Calcium intake, calcium supplementation and cardiovascular disease and mortality in the British population: EPIC-norfolk prospective cohort study and meta-analysis.

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 (< 770 mg/day), intakes between 771 and 926 mg/day (second quintile) and 1074-1254 mg/day (fourth quintile) were associated with reduced all-cause mortality (HR 0.91 (0.83-0.99) and 0.85 (0.77-0.93), respectively) and cardiovascular mortality [HR 0.95 (0.87-1.04) and 0.93 (0.83-1.04)]. Compared to the first quintile of calcium intake, second, third, fourth, but not fifth quintiles were associated with fewer incident strokes: respective HR 0.84 (0.72-0.97), 0.83 (0.71-0.97), 0.78 (0.66-0.92) and 0.95 (0.78-1.15). The meta-analysis results suggest that high levels of calcium intake were associated with decreased all-cause mortality, but not cardiovascular mortality, regardless of average calcium intake. Calcium supplementation was associated with cardiovascular and all-cause mortality amongst women, but not men. Moderate dietary calcium intake may protect against cardiovascular and all-cause mortality and incident stroke. Calcium supplementation may reduce mortality in women.

Myocardial infarction after acute ischaemic stroke: Incidence, mortality and risk factors.

OBJECTIVES: To determine the risk factor profiles associated with post-acute ischaemic stroke (AIS) myocardial infarction (MI) over long-term follow-up. METHODS: This observational study includes prospectively identified AIS patients (n = 9840) admitted to a UK regional centre between January 2003 and December 2016 (median follow-up: 4.72 years). Predictors of post-stroke MI during follow-up were examined using logistic and Cox regression models for in-hospital and post-discharge events, respectively. MI incidence was determined using a competing risk non-parametric estimator. The influence of post-stroke MI on mortality was examined using Cox regressions. RESULTS: Mean age (SD) of study participants was 77.3 (12.2) years (48% males). Factors associated with in-hospital MI (OR [95% CI]) were increasing blood glucose (1.80 [1.17-2.77] per 10 mmol/L), total leucocyte count (1.25 [1.01-1.54] per 10 × 109 /L) and CRP (1.05 [1.02-1.08] per 10 mg/L increase). Age (HR [95% CI] = 1.03 [1.01-1.06]), coronary heart disease (1.59 [1.01-2.50]), chronic kidney disease (2.58 [1.44-4.63]) and cancers (1.76 [1.08-2.89]) were associated with incident MI between discharge and one-year follow-up. Age (1.02 [1.00-1.03]), diabetes (1.96 [1.38-2.65]), congestive heart failure (2.07 [1.44-2.99]), coronary heart disease (1.81 [1.31-2.50]), hypertension [1.86 (1.24-2.79)] and peripheral vascular disease (2.25 [1.40-3.63]) were associated with incident MI between 1 and 5 years after discharge. Diabetes (2.01 [1.09-3.72]), hypertension (3.69 [1.44-9.45]) and peripheral vascular disease (2.46 [1.02-5.98]) were associated with incident MI between 5 and 10 years after discharge. Cumulative MI incidence over 10 years was 5.4%. MI during all follow-up periods (discharge-1, 1-5, 5-10 years) was associated with increased risk of death (respective HR [95% CI] = 3.26 [2.51-4.15], 1.96 [1.58-2.42] and 1.92 [1.26-2.93]). CONCLUSIONS: In conclusion, prognosis is poor in post-stroke MI. We highlight a range of potential areas to focus preventative efforts.

Rheumatic Mitral Valve Disease Is Associated With Worse Outcomes in Stroke: A Thailand National Database Study.

