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ISARIC has launched a longitudinal observational study to measure prevalence and risk factors of long-term health and psychosocial consequences of COVID-19. The researchers are inviting hospitals and healthcare sites worldwide to join this new study. The patient survey has been designed to assess long-term health and psychosocial consequences of COVID-19 at serial intervals for up to three to five years, depending on resources.
A landscape analysis of the key global stakeholders working on interventions around preterm birth that improve neonatal mortality and morbidity.
Background Over a decade after the landmark ‘Born too Soon’ report, preterm birth remains a leading cause of under-five mortality. Addressing its global burden is key to meeting United Nations Sustainable Development Goal 3; to end preventable deaths of newborns and children by 2030. We conducted a landscape analysis to explore the types of organisations addressing preterm birth, highlight the scope of interventions and initiatives, and identify gaps and opportunities for shared learning. Methods We combined google searches with citation searching, and opinion of experts in child health, to identify the major global stakeholders working to improve outcomes of preterm birth, with evidence of activity since 2012. We conducted a thematic analysis and narrative synthesis of key stakeholder websites to categorise their functions and priorities, and the types of interventions they were implementing. Results A total of 38 key organisations and 28 interventions were derived from the searches. Organisations were thematically grouped into knowledge sharing (n = 15), knowledge production (n = 12), funders (n = 6), legislation and advocacy (n = 15), implementer (n = 14) and network organisations (n = 11). Interventions covered a wide scope of functions including education (n = 11), research (n = 10), resources (n = 7), legislation (n = 2), and health systems (n = 2) interventions. The majority of global stakeholders were funded from and headquartered within high-income settings. Discussion There is scope for significant learning across global stakeholders, in particular to support carers in low-resource settings. Further opportunities for impact include a need for community-based initiatives and whole systems approach that address the long-term needs of preterm babies and their families, particularly in low- and middle-income countries (LMIC) settings. Greater knowledge production and funding from LMICs is needed to create contextually relevant resources and address implementation challenges.
Presumed Risk Factors and Biomarkers for Severe Respiratory Syncytial Virus Disease and Related Sequelae: Protocol for an Observational Multicenter, Case-Control Study From the Respiratory Syncytial Virus Consortium in Europe (RESCEU).
Respiratory syncytial virus (RSV) is the leading viral pathogen associated with acute lower respiratory tract infection and hospitalization in children < 5 years of age worldwide. While there are known clinical risk factors for severe RSV infection, the majority of those hospitalized are previously healthy infants. There is consequently an unmet need to identify biomarkers that predict host response, disease severity, and sequelae. The primary objective is to identify biomarkers of severe RSV acute respiratory tract infection (ARTI) in infants. Secondary objectives include establishing biomarkers associated with respiratory sequelae following RSV infection and characterizing the viral load, RSV whole-genome sequencing, host immune response, and transcriptomic, proteomic, metabolomic and epigenetic signatures associated with RSV disease severity. Six hundred thirty infants will be recruited across 3 European countries: the Netherlands, Spain, and the United Kingdom. Participants will be recruited into 2 groups: (1) infants with confirmed RSV ARTI (includes upper and lower respiratory tract infections), 500 without and 50 with comorbidities; and (2) 80 healthy controls. At baseline, participants will have nasopharyngeal, blood, buccal, stool, and urine samples collected, plus complete a questionnaire and 14-day symptom diary. At convalescence (7 weeks ± 1 week post-ARTI), specimen collection will be repeated. Laboratory measures will be correlated with symptom severity scores to identify corresponding biomarkers of disease severity.Clinical trials registrationNCT03756766.
Transcriptomic response and immunological responses to chimpanzee adenovirus- and MVA viral-vectored vaccines for RSV in healthy adults
AbstractCohorts of healthy younger adults (18–50yrs) and healthy older adults (60–75yrs) were immunized intramuscularly or intranasally with an adenovirus-vectored RSV vaccine (PanAd3-RSV) as a prime dose and boosted with PanAd3-RSV or a poxvirus-vectored vaccine (MVA-RSV) encoding the same insert. Whole blood gene expression was measured at baseline, 3- and 7-days post vaccination. Intramuscular prime vaccination with PanAd3-RSV induced differential expression of 643 genes (DEGs, FDR < 0.05). Intranasal prime vaccination with PanAd3-RSV did not induce any differentially expressed genes (DEGs) in blood samples at 3 days post vaccination. Intranasally primed participants showed greater numbers of DEGS on boosting than intramuscularly primed participants. The most highly enriched biological processes related to DEGs after both prime and boost vaccination were type-1 interferon related pathways, lymphocytic and humoral immune responses.
