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Effect of a patient-centered hypertension delivery strategy on all-cause mortality: Secondary analysis of SEARCH, a community-randomized trial in rural Kenya and Uganda

Lu, 20/09/2021 - 15:00

by Matthew D. Hickey, James Ayieko, Asiphas Owaraganise, Nicholas Sim, Laura B. Balzer, Jane Kabami, Mucunguzi Atukunda, Fredrick J. Opel, Erick Wafula, Marilyn Nyabuti, Lillian Brown, Gabriel Chamie, Vivek Jain, James Peng, Dalsone Kwarisiima, Carol S. Camlin, Edwin D. Charlebois, Craig R. Cohen, Elizabeth A. Bukusi, Moses R. Kamya, Maya L. Petersen, Diane V. Havlir

Background

Hypertension treatment reduces morbidity and mortality yet has not been broadly implemented in many low-resource settings, including sub-Saharan Africa (SSA). We hypothesized that a patient-centered integrated chronic disease model that included hypertension treatment and leveraged the HIV care system would reduce mortality among adults with uncontrolled hypertension in rural Kenya and Uganda.

Methods and findings

This is a secondary analysis of the SEARCH trial (NCT:01864603), in which 32 communities underwent baseline population-based multidisease testing, including hypertension screening, and were randomized to standard country-guided treatment or to a patient-centered integrated chronic care model including treatment for hypertension, diabetes, and HIV. Patient-centered care included on-site introduction to clinic staff at screening, nursing triage to expedite visits, reduced visit frequency, flexible clinic hours, and a welcoming clinic environment. The analytic population included nonpregnant adults (≥18 years) with baseline uncontrolled hypertension (blood pressure ≥140/90 mm Hg). The primary outcome was 3-year all-cause mortality with comprehensive population-level assessment. Secondary outcomes included hypertension control assessed at a population level at year 3 (defined per country guidelines as at least 1 blood pressure measure <140/90 mm Hg on 3 repeated measures). Between-arm comparisons used cluster-level targeted maximum likelihood estimation.Among 86,078 adults screened at study baseline (June 2013 to July 2014), 10,928 (13%) had uncontrolled hypertension. Median age was 53 years (25th to 75th percentile 40 to 66); 6,058 (55%) were female; 677 (6%) were HIV infected; and 477 (4%) had diabetes mellitus. Overall, 174 participants (3.2%) in the intervention group and 225 participants (4.1%) in the control group died during 3 years of follow-up (adjusted relative risk (aRR) 0.79, 95% confidence interval (CI) 0.64 to 0.97, p = 0.028). Among those with baseline grade 3 hypertension (≥180/110 mm Hg), 22 (4.9%) in the intervention group and 42 (7.9%) in the control group died during 3 years of follow-up (aRR 0.62, 95% CI 0.39 to 0.97, p = 0.038). Estimated population-level hypertension control at year 3 was 53% in intervention and 44% in control communities (aRR 1.22, 95% CI 1.12 to 1.33, p < 0.001). Study limitations include inability to identify specific causes of death and control conditions that exceeded current standard hypertension care.

Conclusions

In this cluster randomized comparison where both arms received population-level hypertension screening, implementation of a patient-centered hypertension care model was associated with a 21% reduction in all-cause mortality and a 22% improvement in hypertension control compared to standard care among adults with baseline uncontrolled hypertension. Patient-centered chronic care programs for HIV can be leveraged to reduce the overall burden of cardiovascular mortality in SSA.

Trial registration

ClinicalTrials.gov NCT:01864603.

The blood metabolome of incident kidney cancer: A case–control study nested within the MetKid consortium

Lu, 20/09/2021 - 15:00

by Florence Guida, Vanessa Y. Tan, Laura J. Corbin, Karl Smith-Byrne, Karine Alcala, Claudia Langenberg, Isobel D. Stewart, Adam S. Butterworth, Praveen Surendran, David Achaintre, Jerzy Adamski, Pilar Amiano Exezarreta, Manuela M. Bergmann, Caroline J. Bull, Christina C. Dahm, Audrey Gicquiau, Graham G. Giles, Marc J. Gunter, Toomas Haller, Arnulf Langhammer, Tricia L. Larose, Börje Ljungberg, Andres Metspalu, Roger L. Milne, David C. Muller, Therese H. Nøst, Elin Pettersen Sørgjerd, Cornelia Prehn, Elio Riboli, Sabina Rinaldi, Joseph A. Rothwell, Augustin Scalbert, Julie A. Schmidt, Gianluca Severi, Sabina Sieri, Roel Vermeulen, Emma E. Vincent, Melanie Waldenberger, Nicholas J. Timpson, Mattias Johansson

Background

Excess bodyweight and related metabolic perturbations have been implicated in kidney cancer aetiology, but the specific molecular mechanisms underlying these relationships are poorly understood. In this study, we sought to identify circulating metabolites that predispose kidney cancer and to evaluate the extent to which they are influenced by body mass index (BMI).

Methods and findings

We assessed the association between circulating levels of 1,416 metabolites and incident kidney cancer using pre-diagnostic blood samples from up to 1,305 kidney cancer case–control pairs from 5 prospective cohort studies. Cases were diagnosed on average 8 years after blood collection. We found 25 metabolites robustly associated with kidney cancer risk. In particular, 14 glycerophospholipids (GPLs) were inversely associated with risk, including 8 phosphatidylcholines (PCs) and 2 plasmalogens. The PC with the strongest association was PC ae C34:3 with an odds ratio (OR) for 1 standard deviation (SD) increment of 0.75 (95% confidence interval [CI]: 0.68 to 0.83, p = 2.6 × 10−8). In contrast, 4 amino acids, including glutamate (OR for 1 SD = 1.39, 95% CI: 1.20 to 1.60, p = 1.6 × 10−5), were positively associated with risk. Adjusting for BMI partly attenuated the risk association for some—but not all—metabolites, whereas other known risk factors of kidney cancer, such as smoking and alcohol consumption, had minimal impact on the observed associations. A mendelian randomisation (MR) analysis of the influence of BMI on the blood metabolome highlighted that some metabolites associated with kidney cancer risk are influenced by BMI. Specifically, elevated BMI appeared to decrease levels of several GPLs that were also found inversely associated with kidney cancer risk (e.g., −0.17 SD change [ßBMI] in 1-(1-enyl-palmitoyl)-2-linoleoyl-GPC (P-16:0/18:2) levels per SD change in BMI, p = 3.4 × 10−5). BMI was also associated with increased levels of glutamate (ßBMI: 0.12, p = 1.5 × 10−3). While our results were robust across the participating studies, they were limited to study participants of European descent, and it will, therefore, be important to evaluate if our findings can be generalised to populations with different genetic backgrounds.

