A European survey of older peoples' preferences, and perceived barriers and facilitators to inform development of a medication-related fall-prevention patient portal.

PURPOSE: Falls are a major and growing health care problem in older adults. A patient portal has the potential to provide older adults with fall-prevention advice to reduce fall-risk. However, to date, the needs and preferences regarding a patient portal in older people who have experienced falls have not been explored. This study assesses content preferences, potential barriers and facilitators with regard to using a patient portal, as perceived by older people who have experienced falls, and explores regional differences between European participants. METHODS: We conducted a survey of older adults attending an outpatient clinic due to a fall or fall-related injury, to explore their content preferences, perceived barriers, and facilitators with respect to a fall-prevention patient portal. Older adults (N = 121, 69.4% female, mean age: 77.9) were recruited from seven European countries. RESULTS: Almost two-thirds of respondents indicated they would use a fall-prevention patient portal. The portal would preferably include information on Fall-Risk-Increasing Drugs (FRIDs), and ways to manage other related/relevant medical conditions. Facilitators included a user-friendly portal, with easily accessible information and physician recommendations to use the portal. The most-commonly-selected barriers were privacy issues and usage fees. A family member's recommendation to use the portal was seemingly more important for Southern and Eastern European participants compared to the other regions. CONCLUSION: The majority of older people with lived falls experience expressed an interest in a fall-prevention patient portal providing personalized treatment advice to prevent further falls. The results will be used to inform the development of a fall-prevention patient portal. The fall-prevention patient portal is intended to be used in addition to a consultation with a physician. Future research is needed to explore how to prevent falls in older patients who are not interested in a fall-prevention patient portal.

The role of plasma concentrations and drug characteristics of beta-blockers in fall risk of older persons.

Beta-blocker usage is inconsistently associated with increased fall risk in the literature. However, due to age-related changes and interindividual heterogeneity in pharmacokinetics and dynamics, it is difficult to predict which older adults are more at risk for falls. Therefore, we wanted to explore whether elevated plasma concentrations of selective and nonselective beta-blockers are associated with an increased risk of falls in older beta-blocker users. To answer our research question, we analyzed samples of selective (metoprolol, n = 316) and nonselective beta-blockers (sotalol, timolol, propranolol, and carvedilol, n = 179) users from the B-PROOF cohort. The associations between the beta-blocker concentration and time to first fall were assessed using Cox proportional hazard models. Change of concentration over time in relation to fall risk was assessed with logistic regression models. Models were adjusted for potential confounders. Our results showed that above the median concentration of metoprolol was associated with an increased fall risk (HR 1.55 [1.11-2.16], p = .01). No association was found for nonselective beta-blocker concentrations. Also, changes in concentration over time were not associated with increased fall risk. To conclude, metoprolol plasma concentrations were associated with an increased risk of falls in metoprolol users while no associations were found for nonselective beta-blockers users. This might be caused by a decreased ß1-selectivity in high plasma concentrations. In the future, beta-blocker concentrations could potentially help clinicians estimate fall risk in older beta-blockers users and personalize treatment.

Are higher antidepressant plasma concentrations associated with fall risk in older antidepressant users?

PURPOSE: Antidepressants are well-established fall-risk increasing drugs (FRIDs) and therefore falls should be considered an important adverse drug event (ADE) of antidepressants. However, not all antidepressant users experience fall incidents and factors associated with increased fall risk among antidepressant users are incompletely understood. Our objective was to explore whether antidepressant plasma concentrations are associated with falls in older antidepressant users. METHODS: For this study, we included antidepressant users of the multicenter B-PROOF study. Fall incidents were recorded prospectively using fall calendars. Antidepressant plasma concentrations were analyzed by Liquid chromatography-mass spectrometry (LC-MS) at baseline and at 2 years follow-up. The associations between the observed antidepressant concentration and fall risk were assessed using Cox proportional hazard and logistic regression models and adjusted for potential confounders. RESULTS: In total 93 selective serotonin reuptake inhibitor (SSRI) and 41 antidepressant (TCA) users were identified. There was a significant association between baseline TCA plasma concentration and fall risk within users (HR 2.50, 95% CI 1.07-5.87, crude model). In the adjusted model, there were no significant associations between concentrations of SSRIs and fall risk. CONCLUSION: There might be an association between plasma concentrations of TCAs and the risk of falling in older users. However, these results needs to be interpreted with caution considering the small sample size and accompanying limitation of confinement to crude analyses. Therefore, these novel findings need to replicated in a larger cohort, preferably including adjustment for potential confounders and more frequent measures of plasma concentrations is needed.

