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Background: Overactive bladder (OAB) is a common non-motor symptom of Parkinson disease (PD), often treated with antimuscarinics or beta-3 agonists. There is lack of evidence to guide OAB management in PD., Objectives: To assess the comparative safety of antimuscarinics versus beta-3 agonists for OAB treatment in PD., Methods: We employed a new-user, active-comparator cohort study design. We included Medicare beneficiaries age ≥65 years with PD who were new users of either antimuscarinic or beta-3 agonist. The primary outcome was any acute care encounter (i.e., non-elective hospitalization or emergency department visit) within 90 days of OAB drug initiation. The main secondary outcome was a composite measure of acute care encounters for anticholinergic related adverse events (AEs). Matching on high-dimensional propensity score (hdPS) was used to address potential confounding. We used Cox proportional hazards models to examine the association between OAB drug category and outcomes. We repeated analyses for 30- and 180-day follow-up periods., Results: We identified 27,091 individuals meeting inclusion criteria (mean age: 77.8 years). After hdPS matching, antimuscarinic users had increased risks for any acute care encounter (hazard ratio [HR] 1.23, 95% confidence interval [CI] 1.12-1.37) and encounters for anticholinergic related AEs (HR 1.18, 95% CI 1.04-1.34) compared to beta-3 agonist users. Similar associations were observed for sensitivity analyses., Conclusions: Among persons with PD, anticholinergic initiation was associated with a higher risk of acute care encounters compared with beta-3 agonist initiation. The long-term safety of anticholinergic vs. beta-3 agonist therapy in the PD population should be evaluated in a prospective study., Competing Interests: Declaration of competing interest Dr. Abraham received financial compensation from the Parkinson's Foundation. Dr. Pham Nguyen is a member of the 2022–2023 Junior Investigator Intensive Program of the U.S. Deprescribing Research Network, which is funded by the National Institute on Aging [Grant #R24AG064025] and receives support from the National Institutes of Health [Grants #R01NS099129, #R01AG02515215, #R01AG06458903] and Acadia Pharmaceuticals Inc. Dr. Hennessy directs the University of Pennsylvania's Center for Real-world Effectiveness and Safety of Therapeutics (CREST), which receives funds from Pfizer and Sanofi to support pharmacoepidemiology education and has received grants from Pfizer, and Johnson and Johnson during the conduct of the study, consulted for Novo Nordisk, Arbor Pharmaceuticals, the Medullary Thyroid Cancer Consortium (Novo Nordisk, AstraZeneca, GlaxoSmithKline and Eli Lilly), Biogen, Intercept Pharmaceuticals, Provention Bio, bluebird bio, and Amylyx Pharmaceuticals, and is a special government employee of the U.S. Food and Drug Administration. Dr. Leonard is an Executive Committee Member of the University of Pennsylvania's CREST and recently received honoraria from the American College of Clinical Pharmacy Foundation, the Consortium for Medical Marijuana Clinical Outcomes Research, the University of Florida, the University of Massachusetts, and the Scientific and Data Coordinating Center for the NIDDK-funded Chronic Renal Insufficiency Cohort Study; he is a Special Government Employee of the United States (US) Food and Drug Administration and consults for their Reagan-Udall Foundation and receives travel support from John Wiley & Sons. Dr. Leonard consults for TriNetX and Novo Nordisk. Dr. Leonard's spouse is an employee of Merck; neither Dr. Leonard nor his spouse owns stock in the company. Dr. Weintraub receives support from the National Institutes of Health [Grant #R01NS099129] and has also received research funding or support from Michael J. Fox Foundation for Parkinson's Research, Alzheimer's Therapeutic Research Initiative (ATRI), Alzheimer's Disease Cooperative Study (ADCS), the International Parkinson and Movement Disorder Society (IPMDS); honoraria for consultancy from Acadia Pharmaceuticals Inc., Aptinyx, Biogen, Bracket, CHDI Foundation, Clintrex LLC, Enterin, F. Hoffmann-La Roche Ltd, Ferring, Promentis, Sunovion, and Takeda; and license fee