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Incidence of possible serious bacterial infection in young infants in the three high-burden countries of the Democratic Republic of the Congo, Kenya, and Nigeria: A secondary analysis of a large, multi-country, multi-centre clinical trial.
Get PDFBACKGROUND: Neonatal infections are a major public health concern worldwide, particularly in low- and middle-income countries, where most of the infection-related deaths in under-five children occur. Sub-Saharan Africa has the highest mortality rates, but there is a lack of data on the incidence of sepsis from this region, hindering efforts to improve child survival. We aimed to determine the incidence of possible serious bacterial infection (PSBI) in young infants in three high-burden countries in Africa.
METHODS: This is a secondary analysis of data from the African Neonatal Sepsis (AFRINEST) trial, conducted in the Democratic Republic of the Congo (DRC), Kenya, and Nigeria between 15 March 2012 and 15 July 2013. We recorded baseline characteristics, the incidence of PSBI (as defined by the World Health Organization), and the incidence of local infections among infants from 0-59 days after birth. We report descriptive statistics.
RESULTS: The incidence of PSBI among 0-59-day-old infants across all three countries was 11.2% (95% confidence interval (CI) = 11.0-11.4). The DRC had the highest incidence of PSBI (19.0%; 95% CI = 18.2-19.8). Likewise, PSBI rates were higher in low birth weight infants (24.5%; 95% CI = 23.1-26.0) and infants born to mothers aged <20 years (14.1%; 95% CI = 13.4-14.8). The incidence of PSBI was higher among infants delivered at home (11.7%; 95% CI = 11.4-12.0).
CONCLUSIONS: The high burden of PSBI among young infants in DRC, Kenya, and Nigeria demonstrates the importance of addressing PSBI in improving child survival in sub-Saharan Africa to reach the Sustainable Development Goals (SDGs). These data can support government authorities, policymakers, programme implementers, non-governmental organisations, and international partners in reducing preventable under-five deaths.
REGISTRATION: Australian New Zealand Clinical Trials Registry: ACTRN12610000286044
In the line of duty: Militarising African epidemics
Get PDFThe deployment of soldiers for epidemic control in Africa has become more acceptable, even when human rights violations occur. This article outlines how this situation has arisen, foregrounding overlapping processes since the 1990s and the implications of Security Council Resolution 2177. It then explores effects with reference to Sierra Leone and Uganda. Drawing on long‐term fieldwork, it discusses militarised epidemic control programmes during Ebola and COVID‐19 outbreaks. It points out similarities in the responses to epidemics in these two countries, including the violent enforcement of regulations, but also striking differences. In Sierra Leone, a democratic transition of governmental power occurred, whereas militarised epidemic control in Uganda helped entrench autocratic public authority. To the extent that there is data available, disease control outcomes in the two countries were not widely divergent, yet the Ugandan response has been valorised. This highlights a drift towards less accountable forms of governance, justified by purported public health objectives
How much should we still worry about QTc prolongation in rifampicin-resistant tuberculosis? ECG findings from TB-PRACTECAL clinical trial.
Get PDFRegimens for the treatment of rifampicin-resistant tuberculosis currently rely on the use of QT-prolonging agents. Using data from the randomized controlled trial, TB-PRACTECAL, we investigated differences in QTcF among participants in the three interventional arms: BPaL (bedaquiline, pretomanid, and linezolid), BPaLC (BPaL with clofazimine), and BPaLM (BPaL with moxifloxacin). Additionally, we assessed whether age, body mass index, and country were causally associated with QTcF prolongation. The trial included participants from South Africa, Uzbekistan, and Belarus. A post hoc analysis of electrocardiogram data was undertaken. Random effects regression was used to model QTcF longitudinally over 24 weeks and causal frameworks guided the analysis of non-randomized independent variables. 328 participants were included in BPaL-based arms. The longitudinal analysis of investigational arms showed an initial QTcF steep increase in the first week. QTcF trajectories between weeks 2 and 24 differed slightly by regimen, with highest mean peak for BPaLC (QTcF 446.5 ms). Overall, there were 397 QTcF >450 ms (of 3,744) and only one QTcF >500 ms. The odds of QTcF >450 ms among participants in any investigational arm, was 8.33 times higher in Uzbekistan compared to Belarus (95% confidence interval: 3.25-21.33). No effect on QTcF prolongation was found for baseline age or body mass index (BMI). Clinically significant QTc prolongation was rare in this cohort of closely monitored participants. Across BPaL-based regimens, BPaLC showed a slightly longer and sustained effect on QTcF prolongation, but the differences (both in magnitude of change and trajectory over time) were clinically unimportant. The disparity in the risk of QTc prolongation across countries would be an important factor to further investigate when evaluating monitoring strategies.
