Olalekan A. Uthman

Global, regional, and national disability‐adjusted life years (DALYs) for 315 diseases and injuries and healthy life expectancy (HALE) for 195 countries and territories, 1990‐2015 : a systematic analysis for the Global Burden of Diseases, Injuries, and Risk Factors (GBD) 2015 Study

Summary Background Healthy life expectancy (HALE) and disability-adjusted life-years (DALYs) provide summary measures of health across geographies and time that can inform assessments of epidemiological patterns and health system performance, help to prioritise investments in research and development, and monitor progress toward the Sustainable Development Goals (SDGs). We aimed to provide updated HALE and DALYs for geographies worldwide and evaluate how disease burden changes with development. Methods We used results from the Global Burden of Diseases, Injuries, and Risk Factors Study 2015 (GBD 2015) for all-cause mortality, cause-specific mortality, and non-fatal disease burden to derive HALE and DALYs by sex for 195 countries and territories from 1990 to 2015. We calculated DALYs by summing years of life lost (YLLs) and years of life lived with disability (YLDs) for each geography, age group, sex, and year. We estimated HALE using the Sullivan method, which draws from age-specific death rates and YLDs per capita. We then assessed how observed levels of DALYs and HALE differed from expected trends calculated with the Socio-demographic Index (SDI), a composite indicator constructed from measures of income per capita, average years of schooling, and total fertility rate. Findings Total global DALYs remained largely unchanged from 1990 to 2015, with decreases in communicable, neonatal, maternal, and nutritional (Group 1) disease DALYs offset by increased DALYs due to non-communicable diseases (NCDs). Much of this epidemiological transition was caused by changes in population growth and ageing, but it was accelerated by widespread improvements in SDI that also correlated strongly with the increasing importance of NCDs. Both total DALYs and age-standardised DALY rates due to most Group 1 causes significantly decreased by 2015, and although total burden climbed for the majority of NCDs, age-standardised DALY rates due to NCDs declined. Nonetheless, age-standardised DALY rates due to several high-burden NCDs (including osteoarthritis, drug use disorders, depression, diabetes, congenital birth defects, and skin, oral, and sense organ diseases) either increased or remained unchanged, leading to increases in their relative ranking in many geographies. From 2005 to 2015, HALE at birth increased by an average of 2·9 years (95% uncertainty interval 2·9–3·0) for men and 3·5 years (3·4–3·7) for women, while HALE at age 65 years improved by 0·85 years (0·78–0·92) and 1·2 years (1·1–1·3), respectively. Rising SDI was associated with consistently higher HALE and a somewhat smaller proportion of life spent with functional health loss; however, rising SDI was related to increases in total disability. Many countries and territories in central America and eastern sub-Saharan Africa had increasingly lower rates of disease burden than expected given their SDI. At the same time, a subset of geographies recorded a growing gap between observed and expected levels of DALYs, a trend driven mainly by rising burden due to war, interpersonal violence, and various NCDs. Interpretation Health is improving globally, but this means more populations are spending more time with functional health loss, an absolute expansion of morbidity. The proportion of life spent in ill health decreases somewhat with increasing SDI, a relative compression of morbidity, which supports continued efforts to elevate personal income, improve education, and limit fertility. Our analysis of DALYs and HALE and their relationship to SDI represents a robust framework on which to benchmark geography-specific health performance and SDG progress. Country-specific drivers of disease burden, particularly for causes with higher-than-expected DALYs, should inform financial and research investments, prevention efforts, health policies, and health system improvement initiatives for all countries along the development continuum. Funding Bill & Melinda Gates Foundation.

Adherence to antiretroviral therapy during and after pregnancy in low-income, middle-income, and high-income countries: a systematic review and meta-analysis.

Objective:To estimate antiretroviral therapy (ART) adherence rates during pregnancy and postpartum in high-income, middle-income, and low-income countries. Design:Systematic review and meta-analysis. Methods:MEDLINE, EMBASE, SCI Web of Science, NLM Gateway, and Google scholar databases were searched. We included all studies reporting adherence rates as a primary or secondary outcome among HIV-infected pregnant women. Two independent reviewers extracted data on adherence and study characteristics. A random-effects model was used to pool adherence rates; sensitivity, heterogeneity, and publication bias were assessed. Results:Of 72 eligible articles, 51 studies involving 20 153 HIV-infected pregnant women were included. Most studies were from United States (n = 14, 27%) followed by Kenya (n = 6, 12%), South Africa (n = 5, 10%), and Zambia (n = 5, 10%). The threshold defining good adherence to ART varied across studies (>80, >90, >95, 100%). A pooled analysis of all studies indicated a pooled estimate of 73.5% [95% confidence interval (CI) 69.3–77.5%] of pregnant women who had adequate (>80%) ART adherence. The pooled proportion of women with adequate adherence levels was higher during the antepartum (75.7%, 95% CI 71.5–79.7%) than during postpartum (53.0%, 95% CI 32.8–72.7%; P = 0.005). Selected reported barriers for nonadherence included physical, economic and emotional stresses, depression (especially postdelivery), alcohol or drug use, and ART dosing frequency or pill burden. Conclusion:Our findings indicate that only 73.5% of pregnant women achieved optimal ART adherence. Reaching adequate ART adherence levels was a challenge in pregnancy, but especially during the postpartum period. Further research to investigate specific barriers and interventions to address them is urgently needed globally.

