The Prognostic Accuracy of Clinical Judgment Versus a Validated Frailty Screening Instrument in Older Patients at the Emergency Department: Findings of the AmsterGEM Study.

STUDY OBJECTIVE: To compare the prognostic accuracy of clinical judgment for frailty in older patients at the emergency department with a validated screening instrument and patient-perceived frailty. METHODS: A prospective cohort study in patients 70 years of age and older in 2 Dutch EDs with a follow-up of 3 months. A dichotomous question was asked to the physician and patient: "Do you consider the patient / yourself to be frail?" The Identification of Seniors At Risk-Hospitalized Patients (ISAR-HP) was used as a validated screening instrument. The primary composite outcome consisted of either functional decline, institutionalization, or mortality. RESULTS: A total of 736 patients were included. The physician identified 59% as frail, compared with 49% by ISAR-HP and 43% by patients themselves. The level of agreement was fair (Fleiss Kappa, 0.31). After 3 months, 31% of the patients experienced at least 1 adverse health outcome. The sensitivity was 79% for the physician, 72% for ISAR-HP, 61% for the patient, and 48% for all 3 combined. The specificity was 50% for the physician, 63% for ISAR-HP, 66% for the patient, and 85% for all 3 positive. The highest positive likelihood ratio was 3.03 (physician, ISAR-HP, patient combined), and the lowest negative likelihood ratio was 0.42 (physician). The areas under the receiver operating curves were all poor: 0.68 at best for ISAR-HP. CONCLUSION: Clinical judgment for frailty showed fair agreement with a validated screening instrument and patient-perceived frailty. All 3 instruments have poor prognostic accuracy, which does not improve when combined. These findings illustrate the limited prognostic value of clinical judgment as a frailty screener in older patients at the ED.

Nutrient Intake and Muscle Measures in Geriatric Outpatients.

OBJECTIVE: Low muscle mass and muscle function are associated with adverse health outcomes in older adults. This study examined nutrient intake as a potential contributing factor for low muscle mass, muscle strength, and muscle power in geriatric outpatients. METHOD: This cross-sectional study included geriatric outpatients (n = 58, 38 female) with a mean age of 77.2 ± 9.0 years referred to the Falls and Balance outpatient clinic between December 2017 and January 2019. Nutrient intake (macro- and micronutrients) was examined using a 3-day food diary. Energy-adjusted nutrient intake was calculated using the residual method. Sex-standardized muscle measures included muscle mass assessed using bioelectrical impedance analysis (skeletal muscle mass [SMM in kilograms], SMM index [SMM/height2 in kg/m2], and SMM/body mass index), handgrip strength (muscle strength) assessed using a dynamometer, and chair-stand test (muscle power). Univariate linear regression analyses were used to examine the associations of nutrient intake with muscle measures adjusted for age and body weight. A Bonferroni correction was applied to account for multiple testing (p < 0.001). RESULTS: Higher energy, iodine, and folate intake were associated with higher muscle mass, and higher folate intake was associated with higher muscle strength (p < 0.05). After Bonferroni correction, none of the nutrient intakes remained statistically significant. None of the other nutrients was associated with muscle measures. CONCLUSIONS: Only a few nutrients were associated with muscle measures. Nutrient intake appears to be more related to muscle mass than muscle strength and muscle power in geriatric outpatients.

The Accuracy of Four Frequently Used Frailty Instruments for the Prediction of Adverse Health Outcomes Among Older Adults at Two Dutch Emergency Departments: Findings of the AmsterGEM Study.