Conclusions

This study suggests a potentially important role of the blood metabolome in kidney cancer aetiology by highlighting a wide range of metabolites associated with the risk of developing kidney cancer and the extent to which changes in levels of these metabolites are driven by BMI—the principal modifiable risk factor of kidney cancer.

Differences in outcomes of mandatory motorcycle helmet legislation by country income level: A systematic review and meta-analysis

Ve, 17/09/2021 - 15:00

by Jacob R. Lepard, Riccardo Spagiari, Jacquelyn Corley, Ernest J. Barthélemy, Eliana Kim, Rolvix Patterson, Sara Venturini, Megan E. H. Still, Yu Tung Lo, Gail Rosseau, Rania A. Mekary, Kee B. Park

Background

The recent Lancet Commission on Legal Determinants of Global Health argues that governance can provide the framework for achieving sustainable development goals. Even though over 90% of fatal road traffic injuries occur in low- and middle-income countries (LMICs) primarily affecting motorcyclists, the utility of helmet laws outside of high-income settings has not been well characterized. We sought to evaluate the differences in outcomes of mandatory motorcycle helmet legislation and determine whether these varied across country income levels.

Methods and findings

A systematic review and meta-analysis were completed using the PRISMA checklist. A search for relevant articles was conducted using the PubMed, Embase, and Web of Science databases from January 1, 1990 to August 8, 2021. Studies were included if they evaluated helmet usage, mortality from motorcycle crash, or traumatic brain injury (TBI) incidence, with and without enactment of a mandatory helmet law as the intervention. The Newcastle–Ottawa Scale (NOS) was used to rate study quality and funnel plots, and Begg’s and Egger’s tests were used to assess for small study bias. Pooled odds ratios (ORs) and their 95% confidence intervals (CIs) were stratified by high-income countries (HICs) versus LMICs using the random-effects model. Twenty-five articles were included in the final analysis encompassing a total study population of 31,949,418 people. There were 17 retrospective cohort studies, 2 prospective cohort studies, 1 case–control study, and 5 pre–post design studies. There were 16 studies from HICs and 9 from LMICs. The median NOS score was 6 with a range of 4 to 9. All studies demonstrated higher odds of helmet usage after implementation of helmet law; however, the results were statistically significantly greater in HICs (OR: 53.5; 95% CI: 28.4; 100.7) than in LMICs (OR: 4.82; 95% CI: 3.58; 6.49), p-value comparing both strata < 0.0001. There were significantly lower odds of motorcycle fatalities after enactment of helmet legislation (OR: 0.71; 95% CI: 0.61; 0.83) with no significant difference by income classification, p-value: 0.27. Odds of TBI were statistically significantly lower in HICs (OR: 0.61, 95% CI 0.54 to 0.69) than in LMICs (0.79, 95% CI 0.72 to 0.86) after enactment of law (p-value: 0.0001). Limitations of this study include variability in the methodologies and data sources in the studies included in the meta-analysis as well as the lack of available literature from the lowest income countries or from the African WHO region, in which helmet laws are least commonly present.

Conclusions

In this study, we observed that mandatory helmet laws had substantial public health benefits in all income contexts, but some outcomes were diminished in LMIC settings where additional measures such as public education and law enforcement might play critical roles.

All-cause and cause-specific mortality during and following incarceration in Brazil: A retrospective cohort study

Ve, 17/09/2021 - 15:00

by Yiran E. Liu, Everton Ferreira Lemos, Crhistinne Cavalheiro Maymone Gonçalves, Roberto Dias de Oliveira, Andrea da Silva Santos, Agne Oliveira do Prado Morais, Mariana Garcia Croda, Maria de Lourdes Delgado Alves, Julio Croda, Katharine S. Walter, Jason R. Andrews

Background

Mortality during and after incarceration is poorly understood in low- and middle-income countries (LMICs). The need to address this knowledge gap is especially urgent in South America, which has the fastest growing prison population in the world. In Brazil, insufficient data have precluded our understanding of all-cause and cause-specific mortality during and after incarceration.

Methods and findings

We linked incarceration and mortality databases for the Brazilian state of Mato Grosso do Sul to obtain a retrospective cohort of 114,751 individuals with recent incarceration. Between January 1, 2009 and December 31, 2018, we identified 3,127 deaths of individuals with recent incarceration (705 in detention and 2,422 following release). We analyzed age-standardized, all-cause, and cause-specific mortality rates among individuals detained in different facility types and following release, compared to non-incarcerated residents. We additionally modeled mortality rates over time during and after incarceration for all causes of death, violence, or suicide. Deaths in custody were 2.2 times the number reported by the national prison administration (n = 317). Incarcerated men and boys experienced elevated mortality, compared with the non-incarcerated population, due to increased risk of death from violence, suicide, and communicable diseases, with the highest standardized incidence rate ratio (IRR) in semi-open prisons (2.4; 95% confidence interval [CI]: 2.0 to 2.8), police stations (3.1; 95% CI: 2.5 to 3.9), and youth detention (8.1; 95% CI: 5.9 to 10.8). Incarcerated women experienced increased mortality from suicide (IRR = 6.0, 95% CI: 1.2 to 17.7) and communicable diseases (IRR = 2.5, 95% CI: 1.1 to 5.0). Following release from prison, mortality was markedly elevated for men (IRR = 3.0; 95% CI: 2.8 to 3.1) and women (IRR = 2.4; 95% CI: 2.1 to 2.9). The risk of violent death and suicide was highest immediately post-release and declined over time; however, all-cause mortality remained elevated 8 years post-release. The limitations of this study include inability to establish causality, uncertain reliability of data during incarceration, and underestimation of mortality rates due to imperfect database linkage.

