Cardiac rehabilitation meta-analysis of trials in patients with coronary heart disease using individual participant data (CaReMATCH): Project protocol

Background: Exercise-based cardiac rehabilitation (CR) has long been a cornerstone in the secondary prevention of coronary heart disease (CHD). Despite meta-analyses of randomised trials demonstrating a positive impact of CR on cardiovascular mortality, hospitalisation, exercise capacity and health related quality of life, the impact of CR on all-cause mortality remains uncertain, especially in the context of contemporary clinical practice. This CR meta-analysis of trials in patients with coronary heart disease using individual participant data (IPD) (CaReMATCH) seeks to (1) provide definitive estimates of the effectiveness of CR in terms of all-cause mortality, cardiovascular mortality, hospitalisation and health-related quality of life, and (2) determine the influence of individual patient characteristics (e.g. age, sex, risk factors) on the effectiveness of CR to inform a personalised CR-approach. Methods: Randomised controlled trials will be identified that were performed in the last decade, to ensure that CR was performed in combination with contemporary medical care (2010–2020). For our first aim, outcomes of interest include all cause- and CVD-related mortality and hospitalisations. To answer our second research question, we will collect data on exercise capacity, health-related quality of life, and patient baseline demographic and clinical data. Original IPD will be requested from the authors of all eligible trials; we will check original data and compile a master dataset. IPD meta-analyses will be conducted using a one-step meta-analysis approach where the IPD from all studies are modelled simultaneously whilst accounting for the clustering of participants within studies. Discussion: Findings from CaReMATCH will inform future (inter)national clinical and policy decision-making on the (personalised) application of exercise-based CR for patients with CHD

Recurrent delirium over 12 months predicts dementia: results of the Delirium and Cognitive Impact in Dementia (DECIDE) study

Background: Delirium is common, distressing and associated with poor outcomes. Previous studies investigating the impact of delirium on cognitive outcomes have been limited by incomplete ascertainment of baseline cognition or lack of prospective delirium assessments. This study quantified the association between delirium and cognitive function over time by prospectively ascertaining delirium in a cohort aged ≥ 65 years in whom baseline cognition had previously been established. Methods: For 12 months, we assessed participants from the Cognitive Function and Ageing Study II-Newcastle for delirium daily during hospital admissions. At 1-year, we assessed cognitive decline and dementia in those with and without delirium. We evaluated the effect of delirium (including its duration and number of episodes) on cognitive function over time, independently of baseline cognition and illness severity. Results: Eighty two of 205 participants recruited developed delirium in hospital (40%). One-year outcome data were available for 173 participants: 18 had a new dementia diagnosis, 38 had died. Delirium was associated with cognitive decline (−1.8 Mini-Mental State Examination points [95% CI –3.5 to –0.2]) and an increased risk of new dementia diagnosis at follow up (OR 8.8 [95% CI 1.9–41.4]). More than one episode and more days with delirium (>5 days) were associated with worse cognitive outcomes. Conclusions: Delirium increases risk of future cognitive decline and dementia, independent of illness severity and baseline cognition, with more episodes associated with worse cognitive outcomes. Given that delirium has been shown to be preventable in some cases, we propose that delirium is a potentially modifiable risk factor for dementi

Hospitalisation without delirium is not associated with cognitive decline in a population-based sample of older people-results from a nested, longitudinal cohort study

Background: Acute hospitalisation and delirium have individually been shown to adversely affect trajectories of cognitive decline but have not previously been considered together. This work aimed to explore the impact on cognition of hospital admission with and without delirium, compared to a control group with no hospital admissions. // Methods: The Delirium and Cognitive Impact in Dementia (DECIDE) study was nested within the Cognitive Function and Ageing Study II (CFAS II)–Newcastle cohort. CFAS II participants completed two baseline interviews, including the Mini-Mental State Examination (MMSE). During 2016, surviving participants from CFAS II–Newcastle were recruited to DECIDE on admission to hospital. Participants were reviewed daily to determine delirium status. During 2017, all DECIDE participants and age, sex and years of education matched controls without hospital admissions during 2016 were invited to repeat the CFAS II interview. Delirium was excluded in the control group using the Informant Assessment of Geriatric Delirium Scale (i-AGeD). Linear mixed effects modelling determined predictors of cognitive decline. // Results: During 2016, 82 of 205 (40%) DECIDE participants had at least one episode of delirium. At 1 year, 135 of 205 hospitalised participants completed an interview along with 100 controls. No controls experienced delirium (i-AGeD>4). Delirium was associated with a faster rate of cognitive decline compared to those without delirium (β = −2.2, P < 0.001), but number of hospital admissions was not (P = 0.447). // Conclusions: These results suggest that delirium during hospitalisation rather than hospitalisation per se is a risk factor for future cognitive decline, emphasising the need for dementia prevention studies that focus on delirium intervention

