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Child morbidity and mortality associated with alternative policy responses to the economic crisis in Brazil: A nationwide microsimulation study

Ma, 22/05/2018 - 23:00

by Davide Rasella, Sanjay Basu, Thomas Hone, Romulo Paes-Sousa, Carlos Octávio Ocké-Reis, Christopher Millett

Background

Since 2015, a major economic crisis in Brazil has led to increasing poverty and the implementation of long-term fiscal austerity measures that will substantially reduce expenditure on social welfare programmes as a percentage of the country’s GDP over the next 20 years. The Bolsa Família Programme (BFP)—one of the largest conditional cash transfer programmes in the world—and the nationwide primary healthcare strategy (Estratégia Saúde da Família [ESF]) are affected by fiscal austerity, despite being among the policy interventions with the strongest estimated impact on child mortality in the country. We investigated how reduced coverage of the BFP and ESF—compared to an alternative scenario where the level of social protection under these programmes is maintained—may affect the under-five mortality rate (U5MR) and socioeconomic inequalities in child health in the country until 2030, the end date of the Sustainable Development Goals.

Methods and findings

We developed and validated a microsimulation model, creating a synthetic cohort of all 5,507 Brazilian municipalities for the period 2017–2030. This model was based on the longitudinal dataset and effect estimates from a previously published study that evaluated the effects of poverty, the BFP, and the ESF on child health. We forecast the economic crisis and the effect of reductions in BFP and ESF coverage due to current fiscal austerity on the U5MR, and compared this scenario with a scenario where these programmes maintain the levels of social protection by increasing or decreasing with the size of Brazil’s vulnerable populations (policy response scenarios). We used fixed effects multivariate regression models including BFP and ESF coverage and accounting for secular trends, demographic and socioeconomic changes, and programme duration effects. With the maintenance of the levels of social protection provided by the BFP and ESF, in the most likely economic crisis scenario the U5MR is expected to be 8.57% (95% CI: 6.88%–10.24%) lower in 2030 than under fiscal austerity—a cumulative 19,732 (95% CI: 10,207–29,285) averted under-five deaths between 2017 and 2030. U5MRs from diarrhoea, malnutrition, and lower respiratory tract infections are projected to be 39.3% (95% CI: 36.9%–41.8%), 35.8% (95% CI: 31.5%–39.9%), and 8.5% (95% CI: 4.1%–12.0%) lower, respectively, in 2030 under the maintenance of BFP and ESF coverage, with 123,549 fewer under-five hospitalisations from all causes over the study period. Reduced coverage of the BFP and ESF will also disproportionately affect U5MR in the most vulnerable areas, with the U5MR in the poorest quintile of municipalities expected to be 11.0% (95% CI: 8.0%–13.8%) lower in 2030 under the maintenance of BFP and ESF levels of social protection than under fiscal austerity, compared to no difference in the richest quintile. Declines in health inequalities over the last decade will also stop under a fiscal austerity scenario: the U5MR concentration index is expected to remain stable over the period 2017–2030, compared to a 13.3% (95% CI: 5.6%–21.8%) reduction under the maintenance of BFP and ESF levels of protection. Limitations of our analysis are the ecological nature of the study, uncertainty around future macroeconomic scenarios, and potential changes in other factors affecting child health. A wide range of sensitivity analyses were conducted to minimise these limitations.

Conclusions

The implementation of fiscal austerity measures in Brazil can be responsible for substantively higher childhood morbidity and mortality than expected under maintenance of social protection—threatening attainment of Sustainable Development Goals for child health and reducing inequality.

Clinical, socioeconomic, and behavioural factors at age 50 years and risk of cardiometabolic multimorbidity and mortality: A cohort study

Lu, 21/05/2018 - 23:00

by Archana Singh-Manoux, Aurore Fayosse, Séverine Sabia, Adam Tabak, Martin Shipley, Aline Dugravot, Mika Kivimäki

Background

Multimorbidity is increasingly common and is associated with adverse health outcomes, highlighting the need to broaden the single-disease framework that dominates medical research. We examined the role of midlife clinical characteristics, socioeconomic position, and behavioural factors in the development of cardiometabolic multimorbidity (at least 2 of diabetes, coronary heart disease, and stroke), along with how these factors modify risk of mortality.

Methods and findings

Data on 8,270 men and women were drawn from the Whitehall II cohort study, with mean follow-up of 23.7 years (1985 to 2017). Three sets of risk factors were assessed at age 50 years, each on a 5-point scale: clinical profile (hypertension, hypercholesterolemia, overweight/obesity, family history of cardiometabolic disease), occupational position, and behavioural factors (smoking, alcohol consumption, diet, physical activity). The outcomes examined were cardiometabolic disease (diabetes, coronary heart disease, stroke), cardiometabolic multimorbidity, and mortality. We used multi-state models to examine the role of risk factors in 5 components of the cardiometabolic disease trajectory: from healthy state to first cardiometabolic disease, from first cardiometabolic disease to cardiometabolic multimorbidity, from healthy state to death, from first cardiometabolic disease to death, and from cardiometabolic multimorbidity to death. A total of 2,501 participants developed 1 of the 3 cardiometabolic diseases, 511 developed cardiometabolic multimorbidity, and 1,406 died. When behavioural and clinical risk factors were considered individually, only smoking was associated with all five transitions. In a model containing all 3 risk factor scales, midlife clinical profile was the strongest predictor of first cardiometabolic disease (hazard ratio for the least versus most favourable profile: 3.74; 95% CI: 3.14–4.45) among disease-free participants. Among participants with 1 cardiometabolic disease, adverse midlife socioeconomic (1.54; 95% CI: 1.10–2.15) and behavioural factors (2.00; 95% CI: 1.40–2.85), but not clinical characteristics, were associated with progression to cardiometabolic multimorbidity. Only midlife behavioural factors predicted mortality among participants with cardiometabolic disease (2.12; 95% CI: 1.41–3.18) or cardiometabolic multimorbidity (3.47; 95% CI: 1.81–6.66). A limitation is that the study was not large enough to estimate transitions between each disease and subsequent outcomes and between all possible pairs of diseases.

