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Knowing the target oxygen saturation (SpO2) range that results in the best outcomes for acutely hypoxemic adults is important for clinical care, training, and research in low-income and lower-middle income countries (collectively LMICs). The evidence we have for SpO2 targets emanates from high-income countries (HICs), and therefore may miss important contextual factors for LMIC settings. Furthermore, the evidence from HICs is mixed, amplifying the importance of specific circumstances. For this literature review and analysis, we considered SpO2 targets used in previous trials, international and national society guidelines, and direct trial evidence comparing outcomes using different SpO2 ranges (all from HICs). We also considered contextual factors, including emerging data on pulse oximetry performance in different skin pigmentation ranges, the risk of depleting oxygen resources in LMIC settings, the lack of access to arterial blood gases that necessitates consideration of the subpopulation of hypoxemic patients who are also hypercapnic, and the impact of altitude on median SpO2 values. This process of integrating prior study protocols, society guidelines, available evidence, and contextual factors is potentially useful for the development of other clinical guidelines for LMIC settings. We suggest that a goal SpO2 range of 90-94% is reasonable, using high-performing pulse oximeters. Answering context-specific research questions, such as an optimal SpO2 target range in LMIC contexts, is critical for advancing equity in clinical outcomes globally.

Objective To estimate the prevalence of individual chronic conditions and multimorbidity among adults admitted to hospital in countries in sub-Saharan Africa. Methods We systematically searched MEDLINE[R], Embase[R], Global Index Medicus, Global Health and SciELO for publications reporting on patient cohorts recruited between 1 January 2010 and 12 May 2023. We included articles reporting prevalence of pre-specified chronic diseases within unselected acute care services (emergency departments or medical inpatient settings). No language restrictions were applied. We generated prevalence estimates using random-effects meta-analysis alongside 95% confidence intervals, 95% prediction intervals and [I.sup.2] statistics for heterogeneity. To explore associations with age, sex, country-level income status, geographical region and risk of bias, we conducted pre-specified meta-regression, sub-group and sensitivity analyses. Findings Of 6976 identified studies, 61 met the inclusion criteria, comprising data from 20 countries and 376 676 people. None directly reported multimorbidity, but instead reported prevalence for individual conditions. Among medical admissions, the highest prevalence was human immunodeficiency virus infection (36.4%; 95% CI: 31.3-41.8); hypertension (24.4%; 95% CI: 16.7-34.2); diabetes (11.9%; 95% CI: 9.9-14.3); heart failure (8.2%; 95% CI: 5.6-11.9); chronic kidney disease (7.7%; 95% CI: 3.9-14.7); and stroke (6.8%; 95% CI: 4.7-9.6). Conclusion Among patients seeking hospital care in sub-Saharan Africa, multimorbidity remains poorly described despite high burdens of individual chronic diseases. Prospective public health studies of multimorbidity burden are needed to generate integrated and context-specific health system interventions that act to maximize patient survival and well-being. Objectif Mesurer le taux de prevalence des maladies chroniques Indlvldueiles et de la multimorbidite chez les adultes hospitalises en Afrique subsaharienne. Methodes Nous avons analyse systematiquement MEDLINE[R], Embase[R], l'Index Medicus mondial, Global Health et SciELO a la recherche de publications mentionnant des cohortes de patients recrutes entre le 1er janvier 2010 et le 12 mai 2023. Nous avons retenu les articles traitant de la prevalence de certaines maladies chroniques predefinies au sein des services de soins intensifs, sans selection prealable (aux urgences ou en