Conclusions

Incarcerated individuals in Brazil experienced increased mortality from violence, suicide, and communicable diseases. Mortality was heightened following release for all leading causes of death, with particularly high risk of early violent death and elevated all-cause mortality up to 8 years post-release. These disparities may have been underrecognized in Brazil due to underreporting and insufficient data.

Community-facility linkage models and maternal and infant health outcomes in Malawi’s PMTCT/ART program: A cohort study

Ve, 17/09/2021 - 15:00

by Michael E. Herce, Maganizo B. Chagomerana, Lauren C. Zalla, Nicole B. Carbone, Benjamin H. Chi, Michael T. Eliya, Sam Phiri, Stephanie M. Topp, Maria H. Kim, Emily B. Wroe, Chileshe Chilangwa, Jacqueline Chinkonde, Innocent A. Mofolo, Mina C. Hosseinipour, Jessie K. Edwards

Background

In sub-Saharan Africa, 3 community-facility linkage (CFL) models—Expert Clients, Community Health Workers (CHWs), and Mentor Mothers—have been widely implemented to support pregnant and breastfeeding women (PBFW) living with HIV and their infants to access and sustain care for prevention of mother-to-child transmission of HIV (PMTCT), yet their comparative impact under real-world conditions is poorly understood.

Methods and findings

We sought to estimate the effects of CFL models on a primary outcome of maternal loss to follow-up (LTFU), and secondary outcomes of maternal longitudinal viral suppression and infant “poor outcome” (encompassing documented HIV-positive test result, LTFU, or death), in Malawi’s PMTCT/ART program. We sampled 30 of 42 high-volume health facilities (“sites”) in 5 Malawi districts for study inclusion. At each site, we reviewed medical records for all newly HIV-diagnosed PBFW entering the PMTCT program between July 1, 2016 and June 30, 2017, and, for pregnancies resulting in live births, their HIV-exposed infants, yielding 2,589 potentially eligible mother–infant pairs. Of these, 2,049 (79.1%) had an available HIV treatment record and formed the study cohort. A randomly selected subset of 817 (40.0%) cohort members underwent a field survey, consisting of a questionnaire and HIV biomarker assessment. Survey responses and biomarker results were used to impute CFL model exposure, maternal viral load, and early infant diagnosis (EID) outcomes for those missing these measures to enrich data in the larger cohort. We applied sampling weights in all statistical analyses to account for the differing proportions of facilities sampled by district. Of the 2,049 mother–infant pairs analyzed, 62.2% enrolled in PMTCT at a primary health center, at which time 43.7% of PBFW were ≤24 years old, and 778 (38.0%) received the Expert Client model, 640 (31.2%) the CHW model, 345 (16.8%) the Mentor Mother model, 192 (9.4%) ≥2 models, and 94 (4.6%) no model. Maternal LTFU varied by model, with LTFU being more likely among Mentor Mother model recipients (adjusted hazard ratio [aHR]: 1.45; 95% confidence interval [CI]: 1.14, 1.84; p = 0.003) than Expert Client recipients. Over 2 years from HIV diagnosis, PBFW supported by CHWs spent 14.3% (95% CI: 2.6%, 26.1%; p = 0.02) more days in an optimal state of antiretroviral therapy (ART) retention with viral suppression than women supported by Expert Clients. Infants receiving the Mentor Mother model (aHR: 1.24, 95% CI: 1.01, 1.52; p = 0.04) and ≥2 models (aHR: 1.44, 95% CI: 1.20, 1.74; p < 0.001) were more likely to undergo EID testing by age 6 months than infants supported by Expert Clients. Infants receiving the CHW and Mentor Mother models were 1.15 (95% CI: 0.80, 1.67; p = 0.44) and 0.84 (95% CI: 0.50, 1.42; p = 0.51) times as likely, respectively, to experience a poor outcome by 1 year than those supported by Expert Clients, but not significantly so. Study limitations include possible residual confounding, which may lead to inaccurate conclusions about the impacts of CFL models, uncertain generalizability of findings to other settings, and missing infant medical record data that limited the precision of infant outcome measurement.

Conclusions

In this descriptive study, we observed widespread reach of CFL models in Malawi, with favorable maternal outcomes in the CHW model and greater infant EID testing uptake in the Mentor Mother model. Our findings point to important differences in maternal and infant HIV outcomes by CFL model along the PMTCT continuum and suggest future opportunities to identify key features of CFL models driving these outcome differences.

Correction: Benefit and harm of intensive blood pressure treatment: Derivation and validation of risk models using data from the SPRINT and ACCORD trials

Gi, 16/09/2021 - 15:00

by Sanjay Basu, Jeremy B. Sussman, Joseph Rigdon, Lauren Steimle, Brian T. Denton, Rodney A. Hayward

Associations between women’s empowerment and child development, growth, and nurturing care practices in sub-Saharan Africa: A cross-sectional analysis of demographic and health survey data

Gi, 16/09/2021 - 15:00

by Lilia Bliznashka, Ifeyinwa E. Udo, Christopher R. Sudfeld, Wafaie W. Fawzi, Aisha K. Yousafzai

Background

Approximately 40% of children 3 to 4 years of age in low- and middle-income countries have suboptimal development and growth. Women’s empowerment may help provide inputs of nurturing care for early development and growth by building caregiver capacity and family support. We examined the associations between women’s empowerment and child development, growth, early learning, and nutrition in sub-Saharan Africa (SSA).

