Appropriateness of Antibiotic Prescribing for Acute Conjunctivitis: A Cross-Sectional Study at a Specialist Eye Hospital in Ghana, 2021

Most presentations of conjunctivitis are acute. Studies show that uncomplicated cases resolve within 14 days without medication. However, antibiotic prescription remains standard practice. With antimicrobial resistance becoming a public health concern, we undertook this study to assess antibiotic prescription patterns in managing acute conjunctivitis in an eye hospital in Ghana. We recorded 3708 conjunctivitis cases; 201 were entered as acute conjunctivitis in the electronic medical records (January to December 2021). Of these, 44% were males, 56% were females, 39% were under 5 years, 21% were children and adolescents (5–17 years) and 40% were adults (≥18 years). A total of 111 (55.2%) patients received antibiotics, of which 71.2% were appropriately prescribed. The use of antibiotics was more frequent in children under 17 years compared to adults (p < 0.0001). Of the prescribed antibiotics, 44% belonged to the AWaRe “Access” category (Gentamycin, Tetracycline ointment), while 56% received antibiotics in the “Watch” category (Ciprofloxacin, Tobramycin). Although most of the antibiotic prescribing were appropriate, the preponderance of use of the Watch category warrants stewardship to encompass topical antibiotics. The rational use of topical antibiotics in managing acute conjunctivitis will help prevent antimicrobial resistance, ensure effective health care delivery, and contain costs for patients and the health system

Global, regional, and national sex-specific burden and control of the HIV epidemic, 1990-2019, for 204 countries and territories: the Global Burden of Diseases Study 2019

Background: The sustainable development goals (SDGs) aim to end HIV/AIDS as a public health threat by 2030. Understanding the current state of the HIV epidemic and its change over time is essential to this effort. This study assesses the current sex-specific HIV burden in 204 countries and territories and measures progress in the control of the epidemic. Methods: To estimate age-specific and sex-specific trends in 48 of 204 countries, we extended the Estimation and Projection Package Age-Sex Model to also implement the spectrum paediatric model. We used this model in cases where age and sex specific HIV-seroprevalence surveys and antenatal care-clinic sentinel surveillance data were available. For the remaining 156 of 204 locations, we developed a cohort-incidence bias adjustment to derive incidence as a function of cause-of-death data from vital registration systems. The incidence was input to a custom Spectrum model. To assess progress, we measured the percentage change in incident cases and deaths between 2010 and 2019 (threshold >75% decline), the ratio of incident cases to number of people living with HIV (incidence-to-prevalence ratio threshold <0·03), and the ratio of incident cases to deaths (incidence-to-mortality ratio threshold <1·0). Findings: In 2019, there were 36·8 million (95% uncertainty interval [UI] 35·1–38·9) people living with HIV worldwide. There were 0·84 males (95% UI 0·78–0·91) per female living with HIV in 2019, 0·99 male infections (0·91–1·10) for every female infection, and 1·02 male deaths (0·95–1·10) per female death. Global progress in incident cases and deaths between 2010 and 2019 was driven by sub-Saharan Africa (with a 28·52% decrease in incident cases, 95% UI 19·58–35·43, and a 39·66% decrease in deaths, 36·49–42·36). Elsewhere, the incidence remained stable or increased, whereas deaths generally decreased. In 2019, the global incidence-to-prevalence ratio was 0·05 (95% UI 0·05–0·06) and the global incidence-to-mortality ratio was 1·94 (1·76–2·12). No regions met suggested thresholds for progress. Interpretation: Sub-Saharan Africa had both the highest HIV burden and the greatest progress between 1990 and 2019. The number of incident cases and deaths in males and females approached parity in 2019, although there remained more females with HIV than males with HIV. Globally, the HIV epidemic is far from the UNAIDS benchmarks on progress metrics. Funding: The Bill & Melinda Gates Foundation, the National Institute of Mental Health of the US National Institutes of Health (NIH), and the National Institute on Aging of the NIH

The global burden of adolescent and young adult cancer in 2019 : a systematic analysis for the Global Burden of Disease Study 2019

