A Framework to Prioritise Health Research Proposals for Funding: Integrating Value for Money

© 2019, Springer Nature Switzerland AG. When making funding decisions, research organisations largely consider the merits (e.g. scientific rigour and feasibility) of submitted research proposals; yet, there is often little or no reference to their value for money. This may be attributed to the challenges of assessing and integrating value of research into existing research prioritisation processes. We propose a framework that considers both the merits of research and its value for money to guide health research funding decisions. A practical framework is developed based on current processes followed by funding organizations for assessing investigator-initiated research proposals, and analytical methods for evaluating the expected value of research. We apply the analytical methods to estimate the expected return on investment of two real-world grant applications. The framework comprises four sequential steps: (1) initial screening of applications for eligibility and completeness; (2) merit assessment of eligible proposals; (3) estimating the expected value of research for the shortlisted proposals that pass the first two steps and ranking of proposals based on return on investment; and (4) selecting research proposals for funding. We demonstrate how the expected value for money can be efficiently estimated using certain information provided in funding applications. The proposed framework integrates value-for-money assessment into the existing research prioritisation processes. Considering value for money to inform research funding decisions is vital to achieve efficient utilisation of research budgets and maximise returns on research investments

The association between airborne pollen monitoring and sensitization in the hot desert climate

Background: Pollen is a major cause of allergic respiratory diseases. In Qatar, data on the presence and prevalence of allergenic airborne types of pollen is quite limited. / Methods: The study aimed to determine and correlate the most frequently implicated airborne pollen detected by aerobiological monitoring samplers in respiratory allergy symptoms. An aerobiological survey was started on May 8, 2017. Airborne pollen was collected using two Hirst type seven-day recorder volumetric traps. Skin prick test in patients attending allergy clinics in Doha using commercial extracts was conducted. / Results: Twenty-five pollen types representing the native, as well as the introduced plants, with a relatively low daily mean concentration were observed from May 2017 to May 2019. The highest pollen concentrations were reached by Amaranthaceae (58.9%), followed by Poaceae (21.7%). SPT revealed a comparatively higher degree of sensitization to pollen. Among 940 patients, 204 were sensitized to pollen (54% female) with 135 (66.2%) and 114 (55.8%) to Amaranthaceae and Poaceae, respectively. Some patients had polysensitization. There was a statistically significant association between Amaranthaceae, and asthma (r = 0.169, P = 0.016) and allergic rhinitis (r = 0.177, P = 0.012). / Conclusions: This is the first study to monitor airborne pollen in the state of Qatar. The main pollen detected were Amaranthaceae and Poaceae. Pollen may represent a possible exacerbating factor in adult patients with allergic diseases such as asthma and allergic rhinitis

Stimulated grip strength measurement: Validation of a novel method for functional assessment

BackgroundReliable measurement of functional recovery is critical in translational peripheral nerve regeneration research. Behavioral functional assessments such as volitional grip strength testing (vGST) are limited by inherent behavioral variability. Isometric tetanic force testing (ITFT) is highly reliable but precludes serial measurements. Combining elements of vGST and ITFT, stimulated grip strength testing (sGST) involves percutaneous median nerve stimulation to elicit maximal tetanic contraction of digital flexors, thereby allowing for consistent measurement of maximal grip strength.MethodsWe measured side‐to‐side equivalence of force using sGST, vGST, and ITFT to determine relative reliability and repeatability. We also performed weekly force measurements following median nerve repair.ResultssGST demonstrated greater reliability and inter‐trial repeatability than vGST and similar reliability to ITFT, with the added benefit of serial measurements.ConclusionssGST is a valid method for assessing functional recovery that addresses the limitations of the currently available modalities used in translational peripheral nerve regeneration research.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/151883/1/mus26646.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/151883/2/mus26646_am.pd

Health in times of uncertainty in the eastern Mediterranean region, 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013

