An investigation of psychoactive polypharmacy and related gender-differences in older adults with dementia: a retrospective cohort study.

BACKGROUND: Older adults living with dementia may express challenging responsive behaviours. One management strategy is pharmacologic treatment though these options often have limited benefit, which may lead to multiple treatments being prescribed. METHODS: The aim of the present study was to describe psychoactive medication polypharmacy and explore factors associated with psychoactive polypharmacy in a cohort of older adults living with dementia in Nova Scotia, Canada, including a gender-stratified analysis. This was a retrospective cohort study of those aged 65 years or older with a recorded diagnosis of dementia between 2005 and 2015. Medication dispensation data was collected from April 1, 2010, or dementia diagnosis (cohort entry) to either death or March 31, 2015 (cohort exit). Psychoactive medication claims were captured. Psychoactive medication polypharmacy was defined as presence of three or more psychoactive prescription medications dispensed to one subject and overlapping for more than 30 days. Psychoactive polypharmacy episodes were described in duration, quantity, and implicated medications. Regression analysis examined factors associated with experience and frequency of psychoactive polypharmacy. All analysis were stratified by gender. RESULTS: The cohort included 15,819 adults living with dementia (mean age 80.7 years; 70.0% female), with 99.4% (n = 15,728) receiving at least one psychoactive medication over the period of follow-up. Psychoactive polypharmacy was present in 19.3% of the cohort. The gender specific logistic regressions demonstrated that for both men and women a younger age was associated with an increased risk of psychoactive polypharmacy (women: OR 0.97, 95%CI[0.96, 0.98], men: OR 0.96, 95%CI[0.95, 0.97]). Men were less likely to experience psychoactive polypharmacy if their location of residence was urban (OR 0.86, 95%CI[0.74, 0.99]). There was no significant association between location of residence (urban or rural) and psychoactive polypharmacy for women living with dementia. Antidepressants were the most dispensed medication class, while quetiapine was the most dispensed medication. CONCLUSIONS: This study suggests that of adults living with dementia those of younger ages were more likely to experience psychoactive polypharmacy and that men living with dementia in rural locations may benefit from increased access to non-pharmacological options for dementia management.

Non-arteritic anterior ischemic and glaucomatous optic neuropathy: Implications for neuroretinal rim remodeling with disease severity.

PURPOSE: Post-acute non-arteritic ischemic optic neuropathy (NAION) and glaucomatous optic neuropathy (GON) can be difficult to differentiate clinically. Our objective was to identify optical coherence tomography (OCT) parameters to help differentiate these optic neuropathies. METHODS: We compared 12 eyes of 8 patients with NAION and 12 eyes of 12 patients with GON, matched for age and visual field mean deviation (MD). All patients underwent clinical assessment, automated perimetry (Humphrey Field Analyzer II; Carl Zeiss Meditec, Dublin, CA, USA), and OCT imaging (Spectralis OCT2; Heidelberg Engineering, Heidelberg, Germany) of the optic nerve head and macula. We derived the neuroretinal minimum rim width (MRW), peripapillary retinal nerve fibre layer (RNFL) thickness, central anterior lamina cribrosa depth, and macular retinal thickness. RESULTS: MRW was markedly thicker, both globally and in all sectors, in the NAION group compared to the GON group. There was no significant group difference in RFNL thickness, globally or in any sector, with the exception of the temporal sector that was thinner in the NAION group. The group difference in MRW increased with increasing visual field loss. Other differences observed included lamina cribrosa depth significantly greater in the GON group and significantly thinner central macular retinal layers in the NAION group. The ganglion cell layer was not significantly different between the groups. CONCLUSIONS: The neuroretinal rim is altered in a dissimilar manner in NAION and GON and MRW is a clinically useful index for differentiating these two neuropathies. The fact that the difference in MRW between the two groups increased with disease severity suggests distinct remodelling patterns in response to differing insults with NAION and GON.