CLINICAL TRIALS: This study is registered with ClinicalTrials.gov as NCT02589782
Sustained Hypothetical Interventions on Midlife Alcohol Consumption in Relation to All-Cause and Cancer Mortality: The Australian Longitudinal Study on Women's Health.
Get PDFNo randomized controlled trial has evaluated the effect of long-term alcohol interventions on mortality. Results reported in existing observational studies may be subject to selection bias and time-varying confounding. Using data from the Australian Longitudinal Study on Women's Health 1946-1951 birth cohort, collected regularly from 1996-2016, we estimated all-cause and cancer mortality had women been assigned various alcohol interventions (in categories ranging from 0 to >30 g/day ethanol, or reduced to ≤20 g/day if higher) at baseline, and had they maintained these levels of consumption. The cumulative risks for all-cause and cancer mortality were 5.6% (10,118 women followed for 20 years) and 2.9% (18 years), respectively. For all-cause and cancer mortality, baseline ethanol up to 30 g/day showed lower risk and >30 g/day showed higher risk relative to abstention. Had women sustainedly followed the interventions, a similar relationship was observed for all-cause mortality. However, the negative association observed for intakes ≤30 g/day and positive association for intakes >30 g/day was not evident for cancer mortality. Our findings suggest that all-cause mortality could have been lower than observed if this cohort of women had consumed some alcohol (no more than 30 g/day) rather than no consumption, but cancer mortality might not
National, regional, and global estimates of low birthweight in 2020, with trends from 2000: a systematic analysis.
Get PDFBACKGROUND: Low birthweight (LBW; <2500 g) is an important predictor of health outcomes throughout the life course. We aimed to update country, regional, and global estimates of LBW prevalence for 2020, with trends from 2000, to assess progress towards global targets to reduce LBW by 30% by 2030.
METHODS: For this systematic analysis, we searched population-based, nationally representative data on LBW from Jan 1, 2000, to Dec 31, 2020. Using 2042 administrative and survey datapoints from 158 countries and areas, we developed a Bayesian hierarchical regression model incorporating country-specific intercepts, time-varying covariates, non-linear time trends, and bias adjustments based on data quality. We also provided novel estimates by birthweight subgroups.
FINDINGS: An estimated 19·8 million (95% credible interval 18·4-21·7 million) or 14·7% (13·7-16·1) of liveborn newborns were LBW worldwide in 2020, compared with 22·1 million (20·7-23·9 million) and 16·6% (15·5-17·9) in 2000-an absolute reduction of 1·9 percentage points between 2000 and 2020. Using 2012 as the baseline, as this is when the Global Nutrition Target began, the estimated average annual rate of reduction from 2012 to 2020 was 0·3% worldwide, 0·85% in southern Asia, and 0·59% in sub-Saharan Africa. Nearly three-quarters of LBW births in 2020 occurred in these two regions: of 19 833 900 estimated LBW births worldwide, 8 817 000 (44·5%) were in southern Asia and 5 381 300 (27·1%) were in sub-Saharan Africa. Of 945 300 estimated LBW births in northern America, Australia and New Zealand, central Asia, and Europe, approximately 35·0% (323 700) weighed less than 2000 g: 5·8% (95% CI 5·2-6·4; 54 800 [95% CI 49 400-60 800]) weighed less than 1000 g, 9·0% (8·7-9·4; 85 400 [82 000-88 900]) weighed between 1000 g and 1499 g, and 19·4% (19·0-19·8; 183 500 [180 000-187 000]) weighed between 1500 g and 1999 g.
