Epidemiology of harmful use of alcohol in Nigeria: a systematic review and meta-analysis

Background: Nigeria, the most populous country in Africa, has reported relatively high levels of alcohol misuse, yet limited resources to guide effective population-wide response. There is a need to integrate existing empirical information in order to increase the power and precision of estimating epidemiological evidence necessary for informing policies and developing prevention programs. Objectives: We aimed to estimate nationwide and zonal prevalence of harmful use of alcohol in Nigeria to inform public health policy and planning. Methods: Epidemiologic reports on alcohol use in Nigeria from 1990 through 2018 were systematically searched and abstracted. We employed random-effects meta-analysis and meta-regression model to determine the number of harmful alcohol users. Results: 35 studies (n = 37,576 Nigerians) were identified. Pooled crude prevalence of harmful use of alcohol was 34.3% (95% CI: 28.6-40.1); twice as high among men (43.9%, 31.1-56.8) compared to women (23.9%, 16.4-31.4). Harmful alcohol use was higher in rural settings (40.1%, 24.2-56.1) compared to urban settings (31.2%, 22.9-39.6). The number of harmful alcohol users aged ≥15 years increased from 24 to 34 million from 1995 to 2015. However, actual age-adjusted prevalence of harmful use of alcohol in Nigeria decreased from 38.5% to 32.6% over the twenty-year period. Conclusions: While the prevalence of the total population that drinks harmfully appears to be dropping, absolute number of individuals that would be classified as harmful drinkers is increasing. This finding highlights the complexity of identifying and advocating for substance abuse policies in rapidly changing demographic settings common in Africa, Asia, and other developing countries

Current prevalence pattern of tobacco smoking in Nigeria: a systematic review and meta-analysis

Background National smoking cessation strategies in Nigeria are hindered by lack of up-to-date epidemiologic data. We aimed to estimate prevalence of tobacco smoking in Nigeria to guide relevant interventions. Methods We conducted systematic search of publicly available evidence from 1990 through 2018. A random-effects meta-analysis and meta-regression epidemiologic model were employed to determine prevalence and number of smokers in Nigeria in 1995 and 2015. Results Across 64 studies (n = 54,755), the pooled crude prevalence of current smokers in Nigeria was 10.4% (9.0–11.7) and 17.7% (15.2–20.2) for ever smokers. This was higher among men compared to women in both groups. There was considerable variation across geopolitical zones, ranging from 5.4% (North-west) to 32.1% (North-east) for current smokers, and 10.5% (South-east) to 43.6% (North-east) for ever smokers. Urban and rural dwellers had relatively similar rates of current smokers (10.7 and 9.1%), and ever smokers (18.1 and 17.0%). Estimated median age at initiation of smoking was 16.8 years (IQR: 13.5–18.0). From 1995 to 2015, we estimated an increase in number of current smokers from 8 to 11 million (or a decline from 13 to 10.6% of the population). The pooled mean cigarettes consumption per person per day was 10.1 (6.1–14.2), accounting for 110 million cigarettes per day and over 40 billion cigarettes consumed in Nigeria in 2015. Conclusions While the prevalence of smokers may be declining in Nigeria, one out of ten Nigerians still smokes daily. There is need for comprehensive measures and strict anti-tobacco laws targeting tobacco production and marketing

Estimating the prevalence of overweight and obesity in Nigeria in 2020: a systematic review and meta-analysis

Background Targeted public health response to obesity in Nigeria is relatively low due to limited epidemiologic understanding. We aimed to estimate nationwide and sub-national prevalence of overweight and obesity in the adult Nigerian population. Methods MEDLINE, EMBASE, Global Health, and Africa Journals Online were systematically searched for relevant epidemiologic studies in Nigeria published on or after 01 January 1990. We assessed quality of studies and conducted a random-effects meta-analysis on extracted crude prevalence rates. Using a meta-regression model, we estimated the number of overweight and obese persons in Nigeria in the year 2020. Results From 35 studies (n = 52,816), the pooled crude prevalence rates of overweight and obesity in Nigeria were 25.0% (95% confidence interval, CI: 20.4–29.6) and 14.3% (95% CI: 12.0–15.5), respectively. The prevalence in women was higher compared to men at 25.5% (95% CI: 17.1–34.0) versus 25.2% (95% CI: 18.0–32.4) for overweight, and 19.8% (95% CI: 3.9–25.6) versus 12.9% (95% CI: 9.1–16.7) for obesity, respectively. The pooled mean body mass index (BMI) and waist circumference were 25.6 kg/m2 and 86.5 cm, respectively. We estimated that there were 21 million and 12 million overweight and obese persons in the Nigerian population aged 15 years or more in 2020, accounting for an age-adjusted prevalence of 20.3% and 11.6%, respectively. The prevalence rates of overweight and obesity were consistently higher among urban dwellers (27.2% and 14.4%) compared to rural dwellers (16.4% and 12.1%). Conclusions Our findings suggest a high prevalence of overweight and obesity in Nigeria. This is marked in urban Nigeria and among women, which may in part be due to widespread sedentary lifestyles and a surge in processed food outlets, largely reflective of a trend across many African settings

Protein-coding variants implicate novel genes related to lipid homeostasis contributing to body-fat distribution.