Methods and findings

We pooled data on married women (15 to 49 years) and their children (36 to 59 months) from Demographic and Health Surveys that collected data on child development (2011 to 2018) in 9 SSA countries (N = 21,434): Benin, Burundi, Cameroon, Chad, Congo, Rwanda, Senegal, Togo, and Uganda. We constructed a women’s empowerment score using factor analysis and assigned women to country-specific quintile categories. The child outcomes included cognitive, socioemotional, literacy–numeracy, and physical development (Early Childhood Development Index), linear growth (height-for-age Z-score (HAZ) and stunting (HAZ <−2). Early learning outcomes were number of parental stimulation activities (range 0 to 6) and learning resources (range 0 to 4). The nutrition outcome was child dietary diversity score (DDS, range 0 to 7). We assessed the relationship between women’s empowerment and child development, growth, early learning, and nutrition using multivariate generalized linear models.On average, households in our sample were large (8.5 ± 5.7 members) and primarily living in rural areas (71%). Women were 31 ± 6.6 years on average, 54% had no education, and 31% had completed primary education. Children were 47 ± 7 months old and 49% were female. About 23% of children had suboptimal cognitive development, 31% had suboptimal socioemotional development, and 90% had suboptimal literacy–numeracy development. Only 9% of children had suboptimal physical development, but 35% were stunted. Approximately 14% of mothers and 3% of fathers provided ≥4 stimulation activities. Relative to the lowest quintile category, children of women in the highest empowerment quintile category were less likely to have suboptimal cognitive development (relative risk (RR) 0.89; 95% confidence interval (CI) 0.80, 0.99), had higher HAZ (mean difference (MD) 0.09; 95% CI 0.02, 0.16), lower risk of stunting (RR 0.93; 95% CI 0.87, 1.00), higher DDS (MD 0.17; 95% CI 0.06, 0.29), had 0.07 (95% CI 0.01, 0.13) additional learning resources, and received 0.16 (95% CI 0.06, 0.25) additional stimulation activities from their mothers and 0.23 (95% CI 0.17 to 0.29) additional activities from their fathers. We found no evidence that women’s empowerment was associated with socioemotional, literacy–numeracy, or physical development. Study limitations include the possibility of reverse causality and suboptimal assessments of the outcomes and exposure.

Conclusions

Women’s empowerment was positively associated with early child cognitive development, child growth, early learning, and nutrition outcomes in SSA. Efforts to improve child development and growth should consider women’s empowerment as a potential strategy.

Association of physical activity intensity and bout length with mortality: An observational study of 79,503 UK Biobank participants

Me, 15/09/2021 - 15:00

by Lousise A. C. Millard, Kate Tilling, Tom R. Gaunt, David Carslake, Deborah A. Lawlor

Background

Spending more time active (and less sedentary) is associated with health benefits such as improved cardiovascular health and lower risk of all-cause mortality. It is unclear whether these associations differ depending on whether time spent sedentary or in moderate-vigorous physical activity (MVPA) is accumulated in long or short bouts. In this study, we used a novel method that accounts for substitution (i.e., more time in MVPA means less time sleeping, in light activity or sedentary) to examine whether length of sedentary and MVPA bouts associates with all-cause mortality.

Methods and findings

We used data on 79,503 adult participants from the population-based UK Biobank cohort, which recruited participants between 2006 and 2010 (mean age at accelerometer wear 62.1 years [SD = 7.9], 54.5% women; mean length of follow-up 5.1 years [SD = 0.73]). We derived (1) the total time participants spent in activity categories—sleep, sedentary, light activity, and MVPA—on average per day; (2) time spent in sedentary bouts of short (1 to 15 minutes), medium (16 to 40 minutes), and long (41+ minutes) duration; and (3) MVPA bouts of very short (1 to 9 minutes), short (10 to 15 minutes), medium (16 to 40 minutes), and long (41+ minutes) duration. We used Cox proportion hazards regression to estimate the association of spending 10 minutes more average daily time in one activity or bout length category, coupled with 10 minutes less time in another, with all-cause mortality. Those spending more time in MVPA had lower mortality risk, irrespective of whether this replaced time spent sleeping, sedentary, or in light activity, and these associations were of similar magnitude (e.g., hazard ratio [HR] 0.96 [95% CI: 0.94, 0.97; P < 0.001] per 10 minutes more MVPA, coupled with 10 minutes less light activity per day). Those spending more time sedentary had higher mortality risk if this replaced light activity (HR 1.02 [95% CI: 1.01, 1.02; P < 0.001] per 10 minutes more sedentary time, with 10 minutes less light activity per day) and an even higher risk if this replaced MVPA (HR 1.06 [95% CI: 1.05, 1.08; P < 0.001] per 10 minutes more sedentary time, with 10 minutes less MVPA per day). We found little evidence that mortality risk differed depending on the length of sedentary or MVPA bouts. Key limitations of our study are potential residual confounding, the limited length of follow-up, and use of a select sample of the United Kingdom population.

Conclusions

We have shown that time spent in MVPA was associated with lower mortality, irrespective of whether it replaced time spent sleeping, sedentary, or in light activity. Time spent sedentary was associated with higher mortality risk, particularly if it replaced MVPA. This emphasises the specific importance of MVPA. Our findings suggest that the impact of MVPA does not differ depending on whether it is obtained from several short bouts or fewer longer bouts, supporting the recent removal of the requirement that MVPA should be accumulated in bouts of 10 minutes or more from the UK and the United States policy. Further studies are needed to investigate causality and explore health outcomes beyond mortality.

Socioeconomic inequalities in prevalence and development of multimorbidity across adulthood: A longitudinal analysis of the MRC 1946 National Survey of Health and Development in the UK

Ma, 14/09/2021 - 15:00

by Amal R. Khanolkar, Nishi Chaturvedi, Valerie Kuan, Daniel Davis, Alun Hughes, Marcus Richards, David Bann, Praveetha Patalay

Background

We aimed to estimate multimorbidity trajectories and quantify socioeconomic inequalities based on childhood and adulthood socioeconomic position (SEP) in the risks and rates of multimorbidity accumulation across adulthood.

