Estimation of Health State Utility Values in Fabry Disease Using Vignette Development and Valuation

Background: Health state utilities are measures of health-related quality of life that reflect the value placed on improvements in patients' health status and are necessary for estimation of quality-adjusted life-years. Health state utility data on Fabry disease (FD) are limited. In this study we used vignette (scenario) construction and valuation to develop health state utilities. Objectives: The aim of this study was to use vignette construction and valuation to estimate health state utility values suitable for inclusion in economic models of FD treatments. Methods: Health state vignettes were developed from semistructured qualitative telephone interviews with patients with FD and informed by published literature and input from an expert. Each vignette was valued in an online survey by members of the United Kingdom (UK) general population using the composite time trade-off (TTO) method, which aims to determine the time the respondent would trade to live in full health compared with each impaired health state. Results: Eight adults (50% women) with FD from the UK were interviewed. They were recruited via various approaches, including patient organizations and social media. The interviewees' responses, evidence from published literature, and input from a clinical expert informed the development of 6 health state vignettes (pain, moderate clinically evident FD [CEFD], severe CEFD, end-stage renal disease [ESRD], stroke, and cardiovascular disease [CVD]) and 3 combined health states (severe CEFD + ESRD, severe CEFD + CVD, and severe CEFD + stroke). A vignette valuation survey was administered to 1222 participants from the UK general population who were members of an external surveying organization and agreed to participate in this study; 1175 surveys were successfully completed and included in the analysis. Responses to TTO questions were converted into utility values for each health state. Pain was the highest valued health state (0.465), and severe CEFD + ESRD was the lowest (0.033). Discussion: Overall, mean utility values declined as the severity of the vignettes increased, indicating that respondents were more willing to trade life-years to avoid a severe health state. Conclusions: Health state vignettes reflect the effects of FD on all major health-related quality-of-life domains and may help to support economic modeling for treatment of FD

Estimation of health state utility values in Fabry disease using vignette development and valuation

Background: Health state utilities are measures of health-related quality of life that reflect the value placed on improvements in patients’ health status and are necessary for estimation of quality-adjusted life-years. Health state utility data on Fabry disease (FD) are limited. In this study we used vignette (scenario) construction and valuation to develop health state utilities. Objectives: The aim of this study was to use vignette construction and valuation to estimate health state utility values suitable for inclusion in economic models of FD treatments. Methods: Health state vignettes were developed from semistructured qualitative telephone interviews with patients with FD and informed by published literature and input from an expert. Each vignette was valued in an online survey by members of the United Kingdom (UK) general population using the composite time trade-off (TTO) method, which aims to determine the time the respondent would trade to live in full health compared with each impaired health state. Results: Eight adults (50% women) with FD from the UK were interviewed. They were recruited via various approaches, including patient organizations and social media. The interviewees’ responses, evidence from published literature, and input from a clinical expert informed the development of 6 health state vignettes (pain, moderate clinically evident FD [CEFD], severe CEFD, end-stage renal disease [ESRD], stroke, and cardiovascular disease [CVD]) and 3 combined health states (severe CEFD + ESRD, severe CEFD + CVD, and severe CEFD + stroke). A vignette valuation survey was administered to 1222 participants from the UK general population who were members of an external surveying organization and agreed to participate in this study; 1175 surveys were successfully completed and included in the analysis. Responses to TTO questions were converted into utility values for each health state. Pain was the highest valued health state (0.465), and severe CEFD + ESRD was the lowest (0.033). Discussion: Overall, mean utility values declined as the severity of the vignettes increased, indicating that respondents were more willing to trade life-years to avoid a severe health state. Conclusions: Health state vignettes reflect the effects of FD on all major health-related quality-of-life domains and may help to support economic modeling for treatment of FD

Clinical Validation of a Primary Antibody Deficiency Screening Algorithm for Primary Care

Purpose: The diagnostic delay of primary antibody deficiencies (PADs) is associated with increased morbidity, mortality, and healthcare costs. Therefore, a screening algorithm was previously developed for the early detection of patients at risk of PAD in primary care. We aimed to clinically validate and optimize the PAD screening algorithm by applying it to a primary care database in the Netherlands. Methods: The algorithm was applied to a data set of 61,172 electronic health records (EHRs). Four hundred high-scoring EHRs were screened for exclusion criteria, and remaining patients were invited for serum immunoglobulin analysis and referred if clinically necessary. Results: Of the 104 patients eligible for inclusion, 16 were referred by their general practitioner for suspected PAD, of whom 10 had a PAD diagnosis. In patients selected by the screening algorithm and included for laboratory analysis, prevalence of PAD was ~ 1:10 versus 1:1700–1:25,000 in the general population. To optimize efficiency of the screening process, we refitted the algorithm with the subset of high-risk patients, which improved the area under the curve–receiver operating characteristics curve value to 0.80 (95% confidence interval 0.63–0.97). We propose a two-step screening process, first applying the original algorithm to distinguish high-risk from low-risk patients, then applying the optimized algorithm to select high-risk patients for serum immunoglobulin analysis. Conclusion: Using the screening algorithm, we were able to identify 10 new PAD patients from a primary care population, thus reducing diagnostic delay. Future studies should address further validation in other populations and full cost-effectiveness analyses. Registration: Clinicaltrials.go

Measuring and forecasting progress in education: what about early childhood?