Exercise for lower limb osteoarthritis: systematic review incorporating trial sequential analysis and network meta-analysis

Objective To determine whether there is sufficient evidence to conclude that exercise interventions are more effective than no exercise control and to compare the effectiveness of different exercise interventions in relieving pain and improving function in patients with lower limb osteoarthritis. Data sources Nine electronic databases searched from inception to March 2012. Study selection Randomised controlled trials comparing exercise interventions with each other or with no exercise control for adults with knee or hip osteoarthritis. Data extraction Two reviewers evaluated eligibility and methodological quality. Main outcomes extracted were pain intensity and limitation of function. Trial sequential analysis was used to investigate reliability and conclusiveness of available evidence for exercise interventions. Bayesian network meta-analysis was used to combine both direct (within trial) and indirect (between trial) evidence on treatment effectiveness. Results 60 trials (44 knee, two hip, 14 mixed) covering 12 exercise interventions and with 8218 patients met inclusion criteria. Sequential analysis showed that as of 2002 sufficient evidence had been accrued to show significant benefit of exercise interventions over no exercise control. For pain relief, strengthening, flexibility plus strengthening, flexibility plus strengthening plus aerobic, aquatic strengthening, and aquatic strengthening plus flexibility, exercises were significantly more effective than no exercise control. A combined intervention of strengthening, flexibility, and aerobic exercise was also significantly more effective than no exercise control for improving limitation in function (standardised mean difference −0.63, 95% credible interval −1.16 to −0.10). Conclusions As of 2002 sufficient evidence had accumulated to show significant benefit of exercise over no exercise in patients with osteoarthritis, and further trials are unlikely to overturn this result. An approach combining exercises to increase strength, flexibility, and aerobic capacity is likely to be most effective in the management of lower limb osteoarthritis. The evidence is largely from trials in patients with knee osteoarthritis. Protocol registration PROSPERO (www.crd.york.ac.uk/prospero/) No CRD42012002267.

Lower Pill Burden and Once-Daily Antiretroviral Treatment Regimens for HIV Infection: A Meta-Analysis of Randomized Controlled Trials

Once-daily compared with twice-daily antiretroviral therapy regimens increased adherence; however, the difference was modest and not associated with a difference in virological suppression. In addition, higher pill burden was associated with lower rates of virological suppression, whether once- or twice-daily regimens.

Global Burden of Hypertension and Systolic Blood Pressure of at Least 110 to 115 mm Hg, 1990-2015