Candidate genetic variants and antidepressant-related fall risk in middle-aged and older adults.

BACKGROUND: Antidepressant use has been associated with increased fall risk. Antidepressant-related adverse drug reactions (e.g. orthostatic hypotension) depend partly on genetic variation. We hypothesized that candidate genetic polymorphisms are associated with fall risk in older antidepressant users. METHODS: The association between antidepressant use and falls was cross-sectionally investigated in a cohort of Dutch older adults by logistic regression analyses. In case of significant interaction product term of antidepressant use and candidate polymorphism, the association between the variant genotype and fall risk was assessed within antidepressant users and the association between antidepressant use and fall risk was investigated stratified per genotype. Secondly, a look-up of the candidate genes was performed in an existing genome-wide association study on drug-related falls in antidepressant users within the UK Biobank. In antidepressant users, genetic associations for our candidate polymorphisms for fall history were investigated. RESULTS: In antidepressant users(n = 566), for rs28371725 (CYP2D6*41) fall risk was decreased in TC/variant allele carriers compared to CC/non-variant allele carriers (OR = 0.45, 95% CI 0.26-0.80). Concerning rs1057910 (CYP2C9*3), fall risk was increased in CA/variant allele carriers compared to AA/non-variant allele carriers (OR = 1.95, 95% CI 1.17-3.27). Regarding, rs1045642 (ABCB1), fall risk was increased in AG/variant allele carriers compared to GG/non-variant allele carriers (OR = 1.69, 95% CI 1.07-2.69). Concerning the ABCB1-haplotype (rs1045642/rs1128503), fall risk was increased in AA-AA/variant allele carriers compared to GG-GG/non-variant allele carriers (OR = 1.86, 95% CI 1.05-3.29). In the UK Biobank, in antidepressant users(n = 34,000) T/variant-allele of rs28371725 (CYP2D*41) was associated with increased fall risk (OR = 1.06, 95% CI 1.01-1.12). G/non-variant-allele of rs4244285 (CY2C19*2) was associated with decreased risk (OR = 0.96, 95% CI 0.92-1.00). CONCLUSION: This is the first study showing that certain genetic variants modify antidepressant-related fall risk. The results were not always consistent across the studies and should be validated in a study with a prospective design. However, pharmacogenetics might have value in antidepressant (de)prescribing in falls prevention.

A Propensity Score Matched Approach to Assess the Associations of Commonly Prescribed Medications with Fall Risk in a Large Harmonized Cohort of Older Ambulatory Persons.

INTRODUCTION: Several medication classes are considered to present risk factors for falls. However, the evidence is mainly based on observational studies that often lack adequate adjustment for confounders. Therefore, we aimed to assess the associations of medication classes with fall risk by carefully selecting confounders and by applying propensity score matching (PSM). METHODS: Data from several European cohorts, harmonized into the ADFICE_IT cohort, was used. Our primary outcome was time until the first fall within 1-year follow-up. The secondary outcome was a fall in the past year. Our exposure variables were commonly prescribed medications. We used 1:1 PSM to match the participants with reported intake of specific medication classes with participants without. We constructed Cox regression models stratified by the pairs matched on the propensity score for our primary outcome and conditional logistic regression models for our secondary outcome. RESULTS: In total, 32.6% of participants fell in the 1-year follow-up and 24.4% reported falling in the past year. ACE inhibitor users (prevalence of use 15.3%) had a lower fall risk during follow-up when matched to non-users, with a hazard ratio (HR) of 0.82 (95% CI 0.68-0.98). Also, statin users (prevalence of use 20.1%) had a lower risk, with an HR of 0.76 (95% CI 0.65-0.90). Other medication classes showed no association with risk of first fall. Also, in our secondary outcome analyses, statin users had a significantly lower risk. Furthermore, ß-blocker users had a lower fall risk and proton pump inhibitor use was associated with a higher risk in our secondary outcome analysis. CONCLUSION: Many commonly prescribed medication classes showed no associations with fall risk in a relatively healthy population of community-dwelling older persons. However, the treatment effects and risks can be heterogeneous between individuals. Therefore, focusing on identification of individuals at risk is warranted to optimize personalized falls prevention.

