No evidence for amyloid pathology as a key mediator of neurodegeneration post-stroke - a seven-year follow-up study.

BACKGROUND: Cognitive impairment (CI) with mixed vascular and neurodegenerative pathologies after stroke is common. The role of amyloid pathology in post-stroke CI is unclear. We hypothesize that amyloid deposition, measured with Flutemetamol (18F-Flut) positron emission tomography (PET), is common in seven-year stroke survivors diagnosed with CI and, further, that quantitatively assessed 18F-Flut-PET uptake after 7 years correlates with amyloid-ß peptide (Aß42) levels in cerebrospinal fluid (CSF) at 1 year, and with measures of neurodegeneration and cognition at 7 years post-stroke. METHODS: 208 patients with first-ever stroke or transient Ischemic Attack (TIA) without pre-existing CI were included during 2007 and 2008. At one- and seven-years post-stroke, cognitive status was assessed, and categorized into dementia, mild cognitive impairment or normal. Etiologic sub-classification was based on magnetic resonance imaging (MRI) findings, CSF biomarkers and clinical cognitive profile. At 7 years, patients were offered 18F-Flut-PET, and amyloid-positivity was assessed visually and semi-quantitatively. The associations between 18F-Flut-PET standardized uptake value ratios (SUVr) and measures of neurodegeneration (medial temporal lobe atrophy (MTLA), global cortical atrophy (GCA)) and cognition (Mini-Mental State Exam (MMSE), Trail-making test A (TMT-A)) and CSF Aß42 levels were assessed using linear regression. RESULTS: In total, 111 patients completed 7-year follow-up, and 26 patients agreed to PET imaging, of whom 13 had CSF biomarkers from 1 year. Thirteen out of 26 patients were diagnosed with CI 7 years post-stroke, but only one had visually assessed amyloid positivity. CSF Aß42 levels at 1 year, MTA grade, GCA scale, MMSE score or TMT-A at 7 years did not correlate with 18F-Flut-PET SUVr in this cohort. CONCLUSIONS: Amyloid binding was not common in 7-year stroke survivors diagnosed with CI. Quantitatively assessed, cortical amyloid deposition did not correlate with other measures related to neurodegeneration or cognition. Therefore, amyloid pathology may not be a key mediator of neurodegeneration 7 years post-stroke. TRIAL REGISTRATION: Clinicaltrials.gov (NCT00506818). July 23, 2007. Inclusion from February 2007, randomization and intervention from May 2007 and trial registration in July 2007.

Blood pressure variability in hypertensive patients with atrial fibrillation in the VALUE trial.

PURPOSE: Blood pressure variability is associated with traditional cardiovascular risk factors, but little is known about the association with atrial fibrillation. We compared blood pressure variability in patients with and without atrial fibrillation using data from the Valsartan Antihypertensive Long-term Use Evaluation (VALUE) trial. MATERIALS AND METHODS: The VALUE trial was a randomised-controlled trial of valsartan versus amlodipine in patients with hypertension and high cardiovascular risk, followed for 4.2 years (mean). For the present analysis we included patients with electrocardiogram at baseline and during follow-up, and ≥3 visits from 6 months onwards. We compared standard deviation (SD) of all blood pressures within each visit averaged across all visits (within-visit variability) and of mean blood pressure at each visit (visit-to-visit variability) in patients with and without atrial fibrillation at baseline. We similarly compared patients who developed non-persistent or persistent atrial fibrillation during follow-up with those who did not, using t-tests, ANOVA and linear regression. RESULTS: Of 15,245 patients in the VALUE trial, 13,827 were eligible for analysis. SD of visit-to-visit systolic blood pressure was not significantly different between patients with and without atrial fibrillation at baseline (mean difference 0.3 mm Hg, p = 0.4), but significantly higher in patients with incident non-persistent or persistent atrial fibrillation during follow-up than in those who never developed atrial fibrillation (differences 1.2 and 1.8 mm Hg, respectively, p-values <0.0001). Associations with non-persistent and persistent atrial fibrillation were confirmed in linear regression models (p-values <0.0001). SD of within-visit systolic blood pressure was not significantly different between patients with and without atrial fibrillation at baseline (p = 0.4) but significantly higher in patients with persistent atrial fibrillation during follow-up (p = 0.04). CONCLUSION: In patients treated for hypertension, atrial fibrillation was not associated with increased blood pressure variability, but blood pressure variability was higher in those who developed atrial fibrillation during follow-up.

Geriatric assessment is superior to oncologists' clinical judgement in identifying frailty.