INTERPRETATION: Insufficient progress has occurred over the past two decades to meet the Global Nutrition Target of a 30% reduction in LBW between 2012 and 2030. Accelerating progress requires investments throughout the lifecycle focused on primary prevention, especially for adolescent girls and women living in the most affected countries. With increasing numbers of births in facilities and advancing electronic information systems, improvements in the quality and availability of administrative LBW data are also achievable.
FUNDING: The Children's Investment Fund Foundation; the UNDP-UNFPA-UNICEF-WHO World Bank Special Programme of Research, Development and Research Training in Human Reproduction; and the Bill & Melinda Gates Foundation
Evidence Collections for Climate and Health: Active Travel Evidence Collection
Get PDFThe Active Travel Evidence Collection forms part of the Evidence Collections for Climate and Health project. It accompanies the main report, consisting of a methodology report (Appendix C) and three rapid reviews (Appendices D, E, F)
Potassium Supplementation and Prevention of Atrial Fibrillation After Cardiac Surgery: The TIGHT K Randomized Clinical Trial.
Get PDFIMPORTANCE: Supplementing potassium in an effort to maintain high-normal serum concentrations is a widespread strategy used to prevent atrial fibrillation after cardiac surgery (AFACS), but is not evidence-based, carries risks, and is costly. OBJECTIVE: To determine whether a lower serum potassium concentration trigger for supplementation is noninferior to a high-normal trigger. DESIGN, SETTING, AND PARTICIPANTS: This open-label, noninferiority, randomized clinical trial was conducted at 23 cardiac surgical centers in the United Kingdom and Germany. Between October 20, 2020, and November 16, 2023, patients with no history of atrial dysrhythmias scheduled for isolated coronary artery bypass grafting (CABG) surgery were enrolled. The last study patient was discharged from the hospital on December 11, 2023. INTERVENTIONS: Patients were randomly assigned to a strategy of tight or relaxed potassium control (only supplementing if serum potassium concentration fell below 4.5 mEq/L or 3.6 mEq/L, respectively). Patients wore an ambulatory heart rhythm monitor, which was analyzed by a core laboratory masked to treatment assignment. MAIN OUTCOMES AND MEASURES: The prespecified primary end point was clinically detected and electrocardiographically confirmed new-onset AFACS in the first 120 hours after CABG surgery or until hospital discharge, whichever occurred first. All primary outcome events were validated by an event validation committee, which was masked to treatment assignment. Noninferiority of relaxed potassium control was defined as a risk difference for new-onset AFACS with associated upper bound of a 1-sided 97.5% CI of less than 10%. Secondary outcomes included other heart rhythm-related events, clinical outcomes, and cost related to the intervention. RESULTS: A total of 1690 patients (mean age, 65 years; 256 [15%] females) were randomized. The primary end point occurred in 26.2% of patients (n = 219) in the tight group and 27.8% of patients (n = 231) in the relaxed group, which is a risk difference of 1.7% (95% CI, -2.6% to 5.9%). There was no difference between the groups in the incidence of at least 1 AFACS episode detected by any means or by ambulatory heart rhythm monitor alone, non-AFACS dysrhythmias, in-patient mortality, or length of stay. Per-patient cost for purchasing and administering potassium was significantly lower in the relaxed group (mean difference, 103.60-$120.19]; P <.001). CONCLUSIONS AND RELEVANCE: For AFACS prophylaxis, supplementation only when serum potassium concentration fell below 3.6 mEq/L was noninferior to the current widespread practice of supplementing potassium to maintain a serum potassium concentration greater than or equal to 4.5 mEq/L. The lower threshold of supplementation was not associated with any increase in dysrhythmias or adverse clinical outcomes. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04053816
Regional variation in the role of humidity on city-level heat-related mortality.