payments from the University of Pennsylvania for the QUIP and QUIP-RS. Dr. Willis receives financial support from National Institutes of Health [Grants #R01NS099129, #K24AG075234, #P30AG059302], the Parkinson's Foundation, Acadia Pharmaceuticals Inc., and the University of Pennsylvania. All other authors declared no competing interests for this work., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Direct methanol fuel cell (DMFC) technology has grabbed much attention from researchers worldwide in the realm of green and renewable energy-generating technologies. Practical applications of DMFCs are marked by the development of highly active, efficient, economical, and long-lasting anode catalysts. Layered double hydroxide (LDH) nanohybrids are found to be efficient electrode materials for methanol oxidation. In this study, we synthesized NiCu-LDH/MXene nanocomposites (NCMs) and investigated their electrochemical performance for methanol oxidation. The formation of NCM was verified through field emission scanning electron microscopy (FE-SEM), energy-dispersive X-ray spectroscopy (EDX), X-ray diffraction (XRD), Fourier transform infrared (FTIR) spectroscopy, Brunauer-Emmett-Teller (BET), and X-ray photoemission spectroscopy (XPS) analyses. The cyclic voltammetry, chronoamperometry, and electron impedance spectroscopy techniques were carried out to assess the electrocatalytic ability of the methanol oxidation reaction. The incorporation of MXene enhanced the methanol oxidation 2-fold times higher than NiCu-LDH. NCM-45 exhibited high peak current density (86.9 mA cm -2 ), enhanced electrochemical active surface area (7.625 cm 2 ), and long-term stability (77.8% retention after 500 cycles). The superior performance of NCM can be attributed to the synergistic effect between Ni and Cu and, further, the electronic coupling between LDH and MXene. Based on the results, NCM nanocomposite is an efficient anodic material for the electrocatalytic oxidation of methanol. This study will open the door for the development of various LDH/MXene nanocomposite electrode materials for the application of direct methanol fuel cells.

This study aimed to examine differential prescribing due to channeling and propensity score non-overlap over time in new versus established treatments for common neurological conditions. We conducted cross-sectional analyses on a national sample of US commercially insured adults using 2005-2019 data. We compared new users of recently approved versus established medications for management of diabetic peripheral neuropathy (pregabalin versus gabapentin), Parkinson disease psychosis (pimavanserin versus quetiapine), and epilepsy (brivaracetam versus levetiracetam). Within these drug pairs, we compared demographic, clinical, and healthcare utilization characteristics of recipients of each drug. In addition, we fit yearly propensity score models for each condition and assessed propensity score non-overlap over time. For all three drug pairs, users of the more recently approved medications more frequently had prior treatment (pregabalin = 73.9%, gabapentin = 38.7%; pimavanserin = 41.1%, quetiapine = 14.0%; brivaracetam = 93.4%, levetiracetam = 32.1%). Propensity score non-overlap and its resulting sample loss after trimming were the greatest in the first year that the more recently approved medication was available (diabetic peripheral neuropathy, 12.4% non-overlap; Parkinson disease psychosis, 6.1%; epilepsy, 43.2%) and subsequently improved. Newer neuropsychiatric therapies appear to be channeled to individuals with refractory disease or intolerance to other treatments, leading to potential confounding and biased comparative effectiveness and safety study findings when compared to established treatments. Propensity score non-overlap should be reported in comparative studies that include newer medications. When studies comparing newer and established treatments are critically needed as soon as new treatments enter the market, investigators should recognize the potential for channeling bias and implement methodological approaches like those demonstrated in this study to understand and improve this issue in such studies., (© 2023. The American Society for Experimental Neurotherapeutics, Inc.)