Not just surveys and indicators: narratives capture what really matters for health system strengthening.
Health system strengthening remains elusive and challenging. Health systems in many countries in sub-Saharan Africa are frequently characterised as weak, with inadequate management and accountability mechanisms, and poor human and financial resources. Putting patients and staff at the heart of health systems is an essential step towards strengthening them. As one of the three pillars of quality in health care, understanding patient experiences is key to moving towards people-centred care. Yet patient experiences are not a singular concept. Patient narratives can convey individual experiences of illness and health care, which complement and augment epidemiological and public health evidence. These narratives, gathered with rigorous, interview-based research and shared with digital tools (audio and video), can generate persuasive evidence. This evidence has important potential for influencing policy and practice, and for supporting people-centred care, but has not been tested systematically in low-income countries. In the Kenyan context of newborn health, work under way is generating evidence to show the transformative potential of patient narratives.
Diagnostic challenges and antibody kinetics in a paediatric traveller with scrub typhus
Diagnosing scrub typhus in travellers is challenging due to symptom similarities with other travel-related illnesses and limited early diagnostic tools. We present a distinctive case of scrub typhus in a child traveller, providing a comprehensive account of the case, the diagnostic challenges encountered, laboratory findings and the dynamics of antibodies.
Global fertility in 204 countries and territories, 1950-2021, with forecasts to 2100: a comprehensive demographic analysis for the Global Burden of Disease Study 2021.
BACKGROUND: Accurate assessments of current and future fertility-including overall trends and changing population age structures across countries and regions-are essential to help plan for the profound social, economic, environmental, and geopolitical challenges that these changes will bring. Estimates and projections of fertility are necessary to inform policies involving resource and health-care needs, labour supply, education, gender equality, and family planning and support. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 produced up-to-date and comprehensive demographic assessments of key fertility indicators at global, regional, and national levels from 1950 to 2021 and forecast fertility metrics to 2100 based on a reference scenario and key policy-dependent alternative scenarios. METHODS: To estimate fertility indicators from 1950 to 2021, mixed-effects regression models and spatiotemporal Gaussian process regression were used to synthesise data from 8709 country-years of vital and sample registrations, 1455 surveys and censuses, and 150 other sources, and to generate age-specific fertility rates (ASFRs) for 5-year age groups from age 10 years to 54 years. ASFRs were summed across age groups to produce estimates of total fertility rate (TFR). Livebirths were calculated by multiplying ASFR and age-specific female population, then summing across ages 10-54 years. To forecast future fertility up to 2100, our Institute for Health Metrics and Evaluation (IHME) forecasting model was based on projections of completed cohort fertility at age 50 years (CCF50; the average number of children born over time to females from a specified birth cohort), which yields more stable and accurate measures of fertility than directly modelling TFR. CCF50 was modelled using an ensemble approach in which three sub-models (with two, three, and four covariates variously consisting of female educational attainment, contraceptive met need, population density in habitable areas, and under-5 mortality) were given equal weights, and analyses were conducted utilising the MR-BRT (meta-regression-Bayesian, regularised, trimmed) tool. To capture time-series trends in CCF50 not explained by these covariates, we used a first-order autoregressive model on the residual term. CCF50 as a proportion of each 5-year ASFR was predicted using a linear mixed-effects model with fixed-effects covariates (female educational attainment and contraceptive met need) and random intercepts for geographical regions. Projected TFRs were then computed for each calendar year as the sum of single-year ASFRs across age groups. The reference forecast is our estimate of the most likely fertility future given the