Citations

Background: Atrial fibrillation (AF) adversely impacts health-related quality of life (hrQoL). While some patients demonstrate improvements in hrQoL, the factors associated with large improvements in hrQoL are not well described. Methods: We assessed factors associated with a 1-year increase in the Atrial Fibrillation Effect on Quality-of-Life score of 1 SD (≥18 points; 3× clinically important difference), among outpatients in the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation I registry. Results: Overall, 28% (181/636) of patients had such a hrQoL improvement. Compared with patients not showing large hrQoL improvement, they were of similar age (median 73 versus 74, P =0.3), equally likely to be female (44% versus 48%, P =0.3), but more likely to have newly diagnosed AF at baseline (18% versus 8%; P =0.0004), prior antiarrhythmic drug use (52% versus 40%, P =0.005), baseline antiarrhythmic drug use (34.8% versus 26.8%, P =0.045), and more likely to undergo AF-related procedures during follow-up (AF ablation: 6.6% versus 2.0%, P =0.003; cardioversion: 12.2% versus 5.9%, P =0.008). In multivariable analysis, a history of alcohol abuse (adjusted OR, 2.41; P =0.01) and increased baseline diastolic blood pressure (adjusted OR, 1.23 per 10-point increase and >65 mm Hg; P =0.04) were associated with large improvements in hrQoL at 1 year, whereas patients with prior stroke/transient ischemic attack, chronic obstructive pulmonary disease, and peripheral arterial disease were less likely to improve ( P <0.05 for each). Conclusions: In this national registry of patients with AF, potentially treatable AF risk factors are associated with large hrQoL improvement, whereas less reversible conditions appeared negatively associated with hrQoL improvement. Understanding which patients are most likely to have large hrQoL improvement may facilitate targeting interventions for high-value care that optimizes patient-reported outcomes in AF. Registration: URL: http://www.clinicaltrials.gov . Unique identifier: NCT01165710.

Abstract Background and study aims Refractory and recurrent esophageal variceal (EV) bleeding can be life threatening. Self-expanding metal stents (SEMS) have been used as a “bridge” therapy. However, their role in the treatment protocol is not established due to paucity in data. Methods We searched multiple databases from inception through May 2019 to identify studies that reported on SEMS and TIPS in refractory EV hemorrhage. Our primary goals were to analyze and compare the pooled all-cause mortality, immediate bleeding control and rebleeding rates. Results Five hundred forty-seven patients from 21 studies were analyzed (SEMS: 12 studies, 176 patients; TIPS: 9 studies, 398 patients). The pooled rate of all-cause mortality with SEMS was 43.6 % (95 % CI 28.6–59.8, I2 = 38) and with TIPS was 27.9 % (95 % CI 16.3–43.6, I2 = 91). The pooled rate of immediate bleeding control with SEMS was 84.5 % (95 % CI 74–91.2, I2 = 40) and with TIPS was 97.9 % (95 % CI 87.7–99.7, I2 = 0). The pooled rate of rebleeding with SEMS was 19.4 % (95 % CI 11.9–30.4, I2 = 32) and with TIPS was 8.8 % (95 % CI 4.8–15.7, I2 = 40). Conclusion Use of SEMS in refractory EV hemorrhage demonstrates acceptable immediate bleeding control with good technical success rate. Mortality and rebleeding rates were lesser with TIPS, however, its superiority and/ or inferiority cannot be validated due to limitations in the comparison methodology.

Twelve cases (6 M, 6F; mean age 87.9) with incidental Lewy bodies (no clinical diagnosis of parkinsonism or dementia) had medical histories of supraventricular arrhythmia (6/12), dysphagia (5/12), depression (5/12) and falls (4/12). Standardized movement disorder assessments were performed antemortem on 6 cases. The mean Part III UPDRS score was 7 (range 2–14). Motor findings included kinetic tremor (5/6), rest tremor (3/6), postural instability (3/6), postural tremor (2/6), and voice tremor (2/6). Of these 6 cases one was considered to have a normal movement exam, 2 were diagnosed as essential tremor, and 3 as nonspecific tremor disorder. Mean MMSE score in 7 cases was 26.6 (range 23–30). Medical records review revealed 4/12 cases had cognitive impairment not meeting criteria for dementia. Of these 12 cases, 5 had received standardized cognitive assessments: 3 were categorized as cognitively normal and 2 as mild cognitive impairment. Our series of incidental Lewy body disease cases reveal a range of neurologic findings including tremor and cognitive impairment. Antemortem standardized evaluations suggest there may be early clinical markers for Lewy body disorders. Supported by the State of AZ Department of Health Services, NIA P30 AG19610 and the Prescott Family Parkinson's Initiative: a Partnership of the Michael J. Fox Foundation and the Arizona Parkinson's Disease Consortium.

