Pharmacological treatment of increased vascular risk and cognitive performance in middle-aged and old persons: six-year observational longitudinal study.

BACKGROUND: Lowering vascular risk is associated with a decrease in the prevalence of cardiovascular disease and dementia. However, it is still unknown whether lowering of vascular risk with pharmacological treatment preserves cognitive performance in general. Therefore, we compared the change in cognitive performance in persons with and without treatment of vascular risk factors. METHODS: In this longitudinal observational study, 256 persons (mean age, 58 years) were treated for increased vascular risk during a mean follow-up period of 5.5 years (treatment group), whereas 1678 persons (mean age, 50 years) did not receive treatment (control group). Cognitive performance was three times measured during follow-up using the Ruff Figural Fluency Test (RFFT) and Visual Association Test (VAT), and calculated as the average of standardized RFFT and VAT score per participant. Because treatment allocation was nonrandomized, additional analyses were performed in demographic and vascular risk-matched samples and adjusted for propensity scores. RESULTS: In the treatment group, mean (SD) cognitive performance changed from - 0.30 (0.80) to - 0.23 (0.80) to 0.02 (0.87), and in control group, from 0.08 (0.77) to 0.24 (0.79) to 0.49 (0.74) at the first, second and third measurement, respectively (ptrend < 0.001). After adjustment for demographics and vascular risk, the change in cognitive performance during follow-up was not statistically significantly different between the treatment and control group: mean estimated difference, - 0.10 (95%CI - 0.21 to 0.01; p = 0.08). Similar results were found in matched samples and after adjustment for propensity score. CONCLUSION: Change in cognitive performance during follow-up was similar in treated and untreated persons. This suggests that lowering vascular risk preserves cognitive performance.

Vitamin Status and the Development of Postoperative Cognitive Decline in Elderly Surgical Oncologic Patients.

BACKGROUND: This study aimed to evaluate the influence that serum levels of vitamin B12, folate, and homocysteine have on the development of short-term postoperative cognitive decline in the elderly surgical oncology patient. METHODS: This study was part of a prospective cohort study focused on postoperative cognitive outcomes for patients 65 years of age or older undergoing surgery for a solid malignancy. Postoperative cognitive decline was defined as the change in the combined results of the Ruff Figural Fluency Test and the Trail-Making Test Parts A and B. Patients with the highest change in scores 2 weeks postoperatively compared with baseline were considered to be patients with cognitive decline. Patients with the lowest change were considered to be patients without cognitive decline. To analyze the effect of vitamin levels on the changes in postoperative cognitive scores, uni- and multivariate logistic regression analysis were performed. RESULTS: The study enrolled 61 patients with and 59 patients without postoperative cognitive decline. Hyperhomocysteinemia was present in 14.2% of the patients. Patients with postoperative cognitive decline more often had hyperhomocysteinemia (27.9 vs 10.2%). Hyperhomocysteinemia was associated with a higher chance for the development of postoperative cognitive decline (odds ratioadjusted, 11.9; 95% confidence interval, 2.4-59.4). Preoperative vitamin B12 or folate deficiency were not associated with the development of postoperative cognitive decline. CONCLUSION: Preoperative hyperhomocysteinemia is associated with the development of postoperative cognitive decline. The presence of preoperative hyperhomocysteinemia could be an indicator for an increased risk of postoperative cognitive decline developing in the elderly.

Predicting postoperative delirium after vascular surgical procedures.

