A Review of the Use of EQ-5D for Clinical Outcome Assessment in Health Technology Assessment, Regulatory Claims, and Published Literature.

The aim is to identify the extent to which EQ-5D is used as a clinical outcome assessment (COA) endpoint in a non-economic context in health technology assessment (HTA) decisions, regulatory labelling claims and published literature. Drug technology appraisals (TAs) published by HTA agencies in England, France, Germany and the USA between 2019 and 2021 were identified. Product labelling for drugs approved by the European Medicines Agency (EMA) and US Food and Drug Administration (FDA) between 2016 and 2021 were also identified. A systematic literature review (SLR) was also performed. Documents reporting EQ-5D in the context of economic evaluation only were excluded. EQ-5D data were reported for COA in 195 of 1072 (18%) published TAs, with the majority reported for Germany (n = 138). The EQ-5D visual analogue scale (EQ-VAS) was reported most frequently, in 68% of all TAs, and accounted for 100% of Institut für Qualität und Wirtschaftlichkeit im Gesundheitswesen (IQWiG) and 94% of Gemeinsamer Bundesausschuss (G-BA) TAs. In total, 320 drugs were approved or reviewed by the EMA and 735 by the FDA. Of these, 15 reported EQ-5D data from the EMA and 35 from the FDA; however, all EQ-5D data submitted to the FDA were reported in supporting documentation. Reporting of both EQ-5D index and EQ-VAS was most frequent, occurring in 32% of all documents. For the SLR, 329 of 4248 (8%) retrieved records were included. Reporting of both EQ-5D index and EQ-VAS was most frequent, occurring in 36% of studies. Clinical evaluation of recent drug approvals, based on regulatory, HTA and systematic literature reviews, demonstrated limited use of EQ-5D outside the context of economic evaluations. This may be due to the likelihood that the EQ-5D may lack sensitivity to detect improvement in conditions with small expected therapeutic benefit, or because the EQ-5D is not considered an adequate COA tool for clinical evaluation of treatment benefit. EQ-5D, as a COA, was more likely to be used in clinical evaluation of cancer drugs than drugs for treatment in any other disease category. HTA bodies were more likely to use the EQ-5D for COA, especially in Germany.

The Epidemiology of Domain-Specific Physical Activity in New Zealand Adults: A Nationally Representative Cross-Sectional Survey.

BACKGROUND: Surveillance of domain-specific physical activity (PA) helps to target interventions to promote PA. We examined the sociodemographic correlates of domain-specific PA in New Zealand adults. METHODS: A nationally representative sample of 13,887 adults completed the International PA Questionnaire-long form in 2019/20. Three measures of total and domain-specific (leisure, travel, home, and work) PA were calculated: (1) weekly participation, (2) mean weekly metabolic energy equivalent minutes (MET-min), and (3) median weekly MET-min among those who undertook PA. Results were weighted to the New Zealand adult population. RESULTS: The average contribution of domain-specific activity to total PA was 37.5% for work activities (participation = 43.6%; median participating MET-min = 2790), 31.9% for home activities (participation = 82.2%; median participating MET-min = 1185), 19.4% for leisure activities (participation = 64.7%; median participating MET-min = 933), and 11.2% for travel activities (participation = 64.0%; median MET-min among participants = 495). Women accumulated more home PA and less work PA than men. Total PA was higher in middle-aged adults, with diverse patterns by age within domains. Maori accumulated less leisure PA than New Zealand Europeans but higher total PA. Asian groups reported lower PA across all domains. Higher area deprivation was negatively associated with leisure PA. Sociodemographic patterns varied by measure. For example, gender was not associated with total PA participation, but men accumulated higher MET-min when taking part in PA than women. CONCLUSIONS: Inequalities in PA varied by domain and sociodemographic group. These results should be used to inform interventions to improve PA.

Reduced fetal growth velocity and weight loss are associated with adverse perinatal outcome in fetuses at risk of growth restriction.

