The experiences of children, adolescents and their parents in isolation in a Danish paediatric unit: A qualitative study.

BACKGROUND: Previous studies on adult patients in hospital isolation show that it can be highly stressful, with some patients affected by depression and anxiety. This study aimed to explore how children, adolescents, and their parents perceive isolation and how it affects them physically, psychologically, and socially. METHODS: A qualitative approach was used comprising semi-structured interviews, participant observations, and field notes. FINDINGS: Two adolescents and 13 parents were selected to participate in the interviews, while three children and their parents participated in participant observation. Besides the participant observation one of the adolescents and one parent also participated in interviews. The children and adolescents were isolated at the hospital due to bacterial or viral infections or were carriers of an antibiotic resistant bacteria. After performing a thematic analysis to identify patterns in the data, four themes emerged: 1. Differing information provided about bacteria, virus, hygiene precautions, and isolation, 2. Dependence on healthcare professionals, 3. Impact of the environment, and 4. Coping and psychological reactions on isolation. DISCUSSION: The participants conveyed positive and negative experiences and emotions during isolation in relation to daily activities, psychological well-being, and social life. Adolescents and their parents requested clear comprehensible and consistent information on isolation from healthcare professionals. APPLICATION TO PRACTICE: To improve hospital isolation for children, adolescents, and their parents, well-written information on isolation and hygiene precautions is crucial, as are evolving strategies to minimise social exclusion and the emotional impact of isolation.

Derivation and Validation of a 10-Year Risk Score for Symptomatic Abdominal Aortic Aneurysm: Cohort Study of Nearly 500 000 Individuals.

BACKGROUND: Abdominal aortic aneurysm (AAA) can occur in patients who are ineligible for routine ultrasound screening. A simple AAA risk score was derived and compared with current guidelines used for ultrasound screening of AAA. METHODS: United Kingdom Biobank participants without previous AAA were split into a derivation cohort (n=401 820, 54.6% women, mean age 56.4 years, 95.5% White race) and validation cohort (n=83 816). Incident AAA was defined as first hospital inpatient diagnosis of AAA, death from AAA, or an AAA-related surgical procedure. A multivariable Cox model was developed in the derivation cohort into an AAA risk score that did not require blood biomarkers. To illustrate the sensitivity and specificity of the risk score for AAA, a theoretical threshold to refer patients for ultrasound at 0.25% 10-year risk was modeled. Discrimination of the risk score was compared with a model of US Preventive Services Task Force (USPSTF) AAA screening guidelines. RESULTS: In the derivation cohort, there were 1570 (0.40%) cases of AAA over a median 11.3 years of follow-up. Components of the AAA risk score were age (stratified by smoking status), weight (stratified by smoking status), antihypertensive and cholesterol-lowering medication use, height, diastolic blood pressure, baseline cardiovascular disease, and diabetes. In the validation cohort, over 10 years of follow-up, the C-index for the model of the USPSTF guidelines was 0.705 (95% CI, 0.678-0.733). The C-index of the risk score as a continuous variable was 0.856 (95% CI, 0.837-0.878). In the validation cohort, the USPSTF model yielded sensitivity 63.9% and specificity 71.3%. At the 0.25% 10-year risk threshold, the risk score yielded sensitivity 82.1% and specificity 70.7% while also improving the net reclassification index compared with the USPSTF model +0.176 (95% CI, 0.120-0.232). A combined model, whereby risk scoring was combined with the USPSTF model, also improved prediction compared with USPSTF alone (net reclassification index +0.101 [95% CI, 0.055-0.147]). CONCLUSIONS: In an asymptomatic general population, a risk score based on patient age, height, weight, and medical history may improve identification of asymptomatic patients at risk for clinical events from AAA. Further development and validation of risk scores to detect asymptomatic AAA are needed.

Cardiac Troponin T and Troponin I in the General Population.