OBJECTIVE: The objective of this study was to determine the incidence of and specific preoperative and intraoperative risk factors for postoperative delirium (POD) in electively treated vascular surgery patients. METHODS: Between March 2010 and November 2013, all vascular surgery patients were included in a prospective database. Various preoperative, intraoperative, and postoperative risk factors were collected during hospitalization. The primary outcome variable was the incidence of POD. Secondary outcome variables were any surgical complication, hospital length of stay, and mortality. RESULTS: In total, 566 patients were prospectively evaluated; 463 patients were 60 years or older at the time of surgery and formed our study cohort. The median age was 72 years (interquartile range, 66-77), and 76.9% were male. Twenty-two patients (4.8%) developed POD. Factors that differed significantly by univariate analysis included current smoking (P = .001), increased comorbidity (P = .001), hypertension (P = .003), diabetes mellitus (P = .001), cognitive impairment (P < .001), open aortic surgery or amputation surgery (P < .001), elevated C-reactive protein level (P < .001), and blood loss (P < .001). Multivariate logistic regression analysis revealed preoperative cognitive impairment (odds ratio [OR], 16.4; 95% confidence interval [CI], 4.7-57.0), open aortic surgery or amputation surgery (OR, 14.0; 95% CI, 3.9-49.8), current smoking (OR, 10.5; 95% CI, 2.8-40.2), hypertension (OR, 7.6; 95% CI, 1.9-30.5) and age ≥80 years (OR, 7.3; 95% CI, 1.8-30.1) to be independent predictors of the occurrence of POD. The combination of these parameters allows us to predict delirium with a sensitivity of 86% and a specificity of 92%. The area under the curve of the corresponding receiver operating characteristics was 0.93. Delirium was associated with longer hospital length of stay (P < .001), more frequent and increased intensive care unit stays (P = .008 and P = .003, respectively), more surgical complications (P < .001), more postdischarge institutionalization (P < .001), and higher 1-year mortality rates (P = .0026). CONCLUSIONS: In vascular surgery patients, preoperative cognitive impairment and open aortic or amputation surgery were highly significant risk factors for the occurrence of POD. In addition, POD was significantly associated with a higher mortality and more institutionalization. Patients with these risk factors should be considered for high-standard delirium care to improve these outcomes.

Vascular burden and cognitive function in late-life depression.

OBJECTIVE: To evaluate the relation of vascular risk factors, subclinical, and manifest vascular disease with four domains of cognitive functioning in a large sample of clinically depressed older persons. METHODS: A cross-sectional analysis was used, and depressed patients were recruited from general practices and mental healthcare institutes. Presence of a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, depressive episode was established with the Composite International Diagnostic Interview. Framingham Risk Score (FRS) was used as a measure for vascular risk profile, ankle-brachial index for subclinical vascular disease, and history of a cardiovascular event as a measure for manifest vascular disease. Three neurocognitive tasks evaluated processing speed, working memory, verbal memory, and interference control. RESULTS: In 378 participants, linear regression analysis showed that FRS was related to poorer interference control (t = -2.353; df = 377; p <0.05) but to no other cognitive domain after adjustment for age, sex, education level, and depressive symptom severity. Lower ankle-brachial index and history of cardiovascular event were related to slower processing speed (t = 2.659; df = 377; p <0.05 and t = -3.328; df = 377; p <0.01, respectively) but to no other cognitive domain. In 267 participants without manifest vascular disease, higher FRS was related to slower processing speed (t = -2.425; df = 266; p <0.05) and poorer interference control (t = -2.423; df = 266; p <0.05), and lower ankle brachial index was related to slower processing speed (t = 2.171; df = 266; p <0.05). CONCLUSION: In depressed older persons, vascular burden is related to slower processing speed also in the absence of manifest vascular disease. Poorer interference control was only related to vascular risk factors but not to subclinical or manifest vascular disease.

C-reactive protein predicts postoperative delirium following vascular surgery.

BACKGROUND: The etiology of postoperative delirium (POD) following vascular surgery is generally unknown. The incidence, however, can be as high as 35%. A possible neuroinflammatory basis for delirium is likely and C-reactive protein (CRP) as a marker for inflammation can possibly play a predictive role. METHODS: Between March 2010 and September 2012, 277 consecutive elective vascular surgery patients were prospectively evaluated for the diagnosis of POD. Various potential risk factors, including postoperative CRP values, were collected. RESULTS: The mean age of the patients was 69 ± 11 years (range 21-92). The mean hospital length of stay was 6 ± 4 days (range 1-33). Sixteen patients (6%) developed POD during hospital stay. Univariate analysis revealed multiple comorbidities (P = 0.001), postoperative elevated CRP levels (P = 0.001), intensive care unit admittance (P = 0.01), and open aortic surgery or amputation procedures (P = 0.0001) to be significantly related to the diagnosis POD. Multivariate logistic regression analysis confirmed the relationship between an elevated CRP value and POD (odds ratio [OR] 1.01, 95% confidence interval 1.00-1.03, P = 0.04). The sensitivity analyses yielded essentially similar results. Based on OR, it can be calculated that the risk of POD is increased by approximately 35% if the CRP concentration is 50 mg/L, and by approximately 90% if the CRP concentration is 100 mg/L (compared with a CRP concentration of 5 mg/L). Thirty-one percent (5/16) of patients with POD needed a long-stay care facility after discharge (P = 0.0001). CONCLUSIONS: In this study, CRP can be used as a marker for an increased risk of POD after vascular surgery. In addition, it was found that POD was associated with a 10-fold increase in the need of long-stay care after discharge.