Background: Hip fractures are a public health problem among older adults, but most research on recovery after hip fracture has been limited to females. With growing numbers of hip fractures among males, it is important to determine how recovery outcomes may differ between the sexes., Methods: 168 males and 171 females were enrolled within 15 days of hospitalization with follow-up visits at 2, 6, and 12 months postadmission to assess changes in disability, physical performance, cognition, depressive symptoms, body composition, and strength, and all-cause mortality. Generalized estimating equations examined whether males and females followed identical outcome recovery assessed by the change in each outcome., Results: The mean age at fracture was similar for males (80.4) and females (81.4), and males had more comorbidities (2.5 vs 1.6) than females. Males were significantly more likely to die over 12 months (hazard ratio 2.89, 95% confidence interval: 1.56-5.34). Changes in outcomes were significantly different between males and females for disability, gait speed, and depressive symptoms (p < .05). Both sexes improved from baseline to 6 months for these measures, but only males continued to improve between 6 and 12 months. There were baseline differences for most body composition measures and strength; however, there were no significant differences in change by sex., Conclusions: Findings confirm that males have higher mortality but suggest that male survivors have continued functional recovery over the 12 months compared to females. Research is needed to determine the underlying causes of these sex differences for developing future prognostic information and rehabilitative interventions., (© The Author(s) 2021. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: The American Academy of Neurology Parkinson Disease (PD) quality measures include an annual diagnostic review., Objective: To investigate the frequency and pattern of changes in diagnoses between PD and other causes of parkinsonism., Methods: This prospective longitudinal cohort study included consented patients diagnosed with PD at least once and a minimum of two times at the Movement Disorders Center between 2002 and 2017. Movement disorder specialists confirmed and documented diagnoses at every visit. Longitudinal changes in diagnoses were identified across visits., Results: Of 1567 patients with parkinsonism, 174 had non-PD parkinsonism with no change over time. Of 1393 patients diagnosed with PD at least once, 94% ( N  = 1308) had no change of diagnosis over time and 6% ( N  = 85) had a change of diagnosis including PD ⟷ drug-induced parkinsonism (DIP) (27.1%), PD ⟷ multiple system atrophy (MSA) (20.0%), PD ⟷ progressive supranuclear palsy (PSP) (18.8%), PD ⟷ Lewy body dementia (DLB) (16.5%), PD⟷ vascular parkinsonism (9.4%), more than two diagnoses (4.7%), and PD ⟷ corticobasal syndrome (CBS) (3.5%). The direction of diagnostic switches was as follows: PD ⟶ other parkinsonism diseases (36.5%), other parkinsonism diseases ⟶ PD (31.8%), and 31.8% of multiple switches. There were no significant differences in duration of follow-up, age at first visit, gender, race, marital status, education, income, cognition, or employment between the stable and unstable groups. Diagnostic change was associated with greater PD severity and greater medical comorbidity., Conclusion: Over a 15-year period, movement disorder specialists changed their clinical diagnosis of PD in 6% of patients. The most common diagnostic switches, to or from PD, were DIP, MSA, PSP, and DLB. This study describes routine clinical diagnostic patterns in the absence of pathologic confirmation. The presence of diverse diagnostic changes over time underscores the value of confirming PD diagnosis., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Marzieh Keshtkarjahromi et al.)

Background: Frailty is a geriatric syndrome with negative health impacts not captured by comorbidity and disability alone. The prevalence of frailty in Parkinson's disease (PD) has been described, but data on frailty-associated outcomes are limited., Objective: To describe the level of frailty and investigate the association between frailty and outcomes in a Medicare sample of persons diagnosed with PD., Methods: We used the claims-based frailty index to assess frailty in a cohort of Medicare beneficiaries with PD in 2013. Frailty was categorized as non-frail/pre-frail, mildly frail, moderately frail, and severely frail. Adjusted logistic regression models examined the relationship between frailty and mortality, hospitalization, emergency department visits, and fall-related injuries through 2014., Results: Of 62,786 beneficiaries with PD in 2013, 55.3% were frail. Frail individuals were more likely to be female, older, Black, metropolitan dwelling, without neurologist care, nursing facility residents, or multimorbid. The average daily levodopa equivalent dose initially increased, then decreased from the pre-frail to the severely frail groups. Compared to non-frail/pre-frail persons, severely frail persons had higher adjusted odds of 1-year mortality (AOR 2.74, 95% CI 1.98, 3.78), hospitalization (AOR 2.34, 95% CI 1.74, 3.14), emergency department visits (AOR 2.97, 95% CI 2.14, 4.13), and fall-related injury (AOR 1.43, 95% CI 0.90, 2.26)., Conclusions: Frailty is common and differentially distributed among older adults with PD. Frailty in PD is associated with adverse health outcomes and death. Observational study analyses may benefit from adjustment for frailty; claims-based frailty surveillance may identify vulnerable PD patients in health system, registry, or administrative data. © 2021 International Parkinson and Movement Disorder Society., (© 2021 International Parkinson and Movement Disorder Society.)