BACKGROUND AND PURPOSE: Rheumatic valvular heart disease is associated with the increased risk of cerebrovascular events, although there are limited data on the prognosis of patients with rheumatic mitral valve disease (RMVD) after stroke. METHODS: We examined the association between RMVD and both serious and common cardiovascular and noncardiovascular (respiratory and infective) complications in a cohort of hospitalized stroke patients based in Thailand. Factors associated with in-hospital mortality were also explored. Data were obtained from a National Insurance Database. All hospitalized strokes between October 1, 2004, and January 31, 2013, were included in the current study. Characteristics and outcomes were compared for RMVD and non-RMVD patients. Logistic regression, propensity score matching, and multivariate models were used to assess study outcomes. RESULTS: In total, 594 681 patients (mean [SD] age=64 [14.5] years) with a diagnosis of stroke (ischemic=306 154; hemorrhagic=195 392; undetermined=93 135) were included in this study, of whom 5461 had RMVD. Results from primary analyses showed that after ischemic stroke, and controlling for potential confounding covariates, RMVD was associated (P<0.001) with increased odds for cardiac arrest (odds ratio [95% confidence interval]=2.13 [1.68-2.70]), shock (2.13 [1.64-2.77]), arrhythmias (1.70 [1.21-2.39]), respiratory failure (2.09 [1.87-2.33]), pneumonia (2.00 [1.81-2.20]), and sepsis (1.39 [1.19-1.63]). In hemorrhagic stroke patients, RMVD was associated with increased odds (fully adjusted model) for respiratory failure (1.26 [1.01-1.57]), and in patients with undetermined stroke, RMVD was associated with increased odds (fully adjusted analyses) for shock (3.00 [1.46-6.14]), respiratory failure (2.70 [1.91-3.79]), and pneumonia (2.42 [1.88-3.11]). CONCLUSIONS: RMVD is associated with the development of cardiac arrest, shock, arrhythmias, respiratory failure, pneumonia, and sepsis after acute stroke.

Patterns of dietary intake and serum carotenoid and tocopherol status are associated with biomarkers of chronic low-grade systemic inflammation and cardiovascular risk.

Dietary modification may affect inflammatory processes and protect against chronic disease. In the present study, we examined the relationship between dietary patterns, circulating carotenoid and tocopherol concentrations, and biomarkers of chronic low-grade systemic inflammation in a 10-year longitudinal study of Scottish postmenopausal women. Diet was assessed by FFQ during 1997-2000 (n 3237, mean age 54·8 (SD 2·2) years). Participants (n 2130, mean age 66·0 (SD 2·2) years) returned during 2007-11 for follow-up. Diet was assessed by FFQ (n 1682) and blood was collected for the analysis of serum high-sensitivity C-reactive protein (hs-CRP), IL-6, serum amyloid A, E-selectin, lipid profile and dietary biomarkers (carotenoids, tocopherols and retinol). Dietary pattern and dietary biomarker (serum carotenoid) components were generated by principal components analysis. A past 'prudent' dietary pattern predicted serum concentrations of hs-CRP and IL-6 (which decreased across the quintiles of the dietary pattern; P= 0·002 and P= 0·001, respectively; ANCOVA). Contemporary dietary patterns were also associated with inflammatory biomarkers. The concentrations of hs-CRP and IL-6 decreased across the quintiles of the 'prudent' dietary pattern (P= 0·030 and P= 0·006, respectively). hs-CRP concentration increased across the quintiles of a 'meat-dominated' dietary pattern (P= 0·001). Inflammatory biomarker concentrations decreased markedly across the quintiles of carotenoid component score (P< 0·001 for hs-CRP and IL-6, and P= 0·016 for E-selectin; ANCOVA). Prudent dietary pattern and carotenoid component scores were negatively associated with serum hs-CRP concentration (unstandardised ß for prudent component: -0·053, 95% CI -0·102, -0·003; carotenoid component: -0·183, 95% CI -0·233, -0·134) independent of study covariates. A prudent dietary pattern (which reflects a diet high in the intakes of fish, yogurt, pulses, rice, pasta and wine, in addition to fruit and vegetable consumption) and a serum carotenoid profile characteristic of a fruit and vegetable-rich diet are associated with lower concentrations of intermediary markers that are indicative of CVD risk reduction.

Postcode Lottery in Healthcare? Findings from the Scottish National Comprehensive Geriatric Assessment in Secondary Care Audit 2019.

