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Background: Carotid stenosis is thought to be the primary risk factor for central retinal artery occlusion (CRAO); however, it is not known whether atrial fibrillation (AF)—a cardiac arrhythmia that underlies over 25% of cerebral ischemic strokes—predisposes patients to CRAO. Methods: A retrospective, observational, cohort study was performed using data from the State Inpatient Databases and State Emergency Department Databases from New York (2006–2015), California (2003–2011), and Florida (2005–2015) to determine the association between AF and CRAO. The primary exposure was hospital-documented AF. The primary end point was hospital-documented CRAO, defined as having an International Classification of Diseases, Ninth Revision, Clinical Modification , code 362.31 in the primary diagnosis position. Cause-specific hazard models were used to model CRAO-free survival among patients according to hospital-documented AF status. Results: Of 39 834 885 patients included in the study, 2 723 842 (median age, 72.7 years; 48.5% women) had AF documented during the exposure window. The median follow-up duration was 6 years and 1 month. Patients with AF were older, more likely to be of non-Hispanic White race/ethnicity, and had a higher burden of cardiovascular comorbidities compared with patients without AF. The cumulative incidence of CRAO determined prospectively after exclusions was 8.69 per 100 000 at risk in those with AF and 2.39 per 100 000 at risk in those without AF over the study period. Before adjustment, AF was associated with higher risk of CRAO (hazard ratio, 2.55 [95% CI, 2.15–3.03]). However, after adjustment for demographics, state, and cardiovascular comorbidities, there was an inverse association between AF and risk of CRAO (adjusted hazard ratio, 0.72 [95% CI, 0.60–0.87]). These findings were robust in our prespecified sensitivity analyses. By contrast, positive control outcomes of embolic and ischemic stroke showed an expected strong relationship between AF and risk of stroke. Conclusions: We found an inverse association between AF and CRAO in a large, representative study of hospitalized patients; however, this cohort did not ascertain AF or CRAO occurring outside of hospital or emergency department settings.

Writer's cramp (WC) dystonia is a rare disease that causes abnormal postures during the writing task. Successful research studies for WC and other forms of dystonia are contingent on identifying sensitive and specific measures that relate to the clinical syndrome and achieve a realistic sample size to power research studies for a rare disease. Although prior studies have used writing kinematics, their diagnostic performance remains unclear.This study aimed to evaluate the diagnostic performance of automated measures that distinguish subjects with WC from healthy volunteers.A total of 21 subjects with WC and 22 healthy volunteers performed a sentence-copying assessment on a digital tablet using kinematic and hand recognition softwares. The sensitivity and specificity of automated measures were calculated using a logistic regression model. Power analysis was performed for two clinical research designs using these measures. The test and retest reliability of select automated measures was compared across repeat sentence-copying assessments. Lastly, a correlational analysis with subject- and clinician-rated outcomes was performed to understand the clinical meaning of automated measures.Of the 23 measures analyzed, the measures of word legibility and peak accelerations distinguished subjects with WC from healthy volunteers with high sensitivity and specificity and demonstrated smaller sample sizes suitable for rare disease studies, and the kinematic measures showed high reliability across repeat visits, while both word legibility and peak accelerations measures showed significant correlations with the subject- and clinician-rated outcomes.Novel automated measures that capture key aspects of the disease and are suitable for use in clinical research studies of WC dystonia were identified. © 2022 International Parkinson and Movement Disorder Society.

Introduction: Atrial fibrillation (AF) is a major risk factor for cerebral ischemic stroke. However, it is not known whether AF predicts the development of central retinal artery occlusion (CRAO), a form of ischemic stroke affecting the retina. Methods: A retrospective cohort study was undertaken using data from the California Healthcare Cost and Utilization Project (HCUP) State Inpatient and State Emergency Department Datasets (SID/SEDDs). Patients 18 years and older discharged from non-federal hospitals between 2005 and 2011 who did not have a history of CRAO were analyzed. The exposure variable was AF and the endpoint was CRAO, each identified using validated ICD-9-CM diagnosis codes. Association between AF and CRAO was modeled using a Fine-Gray method with death as a competing risk with adjustment for age, biological sex, race, and vascular co-morbidities. Results: A total of 12,181,778 patients were included, among these 806,397 with AF and 11,375,381 without AF. In total, 309 patients had CRAO. In an unadjusted analysis, there was a higher risk of CRAO in patients with versus without AF (HR 2.24 (95% CI: 1.51 to 3.32)). After adjustment for pre-specified covariates, there appeared to be a lower hazard of CRAO in patients with AF (aHR 0.61 (95% CI: 0.45 to 0.98)). Further analyses including cerebral ischemic stroke (aHR 1.16 (95% CI: 1.14 to 1.18)) and specifically embolic stroke (aHR 4.29 (95% CI 4.10-4.48)) as positive controls argued against overadjustment bias. We present sensitivity analyses including CRAO identified in any position of the discharge ICD list, using different ascertainment windows for AF and using broader categories of retinal ischemia. Conclusion: The incidence of CRAO was higher in patients with AF than those without AF, but the hazard of CRAO was not higher for patients with AF after adjustment for measured covariates. Endpoint and exposure ascertainment may have been limited by inclusion only of inpatient and emergency department encounters.

