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BACKGROUND: This cohort study aimed to determine the association between body fat percentage (BF%), incident fractures and calcaneal broadband ultrasound attenuation (BUA). METHODS: Participants were drawn from the EPIC-Norfolk Prospective Population Cohort Study (median follow-up = 16.4 years). Cox models analysed the relationship between BF% and incident fractures (all and hip). Linear and restricted cubic spline (RCS) regressions modelled the relationship between BF% and BUA. RESULTS: 14,129 participants (56.2 % women) were included. There were 1283 and 537 incident all and hip fractures respectively. The participants had a mean (standard deviation) age of 61.5 (9.0) years for women and 62.9 (9.0) years for men. Amongst men, BF% was not associated with incident all fractures. While BF% < 23 % (median) was not associated with hip fractures, BF% > 23 % was associated with increased risk of hip fractures by up to 50 % (hazard ratio (95 % confidence interval) = 1.49 (1.06-2.12)). In women, BF% < 39 % (median) was associated with up to 32 % higher risk of all fractures (1.32 (1.13-1.44)), while BF% > 35 % was not associated with this outcome. Higher BF% was associated with lower risk of incident hip fractures in women. Higher BF% was associated with higher BUA amongst women. Higher BF% up to ~23 % was associated with higher BUA amongst men. CONCLUSIONS: Higher BF% is associated with lower risk of fractures in women. While there was no association between BF% and all fractures in men, increasing BF% >23 % was associated with higher risk of hip fractures in men. This appears to be independent of estimated bone mineral density. Fracture prevention efforts need to consider wider physical, clinical, and environmental factors.

This paper using Scottish audit data found that frailty was associated with longer waiting times at almost all stages of the preoperative emergency general surgical pathway. Frailty and ASA fitness grade were also good indicators of mortality in this cohort.

Aims Little is known about the association between the type of admission ward and quality of care and outcomes for non-ST-segment elevation myocardial infarction (NSTEMI). Methods and results We analysed data from 337 155 NSTEMI admissions between 2010 and 2017 in the UK Myocardial Ischaemia National Audit Project (MINAP) database. The cohort was dichotomised according to receipt of care either on a medical (n = 142,876) or cardiac ward, inclusive of acute cardiac wards and cardiac care unit (n = 194,279) on admission to hospital. Patients admitted to a cardiac ward were younger (median age 70 y vs. 75 y, P Conclusion Patients with NSTEMI admitted to a cardiac ward on admission were more likely to receive guideline directed management and had better clinical outcomes.

We aimed to determine whether chronic kidney disease (CKD) is associated with adverse in-hospital outcomes after acute ischaemic stroke (AIS) and whether this association is dependent on thrombolysis administration.885,537 records representative of 4,283,086 AIS admissions were extracted from the US National Inpatient Sample (2005-2015) and categorized into 3 mutually exclusive groups: no CKD, CKD without end-stage renal disease (ESRD) and ESRD. Outcomes (mortality, prolonged hospitalisation4 days and disability on discharge-derived using discharge destination as a proxy) were compared between groups using multivariable logistic regressions. Separate models containing interaction terms with thrombolysis were also computed.The median age (interquartile range) of the cohort was 73 (61-83) years and 47.32% were men. Compared with the no CKD group, both CKD/no ESRD group (odds ratio (99% confidence interval) = 1.04 (1.0003-1.09), p = 0.009) and the ESRD groups (2.06 (1.90-2.25), p 0.001) had significantly increased odds of in-hospital mortality. Patients with CKD/No ESRD (1.03 (1.02-1.06), p 0.001) and ESRD (1.44 (1.37-1.51), p 0.001) were at higher odds of prolonged hospitalisation. Patients with CKD/No ESRD (1.13 (1.10-1.15), p 0.001) and ESRD (1.34 (1.26-1.41), p 0.001) were also at higher odds of moderate-to-severe disability on discharge. Interaction terms between thrombolysis and the CKD/ESRD groups were not statistically significant (p 0.01) for any outcome.Renal dysfunction was independently associated with worse in-hospital outcomes in the acute phase of AIS. These associations were not influenced by the use of thrombolysis as an emergency treatment for AIS. CKD/ESRD should not represent sole contraindications to thrombolysis for AIS.

OBJECTIVE: Gender differences in mortality after stroke remains unclear in the current literature. We therefore aimed to systematically review the gender differences in mortality up to five years after ischaemic (IS) or haemorrhagic stroke (HS) to address this evidence gap. METHODS: The literature was systematically searched using Ovid EMBASE, Ovid Medline, and Web of Science databases, from inception-November 2021. The quality of evidence was appraised using the CASP Cohort-study checklist. Unadjusted and adjusted odds and hazard ratios were meta-analysed, separately for IS and HS and a subgroup analysis of age-stratified mortality data was conducted. RESULTS: Forty-one studies were included (n = 8,128,700; mean-age 68.5 yrs; 47.1% female). 37 studies were included in meta-analysis (n = 8, 8008, 110). Compared to men, women who had an IS had lower mortality risk in-hospital (0.94; 95%CI 0.91-0.97), at one-month (0.87; 95%CI 0.77-0.98), 12-months (0.94; 95%CI 0.91-0.98) and five-years (0.93 95%CI 0.90-0.96). The subgroup analysis showed that this gender difference in mortality was present in women ≥ 70 years up to one-month post-IS (in-hospital: 0.94; 95%CI 0.91-0.97; one-month: 0.87; 95% CI 0.77-0.98), however, in women

Gestational diabetes mellitus (GDM) is a common pregnancy complication. This study aims to investigate the association between a history of GDM and bone mineral density (BMD), fractures, and falls in later life.We used data from the Norfolk cohort of the European Prospective Investigation into Cancer (EPIC-Norfolk) where BMD at calcaneum was measured at second health check (1997-2000) using broadband ultrasound attenuation (BUA) and velocity of sound (VOS) in 7,515 women. Fractures and falls were documented from hospital admissions data via linkage with ENCORE (East Norfolk Commission Record) and history of GDM from health questionnaires at baseline. We examined the relationship between GDM and BUA/VOS using linear regression. Cox regression was used to estimate hazard ratios (HRs) for incident fractures and falls, controlling for age, BMI, smoking status, physical activity, area deprivation, self-reported stroke, use of diuretics, calcium and vitamin D supplements, social class and education, statin and total blood cholesterol, prevalent diabetes, hormone therapy and menopausal status.History of GDM (n = 183) was not statistically significantly associated with BUA/VOS in fully adjusted linear regression models with unstandardised beta coefficients (standard error): -0.37 (1.40) and -5.41 (3.48). GDM was significantly (p 0.05) associated with risk of hip and all fractures, fully adjusted HRs(95 %CI) 2.46(1.54-3.92) and 1.60(1.09-2.35), respectively. Median follow-up from first live birth to date of admission was 53 and 52 years, respectively.There was an association between history of GDM and risk of any fracture as well as hip fracture specifically. Further research is required to confirm this.

Purpose Previous studies investigating the association between anticholinergic burden (ACB) and health-related quality of life (HRQoL) showed conflicting results and focused on older adults or specific patient groups only. Methods Participants from the European Prospective Investigation of Cancer-Norfolk study were divided into three groups according to their ACB from medications at baseline, representing ACB scores of 0, 1 and ≥2. Outcomes of interest were the physical and mental component summary scores (PCS and MCS) of the Short Form-36, collected at 18 months from the baseline and again after a mean 13 years of follow-up. Linear regression and logistic regression for cross-sectional and longitudinal associations between ACB and HRQoL were constructed adjusting for potential confounders. Results A total of 16 675 participants, mean age 58.9 ± 9.1 years (55.6% female) and 7133 participants, mean age at follow-up 69.1 ± 8.7 years (56.8% female), were included in the cross-sectional and longitudinal analyses, respectively. In cross-sectional analysis, higher anticholinergic burden was associated with higher odds of being in the lowest quartile of PCS (ACB = 1; OR, 1.85[1.64, 2.09] and ACB ≥ 2:2.19[1.85, 2.58] and MCS (ACB = 1:1.47[1.30, 1.66] and ACB ≥ 2:1.68[1.42, 1.98]). In longitudinal analysis, higher anticholinergic burden was similarly associated with higher odds of being in the lowest quartile of PCS (ACB = 1:1.56[1.24, 1.95] and ACB ≥ 2:1.48[1.07, 2.03]) compared with ACB 0 group. The association with MCS scores did not reach statistical significance. Conclusion The use of anticholinergic medications is associated with both short and long-term poorer physical functions but association with mental functioning appears more short-term.

