Unexplained chronic liver disease in Ethiopia: a cross-sectional study

BACKGROUND: Hepatitis B virus (HBV) infection is assumed to be the major cause of chronic liver disease (CLD) in sub-Saharan Africa. The contribution of other aetiological causes of CLD is less well documented and hence opportunities to modulate other potential risk factors are being lost. The aims of this study were to explore the aetiological spectrum of CLD in eastern Ethiopia and to identify plausible underlying risk factors for its development. METHODS: A cross-sectional study was undertaken between April 2015 and April 2016 in two public hospitals in Harar, eastern Ethiopia. The study population comprised of consenting adults with clinical and radiological evidence of chronic liver disease. The baseline evaluation included: (i) a semi-structured interview designed to obtain information about the ingestion of alcohol, herbal medicines and local recreational drugs such as khat (Catha edulis); (ii) clinical examination; (iii) extensive laboratory testing; and, (iv) abdominal ultrasonography. RESULTS: One-hundred-and-fifty patients with CLD (men 72.0%; median age 30 [interquartile range 25-40] years) were included. CLD was attributed to chronic HBV infection in 55 (36.7%) individuals; other aetiological agents were identified in a further 12 (8.0%). No aetiological factors were identified in the remaining 83 (55.3%) patients. The overall prevalence of daily khat use was 78.0%, while alcohol abuse, defined as > 20 g/day in women and > 30 g/day in men, was rare (2.0%). Histological features of toxic liver injury were observed in a subset of patients with unexplained liver injury who underwent liver biopsy. CONCLUSION: The aetiology of CLD in eastern Ethiopia is largely unexplained. The widespread use of khat in the region, together with histopathological findings indicating toxic liver injury, suggests an association which warrants further investigation

A composite light-harvesting layer from photoactive polymer and halide perovskite for planar heterojunction solar cells

A new route for fabrication of photoactive materials in organic-inorganic hybrid solar cells is presented in this report. Photoactive materials by blending a semiconductive conjugated polymer with an organolead halide perovskite were fabricated for the first time. The composite active layer was then used to make planar heterojunction solar cells with the PCBM film as the electron-acceptor. Photovoltaic performance of solar cells was investigated by J-V curves and external quantum efficiency spectra. We demonstrated that the incorporation of the conjugated photoactive polymer into organolead halide perovskites did not only contribute to the generation of charges, but also enhance stability of solar cells by providing a barrier protection to halide perovskites. It is expected that versatile of conjugated semi-conductive polymers and halide perovskites in photoactive properties enables to create various combinations, forming composites with advantages offered by both types of photoactive materials

Unexplained chronic liver disease in Ethiopia: a cross-sectional study

Background: Hepatitis B virus (HBV) infection is assumed to be the major cause of chronic liver disease (CLD) in sub-Saharan Africa. The contribution of other aetiological causes of CLD is less well documented and hence opportunities to modulate other potential risk factors are being lost. The aims of this study were to explore the aetiological spectrum of CLD in eastern Ethiopia and to identify plausible underlying risk factors for its development. Methods: A cross-sectional study was undertaken between April 2015 and April 2016 in two public hospitals in Harar, eastern Ethiopia. The study population comprised of consenting adults with clinical and radiological evidence of chronic liver disease. The baseline evaluation included: (i) a semi-structured interview designed to obtain information about the ingestion of alcohol, herbal medicines and local recreational drugs such as khat (Catha edulis); (ii) clinical examination; (iii) extensive laboratory testing; and, (iv) abdominal ultrasonography. Results: One-hundred-and-fifty patients with CLD (men 72.0%; median age 30 [interquartile range 25–40] years) were included. CLD was attributed to chronic HBV infection in 55 (36.7%) individuals; other aetiological agents were identified in a further 12 (8.0%). No aetiological factors were identified in the remaining 83 (55.3%) patients. The overall prevalence of daily khat use was 78.0%, while alcohol abuse, defined as > 20 g/day in women and > 30 g/day in men, was rare (2.0%). Histological features of toxic liver injury were observed in a subset of patients with unexplained liver injury who underwent liver biopsy. Conclusion: The aetiology of CLD in eastern Ethiopia is largely unexplained. The widespread use of khat in the region, together with histopathological findings indicating toxic liver injury, suggests an association which warrants further investigation

Chronic hepatosplenomegaly in African school children: a common but neglected morbidity associated with schistosomiasis and malaria.