The development of a comprehensive multidisciplinary care pathway for patients with a hip fracture: design and results of a clinical trial.

BACKGROUND: Hip fractures frequently occur in older persons and severely decrease life expectancy and independence. Several care pathways have been developed to lower the risk of negative outcomes but most pathways are limited to only one aspect of care. The aim of this study was therefore to develop a comprehensive care pathway for older persons with a hip fracture and to conduct a preliminary analysis of its effect. METHODS: A comprehensive multidisciplinary care pathway for patients aged 60 years or older with a hip fracture was developed by a multidisciplinary team. The new care pathway was evaluated in a clinical trial with historical controls. The data of the intervention group were collected prospectively. The intervention group included all patients with a hip fracture who were admitted to University Medical Center Groningen between 1 July 2009 and 1 July 2011. The data of the control group were collected retrospectively. The control group comprised all patients with a hip fracture who were admitted between 1 January 2006 and 1 January 2008. The groups were compared with the independent sample t-test, the Mann-Whitney U-test or the Chi-squared test (Phi test). The effect of the intervention on fasting time and length of stay was adjusted by linear regression analysis for differences between the intervention and control group. RESULTS: The intervention group included 256 persons (women, 68%; mean age (SD), 78 (9) years) and the control group 145 persons (women, 72%; mean age (SD), 80 (10) years). Median preoperative fasting time and median length of hospital stay were significantly lower in the intervention group: 9 vs. 17 hours (p < 0.001), and 7 vs. 11 days (p < 0.001), respectively. A similar result was found after adjustment for age, gender, living condition and American Society of Anesthesiologists (ASA) classification. In-hospital mortality was also lower in the intervention group: 2% vs. 6% (p < 0.05). There were no statistically significant differences in other outcome measures. CONCLUSIONS: The new comprehensive care pathway was associated with a significant decrease in preoperative fasting time and length of hospital stay.

Cardiovascular risk profile and cognitive function in young, middle-aged, and elderly subjects.

BACKGROUND AND PURPOSE: Cognitive decline occurs earlier than previously realized and is already evident at the age of 45. Because cardiovascular risk factors are established risk factors for cognitive decline in old age, we investigated whether cardiovascular risk factors are also associated with cognitive decline in young and middle-aged groups. METHODS: The cross-sectional study included 3778 participants aged 35 to 82 years (mean age, 54 years) and free of cardiovascular disease and stroke. Cognitive function was measured with the Ruff Figural Fluency Test (RFFT; worst score, 0; best score, 175 points) and the Visual Association Test (VAT; worst score, 0; best score, 12 points). Overall cardiovascular risk was assessed with the Framingham Risk Score (FRS) for general cardiovascular disease (best score, -5; worst score, 33 points). RESULTS: Mean RFFT score (SD) was 70 (26) points, median VAT score (interquartile range) was 10 (9-11) points, and mean FRS (SD) was 10 (6) points. Using linear regression analysis adjusting for educational level, RFFT was negatively associated with FRS. RFFT score decreased by 1.54 points (95% confidence interval, -1.66 to -1.44; P<0.001) per point increase in FRS. This negative association was not only limited to older age groups, but also found in the young (35-44 years). The main influencing components of the FRS were age (P<0.001), diabetes mellitus (P=0.001), and smoking (P<0.001). Similar results were found for VAT score as outcome measure. CONCLUSIONS: In this large population-based cohort, a worse overall cardiovascular risk profile was associated with poorer cognitive function. This association was already present in young adults aged 35 to 44 years.

Evaluation of the effect of a comprehensive multidisciplinary care pathway for hip fractures: design of a controlled study.

