Trends in survival of older care home residents in England: A 10-year multi-cohort study

Increases in longevity combined with a policy emphasis on caring for older people in their own homes could have widened or narrowed the survival gap between care home and community-dwelling resident older people. Knowledge of pre-COVID-19 trends in this gap is needed to assess the longer-term impacts of the pandemic. We provide evidence for England on recent trends in 1, 2 and 3-year mortality amongst care home residents aged 65+ compared with similar community-dwelling residents. We use the Clinical Practice Research Datalink, a nationally representative primary care database. For each of the ten years from 2006 to 2015, care home and community-dwelling residents aged 65+ were identified and matched in the ratio 1:3, according to age, gender, area deprivation and region. Cox survival analyses were used to estimate mortality risks for care home residents in comparison with similar community-dwelling people, adjusting for age, gender, area deprivation and region. The study sample consisted of ten overlapping cohorts averaging 5495 care home residents per cohort. Adjusted mortality risks increased over the study period for care home residents while decreasing slightly for matched community-dwelling residents. The relative risks (RRs) of mortality associated with care home residence were higher for younger ages and shorter follow-up periods, in all years. Over the decade, the RRs increased, most at younger ages and for shorter follow-up periods (e.g. for the age group 65-74 years, 1-year average RR increased by 61% from 5.4 to 8.8, while for those aged 85-94 years and over, 3-year RR increased by 22% from 1.3 to 1.6). Thus the survival gap between older care home and community-dwelling residents has been widening, especially at younger ages. In due course, it will be possible to establish to what extent the COVID-19 pandemic has resulted in further growth in this gap

Trends in survival of older care home residents in England: A 10-year multi-cohort study

Increases in longevity combined with a policy emphasis on caring for older people in their own homes could have widened or narrowed the survival gap between care home and community-dwelling resident older people. Knowledge of pre-COVID-19 trends in this gap is needed to assess the longer-term impacts of the pandemic. We provide evidence for England on recent trends in 1, 2 and 3-year mortality amongst care home residents aged 65+ compared with similar community-dwelling residents. We use the Clinical Practice Research Datalink, a nationally representative primary care database. For each of the ten years from 2006 to 2015, care home and community-dwelling residents aged 65+ were identified and matched in the ratio 1:3, according to age, gender, area deprivation and region. Cox survival analyses were used to estimate mortality risks for care home residents in comparison with similar community-dwelling people, adjusting for age, gender, area deprivation and region. The study sample consisted of ten overlapping cohorts averaging 5495 care home residents per cohort. Adjusted mortality risks increased over the study period for care home residents while decreasing slightly for matched community-dwelling residents. The relative risks (RRs) of mortality associated with care home residence were higher for younger ages and shorter follow-up periods, in all years. Over the decade, the RRs increased, most at younger ages and for shorter follow-up periods (e.g. for the age group 65–74 years, 1-year average RR increased by 61% from 5.4 to 8.8, while for those aged 85–94 years and over, 3-year RR increased by 22% from 1.3 to 1.6). Thus the survival gap between older care home and community-dwelling residents has been widening, especially at younger ages. In due course, it will be possible to establish to what extent the COVID-19 pandemic has resulted in further growth in this gap

Market concentration, supply, quality and prices paid by local authorities in the English care home market.

We investigate the impact of exogenous local conditions which favor high market concentration on supply, price and quality in local markets for care homes for older people in England. We extend the existing literature in: (i) considering supply capacity as a market outcome alongside price and quality; (ii) taking account of the chain structure of care home supply and differences between the nursing home and residential care home sectors; (iii) using an econometric approach based on reduced form relationships that treats market concentration as a jointly determined outcome of a complex market. We find that areas susceptible to a high degree of market concentration tend to have greatly restricted supply of care home places and (to a lesser extent) a higher average public cost, than areas susceptible to low degree of market concentration. There is no significant evidence that conditions favoring high market concentration affect average care home quality

Design and optimization of oestrogen receptor PROTACs based on 4-hydroxytamoxifen.