Background: Antipsychotics are used in Parkinson disease (PD) to treat psychosis, mood, and behavioral disturbances. Commonly used antipsychotics differ substantially in their potential to worsen motor symptoms through dopaminergic receptor blockade. Recent real-world data on the use and continuation of antipsychotic therapy in PD are lacking. The objectives of this study are to (1) examine the continuation of overall and initial antipsychotic therapy in individuals with PD and (2) determine whether continuation varies by drug dopamine receptor blocking activity., Methods: We conducted a retrospective cohort study using U.S. commercially insured individuals in Optum 2001-2019. Adults aged 40 years or older with PD initiating antipsychotic therapy, with continuous insurance coverage for at least 6 months following drug initiation, were included. Exposure to pimavanserin, quetiapine, clozapine, aripiprazole, risperidone, or olanzapine was identified based on pharmacy claims. Six-month continuation of overall and initial antipsychotic therapy was estimated by time to complete discontinuation or switching to a different antipsychotic. Cox proportional hazards models evaluated factors associated with discontinuation., Results: Overall, 38.6% of 3566 PD patients in our sample discontinued antipsychotic therapy after the first prescription, 61.4% continued with overall treatment within 6 months of initiation. Clozapine use was too rare to include in statistical analyses. Overall therapy discontinuation was more likely for those who initiated medications with known dopamine-receptor blocking activity (adjusted hazard ratios 1.76 [95% confidence interval 1.40-2.20] for quetiapine, 2.15 [1.61-2.86] for aripiprazole, 2.12 [1.66-2.72] for risperidone, and 2.07 [1.60-2.67] for olanzapine), compared with serotonin receptor-specific pimavanserin. Initial antipsychotic therapy discontinuation also associated with greater dopamine-receptor blocking activity medication use - adjusted hazard ratios 1.57 (1.28-1.94), 1.88 (1.43-2.46), 2.00 (1.59-2.52) and 2.03 (1.60-2.58) for quetiapine, aripiprazole, risperidone, and olanzapine, respectively, compared with pimavanserin. Similar results were observed in sensitivity analyses., Conclusions: Over one-third of individuals with PD discontinued antipsychotic therapy, especially if the initial drug has greater dopamine-receptor blocking activity. Understanding the drivers of antipsychotic discontinuation, including ineffectiveness, potentially inappropriate use, clinician inertia, patient adherence and adverse effects, is needed to inform clinical management of psychosis in PD and appropriate antipsychotic use in this population.

Objective: To examine the national prevalence of pharmacological treatment of affective disorders in older adults with Parkinson's disease (PD), and determine the prevalence and risk factors for receipt of an American Geriatrics Society Beers Criteria® defined potentially inappropriate medication (PIM) for affective disorder treatment., Design: Cross-sectional analysis of 2014 Medicare data., Setting: Research Identifiable File data from the Centers for Medicare and Medicaid Services., Participants: Individuals ≥65 years of age with PD whose inpatient, outpatient, and prescription care is administered through the U.S. Medicare Program., Measurements: The 2014 prevalence of affective (i.e., depressive and anxiety) disorders was calculated. We assessed prescription fills for affective disorder treatment and classified prescriptions according to PIM status. Patient and clinician factors associated with PIM prescriptions were determined., Results: Of 84,323 beneficiaries with PD, 15.1% had prevalent depression only, 7.5% had anxiety only, and 8.5% had comorbid depression and anxiety. Among those with depression only, 80.7% were treated in 2014 (12.8% of treated received at least one PIM). The annual treatment prevalence was 62.9% (75.9% PIM) and 93.1% (63.9% PIM) in the anxiety only and comorbid group, respectively. In most groups, PIM use was less likely among men and those with dementia; geriatricians were less likely to prescribe PIMs., Conclusion: Treatment of affective disorders in persons diagnosed with PD is high. PIM use is also common, particularly in persons with anxiety. Future research will quantify the potential effects of these PIMs on clinical and patient outcomes., (Copyright © 2020 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.)

Background: Visual impairment is associated with hip fracture, depression, anxiety, and dementia in the general population, and many causes of visual impairment are preventable or treatable with early detection. However, the prevalence, outcomes, and healthcare utilization patterns associated with visual impairment have not been examined in Parkinson's disease (PD)., Methods: We performed a cross-sectional analysis of all Medicare beneficiaries with complete data in 2014 and longitudinal analysis of beneficiaries with PD from 2010 to 2014. We used diagnosis and procedure codes to identify PD, visual impairment, eye exams, hip fracture, and neuropsychiatric disorders. We compared the prevalence of visual impairment using logistic regression and used Cox proportional hazards regression to examine visual impairment and incident hip fracture, depression, anxiety, dementia, and death. We also examined the frequency of eye exams in PD using repeated-measures logistic regression., Results: Among 26,209,997 Medicare beneficiaries in 2014, visual impairment was significantly more prevalent in PD (1.7%) than non-PD (0.71%) (adjusted odds ratio, 1.60; 95% confidence interval [CI], 1.56-1.65). In a longitudinal cohort of 542,224 Medicare beneficiaries with PD, less than 60% had a yearly eye exam. Visual impairment associated with increased hazard of depression (hazard ratio [HR], 1.23; 95% CI, 1.14-1.32), anxiety (HR, 1.34; 95% CI, 1.24-1.43), dementia (HR, 1.28; 95% CI, 1.21-1.36), and death (HR, 1.49; 95% CI, 1.44-1.55)., Conclusion: Visual impairment is more common in PD than the general population and is associated with negative PD-related outcomes. Understanding the mechanisms for these relationships is important for guiding future interventions to improve health outcomes in PD. © 2020 International Parkinson and Movement Disorder Society., (© 2020 International Parkinson and Movement Disorder Society.)