BACKGROUND: Hip fractures constitute an economic burden on healthcare resources. Most persons with a hip fracture undergo surgery. As morbidity and mortality rates are high, perioperative care leaves room for improvement. Improvement can be achieved if it is organized in comprehensive care pathways, but the effectiveness of these pathways is not yet clear. Hence the objective of this study is to compare the clinical effectiveness of a comprehensive care pathway with care as usual on self-reported limitations in Activities of Daily Living. METHODS/DESIGN: A controlled trial will be conducted in which the comprehensive care pathway of University Medical Center Groningen will be compared with care as usual in two other, nonacademic, hospitals. In this trial, propensity scores will be used to adjust for differences at baseline between the intervention and control group. Propensity scores can be used in intervention studies where a classical randomized controlled trial is not feasible. Patients aged 60 years and older will be included. The hypothesis is that 15% more patients at University Medical Center Groningen compared with patients in the care-as-usual condition will have recovered at least as well at 6 months follow-up to pre-fracture levels for Activities of Daily Living. DISCUSSION: This study will yield new knowledge with respect to the clinical effectiveness of a comprehensive care pathway for the treatment of hip fractures. This is relevant because of the growing incidence of hip fractures and the consequent massive burden on the healthcare system. Additionally, this study will contribute to the growing knowledge of the application of propensity scores, a relatively novel statistical technique to simulate a randomized controlled trial in studies where it is not possible or difficult to execute this kind of design. TRIAL REGISTRATION: Nederlands Trial Register NTR3171.

Thinking through postoperative cognitive dysfunction: How to bridge the gap between clinical and pre-clinical perspectives.

Following surgery, patients may experience cognitive decline, which can seriously reduce quality of life. This postoperative cognitive dysfunction (POCD) is mainly seen in the elderly and is thought to be mediated by surgery-induced inflammatory reactions. Clinical studies tend to define POCD as a persisting, generalised decline in cognition, without specifying which cognitive functions are impaired. Pre-clinical research mainly describes early hippocampal dysfunction as a consequence of surgery-induced neuroinflammation. These different approaches to study POCD impede translation between clinical and pre-clinical research outcomes and may hamper the development of appropriate interventions. This article analyses which cognitive domains deteriorate after surgery and which brain areas might be involved. The most important outcomes are: (1) POCD encompasses a wide range of cognitive impairments; (2) POCD affects larger areas of the brain; and (3) individual variation in the vulnerability of neuronal networks to neuroinflammatory mechanisms may determine if and how POCD manifests itself. We argue that, for pre-clinical and clinical research of POCD to advance, the effects of surgery on various cognitive functions and brain areas should be studied. Moreover, in addition to general characteristics, research should take inter-relationships between cognitive complaints and physical and mental characteristics into account.

Exploration of the difference in incidence of renal replacement therapy between Flanders and the Netherlands--investigation of explanatory variables.

AIM: This study investigates the difference in the incidence of renal replacement therapy (RRT) between Flanders and the Netherlands and possible explanations for this difference. METHODS: End-stage renal disease incidence data were obtained from the European Renal Association-European Dialysis and Transplant Association (ERA-EDTA). Additional sources were the National Institute of Statistics (NIS), the Central Bureau of Statistics (CBS), the Organisation for Economic Cooperation and Development (OECD) health data and the WHO Health For All database (WHO-HFA). RESULTS: There is remarkable difference in incidence rate of RRT between Flanders and the Netherlands, with a higher rate in Flanders. This difference is already present in patients aged 45-64 years and increases with age, being >2-fold higher in subjects of ≥ 75 years. With respect to the renal diagnoses leading to need for RRT, a higher share of especially diabetes mellitus type 2 and renovascular disease was observed in Flanders. Remarkably, the difference in incidence rate of RRT is not associated with a difference in survival on RRT, not even in the elderly, arguing against a restricted access to RRT in the Netherlands. In the general population, the expected number of healthy life years at birth is lower in Belgium than in the Netherlands, and in Belgium, the hospital discharge rates for diabetes, acute myocardial infarction and cerebrovascular accident and the number of coronary bypass procedures and percutaneous coronary interventions per capitum is higher, as is the prevalence of obesity. CONCLUSION: Our data do not support the assumption that the differences in RRT incidence in the elderly between Flanders and the Netherlands are due to a more restricted access to RRT in the Netherlands but may be due to differences in underlying comorbidity and life style between the two populations.

Exploration of the difference in incidence of renal replacement therapy in elderly patients in Flanders and the Netherlands--a comparison of referral policy.