Recurrent delirium over 12 months predicts dementia: results of the Delirium and Cognitive Impact in Dementia (DECIDE) study

This is the final version. Available on open access from Oxford University Press via the DOI in this recordBackground: Delirium is common, distressing and associated with poor outcomes. Previous studies investigating the impact of delirium on cognitive outcomes have been limited by incomplete ascertainment of baseline cognition or lack of prospective delirium assessments. This study quantified the association between delirium and cognitive function over time by prospectively ascertaining delirium in a cohort aged ≥65 years in whom baseline cognition had previously been established. Methods: For 12 months, we assessed participants from the Cognitive Function and Ageing Study II-Newcastle for delirium daily during hospital admissions. At one-year, we assessed cognitive decline and dementia in those with and without delirium. We evaluated the effect of delirium (including its duration and number of episodes) on cognitive function over time, independently of baseline cognition and illness severity. Results: 82 of 205 participants recruited developed delirium in hospital (40%). One-year outcome data were available for 173 participants: 18 had a new dementia diagnosis, 38 had died. Delirium was associated with cognitive decline (-1·8 MMSE points [95% CI -3·5 - -0·2]) and an increased risk of new dementia diagnosis at follow up (OR 8·8 [95% CI 1·9 – 41·4]). More than one episode and more days with delirium (>5 days) were associated with worse cognitive outcomes. Conclusions: Delirium increases risk of future cognitive decline and dementia, independent of illness severity and baseline cognition, with more episodes associated with worse cognitive outcomes. Given that delirium has been shown to be preventable in some cases, we propose that delirium is a potentially modifiable risk factor for dementia

Hospitalisation without delirium is not associated with cognitive decline in a population-based sample of older people – results from a nested, longitudinal cohort study

This is the final version. Available on open access from Oxford University Press via the DOI in this recordBackground Acute hospitalisation and delirium have individually been shown to adversely affect trajectories of cognitive decline but have not previously been considered together. This work aimed to explore the impact on cognition of hospital admission with and without delirium, compared to a control group with no hospital admissions. Methods The Delirium and Cognitive Impact in Dementia (DECIDE) study was nested within the Cognitive Function and Ageing Study II (CFAS II)–Newcastle cohort. CFAS II participants completed two baseline interviews, including the MiniMental State Examination (MMSE). During 2016, surviving participants from CFAS II–Newcastle were recruited to DECIDE on admission to hospital. Participants were reviewed daily to determine delirium status. During 2017, all DECIDE participants and age, sex and years of education matched controls without hospital admissions during 2016 were invited to repeat the CFAS II interview. Delirium was excluded in the control group using the Informant Assessment of Geriatric Delirium Scale (i-AGeD). Linear mixed effects modelling determined predictors of cognitive decline. Results During 2016, 82 of 205 (40%) DECIDE participants had at least one episode of delirium. At one-year, 135 of 205 hospitalised participants completed an interview along with 100 controls. No controls experienced delirium (iAGeD>4). Delirium was associated with a faster rate of cognitive decline compared to those without delirium (β=-2.2, p<0.001), but number of hospital admissions was not (p=0.447). Conclusions These results suggest that delirium during hospitalisation rather than hospitalisation per se is a risk factor for future cognitive decline, emphasising the need for dementia prevention studies that focus on delirium intervention.Alzheimer’s SocietyMedical Research Council (MRC

Gender and age differences among current smokers in a general population survey

BACKGROUND: Evidence suggests a higher proportion of current smokers among female than among male ever smokers at the age above 50. However, little is known about the proportion of current smokers among ever smokers in old age groups with consideration of women in comparison to men from general population samples. The goal was to analyze the proportions of current smokers among female and among male ever smokers including those older than 80. METHODS: Cross-sectional survey study with a national probability household sample in Germany. Data of 179,472 participants aged 10 or older were used based on face-to-face in-home interviews or questionnaires. The proportions of current smokers among ever smokers were analyzed dependent on age, age of onset of smoking and cigarettes per day including effect modification by gender. RESULTS: Proportions of current smokers tended to be larger among female than among male ever smokers aged 40 or above. Women compared to men showed adjusted odds ratios of 1.7 to 6.9 at ages 40 to 90 or older in contrast to men. No such interaction existed for age of onset of smoking or cigarettes per day. CONCLUSION: Special emphasis should be given to current smokers among the female general population at the age of 40 or above in public health intervention