Background: impairments in neurotransmitter pathways put Parkinson's disease (PD) patients at risk for drug-disease interactions and adverse medication events., Objective: to determine the prevalence and risk factors for potentially inappropriate medication (PIM) prescriptions, as defined by the 2015 Beers List, in PD., Methods: cross-sectional analysis was conducted on 2014 Medicare beneficiaries with PD who had parts A, B and D coverage. The prevalence of PIM prescriptions for older adults was determined overall, and specifically for medications that can exacerbate motor symptoms or cognitive impairment in PD. Logistic regression models were constructed to determine the association between age, sex, race, geography and poverty with PIM prescriptions., Results: the final sample included 458,086 beneficiaries. In 2014, 35.8% of beneficiaries with PD filled a prescription for at least one PIM for older adults. In total, 8.7% of beneficiaries received a PIM that could exacerbate motor symptoms and 29.0% received a PIM that could worsen cognitive impairment. After adjustment, in all models, beneficiaries who were younger, female, white, urban-dwelling and eligible for Medicaid benefits were more likely to receive a PIM., Conclusion: PIM prescriptions are not uncommon in PD, particularly for medications that can exacerbate cognitive impairment. Future research will examine underlying drivers of sex and other disparities in PIM prescribing. Additional studies are needed to understand the impact of PIMs on disease symptoms, healthcare utilisation and patient outcomes., (© The Author(s) 2020. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Our objectives were to (1) characterize patient and clinical characteristics of adults hospitalized with meningitis; (2) describe meningitis hospitalization outcomes, including 30- and 90-day readmissions; and (3) determine whether clinical, patient, or index hospitalization characteristics are associated with readmission and readmission outcomes., Methods: This retrospective study of the 2014 National Readmissions Database extracted data on hospitalized adults with a principal diagnosis of meningitis and examined hospitalization outcomes using descriptive statistics. Logistic regression models were built to determine whether characteristics were associated with 30- or 90-day readmissions., Results: For the 30-day readmission analyses, 18,883 adults qualified. Meningitis hospitalizations commonly involved adults 25 to 54 years of age who were insured by private carriers. The readmission rates were 7.0% at 30 days and 11.4% at 90 days. Readmission was associated with greater comorbidity burden (2 conditions: adjusted odds ratio [AOR] = 1.60, range 1.24-2.08; 3 conditions: AOR = 1.92, range 1.43-2.58; 4+ conditions: AOR = 2.68, range 2.04-3.51 vs 0 or 1 condition), public insurance (Medicare: AOR = 1.85, range 1.30-2.62; Medicaid: AOR = 1.48, range 1.16-1.90 vs private insurance), and medical error (AOR = 1.43, range 1.07-1.91). Readmissions were most often for meningitis, septicemia, or medical complications., Conclusions: Readmission after hospitalization for meningitis is associated with both fixed and modifiable factors. More research is needed to determine which post-meningitis readmissions are preventable., (Copyright © 2019 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.)