Comprehensive Geriatric Assessment (CGA) is provided differently across Scotland. The Scottish Care of Older People (SCoOP) CGA Audit was a national audit conducted in 2019 to assess this variation in acute hospitals. Two versions of audit questionnaires about the provision of CGA were developed (one each for larger hospitals and remote/rural areas) and piloted. The questionnaires were sent to representatives from all hospitals in Scotland using the REDCap (Research Electronic Data Capture) system. The survey asked each service to provide information on CGA service delivery at the 'front door'. The questionnaire was open for completion between February and July 2019. Of the 28 Scottish hospitals which receive acute admissions, we received information from 26 (92.9% response rate). Reporting sites included seven hospitals from remote and rural locations in the Scottish Highlands and Islands. Significant variations were observed across participating sites for all key aspects studied: dedicated frailty units, routes of admission, staffing, liaison with other services and rehabilitation provision. The 2019 SCoOP CGA audit highlights areas of CGA services that could be improved and variation in specialist CGA service access, structure and staffing at the front door across Scotland. Whether this variation has an impact on the outcomes of older people requires further evaluation.

Bioelectrical Impedance Versus Biochemical Analysis of Hydration Status: Predictive Value for Prolonged Hospitalisation and Poor Discharge Destination for Older Patients.

Dehydration is prevalent in hospitalised patients and is associated with increased morbidity and mortality, particularly among the elderly (≥65 years). We aimed at comparing the performance of intracellular water to extracellular water ratio (ICW/ECW), calculated through a bioelectrical impedance analysis (BIA) of blood urea nitrogen, with the creatinine ratio (BUN/Cr) to predict poor outcomes in a cohort of prospectively identified patients. Data were combined from a cohort of elderly patients (≥65 years) admitted to hospital with fragility fracture (n = 125) and older adults aged ≥50 years admitted to hospital with stroke (n = 40). The association between hydration status and study outcomes (unfavourable discharge destination (rehabilitation, another ward, or death) and prolonged hospitalisation (>10 days)) was examined using logistic regression. The overall diagnostic accuracy of each hydration status measurement was assessed using the area under the receiver operating characteristic (ROC) curve. In 165 participants (mean age (SD) of 76.7 (9.2) years), an ICW/ECW ratio below the 25th percentile was associated with increased odds of poor discharge destination (OR (95% CI) = 4.25 (1.59-11.34)). Neither the relationship between the BUN/Cr ratio and prolonged stay nor discharge destination was significant. A BIA could be used utilised in conjunction with biochemical measurements to inform patient prognosis.

Impact of Surgery on Older Patients Hospitalized With an Acute Abdomen: Findings From the Older Persons Surgical Outcome Collaborative.

Background: The impact of surgery compared to non-surgical management of older general surgical patients is not well researched. Methods: We examined the association between management and adverse outcomes in a cohort of emergency general surgery patients aged > 65 years. This multi-center study included 727 patients (mean+/-SD, 77.1 ± 8.2 years, 54% female) admitted to five UK hospitals. Data were analyzed using multi-level crude and multivariable logistic regression. Outcomes were: mortality at Day 30 and 90, length of stay, and readmission within 30 days of discharge. Covariates assessed were management approach, age, sex, frailty, polypharmacy, anemia, and hypoalbuminemia. Results: Approximately 25% of participants (n = 185) underwent emergency surgery. Frailty and albumin were associated with mortality at 30 (frailty OR = 3.52 [95% CI 1.66-7.49], albumin OR = 3.78 ([95% CI 1.53-9.31]), and 90 days post discharge (frailty OR = 3.20 [95% CI 1.86-5.51], albumin OR=3.25 [95% CI 1.70-6.19]) and readmission (frailty OR = 1.56 [95% CI (1.04-2.35)]). Surgically managed patients and frailty had increased odds of prolonged hospitalization (surgery OR = 5.69 [95% CI 3.67-8.80], frailty OR = 2.17 [95% CI 1.46-3.23]). Conclusion: We found the impact of surgery on length of hospitalization in older surgical patients is substantial. Whether early comprehensive geriatric assessment and post-op rehabilitation would improve this outcome require further evaluation.