What is the utilization of direct-to-consumer fertility tests (DTCFT) among fertility patients? How does the perceived utility of DTCFT differ between patients and reproductive endocrinologists (REI)?Infertility patients visiting the Duke Fertility Center between December 2020 and December 2021 were sent an electronic invitation to participate in a patient survey. Members of the Society of Reproductive Endocrinology and Infertility were also sent e-mail invitations to participate in the REI survey. DTCFT were defined as tests not ordered by a physician or performed at a physician's office, including calendar methods of ovulation prediction, urinary ovulation prediction kits, basal body temperature (BBT) monitoring, hormone analysis, ovarian reserve testing and semen analysis. Patients and REI were asked how likely they were to recommend a given DTCFT, on a 0-10 Likert scale.In total, 425 patients (response rate 50.5%) and 178 REI (response rate 21.4%) completed the surveys. Patients reported the utilization of calendar methods of ovulation prediction (83.8%), urinary ovulation prediction (78.8%), BBT monitoring (30.8%), hormone analysis (15.3%), semen analysis (10.1%) and ovarian reserve testing (9.2%). REI rated the utility of all DTCFT significantly lower than patients did (average discordance -4.2, P 0.001), except for urinary ovulation prediction, which REI gave a significantly higher score (discordance +1.0, P 0.001). Prior pregnancy was significantly associated with home ovulation prediction utilization among patients (adjusted odds ratio 3.21, 95% confidence interval 1.2-9.83).Methods of ovulation prediction are commonly used by fertility patients. Significant discordance exists in the perceived utility of DTCFT between patients and REI. Patient education and guidelines are needed to better inform individuals considering DTCFT.

Pathogenic leucine-rich repeat kinase 2 LRRK2 mutations may increase LRRK2 kinase activity and Rab substrate phosphorylation. Genetic association studies link variation in LRRK2 to idiopathic Parkinson disease (iPD) risk.Through measurements of the LRRK2 kinase substrate pT73-Rab10 in urinary extracellular vesicles, this study seeks to understand how LRRK2 kinase activity might change with iPD progression.Using an immunoblotting approach validated in LRRK2 transgenic mice, the ratio of pT73-Rab10 to total Rab10 protein was measured in extracellular vesicles from a cross-section of G2019S LRRK2 mutation carriers (N = 45 participants) as well as 485 urine samples from a novel longitudinal cohort of iPD and controls (N = 85 participants). Generalized estimating equations were used to conduct analyses with commonly used clinical scales.Although the G2019S LRRK2 mutation did not increase pT73-Rab10 levels, the ratio of pT73-Rab10 to total Rab10 nominally increased over baseline in iPD urine vesicle samples with time, but did not increase in age-matched controls (1.34-fold vs. 1.05-fold, 95% confidence interval [CI], 0.004-0.56; P = 0.046; Welch's t test). Effect estimates adjusting for sex, age, disease duration, diagnosis, and baseline clinical scores identified increasing total Movement Disorder Society-Sponsored Revision of the Unified (MDS-UPDRS) scores (β = 0.77; CI, 0.52-1.01; P = 0.0001) with each fold increase of pT73-Rab10 to total Rab10. Lower Montreal Cognitive Assessment (MoCA) score in iPD is also associated with increased pT73-Rab10.These results provide initial insights into peripheral LRRK2-dependent Rab phosphorylation, measured in biobanked urine, where higher levels of pT73-Rab10 are associated with worse disease progression. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson Movement Disorder Society.