during the study period.

Conclusions

Substantial declines in HIV incidence among AGYW were observed, but most began before DREAMS introduction and did not accelerate in the first 3 years of DREAMS implementation. Like the declines observed among young men, they are likely driven by earlier and ongoing investments in HIV testing and treatment. Longer-term implementation and evaluation are needed to assess the impact of such a complex HIV prevention intervention and to help accelerate reductions in HIV incidence among young women.

Effectiveness of knowledge brokering and recommendation dissemination for influencing healthcare resource allocation decisions: A cluster randomised controlled implementation trial

Ve, 22/10/2021 - 15:00

by Mitchell N. Sarkies, Lauren M. Robins, Megan Jepson, Cylie M. Williams, Nicholas F. Taylor, Lisa O’Brien, Jenny Martin, Anne Bardoel, Meg E. Morris, Leeanne M. Carey, Anne E. Holland, Katrina M. Long, Terry P. Haines

Background

Implementing evidence into clinical practice is a key focus of healthcare improvements to reduce unwarranted variation. Dissemination of evidence-based recommendations and knowledge brokering have emerged as potential strategies to achieve evidence implementation by influencing resource allocation decisions. The aim of this study was to determine the effectiveness of these two research implementation strategies to facilitate evidence-informed healthcare management decisions for the provision of inpatient weekend allied health services.

Methods and findings

This multicentre, single-blinded (data collection and analysis), three-group parallel cluster randomised controlled trial with concealed allocation was conducted in Australian and New Zealand hospitals between February 2018 and January 2020. Clustering and randomisation took place at the organisation level where weekend allied health staffing decisions were made (e.g., network of hospitals or single hospital). Hospital wards were nested within these decision-making structures. Three conditions were compared over a 12-month period: (1) usual practice waitlist control; (2) dissemination of written evidence-based practice recommendations; and (3) access to a webinar-based knowledge broker in addition to the recommendations. The primary outcome was the alignment of weekend allied health provision with practice recommendations at the cluster and ward levels, addressing the adoption, penetration, and fidelity to the recommendations. The secondary outcome was mean hospital length of stay at the ward level. Outcomes were collected at baseline and 12 months later. A total of 45 clusters (n = 833 wards) were randomised to either control (n = 15), recommendation (n = 16), or knowledge broker (n = 14) conditions. Four (9%) did not provide follow-up data, and no adverse events were recorded. No significant effect was found with either implementation strategy for the primary outcome at the cluster level (recommendation versus control β 18.11 [95% CI −8,721.81 to 8,758.02] p = 0.997; knowledge broker versus control β 1.24 [95% CI −6,992.60 to 6,995.07] p = 1.000; recommendation versus knowledge broker β −9.12 [95% CI −3,878.39 to 3,860.16] p = 0.996) or ward level (recommendation versus control β 0.01 [95% CI 0.74 to 0.75] p = 0.983; knowledge broker versus control β −0.12 [95% CI −0.54 to 0.30] p = 0.581; recommendation versus knowledge broker β −0.19 [−1.04 to 0.65] p = 0.651). There was no significant effect between strategies for the secondary outcome at ward level (recommendation versus control β 2.19 [95% CI −1.36 to 5.74] p = 0.219; knowledge broker versus control β −0.55 [95% CI −1.16 to 0.06] p = 0.075; recommendation versus knowledge broker β −3.75 [95% CI −8.33 to 0.82] p = 0.102). None of the control or knowledge broker clusters transitioned to partial or full alignment with the recommendations. Three (20%) of the clusters who only received the written recommendations transitioned from nonalignment to partial alignment. Limitations include underpowering at the cluster level sample due to the grouping of multiple geographically distinct hospitals to avoid contamination.

Conclusions

Owing to a lack of power at the cluster level, this trial was unable to identify a difference between the knowledge broker strategy and dissemination of recommendations compared with usual practice for the promotion of evidence-informed resource allocation to inpatient weekend allied health services. Future research is needed to determine the interactions between different implementation strategies and healthcare contexts when translating evidence into healthcare practice.

Trial registration

Australian New Zealand Clinical Trials Registry ACTRN12618000029291.

Cancer risk in individuals with intellectual disability in Sweden: A population-based cohort study

Gi, 21/10/2021 - 15:00

by Qianwei Liu, Hans-Olov Adami, Abraham Reichenberg, Alexander Kolevzon, Fang Fang, Sven Sandin

Background

A knowledge gap exists about the risk of cancer in individuals with intellectual disability (ID). The primary aim of this study was to estimate the cancer risk among individuals with ID compared to individuals without ID.