Background In estimating the global burden of cancer, adolescents and young adults with cancer are often overlooked, despite being a distinct subgroup with unique epidemiology, clinical care needs, and societal impact. Comprehensive estimates of the global cancer burden in adolescents and young adults (aged 15-39 years) are lacking. To address this gap, we analysed results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019, with a focus on the outcome of disability-adjusted life-years (DALYs), to inform global cancer control measures in adolescents and young adults. Methods Using the GBD 2019 methodology, international mortality data were collected from vital registration systems, verbal autopsies, and population-based cancer registry inputs modelled with mortality-to-incidence ratios (MIRs). Incidence was computed with mortality estimates and corresponding MIRs. Prevalence estimates were calculated using modelled survival and multiplied by disability weights to obtain years lived with disability (YLDs). Years of life lost (YLLs) were calculated as age-specific cancer deaths multiplied by the standard life expectancy at the age of death. The main outcome was DALYs (the sum of YLLs and YLDs). Estimates were presented globally and by Socio-demographic Index (SDI) quintiles (countries ranked and divided into five equal SDI groups), and all estimates were presented with corresponding 95% uncertainty intervals (UIs). For this analysis, we used the age range of 15-39 years to define adolescents and young adults. Findings There were 1.19 million (95% UI 1.11-1.28) incident cancer cases and 396 000 (370 000-425 000) deaths due to cancer among people aged 15-39 years worldwide in 2019. The highest age-standardised incidence rates occurred in high SDI (59.6 [54.5-65.7] per 100 000 person-years) and high-middle SDI countries (53.2 [48.8-57.9] per 100 000 person-years), while the highest age-standardised mortality rates were in low-middle SDI (14.2 [12.9-15.6] per 100 000 person-years) and middle SDI (13.6 [12.6-14.8] per 100 000 person-years) countries. In 2019, adolescent and young adult cancers contributed 23.5 million (21.9-25.2) DALYs to the global burden of disease, of which 2.7% (1.9-3.6) came from YLDs and 97.3% (96.4-98.1) from YLLs. Cancer was the fourth leading cause of death and tenth leading cause of DALYs in adolescents and young adults globally. Interpretation Adolescent and young adult cancers contributed substantially to the overall adolescent and young adult disease burden globally in 2019. These results provide new insights into the distribution and magnitude of the adolescent and young adult cancer burden around the world. With notable differences observed across SDI settings, these estimates can inform global and country-level cancer control efforts. Copyright (C) 2021 The Author(s). Published by Elsevier Ltd.Peer reviewe

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

Competitive Transplants to Evaluate Hematopoietic Stem Cell Fitness.

International audienceThe gold standard definition of a hematopoietic stem cell (HSC) is a cell that when transferred into an irradiated recipient will have the ability to reestablish blood cell production for the lifespan of the recipient. This protocol explains how to set up a functional assay to compare the HSC capacities of two different populations of cells, such as bone marrow from mice of two different genotypes, and how to analyze the recipient mice by flow cytometry. The protocol uses HSC equivalents rather than cell sorting for standardization and discusses the advantages and disadvantages of both approaches. We further discuss different variations to the basic protocol, including serial transplants, limiting dilution assays, homing assays and non-competitive transplants, including the advantages and preferred uses of these varied approaches. These assays are central for the study of HSC function and could be used not only for the investigation of fundamental HSC intrinsic aspects of biology but also for the development of preclinical assays for bone marrow transplant and HSC expansion in culture

A pathological and clinical study of 706 primary tumours of the ovary in the largest tertiary hospital in Ghana

Abstract Background Ovarian tumours are a leading cause of death in Ghana. Even though geographical and racial differences exist in the frequency, types and age distribution of primary ovarian tumours, information about the clinical and pathological characteristics of ovarian tumours in Ghana and its neighboring countries is scanty. We determined the frequency, age distribution, histopathological types and clinical features of primary ovarian tumours diagnosed at the Korle-Bu Teaching Hospital in Ghana to aid in the management of patients. Method All pathology records of ovarian tumours diagnosed from January 2001 to December 2010 were reviewed. Histopathologically, tumours were classified according to the then World Health Organization 1999 classification. Biographical and clinical data of patients were also collected and entered into Epi-info to determine the frequency, age distribution and other clinical features of the types of ovarian tumour. Results Seven hundred and six ovarian tumours were studied. Germ cell tumours were the most common (41.9%), with mean age of occurrence being 30.7 years (SD 12.7), they were dominated by mature teratomas (39.2%). Surface epithelial tumours were second, and commonly occurred in women aged 35–44years, 77 (26.8%). Sex cord stromal tumours followed with mean age of occurrence of 40.2 years (SD 17.9). The most common malignant tumours were surface epithelial (52.1%) dominated by serous carcinomas with mean age 50.1 years. Most patients (47.7%) presented within 1 month of onset of symptoms, feeling a lower abdominal mass (38.5%). Conclusion The most common primary ovarian tumours in this study are Germ cell tumours, dominated by mature teratomas. Adenocarcinomas are mostly serous and occur in younger women compared to findings of other Western studies. The single most common malignant ovarian tumour in children and adolescents is Burkitt lymphoma. Patients who develop ovarian tumours have no specific symptoms or signs at presentation, to aid early diagnosis