Conclusions

The importance of specific midlife factors in disease progression, from disease-free state to single disease, multimorbidity, and death, varies depending on the disease stage. While clinical risk factors at age 50 determine the risk of incident cardiometabolic disease in a disease-free population, midlife socioeconomic and behavioural factors are stronger predictors of progression to multimorbidity and mortality in people with cardiometabolic disease.

Ibuprofen versus pivmecillinam for uncomplicated urinary tract infection in women—A double-blind, randomized non-inferiority trial

Ma, 15/05/2018 - 23:00

by Ingvild Vik, Marianne Bollestad, Nils Grude, Anders Bærheim, Eivind Damsgaard, Thomas Neumark, Lars Bjerrum, Gloria Cordoba, Inge Christoffer Olsen, Morten Lindbæk

Background

Although uncomplicated urinary tract infections (UTIs) are often self-limiting, most patients will be prescribed antibiotic treatment. We assessed whether treatment with ibuprofen was non-inferior to pivmecillinam in achieving symptomatic resolution by day 4, with a non-inferiority margin of 10%.

Methods and findings

This was a randomized, controlled, double-blind non-inferiority trial. We recruited patients from 16 sites in a general practice setting in Norway, Sweden, and Denmark. Non-pregnant women aged 18–60 years presenting with symptoms of uncomplicated UTI were screened for eligibility from 11 April 2013 to 22 April 2016. Patients with informed consent were randomized (1:1 ratio) to treatment with either 600 mg ibuprofen or 200 mg pivmecillinam 3 times a day for 3 days. The patient, treating physician, and study personnel were blinded to treatment allocation. The primary outcome was the proportion of patients who felt cured by day 4, as assessed from a patient diary. Secondary outcomes included the proportion of patients in need of secondary treatment with antibiotics and cases of pyelonephritis. A total of 383 women were randomly assigned to treatment with either ibuprofen (n = 194, 181 analyzed) or pivmecillinam (n = 189, 178 analyzed). By day 4, 38.7% of the patients in the ibuprofen group felt cured versus 73.6% in the pivmecillinam group. The adjusted risk difference with 90% confidence interval was 35% (27% to 43%) in favor of pivmecillinam, which crossed the prespecified non-inferiority margin. Secondary endpoints were generally in favor of pivmecillinam. After 4 weeks’ follow-up, 53% of patients in the ibuprofen group recovered without antibiotic treatment. Seven cases of pyelonephritis occurred, all in the ibuprofen group, giving a number needed to harm of 26 (95% CI 13 to 103). Five of these patients were hospitalized and classified as having serious adverse events; 2 recovered as outpatients. A limitation of the study was the extensive list of exclusion criteria, eliminating almost half of the patients screened. We did not register symptoms in the screening process; hence, we do not know the symptom burden for those who declined to participate. This might make our results less generalizable.

Conclusions

Ibuprofen was inferior to pivmecillinam for treating uncomplicated UTIs. More than half of the women in the ibuprofen group recovered without antibiotics. However, pyelonephritis occurred in 7 out of 181 women using ibuprofen. Until we can identify those women who will develop complications, we cannot recommend ibuprofen alone as initial treatment to women with uncomplicated UTIs.

Trial registration

ClinicalTrials.gov NCT01849926EU Clinical Trials Register (EU-CTR), EudraCT Number 2012-002776-14

Injury and death during the ISIS occupation of Mosul and its liberation: Results from a 40-cluster household survey

Ma, 15/05/2018 - 23:00

by Riyadh Lafta, Maha A. Al-Nuaimi, Gilbert Burnham

Background

Measurement of mortality and injury in conflict situations presents many challenges compared with stable situations. However, providing information is important to assess the impact of conflict on populations and to estimate humanitarian needs, both in the immediate and longer term. Mosul, Iraq’s second largest city, was overrun by fighters of the Islamic State of Iraq and Syria (ISIS) on June 4, 2014. In this study, we conducted household surveys to measure reported deaths, injuries, and kidnappings in Mosul, Iraq, both during the occupation of the city by fighters of ISIS and the months of Iraqi military action known as the liberation.

Methods and findings

Mosul was overrun by ISIS forces on June 4, 2014, and was under exclusive ISIS control for 29 months. The military offensive by Iraqi forces, supported by coalition artillery and airstrikes, began on October 17, 2016, in east Mosul and concluded in west Mosul with the defeat of ISIS on June 29, 2017. We conducted a 40-cluster population-based survey as soon as the security forces permitted access for the survey team. The objective of the survey was to measure reported deaths, injuries, and kidnappings in Mosul households during 29 months of ISIS-exclusive control (June 2014–October 2016) and the nine months of Iraqi military action known as the liberation (October 2016–June 2017). In east Mosul, the survey was conducted from March 23 to March 31, 2017, and in west Mosul from July 18 to July 31, 2017. Sampling was based on pre-ISIS population distribution, with revisions made following the extensive destruction in west Mosul. The 1,202 sampled households included 7,559 persons: 4,867 in east Mosul and 2,692 in west Mosul. No households declined to participate. During the time from June 4, 2014, to the time of the survey, there were 628 deaths reported from the sampled households, of which 505 were due to intentional violence, a mortality rate of 2.09 deaths per 1,000 person-months. Over the entire time period, the group with the highest mortality rates from intentional violence was adults aged 20 to 39: 1.69 deaths per 1,000 person-months among women and 3.55 among men. In the 29 months of ISIS-exclusive control, mortality rates among all males were 0.71 reported deaths per 1,000 person-months and for all females were 0.50 deaths per 1,000 person-months. During the nine months of the military liberation, the mortality rates jumped to 13.36 deaths per 1,000 person-months for males and 8.33 for females. The increase was particularly dramatic in west Mosul. The leading cause of reported deaths from intentional violence was airstrikes—accounting for 201 civilian deaths—followed by 172 deaths from explosions. Reported deaths from airstrikes were most common in west Mosul, while reported deaths from explosions were similar on both sides of Mosul. Gunshots accounted for 86 cases, predominantly in west Mosul where ISIS snipers were particularly active. There were 35 persons who were reported to have been kidnapped, almost entirely prior to the military offensive. By the time of the survey, 20 had been released, 8 were dead, and 7 still missing, according to household reports. Almost all of the 223 injuries reported were due to intentional violence. Limitations to population-based surveys include a probable large survivor bias, the reliance on preconflict population distribution figures for sampling, and potential recall bias among respondents.

