Estimation of health utility values for alopecia areata.

PURPOSE: Alopecia areata (AA) is an autoimmune-mediated inflammatory dermatological disease characterised by non-scarring hair loss affecting the scalp and sometimes other hair-bearing sites. This study aimed to elicit health state utility values (HSUVs) from the UK general population for AA using time trade off (TTO) interviews. METHODS: Vignette descriptions of health states defined by the extent of hair loss were developed (as well as one describing caregiver burden). These were developed using data from standardised patient reported outcome (PRO) measures, a literature review and qualitative interviews. Health states were defined based on the severity of alopecia tool (SALT), which assesses extensiveness of scalp hair loss. HSUVs were then elicited for each health state in TTO interviews with the UK public. RESULTS: One caregiver and five patient health states were developed based on the literature review findings, clinical trial PRO (Hospital Anxiety and Depression Scale and Alopecia Areata Patient Priority Outcomes Questionnaire) data and qualitative interviews with patients (N = 11), clinical experts (N = 4) and caregivers of adolescents with AA (N = 10). These data showed a more severe impact among patients with more extensive hair loss. One hundred and twenty participants evaluated the vignettes in TTO interviews. Patient HSUVs ranged from 0.502 for the most extensive hair loss health state (SALT 50-100 + eyebrow and eyelash loss) to 0.919 (SALT 0-10) for the mildest health state. The caregiver HSUV was 0.882. CONCLUSION: Quantitative and qualitative data sources were used to develop and validate vignettes describing different AA health states. Patient and caregiver HSUVs demonstrate a large impact associated with AA, especially for states defined by more extensive hair loss.

Patient preferences for advanced hepatocellular carcinoma treatment: a multicountry stated preference study.

The present study aimed to explore patient preferences for attributes of advanced hepatocellular carcinoma (HCC) treatments. A stated preference survey was completed by 150 patients with HCC living in Europe. Overall survival (OS) was the most important attribute, closely followed by risk of diarrhea and hypertension, and other adverse event (AE) risks. Patients were willing to trade OS to reduce AE risks. While less important than OS and AEs, patients also preferred shorter waiting times, and one-off administration of selective internal radiation therapy and oral tablets over intravenous infusions. Although patients placed the most value on extending OS, they were willing to forego OS to avoid risk of treatment-related AEs, to maintain their quality of life.

Lay abstract This study aimed to understand patient preferences for characteristics of advanced hepatocellular carcinoma (HCC) treatments. A total of 150 people with HCC in Europe were presented a series of questions asking them to choose between two hypothetical treatments. Overall, length of life was the most important issue for patients, followed by avoiding diarrhea and hypertension, and then other side effects and treatment risks. Patients were willing to forego some months of life to avoid side effects or risks. Patients preferred to be given their treatment via a single minimally invasive hospital procedure or oral daily tablets compared with intravenous drips. In conclusion, although patients placed the most value on overall length of life, side effects and treatment risks were also important.

Association Between 20-Year Trajectories of Nonoccupational Physical Activity From Midlife to Old Age and Biomarkers of Cardiovascular Disease: A 20-Year Longitudinal Study of British Men.

The trajectories of physical activity (PA) from midlife into old age and their associations with established and novel cardiovascular disease (CVD) risk factors in later life remain unclear. This study examined associations between 20-year nonoccupational PA trajectories and a range of CVD biomarkers at ages 60-79 years. We used data from a sample of 3,331 men (mean baseline age = 50.2 ± 5.8 years) recruited in 1978-1980, with follow-up after 12, 16, and 20 years, reporting habitual nonoccupational PA at each wave. At the 20-year follow-up, surviving men attended a physical examination and provided a fasting blood sample. Group-based trajectory modeling was used to identify trajectories. Adjusted regression analyses examined the association between trajectory-group membership and several cardiometabolic, cardiac, and inflammatory markers at follow-up. Three distinct 20-year trajectories were identified: low/decreasing (21.3%), light/stable (51.8%), and moderate/increasing (27.0%). Compared with the low/decreasing group, membership in the light/stable and moderate/increasing trajectory groups was associated with a more favorable cardiometabolic profile and lower levels of inflammation and endothelial dysfunction. Although following a moderate-increasing PA trajectory was most favorable, more modest but sustained doses of PA into old age may be sufficient to lower CVD risk.