Seasonality of stroke: Winter admissions and mortality excess: A Thailand National Stroke population database study.

OBJECTIVES: 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. PATIENTS AND METHODS: 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. RESULTS: 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)). CONCLUSIONS: We provide robust evidence for the existence of an excess in winter stroke admissions and subsequent in-hospital deaths within a tropical region.

Anticholinergic burden in middle-aged women and recurrent falls in later life: findings from the Aberdeen prospective osteoporosis screening study (APOSS).

BACKGROUND: Anticholinergic burden (ACB) is a recognised risk factor for falls in older people; however, whether ACB in middle age predicts falls in later life is unknown. METHODS: We examined this association in the middle-aged women of the Aberdeen Prospective Osteoporosis Screening Study (APOSS). ACB was calculated at the second health visit (1997-1999, study baseline) using the Anticholinergic Cognitive Burden Scale. Outcomes were incidence of 1 fall and recurrent falls (⩾2 falls) during the 12 months prior to follow up 2007-2011. Multinomial logistic regression analyses adjusted for potential confounders including demographics, comorbidities and falls history. RESULTS: A total of 2125 women {mean age (standard deviation [SD]): 54.7 (2.2) years at baseline and 66.0 (2.2) years at follow up} were included. Prevalence of baseline ACB score of 0, 1 and ⩾2 was 87.1%, 7.3% and 5.6%, respectively. Compared with no ACB, ACB ⩾2 was associated with recurrent falls in the previous 12 months [adjusted odds ratio (OR): 2.34, 95% confidence interval (CI): 1.31, 4.19] at an average of 11 years after initial exposure. No such association was found for an ACB score of 1. CONCLUSIONS: These findings highlight the potential negative effects of anticholinergic medications in middle age. While cautious use of anticholinergic medications is advisable, further longitudinal research should be conducted to confirm these findings before any specific clinical recommendations can be made.

Impact of heart failure on stroke mortality and recurrence.

OBJECTIVE: We aimed to examine the impact of heart failure (HF) on stroke mortality (in-hospital and postdischarge) and recurrence in a national stroke cohort from Thailand. METHODS: We used a large, insurance-based database including all stroke admissions in the public health sector in Thailand between 2004 and 2015. Logistic and Royston-Parmar regressions were used to quantify the effect of HF on in-hospital and long-term outcomes, respectively. All models were adjusted for age, sex and comorbidities and stratified by stroke type: acute ischaemic stroke (AIS) or intracerebral haemorrhage (ICH). Multistate models were constructed using flexible survival techniques to predict the impact of HF on the disease course of a patient with stroke (baseline-[recurrence]-death). Only first-ever cases of AIS or ICH were included in the multistate analysis. RESULTS: 608 890 patients (mean age 64.29±13.72 years, 55.07% men) were hospitalised (370 527 AIS, 173 236 ICH and 65 127 undetermined pathology). There were 398 663 patients with first-ever AIS and ICH. Patients were followed up for a median (95% CI) of 4.47 years (4.45 to 4.49). HF was associated with an increase in postdischarge mortality in AIS (HR [99% CI] 1.69 [1.64 to 1.74]) and ICH (2.59 [2.07 to 3.26]). HF was not associated with AIS recurrence, while ICH recurrence was only significantly increased within the first 3 years after discharge (1.79 [1.18 to 2.73]). CONCLUSIONS: HF increases the risk of mortality in both AIS and ICH. We are the first to report on high-risk periods of stroke recurrence in patients with HF with ICH. Specific targeted risk reduction strategies may have significant clinical impact for mortality and recurrence in stroke.

Dimension of pain-related quality of life and self-reported mental health in men and women of the European Prospective Investigation into Cancer-Norfolk cohort: a population-based cross-sectional study.