BACKGROUND: There is great interest in widening the use of high-sensitivity cardiac troponins for population cardiovascular disease (CVD) and heart failure screening. However, it is not clear whether cardiac troponin T (cTnT) and troponin I (cTnI) are equivalent measures of risk in this setting. We aimed to compare and contrast (1) the association of cTnT and cTnI with CVD and non-CVD outcomes, and (2) their determinants in a genome-wide association study. METHODS: High-sensitivity cTnT and cTnI were measured in serum from 19 501 individuals in Generation Scotland Scottish Family Health Study. Median follow-up was 7.8 years (quartile 1 to quartile 3, 7.1-9.2). Associations of each troponin with a composite CVD outcome (1177 events), CVD death (n=266), non-CVD death (n=374), and heart failure (n=216) were determined by using Cox models. A genome-wide association study was conducted using a standard approach developed for the cohort. RESULTS: Both cTnI and cTnT were strongly associated with CVD risk in unadjusted models. After adjusting for classical risk factors, the hazard ratio for a 1 SD increase in log transformed troponin was 1.24 (95% CI, 1.17-1.32) and 1.11 (1.04-1.19) for cTnI and cTnT, respectively; ratio of hazard ratios 1.12 (1.04-1.21). cTnI, but not cTnT, was associated with myocardial infarction and coronary heart disease. Both cTnI and cTnT had strong associations with CVD death and heart failure. By contrast, cTnT, but not cTnI, was associated with non-CVD death; ratio of hazard ratios 0.77 (0.67-0.88). We identified 5 loci (53 individual single-nucleotide polymorphisms) that had genome-wide significant associations with cTnI, and a different set of 4 loci (4 single-nucleotide polymorphisms) for cTnT. CONCLUSIONS: The upstream genetic causes of low-grade elevations in cTnI and cTnT appear distinct, and their associations with outcomes also differ. Elevations in cTnI are more strongly associated with some CVD outcomes, whereas cTnT is more strongly associated with the risk of non-CVD death. These findings help inform the selection of an optimal troponin assay for future clinical care and research in this setting.

Comparison of Conventional Lipoprotein Tests and Apolipoproteins in the Prediction of Cardiovascular Disease.

BACKGROUND: Total cholesterol and high-density lipoprotein cholesterol (HDL-C) measurements are central to cardiovascular disease (CVD) risk assessment, but there is continuing debate around the utility of other lipids for risk prediction. METHODS: Participants from UK Biobank without baseline CVD and not taking statins, with relevant lipid measurements (n=346 686), were included in the primary analysis. An incident fatal or nonfatal CVD event occurred in 6216 participants (1656 fatal) over a median of 8.9 years. Associations of nonfasting lipid measurements (total cholesterol, HDL-C, non-HDL-C, direct and calculated low-density lipoprotein cholesterol [LDL-C], and apolipoproteins [Apo] A1 and B) with CVD were compared using Cox models adjusting for classical risk factors, and predictive utility was determined by the C-index and net reclassification index. Prediction was also tested in 68 649 participants taking a statin with or without baseline CVD (3515 CVD events). RESULTS: ApoB, LDL-C, and non-HDL-C were highly correlated (r>0.90), while HDL-C was strongly correlated with ApoA1 (r=0.92). After adjustment for classical risk factors, 1 SD increase in ApoB, direct LDL-C, and non-HDL-C had similar associations with composite fatal/nonfatal CVD events (hazard ratio, 1.23, 1.20, 1.21, respectively). Associations for 1 SD increase in HDL-C and ApoA1 were also similar (hazard ratios, 0.81 [both]). Adding either total cholesterol and HDL-C, or ApoB and ApoA, to a CVD risk prediction model (C-index, 0.7378) yielded similar improvement in discrimination (C-index change, 0.0084; 95% CI, 0.0065, 0.0104, and 0.0089; 95% CI, 0.0069, 0.0109, respectively). Once total and HDL-C were in the model, no further substantive improvement was achieved with the addition of ApoB (C-index change, 0.0004; 95% CI, 0.0000, 0.0008) or any measure of LDL-C. Results for predictive utility were similar for a fatal CVD outcome, and in a discordance analysis. In participants taking a statin, classical risk factors (C-index, 0.7118) were improved by non-HDL-C (C-index change, 0.0030; 95% CI, 0.0012, 0.0048) or ApoB (C-index change, 0.0030; 95% CI, 0.0011, 0.0048). However, adding ApoB or LDL-C to a model already containing non-HDL-C did not further improve discrimination. CONCLUSIONS: Measurement of total cholesterol and HDL-C in the nonfasted state is sufficient to capture the lipid-associated risk in CVD prediction, with no meaningful improvement from addition of apolipoproteins, direct or calculated LDL-C.