Association of admission frailty and frailty changes during cardiac rehabilitation with 5-year outcomes.

AIMS: Examine the association between (1) admission frailty and (2) frailty changes during cardiac rehabilitation (CR) with 5-year outcomes (i.e. time to mortality, first hospitalization, first emergency department (ED) visit, and number of hospitalizations, hospital days, and ED visits). METHODS AND RESULTS: Data from patients admitted to a 12-week CR programme in Halifax, Nova Scotia, from May 2005 to April 2015 (n = 3371) were analysed. A 25-item frailty index (FI) estimated frailty levels at CR admission and completion. FI improvements were determined by calculating the difference between admission and discharge FI. CR data were linked to administrative health data to examine 5-year outcomes [due to all causes and cardiovascular diseases (CVDs)]. Cox regression, Fine-Gray models, and negative binomial hurdle models were used to determine the association between FI and outcomes. On average, patients were 61.9 (SD: 10.7) years old and 74% were male. Mean admission FI scores were 0.34 (SD: 0.13), which improved by 0.07 (SD: 0.09) by CR completion. Admission FI was associated with time to mortality [HRs/IRRs per 0.01 FI increase: all causes = 1.02(95% CI 1.01,1.04); CVD = 1.03(1.02,1.05)], hospitalization [all causes = 1.02(1.01,1.02); CVD = 1.02(1.01,1.02)], ED visit [all causes = 1.01(1.00,1.01)], and the number of hospitalizations [all causes = 1.02(95% CI 1.01,1.03); CVD = 1.02(1.00,1.04)], hospital days [all causes = 1.01(1.01,1.03)], and ED visits [all causes = 1.02(1.02,1.03)]. FI improvements during CR had a protective effect regarding time to all-cause hospitalization [0.99(0.98,0.99)] but were not associated with other outcomes. CONCLUSION: Frailty status at CR admission was related to long-term adverse outcomes. Frailty improvements during CR were associated with delayed all-cause hospitalization, in which a larger effect was associated with a greater chance of improved outcome.

This work improves our understanding of the relationship between admission frailty and frailty changes with mortality, hospitalization, and emergency department (ED) use in a cardiac rehabilitation (CR) setting. Frailty changes during CR were related with time to hospitalization due to any cause.Higher frailty levels at admission of CR were related to lower time to death, re-hospitalization, and ED visit and to a higher total number of hospitalizations and ED visits due to all causes or due to cardiovascular diseases.Overall, this work underscores the importance of considering the degree of frailty in the CR setting for the purpose of predicting adverse outcomes.

Asymmetry of Peripapillary Retinal Blood Vessel and Retinal Nerve Fiber Layer Thickness Between Healthy Right and Left Eyes.

Purpose: The purpose of this study was to determine if there is asymmetry in retinal blood vessel (RBV) position and thickness between right and left eyes (R-L) and evaluate whether R-L asymmetry in RBV thickness is related to R-L asymmetry of retinal nerve fiber layer thickness (RNFLT). Methods: We analyzed peripapillary circle scan optical coherence tomography (OCT) examinations from healthy White subjects to measure RNFLT and RBV thickness and position relative to the fovea to Bruch's membrane opening axis, for all visible RBV. The R-L asymmetries of RNFLT and RBV thickness were computed for each A-scan. Four major vessels (superior temporal artery [STA] and superior temporal vein [STV], inferior temporal artery [ITA], and vein [ITV]) were identified using infrared images. Results: We included 219 individuals. The mean (standard deviation) number of RBV measured per eye was 15.0 (SD = 2.2). The position of the STV and STA was more superior in left eyes than in right eyes, by 2.4 degrees and 3.7 degrees, respectively (P < 0.01). There was no region with significant R-L asymmetry in RBV thickness. RNFLT was thicker in right eyes in the temporal superior region and thicker in left eyes in the superior and nasal superior regions, with the asymmetry profile resembling in a "W" shape. This shape was also present in post hoc analyses in two different populations. The R-L asymmetries of RBV and RNFLT at each A-scan were not significantly associated (P = 0.37). Conclusions: There is little R-L asymmetry in RBV, and it is not related to RNFLT asymmetry. This study suggests that R-L RNFLT asymmetry is due to factors other than RBV.

