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Surgery and the first 8000 days of life: a review.
Get PDFThe first 8000 days of life, from birth to adulthood, encompasses critical phases that shape a child's health and development. While global health efforts have focused on the first 1000 days, the next 7000 days (ages 2-21) are equally vital, especially concerning the unmet burden of surgical conditions in low- and middle-income countries (LMICs). Approximately 1.7 billion children globally lack access to essential surgical care, with LMICs accounting for 85% of these unmet needs. Common surgical conditions, including congenital anomalies, injuries, infections, and pediatric cancers, often go untreated, contributing to significant mortality and disability. Despite the substantial need, LMICs face severe workforce and infrastructure shortages, with most pediatric surgical conditions requiring specialized skills, equipment, and tailored healthcare systems. Economic analyses have shown that pediatric surgical interventions are cost-effective, with substantial societal benefits. Expanding surgical care for children in LMICs demands investments in workforce training, infrastructure, and health systems integration, complemented by innovative funding and equitable global partnerships. Prioritizing surgical care within national health policies and scaling up children's surgery through initiatives like the Optimal Resources for Children's Surgical Care can improve health outcomes, align with Sustainable Development Goals, and foster equity in global health. Addressing the surgical care gap in LMICs will reduce preventable mortality, enhance quality of life, and drive sustainable growth, emphasizing surgery as an essential component of universal health coverage for children
Post-term births as a risk factor for small for gestational age births and infant mortality in Brazil, Mexico, and Palestinian refugees: An analysis of electronic birth records.
Get PDFBackground: Post-term pregnancy, defined as reaching or exceeding 42 + 0 weeks of gestation, is known to be associated with unfavourable birth outcomes. High-income countries have responded to this risk by widely adopting labour induction protocols in late-term, but many low- and middle-income countries have not. However, understanding underlying mechanisms linking post-term births to adverse newborn and infant outcomes remains limited.
Objective: To investigate the (a) prevalence of post-term, (b) the risk factors associated with post-term (c) the association between post-term births and the risk of small-for-gestational-age (SGA) neonates and of infant mortality in middle-income settings.
Methods: We used existing electronic datasets from the general population of Brazil, Mexico, and Palestinian refugees. Regression models were used to explore the associations between post-term birth and SGA and infant mortality.
Results: We analysed 21,335,033 live births in Brazil (2011-2018), 23,416,126 in Mexico (2008-2019), and 966,102 in Palestinian refugees (2010-2020) (N = 45,717,261). Post-term deliveries accounted for 3.1% of births in Brazil, 1.2% in Mexico, and 2.1% in Palestinian refugees. Post-term births had approximately three times the risk of resulting in SGA neonates compared to term births. Additionally, post-term neonates exhibited a 15% to 40% increased risk of infant mortality compared to term infants. Notably, post-term SGA neonates faced a significantly increased risk of infant mortality compared to term appropriate for gestational age neonates.
Conclusions: These findings emphasise the critical significance of implementing induction strategies to prevent post-term pregnancies and mitigate the associated risks of SGA neonates and subsequent infant mortality. Moreover, the study highlights the importance of accurately determining gestational age and using INTERGROWTH-21st charts to improve the identification of SGA cases, enabling targeted interventions. This is especially relevant because post-term SGA neonates may not exhibit low birthweight (a commonly used risk marker) and, therefore, may miss out on required specialised attention
Evaluating the effectiveness and cost-effectiveness of integrating mass drug administration for helminth control with seasonal malaria chemoprevention in Ghanaian children: Protocol for a cluster randomised controlled trial
Get PDFObjectives: To evaluate the effectiveness and cost-effectiveness of integrating seasonal malaria chemoprevention (SMC) with mass drug administration for helminth control among school-aged children living in communities where the burden of malaria and helminths is high in Ghana, West Africa.
