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.

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.

Uterine and fetal placental Doppler indices are associated with maternal cardiovascular function.

BACKGROUND: The mechanism underlying fetal-placental Doppler index changes in preeclampsia and/or fetal growth restriction are unknown, although both are associated with maternal cardiovascular dysfunction. OBJECTIVE: We sought to investigate whether there was a relationship between maternal cardiac output and vascular resistance and fetoplacental Doppler findings in healthy and complicated pregnancy. STUDY DESIGN: Women with healthy pregnancies (n=62), preeclamptic pregnancies (n=13), preeclamptic pregnancies with fetal growth restriction (n=15), or fetal growth restricted pregnancies (n=17) from 24-40 weeks gestation were included. All of them underwent measurement of cardiac output with the use of an inert gas rebreathing technique and derivation of peripheral vascular resistance. Uterine and fetal Doppler indices were recorded; the latter were z scored to account for gestation. Associations were determined by polynomial regression analyses. RESULTS: Mean uterine artery pulsatility index was higher in fetal growth restriction (1.37; P=.026) and preeclampsia+fetal growth restriction (1.63; P=.001) but not preeclampsia (0.92; P=1) compared with control subjects (0.8). There was a negative relationship between uterine pulsatility index and cardiac output (r2=0.101; P=.025) and umbilical pulsatility index z score and cardiac output (r2=0.078; P=.0015), and there were positive associations between uterine pulsatility index and peripheral vascular resistance (r2=0.150; P=.003) and umbilical pulsatility index z score and peripheral vascular resistance (r2= 0.145; P=.001). There was no significant relationship between cardiac output and peripheral vascular resistance with cerebral Doppler indices. CONCLUSION: Uterine artery Doppler change is abnormally elevated in fetal growth restriction with and without preeclampsia, but not in preeclampsia, which may explain the limited sensitivity of uterine artery Doppler changes for all these complications when considered in aggregate. Furthermore, impedance within fetoplacental arterial vessels is at least, in part, associated with maternal cardiovascular function. This relationship may have important implications for fetal surveillance and would inform therapeutic options in those pathologic pregnancy conditions currently, and perhaps erroneously, attributed purely to placental maldevelopment. Uterine and fetal placental Doppler indices are associated significantly with maternal cardiovascular function. The classic description of uterine and fetal Doppler changes being initiated by placental maldevelopment is a less plausible explanation for the pathogenesis of the conditions than that relating to maternal cardiovascular changes.

Service organisation for people with dementia after an injurious fall: challenges and opportunities.

INTRODUCTION: people with dementia are more likely to fall and less likely to recover well after a fall than cognitively intact older people. Little is known about how best to deliver services to this patient group. This paper explored current service provision to help inform the development of a new intervention. METHODS: qualitative approaches were used to explore the views and experiences of people with dementia, family carers and professionals providing services to people with dementia following an injurious fall. These data were analysed using a thematic, iterative analysis. FINDINGS: while a wide range of services potentially relevant to people with dementia was identified, there were no dedicated services for people with dementia with fall-related injuries in our three geographical areas. Factors influencing service uptake included a lack of knowledge of local provision amongst professionals and underdeveloped information sharing systems. Some aspects of current service organisation were incompatible with the needs of people with dementia. These include an emphasis on time-limited interventions; lack of longer-term follow-up; and service delivery in environments that could be challenging for people with dementia. CONCLUSIONS: care pathways for people with dementia who fall are fragmented and unclear. This is likely to preclude people with dementia from receiving all appropriate support and contribute to poor recovery following a fall. The findings highlight the need for new approaches to service organisation and delivery which address the specific needs of people with dementia who fall.

Developing an Intervention for Fall-Related Injuries in Dementia (DIFRID): an integrated, mixed-methods approach.