Comparing Virtual and Center-Based Cardiac Rehabilitation on Changes in Frailty.

Many patients with cardiovascular disease (CVD) are frail. Center-based cardiac rehabilitation (CR) can improve frailty; however, whether virtual CR provides similar frailty improvements has not been examined. To answer this question, we (1) compared the effect of virtual and accelerated center-based CR on frailty and (2) determined if admission frailty affected frailty change and CVD biomarkers. The virtual and accelerated center-based CR programs provided exercise and education on nutrition, medication, exercise safety, and CVD. Frailty was measured with a 65-item frailty index. The primary outcome, frailty change, was analyzed with a two-way mixed ANOVA. Simple slopes analysis determined whether admission frailty affected frailty and CVD biomarker change by CR model type. Our results showed that admission frailty was higher in center-based versus virtual participants. However, we observed no main effect of CR model on frailty change. Results also revealed that participants who were frailer at CR admission observed greater frailty improvements and reductions in triglyceride and cholesterol levels when completing virtual versus accelerated center-based CR. Even though both program models did not change frailty, higher admission frailty was associated with greater frailty reductions and change to some CVD biomarkers in virtual CR.

The impact of cardiovascular health and frailty on mortality for males and females across the life course.

BACKGROUND: The effect of frailty and poor cardiovascular health on mortality for males and females is not fully elucidated. We investigated whether the combined burden of frailty and poor cardiovascular health is associated with all-cause and cardiovascular disease (CVD) mortality by sex and age. METHODS: We analyzed data of 35,207 non-institutionalized US residents aged 20-85 years old (mean age [standard deviation]: 46.6 [16.7 years], 51.4% female, 70.8% White, 10.3% Black, 13.2% Hispanic) from the National Health and Nutrition Examination Survey (1999-2015). Cardiovascular health was measured with the American Heart Association's Life's Simple 7 score (LS7). A 33-item frailty index (FI) was constructed to exclude cardiovascular health deficits. We grouped the FI into 0.1 increments (non-frail: FI < 0.10, very mildly frail: 0.1 ≤ FI < 0.20, mildly frail: 0.20 ≤ FI < 0.30, and moderately/severely frail: FI ≥ 0.30) and LS7 into tertiles (T1[poor] = 0-7, T2[intermediate] = 8-9, T3[ideal] = 10-14). All-cause and CVD mortality data were analyzed up to 16 years. All regression models were stratified by sex. RESULTS: The average FI was 0.09 (SD 0.10); 29.6% were at least very mildly frail, and the average LS7 was 7.9 (2.3). Mortality from all-causes and CVD were 8.5% (4228/35,207) and 6.1% (2917/35,207), respectively. The median length of follow-up was 8.1 years. The combined burden of frailty and poor cardiovascular health on mortality risk varied according to age in males (FI*age interaction p = 0.01; LS7*age interaction p < 0.001) but not in females. In females, poor FI and LS7 combined to predict all-cause and CVD mortality in a dose-response manner. All-cause and CVD mortality risk was greater for older males (60 and 70 years old) who were at least mildly frail and had intermediate cardiovascular health or worse (hazard ratio [lower/higher confidence interval ranges] range: all-cause mortality = 2.02-5.30 [1.20-4.04, 3.15-6.94]; CVD-related mortality = 2.22-7.16 [1.03-4.46, 4.49-11.50]) but not for younger males (30, 40, and 50 years old). CONCLUSIONS: The combined burden of frailty and LS7 on mortality is similar across all ages in females. In males, this burden is greater among older people. Adding frailty to assessments of overall cardiovascular health may identify more individuals at risk for mortality and better inform decisions to implement preventative or treatment approaches.