BACKGROUND: Although fetal size is associated with adverse perinatal outcome, the relationship between fetal growth velocity and adverse perinatal outcome is unclear. OBJECTIVE: This study aimed to evaluate the relationship between fetal growth velocity and signs of cerebral blood flow redistribution, and their association with birthweight and adverse perinatal outcome. STUDY DESIGN: This study was a secondary analysis of the TRUFFLE-2 multicenter observational prospective feasibility study of fetuses at risk of fetal growth restriction between 32+0 and 36+6 weeks of gestation (n=856), evaluated by ultrasound biometry and umbilical and middle cerebral artery Doppler. Individual fetal growth velocity was calculated from the difference of birthweight and estimated fetal weight at 3, 2, and 1 week before delivery, and by linear regression of all available estimated fetal weight measurements. Fetal estimated weight and birthweight were expressed as absolute value and as multiple of the median for statistical calculation. The coefficients of the individual linear regression of estimated fetal weight measurements (growth velocity; g/wk) were plotted against the last umbilical-cerebral ratio with subclassification for perinatal outcome. The association of these measurements with adverse perinatal outcome was assessed. The adverse perinatal outcome was a composite of abnormal condition at birth or major neonatal morbidity. RESULTS: Adverse perinatal outcome was more frequent among fetuses whose antenatal growth was <100 g/wk, irrespective of signs of cerebral blood flow redistribution. Infants with birthweight <0.65 multiple of the median were enrolled earlier, had the lowest fetal growth velocity, higher umbilical-cerebral ratio, and were more likely to have adverse perinatal outcome. A decreasing fetal growth velocity was observed in 163 (19%) women in whom the estimated fetal weight multiple of the median regression coefficient was <-0.025, and who had higher umbilical-cerebral ratio values and more frequent adverse perinatal outcome; 67 (41%; 8% of total group) of these women had negative growth velocity. Estimated fetal weight and umbilical-cerebral ratio at admission and fetal growth velocity combined by logistic regression had a higher association with adverse perinatal outcome than any of those parameters separately (relative risk, 3.3; 95% confidence interval, 2.3-4.8). CONCLUSION: In fetuses at risk of late preterm fetal growth restriction, reduced growth velocity is associated with an increased risk of adverse perinatal outcome, irrespective of signs of cerebral blood flow redistribution. Some fetuses showed negative growth velocity, suggesting catabolic metabolism.

Doctors' travel in the Anthropocene.

The health sector is uniquely placed as both a significant contributor to greenhouse gas emissions and a first responder to the impacts of climate change. The breadth and complexity of the health sector mean that decarbonisation will be a substantial challenge to current practice. Doctors are leaders in the health system and in their communities, and there are multiple imperatives for doctors to lead on decarbonisation. Here we specifically examine the impact of travel undertaken by hospital-based senior doctors for the purpose of continuing medical education. Where quantified, doctors' travel is a significant source of greenhouse gas emissions for district health boards, although there is significant uncertainty about the estimates. This travel occurs within a system that encourages and enables it through educational, financial, regulatory and cultural mechanisms, and is for many doctors an important component of their job satisfaction. This system needs to be redesigned to optimise education, job satisfaction, collaboration and wellbeing in the decarbonised health sector of the future.

Chronic Hypoxia in Ovine Pregnancy Recapitulates Physiological and Molecular Markers of Preeclampsia in the Mother, Placenta, and Offspring.

BACKGROUND: Preeclampsia continues to be a prevalent pregnancy complication and underlying mechanisms remain controversial. A common feature of preeclampsia is utero-placenta hypoxia. In contrast to the impact of hypoxia on the placenta and fetus, comparatively little is known about the maternal physiology. METHODS: We adopted an integrative approach to investigate the inter-relationship between chronic hypoxia during pregnancy with maternal, placental, and fetal outcomes, common in preeclampsia. We exploited a novel technique using isobaric hypoxic chambers and in vivo continuous cardiovascular recording technology for measurement of blood pressure in sheep and studied the placental stress in response to hypoxia at cellular and subcellular levels. RESULTS: Chronic hypoxia in ovine pregnancy promoted fetal growth restriction (FGR) with evidence of fetal brain-sparing, increased placental hypoxia-mediated oxidative damage, and activated placental stress response pathways. These changes were linked with dilation of the placental endoplasmic reticulum (ER) cisternae and increased placental expression of the antiangiogenic factors sFlt-1 (soluble fms-like tyrosine kinase 1) and sEng (soluble endoglin), combined with a shift towards an angiogenic imbalance in the maternal circulation. Chronic hypoxia further led to an increase in uteroplacental vascular resistance and the fall in maternal blood pressure with advancing gestation measured in normoxic pregnancy did not occur in hypoxic pregnancy. CONCLUSIONS: Therefore, we show in an ovine model of sea-level adverse pregnancy that chronic hypoxia recapitulates physiological and molecular features of preeclampsia in the mother, placenta, and offspring.