Objectives: While sarcopenia is prevalent after hip fracture in the acute postfracture period, little is known about the prevalence after discharge. This study assessed longitudinal trends in sarcopenia prevalence over 12 months after hip fracture using three different operational definitions., Design: Prospective observational study., Setting: Baltimore Hip Studies seventh cohort., Participants: A total of 82 men and 78 women, aged 65 years and older, with surgical repair of a nonpathological hip fracture., Measurements: Baseline assessment included a dual-energy X-ray absorptiometry scan and interview. Follow-up assessments, which additionally included performance measures, occurred 2, 6, and 12 months after admission. Using these measures, three sarcopenia definitions were assessed over the year following hip fracture: European Working Group on Sarcopenia in Older Persons (EWGSOP), International Working Group on Sarcopenia (IWGS), and Foundation for the National Institutes of Health (FNIH)., Results: EWGSOP and IWGS provided the highest prevalence of sarcopenia (62%-69% in men, 42%-62% in women), while prevalence by FNIH was much lower for men (15%-19%) and women (5%-12%). For both men and women, the agreement between EWGSOP and IWGS definitions was excellent, and FNIH showed poor agreement with them, supported by various statistical measures across first-year follow-up. Prevalence was stable over time in men by all definitions, while the prevalence in women by FNIH was lowest at 2 months, significantly increased at 6 months (P = .03), and remained higher at 12 months. Whether sarcopenia prevalence differed significantly by sex varied by time point and definition; however, when different, men had a higher prevalence than women (P < .05). While some participants recovered from sarcopenia over time, some also became newly sarcopenic., Conclusion: The prevalence of sarcopenia after fracture differed greatly for EWGSOP and IWGS compared to FNIH. Overall, there appeared to be no reduction in sarcopenia over the year after hip fracture, regardless of definition. Future research should examine the relationship between sarcopenia prevalence and functional recovery. J Am Geriatr Soc 68:1537-1544, 2020., (Published 2020. This article is a U.S. Government work and is in the public domain in the USA.)

Introduction: Deep brain stimulation (DBS) surgery is an efficacious, underutilized treatment for Parkinson's disease (PD). Studies of DBS post-operative outcomes are often restricted to data from a single center and consider DBS in isolation. National estimates of DBS readmission and post-operative outcomes are needed, as are comparisons to commonly performed surgeries., Methods: This study used datasets from the 2013 and 2014 Nationwide Readmissions Database (NRD). Our sample was restricted to PD patients discharged alive after hospitalization for DBS surgery. Descriptive analyses examined patient, clinical, hospital and index hospitalization characteristics. The all-cause, non-elective 30-day readmission rate after DBS was calculated, and logistic regression models were built to examine factors associated with readmission. Readmission rates for the most common surgical procedures were calculated and compared to DBS., Results: There were 6058 DBS surgeries for PD in our sample, most often involving a male aged 65 and older, who lived in a high socioeconomic status zip code. DBS patients had an average of four comorbidities. With respect to outcomes, the majority of patients were discharged home (95.3%). Non-elective readmission was rare (4.9%), and was associated with socioeconomic status, comorbidity burden, and teaching hospital status. Much higher acute, non-elective readmission rates were observed for common procedures such as upper gastrointestinal endoscopy (16.2%), colonoscopy (14.0%), and cardiac defibrillator and pacemaker procedures (11.1%)., Conclusion: Short-term hospitalization outcomes after DBS are generally favorable. Socioeconomic disparities in DBS use persist. Additional efforts may be needed to improve provider referrals for and patient access to DBS., Competing Interests: Declaration of competing interest RBS: Has no conflicts of interest relevant to this work but reports grant support from the National Institute of Neurological Disorders and Stroke, Biohaven Pharmaceuticals, CHDI Foundation, Teva Pharmaceuticals, Pfizer, Nuredis Inc., The Michael J. Fox Foundation, and the Canadian Institute of Health Research as well as financial support from the Parkinson's Foundation. JJ-S: Reports research support from Medtronic and St. Jude Medical/Abbott as well as consulting agreements with Medtronic, St. Jude Medical/Abbott, and Boston Scientific relevant to this work. Also reports research support from Teva and Lilly; consulting agreements with Bracket and Nuvelution; and grant support from the National Institute of Neurological Disorders and Stroke, the Michael J. Fox Foundation, and the Simons Foundation. DSA: Has no conflicts of interest relevant to this work but reports research support from the National Institutes of Health and financial support from the Parkinson's Foundation. DPT: None. SM: None. MF: Has no conflicts of interest relevant to this work but reports active research funding from the American Academy of Neurology, American Brain Foundation, and the Parkinson's Foundation. MAB: Has no conflicts of interest relevant to this work but reports