Previous studies have found an association between chronic kidney disease and poor outcomes in stroke patients. However, there is a paucity of literature evaluating this association by stroke type. We therefore aimed to explore the association between CKD and stroke outcomes according to type of stroke. The data consisting of 594,681 stroke patients were acquired from Universal Coverage Health Security Insurance Scheme Database in Thailand. Binary logistic regression was used to assess the relationship of CKD and outcomes, which were as follows; in-hospital mortality, long length of stay (>3 days), pneumonia, sepsis, respiratory failure and myocardial infarction. Results: after fully adjusting for covariates, CKD was associated with increased odds of in-hospital mortality in patients with ischemic (OR 1.32; 95% CI = 1.27–1.38), haemorrhagic (OR 1.31; 95% CI = 1.24–1.39), and other undetermined stroke type (OR 1.44; 95% CI = 1.21–1.73). CKD was found to be associated with increased odds of pneumonia, sepsis, respiratory failure and myocardial infarction in ischaemic stroke. While CKD was found to be associated with increase odds of sepsis, respiratory failure, and myocardial infarction, decrease odds of pneumonia was observed in patients with haemorrhagic stroke. In other undetermined stroke type, CKD was found to only be associated with increase odds of sepsis and respiratory failure, while there is no significant association of CKD and increase or decrease odds with pneumonia and myocardial infarction. CKD was associated with poor outcomes in all stroke types. CKD should be considered as part of stroke prognosis as well as identifying at risk patient population for in-hospital complications.

Background:\ud Benzodiazepines and anticholinergic drugs have been implicated in causing cognitive decline and potentially increasing dementia risk. However, evidence for an association with neuropathology is limited.\ud \ud Objective:\ud To estimate the correlation between neuropathology at death and prior use of benzodiazepines and anticholinergic drugs.\ud \ud Methods:\ud We categorized 298 brain donors from the population-based Medical Research Council Cognitive Function and Ageing Study, according to their history of benzodiazepine (including Z-drugs) or anticholinergic medication (drugs scoring 3 on the Anticholinergic Cognitive Burden scale) use. We used logistic regression to compare dichotomized neuropathological features for those with and without history of benzodiazepine and anticholinergic drug use before dementia, adjusted for confounders.\ud \ud Results:\ud Forty-nine (16%) and 51 (17%) participants reported benzodiazepine and anticholinergic drug use. Alzheimer’s disease neuropathologic change was similar whether or not exposed to either drug, for example 46% and 57% had intermediate/high levels among those with and without anticholinergic drug use. Although not significant after multiple testing adjustments, we estimated an odds ratio (OR) of 0.40 (95% confidence interval [95% CI] 0.18–0.87) for anticholinergic use and cortical atrophy. For benzodiazepine use, we estimated ORs of 4.63 (1.11–19.24) and 3.30 (1.02–10.68) for neuronal loss in the nucleus basalis and substantial nigra. There was evidence of neuronal loss in the nucleus basalis with anticholinergic drug use, but the association reduced when adjusted for confounders.\ud \ud Conclusions:\ud We found no evidence that benzodiazepine or anticholinergic drug use is associated with typical pathological features of Alzheimer’s disease; however, we cannot rule out effects owing to small numbers.

Cardiovascular risk is associated with cognitive decline and this effect is attributed to brain pathology, including white matter hyperintensity (WMH) burden. Low-dose aspirin is frequently recommended for reducing vascular events. We investigated the effect of taking aspirin on the association between cardiovascular risk, WMH burden and cognitive function.The study sample was drawn from 318 dementia-free adults aged 67-71 years. Brain magnetic resonance imaging (MRI) scans were acquired from 239 participants.WMH total lesion volumes (TLV) were extracted using the automated lesion segmentation algorithm. We measured cardiovascular risk by calculating ASSIGN score. Cognitive ability was measured using a test of processing speed. We developed structural equation models to test our hypothesis.Sixty-eight participants (47.1 % male, mean age = 68.8 years) reported that they took aspirin. The demographic measures did not differ significantly by aspirin use. Among aspirin users, there was a strong negative association between WMH TLV and cognition (β = -0.43, p-value0.001), while in non-users of aspirin the only significant predictor of poorer cognition was cardiovascular risk (β = -0.17, p-value = 0.001).Aspirin use moderates the negative effect of WMH burden on cognition. Considering WMH burden in addition to cardiovascular risk could improve the prediction of cognitive decline in older adults with aspirin use.

BACKGROUND: International guidelines recommend that for NSTEMI, the timing of invasive strategy (IS) is a function of patient's baseline risk. The extent to which this is delivered across and within healthcare systems is unknown. METHODS: Data were derived from 137,265 patients admitted with an NSTEMI diagnosis between 2010 and 2015 in England and Wales. Patients were stratified into low, intermediate and high-risk in keeping with international guidelines. Time to IS was categorised into early (24 h), intermediate (25-72 h) and late (>72 h). Multivariable logistic regression models were used to identify independent predictors of guidelines recommended receipt of IS. RESULTS: There were 3608 (2.6%) low, 5037 (3.7%) intermediate and 128,621 (93.7%) high-risk patients. Guidelines recommended use of IS was significantly lower in high-risk (16.4%) compared to intermediate (64.7%) and low-risk (62.5%) groups. Both men and women in the low-risk category were almost twice as likely to receive early IS compared to high-risk men (28.9% vs 17%, p

Aims We aimed to determine the sex differences in longitudinal systolic and diastolic blood pressure (SBP and DBP) trajectories in mid-life and delineate the associations between these and mortality (all-cause, cardiovascular, and non-cardiovascular) and incident cardiovascular disease (CVD) in old age. Methods and results Participants were selected from the European Prospective Investigation into Cancer, Norfolk (EPIC-Norfolk) cohort study. Sex-specific trajectories were determined using group-based trajectory models using three clinic BP measurements acquired between 1993 and 2012 (mean exposure ∼12.9 years). Multivariable Cox regressions determined the associations between trajectories and incident outcomes over the follow-up (median follow-up 9.4 years). A total of 2897 men (M) and 3819 women (F) were included. At baseline, women were younger (F-55.5, M-57.1), had a worse cardiometabolic profile and were less likely to receive primary CVD prevention including antihypertensive treatment (F-36.0%, M-42.0%). Over the exposure period, women had lower SBP trajectories while men exhibited more pronounced SBP decreases over this period. Over the follow-up period, women had lower mortality (F-11.9%, M-20.5%) and CVD incidence (F-19.8%, M-29.6%). Compared to optimal SBP (≤120 mmHg) and DBP (≤70 mmHg) trajectories, hypertensive trajectories were associated with increased mortality and incident CVD in both men and women during follow-up at univariable level. These associations were nevertheless not maintained upon extensive confounder adjustment including antihypertensive therapies. Conclusion We report sex disparities in CVD prevention which may relate to worse cardiometabolic profiles and less pronounced longitudinal SBP decreases in women. Effective anti-hypertensivetherapy may offset the adverse outcomes associated with prolonged exposure to high blood pressure.

Predicting long-term stroke mortality is a clinically important and unmet need. We aimed to develop and internally validate a 10-year ischaemic stroke mortality prediction score. In this UK cohort study, 10,366 patients with first-ever ischaemic stroke between January 2003 and December 2016 were followed up for a median (interquartile range) of 5.47 (2.96–9.15) years. A Cox proportional-hazards model was used to predict 10-year post-admission mortality. The predictors associated with 10-year mortality included age, sex, Oxfordshire Community Stroke Project classification, estimated glomerular filtration rate (eGFR), pre-stroke modified Rankin Score, admission haemoglobin, sodium, white blood cell count and comorbidities (atrial fibrillation, coronary heart disease, heart failure, cancer, hypertension, chronic obstructive pulmonary disease, liver disease and peripheral vascular disease). The model was internally validated using bootstrap resampling to assess optimism in discrimination and calibration. A nomogram was created to facilitate application of the score at the point of care. Mean age (SD) was 78.5 ± 10.9 years, 52% female. Most strokes were partial anterior circulation syndromes (38%). 10-year mortality predictors were: total anterior circulation stroke (hazard ratio, 95% confidence intervals) (2.87, 2.62–3.14), eGFR

Background: The impact of stroke associated pneumonia (SAP) on stroke complications is not well understood; we aimed to study the association between SAP and adverse outcomes including in-hospital mortality, prolonged length of stay and the risk of developing common serious complications (sepsis, respiratory failure, and convulsions). Methods: We retrospectively analyzed data from a cohort of 610,668 stroke patients drawn from the Universal Coverage Health Security Scheme (a national insurance database) in Thailand which covers ∼80% of the Thai population. Patients were hospitalized between October 2004 and January 2013. Results: Pneumonia was present in 9.6 % (n = 58,586) of patients. Aspiration pneumonia was present in 6.2% (n = 38,060) and nonaspiration pneumonia in 3.4% (n = 20,526). After adjusting for age, sex, stroke type, and comorbidities, patients with SAP had significantly higher odds of in-hospital mortality (odds ratio [OR] 2.90: 2.83-2.96), long length of stay (OR 13.11: 12.83-13.40), sepsis (OR 8.49: 8.22-8.76), respiratory failure (OR 4.37: 4.27-4.48), and convulsions (OR 2.09: 2.00-2.17). On subanalysis, patients with nonaspiration pneumonia were found to have higher odds of adverse outcomes compared to aspiration pneumonia; the corresponding ORs (95% confidence interval) for above outcomes were 1.25 (1.21-1.30), 2.40 (2.32-2.49), 1.34 (1.28-1.40), 1.80 (1.73-1.88), and 1.19 (1.11-1.28), respectively. Conclusions: SAP is associated with higher odds of inpatient mortality, long length of stay, and risk of developing serious stroke complications. Nonaspiration pneumonia is associated with significantly higher likelihood of adverse outcomes compared to aspiration pneumonia in this patient population. Early identification and treatment of SAP is vital in reducing adverse outcomes in acute stroke.