BACKGROUND: Frailty is a syndrome associated with increased vulnerability and an important predictor of outcomes in older cancer patients. Systematic assessments to identify frailty are seldom applied, and oncologists' ability to identify frailty is scarcely investigated. METHODS: We compared oncologists' classification of frailty (onc-frail) based on clinical judgement with a modified geriatric assessment (mGA), and investigated associations between frailty and overall survival. Patients ⩾70 years referred for medical cancer treatment were eligible. mGA-frailty was defined as impairment in at least one of the following: daily activities, comorbidity, polypharmacy, physical function or at least one geriatric syndrome (cognitive impairment, depression, malnutrition, falls). RESULTS: Three hundred and seven patients were enroled, 288 (94%) completed the mGA, 286 (93%) were rated by oncologists. Median age was 77 years, 56% had metastases, 85% performance status (PS) 0-1. Overall, 104/286 (36%) were onc-frail and 140/288 (49%) mGA-frail, the agreement was fair (kappa value 0.30 (95% CI 0.19; 0.41)), and 67 mGA-frail patients who frequently had localised disease, good PS and received curative treatment, were missed by the oncologists. Only mGA-frailty was independently prognostic for survival (HR 1.61, 95% CI 1.14; 2.27; P=0.007). CONCLUSIONS: Systematic assessment of geriatric domains is needed to aid oncologists in identifying frail patients with poor survival.

Frailty is an independent predictor of survival in older patients with colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) is prevalent in the older population. Geriatric assessment (GA) has previously been found to predict treatment tolerance and postoperative complications in older cancer patients. The aim of this study was to explore whether GA also predicts 1-year and 5-year survival after CRC surgery in older patients and to compare the predictive power of GA with that of established prognostic factors such as TNM classification of malignant tumors (TNM) stage and age. MATERIALS AND METHODS: A cohort of 178 CRC patients aged 70 and older were followed prospectively. All patients went through elective surgery, and GA was performed presurgery. The GA resulted in patients being divided into two groups: frail or nonfrail. All patients were followed for 5 years or until death. Data were analyzed by Kaplan-Meier plots and the Cox proportional hazards model. RESULTS: Seventy-six patients (43%) were frail, and one hundred and two (57%) were nonfrail. Twenty-three patients (13%) died during the first year after surgery. One-year survival was 80% in the frail group and 92% in the nonfrail group. Five-year survival was significantly lower in frail (24%) than nonfrail patients (66%), and this difference was apparent both within the stratums of TNM stages 0-II and TNM stage III. In multivariable analysis adjusting for TNM stage, age, and sex, frailty was an independent prognostic factor for survival. CONCLUSION: A GA-based frailty assessment predicts 1-year and 5-year survival in older patients after surgery for CRC. In localized and regional disease, the impact of frailty upon 5-year survival is comparable with that of TNM stage.

Association between inherited CYP2D6/2C19 phenotypes and anticholinergic measures in elderly patients using anticholinergic drugs.

BACKGROUND: To compare measures of anticholinergic activity between metabolic phenotypes of the polymorphic enzymes cytochrome P450 2D6 (CYP2D6) and CYP2C19 in the elderly patients exposed to anticholinergic agents. METHODS: Long-term nursing home patients (n = 80) with an anticholinergic drug scale (ADS) score ≥3 were recruited from 22 nursing homes in Norway. Based on pharmacogenetic analyses of mutations encoding absent CYP2D6 or CYP2C19 metabolism, patients were divided into subgroups of poor metabolizers (PMs) (n = 8) and extensive metabolizers (n = 72). Serum anticholinergic activity (SAA) was determined by a validated, 96-well format radio receptor assay and adjusted for ADS score. Unadjusted and adjusted SAAs, mouth dryness, and cognitive function (Mini-Mental State Examination and verbal recall tests from Consortium to Establish a Registry for Alzheimer Disease) were compared between the subgroups with Mann-Whitney tests. RESULTS: The study population was represented by 78% women, 68% had mild to moderate dementia, and mean age was 86 years. More than 80% used more than 1 anticholinergic agent, and their median ADS score was 4. The subpopulation of PMs had significantly higher median SAA than the extensive metabolizers (10.3 versus 4.2 pmol atropine equivalents per milliliter, P = 0.012). This difference remained significant after adjusting for ADS score (P = 0.013). No significant differences in mouth dryness and cognitive function were observed between the subgroups (P > 0.3). CONCLUSIONS: These preliminary findings suggest that elderly CYP2D6/CYP2C19 PMs with a high anticholinergic drug burden are at increased risk of elevated SAA. Whether PMs are also more prone to experience anticholinergic side effects needs to be further studied in larger patient populations.