Trajectories of self-reported physical activity and predictors during the transition to old age: a 20-year cohort study of British men.

BACKGROUND: Maintenance of physical activity (PA) during later life is associated with optimal health; however, the long-term trajectories of PA into old age and their predictors have not been extensively researched using latent class methods. This study aimed to identify trajectories of self-reported PA and their predictors in men transitioning from midlife to old age. METHODS: 7735 men (aged 40-59 years) recruited in 1978-80 were followed up after 12, 16 and 20 years, reporting PA, health status, lifestyle behaviours and socio-demographic characteristics. Group-based trajectory modelling identified the trajectories of PA and associations with time-stable and time-varying covariates. We considered a range of sociodemographic and health and lifestyle factors as potential covariates. RESULTS: 4952 men (mean baseline age 49.1 ± 5.6 years) providing PA data at ≥3 time points were included in analyses. Three distinct 20-year trajectories were identified: low decreasing (24.6%, n = 1218), light stable (51.1%, n = 2530) and moderate increasing (24.3%, n = 1204). Being older, having a manual occupation, having never married or had children, residing in the midlands or North of England, suffering from a range of health conditions, being a smoker/ex-smoker and never consuming breakfast cereal or alcohol were independently associated with reduced odds of belonging to the moderate increasing trajectory group compared to the low decreasing group. Of the time-varying covariates considered, leaving employment was associated with a decrease in PA in the low decreasing group (ß -0.306, p < 0.001) but an increase in the light stable (ß 0.324, p < 0.001) and moderate increasing groups (ß 0.847, p < 0.001). Developing cardiovascular-related conditions was associated with a decrease in PA in the low decreasing (ß -0.408, p < 0.001) and light stable groups (ß -0.118, p < 0.001) but no association was observed in the moderate increasing group (ß -0.060, p = 0.313). CONCLUSIONS: Three distinct trajectories of PA were identified in men transitioning from midlife to old age, of which nearly a quarter had persistently low levels of PA. Promotion efforts may need to focus attention prior to middle age and consider a number of sociodemographic, health and lifestyle factors to sustain PA into old age. The effects of retirement and development of cardiovascular disease may vary according to PA trajectories.

Objectively Measured Daily Physical Activity and Postural Changes as Related to Positive and Negative Affect Using Ambulatory Monitoring Assessments.

OBJECTIVE: The aim of the study was to determine whether objectively measured daily physical activity and posture of sitting, standing, and sit-to-stand transitions are associated with daily assessments of affect. METHODS: Participants (N = 51, 49% female) wore ActivPal accelerometers for 24 h/d for seven consecutive days. Time spent sitting, standing, and being physically active and sit-to-stand transitions were derived for each day. Participants also completed a mood inventory each evening. Multilevel models examined within- and between-person associations of daily physical activity with positive and negative affect, adjusting for age, sex, body mass index, education, and sleep duration. RESULTS: Within-person associations showed that a 1-hour increase in daily physical activity was associated with a decrease in negative affect over the same day (B = -0.11, 95% confidence interval [CI], -0.21 to -0.01). Between-person associations indicated a borderline significant association between higher average daily physical activity levels and higher positive affect (B = 1.85, 95% CI = -0.25 to 3.94). There were no between- or within-person associations between sitting, standing, and sit-to-stand transitions with affect. CONCLUSIONS: Promoting physical activity may be a potential intervention strategy to acutely suppress negative affective states.

Active travel to non-school destinations but not to school is associated with higher physical activity levels in an ethnically diverse sample of inner-city schoolchildren.

BACKGROUND: This study investigated the association of travel mode to school and non-school destinations with objectively assessed health markers and physical activity in an ethnically diverse sample of inner-city UK schoolchildren. METHODS: We used data from the Camden Active Spaces project (n = 450 children aged 9.1 yrs) to examine associations of school travel mode and frequency of active travel to non-school destinations with daily and out-of-school physical activity, sedentary time and health markers; whilst controlling for appropriate covariates including objectively measured route length. RESULTS: High frequency of active travel to non-school destinations was associated with more time in moderate-to-vigorous physical activity during out-of-school periods (3.8, 0.8-6.9 min/d) and greater out-of-school (738, 197.4-1278.6 steps/d) and daily step counts (588.1, 51.6-1124.6 steps/d). No associations were observed between school travel mode, health outcomes and activity levels. CONCLUSION: High frequency of active travel to non-school destinations is associated with higher levels of physical activity. These findings highlight the contribution of travel to non-school destinations to overall physical activity levels in schoolchildren.