Association Between Walking Pace and Stroke Incidence: Findings From the UK Biobank Prospective Cohort Study.

Background and Purpose- Stroke incidence in younger and middle-aged people is growing. Despite this, its associations in this subset of the stroke population are unknown, and prevention strategies are not tailored to meet their needs. This study examined the association between self-reported walking pace and incident stroke. Methods- Data from the UK Biobank were used in a prospective population-based study. Three hundred and sixty-three thousand, one hundred and thirty-seven participants aged 37 to 73 years (52% women) were recruited. The associations of self-reported walking pace with stroke incidence over follow-up were investigated using Cox proportional-hazard models. Results- Among 363,137 participants, 2705 (0.7%) participants developed a fatal or nonfatal stroke event over the mean follow-up period of 6.1 years (interquartile range, 5.4-6.7). Slow walking pace was associated with a higher hazard for stroke incidence (hazard ratio [HR], 1.45 [95% CI, 1.26-1.66]; P<0.0001). Stroke incidence was not associated with walking pace among people <65 years of age. However, slow walking pace was associated with a higher risk of stroke among participants aged ≥65 years (HR, 1.42 [95% CI, 1.17-1.72]; P<0.0001). A higher risk for stroke was observed on those with middle (HR, 1.28 [95% CI, 1.01-1.63]; P=0.039) and higher (HR, 1.29 [95% CI, 1.05-1.69]; P=0.012) deprivation levels but not in the least deprived individuals. Similarly, overweight (HR, 1.30 [95% CI, 1.04-1.63]; P=0.019) and obese (HR, 1.33 [95% CI, 1.09-1.63]; P=0.004) but not normal-weight individuals had a higher risk of stroke incidence. Conclusions- Slow walking pace was associated with a higher risk of stroke among participants over 64 years of age in this population-based cohort study. The addition of the measurement of self-reported walking pace to primary care or public health clinical consultations may be a useful screening tool for stroke risk.

Association of Total and Differential Leukocyte Counts With Cardiovascular Disease and Mortality in the UK Biobank.

OBJECTIVE: Elevated white blood cell count is associated with a higher risk of cardiovascular disease (CVD). We aimed to investigate whether specific leukocyte subpopulations, which may more closely indicate a specific inflammatory pathway, are specifically associated with CVD. APPROACH AND RESULTS: Participants (478 259) from UK Biobank with data for white blood cell count were included. Death because of CVD (n=1377) and non-CVD causes (n=8987) occurred during median follow-up time of 7.0 years (interquartile range, 6.3-7.6). In Cox models, deciles of leukocyte counts (lymphocytes, monocytes, neutrophils, eosinophils, and basophils) were examined using the fifth decile as the referent group. Models were stratified by sex and adjusted for a range of classical risk factors. A sensitivity analysis excluded participants with baseline comorbidites and the first 2 years of follow-up. Men (hazard ratio [HR], 1.59; 95% confidence interval, 1.22-2.08) and women (HR, 2.15; 95% confidence interval, 1.38-3.35) in the highest decile of neutrophil count were at higher risk of CVD mortality and nonfatal CVD (men HR, 1.28; 95% confidence interval, 1.16-1.42 and women HR, 1.21; 95% confidence interval, 1.06-1.38). In the sensitivity analysis, the power to investigate CVD mortality was limited, but for both sexes combined, the linear HRs for a 1×109/L cell count increase in white blood cell count and neutrophils, respectively, was 1.05 (1.03-1.07) and 1.07 (1.04-1.11). CONCLUSIONS: Among circulating leukocyte subpopulations, neutrophil count in men was most consistently associated with fatal and nonfatal CVD. Further studies of interventions that lower circulating neutrophils, such as canakinumab, are required to investigate causality.

The association of grip strength with health outcomes does not differ if grip strength is used in absolute or relative terms: a prospective cohort study.