Summary: Background/objective: The impact of medications with anti-cholinergic properties on morbidity and mortality of unselected adult patients admitted to the emergency general surgical setting has not been investigated. Methods: All cases were identified prospectively from unselected adult patients admitted to the emergency general surgical ward between May to July 2016 in a UK centre with a catchment population circa 500,000. Prescribed medication lists were ascertained from case notes and electronic medical records. Anti-Cholinergic Burden (ACB) was calculated from medication lists. Patients were categorised into three groups based on ACB; none (ACB score of 0); moderate (up to ACB score of two); high (ACB score more than two). The effect of increasing ACB on selected outcomes of 30- and 90-day mortality, hospital readmission within 30-days of discharge and increased length of hospital stay were examined using multivariable logistic regression models. Results: The 452 patients had a mean age (SD) of 51.7 (±20.6) years, 273 (60.4%) patients had no ACB burden, 106 (23.5%) had a ACB burden of up to two; and 73 (16.2%) had an ACB burden of > 2. Multivariable analyses showed no association between high ACB burden and 90-day (fully adjusted odds ratio [OR] 0.56 (95%CI 0.12–2.85); P = 0.48) and 30-day mortality (fully adjusted OR = 0.75 (95%CI 0.05–11.04); P = 0.84). A significant association was observed between moderate ACB burden and 30-day hospital readmission (fully adjusted OR = 2.01 (95%CI 1.09–3.71); P = 0.03). Conclusions: Anti-cholinergic burden may be linked to hospital readmission in adults admitted to an emergency general surgical ward. Keywords: Anti-Cholinergic Burden, 30-Day mortality, 90-Day mortality, 30-Day readmission, Length of hospital stay, Change in destination, Emergency surgery

Previous estimates of whether long-term exposure to benzodiazepines increases dementia risk are conflicting and are compromised by the difficulty of controlling for confounders and by reverse causation. We investigated how estimates for the association between benzodiazepine use and later dementia incidence varied based on study design choices, using a case-control study nested within the United Kingdom’s Clinical Practice Research Datalink. A total of 40,770 dementia cases diagnosed between April 2006 and July 2015 were matched on age, sex, available data history, and deprivation to 283,933 control subjects. Benzodiazepines and Z-drug prescriptions were ascertained in a drug-exposure period 4–20 years before dementia diagnosis. Estimates varied with the inclusion of new or prevalent users, with the timing of covariate ascertainment, and with varying time between exposure and outcome. There was no association between any new prescription of benzodiazepines and dementia (adjusted odds ratio (OR) = 1.03, 95% confidence interval (CI): 1.00, 1.07), whereas an inverse association was observed among prevalent users (adjusted OR = 0.91, 95% CI: 0.87, 0.95), although this was likely induced by unintentional adjustment for colliders. By considering the choice of confounders and timing of exposure and covariate measurement, our findings overall are consistent with no causal effect of benzodiazepines or Z-drugs on dementia incidence.

BACKGROUND/OBJECTIVES: Cancerous and non-cancerous respiratory diseases are common and contribute significantly to global disease burden. We aim to quantify the association between plasma vitamin C concentrations as an indicator of high fruit and vegetable consumption and the risk of incident respiratory diseases and associated mortality in a general population. SUBJECTS/METHODS: Nineteen thousand three hundred and fifty-seven men and women aged 40-79 years without prevalent respiratory diseases at the baseline (1993-1997) and participating in the European Prospective Investigation into Cancer (EPIC)-Norfolk study in the United Kingdom were followed through March 2015 for both incidence and mortality from respiratory diseases. RESULTS: There were a total of 3914 incident events and 407 deaths due to any respiratory diseases (excluding lung cancers), 367 incident lung cancers and 280 lung cancer deaths during the follow-up (total person-years >300,000 years). Cox's proportional hazards models showed that persons in the top quartiles of baseline plasma vitamin C concentrations had a 43% lower risk of lung cancer (hazard ratio (HR) 0.57; 95% confidence interval (CI): 0.41-0.81) than did those in the bottom quartile, independently of potential confounders. The results are similar for any non-cancerous respiratory diseases (HR 0.85; 0.77-0.95), including chronic respiratory diseases (HR 0.81; 0.69-0.96) and pneumonia (HR 0.70; 0.59-0.83). The corresponding values for mortality were 0.54 (0.35-0.81), 0.81 (0.59-1.12), 0.85 (0.44-1.66) and 0.61 (0.37-1.01), respectively. Confining analyses to non-smokers showed 42% and 53% risk reduction of non-smoking-related lung cancer incidence and death. CONCLUSIONS: Higher levels of vitamin C concentrations as a marker of high fruit and vegetable consumption reduces the risk of cancerous and non-cancerous respiratory illnesses including non-smoking-related cancer incidence and deaths.

Background Guidelines recommend ambulatory or home blood pressure monitoring to improve hypertension diagnosis and monitoring. Both these methods are ascribed the same threshold values, but whether they produce similar results has not been established in certain patient groups. Methods Adults with mild/moderate stroke or transient ischemic attack (N = 80) completed 2 sets of ambulatory and home blood pressure monitoring. Systolic and diastolic blood pressure values from contemporaneous measurements were compared, and the limits of agreement were assessed. Exploratory analyses for predictive factors of any difference were conducted. Results Daytime ambulatory blood pressure values were consistently lower than home values, the mean difference in systolic blood pressure for initial ambulatory versus first home monitoring was −6.6 ± 13.5 mm Hg (P≤.001), and final ambulatory versus second home monitoring was −7.1 ± 11.0mm Hg (P≤.001). Mean diastolic blood pressure differences were −2.1 ± 8.5mm Hg (P=.03) and −2.0 ± 7.2mm Hg (P=.02). Limits of agreement for systolic blood pressure were −33.0 to 19.9mm Hg and −28.7 to 14.5mm Hg for the 2 comparisons and for DBP were −18.8 to 14.5mm Hg and −16.1 to 12.2mm Hg, respectively. The individual mean change in systolic blood pressure difference was 11.0 ± 8.3mm Hg across the 2 comparisons. No predictive factors for these differences were identified. Conclusions Daytime ambulatory systolic and diastolic blood pressure values were significantly lower than home monitored values at both time points. Differences between the 2 methods were not reproducible for individuals. Using the same threshold value for both out-of-office measurement methods may not be appropriate in patients with cerebrovascular disease.

Rationale: Proinflammatory cytokines have been identified as potential targets for lowering vascular risk. Experimental evidence and Mendelian randomization suggest a role of MCP-1 (monocyte chemoattractant protein-1) in atherosclerosis and stroke. However, data from large-scale observational studies are lacking. Objective: To determine whether circulating levels of MCP-1 are associated with risk of incident stroke in the general population. Methods and Results: We used previously unpublished data on 17 180 stroke-free individuals (mean age, 56.7±8.1 years; 48.8% men) from 6 population-based prospective cohort studies and explored associations between baseline circulating MCP-1 levels and risk of any stroke, ischemic stroke, and hemorrhagic stroke during a mean follow-up interval of 16.3 years (280 522 person-years at risk; 1435 incident stroke events). We applied Cox proportional-hazards models and pooled hazard ratios (HRs) using random-effects meta-analyses. After adjustments for age, sex, race, and vascular risk factors, higher MCP-1 levels were associated with increased risk of any stroke (HR per 1-SD increment in ln-transformed MCP-1, 1.07; 95% CI, 1.01–1.14). Focusing on stroke subtypes, we found a significant association between baseline MCP-1 levels and higher risk of ischemic stroke (HR, 1.11 [1.02–1.21]) but not hemorrhagic stroke (HR, 1.02 [0.82–1.29]). The results followed a dose-response pattern with a higher risk of ischemic stroke among individuals in the upper quartiles of MCP-1 levels as compared with the first quartile (HRs, second quartile: 1.19 [1.00–1.42]; third quartile: 1.35 [1.14–1.59]; fourth quartile: 1.38 [1.07–1.77]). There was no indication for heterogeneity across studies, and in a subsample of 4 studies (12 516 individuals), the risk estimates were stable after additional adjustments for circulating levels of IL (interleukin)-6 and high-sensitivity CRP (C-reactive protein). Conclusions: Higher circulating levels of MCP-1 are associated with increased long-term risk of stroke. Our findings along with genetic and experimental evidence suggest that MCP-1 signaling might represent a therapeutic target to lower stroke risk.Visual Overview: An online visual overview is available for this article.