Effect of major school playground reconstruction on physical activity and sedentary behaviour: Camden active spaces.

BACKGROUND: The physical school environment is a promising setting to increase children's physical activity although robust evidence is sparse. We examined the effects of major playground reconstruction on physical activity and sedentary time in primary schools using a quasi-experimental design (comparison group pre-test/post-test design). METHODS: Five experimental and two control schools from deprived areas of inner city London were recruited at baseline. Main outcome was physical activity and sedentary time measured from objective monitoring (Actigraph accelerometer) at one year follow up. Pupils' impressions of the new playground were qualitatively assessed post construction. RESULTS: A total of 347 pupils (mean age = 8 years, 55% boys; 36% Caucasian) were recruited into the study at baseline; 303 provided valid baseline Actigraph data. Of those, 231 (76%) completed follow-up (n = 169 intervention; n = 62 control) and 77.4% of the sample recorded at least 4 days of Actigraph wear. In mixed models adjusted for age, sex, ethnicity, ratio activity or sedentary/wear time at baseline, wear time at follow up, and school, no differences were observed in total moderate - vigorous activity (B = -1.4, 95% CI, -7.1, 4.2 min/d), light activity (B = 4.1, 95% CI, -17.9, 26.1), or sedentary time (B = -3.8, 95% CI, -29.2, 21.6 min/d) between groups. There were significant age interactions for sedentary (p = 0.002) and light intensity physical activity (p = 0.008). We observed significant reductions in total sedentary (-28.0, 95% CI, -1.9, -54.1 min/d, p = 0.037) and increases in total light intensity activity (24.6, 95% CI, 0.3, 48.9 min/d, p = 0.047) for children aged under 9 yrs. old in the intervention. CONCLUSION: Major playground reconstruction had limited effects on physical activity, but reduced sedentary time was observed in younger children. Qualitative data suggested that the children enjoyed the new playgrounds and experienced a perceived positive change in well-being and social interactions.

Context-Specific Associations of Physical Activity and Sedentary Behavior With Cognition in Children.

In the present study, we investigated how overall and specific domains of physical activity and sedentary behavior at the age of 7 years were associated with cognition at the age of 11 years in 8,462 children from the Millennium Cohort Study. Data were collected from 2001 to 2013. Participation in domains of physical activity and sedentary behavior at 7 years of age were reported. Activity levels were also measured objectively. Cognition was assessed using the British Ability Scales. General linear models were used to assess longitudinal associations of physical activity and sedentary behavior, measured both objectively and via self-report, with cognition. Analyses were adjusted for prespecified covariates. Sports/physical activity club attendance (B = 0.6, 95% confidence interval (CI): 0.2, 1.1), doing homework (B = 0.5, 95% CI: 0.0, 0.9), and objectively measured sedentary time (B = 0.8, 95% CI: 0.1, 1.4) at age 7 years were positively associated with cognition at age 11 years in final the models. Television viewing was negatively associated with cognition (B = -1.7, 95% CI: -2.4, -1.0), although the association was attenuated to the null after adjustments for baseline cognition. Objectively measured light physical activity was inversely associated with cognition (B = -0.7, 95% CI: -1.3, -0.1). Moderate-to-vigorous physical activity was also inversely associated with cognition in girls only (B = -1.1, 95% CI: -2.0, -0.3). Associations of physical activity and sedentary behavior with cognition appear to be context-specific in young people.

Cross-sectional associations of objectively measured physical activity and sedentary time with sarcopenia and sarcopenic obesity in older men.