Immunological factors, but not clinical features, predict visceral leishmaniasis relapse in patients co-infected with HIV.

Visceral leishmaniasis (VL) has emerged as a clinically important opportunistic infection in HIV patients, as VL/HIV co-infected patients suffer from frequent VL relapse. Here, we follow cohorts of VL patients with or without HIV in Ethiopia. By the end of the study, 78.1% of VL/HIV-but none of the VL patients-experience VL relapse. Despite a clinically defined cure, VL/HIV patients maintain higher parasite loads, lower BMI, hepatosplenomegaly, and pancytopenia. We identify three immunological markers associated with VL relapse in VL/HIV patients: (1) failure to restore antigen-specific production of IFN-γ, (2) persistently lower CD4+ T cell counts, and (3) higher expression of PD1 on CD4+ and CD8+ T cells. We show that these three markers, which can be measured in primary hospital settings in Ethiopia, combine well in predicting VL relapse. The use of our prediction model has the potential to improve disease management and patient care.

The Impact of Transport on Population Health and Health Equity for Maori in Aotearoa New Zealand: A Prospective Burden of Disease Study.

BACKGROUND: The land transport system influences health via a range of pathways. This study aimed to quantify the amount and distribution of health loss caused by the current land transport system in Aotearoa New Zealand (NZ) through the pathways of road injury, air pollution and physical inactivity. METHODS: We used an existing multi-state life table model to estimate the long-term health impacts (in health-adjusted life years (HALYs)) and changes in health system costs of removing road injury and transport related air pollution and increasing physical activity to recommended levels through active transport. Health equity implications were estimated using relative changes in HALYs and life expectancy for Maori and non-Maori. RESULTS: If the NZ resident population alive in 2011 was exposed to no further air pollution from transport, had no road traffic injuries and achieved at least the recommended weekly amount of physical activity through walking and cycling from 2011 onwards, 1.28 (95% UI: 1.11-1.5) million HALYs would be gained and $7.7 (95% UI: 10.2 to 5.6) billion (2011 NZ Dollars) would be saved from the health system over the lifetime of this cohort. Maori would likely gain more healthy years per capita than non-Maori, which would translate to small but important reductions (2-3%) in the present gaps in life expectancy. CONCLUSION: The current transport system in NZ, like many other car-dominated transport systems, has substantial negative impacts on health, at a similar level to the effects of tobacco and obesity. Transport contributes to health inequity, as Maori bear greater shares of the negative health impacts. Creating a healthier transport system would bring substantial benefits for health, society and the economy.

Public health interventions: the elephant in the room of the health system crisis.

Nil.

New Zealand's Climate Change Commission report: the critical need to address the missing health co-benefits of reducing emissions.

The Climate Change Commission's draft report and recommendations provide a pathway towards achieving the New Zealand Government's commitment to net zero emissions by 2050. However, the Commission has not adequately considered the health co-benefits of climate change mitigation. In this viewpoint, we assess how the Commission has considered health co-benefits in the key response domains. Extrapolating UK evidence to the New Zealand context suggests climate change mitigation strategies that reduce air pollution, transition the population towards plant-based diets and increase physical activity via active transport could prevent thousands of deaths per year in coming decades. Substantial health co-benefits would also arise from improved housing, cleaner water, noise reductions, afforestation and more compact cities. The Commission's draft report only briefly mentions many of these health co-benefits, and some are completely absent. We recommend the Commission's final report: (i) use health co-benefits as an explicit frame; (ii) ensure the government's Treaty of Waitangi obligations are met in all the domains covered to maximise benefits for Maori health and wellbeing; (iii) build on the successful COVID-19 response that demonstrated rapid, science-informed and vigorous government action can address major global health threats; (iv) include both public health expertise and Maori health expertise among its commissioners; (v) explain how health co-benefits are likely to generate major cost-savings to the health system.

The carbon footprint of cataract surgery in Wellington.