Methods and findings

Participants from the UK 1946 National Survey of Health and Development (NSHD) birth cohort study who attended the age 36 years assessment in 1982 and any one of the follow-up assessments at ages 43, 53, 63, and 69 years (N = 3,723, 51% males). Information on 18 health conditions was based on a combination of self-report, biomarkers, health records, and prescribed medications. We estimated multimorbidity trajectories and delineated socioeconomic inequalities (based on childhood and adulthood social class and highest education) in multimorbidity at each age and in longitudinal trajectories.Multimorbidity increased with age (0.7 conditions at 36 years to 3.7 at 69 years). Multimorbidity accumulation was nonlinear, accelerating with age at the rate of 0.08 conditions/year (95% CI 0.07 to 0.09, p < 0.001) at 36 to 43 years to 0.19 conditions/year (95% CI 0.18 to 0.20, p < 0.001) at 63 to 69 years. At all ages, the most socioeconomically disadvantaged had 1.2 to 1.4 times greater number of conditions on average compared to the most advantaged. The most disadvantaged by each socioeconomic indicator experienced an additional 0.39 conditions (childhood social class), 0.83 (adult social class), and 1.08 conditions (adult education) at age 69 years, independent of all other socioeconomic indicators. Adverse adulthood SEP was associated with more rapid accumulation of multimorbidity, resulting in 0.49 excess conditions in partly/unskilled compared to professional/intermediate individuals between 63 and 69 years. Disadvantaged childhood social class, independently of adulthood SEP, was associated with accelerated multimorbidity trajectories from age 53 years onwards.Study limitations include that the NSHD cohort is composed of individuals of white European heritage only, and findings may not be generalizable to the non-white British population of the same generation and did not account for other important dimensions of SEP such as income and wealth.

Conclusions

In this study, we found that socioeconomically disadvantaged individuals have earlier onset and more rapid accumulation of multimorbidity resulting in widening inequalities into old age, with independent contributions from both childhood and adulthood SEP.

Closing the health equity gap: A role for implementation science?

Ma, 14/09/2021 - 15:00

by Beryne Odeny

Beryne Odeny discusses strategies to improve equity in health care and health research.

The burden of traumatic brain injury from low-energy falls among patients from 18 countries in the CENTER-TBI Registry: A comparative cohort study

Ma, 14/09/2021 - 15:00

by Fiona E. Lecky, Olubukola Otesile, Carl Marincowitz, Marek Majdan, Daan Nieboer, Hester F. Lingsma, Marc Maegele, Giuseppe Citerio, Nino Stocchetti, Ewout W. Steyerberg, David K. Menon, Andrew I. R. Maas, CENTER-TBI Participants and Investigators

Background

Traumatic brain injury (TBI) is an important global public health burden, where those injured by high-energy transfer (e.g., road traffic collisions) are assumed to have more severe injury and are prioritised by emergency medical service trauma triage tools. However recent studies suggest an increasing TBI disease burden in older people injured through low-energy falls. We aimed to assess the prevalence of low-energy falls among patients presenting to hospital with TBI, and to compare their characteristics, care pathways, and outcomes to TBI caused by high-energy trauma.

Methods and findings

We conducted a comparative cohort study utilising the CENTER-TBI (Collaborative European NeuroTrauma Effectiveness Research in TBI) Registry, which recorded patient demographics, injury, care pathway, and acute care outcome data in 56 acute trauma receiving hospitals across 18 countries (17 countries in Europe and Israel). Patients presenting with TBI and indications for computed tomography (CT) brain scan between 2014 to 2018 were purposively sampled. The main study outcomes were (i) the prevalence of low-energy falls causing TBI within the overall cohort and (ii) comparisons of TBI patients injured by low-energy falls to TBI patients injured by high-energy transfer—in terms of demographic and injury characteristics, care pathways, and hospital mortality. In total, 22,782 eligible patients were enrolled, and study outcomes were analysed for 21,681 TBI patients with known injury mechanism; 40% (95% CI 39% to 41%) (8,622/21,681) of patients with TBI were injured by low-energy falls. Compared to 13,059 patients injured by high-energy transfer (HE cohort), the those injured through low-energy falls (LE cohort) were older (LE cohort, median 74 [IQR 56 to 84] years, versus HE cohort, median 42 [IQR 25 to 60] years; p < 0.001), more often female (LE cohort, 50% [95% CI 48% to 51%], versus HE cohort, 32% [95% CI 31% to 34%]; p < 0.001), more frequently taking pre-injury anticoagulants or/and platelet aggregation inhibitors (LE cohort, 44% [95% CI 42% to 45%], versus HE cohort, 13% [95% CI 11% to 14%]; p < 0.001), and less often presenting with moderately or severely impaired conscious level (LE cohort, 7.8% [95% CI 5.6% to 9.8%], versus HE cohort, 10% [95% CI 8.7% to 12%]; p < 0.001), but had similar in-hospital mortality (LE cohort, 6.3% [95% CI 4.2% to 8.3%], versus HE cohort, 7.0% [95% CI 5.3% to 8.6%]; p = 0.83). The CT brain scan traumatic abnormality rate was 3% lower in the LE cohort (LE cohort, 29% [95% CI 27% to 31%], versus HE cohort, 32% [95% CI 31% to 34%]; p < 0.001); individuals in the LE cohort were 50% less likely to receive critical care (LE cohort, 12% [95% CI 9.5% to 13%], versus HE cohort, 24% [95% CI 23% to 26%]; p < 0.001) or emergency interventions (LE cohort, 7.5% [95% CI 5.4% to 9.5%], versus HE cohort, 13% [95% CI 12% to 15%]; p < 0.001) than patients injured by high-energy transfer. The purposive sampling strategy and censorship of patient outcomes beyond hospital discharge are the main study limitations.

Conclusions

We observed that patients sustaining TBI from low-energy falls are an important component of the TBI disease burden and a distinct demographic cohort; further, our findings suggest that energy transfer may not predict intracranial injury or acute care mortality in patients with TBI presenting to hospital. This suggests that factors beyond energy transfer level may be more relevant to prehospital and emergency department TBI triage in older people. A specific focus to improve prevention and care for patients sustaining TBI from low-energy falls is required.

Evaluating the frequency of English language requirements in clinical trial eligibility criteria: A systematic analysis using ClinicalTrials.gov

Ma, 14/09/2021 - 15:00

by Akila V. Muthukumar, Walker Morrell, Barbara E. Bierer

Background

A number of prior studies have demonstrated that research participants with limited English proficiency in the United States are routinely excluded from clinical trial participation. Systematic exclusion through study eligibility criteria that require trial participants to be able to speak, read, and/or understand English affects access to clinical trials and scientific generalizability. We sought to establish the frequency with which English language proficiency is required and, conversely, when non-English languages are affirmatively accommodated in US interventional clinical trials for adult populations.