milieu hospitalier). Aucune restriction de langue n'a ete appliquee. Nous avons ensuite estime le taux de prevalence au moyen d'une meta-analyse a effets aleatoires, tout en appliquant des intervalles de confiance de 95%, des intervalles de prevision de 95% et une statistique I2 pour l'heterogeneite. Enfin, en vue d'examiner les liens avec l'age, le sexe, le statut de revenu du pays, la situation geographique et le risque de biais, nous avons mene des analyses predefinies de meta-regression, de sous-groupe et de sensibilite. Resultats Sur les 6976 etudes identifiees, 61 correspondaient aux criteres d'inclusion et contenaient des informations relatives a 20 pays et 376 676 personnes. Bien qu'aucune n'evoquait directement une multimorbidite, la prevalence des cas individuels etait indiquee. Parmi les admissions a l'hopital, le plus haut taux de prevalence concernait: les infections au virus de l'immunodeficience humaine (36,4%; IC de 95%: 31,3-41,8), l'hypertension (24,4%; IC de 95%: 16,7-34.2), le diabete (11,9%; IC de 95%: 9,9-14,3), l'insuffisance cardiaque (8,2%; IC de 95%: 5,6-11,9), les maladies renales chroniques (7,7%; IC de 95%: 3,9-14,7) et les accidents vasculaires cerebraux (6,8%; IC de 95%: 4,7-9,6). Conclusion La multimorbidite des patients se rendant a l'hopital en Afrique subsaharienne demeure peu documentee, en depit de la lourde charge que font peser les maladies chroniques individuelles. Des etudes prospectives de sante publique sont necessaires a ce sujet pour declencher des interventions du systeme de sante adaptees au contexte et ameliorer ainsi les chances de survie et le bien-etre des patients. Objetivo Estimar la prevalence de enfermedades cronicas individuales y la multimorbilidad en adultos ingresados en hospitales en paises del Africa Subsahariana. Metodos Buscamos publicaciones de manera sistematica en MEDLINE[R], Embase[R], Global Index Medicus, Global Health y SciELO que registraran grupos de pacientes reclutados entre el 1 de enero de 2010 y el 12 de mayo de 2023. Incluimos articulos que informaban sobre la prevalencia de enfermedades cronicas predefinidas en el marco de los servicios de cuidados intensivos no seleccionados (salas de urgencias o centros medicos hospitalarios). No se aplicaron restricciones linguisticas. Generamos estimaciones sobre la prevalencia utilizando un metaanalisis de efectos aleatorios, junto con intervalos de confianza del 95%, intervalos de prediccion del 95% y estadistica I2 de heterogeneidad. Para analizar la relacion con la edad, el sexo, el nivel de ingresos del pais, la zona geografica y el riesgo de sesgo, llevamos a cabo una metarregresion predefinida y un analisis de subgrupos y sensibilidad. Resultados De los 6976 estudios seleccionados, 61 cumplian los criterios de inclusion, y englobaban datos de 20 paises y 376 676 personas. Ninguno registraba multimorbilidad de manera directa, sino prevalencia de enfermedades individuales. Entre los ingresos medicos, la prevalencia mas alta correspondio a: la infeccion del virus de la inmunodeficiencia humana (36,4%; IC del 95%: 31,3-41,8), hipertension (24,4%; IC del 95%: 16,7-34,2), diabetes (11,9%; IC del 95%: 9,9-14,3), insuficiencia cardiaca (8,2%; IC del 95%: 5,6-11,9), enfermedad cronica renal (7,7%; IC del 95%: 3,9-14,7) e ictus (6,8%; IC del 95%: 4,7-9,6). Conclusion Entre los pacientes que buscan atencion hospitalaria en el Africa Subsahariana, la multimorbilidad sigue estando escasamente descrita, a pesar de las elevadas tasas de enfermedades cronicas individuales. Los estudios prospectivos de salud publica que versan sobre tasas de multimorbilidad son necesarios para generar intervenciones integradas y adaptadas a las circunstancias por parte del sistema sanitario, para poder aumentar asi la supervivencia y el bienestar de los pacientes. [phrase omitted], Introduction As life expectancy increases in sub-Saharan Africa, so too does the number of people who live with chronic conditions. Multimorbidity is defined as living with two or more chronic [...]

