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Residual lung abnormality following COVID-19 hospitalisation is characterised by biomarkers of epithelial injury.
Get PDFBACKGROUND: Long term respiratory symptoms are reported following recovery of acute COVID-19 infection and residual lung abnormalities (RLA) on follow-up thoracic computed tomography (CT) after COVID-19 hospitalisation have been observed. It is unknown whether RLA are associated with epithelial lung injury. METHODS: Plasma was sampled from the observational Post HOSPitalisation-COVID cohort at five months post-hospitalisation. Epithelial injury biomarkers Krebs von den Lungen-6 (KL-6), matrix metalloproteinase 7 (MMP-7), surfactant protein-D (SP-D) and surfactant protein-A (SP-A) were assayed. In those without follow-up CT, RLA at-risk was defined by percent predicted DLCO <80% and/or abnormal chest X-ray, otherwise they were considered low-risk. Follow-up CT RLA was defined as combined involvement of ground glass opacity and reticulation ≥10%. FINDINGS: A total of 957 people were included, 846 people with no CT (at-risk n = 103; 12.2%), 111 people with follow-up CT (RLA ≥10% n = 85; 76.6%). All epithelial injury biomarkers were significantly elevated in people at-risk of RLA compared with low-risk. KL-6 and MMP-7 were significantly higher in people with ≥10% RLA than those with <10%, SP-D and SP-A did not reach significance. SP-D and SP-A were associated with percent involvement of reticulation (3.22%, 95% CI 1.19-5.24; 3.03%, 95% CI 0.76-5.30, respectively). INTERPRETATION: RLA after acute COVID-19 infection were consistent with elevated epithelial injury biomarkers and pro-fibrotic signalling. Future studies should address the temporal association between fibrotic biomarkers and resolution or progression of radiological involvement. FUNDING: MRC-UK Research and Innovation and National Institute for Health Research (NIHR) rapid response panel to tackle COVID-19 (MR/V027859/1; COV0319; MR/W006111/1)
Evaluation of fluorometholone as adjunctive medical therapy for trachomatous trichiasis surgery (FLAME): a parallel, double-blind, randomised controlled field trial in the Jimma Zone, Ethiopia.
Get PDFBACKGROUND: In trachoma, trachomatous trichiasis mediates visual impairment. Trachomatous trichiasis surgery has an unacceptably high relapse incidence. We hypothesised that anti-inflammatory therapy with fluorometholone 0·1% suspension (hereafter fluorometholone) eyedrops perioperatively twice daily for 28 days would safely, efficaciously, and cost-effectively reduce postoperative trachomatous trichiasis relapse (PTT). METHODS: In this randomised, parallel, placebo-controlled trial, we compared placebo (artificial tears) with fluorometholone for eyes undergoing trachomatous trichiasis surgery in participants aged 15 years and older at rural health centres and post sites in the Jimma zone, Ethiopia. Participants were randomly allocated (1:1) to either placebo or fluorometholone. Treatment randomisation was stratified and blocked by surgeon. Participants, surgeons, and outcome assessors were masked to treatment assignment. Outcomes were evaluated at 4 weeks, 6 months, and 12 months postoperatively. The primary outcome was cumulative 12-month incidence of PTT, defined as any of: one or more lashes touching the globe; evidence of epilation; or occurrence of repeat trachomatous trichiasis surgery. This study is registered with ClinicalTrials.gov, NCT04149210. FINDINGS: Between Aug 19, 2021, and Nov 30, 2024, 2410 participants (1692 [70·2%] self-reported as female and 718 [29·8%] as male; 3235 eyes) were recruited. 1204 participants were randomly allocated to fluorometholone and 1206 to placebo. 823 (34·1%) participants had bilateral trachomatous trichiasis surgery. Baseline treatment group characteristics were similar; 1180 (98·0%) participants in the fluorometholone group and 1181 (97·9%) in the placebo group were evaluated at the 12-month timepoint. In the intention-to-treat analysis, the cumulative incidences of PTT during 12 months of follow-up were 218 (13·4%) of 1625 eyes in the placebo group and 213 (13·4%) of 1593 eyes in the fluorometholone group (95% CI for difference -2% to 2%). Prespecified secondary efficacy and safety outcomes were not statistically different between groups (all p≥0·10). The incidence of adverse events attributed to study treatment was nine (0·7%) in the placebo group and four (0·3%) in the fluorometholone group (p=0·17); satisfaction with surgery (satisfied or very satisfied) was recorded for 3156 (99·7%) of 3167 eyes. Health economic considerations did not favour programmatic use of fluorometholone given its inefficacy. INTERPRETATION: Fluorometholone twice daily for 4 weeks was safe but not efficacious or cost-effective for reducing PTT, and hence is not recommended for programmatic use. FUNDING: National Eye Institute (National Institutes of Health) and AbbVie. TRANSLATIONS: For the Amharic and Oromifa translations of the abstract see Supplementary Materials section
Future Directions of the National Prostate Cancer Audit.