Importance Elevated systolic blood (SBP) pressure is a leading global health risk. Quantifying the levels of SBP is important to guide prevention policies and interventions. Objective To estimate the association between SBP of at least 110 to 115 mm Hg and SBP of 140 mm Hg or higher and the burden of different causes of death and disability by age and sex for 195 countries and territories, 1990-2015. Design A comparative risk assessment of health loss related to SBP. Estimated distribution of SBP was based on 844 studies from 154 countries (published 1980-2015) of 8.69 million participants. Spatiotemporal Gaussian process regression was used to generate estimates of mean SBP and adjusted variance for each age, sex, country, and year. Diseases with sufficient evidence for a causal relationship with high SBP (eg, ischemic heart disease, ischemic stroke, and hemorrhagic stroke) were included in the primary analysis. Main Outcomes and Measures Mean SBP level, cause-specific deaths, and health burden related to SBP (≥110-115 mm Hg and also ≥140 mm Hg) by age, sex, country, and year. Results Between 1990-2015, the rate of SBP of at least 110 to 115 mm Hg increased from 73 119 (95% uncertainty interval [UI], 67 949-78 241) to 81 373 (95% UI, 76 814-85 770) per 100 000, and SBP of 140 mm Hg or higher increased from 17 307 (95% UI, 17 117-17 492) to 20 526 (95% UI, 20 283-20 746) per 100 000. The estimated annual death rate per 100 000 associated with SBP of at least 110 to 115 mm Hg increased from 135.6 (95% UI, 122.4-148.1) to 145.2 (95% UI 130.3-159.9) and the rate for SBP of 140 mm Hg or higher increased from 97.9 (95% UI, 87.5-108.1) to 106.3 (95% UI, 94.6-118.1). Loss of disability-adjusted life-years (DALYs) associated with SBP of at least 110 to 115 mm Hg increased from 148 million (95% UI, 134-162 million) to 211 million (95% UI, 193-231 million), and for SBP of 140 mm Hg or higher, the loss increased from 5.2 million (95% UI, 4.6-5.7 million) to 7.8 million (95% UI, 7.0-8.7 million). The largest numbers of SBP-related deaths were caused by ischemic heart disease (4.9 million [95% UI, 4.0-5.7 million]; 54.5%), hemorrhagic stroke (2.0 million [95% UI, 1.6-2.3 million]; 58.3%), and ischemic stroke (1.5 million [95% UI, 1.2-1.8 million]; 50.0%). In 2015, China, India, Russia, Indonesia, and the United States accounted for more than half of the global DALYs related to SBP of at least 110 to 115 mm Hg. Conclusions and Relevance In international surveys, although there is uncertainty in some estimates, the rate of elevated SBP (≥110-115 and ≥140 mm Hg) increased substantially between 1990 and 2015, and DALYs and deaths associated with elevated SBP also increased. Projections based on this sample suggest that in 2015, an estimated 3.5 billion adults had SBP of at least 110 to 115 mm Hg and 874 million adults had SBP of 140 mm Hg or higher.

Individual and contextual factors associated with low childhood immunisation coverage in sub-Saharan Africa: a multilevel analysis

Background In 2010, more than six million children in sub-Saharan Africa did not receive the full series of three doses of the diphtheria-tetanus-pertussis vaccine by one year of age. An evidence-based approach to addressing this burden of un-immunised children requires accurate knowledge of the underlying factors. We therefore developed and tested a model of childhood immunisation that includes individual, community and country-level characteristics. Method and Findings We conducted multilevel logistic regression analysis of Demographic and Health Survey data for 27,094 children aged 12–23 months, nested within 8,546 communities from 24 countries in sub-Saharan Africa. According to the intra-country and intra-community correlation coefficient implied by the estimated intercept component variance, 21% and 32% of the variance in unimmunised children were attributable to country- and community-level factors respectively. Children born to mothers (OR 1.35, 95%CI 1.18 to 1.53) and fathers (OR 1.13, 95%CI 1.12 to 1.40) with no formal education were more likely to be unimmunised than those born to parents with secondary or higher education. Children from the poorest households were 36% more likely to be unimmunised than counterparts from the richest households. Maternal access to media significantly reduced the odds of children being unimmunised (OR 0.94, 95%CI 0.94 to 0.99). Mothers with health seeking behaviours were less likely to have unimmunised children (OR 0.56, 95%CI 0.54 to 0.58). However, children from urban areas (OR 1.12, 95% CI 1.01 to 1.23), communities with high illiteracy rates (OR 1.13, 95% CI 1.05 to 1.23), and countries with high fertility rates (OR 4.43, 95% CI 1.04 to 18.92) were more likely to be unimmunised. Conclusion We found that individual and contextual factors were associated with childhood immunisation, suggesting that public health programmes designed to improve coverage of childhood immunisation should address people, and the communities and societies in which they live.

The independent contribution of individual-, neighbourhood-, and country-level socioeconomic position on attitudes towards intimate partner violence against women in sub-Saharan Africa: a multilevel model of direct and moderating effects.

We examined associations between country, neighbourhood, and individual socioeconomic position (SEP) and attitudes towards intimate partner violence against women (IPVAW). We applied multivariable multilevel logistic regression analysis on Demographic and Health Survey data for 165,983 women and 68,501 men nested within 7465 communities from 17 countries in sub-Saharan Africa collected between 2003 and 2007. Contrary to expectation women were 34% more likely to justify IPVAW than men. We found that sex moderates associations of individual-, neighbourhood-, and country-level SEP with attitudes towards IPVAW. There was a significant positive interaction effect between sex and education attainment; women with no education were more likely to justify IPVAW than men with no education. Negative sex interaction with household wealth status indicates that differences in attitude are less pronounced among women. Unemployed men were more likely to justify IPVAW. Interaction effects indicate that the association of neighbourhood socioeconomic disadvantage with attitudes was more pronounced among women than among men. The association of country-level SEP with attitudes towards IPVWA was inconclusive. There was some evidence that neighbourhood modified the association between individual SEP and attitudes towards IPV. Also, there was cross-level interaction between country and neighbourhood SEP. Neighbourhood and individual SEP were independently associated with attitudes towards IPVAW. The relationship with country-level SEP was inconclusive. The findings underscore the need to implement public health prevention/intervention strategies not only at the level of individual SEP but also at the neighbourhood level.