There is a high burden of critical illness in low-income countries (LICs), adding pressure to already strained health systems. Over the next decade, the need for critical care is expected to grow due to ageing populations with increasing medical complexity; limited access to primary care; climate change; natural disasters; and conflict. In 2019, the 72nd World Health Assembly emphasised that an essential part of universal health coverage is improved access to effective emergency and critical care and to 'ensure the timely and effective delivery of life-saving health care services to those in need'. In this narrative review, we examine critical care capacity building in LICs from a health systems perspective. We conducted a systematic literature search, using the World Heath Organisation (WHO) health systems framework to structure findings within six core components or 'building blocks': (1) service delivery; (2) health workforce; (3) health information systems; (4) access to essential medicines and equipment; (5) financing; and (6) leadership and governance. We provide recommendations using this framework, derived from the literature identified in our review. These recommendations are useful for policy makers, health service researchers and healthcare workers to inform critical care capacity building in low-resource settings., Author(s): Stephen A. Spencer [sup.1] [sup.2] [sup.3], Faustina Excel Adipa [sup.4], Tim Baker [sup.5] [sup.6] [sup.7], Ana Maria Crawford [sup.8], Paul Dark [sup.9], Dingase Dula [sup.1] [sup.2], Stephen B. Gordon [...]

BackgroundIn Sub-Saharan Africa cross-sectional studies report a high prevalence of abnormal lung function indicative of chronic respiratory disease. The natural history and health impact of this abnormal lung function in low-and middle-income countries is largely unknown.MethodsA cohort of 1481 adults representative of rural Chikwawa in Malawi were recruited in 2014 and followed-up in 2019. Respiratory symptoms and health-related quality of life (HRQoL) were quantified. Lung function was measured by spirometry.Findings1232 (83%) adults participated; spirometry was available for 1082 (73%). Mean (SD) age 49.5 (17.0) years, 278(23%) had ever smoked, and 724 (59%) were women. Forced expiratory volume in one second (FEV1) declined by 53.4 ml/year (95% CI: 49.0, 57.8) and forced vital capacity (FVC) by 45.2 ml/year (95% CI: 39.2, 50.5) . Chronic airflow obstruction increased from 9.5% (7.6, 11.6%) in 2014 to 17.5% (15.3, 19.9%) in 2019. There was no change in diagnosed asthma or in spirometry consistent with asthma or restriction. Rate of FEV1 decline was not associated with diagnosed Chronic obstructive pulmonary disease (COPD), asthma, or spirometry consistent with asthma, COPD, or restriction. HRQoL was adversely associated with respiratory symptoms (dyspnoea, wheeze, cough), previous tuberculosis, declining FEV1 and spirometry consistent with asthma or restriction. These differences exceeded the minimally important difference.InterpretationIn this cohort, the increasing prevalence of COPD is associated with the high rate of FEV1 decline and lung function deficits present before recruitment. Respiratory symptoms and sub-optimal lung function are independently associated with reduced HRQoL.

BackgroundExposure to household air pollution is associated with an increased risk of pneumonia in children in low- and middle-income countries; however, exposure-response data are limited, and there are uncertainties around the extent to which biomass-fueled cookstoves can reduce these exposures.Research questionWhat is the association between exposure to household air pollution and pneumonia in children under the age of 5 years in rural Malawi and what are the effects of a biomass-fueled cookstove intervention on personal exposure to household air pollution?Study design and methodsWe measured personal exposure to carbon monoxide (CO; 48 hours of continuous measurement and transcutaneous carboxyhemoglobin) every 6 months in children who participated in a cluster-randomized controlled trial of a cleaner burning biomass-fueled cookstove intervention to prevent pneumonia in children under the age of 5 years in rural Malawi (the Cooking And Pneumonia Study). Exposure-response and multivariable analyses were done.ResultsWe recruited 1805 (928 intervention; 877 control) children (mean age, 25.6 months; 50.6% female). We found no evidence of an association between exposure to CO (incident rate ratio, 1.0; 95% CI, 0.967 to 1.014; P = .53) or carboxyhemoglobin (incident rate ratio, 1.00; 95% CI, 0.993 to 1.003; P = .41) in children who experienced pneumonia vs those who did not. Median exposure to CO in the intervention and control groups was was 0.34 (interquartile range, 0.15 to 0.81) and 0.37 parts per million (interquartile range, 0.15 toa 0.97), respectively. The group difference in means was 0.46 (95% CI, -0.95 to 0.012; P = .06).InterpretationExposure to CO in our population was low with no association seen between exposure to CO and pneumonia incidence and no effect of the Cooking And Pneumonia Study intervention on these exposures. These findings suggest that CO may not be an appropriate measure of household air pollution exposure in settings such as rural Malawi and that there is a need to develop ways to measure particulate matter exposures directly in young children instead.Clinical trial registrationISRCTN59448623.