A recent Nature article modelled within-country inequalities in primary, secondary, and tertiary education and forecast progress towards Sustainable Development Goal (SDG) targets related to education (SDG 4). However, their paper entirely overlooks inequalities in achieving Target 4.2, which aims to achieve universal access to quality early childhood development, care and preschool education by 2030. This is an important omission because of the substantial brain, cognitive and socioemotional developments that occur in early life and because of increasing evidence of early-life learning's large impacts on subsequent education and lifetime wellbeing. We provide an overview of this evidence and use new analyses to illustrate medium- and long-term implications of early learning, first by presenting associations between pre-primary programme participation and adolescent mathematics and science test scores in 73 countries and secondly, by estimating the costs of inaction (not making pre-primary programmes universal) in terms of forgone lifetime earnings in 134 countries. We find considerable losses, comparable to or greater than current governmental expenditures on all education (as percentages of GDP), particularly in low- and lower-middle-income countries. In addition to improving primary, secondary and tertiary schooling, we conclude that to attain SDG 4 and reduce inequalities in a post-COVID era, it is essential to prioritize quality early childhood care and education, including adopting policies that support families to promote early learning and their children's education

Feeding spectra and activity of the freshwater crab Trichodactylus kensleyi (Decapoda: Brachyura: Trichodactylidae) at La Plata basin

Background: In inland water systems, it is important to characterize the trophic links in order to identify the ‘trophic species’ and, from the studies of functional diversity, understand the dynamics of matter and energy in these environments. The aim of this study is to analyze the natural diet of Trichodactylus kensleyi of subtropical rainforest streams and corroborate the temporal variation in the trophic activity during day hours. Results: A total of 15 major taxonomic groups were recognized in gut contents. The index of relative importance identified the following main prey items in decreasing order of importance: vegetal remains, oligochaetes, chironomid larvae, and algae. A significant difference was found in the amount of full stomachs during day hours showing a less trophic activity at midday and afternoon. The index of relative importance values evidenced the consumption of different prey according to day moments. Results of the gut content indicate that T. kensleyi is an omnivorous crab like other trichodactylid species. Opportunistic behavior is revealed by the ingestion of organisms abundant in streams such as oligochaetes and chironomid larvae. The consumption of allochthonous plant debris shows the importance of this crab as shredder in subtropical streams. However, the effective assimilation of plant matter is yet unknown in trichodactylid crabs. Conclusions: This research provides knowledge that complements previous studies about trophic relationships of trichodactylid crabs and supported the importance of T. kensleyi in the transference of energy and matter from benthic community and riparian sources to superior trophic levels using both macro- and microfauna.Fil: Williner, Verónica. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto Nacional de Limnología. Universidad Nacional del Litoral. Instituto Nacional de Limnología; Argentina. Universidad Nacional del Litoral. Facultad de Humanidades y Ciencias; ArgentinaFil: de Azevedo Carvalho, Debora. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto Nacional de Limnología. Universidad Nacional del Litoral. Instituto Nacional de Limnología; ArgentinaFil: Collins, Pablo Agustin. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto Nacional de Limnología. Universidad Nacional del Litoral. Instituto Nacional de Limnología; Argentina. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas; Argentin

Spatio-temporal variability in underwater light climate in a turbid river-floodplain system. Driving factors and estimation using Secchi disc

The underwater light climate has important effects on primary producers. The aim of this research was to evaluate its variability in a turbid river-floodplain system. Photosynthetically active radiation (PAR) was measured in the Middle Paraná River during different hydrological phases to (a) analyse the photosynthetically active radiation attenuation coefficient (k) and euphotic depth (Zeu) as well as their associations with optically active components and (b) develop and evaluate indices and regression models based on Secchi disc (SD) measurements to estimate k and Zeu. Values of k were higher in the fluvial system than in the floodplain and during low-water stage than high-water stage. Particulate components controlled the light climate variability. Chromophoric dissolved organic matter and chlorophyll-a had significant effects during floods. The estimation of k and Zeu was sensitive to temporal but not to spatial variations. The highest prediction accuracy was observed when using specific non-linear regressions for each hydrological phase, especially for Zeu estimation (low stage: k = 1.76 × SD−0.80, Zeu = 2.62 × 1/SD−0.80; high stage: k = 2.04 × SD−0.53, Zeu = 2.26 × 1/SD−0.53). The indices k × SD and Zeu/SD were significantly different from those proposed for clear water environments. It is concluded that temporal variations should be considered when estimating k and Zeu in turbid river-floodplain systems because of the temporal heterogeneity in optically active components. Considering that ecological implication of the light climate depends on Zeu:depth ratio, we propose to estimate Zeu instead of k. Finally, indices proposed for clear water environments are not recommended to be applied to turbid environments.Fil: Mayora, Gisela Paola. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto Nacional de Limnología. Universidad Nacional del Litoral. Instituto Nacional de Limnología; ArgentinaFil: Devercelli, Melina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto Nacional de Limnología. Universidad Nacional del Litoral. Instituto Nacional de Limnología; Argentin

