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Assessments and developments in constructing a National Health Index for policy-making, in the UK
Composite indicators are useful for summarizing and comparing changes among different communities. The UK Office for National Statistics has created an annual England Health Index (2015-2018) comprised of three main health domains - lives, places, and people - to monitor health over time and across different geographical areas and evaluate the nation's health. We reviewed the conceptual coherence and statistical requirements, focusing on three main steps: correlation analysis at different levels, comparison of the implemented weights, and a sensitivity and uncertainty analysis. Based on the results, we have highlighted features that have improved the statistical requirements of the forthcoming UK Health Index.
Delineating Mpl-dependent and -independent phenotypes of Jak2 V617F- positive MPNs in vivo.
The Jak2 V617F mutation stands as the main driver of myeloproliferative neoplasms (MPNs) by constitutively activating signaling of several type I cytokine receptors, namely those for erythropoietin (EpoR), thrombopoietin (TpoR), and Granulocyte Colony Stimulating Factor (G-CSFR). Among these, TpoR assumes a pivotal role in hematopoietic stem cell renewal and differentiation, being positioned as a key driver of MPNs alongside mutated Jak2. However, the impact of TpoR/MPL absence in the context of Jak2 V617F in vivo has been explored only through a transgenic Jak2 V617F mouse model, where regulation of Jak2 expression does not depend on its natural promoter. In this study, we use a novel mouse model expressing Jak2 V617F under its endogenous promoter at the heterozygous state within a Mpl knock-out background. Our findings indicate that erythrocytosis, leukocytosis and moderate splenomegaly with mild spleen peri-vascular fibrosis persist even in the absence of Mpl expression. Notably, the inherent growth-stimulating effect induced by Jak2 V617F remains consistent across diverse early hematopoietic progenitor populations in the absence of Mpl but is reduced at the stem cell level and does not allow clonal expansion in competitive transplantation. Our results delineate Mpl-dependent and -independent phenotypes induced by Jak2 V617F and confirm that inhibiting Mpl expression at the stem cell level negates the long-term advantage of the mutant clone. Consequently, while MPL emerges as a major player in Jak2 V617F positive MPNs, our study underscores that it is not the exclusive contributor, broadening the spectrum for therapeutic intervention.
Pediatric Outcomes Data Collection Instrument is a Useful Patient-Reported Outcome Measure for Physical Function in Children with Osteogenesis Imperfecta.
PurposePatient-reported outcome measures (PROMs) are increasingly recognized as valuable endpoints in clinical trials. The Pediatric Outcomes Data Collection Instrument (PODCI) is a PROM utilized in children with musculoskeletal disorders. We evaluated the validity and reliability of PODCI in children with osteogenesis imperfecta (OI).MethodsPhysical functioning and psychological well-being were assessed using PODCI in a large cohort of children enrolled in a multicenter study conducted by the Brittle Bone Disorders Consortium. Physical function scores were correlated with a validated, observer-rated scale, Brief Assessment of Motor Function (BAMF), and with psychological well-being scores. We calculated sample sizes required to detect clinically meaningful differences in physical function.ResultsFour hundred seventeen children with OI types I, III, and IV were enrolled. Physical function scores in OI type III were significantly lower than those in OI types I and IV. There were no significant differences in psychological well-being. PODCI physical function scores showed moderate-to-strong correlation with BAMF. The Global Functioning Scale, a composite of physical function, did not consistently correlate with psychological well-being.ConclusionPODCI can be a reliable measure of physical functioning in children with OI and offers valuable information about patient-reported health status and new ways to examine the utility of interventions in this population.
Familial coaggregation and shared familiality of functional and internalizing disorders in the Lifelines cohort.
BackgroundFunctional disorders (FDs) are characterized by persistent somatic symptoms and are highly comorbid with internalizing disorders (IDs). To provide much-needed insight into FD etiology, we evaluated FD and ID familial coaggregation and shared familiality.MethodsLifelines is a three-generation cohort study, which assessed three FDs (myalgic encephalomyelitis/chronic fatigue syndrome [ME/CFS], irritable bowel syndrome [IBS], and fibromyalgia [FM]) and six IDs (major depressive disorder [MDD], dysthymia [DYS], generalized anxiety disorder [GAD], agoraphobia [AGPH], social phobia [SPH], and panic disorder [PD]) according to diagnostic criteria. Based on 153,803 individuals, including 90,397 with a first-degree relative in Lifelines, we calculated recurrence risk ratios (λRs) and tetrachoric correlations to evaluate familial aggregation and coaggregation of these disorders in first-degree relatives. We then estimated their familiality and familial correlations.ResultsFamilial aggregation was observed across disorders, with λR ranging from 1.45 to 2.23 within disorders and from 1.17 to 1.94 across disorders. Familiality estimates ranged from 22% (95% confidence interval [CI]: 16-29) for IBS to 42% (95% CI: 33-50) for ME/CFS. Familial correlations ranged from +0.37 (95% CI: 0.24-0.51) between FM and AGPH to +0.97 (95% CI: 0.80-1) between ME/CFS and FM. The highest familial correlation between an ID and FD was +0.83 (95% CI: 0.66-0.99) for MDD and ME/CFS.ConclusionsThere is a clear familial component to FDs, which is partially shared with IDs. This suggests that IDs and FDs share both genetic and family-environmental risk factors. Of the FDs, ME/CFS is most closely related to IDs.