RationaleThere are no population-based studies from sub-Saharan Africa describing longitudinal lung function in adults.ObjectivesTo explore the lung function trajectories and their determinants, including the effects of air pollution exposures and the cleaner-burning biomass-fuelled cookstove intervention of the Cooking and Pneumonia Study (CAPS), in adults living in rural Malawi.MethodsWe assessed respiratory symptoms and exposures, spirometry and measured 48-hour personal exposure to fine particulate matter (PM2.5) and carbon monoxide (CO), on three occasions over 3 years. Longitudinal data were analysed using mixed-effects modelling by maximum likelihood estimation.Measurements and main resultsWe recruited 1481 adults, mean (SD) age 43.8 (17.8) years, including 523 participants from CAPS households (271 intervention; 252 controls), and collected multiple spirometry and air pollution measurements for 654 (44%) and 929 (63%), respectively. Compared with Global Lung Function Initiative African-American reference ranges, mean (SD) FEV1 (forced expiratory volume in 1 s) and FVC (forced vital capacity) z-scores were -0.38 (1.14) and -0.19 (1.09). FEV1 and FVC were determined by age, sex, height, previous TB and body mass index, with FEV1 declining by 30.9 mL/year (95% CI: 21.6 to 40.1) and FVC by 38.3 mL/year (95% CI: 28.5 to 48.1). There was decreased exposure to PM2.5 in those with access to a cookstove but no effect on lung function.ConclusionsWe did not observe accelerated lung function decline in this cohort of Malawian adults, compared with that reported in healthy, non-smoking populations from high-income countries; this suggests that the lung function deficits we measured in adulthood may have origins in early life.

Household air pollution is estimated to cause half a million deaths from pneumonia in children worldwide. The Cooking and Pneumonia Study (CAPS) was conducted to determine whether the use of cleaner-burning biomass-fueled cookstoves would reduce household air pollution and thereby the incidence of pneumonia in young children in rural Malawi. Here we report a cross-sectional assessment of carbon monoxide (CO) exposure and carboxyhemoglobin (COHgB) levels at recruitment to CAPS. Mean (SD; range) 48-h CO exposure of 1928 participating children was 0.90 (2.3; 0⁻49) ppm and mean (SD; range) COHgB level was 5.8% (3.3; 0⁻20.3). Higher mean CO and COHgB levels were associated with location (Chikhwawa versus Chilumba) (OR 3.55 (1.73⁻7.26)); (OR 2.77 (1.08⁻7.08)). Correlation between mean CO and COHgB was poor (Spearman's ρ = 0.09, p < 0.001). The finding of high COHgB levels in young children in rural Malawi that are at levels at which adverse neurodevelopmental and cognitive effects occur is of concern. Effective approaches for reducing exposure to CO and other constituents of air pollution in rural sub-Saharan African settings are urgently needed.

Tools to evaluate and accelerate tuberculosis (TB) vaccine development are needed to advance global TB control strategies. Validated human infection studies for TB have the potential to facilitate breakthroughs in understanding disease pathogenesis, identify correlates of protection, develop diagnostic tools, and accelerate and de-risk vaccine and drug development. However, key challenges remain for realizing the clinical utility of these models, which require further discussion and alignment among key stakeholders. In March 2023, the Wellcome Trust and the International AIDS Vaccine Initiative convened international experts involved in developing both TB and bacillus Calmette-Guérin (BCG) human infection studies (including mucosal and intradermal challenge routes) to discuss the status of each of the models and the key enablers to move the field forward. This report provides a summary of the presentations and discussion from the meeting. Discussions identified key issues, including demonstrating model validity, to provide confidence for vaccine developers, which may be addressed through demonstration of known vaccine effects (eg, BCG vaccination in specific populations), and by comparing results from field efficacy and human infection studies. The workshop underscored the importance of establishing safe and acceptable studies in high-burden settings, and the need to validate >1 model to allow for different scientific questions to be addressed as well as to provide confidence to vaccine developers and regulators around use of human infection study data in vaccine development and licensure pathways. [ABSTRACT FROM AUTHOR]