Background: The eastern Mediterranean region is comprised of 22 countries: Afghanistan, Bahrain, Djibouti, Egypt, Iran, Iraq, Jordan, Kuwait, Lebanon, Libya, Morocco, Oman, Pakistan, Palestine, Qatar, Saudi Arabia, Somalia, Sudan, Syria, Tunisia, the United Arab Emirates, and Yemen. Since our Global Burden of Disease Study 2010 (GBD 2010), the region has faced unrest as a result of revolutions, wars, and the so-called Arab uprisings. The objective of this study was to present the burden of diseases, injuries, and risk factors in the eastern Mediterranean region as of 2013. Methods: GBD 2013 includes an annual assessment covering 188 countries from 1990 to 2013. The study covers 306 diseases and injuries, 1233 sequelae, and 79 risk factors. Our GBD 2013 analyses included the addition of new data through updated systematic reviews and through the contribution of unpublished data sources from collaborators, an updated version of modelling software, and several improvements in our methods. In this systematic analysis, we use data from GBD 2013 to analyse the burden of disease and injuries in the eastern Mediterranean region specifically. Findings: The leading cause of death in the region in 2013 was ischaemic heart disease (90·3 deaths per 100 000 people), which increased by 17·2% since 1990. However, diarrhoeal diseases were the leading cause of death in Somalia (186·7 deaths per 100 000 people) in 2013, which decreased by 26·9% since 1990. The leading cause of disability-adjusted life-years (DALYs) was ischaemic heart disease for males and lower respiratory infection for females. High blood pressure was the leading risk factor for DALYs in 2013, with an increase of 83·3% since 1990. Risk factors for DALYs varied by country. In low-income countries, childhood wasting was the leading cause of DALYs in Afghanistan, Somalia, and Yemen, whereas unsafe sex was the leading cause in Djibouti. Non-communicable risk factors were the leading cause of DALYs in high-income and middle-income countries in the region. DALY risk factors varied by age, with child and maternal malnutrition affecting the younger age groups (aged 28 days to 4 years), whereas high bodyweight and systolic blood pressure affected older people (aged 60–80 years). The proportion of DALYs attributed to high body-mass index increased from 3·7% to 7·5% between 1990 and 2013. Burden of mental health problems and drug use increased. Most increases in DALYs, especially from non-communicable diseases, were due to population growth. The crises in Egypt, Yemen, Libya, and Syria have resulted in a reduction in life expectancy; life expectancy in Syria would have been 5 years higher than that recorded for females and 6 years higher for males had the crisis not occurred. Interpretation: Our study shows that the eastern Mediterranean region is going through a crucial health phase. The Arab uprisings and the wars that followed, coupled with ageing and population growth, will have a major impact on the region's health and resources. The region has historically seen improvements in life expectancy and other health indicators, even under stress. However, the current situation will cause deteriorating health conditions for many countries and for many years and will have an impact on the region and the rest of the world. Based on our findings, we call for increased investment in health in the region in addition to reducing the conflicts.Ali H Mokdad ... Azmeraw T Amare ... et al

Children with Respiratory Disease Associated with Metapneumovirus in Hong Kong

Human metapneumovirus (HMPV) is a newly discovered pathogen thought to be associated with respiratory disease. We report the results of a study of 587 children hospitalized with respiratory infection over a 13-month period. HMPV was detected in the nasopharyngeal aspirates from 32 (5.5%) children by reverse transcription-polymerase chain reaction. HMPV infection was associated with clinical diagnoses of pneumonia (36%), asthma exacerbation (23%), or acute bronchiolitis (10%). When compared to those with respiratory syncytial virus infection, children with HMPV infection were older, and wheezing was more likely to represent asthma exacerbation rather than acute bronchiolitis. HMPV viral activity peaked during the spring-summer period in Hong Kong. Phylogenetically, all HMPV virus strains from Hong Kong belonged to one of the two genetic lineages previously described. HMPV contributed to 441.6 hospital admissions per 100,000 population <6 years of age

Pegunigalsidase alfa, a novel PEGylated enzyme replacement therapy for Fabry disease, provides sustained plasma concentrations and favorable pharmacodynamics: A 1-year Phase 1/2 clinical trial