Methods: This cluster randomised controlled trial will enrol 1200 children aged 5–10 years. Eligible children randomised to intervention clusters will receive SMC drugs (sulphadoxine-pyrimethamine plus amodiaquine) and anthelminthic drugs for soil-transmitted helminths—(albendazole), and for schistosomiasis (praziquantel), while children randomised to control clusters will receive SMC drugs alone. Pre- and post-intervention blood, urine and stool samples will be collected from children in both clusters. The effectiveness of the concomitant delivery will be determined by checking whether the combination of SMC and anthelminthic drugs prevents anaemia in the children randomised to the intervention clusters compared to the children in the control clusters. Cost analysis and cost-effectiveness of this integrated delivery approach will be determined by estimating the incremental costs and effects of co-administration of SMC drugs with mass drug administration of anthelminthic drugs compared to SMC alone, including cost savings due to cases of moderate and severe anaemia averted.
Expected findings: The findings of this study will provide evidence to inform public health recommendations for an integrated control of malaria and helminths among children living in the poorest countries of the world
Targeting Aurora Kinases as Essential Cell-Cycle Regulators to Deliver Multi-Stage Antimalarials Against Plasmodium Falciparum.
Get PDFKinases play critical roles in the development and adaptation of Plasmodium falciparum and present novel opportunities for chemotherapeutic intervention. Mitotic kinases that regulate the proliferation of the parasites by controlling nuclear division, segregation, and cytokinesis. We evaluated the potential of human Aurora kinase (Aur) inhibitors to prevent P. falciparum development by targeting members of the Aurora-related kinase (Ark) family in this parasite. Several human AurB inhibitors exhibited multistage potency ( 1000x selectivity towards the parasite. Importantly, we identified PfArk1 as the principal vulnerable Ark family member, with specific inhibition of PfArk1 as the primary target for hesperadin. Hesperadin's whole-cell and protein activity validates it as a unique PfArk1 tool compound. Inhibition of PfArk1 results in the parasite's inability to complete mitotic processes, presenting with unsegregated, multi-lobed nuclei caused by aberrant microtubule organization. This suggests PfArk1 is the main Aur mitotic kinase in proliferative stages of Plasmodium, characterized by bifunctional AurA and B activity. This paves the way for drug-discovery campaigns based on hesperadin targeting PfArk1
Measuring adult mortality from mobile phone surveys in Burkina Faso, Malawi and the Democratic Republic of the Congo.
Get PDFIn many low and middle-income countries, adult mortality estimates are derived from surveys and censuses conducted through face-to-face interviews. These interviews can be time-intensive and are often impractical during health crises or humanitarian emergencies. The expansion in cellphone ownership and network coverage has created new opportunities for collecting demographic data through mobile phone surveys, but our understanding of selection biases and reporting errors of such data remains incomplete. This study reports on adult mortality estimates obtained through mobile phone surveys conducted in Burkina Faso, Malawi and the Democratic Republic of the Congo in 2021 and 2022. To mitigate respondent fatigue and network interruptions, we used a shortened version of the set of questions generally used in surveys to ask about the survival of respondents' siblings. Mortality estimates obtained from mobile phone interviews were lower than those from face-to-face demographic surveys. Mortality rates from the mobile phone surveys were also approximately half those expected from World Population Prospects (WPP) estimates. We attribute this underestimation primarily to reporting errors, including inaccuracies in the ages and timing of sibling deaths collected through the shortened instrument. Coverage biases due to mobile phone ownership likely played a secondary role in the reduced mortality estimates. After imputing ages and dates based on full sibling histories collected in previous face-to-face surveys, mortality rates were more consistent with WPP and Demographic and Health Survey estimates. However, estimates would be improved with more accurate age at death and time of death reports. Mobile phone surveys offer a promising alternative for monitoring adult mortality in settings where face-to-face data collection is not feasible, but they seem to be susceptible to more frequent reporting errors
Learning From Self-Care Practices Among Marginalised Women: Towards Embedding Health Justice in the UK Health Policy.
