Challenges of stroke management in resource-limited settings: A case- based reflection

A 19-year-old man presented with a 1-year history of headache, generalised body weakness, progressive memory loss, and disorientation. One month prior to admission, there was aggravation of the weakness of the right upper limb, with new-onset difficulty with mastication, speech impairment, apathy, and urinary incontinence. On clinical examination, the patient had a motor aphasia and a right-sided hemiparesis with increased muscle tone and hyperreflexia. A noncontrast computed tomography (CT) scan of the brain revealed large ischaemic strokes extending beyond the classical vascular territories. Cerebrospinal fluid analysis showed a mildly increased protein level. The electrocardiogram revealed an irregular sinus bradycardia. The remainder of the cardiovascular and laboratory workup was unremarkable. Considering a working diagnosis of central nervous system vasculitis, the patient was treated with aspirin, prednisolone, and physiotherapy. However, he died suddenly a few weeks later. Based on this case, we discuss the challenges of stroke management in resource-limited settings, provide practical tips for general practitioners, reflect on the potential avenues for short- and long-term action, and introduce the budding collaboration platform between the University College London, the University of Liverpool, the Queen Elizabeth Central Hospital, and the Malawi-Liverpool-Wellcome Trust Clinical Research Programme

Targeting Antibiotics to Households for Trachoma Control

Repeated ocular infection with the bacterium Chlamydia trachomatis leads to the development of trachoma, a major cause of infectious blindness worldwide. Mass distribution of antibiotics, a component of the current trachoma control strategy, has had success in reducing infection in some areas, but results in a large number of uninfected people receiving antibiotics. We have previously shown that transmission of the bacteria between people in the same household is very efficient. Here, we investigated the effectiveness and cost-effectiveness of targeting antibiotics to households with active trachoma (inflammatory disease) compared to mass distribution, using data from four trachoma-endemic populations and a mathematical model of transmission. We found a high correspondence between households with active trachoma and infected households. In all populations the household targeted approach was predicted to be as effective as mass distribution, but it reduced the number of uninfected individuals receiving antibiotics, making the targeted strategy more cost-effective when antibiotics are not donated. Assuming antibiotics are donated, we predicted the targeted strategy to be more cost effective if it increases the proportion of infected individuals receiving treatment. Further work to address the feasibility and the cost variability in implementing the targeted approach in different settings is now required

The Development of an Age-Structured Model for Trachoma Transmission Dynamics, Pathogenesis and Control

Trachoma is the worldwide leading infectious cause of blindness and is due to repeated conjunctival infection with Chlamydia trachomatis bacteria. The effects of control interventions on population levels of infection and active disease can be promptly measured, but the effects on severe ocular disease outcomes require long-term monitoring. We present a mathematical model of trachoma transmission and disease to predict the impact of interventions on blinding trachoma. The model is based on the concept of multiple re-infections leading to progressive scarring of the eye and the potentially blinding disease sequelae. It includes aspects of trachoma natural history such as an increasing rate of recovery from infection, and a decreasing chlamydial load with subsequent infections. The model reproduces key features of trachoma epidemiology such as the age-profile of infection prevalence; a shift in the prevalence peak toward younger ages in higher-transmission environments; and a rising profile of the prevalence of the severe sequelae (scarring, trichiasis), as well as estimates of the number of infections experienced before these sequelae appear. The model can be used to examine the outcomes of various control strategies on infection and disease and can help to plan treatment interventions for different endemic settings

Quantifying the Genetic Correlation between Multiple Cancer Types.