STUDY OBJECTIVE: Older adults presenting to the emergency department (ED) are at high risk of adverse health outcomes. This study aimed to evaluate the accuracy of 4 frequently used screening instruments for the prediction of adverse health outcomes among older adults in the ED. METHODS: This was a prospective cohort study in patients ≥70 years of age presenting to the ED in 2 hospitals in the Netherlands. Screening instruments included the acutely presenting older patient screening program (APOP) (providing 2 risk scores-functional decline [APOP1] and mortality [APOP2]), the International Resident Assessment Instrument Emergendy Department screener (InterRAI ED), the Identification of Seniors At Risk-Hospitalized Patients (ISAR-HP), and the safety management system (VMS). The primary outcome measure was a composite outcome encompassing functional decline, institutionalization, and mortality at 3 months after ED presentation. Other follow-up time points were 1 and 6 months. Analyses were performed to assess prognostic accuracy. RESULTS: In total, 889 patients were included. After 3 months, 267 (31%) patients experienced at least 1 adverse outcome. The positive likelihood ratio ranged from 1.67 (VMS) to 3.33 (APOP1), and the negative likelihood ratio ranged from 0.41 (ISAR-HP) to 0.88 (APOP2). Sensitivity ranged from 17% (APOP2) to 74% (ISAR-HP), and specificity ranged from 63% (ISAR-HP) to 94% (APOP2). The area under the curve ranged from 0.62 (APOP2) to 0.72 (APOP1 and ISAR-HP). Calibration was reasonable for APOP1 and VMS. The prognostic accuracy was comparable across all outcomes and at all follow-up time points. CONCLUSION: The frailty screening instruments assessed in this study showed poor to moderate prognostic accuracy, which brings into question their usability in the prediction of adverse health outcomes among older adults who present to the ED.

Mortality Risk and Its Association with Geriatric Domain Deficits in Older Outpatients: The Amsterdam Ageing Cohort.

INTRODUCTION: In older patients, life expectancy is determined by a complex interaction of multiple geriatric domains. A comprehensive geriatric assessment (CGA) captures different geriatric domains. Yet, if and how components of the CGA are related to mortality in an outpatient geriatric setting is unknown. In the Amsterdam Ageing Cohort, we therefore studied distribution and accumulation of geriatric domain deficits in relation to mortality. METHODS: All patients received a CGA as part of standard care, independent of referral reason. We summarized deficits on the CGA, using predefined cutoffs, in 5 geriatric domains: somatic, mental, nutritional, physical, and social domain. Information on mortality was obtained from the Dutch municipal register. We used age- and sex-adjusted Cox proportional hazards analyses to relate the separate domains and accumulation of impaired domains to overall mortality. RESULTS: From the 1,055 geriatric outpatients (53% female; age 79 ± 7 years), 172 patients (16%) had died after 1.7 ± 1.1 years. In 626 patients (59%), 3 or more domains were impaired. All domains were independently associated with mortality, with the highest hazard for the somatic domain (HR 3.7 [1.7-8.0]) and the lowest hazard for the mental domain (HR 1.5 [1.1-12.0]). In addition, accumulation of impaired domains showed a gradually increased mortality risk, ranging from HR 2.2 (0.8-6.1) for 2 domains to HR 9.6 (3.7-24.7) for all 5 domains impaired. CONCLUSIONS: This study provides evidence that impairment in multiple geriatric domains is highly prevalent and independently and cumulatively associated with mortality in an outpatient geriatric setting.

Robustness of In-Laboratory and Daily-Life Gait Speed Measures over One Year in High Functioning 61- to 70-Year-Old Adults.

INTRODUCTION: Gait speed is a simple and safe measure with strong predictive value for negative health outcomes in clinical practice, yet in-laboratory gait speed seems not representative for daily-life gait speed. This study aimed to investigate the interrelation between and robustness of in-laboratory and daily-life gait speed measures over 12 months in 61- to 70-year-old adults. METHODS: Gait speed was assessed in laboratory through standardized stopwatch tests and in daily life by 7 days of trunk accelerometry in the PreventIT cohort, at baseline, and after 6 and 12 months. The interrelation was investigated using Pearson's correlations between gait speed measures at each time point. For robustness, changes over time and variance components were assessed by ANOVA and measurement agreement over time by Bland-Altman analyses. RESULTS: Included were 189 participants (median age 67 years [interquartile range: 64-68], 52.2% females). In-laboratory and daily-life gait speed measures showed low correlations (Pearson's r = 0.045-0.455) at each time point. Moreover, both in-laboratory and daily-life gait speed measures appeared robust over time, with comparable and smaller within-subject than between-subject variance (range 0.001-0.095 m/s and 0.032-0.397 m/s, respectively) and minimal differences between measurements over time (Bland-Altman) with wide limits of agreement (standard deviation of mean difference range: 0.12-0.34 m/s). DISCUSSION/CONCLUSION: In-laboratory and daily-life gait speed measures show robust assessments of gait speed over 12 months and are distinct constructs in this population of high-functioning adults. This suggests that (a combination of) both measures may have added value in predicting health outcomes.