Get PDFSelf-care is a recurring theme in health policy, frequently positioned as a means of reducing demand on overstretched healthcare systems. In the United Kingdom, the growing interest in self-care as a policy solution has been ascribed to the heightened prevalence of chronic illnesses, over 15 years of austerity and their interaction with neoliberalism. This article juxtaposes policy framing of self-care with how it is conceptualised, practised and experienced by women from racialised minorities and low-income households living in the United Kingdom-groups that routinely encounter structural barriers to healthcare access. This study centres marginalised communities, drawing on arguments that those in such positions hold epistemic advantage, as they often develop nuanced understandings of the social relations that shape their marginalisation. Through thematic analysis of focus groups and interviews, we identify two dominant ways women described and practised self-care: (1) as a response to systemic care scarcity in healthcare services, workplaces and intimate relationships, and (2) as a relational practice embedded within informal networks of support. Grounded in an intersectional analysis, we argue these practices challenge dominant narratives of self-care as an individualised responsibility. Recognising existing self-care labour in marginalised communities requires health policies that address structural inequalities rather than shift burdens onto already constrained individuals
Non-invasive respiratory support in paediatric critical care: protocol for a cohort study emulating the FIRST-line support for Assistance in Breathing in Children (FIRST-ABC) step-up randomised clinical trial using routinely collected data from the Paediatric Intensive Care Audit Network (PICANet) database.
Get PDFINTRODUCTION: The development of the target trial emulation (TTE) methodology has enhanced the conduct of non-randomised studies. By leveraging readily available routinely collected data, TTEs offer opportunities for complementing randomised controlled trials (RCTs), providing more precise estimates and improving the external validity of RCTs. To explore this potential, we selected a successfully completed RCT as a case study. In the FIRST-line support for Assistance in Breathing in Children (FIRST-ABC) step-up RCT, high flow nasal cannula (HFNC) was found to be non-inferior to continuous positive airway pressure (CPAP) in terms of time to liberation from respiratory support in the paediatric critical care setting. We will emulate the FIRST-ABC step-up trial using routinely collected data from the Paediatric Intensive Care Audit Network (PICANet) database.
METHODS AND ANALYSIS: This is a protocol for a TTE that will use longitudinally collected data from the PICANet database. The study aims to emulate the FIRST-ABC step-up RCT using an observational study design in a frequentist framework. We will benchmark the results against the published trial. The study will apply a new-user design by selecting children admitted to paediatric intensive care units that started HFNC or non-invasive ventilatory support (as a surrogate for CPAP). The eligibility criteria and selected outcomes will reflect those of FIRST-ABC within the constraints of the available routinely collected data. We will use advanced quantitative doubly robust methods to minimise the impact of confounding by indication and allow for heterogeneity according to child characteristics. The analysis will be repeated using a Bayesian approach for follow-up research.
ETHICS AND DISSEMINATION: The research received ethics approval from the London School of Hygiene & Tropical Medicine Research Ethics Committee. This study will expand the findings from the FIRST-ABC step-up RCT, providing additional insight from a large representative sample using real-world data. The frequentist and Bayesian approaches will enable a discussion about the advantages and drawbacks of the two strategies. The results will be disseminated to the research and clinical community and made accessible to the public. In addition, the study results will be used in future research, which aims to supplement RCTs with additional evidence from a TTE
Global burden of 292 causes of death in 204 countries and territories and 660 subnational locations, 1990-2023: a systematic analysis for the Global Burden of Disease Study 2023.