Effectiveness of Cardiovascular Evaluations and Interventions on Fall Risk: A Scoping Review.

OBJECTIVE: Cardiovascular abnormalities are consistently associated with fall risk in older people. However, little research has been done to assess the effect of cardiovascular interventions on fall risk. The aim of this scoping review is to explore the current literature on the effectiveness of cardiovascular evaluations and interventions in reducing fall risk in older people. DESIGN: Scoping review. DATA SOURCES: Medline, Cochrane Library, and WHO ICTRP Search Portal were systematically searched. SELECTION CRITERIA: Randomized controlled trials (RCTs) and intervention studies of community-dwelling adults aged ≥50 years or with a mean age of >60 years that assessed the effect of a cardiovascular assessment and interventions in reducing fall risk. Key search concepts were "falls" and "aged", and terms for different cardiovascular evaluations and interventions were included. The Cochrane Checklist for risk of bias and the ROBINS-I tool were used to assess the quality of the studies. RESULTS: Seven studies were included. The majority showed a reduction in falls after cardiovascular evaluation and intervention. Two out of four studies that focused on carotid sinus hypersensitivity (CSH) as a modifiable cardiovascular risk factor for falls, showed a significant reduction in falls after pacemaker implantation. Two studies that looked at sinus node dysfunction (SND) both showed a significant reduction in falls after pacemaker implantation. One study showed that 33% of the patients experienced a fall after cardiovascular evaluation and intervention, whereas all patients fell before assessment. CONCLUSIONS: The majority of the included studies showed a reduction in falls after the intervention. However, the number of published papers regarding the effect of cardiovascular assessment and interventions on falls is small. A standardized assessment of cardiovascular risk factors may be essential in preventing falls in older adults and could consequently reduce injuries, loss of quality of life, deaths, and fall-related expenditures.

EuGMS Task and Finish group on Fall-Risk-Increasing Drugs (FRIDs): Position on Knowledge Dissemination, Management, and Future Research.

Falls are a major public health concern in the older population, and certain medication classes are a significant risk factor for falls. However, knowledge is lacking among both physicians and older people, including caregivers, concerning the role of medication as a risk factor. In the present statement, the European Geriatric Medicine Society (EuGMS) Task and Finish group on fall-risk-increasing drugs (FRIDs), in collaboration with the EuGMS Special Interest group on Pharmacology and the European Union of Medical Specialists (UEMS) Geriatric Medicine Section, outlines its position regarding knowledge dissemination on medication-related falls in older people across Europe. The EuGMS Task and Finish group is developing educational materials to facilitate knowledge dissemination for healthcare professionals and older people. In addition, steps in primary prevention through judicious prescribing, deprescribing of FRIDs (withdrawal and dose reduction), and gaps in current research are outlined in this position paper.

EuGMS Task and Finish group on Fall-Risk-Increasing Drugs (FRIDs): Position on Knowledge Dissemination, Management, and Future Research.

Falls are a major public health concern in the older population, and certain medication classes are a significant risk factor for falls. However, knowledge is lacking among both physicians and older people, including caregivers, concerning the role of medication as a risk factor. In the present statement, the European Geriatric Medicine Society (EuGMS) Task and Finish group on fall-risk-increasing drugs (FRIDs), in collaboration with the EuGMS Special Interest group on Pharmacology and the European Union of Medical Specialists (UEMS) Geriatric Medicine Section, outlines its position regarding knowledge dissemination on medication-related falls in older people across Europe. The EuGMS Task and Finish group is developing educational materials to facilitate knowledge dissemination for healthcare professionals and older people. In addition, steps in primary prevention through judicious prescribing, deprescribing of FRIDs (withdrawal and dose reduction), and gaps in current research are outlined in this position paper.