The use of a portable metabolic monitoring device for measuring RMR in healthy adults.

Objective measurement of RMR may be important for optimal nutritional care but is hindered by the price and practicality of the metabolic monitoring device. This study compared two metabolic monitoring devices for measuring RMR and VO2 and compared the measured RMR with the predicted RMR calculated from equations. RMR was measured using QUARK RMR (reference device) and Fitmate GS (COSMED) in a random order for 30 min, each on fasted participants. In total, sixty-eight adults participated (median age 22 years, interquartile range 21-32). Pearson correlation showed that RMR (r 0·86) and VO2 (r 0·86) were highly correlated between the two devices (P < 0·05). Intraclass correlation coefficients (ICC) showed good relative agreements regarding RMR (ICC = 0·84) and VO2 (ICC = 0·84) (P < 0·05). RMR measured by QUARK RMR was significantly higher (649 (sd 753) kJ/d) than Fitmate GS. Equations significantly overpredicted RMR. Accurate RMR (i.e. within ±10 % of the RMR measured by QUARK RMR) was found among 38 % of the participants for Fitmate GS and among 46-68 % depending on the equations. Bland-Altman analysis showed a low absolute agreement with QUARK RMR at an individual level for both Fitmate GS (limits of agreement (LOA): -828 to +2125 kJ/d) and equations (LOA ranged from -1979 to +1879 kJ/d). In conclusion, both Fitmate GS and predictive equations had low absolute agreements with QUARK RMR at an individual level. Therefore, these limitations should be considered when determining RMR using Fitmate GS or equations.

Malnutrition is associated with dynamic physical performance.

BACKGROUND: Malnutrition and poor physical performance are both conditions that increase in prevalence with age; however, their interrelation in a clinically relevant population has not been thoroughly studied. AIMS: This study aimed to determine the strength of the association between malnutrition and measures of both static and dynamic physical performance in a cohort of geriatric outpatients. METHODS: This cross-sectional study included 286 older adults (mean age 81.8, SD 7.2 years, and 40.6% male) who were referred to geriatric outpatient mobility clinics. The presence of malnutrition was determined using the Short Nutritional Assessment Questionnaire (SNAQ, cut-off ≥ 2 points). Measures of dynamic physical performance included timed up and go (TUG), 4-m walk test, and chair stand test (CST). Static performance encompassed balance tests and hand grip strength (HGS). Physical performance was standardized into sex-specific Z-scores. The association between malnutrition and each individual measure of physical performance was assessed using linear regression analysis. RESULTS: 19.9% of the cohort was identified as malnourished. Malnutrition was most strongly associated with CST and gait speed; less strong but significant associations were found between malnutrition and TUG. There was no significant association between malnutrition and HGS or balance. DISCUSSION: Physical performance was associated with malnutrition, specifically, dynamic rather than static measures. This may reflect muscle power being more impacted by nutritional status than muscle strength; however, this needs to be further addressed. CONCLUSIONS: Malnutrition is associated with dynamic physical performance in geriatric outpatients, which should inform diagnosis and treatment/prevention strategies.

Erythrocyte sedimentation rate and albumin as markers of inflammation are associated with measures of sarcopenia: a cross-sectional study.