This study investigated associations between objectively measured physical activity (PA) with sarcopenia and sarcopenic obesity in older British men. Participants were men aged 70-92years (n=1286) recruited from UK Primary Care Centres. Outcomes included (i) sarcopenia, defined as low muscle mass (lowest two fifths of the mid-upper arm muscle circumference distribution) accompanied by low muscular strength (hand grip strength <30kg) or low physical performance (gait speed≤0.8m/s); (ii) severe sarcopenia, required all three conditions; (iii) sarcopenic obesity defined as sarcopenia or severe sarcopenia and a waist circumference of >102cm. Independent variables included time spent in PA intensities measured by GT3x accelerometers, worn during one week in 2010-12. Multinomial regression models were used for cross-sectional analyses relating PA and sarcopenia. In total, 14.2% (n=183) of men had sarcopenia and a further 5.4% (n=70) had severe sarcopenia. 25.3% of sarcopenic or severely sarcopenic men were obese. Each extra 30min per day of moderate-to-vigorous PA (MVPA) was associated with a reduced risk of severe sarcopenia (relative risk [RR] 0.53, 95% confidence interval [CI] 0.30, 0.93) and sarcopenic obesity (RR 0.47 [95% CI 0.27, 0.84]). Light PA (LPA) and sedentary breaks were marginally associated with a reduced risk of sarcopenic obesity. Sedentary time was marginally associated with an increased risk of sarcopenic obesity independent of MVPA (RR 1.18 [95% CI 0.99, 1.40]). MVPA may reduce the risk of severe sarcopenia and sarcopenic obesity among older men. Reducing sedentary time and increasing LPA and sedentary breaks may also protect against sarcopenic obesity.

Effects of reallocating time in different activity intensities on health and fitness: a cross sectional study.

BACKGROUND: The effects of replacing time in specific activity categories for other categories (e.g. replacing sedentary time with light activity) on health and fitness are not well known. This study used isotemporal substitution to investigate the effects of substituting activity categories in an equal time exchange fashion on health and fitness in young people. METHODS: Participants were drawn from schools in Camden, London (n = 353, mean age 9.3 ± 2.3 years). Time sedentary, in light and in moderate-to-vigorous activity (MVPA) was measured via accelerometry. The effects of substituting time in activity categories (sedentary, light and MVPA) with equivalent time in another category on health and fitness were examined using isotemporal substitution. RESULTS: In single and partition models, MVPA was favourably associated with body fat %, horizontal jump distance and flexibility. Time sedentary and in light activity were not associated with health and fitness outcomes in these models. In substitution models, replacing one hour of sedentary time with MVPA was favourably associated with body fat % (B = -4.187; 95% confidence interval (CI), -7.233, -1.142), horizontal jump distance (B = 16.093; 95% CI, 7.476, 24.710) and flexibility (B = 4.783; 95% CI, 1.910, 7.656). Replacing time in light activity with MVPA induced similar benefits but there were null effects for replacing sedentary with light intensity. CONCLUSION: Substituting time sedentary and in light activity with MVPA was associated with favourable health and fitness. Time in sedentary behaviour may only be detrimental to health and fitness when it replaces time in MVPA in young people.

Association between participation in outdoor play and sport at 10 years old with physical activity in adulthood.

OBJECTIVE: This study aimed to investigate whether active outdoor play and/or sports at age 10 is associated with sport/physical activity at 32 year follow-up using a birth cohort study. METHODS: Data were from the 1970 British Cohort Study, a longitudinal observational study. The present paper included data from the age 10 years and age 42 years surveys. At age 10 the participant's mother provided information regarding how often their child played sports, and played outside on streets, parks or playgrounds. At age 42 participants reported frequency of participation in physical activities and sports. Associations between participation in sport/active outdoor play at age 10 years and adult sport/physical activity were investigated using adjusted (gender, fathers socio-occupational class, child's BMI, father's BMI, self-rated health at age 42, assessment of own weight at age 42, participant's education) Cox regression. RESULTS: Final adjusted Cox regression models showed that participants (n=6458) who often participated in sports at age 10 were significantly more likely to participate in sport/physical activity at age 42 (RR 1.10; 95% CI 1.01 to 1.19). Active outdoor play at age 10 was not associated with participation in sport/physical activity at age 42 (RR 0.99; 95% CI 0.91 to 1.07). CONCLUSION: Childhood activity interventions might best achieve lasting change by promoting engagement in sport rather than active outdoor play.

Mothers' perceived proximity to green space is associated with TV viewing time in children: the Growing Up in Scotland study.