Get PDFSince its inception in 2013, the National Prostate Cancer Audit (NPCA) has aimed to assess patterns of care and delivery, reporting on the diagnosis, treatment, and outcomes for men diagnosed with prostate cancer in England and Wales [1,2]. This is achieved by utilising national existing linked datasets which allows for methodologically robust analysis to take place and to reduce burden on National Health Service (NHS) organisations and Cancer Alliances [1,2]. Outcomes are derived from national guidance and quality standards, including National Institute for Health and Care Excellence (NICE) guidelines, and performance is measured across a series of performance indicators (PIs) (Figure 1) on both a quarterly basis (known as ‘Quarterly Reports’, based on more timely Rapid Cancer Registration Dataset [RCRD] reporting) and an annual basis (known as ‘State of the Nation’ reports, based primarily on ‘gold standard’ data from the National Cancer Registration Dataset [NCRD]) [1]. Alongside this, the NPCA runs annual quality improvement workshops to ‘close’ the audit cycle loop using enhanced audit and feedback [1,3]. For more information on the NPCA, visit: https://www.npca.org.uk/
Inequalities in health and healthcare utilization among people with disabilities in Ethiopia: evidence from the 2021/2022 Ethiopian Socio-Economic Panel Survey.
Get PDFPURPOSE: People with disabilities, on average, have higher healthcare needs than others in the population. However, evidence shows that they frequently face barriers to accessing healthcare services and incur greater costs when seeking care, although data is lacking for sub-Saharan Africa. This study aimed to assess inequalities in health status and healthcare utilization among people with disabilities in Ethiopia.
METHODS: This study used data from the 2021/22 Ethiopian Socio-Economic Panel Survey (ESPS) and included 17 181 respondents. Logistic regression models were employed for the analysis of the independent association between disability status and both reported illness and healthcare utilization, adjusting sequentially, first for predisposing factors (primarily age and sex) and then for additional variables.
RESULTS: People with disabilities were more likely to report illness compared to those without disabilities (AOR = 2.91, 95% CI: 1.56-5.43). This pattern was consistent among both men (AOR = 3.06, 95% CI: 1.21-7.71) and women (AOR = 2.67, 95% CI: 1.26-5.68). People with disabilities also reported more frequent use of healthcare services (AOR = 1.49, 95% CI: 1.01-2.21). This association remained apparent among men with disabilities compared to those without disabilities (AOR = 1.99, 95% CI: 1.16-3.43), but not among women (AOR = 1.22, 95% CI: 0.67-2.24). Additionally, people with disabilities incurred higher mean annual healthcare expenditures (US 37.89, p = 0.04).
CONCLUSION: People with disabilities in Ethiopia had greater healthcare needs than people without disabilities, which were not fully matched by increased levels of healthcare utilization, and they incurred higher healthcare costs, indicating systemic inequalities in health. A twin-track approach could help address these gaps and support the realization of the human rights of people with disabilities in Ethiopia
Understanding what factors influence community health worker involvement in hypertension service delivery in Kenya: applying a community health system lens.