INTRODUCTION: Efforts to improve the sustainability of ophthalmic care require methods to measure its environmental impact and a baseline measurement to compare against in the future. We aimed to measure the carbon footprint of cataract surgery in Wellington. METHODS: We used Eyefficiency, an application using established footprinting methods, to estimate the emissions produced by phacoemulsification surgery in two public and two private hospitals. We measured (1) power consumption, (2) procurement of disposable items and pharmaceuticals, (3) waste disposal emissions and (4) travel (other potential sources were excluded). Where possible we used New Zealand emissions coefficients. RESULTS: We recorded data from 142 cataract surgeries. The average emissions produced by cataract surgery in the region was estimated to be 152kg of carbon dioxide equivalent. This is equivalent to 62L of petrol and would take 45m2 of forest one year to absorb. The great majority of emissions were from procurement, mostly disposable materials, and the second greatest contribution was from travel (driving). CONCLUSION: Estimating the carbon footprint of cataract surgery is becoming easier, but improved methods for measuring the footprint of procured supplies are needed. There are significant opportunities for emissions reduction in the most common surgical procedure in New Zealand.

The potential of school-based physical education to increase physical activity in Aotearoa New Zealand children and young people: a modelling study.

AIMS: Regular physical activity (PA) is critical for children and young people's health and wellbeing. Schools are an important setting for promoting PA. This study aimed to examine prevalence of PA through physical education in New Zealand schools and the potential impact of increasing physical education on young people's PA levels. METHODS: We used data from the Active NZ Young People Survey of over 8,000 young people and modelled the impact of a hypothetical intervention that increased school-based physical education time to 2.5 hours (consistent with international best practice) on the distribution of PA. RESULTS: At baseline, 61.3% (95%UI 60.2-62.5) of young people were classified as being sufficiently active (7+ hours/week), 19.8% (95%UI 18.9-20.8) were moderately active, and 18.8% (95%CI 17.9-19.7) were minimally active. The intervention scenario would more than halve the prevalence of minimal activity to 8.1% (95%UI 7.5-8.8) and increase the proportion of sufficiently active young people to 68.4% (95%UI 67.3-69.5). CONCLUSION: Increasing time being active through physical education has the potential to reduce the prevalence of minimally active young people in New Zealand. Policies to support increased physical education time, such as time-based requirements, would increase PA levels.

Pregnancy and neonatal outcomes in COVID-19: study protocol for a global registry of women with suspected or confirmed SARS-CoV-2 infection in pregnancy and their neonates, understanding natural history to guide treatment and prevention.

INTRODUCTION: Previous novel COVID-19 pandemics, SARS and middle east respiratory syndrome observed an association of infection in pregnancy with preterm delivery, stillbirth and increased maternal mortality. COVID-19, caused by SARS-CoV-2 infection, is the largest pandemic in living memory.Rapid accrual of robust case data on women in pregnancy and their babies affected by suspected COVID-19 or confirmed SARS-CoV-2 infection will inform clinical management and preventative strategies in the current pandemic and future outbreaks. METHODS AND ANALYSIS: The pregnancy and neonatal outcomes in COVID-19 (PAN-COVID) registry are an observational study collecting focused data on outcomes of pregnant mothers who have had suspected COVID-19 in pregnancy or confirmed SARS-CoV-2 infection and their neonates via a web-portal. Among the women recruited to the PAN-COVID registry, the study will evaluate the incidence of: (1) miscarriage and pregnancy loss, (2) fetal growth restriction and stillbirth, (3) preterm delivery, (4) vertical transmission (suspected or confirmed) and early onset neonatal SARS-CoV-2 infection.Data will be centre based and collected on individual women and their babies. Verbal consent will be obtained, to reduce face-to-face contact in the pandemic while allowing identifiable data collection for linkage. Statistical analysis of the data will be carried out on a pseudonymised data set by the study statistician. Regular reports will be distributed to collaborators on the study research questions. ETHICS AND DISSEMINATION: This study has received research ethics approval in the UK. For international centres, evidence of appropriate local approval will be required to participate, prior to entry of data to the database. The reports will be published regularly. The outputs of the study will be regularly disseminated to participants and collaborators on the study website (https://pan-covid.org) and social media channels as well as dissemination to scientific meetings and journals. STUDY REGISTRATION NUMBER: ISRCTN68026880.

Effects of Antenatal Betamethasone on Fetal Doppler Indices and Short Term Fetal Heart Rate Variation in Early Growth Restricted Fetuses.