Background The association between systemic hypertension and cerebrovascular disease is well documented. However, the impact of pulmonary hypertension (PH) on acute ischemic stroke outcomes is unknown despite PH being recognized as a risk factor for acute ischemic stroke. We aimed to determine the association between PH and adverse in‐hospital outcomes after acute ischemic stroke, as well as whether there are sex differences in this association. Methods and Results Acute ischemic stroke admissions from the US National Inpatient Sample between October 2015 and December 2017 were included. The relationship between PH and outcomes (mortality, prolonged hospitalization >4 days, and routine home discharge) was analyzed using logistic regressions adjusting for demographics, comorbidities, and revascularization therapies. Interaction terms between PH and sex and age groups were also included. A total of 221 249 records representative of 1 106 045 admissions were included; 2.9% of patients had co‐morbid PH, and 35.34% of those were male. PH was not associated with in‐hospital mortality (odds ratio [OR], 0.96; 95% CI, 0.86–1.09) but was associated with increased odds of prolonged hospitalization (OR, 1.15; 95% CI, 1.09–1.22) and decreased odds of routine discharge (OR, 0.87; 95% CI, 0.81–0.94) for both sexes. Older patients with PH were significantly less likely to be discharged routinely ( P =0.028) than their younger counterparts. Compared with female patients with PH, men were 31% more likely to die in hospital ( P =0.024). Conclusions PH was not significantly associated with in‐hospital mortality but was associated with prolonged hospitalization and adverse discharge status. Male patients with PH were more likely to die in hospital than female patients.

The role of dietary calcium in cardiovascular disease prevention is unclear. We aimed to determine the association between calcium intake and incident cardiovascular disease and mortality. Data were extracted from the European Prospective Investigation of Cancer, Norfolk (EPIC-Norfolk). Multivariable Cox regressions analysed associations between calcium intake (dietary and supplemental) and cardiovascular disease (myocardial infarction, stroke, heart failure, aortic stenosis, peripheral vascular disease) and mortality (cardiovascular and all-cause). The results of this study were pooled with those from published prospective cohort studies in a meta-analsyis, stratifying by average calcium intake using a 700 mg/day threshold. A total of 17,968 participants aged 40–79 years were followed up for a median of 20.36 years (20.32–20.38). Compared to the first quintile of calcium intake (

BACKGROUNDChronic subdural hematoma is a common neurologic disorder that is especially prevalent among older people. The effect of dexamethasone on outcomes in patients with chronic subdural hematoma has not been well studied.METHODSWe conducted a multicenter, randomized trial in the United Kingdom that enrolled adult patients with symptomatic chronic subdural hematoma. The patients were assigned in a 1:1 ratio to receive a 2-week tapering course of oral dexamethasone, starting at 8 mg twice daily, or placebo. The decision to surgically evacuate the hematoma was made by the treating clinician. The primary outcome was a score of 0 to 3, representing a favorable outcome, on the modified Rankin scale at 6 months after randomization; scores range from 0 (no symptoms) to 6 (death).RESULTSFrom August 2015 through November 2019, a total of 748 patients were included in the trial after randomization — 375 were assigned to the dexamethasone group and 373 to the placebo group. The mean age of the patients was 74 years, and 94% underwent surgery to evacuate their hematomas during the index admission; 60% in both groups had a score of 1 to 3 on the modified Rankin scale at admission. In a modified intention-to-treat analysis that excluded the patients who withdrew consent for participation in the trial or who were lost to follow-up, leaving a total of 680 patients, a favorable outcome was reported in 286 of 341 patients (83.9%) in the dexamethasone group and in 306 of 339 patients (90.3%) in the placebo group (difference, −6.4 percentage points [95% confidence interval, −11.4 to −1.4] in favor of the placebo group; P=0.01). Among the patients with available data, repeat surgery for recurrence of the hematoma was performed in 6 of 349 patients (1.7%) in the dexamethasone group and in 25 of 350 patients (7.1%) in the placebo group. More adverse events occurred in the dexamethasone group than in the placebo group.CONCLUSIONSAmong adults with symptomatic chronic subdural hematoma, most of whom had undergone surgery to remove their hematomas during the index admission, treatment with dexamethasone resulted in fewer favorable outcomes and more adverse events than placebo at 6 months, but fewer repeat operations were performed in the dexamethasone group. (Funded by the National Institute for Health Research Health Technology Assessment Programme; Dex-CSDH ISRCTN number, ISRCTN80782810. opens in new tab.)

Highlights • Exposure to anticholinergic medication predicts lower physical capability. • Associations were seen in a sample of men and women aged 48–92 years from a general population. • Differences in walking speed were equivalent to 3–9 years’ difference in age. • Exposure to anticholinergic medication is prevalent and potentially modifiable. • Identifying modifiable risk factors is necessary to optimise late-life function., Objectives To examine whether anticholinergic medication exposure in middle and late life is associated with physical capability. Study design We used data from 8477 men and women who had enrolled in the European Prospective Investigation of Cancer-Norfolk study at baseline (1HC; 1993–1997) and who had attended its third health examination (3HC; 2004–2010). Medication history at the 1HC and 3HC was used to score participants according to the Anticholinergic Cognitive Burden (ACB) Scale at baseline and 3HC; participants were categorised as ACB = 0, ACB = 1, ACB>2. Main outcome measure At 3HC, physical capability was objectively measured by: usual walking speed, maximum grip strength, timed chair stands speed (TCSS) and standing balance. Linear and logistic regression models examined prospective and cross-sectional associations between ACB and physical capability, controlling for co-morbidity, sociodemographic and lifestyle factors. Results The analyses included 3386 men and 4110 women who were 56.4 (SD 7.9) and 55.0 (7.7) years old respectively at baseline and 69.4 (8.1) and 67.9 (8.0) years old at follow-up. Significant cross-sectional and prospective relationships were observed for all physical capability measures in women, except grip strength. For example, women with ACB ≥ 2 compared with ACB = 0 at baseline had 0.07 m/s (95 % CI -0.11, -0.03) slower usual walking speed, 2.61 stands/min (-4.17, -1.05) slower TCSS and higher odds of being unable to complete a tandem stand (odds ratio 2.40, 95 % CI 1.53, 3.76). These trends were observed in men but were less consistent in prospective analyses. Conclusion Exposure to anticholinergic medication predicts poor physical capability and is a potentially reversible risk factor.

Background While anticholinergic use is associated with stroke, dementia and mortality, few have evaluated its potential link with falls. To determine the relationship between anticholinergic cognitive burden (ACB) and falls over five years using the Malaysian Elders Longitudinal Research (MELoR). Methods Community-dwelling adults aged 55 years and over were recruited through electoral roll sampling. Data obtained at baseline and follow-up (FU) at two and five years were included. Falls in the preceding 12 months were recorded. Results Of the 1499 individuals (mean (SD) age= 68.9(7.5) yrs and 53.3% female) with information on baseline ACB exposure, 575(38.4%) had ACB scores of 1-2 and 117(7.8%) had ACB scores ≥ 3 . Differences in age, ethnicity, smoking status, diabetes, hypertension, cardiovascular disease, arthritis and education existed between ACB groups. Fall occurrence differed between ACB groups at recruitment (p = 0.004) and 2-year FU (p = 0.001) but not at 5-year FU (p = 0.053). Logistic regression revealed an independent association between ACB 1-2 and falls at baseline (odds ratio, OR (95% confidence interval, CI) =1.412(1.035-1.926)) and ACB ≥ 3 and falls at 2-yr FU (OR (95%CI) =2.098(1.032-4.263)) following adjustment for confounders. Conclusion Low level exposure to drugs with anticholinergic properties was associated cross-sectionally with falls, while exposure to higher levels were prospectively associated with falls at 2-year but not at 5-year FU. Future studies should determine whether avoidance of drugs with anticholinergic effects will lead to reduction in falls.

Background Cognitive impairment and dementia following cerebrovascular disease are increasingly common in the UK. One potential strategy to prevent post-stroke cognitive decline is multimodal vascular risk factor management. However, its efficacy remains uncertain and its application in vulnerable patients with incident cerebrovascular disease and early cognitive impairment has not been assessed. The primary aim of this study was to assess the feasibility of recruitment and retention of patients with early cognitive impairment post-stroke or transient ischaemic attack (TIA) to a trial of enhanced vascular risk factor management combining primary and secondary care. Methods In this single centre, open label trial adults with a recent stroke or TIA and mild cognitive impairment (MCI) were randomised 1:1 to a three-monthly multimodal vascular risk factor intervention jointly delivered by the trial team and General Practitioner (GP), or control (defined as usual care from the GP). Chosen risk factors were blood pressure (BP), total cholesterol, blood glucose (HbA1C) in those with diabetes, and heart rate and adequacy of anticoagulation in those with atrial fibrillation (AF). Similar patients with normal cognition were enrolled in an embedded observational cohort and also received usual care from the GP. Repeat cognitive screening was undertaken in all participants after 12 months. Results Seventy three participants were recruited to the randomised trial and 94 to the observational cohort (21.8% of those screened). From the randomised trial 35/73 (47.9%) dropped out before final follow-up. In all groups guideline based rates of risk factor control were mostly poor at baseline and did not significantly improve during follow-up. The observational cohort demonstrated greater decline in cognitive test scores at 12 months, with no difference between the randomised groups. Conclusions Recruitment to such a study was feasible, but retention of participants was difficult and generally poor rates of risk factor control suggested insufficient application of the intervention. Consequently, successful scaling up of the trial would require protocol changes with less reliance on primary care services. Any future trial should include participants with normal cognition post-stroke as they may be at greatest risk of cognitive decline. Trial registration ISRCTN, ISRCTN42688361. Registered 16 April 2015.