Effects of candesartan in acute stroke on cognitive function and quality of life: results from the Scandinavian Candesartan Acute Stroke Trial.

BACKGROUND AND PURPOSE: High blood pressure is common in the acute phase of stroke and is associated with poor outcome. We examined whether blood pressure-lowering treatment with candesartan in the acute phase affects long-term cognitive function and quality of life. METHODS: Scandinavian Candesartan Acute Stroke Trial was a randomized-controlled and placebo-controlled trial of candesartan in 2029 patients with acute stroke and raised blood pressure. At 6 months, cognitive function was assessed by the Mini Mental State Examination and quality of life by the EuroQol instrument. We used ordinal logistic and multiple linear regression for statistical analysis, adjusting for predefined key variables. RESULTS: Median Mini Mental State Examination score was 28 in both groups, and there was no significant difference between the distribution of Mini Mental State Examination scores in the 2 groups (common odds ratio, 1.11; 95% confidence interval, 0.91-1.34; P=0.32). Median EuroQol-5D index were 0.74 and 0.78 (P=0.034), and the mean EuroQol-visual analogue scale scores were 66.0 and 67.3 in the candesartan and placebo groups, respectively (P=0.11). CONCLUSIONS: Candesartan did not improve cognitive function or quality of life. Rather, there were signs of harmful effects. These findings support the conclusion from our previous report that there is no indication for routine blood pressure-lowering treatment with candesartan in the acute phase of stroke. CLINICAL TRIAL REGISTRATION URL: www.clinicaltrials.gov. Unique identifier: NCT00120003.

A new automated national register-based surveillance system for outbreaks in long-term care facilities in Norway detected three times more severe acute respiratory coronavirus virus 2 (SARS-CoV-2) clusters than traditional methods.

OBJECTIVE: To develop and test a new automated surveillance system that can detect, define and characterize infection clusters, including coronavirus disease 2019 (COVID-19), in long-term care facilities (LTCFs) in Norway by combining existing national register data. BACKGROUND: The numerous outbreaks in LTCFs during the COVID-19 pandemic highlighted the need for accurate and timely outbreak surveillance. As traditional methods were inadequate, we used severe acute respiratory coronavirus virus 2 (SARS-CoV-2) as a model to test automated surveillance. METHODS: We conducted a nationwide study using data from the Norwegian preparedness register (Beredt C19) and defined the study population as an open cohort from January 2020 to December 2021. We analyzed clusters (≥3 individuals with positive SARS-CoV-2 test ≤14 days) by 4-month periods including cluster size, duration and composition, and residents' mortality associated with clusters. RESULTS: The study population included 173,907 individuals; 78% employees and 22% residents. Clusters were detected in 427 (43%) of 993 LTCFs. The median cluster size was 4-8 individuals (maximum, 50) by 4-month periods, with a median duration of 9-17 days. Employees represented 60%-82% of cases in clusters and were index cases in 60%-90%. In the last 4-month period of 2020, we detected 107 clusters (915 cases) versus 428 clusters (2,998 cases) in the last period of 2021. The 14-day all-cause mortality rate was higher in resident cases from the clusters. Varying the cluster definitions changed the number of clusters. CONCLUSION: Automated national surveillance for SARS-CoV-2 clusters in LTCFs is possible based on existing data sources and provides near real-time detailed information on size, duration, and composition of clusters. Thus, this system can assist in early outbreak detection and improve surveillance.

Diagnostic validity of fatal cerebral strokes and coronary deaths in mortality statistics: an autopsy study.

Mortality statistics represent important endpoints in epidemiological studies. The diagnostic validity of cerebral stroke and ischemic heart disease recorded as the underlying cause of death in Norwegian mortality statistics was assessed by using mortality data of participants in the Bergen Clinical Blood Pressure Study in Norway and autopsy records from the Gade Institute in Bergen. In the 41 years of the study (1965-2005) 4,387 subjects had died and 1,140 (26%) had undergone a post mortem examination; 548 (12%) died from cerebral stroke and 1,120 (24%) from ischemic heart disease according to the mortality statistics, compared to 113 (10%) strokes and 323 (28%) coronary events registered in the autopsy records. The sensitivity and positive predictive value of fatal cerebral strokes in the mortality statistics were 0.75, 95% confidence interval (CI) [0.66, 0.83] and 0.86 [0.77, 0.92], respectively, whereas those of coronary deaths were 0.87 [0.84, 0.91] and 0.85 [0.81, 0.89] respectively. Cohen's Kappa coefficients were 0.78 [0.72, 0.84] for stroke and 0.80 [0.76, 0.84] for coronary deaths. In addition to female gender and increasing age at death, cerebral stroke was a negative predictor of an autopsy being carried out (odds ratio (OR) 0.69, 95% CI [0.54, 0.87]), whereas death from coronary heart disease was not (OR 1.14, 95% CI [0.97, 1,33]), both adjusted for gender and age at death. There was substantial agreement between mortality statistics and autopsy findings for both fatal strokes and coronary deaths. Selection for post mortem examinations was associated with age, gender and cause of death.