Methods and findings

We used the advanced search function on ClinicalTrials.gov specifying interventional studies for adults with at least 1 site in the US. In addition, we used these search criteria to find studies with an available posted protocol. A computer program was written to search for evidence of English or Spanish language requirements, or the posted protocol, when available, was manually read for these language requirements. Of the 14,367 clinical trials registered on ClinicalTrials.gov between 1 January 2019 and 1 December 2020 that met baseline search criteria, 18.98% (95% CI 18.34%–19.62%; n = 2,727) required the ability to read, speak, and/or understand English, and 2.71% (95% CI 2.45%–2.98%; n = 390) specifically mentioned accommodation of translation to another language. The remaining trials in this analysis and the following sub-analyses did not mention English language requirements or accommodation of languages other than English. Of 2,585 federally funded clinical trials, 28.86% (95% CI 27.11%–30.61%; n = 746) required English language proficiency and 4.68% (95% CI 3.87%–5.50%; n = 121) specified accommodation of other languages; of the 5,286 industry-funded trials, 5.30% (95% CI 4.69%–5.90%; n = 280) required English and 0.49% (95% CI 0.30%–0.69%; n = 26) accommodated other languages. Trials related to infectious disease were less likely to specify an English requirement than all registered trials (10.07% versus 18.98%; relative risk [RR] = 0.53; 95% CI 0.44–0.64; p < 0.001). Trials related to COVID-19 were also less likely to specify an English requirement than all registered trials (8.18% versus 18.98%; RR = 0.43; 95% CI 0.33–0.56; p < 0.001). Trials with a posted protocol (n = 366) were more likely than all registered clinical trials to specify an English requirement (36.89% versus 18.98%; RR = 1.94, 95% CI 1.69–2.23; p < 0.001). A separate analysis of studies with posted protocols in 4 therapeutic areas (depression, diabetes, breast cancer, and prostate cancer) demonstrated that clinical trials related to depression were the most likely to require English (52.24%; 95% CI 40.28%–64.20%). One limitation of this study is that the computer program only searched for the terms “English” and “Spanish” and may have missed evidence of other language accommodations. Another limitation is that we did not differentiate between requirements to read English, speak English, understand English, and be a native English speaker; we grouped these requirements together in the category of English language requirements.

Conclusions

A meaningful percentage of US interventional clinical trials for adults exclude individuals who cannot read, speak, and/or understand English, or are not native English speakers. To advance more inclusive and generalizable research, funders, sponsors, institutions, investigators, institutional review boards, and others should prioritize translating study materials and eliminate language requirements unless justified either scientifically or ethically.

Impact of decreasing the proportion of higher energy foods and reducing portion sizes on food purchased in worksite cafeterias: A stepped-wedge randomised controlled trial

Ma, 14/09/2021 - 15:00

by James P. Reynolds, Minna Ventsel, Daina Kosīte, Brier Rigby Dames, Laura Brocklebank, Sarah Masterton, Emily Pechey, Mark Pilling, Rachel Pechey, Gareth J. Hollands, Theresa M. Marteau

Background

Overconsumption of energy from food is a major contributor to the high rates of overweight and obesity in many populations. There is growing evidence that interventions that target the food environment may be effective at reducing energy intake. The current study aimed to estimate the effect of decreasing the proportion of higher energy (kcal) foods, with and without reducing portion size, on energy purchased in worksite cafeterias.

Methods and findings

This stepped-wedge randomised controlled trial (RCT) evaluated 2 interventions: (i) availability: replacing higher energy products with lower energy products; and (ii) size: reducing the portion size of higher energy products. A total of 19 cafeterias were randomised to the order in which they introduced the 2 interventions. Availability was implemented first and maintained. Size was added to the availability intervention. Intervention categories included main meals, sides, cold drinks, snacks, and desserts. The study setting was worksite cafeterias located in distribution centres for a major United Kingdom supermarket and lasted for 25 weeks (May to November 2019). These cafeterias were used by 20,327 employees, mainly (96%) in manual occupations. The primary outcome was total energy (kcal) purchased from intervention categories per day. The secondary outcomes were energy (kcal) purchased from nonintervention categories per day, total energy purchased per day, and revenue. Regression models showed an overall reduction in energy purchased from intervention categories of −4.8% (95% CI −7.0% to −2.7%), p < 0.001 during the availability intervention period and a reduction of −11.5% (95% CI −13.7% to −9.3%), p < 0.001 during the availability plus size intervention period, relative to the baseline. There was a reduction in energy purchased of −6.6% (95% CI −7.9% to −5.4%), p < 0.001 during the availability plus size period, relative to availability alone. Study limitations include using energy purchased as the primary outcome (and not energy consumed) and the availability only of transaction-level sales data per site (and not individual-level data).

Conclusions

Decreasing the proportion of higher energy foods in cafeterias reduced the energy purchased. Decreasing portion sizes reduced this further. These interventions, particularly in combination, may be effective as part of broader strategies to reduce overconsumption of energy from food in out-of-home settings.

Trial registration

ISRCTN registry ISRCTN87225572.

Tuberculosis preventive therapy for people living with HIV: A systematic review and network meta-analysis

Ma, 14/09/2021 - 15:00

by Mercedes Yanes-Lane, Edgar Ortiz-Brizuela, Jonathon R. Campbell, Andrea Benedetti, Gavin Churchyard, Olivia Oxlade, Dick Menzies

Background

Tuberculosis (TB) preventive therapy (TPT) is an essential component of care for people living with HIV (PLHIV). We compared efficacy, safety, completion, and drug-resistant TB risk for currently recommended TPT regimens through a systematic review and network meta-analysis (NMA) of randomized trials.

