Validation of the ADFICE_IT Models for Predicting Falls and Recurrent Falls in Geriatric Outpatients.

OBJECTIVES: Before being used in clinical practice, a prediction model should be tested in patients whose data were not used in model development. Previously, we developed the ADFICE_IT models for predicting any fall and recurrent falls, referred as Any_fall and Recur_fall. In this study, we externally validated the models and compared their clinical value to a practical screening strategy where patients are screened for falls history alone. DESIGN: Retrospective, combined analysis of 2 prospective cohorts. SETTING AND PARTICIPANTS: Data were included of 1125 patients (aged ≥65 years) who visited the geriatrics department or the emergency department. METHODS: We evaluated the models' discrimination using the C-statistic. Models were updated using logistic regression if calibration intercept or slope values deviated significantly from their ideal values. Decision curve analysis was applied to compare the models' clinical value (ie, net benefit) against that of falls history for different decision thresholds. RESULTS: During the 1-year follow-up, 428 participants (42.7%) endured 1 or more falls, and 224 participants (23.1%) endured a recurrent fall (≥2 falls). C-statistic values were 0.66 (95% CI 0.63-0.69) and 0.69 (95% CI 0.65-0.72) for the Any_fall and Recur_fall models, respectively. Any_fall overestimated the fall risk and we therefore updated only its intercept whereas Recur_fall showed good calibration and required no update. Compared with falls history, Any_fall and Recur_fall showed greater net benefit for decision thresholds of 35% to 60% and 15% to 45%, respectively. CONCLUSIONS AND IMPLICATIONS: The models performed similarly in this data set of geriatric outpatients as in the development sample. This suggests that fall-risk assessment tools that were developed in community-dwelling older adults may perform well in geriatric outpatients. We found that in geriatric outpatients the models have greater clinical value across a wide range of decision thresholds compared with screening for falls history alone.

Association of estimated glomerular filtration rate with muscle function in older persons who have fallen.

Background: studies suggest that estimated glomerular filtration rate (eGFR) is less reliable in older persons and that a low serum-creatinine might reflect reduced muscle mass rather than high kidney function. This study investigates the possible relationship between eGFR and multiple elements of physical performance in older fallers. Methods: baseline data of the IMPROveFALL-study were examined in participants ≥65 years. Serum-creatinine based eGFR was classified as normal (≥90 ml/min), mildly reduced (60-89 ml/min) or moderately-severely reduced (<60 ml/min). Timed-Up-and-Go-test and Five-Times-Sit-to-Stand-test were used to assess mobility; calf circumference and handgrip strength to assess muscle status. Ancova models adjusted for age, sex, Charlson comorbidity index and body mass index were performed. Results: a total of 578 participants were included. Participants with a normal eGFR had lower handgrip strength than those with a mildly reduced eGFR (-9.5%, P < 0.001) and those with a moderately-severely reduced eGFR (-6.3%, P = 0.033) with mean strengths of 23.4, 25.8 and 24.9 kg, respectively. Participants with a normal eGFR had a smaller calf circumference than those with a mildly reduced eGFR (35.5 versus 36.5 cm, P = 0.006). Mean time to complete the mobility tests did not differ. Conclusions: in this study we found that older fallers with an eGFR ≥ 90 ml/min had smaller calf circumference and up to 10% lower handgrip strength than those with a reduced eGFR. This lower muscle mass is likely to lead to an overestimation of kidney function. This outcome therefore supports the search for biomarkers independent of muscle mass to estimate kidney function in older persons.

Effectiveness of medication withdrawal in older fallers: results from the Improving Medication Prescribing to reduce Risk Of FALLs (IMPROveFALL) trial.