Age modifies the association between apathy and recurrent falling in Dutch ambulant older persons with a high fall risk: Recurrent falling in Dutch outpatients, does apathy play a role?

Apathy, a common and disabling behavioural syndrome in older persons, has been associated with impaired physical performance and executive dysfunction. Both are fall risk factors and they share pathophysiological pathway. We cross-sectionally examined the association between apathy and recurrent falling (≥2 falls in the past 12 months) and number of falls in the past 12 months in 243 outpatients aged ≥65 years with ≥3 fall risk-factors visiting a fall-clinic after a fall. We calculated Odds Ratio's (ORs), Incidence Rate Ratio's (IRRs) and their 95% Confidential Intervals (CI95) using multivariable regression and negative binomial regression analyses. We adjusted for cognitive functioning, depression, the use of fall risk increasing drugs, visual impairment, urine incontinence, comorbidity, smoking, use of alcohol, body mass index (BMI), and the number of months between assessment of fall risk and of apathy. We assessed effect modification by age and gender. In our study, apathy was independently associated with recurrent falling in patients aged 65-75 years: OR 2.8 (CI95 1.0-7.7). Overall, patients with apathy experienced 1.46 times as many falls in the past 12 months compared to patients without apathy (IRR 1.46 (CI95 1.0-2.1). To conclude, in high fall-risk older outpatients, apathy was cross-sectionally associated with recurrent falling in patients aged 65-75 years and the number of falls. Apathy appeared to be especially relevant in relation to falling in this age group. Whether apathy predicts recurrent falling is yet to be determined.

Wide-angle ITER-prototype tangential infrared and visible viewing system for DIII-D.

An imaging system with a wide-angle tangential view of the full poloidal cross-section of the tokamak in simultaneous infrared and visible light has been installed on DIII-D. The optical train includes three polished stainless steel mirrors in vacuum, which view the tokamak through an aperture in the first mirror, similar to the design concept proposed for ITER. A dichroic beam splitter outside the vacuum separates visible and infrared (IR) light. Spatial calibration is accomplished by warping a CAD-rendered image to align with landmarks in a data image. The IR camera provides scrape-off layer heat flux profile deposition features in diverted and inner-wall-limited plasmas, such as heat flux reduction in pumped radiative divertor shots. Demonstration of the system to date includes observation of fast-ion losses to the outer wall during neutral beam injection, and shows reduced peak wall heat loading with disruption mitigation by injection of a massive gas puff.

Experimental comparison of a Shack-Hartmann sensor and a phase-shifting interferometer for large-optics metrology applications.

We performed a direct side-by-side comparison of a Shack-Hartmann wave-front sensor and a phase-shifting interferometer for the purpose of characterizing large optics. An expansion telescope of our own design allowed us to measure the surface figure of a 400-mm-square mirror with both instruments simultaneously. The Shack-Hartmann sensor produced data that closely matched the interferometer data over spatial scales appropriate for the lenslet spacing, and much of the <20-nm rms systematic difference between the two measurements was due to diffraction artifacts that were present in the interferometer data but not in the Shack-Hartmann sensor data. The results suggest that Shack-Hartmann sensors could replace phase-shifting interferometers for many applications, with particular advantages for large-optic metrology.

Inhibition of soluble catechol-O-methyltransferase and single-dose pharmacokinetics after oral and intravenous administration of entacapone.