Methods and findings

We conducted a population-based cohort study of all children live-born in Sweden between 1974 and 2013 and whose mothers were born in a Nordic country. All individuals were followed from birth until cancer diagnosis, emigration, death, or 31 December 2016 (up to age 43 years), whichever came first. Incident cancers were identified from the Swedish Cancer Register. We fitted Cox regression models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) as measures of cancer risk in relation to ID after adjusting for several potential confounders. We analyzed ID by severity, as well as idiopathic ID and syndromic ID separately. We performed a sibling comparison to investigate familial confounding. The study cohort included a total of 3,531,305 individuals, including 27,956 (0.8%) individuals diagnosed with ID. Compared with the reference group (individuals without ID and without a full sibling with ID), individuals with ID were in general more likely to be male. The median follow-up time was 8.9 and 23.0 years for individuals with ID and individuals without ID, respectively. A total of 188 cancer cases were identified among individuals with ID (incidence rate [IR], 62 per 1,000 person-years), and 24,960 among individuals in the reference group (IR, 31 per 1,000 person-years). A statistically significantly increased risk was observed for any cancer (HR 1.57, 95% CI 1.35–1.82; P < 0.001), as well as for several cancer types, including cancers of the esophagus (HR 28.4, 95% CI 6.2–130.6; P < 0.001), stomach (HR 6.1, 95% CI 1.5–24.9; P = 0.013), small intestine (HR 12.0, 95% CI 2.9–50.1; P < 0.001), colon (HR 2.0, 95% CI 1.0–4.1; P = 0.045), pancreas (HR 6.0, 95% CI 1.5–24.8; P = 0.013), uterus (HR 11.7, 95% CI 1.5–90.7; P = 0.019), kidney (HR 4.4, 95% CI 2.0–9.8; P < 0.001), central nervous system (HR 2.7, 95% CI 2.0–3.7; P < 0.001), and other or unspecified sites (HR 4.8, 95% CI 1.8–12.9; P = 0.002), as well as acute lymphoid leukemia (HR 2.4, 95% CI 1.3–4.4; P = 0.003) and acute myeloid leukemia (HR 3.0, 95% CI 1.4–6.4; P = 0.004). Cancer risk was not modified by ID severity or sex but was higher for syndromic ID. The sibling comparison showed little support for familial confounding. The main study limitations were the limited statistical power for the analyses of specific cancer types, and the potential for underestimation of the studied associations (e.g., due to potential underdetection or delayed diagnosis of cancer among individuals with ID).

Conclusions

In this study, we found that individuals with ID showed an increased risk of any cancer, as well as of several specific cancer types. These findings suggest that extended surveillance and early intervention for cancer among individuals with ID are warranted.

Offering ART refill through community health workers versus clinic-based follow-up after home-based same-day ART initiation in rural Lesotho: The VIBRA cluster-randomized clinical trial

Gi, 21/10/2021 - 15:00

by Alain Amstutz, Thabo Ishmael Lejone, Lefu Khesa, Mathebe Kopo, Mpho Kao, Josephine Muhairwe, Moniek Bresser, Fabian Räber, Thomas Klimkait, Manuel Battegay, Tracy Renée Glass, Niklaus Daniel Labhardt

Background

Community-based antiretroviral therapy (ART) dispensing by lay workers is an important differentiated service delivery model in sub-Sahara Africa. However, patients new in care are generally excluded from such models. Home-based same-day ART initiation is becoming widespread practice, but linkage to the clinic is challenging. The pragmatic VIBRA (Village-Based Refill of ART) trial compared ART refill by existing lay village health workers (VHWs) versus clinic-based refill after home-based same-day ART initiation.

Methods and findings

The VIBRA trial is a cluster-randomized open-label clinical superiority trial conducted in 249 rural villages in the catchment areas of 20 health facilities in 2 districts (Butha-Buthe and Mokhotlong) in Lesotho. In villages (clusters) randomized to the intervention arm, individuals found to be HIV-positive during a door-to-door HIV testing campaign were offered same-day ART initiation with the option of refill by VHWs. The trained VHWs dispensed drugs and scheduled clinic visits for viral load measurement at 6 and 12 months. In villages randomized to the control arm, participants were offered same-day ART initiation with clinic-based ART refill. The primary outcome was 12-month viral suppression. Secondary endpoints included linkage and 12-month engagement in care. Analyses were intention-to-treat. The trial was registered on ClinicalTrials.gov (NCT03630549). From 16 August 2018 until 28 May 2019, 118 individuals from 108 households in 57 clusters in the intervention arm, and 139 individuals from 130 households in 60 clusters in the control arm, were enrolled (150 [58%] female; median age 36 years [interquartile range 30–48]; 200 [78%] newly diagnosed). In the intervention arm, 48/118 (41%) opted for VHW refill. At 12 months, 46/118 (39%) participants in the intervention arm and 64/139 (46%) in the control arm achieved viral suppression (adjusted risk difference −0.07 [95% CI −0.20 to 0.06]; p = 0.256). Arms were similar in linkage (adjusted risk difference 0.03 [−0.10 to 0.16]; p = 0.630), but engagement in care was non-significantly lower in the intervention arm (adjusted risk difference −0.12 [−0.23 to 0.003]; p = 0.058). Seven and 0 deaths occurred in the intervention and control arm, respectively. Of the intervention participants who did not opt for drug refill from the VHW at enrollment, 41/70 (59%) mentioned trust or conflict issues as the primary reason. Study limitations include a rather small sample size, 9% missing viral load measurements in the primary endpoint window, the low uptake of the VHW refill option in the intervention arm, and substantial migration among the study population.