Background: The COVID-19 pandemic has placed unprecedented strain on health-care systems. Frailty is being used in clinical decision making for patients with COVID-19, yet the prevalence and effect of frailty in people with COVID-19 is not known. In the COVID-19 in Older PEople (COPE) study we aimed to establish the prevalence of frailty in patients with COVID-19 who were admitted to hospital and investigate its association with mortality and duration of hospital stay. Methods: This was an observational cohort study conducted at ten hospitals in the UK and one in Italy. All adults (≥18 years) admitted to participating hospitals with COVID-19 were included. Patients with incomplete hospital records were excluded. The study analysed routinely generated hospital data for patients with COVID-19. Frailty was assessed by specialist COVID-19 teams using the clinical frailty scale (CFS) and patients were grouped according to their score (1–2=fit; 3–4=vulnerable, but not frail; 5–6=initial signs of frailty but with some degree of independence; and 7–9=severe or very severe frailty). The primary outcome was in-hospital mortality (time from hospital admission to mortality and day-7 mortality). Findings: Between Feb 27, and April 28, 2020, we enrolled 1564 patients with COVID-19. The median age was 74 years (IQR 61–83); 903 (57·7%) were men and 661 (42·3%) were women; 425 (27·2%) had died at data cutoff (April 28, 2020). 772 (49·4%) were classed as frail (CFS 5–8) and 27 (1·7%) were classed as terminally ill (CFS 9). Compared with CFS 1–2, the adjusted hazard ratios for time from hospital admission to death were 1·55 (95% CI 1·00–2·41) for CFS 3–4, 1·83 (1·15–2·91) for CFS 5–6, and 2·39 (1·50–3·81) for CFS 7–9, and adjusted odds ratios for day-7 mortality were 1·22 (95% CI 0·63–2·38) for CFS 3–4, 1·62 (0·81–3·26) for CFS 5–6, and 3·12 (1·56–6·24) for CFS 7–9. Interpretation: In a large population of patients admitted to hospital with COVID-19, disease outcomes were better predicted by frailty than either age or comorbidity. Our results support the use of CFS to inform decision making about medical care in adult patients admitted to hospital with COVID-19. Funding: None.

The ACPGBI have recently released recommendations for re-starting elective colorectal surgery to address the concerns that significant numbers of patients have been deferred during this pandemic worldwide (1). It is a credit to the specialty that most units have managed to continue with urgent cancer surgery through the pandemic, with leading units undertaking 4 to 5 urgent cases per week . Despite this there is now a need to accommodate other patient groups who need colorectal surgery such as those with inflammatory bowel disease and others with benign colorectal conditions who have been placed on hold.

Objective To evaluate post-stroke outcomes in patients with Parkinson's disease (PD). Methods A matched cohort study was performed. Stroke patients with PD and non-PD controls were extracted from the Thailand Universal Insurance Database. Logistic regressions were used to evaluate the association between PD and in-hospital outcomes (mortality and complications). The PD-associated long-term mortality was evaluated using Royston-Parmar models. Results A total of 1967 patients with PD were identified between 2003 and 2015 and matched to controls (1:4) by age, sex, admission year, and stroke type. PD patients had decreased odds of in-hospital death: OR (95% CI) 0.66 (0.52 – 0.84) and 0.61 (0.43 – 0.85) after ischaemic and haemorrhagic strokes, respectively. PD was associated with a length-of-stay greater than median (4 days) after both stroke types: 1.37 (1.21 – 1.56) and 1.45 (1.05 – 2.00), respectively. Ischaemic stroke patients with PD also had increased odds of developing pneumonia, sepsis and AKI: 1.52 (1.2 – 1.83), 1.54 (1.16 – 2.05), and 1.33 (1.02 – 1.73). In haemorrhagic stroke patients, PD was associated with pneumonia: 1.89 (1.31 – 2.72). Survival analyses showed that PD was protective against death in the short term (HR=0.66; 95% CI 0.53–0.83 ischaemic, and HR=0.50; 95% CI 0.37 – 0.68 haemorrhagic stroke), but leads to an increased mortality risk approximately 1 and 3 months after ischaemic and haemorrhagic stroke, respectively. Conclusion PD is associated with a reduced mortality risk during the first 2–4 weeks post-admission but an increased risk thereafter, in addition to increased odds of in-hospital complications and prolonged hospitalisation.

Background Increased use of invasive coronary strategies in patients admitted to hospitals with on-site cardiac catheter laboratory (CCL) facilities has been reported, but the utilisation of invasive coronary strategies according to types of CCL facilities at the first admitting hospital and clinical outcomes is unknown. Methods We included 452,216 patients admitted with a diagnosis of non–ST-segment-elevation myocardial infarction (NSTEMI) in England and Wales from 2007 to 2015. The admitting hospitals were categorized into no-laboratory, diagnostic, and PCI hospitals according to CCL facilities. Multilevel logistic regression models were used to study associations between CCL facilities and in-hospital outcomes. Results A total of 97,777 (21.6%) of the patients were admitted to no-laboratory hospitals, and 134,381 (29.7%) and 220,058 (48.7%) were admitted to diagnostic and PCI hospitals, respectively. Use of coronary angiography was significantly higher in PCI hospitals (77.3%) than in diagnostic (63.2%) and no-laboratory (61.4%) hospitals. The adjusted odds of in-hospital mortality were similar for diagnostic (odds ratio [OR] 0.93, 95% confidence interval [CI] 0.83-1.04) and PCI hospitals (OR 1.09, 95% CI 0.96-1.24) compared with no-laboratory hospitals. However, in high-risk NSTEMI subgroup (defined as Global Registry of Acute Coronary Events score > 140), an admission to diagnostic hospitals was associated with significantly increased in-hospital mortality (OR 1.36, 95% CI 1.06-1.75) compared with no-laboratory and PCI hospitals. Conclusions This study highlights important differences in both the utilisation of invasive coronary strategies and subsequent management and outcomes of NSTEMI patients according to admitting hospital CCL facilities. High-risk NSTEMI patients admitted to diagnostic hospitals had greater in-hospital mortality, possibly because of reduced PCI use, which needs to be addressed.

Background and Purpose— Fatigue is a common symptom among stroke survivors and in general practice. However, the clinical significance of fatigue and its relationship to incident stroke is unclear. The aim of this study was to examine the relationship between self-reported fatigue and the incidence of stroke in a general population. Methods— This was a prospective, population-based study. The study population was 15 654 men and women aged 39 to 79 years recruited in 1993 to 1997 and followed till March 2016. Fatigue was assessed at 18 months after baseline using the vitality domain of the Short Form 36 questionnaire. Cox proportional hazard models were constructed to describe the prospective relationship between baseline fatigue and incident stroke adjusting for age, sex, systolic blood pressure, cholesterol, physical activity, smoking status, alcohol consumption, fruit and vegetable consumption, diabetes mellitus, body mass index, vitamin supplement use, education level, Townsend deprivation index, and occupational social class. Incident stroke was ascertained using death certificates and hospital record linkage data. Results— Through 249 248 person-years of follow-up, 1509 incident strokes occurred. Participants who reported the highest level of fatigue (quartile 4) were more likely to be women, to be multimorbid, and to perceive their health as fair or poor. We observed ≈50% relative risk increase in stroke risk (hazard ratio, 1.49 [95% CI, 1.29–1.71]) in those who reported the highest level of fatigue compared with those who reported the lowest level of fatigue (Q4 versus Q1). This relationship remained unaltered regardless of anemia status, the presence or absence of chronic bronchitis, thyroid dysfunction, or depression. Conclusions— Self-report fatigue assessed by the vitality domain of the Short Form 36 questionnaire predicts the risk of future stroke at the general population level. Identifying and addressing stroke risk factors in those who report fatigue in general practice may have substantial benefit at the population level.

Summary This study investigates if the day of the week a person is admitted with a hip fracture influences the quality of care they receive. We found those admitted Thursday and Friday were likely to obtain poorer postoperative care, indicating a need to optimize services ensuring equality for all. Purpose We sought to investigate how the day of admission affects the quality of care provided to hip fracture patients according to national standards (The Scottish Standards of Care for Hip Fracture Patients [SSCHFP]). Methods Retrospective analysis of national cohort data. Data were collected by the Scottish Hip Fracture Audit (SHFA) local audit co-ordinators (LACs) at participating Scottish hospitals on behalf of NHS Scotland and the Scottish Government. Adherence to the SSCHFP included assessment of both individual and cumulative standard attainment as a marker for quality of patient care. Results From January 2014 to April 2018, 15,351 admissions for hip fracture were recorded. Compared with Monday admission (reference day), patients admitted on a Thursday or Friday had a significantly lower likelihood of achieving the postoperative standards of prompt mobilization (OR 1.77; p p p p p p p = 0.001 & OR 1.23; p = 0.002, respectively) and avoidance of repeat fasting (OR 1.22; p = 0.009 & OR 1.22; p = 0.01, respectively). Conclusion Patients admitted on Thursday or Friday were significantly more likely to not receive postoperative care standards than patients admitted on the reference day (Monday). This appears to be related to inequalities in service provision for Saturday and Sunday compared with the rest of the week.