Abstract Osteoporosis-related fractures are undertreated, due in part to misinformation about recommended approaches to patient care and discrepancies among treatment guidelines. To help bridge this gap and improve patient outcomes, the American Society for Bone and Mineral Research assembled a multistakeholder coalition to develop clinical recommendations for the optimal prevention of secondary fractureamong people aged 65 years and older with a hip or vertebral fracture. The coalition developed 13 recommendations (7 primary and 6 secondary) strongly supported by the empirical literature. The coalition recommends increased communication with patients regarding fracture risk, mortality and morbidity outcomes, and fracture risk reduction. Risk assessment (including fall history) should occur at regular intervals with referral to physical and/or occupational therapy as appropriate. Oral, intravenous, andsubcutaneous pharmacotherapies are efficaciousandcanreduce risk of future fracture.Patientsneededucation,however, about thebenefitsandrisks of both treatment and not receiving treatment. Oral bisphosphonates alendronate and risedronate are first-line options and are generally well tolerated; otherwise, intravenous zoledronic acid and subcutaneous denosumab can be considered. Anabolic agents are expensive butmay be beneficial for selected patients at high risk.Optimal duration of pharmacotherapy is unknown but because the risk for second fractures is highest in the earlypost-fractureperiod,prompt treatment is recommended.Adequate dietary or supplemental vitaminDand calciumintake shouldbe assured. Individuals beingtreatedfor osteoporosis shouldbe reevaluated for fracture risk routinely, includingvia patienteducationabout osteoporosisandfracturesandmonitoringfor adverse treatment effects.Patients shouldbestronglyencouraged to avoid tobacco, consume alcohol inmoderation atmost, and engage in regular exercise and fall prevention strategies. Finally, referral to endocrinologists or other osteoporosis specialists may be warranted for individuals who experience repeated fracture or bone loss and those with complicating comorbidities (eg, hyperparathyroidism, chronic kidney disease).©2019American Society for Bone andMineral Research.

Background: Visual characteristics seen during digital single-operator cholangioscopy (DSOC) have not been validated. The aim of this 2-phase study was to define terminology by consensus for the visual diagnosis of biliary lesions to develop a model for optimization of the diagnostic performance of DSOC. Materials and Methods: In phase 1 (criteria identification), video-cholangioscopy clips were reviewed by 12 expert biliary endoscopists, who were blinded to the final diagnosis. Visual criteria were consolidated into the following categories: (1) stricture, (2) lesion, (3) mucosal features, (4) papillary projections, (5) ulceration, (6) abnormal vessels, (7) scarring, (8) pronounced pit pattern. During the second phase (validation), 14 expert endoscopists reviewed DSOC (SpyGlass DS, Boston Scientific) clips using the 8 criteria to assess interobserver agreement (IOA) rate. Results: In phase 1, consensus for visual findings were categorized into 8 criteria titled the “Monaco Classification.” The frequency of criteria were: (1) presence of stricture—75%, (2) presence of lesion type—55%, (3) mucosal features—55%, (4) papillary projections—45%, (5) ulceration—42.5%, (6) abnormal vessels—10%, (7) scarring—40%, and (8) pronounced pit pattern—10%. The accuracy on final diagnosis based on visual impression alone was 70%. In phase 2, the IOA rate using Monaco Classification criteria ranged from slight to fair. The presumptive diagnosis IOA was fair (κ=0.31, SE=0.02), and overall diagnostic accuracy was 70%. Conclusions: The Monaco classification identifies 8 visual criteria for biliary lesions on single-operator digital cholangioscopy. Using the criteria, the IOA and diagnostic accuracy rate of DSOC is improved compared with prior studies.