Crossing borders to bind proteins—a new concept in protein recognition based on the conjugation of small organic molecules or short peptides to polypeptides from a designed set

A new concept for protein recognition and binding is highlighted. The conjugation of small organic molecules or short peptides to polypeptides from a designed set provides binder molecules that bind proteins with high affinities, and with selectivities that are equal to those of antibodies. The small organic molecules or peptides need to bind the protein targets but only with modest affinities and selectivities, because conjugation to the polypeptides results in molecules with dramatically improved binder performance. The polypeptides are selected from a set of only sixteen sequences designed to bind, in principle, any protein. The small number of polypeptides used to prepare high-affinity binders contrasts sharply with the huge libraries used in binder technologies based on selection or immunization. Also, unlike antibodies and engineered proteins, the polypeptides have unordered three-dimensional structures and adapt to the proteins to which they bind. Binder molecules for the C-reactive protein, human carbonic anhydrase II, acetylcholine esterase, thymidine kinase 1, phosphorylated proteins, the D-dimer, and a number of antibodies are used as examples to demonstrate that affinities are achieved that are higher than those of the small molecules or peptides by as much as four orders of magnitude. Evaluation by pull-down experiments and ELISA-based tests in human serum show selectivities to be equal to those of antibodies. Small organic molecules and peptides are readily available from pools of endogenous ligands, enzyme substrates, inhibitors or products, from screened small molecule libraries, from phage display, and from mRNA display. The technology is an alternative to established binder concepts for applications in drug development, diagnostics, medical imaging, and protein separation

Cardiovascular and hormonal responses to static handgrip in young and older healthy men

The purpose of this study was to investigate the effect of age on cardiovascular changes and plasma concentrations of adrenomedullin (ADM), catecholamines, endothelin-1 (ET-1) and plasma renin activity (PRA) in healthy men. A total of 15 young (21 ± 0.3 years) and 15 older (64 ± 0.7 years) healthy men performed two 3-min bouts of static handgrip at 30% of maximal voluntary contraction, alternately with each hand without any break between the bouts. During exercise heart rate (HR), blood pressure (BP), stroke volume (SV) and pre-ejection period (PEP) and left ventricle ejection time (LVET) were measured. Blood samples were taken before exercise, at the end of both exercise bouts and in the fifth minute of the recovery period. The handgrip-induced increases in HR and cardiac output were significantly smaller in older than in young men (p < 0.01). SV decreased only in older men (p < 0.001). There were no differences between groups in BP increases. The baseline plasma ADM and catecholamines were higher in older man compared to young subjects. Handgrip caused increases in plasma ADM, ET-1 and PRA only in older men (p < 0.05). The increases in plasma ADM correlated positively with those of noradrenaline (NA), PRA, ET-1 and LVET and negatively with changes in total peripheral resistance (TPR), SV, PEP and PEP/LVET ratio. The increases in plasma ET-1 correlated positively with those of NA, PRA, TPR, mean BP and SV. These results revealed that ADM, ET-1 and angiotensin II can contribute to maintain vascular tone during static exercise in older but not in younger men

Self-force: Computational Strategies

Building on substantial foundational progress in understanding the effect of a small body's self-field on its own motion, the past 15 years has seen the emergence of several strategies for explicitly computing self-field corrections to the equations of motion of a small, point-like charge. These approaches broadly fall into three categories: (i) mode-sum regularization, (ii) effective source approaches and (iii) worldline convolution methods. This paper reviews the various approaches and gives details of how each one is implemented in practice, highlighting some of the key features in each case.Comment: Synchronized with final published version. Review to appear in "Equations of Motion in Relativistic Gravity", published as part of the Springer "Fundamental Theories of Physics" series. D. Puetzfeld et al. (eds.), Equations of Motion in Relativistic Gravity, Fundamental Theories of Physics 179, Springer, 201

Impact of inactivity and exercise on the vasculature in humans

The effects of inactivity and exercise training on established and novel cardiovascular risk factors are relatively modest and do not account for the impact of inactivity and exercise on vascular risk. We examine evidence that inactivity and exercise have direct effects on both vasculature function and structure in humans. Physical deconditioning is associated with enhanced vasoconstrictor tone and has profound and rapid effects on arterial remodelling in both large and smaller arteries. Evidence for an effect of deconditioning on vasodilator function is less consistent. Studies of the impact of exercise training suggest that both functional and structural remodelling adaptations occur and that the magnitude and time-course of these changes depends upon training duration and intensity and the vessel beds involved. Inactivity and exercise have direct “vascular deconditioning and conditioning” effects which likely modify cardiovascular risk