BACKGROUND: The incidence of renal replacement therapy (RRT) among patients aged ≥65 years is much higher in Flanders, the Dutch speaking region of Belgium, than in the Netherlands. We studied whether differences in referral policy to nephrologists by primary care physicians (PCPs) and specialists between Flanders and the Netherlands may play a role. METHODS: A vignette study was performed among 329 PCPs and 96 specialists in Flanders and compared to the vignette study that was conducted among 209 PCPs and 162 specialists in the Netherlands. Physicians were offered six vignettes concerning case reports of patients with chronic kidney disease and varying co-morbidities or social circumstances. Each vignette was presented for a 65- and an 80-year-old patient. Physicians were asked about the likelihood of referral of the patients in the given circumstances. Univariate and logistic regression analyses were performed to identify whether country affected the likelihood of referral. RESULTS: Univariate analyses showed that the percentage of PCPs who would probably or definitely refer a 65- or an 80-year-old patient with less severe co-morbidity was significantly (P ≤ 0.001) higher in the Netherlands than in Flanders. However, the likelihood of referral of PCPs-concerning patients with more severe co-morbidity did not differ significantly. Specialists in Flanders did not differ in the likelihood to refer patients from that of specialists in the Netherlands. Logistic regression analysis showed that country (higher referral in the Netherlands) was an important predictor for the referral of PCPs, and this was especially the case for patients with less severe co-morbidity. These patterns persisted, even after controlling for other possible predictors as physicians' age, gender, religion and years in practice. CONCLUSIONS: This study suggests that the lower RRT incidence in the Netherlands cannot be explained by a more restrictive referral policy among physicians in the Netherlands. The data suggested that the latter group had a similar or even more liberal attitude to the referral of older patients than physicians in Flanders.

Routine use of the confusion assessment method for the intensive care unit: a multicenter study.

RATIONALE: Delirium is often unrecognized in ICU patients and associated with poor outcome. Screening for ICU delirium is recommended by several medical organizations to improve early diagnosis and treatment. The Confusion Assessment Method for the ICU (CAM-ICU) has high sensitivity and specificity for delirium when administered by research nurses. However, test characteristics of the CAM-ICU as performed in routine practice are unclear. OBJECTIVES: To investigate the diagnostic value of the CAM-ICU in daily practice. METHODS: Teams of three delirium experts including psychiatrists, geriatricians, and neurologists visited 10 ICUs twice. Based on cognitive examination, inspection of medical files, and Diagnostic and Statistic Manual of Mental Disorders, 4th edition, Text Revision criteria for delirium, the expert teams classified patients as awake and not delirious, delirious, or comatose. This served as a gold standard to which the CAM-ICU as performed by the bedside ICU-nurses was compared. Assessors were unaware of each other's conclusions. MEASUREMENTS AND MAIN RESULTS: Fifteen delirium experts assessed 282 patients of whom 101 (36%) were comatose and excluded. In the remaining 181 (64%) patients, the CAM-ICU had a sensitivity of 47% (95% confidence interval [CI], 35%-58%); specificity of 98% (95% CI, 93%-100%); positive predictive value of 95% (95% CI, 80%-99%); and negative predictive value of 72% (95% CI, 64%-79%). The positive likelihood ratio was 24.7 (95% CI, 6.1-100) and the negative likelihood ratio was 0.5 (95% CI, 0.4-0.8). CONCLUSIONS: Specificity of the CAM-ICU as performed in routine practice seems to be high but sensitivity is low. This hampers early detection of delirium by the CAM-ICU.

A comprehensive multidisciplinary care pathway for hip fractures better outcome than usual care?

INTRODUCTION: Hip fracture surgery is among the most performed surgical procedures in elderly patients. Mortality rates are high, however, and patients often fail to live independently following a hip fracture. To improve outcome, multidisciplinary care pathways have been initiated, but longer-term results are lacking. Aim of this study was to compare functional outcome and living situation six months after hip fracture treatment with and without a care pathway. PATIENTS AND METHODS: A multicentre prospective controlled trial was conducted with three hospitals: in one hospital patients were treated with a care pathway, in the other hospitals patients received usual care. All patients aged ≥ 60 years with a hip fracture were asked to participate. Besides basic characteristics, health-related quality of life (EQ-5D) and performance scores of activities of daily living (Katz Index and Lawton IADL) were assessed. Differences in scores were analysed using linear regression. Propensity score adjustment was used to correct for differences between the care pathway and the usual care group. Missing data were imputed. RESULTS: No differences in rate of return to prefracture ADL level were found between patients in the care pathway group and the usual care group. The percentage of participants in the same situation as before the fracture was the same in both treatment groups (81%). There were no significant differences in quality of life, activities of daily living or mortality (15% vs 10%, p = 0.17), but hospital stay in the care pathway group was significantly shorter (median 7 vs 10 days). DISCUSSION: Treatment of elderly patients with a hip fracture is commonly organised in care pathways. Although short-term advantages are reported, positive effects on longer-term functional results could not be proven in our study. This study confirmed a shorter hospital stay in the care pathway group, which potentially may lead to a reduction in costs. CONCLUSIONS: Functional outcome and living situation six months after a hip fracture is the same for patients treated with or without a care pathway.