Methods and findings

We searched MEDLINE, Embase, and the Cochrane Library from inception through June 9, 2020 for randomized controlled trials (RCTs) comparing 2 or more TPT regimens (or placebo/no treatment) in PLHIV. Two independent reviewers evaluated eligibility, extracted data, and assessed the risk of bias. We grouped TPT strategies as follows: placebo/no treatment, 6 to 12 months of isoniazid, 24 to 72 months of isoniazid, and rifamycin-containing regimens. A frequentist NMA (using graph theory) was carried out for the outcomes of development of TB disease, all-cause mortality, and grade 3 or worse hepatotoxicity. For other outcomes, graphical descriptions or traditional pairwise meta-analyses were carried out as appropriate. The potential role of confounding variables for TB disease and all-cause mortality was assessed through stratified analyses.A total of 6,466 unique studies were screened, and 157 full texts were assessed for eligibility. Of these, 20 studies (reporting 16 randomized trials) were included. The median sample size was 616 (interquartile range [IQR], 317 to 1,892). Eight were conducted in Africa, 3 in Europe, 3 in the Americas, and 2 included sites in multiple continents. According to the NMA, 6 to 12 months of isoniazid were no more efficacious in preventing microbiologically confirmed TB than rifamycin-containing regimens (incidence rate ratio [IRR] 1.0, 95% CI 0.8 to 1.4, p = 0.8); however, 6 to 12 months of isoniazid were associated with a higher incidence of all-cause mortality (IRR 1.6, 95% CI 1.2 to 2.0, p = 0.02) and a higher risk of grade 3 or higher hepatotoxicity (risk difference [RD] 8.9, 95% CI 2.8 to 14.9, p = 0.004). Finally, shorter regimens were associated with higher completion rates relative to longer regimens, and we did not find statistically significant differences in the risk of drug-resistant TB between regimens. Study limitations include potential confounding due to differences in posttreatment follow-up time and TB incidence in the study setting on the estimates of incidence of TB or all-cause mortality, as well as an underrepresentation of pregnant women and children.

Conclusions

Rifamycin-containing regimens appear safer and at least as effective as isoniazid regimens in preventing TB and death and should be considered part of routine care in PLHIV. Knowledge gaps remain as to which specific rifamycin-containing regimen provides the optimal balance of efficacy, completion, and safety.

Economic and modeling evidence for tuberculosis preventive therapy among people living with HIV: A systematic review and meta-analysis

Ma, 14/09/2021 - 15:00

by Aashna Uppal, Samiha Rahman, Jonathon R. Campbell, Olivia Oxlade, Dick Menzies

Background

Human immunodeficiency virus (HIV) is the strongest known risk factor for tuberculosis (TB) through its impairment of T-cell immunity. Tuberculosis preventive treatment (TPT) is recommended for people living with HIV (PLHIV) by the World Health Organization, as it significantly reduces the risk of developing TB disease. We conducted a systematic review and meta-analysis of modeling studies to summarize projected costs, risks, benefits, and impacts of TPT use among PLHIV on TB-related outcomes.

Methods and findings

We searched MEDLINE, Embase, and Web of Science from inception until December 31, 2020. Two reviewers independently screened titles, abstracts, and full texts; extracted data; and assessed quality. Extracted data were summarized using descriptive analysis. We performed quantile regression and random effects meta-analysis to describe trends in cost, effectiveness, and cost-effectiveness outcomes across studies and identified key determinants of these outcomes. Our search identified 6,615 titles; 61 full texts were included in the final review. Of the 61 included studies, 31 reported both cost and effectiveness outcomes. A total of 41 were set in low- and middle-income countries (LMICs), while 12 were set in high-income countries (HICs); 2 were set in both. Most studies considered isoniazid (INH)-based regimens 6 to 2 months long (n = 45), or longer than 12 months (n = 11). Model parameters and assumptions varied widely between studies. Despite this, all studies found that providing TPT to PLHIV was predicted to be effective at averting TB disease. No TPT regimen was substantially more effective at averting TB disease than any other. The cost of providing TPT and subsequent downstream costs (e.g. post-TPT health systems costs) were estimated to be less than $1,500 (2020 USD) per person in 85% of studies that reported cost outcomes (n = 36), regardless of study setting. All cost-effectiveness analyses concluded that providing TPT to PLHIV was potentially cost-effective compared to not providing TPT. In quantitative analyses, country income classification, consideration of antiretroviral therapy (ART) use, and TPT regimen use significantly impacted cost-effectiveness. Studies evaluating TPT in HICs suggested that TPT may be more effective at preventing TB disease than studies evaluating TPT in LMICs; pooled incremental net monetary benefit, given a willingness-to-pay threshold of country-level per capita gross domestic product (GDP), was $271 in LMICs (95% confidence interval [CI] −$81 to $622, p = 0.12) and was $2,568 in HICs (−$32,115 to $37,251, p = 0.52). Similarly, TPT appeared to be more effective at averting TB disease in HICs; pooled percent reduction in active TB incidence was 20% (13% to 27%, p < 0.001) in LMICs and 37% (−34% to 100%, p = 0.13) in HICs. Key limitations of this review included the heterogeneity of input parameters and assumptions from included studies, which limited pooling of effect estimates, inconsistent reporting of model parameters, which limited sample sizes of quantitative analyses, and database bias toward English publications.

Conclusions

The body of literature related to modeling TPT among PLHIV is large and heterogeneous, making comparisons across studies difficult. Despite this variability, all studies in all settings concluded that providing TPT to PLHIV is potentially effective and cost-effective for preventing TB disease.

Tuberculosis preventive treatment in people living with HIV—Is the glass half empty or half full?

Ma, 14/09/2021 - 15:00

by Olivia Oxlade, Hannah Rochon, Jonathon R. Campbell, Dick Menzies

Olivia Oxlade and co-authors introduce a Collection on tuberculosis preventive therapy in people with HIV infection.