BACKGROUND: Falls in people with dementia can result in a number of physical and psychosocial consequences. However, there is limited evidence to inform how best to deliver services to people with dementia following a fall. The aim of the DIFRID study was to determine the feasibility of developing and implementing a new intervention to improve outcomes for people with dementia with fall-related injuries; this encompasses both short-term recovery and reducing the likelihood of future falls. This paper details the development of the DIFRID intervention. METHODS: The intervention was designed using an integrated, mixed-methods approach. This involved a realist synthesis of the literature and qualitative data gathered through interviews and focus groups with health and social care professionals (n = 81). An effectiveness review and further interviews and observation were also conducted and are reported elsewhere. A modified Delphi panel approach with 24 experts was then used to establish a consensus on how the findings should translate into a new intervention. After feedback from key stakeholders (n = 15) on the proposed model, the intervention was manualised and training developed. RESULTS: We identified key components of a new intervention covering three broad areas: • Ensuring that the circumstances of rehabilitation are optimised for people with dementia • Compensating for the reduced ability of people with dementia to self-manage • Equipping the workforce with the necessary skills and information to care for this patient group Consensus was achieved on 54 of 69 statements over two rounds of the Delphi surveys. The statements were used to model the intervention and finalise the accompanying manual and protocol for a feasibility study. Stakeholder feedback was generally positive and the majority of suggested intervention components were approved. The proposed outcome was a 12-week complex multidisciplinary intervention primarily based at the patient's home. CONCLUSIONS: A new intervention has been developed to improve outcomes for people with dementia following a fall requiring healthcare attention. The feasibility of this intervention is currently being tested. TRIAL REGISTRATION: ISRCTN41760734 (16/11/2015).

Equipping staff with the skills to maximise recovery of people with dementia after an injurious fall.

Objectives: People with dementia are more likely to fall and less likely to recover well after a fall than cognitively intact older people. Little is known about how best to deliver services to this patient group. This paper explores the importance of compensating for cognitive impairment when working with people with dementia. Methods: Qualitative methods - interviews, focus groups and observation - were used to explore the views and experiences of people with dementia, family carers and professionals providing services to people with dementia following an injurious fall. A thematic, iterative analysis was undertaken in which emerging themes were identified from each individual dataset, prior to an integrative analysis. Results: A key theme across all datasets was the need to deliver services in ways that compensate for cognitive impairment, such as negotiating meaningful activities that can be embedded into the routines of people with dementia. Professionals varied in their ability to adapt their practice to meet the needs of people with dementia. Negative attitudes towards dementia, a lack of knowledge and understanding of dementia limited the ability of some professionals to work in person-centred ways. Conclusion: Improving outcomes for people with dementia following a fall requires the principles of person-centred care to be enacted by professionals with a generic role, as well as specialist staff. This requires additional training and support by specialist staff to address the wide variability in current practice.

Physical activity and risk of testicular cancer: a systematic review.

BACKGROUND: Physical activity has been implicated as a risk factor in the development of testicular cancer (TC), but the relationship remains controversial. This systematic review pooled available evidence regarding this association. METHODS: Using Boolean search terms and following PRISMA guidelines, we examined the risk of TC across three categories of exposure: intensity (i.e. comparison of risk between those previously exposed to high, moderate and low levels of physical activity); dose-response (i.e. whether risk of TC increases or decreases with increasing exposure to physical activity); and the role of timing of physical activity (i.e. during early childhood or adolescence). RESULTS: Thirteen studies (11 case-control studies, 2 cohort studies) were included in the review. While some studies have reported a strong protective effect of high levels of physical activity on risk of TC, others have reported either no relationship or a weak direct association; and while a dose-response relationship has been identified across several studies, this relationship has been observed in both directions. Similarly conflicting results exist in terms of individual types of activity and the lifecourse timing of the physical activity. Reasons for this inconsistency may include the absence of any association, heterogeneous assessment of physical activity, misclassification bias and difference in sample sizes. CONCLUSIONS: On balance, there is presently no strong evidence of an association between physical activity and risk of subsequent TC. This review highlights key areas for future investigation that may clarify any association between physical activity and risk of testicular cancer.

Primary care physicians' attitudes to the adoption of electronic medical records: a systematic review and evidence synthesis using the clinical adoption framework.