Reply to: What evidence is required to justify the NHS Health Check programme?
Medications that reduce blood pressure and cholesterol are among the most cost-effective healthcare interventions available, but their delivery remains suboptimal. In 2009, the National Health Service (NHS) Health Check was introduced to increase the detection and treatment of major cardiovascular risk factors in people aged 40-74 years. In a prospective observational study using the UK Biobank, we compared health outcomes between NHS Health Check attenders and matched non-attenders. Attenders exhibited higher early rates of new hypertension, hyperlipidaemia, and chronic kidney disease, followed by significantly lower long-term multi-system disease and mortality. A recent critique of our work raises questions regarding observational design limitations, self-selection bias, and discrepancies with randomised controlled trials (RCTs). However, RCTs face ethical and feasibility challenges in large-scale public health interventions and are not immune to self-selection. Furthermore, the argument that self-selection explains our findings is inconsistent with our results. If healthier individuals were disproportionately attending NHS Health Checks, we would expect lower risk across all outcomes. However, we observed an initial increase in new diagnoses suggesting that NHS Health Checks are detecting pre-existing conditions earlier rather than merely attracting healthier individuals. Additionally, the cited RCTs predate modern antihypertensive and statin treatments, and considered heterogenous non-validated interventions. In summary, this critique relies on selective citation of outdated and inappropriate RCTs, an overstatement of selection bias, and an underappreciation of the role of observational research in shaping public health improvements. Our findings indicate that NHS Health Checks contribute to the prevention of multi-system morbidity and mortality, warranting continued investment.
MSP-tracker: A versatile vesicle tracking software tool used to reveal the spatial control of polarized secretion in Drosophila epithelial cells.
Understanding how specific secretory cargoes are targeted to distinct domains of the plasma membrane in epithelial cells requires analyzing the trafficking of post-Golgi vesicles to their sites of secretion. We used the RUSH (retention using selective hooks) system to synchronously release an apical cargo, Cadherin 99C (Cad99C), and a basolateral cargo, the ECM protein Nidogen, from the endoplasmic reticulum and follow their movements to the plasma membrane. We also developed an interactive vesicle tracking framework, MSP-tracker and viewer, that exploits developments in computer vision and deep learning to determine vesicle trajectories in a noisy environment without the need for extensive training data. MSP-tracker outperformed other tracking software in detecting and tracking post-Golgi vesicles, revealing that Cad99c vesicles predominantly move apically with a mean speed of 1.1µm/sec. This is reduced to 0.85 µm/sec by a dominant slow dynein mutant, demonstrating that dynein transports Cad99C vesicles to the apical cortex. Furthermore, both the dynein mutant and microtubule depolymerization cause lateral Cad99C secretion. Thus, microtubule organization plays a central role in targeting apical secretion, suggesting that Drosophila does not have distinct apical versus basolateral vesicle fusion machinery. Nidogen vesicles undergo planar-polarized transport to the leading edge of follicle cells as they migrate over the ECM, whereas most Collagen is secreted at trailing edges. The follicle cells therefore bias secretion of different ECM components to opposite sides of the cell, revealing that the secretory pathway is more spatially organized than previously thought.
Using a Machine Learning Approach to Predict Snakebite Envenoming Outcomes Among Patients Attending the Snakebite Treatment and Research Hospital in Kaltungo, Northeastern Nigeria
The Snakebite Treatment and Research Hospital (SBTRH) is a leading centre for snakebite envenoming care and research in sub-Saharan Africa, treating over 2500 snakebite patients annually. Despite routine data collection, routine analyses are seldom conducted to identify trends or guide clinical practices. This study retrospectively analyzes 1022 snakebite cases at SBTRH from January to June 2024. Most patients were adults (62%) and were predominantly male (72%). Key factors such as age, sex, and time between bite and hospital presentation were associated with outcomes, including recovery, amputation, debridement, and death. Adult males who took more than four hours to arrive to hospital were identified as a high-risk group for poor outcomes. Using patient characteristics, an XGBoost model was developed and was compared to Random Forest and logistic regression models. In general, all models had high positive predictive value and low sensitivity, meaning that if they predicted a patient to experience amputation, debridement, or death, that patient almost always actually experienced amputation, debridement, or death; however, most models rarely made this prediction. The XGBoost model with all features was optimal, given that it had both a high positive predictive value and relatively high sensitivity. This may be of significance to resource-limited settings like SBTRH, where antivenoms can be scarce; however, more research is needed to build better predictive models. These findings underscore the need for targeted interventions for high-risk groups, and further research and integration of machine-learning-driven decision support tools in low-resource-limited clinical settings.
Prevalence of undiagnosed hypertension and associated factors in Ndera sector, Gasabo district of Rwanda: a cross-sectional study.