BACKGROUND: higher grip strength is associated with better health outcomes. The optimal way to report grip strength (i.e. absolute vs. relative) for prediction, however, remains to be established. METHODS: in participants (aged 37-73 at baseline) from the UK Biobank, we examined the associations of grip strength, expressed in absolute terms (kilograms) and relative to anthropometric variables, with mortality and disease incidence, after exclusion of the first 2 years of follow-up, and compared risk predictions scores of handgrip strength when differentially expressed. RESULTS: of the 356 721 participants included in the analysis 6,234 died (1.7%) and 4,523 developed CVD (1.3%) over a mean follow-up of 5.0 years (ranging from 3.3 to 7.8) for mortality and 4.1 years (ranging from 2.4 to 7.0) for disease incidence data. As expected, baseline higher grip strength was associated with lower risk of all-cause and cause specific mortality and incidence. These associations did not meaningfully differ when grip-strength was expressed in absolute terms, vs. relative to height, weight, fat-free mass, BMI, fat-free mass index and fat-free mass, or as z-scores. Similarly the different ways of expressing grip strength had little effect on the ability of grip strength to improve risk prediction, based on C-index change, of an office-based risk score. CONCLUSIONS: the ability of grip strength to predict mortality is not altered by changing how it is expressed.

Comparison between High-Sensitivity Cardiac Troponin T and Cardiac Troponin I in a Large General Population Cohort.

BACKGROUND: Few data compare cardiac troponin T (cTnT) and cardiac troponin I (cTnI) in a general population. We sought to evaluate the distribution and association between cTnT, cTnI, and cardiovascular risk factors in a large general population cohort. METHODS: High-sensitivity cTnT and cTnI were measured in serum from 19501 individuals in the Generation Scotland Scottish Family Health Study. Associations with cardiovascular risk factors were compared using age- and sex-adjusted regression. Observed age- and sex-stratified 99th centiles were compared with 99th centiles for cTnT (men, 15.5 ng/L; women, 9.0 ng/L) and cTnI (men, 34.2 ng/L; women, 15.6 ng/L) used in clinical practice. RESULTS: cTnT and cTnI concentrations were detectable in 53.3% and 74.8% of participants, respectively, and were modestly correlated in unadjusted analyses (R 2 = 21.3%) and only weakly correlated after adjusting for age and sex (R 2 = 9.5%). Cardiovascular risk factors were associated with both troponins, but in age- and sex-adjusted analyses, cTnI was more strongly associated with age, male sex, body mass index, and systolic blood pressure (P < 0.0001 for all vs cTnT). cTnT was more strongly associated with diabetes (P < 0.0001 vs cTnI). The observed 99th centiles were broadly consistent with recommended 99th centiles in younger men and women. After the age of 60 years, observed 99th centiles increased substantially for cTnT, and beyond 70 years of age, the 99th centiles approximately doubled for both troponins. CONCLUSIONS: In the general population, cTnT and cTnI concentrations are weakly correlated and are differentially associated with cardiovascular risk factors. The 99th centiles currently in use are broadly appropriate for men and women up to but not beyond the age of 60 years.

Increasing access to fresh produce by pairing urban farms with corner stores: a case study in a low-income urban setting.

OBJECTIVE: Our objective was to pilot collaborations between two urban farms with two corner stores to increase access to fresh produce in low-income neighbourhoods. DESIGN: We conducted a pre-post evaluation of two farm-store collaborations using quantitative distribution and sales data. Using semi-structured interviews, we qualitatively assessed feasibility of implementation and collaboration acceptability to farmers and storeowners. SETTING: Low-income urban neighbourhoods in Baltimore, MD, USA in 2012. SUBJECTS: Pair #1 included a 0·25 acre (0·1 ha) urban farm with a store serving local residents and was promoted by the neighbourhood association. Pair #2 included a 2 acre (0·8 ha) urban farm with a store serving bus commuters. RESULTS: Produce was delivered all nine intervention weeks in both pairs. Pair #1 produced a significant increase in the mean number of produce varieties carried in the store by 11·3 (P<0·01) and sold 86 % of all items delivered. Pair #2 resulted in a non-significant increase in the number of produce varieties carried by 2·2 (P=0·44) and sold 63 % of all items delivered. CONCLUSIONS: Our case study suggests that pairing urban farms with corner stores for produce distribution may be feasible and could be a new model to increase access to fruits and vegetables among low-income urban neighbourhoods. For future programmes to be successful, strong community backing may be vital to support produce sales.