Accepting or declining dialysis: considerations taken into account by elderly patients with end-stage renal disease.

BACKGROUND: Elderly patients with end-stage renal disease have to make a difficult decision whether or not to start dialysis. This study explores the considerations taken into account by these patients in decision-making regarding renal replacement therapy. METHOD: In-depth interviews were conducted to gain an enhanced understanding of the considerations in treatment decision-making. Fourteen patients aged 65 years or older participated in the interviews, of whom 8 patients had made the decision to start, and 6 patients the decision to decline, dialysis. RESULTS: All participating patients had a variety of health problems, but appeared to have normal cognitive functions. Patients who declined dialysis were older and more often men and widow(er)s compared with patients who accepted dialysis. Patients chose to start dialysis because they enjoyed life, were not prepared to face the end of life, felt they had no other choice or had care-giving responsibilities for family members. Patients declined dialysis because of the speculated loss of autonomy, their age-associated decrease in vitality, distance from dialysis center and reluctance to think about the future. CONCLUSION: Results suggest that patients' decisions to decline or accept dialysis are not based on the effectiveness of the treatment, but rather on personal values, beliefs and feelings toward life, suffering and death, and the expected difficulties in fitting the treatment into their life.

Strict adherence to evidence-based protocol in choice of implants and surgical technique leads to fewer hip fracture reoperations.

BACKGROUND AND PURPOSE: Surgery for hip fractures is frequently followed by complications that hinder the rehabilitation. Only part of the complications are surgery-related, however these, including reoperation may have the highest impact. Operative protocols are designed to treat all patients equally, according to evidence based guidelines. Aim of this study was to investigate the association between strict adherence to an operative protocol and postoperative complications, especially reoperations. MATERIALS AND METHODS: A retrospective analyses of a prospective cohort. The cohort included all patients aged ≥60 treated for a hip fracture at University Medical Center Groningen between July 2009 and June 2013. The files of the patients were searched for complications, including reoperations. To evaluate adherence to the operative protocol all X-rays were retrospectively reviewed and the fracture type was reclassified. This retrospective fracture classification was compared with the treatment method used. Logistic regression analyses were used to assess whether patients that were not treated strictly according to the operative protocol have higher odds of developing a complication or of undergoing a reoperation. RESULTS: The study population consisted of 479 patients with a mean age of 78.4 (SD 9.5) years. Reoperation was performed in 11% of the patients during the follow-up period. The operative protocol was not followed strictly in 12% of the patients. When the operative protocol was not followed, the odds of having a reoperation was 2.41 times higher (p = 0.02). The overall complication rate was 75% and did not differ in both groups. CONCLUSION: Strict adherence to an evidence-based operative protocol is of major importance toward preventing implant-related problems and reoperations.

Fracture prevention with vitamin D supplementation: considering the inconsistent results.