PURPOSE Anticholinergic burden (ACB), the cumulative effect of anticholinergic medications, is associated with adverse outcomes in older people but is less studied in middle-aged populations. Numerous scales exist to quantify ACB. The aims of this study were to quantify ACB in a large cohort using the 10 most common anticholinergic scales, to assess the association of each scale with adverse outcomes, and to assess overlap in populations identified by each scale.\ud \ud METHODS We performed a longitudinal analysis of the UK Biobank community cohort (502,538 participants, baseline age: 37-73 years, median years of follow-up: 6.2). The ACB was calculated at baseline using 10 scales. Baseline data were linked to national mortality register records and hospital episode statistics. The primary outcome was a composite of all-cause mortality and major adverse cardiovascular event (MACE). Secondary outcomes were all-cause mortality, MACE, hospital admission for fall/fracture, and hospital admission with dementia/delirium. Cox proportional hazards models (hazard ratio [HR], 95% CI) quantified associations between ACB scales and outcomes adjusted for age, sex, socioeconomic status, body mass index, smoking status, alcohol use, physical activity, and morbidity count.\ud \ud RESULTS Anticholinergic medication use varied from 8% to 17.6% depending on the scale used. For the primary outcome, ACB was significantly associated with all-cause mortality/MACE for each scale. The Anticholinergic Drug Scale was most strongly associated with mortality/MACE (HR = 1.12; 95% CI, 1.11-1.14 per 1-point increase in score). The ACB was significantly associated with all secondary outcomes. The Anticholinergic Effect on Cognition scale was most strongly associated with dementia/delirium (HR = 1.45; 95% CI, 1.3-1.61 per 1-point increase).\ud \ud CONCLUSIONS The ACB was associated with adverse outcomes in a middle- to older-aged population. Populations identified and effect size differed between scales. Scale choice influenced the population identified as potentially requiring reduction in ACB in clinical practice or intervention trials.

We examined the existence and potential burden of seasonality of stroke admissions and mortality within a tropical climate using cohort data collected between 1 st November 2003 and 31 st October 2012.In a prospective cohort of hospitalised stroke patients from the catchment of ∼75 % of the Thai population (n = 569,307; mean SD age = 64(14.5)), incident stroke admissions, in-hospital mortality, prolonged hospitalisations, and stroke related complications by season were determined. Rates of incident stroke admissions by month and season were plotted. Winter excess indexes for study outcomes expressed as a percentage were calculated. Using logistic regression we examined the association between winter admission and in-hospital mortality (non-winter admission as reference) adjusting for age, sex, stroke type, year of admission, and presence of pre-existing comorbidities.We observed a winter excess in mortality during hospitalisation (+10.3 %) and prolonged length of stay (+7.3 %). Respective winter excess indexes for dyslipidaemias, arrhythmias, anaemia, and alcohol related disorders in patients that died during hospitalisation were +1.4 %, +6.2 %, +0.2 %, +1.5 %. In these patients, respective winter excess indexes for post-stroke complications of pneumonia and sepsis were +6.7 % and +3.2 %. In fully adjusted analyses, winter admission (compared to non-winter admission) was associated with increased odds of in-hospital mortality (OR (95 % CI) = 1.023 (1.006-1.040)).We provide robust evidence for the existence of an excess in winter stroke admissions and subsequent in-hospital deaths within a tropical region.

Background: Patients with diabetes mellitus (DM) have been found to be at an increased risk of suffering a stroke. However, research on the impact of DM on stroke outcomes is limited. Objectives: We aimed to examine the influence of DM on outcomes in ischaemic (IS) and haemorrhagic stroke (HS) patients. Methods: We included 608,890 consecutive stroke patients from the Thailand national insurance registry. In-hospital mortality, sepsis, pneumonia, acute kidney injury (AKI), urinary tract infection (UTI) and cardiovascular events were evaluated using logistic regressions. Long-term analysis was performed on first-stroke patients with a determined pathology (n = 398,663) using Royston-Parmar models. Median follow-ups were 4.21 and 4.78 years for IS and HS, respectively. All analyses were stratified by stroke sub-type. Results: Mean age (SD) was 64.3 (13.7) years, 44.9% were female with 61% IS, 28% HS and 11% undetermined strokes. DM was associated with in-hospital death, pneumonia, sepsis, AKI and cardiovascular events (odds ratios ranging from 1.13-1.78, p < 0.01) in both stroke types. In IS, DM was associated with long-term mortality and recurrence throughout the follow-up: HRmax (99% CI) at t = 4108 days: 1.54 (1.27, 1.86) and HR (99% CI) = 1.27(1.23,1.32), respectively. In HS, HRmax (t = 4108 days) for long-term mortality was 2.10 (1.87, 2.37), significant after day 14 post-discharge. HRmax (t = 455) for long-term recurrence of HS was 1.29 (1.09, 1.53), significant after day 116 post-discharge. Conclusions: Regardless of stroke type, DM was associated with in-hospital death and complications, long-term mortality and stroke recurrence.

Objectives To examine national-level differences in management strategies and outcomes in patients with autoimmune rheumatic disease (AIRD) with acute myocardial infarction (AMI) from 2004 through 2014. Methods All AMI hospitalizations were analyzed from the National Inpatient Sample, stratified according to AIRD diagnosis into 4 groups: no AIRD, rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and systemic sclerosis (SSC). The associations between AIRD subtypes and (1) receipt of coronary angiography and percutaneous coronary intervention (PCI) and (2) clinical outcomes were examined compared with patients without AIRD. Results Of 6,747,797 AMI hospitalizations, 109,983 patients (1.6%) had an AIRD diagnosis (RA: 1.3%, SLE: 0.3%, and SSC: 0.1%). The prevalence of RA rose from 1.0% (2004) to 1.5% (2014), and SLE and SSC remained stable. Patients with SLE were less likely to receive invasive management (odds ratio [OR] [95% CI]: coronary angiography—0.87; 0.84 to 0.91; PCI—0.93; 0.90 to 0.96), whereas no statistically significant differences were found in the RA and SSC groups. Subsequently, the ORs (95% CIs) of mortality (1.15; 1.07 to 1.23) and bleeding (1.24; 1.16 to 1.31) were increased in patients with SLE; SSC was associated with increased ORs (95% CIs) of major adverse cardiovascular and cerebrovascular events (1.52; 1.38 to 1.68) and mortality (1.81; 1.62 to 2.02) but not bleeding or stroke; the RA group was at no increased risk for any complication. Conclusion In a nationwide cohort of AMI hospitalizations we found lower use of invasive management in patients with SLE and worse outcomes after AMI in patients with SLE and SSC compared with those without AIRD.

The optimal regimen of antiplatelet therapy for secondary prevention in noncardioembolic ischemic stroke remains controversial. We aimed to determine which regimen was associated with the greatest reduction in adverse outcomes. We analysed prospectively collected data from the Norfolk and Norwich University Hospital Stroke Register. The sample population consisted of 3,572 participants (mean age 74.96 ± 12.67) with ischemic stroke, who were consecutively admitted between 2003 and 2015. Patients were placed on one of three antiplatelet regimens at hospital discharge; aspirin monotherapy, aspirin plus dipyridamole and clopidogrel. Clopidogrel and aspirin plus dipyridamole were compared to aspirin. A direct comparison between clopidogrel and aspirin plus dipyridamole was also performed. Outcomes included all-cause mortality and a combined end point of all-cause mortality and incidence of major adverse cardiac events (stroke or myocardial infarction). Cox-regression models adjusted for potential confounders at the following time periods after discharge; 0 to 90 days, 91 to 365 days, and 1 to 3 years. Aspirin plus dipyridamole was associated with a lower risk of mortality at 0 to 90 days; hazard ratio (HR) 0.62 (0.43 to 0.91). Clopidogrel was associated with a lower risk of mortality at 1 to 3 years; HR of 0.39 (0.26 to 0.60). Similar HRs were observed for the corresponding time points in the composite outcome. In conclusion, patients with noncardioembolic stroke may gain maximum benefits from aspirin plus dipyridamole initially (≤1 year) with a subsequent switch to clopidogrel, with regard to mortality and major adverse cardiac eventsoutcomes.

The consumption of medications with anticholinergic activity has been suggested to result in the adverse effects of mental confusion, visual disturbance, and muscle weakness, which may lead to falls. Existing published evidence linking anticholinergic drugs with falls, however, remains weak. This study was conducted to evaluate the relationship between anticholinergic cognitive burden (ACB) and the long-term risk of hospitalization with falls and fractures in a large population study. The dataset comprised information from 25,639 men and women (aged 40–79 years) recruited from 1993 to 1997 from Norfolk, United Kingdom into the European Prospective Investigation into Cancer (EPIC)-Norfolk study. The time to first hospital admission with a fall with or without fracture was obtained from the National Health Service hospital information system. Cox-proportional hazards analyses were conducted to adjust for confounders and competing risks. The fall hospitalization rate was 5.8% over a median follow-up of ~ 19.4 years. The unadjusted incidence rate ratio for the use of any drugs with anticholinergic properties was 1.79 (95% CI 1.66–1.93). The hazard ratios (95% CI) for ACB scores of 1, 2–3, and ≥ 4 compared with ACB = 0 for fall hospitalization were 1.20 (1.09–1.33), 1.42 (1.25–1.60), and 1.39 (1.21–1.60) after adjustment for age, gender, medical conditions, physical activity, and blood pressure. Medications with anticholinergic activity are associated with an increased risk of subsequent hospitalization with a fall over a 19-year follow-up period. The biological mechanisms underlying the long-term risk of hospitalization with a fall or fracture following baseline ACB exposure remains unclear and requires further evaluation.