Cognitive impairment and the role of the ApoE epsilon4-allele after stroke--a 13 months follow-up study.

OBJECTIVE: To examine the relationship between the ApoE epsilon4 allele and cognitive impairment 13 months after stroke. METHODS: One hundred four stroke rehabilitation patients were cognitively tested on average 18 days after hospital admission and again 13 months later with the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). The following potential risk factors for post-stroke cognitive impairment (defined by a RBANS total index score below 77.5 points) at 13 months follow-up were analyzed in bivariate and logistic regression analyses: ApoE-genotype, socio-demographic variables, pre-stroke cognitive reduction (The Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE)), vascular factors, lesion characteristics, and neurological impairment (The National Institute of Health Stroke Scale (NIHSS)). Differences in general cognitive performance (pre-stroke, baseline, and follow-up) across patients with different ApoE-genotypes were analyzed, and lastly differences between epsilon4-carriers and non-carriers for changes in performance in various cognitive domains over the 13 months period were examined. RESULTS: Significant risk factors for cognitive impairment at 13 months were ApoE epsilon4, pre-stroke cognitive reduction (IQCODE 3.44+), previous stroke, and neurological impairment (NIHSS Total Score >5). A significant dose-dependent effect of the ApoE-genotype in relation to overall post-stroke cognitive functioning was found at baseline and follow-up, but not pre-stroke. The epsilon4 carriers showed a significant decline in tests related to verbal learning and memory compared to the non-carriers. CONCLUSIONS: The ApoE epsilon4-allele constitutes an independent risk factor for cognitive impairment at 13 months post-stroke, and is associated with progression of cognitive decline in tasks related to verbal learning and memory.

Balance and Gait After First Minor Ischemic Stroke in People 70 Years of Age or Younger: A Prospective Observational Cohort Study.

BACKGROUND: Two-thirds of patients with stroke experience only mild impairments in the acute phase, and the proportion of patients <70 years is increasing. Knowledge about balance and gait and predictive factors are scarce for this group. OBJECTIVE: The objective of this study was to explore balance and gait in the acute phase and after 3 and 12 months in patients ≤70 years with minor ischemic stroke (National Institutes of Health Stroke Scale score ≤3). This study also explored factors predicting impaired balance after 12 months. DESIGN: This study was designed as an explorative longitudinal cohort study. METHODS: Patients were recruited consecutively from 2 stroke units. Balance and gait were assessed with the Mini-Balance Evaluation Systems Test (Mini-BESTest), Timed Up and Go, and preferred gait speed. Predictors for impaired balance were explored using logistic regression. RESULTS: This study included 101 patients. Mean (SD) age was 55.5 (11.4) years, 20% were female, and mean (SD) National Institutes of Health Stroke Scale score was 0.6 (0.9) points. The Mini-BESTest, gait speed, and Timed Up and Go improved significantly from the acute phase to 3 months, and gait speed also improved from 3 to 12 months. At 12 months, 26% had balance impairments and 33% walked slower than 1.0 m/s. Poor balance in the acute phase (odds ratio = 0.92, 95% confidence interval = 0.85-0.95) was the only predictor of balance impairments (Mini-BESTest score ≤22) at 12 months poststroke. LIMITATIONS: Limitations include lack of information about pre-stroke balance and gait impairment and poststroke exercise. Few women limited the generalizability. CONCLUSION: This study observed improvements in both balance and gait during the follow-up; still, about one-third had balance or gait impairments at 12 months poststroke. Balance in the acute phase predicted impaired balance at 12 months.

Effect of Clinical Geriatric Assessments and Collaborative Medication Reviews by Geriatrician and Family Physician for Improving Health-Related Quality of Life in Home-Dwelling Older Patients Receiving Polypharmacy: A Cluster Randomized Clinical Trial.