BACKGROUND: Recent decades have seen rapid growth in the implementation of Electronic Medical Records (EMRs) in healthcare settings in both developed regions as well as low and middle income countries. Yet despite substantial investment, the implementation of EMRs in some primary care systems has lagged behind other settings, with piecemeal adoption of EMR functionality by primary care physicians (PCPs) themselves. We aimed to review and synthesise international literature on the attitudes of PCPs to EMR adoption using the Clinical Adoption (CA) Framework. METHODS: MEDLINE, PsycINFO, and EMBASE were searched from 1st January 1996 to 1st August 2017 for studies investigating PCP attitudes towards EMR adoption. Papers were screened by two independent reviewers, and eligible studies selected for further assessment. Findings were categorised against the CA Framework and the quality of studies assessed against one of three appropriate tools. RESULTS: Out of 2263 potential articles, 33 were included, based in North and South America, Europe, Middle East and Hong Kong. Concerns about the accessibility, reliability and EMR utility exerted an adverse influence on PCPs' attitudes to adoption. However many were positive about their potential to improve clinical productivity, patient safety and care quality. Younger, computer-literate PCPs, based in large/multi-group practices, were more likely to be positively inclined to EMR use than older physicians, less-skilled in technology use, based in solo practices. Adequate training, policies and procedures favourably impacted on PCPs' views on EMR implementation. Financial factors were common system level influencers shaping EMR adoption, from start-up costs to the resources required by ongoing use. CONCLUSIONS: By using the CA Framework to synthesise the evidence, we identified a linked series of factors influencing PCPs attitudes to EMR adoption. Findings underline the need to involve end-users in future implementation programmes from the outset, to avoid the development of an EMR which is neither feasible nor acceptable for use in practice. TRIAL REGISTRATION: PROSPERO CRD42016038790 .

Phase-rectified signal averaging method to predict perinatal outcome in infants with very preterm fetal growth restriction- a secondary analysis of TRUFFLE-trial.

BACKGROUND: Phase-rectified signal averaging, an innovative signal processing technique, can be used to investigate quasi-periodic oscillations in noisy, nonstationary signals that are obtained from fetal heart rate. Phase-rectified signal averaging is currently the best method to predict survival after myocardial infarction in adult cardiology. Application of this method to fetal medicine has established significantly better identification than with short-term variation by computerized cardiotocography of growth-restricted fetuses. OBJECTIVE: The aim of this study was to determine the longitudinal progression of phase-rectified signal averaging indices in severely growth-restricted human fetuses and the prognostic accuracy of the technique in relation to perinatal and neurologic outcome. STUDY DESIGN: Raw data from cardiotocography monitoring of 279 human fetuses were obtained from 8 centers that took part in the multicenter European "TRUFFLE" trial on optimal timing of delivery in fetal growth restriction. Average acceleration and deceleration capacities were calculated by phase-rectified signal averaging to establish progression from 5 days to 1 day before delivery and were compared with short-term variation progression. The receiver operating characteristic curves of average acceleration and deceleration capacities and short-term variation were calculated and compared between techniques for short- and intermediate-term outcome. RESULTS: Average acceleration and deceleration capacities and short-term variation showed a progressive decrease in their diagnostic indices of fetal health from the first examination 5 days before delivery to 1 day before delivery. However, this decrease was significant 3 days before delivery for average acceleration and deceleration capacities, but 2 days before delivery for short-term variation. Compared with analysis of changes in short-term variation, analysis of (delta) average acceleration and deceleration capacities better predicted values of Apgar scores <7 and antenatal death (area under the curve for prediction of antenatal death: delta average acceleration capacity, 0.62 [confidence interval, 0.19-1.0]; delta short-term variation, 0.54 [confidence interval, 0.13-0.97]; P=.006; area under the curve for prediction Apgar <7: average deceleration capacity <24 hours before delivery, 0.64 [confidence interval, 0.52-0.76]; short-term variation <24 hours before delivery, 0.53 [confidence interval, 0.40-0.65]; P=.015). Neither phase-rectified signal averaging indices nor short-term variation showed predictive power for developmental disability at 2 years of age (Bayley developmental quotient, <95 or <85). CONCLUSION: The phase-rectified signal averaging method seems to be at least as good as short-term variation to monitor progressive deterioration of severely growth-restricted fetuses. Our findings suggest that for short-term outcomes such as Apgar score, phase-rectified signal averaging indices could be an even better test than short-term variation. Overall, our findings confirm the possible value of prospective trials based on phase-rectified signal averaging indices of autonomic nervous system of severely growth-restricted fetuses.

Fetal movements as a predictor of health.