Get PDFBACKGROUND: Timely and comprehensive analyses of causes of death stratified by age, sex, and location are essential for shaping effective health policies aimed at reducing global mortality. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2023 provides cause-specific mortality estimates measured in counts, rates, and years of life lost (YLLs). GBD 2023 aimed to enhance our understanding of the relationship between age and cause of death by quantifying the probability of dying before age 70 years (70q0) and the mean age at death by cause and sex. This study enables comparisons of the impact of causes of death over time, offering a deeper understanding of how these causes affect global populations. METHODS: GBD 2023 produced estimates for 292 causes of death disaggregated by age-sex-location-year in 204 countries and territories and 660 subnational locations for each year from 1990 until 2023. We used a modelling tool developed for GBD, the Cause of Death Ensemble model (CODEm), to estimate cause-specific death rates for most causes. We computed YLLs as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. Probability of death was calculated as the chance of dying from a given cause in a specific age period, for a specific population. Mean age at death was calculated by first assigning the midpoint age of each age group for every death, followed by computing the mean of all midpoint ages across all deaths attributed to a given cause. We used GBD death estimates to calculate the observed mean age at death and to model the expected mean age across causes, sexes, years, and locations. The expected mean age reflects the expected mean age at death for individuals within a population, based on global mortality rates and the population's age structure. Comparatively, the observed mean age represents the actual mean age at death, influenced by all factors unique to a location-specific population, including its age structure. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 250-draw distribution for each metric. Findings are reported as counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2023 include a correction for the misclassification of deaths due to COVID-19, updates to the method used to estimate COVID-19, and updates to the CODEm modelling framework. This analysis used 55 761 data sources, including vital registration and verbal autopsy data as well as data from surveys, censuses, surveillance systems, and cancer registries, among others. For GBD 2023, there were 312 new country-years of vital registration cause-of-death data, 3 country-years of surveillance data, 51 country-years of verbal autopsy data, and 144 country-years of other data types that were added to those used in previous GBD rounds. FINDINGS: The initial years of the COVID-19 pandemic caused shifts in long-standing rankings of the leading causes of global deaths: it ranked as the number one age-standardised cause of death at Level 3 of the GBD cause classification hierarchy in 2021. By 2023, COVID-19 dropped to the 20th place among the leading global causes, returning the rankings of the leading two causes to those typical across the time series (ie, ischaemic heart disease and stroke). While ischaemic heart disease and stroke persist as leading causes of death, there has been progress in reducing their age-standardised mortality rates globally. Four other leading causes have also shown large declines in global age-standardised mortality rates across the study period: diarrhoeal diseases, tuberculosis, stomach cancer, and measles. Other causes of death showed disparate patterns between sexes, notably for deaths from conflict and terrorism in some locations. A large reduction in age-standardised rates of YLLs occurred for neonatal disorders. Despite this, neonatal disorders remained the leading cause of global YLLs over the period studied, except in 2021, when COVID-19 was temporarily the leading cause. Compared to 1990, there has been a considerable reduction in total YLLs in many vaccine-preventable diseases, most notably diphtheria, pertussis, tetanus, and measles. In addition, this study quantified the mean age at death for all-cause mortality and cause-specific mortality and found noticeable variation by sex and location. The global all-cause mean age at death increased from 46·8 years (95% UI 46·6-47·0) in 1990 to 63·4 years (63·1-63·7) in 2023. For males, mean age increased from 45·4 years (45·1-45·7) to 61·2 years (60·7-61·6), and for females it increased from 48·5 years (48·1-48·8) to 65·9 years (65·5-66·3), from 1990 to 2023. The highest all-cause mean age at death in 2023 was found in the high-income super-region, where the mean age for females reached 80·9 years (80·9-81·0) and for males 74·8 years (74·8-74·9). By comparison, the lowest all-cause mean age at death occurred in sub-Saharan Africa, where it was 38·0 years (37·5-38·4) for females and 35·6 years (35·2-35·9) for males in 2023. Lastly, our study found that all-cause 70q0 decreased across each GBD super-region and region from 2000 to 2023, although with large variability between them. For females, we found that 70q0 notably increased from drug use disorders and conflict and terrorism. Leading causes that increased 70q0 for males also included drug use disorders, as well as diabetes. In sub-Saharan Africa, there was an increase in 70q0 for many non-communicable diseases (NCDs). Additionally, the mean age at death from NCDs was lower than the expected mean age at death for this super-region. By comparison, there was an increase in 70q0 for drug use disorders in the high-income super-region, which also had an observed mean age at death lower than the expected value. INTERPRETATION: We examined global mortality patterns over the past three decades, highlighting-with enhanced estimation methods-the impacts of major events such as the COVID-19 pandemic, in addition to broader trends such as increasing NCDs in low-income regions that reflect ongoing shifts in the global epidemiological transition. This study also delves into premature mortality patterns, exploring the interplay between age and causes of death and deepening our understanding of where targeted resources could be applied to further reduce preventable sources of mortality. We provide essential insights into global and regional health disparities, identifying locations in need of targeted interventions to address both communicable and non-communicable diseases. There is an ever-present need for strengthened health-care systems that are resilient to future pandemics and the shifting burden of disease, particularly among ageing populations in regions with high mortality rates. Robust estimates of causes of death are increasingly essential to inform health priorities and guide efforts toward achieving global health equity. The need for global collaboration to reduce preventable mortality is more important than ever, as shifting burdens of disease are affecting all nations, albeit at different paces and scales. FUNDING: Gates Foundation
Moderate agreement between the spot albumin‒Creatinine ratio (ACR) and urine albumin (UA) among virally suppressed adults living with HIV in botswana: a cross sectional study.