Exposure to household air pollution (HAP) from solid fuel combustion affects almost half of the world population. Adverse respiratory outcomes such as respiratory infections, impaired lung growth and chronic obstructive pulmonary disease have been linked to HAP exposure. Solid fuel smoke is a heterogeneous mixture of various gases and particulates. Cell culture and animal studies with controlled exposure conditions and genetic homogeneity provide important insights into HAP mechanisms. Impaired bacterial phagocytosis in exposed human alveolar macrophages possibly mediates several HAP-related health effects. Lung pathological findings in HAP-exposed individuals demonstrate greater small airways fibrosis and less emphysema compared with cigarette smokers. Field studies using questionnaires, air pollution monitoring and/or biomarkers are needed to better establish human risks. Some, but not all, studies suggest that improving cookstove efficiency or venting emissions may be associated with reduced respiratory symptoms, lung function decline in women and severe pneumonia in children. Current studies focus on fuel switching, stove technology replacements or upgrades and air filter devices. Several governments have initiated major programmes to accelerate the upgrade from solid fuels to clean fuels, particularly liquid petroleum gas, which provides research opportunities for the respiratory health community.

BackgroundIn urban settings of Africa with rapidly increasing population, traffic-related air pollution is a major contributor to outdoor air pollution (OAP). Although OAP has been identified as a leading cause of global morbidity and mortality, there is however, lack of a simple biomarker to assess levels of exposure to OAP in resource-poor settings. This study evaluated the role of exhaled carbon monoxide (exhCO) as a potential biomarker of exposure to ambient carbon monoxide (ambCO) from OAP.MethodsThis was a descriptive study conducted among male commercial motorcycle riders in Cotonou - the economic capital of Benin. The participants' AmbCO was measured using a portable carbon monoxide (CO) data logger for 8 h during the period of their shift. ExhCO was measured just before and immediately after their shift (8-h) Participants were asked not to cook or to smoke during the day of the measurements. Linear regression analysis was used to assess the association between ambCO and exhCO for the last 2, 4 and 6 h of their shift.ResultsOf 170 participants who completed the study, their mean ± SD age was 42.2 ± 8.4 years, and their mean ± SD daily income was 7.3 ± 2.7$. Also, 95% of the participants' used solid fuels for cooking and only 2% had ever smoked. Average exhCO increased by 5.1 ppm at the end of the shift (p = 0.004). Post-shift exhCO was significantly associated to ambCO, this association was strongest for the last 2 h of OAP exposure before exhCO measurement (β = 0.34, p

BackgroundWHO estimates exposure to air pollution from cooking with solid fuels is associated with over 4 million premature deaths worldwide every year including half a million children under the age of 5 years from pneumonia. We hypothesised that replacing open fires with cleaner burning biomass-fuelled cookstoves would reduce pneumonia incidence in young children.MethodsWe did a community-level open cluster randomised controlled trial to compare the effects of a cleaner burning biomass-fuelled cookstove intervention to continuation of open fire cooking on pneumonia in children living in two rural districts, Chikhwawa and Karonga, of Malawi. Clusters were randomly allocated to intervention and control groups using a computer-generated randomisation schedule with stratification by site, distance from health centre, and size of cluster. Within clusters, households with a child under the age of 4·5 years were eligible. Intervention households received two biomass-fuelled cookstoves and a solar panel. The primary outcome was WHO Integrated Management of Childhood Illness (IMCI)-defined pneumonia episodes in children under 5 years of age. Efficacy and safety analyses were by intention to treat. The trial is registered with ISRCTN, number ISRCTN59448623.FindingsWe enrolled 10 750 children from 8626 households across 150 clusters between Dec 9, 2013, and Feb 28, 2016. 10 543 children from 8470 households contributed 15 991 child-years of follow-up data to the intention-to-treat analysis. The IMCI pneumonia incidence rate in the intervention group was 15·76 (95% CI 14·89-16·63) per 100 child-years and in the control group 15·58 (95% CI 14·72-16·45) per 100 child-years, with an intervention versus control incidence rate ratio (IRR) of 1·01 (95% CI 0·91-1·13; p=0·80). Cooking-related serious adverse events (burns) were seen in 19 children; nine in the intervention and ten (one death) in the control group (IRR 0·91 [95% CI 0·37-2·23]; p=0·83).InterpretationWe found no evidence that an intervention comprising cleaner burning biomass-fuelled cookstoves reduced the risk of pneumonia in young children in rural Malawi. Effective strategies to reduce the adverse health effects of household air pollution are needed.FundingMedical Research Council, UK Department for International Development, and Wellcome Trust.