No full textThe systematic involvement of community health workers (CHWs) in hypertension management can improve outcomes and achieve blood pressure control. However, much of this evidence is from effectiveness trials conducted under ideal conditions, with little evidence from programmes operating in routine conditions. In Kenya, recent policy changes have expanded CHW roles to routinely incorporate non-communicable disease (including hypertension) service delivery. We undertook an exploratory descriptive qualitative study in one county, examining what CHWs now referred to as Community Health Promoters (CHPs) do in relation to hypertension service delivery, influences on their involvement and considerations for sustainability. We found ad hoc and fragmented CHP involvement in practice despite policy guidance for community-level hypertension service delivery. Drawing on the extended health systems building blocks framework, we identified multiple capacities that can support expanded CHPs roles in hypertension care including the pre-existing community health service structure and societal partnerships, as well as their level of motivation. Policy provisions for CHP professionalisation (payment of stipends, provision of CHP kits with varied commodities and training) create an enabling environment. However, sustained adoption of the new CHP roles may be impeded by i) challenges in meeting the financial and supply chain obligations for stipend payments and commodities respectively; and ii) inadequate sensitisation of communities and frontline-providers concerning expanded CHP roles and implications for facility-level hypertension care. To effectively implement recent policies, strengthening coordination and communication across all community and health system actors is needed, as well as clarity and deliberation on long-term financing for the community health system
Defining frailty using a modified Fried's Frailty Phenotype in a Southern African context.
Get PDFINTRODUCTION: Frailty leads to disability, morbidity, and mortality in older persons. The Fried's Frailty Phenotype (FFP), derived in the American Cardiovascular Health Study (CHS), is widely used around the world to define frailty, but lacks adaptation in African populations. OBJECTIVE: To derive a modified FFP definition which best identifies frailty in a Southern African context.
METHODS: A population-based cross-sectional study of adults aged ≥40 years collected data from questionnaires and physical assessments. Original CHS, population-dependent, European Working Group on Sarcopenia in Older People2 (EWGSOP2) and Sarcopenia Definitions and Outcomes Consortium (SDOC) and independent thresholds were all applied to the five FFP criteria (weight loss, exhaustion, low physical activity [PA], low grip strength [GS] and slow walking speed [WS]) to assess non-differentiality, internal consistency, and plausibility.
RESULTS: The 919 participants had a median age of 59 years [IQR 50-70], 53.3% were female. Self-reported exhaustion was reported by 37.5%nd self-reported weight loss by 34.9%. Using the lowest quintile of body mass index (BMI), missed 15.2% of overweight and obese participants who reported weight loss. Using CHS thresholds, low PA was present in 36.7%. Grip strength correlated better with age (r = -0.45) than BMI (r = -0.19). Therefore, the sex-specific tenth percentile of the 40-49-years-age band of the study population was used rather than the CHS approach. The modified SDOC threshold identified slow WS in almost all (85.8%) and was therefore non-differential. The EWGSOP2 and CHS thresholds identified slow WS in 52.9% and 22.9%, respectively, compared to 34.5% using the study population's lowest quintile.
CONCLUSION: Culture and language sensitive questions for self-reported exhaustion and weight loss, CHS thresholds for low PA, and population dependent thresholds for GS and WS were the most suitable modifications in a Southern African setting, highlighting the need for region-specific adaptations when diagnosing frailty
Bridging genomics and pharmacoepidemiology to expand treatment options for alcohol use disorder.