Geography of Africa biomedical publications: An analysis of 1996–2005 PubMed papers

BackgroundScientific publications play an important role in scientific process providing a key linkage between knowledge production and use. Scientific publishing activity worldwide over the past decades shows that most countries in Africa have low levels of publication. We sought to examine trends and contribution of different Africa subregions and individual countries as represented by the articles indexed by PubMed between 1996 and 2005.ResultsResearch production in Africa is highly skewed; South Africa, Egypt, and Nigeria make up a striking 60% of the total number of articles indexed by PubMed between 1996 and 2005. When adjusted for population size smaller countries, such as The Gambia, Gabon and Botswana, were more productive than Nigeria and Kenya. The Gambia and Eritrea had better records when total production was adjusted for gross domestic product. The contribution of Africa to global research production was persistently low through the period studied.ConclusionIn this study, we found that most populous and rich countries (such as South Africa, Egypt, and Nigeria) have correspondingly higher research production; but smaller countries can be productive. We noted continuous increases and reassuring trends in the production of research articles from all African subregions during the period 1996 – 2005. However, contribution of Africa to global research production was limited.

Accuracy of non-invasive prenatal testing using cell-free DNA for detection of Down, Edwards and Patau syndromes : a systematic review and meta-analysis

Objective To measure test accuracy of non-invasive prenatal testing (NIPT) for Down, Edwards and Patau syndromes using cell-free fetal DNA and identify factors affecting accuracy. Design Systematic review and meta-analysis of published studies. Data sources PubMed, Ovid Medline, Ovid Embase and the Cochrane Library published from 1997 to 9 February 2015, followed by weekly autoalerts until 1 April 2015. Eligibility criteria for selecting studies English language journal articles describing case–control studies with ≥15 trisomy cases or cohort studies with ≥50 pregnant women who had been given NIPT and a reference standard. Results 41, 37 and 30 studies of 2012 publications retrieved were included in the review for Down, Edwards and Patau syndromes. Quality appraisal identified high risk of bias in included studies, funnel plots showed evidence of publication bias. Pooled sensitivity was 99.3% (95% CI 98.9% to 99.6%) for Down, 97.4% (95.8% to 98.4%) for Edwards, and 97.4% (86.1% to 99.6%) for Patau syndrome. The pooled specificity was 99.9% (99.9% to 100%) for all three trisomies. In 100 000 pregnancies in the general obstetric population we would expect 417, 89 and 40 cases of Downs, Edwards and Patau syndromes to be detected by NIPT, with 94, 154 and 42 false positive results. Sensitivity was lower in twin than singleton pregnancies, reduced by 9% for Down, 28% for Edwards and 22% for Patau syndrome. Pooled sensitivity was also lower in the first trimester of pregnancy, in studies in the general obstetric population, and in cohort studies with consecutive enrolment. Conclusions NIPT using cell-free fetal DNA has very high sensitivity and specificity for Down syndrome, with slightly lower sensitivity for Edwards and Patau syndrome. However, it is not 100% accurate and should not be used as a final diagnosis for positive cases. Trial registration number CRD42014014947.

Antiretroviral therapy adherence and drug-drug interactions in the aging HIV population

It is estimated that by 2015 more than half of all HIV-infected individuals in the United States will be 50 years of age or older. As this population ages, the frequency of non-AIDS related comorbidities increases, which includes cardiovascular, metabolic, gastrointestinal, genitourinary and psychiatric disorders. As a result, medical management of the aging HIV population can be complicated by polypharmacy and higher pill burden, leading to poorer antiretroviral therapy (ART) adherence. Adherence to ART is generally better in older populations when compared to younger populations; however, cognitive impairment in elderly patients can impair adherence, leading to worse treatment outcomes. Practical monitoring tools can improve adherence and increase rates of viral load suppression. Several antiretroviral drugs exhibit inhibitory and/or inducing effects on cytochrome P450 isoenzymes, which are responsible for the metabolism of many medications used for the treatment of comorbidities in the aging HIV population. The combination of ART with polypharmacy significantly increases the chance of potentially serious drug–drug interactions (DDIs), which can lead to drug toxicity, poorer ART adherence, loss of efficacy of the coadministered medication, or virologic breakthrough. Increasing clinicians awareness of common DDIs and the use of DDI programs can prevent coadministration of potentially harmful combinations in elderly HIV-infected individuals. Well designed ART adherence interventions and DDI studies are needed in the elderly HIV population.