Objectives: To investigate the effect of withdrawal of fall-risk-increasing-drugs (FRIDs) versus 'care as usual' on reducing falls in community-dwelling older fallers. Design: Randomised multicentre trial Participants: Six hundred and twelve older adults who visited an Emergency Department (ED) because of a fall. Interventions: Withdrawal of FRIDs. Main Outcomes and Measures: Primary outcome was time to the first self-reported fall. Secondary outcomes were time to the second self-reported fall and to falls requiring a general practitioner (GP)-consultation or ED-visit. Intention-to-treat (primary) and a per-protocol (secondary) analysis were conducted. The hazard ratios (HRs) for time-to-fall were calculated using a Cox-regression model. Differences in cumulative incidence of falls were analysed using Poisson regression. Results: During 12 months follow-up, 91 (34%) control and 115 (37%) intervention participants experienced a fall; 35% of all attempted interventions were unsuccessful, either due to recurrence of the initial indication for prescribing, additional medication for newly diagnosed conditions or non-compliance. Compared to baseline, the overall percentage of users of ≥3 FRIDs at 12 months did not change in either the intervention or the control group. Our intervention did not have a significant effect on time to first fall (HR 1.17; 95% confidence interval 0.89­1.54), time to second fall (1.19; 0.78­1.82), time to first fall-related GP-consultation (0.66; 0.42­1.06) or time to first fall-related ED-visit (0.85; 0.43­1.68). Conclusion: In this population of complex multimorbid patients visiting an ED because of a fall, our single intervention of FRIDs-withdrawal was not effective in reducing falls. Trial Registration: Netherlands Trial Register NTR1593.

Cost-utility of medication withdrawal in older fallers: results from the improving medication prescribing to reduce risk of FALLs (IMPROveFALL) trial.

BACKGROUND: The use of Fall-Risk-Increasing-Drugs (FRIDs) has been associated with increased risk of falls and associated injuries. This study investigates the effect of withdrawal of FRIDs versus 'care as usual' on health-related quality of life (HRQoL), costs, and cost-utility in community-dwelling older fallers. METHODS: In a prospective multicenter randomized controlled trial FRIDs assessment combined with FRIDs-withdrawal or modification was compared with 'care as usual' in older persons, who visited the emergency department after experiencing a fall. For the calculation of costs the direct medical costs (intramural and extramural) and indirect costs (travel costs) were collected for a 12 month period. HRQoL was measured at baseline and at 12 months follow-up using the EuroQol-5D and Short Form-12 version 2. The change in EuroQol-5D and Short Form-12 scores over 12 months follow-up within the control and intervention groups was compared using the Wilcoxon Signed Rank test for continuous variables and the McNemar test for dichotomous variables. The change in scores between the control and intervention groups were compared using a two-way analysis of variance. RESULTS: We included 612 older persons who visited an emergency department because of a fall. The mean cost of the FRIDs intervention was €120 per patient. The total fall-related healthcare costs (without the intervention costs) did not differ significantly between the intervention group and the control group (€2204 versus €2285). However, the withdrawal of FRIDs reduced medication costs with a mean of €38 per participant. Furthermore, the control group had a greater decline in EuroQol-5D utility score during the 12-months follow-up than the intervention group (p = 0.02). The change in the Short Form-12 Physical Component Summary and Mental Component Summary scores did not differ significantly between the two groups. CONCLUSIONS: Withdrawal of FRID's in older persons who visited an emergency department due to a fall, did not lead to reduction of total health-care costs. However, the withdrawal of FRIDs reduced medication costs with a mean of €38 per participant in combination with less decline in HRQoL is an important result. TRIAL REGISTRATION: The trial is registered in the Netherlands Trial Register ( NTR1593 - October 1st 2008).

Physical performance and quality of life in single and recurrent fallers: data from the Improving Medication Prescribing to Reduce Risk of Falls study.