Effect of a physical activity intervention and frailty on frailty trajectory and major mobility disability.

BACKGROUND: Physical activity (PA) interventions may reduce the burden of frailty and can prevent mobility disability for older adults. We explored whether a 2-year PA intervention would improve frailty trajectory, lead to clinically meaningful frailty changes (CMC), or impact major mobility disability (MMD) across baseline frailty levels. METHODS: We analyzed data for 1635 community-dwelling participants who were 70-89 years old (mean baseline age [SD]: 78.9 [5.2] years, 67.2% female) from the Lifestyle Interventions and Independence Study. Participants were randomized to either PA or health education (HE) intervention. A 44-item frailty index (FI) was constructed at baseline and 0.5, 1, 1.5, and 2 years after baseline. CMC was defined as change in FI of ≥0.03. MMD was the inability to complete a 400 m-walk within 15 min without assistance. Mixed-effects models were used to estimate frailty trajectory and CMC. Cox regression models were used to determine whether the effect of PA on the composite of MMD or death differed by baseline FI. RESULTS: Mean FI (SD) at baseline for both the PA and HE groups was 0.18 (0.10). Two years after baseline, mean FIs were 0.23 (0.12) for PA and 0.24 (0.12) for HE. The MMD rates were 30.1% (246/818) and 35.5% (290/817) for PA and HE, respectively. There was no time-by-intervention interaction for frailty trajectory or for CMC. Regarding the composite MMD and death, there was no FI-by-intervention interaction. Simple association analyses revealed that when baseline FI was centered at 0.15 or higher, the PA intervention was associated with lower risk of MMD or death compared to HE (HR [CI] range for FI ≥ 0.15: 0.65-0.81 [0.43-0.67, 0.90-0.98]). CONCLUSION: Participants in both groups showed similar frailty trajectories and CMC. Those who were frailer benefitted more from the PA intervention regarding MMD and death and may be a focus of recruitments for future PA program.

Comparing Five Criteria for Evaluating Glaucomatous Visual Fields.

PURPOSE: No consensus exists on the relative superiority among criteria for evaluating glaucomatous visual field (VF) damage. We compared the sensitivities and specificities of 5 criteria-Glaucoma Hemifield Test (GHT), Hoddap-Anderson-Parrish 2 (HAP2), Foster, United Kingdom Glaucoma Treatment Study (UKGTS), and Low-pressure Glaucoma Treatment Study (LoGTS)-across various levels of functional and structural glaucomatous damage. DESIGN: Retrospective cross-sectional study. METHODS: This single-center study included patients with suspect or known glaucoma with reliable VF (Humphrey 24-2 Swedish Interactive Thresholding Algorithm) and optical coherence tomography (OCT; Spectralis, Heidelberg Engineering) examinations within a 4-month period. One eye per patient was included. The level of functional and structural damage was defined by mean deviation (MD) and by an OCT score, respectively. We created the OCT score by counting the number of abnormal (MD percentile [P] <1%) global and sectoral averages of optic nerve head MRW, circumpapillary RNFL thickness, and macular GCL thickness. We inferred specificities and sensitivities from positive rates of the criteria in patients with low glaucomatous damage (MD at P ≥ 10% or OCT score = 0) and with higher damage (MD at P < 10% or OCT score > 0), respectively. RESULTS: We included 1230 patients. In patients with low glaucomatous damage, HAP2 and UKGTS had higher positive rates, suggesting lower specificities, whereas GHT, Foster, and LoGTS had lower positive rates, suggesting higher specificities. In patients with higher glaucomatous damage, HAP2 and UKGTS had higher positive rates, indicating higher sensitivities, whereas GHT, Foster, and LoGTS had lower positive rates, indicating lower sensitivities. CONCLUSIONS: No criteria had uniformly superior performance. Selection of criteria should consider the degree of damage anticipated and the desire for either higher sensitivity or specificity.