model, past fertility, forecasts of covariates, and historical relationships between covariates and fertility. We additionally produced forecasts for multiple alternative scenarios in each location: the UN Sustainable Development Goal (SDG) for education is achieved by 2030; the contraceptive met need SDG is achieved by 2030; pro-natal policies are enacted to create supportive environments for those who give birth; and the previous three scenarios combined. Uncertainty from past data inputs and model estimation was propagated throughout analyses by taking 1000 draws for past and present fertility estimates and 500 draws for future forecasts from the estimated distribution for each metric, with 95% uncertainty intervals (UIs) given as the 2·5 and 97·5 percentiles of the draws. To evaluate the forecasting performance of our model and others, we computed skill values-a metric assessing gain in forecasting accuracy-by comparing predicted versus observed ASFRs from the past 15 years (2007-21). A positive skill metric indicates that the model being evaluated performs better than the baseline model (here, a simplified model holding 2007 values constant in the future), and a negative metric indicates that the evaluated model performs worse than baseline. FINDINGS: During the period from 1950 to 2021, global TFR more than halved, from 4·84 (95% UI 4·63-5·06) to 2·23 (2·09-2·38). Global annual livebirths peaked in 2016 at 142 million (95% UI 137-147), declining to 129 million (121-138) in 2021. Fertility rates declined in all countries and territories since 1950, with TFR remaining above 2·1-canonically considered replacement-level fertility-in 94 (46·1%) countries and territories in 2021. This included 44 of 46 countries in sub-Saharan Africa, which was the super-region with the largest share of livebirths in 2021 (29·2% [28·7-29·6]). 47 countries and territories in which lowest estimated fertility between 1950 and 2021 was below replacement experienced one or more subsequent years with higher fertility; only three of these locations rebounded above replacement levels. Future fertility rates were projected to continue to decline worldwide, reaching a global TFR of 1·83 (1·59-2·08) in 2050 and 1·59 (1·25-1·96) in 2100 under the reference scenario. The number of countries and territories with fertility rates remaining above replacement was forecast to be 49 (24·0%) in 2050 and only six (2·9%) in 2100, with three of these six countries included in the 2021 World Bank-defined low-income group, all located in the GBD super-region of sub-Saharan Africa. The proportion of livebirths occurring in sub-Saharan Africa was forecast to increase to more than half of the world's livebirths in 2100, to 41·3% (39·6-43·1) in 2050 and 54·3% (47·1-59·5) in 2100. The share of livebirths was projected to decline between 2021 and 2100 in most of the six other super-regions-decreasing, for example, in south Asia from 24·8% (23·7-25·8) in 2021 to 16·7% (14·3-19·1) in 2050 and 7·1% (4·4-10·1) in 2100-but was forecast to increase modestly in the north Africa and Middle East and high-income super-regions. Forecast estimates for the alternative combined scenario suggest that meeting SDG targets for education and contraceptive met need, as well as implementing pro-natal policies, would result in global TFRs of 1·65 (1·40-1·92) in 2050 and 1·62 (1·35-1·95) in 2100. The forecasting skill metric values for the IHME model were positive across all age groups, indicating that the model is better than the constant prediction. INTERPRETATION: Fertility is declining globally, with rates in more than half of all countries and territories in 2021 below replacement level. Trends since 2000 show considerable heterogeneity in the steepness of declines, and only a small number of countries experienced even a slight fertility rebound after their lowest observed rate, with none reaching replacement level. Additionally, the distribution of livebirths across the globe is shifting, with a greater proportion occurring in the lowest-income countries. Future fertility rates will continue to decline worldwide and will remain low even under successful implementation of pro-natal policies. These changes will have far-reaching economic and societal consequences due to ageing populations and declining workforces in higher-income countries, combined with an increasing share of livebirths among the already poorest regions of the world. FUNDING: Bill & Melinda Gates Foundation.
Time to full enteral feeds in hospitalised preterm and very low birth weight infants in Nigeria and Kenya.