active research funding from the Parkinson's Foundation. KLC: Has no conflicts of interest relevant to this work but reports active research funds from the National Institutes of Health and the Parkinson Study Group, consulting agreements with Sunovion Pharmaceuticals, and royalties from UpToDate and Springer. MS: Has no conflicts of interest relevant to this work but reports active research funding from Abbvie, USWorldMeds, Sanofi, Lundbeck, and Abbott. WJJ: None. P-FD: Has no conflicts of interest relevant to this work but reports service as an Officer of Neurotargeting LLC. MKY: Has no conflicts of interest relevant to this work but reports personal compensation for consultant, Steering Committee, and Data Safety Monitoring Board service from the Michael J. Fox Foundation and Boston Scientific. JCK: None. JMS: Has no conflicts of interest relevant to this work but reports research grants from Medtronic, service as a consultant for Guidant, LLC, and salary support from Blue Cross Blue Shield of Michigan. AJE: Has no conflicts of interest relevant to this work but reports grant support from the National Institutes of Health, Great Lakes Neurotechnologies, and the Michael J Fox Foundation; personal compensation as a consultant/scientific advisory board member for Abbvie, Neuroderm, TEVA, Impax, Acadia, Acorda, Cynapsus/Sunovion, Lundbeck, Osmotica Pharmaceutical, and USWorldMeds; publishing royalties from Lippincott Williams & Wilkins, Cambridge University Press, and Springer; and honoraria from Abbvie, UCB, USWorldMeds, Lundbeck, Acadia, the American Academy of Neurology, and the Movement Disorders Society. LCS: Has no conflicts of interest relevant to this work but reports employment with Biogen, Inc. DKS: Has no conflicts of interest relevant to this work but reports research funding from BioElectron Technology, Lysosomal Therapeutics, Mission Therapeutics, Voyager Therapeutics, the Weston Brain Institute, and the National Institutes of Health as well as honorarium for Steering Committee service from the Michael J. Fox Foundation and Biogen. CH: None. JAGC: Has no conflicts of interest relevant to this work but reports research support from the Northern Ontario Academic Medicine Association. AWW: Has no conflicts of interest relevant to this work but reports research funding from the National Institutes of Health and the Parkinson's Foundation., (Copyright © 2019. Published by Elsevier Ltd.)

Introduction: Females have a reduced risk of Parkinson's disease (PD). However, it is unclear if sex is a prognostic factor. We aimed to examine differences in presentation, physician- and patient-reported PD outcomes, and progression by sex in a large clinical cohort., Methods: This study was a secondary analysis of a cohort of PD patients seen at a tertiary care center. Sociodemographic and clinical characteristics, treatment, care timing, and outcomes were examined by sex. Sex differences in progression of impairment, disability, and health-related quality of life (HRQoL) were tested with five-year piecewise linear mixed-effects models. A mediation analysis assessed drivers of sex differences., Results: The study included 914 males and 549 females. Females had significantly less social support, more psychological distress, and worse self-reported (but not physician-reported) disability and HRQoL at initial PD care visits, compared to males. Addressing anxiety symptoms may attenuate this difference. PD progression sex differences were minimal., Conclusion: PD progression does not differ by sex, yet patient-reported measures of disease severity are worse in females than males. To attenuate this sex difference in disease experience, psychological distress screening and management, particularly targeting females, should be implemented as part of PD clinical care., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Purpose: To compare the amount of phacoemulsification ultrasound energy used between eyes undergoing femtosecond laser-assisted cataract surgery (FLACS) and conventional phacoemulsification., Methods: One eye of consecutive patients undergoing routine non-complicated phacoemulsification from January 2014 to December of 2015 was included in the analysis. FLACS was performed using the Alcon LenSx. Linear regression was used for analysis with type of surgery (FLACS versus conventional phacoemulsification) as the exposure and cumulative dispersed energy (CDE) as the outcome variable. Age, surgeon, eye side, and eye sequence (first versus second eye) were covariates., Results: A total of 1159 surgeries met inclusion criteria. The average age of the cohort was 70.6 (SD 8.6) years, 590 cases (51%) were performed by surgeon 1, and 582 cases (50%) were right eyes. Overall, FLACS resulted in significantly lower CDE as compared to conventional phacoemulsification (β = 0.89, 95% CI 0.83, 0.95). When stratified by eye side and surgeon, FLACS performed on left eyes operated on by surgeon 1 resulted in lower CDE as compared to conventional phacoemulsification (β = 0.76, 95% CI 0.66, 0.87), but not for right eyes operated on by surgeon 1 (β = 0.92, 95% CI 0.79, 1.07) or for eyes operated on by surgeons 2 or 3., Conclusions: The use of FLACS on the Alcon LenSx platform results in a small decrease in phacoemulsification energy as compared to conventional phacoemulsification in certain cases. Further study assessing optimal laser settings and surgical technique is necessary.