Serial Changes in Lamina Cribrosa Depth and Neuroretinal Parameters in Glaucoma: Impact of Choroidal Thickness.

PURPOSE: To determine whether: (1) change in lamina cribrosa depth occurs more frequently than change in neuroretinal parameters in glaucoma, and (2) Bruch's membrane or anterior sclera should be used as a reference plane when measuring laminar depth. DESIGN: Prospective observational study. PARTICIPANTS: One hundred fifty-five glaucoma patients and 35 healthy controls. METHODS: Anterior laminar depth from a Bruch's membrane (LD-BM) or anterior sclera (LD-AS) reference plane were measured with optical coherence tomography. Two neuroretinal parameters, minimum rim width and retinal nerve fiber layer thickness, in addition to peripapillary choroidal thickness were measured. Factors related to laminar depth were determined with mixed-effects modeling. Cutoffs for significant change in each parameter were estimated from variability in healthy controls over 1 year. The occurrences of significant change in laminar depth and neuroretinal parameters were compared with survival models. Because normal aging has a clear effect on neuroretinal parameters, but not on laminar depth, changes in neuroretinal parameters were adjusted for age-related reduction. MAIN OUTCOME MEASURES: Longitudinal changes in laminar depth and neuroretinal parameters. RESULTS: Glaucoma patients were followed up for a mean of 3.90 years (range, 2.03-5.44 years). The LD-BM was influenced significantly more by choroidal thickness (1.14 µm/µm; 95% confidence interval, 1.07-1.21) than was the LD-AS (0.15 µm/µm; 95% confidence interval, 0.08-0.22). Posterior movement of the lamina (LD-BM increase or LD-AS increase) occurred with the same frequencies as thinning in neuroretinal parameters. Anterior movement of the lamina was detected more frequently with the Bruch's membrane (LD-BM decrease) compared with the anterior sclera (LD-AS decrease) reference plane (hazard ratio, 3.23; P < 0.01). Significant choroidal thinning occurred in most patients (25/28 [89%]) in whom anterior movement of the lamina occurred with the Bruch's membrane, but not the anterior sclera, reference plane (LD-BM decrease without LD-AS decrease). Patients had a wide range of individual rates of change of choroidal thickness, from -20.00 to 17.09 µm/year (mean, -1.62 µm/year). CONCLUSIONS: Lamina cribrosa depth should be measured from an anterior sclera reference plane to reduce the influence of choroidal thickness changes. In glaucoma patients, lamina cribrosa depth changes are detected with similar frequency as neuroretinal parameter changes.

Acoustic Transmission Characteristics of a Eustachian Tube Volitionally Opened in Two Living Subjects.

OBJECTIVE: To assess the acoustic transmission characteristics of the Eustachian tube (ET) in living subjects in verified patent and closed ET states to facilitate the detection and quantification of ET function using acoustic measures such as sonotubometry. PATIENTS: The two subjects in this study had no history of ear disease nor previous ear surgery and were capable of volitionally opening and closing their ET. INTERVENTIONS: Tympanometry and otologic examinations were used to confirm ET patent and closed states by observing tympanic membrane movement with respiration and by acoustic immitance measurements during forced respiration. A series of 500-ms long chirps containing frequencies from 100 Hz to 10 kHz were introduced into the nasal cavity during both ET states and recorded by microphones in both the contralateral naris and external auditory canal. MAIN OUTCOME MEASURES: Acoustic energy transmission through the ET across the 0.1 to 10 kHz frequency range in the closed state versus the patent state. RESULTS: An increase in acoustic energy transmission occurs across the frequencies of 1 to 4 kHz between the closed and patent ET states, particularly in frequencies below 2.5 kHz. CONCLUSIONS: Results support sonotubometry as a potential diagnostic tool for ET dysfunction. Acoustic differences between the ET states manifest as a general increase in transmitted signal amplitude. Characterizing the acoustic properties in the verified patent and closed ET states allows investigators to more reliably interpret sonotubometric tests of ET function.