Age, CAG repeat length, and clinical progression in Huntington's disease.

The objective of this study was to further explore the effect of CAG repeat length on the rate of clinical progression in patients with Huntington's disease. The dataset included records for 569 subjects followed prospectively at the Baltimore Huntington's Disease Center. Participants were seen for a mean of 7.1 visits, with a mean follow-up of 8.2 years. Subjects were evaluated using the Quantified Neurologic Examination and its Motor Impairment subscale, the Mini-Mental State Examination, and the Huntington's disease Activities of Daily Living Scale. By itself, CAG repeat length showed a statistically significant but small effect on the progression of all clinical measures. Contrary to our previous expectations, controlling for age of onset increased the correlation between CAG repeat length and progression of all variables by 69% to 159%. Graphical models further supported the idea that individuals with smaller triplet expansions experience a more gradual decline. CAG repeat length becomes an important determinant of clinical prognosis when accounting for age of onset. This suggests that the aging process itself influences clinical outcomes in Huntington's disease. Inconsistent results in prior studies examining CAG repeat length and progression may indeed reflect a lack of age adjustment.

Static Socio-Ecological COVID-19 Vulnerability Index and Vaccine Hesitancy Index for England.

BACKGROUND: Population characteristics can be used to infer vulnerability of communities to COVID-19, or to the likelihood of high levels of vaccine hesitancy. Communities harder hit by the virus, or at risk of being so, stand to benefit from greater resource allocation than their population size alone would suggest. This study reports a simple but efficacious method of ranking small areas of England by relative characteristics that are linked with COVID-19 vulnerability and vaccine hesitancy. METHODS: Publicly available data on a range of characteristics previously linked with either poor COVID-19 outcomes or vaccine hesitancy were collated for all Middle Super Output Areas of England (MSOA, n=6790, excluding Isles of Scilly), scaled and combined into two numeric indices. Multivariable linear regression was used to build a parsimonious model of vulnerability (static socio-ecological vulnerability index, SEVI) in 60% of MSOAs, and retained variables were used to construct two simple indices. Assuming a monotonic relationship between indices and outcomes, Spearman correlation coefficients were calculated between the SEVI and cumulative COVID-19 case rates at MSOA level in the remaining 40% of MSOAs over periods both during and out with national lockdowns. Similarly, a novel vaccine hesitancy index (VHI) was constructed using population characteristics aligned with factors identified by an Office for National Statistics (ONS) survey analysis. The relationship between the VHI and vaccine coverage in people aged 12+years (as of 2021-06-24) was determined using Spearman correlation. The indices were split into quintiles, and MSOAs within the highest vulnerability and vaccine hesitancy quintiles were mapped. FINDINGS: The SEVI showed a moderate to strong relationship with case rates in the validation dataset across the whole study period, and for every intervening period studied except early in the pandemic when testing was highly selective. The SEVI was more strongly correlated with case rates than any of its domains (rs 0·59 95% CI 0.57-0.62) and outperformed an existing MSOA-level vulnerability index. The VHI was significantly negatively correlated with COVID-19 vaccine coverage in the validation data at the time of writing (rs -0·43 95% CI -0·46 to -0·41). London had the largest number and proportion of MSOAs in quintile 5 (most vulnerable/hesitant) of SEVI and VHI concurrently. INTERPRETATION: The indices presented offer an efficacious way of identifying geographical disparities in COVID-19 risk, thus helping focus resources according to need. FUNDING: Funder: Integrated Covid Hub North East. AWARD NUMBER: n/a. GRANT RECIPIENT: Fiona Matthews.

Inequalities in the evolution of the COVID-19 pandemic: an ecological study of inequalities in mortality in the first wave and the effects of the first national lockdown in England.