No full textBACKGROUND: Alcohol use disorder (AUD) is a chronic, relapsing condition and a major public health problem. However, few medications are approved to treat AUD, and those available show limited efficacy. Drug repurposing is a cost-effective strategy to identify novel therapeutic uses for existing medications. Here, we describe a pipeline that integrates genetic and electronic health record (EHR) data to identify and evaluate drugs to be repurposed for treating AUD. METHODS: Our approach comprises (1) alcohol-associated gene identification and biological network generation; (2) mapping drugs to target proteins; (3) filtering promising repurposing candidates; and (4) an exemplar pharmacoepidemiologic analysis of the effect of an identified drug (i.e., baclofen) on alcohol consumption. RESULTS: Linking loci to genes from a genome-wide association study (GWAS) of problematic alcohol use identified 94 genes, which we expanded to 327 alcohol-related genes through network-based analyses. Across these analyses, 52 genes were linked to 195 FDA-approved drugs, including four already approved or used off-label to treat AUD. After filtering for safety, relevance, and data availability, 26 candidate drugs, including baclofen, were selected for further evaluation. An evaluation of the real-world effectiveness of baclofen using national EHR data from the United States Department of Veterans Affairs provided evidence that baclofen-exposed patients reduced alcohol consumption more than propensity-score-matched unexposed patients. CONCLUSIONS: This approach, which aligns genomic findings with real-world clinical data, provides an efficient method for identifying promising drug repurposing candidates and prioritizing those that merit evaluation in randomized trials to ultimately advance pharmacotherapies for AUD
Trimester-specific exposure to multiple heat indicators and adverse birth outcomes across four European countries.
Get PDFThe health of pregnant women and their fetuses is increasingly challenged by abnormal heat events. Few studies have disentangled the trimester-specific effects of heat exposure during pregnancy on perinatal outcomes and examined potential differences across multiple heat indicators. This study included singleton births from multiple national and region registries across Europe: Sweden (2014-2019), Belgium (2012-2022), Italy (Lazio Region) (2001-2019), and Greece (1999-2021). We obtained 2-m air temperature, Universal Thermal Climate Index (UTCI), Wet Bulb Globe Temperature (WBGT), and Heat Index data from the ERA5 reanalysis dataset. Our study outcomes were preterm birth (PTB), stillbirth (SB), small for gestational age (SGA), and large for gestational age (LGA). Cox proportional hazard models, with gestational age as the underlying time scale, were applied to evaluate trimester-specific associations between multiple heat indicators and adverse birth outcomes. Country-specific estimates were then combined through meta-analyses. In total, 4,924,422 mother-child pairs were included in the analysis. An increase in mean temperature from the 75th to the 99th percentile in the third trimester was associated with PTB (HR = 1.51, 95% CI: 1.34-1.71), SB (HR = 1.54, 95% CI: 1.44-1.65), SGA (HR = 1.16, 95% CI: 1.11-1.20), and LGA (HR = 1.12, 95% CI: 1.07-1.17). Comparable associations were observed across heat indicators and countries for each trimester. Our findings suggest that the third trimester is a critical exposure window of vulnerability for heat during pregnancy. The comparable effect estimates among heat indicators highlight the usefulness of mean air temperature in Europe
"If there is no data, how do we improve?" Exploring health workers' perspective on stillbirth recording in the Ashanti Region of Ghana.
Get PDFBackground: Health workers play a critical role in documenting the estimated 2 million stillbirths that occur annually. From the moment a stillbirth occurs, a health worker is responsible for recording the birth outcome. The reliability of stillbirth data for informing global and national-level strategies on stillbirths depends on the information recorded by the health worker at the point of care. This study aimed to gain insights into the health worker practices and challenges related to stillbirth recording and reporting.
Methods: The qualitative study explored three objectives using an a priori framework: 1) experiences, perceptions, and attitudes; 2) barriers; and 3) support mechanisms available to health workers for stillbirth recording and reporting. Semi-structured interviews were conducted with 28 health workers, including midwives, medical officers, physician assistants, and health information officers. The study was conducted across four secondary and four primary care facilities in the Ashanti Region of Ghana. All health facilities are government owned. Thematic analysis was performed.