Intrinsic capacity and its associations with incident dependence and mortality in 10/66 Dementia Research Group studies in Latin America, India, and China: A population-based cohort study

Ma, 14/09/2021 - 15:00

by Martin J. Prince, Daisy Acosta, Mariella Guerra, Yueqin Huang, K. S. Jacob, Ivonne Z. Jimenez-Velazquez, A. T. Jotheeswaran, Juan J. Llibre Rodriguez, Aquiles Salas, Ana Luisa Sosa, Isaac Acosta, Rosie Mayston, Zhaorui Liu, Jorge J. Llibre-Guerra, A. Matthew Prina, Adolfo Valhuerdi

Background

The World Health Organization (WHO) has reframed health and healthcare for older people around achieving the goal of healthy ageing. The recent WHO Integrated Care for Older People (ICOPE) guidelines focus on maintaining intrinsic capacity, i.e., addressing declines in neuromusculoskeletal, vitality, sensory, cognitive, psychological, and continence domains, aiming to prevent or delay the onset of dependence. The target group with 1 or more declines in intrinsic capacity (DICs) is broad, and implementation may be challenging in less-resourced settings. We aimed to inform planning by assessing intrinsic capacity prevalence, by characterising the target group, and by validating the general approach—testing hypotheses that DIC was consistently associated with higher risks of incident dependence and death.

Methods and findings

We conducted population-based cohort studies (baseline, 2003–2007) in urban sites in Cuba, Dominican Republic, Puerto Rico, and Venezuela, and rural and urban sites in Peru, Mexico, India, and China. Door-knocking identified eligible participants, aged 65 years and over and normally resident in each geographically defined catchment area. Sociodemographic, behaviour and lifestyle, health, and healthcare utilisation and cost questionnaires, and physical assessments were administered to all participants, with incident dependence and mortality ascertained 3 to 5 years later (2008–2010). In 12 sites in 8 countries, 17,031 participants were surveyed at baseline. Overall mean age was 74.2 years, range of means by site 71.3–76.3 years; 62.4% were female, range 53.4%–67.3%. At baseline, only 30% retained full capacity across all domains. The proportion retaining capacity fell sharply with increasing age, and declines affecting multiple domains were more common. Poverty, morbidity (particularly dementia, depression, and stroke), and disability were concentrated among those with DIC, although only 10% were frail, and a further 9% had needs for care. Hypertension and lifestyle risk factors for chronic disease, and healthcare utilisation and costs, were more evenly distributed in the population. In total, 15,901 participants were included in the mortality cohort (2,602 deaths/53,911 person-years of follow-up), and 12,939 participants in the dependence cohort (1,896 incident cases/38,320 person-years). One or more DICs strongly and independently predicted incident dependence (pooled adjusted subhazard ratio 1.91, 95% CI 1.69–2.17) and death (pooled adjusted hazard ratio 1.66, 95% CI 1.49–1.85). Relative risks were higher for those who were frail, but were also substantially elevated for the much larger sub-groups yet to become frail. Mortality was mainly concentrated in the frail and dependent sub-groups. The main limitations were potential for DIC exposure misclassification and attrition bias.

Conclusions

In this study we observed a high prevalence of DICs, particularly in older age groups. Those affected had substantially increased risks of dependence and death. Most needs for care arose in those with DIC yet to become frail. Our findings provide some support for the strategy of optimising intrinsic capacity in pursuit of healthy ageing. Implementation at scale requires community-based screening and assessment, and a stepped-care intervention approach, with redefined roles for community healthcare workers and efforts to engage, train, and support them in these tasks. ICOPE might be usefully integrated into community programmes for detecting and case managing chronic diseases including hypertension and diabetes.

Social Innovation For Health Research: Development of the SIFHR Checklist

Lu, 13/09/2021 - 15:00

by Eneyi E. Kpokiri, Elizabeth Chen, Jingjing Li, Sarah Payne, Priyanka Shrestha, Kaosar Afsana, Uche Amazigo, Phyllis Awor, Jean-Francois de Lavison, Saqif Khan, Jana Mier-Alpaño, Alberto Ong Jr, Shivani Subhedar, Isabelle Wachmuth, Luis Gabriel Cuervo, Kala M. Mehta, Beatrice Halpaap, Joseph D. Tucker

Background

Social innovations in health are inclusive solutions to address the healthcare delivery gap that meet the needs of end users through a multi-stakeholder, community-engaged process. While social innovations for health have shown promise in closing the healthcare delivery gap, more research is needed to evaluate, scale up, and sustain social innovation. Research checklists can standardize and improve reporting of research findings, promote transparency, and increase replicability of study results and findings.

Methods and findings

The research checklist was developed through a 3-step community-engaged process, including a global open call for ideas, a scoping review, and a 3-round modified Delphi process. The call for entries solicited checklists and related items and was open between November 27, 2019 and February 1, 2020. In addition to the open call submissions and scoping review findings, a 17-item Social Innovation For Health Research (SIFHR) Checklist was developed based on the Template for Intervention Description and Replication (TIDieR) Checklist. The checklist was then refined during 3 rounds of Delphi surveys conducted between May and June 2020. The resulting checklist will facilitate more complete and transparent reporting, increase end-user engagement, and help assess social innovation projects. A limitation of the open call was requiring internet access, which likely discouraged participation of some subgroups.

Conclusions

The SIFHR Checklist will strengthen the reporting of social innovation for health research studies. More research is needed on social innovation for health.

Correction: Associations of obesity and malnutrition with cardiac remodeling and cardiovascular outcomes in Asian adults: A cohort study

Lu, 13/09/2021 - 15:00

by Shih-Chieh Chien, Chanchal Chandramouli, Chi-In Lo, Chao-Feng Lin, Kuo-Tzu Sung, Wen-Hung Huang, Yau-Huei Lai, Chun-Ho Yun, Cheng Huang, Hung-I Yeh, Ta-Chuan Hung, Chung-Lieh Hung, Carolyn S. P. Lam

Achieving global equity for COVID-19 vaccines: Stronger international partnerships and greater advocacy and solidarity are needed

Lu, 13/09/2021 - 15:00

by J Peter Figueroa, Peter J. Hotez, Carolina Batista, Yanis Ben Amor, Onder Ergonul, Sarah Gilbert, Mayda Gursel, Mazen Hassanain, Gagandeep Kang, David C. Kaslow, Jerome H. Kim, Bhavna Lall, Heidi Larson, Denise Naniche, Timothy Sheahan, Shmuel Shoham, Annelies Wilder-Smith, Samba O. Sow, Nathalie Strub-Wourgaft, Prashant Yadav, Maria Elena Bottazzi

Peter Figueroa and co-authors advocate for equity in the worldwide provision of COVID-19 vaccines.