BACKGROUND: Chronic inflammation is considered to affect physical performance, muscle strength and muscle mass, i.e. measures of sarcopenia. We need to identify a marker of inflammation that is univocally associated with measures of sarcopenia. We aimed to associate three markers of inflammation, erythrocyte sedimentation rate, albumin and white blood cell count, with measures of sarcopenia in geriatric outpatients. METHODS: Data from the Centre Of Geriatrics Amsterdam cohort was used. Geriatric outpatients at the VU university medical centre in Amsterdam were recruited based on referral between January 1st 2014 and the 31st of December 2015. Erythrocyte sedimentation rate, albumin and white blood cell count were assessed from venous blood samples. Measures of sarcopenia included physical performance by measuring gait speed with the 4 meter walk test, duration of the timed up and go test and of the chair stand test, muscle strength by assessing handgrip strength using handheld dynamometry and skeletal muscle mass by performing bioelectrical impedance analysis. Multivariable linear regression analyses were performed to assess the associations between erythrocyte sedimentation rate, albumin, white blood cell count and measures of sarcopenia. RESULTS: A total of 442 patients (mean age 80.8 years, SD 6.7, 58.1% female) were included. A higher erythrocyte sedimentation rate was significantly associated with lower gait speed (ß = - 0.005; 95% CI = - 0.007, - 0.003), longer duration of timed up and go test (Ln ß = 0.006; 95% CI = 0.003, 0.010), longer duration of chair stand test (Ln ß = 0.005; 95% CI = 0.002, 0.008), lower handgrip strength (ß = - 0.126; 95% CI = - 0.189, - 0.063) and lower relative skeletal muscle mass (ß = - 0.179; 95% CI = - 0.274, - 0.084). Lower albumin levels were significantly associated with lower gait speed (ß = - 0.020; 95% CI = - 0.011, - 0.028) and handgrip strength (ß = - 0.596; 95% CI = - 0.311, - 0.881). Associations remained significant after adjustment for age, sex and number of morbidities. No significant associations were found for white blood cell count and measures of sarcopenia. CONCLUSIONS: In geriatric outpatients, erythrocyte sedimentation rate was associated with all three measures of sarcopenia, underpinning the potential role of inflammation in sarcopenia.

Knee extension strength measurements should be considered as part of the comprehensive geriatric assessment.

BACKGROUND: Comprehensive geriatric assessment (CGA) generally includes handgrip strength (HGS) as a measure of overall muscle strength that is associated with various health characteristics in geriatric outpatients. Whether this is also true for knee extension strength (KES) is yet unknown. This study aims to compare the associations between health characteristics from the CGA with both HGS and KES in geriatric outpatients. METHODS: Data were retrieved from a cross-sectional study. A total of 163 community-dwelling older adults referred to a geriatric outpatient clinic of a middle-sized teaching hospital were included. Health characteristics included physical, nutritional, social, psychological, diseases, cognitive, and behavioural factors. HGS and KES were assessed three times for each limb and the best performance was used for analysis. Sex-specific z-scores of HGS and KES were used to allow comparison of effect estimates. Associations between health characteristics with standardized HGS and KES were analysed with linear regression adjusted for age, sex and further adjustment for standardized KES (for model of HGS) or standardized HGS (for model of KES). RESULTS: Physical, nutritional and psychological health characteristics were positively associated with both HGS and KES after adjustment for age and sex, with overall stronger associations with KES compared to HGS. All significant associations with HGS were lost after further adjustment for KES; significant associations with KES remained after further adjustment for HGS, except for nutritional characteristics. CONCLUSIONS: Stronger associations of health characteristics with KES compared to HGS indicate its additional value and therefore inclusion of KES in the CGA is recommended.

Blood pressure change does not associate with Center of Pressure movement after postural transition in geriatric outpatients.

BACKGROUND: Orthostatic hypotension (OH), a blood pressure drop after postural change, is associated with impaired standing balance and falls in older adults. This study aimed to assess the association between blood pressure (BP) and a measure of quality of standing balance, i.e. Center of Pressure (CoP) movement, after postural change from supine to standing position in geriatric outpatients, and to compare CoP movement between patients with and without OH. METHODS: In a random subgroup of 75 consecutive patients who were referred to a geriatric outpatient clinic, intermittent BP measurements were obtained simultaneously with CoP measurements in mediolateral and anterior-posterior direction directly after postural change during 3 min of quiet stance with eyes open on a force plate. Additional measurements of continuous BP were available in n = 38 patients. Associations between BP change during postural change and CoP movement were analyzed using Spearman correlation. Mann-Whitney-U tests were used to compare CoP movement between patients with OH and without OH, in which OH was defined as a BP drop exceeding 20 mmHg of systolic BP (SBP) and/or 10 mmHg of diastolic BP (DBP) within 3 min after postural change. RESULTS: OH measured intermittently was found in 8 out of 75 (11%) and OH measured continuously in 22 out of 38 patients (57.9%). BP change did not associate with CoP movement. CoP movement did not differ significantly between patients with and without OH. CONCLUSIONS: Results do not underpin the added value of CoP movement measurements in diagnosing OH in a clinical setting. Neither could we identify the role of CoP measurements in the understanding of the relation between OH and impaired standing balance.

Resilience to cognitive impairment in the oldest-old: design of the EMIF-AD 90+ study.