Conclusions

The offer of village-based ART refill after same-day initiation led to similar outcomes as clinic-based refill. The intervention did not amplify the effect of home-based same-day ART initiation alone. The findings raise concerns about acceptance and safety of ART delivered by lay health workers after initiation in the community.

Trial registration

Registered with Clinicaltrials.gov (NCT03630549).

Changes in the associations of race and rurality with SARS-CoV-2 infection, mortality, and case fatality in the United States from February 2020 to March 2021: A population-based cohort study

Gi, 21/10/2021 - 15:00

by George N. Ioannou, Jacqueline M. Ferguson, Ann M. O’Hare, Amy S. B. Bohnert, Lisa I. Backus, Edward J. Boyko, Thomas F. Osborne, Matthew L. Maciejewski, C. Barrett Bowling, Denise M. Hynes, Theodore J. Iwashyna, Melody Saysana, Pamela Green, Kristin Berry

Background

We examined whether key sociodemographic and clinical risk factors for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection and mortality changed over time in a population-based cohort study.

Methods and findings

In a cohort of 9,127,673 persons enrolled in the United States Veterans Affairs (VA) healthcare system, we evaluated the independent associations of sociodemographic and clinical characteristics with SARS-CoV-2 infection (n = 216,046), SARS-CoV-2–related mortality (n = 10,230), and case fatality at monthly intervals between February 1, 2020 and March 31, 2021. VA enrollees had a mean age of 61 years (SD 17.7) and were predominantly male (90.9%) and White (64.5%), with 14.6% of Black race and 6.3% of Hispanic ethnicity. Black (versus White) race was strongly associated with SARS-CoV-2 infection (adjusted odds ratio [AOR] 5.10, [95% CI 4.65 to 5.59], p-value <0.001), mortality (AOR 3.85 [95% CI 3.30 to 4.50], p-value < 0.001), and case fatality (AOR 2.56, 95% CI 2.23 to 2.93, p-value < 0.001) in February to March 2020, but these associations were attenuated and not statistically significant by November 2020 for infection (AOR 1.03 [95% CI 1.00 to 1.07] p-value = 0.05) and mortality (AOR 1.08 [95% CI 0.96 to 1.20], p-value = 0.21) and were reversed for case fatality (AOR 0.86, 95% CI 0.78 to 0.95, p-value = 0.005). American Indian/Alaska Native (AI/AN versus White) race was associated with higher risk of SARS-CoV-2 infection in April and May 2020; this association declined over time and reversed by March 2021 (AOR 0.66 [95% CI 0.51 to 0.85] p-value = 0.004). Hispanic (versus non-Hispanic) ethnicity was associated with higher risk of SARS-CoV-2 infection and mortality during almost every time period, with no evidence of attenuation over time. Urban (versus rural) residence was associated with higher risk of infection (AOR 2.02, [95% CI 1.83 to 2.22], p-value < 0.001), mortality (AOR 2.48 [95% CI 2.08 to 2.96], p-value < 0.001), and case fatality (AOR 2.24, 95% CI 1.93 to 2.60, p-value < 0.001) in February to April 2020, but these associations attenuated over time and reversed by September 2020 (AOR 0.85, 95% CI 0.81 to 0.89, p-value < 0.001 for infection, AOR 0.72, 95% CI 0.62 to 0.83, p-value < 0.001 for mortality and AOR 0.81, 95% CI 0.71 to 0.93, p-value = 0.006 for case fatality). Throughout the observation period, high comorbidity burden, younger age, and obesity were consistently associated with infection, while high comorbidity burden, older age, and male sex were consistently associated with mortality. Limitations of the study include that changes over time in the associations of some risk factors may be affected by changes in the likelihood of testing for SARS-CoV-2 according to those risk factors; also, study results apply directly to VA enrollees who are predominantly male and have comprehensive healthcare and need to be confirmed in other populations.

Conclusions

In this study, we found that strongly positive associations of Black and AI/AN (versus White) race and urban (versus rural) residence with SARS-CoV-2 infection, mortality, and case fatality observed early in the pandemic were ameliorated or reversed by March 2021.