Importance: Polypharmacy and inappropriate drug regimens are major health concerns among older adults. Various interventions focused on medication optimization strategies have been carried out, but the effect on patient-relevant outcomes remains uncertain. Objective: To investigate the effect of clinical geriatric assessments and collaborative medication reviews by geriatrician and family physician (FP) on health-related quality of life and other patient-relevant outcomes in home-dwelling older patients receiving polypharmacy. Design, Setting, and Participants: Cluster randomized, single-blind, clinical trial. Norwegian FPs were recruited from March 17, 2015, to March 16, 2017, to participate in the trial with their eligible patients. Participants were home-dwelling patients 70 years or older, using at least 7 medications regularly, and having their medications administered by the home nursing service. Patients in the control group received usual care. Randomization occurred at the FP level. A modified intent-to-treat analysis was used. Intervention: The intervention consisted of 3 main parts: (1) clinical geriatric assessment of the patients combined with a thorough review of their medications; (2) a meeting between the geriatrician and the FP; and (3) clinical follow-up. Main Outcomes and Measures: The primary outcome was health-related quality of life as assessed by the 15D instrument (score range, 0-1; higher scores indicate better quality of life, with a minimum clinically important change of ±0.015) at week 16. Secondary outcomes included changes in medication appropriateness, physical and cognitive functioning, use of health services, and mortality. Results: Among 174 patients (mean [SD] age, 83.3 [7.3] years; 67.8% women; 87 randomized to the intervention group and 87 randomized to the control [usual care] group) in 70 FP clusters (36 intervention and 34 control), 158 (90.8%) completed the trial. The mean (SD) 15D instrument score at baseline was 0.708 (0.121) in the intervention group and 0.714 (0.113) in the control group. At week 16, the mean (SD) 15D instrument score was 0.698 (0.164) in the intervention group and 0.655 (0.184) in the control group, with an estimated between-group difference of 0.045 (95% CI, 0.004-0.086; P = .03). Several secondary outcomes were also in favor of the intervention. There were more drug withdrawals, reduced dosages, and new drug regimens started in the intervention group. Conclusions and Relevance: This study's findings indicate that, among older patients exposed to polypharmacy, clinical geriatric assessments and collaborative medication reviews carried out by a geriatrician in cooperation with the patient's FP can result in positive effects on health-related quality of life. Trial Registration: ClinicalTrials.gov identifier: NCT02379455.

Blood Pressure-Lowering Profiles and Clinical Effects of Angiotensin Receptor Blockers Versus Calcium Channel Blockers.

Blood pressure-lowering drugs have different blood pressure-lowering profiles. We studied if differences in blood pressure mean and variability can explain the differences in risks of cardiovascular events and death among 15 245 high-risk hypertensive patients randomized to valsartan or amlodipine and followed for 4.2 years in the VALUE trial (Valsartan Antihypertensive Long-Term Use Evaluation). We selected patients with ≥3 visits and performed Cox regression analyses, defining mean blood pressure as a time-dependent covariate and visit-to-visit and within-visit blood pressure variability as the SD. Of 14 996 eligible patients, participants in the valsartan group had higher systolic mean blood pressure by 2.2 mm Hg, higher visit-to-visit systolic variability by 1.4 mm Hg, and higher within-visit systolic variability by 0.2 mm Hg (P values <0.0001). The higher risks of myocardial infarction and stroke in the valsartan group was attenuated after adjustment for mean and variability of systolic blood pressure, from HR 1.19 (95% CI, 1.02-1.39) to 1.11 (0.96-1.30) and from HR 1.13 (0.96-1.33) to 1.00 (0.85-1.18), respectively. The lower risk of congestive heart failure in the valsartan group was accentuated after adjustment, from HR 0.86 (0.74-1.00) to 0.76 (0.65-0.89). A smaller effect was seen on risk of death, from 1.01 (0.92-1.12) to 0.94 (0.85-1.04). In conclusion, the higher risks of myocardial infarction and stroke in patients randomized to valsartan versus amlodipine were related to the drugs' different blood pressure modulating profiles. The risk of congestive heart failure with valsartan was lower, independent of the less favorable blood pressure modulating profile.

Increased mortality in the slim elderly: a 42 years follow-up study in a general population.