Body-fat distribution is a risk factor for adverse cardiovascular health consequences. We analyzed the association of body-fat distribution, assessed by waist-to-hip ratio adjusted for body mass index, with 228,985 predicted coding and splice site variants available on exome arrays in up to 344,369 individuals from five major ancestries (discovery) and 132,177 European-ancestry individuals (validation). We identified 15 common (minor allele frequency, MAF ≥5%) and nine low-frequency or rare (MAF <5%) coding novel variants. Pathway/gene set enrichment analyses identified lipid particle, adiponectin, abnormal white adipose tissue physiology and bone development and morphology as important contributors to fat distribution, while cross-trait associations highlight cardiometabolic traits. In functional follow-up analyses, specifically in Drosophila RNAi-knockdowns, we observed a significant increase in the total body triglyceride levels for two genes (DNAH10 and PLXND1). We implicate novel genes in fat distribution, stressing the importance of interrogating low-frequency and protein-coding variants

Rare and low-frequency coding variants alter human adult height

Height is a highly heritable, classic polygenic trait with ~700 common associated variants identified so far through genome - wide association studies . Here , we report 83 height - associated coding variants with lower minor allele frequenc ies ( range of 0.1 - 4.8% ) and effects of up to 2 16 cm /allele ( e.g. in IHH , STC2 , AR and CRISPLD2 ) , >10 times the average effect of common variants . In functional follow - up studies, rare height - increasing alleles of STC2 (+1 - 2 cm/allele) compromise d proteolytic inhibition of PAPP - A and increased cleavage of IGFBP - 4 in vitro , resulting in higher bioavailability of insulin - like growth factors . The se 83 height - associated variants overlap genes mutated in monogenic growth disorders and highlight new biological candidates ( e.g. ADAMTS3, IL11RA, NOX4 ) and pathways ( e.g . proteoglycan/ glycosaminoglycan synthesis ) involved in growth . Our results demonstrate that sufficiently large sample sizes can uncover rare and low - frequency variants of moderate to large effect associated with polygenic human phenotypes , and that these variants implicate relevant genes and pathways