Conclusions

Death and injuries during the military offensive to liberate Mosul considerably exceeded those during ISIS occupation. Airstrikes were the major reported cause of deaths, with the majority occurring in west Mosul. The extensive use of airstrikes and heavy artillery risks an extensive loss of life in densely populated urban areas. The high probability of survivor bias in this survey suggests that the actual number of injuries, kidnappings, and deaths in the neighborhoods sampled is likely to be higher than we report here.

Distributional change of women’s adult height in low- and middle-income countries over the past half century: An observational study using cross-sectional survey data

Ve, 11/05/2018 - 23:00

by Jewel Gausman, Ivan Meija Guevara, S. V. Subramanian, Fahad Razak

Background

Adult height reflects childhood circumstances and is associated with health, longevity, and maternal–fetal outcomes. Mean height is an important population metric, and declines in height have occurred in several low- and middle-income countries, especially in Africa, over the last several decades. This study examines changes at the population level in the distribution of height over time across a broad range of low- and middle-income countries during the past half century.

Methods and findings

The study population comprised 1,122,845 women aged 25–49 years from 59 countries with women’s height measures available from four 10-year birth cohorts from 1950 to 1989 using data from the Demographic and Health Surveys (DHS) collected between 1993 and 2013. Multilevel regression models were used to examine the association between (1) mean height and standard deviation (SD) of height (a population-level measure of inequality) and (2) median height and the 5th and 95th percentiles of height. Mean-difference plots were used to conduct a graphical analysis of shifts in the distribution within countries over time. Overall, 26 countries experienced a significant increase, 26 experienced no significant change, and 7 experienced a significant decline in mean height between the first and last birth cohorts. Rwanda experienced the greatest loss in height (−1.4 cm, 95% CI: −1.84 cm, −0.96 cm) while Colombia experienced the greatest gain in height (2.6 cm, 95% CI: 2.36 cm, 2.84 cm). Between 1950 and 1989, 24 out of 59 countries experienced a significant change in the SD of women’s height, with increased SD in 7 countries—all of which are located in sub-Saharan Africa. The distribution of women’s height has not stayed constant across successive birth cohorts, and regression models suggest there is no evidence of a significant relationship between mean height and the SD of height (β = 0.015 cm, 95% CI: −0.032 cm, 0.061 cm), while there is evidence for a positive association between median height and the 5th percentile (β = 0.915 cm, 95% CI: 0.820 cm, 1.002 cm) and 95th percentile (β = 0.995 cm, 95% CI: 0.925 cm, 1.066 cm) of height. Benin experienced the largest relative expansion in the distribution of height. In Benin, the ratio of variance between the latest and earliest cohort is estimated as 1.5 (95% CI: 1.4, 1.6), while Lesotho and Uganda experienced the greatest relative contraction of the distribution, with the ratio of variance between the latest and earliest cohort estimated as 0.8 (95% CI: 0.7, 0.9) in both countries. Limitations of the study include the representativeness of DHS surveys over time, age-related height loss, and consistency in the measurement of height between surveys.

Conclusions

The findings of this study indicate that the population-level distribution of women’s height does not stay constant in relation to mean changes. Because using mean height as a summary population measure does not capture broader distributional changes, overreliance on the mean may lead investigators to underestimate disparities in the distribution of environmental and nutritional determinants of health.

The next forum for unraveling FDA off-label marketing rules: State and federal legislatures

Ma, 08/05/2018 - 23:00

by Michael S. Sinha, Aaron S. Kesselheim

In a Guest Editorial, Aaron S. Kesselheim and Michael S. Sinha show how federal and state legislation to allow promotion of drugs for non-approved uses threatens to undermine the FDA's public health mission.

Access to antiretroviral therapy in HIV-infected children aged 0–19 years in the International Epidemiology Databases to Evaluate AIDS (IeDEA) Global Cohort Consortium, 2004–2015: A prospective cohort study

Ve, 04/05/2018 - 23:00

by Sophie Desmonde, Franck Tanser, Rachel Vreeman, Elom Takassi, Andrew Edmonds, Pagakrong Lumbiganon, Jorge Pinto, Karen Malateste, Catherine McGowan, Azar Kariminia, Marcel Yotebieng, Fatoumata Dicko, Constantin Yiannoutsos, Mwangelwa Mubiana-Mbewe, Kara Wools-Kaloustian, Mary-Ann Davies, Valériane Leroy, for the International Epidemiology Databases to Evaluate AIDS (IeDEA) Pediatric Working Group

Introduction

Access to antiretroviral therapy (ART) is a global priority. However, the attrition across the continuum of care for HIV-infected children between their HIV diagnosis and ART initiation is not well known. We analyzed the time from enrollment into HIV care to ART initiation in HIV-infected children within the International Epidemiology Databases to Evaluate AIDS (IeDEA) Global Cohort Consortium.

Methods and findings

We included 135,479 HIV-1-infected children, aged 0–19 years and ART-naïve at enrollment, between 1 January 2004 and 31 December 2015, in IeDEA cohorts from Central Africa (3 countries; n = 4,948), East Africa (3 countries; n = 22,827), West Africa (7 countries; n = 7,372), Southern Africa (6 countries; n = 93,799), Asia-Pacific (6 countries; n = 4,045), and Latin America (7 countries; n = 2,488). Follow-up in these cohorts is typically every 3–6 months. We described time to ART initiation and missed opportunities (death or loss to follow-up [LTFU]: last clinical visit >6 months) since baseline (the date of HIV diagnosis or, if unavailable, date of enrollment). Cumulative incidence functions (CIFs) for and determinants of ART initiation were computed, with death and LTFU as competing risks. Among the 135,479 children included, 99,404 (73.4%) initiated ART, 1.9% died, 1.4% were transferred out, and 20.4% were lost to follow-up before ART initiation. The 24-month CIF for ART initiation was 68.2% (95% CI: 67.9%–68.4%); it was lower in sub-Saharan Africa—ranging from 49.8% (95% CI: 48.4%–51.2%) in Central Africa to 72.5% (95% CI: 71.5%–73.5%) in West Africa—compared to Latin America (71.0%, 95% CI: 69.1%–72.7%) and the Asia-Pacific (78.3%, 95% CI: 76.9%–79.6%). Adolescents aged 15–19 years and infants <1 year had the lowest cumulative incidence of ART initiation compared to other ages: 62.2% (95% CI: 61.6%–62.8%) and 66.4% (95% CI: 65.7%–67.0%), respectively. Overall, 49.1% were ART-eligible per local guidelines at baseline, of whom 80.6% initiated ART. The following children had lower cumulative incidence of ART initiation: female children (p < 0.01); those aged <1 year, 2–4 years, 5–9 years, and 15–19 years (versus those aged 10–14 years, p < 0.01); those who became eligible during follow-up (versus eligible at enrollment, p < 0.01); and those receiving care in low-income or lower-middle-income countries (p < 0.01). The main limitations of our study include left truncation and survivor bias, caused by deaths of children prior to enrollment, and use of enrollment date as a proxy for missing data on date of HIV diagnosis, which could have led to underestimation of the time between HIV diagnosis and ART initiation.