AbstractObjectiveThere are few neuropathological studies on Parkinson's disease with mild cognitive impairment (PD‐MCI). Those published reveal coexisting Lewy body and Alzheimer's disease pathology. Our objective is to determine the pathology that underlies PD‐MCI.MethodsWe used data from the Arizona Study of Aging and Neurodegenerative Disorders, a longitudinal clinicopathological study. Of 736 autopsied subjects with standardized movement and cognitive assessments, 25 had PD‐MCI. Neuropathological findings, including Lewy body and Alzheimer's disease pathology, were compared in PD subjects with amnestic MCI (A‐MCI) and nonamnestic MCI (NA‐MCI).ResultsSignificant pathological heterogeneity within PD‐MCI was found. This included varying Lewy body stages, Alzheimer's disease pathology, and cerebral amyloid angiopathy. There was a significant increase in the severity of Lewy body pathology (meeting The Unified Staging System for Lewy Body disorders neocortical stage) in nonamnestic MCI (7/1, 63%) when compared with amnestic MCI (3/14, 21%, P = 0.032).ConclusionAlthough a small study, distinct pathological changes may contribute to PD‐MCI phenotype. © 2020 International Parkinson and Movement Disorder Society

Abstract Background Gastric variceal bleeding carries significant mortality in the setting of portal hypertension. Among the endoscopic treatment options, endoscopic ultrasound (EUS)-guided glue and/or coil injection is a novel approach, but its role in the treatment of gastric varices is not established due to a lack of robust data. Methods We conducted a comprehensive search of several databases (inception to June 2019) to identify studies evaluating EUS in the treatment of gastric varices. Our primary goals were to estimate the pooled rates of treatment efficacy, obliteration and recurrence of gastric varices, early and late rebleeding, and adverse events with EUS-guided therapy in gastric varices. We also searched for studies that evaluated direct endoscopic glue (END-glue) injection for treatment of gastric varices, and used the pooled rates as comparators. Results 23 studies (851 patients) evaluating EUS-guided therapy were included. The pooled treatment efficacy was 93.7 % (95 % confidence interval [CI] 89.5 – 96.3, I 2 = 53.7), gastric varices obliteration was 84.4 % (95 %CI 74.8 – 90.9, I 2 = 77), gastric varices recurrence was 9.1 % (95 %CI 5.2 – 15.7, I 2 = 32), early rebleeding was 7.0 % (95 %CI 4.6 – 10.7, I 2 = 0), and late rebleeding was 11.6 % (95 %CI 8.8 – 15.1, I 2 = 22). The rates were comparable to END-glue therapy (28 studies, 3467 patients) except for obliteration, which was significantly better with EUS-guided therapy. On subgroup analysis, EUS-coil/glue combination showed superior outcomes. Conclusions EUS-guided therapy demonstrated clinical efficacy for treatment of gastric varices in terms of obliteration, recurrence, and long-term rebleeding, and may be superior to END-glue.