The key determinant to a fetus maintaining its health is through adequate perfusion and oxygen transfer mediated by the functioning placenta. When this equilibrium is distorted, a number of physiological changes, including reduced fetal growth, occur to favor survival. Technologies have been developed to monitor these changes with a view to prolong intrauterine maturity while reducing the risks of stillbirth. Many of these strategies involve complex interpretation, for example Doppler ultrasound for fetal blood flow and computerized analysis of fetal heart rate changes. However, even with these modalities of fetal assessment to determine the optimal timing of delivery, fetal movements remain integral to clinical decision-making. In high-risk cohorts with fetal growth restriction, the manifestation of a reduction in perceived movements may warrant an expedited delivery. Despite this, there has been little evolution in the development of technologies to objectively evaluate fetal movement behavior for clinical application. This review explores the available literature on the value of fetal movement analysis as a method of assessing fetal wellbeing, and demonstrates how interdisciplinary developments in this area may aid in the improvement of clinical outcomes.

Treatments for Hyperemesis Gravidarum and Nausea and Vomiting in Pregnancy: A Systematic Review.

Importance: Nausea and vomiting affects approximately 85% of pregnant women. The most severe form, hyperemesis gravidarum, affects up to 3% of women and can have significant adverse physical and psychological sequelae. Objective: To summarize current evidence on effective treatments for nausea and vomiting in pregnancy and hyperemesis gravidarum. Evidence Review: Databases were searched to June 8, 2016. Relevant websites and bibliographies were also searched. Titles and abstracts were assessed independently by 2 reviewers. Results were narratively synthesized; planned meta-analysis was not possible because of heterogeneity and incomplete reporting of findings. Findings: Seventy-eight studies (n = 8930 participants) were included: 67 randomized clinical trials (RCTs) and 11 nonrandomized studies. Evidence from 35 RCTs at low risk of bias indicated that ginger, vitamin B6, antihistamines, metoclopramide (for mild symptoms), pyridoxine-doxylamine, and ondansetron (for moderate symptoms) were associated with improved symptoms compared with placebo. One RCT (n = 86) reported greater improvements in moderate symptoms following psychotherapy (change in Rhodes score [range, 0 {no symptoms} to 40 {worst possible symptoms}], 18.76 [SD, 5.48] to 7.06 [SD, 5.79] for intervention vs 19.18 [SD, 5.63] to 12.81 [SD, 6.88] for comparator [P < .001]). For moderate-severe symptoms, 1 RCT (n = 60) suggested that pyridoxine-doxylamine combination taken preemptively reduced risk of recurrence of moderate-severe symptoms compared with treatment once symptoms begin (15.4% vs 39.1% [P < .04]). One RCT (n = 83) found that ondansetron was associated with lower nausea scores on day 4 than metoclopramide (mean visual analog scale [VAS] score, 4.1 [SD, 2.9] for ondansetron vs 5.7 [SD, 2.3] for metoclopramide [P = .023]) but not episodes of emesis (5.0 [SD, 3.1] vs 3.3 [SD, 3], respectively [P = .013]). Although there was no difference in trend in nausea scores over the 14-day study period, trend in vomiting scores was better in the ondansetron group (P = .042). One RCT (n = 159) found no difference between metoclopramide and promethazine after 24 hours (episodes of vomiting, 1 [IQR, 0-5] for metoclopramide vs 2 [IQR, 0-3] for promethazine [P = .81], VAS [0-10 scale] for nausea, 2 [IQR, 1-5] vs 2 [IQR, 1-4], respectively [P = .99]). Three RCTs compared corticosteroids with placebo or promethazine or metoclopramide in women with severe symptoms. Improvements were seen in all corticosteroid groups, but only a significant difference between corticosteroids vs metoclopramide was reported (emesis reduction, 40.9% vs 16.5% at day 2; 71.6% vs 51.2% at day 3; 95.8% vs 76.6% at day 7 [n = 40, P < .001]). For other interventions, evidence was limited. Conclusions and Relevance: For mild symptoms of nausea and emesis of pregnancy, ginger, pyridoxine, antihistamines, and metoclopramide were associated with greater benefit than placebo. For moderate symptoms, pyridoxine-doxylamine, promethazine, and metoclopramide were associated with greater benefit than placebo. Ondansetron was associated with improvement for a range of symptom severity. Corticosteroids may be associated with benefit in severe cases. Overall the quality of evidence was low.