Background: Many cancers share specific genetic risk factors, including both rare high-penetrance mutations and common SNPs identified through genome-wide association studies (GWAS). However, little is known about the overall shared heritability across cancers. Quantifying the extent to which two distinct cancers share genetic origin will give insights to shared biological mechanisms underlying cancer and inform design for future genetic association studies.Methods: In this study, we estimated the pair-wise genetic correlation between six cancer types (breast, colorectal, lung, ovarian, pancreatic, and prostate) using cancer-specific GWAS summary statistics data based on 66,958 case and 70,665 control subjects of European ancestry. We also estimated genetic correlations between cancers and 14 noncancer diseases and traits.Results: After adjusting for 15 pair-wise genetic correlation tests between cancers, we found significant (P < 0.003) genetic correlations between pancreatic and colorectal cancer (rg = 0.55, P = 0.003), lung and colorectal cancer (rg = 0.31, P = 0.001). We also found suggestive genetic correlations between lung and breast cancer (rg = 0.27, P = 0.009), and colorectal and breast cancer (rg = 0.22, P = 0.01). In contrast, we found no evidence that prostate cancer shared an appreciable proportion of heritability with other cancers. After adjusting for 84 tests studying genetic correlations between cancer types and other traits (Bonferroni-corrected P value: 0.0006), only the genetic correlation between lung cancer and smoking remained significant (rg = 0.41, P = 1.03 × 10-6). We also observed nominally significant genetic correlations between body mass index and all cancers except ovarian cancer.Conclusions: Our results highlight novel genetic correlations and lend support to previous observational studies that have observed links between cancers and risk factors.Impact: This study demonstrates modest genetic correlations between cancers; in particular, breast, colorectal, and lung cancer share some degree of genetic basis. Cancer Epidemiol Biomarkers Prev; 26(9); 1427-35. ©2017 AACR

Diabetes and risk of pancreatic cancer: a pooled analysis from the pancreatic cancer cohort consortium

Diabetes is a suspected risk factor for pancreatic cancer, but questions remain about whether it is a risk factor or a result of the disease. This study prospectively examined the association between diabetes and the risk of pancreatic adenocarcinoma in pooled data from the NCI pancreatic cancer cohort consortium (PanScan). The pooled data included 1,621 pancreatic adenocarcinoma cases and 1,719 matched controls from twelve cohorts using a nested case-control study design. Subjects who were diagnosed with diabetes near the time (< 2 years) of pancreatic cancer diagnosis were excluded from all analyses. All analyses were adjusted for age, race, gender, study, alcohol use, smoking, BMI, and family history of pancreatic cancer. Self-reported diabetes was associated with a forty percent increased risk of pancreatic cancer (OR = 1.40, 95 % CI: 1.07, 1.84). The association differed by duration of diabetes; risk was highest for those with a duration of 2-8 years (OR = 1.79, 95 % CI: 1.25, 2.55); there was no association for those with 9+ years of diabetes (OR = 1.02, 95 % CI: 0.68, 1.52). These findings provide support for a relationship between diabetes and pancreatic cancer risk. The absence of association in those with the longest duration of diabetes may reflect hypoinsulinemia and warrants further investigation

An exploration of the relationship between educational background and the coaching behaviours and practice activities of professional youth soccer coaches

This paper is closed access until 12 December 2019.Background and purpose: Despite the proliferation in recent years of higher education establishments offering tertiary-level study in the field of sports coaching, there is a lack of research into the impact of such courses on coaching practice. The behaviours employed and activities used by coaches during practice sessions is an area where one might expect to see such impact, indeed certain studies have tentatively noted the educational qualifications of coaches and suggested that this may play a role in the application of behaviours more aligned with player learning. The purpose of this study was therefore to compare youth soccer coaches with and without tertiary-level qualifications, examining their coaching behaviours and practice activities. Method: The participants were 10 male professional youth soccer coaches aged 24–55 with an average of 13 years coaching experience. Five of the coaches had completed undergraduate degree courses related to sport coaching. All of the coaches worked with players aged under 9 to under 18 in the youth academy of an English professional soccer club. Systematic observation of coach behaviour and practice activities was carried out using the Coach Analysis and Intervention System (Cushion et al. 2012), while follow-up interviews were used to elicit the coaches’ perceptions of, and rationale for, their behaviour. Findings: The observation data showed that graduate coaches used significantly more divergent questioning than non-graduate coaches, while the interview data revealed a general trend for graduate coaches to show greater self-awareness of behaviours and changes in behaviour between practice types. Graduate coaches also provided more comprehensive rationales, for example, seeing silence as a means of facilitating player decision-making as well as for observation. In contrast to previous research, sessions featured a higher proportion of playing form than training form activities and at over 20% of session duration, the ‘other’ practice state was a prominent feature of contact time with players. While some coaches saw ‘other’ as wasted time, graduate coaches identified this as an opportunity for group discussion and social interaction. The study adds to existing data about coach behaviours and practice activities, providing evidence that education background may indeed influence coaching practice

Trends in future health financing and coverage: future health spending and universal health coverage in 188 countries, 2016–40