Canagliflozin and renal outcomes in type 2 diabetes and nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to <90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], >300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BACKGROUND Regular, detailed reporting on population health by underlying cause of death is fundamental for public health decision making. Cause-specific estimates of mortality and the subsequent effects on life expectancy worldwide are valuable metrics to gauge progress in reducing mortality rates. These estimates are particularly important following large-scale mortality spikes, such as the COVID-19 pandemic. When systematically analysed, mortality rates and life expectancy allow comparisons of the consequences of causes of death globally and over time, providing a nuanced understanding of the effect of these causes on global populations. METHODS The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 cause-of-death analysis estimated mortality and years of life lost (YLLs) from 288 causes of death by age-sex-location-year in 204 countries and territories and 811 subnational locations for each year from 1990 until 2021. The analysis used 56 604 data sources, including data from vital registration and verbal autopsy as well as surveys, censuses, surveillance systems, and cancer registries, among others. As with previous GBD rounds, cause-specific death rates for most causes were estimated using the Cause of Death Ensemble model-a modelling tool developed for GBD to assess the out-of-sample predictive validity of different statistical models and covariate permutations and combine those results to produce cause-specific mortality estimates-with alternative strategies adapted to model causes with insufficient data, substantial changes in reporting over the study period, or unusual epidemiology. YLLs were computed as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 1000-draw distribution for each metric. We decomposed life expectancy by cause of death, location, and year to show cause-specific effects on life expectancy from 1990 to 2021. We also used the coefficient of variation and the fraction of population affected by 90% of deaths to highlight concentrations of mortality. Findings are reported in counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2021 include the expansion of under-5-years age group to include four new age groups, enhanced methods to account for stochastic variation of sparse data, and the inclusion of COVID-19 and other pandemic-related mortality-which includes excess mortality associated with the pandemic, excluding COVID-19, lower respiratory infections, measles, malaria, and pertussis. For this analysis, 199 new country-years of vital registration cause-of-death data, 5 country-years of surveillance data, 21 country-years of verbal autopsy data, and 94 country-years of other data types were added to those used in previous GBD rounds. FINDINGS The leading causes of age-standardised deaths globally were the same in 2019 as they were in 1990; in descending order, these were, ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and lower respiratory infections. In 2021, however, COVID-19 replaced stroke as the second-leading age-standardised cause of death, with 94·0 deaths (95% UI 89·2-100·0) per 100 000 population. The COVID-19 pandemic shifted the rankings of the leading five causes, lowering stroke to the third-leading and chronic obstructive pulmonary disease to the fourth-leading position. In 2021, the highest age-standardised death rates from COVID-19 occurred in sub-Saharan Africa (271·0 deaths [250·1-290·7] per 100 000 population) and Latin America and the Caribbean (195·4 deaths [182·1-211·4] per 100 000 population). The lowest age-standardised death rates from COVID-19 were in the high-income super-region (48·1 deaths [47·4-48·8] per 100 000 population) and southeast Asia, east Asia, and Oceania (23·2 deaths [16·3-37·2] per 100 000 population). Globally, life expectancy steadily improved between 1990 and 2019 for 18 of the 22 investigated causes. Decomposition of global and regional life expectancy showed the positive effect that reductions in deaths from enteric infections, lower respiratory infections, stroke, and neonatal deaths, among others have contributed to improved survival over the study period. However, a net reduction of 1·6 years occurred in global life expectancy between 2019 and 2021, primarily due to increased death rates from COVID-19 and other pandemic-related mortality. Life expectancy was highly variable between super-regions over the study period, with southeast Asia, east Asia, and Oceania gaining 8·3 years (6·7-9·9) overall, while having the smallest reduction in life expectancy due to COVID-19 (0·4 years). The largest reduction in life expectancy due to COVID-19 occurred in Latin America and the Caribbean (3·6 years). Additionally, 53 of the 288 causes of death were highly concentrated in locations with less than 50% of the global population as of 2021, and these causes of death became progressively more concentrated since 1990, when only 44 causes showed this pattern. The concentration phenomenon is discussed heuristically with respect to enteric and lower respiratory infections, malaria, HIV/AIDS, neonatal disorders, tuberculosis, and measles. INTERPRETATION Long-standing gains in life expectancy and reductions in many of the leading causes of death have been disrupted by the COVID-19 pandemic, the adverse effects of which were spread unevenly among populations. Despite the pandemic, there has been continued progress in combatting several notable causes of death, leading to improved global life expectancy over the study period. Each of the seven GBD super-regions showed an overall improvement from 1990 and 2021, obscuring the negative effect in the years of the pandemic. Additionally, our findings regarding regional variation in causes of death driving increases in life expectancy hold clear policy utility. Analyses of shifting mortality trends reveal that several causes, once widespread globally, are now increasingly concentrated geographically. These changes in mortality concentration, alongside further investigation of changing risks, interventions, and relevant policy, present an important opportunity to deepen our understanding of mortality-reduction strategies. Examining patterns in mortality concentration might reveal areas where successful public health interventions have been implemented. Translating these successes to locations where certain causes of death remain entrenched can inform policies that work to improve life expectancy for people everywhere. FUNDING Bill & Melinda Gates Foundation

ARTICLE Whole exome sequencing reveals a C-terminal germline variant in CEBPA-associated acute myeloid leukemia: 45-year follow up of a large family

F amilial acute myeloid leukemia is rare and linked to germline mutations in RUNX1, GATA2 or CCAAT/enhancer binding protein-a (CEBPA). We re-evaluated a large family with acute myeloid leukemia originally seen at NIH in 1969. We used whole exome sequencing to study this family, and conducted in silico bioinformatics analysis, protein structural modeling and laboratory experiments to assess the impact of the identified CEBPA Q311P mutation. Unlike most previously identified germline mutations in CEBPA, which were N-terminal frameshift mutations, we identified a novel Q311P variant that was located in the C-terminal bZip domain of C/EBPa. Protein structural modeling suggested that the Q311P mutation alters the ability of the CEBPA dimer to bind DNA. Electrophoretic mobility shift assays showed that the Q311P mu-tant had attenuated binding to DNA, as predicted by the protein modeling. Consistent with these findings, we found that the Q311P mutation has reduced transactivation, consistent with a loss-of-function mutation. From 45 years of follow up, we observed incomplete penetrance (46%) of CEBPA Q311P. This study of a large multi-generational pedigree reveals that a germline mutation in the C-terminal bZip domain can alter the ability of C/EBP-a to bind DNA and reduces transactivation, leading to acute myeloid leukemia