BackgroundPreterm (born < 37 weeks' gestation) and very low birthweight (VLBW; <1.5kg) infants are at the greatest risk of morbidity and mortality within the first 28 days of life. Establishing full enteral feeds is a vital aspect of their clinical care. Evidence predominantly from high income countries shows that early and rapid advancement of feeds is safe and reduces length of hospital stay and adverse health outcomes. However, there are limited data on feeding practices and factors that influence the attainment of full enteral feeds among these vulnerable infants in sub-Saharan Africa.AimTo identify factors that influence the time to full enteral feeds, defined as tolerance of 120ml/kg/day, in hospitalised preterm and VLBW infants in neonatal units in two sub-Saharan African countries.MethodsDemographic and clinical variables were collected for newborns admitted to 7 neonatal units in Nigeria and Kenya over 6-months. Multiple linear regression analysis was conducted to identify factors independently associated with time to full enteral feeds.ResultsOf the 2280 newborn infants admitted, 484 were preterm and VLBW. Overall, 222/484 (45.8%) infants died with over half of the deaths (136/222; 61.7%) occurring before the first feed. The median (inter-quartile range) time to first feed was 46 (27, 72) hours of life and time to full enteral feeds (tFEF) was 8 (4.5,12) days with marked variation between neonatal units. Independent predictors of tFEF were time to first feed (unstandardised coefficient B 1.69; 95% CI 1.11 to 2.26; p value <0.001), gestational age (1.77; 0.72 to 2.81; <0.001), the occurrence of respiratory distress (-1.89; -3.50 to -0.79; <0.002) and necrotising enterocolitis (4.31; 1.00 to 7.62; <0.011).ConclusionThe use of standardised feeding guidelines may decrease variations in clinical practice, shorten tFEF and thereby improve preterm and VLBW outcomes.
The path to universal health coverage in five African and Asian countries: examining the association between insurance status and health-care use.
Despite major efforts to achieve universal health coverage (UHC), progress has lagged in many African and Asian countries. A key strategy pursued by many countries is the use of health insurance to increase access and affordability. However, evidence on insurance coverage and on the association between insurance and UHC is mixed. We analysed nationally representative cross-sectional data collected between 2022 and 2023 in Ethiopia, Kenya, South Africa, India, and Laos. We described public and private insurance coverage by sociodemographic factors and used logistic regression to examine the associations between insurance status and seven health-care use outcomes. Health insurance coverage ranged from 25% in India to 100% in Laos. The share of private insurance ranged from 1% in Ethiopia to 13% in South Africa. Relative to the population with private insurance, the uninsured population had reduced odds of health-care use (adjusted odds ratio 0·68, 95% CI 0·50-0·94), cardiovascular examinations (0·63, 0·47-0·85), eye and dental examinations (0·54, 0·42-0·70), and ability to get or afford care (0·64, 0·48-0·86); private insurance was not associated with unmet need, mental health care, and cancer screening. Relative to private insurance, public insurance was associated with reduced odds of health-care use (0·60, 0·43-0·82), mental health care (0·50, 0·31-0·80), cardiovascular examinations (0·62, 0·46-0·84), and eye and dental examinations (0·50, 0·38-0·65). Results were highly heterogeneous across countries. Public health insurance appears to be only weakly associated with access to health services in the countries studied. Further research is needed to improve understanding of these associations and to identify the most effective financing strategies to achieve UHC.
Population confidence in the health system in 15 countries: results from the first round of the People's Voice Survey.
Population confidence is essential to a well functioning health system. Using data from the People's Voice Survey-a novel population survey conducted in 15 low-income, middle-income, and high-income countries-we report health system confidence among the general population and analyse its associated factors. Across the 15 countries, fewer than half of respondents were health secure and reported being somewhat or very confident that they could get and afford good-quality care if very sick. Only a quarter of respondents endorsed their current health system, deeming it to work well with no need for major reform. The lowest support was in Peru, the UK, and Greece-countries experiencing substantial health system challenges. Wealthy, more educated, young, and female respondents were less likely to endorse the health system in many countries, portending future challenges for maintaining social solidarity for publicly financed health systems. In pooled analyses, the perceived quality of the public health system and government responsiveness to public input were strongly associated with all confidence measures. These results provide a post-COVID-19 pandemic baseline of public confidence in the health system. The survey should be repeated regularly to inform policy and improve health system accountability.