Background: Achieving universal health coverage (UHC) requires health financing systems that provide prepaid pooled resources for key health services without placing undue financial stress on households. Understanding current and future trajectories of health financing is vital for progress towards UHC. We used historical health financing data for 188 countries from 1995 to 2015 to estimate future scenarios of health spending and pooled health spending through to 2040. Methods: We extracted historical data on gross domestic product (GDP) and health spending for 188 countries from 1995 to 2015, and projected annual GDP, development assistance for health, and government, out-of-pocket, and prepaid private health spending from 2015 through to 2040 as a reference scenario. These estimates were generated using an ensemble of models that varied key demographic and socioeconomic determinants. We generated better and worse alternative future scenarios based on the global distribution of historic health spending growth rates. Last, we used stochastic frontier analysis to investigate the association between pooled health resources and UHC index, a measure of a country's UHC service coverage. Finally, we estimated future UHC performance and the number of people covered under the three future scenarios. Findings: In the reference scenario, global health spending was projected to increase from US$10 trillion (95$20 trillion (18 trillion to 22 trillion) in 2040. Per capita health spending was projected to increase fastest in upper-middle-income countries, at 4·2% (3·4–5·1) per year, followed by lower-middle-income countries (4·0%, 3·6–4·5) and low-income countries (2·2%, 1·7–2·8). Despite global growth, per capita health spending was projected to range from only $40 (24–65) to$413 (263–668) in 2040 in low-income countries, and from $140 (90–200) to$1699 (711–3423) in lower-middle-income countries. Globally, the share of health spending covered by pooled resources would range widely, from 19·8% (10·3–38·6) in Nigeria to 97·9% (96·4–98·5) in Seychelles. Historical performance on the UHC index was significantly associated with pooled resources per capita. Across the alternative scenarios, we estimate UHC reaching between 5·1 billion (4·9 billion to 5·3 billion) and 5·6 billion (5·3 billion to 5·8 billion) lives in 2030. Interpretation: We chart future scenarios for health spending and its relationship with UHC. Ensuring that all countries have sustainable pooled health resources is crucial to the achievement of UHC. Funding: The Bill & Melinda Gates Foundation

Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049

Assessment of polygenic architecture and risk prediction based on common variants across fourteen cancers

Abstract: Genome-wide association studies (GWAS) have led to the identification of hundreds of susceptibility loci across cancers, but the impact of further studies remains uncertain. Here we analyse summary-level data from GWAS of European ancestry across fourteen cancer sites to estimate the number of common susceptibility variants (polygenicity) and underlying effect-size distribution. All cancers show a high degree of polygenicity, involving at a minimum of thousands of loci. We project that sample sizes required to explain 80% of GWAS heritability vary from 60,000 cases for testicular to over 1,000,000 cases for lung cancer. The maximum relative risk achievable for subjects at the 99th risk percentile of underlying polygenic risk scores (PRS), compared to average risk, ranges from 12 for testicular to 2.5 for ovarian cancer. We show that PRS have potential for risk stratification for cancers of breast, colon and prostate, but less so for others because of modest heritability and lower incidence

Tropical Data: Approach and Methodology as Applied to Trachoma Prevalence Surveys

PURPOSE: Population-based prevalence surveys are essential for decision-making on interventions to achieve trachoma elimination as a public health problem. This paper outlines the methodologies of Tropical Data, which supports work to undertake those surveys. METHODS: Tropical Data is a consortium of partners that supports health ministries worldwide to conduct globally standardised prevalence surveys that conform to World Health Organization recommendations. Founding principles are health ministry ownership, partnership and collaboration, and quality assurance and quality control at every step of the survey process. Support covers survey planning, survey design, training, electronic data collection and fieldwork, and data management, analysis and dissemination. Methods are adapted to meet local context and needs. Customisations, operational research and integration of other diseases into routine trachoma surveys have also been supported. RESULTS: Between 29th February 2016 and 24th April 2023, 3373 trachoma surveys across 50 countries have been supported, resulting in 10,818,502 people being examined for trachoma. CONCLUSION: This health ministry-led, standardised approach, with support from the start to the end of the survey process, has helped all trachoma elimination stakeholders to know where interventions are needed, where interventions can be stopped, and when elimination as a public health problem has been achieved. Flexibility to meet specific country contexts, adaptation to changes in global guidance and adjustments in response to user feedback have facilitated innovation in evidence-based methodologies, and supported health ministries to strive for global disease control targets