BackgroundHypertension remains a major global health challenge, including in low- and middle-income countries. In Rwanda, a lack of adequate information and healthcare services impacts healthcare-seeking behaviors, contributing to undiagnosed hypertension in rural areas. Therefore, the need to determine its prevalence and associated factors.MethodsA cross-sectional study was conducted with 393 adults in the Ndera Sector, of Rwanda's Gasabo District, through a multistage sampling technique. Data was gathered using the WHO STEP-wise approach to non-communicable disease risk factor surveillance (STEPS) questionnaire; physical examination was done to determine blood pressure and body-mass index (BMI), after which the data collected was analyzed using SPSS. Newly diagnosed hypertension was determined when on two different intervals, systolic blood pressure readings was > 140 mmHg, and/or the diastolic blood pressure readings was > 90 mmHg, in the absence of previous hypertension diagnosis.ResultsThe overall prevalence of hypertension among patients at Ndera sector was 15%, all of which were newly diagnosed. The mean (SD) age of the participants was 37 (13.7) years and half (53%) were women. The mean systolic blood pressure for men was 124.3 mmHg compared to 120.9 mmHg for women (p = 0.043, 95%CI: 0.12-6.74). Women had a significantly higher mean BMI (26.0) compared to men (22.8) (p ConclusionsThe high prevalence of undiagnosed hypertension in Ndera Sector is linked to gender, older age, higher BMI, location, and lack of hypertension knowledge. These findings call for multifaceted approaches, combining educational initiatives, geographical targeting, lifestyle modifications, and policy implementations, all aimed at mitigating the burden of undiagnosed hypertension and enhancing community health within the Ndera Sector.
Usefulness of MRI-Based Local Surveillance After Surgical Treatment of Musculoskeletal Soft-Tissue Sarcomas: A Systematic Review and Meta-Analysis.
BACKGROUND. The value of routine MRI follow-up after surgical treatment of musculoskeletal soft-tissue sarcoma (STS) is controversial. OBJECTIVE. The purpose of this study was to evaluate the usefulness of MRI-based surveillance for musculoskeletal STS represented by the proportion of local recurrences (LRs) discovered by MRI versus clinically, stratified by imaging surveillance intensity; the characteristics of LRs detected on imaging versus clinically; and the impact of imaging surveillance on survival. EVIDENCE ACQUISITION. Multiple electronic databases were searched systematically for articles published through November 28, 2022, about controlled trials and cohort studies on the usefulness of MRI-based surveillance for musculoskeletal STS. The risk of bias was assessed using an adapted Newcastle-Ottawa scale. Random-effects meta-analyses of the proportion of LRs discovered by MRI as opposed to clinically were conducted. The association of low- versus high-intensity surveillance with the proportion of LR detected on MRI was assessed with a chi-square test of subgroup differences; for this latter assessment, high intensity was defined as at least one local surveillance imaging examination for low-risk tumors and at least three imaging examinations for high-risk tumors during the first 2 posttreatment years. EVIDENCE SYNTHESIS. A total of 4821 titles and abstracts were identified, and 19 studies were included. All studies were retrospective cohorts. There was substantial variability in follow-up approaches. The risk of bias was moderate in 32% and high in 68% of studies. The pooled proportion of LRs detected on MRI was 53% (95% CI, 36-71%) with high-intensity surveillance and 6% (95% CI, 3-9%) with low-intensity surveillance (p < .01). Comparison of LR characteristics (LR size, depth, grade, location, resection margins) detected on imaging versus clinically identified inconsistent results between studies. Trends toward better survival for imaging-detected LRs or more frequent imaging use were noted in four studies. CONCLUSION. When used at a high intensity, MRI-based surveillance can detect many clinically occult LRs, although the studies are small, occasionally yielded conflicting results, and are often of poor quality. A survival benefit could be associated with imaging use, but further research is needed to evaluate the causality of any observed survival differences. CLINICAL IMPACT. MRI-based surveillance after surgical treatment of musculoskeletal STS is useful to detect clinically occult LRs and could improve patient outcomes.
Costs of Tuberculosis at 3 Treatment Centers, Canada, 2010-2016.
We estimated costs of managing different forms of tuberculosis (TB) across Canada by conducting a retrospective chart review and cost assessment of patients treated for TB infection, drug-susceptible TB (DS TB), isoniazid-resistant TB, or multidrug-resistant TB (MDR TB) at 3 treatment centers. We included 90 patients each with TB infection and DS TB, 71 with isoniazid-resistant TB, and 62 with MDR TB. Median per-patient costs for TB infection (in 2020 Canadian dollars) were $804 (interquartile range [IQR] $587-$1,205), for DS TB $12,148 (IQR $4,388-$24,842), for isoniazid-resistant TB $19,319 (IQR $7,117-$41,318), and for MDR TB $119,014 (IQR $80,642-$164,015). Compared with costs for managing DS TB, costs were 11.1 (95% CI 9.1-14.3) times lower for TB infection, 1.7 (95% CI 1.3-2.1) times higher for isoniazid-resistant TB, and 8.1 (95% CI 6.1-10.6) times higher for MDR TB. Broadened TB infection treatment could avert high costs associated with managing TB disease.