Abstract Comorbid Lewy body pathology is very common in Alzheimer’s disease and may confound clinical trial design, yet there is no in vivo test to identify patients with this. Tissue (and/or radioligand imaging) studies have shown cardiac sympathetic denervation in Parkinson’s disease and dementia with Lewy bodies, but this has not been explored in Alzheimer’s subjects with Lewy bodies not meeting dementia with Lewy bodies clinicopathological criteria. To determine if Alzheimer’s disease with Lewy bodies subjects show sympathetic cardiac denervation, we analysed epicardial and myocardial tissue from autopsy-confirmed cases using tyrosine hydroxylase and neurofilament immunostaining. Comparison of tyrosine hydroxylase fibre density in 19 subjects with Alzheimer’s disease/dementia with Lewy bodies, 20 Alzheimer’s disease with Lewy bodies, 12 Alzheimer’s disease subjects without Lewy body disease, 19 Parkinson’s disease, 30 incidental Lewy body disease and 22 cognitively normal without Alzheimer’s disease or Lewy body disease indicated a significant group difference (P &lt; 0.01; Kruskal–Wallis analysis of variance) and subsequent pair-wise Mann–Whitney U tests showed that Parkinson’s disease (P &lt; 0.05) and Alzheimer’s disease/dementia with Lewy bodies (P &lt; 0.01) subjects, but not Alzheimer’s disease with Lewy bodies subjects, had significantly reduced tyrosine hydroxylase fibre density as compared with cognitively normal. Both Parkinson’s disease and Alzheimer’s disease/dementia with Lewy bodies subjects also showed significant epicardial losses of neurofilament protein-immunoreactive nerve fibre densities within the fibre bundles as compared with cognitively normal subjects (P &lt; 0.01) and both groups showed high pathologic alpha-synuclein densities (P &lt; 0.0001). Cardiac alpha-synuclein densities correlated significantly with brain alpha-synuclein (P &lt; 0.001), while cardiac tyrosine hydroxylase and neurofilament immunoreactive nerve fibre densities were negatively correlated with the densities of both brain and cardiac alpha-synuclein, as well as Unified Parkinson’s Disease Rating Scale scores (P &lt; 0.05). The clear separation of Alzheimer’s disease/dementia with Lewy bodies subjects from Alzheimer’s disease and cognitively normal, based on cardiac tyrosine hydroxylase fibre density, is the first report of a statistically significant difference between these groups. Our data do not show significant sympathetic cardiac denervation in Alzheimer’s disease with Lewy bodies, but strongly confirm that cardiac nuclear imaging with a noradrenergic radioligand is worthy of further study as a potential means to separate Alzheimer’s disease from Alzheimer’s disease/dementia with Lewy bodies during life.

Background: QEEG could provide physiological biomarkers for changes over time in Parkinson's disease (PD) cognitive decline if they track with longitudinal neuropsychological performance. Objective: Our aim was to correlate longitudinal changes in frequency domain quantitative electroencephalography (QEEG) measures with change in neuropsychological performance testing in PD. Methods: 71 PD subjects, not demented at baseline, were studied from the Arizona Study of Aging and Neurodegenerative Disorders cohort. Baseline and follow-up digital EEG from PD subjects were analyzed for QEEG measures of background rhythm frequency and global relative power in delta (2.5–4 Hz), theta (4–8 Hz), alpha (8–13 Hz), and beta (13–30 Hz) bands. Baseline and subsequent evaluation included Mini Mental Status Examination and five other neuropsychological tests that load on cognitive domains known to decline in PD. Pearson coefficient was used to assess correlations. Multiple linear regression modeling was used to assess the effect of variable combinations of QEEG and other measures, including age and PD duration. Results: Changes in delta bandpower showed the highest and most consistent pattern of correlations with longitudinal changes in neuropsychological testing. The highest correlation was between delta bandpower increase and decline in the Rey Auditory-Verbal Learning Test (−0.59:p < 0.001). Delta bandpower was also increased in the incident dementia group compared to non-dementia at followup. Conclusions: 1) Longitudinal change in the QEEG frequency domain measure of delta bandpower correlated best with longitudinal neuropsychological performance change in PD; 2) These results constitute preliminary evidence that delta bandpower may be a suitable biomarker for evaluating PD cognitive deterioration longitudinally.

Background: Low-contrast vision is thought to be reduced in Parkinson's disease (PD). This may have a direct impact on quality of life such as driving, using tools, finding objects, and mobility in low-light condition. Low-contrast letter acuity testing has been successful in assessing low-contrast vision in multiple sclerosis. We report the use of a new iPad application to measure low-contrast acuity in patients with PD. Objective: To evaluate low- and high-contrast letter acuity in PD patients and controls using a variable contrast acuity eye chart developed for the Apple iPad. Methods: Thirty-two PD and 71 control subjects were studied. Subjects viewed the Variable Contrast Acuity Chart on an iPad with both eyes open at two distances (40 cm and 2 m) and at high contrast (black and white visual acuity) and 2.5% low contrast. Acuity scores for the two groups were compared. Results: PD patients had significantly lower scores (indicating worse vision) for 2.5% low contrast at both distances and for high contrast at 2 m (p < 0.003) compared to controls. No significant difference was found between the two groups for high contrast at 40 cm (p = 0.12). Conclusions: Parkinson's disease patients have reduced low and high contrast acuity compared to controls. An iPad app, as used in this study, could serve as a quick screening tool to complement more formal testing of patients with PD and other neurologic disorders.