It is unclear how age affects rates and causes of unplanned early readmissions after percutaneous coronary intervention (PCI). We analyzed patients in the Nationwide Readmission Database in the United States from 2010 to 2014 and examined the impact of age on readmissions after PCI. The primary outcomes were age-specific 30-day rates and causes of unplanned readmissions. A total of 2,294,345 procedures were analyzed with a 9.6% unplanned readmission rate within 30 days. Unplanned readmissions were 8.1%, 8.1%, 9.5%, and 12.6% for age groups

Aim The determinants of cognitive impairment and delirium during acute illness are poorly understood, despite being common among older people. Anemia is common in older people, and there is ongoing debate regarding the association between anemia, cognitive impairment and delirium, primarily in non‐surgical patients. Methods Using data from the Older Persons Surgical Outcomes Collaboration 2013 and 2014 audit cycles, we examined the association between anemia and cognitive outcomes in patients aged ≥65 years admitted to five UK acute surgical units. On admission, the Confusion Assessment Method was carried out to detect delirium. Cognition was assessed using the Montreal Cognitive Assessment, and two levels of impairment were defined as Montreal Cognitive Assessment

Shock index (SI - heart rate/systolic blood pressure) has been studied as a measure of haemodynamic status. We aimed to determine whether SI measures within 72 h of admission were associated with adverse outcomes in intracerebral haemorrhage (ICH).Patients were drawn from the Virtual International Stroke Trials Archive-Intracerebral Haemorrhage (VISTA-ICH). Multivariable Cox regressions modelled the relationship between SI (on admission, 24, 48, 72 h) and mortality (at 3-, 7-, and 90-days), 90-day incident pneumonia and cardiovascular events (MACE). Ordinal logistic regressions modelled the relationship between SI and 90-day modified Rankin Scale (mRS).979 patients were included. Baseline SI was not associated with mortality. 24 h SI 0.7 was associated with 7-day mortality (hazard ratio (95% confidence interval) = 3.14 (1.37-7.19)). 48 h and 72 h SI 0.7 were associated with 7-day (4.23 (2.07-8.66) and 3.24 (1.41-7.42) respectively) and 90-day mortality (2.97 (1.82-4.85) and 2.05 (1.26-3.61) respectively). SI 0.5 at baseline, 48 h and 72 h was associated with decreased pneumonia risk. 24 h and 48 h SI 0.7was associated with increased MACE risk. 48 h and 72 h SI 0.7 was associated with increased odds of higher 90-day mRS.Higher-than-normal SI subsequent to initial encounter was associated with higher post-ICH mortality at 3, 7, and 90 days. Lower-than-normal SI was associated with a decreased risk of incident pneumonia.

BackgroundPrevious research has demonstrated an association between anaemia and poor outcomes in acute stroke. This study aimed to assess the impact of anaemia on stroke by anaemia subtype. MethodsData from a prospective UK Regional Stroke Register were used to assess the association between hypochromic microcytic and normochromic normocytic anaemia on inpatient-mortality, length of stay (LOS) and discharge modified Rankin scale (mRS). Analysis was stratified by stroke subtypes and multivariable logistic regression, adjusting for potential confounders, was used to quantify this association. Patients who were not anaemic were the reference category. ResultsA total of 8167 stroke patients (admitted between 2003 and 2015) were included, mean age (SD) 77.39 ± 11.90 years. Of these, 3.4% (n = 281) had hypochromic microcytic anaemia and 15.5% (n = 1262) had normochromic normocytic anaemia on admission. Normochromic normocytic anaemia was associated with increased odds of in-patient mortality OR 1.48 (1.24–1.77), 90-day mortality OR 1.63 (1.38–1.92), longer LOS OR 1.21 (1.06–1.40), defined as > 7 days, and severe disability defined as discharge mRS ≥ 3 OR 1.31 (1.06–1.63), in patients with ischaemic stroke. Hypochromic microcytic anaemia was associated with 90-day mortality OR 1.90 (1.40–2.58) and a longer LOS OR 1.57 (1.20–2.05) in patients with ischaemic stroke. ConclusionsHypochromic microcytic and normochromic normocytic anaemia are associated with differing outcomes in terms of inpatient mortality and post stroke disability. While it is unclear if anaemia per se or another underlying cause is responsible for adverse outcomes, subtype of anaemia appears to be relevant in stroke prognosis.

Background Currently, only one in three UK medical students undertake an intercalated degree. This has often been implicated as a result of financial obstacles or a lack of interest in research due to inadequate exposure to academic medicine. The aims of this study were to determine whether exposure to research early in medical school, through the initiation of an early years clinical academic training programme has a positive influence on the decision-making related to intercalating and a career long interest in research. This study also aims to evaluate the perceived views of the recipients of such a scholarship programme. Methods All previous recipients of the Aberdeen Summer Research Scholarship (ASRS) (n = 117) since its inception in 2010 until 2015 were invited via email in June 2016, to take part in the survey. Data were analysed using SPSS for quantitative data and a thematic approach was used to derive themes from free text. Results The overall response rate was 56% (66/117). Of the respondents, seven received the scholarship twice. Seventy-three percent were still at medical school and 26% were foundation doctors. One respondent indicated that they were currently not in training. Seventy percent of respondents have continued to be involved in research since completing the scholarship. Fifty percent embarked on an intercalated degree following the ASRS. Furthermore, two thirds of the respondents who were undecided about undertaking an intercalated degree before the scholarship, chose to intercalate after completing the programme. ASRS was generally thought of as a positive, influential programme, yet the success of individual ASRS projects was dependent on the allocated supervisors and the resources available for specific projects. Conclusions Our findings indicate that early research exposure in medical school can provide students with a positive influence on involvement in research and allows students to make an informed decision about embarking on an intercalated degree. We therefore recommend the encouragement of similar programmes in medical schools to promote clinical academia at an early stage for medical students. Electronic supplementary material The online version of this article (doi:10.1186/s12909-017-1066-1) contains supplementary material, which is available to authorized users.

Objective:To compare the prognostic accuracy of various acute stroke prognostic scales using a large, independent, clinical trials dataset.Methods:We directly compared 8 stroke prognostic scales, chosen based on focused literature review (Acute Stroke Registry and Analysis of Lausanne [ASTRAL]; iSCORE; iSCORE-revised; preadmission comorbidities, level of consciousness, age, and neurologic deficit [PLAN]; stroke subtype, Oxfordshire Community Stroke Project, age, and prestroke modified Rankin Scale [mRS] [SOAR]; modified SOAR; Stroke Prognosis Instrument 2 [SPI2]; and Totaled Health Risks in Vascular Events [THRIVE]) using individual patient-level data from a clinical trials archive (Virtual International Stroke Trials Archive [VISTA]). We calculated area under receiver operating characteristic curves (AUROC) for each scale against 90-day outcomes of mRS (dichotomized at mRS >2), Barthel Index (>85), and mortality. We performed 2 complementary analyses: the first limited to patients with complete data for all components of all scales (simultaneous) and the second using as many patients as possible for each individual scale (separate). We compared AUROCs and performed sensitivity analyses substituting extreme outcome values for missing data.Results:In total, 10,777 patients contributed to the analyses. Our simultaneous analyses suggested that ASTRAL had greatest prognostic accuracy for mRS, AUROC 0.78 (95% confidence interval [CI] 0.75–0.82), and SPI2 had poorest AUROC, 0.61 (95% CI 0.57–0.66). Our separate analyses confirmed these results: ASTRAL AUROC 0.79 (95% CI 0.78–0.80 and SPI2 AUROC 0.60 (95% CI 0.59–0.61). On formal comparative testing, there was a significant difference in modified Rankin Scale AUROC between ASTRAL and all other scales. Sensitivity analysis identified no evidence of systematic bias from missing data.Conclusions:Our comparative analyses confirm differences in the prognostic accuracy of stroke scales. However, even the best performing scale had prognostic accuracy that may not be sufficient as a basis for clinical decision-making.

ObjectiveTo determine if age is a factor in a patients’ likelihood of breaching the 4 hour time target to admission/discharge in emergency departments (EDs) within NHS Scotland.MethodsWe used data from the Information Service Division Scotland to analyse all ED attendances in Scotland between January 2015 and September 2018 (n=5 596 642). We assessed the likelihood of time to admission/discharge being within 4 hours, 8 hours and 12 hours for all age categories (reference category 20 to 24 years). Univariable logistic regressions were carried out for sex, Scottish Index of Multiple Deprivation level and both major (potentially life threatening) and minor (not immediately life threatening) incidences.ResultsThe likelihood of breaching the 4-hour target increased linearly with age from 15 to 19 years upward. Patients ≥85 years were significantly (pConclusionsOlder age is associated with a higher probability of breaching waiting time targets in a linear fashion within NHS Scotland, which is consistent with previous single hospital or regional studies. This association may be due to the higher proportion of elderly patients being admitted or a more systemic issue, but regardless, the elderly are being put more at risk.