Both cognitive and behavioural factors are linked to the experience of pain as well as its interference with quality of life. Psychological distress has been shown to be associated to several emotional and social impairments. Although, the association between pain and mental health has been widely discussed, the understanding of life interference and outcome is not fully understood. This study examined the association of pain dimension and mental health domain in 16,051 participants of the EPIC-Norfolk cohort (mean age = 58.9 ± 9.1 years). Study outcomes were depressive or anxious behaviour and limitations due to emotional problems and impairments in social functioning (mental functional health components of the Short Form-36 (SF-36)). Logistic regression models were constructed controlling for the potentially confounding factors including socio-economic variables (occupational social class, deprivation, marital status, education), lifestyle behaviour (physical activity, smoking, alcohol, dietary) and previous medical history. Strong interference in quality of life due to pain (bottom 20% of pain dimension score of SF-36) was significantly associated with poor MH in men and women (odds ratios (ORs) (95% confidence intervals (CIs)): 1.35 (1.19, 1.54) and 1.39 (1.25, 1.55), respectively; p < 0.0001) in fully adjusted models. Moreover, strong interference due to pain was also significantly associated with poor overall MH including emotional and social functioning (ORs (95% CIs): 1.42 (1.25, 1.62) and 1.39 (1.25, 1.55) respectively; p < 0.0001) in fully adjusted models; subsidiary analysis using linear regression models demonstrated similar results for these domains. Although a strong association has been shown, further research is needed to provide information on the different site and/or causes of pain which would allow stratification. Moreover, assuming a bi-directional nature of both domains, systematic assessment and management of pain have a lot of potential to improve the MH-related quality of life in the general population and vice versa.

25-Hydroxyvitamin D Threshold for the Effects of Vitamin D Supplements on Bone Density: Secondary Analysis of a Randomized Controlled Trial.

Most trials of vitamin D supplementation have shown no benefits on bone mineral density (BMD), although severe vitamin D deficiency causes osteomalacia, which is associated with profound BMD deficits. Recently, the ViDA-BMD study from New Zealand demonstrated a threshold of baseline 25-hydroxyvitamin D (25OHD; 30 nmol/L) below which vitamin D supplementation did benefit BMD. We have now reexamined data from a similar trial in Aberdeen to determine whether a baseline 25OHD threshold of 30 nmol/L is also observed in that database. The Aberdeen study recruited 305 postmenopausal women in late winter and randomized them to receive placebo, vitamin D 400 IU/d, or vitamin D 1000 IU/d over 1 year. As previously reported, BMD loss at the hip was reduced by vitamin D 1000 IU/d only, and there was no significant treatment effect of either dose at the lumbar spine. In the present analysis, when the trial participants were grouped according to whether their baseline 25OHD was ≤30 nmol/L or above this threshold, significant treatment effects were apparent at both the spine and hip in those with baseline 25OHD ≤30 nmol/L, but no significant effects were apparent in those with baseline 25OHD above this level. There was evidence of a similar threshold for effects on parathyroid hormone, but no groups showed changes in bone turnover markers during the study. It is concluded that vitamin D supplements only increase bone density in adults with nadir 25OHD ≤30 nmol/L. This moves us further toward a trial-based definition of vitamin D deficiency in adults with adequate calcium intakes and suggests that supplement use should be targeted accordingly. Future trials of vitamin D supplementation should focus on individuals with 25OHD concentrations in this range. © 2018 American Society for Bone and Mineral Research.

Quality of Care in Hip Fracture Patients: The Relationship Between Adherence to National Standards and Improved Outcomes.