The Bergen Clinical Blood Pressure Study in Norway was used to examine the relationship between body mass index (BMI (kg/m(2))) and total mortality in different age segments. Of 6,811 invited subjects, 5,653 (84%) participated in the study (1965-1971) and 4,520 (66%) died during 182,798 person-years of follow-up (1965-2007). Mean age at baseline was 47.5 years; range 22-75 years. BMI (kg/m(2)) was calculated from standardized measurements of body height and weight and divided into four groups (<22.0, 22.0-24.9, 25.0-27.9, > or =28.0). The 20 years cumulative risk of death related to baseline BMI was U-shaped in the elderly (aged 65-75 years), whereas the pattern was more linear in the youngest age group (20-44 years). In contrast to the younger age groups, the highest mortality in the elderly was in the lower BMI range (<22.0 kg/m(2)) (adjusted Cox proportional Hazard Ratio 1.39, 95% Confidence Interval 1.10, 1.75) compared to the BMI reference group (22.0-24.9 kg/m(2)). This pattern persisted after 72 months of early follow-up exclusion and it was robust to adjustments for a wide range of possible confounders including gender, history of cardiovascular disease, respiratory disease or hypertension, smoking habits, physical activity, socioeconomic status, physical appearance and other anthropometric measures. The study shows that a low BMI is an appreciable independent risk factor of total mortality in the elderly, and not a result of subclinical disease or confounding factors such as current or previous smoking. Awareness of this issue ought to be emphasized in advice, care and treatment of elderly subjects.

Effects of nutritional intervention upon bone turnover in elderly hip fracture patients. Randomized controlled trial.

BACKGROUND AND AIM: Hip fracture patients are at great risk of malnutrition, but documentation of the effect of nutrition supplementation in this group is sparse and inconclusive. The aim of this study was to examine if personalized nutrition advice combined with vitamin K1, Ca and vitamin D could improve bone turnover 4 months after hip fracture. DESIGN: This is a preplanned sub study of a randomized controlled trial of orthogeriatric care. The intervention group received orthogeriatric care, including nutrition advice and supplementation. The control group received usual care at the orthopedic ward. Blood was drawn for measurements of a number of vitamins and of bone turnover markers upon admission and at four months follow up. RESULTS: 71 patients (31 in the intervention group and 40 controls) had available data at 4 months as well as at baseline. After four months, vitamin K1 and 25(OH)D were higher in the intervention group compared with controls; vitamin K1: 1.0 ± 1.2 vs 0.6 ± 0.6 ng/ml, p = 0.09, 25(OH)D: 60 ± 29 vs 43 ± 22 nmol/L, p = 0.01 when adjusted for baseline differences. In a secondary, unadjusted analysis, comprising all patients with available four months data (n = 136), the differences were statistically significant for vitamin K1 as well as 25(OH)D (p = 0.03 and p < 0.001, respectively). There was a non-significant increase in 25(OH)D in the intervention group from baseline to 4 months follow up, and a significant decrease in the control group. There was no difference in bone turnover markers between the two groups at 4 months follow up. A substantial loss of weight and physical function was found in both groups. CONCLUSIONS: The supplementation of 25(OH)D and vitamin K1 improved serum concentrations of these vitamins, but this did not translate into any improvement in the bone turnover markers. The RCT is registered in ClinicalTrials.govNCT01009268 and NCT01738776.

Long-term effects on survival after a 1-year multifactorial vascular risk factor intervention after stroke or TIA: secondary analysis of a randomized controlled trial, a 7-year follow-up study.

BACKGROUND: Stroke and coronary heart disease share the same risk factors, and a multifactorial intervention after stroke may potentially result in the same reduction in cardiovascular mortality as seen after coronary events. We aimed to evaluate the effect on survival 7 years after a 1-year multifactorial risk factor intervention, and identify clinical predictors for long-term survival in a hospital-based cohort of patients with first-ever stroke or transient ischemic attack (TIA). MATERIALS AND METHODS: We performed a secondary analysis of a randomized controlled trial including patients between February 2007 and July 2008 comparing an intensive risk factor intervention vs usual care the first year poststroke to prevent cognitive impairment. From February 2014 to July 2016, all patients were invited to a follow-up. For patients dying throughout the follow-up period, date of death was obtained from the medical record. Examination at baseline and 1-year follow-up included extensive assessment of vascular risk factors and cognitive assessments. RESULTS: A total of 195 patients were randomized. Mean (SD) age was 71.6 (12.5) years, 53.3% were male, mean (SD) body mass index (BMI) was 25.6 (4.1) kg/m2. During follow-up, 35 patients in the intervention group and 41 in the control group died. Kaplan-Meier survival estimates show no significant difference in intention-to-treat (ITT) population or complete case (CC) population (log-rank P=0.29 vs log-rank P=0.07). In multivariable Cox proportional hazards regression analyses, lower age and higher BMI was independently associated with long-term survival, adjusted HR (95% CI) 1.08 (1.05-1.11) per year and 0.91 (0.85-0.97) per kg/m2. CONCLUSION: In this post hoc analysis, we found no significant effect on survival after 7 years of a multifactorial risk factor program given during the first year after first-ever stroke or TIA. Higher BMI was an independent predictor for long-term survival in this cohort.