Conclusions

In this study, 68% of HIV-infected children initiated ART by 24 months. However, there was a substantial risk of LTFU before ART initiation, which may also represent undocumented mortality. In 2015, many obstacles to ART initiation remained, with substantial inequities. More effective and targeted interventions to improve access are needed to reach the target of treating 90% of HIV-infected children with ART.

All science should inform policy and regulation

Gi, 03/05/2018 - 23:00

by John P. A. Ioannidis

In the context of a recent proposal to exclude research from consideration at the Environmental Protection Agency, John Ioannidis points out that “perceived perfection is not a characteristic of science, but of dogma” and envisions how governments can promote a standard of openness in science.

Association of vitamin D with risk of type 2 diabetes: A Mendelian randomisation study in European and Chinese adults

Me, 02/05/2018 - 23:00

by Ling Lu, Derrick A. Bennett, Iona Y. Millwood, Sarah Parish, Mark I. McCarthy, Anubha Mahajan, Xu Lin, Fiona Bragg, Yu Guo, Michael V. Holmes, Shoaib Afzal, Børge G. Nordestgaard, Zheng Bian, Michael Hill, Robin G. Walters, Liming Li, Zhengming Chen, Robert Clarke

Background

Observational studies have reported that higher plasma 25-hydroxyvitamin D (25[OH]D) concentrations are associated with lower risks of diabetes, but it is unclear if these associations are causal. The aim of this study was to test the relevance of 25(OH)D for type 2 diabetes using genetically instrumented differences in plasma 25(OH)D concentrations.

Methods and findings

Data were available on four 25(OH)D single nucleotide polymorphisms (SNPs; n = 82,464), plasma 25(OH)D concentrations (n = 13,565), and cases with diabetes (n = 5,565) in the China Kadoorie Biobank (CKB). The effects on risk of diabetes were assessed by a genetic score using two 25(OH)D synthesis SNPs (DHCR7-rs12785878 and CYP2R1-rs10741657), with and without the addition of SNPs affecting the transport (GC/DBP-rs2282679) and catabolism (CYP24A1-rs6013897) of 25(OH)D. The CKB results were combined in a meta-analysis of 10 studies for the 2 synthesis SNPs (n = 58,312 cases) and 7 studies for all 4 SNPs (n = 32,796 cases). Mean (SD) 25(OH)D concentration was 62 (20) nmol/l in CKB, and the per allele effects of genetic scores on 25(OH)D were 2.87 (SE 0.39) for the synthesis SNPs and 3.54 (SE 0.32) for all SNPs. A 25-nmol/l higher biochemically measured 25(OH)D was associated with a 9% (95% CI: 0%–18%) lower risk of diabetes in CKB. In a meta-analysis of all studies, a 25-nmol/l higher genetically instrumented 25(OH)D concentration was associated with a 14% (95% CI: 3%–23%) lower risk of diabetes (p = 0.01) using the 2 synthesis SNPs. An equivalent difference in 25(OH)D using a genetic score with 4 SNPs was not significantly associated with diabetes (odds ratio 8%, 95% CI: −1% to 16%, lower risk, p = 0.07), but had some evidence of pleiotropy. A limitation of the meta-analysis was the access only to study level rather than individual level data.

Conclusions

The concordant risks of diabetes for biochemically measured and genetically instrumented differences in 25(OH)D using synthesis SNPs provide evidence for a causal effect of higher 25(OH)D for prevention of diabetes.

Public versus internal conceptions of addiction: An analysis of internal Philip Morris documents

Ma, 01/05/2018 - 23:00

by Jesse Elias, Yogi Hale Hendlin, Pamela M. Ling

Background

Tobacco addiction is a complex, multicomponent phenomenon stemming from nicotine’s pharmacology and the user’s biology, psychology, sociology, and environment. After decades of public denial, the tobacco industry now agrees with public health authorities that nicotine is addictive. In 2000, Philip Morris became the first major tobacco company to admit nicotine’s addictiveness. Evolving definitions of addiction have historically affected subsequent policymaking. This article examines how Philip Morris internally conceptualized addiction immediately before and after this announcement.

Methods and findings

We analyzed previously secret, internal Philip Morris documents made available as a result of litigation against the tobacco industry. We compared these documents to public company statements and found that Philip Morris’s move from public denial to public affirmation of nicotine’s addictiveness coincided with pressure on the industry from poor public approval ratings, the Master Settlement Agreement (MSA), the United States government’s filing of the Racketeer Influenced and Corrupt Organizations (RICO) suit, and the Institute of Medicine’s (IoM’s) endorsement of potentially reduced risk products. Philip Morris continued to research the causes of addiction through the 2000s in order to create successful potentially reduced exposure products (PREPs). While Philip Morris’s public statements reinforce the idea that nicotine’s pharmacology principally drives smoking addiction, company scientists framed addiction as the result of interconnected biological, social, psychological, and environmental determinants, with nicotine as but one component. Due to the fragmentary nature of the industry document database, we may have missed relevant information that could have affected our analysis.

Conclusions

Philip Morris’s research suggests that tobacco industry activity influences addiction treatment outcomes. Beyond nicotine’s pharmacology, the industry’s continued aggressive advertising, lobbying, and litigation against effective tobacco control policies promotes various nonpharmacological determinants of addiction. To help tobacco users quit, policy makers should increase attention on the social and environmental dimensions of addiction alongside traditional cessation efforts.