In the last four decades, treatment of oestrogen receptor positive (ER+) breast cancer (BCa), has focused on targeting the estrogenic receptor signaling pathway. This signaling function is pivotal to sustain cell proliferation. Tamoxifen, a competitive inhibitor of oestrogen, has played a major role in therapeutics. However, primary and acquired resistance to hormone blockade occurs in a large subset of these cancers, and new approaches are urgently needed. Aromatase inhibitors and receptor degraders were approved and alternatively used. Yet, resistance appears in the metastatic setting. Here we report the design and synthesis of a series of proteolysis targeting chimeras (PROTACs) that induce the degradation of estrogen receptor alpha in breast cancer MCF-7 (ER+) cells at nanomolar concentration. Using a warhead based on 4-hydroxytamoxifen, bifunctional degraders recruiting either cereblon or the Von Hippel Lindau E3 ligases were synthesized. Our efforts resulted in the discovery of TVHL-1, a potent ERα degrader (DC50: 4.5 nM) that we envisage as a useful tool for biological study and a platform for potential therapeutics

Cohort study of intervened functionally univentricular heart in England and Wales (2000-2018)

Objective: Given the paucity of long-term outcome data for complex congenital heart disease (CHD), we aimed to describe the treatment pathways and survival for patients who started interventions for functionally univentricular heart (FUH) conditions, excluding hypoplastic left heart syndrome. // Methods: We performed a retrospective cohort study using all procedure records from the National Congenital Heart Diseases Audit for children born in 2000–2018. The primary outcome was mortality, ascertained from the Office for National Statistics in 2020. // Results: Of 53 615 patients, 1557 had FUH: 55.9% were boys and 67.4% were of White ethnic groups. The largest diagnostic categories were tricuspid atresia (28.9%), double inlet left ventricle (21.0%) and unbalanced atrioventricular septal defect (AVSD) (15.2%). The ages at staged surgery were: initial palliation 11.5 (IQR 5.5–43.5) days, cavopulmonary shunt 9.2 (IQR 6.0–17.1) months and Fontan 56.2 (IQR 45.5–70.3) months. The median follow-up time was 10.8 (IQR 7.0–14.9) years and the 1, 5 and 10-year survival rates after initial palliation were 83.6% (95% CI 81.7% to 85.4%), 79.4% (95% CI 77.3% to 81.4%) and 77.2% (95% CI 75.0% to 79.2%), respectively. Higher hazards were present for unbalanced AVSD HR 2.75 (95% CI 1.82 to 4.17), atrial isomerism HR 1.75 (95% CI 1.14 to 2.70) and low weight HR 1.65 (95% CI 1.13 to 2.41), critical illness HR 2.30 (95% CI 1.67 to 3.18) or acquired comorbidities HR 2.71 (95% CI 1.82 to 4.04) at initial palliation. // Conclusion: Although treatment pathways for FUH are complex and variable, nearly 8 out of 10 children survived to 10 years. Longer-term analyses of outcome based on diagnosis (rather than procedure) can inform parents, patients and clinicians, driving practice improvements for complex CHD

Effect of the presence of the plant growth promoting rhizobacterium (PGPR) Chryseobacterium balustinum Aur9 and salt stress in the pattern of flavonoids exuded by soybean roots