CSF sodium at toxic levels precedes delirium in hip fracture patients.

Delirium is an acute state of confusion and a fluctuating level of consciousness. It is precipitated by physical illness or trauma, such as pneumonia, heart infarction, or hip fracture. Delirium is common among elderly hospitalized patients, and as many as 50% of hip fracture patients may develop delirium. Delirium may precipitate dementia, but recent studies indicate that delirium is caused by unknown neurotoxic mechanisms that are different from those that are associated with dementia. Experimental studies have shown that high extracellular levels of sodium are neurotoxic. We sampled lumbar cerebrospinal fluid (CSF) from hip fracture patients during hip surgery and analyzed metal ions that influence neuronal function. Eight patients who developed delirium after surgery had 21% higher CSF sodium than 17 patients who did not develop delirium (median value 175 mmol/L; range 154-188, vs. 145 mmol/L (112-204; p < 0.008) or 39 patients who underwent elective surgery under spinal anesthesia without developing delirium (145 mmol/L; 140-149; p = 0.0004). Seven patients who had developed delirium before CSF sampling had a median CSF sodium of 150 mmol/L (144-185; p = 0.3). CSF potassium was also 21% higher in patients who developed delirium (p = 0.024), but remained within the physiological range. Serum sodium and potassium were normal in all patient groups. This study, on a small sample of patients, confirms the neurotoxic potential and clinical importance of high extracellular levels of sodium in the brain. High CSF sodium would likely affect cerebral function and could precipitate delirium; further, it could interact with dementia-specific mechanisms to precipitate dementia development.

Promoting psychosocial well-being following stroke: study protocol for a randomized, controlled trial.

BACKGROUND: Stroke is a major public health threat globally. Psychosocial well-being may be affected following stroke. Depressive symptoms, anxiety, general psychological distress and social isolation are prevalent. Approximately one third report depressive symptoms and 20% report anxiety during the first months or years after the stroke. Psychosocial difficulties may impact significantly on long-term functioning and quality of life, reduce the effects of rehabilitation services and lead to higher mortality rates. The aim of the study is to evaluate the effect of a previously developed and feasibility tested dialogue-based psychosocial intervention aimed at promoting psychosocial well-being and coping following stroke among stroke survivors with and without aphasia. METHODS: The study will be conducted as a multicenter, randomized, single blind controlled trial with one intervention and one control arm. It will include a total of 330 stroke survivors randomly allocated into either an intervention group (dialogue-based intervention to promote psychosocial well-being) or a control group (usual care). Participants in the intervention group will receive eight individual sessions of supported dialogues in their homes during the first six months following an acute stroke. The primary outcome measure will be psychosocial well-being measured by the General Health Questionnaire (GHQ). Secondary outcome measures will be quality of life (SAQoL), sense of coherence (SOC), and depression (Yale). Process evaluation will be conducted in a longitudinal mixed methods study by individual qualitative interviews with 15-20 participants in the intervention and control groups, focus group interviews with the intervention personnel and data collectors, and a comprehensive analysis of implementation fidelity. DISCUSSION: The intervention described in this study protocol is based on thorough development and feasibility work, guided by the UK medical research council framework for developing and testing complex interventions. It combines classical effectiveness evaluation with a thorough process evaluation. The results from this study may inform the development of further trials aimed at promoting psychosocial well-being following stroke as well as inform the psychosocial follow up of stroke patients living at home. TRIAL REGISTRATION: NCT02338869 ; registered 10/04/2014 (On-going trial).

Micronutrients and the risk of hip fracture: Case-control study.