AIM: Although guidelines regarding falls prevention make a clear distinction between single and recurrent fallers, differences in functional status, physical performance, and quality of life in single and recurrent fallers have not been thoroughly investigated. Therefore, we investigated the differences in functional status, physical performance and health-related quality of life (HRQoL) between single and recurrent fallers. METHODS: From October 2008 to October 2011, 616 community-dwelling older adults who visited the emergency department as a result of a fall were enrolled. Physical performance was assessed with the Timed Up & Go (TUG) test, the Five Times Sit to Stand (FTSS) test, handgrip strength and the tandem stand test. Functional status was measured using the activities of daily living and instrumental activities of daily living scales. HRQoL was measured using the European Quality of Life five dimensions (EQ-5D), and the Short Form-12 version 2. A general linear model was used to compare the means of the scores. RESULTS: Recurrent falls in community-dwelling older adults were associated with poorer physical performance as measured by the TUG test (P < 0.001), FTSS test (P = 0.011), handgrip strength (P < 0.001) and tandem stand (P < 0.001), and lower HRQoL scores as measured by the EQ-5D (P = 0.006) and SF-12 (P = 0.006 and P = 0.012). CONCLUSION: The present findings provide further evidence that recurrent fallers have poorer physical performance and quality of life than single fallers. Recurrent falls might be a symptom of underlying disease and frailty, and reason for further assessment.

Circumstances leading to injurious falls in older men and women in the Netherlands.

BACKGROUND: Fall-induced injuries in persons aged 65 years and older are a major public health problem. Data regarding circumstances leading to specific injuries, such as traumatic brain injury (TBI) and hip fractures in older adults are scarce. OBJECTIVE: To investigate the activity distributions leading to indoor and outdoor falls requiring an emergency department (ED) visit, and those resulting in TBIs and hip fractures. PARTICIPANTS: 5880 older adults who visited the ED due to a fall. METHODS: Data is descriptive and stratified by age and gender. RESULTS: Two-thirds of all falls occurred indoors. However, there were higher proportions of outdoor falls at ages 65-79 years (48%). Walking up or down stairs (51%) and housekeeping (17%) were the most common indoor activities leading to a TBIs. Walking (42%) and sitting or standing (16%) was the most common indoor activities leading to a hip fracture. The most common outdoor activities were walking (61% for TBIs and 57% for hip fractures) and cycling (10% for TBIs and 24% for hip fractures). CONCLUSION: In the present study we found that the indoor activities distribution leading to TBIs and hip fractures differed. Notably, about half of the traumatic brain injuries and hip fractures in men and women aged 65-79 years occurred outdoors. This study provides new insights into patterns leading to injurious falls by age, gender and injury type, and may guide the targeting of falls prevention at specific activities and risk groups, including highly functional older men and women.

Vitamin D and physical performance in older men and women visiting the emergency department because of a fall: data from the improving medication prescribing to reduce risk of falls (IMPROveFALL) study.

OBJECTIVES: To investigate whether serum 25-hydroxy vitamin D (25(OH)D) is associated with physical performance in men and women. DESIGN: Cross-sectional. SETTING: Emergency departments (EDs) of five hospitals. PARTICIPANTS: Older adults who visited an ED because of a fall (N = 616). MEASUREMENTS: Physical performance was assessed using the Timed Up and Go Test, the Five Time Sit to Stand Test, handgrip strength, and the tandem stand test. Multivariate linear regression was used to assess the association between physical performance and log-transformed 25(OH)D concentration adjusted for potential confounders. RESULTS: In men, higher serum 25(OH)D concentration was significantly associated with better handgrip strength (regression coefficient (B) = 3.86, 95% confidence interval (CI) = 2.04-5.69), faster TUG time (B = -2.82, 95% CI = -4.91 to -0.73), and faster FTSS time (B = -3.39, 95% CI = -5.67 to -1.11). In women, higher serum 25(OH)D concentration was significantly associated with faster TUG time (B = -2.68, 95% CI = -4.87 to -0.49). CONCLUSION: A positive association was found between serum 25(OH)D level and physical performance in men and women. Intervention studies are needed of vitamin D-deficient older men and women to further investigate the effect of vitamin D supplementation in this group.

Single-nucleotide polymorphisms in the Toll-like receptor pathway increase susceptibility to infections in severely injured trauma patients.