BACKGROUND: Optimizing the perioperative care of patients with a hip fracture is a key health-care priority. We aimed to determine whether adherence to the Scottish Standards of Care for Hip Fracture Patients (SSCHFP) was associated with improved patient outcomes. METHODS: In this retrospective cohort study of prospectively collected data from the Scottish National Hip Fracture Audit, we assessed adherence to the SSCHFP in 21 Scottish hospitals over a 9-month period in 2014 and examined the effect of the guidelines on 30 and 120-day mortality, length of hospital stay, and discharge destination. RESULTS: A total of 1,162 patients who were ≥50 years old and admitted with a hip fracture were included. There was a significant association between low adherence to the SSCHFP and increased mortality at 30 and 120 days (odds ratio [OR], 3.58 [95% confidence interval (CI), 1.75 to 7.32; p < 0.001] and 2.01 [95% CI, 1.28 to 3.12; p = 0.003], respectively). Low adherence was associated with a reduced likelihood of a short length of stay (OR, 0.58; 95% CI, 0.42 to 0.78; p < 0.0001), but increased odds of discharge to a high-care setting (OR, 1.63; 95% CI, 1.12 to 2.36; p = 0.01). Early physiotherapy input and occupational therapy input were associated with a reduced likelihood of discharge to a high-care setting (OR, 0.64 [95% CI, 0.44 to 0.98; p = 0.04] and 0.34 [95% CI, 0.23 to 0.48; p <0.001], respectively). CONCLUSIONS: Adherence to the SSCHFP is associated with better patient outcomes. These findings confirm the clinical utility of the SSCHFP and support their use as a benchmarking tool to improve quality of care for hip fractures. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

A high anticholinergic burden is associated with a history of falls in the previous year in middle-aged women: findings from the Aberdeen Prospective Osteoporosis Screening Study.

PURPOSE: To examine the cross-sectional association between anticholinergic medication burden (ACB) and a history of falls, bone mineral density, and low trauma fractures in middle-aged women aged under 65 years from the Aberdeen Prospective Osteoporosis Screening Study. METHODS: ACB (0 = none, 1 = possible, ≥2 = definite) was calculated from medication use for 3883 Caucasian women [mean age (SD) = 54.3 (2.3) years] attending the second Aberdeen Prospective Osteoporosis Screening Study visit (1997-2000). Outcomes were examined using logistic regression. Model adjustments were selected a priori based on expert opinion. RESULTS: Of 3883 participants, 3293 scored ACB = 0, 328 scored ACB = 1, and 262 scored ACB ≥2. High ACB burden (≥2) was associated with increased odds (ACB = 0 reference) for falls (fully adjusted odds ratio [95% confidence intervals] = 1.81 [1.25-2.62]; P = 0.002) and having low bone mineral density (lowest quintile-20%) at Ward's triangle (3.22 [1.30-7.99]; P = 0.01). A history of falls over the year prior to the study visit in participants with ACB score ≥2 was 32 per 100. For ACB categories 1 and 0, a history of falls per 100 was 21 and 22, respectively. CONCLUSIONS: The risk of falling associated with ACB observed in older age may also extend to middle-aged women.

A History of Falls is Associated with a Significant Increase in Acute Mortality in Women after Stroke.

BACKGROUND AND PURPOSE: The risks of falls and fractures increase after stroke. Little is known about the prognostic significance of previous falls and fractures after stroke. This study examined whether having a history of either event is associated with poststroke mortality. METHODS: We analyzed stroke register data collected prospectively between 2003 and 2015. Eight sex-specific models were analyzed, to which the following variables were incrementally added to examine their potential confounding effects: age, type of stroke, Oxfordshire Community Stroke Project classification, previous comorbidities, frailty as indicated by the prestroke modified Rankin Scale score, and acute illness parameters. Logistic regression was applied to investigate in-hospital and 30-day mortality, and Cox proportional-hazards models were applied to investigate longer-term outcomes of mortality. RESULTS: In total, 10,477 patients with stroke (86.1% ischemic) were included in the analysis. They were aged 77.7±11.9 years (mean±SD), and 52.2% were women. A history of falls was present in 8.6% of the men (n=430) and 20.2% of the women (n=1,105), while 3.8% (n=189) of the men and 12.9% of the women (n=706) had a history of both falls and fractures. Of the outcomes examined, a history of falls alone was associated with increased in-hospital mortality [odds ratio (OR)=1.33, 95% confidence interval (CI)=1.03-1.71] and 30-day mortality (OR=1.34, 95% CI=1.03-1.73) in women in the fully adjusted models. The Cox proportional-hazards models for longer-term outcomes and the history of falls and fractures combined showed no significant results. CONCLUSIONS: The history of falls is an important factor for acute stroke mortality in women. A previous history of falls may therefore be an important factor to consider in the short-term stroke prognosis, particularly in women.