Health insurance coverage with or without a nurse-led task shifting strategy for hypertension control: A pragmatic cluster randomized trial in Ghana

Ma, 01/05/2018 - 23:00

by Gbenga Ogedegbe, Jacob Plange-Rhule, Joyce Gyamfi, William Chaplin, Michael Ntim, Kingsley Apusiga, Juliet Iwelunmor, Kwasi Yeboah Awudzi, Kofi Nana Quakyi, Jazmin Mogaverro, Kiran Khurshid, Bamidele Tayo, Richard Cooper

Background

Poor access to care and physician shortage are major barriers to hypertension control in sub-Saharan Africa. Implementation of evidence-based systems-level strategies targeted at these barriers are lacking. We conducted a study to evaluate the comparative effectiveness of provision of health insurance coverage (HIC) alone versus a nurse-led task shifting strategy for hypertension control (TASSH) plus HIC on systolic blood pressure (SBP) reduction among patients with uncontrolled hypertension in Ghana.

Methods and findings

Using a pragmatic cluster randomized trial, 32 community health centers within Ghana’s public healthcare system were randomly assigned to either HIC alone or TASSH + HIC. A total of 757 patients with uncontrolled hypertension were recruited between November 28, 2012, and June 11, 2014, and followed up to October 7, 2016. Both intervention groups received health insurance coverage plus scheduled nurse visits, while TASSH + HIC comprised cardiovascular risk assessment, lifestyle counseling, and initiation/titration of antihypertensive medications for 12 months, delivered by trained nurses within the healthcare system. The primary outcome was change in SBP from baseline to 12 months. Secondary outcomes included lifestyle behaviors and blood pressure control at 12 months and sustainability of SBP reduction at 24 months. Of the 757 patients (389 in the HIC group and 368 in the TASSH + HIC group), 85% had 12-month data available (60% women, mean BP 155.9/89.6 mm Hg). In intention-to-treat analyses adjusted for clustering, the TASSH + HIC group had a greater SBP reduction (−20.4 mm Hg; 95% CI −25.2 to −15.6) than the HIC group (−16.8 mm Hg; 95% CI −19.2 to −15.6), with a statistically significant between-group difference of −3.6 mm Hg (95% CI −6.1 to −0.5; p = 0.021). Blood pressure control improved significantly in both groups (55.2%, 95% CI 50.0% to 60.3%, for the TASSH + HIC group versus 49.9%, 95% CI 44.9% to 54.9%, for the HIC group), with a non-significant between-group difference of 5.2% (95% CI −1.8% to 12.4%; p = 0.29). Lifestyle behaviors did not change appreciably in either group. Twenty-one adverse events were reported (9 and 12 in the TASSH + HIC and HIC groups, respectively). The main study limitation is the lack of cost-effectiveness analysis to determine the additional costs and benefits, if any, of the TASSH + HIC group.

Conclusions

Provision of health insurance coverage plus a nurse-led task shifting strategy was associated with a greater reduction in SBP than provision of health insurance coverage alone, among patients with uncontrolled hypertension in Ghana. Future scale-up of these systems-level strategies for hypertension control in sub-Saharan Africa requires a cost–benefit analysis.

Trial registration

ClinicalTrials.gov NCT01802372

Attacks on medical workers in Syria: Implications for conflict research

Ma, 24/04/2018 - 23:00

by Michael Spagat

In a Perspective linked to the Research Article by Haar and colleagues, Michael Spagat discusses the challenges and importance of conducting research on mortality in regions affected by violent conflicts.

Determining the scope of attacks on health in four governorates of Syria in 2016: Results of a field surveillance program

Ma, 24/04/2018 - 23:00

by Rohini J. Haar, Casey B. Risko, Sonal Singh, Diana Rayes, Ahmad Albaik, Mohammed Alnajar, Mazen Kewara, Emily Clouse, Elise Baker, Leonard S. Rubenstein

Background

Violent attacks on and interferences with hospitals, ambulances, health workers, and patients during conflict destroy vital health services during a time when they are most needed and undermine the long-term capacity of the health system. In Syria, such attacks have been frequent and intense and represent grave violations of the Geneva Conventions, but the number reported has varied considerably. A systematic mechanism to document these attacks could assist in designing more protection strategies and play a critical role in influencing policy, promoting justice, and addressing the health needs of the population.

Methods and findings

We developed a mobile data collection questionnaire to collect data on incidents of attacks on healthcare directly from the field. Data collectors from the Syrian American Medical Society (SAMS), using the tool or a text messaging system, recorded information on incidents across four of Syria’s northern governorates (Aleppo, Idleb, Hama, and Homs) from January 1, 2016, to December 31, 2016. SAMS recorded a total of 200 attacks on healthcare in 2016, 102 of them using the mobile data collection tool. Direct attacks on health facilities comprised the majority of attacks recorded (88.0%; n = 176). One hundred and twelve healthcare staff and 185 patients were killed in these incidents. Thirty-five percent of the facilities were attacked more than once over the data collection period; hospitals were significantly more likely to be attacked more than once compared to clinics and other types of healthcare facilities. Aerial bombs were used in the overwhelming majority of cases (91.5%). We also compared the SAMS data to a separate database developed by Physicians for Human Rights (PHR) based on media reports and matched the incidents to compare the results from the two methods (this analysis was limited to incidents at health facilities). Among 90 relevant incidents verified by PHR and 177 by SAMS, there were 60 that could be matched to each other, highlighting the differences in results from the two methods. This study is limited by the complexities of data collection in a conflict setting, only partial use of the standardized reporting tool, and the fact that limited accessibility of some health facilities and workers and may be biased towards the reporting of attacks on larger or more visible health facilities.

Conclusions

The use of field data collectors and use of consistent definitions can play an important role in the tracking incidents of attacks on health services. A mobile systematic data collection tool can complement other methods for tracking incidents of attacks on healthcare and ensure the collection of detailed information about each attack that may assist in better advocacy, programs, and accountability but can be practically challenging. Comparing attacks between SAMS and PHR suggests that there may have been significantly more attacks than previously captured by any one methodology. This scale of attacks suggests that targeting of healthcare in Syria is systematic and highlights the failure of condemnation by the international community and medical groups working in Syria of such attacks to stop them.