Get PDFThe rising humid heat is regarded as a severe threat to human survivability, but the proper integration of humid heat into heat-health alerts is still being explored. Using state-of-the-art epidemiological and climatological datasets, we examined the association between multiple heat stress indicators (HSIs) and daily human mortality in 739 cities worldwide. Notable differences were observed in the long-term trends and timing of heat events detected by HSIs. Air temperature (Tair) predicts heat-related mortality well in cities with a robust negative Tair-relative humidity correlation (CT-RH). However, in cities with near-zero or weak positive CT-RH, HSIs considering humidity provide enhanced predictive power compared to Tair. Furthermore, the magnitude and timing of heat-related mortality measured by HSIs could differ largely from those associated with Tair in many cities. Our findings provide important insights into specific regions where humans are vulnerable to humid heat and can facilitate the further enhancement of heat-health alert systems
An assessment of the Henssge method for forensic death time estimation in the early post-mortem interval.
Get PDFBACKGROUND: Time-since-death (TSD) diagnostics are crucial in forensic medical casework. The compound method by Henssge and Madea, which combines temperature and non-temperature-based techniques, is widely used to estimate TSD. This study aims to validate the predictive ability of this method in a cohort of 76 deceased individuals with known times of death (TOD). METHODS: A convenience sample of 76 deceased individuals was examined at the Institute of Legal Medicine, University Medical Center Hamburg-Eppendorf. The study included individuals who died at the hospital and those with sudden death in public. Exclusion criteria included age under 18, known infection or sepsis, polytrauma, bleeding, and hyperthermia. The TSD interval was calculated using the Deathtime software. RESULTS: The overall agreement between the actual TOD and the 95% prediction interval for the TSD was 36.8% (95% CI: 26.1 to 48.7). Warm-stored corpses showed a higher agreement (61.9% [95% CI: 38.4 to 81.9]) compared to cold-stored corpses (27.3% [95% CI: 16.1 to 41.0]). Factors such as body mass index (BMI) and body surface area (BSA) were found to influence the odds of agreement. Assuming a plausible range of ambient temperatures between death and admission improved the agreement in cold-stored cases. CONCLUSION: The study found low to moderate agreement between the actual TOD and the 95% prediction interval using the Henssge method. Incorporating BMI and BSA could improve the predictive accuracy of TSD estimations. Further research with larger sample sizes and external validation is recommended to refine the model
Research priorities to support typhoid conjugate vaccine decision-making in India: evidence assessment and stakeholder survey.
Get PDFBACKGROUND: India has a high typhoid fever burden. In 2022, the National Technical Advisory Group on Immunisation recommended introducing typhoid conjugate vaccine (TCV) into the Universal Immunisation Programme. Our study aims to identify research priorities to support ongoing TCV decision-making in India. METHODS: We identified 45 evidence factors for TCV decision-making in India by adapting WHO's Evidence-to-Recommendation framework. We assigned an evidence gap score for each evidence factor from 0 (low) to 4 (high) based on the availability and sufficiency, quality, breadth and applicability of evidence identified in a literature review (end date 30 November 2023). We assigned each evidence factor an importance score based on the results of an online survey conducted among national immunisation stakeholders (n=22, 1 July 2023-31 October 2023), where they ranked the importance of seven WHO's Evidence-to-Recommendation criteria and several evidence factors within them. We rescaled mean stakeholder rankings into importance scores from 0 (low) to 4 (high). Finally, we added the evidence gap score to the importance score and used the overall scores to identify research priorities to support ongoing TCV decision-making in India. RESULTS: We estimated the highest evidence priority scores for public perception of typhoid fever, vaccination budget impact, vaccine availability, socioeconomic impact, fiscal space, antimicrobial resistance tracking, typhoid fever mortality, public perception of TCV, immunisation managers' acceptance and vaccine schedule preferences among caregivers. CONCLUSION: By adapting WHO's Evidence-to-Recommendation framework to the Indian context, we systematically identified several research priorities to support ongoing decision-making on TCV in India. These priorities will evolve as new research studies and questions emerge about the optimal scheduling, roll-out and implementation of TCV in India