Chronic hepatosplenomegaly, which is known to have a complex aetiology, is common amongst children who reside in rural areas of sub-Saharan Africa. Two of the more common infectious agents of hepatosplenomegaly amongst these children are malarial infections and schistosomiasis. The historical view of hepatosplenomegaly associated with schistosomiasis is that it is caused by gross periportal fibrosis and resulting portal hypertension. The introduction of ultrasound examinations into epidemiology studies, used in tandem with clinical examination, showed a dissociation within endemic communities between presentation with hepatosplenomegaly and ultrasound periportal fibrosis, while immuno-epidemiological studies indicate that rather than the pro-fibrotic Th2 response that is associated with periportal fibrosis, childhood hepatosplenomegaly without ultrasound-detectable fibrosis is associated with a pro-inflammatory response. Correlative analysis has shown that the pro-inflammatory response is also associated with chronic exposure to malarial infections and there is evidence of exacerbation of hepatosplenomegaly when co-exposure to malaria and schistosomiasis occurs. The common presentation with childhood hepatosplenomegaly in rural communities means that it is an important example of a multi-factorial disease and its association with severe and subtle morbidities underlies the need for well-designed public health strategies for tackling common infectious diseases in tandem rather than in isolation

Association between depression, anxiety and weight change in young adults

Background To investigate whether there are bi-directional associations between anxiety and mood disorders and body mass index (BMI) in a cohort of young adults. Methods We analysed data from the 2004–2006 (baseline) and 2009–2011 (follow-up) waves of the Childhood Determinants of Adult Health study. Lifetime DSM-IV anxiety and mood disorders were retrospectively diagnosed with the Composite International Diagnostic Interview. Potential mediators were individually added to the base models to assess their potential role as a mediator of the associations. Results In males, presence of mood disorder history at baseline was positively associated with BMI gain (β = 0.77, 95% CI: 0.14–1.40), but baseline BMI was not associated with subsequent risk of mood disorder. Further adjustment for covariates, including dietary pattern, physical activity, and smoking reduced the coefficient (β) to 0.70 (95% CI: 0.01–1.39), suggesting that the increase in BMI was partly mediated by these factors. In females, presence of mood disorder history at baseline was not associated with subsequent weight gain, however, BMI at baseline was associated with higher risk of episode of mood disorder (RR per kg/m2: 1.04, 95% CI: 1.01–1.08), which was strengthened (RR per kg/m2 = 1.07, 95% CI: 1.00–1.15) after additional adjustment in the full model. There was no significant association between anxiety and change in BMI and vice-versa. Conclusion The results do not suggest bidirectional associations between anxiety and mood disorders, and change in BMI. Interventions promoting healthy lifestyle could contribute to reducing increase in BMI associated with mood disorder in males, and excess risk of mood disorder associated with BMI in females

Tixagevimab–cilgavimab for treatment of patients hospitalised with COVID-19: a randomised, double-blind, phase 3 trial

Background: Tixagevimab–cilgavimab is a neutralising monoclonal antibody combination hypothesised to improve outcomes for patients hospitalised with COVID-19. We aimed to compare tixagevimab–cilgavimab versus placebo, in patients receiving remdesivir and other standard care. Methods: In a randomised, double-blind, phase 3, placebo-controlled trial, adults with symptoms for up to 12 days and hospitalised for COVID-19 at 81 sites in the USA, Europe, Uganda, and Singapore were randomly assigned in a 1:1 ratio to receive intravenous tixagevimab 300 mg–cilgavimab 300 mg or placebo, in addition to remdesivir and other standard care. Patients were excluded if they had acute organ failure including receipt of invasive mechanical ventilation, extracorporeal membrane oxygenation, vasopressor therapy, mechanical circulatory support, or new renal replacement therapy. The study drug was prepared by an unmasked pharmacist; study participants, site study staff, investigators, and clinical providers were masked to study assignment. The primary outcome was time to sustained recovery up to day 90, defined as 14 consecutive days at home after hospital discharge, with co-primary analyses for the full cohort and for participants who were neutralising antibody-negative at baseline. Efficacy and safety analyses were done in the modified intention-to-treat population, defined as participants who received a complete or partial infusion of tixagevimab–cilgavimab or placebo. This study is registered with ClinicalTrials.gov, NCT04501978 and the participant follow-up is ongoing. Findings: From Feb 10 to Sept 30, 2021, 1455 patients were randomly assigned and 1417 in the primary modified intention-to-treat population were infused with tixagevimab–cilgavimab (n=710) or placebo (n=707). The estimated cumulative incidence of sustained recovery was 89% for tixagevimab–cilgavimab and 86% for placebo group participants at day 90 in the full cohort (recovery rate ratio [RRR] 1·08 [95% CI 0·97–1·20]; p=0·21). Results were similar in the seronegative subgroup (RRR 1·14 [0·97–1·34]; p=0·13). Mortality was lower in the tixagevimab–cilgavimab group (61 [9%]) versus placebo group (86 [12%]; hazard ratio [HR] 0·70 [95% CI 0·50–0·97]; p=0·032). The composite safety outcome occurred in 178 (25%) tixagevimab–cilgavimab and 212 (30%) placebo group participants (HR 0·83 [0·68–1·01]; p=0·059). Serious adverse events occurred in 34 (5%) participants in the tixagevimab–cilgavimab group and 38 (5%) in the placebo group. Interpretation: Among patients hospitalised with COVID-19 receiving remdesivir and other standard care, tixagevimab–cilgavimab did not improve the primary outcome of time to sustained recovery but was safe and mortality was lower. Funding: US National Institutes of Health (NIH) and Operation Warp Speed