Journal of Inherited Metabolic Disease published by John Wiley & Sons Ltd on behalf of SSIEM Pegunigalsidase alfa, a novel PEGylated, covalently crosslinked form of α-galactosidase A developed as enzyme replacement therapy (ERT) for Fabry disease (FD), was designed to increase plasma half-life and reduce immunogenicity, thereby enhancing efficacy compared with available products. Symptomatic adults with FD participated in this open-label, 3-month dose-ranging study, followed by a 9-month extension. Three cohorts were enrolled in a stepwise manner, each receiving increased doses of pegunigalsidase alfa: 0.2, 1.0, 2.0 mg/kg, via intravenous infusion every other week. Pharmacokinetic analysis occurred on Day 1 and Months 3, 6, and 12. Kidney biopsies at baseline and Month 6 assessed peritubular capillary globotriaosylceramide (Gb3) content. Renal function, cardiac parameters, and other clinical endpoints were assessed throughout. Treatment-emergent adverse events (AEs) and presence of immunoglobulin G (IgG) antidrug antibodies (ADAs) were assessed. Sixteen patients completed 1 year's treatment. Mean terminal plasma half-life (each cohort) ranged from 53 to 121 hours. All 11 male and 1 of 7 female patients presented with classic FD phenotype, in whom renal peritubular capillary Gb3 inclusions were reduced by 84%. Mean estimated glomerular filtration rate was 111 mL/min/1.73 m 2 at baseline, remaining stable throughout treatment. Three patients developed treatment-induced IgG ADAs; following 1 year's treatment, all became ADA-negative. Nearly all treatment-emergent AEs were mild or moderate. One patient withdrew from the study following a serious related AE. Pegunigalsidase alfa may represent an advance in ERT for FD, based on its unique pharmacokinetics and apparent low immunogenicity

Health in times of uncertainty in the eastern Mediterranean region, 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013

Background: The eastern Mediterranean region is comprised of 22 countries: Afghanistan, Bahrain, Djibouti, Egypt, Iran, Iraq, Jordan, Kuwait, Lebanon, Libya, Morocco, Oman, Pakistan, Palestine, Qatar, Saudi Arabia, Somalia, Sudan, Syria, Tunisia, the United Arab Emirates, and Yemen. Since our Global Burden of Disease Study 2010 (GBD 2010), the region has faced unrest as a result of revolutions, wars, and the so-called Arab uprisings. The objective of this study was to present the burden of diseases, injuries, and risk factors in the eastern Mediterranean region as of 2013. Methods: GBD 2013 includes an annual assessment covering 188 countries from 1990 to 2013. The study covers 306 diseases and injuries, 1233 sequelae, and 79 risk factors. Our GBD 2013 analyses included the addition of new data through updated systematic reviews and through the contribution of unpublished data sources from collaborators, an updated version of modelling software, and several improvements in our methods. In this systematic analysis, we use data from GBD 2013 to analyse the burden of disease and injuries in the eastern Mediterranean region specifically. Findings: The leading cause of death in the region in 2013 was ischaemic heart disease (90·3 deaths per 100 000 people), which increased by 17·2% since 1990. However, diarrhoeal diseases were the leading cause of death in Somalia (186·7 deaths per 100 000 people) in 2013, which decreased by 26·9% since 1990. The leading cause of disability-adjusted life-years (DALYs) was ischaemic heart disease for males and lower respiratory infection for females. High blood pressure was the leading risk factor for DALYs in 2013, with an increase of 83·3% since 1990. Risk factors for DALYs varied by country. In low-income countries, childhood wasting was the leading cause of DALYs in Afghanistan, Somalia, and Yemen, whereas unsafe sex was the leading cause in Djibouti. Non-communicable risk factors were the leading cause of DALYs in high-income and middle-income countries in the region. DALY risk factors varied by age, with child and maternal malnutrition affecting the younger age groups (aged 28 days to 4 years), whereas high bodyweight and systolic blood pressure affected older people (aged 60–80 years). The proportion of DALYs attributed to high body-mass index increased from 3·7% to 7·5% between 1990 and 2013. Burden of mental health problems and drug use increased. Most increases in DALYs, especially from non-communicable diseases, were due to population growth. The crises in Egypt, Yemen, Libya, and Syria have resulted in a reduction in life expectancy; life expectancy in Syria would have been 5 years higher than that recorded for females and 6 years higher for males had the crisis not occurred. Interpretation: Our study shows that the eastern Mediterranean region is going through a crucial health phase. The Arab uprisings and the wars that followed, coupled with ageing and population growth, will have a major impact on the region's health and resources. The region has historically seen improvements in life expectancy and other health indicators, even under stress. However, the current situation will cause deteriorating health conditions for many countries and for many years and will have an impact on the region and the rest of the world. Based on our findings, we call for increased investment in health in the region in addition to reducing the conflicts