OBJECTIVES: To examine how ecological inequalities in COVID-19 mortality rates evolved in England, and whether the first national lockdown impacted them. This analysis aimed to provide evidence for important lessons to inform public health planning to reduce inequalities in any future pandemics. DESIGN: Longitudinal ecological study. SETTING: 307 lower-tier local authorities in England. PRIMARY OUTCOME MEASURE: Age-standardised COVID-19 mortality rates by local authority, regressed on Index of Multiple Deprivation (IMD) and relevant epidemic dynamics. RESULTS: Local authorities that started recording COVID-19 deaths earlier were more deprived, and more deprived authorities saw faster increases in their death rates. By 6 April 2020 (week 15, the earliest time that the 23 March lockdown could have begun affecting death rates) the cumulative death rate in local authorities in the two most deprived deciles of IMD was 54% higher than the rate in the two least deprived deciles. By 4 July 2020 (week 27), this gap had narrowed to 29%. Thus, inequalities in mortality rates by decile of deprivation persisted throughout the first wave, but reduced during the lockdown. CONCLUSIONS: This study found significant differences in the dynamics of COVID-19 mortality at the local authority level, resulting in inequalities in cumulative mortality rates during the first wave of the pandemic. The first lockdown in England was fairly strict-and the study found that it particularly benefited those living in more deprived local authorities. Care should be taken to implement lockdowns early enough, in the right places-and at a sufficiently strict level-to maximally benefit all communities, and reduce inequalities.

Explaining the deprivation gap in COVID-19 mortality rates: A decomposition analysis of geographical inequalities in England.

One of the most consistent and worrying features of the COVID-19 pandemic globally has been the disproportionate burden of the epidemic in the most deprived areas. Most of the literature so far though has focused on estimating the extent of these inequalities. There has been much less attention paid to exploring the main pathways underpinning them. In this study, we employ the syndemic pandemic theoretical framework and apply novel decomposition methods to investigate the proportion of the COVID-19 mortality gap by area-level deprivation in England during the first wave of the pandemic (January to July 2020) was accounted for by pre-existing inequalities in the compositional and contextual characteristics of place. We use a decomposition approach to explicitly quantify the independent contribution of four inequalities pathways (vulnerability, susceptibility, exposure and transmission) in explaining the more severe COVID-19 outcomes in the most deprived local authorities compared to the rest. We find that inequalities in transmission (73%) and in vulnerability (49%) factors explained the highest proportion of mortality by deprivation. Our results suggest that public health agencies need to develop short- and long-term strategies to alleviate these underlying inequalities in order to alleviate the more severe impacts on the most vulnerable communities.

Lipoprotein(a) and cardiovascular disease: prediction, attributable risk fraction, and estimating benefits from novel interventions.

AIMS: To investigate the population attributable fraction due to elevated lipoprotein (a) (Lp(a)) and the utility of measuring Lp(a) in cardiovascular disease (CVD) risk prediction. METHODS AND RESULTS: In 413 734 participants from UK Biobank, associations of serum Lp(a) with composite fatal/non-fatal CVD (n = 10 066 events), fatal CVD (n = 3247), coronary heart disease (CHD; n = 18 292), peripheral vascular disease (PVD; n = 2716), and aortic stenosis (n = 901) were compared using Cox models. Median Lp(a) was 19.7 nmol/L (interquartile interval 7.6-75.3 nmol/L). About 20.8% had Lp(a) values >100 nmol/L; 9.2% had values >175 nmol/L. After adjustment for classical risk factors, 1 SD increment in log Lp(a) was associated with a hazard ratio for fatal/non-fatal CVD of 1.12 [95% confidence interval (CI) 1.10-1.15]. Similar associations were observed with fatal CVD, CHD, PVD, and aortic stenosis. Adding Lp(a) to a prediction model containing traditional CVD risk factors in a primary prevention group improved the C-index by +0.0017 (95% CI 0.0008-0.0026). In the whole cohort, Lp(a) above 100 nmol/L was associated with a population attributable fraction (PAF) of 5.8% (95% CI 4.9-6.7%), and for Lp(a) above 175 nmol/L the PAF was 3.0% (2.4-3.6%). Assuming causality and an achieved Lp(a) reduction of 80%, an ongoing trial to lower Lp(a) in patients with CVD and Lp(a) above 175 nmol/L may reduce CVD risk by 20.0% and CHD by 24.4%. Similar benefits were also modelled in the whole cohort, regardless of baseline CVD. CONCLUSION: Population screening for elevated Lp(a) may help to predict CVD and target Lp(a) lowering drugs, if such drugs prove efficacious, to those with markedly elevated levels.

Factors contributing to institutionalization in patients with Huntington's disease.