BACKGROUND: The oldest-old (subjects aged 90 years and older) population represents the fastest growing segment of society and shows a high dementia prevalence rate of up to 40%. Only a few studies have investigated protective factors for cognitive impairment in the oldest-old. The EMIF-AD 90+ Study aims to identify factors associated with resilience to cognitive impairment in the oldest-old. In this paper we reviewed previous studies on cognitive resilience in the oldest-old and described the design of the EMIF-AD 90+ Study. METHODS: The EMIF-AD 90+ Study aimed to enroll 80 cognitively normal subjects and 40 subjects with cognitive impairment aged 90 years or older. Cognitive impairment was operationalized as amnestic mild cognitive impairment (aMCI), or possible or probable Alzheimer's Disease (AD). The study was part of the European Medical Information Framework for AD (EMIF-AD) and was conducted at the Amsterdam University Medical Centers (UMC) and at the University of Manchester. We will test whether cognitive resilience is associated with cognitive reserve, vascular comorbidities, mood, sleep, sensory system capacity, physical performance and capacity, genetic risk factors, hallmarks of ageing, and markers of neurodegeneration. Markers of neurodegeneration included an amyloid positron emission tomography, amyloid ß and tau in cerebrospinal fluid/blood and neurophysiological measures. DISCUSSION: The EMIF-AD 90+ Study will extend our knowledge on resilience to cognitive impairment in the oldest-old by extensive phenotyping of the subjects and the measurement of a wide range of potential protective factors, hallmarks of aging and markers of neurodegeneration. TRIAL REGISTRATION: Nederlands Trial Register NTR5867 . Registered 20 May 2016.

Standing Up Slowly Antagonises Initial Blood Pressure Decrease in Older Adults with Orthostatic Hypotension.

BACKGROUND: Orthostatic hypotension (OH) is common in older adults and associated with increased morbidity and mortality, loss of independence and high health-care costs. Standing up slowly is a recommended non-pharmacological intervention. However, the effectiveness of this advice has not been well studied. OBJECTIVES: The aim of this study was to investigate whether standing up slowly antagonises posture-related blood pressure (BP) decrease in a clinically relevant population of geriatric outpatients. METHODS: In this cross-sectional study, 24 community-dwelling older adults referred to a geriatric outpatient clinic and diagnosed with OH were included. BP was measured continuously during 3 consecutive transitions from supine to standing position during normal, slow and fast transition. RESULTS: The relative BP decrease at 0-15 s after slow transition was significantly lower than after normal transition (p = 0.003 for both systolic BP and diastolic BP) and fast transition (p = 0.045 for systolic BP; diastolic BP: non-significant). The relative diastolic BP decrease at 60-180 s after normal transition was significantly lower than after fast transition (p = 0.029). CONCLUSION: Standing up slowly antagonises BP decrease predominantly during the first 15 s of standing up in a clinically relevant population of geriatric outpatients diagnosed with OH. Results support the non-pharmacological intervention in clinical practice to counteract OH.

The Impact of Different Diagnostic Criteria on the Prevalence of Sarcopenia in Healthy Elderly Participants and Geriatric Outpatients.

BACKGROUND: A consensus on the diagnostic criteria for sarcopenia, a common syndrome in the elderly, has not been reached yet. Prevalence rates vary between studies due to the use of different criteria encompassing different measures, correction factors and cutoff points. OBJECTIVE: This study compared prevalence rates of sarcopenia using nine sets of diagnostic criteria applied in two different elderly populations. METHODS: The study population encompassed 308 healthy elderly participants (152 males, 156 females; mean age 74 years) and 123 geriatric outpatients (54 males, 69 females; mean age 81 years). Diagnostic criteria included relative muscle mass, absolute muscle mass, muscle strength and physical performance. RESULTS: Prevalence rates of sarcopenia varied between 0 and 15% in healthy elderly participants and between 2 and 34% in geriatric outpatients. CONCLUSION: This study clearly demonstrates the dependency of sarcopenia prevalence rates on the applied diagnostic criteria.

Orthostatic hypotension and its association with cerebral small vessel disease in a memory clinic population.