Background Whilst antithrombotic therapy is recommended in people with atrial fibrillation, little is known about the survival benefits of antithrombotic treatment in those with both high ischaemic and bleeding risk scores. We aim to describe the distribution of these risk scores in those with a prior diagnosis of atrial fibrillation who have suffered stroke and to determine the net clinical benefit of antithrombotic treatment. Methods We used regional stroke register data in the UK. Patients with a prior diagnosis of atrial fibrillation and ischaemic or haemorrhagic stroke patients were selected and their ischaemic stroke risk score (CHA2DS2-VASc) and bleeding risk score (HEMORR2HAGES) scores retrospectively calculated. Logistic regression and Cox proportional hazards models were constructed to determine the association between antithrombotic therapy prior to stroke and in-hospital and long-term mortality. Results A total of 1928 stroke patients (mean age 81.3 years (standard deviation 8.5), 56.8% women) with prior atrial fibrillation were included. Of these, 1761 (91.3%) suffered ischaemic stroke. The most common phenotype (64%) was of those with both high CHA2DS2-VASc (≥2) and high HEMORR2HAGES score (≥4). In our fully adjusted model, patients on antithrombotic treatment with both high ischaemic and bleeding risk had a significant reduction in odds of 31% for in-hospital mortality (odds ratio 0.69 (95% confidence interval 0.48–1.00: p = 0.049)) and 17% relative risk reduction for long-term mortality (hazard ratio 0.83 (95% confidence interval 0.71–0.97: p = 0.02)). Conclusions Our study suggests that antithrombotic treatment has a prognostic benefit following incident stroke in those with both high ischaemic risk and high bleeding risk. This should be considered when choosing treatment options in this group of patients.

BACKGROUND: Clinical predictors of future ischemic events in patients with acute coronary syndrome (ACS) are also risk factors for bleeding, with patients often at high-risk of both outcomes. We aimed to define the clinical outcomes and provision of guideline-recommended care in ACS management for different combinations of ischemic and bleeding risk defined using a combined GRACE and CRUSADE score.METHODS: A retrospective observational analysis of a national ACS database was performed for patients with ACS admitted to three tertiary centres from January 2010 to March 2016. Patients were stratified into 9 groups based on possible CRUSADE-GRACE risk combinations. Multiple logistic regression was used to estimate adjusted odds ratios (ORs [95% CI]) for outcomes (in-hospital net adverse cardiac events (NACE), in-hospital all-cause mortality, 30-day mortality and treatment strategy).RESULTS: A total of 17,701 patients were included in the analysis. We observed a graded risk of mortality and adverse events in the high-risk GRACE strata (Groups 3, 6 and 9). Almost a third of patients with ACS were at a 'dual high-risk' (Group 9, 32%) and were independently associated with higher in-hospital NACE (composite of cardiac mortality, all-cause bleeding and re-infarction): aOR 6.33 [3.55, 11.29], all-cause mortality: aOR 14.17 [5.27, 38.1], all-cause bleeding: aOR 4.82 [1.96, 11.86], and 30-day mortality: aOR 10.79 [5.33, 21.81]. This group was also the least likely to be offered coronary angiography (aOR 0.24 [0.20, 0.29]) and dual anti-platelet therapy (aOR 0.26 [0.20, 0.34]).CONCLUSIONS: One in five patients presenting with an ACS are high ischemic and high bleeding risk, and these patients are more likely to experience poor clinical outcomes and reduced odds of receiving guideline-recommended therapy.

Background: To investigate the demographic and lifestyles factors associated with vitamin C deficiency and to examine the association between plasma vitamin C level and self-reported physical functional health. Methods: A population-based cross-sectional study using the European Prospective Investigation into Cancer-Norfolk study. Plasma vitamin C level &lt, 11 &micro, mol/L indicated vitamin C deficiency. Unconditional logistic regression models assessed the association between vitamin C deficiency and potential risk factors. Associations between quartiles of vitamin C and self-reported functional health measured by the 36-item short-form questionnaire (SF-36) were assessed. Results: After adjustment, vitamin C deficiency was associated with older age, being male, lower physical activity, smoking, more socially deprived area (Townsend index) and a lower educational attainment. Compared to the highest, those in the lowest quartile of vitamin C were more likely to score in the lowest decile of physical function (adjusted odds ratio (aOR): 1.43 (95%CI: 1.21&ndash, 1.70)), bodily pain (aOR: 1.29 (95% CI: 1.07&ndash, 1.56)), general health (aOR: 1.4 (95%CI: 1.18&ndash, 1.66)), and vitality (aOR: 1.23 (95%CI: 1.04&ndash, 1.45)) SF-36 scores. Conclusions: Simple public health interventions should be aimed at populations with risk factors for vitamin C deficiency. Poor self-reported functional health was associated with lower plasma vitamin C levels, which may reflect symptoms of latent scurvy.

Background and Purpose- We aimed to determine individual and combined effects of atrial fibrillation (AF) and heart failure (HF) on acute ischemic stroke outcomes: in-hospital mortality, length-of-stay, and poststroke disability; long-term mortality and stroke recurrence. Methods- Prospective cohort study of patients with acute ischemic stroke admitted to a UK center with a catchment population of ≈900 000 between 2004 and 2016. Exposure groups were patients with neither AF nor HF (reference group), those with AF but without HF, those with HF but without AF, and those with AF+HF. Logistic and Cox regressions were used to model in-hospital and long-term outcomes, respectively. Results- A total of 10 816 patients with a mean age±SD =77.9±12.1 years, 48% male were included. Only 30 (4.9%) of the patients with HF but not AF were anticoagulated at discharge. Both AF (odds ratio, 1.24 [95% CI, 1.07-1.43]), HF (odds ratio, 1.40 [1.10-1.79]), and their combination (odds ratio, 2.23 [1.83-2.72]) were associated with increased odds of in-hospital mortality. All 3 exposure groups were associated with increased length-of-stay, while only AF predicted increased disability (1.36 [1.12-1.64]). Patients were followed for a median of 5.5 and 3.7 years for mortality and recurrence, respectively. Long-term mortality was associated with AF (hazard ratio, 1.45 [95% CI, 1.33-1.59]), HF (2.07 [1.83-2.36]), and their combination (2.20 [1.96-2.46]). Recurrent stroke was associated with AF 1.50 (1.26-1.78), HF (1.33 [1.01-1.75]), and AF with HF (1.62 [1.28-2.07]). Conclusions- The AF-associated excess risk of stroke recurrence was independent of comorbid HF. HF without AF was also associated with a significant risk of recurrence. Anticoagulation for secondary stroke prevention in patients with HF without AF may require further evaluation in a clinical trial setting.

Whilst stroke-associated pneumonia (SAP) is common and associated with poor outcomes, less is known about the determinants of these adverse clinical outcomes in SAP. To identify the factors that influence mortality and morbidity in SAP. Data for patients with SAP (n = 854) were extracted from a regional Hospital Stroke Register in Norfolk, UK (2003–2015). SAP was defined as pneumonia occurring within 7 days of admission by the treating clinicians. Mutlivariable regression models were constructed to assess factors influencing survival and the level of disability at discharge using modified Rankin Scale [mRS]. Mean (SD) age was 83.0 (8.7) years and ischaemic stroke occurred in 727 (85.0%). Mortality was 19.0% at 30 days and 44.0% at 6 months. Stroke severity assessment using National Institutes of Health Stroke Scale was not recorded in the data set although Oxfordshire Community Stroke Project was Classification. In the multivariable analyses, 30-day mortality was independently associated with age (OR 1.04, 95% CI 1.01–1.07, p = 0.01), haemorrhagic stroke (2.27, 1.07–4.78, p = 0.03) and pre-stroke disability (mRS 4–5 v 0–1: 6.45, 3.12–13.35, p p p p = 0.017) and previous transient ischemic attack (1.94, 1.12–3.36, p = 0.019). Disability defined by mRS at discharge was independently associated with age (1.10, 1.05–1.16, p p = 0.012). We have identified non-modifiable determinants of poor prognosis in patients with SAP. Further studies are required to identify modifiable factors which may guide areas for intervention to improve the prognosis in SAP in these patients.

Objectives: To assess the impact of anaemia on incidence of post-stroke dementia. Patients and Methods: We used data from a UK regional stroke register. To be eligible, patient must have survived to discharge and had anaemia by WHO criteria. Dementia status and other prevalent co-morbidities were assessed using ICD-10 codes. Patients were followed till May 2015 (mean follow-up 3.7 years, total person years = 27,769). Hazard Ratio for incident dementia was calculated using Cox-proportional hazards model controlling for potential confounders. Fine and Gray model was additionally constructed using mortality as the competing risk. Results: A total of 7454 stroke patients were included with mean age SD of 75.912.3 years 50.2 % men). Those with anaemia were older, has higher disability and co-morbidity burden prior to stroke. We observed a large amount of variation in the dementia incidence rates over time and that the hazard ratio increased every year. The significant association between anaemia and dementia incidence was lost after controlling for pre-stroke Modified Rankin score (HR1.17(0.97,1.40)). With every 20 g/dL increase in Hb was associated with a significant reduction in the risk of dementia after adjustment for age, sex, stroke factors and disability but lost significance after adjustment for vascular risk factors. Competing risk analyses showed similar results. Conclusion: Whilst we found no evidence of anaemia as a risk factor for post-stroke dementia, the findings may be limited by potential under recognition of post stroke dementia.