BACKGROUND: Sepsis and subsequent multiple-organ failure are the predominant causes of late mortality in trauma patients. Susceptibility and response to infection is, in part, heritable. Single-nucleotide polymorphisms (SNPs) in Toll-like receptor (TLR) and cluster of differentiation 14 (CD14) genes of innate immunity may play a key role. The aim of this study was to assess if SNPs in TLR/CD14 predisposed trauma patients to infection. METHODS: A prospective cohort of trauma patients (age 18-80 years; injury severity score [ISS] ≥ 16) admitted to a Level I trauma center between January 2008 and April 2011 was genotyped for SNPs in TLR2 (T-16934A and R753Q), TLR4 (D299G and T399I), TLR9 (T-1486C and T-1237C), and CD14 (C-159T) using high-resolution melting analysis. Association of genotype with prevalence of positive culture findings (gram positive, gram negative, fungi), systemic inflammatory response syndrome (SIRS), sepsis, septic shock, and mortality was tested with χ(2) and logistic regression analysis. RESULTS: Genotyping was performed for 219 patients, of whom 51% developed positive culture findings in sputum, wounds, blood, or urine. SIRS developed in 64%, sepsis in 36%, and septic shock in 17%. The TLR2 T-16934A TA genotype increased the risk of a gram-positive infection (odds ratio, 2.816; 95% confidence interval, 1.249-6.348; p = 0.013) and SIRS (odds ratio, 2.386; 95% confidence interval, 1.011-5.632; p = 0.047). Trends were noted for TLR9 and CD14 SNPs but did not reach statistical significance. Sepsis and septic shock were unrelated to any of the SNPs studied. CONCLUSION: Aberrant functioning of the TLR/CD14 pathway of innate immunity changes the risk of infectious complications in severely injured trauma patients. Of the seven SNPs studied, the TLR2 T-16934A increased the risk, the TLR9 T-1486C SNPs may decrease the risk, and TLR4 variation seemed unrelated to outcome. Early genotyping may prove to be helpful in the future in identifying polytraumatized patients at risk for infectious outcome. LEVEL OF EVIDENCE: Prognostic and epidemiologic study, level II.

[Cost] effectiveness of withdrawal of fall-risk increasing drugs versus conservative treatment in older fallers: design of a multicenter randomized controlled trial (IMPROveFALL-study).

BACKGROUND: Fall incidents represent an increasing public health problem in aging societies worldwide. A major risk factor for falls is the use of fall-risk increasing drugs. The primary aim of the study is to compare the effect of a structured medication assessment including the withdrawal of fall-risk increasing drugs on the number of new falls versus 'care as usual' in older adults presenting at the Emergency Department after a fall. METHODS/DESIGN: A prospective, multi-center, randomized controlled trial will be conducted in hospitals in the Netherlands. Persons aged ≥65 years who visit the Emergency Department due to a fall are invited to participate in this trial. All patients receive a full geriatric assessment at the research outpatient clinic. Patients are randomized between a structured medication assessment including withdrawal of fall-risk increasing drugs and 'care as usual'. A 3-monthly falls calendar is used for assessing the number of falls, fallers and associated injuries over a one-year follow-up period. Measurements will be at three, six, nine, and twelve months and include functional outcome, healthcare consumption, socio-demographic characteristics, and clinical information. After twelve months a second visit to the research outpatient clinic will be performed, and adherence to the new medication regimen in the intervention group will be measured. The primary outcome will be the incidence of new falls. Secondary outcome measurements are possible health effects of medication withdrawal, health-related quality of life (Short Form-12 and EuroQol-5D), costs, and cost-effectiveness of the intervention. Data will be analyzed using an intention-to-treat analysis. DISCUSSION: The successful completion of this trial will provide evidence on the effectiveness of withdrawal of fall-risk increasing drugs in older patients as a method for falls reduction. TRIAL REGISTRATION: The trial is registered in the Netherlands Trial Register (NTR1593).