BACKGROUND: Orthostatic hypotension (OH), an impaired blood pressure (BP) response to postural change, has been associated with cognitive decline and dementia, possibly through cerebral small vessel disease (CSVD). We hypothesized that longer duration of BP drop and a larger BP drop is associated with increased risk of CSVD. METHODS: This cross-sectional study included 3971 memory clinic patients (mean age 68 years, 45% female, 42% subjective cognitive complaints, 17% mild cognitive impairment, 41% dementia) from the Amsterdam Ageing Cohort and Amsterdam Dementia Cohort. Early OH (EOH) was defined as a drop in BP of ±20 mmHg systolic and/or 10 mmHg diastolic only at 1 min after standing, and delayed/prolonged OH (DPOH) at 1 and/or 3 min after standing. Presence of CSVD [white matter hyperintensities (WMH), lacunes, microbleeds] was assessed with MRI ( n  = 3584) or CT brain (n = 389). RESULTS: The prevalence of early OH was 9% and of delayed/prolonged OH 18%. Age- and sex-adjusted logistic regression analyses showed that delayed/prolonged OH, but not early OH, was significantly associated with a higher burden of WMH (OR, 95%CI: 1.21, 1.00-1.46) and lacunes (OR, 95%CI 1.34, 1.06-1.69), but not microbleeds (OR, 95%CI 1.22, 0.89-1.67). When adjusting for supine SBP, these associations attenuated (ORs, 95%CI for WMH 1.04, 0.85-1.27; for lacunes 1.21, 0.91-1.62; for microbleeds 0.95, 0.68-1.31). A larger drop in SBP was associated with increased risk of WMH and microbleeds, however, when adjusted for supine SBP, this effect diminished. CONCLUSIONS: Among memory clinic patients, DPOH is more common than EOH. While longer duration and larger magnitude of BP drop coincided with a higher burden of CSVD, these associations were largely explained by high supine BP.

Patterns of Objectively Measured Sedentary Behavior and Physical Activity and Their Association with Changes in Physical and Functional Performance in Geriatric Rehabilitation Inpatients.

OBJECTIVES: To examine whether The Ending PyJama (PJ) Paralysis campaign, focused on increasing in-hospital physical activity, affects objectively measured sedentary behavior and physical activity patterns and if these are associated with changes in physical and functional performance in geriatric rehabilitation inpatients. DESIGN: Quasi-experimental study. SETTING AND PARTICIPANTS: Within the REStORing health of acutely unwell adulTs (RESORT) observational, longitudinal cohort of geriatric rehabilitation inpatients, the Ending PJ Paralysis campaign was implemented on 2 out of 4 wards. METHODS: Objectively measured sedentary behavior and physical activity were measured by an inertial sensor (ActivPAL4) for 1 week, comparing control (non-PJ) and intervention (PJ) groups using linear mixed models. Mean sedentary behavior and physical activity measures and their association with physical and functional performance changes were investigated by linear regression analyses, stratified by low vs high performance at admission using the median as a cut-off. RESULTS: A total of 145 (n = 68 non-PJ and n = 77 PJ) inpatients with a mean age of 83.0 (7.7) years (55.9% female inpatients) were included. The median nonupright time was 23.1 [22.1-23.6] and 23.0 [21.8-23.6] hours/day for non-PJ and PJ groups, respectively. Objectively measured sedentary behavior and physical activity measures did not significantly change over measurement days and were independent of the Ending PJ Paralysis campaign. For inpatients with low performance at admission, lower sedentary behavior [B(SE) -0.013 (0.005) to -0.157 (0.045), P < .01] and higher physical activity [B(SE) 0.033 (0.007) to 0.814 (0.200), P < .01] measures were associated with improved physical performance. In addition, lower sedentary behaviour [B(SE) = -0.058 (0.024), P < .05 and higher physical activity [B (SE) 0.060 (0.024) to 0.683 (0.182), P < .05] were associated with improved instrumental functional performance. CONCLUSIONS AND IMPLICATIONS: In geriatric rehabilitation inpatients, the Ending PJ Paralysis campaign did not affect objectively measured sedentary behavior and physical activity patterns. Lower mean sedentary behaviour and higher physical activity measures were associated with improved physical and functional performance in inpatients with low performance.

Applying systems thinking to unravel the mechanisms underlying orthostatic hypotension related fall risk.