Maternal age and offspring developmental vulnerability at age five: A population-based cohort study of Australian children

Ma, 24/04/2018 - 23:00

by Kathleen Falster, Mark Hanly, Emily Banks, John Lynch, Georgina Chambers, Marni Brownell, Sandra Eades, Louisa Jorm

Background

In recent decades, there has been a shift to later childbearing in high-income countries. There is limited large-scale evidence of the relationship between maternal age and child outcomes beyond the perinatal period. The objective of this study is to quantify a child’s risk of developmental vulnerability at age five, according to their mother’s age at childbirth.

Methods and findings

Linkage of population-level perinatal, hospital, and birth registration datasets to data from the Australian Early Development Census (AEDC) and school enrolments in Australia’s most populous state, New South Wales (NSW), enabled us to follow a cohort of 99,530 children from birth to their first year of school in 2009 or 2012. The study outcome was teacher-reported child development on five domains measured by the AEDC, including physical health and well-being, emotional maturity, social competence, language and cognitive skills, and communication skills and general knowledge. Developmental vulnerability was defined as domain scores below the 2009 AEDC 10th percentile cut point.The mean maternal age at childbirth was 29.6 years (standard deviation [SD], 5.7), with 4,382 children (4.4%) born to mothers aged <20 years and 20,026 children (20.1%) born to mothers aged ≥35 years. The proportion vulnerable on ≥1 domains was 21% overall and followed a reverse J-shaped distribution according to maternal age: it was highest in children born to mothers aged ≤15 years, at 40% (95% CI, 32–49), and was lowest in children born to mothers aged between 30 years and ≤35 years, at 17%–18%. For maternal ages 36 years to ≥45 years, the proportion vulnerable on ≥1 domains increased to 17%–24%. Adjustment for sociodemographic characteristics significantly attenuated vulnerability risk in children born to younger mothers, while adjustment for potentially modifiable factors, such as antenatal visits, had little additional impact across all ages. Although the multi-agency linkage yielded a broad range of sociodemographic, perinatal, health, and developmental variables at the child’s birth and school entry, the study was necessarily limited to variables available in the source data, which were mostly recorded for administrative purposes.

Conclusions

Increasing maternal age was associated with a lesser risk of developmental vulnerability for children born to mothers aged 15 years to about 30 years. In contrast, increasing maternal age beyond 35 years was generally associated with increasing vulnerability, broadly equivalent to the risk for children born to mothers in their early twenties, which is highly relevant in the international context of later childbearing. That socioeconomic disadvantage explained approximately half of the increased risk of developmental vulnerability associated with younger motherhood suggests there may be scope to improve population-level child development through policies and programs that support disadvantaged mothers and children.

From surviving to thriving: What evidence is needed to move early child-development interventions to scale?

Ma, 24/04/2018 - 23:00

by Mark Tomlinson

In a Perspective, Mark Tomlinson discusses research on early interventions to support child development in developing countries.

Impacts 2 years after a scalable early childhood development intervention to increase psychosocial stimulation in the home: A follow-up of a cluster randomised controlled trial in Colombia

Ma, 24/04/2018 - 23:00

by Alison Andrew, Orazio Attanasio, Emla Fitzsimons, Sally Grantham-McGregor, Costas Meghir, Marta Rubio-Codina

Background

Poor early childhood development (ECD) in low- and middle-income countries is a major concern. There are calls to universalise access to ECD interventions through integrating them into existing government services but little evidence on the medium- or long-term effects of such scalable models. We previously showed that a psychosocial stimulation (PS) intervention integrated into a cash transfer programme improved Colombian children’s cognition, receptive language, and home stimulation. In this follow-up study, we assessed the medium-term impacts of the intervention, 2 years after it ended, on children’s cognition, language, school readiness, executive function, and behaviour.

Methods and findings

Study participants were 1,419 children aged 12–24 months at baseline from beneficiary households of the cash transfer programme, living in 96 Colombian towns. The original cluster randomised controlled trial (2009–2011) randomly allocated the towns to control (N = 24, n = 349), PS (N = 24, n = 357), multiple micronutrient (MN) supplementation (N = 24, n = 354), and combined PS and MN (N = 24, n = 359). Interventions lasted 18 months. In this study (26 September 2013 to 11 January 2014), we assessed impacts on cognition, language, school readiness, executive function, and behaviour 2 years after intervention, at ages 4.5–5.5 years. Testers, but not participants, were blinded to treatment allocation. Analysis was on an intent-to-treat basis. We reassessed 88.5% of the children in the original study (n = 1,256). Factor analysis of test scores yielded 2 factors: cognitive (cognition, language, school readiness, executive function) and behavioural. We found no effect of the interventions after 2 years on the cognitive factor (PS: −0.031 SD, 95% CI −0.229–0.167; MN: −0.042 SD, 95% CI −0.249–0.164; PS and MN: −0.111 SD, 95% CI −0.311–0.089), the behavioural factor (PS: 0.013 SD, 95% CI −0.172–0.198; MN: 0.071 SD, 95% CI −0.115–0.258; PS and MN: 0.062 SD, 95% CI −0.115–0.239), or home stimulation. Study limitations include that behavioural development was measured through maternal report and that very small effects may have been missed, despite the large sample size.

Conclusions

We found no evidence that a scalable PS intervention benefited children’s development 2 years after it ended. It is possible that the initial effects on child development were too small to be sustained or that the lack of continued impact on home stimulation contributed to fade out. Both are likely related to compromises in implementation when going to scale and suggest one should not extrapolate from medium-term effects of small efficacy trials to scalable interventions. Understanding the salient differences between small efficacy trials and scaled-up versions will be key to making ECD interventions effective tools for policymakers.

Trial registration

ISRCTN18991160

Two-year impact of community-based health screening and parenting groups on child development in Zambia: Follow-up to a cluster-randomized controlled trial

Ma, 24/04/2018 - 23:00

by Peter C. Rockers, Arianna Zanolini, Bowen Banda, Mwaba Moono Chipili, Robert C. Hughes, Davidson H. Hamer, Günther Fink

Background

Early childhood interventions have potential to offset the negative impact of early adversity. We evaluated the impact of a community-based parenting group intervention on child development in Zambia.