PURPOSE: To investigate the effects of the antenatal administration of betamethasone on fetal Doppler and short term fetal heart rate variation (CTG-STV) in early growth restricted (FGR) fetuses. MATERIALS AND METHODS: Post hoc analysis of data derived from the TRUFFLE study, a prospective, multicenter, randomized management trial of severe early onset FGR. Repeat Doppler and CTG-STV measurements between the last recording within 48 hours before the first dose of betamethasone (baseline value) and for 10 days after were evaluated. Multilevel analysis was performed to analyze the longitudinal course of the umbilico-cerebral ratio (UC ratio), the ductus venosus pulsatility index (DVPIV) and CTG-STV. RESULTS: We included 115 fetuses. A significant increase from baseline in CTG-STV was found on day + 1 (p = 0.019) but no difference thereafter. The DVPIV was not significantly different from baseline in any of the 10 days following the first dose of betamethasone (p = 0.167). Multilevel analysis revealed that, over 10 days, the time elapsed from antenatal administration of betamethasone was significantly associated with a decrease in CTG-STV (p = 0.045) and an increase in the DVPIV (p = 0.001) and UC ratio (p < 0.001). CONCLUSION: Although steroid administration in early FGR has a minimal effect on increasing CTG-STV one day afterwards, the effects on Doppler parameters were extremely slight with regression coefficients of small magnitude suggesting no clinical significance, and were most likely related to the deterioration with time in FGR. Hence, arterial and venous Doppler assessment of fetal health remains informative following antenatal steroid administration to accelerate fetal lung maturation.

Fetal weight change close to term is proportional to the birthweight percentile.

OBJECTIVE: To investigate the relationship between the difference in estimated fetal weight and birthweight at or close to term, and in relation to Doppler parameters. STUDY DESIGN: A cohort study of all term singleton pregnancies who underwent an ultrasound within two weeks of delivery after 36 weeks at one institution in one calendar year. When available, Doppler measurements of umbilical and middle cerebral artery pulsatility index were recorded. Data were analysed by Pearson rank correlation. RESULTS: Of 8517 eligible deliveries, 885 women had an ultrasound scan within 2 weeks of delivery. Mean daily differences between estimated fetal weight and birth weight were: those born <10th percentile lost 26 g per day (95 % CI -36 to -16), 10-50th percentile gained 7 g per day (95 % CI -2 to 15), 50th-90th percentile gained 27 g per day (95 % CI 19-35) and >90th percentile gained 48 g per day (95 % CI 32-64). There was a negative correlation between umbilical: middle cerebral artery pulsatility index and the change in weight per day (n = 348, p = 0.001, r = 0.17). CONCLUSIONS: Difference in the estimated fetal weight and birthweight, expressed as grams growth per day, is proportional to the birthweight percentile. Fetuses with a birthweight >10th percentile gain weight, while those with a birthweight <10th percentile apparently decline in weight between their final ultrasound estimated fetal weight and delivery. In babies with the smallest or apparent negative weight gain there was an association with Doppler parameters that signified hypoxia indicating fetal growth at term may be restricted by impaired placental function. Estimated fetal weight may be a poor predictor of birthweight for reasons other than ultrasound or algorithmic error.

Altered Cardiovascular Defense to Hypotensive Stress in the Chronically Hypoxic Fetus.

The hypoxic fetus is at greater risk of cardiovascular demise during a challenge, but the reasons behind this are unknown. Clinically, progress has been hampered by the inability to study the human fetus non-invasively for long period of gestation. Using experimental animals, there has also been an inability to induce gestational hypoxia while recording fetal cardiovascular function as the hypoxic pregnancy is occurring. We use novel technology in sheep pregnancy that combines induction of controlled chronic hypoxia with simultaneous, wireless recording of blood pressure and blood flow signals from the fetus. Here, we investigated the cardiovascular defense of the hypoxic fetus to superimposed acute hypotension. Pregnant ewes carrying singleton fetuses surgically prepared with catheters and flow probes were randomly exposed to normoxia or chronic hypoxia from 121±1 days of gestation (term ≈145 days). After 10 days of exposure, fetuses were subjected to acute hypotension via fetal nitroprusside intravenous infusion. Underlying in vivo mechanisms were explored by (1) analyzing fetal cardiac and peripheral vasomotor baroreflex function; (2) measuring the fetal plasma catecholamines; and (3) establishing fetal femoral vasoconstrictor responses to the α1-adrenergic agonist phenylephrine. Relative to controls, chronically hypoxic fetal sheep had reversed cardiac and impaired vasomotor baroreflex function, despite similar noradrenaline and greater adrenaline increments in plasma during hypotension. Chronic hypoxia markedly diminished the fetal vasopressor responses to phenylephrine. Therefore, we show that the chronically hypoxic fetus displays markedly different cardiovascular responses to acute hypotension, providing in vivo evidence of mechanisms linking its greater susceptibility to superimposed stress.