Orthostatic hypotension (OH) is an established and common cardiovascular risk factor for falls. An in-depth understanding of the various interacting pathophysiological pathways contributing to OH-related falls is essential to guide improvements in diagnostic and treatment opportunities. We applied systems thinking to multidisciplinary map out causal mechanisms and risk factors. For this, we used group model building (GMB) to develop a causal loop diagram (CLD). The GMB was based on the input of experts from multiple domains related to OH and falls and all proposed mechanisms were supported by scientific literature. Our CLD is a conceptual representation of factors involved in OH-related falls, and their interrelatedness. Network analysis and feedback loops were applied to analyze and interpret the CLD, and quantitatively summarize the function and relative importance of the variables. Our CLD contains 50 variables distributed over three intrinsic domains (cerebral, cardiovascular, and musculoskeletal), and an extrinsic domain (e.g., medications). Between the variables, 181 connections and 65 feedback loops were identified. Decreased cerebral blood flow, low blood pressure, impaired baroreflex activity, and physical inactivity were identified as key factors involved in OH-related falls, based on their high centralities. Our CLD reflects the multifactorial pathophysiology of OH-related falls. It enables us to identify key elements, suggesting their potential for new diagnostic and treatment approaches in fall prevention. The interactive online CLD renders it suitable for both research and educational purposes and this CLD is the first step in the development of a computational model for simulating the effects of risk factors on falls.

Chronic renal failure is accompanied by endothelial activation and a large increase in microparticle numbers with reduced procoagulant capacity.

BACKGROUND: In patients with chronic renal failure (CRF), cardiovascular disease is the leading cause of increased morbidity and mortality. We hypothesized a role for endothelial activation and microparticle (MP) numbers and procoagulant activity in the pre-thrombotic state of these patients. METHODS: We analysed blood samples of 27 patients with CRF [8 chronic kidney disease Stage 4 (CKD4), 9 peritoneal dialysis (PD) and 10 haemodialysis (HD), samples taken before and after HD] and 10 controls. Degree and nature of endothelial activation were assessed by measuring mature von Willebrand factor (vWF) and vWF propeptide levels. Cellular MPs were characterized by flow cytometry and MP-specific thrombin generation (TG) measurements. RESULTS: CRF was accompanied by chronic (CKD4 and PD) or acute (HD) endothelial activation. Patients with CRF had substantially higher MP numbers than controls (median 9400 versus 4350×10(6)/L, P=0.001), without significant differences between the treatment subgroups or between pre- and post-HD. The vast majority of MPs were platelet derived. Of the minor populations, endothelial MPs and tissue factor-bearing MPs were more abundant in CRF. MPs were procoagulant, but the increase in numbers was not reflected in a proportional increase in MP-specific TG. CONCLUSION: Renal failure is accompanied by endothelial activation of a different nature in CKD4 and PD patients compared to HD patients, and results in all subgroups in an increase of mainly platelet-derived MPs that appear to be less procoagulant than in other disease states, possibly because of the uraemic functional defect of their cellular source.

Orthostatic hypotension and mortality risk in geriatric outpatients: the impact of duration and magnitude of the blood pressure drop.

INTRODUCTION: Orthostatic hypotension is a common condition associated with an increased mortality risk. This study investigates this association specifically in geriatric outpatients and additionally focuses on the duration and magnitude of orthostatic hypotension. METHODS: In this observational prospective cohort study with geriatric outpatients from the Amsterdam Ageing cohort, we differentiated orthostatic hypotension in early orthostatic hypotension (EOH) and delayed/prolonged orthostatic hypotension (DPOH). The magnitude of drop in both SBP and DBP after either 1 or 3 min was quantified. Mortality data was obtained from the Dutch municipal register. Cox proportional hazard models were used to determine the association between orthostatic hypotension and mortality, adjusted for sex and age (model 1), additionally adjusted for orthostatic hypotension-inducing drugs + SBP (model 2) and the presence of cardiovascular disease and diabetes (model 3). Stratified analyses in patients with geriatric deficits were performed. RESULTS: We included 1240 patients (mean age 79.4 ±â€Š6.9 years, 52.6% women). Prevalence of orthostatic hypotension was 443 (34.9%); 148 (11.9%) patients had EOH and 285 (23%) DPOH. DPOH was associated with a higher mortality risk [hazard ratio, 95% CI 1.69 (1.28-2.22)] whereas EOH was not associated with mortality risk. This association did not differ in patients with geriatric deficits. Furthermore, the magnitude of drop in both SBP and DBP was associated with a higher mortality risk. CONCLUSION: The presence of DPOH and the magnitude of both systolic and diastolic orthostatic hypotension are related to an increased mortality risk in geriatric outpatients. Whether the duration of orthostatic hypotension and magnitude of the drop in blood pressure is causally related to mortality risk or whether it is a sign of decreased resilience remains to be elucidated.