BACKGROUND: A meta-analysis found that high dose vitamin D, different from low dose, decreased fracture risk by 23% for any nonvertebral fracture and by 26% for hip fracture. Unfortunately, however, this effect was not confirmed by recent trials. The aim of this paper is to explore if this inconsistency can be attributed to publication bias or heterogeneity of the trials. METHODS: The meta-analysis was extended with recent randomised controlled trials (RCTs) that were identified by a systematic review. Risk ratios (RR) and 95% confidence intervals (CI) were calculated from raw data. A funnel plot was used to explore the possibility of publication bias. Forest plots were used to investigate if vitamin D dose, concurrent use of calcium and target population were sources of heterogeneity. Linear regression analysis of log RR on adherence rate and achieved vitamin D level was used to study whether these variables were associated with fracture risk. RESULTS: A total of eleven trials was included: seven RCTs from the meta-analysis and four recently published. For any nonvertebral fracture, the funnel plot was asymmetrical because two small RCTs showed a large positive effect. This was not found for hip fracture. As reported in the meta-analysis, low dose vitamin D (<400 IU daily) was not effective. In contrast to the meta-analysis, however, the effect of high dose vitamin D (> or =700 IU daily) seemed to be dependent on target population. For any nonvertebral fracture, the pooled RR was 0.80 (95% CI, 0.70-0.90) in institutionalised persons, and 0.88 (95% CI, 0.75-1.04) in the general population; for hip fracture, pooled RR 0.72 (95% CI, 0.59 to 0.88) and 1.04 (95% CI, 0.72-1.50), respectively. Other sources of heterogeneity were not clearly found. In the meta-analysis, pooled RRs were mainly based on small trials that showed a large effect or trials in institutionalised persons. CONCLUSION: It is likely that the inconsistency between the meta-analysis and the recent trials is, at least partially, due to publication bias and differences in target population. High dose vitamin D may be effective in institutionalised persons but probably is not effective in the general population.

Improved detection of delirium, implementation and validation of the CAM-ICU in elderly Emergency Department patients.

OBJECTIVE: To evaluate the effect of routine use of the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) on the diagnosis rate of delirium in elderly Emergency Department (ED) patients and the validity of the CAM-ICU in the ED setting. METHODS: This was a prospective observational study in a tertiary care academic ED. We compared the diagnosis rate of delirium before implementation of the CAM-ICU, without routine use of a screening tool, with the diagnosis rate after implementation of the CAM-ICU. All consecutive patients aged 70 years or older were enrolled. The diagnosis rate before implementation was based on chart review and after implementation on a positive CAM-ICU score. In a subsample, the presence of delirium was evaluated independently according to the Diagnostic and Statistical Manual of Mental Disorders, 4th ed., text revision (DSM-IV-TR) criteria to assess the validity of the CAM-ICU. RESULTS: The total study population included 968 patients: 490 before and 478 after implementation of the CAM-ICU. The two groups were not significantly different in patient characteristics. Before implementation of the CAM-ICU, delirium was diagnosed in 14 patients (3%) and after implementation in 48 patients (10%) (P<0.001). The sensitivity of the CAM-ICU for delirium in the ED setting was 100%, specificity was 98%, positive predictive value was 92%, and negative predictive value was 100%. CONCLUSION: The diagnosis rate of delirium after implementation of the CAM-ICU was three-fold higher than before. The CAM-ICU is a reliable screening tool in the ED, with high sensitivity, specificity, and positive and negative predictive value.

Risk of Bleeding and Thrombosis in Patients 70 Years or Older Using Vitamin K Antagonists.

IMPORTANCE: Previous studies have shown that, despite the higher risk of bleeding, the elderly still benefit from taking anticoagulants if they have a stringent indication. However, owing to the relatively low number of patients older than 90 years in these studies, it is unknown whether this benefit is also seen with the eldest patients. OBJECTIVE: To determine how the risk of bleeding and thrombosis is associated with age in patients older than 70 years who were treated with a vitamin K antagonist (VKA). DESIGN, SETTING, AND PARTICIPANTS: A matched cohort study was conducted of patients at a thrombosis service who were treated with a VKA between January 21, 2009, and June 30, 2012. All 1109 patients 90 years or older who were treated with a VKA were randomly matched 1:1:1 with 1100 patients aged 80 to 89 years and 1104 patients aged 70 to 79 years based on duration of VKA treatment. Data analysis was conducted from April 2015 to April 2016. MAIN OUTCOMES AND MEASURES: The primary outcome was a composite of clinically relevant nonmajor and major bleeding. Secondary outcomes included thromboses and quality of VKA control. RESULTS: During 6419 observation-years, 713 of the 3313 patients (1394 men and 1919 women) had 1050 bleeding events. The risk of bleeding was not significantly increased in patients aged 80 to 89 years (event rate per 100 patient-years [ER], 16.7; hazard ratio [HR], 1.07; 95% CI, 0.89-1.27) and mildly increased in patients 90 years or older (ER, 18.1; HR, 1.26; 95% CI, 1.05-1.50) compared with patients aged 70 to 79 years (ER, 14.8). The point estimates for major bleeding (including fatal) were comparable for patients aged 80 to 89 years (ER, 1.0; HR, 1.09; 95% CI, 0.60-1.98) and those 90 years or older (ER, 1.1; HR, 1.20; 95% CI, 0.65-2.22) compared with those aged 70 to 79 years (ER, 0.9). The increase in bleeding risk was sharper in men than in women. Eighty-five patients (2.6%) developed a thrombotic event. Risk of thrombosis was higher for patients in their 90s (HR, 2.14; 95% CI, 1.22-3.75) and 80s (HR, 1.75; 95% CI, 1.002-3.05) than for patients in their 70s. Vitamin K antagonist control became significantly poorer with rising age, which partly explained the increased bleeding risk in patients 90 years or older, but most of the increased risk of thrombosis was not mediated by VKA control. CONCLUSIONS AND RELEVANCE: These clinical practice data of patients considered eligible for anticoagulation show that the bleeding risk with a VKA only mildly increases after the age of 80 years, while there is a sharp increase in the risk of thrombosis in the same age group.