Climate change, cash transfers and health.

The forecast consequences of climate change on human health are profound, especially in low- and middle-income countries and among the most disadvantaged populations. Innovative policy tools are needed to address the adverse health effects of climate change. Cash transfers are established policy tools for protecting population health before, during and after climate-related disasters. For example, the Ethiopian Productive Safety Net Programme provides cash transfers to reduce food insecurity resulting from droughts. We propose extending cash transfer interventions to more proactive measures to improve health in the context of climate change. We identify promising cash transfer schemes that could be used to prevent the adverse health consequences of climatic hazards. Cash transfers for using emission-free, active modes of transport - e.g. cash for cycling to work - could prevent future adverse health consequences by contributing to climate change mitigation and, at the same time, improving current population health. Another example is cash transfers provided to communities that decide to move to areas in which their lives and health are not threatened by climatic disasters. More research on such interventions is needed to ensure that they are effective, ethical, equitable and cost-effective.

Les conséquences attendues du changement climatique sur la santé humaine sont importantes, en particulier dans les pays à revenu faible et intermédiaire et pour les populations les plus défavorisées. Des moyens d'intervention innovants sont nécessaires pour lutter contre les effets néfastes du changement climatique sur la santé. Les transferts d'argent sont des moyens d'intervention éprouvés pour protéger la santé de la population avant, pendant et après les catastrophes climatiques. Le Programme de création de dispositifs de sécurité productifs de l'Éthiopie, par exemple, prévoit des transferts d'argent pour réduire l'insécurité alimentaire découlant des périodes de sécheresse. Nous proposons d'inclure les opérations de transfert d'argent dans des actions plus préventives en vue d'améliorer la santé dans le contexte du changement climatique. Nous avons identifié différents systèmes de transfert d'argent prometteurs qui pourraient être utilisés pour éviter les conséquences néfastes des risques liés au climat sur la santé. Les transferts d'argent visant l'utilisation de moyens de transport actifs et sans émissions ­ pour se rendre au travail à vélo par ex. ­ pourraient prévenir les futures conséquences néfastes sur la santé en contribuant à l'atténuation du changement climatique et en améliorant ainsi l'état actuel de la santé de la population. Un autre exemple concerne les transferts d'argent accordés aux communautés qui décident de s'établir dans des régions où leur vie et leur santé ne sont pas menacées par des catastrophes climatiques. Davantage de recherches sur ces opérations sont nécessaires pour prouver leur efficacité, leur caractère éthique et équitable ainsi que leur rentabilité.

Las consecuencias previstas del cambio climático en la salud humana son severas, especialmente en los países de ingresos bajos y medios y entre los grupos más desfavorecidos. Se necesitan instrumentos normativos innovadoras para afrontar los efectos adversos sobre la salud que el cambio climático produce. Las transferencias de efectivo son instrumentos normativos establecidos para proteger la salud de la población antes, durante y después de los desastres relacionados con el clima. Por ejemplo, el Programa "Red de Seguridad Productiva" de Etiopía proporciona transferencias de efectivo para reducir la inseguridad alimentaria derivada de las sequías. Nosotros proponemos extender las intervenciones de transferencias de efectivo a medidas más proactivas para mejorar la salud en el contexto del cambio climático. Identificamos planes prometedores de transferencia de efectivo que podrían utilizarse para prevenir las consecuencias adversas sobre la salud provocadas por los riesgos climáticos. Las transferencias de efectivo para usar modos de transporte activos y libres de emisiones (por ejemplo, dinero para ir al trabajo en bicicleta) podrían prevenir futuras consecuencias adversas sobre la salud, contribuyendo a la mitigación del cambio climático y, al mismo tiempo, mejorando la salud actual de la población. Otro ejemplo son las transferencias de efectivo realizadas a comunidades que deciden trasladarse a zonas dónde sus vidas y su salud no estén amenazadas por los desastres climáticos. Es necesario llevar a cabo más investigaciones en estas intervenciones para garantizar que sean efectivas, éticas, equitativas y costoefectivas.

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.

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

Nil.

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.

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.

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.

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.