Estimating global injuries morbidity and mortality: methods and data used in the Global Burden of Disease 2017 study

BACKGROUND: While there is a long history of measuring death and disability from injuries, modern research methods must account for the wide spectrum of disability that can occur in an injury, and must provide estimates with sufficient demographic, geographical and temporal detail to be useful for policy makers. The Global Burden of Disease (GBD) 2017 study used methods to provide highly detailed estimates of global injury burden that meet these criteria. METHODS: In this study, we report and discuss the methods used in GBD 2017 for injury morbidity and mortality burden estimation. In summary, these methods included estimating cause-specific mortality for every cause of injury, and then estimating incidence for every cause of injury. Non-fatal disability for each cause is then calculated based on the probabilities of suffering from different types of bodily injury experienced. RESULTS: GBD 2017 produced morbidity and mortality estimates for 38 causes of injury. Estimates were produced in terms of incidence, prevalence, years lived with disability, cause-specific mortality, years of life lost and disability-adjusted life-years for a 28-year period for 22 age groups, 195 countries and both sexes. CONCLUSIONS: GBD 2017 demonstrated a complex and sophisticated series of analytical steps using the largest known database of morbidity and mortality data on injuries. GBD 2017 results should be used to help inform injury prevention policy making and resource allocation. We also identify important avenues for improving injury burden estimation in the future

Epidemiology of neurodegenerative diseases in sub-Saharan Africa: a systematic review

BACKGROUND:Sub-Saharan African (SSA) countries are experiencing rapid transitions with increased life expectancy. As a result the burden of age-related conditions such as neurodegenerative diseases might be increasing. We conducted a systematic review of published studies on common neurodegenerative diseases, and HIV-related neurocognitive impairment in SSA, in order to identify research gaps and inform prevention and control solutions. METHODS: We searched MEDLINE via PubMed, 'Banque de Donnees de Sante Publique' and the database of the 'Institut d'Epidemiologie Neurologique et de Neurologie Tropicale' from inception to February 2013 for published original studies from SSA on neurodegenerative diseases and HIV-related neurocognitive impairment. Screening and data extraction were conducted by two investigators. Bibliographies and citations of eligible studies were investigated. RESULTS: In all 144 publications reporting on dementia (n=49 publications, mainly Alzheimer disease), Parkinsonism (PD, n=20), HIV-related neurocognitive impairment (n=47), Huntington disease (HD, n=19), amyotrophic lateral sclerosis (ALS, n=15), cerebellar degeneration (n=4) and Lewy body dementia (n=1). Of these studies, largely based on prevalent cases from retrospective data on urban populations, half originated from Nigeria and South Africa. The prevalence of dementia (Alzheimer disease) varied between <1% and 10.1% (0.7% and 5.6%) in population-based studies and from <1% to 47.8% in hospital-based studies. Incidence of dementia (Alzheimer disease) ranged from 8.7 to 21.8/1000/year (9.5 to 11.1), and major risk factors were advanced age and female sex. HIV-related neurocognitive impairment's prevalence (all from hospital-based studies) ranged from <1% to 80%. Population-based prevalence of PD and ALS varied from 10 to 235/100,000, and from 5 to 15/100,000 respectively while that for Huntington disease was 3.5/100,000. Equivalent figures for hospital based studies were the following: PD (0.41 to 7.2%), ALS (0.2 to 8.0/1000), and HD (0.2/100,000 to 46.0/100,000). CONCLUSIONS: The body of literature on neurodegenerative disorders in SSA is large with regard to dementia and HIV-related neurocognitive disorders but limited for other neurodegenerative disorders. Shortcomings include few population-based studies, heterogeneous diagnostic criteria and uneven representation of countries on the continent. There are important knowledge gaps that need urgent action, in order to prepare the sub-continent for the anticipated local surge in neurodegenerative diseases