BACKGROUND: Vitamin D, and possibly vitamin K, has an established association to fracture risk. Other vitamins are, however, less studied. AIM: To determine whether specific micronutrients other than 25(OH)D and vitamin K play a role in risk of hip fracture and bone turnover. METHODS: In this case-control study, blood was drawn for measurements of vitamins A, B6, B12, C, E, and folic acid as well as the bone turnover markers osteocalcin and bone-specific alkaline phosphatase upon admission for hip fracture in 116 patients and in 73 home-dwelling non fractured controls. Results for vitamin K1 and 25(OH)D from the same populations have been reported previously. RESULTS: Low vitamin A, C, and E concentrations were independently associated with a risk of hip fracture. The adjusted odds ratio (95% confidence interval) per 10 µmol/L increase in vitamin A concentration was 0.74 (0.65-0.84); for 1 µmol/L vitamin C and E: 0.94 (0.92-0.97) and 0.81 (0.74-0.89) respectively. The results were principally unchanged when 25(OH)D, vitamin K1, Body Mass Index, and other potential confounders were adjusted for. All vitamins except B12 and folic acid correlated positively with total osteocalcin and negatively with bone-specific alkaline phosphatase. CONCLUSIONS: Low vitamin A, C, and E concentrations are associated with an increased risk of hip fracture, possibly mediated through bone turnover mechanisms. This case-control study is registered at: ClinicalTrials.gov. NCT01738776. The patient related outcome is also registered at: ClinicalTrials.gov. NCT01009268.

Effects of candesartan in acute stroke on activities of daily living and level of care at 6 months.

OBJECTIVE: The Scandinavian Candesartan Acute Stroke Trial (SCAST) indicated that blood pressure-lowering treatment with candesartan in the acute phase of stroke has a negative effect on functional outcome at 6 months, measured by the modified Rankin scale. We wanted to see if similar effects can be observed on activities of daily living and level of care. METHODS: SCAST was an international multicentre, randomized and placebo-controlled trial of candesartan in 2029 patients recruited within 30  h of acute ischaemic or haemorrhagic stroke. Treatment lowered blood pressure by 5/2  mmHg from day 2 onwards, and was administered for 7 days. At 6 months, activities of daily living were assessed by the Barthel index, and categorized as 'dependency' (≤55 points), 'assisted dependency' (60-90), or 'independency' (≥95). Level of care was categorized as 'living at own home without public help', 'living at home with public help, or in institution for rehabilitation', or 'living in institution for long or permanent stay'. We used ordinal and binary logistic regression for statistical analysis, and adjusted for predefined key variables. RESULTS: Data were available in 1825 patients, of which 1559 (85%) patients had ischaemic and 247 (13%) had haemorrhagic stroke. There were no statistically significant effects of candesartan on the Barthel index or on level of care (adjusted common odds ratio for poor outcome 1.09, 95% confidence interval 0.88-1.35, P = 0.44; and odds ratio 1.05, 95% confidence interval 0.82-1.34, P = 0.69, respectively). In the individual Barthel index domains, there were also no statistically significant differences. CONCLUSION: Blood pressure-lowering treatment with candesartan had no beneficial effect on activities of daily living and level of care at 6 months. This result is compatible with the results of the main analysis of the modified Rankin scale, and supports the conclusion that there is no indication for routine blood pressure treatment with candesartan in the acute phase of stroke.

Blood pressure control to prevent decline in cognition after stroke.

BACKGROUND: Treatment of hypertension post-stroke preserves cognition through prevention of recurrent stroke, but it is not clear whether it prevents cognitive decline through other mechanisms. We aimed to describe changes in blood pressure from baseline to 1 year post-stroke and to evaluate the association between achieved blood pressure targets and cognitive function, mild cognitive impairment (MCI), and dementia. METHODS: We included patients with first-ever stroke, and defined achieved blood pressure goals as systolic blood pressure (SBP) in the categories ≤125 mmHg, ≤140 mmHg, and ≤160 mmHg, SBP reduction of ≥10 mmHg, and diastolic blood pressure (DBP) reduction of ≥5 mmHg. The main outcome variables were cognitive assessments 1 year post stroke. Secondary outcomes were diagnoses of MCI or dementia. RESULTS: Forty-one of 166 patients (25%) reached SBP ≤125 mmHg after 1 year, 92/166 (55%) reached SBP ≤140 mmHg, and 150/166 (90%) reached SBP ≤160 mmHg. SBP was reduced by ≥10 mmHg in 44/150 (29%) and DBP by ≥5 mmHg in 57/150 (38%). We did not find any statistically significant associations between cognitive test performances and different blood pressure goals (P=0.070-1.0). Nor was there any significant association between achieved goal blood pressure or blood pressure reduction after 1 year and the diagnoses of MCI or dementia (P=0.32-0.56). CONCLUSION: Treatment of hypertension is important for primary and secondary prevention of stroke. Showing a potential beneficial effect of blood pressure control on cognitive function, however, probably needs longer follow-up.