A 6-Point TACS Score Predicts In-Hospital Mortality Following Total Anterior Circulation Stroke.

BACKGROUND AND PURPOSE: Little is known about the factors associated with in-hospital mortality following total anterior circulation stroke (TACS). We examined the characteristics and comorbidity data for TACS patients in relation to in-hospital mortality with the aim of developing a simple clinical rule for predicting the acute mortality outcome in TACS. METHODS: A routine data registry of one regional hospital in the UK was analyzed. The subjects were 2,971 stroke patients with TACS (82% ischemic; median age=81 years, interquartile age range=74-86 years) admitted between 1996 and 2012. Uni- and multivariate regression models were used to estimate in-hospital mortality odds ratios for the study covariates. A 6-point TACS scoring system was developed from regression analyses to predict in-hospital mortality as the outcome. RESULTS: Factors associated with in-hospital mortality of TACS were male sex [adjusted odds ratio (AOR)=1.19], age (AOR=4.96 for ≥85 years vs. <65 years), hemorrhagic subtype (AOR=1.70), nonlateralization (AOR=1.75), prestroke disability (AOR=1.73 for moderate disability vs. no symptoms), and congestive heart failure (CHF) (AOR=1.61). Risk stratification using the 6-point TACS Score [T=type (hemorrhage=1 point) and territory (nonlateralization=1 point), A=age (65-84 years=1 point, ≥85 years=2 points), C=CHF (if present=1 point), S=status before stroke (prestroke modified Rankin Scale score of 4 or 5=1 point)] reliably predicted a mortality outcome: score=0, 29.4% mortality; score=1, 46.2% mortality [negative predictive value (NPV)=70.6%, positive predictive value (PPV)=46.2%]; score=2, 64.1% mortality (NPV=70.6, PPV=64.1%); score=3, 73.7% mortality (NPV=70.6%, PPV=73.7%); and score=4 or 5, 81.2% mortality (NPV=70.6%, PPV=81.2%). CONCLUSIONS: We have identified the key determinants of in-hospital mortality following TACS and derived a 6-point TACS Score that can be used to predict the prognosis of particular patients.

Hip bone loss is attenuated with 1000 IU but not 400 IU daily vitamin D3: a 1-year double-blind RCT in postmenopausal women.

Few year-long vitamin D supplementation trials exist that match seasonal changes. The aim of this study was to determine whether daily oral vitamin D3 at 400 IU or 1000 IU compared with placebo affects annual bone mineral density (BMD) change in postmenopausal women in a 1-year double-blind placebo controlled trial in Scotland. White women aged 60 to 70 years (n = 305) were randomized to one of two doses of vitamin D or placebo. All participants started simultaneously in January/February 2009, attending visits at bimonthly intervals with 265 (87%) women attending the final visit and an additional visit 1 month after treatment cessation. BMD (Lunar iDXA) and 1,25-dihydroxyvitamin D[1,25(OH)2 D], N-terminal propeptide of type 1 collagen [P1NP], C-terminal telopeptide of type I collagen [CTX], and fibroblast growth factor-23 [FGF23] were measured by immunoassay at the start and end of treatment. Circulating PTH, serum Ca, and total 25-hydroxyvitamin D [25(OH)D] (latter by tandem mass spectrometry) were measured at each visit. Mean BMD loss at the hip was significantly less for the 1000 IU vitamin D group (0.05% ± 1.46%) compared with the 400 IU vitamin D or placebo groups (0.57% ± 1.33% and 0.60% ± 1.67%, respectively) (p < 0.05). Mean (± SD) baseline 25(OH)D was 33.8 ± 14.6 nmol/L; comparative 25(OH)D change for the placebo, 400 IU, and 1000 IU vitamin D groups was -4.1 ± 11.5 nmol/L, +31.6 ± 19.8 nmol/L, and +42.6 ± 18.9 nmol/L, respectively. Treatment did not change markers of bone metabolism, except for a small reduction in PTH and an increase in serum calcium (latter with 1000 IU dose only). The discordance between the incremental increase in 25(OH)D between the 400 IU and 1000 IU vitamin D and effect on BMD suggests that 25(OH)D may not accurately reflect clinical outcome, nor how much vitamin D is being stored.