Methods and findings

We conducted a non-masked cluster-randomized controlled trial in Southern Province, Zambia. Thirty clusters of villages were matched based on population density and distance from the nearest health center, and randomly assigned to intervention (15 clusters, 268 caregiver–child dyads) or control (15 clusters, 258 caregiver–child dyads). Caregivers were eligible if they had a child 6 to 12 months old at baseline. In intervention clusters, caregivers were visited twice per month during the first year of the study by child development agents (CDAs) and were invited to attend fortnightly parenting group meetings. Parenting groups selected “head mothers” from their communities who were trained by CDAs to facilitate meetings and deliver a diverse parenting curriculum. The parenting group intervention, originally designed to run for 1 year, was extended, and households were visited for a follow-up assessment at the end of year 2. The control group did not receive any intervention. Intention-to-treat analysis was performed for primary outcomes measured at the year 2 follow-up: stunting and 5 domains of neurocognitive development measured using the Bayley Scales of Infant and Toddler Development–Third Edition (BSID-III). In order to show Cohen’s d estimates, BSID-III composite scores were converted to z-scores by standardizing within the study population. In all, 195/268 children (73%) in the intervention group and 182/258 children (71%) in the control group were assessed at endline after 2 years. The intervention significantly reduced stunting (56/195 versus 72/182; adjusted odds ratio 0.45, 95% CI 0.22 to 0.92; p = 0.028) and had a significant positive impact on language (β 0.14, 95% CI 0.01 to 0.27; p = 0.039). The intervention did not significantly impact cognition (β 0.11, 95% CI −0.06 to 0.29; p = 0.196), motor skills (β −0.01, 95% CI −0.25 to 0.24; p = 0.964), adaptive behavior (β 0.21, 95% CI −0.03 to 0.44; p = 0.088), or social-emotional development (β 0.20, 95% CI −0.04 to 0.44; p = 0.098). Observed impacts may have been due in part to home visits by CDAs during the first year of the intervention.

Conclusions

The results of this trial suggest that parenting groups hold promise for improving child development, particularly physical growth, in low-resource settings like Zambia.

Trial registration

ClinicalTrials.gov NCT02234726

Breastfeeding during infancy and neurocognitive function in adolescence: 16-year follow-up of the PROBIT cluster-randomized trial

Ve, 20/04/2018 - 23:00

by Seungmi Yang, Richard M. Martin, Emily Oken, Mikhail Hameza, Glen Doniger, Shimon Amit, Rita Patel, Jennifer Thompson, Sheryl L. Rifas-Shiman, Konstantin Vilchuck, Natalia Bogdanovich, Michael S. Kramer

Background

Evidence on the long-term effect of breastfeeding on neurocognitive development is based almost exclusively on observational studies. In the 16-year follow-up study of a large, cluster-randomized trial of a breastfeeding promotion intervention, we evaluated the long-term persistence of the neurocognitive benefits of the breastfeeding promotion intervention previously observed at early school age.

Methods and findings

A total of 13,557 participants (79.5% of the 17,046 randomized) of the Promotion of Breastfeeding Intervention Trial (PROBIT) were followed up at age 16 from September 2012 to July 2015. At the follow-up, neurocognitive function was assessed in 7 verbal and nonverbal cognitive domains using a computerized, self-administered test battery among 13,427 participants. Using an intention-to-treat (ITT) analysis as our prespecified primary analysis, we estimated cluster- and baseline characteristic-adjusted mean differences between the intervention (prolonged and exclusive breastfeeding promotion modelled on the Baby-Friendly Hospital Initiative) and control (usual care) groups in 7 cognitive domains and a global cognitive score. In our prespecified secondary analysis, we estimated mean differences by instrumental variable (IV) analysis to account for noncompliance with the randomly assigned intervention and estimate causal effects of breastfeeding. The 16-year follow-up rates were similar in the intervention (79.7%) and control groups (79.3%), and baseline characteristics were comparable between the two. In the cluster-adjusted ITT analyses, children in the intervention group did not show statistically significant differences in the scores from children in the control group. Prespecified additional adjustment for baseline characteristics improved statistical precision and resulted in slightly higher scores among children in the intervention for verbal function (1.4 [95% CI 0.3–2.5]) and memory (1.2 [95% CI 0.01–2.4]). IV analysis showed that children who were exclusively breastfed for ≥3 (versus <3) months had a 3.5-point (95% CI 0.9–6.1) higher verbal function, but no differences were observed in other domains. While our computerized, self-administered cognitive testing reduced the cluster-level variability in the scores, it may have increased individual-level measurement errors in adolescents.

Conclusions

We observed no benefit of a breastfeeding promotion intervention on overall neurocognitive function. The only beneficial effect was on verbal function at age 16. The higher verbal ability is consistent with results observed at early school age; however, the effect size was substantially smaller in adolescence.

PROBIT trial registration

ClinicalTrials.gov NCT01561612

Universal versus conditional day 3 follow-up for children with non-severe unclassified fever at the community level in Ethiopia: A cluster-randomised non-inferiority trial

Ma, 17/04/2018 - 23:00

by Karin Källander, Tobias Alfvén, Tjede Funk, Ayalkibet Abebe, Abreham Hailemariam, Dawit Getachew, Max Petzold, Laura C. Steinhardt, Julie R. Gutman

Background

With declining malaria prevalence and improved use of malaria diagnostic tests, an increasing proportion of children seen by community health workers (CHWs) have unclassified fever. Current community management guidelines by WHO advise that children seen with non-severe unclassified fever (on day 1) should return to CHWs on day 3 for reassessment. We compared the safety of conditional follow-up reassessment only in cases where symptoms do not resolve with universal follow-up on day 3.