OBJECTIVE: The aim of this study is to investigate whether mothers' perception of distance from home to green/open spaces is associated with their child's screen time. METHOD: We used mother-reported data from sweep six (2010-2011) of the Growing Up in Scotland study (n=3586 children aged 5.9yrs) to examine associations between walking distance from home to green/open space and screen time (TV viewing time/computer use). Analyses were adjusted for age, sex and other pre-specified covariates, including sport/exercise participation, mental and general health, birth weight, parental socio-economic group (SEG) and smoking status. RESULTS: Children living the furthest distance from green/open spaces (>20minutes' walking distance) displayed over 2h (95% CI, 0.65 to 3.51) more weekly TV time than the reference category (<5minutes' walking distance). Compared to children in the reference category, those in the >20minute category had worse mental health (mean SDQ [Strengths and Difficulties Questionnaire] score±SD, 7.0±4.6 vs. 8.7±6.2) and general health (% fair-poor, 4.6 vs. 8.6), and were more likely to come from lower SEG households. CONCLUSION: Mothers' perceived distance from home to green/open spaces was associated with child's TV time at age 5.9years.

Psychometric Properties of the EQ-5D-5L in Patients with Alopecia Areata.

BACKGROUND: For many decision makers in Health Technology Assessment the EQ-5D-5L is the standard measure of health-related quality of life (HRQL). However, evidence has shown the limitations of the measure in certain disease areas, including dermatology. Alopecia areata (AA) is associated with a significant HRQL impact, partly due to the emotional impact of hair loss. OBJECTIVES: This study explores the psychometric properties of the EQ-5D-5L in people with AA in reference to the short-form 36 version 2 (SF-36v2), the Alopecia Areata Patient Priority Outcomes (AAPPO), the Severity of Alopecia Tool (SALT) and the Patient Global Impressions of Change (PGI-C). METHODS: Data from participants with AA enrolled in the ALLEGRO-2b/3 trial (NCT03732807) of ritlecitinib were analysed. Participants completed the AAPPO measure (an AA-specific measure assessing emotional symptoms and activity limitations), PGI-C, EQ-5D-5L and SF-36v2 across 48-weeks of follow up. Extent of scalp hair loss was assessed using the SALT. Ceiling effects, known groups validity, convergent validity and responsiveness were examined. Known groups were defined by SALT score and a PGI-C defined response from baseline. Exploratory factor analysis was also performed. RESULTS: Data were available from 612 adult participants. Ceiling effects were observed for the EQ-5D-5L (55.3-61.2%) and analyses suggested that the EQ-5D did not capture important differences between patients that the SF-36v2 did. The EQ-5D-5L very weakly correlated with SALT score, whereas the AAPPO correlated more strongly with the extent of hair loss. Compared with the EQ-5D-5L, the AAPPO was better able to discriminate between known groups defined by SALT and PGI-C. An exploratory factor analysis suggested that the EQ-5D-5L had limitations in content validity compared with the AAPPO. CONCLUSIONS: The EQ-5D-5L may not adequately measure the burden of AA on patients' HRQL. Insensitivity to the burden of AA suggests that the EQ-5D-5L may not measure treatment-related benefit with hair regrowth. Data from other measures could be considered if they are shown to be more relevant.

Alopecia areata (AA) is a disease that causes hair loss on the scalp and, in some cases, other parts of the body. It affects 18.4 million people worldwide. We know that AA can have a significant impact on a person's health-related quality of life (HRQL). Understanding the impact of AA on HRQL is important, but frequently used questionnaires to assess HRQL may not accurately measure the impact of the condition. This study uses data from a clinical trial (ALLEGRO-2b/3 trial) conducted in patients with AA from multiple countries to examine whether frequently used HRQL questionnaires can measure the impact of AA. We compared the HRQL of people with different levels of hair loss to see how well these questionnaires measure the impact of AA. We used data from 612 participants who took part in the trial. We found that some of the frequently used questionnaires did not detect differences between people with different levels of hair loss or those who thought their condition had improved compared with those who did not, suggesting that they may not accurately measure the impact of AA. Overall, some frequently used questionnaires to assess HRQL may not be appropriate for use in people with AA. Other ways of measuring HRQL may be more appropriate for understanding the full impact of AA.

Estimating utility values for non-alcoholic steatohepatitis health states: a discrete choice experiment.