Vitamin D3 supplementation has no effect on conventional cardiovascular risk factors: a parallel-group, double-blind, placebo-controlled RCT.

CONTEXT: Observational studies show an association between low vitamin D status assessed by circulating 25-hydroxyvitamin D and cardiovascular events and mortality. Data from randomized controlled trials are limited. OBJECTIVE: The aim of this study was to test whether daily doses of vitamin D(3) at 400 or 1000 IU/d for 1 yr affected conventional markers of cardiovascular disease (CVD) risk. DESIGN: We conducted a parallel-group, double-blind, placebo-controlled randomized controlled trial. Randomization was computer generated. Participants and study investigators were blinded to intervention groupings throughout the trial. SETTING: The study was conducted at the Clinical Research Facility, University of Aberdeen, United Kingdom. PARTICIPANTS: A total of 305 healthy postmenopausal women aged 60-70 yr were recruited for the study. INTERVENTION: Each woman received a daily capsule of 400 or 1000 IU vitamin D(3) or placebo randomly allocated. MAIN OUTCOME MEASURES: Primary outcomes were serum lipid profile [total, high-density lipoprotein, and low-density lipoprotein cholesterol; triglycerides; and apolipoproteins A-1 and B100], insulin resistance (homeostatic model assessment), inflammatory biomarkers (high-sensitivity C-reactive protein, IL-6, soluble intracellular adhesion molecule-1), and blood pressure. RESULTS: A total of 265 (87%) participants completed all study visits. Small differences between groups for serum apolipoprotein B100 change [repeated measures ANOVA, P=0.04; mean (sd), -1.0 (10.0) mg/dl (400 IU); -1.0 (10.0) mg/dl (1000 IU); and +0.02 (10.0) mg/dl (placebo)] were not considered clinically significant. Other systemic markers for CVD risk remained unchanged. There was significant seasonal variation in systolic and diastolic blood pressure independent of vitamin D dose (P<0.001, linear mixed model). Mean (sd) reduction in systolic blood pressure from winter to summer was -6.6 (10.8) mm Hg. CONCLUSIONS: Improving vitamin D status through dietary supplementation is unlikely to reduce CVD risk factors. Confounding of seasonality should be recognized and addressed in future studies of vitamin D.

Natural salicylates: foods, functions and disease prevention.

Salicylic acid and related compounds are produced by plants as part of their defence systems against pathogen attack and environmental stress. First identified in myrtle and willow, the medical use of salicylate-rich preparations as anti-inflammatory and antipyretic treatments may date back to the third millennium BC. It is now known that salicylates are widely distributed throughout the plant kingdom, and they are therefore present in plant products of dietary relevance. In the UK, major food sources are tomato-based sauces, fruit and fruit juice, tea, wine, and herbs and spices. In mammalian cells, salicylic acid demonstrates several bioactivities that are potentially disease-preventative, including the inhibition of production of potentially neoplastic prostaglandins, which arise from the COX-2 mediated catalysis of arachidonic acid. Moreover, it appears to be readily absorbed from the food matrix. This has led some to suggestions that the recognised effects of consuming fruit and vegetables on lowering the risk of several diseases may be due, in part, to salicylates in plant-based foods. However, published estimates of daily salicylic acid intake vary markedly, ranging from 0.4 to 200 mg day(-1), so it is unclear whether the Western diet can provide sufficient salicylates to exert a disease-preventative activity. Some ethnic cuisines that are associated with lowered disease risk may contain considerably more salicylic acid than is obtainable from a Western diet. However known protective effects of acetylsalicylic acid (Aspirin™) may have lead to an over-emphasis on the importance of dietary salicylates compared with other bioactive plant phenolics in the diet.