Impact of primary kidney disease on the effects of empagliflozin in patients with chronic kidney disease: secondary analyses of the EMPA-KIDNEY trial

Background: The EMPA KIDNEY trial showed that empagliflozin reduced the risk of the primary composite outcome of kidney disease progression or cardiovascular death in patients with chronic kidney disease mainly through slowing progression. We aimed to assess how effects of empagliflozin might differ by primary kidney disease across its broad population. Methods: EMPA-KIDNEY, a randomised, controlled, phase 3 trial, was conducted at 241 centres in eight countries (Canada, China, Germany, Italy, Japan, Malaysia, the UK, and the USA). Patients were eligible if their estimated glomerular filtration rate (eGFR) was 20 to less than 45 mL/min per 1·73 m2, or 45 to less than 90 mL/min per 1·73 m2 with a urinary albumin-to-creatinine ratio (uACR) of 200 mg/g or higher at screening. They were randomly assigned (1:1) to 10 mg oral empagliflozin once daily or matching placebo. Effects on kidney disease progression (defined as a sustained ≥40% eGFR decline from randomisation, end-stage kidney disease, a sustained eGFR below 10 mL/min per 1·73 m2, or death from kidney failure) were assessed using prespecified Cox models, and eGFR slope analyses used shared parameter models. Subgroup comparisons were performed by including relevant interaction terms in models. EMPA-KIDNEY is registered with ClinicalTrials.gov, NCT03594110. Findings: Between May 15, 2019, and April 16, 2021, 6609 participants were randomly assigned and followed up for a median of 2·0 years (IQR 1·5–2·4). Prespecified subgroupings by primary kidney disease included 2057 (31·1%) participants with diabetic kidney disease, 1669 (25·3%) with glomerular disease, 1445 (21·9%) with hypertensive or renovascular disease, and 1438 (21·8%) with other or unknown causes. Kidney disease progression occurred in 384 (11·6%) of 3304 patients in the empagliflozin group and 504 (15·2%) of 3305 patients in the placebo group (hazard ratio 0·71 [95% CI 0·62–0·81]), with no evidence that the relative effect size varied significantly by primary kidney disease (pheterogeneity=0·62). The between-group difference in chronic eGFR slopes (ie, from 2 months to final follow-up) was 1·37 mL/min per 1·73 m2 per year (95% CI 1·16–1·59), representing a 50% (42–58) reduction in the rate of chronic eGFR decline. This relative effect of empagliflozin on chronic eGFR slope was similar in analyses by different primary kidney diseases, including in explorations by type of glomerular disease and diabetes (p values for heterogeneity all &gt;0·1). Interpretation: In a broad range of patients with chronic kidney disease at risk of progression, including a wide range of non-diabetic causes of chronic kidney disease, empagliflozin reduced risk of kidney disease progression. Relative effect sizes were broadly similar irrespective of the cause of primary kidney disease, suggesting that SGLT2 inhibitors should be part of a standard of care to minimise risk of kidney failure in chronic kidney disease. Funding: Boehringer Ingelheim, Eli Lilly, and UK Medical Research Council