Background: This study estimated utility values for non-alcoholic steatohepatitis (NASH). Previous studies have assumed that health-related quality of life does not vary between the early stages of NASH. Materials & Methods: Discrete choice experiment (DCE) surveys estimated the value of avoiding fibrosis progression. Patients also completed the EQ-5D-5L. Marginal rates of substitution estimated utility change associated with fibrosis progression. Results: DCE surveys were completed by the UK general public (n = 520) and patients with NASH (n = 154). The utility decline between fibrosis stages F1 and F4 decompensated was between -0.521 to -0.646 (depending on method). Conclusion: Three methods were used to estimate utilities for NASH, each one showed sensitivity to advancing fibrosis, including in the early stages, which is often considered asymptomatic.

Estimation of Health Utility Scores for Glycogen Storage Disease Type Ia.

BACKGROUND: Glycogen Storage Disease Type Ia (GSDIa) is a rare genetic metabolic disorder characterized by hypoglycemia, hepatomegaly, growth failure, and possible seizures/death. Patients frequently consume cornstarch to maintain blood glucose. Evidence demonstrating the impact of GSDIa on health-related quality of life (HRQoL) is lacking. This study aims to understand the burden of GSDIa by obtaining utility values for economic appraisals. METHODS: A targeted literature review and interviews with experts (n = 4) and caregivers (n = 4) informed the development of health state vignettes describing different GSDIa severities by age and level of hypothetical treatment (i.e., gene therapy) response. Health states reflecting caregivers' experiences were also developed. A convenience sample of the UK general public completed a time trade-off (TTO) exercise. Scores conceptually varied from 0 (dead) to 1 (full health). States were also rated using a visual analog scale (VAS) and the EQ-5D-5L. Data were descriptively summarized. RESULTS: One hundred participants completed the exercise (male: 48%; mean age: 42 years). Scores were lowest for the adolescent pre-treatment state (TTO = 0.38). Large increments in HRQoL were observed for the response (adult: TTO = 0.86; child: TTO = 0.84) and complete response (adult and child: TTO = 0.94) hypothetical treatment response states. Caregiver values were lowest for the pre-treatment state (TTO = 0.57) and highest for the complete response state (TTO = 0.95). VAS and EQ-5D-5L scores followed a similar pattern. CONCLUSION: This study found an HRQoL burden on GSDIa patients and caregivers, with potential large improvement from a hypothetical treatment. These findings may be useful for families, clinicians, regulatory agencies, and in therapy economic evaluations.

Utility Values Associated with Atypical Hemolytic Uremic Syndrome-Related Attributes: A Discrete Choice Experiment in Five Countries.

BACKGROUND: Atypical hemolytic uremic syndrome is a rare disease caused by complement dysregulation that can lead to progressive kidney damage or death if untreated. Owing to its rarity, the impact of atypical hemolytic uremic syndrome and available therapies (eculizumab and ravulizumab) on patients' health-related quality of life is difficult to describe, but such data are required for an economic evaluation. OBJECTIVE: The objective of this study was to estimate utility values for atypical hemolytic uremic syndrome-related attributes in five countries for an economic evaluation. METHODS: Using discrete choice experiment surveys, key atypical hemolytic uremic syndrome-related attributes (life expectancy, administration frequency, risk of meningitis, need for hospitalization, and risk of kidney impairment) were evaluated in adult general population samples from Australia, Canada, the Netherlands, Sweden, and the UK. Survey choice sets were constructed using a published orthogonal array. A mixed-effects logit model estimated preference strength for each attribute. Utilities were estimated using marginal substitution rates between overall survival and other attributes, weighted against average life expectancy. RESULTS: Across all countries (N = 2382), utility weights revealed a consistent pattern: participants were averse to the risk of kidney impairment (disutility/utility weight range: -0.185 to -0.158), risk of meningitis (-0.041 to -0.032), and the need for hospitalization (-0.063 to -0.048), but preferred 8-weekly vs 2-weekly infusions over 1 h (0.013-0.039). CONCLUSIONS: Although all attributes played a role in determining treatment preferences, the largest drivers were life expectancy and risk of kidney impairment. Participants favored 8-weekly dosing (corresponding to ravulizumab administration frequency) vs 2-weekly dosing. The discrete choice experiment was designed such that estimated (dis)utility weights can be used in future cost-effectiveness models in atypical hemolytic uremic syndrome.

Estimation of the Quality-of-Life Impact of X-Linked Myotubular Myopathy.