CXCR4/CXCL12 axis counteracts hematopoietic stem cell exhaustion through selective protection against oxidative stress

International audienceHematopoietic stem cells (HSCs) undergo self-renewal to maintain hematopoietic homeostasis for lifetime, which is regulated by the bone marrow (BM) microenvironment. The chemokine receptor CXCR4 and its ligand CXCL12 are critical factors supporting quiescence and BM retention of HSCs. Here, we report an unknown function of CXCR4/CXCL12 axis in the protection of HSCs against oxidative stress. Disruption of CXCR4 receptor in mice leads to increased endogenous production of reactive oxygen species (ROS), resulting in p38 MAPK activation, increased DNA double-strand breaks and apoptosis leading to marked reduction in HSC repopulating potential. Increased ROS levels are directly responsible for exhaustion of the HSC pool and are not linked to loss of quiescence of CXCR4-deficient HSCs. Furthermore, we report that CXCL12 has a direct rescue effect on oxidative stress-induced HSC damage at the mitochondrial level. These data highlight the importance of CXCR4/CXCL12 axis in the regulation of lifespan of HSCs by limiting ROS generation and genotoxic stress. Reactive oxygen species (ROS) are produced during oxidative respiration or through exogenous environmental stresses, such as ionizing radiations or genotoxic treatments. Physiological concentrations of ROS play a role in signal transduction 1,2 , but at high concentrations they can oxidize cell constituents leading to protein carbonyla-tion, lipid peroxidation and DNA damage that activate multiple apoptosis pathways 3. By far, the most important source for ROS is mitochondria 4,5 and their endogenous production as by-products of aerobic respiration is thought to be the cause of most oxidative damages observed in mammals and particularly during aging 6,7. To avoid accumulation of oxidative stress, cells have evolved mechanisms to fine-tune ROS levels. They involve distinct groups of specialized proteins such as superoxide dismutase (SOD), catalase and glutathione peroxidase. Reduced glutathione (GSH), which also exists in the cell in its oxidized form (GSSG), is considered as the most abundant molecule among endogenous antioxidants. Alteration in its redox status serves as an indicator of oxida-tive stress when antioxidant defense mechanisms are not completely efficient and is a common feature of ageing and many pathological situations including AIDS, neurodegenerative diseases and cancer. Hematopoietic stem cells (HSCs) are defined as cells capable of both self-renewal and differentiation into any of the hematopoietic cell lineages, properties that allow hematopoietic reconstitution 8,9. Long-term maintenance of HSCs is precisely regulated by the equilibrium between proliferation and quiescence to maintain their number

Decolonising International Relations and Its Theory: A Critical Conceptual Meditation

One of the main implications of the push for transition from the monoculture of Eurocentric scientific knowledge towards the ecology of knowledge is to force us to pose the question: what does a decolonial turn in International Relations (IR) entail? This article grapples with this question in light of growing demands for a decolonial turn in knowledge and power. The aim is to meditate on this question with a view to open up new avenues for a structured conversation on decolonising IR and its theory. This imperative to decolonise is linked to the question of epistemic justice with implications for the epistemological structure underpinning IR, methodological frameworks for the study of IR, theoretical outlines and the teaching of the discipline. Epistemic justice is a necessity alongside historical justice for those on the margins of a world system constructed with the help of imperialism, systematic enslavement and colonialism. This article discusses the question of the decolonial turn in IR in the hope of stimulating debates on the views of the margins regarding the present state and the future of this area of knowledge, and thus move us closer to an ecology of knowledge and power.https://www.tandfonline.com/loi/cpsa202019-03-21hj2019Political Science