The inhibition of soluble catechol-O-methyl-transferase (S-COMT) in red blood cells (RBCs) by entacapone, and the pharmacokinetics of entacapone after single oral (5-800 mg) and i.v. (25 mg) doses have been examined in an open study in 12 healthy young male volunteers. Oral entacapone dose-dependently decreased the activity of S-COMT in RBCs with a maximum inhibition of 82% after the highest dose (800 mg). The inhibition of S-COMT in RBCs was reversible and the activity recovered within 4-8 h. Entacapone showed linear pharmacokinetics over the dose range studied: Cmax and AUC were correlated with the dose of the drug. Oral absorption of entacapone was fast, with a tmax ranging from 0.4 to 0.9 h, depending on the dose. Systemic availability of entacapone varied between 30 and 46%. Entacapone was rapidly eliminated by metabolism with a half-life of 0.27-0.30 h after oral doses of 5 to 50 mg. After doses from 100 to 800 mg the disposition was best described by two phases with a t1/2 alpha of 0.27-0.37 h and t1/2 beta of 1.59-3.44 h. Over the dose range studied, the single oral and i.v. doses of entacapone were well tolerated. No haematological, biochemical or haemodynamic adverse effects were seen. The results show that entacapone is an orally effective and reversible COMT inhibitor in man and has simple, linear pharmacokinetics.

The effect of catechol-O-methyl transferase inhibition by entacapone on the pharmacokinetics and metabolism of levodopa in healthy volunteers.

We studied the effect of inhibiting the enzyme catechol-O-methyltransferase (COMT) by a novel COMT inhibitor, entacapone, on the pharmacokinetics and metabolism of levodopa in 12 healthy male volunteers. Single increasing oral doses of entacapone (50-400 mg) were administered concomitantly with a single oral dose of levodopa/carbidopa (100/25 mg). The subjects were treated with carbidopa (100 mg t.i.d.) for 1 day prior to the administration of study drugs. Plasma concentrations of levodopa; its metabolites 3-O-methyldopa (3-OMD), 3,4-dihydroxyphenylacetic acid (DOPAC), and homovanillic acid (HVA); as well as carbidopa and entacapone were determined for pharmacokinetic calculations. Entacapone dose-dependently increased the area under the plasma concentration-time curve (AUC) of levodopa; the increase was 65% after the 400 mg dose of entacapone. Neither Cmax nor Tmax of levodopa was statistically significantly influenced by entacapone. Entacapone dose-dependently decreased the AUC of 3-OMD, maximally by 58%. The AUC of DOPAC was statistically significantly increased but no change in the AUC of HVA was observed after entacapone. No drug-related adverse events or hemodynamic effects were observed. The in vivo biochemical effects of entacapone indicate that it is an orally active COMT inhibitor and that it may improve the therapeutic efficacy of levodopa in Parkinson's disease.

Condenser optics, partial coherence, and imaging for soft-x-ray projection lithography.

A condenser system couples the radiation source to an imaging system, controlling the uniformity and partial coherence at the object, which ultimately affects the characteristics of the aerial image. A soft-x-ray projection lithography system based on a ring-field imaging system and a laser-produced plasma x-ray source places considerable constraints on the design of a condenser system. Two designs are proposed, critical illumination and Köhler illumination, each of which requires three mirrors and scanning for covering the entire ring field with the required uniformity and partial coherence. Images based on Hopkins' formulation of partially coherent imaging are simulated.

Low-cost, high-resolution, single-structure array telescopes for imaging of low-Earth-orbit satellites.

Telescopes that are designed for the unconventional imaging of near-Earth satellites must follow unique design rules. The costs must be reduced substantially over those of the conventional telescope designs, and the design must accommodate a technique to circumvent atmospheric distortion of the image. Apertures of 12 m and more along with altitude-altitude mounts that provide high tracking rates are required. A novel design for such a telescope, optimized for speckle imaging, has been generated. Its mount closely resembles a radar mount, and it does not use the conventional dome. Costs for this design are projected to be considerably lower than those for the conventional designs. Results of a design study are presented with details of the electro-optical and optical designs.

Optical Interpretation of the Merit Function in Grey's Lens Design Program.

A ray and wavefront analysis is the basis of an interpretation of the aberration balancing merit function in Grey's lens design program. From each of several field angles, this program traces a coarse grid of rays through an axially symmetric optical system. A polynomial in a region around each ray describes the wave error. This polynomial includes terms (through second order) in aperture, field angle, and wavelength variables. The coefficients of the terms in the polynomial are calculated from real and differential ray trace data. The merit function is the variance of the wave error, obtained by squaring and integrating the polynomials over appropriate ranges of the variables. Distortion is removed from the wave error polynomials and is included in the merit function in a unique manner.