Get PDFBACKGROUND: Albuminuria predicts end-organ dysfunction in the general population. Its detection in people living with HIV (PLWH) is understudied, despite their heightened risk for end-organ dysfunction. We assessed agreement between albumin‒creatinine ratio (ACR) and urine albumin (UA) tests for albuminuria in a cohort of PLWH in Botswana, where females are more affected by HIV than males.
METHODS: We used cross-sectional convenience sampling to enrol 1533 virally suppressed adults aged ≥ 21 years who were receiving antiretroviral therapy (ART) in Gaborone, Botswana. We measured urine creatinine levels using a colorimetric assay (Jaffe method) and UA levels using an immunoturbidimetric assay. The UA was used due to it being less costly and simpler, making it more feasible for routine use in resource-limited settings compared to the ACR. We defined albuminuria as 30mg/g versus 30 mg/Lusing ACR and UA levels respectively. Agreement between the two tests was assessed using Cohen's kappa for the entire cohort and then separately by sex groups. The optimal UA cut-off point that matched the sex-specific ACR was assessed using Youden's J index.
RESULTS: The ACR detected similar proportion of participants with albuminuria as UA test (17.1% versus 17.6%). There was moderate agreement in the detection of albuminuria using the ACR versus UA test in the entire cohort, among males and females with Kappa statistics of 0.71 (95% CI: 0.67, 0.76; P < 0.001), 0.74 (95% CI: 0.68, 0.80; P < 0.001), and 0.68 (95% CI: 0.60, 0.76; P < 0.001) respectively. Using Youden's J, the optimal cut points for UA levels were 17.9 mg/L (sensitivity = 88.9%, specificity = 87.3%, AUC = 0.94), 25.0 mg/L (sensitivity = 90.4%, specificity = 90.1%, AUC = 0.94) and 15.1 mg/L (sensitivity = 89.7%, specificity = 87.5%, AUC = 0.94) for the entire cohort, males only and females only, respectively.
CONCLUSION: UA and ACR show moderate agreement overall. Optimal UA cutoffs differ slightly by sex, suggesting tailored thresholds may improve detection. Future studies should explore clinical indication(s) for using the ACR versus UA levels among PLWH
Patient-reported perceptions, experiences and preferences around intravenous and oral antibiotics for the treatment of Staphylococcus aureus bacteremia: a descriptive qualitative study.
No full textBACKGROUND: There is growing evidence to support partial oral antibiotic treatment of severe infections such as Staphylococcus aureus bacteremia, but clinical practice is slow to adopt this paradigm. We know little about how patients with severe infection experience and perceive intravenous and oral antibiotics in terms of quality of life and clinical effectiveness. We performed a qualitative study to elicit patients' views on treatment with intravenous and oral antibiotics, aiming to provide insights that could inform collaborative treatment decision-making.
METHODS: We conducted semi-structured interviews with participants in the Staphylococcus aureus Network Adaptive Platform trial pharmacological sub-study PR-O-SNAP by telephone, in person, or via video conferencing. Interviews were recorded, transcribed and coded, and used to analyse and identify themes. Interviews occurred in two phases between November 2024 and January 2025, with interim analysis to refine interview questions between each phase.
RESULTS: We interviewed 17 patients who had received sequential intravenous then oral antibiotics for treatment of Staphylococcus aureus bacteremia. Overall, most participants preferred oral antibiotics for their convenience, which enabled improved mobility and independence, despite a perception that oral regimens were more complex and likely to cause side effects, and that intravenous antibiotics were more effective.
CONCLUSIONS: Choosing a route of antibiotic administration for treatment of severe infection is a nuanced decision which should incorporate not just a patient's clinical status, but also their preferences and personal context. Patient convenience and functional goals should be considered in treatment discussions between clinicians and patients