The objective of this study was to determine which factors are predictive of institutionalization in Huntington's disease. Seven hundred and ninety-nine subjects with 4313 examinations from the Baltimore Huntington's Disease Center were included in the data set; 88 of these patients with an average follow-up time of 9.2 years went from living at home to being institutionalized while being observed in our clinic. We examined demographic, genetic, and clinical variables for a relationship with institutionalization using linear regressions, a Cox proportional hazards model, and χ2 or t tests in certain cases. In our linear models, scores on the Quantified Neurologic Examination (R2=0.203, P<.001), Huntington's disease Activities of Daily Living Scale (R2=0.259, P<.001), and Motor Impairment Score (R2=0.173, P<.001) were found to have the strongest correlation with time until institutionalization. In addition, CAG repeat length (R2=0.248, P<.001) was significantly associated with disease duration at institutionalization, when controlling for age at onset. In the Cox proportional hazards model, scores on the Activities of Daily Living Scale, Mini-Mental State Examination, Quantified Neurologic Examination, and Motor Impairment Score all significantly predicted placement in long-term care. Finally, institutionalized patients were shown to have a higher CAG number and a lower level of educational attainment than patients who avoided institutionalization for at least 15 years after disease onset. Neurologic findings, functional capacity, cognitive impairment, and CAG repeat length are all likely determinants of institutionalization. In contrast with other dementing conditions like Parkinson's and Alzheimer's, psychiatric symptoms were not shown to predict institutionalization in Huntington's disease. This may illustrate the especially debilitating nature of the movement disorder of Huntington's disease in comparison with the other dementias.

Trends in life expectancy and healthy life years at birth and age 65 in the UK, 2008-2016, and other countries of the EU28: An observational cross-sectional study.

BACKGROUND: As society ages, promoting the health of the extra years of life is of paramount importance for health, social care and pension provision. Increases in life expectancy in the UK and elsewhere have slowed in recent years, but the reasons for this are unclear. No formal comparison of trends in healthy life years between the UK and the other countries of the EU28 in recent times has been published. These countries are geographically proximate, and share many social, cultural and demographic properties, making them interesting and useful comparators, especially as the UK prepared to leave the European Union in 2020. METHODS: We calculated sex-specific healthy life years (HLY), unhealthy life years (ULY), mild and severe ULY at birth and age 65 using life tables and age-specific prevalence of activity limitation amongst the EU28 between 2008 and 2016 from EuroHex. Trends in life expectancy, HLY, ULY and proportion of life spent healthy (HLY%) were compared. We then decomposed HLY temporal changes into relative effects of changes in healthy life and mortality, by age group. FINDINGS: Life expectancy at birth, and age 65, in the UK were increasing rapidly in 2008 but slowed around 2011. Germany, Portugal and France showed evidence of a similar slowing. HLY at birth in the UK decreased, whereas it increased in most EU28 countries. The UK experienced a period of absolute expansion of unhealthy life in both sexes. The reduction in HLY at birth in the UK was mainly attributable to increases in unhealthy life in younger age groups. INTERPRETATION: The UK's performance relative to the other countries of the EU28 was poor after 2011, combining static life expectancy and reductions in healthy life years. These trends suggest that the UK government's Ageing Society Grand Challenge (to increase the healthy life expectancy by five years by 2035) will be difficult to attain. FUNDING: National Institute for Health Research (NIHR) Policy Research Programme conducted through the NIHR Older People and Frailty Policy Research Unit, PR-PRU-1217-21502. The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care.

Can vaccination roll-out be more equitable if population risk is taken into account?