Agreement between Computerized and Human Assessment of Performance on the Ruff Figural Fluency Test.

The Ruff Figural Fluency Test (RFFT) is a sensitive test for nonverbal fluency suitable for all age groups. However, assessment of performance on the RFFT is time-consuming and may be affected by interrater differences. Therefore, we developed computer software specifically designed to analyze performance on the RFFT by automated pattern recognition. The aim of this study was to compare assessment by the new software with conventional assessment by human raters. The software was developed using data from the Lifelines Cohort Study and validated in an independent cohort of the Prevention of Renal and Vascular End Stage Disease (PREVEND) study. The total study population included 1,761 persons: 54% men; mean age (SD), 58 (10) years. All RFFT protocols were assessed by the new software and two independent human raters (criterion standard). The mean number of unique designs (SD) was 81 (29) and the median number of perseverative errors (interquartile range) was 9 (4 to 16). The intraclass correlation coefficient (ICC) between the computerized and human assessment was 0.994 (95%CI, 0.988 to 0.996; p<0.001) and 0.991 (95%CI, 0.990 to 0.991; p<0.001) for the number of unique designs and perseverative errors, respectively. The mean difference (SD) between the computerized and human assessment was -1.42 (2.78) and +0.02 (1.94) points for the number of unique designs and perseverative errors, respectively. This was comparable to the agreement between two independent human assessments: ICC, 0.995 (0.994 to 0.995; p<0.001) and 0.985 (0.982 to 0.988; p<0.001), and mean difference (SD), -0.44 (2.98) and +0.56 (2.36) points for the number of unique designs and perseverative errors, respectively. We conclude that the agreement between the computerized and human assessment was very high and comparable to the agreement between two independent human assessments. Therefore, the software is an accurate tool for the assessment of performance on the RFFT.

Statin use and cognitive function: population-based observational study with long-term follow-up.

We aimed to evaluate the association between statin use and cognitive function. Cognitive function was measured with the Ruff Figural Fluency Test (RFFT; worst score, 0; best score, 175 points) and the Visual Association Test (VAT; low performance, 0-10; high performance, 11-12 points) in an observational study that included 4,095 community-dwelling participants aged 35-82 years. Data on statin use were obtained from a computerized pharmacy database. Analysis were done for the total cohort and subsamples matched on cardiovascular risk (N = 1232) or propensity score for statin use (N = 3609). We found that a total of 904 participants (10%) used a statin. Statin users were older than non-users: mean age (SD) 61 (10) vs. 52 (11) years (p < 0.001). The median duration of statin use was 3.8 (interquartile range, 1.6-4.5) years. Unadjusted, statin users had worse cognitive performance than non-users. The mean RFFT score (SD) in statin users and non-users was 58 (23) and 72 (26) points, respectively (p < 0.001). VAT performance was high in 261 (29%) statin users and 1351 (43%) non-users (p < 0.001). However, multiple regression analysis did not show a significant association of RFFT score with statin use (B, -0.82; 95%CI, -2.77 to 1.14; p = 0.41) nor with statin solubility, statin dose or duration of statin use. Statin users with high doses or long-term use had similar cognitive performance as non-users. This was found in persons with low as well as high cardiovascular risk, and in younger as well as older subjects. Also, the mean RFFT score per quintile of propensity score for statin use was comparable for statin users and non-users. Similar results were found for the VAT score as outcome measure. In conclusion, statin use was not associated with cognitive function. This was independent of statin dose or duration of statin use.