Methods and findings

We undertook a 2-arm cluster-randomised controlled non-inferiority trial among children aged 2–59 months presenting with fever and without malaria, pneumonia, diarrhoea, or danger signs to 284 CHWs affiliated with 25 health centres (clusters) in Southern Nations, Nationalities, and Peoples’ Region, Ethiopia. The primary outcome was treatment failure (persistent fever, development of danger signs, hospital admission, death, malaria, pneumonia, or diarrhoea) at 1 week (day 8) of follow-up. Non-inferiority was defined as a 4% or smaller difference in the proportion of treatment failures with conditional follow-up compared to universal follow-up. Secondary outcomes included the percentage of children brought for reassessment, antimicrobial prescription, and severe adverse events (hospitalisations and deaths) after 4 weeks (day 29). From December 1, 2015, to November 30, 2016, we enrolled 4,595 children, of whom 3,946 (1,953 universal follow-up arm; 1,993 conditional follow-up arm) adhered to the CHW’s follow-up advice and also completed a day 8 study visit within ±1 days. Overall, 2.7% had treatment failure on day 8: 0.8% (16/1,993) in the conditional follow-up arm and 4.6% (90/1,953) in the universal follow-up arm (risk difference of treatment failure −3.81%, 95% CI −∞, 0.65%), meeting the prespecified criterion for non-inferiority. There were no deaths recorded by day 29. In the universal follow-up arm, 94.6% of caregivers reported returning for reassessment on day 3, in contrast to 7.5% in the conditional follow-up arm (risk ratio 22.0, 95% CI 17.9, 27.2, p < 0.001). Few children sought care from another provider after their initial visit to the CHW: 3.0% (59/1,993) in the conditional follow-up arm and 1.1% (22/1,953) in the universal follow-up arm, on average 3.2 and 3.4 days later, respectively, with no significant difference between arms (risk difference 1.79%, 95% CI −1.23%, 4.82%, p = 0.244). The mean travel time to another provider was 2.2 hours (95% CI 0.01, 5.3) in the conditional follow-up arm and 2.6 hours (95% CI 0.02, 4.5) in the universal follow-up arm (p = 0.82); the mean cost for seeking care after visiting the CHW was 26.5 birr (95% CI 7.8, 45.2) and 22.8 birr (95% CI 15.6, 30.0), respectively (p = 0.69). Though this study was an important step to evaluate the safety of conditional follow-up, the high adherence seen may have resulted from knowledge of the 1-week follow-up visit and may therefore not transfer to routine practice; hence, in an implementation setting it is crucial that CHWs are well trained in counselling skills to advise caregivers on when to come back for follow-up.

Conclusions

Conditional follow-up of children with non-severe unclassified fever in a low malaria endemic setting in Ethiopia was non-inferior to universal follow-up through day 8. Allowing CHWs to advise caregivers to bring children back only in case of continued symptoms might be a more efficient use of resources in similar settings.

Trial registration

www.clinicaltrials.gov, identifier NCT02926625

Universal versus conditional day 3 follow-up for children with non-severe unclassified fever at the community level in the Democratic Republic of the Congo: A cluster-randomized, community-based non-inferiority trial

Ma, 17/04/2018 - 23:00

by Luke C. Mullany, Elburg W. van Boetzelaer, Julie R. Gutman, Laura C. Steinhardt, Pascal Ngoy, Yolanda Barbera Lainez, Alison Wittcoff, Steven A. Harvey, Lara S. Ho

Background

The World Health Organization’s integrated community case management (iCCM) guidelines recommend that all children presenting with uncomplicated fever and no danger signs return for follow-up on day 3 following the initial consultation on day 1. Such fevers often resolve rapidly, however, and previous studies suggest that expectant home care for uncomplicated fever can be safely recommended. We aimed to determine if a conditional follow-up visit was non-inferior to a universal follow-up visit for these children.

Methods and findings

We conducted a cluster-randomized, community-based non-inferiority trial among children 2–59 months old presenting to community health workers (CHWs) with non-severe unclassified fever in Tanganyika Province, Democratic Republic of the Congo. Clusters (n = 28) of CHWs were randomized to advise caregivers to either (1) return for a follow-up visit on day 3 following the initial consultation on day 1, regardless of illness resolution (as per current WHO guidelines; universal follow-up group) or (2) return for a follow-up visit on day 3 only if illness continued (conditional follow-up group). Children in both arms were assessed again at day 8, and classified as a clinical failure if fever (caregiver-reported), malaria, diarrhea, pneumonia, or decline of health status (development of danger signs, hospitalization, or death) was noted (failure definition 1). Alternative failure definitions were examined, whereby caregiver-reported fever was first restricted to caregiver-reported fever of at least 3 days (failure definition 2) and then replaced with fever measured via axillary temperature (failure definition 3). Study participants, providers, and investigators were not masked. Among 4,434 enrolled children, 4,141 (93.4%) met the per-protocol definition of receipt of the arm-specific advice from the CHW and a timely day 8 assessment (universal follow-up group: 2,210; conditional follow-up group: 1,931). Failure was similar (difference: –0.7%) in the conditional follow-up group (n = 188, 9.7%) compared to the universal follow-up group (n = 230, 10.4%); however, the upper bound of a 1-sided 95% confidence interval around this difference (−∞, 5.1%) exceeded the prespecified non-inferiority margin of 4.0% (non-inferiority p = 0.089). When caregiver-reported fever was restricted to fevers lasting ≥3 days, failure in the conditional follow-up group (n = 159, 8.2%) was similar to that in the universal follow-up group (n = 200, 9.1%) (difference: −0.8%; 95% CI: −∞, 4.1%; p = 0.053). If caregiver-reported fever was replaced by axillary temperature measurement in the definition of failure, failure in the conditional follow-up group (n = 113, 5.9%) was non-inferior to that in the universal follow-up group (n = 160, 7.2%) (difference: −1.4%; 95% CI: −∞, 2.5%; p = 0.012). In post hoc analysis, when the definition of failure was limited to malaria, diarrhea, pneumonia, development of danger signs, hospitalization, or death, failure in the conditional follow-up group (n = 108, 5.6%) was similar to that in the universal follow-up group (n = 147, 6.7%), and within the non-inferiority margin (95% CI: −∞, 2.9%; p = 0.017). Limitations include initial underestimation of the proportion of clinical failures as well as substantial variance in cluster-specific failure rates, reducing the precision of our estimates. In addition, heightened security concerns slowed recruitment in the final months of the study.

Conclusions

We found that advising caregivers to return only if children worsened or remained ill on day 3 resulted in similar rates of caregiver-reported fever and other clinical outcomes on day 8, compared to advising all caregivers to return on day 3. Policy-makers could consider revising guidelines for management of uncomplicated fever within the iCCM framework.

Trial registration

ClinicalTrials.gov NCT02595827