BACKGROUND: COVID-19 vaccination in many countries, including England, has been prioritised primarily by age. However, people of the same age can have very different health statuses. Frailty is a commonly used metric of health and has been found to be more strongly associated with mortality than age among COVID-19 inpatients. METHODS: We compared the number of first vaccine doses administered across the 135 NHS Clinical Commissioning Groups (CCGs) of England to both the over 50 population and the estimated frail population in each area. Area-based frailty estimates were generated using the English Longitudinal Survey of Ageing (ELSA), a national survey of older people. We also compared the number of doses to the number of people with other risk factors associated with COVID-19: atrial fibrillation, chronic kidney disease, diabetes, learning disabilities, obesity and smoking status. RESULTS: We estimate that after 79 days of the vaccine program, across all Clinical Commissioning Group areas, the number of people who received a first vaccine per frail person ranged from 4.4 (95% CI 4.0-4.8) and 20.1 (95% CI 18.3-21.9). The prevalences of other risk factors were also poorly associated with the prevalence of vaccination across England. CONCLUSIONS: Vaccination with age-based priority created area-based inequities in the number of doses administered relative to the number of people who are frail or have other risk factors associated with COVID-19. As frailty has previously been found to be more strongly associated with mortality than age for COVID-19 inpatients, an age-based priority system may increase the risk of mortality in some areas during the vaccine roll-out period. Authorities planning COVID-19 vaccination programmes should consider the disadvantages of an age-based priority system.

What are the consequences of caring for older people and what interventions are effective for supporting unpaid carers? A rapid review of systematic reviews.

OBJECTIVES: To identify and map evidence about the consequences of unpaid caring for all carers of older people, and effective interventions to support this carer population. DESIGN: A rapid review of systematic reviews, focused on the consequences for carers of unpaid caring for older people, and interventions to support this heterogeneous group of carers. Reviews of carers of all ages were eligible, with any outcome measures relating to carers' health, and social and financial well-being. Searches were conducted in MEDLINE, PsycInfo and Epistemonikos (January 2000 to January 2020). Records were screened, and included systematic reviews were quality appraised. Summary data were extracted and a narrative synthesis produced. RESULTS: Twelve systematic reviews reporting evidence about the consequences of caring for carers (n=6) and assessing the effectiveness of carer interventions (n=6) were included. The review evidence typically focused on mental health outcomes, with little information identified about carers' physical, social and financial well-being. Clear estimates of the prevalence and severity of carer outcomes, and how these differ between carers and non-carers, were absent. A range of interventions were identified, but there was no strong evidence of effectiveness. In some studies, the choice of outcome measure may underestimate the full impact of an intervention. CONCLUSIONS: Current evidence fails to fully quantify the impacts that caring for older people has on carers' health and well-being. Information on social patterning of the consequences of caring is absent. Systematic measurement of a broad range of outcomes, with comparison to the general population, is needed to better understand the true consequences of caring. Classification of unpaid caring as a social determinant of health could be an effective lever to bring greater focus and support to this population. Further work is needed to develop and identify suitable interventions in order to support evidence-based policymaking and practice.

Multimorbidity and the risk of major adverse kidney events: findings from the UK Biobank cohort.

BACKGROUND: Multimorbidity [the presence of two or more long-term conditions (LTCs)] is associated with a heightened risk of mortality, but little is known about its relationship with the risk of kidney events. METHODS: Associations between multimorbidity and major adverse kidney events [MAKE: the need for long-term kidney replacement therapy, doubling of serum creatinine, fall of estimated glomerular filtration rate (eGFR) to <15 mL/min/1.73 m2 or 30% decline in eGFR] were studied in 68 505 participants from the UK Biobank cohort. Participants were enrolled in the study between 2006 and 2010. Associations between LTC counts and MAKE were tested using survival analyses accounting for the competing risk of death. RESULTS: Over a median follow-up period of 12.0 years, 2963 participants had MAKE. There were associations between LTC count categories and the risk of MAKE [one LTC adjusted subhazard ratio (sHR) = 1.29, 95% confidence interval (CI) 1.15-1.45; two LTCs sHR = 1.74 (95% CI 1.55-1.96); and three or more LTCs sHR = 2.41 (95% CI 2.14-2.71)]. This finding was more pronounced when only cardiometabolic LTCs were considered [one LTC sHR = 1.58 (95% CI 1.45-1.73); two LTCs sHR = 3.17 (95% CI 2.80-3.59); and three or more LTCs sHR = 5.24 (95% CI 4.34-6.33)]. Combinations of LTCs associated with MAKE were identified. Diabetes, hypertension and coronary heart disease featured most commonly in high-risk combinations. CONCLUSIONS: Multimorbidity, and in particular cardiometabolic multimorbidity, is a risk factor for MAKE. Future research should study groups of patients who are at high risk of progressive kidney disease based on the number and type of LTCs.