Original citation: J Clin Invest. 2019;129(10):4523-4538. https://doi.org/10.1172/JCI128865. Citation for this erratum: J Clin Invest. 2022;132(11):e161565. https://doi.org/10.1172/JCI161565. During the preparation of this manuscript, the labels for Figure 5, A and D, [...]

Streptococcus pneumoniae (Spn) is a common cause of respiratory infection, but also frequently colonizes the nasopharynx in the absence of disease. We used mass cytometry to study immune cells from nasal biopsy samples collected following experimental human pneumococcal challenge in order to identify immunological mechanisms of control of Spn colonization. Using 37 markers, we characterized 293 nasal immune cell clusters, of which 7 were associated with Spn colonization. B cell and [CD161.sup.+][CD8.sup.+] T cell clusters were significantly lower in colonized than in noncolonized subjects. By following a second cohort before and after pneumococcal challenge we observed that B cells were depleted from the nasal mucosa upon Spn colonization. This associated with an expansion of Spn polysaccharide- specific and total plasmablasts in blood. Moreover, increased responses of blood mucosa-associated invariant T (MAIT) cells against in vitro stimulation with pneumococcus prior to challenge associated with protection against establishment of Spn colonization and with increased mucosal MAIT cell populations. These results implicate MAIT cells in the protection against pneumococcal colonization and demonstrate that colonization affects mucosal and circulating B cell populations., Introduction Streptococcus pneumoniae (Spn) is a major cause of morbidity and mortality worldwide (1, 2). It is the most common bacterial cause of otitis media, pneumonia, and meningitis in children [...]

A third of the world's population uses solid fuel derived from plant material (biomass) or coal for cooking, heating, or lighting. These fuels are smoky, often used in an open fire or simple stove with incomplete combustion, and result in a large amount of household air pollution when smoke is poorly vented. Air pollution is the biggest environmental cause of death worldwide, with household air pollution accounting for about 3·5-4 million deaths every year. Women and children living in severe poverty have the greatest exposures to household air pollution. In this Commission, we review evidence for the association between household air pollution and respiratory infections, respiratory tract cancers, and chronic lung diseases. Respiratory infections (comprising both upper and lower respiratory tract infections with viruses, bacteria, and mycobacteria) have all been associated with exposure to household air pollution. Respiratory tract cancers, including both nasopharyngeal cancer and lung cancer, are strongly associated with pollution from coal burning and further data are needed about other solid fuels. Chronic lung diseases, including chronic obstructive pulmonary disease and bronchiectasis in women, are associated with solid fuel use for cooking, and the damaging effects of exposure to household air pollution in early life on lung development are yet to be fully described. We also review appropriate ways to measure exposure to household air pollution, as well as study design issues and potential effective interventions to prevent these disease burdens. Measurement of household air pollution needs individual, rather than fixed in place, monitoring because exposure varies by age, gender, location, and household role. Women and children are particularly susceptible to the toxic effects of pollution and are exposed to the highest concentrations. Interventions should target these high-risk groups and be of sufficient quality to make the air clean. To make clean energy available to all people is the long-term goal, with an intermediate solution being to make available energy that is clean enough to have a health impact.

Household air pollution (HAP) from biomass fuels, coal, and kerosene burned in open fires, primitive stoves, and lamps causes at least 2 million deaths per year. Many of these deaths occur in children