Results: Under experiences, perceptions, and attitudes, inconsistent definitions were used to describe stillbirths. Health workers described stillbirths using various gestational age thresholds, including 24-,28-,36-, and 38-weeks. Some health workers did not reference gestational age when describing stillbirths. Pre-service education shaped knowledge on stillbirths and its recording, with limited opportunities for in-service training. The motivation to record stillbirths was influenced by both intrinsic, driven by the moral imperative to do what is right, and extrinsic factors, influenced by district-level standards. Misclassifications and omissions of stillbirths occurred due to a higher workload, a large volume of forms requiring completion, limited knowledge and experience, and a deliberate effort to minimize facility mortality rates, especially in cases of macerated stillbirths. For barriers to stillbirth recording, midwives reported that blame was evident at three levels: blame from the broader health system, blame within the organizational facility-level, and individual-level blame. The failure to implement audit recommendations was identified as a bottleneck perpetuating negative attitudes toward collecting stillbirth data. The engagement of clinical staff in audit reviews and training was identified as support available to health workers.
Conclusion: We need to understand the health worker experiences, perceptions, and attitudes that underpin stillbirth data to reduce the stillbirth burden. The study suggests several recommendations, including socializing the national stillbirth definition, and reviewing audit protocols
A randomized prospective study of neonatal hepatitis B vaccine immunogenicity in The Gambia and Papua New Guinea.
Get PDFBACKGROUND: Protection of newborns from infection can be achieved through maternal or vaccine-induced antibodies, but the factors influencing vaccine protection (correlate of protection) and subsequent infant immunity remain insufficiently understood. Further investigation is essential to optimize early-life vaccination strategies. OBJECTIVE: We sought to evaluate the impact of timing and sequence of hepatitis B vaccine (HBV) and Bacille Calmette-Guérin (BCG) vaccine within the first week of life on infant HBV immunogenicity and its relationship with maternal antibodies. METHODS: This was an exploratory analysis of a US National Institutes of Health-supported prospective, randomized study of systems biology signatures predictive of HBV immunogenicity in 2 geographically distinct cohorts in The Gambia (GAM; N = 720) and Papua New Guinea (PNG, N = 101) (clinicaltrials.gov NCT03246230). Healthy, hepatitis B surface antigen (anti-HBs)-negative mothers and their infants were enrolled and randomized into 4 vaccine groups: HBV alone, BCG alone, HBV + BCG, or no vaccination (delayed until no later than day of life [DOL]7). Blood samples were collected at birth (DOL0) and on a randomly assigned day (either DOL1, DOL3, or DOL7) with a maximum of 2 blood draws in the first week of life per ethics approval. All infants received catch-up vaccination within DOL7 and the recommended oral polio vaccine within 10 days of birth. Additional blood samples were collected at DOL30 and DOL128 to measure anti-HBs titers and assess immunogenicity. RESULTS: Demographic and clinical characteristics were balanced across vaccine groups, suggesting successful randomization in both cohorts. Similar infant growth trajectories and longitudinal anti-HBs titer trends were observed across all vaccine groups in both cohorts over the first 128 days of life. Maternal and neonatal baseline anti-HBs titers were strongly correlated (GAM: r = 0.98; PNG: r = 0.99). DOL0 titers predicted DOL30 titers (GAM: R 2 = 0.56; PNG: R 2 = 0.945) but not DOL128 titers. Exploratory pairwise comparisons showed that Gambian infants receiving BCG at birth and HBV at DOL7 had higher DOL30 titers than those vaccinated with HBV at DOL1 (Wilcoxon P = .046), whereas in PNG, infants in the HBV + BCG group and the delayed group had higher DOL128 titers than those in the HBV group (Wilcoxon P = .046; Wilcoxon P = .019, respectively). CONCLUSIONS: This study demonstrates the feasibility of conducting large-scale neonatal immunogenicity studies in resource-constrained settings. Our observations underscore the importance of vaccine timing and maternal antibodies in shaping early-life vaccine-induced immunogenicity, offering valuable insights for neonatal vaccination schedules