Characteristics and outcomes of hospitalised adults with COVID-19 in a Global Health Research Network: A cohort study

Objective To examine age, gender, and temporal differences in baseline characteristics and clinical outcomes of adult patients hospitalised with COVID-19. Design A cohort study using deidentified electronic medical records from a Global Research Network. Setting/Participants 67 456 adult patients hospitalised with COVID-19 from the USA; 7306 from Europe, Latin America and Asia-Pacific between February 2020 and January 2021. Results In the US cohort, compared with patients 18-34 years old, patients ≥65 had a greater risk of intensive care unit (ICU) admission (adjusted HR (aHR) 1.73, 95% CI 1.58 to 1.90), acute respiratory distress syndrome(ARDS)/respiratory failure (aHR 1.86, 95% CI 1.76 to 1.96), invasive mechanical ventilation (IMV, aHR 1.93, 95% CI, 1.73 to 2.15), and all-cause mortality (aHR 5.6, 95% CI 4.36 to 7.18). Men appeared to be at a greater risk for ICU admission (aHR 1.34, 95% CI 1.29 to 1.39), ARDS/respiratory failure (aHR 1.24, 95% CI1.21 to 1.27), IMV (aHR 1.38, 95% CI 1.32 to 1.45), and all-cause mortality (aHR 1.16, 95% CI 1.08 to 1.24) compared with women. Moreover, we observed a greater risk of adverse outcomes during the early pandemic (ie, February-April 2020) compared with later periods. In the ex-US cohort, the age and gender trends were similar; for the temporal trend, the highest proportion of patients with all-cause mortality were also in February-April 2020; however, the highest percentages of patients with IMV and ARDS/respiratory failure were in August-October 2020 followed by February-April 2020. Conclusions This study provided valuable information on the temporal trends of characteristics and outcomes of hospitalised adult COVID-19 patients in both USA and ex-USA. It also described the population at a potentially greater risk for worse clinical outcomes by identifying the age and gender differences. Together, the information could inform the prevention and treatment strategies of COVID-19. Furthermore, it can be used to raise public awareness of COVID-19's impact on vulnerable populations

Trends in characteristics and outcomes among US adults hospitalised with COVID-19 throughout 2020: An observational cohort study

Objectives To examine the temporal patterns of patient characteristics, treatments used and outcomes associated with COVID-19 in patients who were hospitalised for the disease between January and 15 November 2020. Design Observational cohort study. Setting COVID-19 subset of the Optum deidentified electronic health records, including more than 1.8 million patients from across the USA. Participants There were 51 510 hospitalised patients who met the COVID-19 definition, with 37 617 in the laboratory positive cohort and 13 893 in the clinical cohort. Primary and secondary outcome measures Incident acute clinical outcomes, including in-hospital all-cause mortality. Results Respectively, 48% and 49% of the laboratory positive and clinical cohorts were women. The 50- 65 age group was the median age group for both cohorts. The use of antivirals and dexamethasone increased over time, fivefold and twofold, respectively, while the use of hydroxychloroquine declined by 98%. Among adult patients in the laboratory positive cohort, absolute age/sex standardised incidence proportion for in-hospital death changed by -0.036 per month (95% CI -0.042 to -0.031) from March to June 2020, but remained fairly flat from June to November, 2020 (0.001 (95% CI -0.001 to 0.003), 17.5% (660 deaths /3986 persons) in March and 10.2% (580/5137) in October); in the clinical cohort, the corresponding changes were -0.024 (95% CI -0.032 to -0.015) and 0.011 (95% CI 0.007 0.014), respectively (14.8% (175/1252) in March, 15.3% (189/1203) in October). Declines in the cumulative incidence of most acute clinical outcomes were observed in the laboratory positive cohort, but not for the clinical cohort. Conclusion The incidence of adverse clinical outcomes remains high among COVID-19 patients with clinical diagnosis only. Patients with COVID-19 entering the hospital are at elevated risk of adverse outcomes