X-linked myotubular myopathy (XLMTM) is a rare, severe, neuromuscular disorder for which novel treatments are under investigation. This study estimated quality-of-life weights (or utilities) for children with XLMTM. The state that was rated the worst described a child unable to sit and requiring invasive ventilation for≥16 hours a day (utility = -0.07 or -0.27 depending on method used). The state describing a child who can stand and walk and does not require invasive ventilation was the most highly rated state and had a utility of 0.91 or 0.77 (depending on method used).Nine health state vignettes were developed for XLMTM defined in terms of respiratory and motor function based on clinical trial data from parents completing the Assessment of Caregiver Experience with Neuromuscular Disease (ACEND) Domain 1 scale assessing mobility, transfers, sitting, playing, eating, grooming and dressing. These data were supplemented with qualitative data from parent interviews on the daily impact of XLMTM, especially in terms of psychological wellbeing, pain and discomfort, and communication. Seven clinical experts reviewed the draft vignettes for accuracy. Vignettes were rated by members of the UK general public using a time trade-off (TTO) interview and an EQ-5D-5L assessment. This study demonstrated a substantial impact of XLMTM on utility weights.

Trajectories of physical activity from midlife to old age and associations with subsequent cardiovascular disease and all-cause mortality.

INTRODUCTION: It is well established that physical activity (PA) protects against mortality and morbidity, but how long-term patterns of PA are associated with mortality and cardiovascular disease (CVD) remains unclear. METHODS: 3231 men recruited to the British Regional Heart Study, a prospective cohort study, reported usual PA levels at baseline in 1978-1980 (aged 40-59 years) and at 12-year, 16-year and 20-year follow ups. Twenty-year trajectories of PA, spanning from 1978/1980 to 2000, were identified using group-based trajectory modelling. Men were subsequently followed up until 30 June 2016 for mortality through National Health Service central registers and for non-fatal CVD events through primary and secondary care records. Data analyses were conducted in 2019. RESULTS: Three PA trajectories were identified: low/decreasing (22.7%), light/stable (51.0%) and moderate/increasing (26.3%). Over a median follow-up of 16.4 years, there were 1735 deaths. Compared with the low/decreasing group, membership of the light/stable (HR 0.83, 95% CI 0.74 to 0.94) and moderate/increasing (HR 0.76, 95% CI 0.66 to 0.88) groups was associated with a lower risk of all-cause mortality. Similar associations were observed for CVD mortality, major coronary heart disease and all CVD events. Associations were only partially explained by a range of confounders. Sensitivity analyses suggested that survival benefits were largely driven by most recent/current PA. CONCLUSIONS: A dose-response relationship was observed, with higher levels of PA from midlife to old age associated with additional benefits. However, even fairly modest and sustained PA was protective and may be more achievable for the most inactive.

Twenty-Year Trajectories of Physical Activity Types from Midlife to Old Age.

PURPOSE: Correlates of physical activity (PA) vary according to type. However, predictors of long-term patterns of PA types into old age are unknown. This study aimed to identify 20-yr trajectories of PA types into old age and their predictors. METHODS: Seven thousand seven hundred thirty-five men (age, 40-59 yr) recruited from UK towns in 1978 to 1980 were followed up after 12, 16, and 20 yr. Men reported participation in sport/exercise, recreational activity and walking, health status, lifestyle behaviors and socio-demographic characteristics. Group-based trajectory modeling identified the trajectories of PA types and associations with time-stable and time-varying covariates. RESULTS: Men with ≥3 measures of sport/exercise (n = 5116), recreational activity (n = 5085) and walking (n = 5106) respectively were included in analyses. Three trajectory groups were identified for sport/exercise, four for recreational activity and three for walking. Poor health, obesity and smoking were associated with reduced odds of following a more favorable trajectory for all PA types. A range of socioeconomic, regional and lifestyle factors were also associated with PA trajectories but the magnitude and direction were specific to PA type. For example, men with manual occupations were less likely to follow a favorable sport/exercise trajectory but more likely to follow an increasing walking trajectory compared to men with nonmanual occupations. Retirement was associated with increased PA but this was largely due to increased sport/exercise participation. CONCLUSIONS: Physical activity trajectories from middle to old age vary by activity type. The predictors of these trajectories and effects of major life events, such as retirement, are also specific to the type of PA.