Polypharmacy, comorbidity and frailty: a complex interplay in older patients at the emergency department.

PURPOSE: Older adults at the emergency department (ED) with polypharmacy, comorbidity, and frailty are at risk of adverse health outcomes. We investigated the association of polypharmacy with adverse health outcomes, in relation to comorbidity and frailty. METHODS: This is a prospective cohort study in ED patients ≥ 70 years. Non-polypharmacy was defined as 0-4 medications, polypharmacy 5-9 and excessive polypharmacy ≥ 10. Comorbidity was classified by the Charlson comorbidity index (CCI). Frailty was defined by the Identification of Seniors At Risk-Hospitalized Patients (ISAR-HP) score. The primary outcome was 3-month mortality. Secondary outcomes were readmission to an ED/hospital ward and a self-reported fall < 3 months. The association between polypharmacy, comorbidity and frailty was analyzed by logistic regression. RESULTS: 881 patients were included. 43% had polypharmacy and 18% had excessive polypharmacy. After 3 months, 9% died, 30% were readmitted, and 21% reported a fall. Compared with non-polypharmacy, the odds ratio (OR) for mortality ranged from 2.62 (95% CI 1.39-4.93) in patients with polypharmacy to 3.92 (95% CI 1.95-7.90) in excessive polypharmacy. The OR weakened after adjustment for comorbidity: 1.80 (95% CI 0.92-3.52) and 2.32 (95% CI 1.10-4.90). After adjusting for frailty, the OR weakened to 2.10 (95% CI 1.10-4.00) and OR 2.40 (95% CI 1.15-5.02). No significant association was found for readmission or self-reported fall. CONCLUSIONS: Polypharmacy is common in older patients at the ED. Polypharmacy, and especially excessive polypharmacy, is associated with an increased risk of mortality. The observed association is complex given the confounding effect of comorbidity and frailty.

Slowing: A Vascular Geriatric Syndrome?

OBJECTIVES: This study aimed to investigate the interrelation between slowing in walking, thinking and mood, and their relationship with cerebral small vessel disease (CSVD) in a geriatric population. DESIGN: Cross-sectional study. SETTING AND PARTICIPANTS: 566 geriatric outpatients from the Amsterdam Aging Cohort (49% female; age 79 ±6 years), who visited the Amsterdam UMC geriatric outpatient memory clinic. METHODS: Patients underwent a comprehensive geriatric assessment, brain imaging, and a neuropsychological assessment as part of medical care. Three slowing aspects were investigated: gait speed, processing speed, and apathy symptoms (higher scores indicating more advanced slowing). We visually rated CSVD [white matter hyperintensities (WMHs), strategic lacunes, and microbleeds] on brain imaging. RESULTS: Regression analyses showed that slowing in walking (gait speed) was associated with slowing in thinking [processing speed; ß = 0.35, 95% confidence interval (CI) 0.22, 0.48] and slowing in mood (apathy symptoms; ß = 0.21, 95% CI 0.13, 0.30), independent of important confounders. Large confluent areas of WMH (Fazekas 3) were associated with all slowing aspects: gait speed (ß = 0.49, 95% CI 0.28, 0.71), processing speed (ß = 0.36, 95% CI 0.19, 0.52) and apathy symptoms (ß = 0.30, 95% CI 0.09, 0.51). In addition, in patients with more slowing aspects below predefined cutoffs, severe WMH was more common. Presence of ≥3 microbleeds was associated with apathy symptoms (ß = 0.39, 95% CI 0.12, 0.66), whereas lacunes were not associated with slowing. CONCLUSIONS AND IMPLICATIONS: This study provides evidence that slowing in walking, thinking, and mood are closely related and associated with CSVD. This phenotype or geriatric syndrome could be helpful to identify and characterize patients with CSVD.