In this work we studied how biotic and abiotic stresses can alter the pattern of flavonoids exuded by Osumi soybean roots. A routine method was developed for the detection and characterization of the flavonoids present in soybean root exudates using HPLC-MS/MS. Then, a systematic screening of the flavonoids exuded under biotic stress, the presence of a plant growth promoting rhizobacterium, and salt stress was carried out. Results obtained indicate that the presence of Chryseobacterium balustinum Aur9 or 50 mM NaCl changes qualitatively the pattern of flavonoids exuded when compared to control conditions. Thus, in the presence of C. balustinum Aur9, soybean roots did not exude quercetin and naringenin and, under salt stress, flavonoids daidzein and naringenin could not be detected. Soybean root exudates obtained under saline conditions showed a diminished capacity to induce the expression of the nodA gene in comparison to the exudates obtained in the absence of salt. Moreover, lipochitooligosaccharides (LCOs) were not detected or weakly detected when Sinorhizobium fredii SMH12 was grown in the exudates obtained under salt stress conditions or under salt stress in the presence of C. balustinum Au9, respectively.Fil: Dardanelli, Marta Susana. Universidad de Sevilla. Facultad de Farmacia; España. Universidad Nacional de Río Cuarto. Facultad de Ciencias Exactas, Fisicoquímicas y Naturales. Departamento de Biología Molecular. Sección Química Biológica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; ArgentinaFil: Manyani, Hamid. Universidad de Sevilla. Facultad de Farmacia; EspañaFil: González Barroso, Sergio. Universidad de Sevilla. Facultad de Farmacia; EspañaFil: Rodríguez Carvajal, Miguel A.. Universidad de Sevilla. Facultad de Farmacia; EspañaFil: Gil Serrano, Antonio M.. Universidad de Sevilla. Facultad de Farmacia; EspañaFil: Espuny, Maria R.. Universidad de Sevilla. Facultad de Farmacia; EspañaFil: López Baena, Francisco Javier. Universidad de Sevilla. Facultad de Farmacia; EspañaFil: Bellogín, Ramon A.. Universidad de Sevilla. Facultad de Farmacia; EspañaFil: Megías, Manuel. Universidad de Sevilla. Facultad de Farmacia; EspañaFil: Ollero, Francisco J.. Universidad de Sevilla. Facultad de Farmacia; Españ

A global optimisation approach to range-restricted survey calibration

Survey calibration methods modify minimally unit-level sample weights to fit domain-level benchmark constraints (BC). This allows exploitation of auxiliary information, e.g. census totals, to improve the representativeness of sample data (addressing coverage limitations, non-response) and the quality of estimates of population parameters. Calibration methods may fail with samples presenting small/zero counts for some benchmark groups or when range restrictions (RR), such as positivity, are imposed to avoid unrealistic or extreme weights. User-defined modifications of BC/RR performed after encountering non-convergence allow little control on the solution, and penalization approaches modelling infeasibility may not guarantee convergence. Paradoxically, this has led to underuse in calibration of highly disaggregated information, when available. We present an always-convergent flexible two-step Global Optimisation (GO) survey calibration approach. The feasibility of the calibration problem is assessed, and automatically controlled minimum errors in BC or changes in RR are allowed to guarantee convergence in advance, while preserving the good properties of calibration estimators. Modelling alternatives under different scenarios, using various error/change and distance measures are formulated and discussed. The GO approach is validated by calibrating the weights of the 2012 Health Survey for England to a fine age-gender-region cross-tabulation (378 counts) from the 2011 Census in England and Wales

A global optimisation approach to range-restricted survey calibration

Survey calibration methods modify minimally unit-level sample weights to fit domain-level benchmark constraints (BC). This allows exploitation of auxiliary information, e.g. census totals, to improve the representativeness of sample data (addressing coverage limitations, non-response) and the quality of estimates of population parameters. Calibration methods may fail with samples presenting small/zero counts for some benchmark groups or when range restrictions (RR), such as positivity, are imposed to avoid unrealistic or extreme weights. User-defined modifications of BC/RR performed after encountering non-convergence allow little control on the solution, and penalization approaches modelling infeasibility may not guarantee convergence. Paradoxically, this has led to underuse in calibration of highly disaggregated information, when available. We present an always-convergent flexible two-step Global Optimisation (GO) survey calibration approach. The feasibility of the calibration problem is assessed, and automatically controlled minimum errors in BC or changes in RR are allowed to guarantee convergence in advance, while preserving the good properties of calibration estimators. Modelling alternatives under different scenarios, using various error/change and distance measures are formulated and discussed. The GO approach is validated by calibrating the weights of the 2012 Health Survey for England to a fine age-gender-region cross-tabulation (378 counts) from the 2011 Census in England and Wales