Objective: To examine trends in 12-month postfracture residual disability, nursing home placement, and mortality among patients with a hip fracture between 1990 and 2011., Design: Secondary analysis of 12-month outcomes from 3 cohort studies and control arms of 2 randomized controlled trials., Setting: Original studies were conducted as part of the Baltimore Hip Studies (BHS)., Participants: Community-dwelling patients ≥65 years of age hospitalized for surgical repair of a nonpathologic hip fracture (N=988)., Main Outcome Measures: Twelve-month residual disability, mortality, and nursing home residency were examined in case-mix adjusted models by sex and study. Residual disability was calculated by subtracting prefracture scores of Lower Extremity Physical Activities of Daily Living from scores at 12 months postfracture. We also examined the proportion of individuals with a 12-month score higher than their prefracture score (residual disability>0)., Results: Only small improvements were seen in residual disability between 1990 and 2011. No significant differences were seen for men between BHS2 (enrollment 1990-1991; mean residual disability=3.1 activities; 95% confidence interval [CI], 2.16-4.10) and BHS7 (enrollment 2006-2011; mean=3.1 activities; 95% CI, 2.41-3.82). In women, residual disability significantly improved from BHS2 (mean=3.5 activities; 95% CI, 2.95-3.99) to BHS3 (enrollment 1992-1995; mean=2.7 activities; 95% CI, 2.01-3.30) with no significant improvements in later studies. After adjustment, a substantial proportion (91% of men and 79% of women) had a negative outcome (residual disability, died, or nursing home residence at 12 months) in the most recently completed study (BHS7)., Conclusions: Over 2 decades, patients undergoing usual care post-hip fracture still had substantial residual disability. Additional clinical and research efforts are needed to determine how to improve hip fracture treatment, rehabilitation, and subsequent outcomes., (Copyright © 2018 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.)

Introduction: Angiotensin converting enzyme inhibitors are commonly prescribed medications after the Norwood procedure. There are little data that can be used to determine if angiotensin converting enzyme inhibitors improve interstage outcomes in children with single ventricle defects. The objective of this study was to investigate the relationship between angiotensin converting enzyme inhibitors and interstage failure among infants born with hypoplastic left heart syndrome., Methods: We conducted a retrospective cohort study using data from the National Pediatric Cardiology Quality Improvement Collaborative database (collected between 2008 and 2015). We used logistic regression models to assess the exposure-outcome associations and propensity score matching to account for differences in baseline patient characteristics associated with use of angiotensin converting enzyme inhibitors., Results: A total of 1 487 neonates participated in the study. Thirty-nine percent of patients were prescribed angiotensin converting enzyme inhibitors after the Norwood procedure; 11% experienced interstage failure (death, heart transplantation, and not being a candidate for the second-stage surgery). Before propensity score matching, patients receiving angiotensin converting enzyme inhibitors were significantly more likely to experience interstage failure, compared to patients not on angiotensin converting enzyme inhibitors (OR = 1.44; 95% CI: 1.04, 1.99; P = 0.03). Although there was an increased odds of interstage failure among patients receiving angiotensin converting enzyme inhibitors compared to patients not receiving angiotensin converting enzyme inhibitors in the propensity score-matched cohort, this association was not significantly different (adjusted OR = 1.29; 95% CI: 0.88, 1.95; P = 0.18)., Conclusion: Angiotensin converting enzyme inhibitor therapy did not demonstrate a beneficial effect on interstage failure among infants with hypoplastic left heart syndrome, even when patient characteristics associated with the use of angiotensin converting enzyme inhibitors were considered., (© 2018 Wiley Periodicals, Inc.)

Background: Low birth and operative weight have been identified as risk factors for death after first-stage single-ventricle palliation. We hypothesize that weight gain after the first-stage operation is associated with transplant-free interstage survival to admission for the second-stage operation., Methods: We used historical data from the National Pediatric Cardiology Quality Improvement Collaborative database to conduct a longitudinal study to assess the association between weight gain and transplant-free interstage survival. The primary predictor was weight gain. The primary outcome was transplant-free survival. We constructed a repeated-measures logistic regression model using the general estimating equation method to examine the association between weight gain and transplant-free interstage survival., Results: The study population included 1,501 infants who were discharged alive from the first-stage single-ventricle palliation between June 2008 and January 2015. Patients who underwent a hybrid operation (n = 132) or were lost to follow-up (n = 11) were excluded. Transplant-free interstage survival was 90% (1,228 of 1,358). The mean weight gain was 2.5 (SD, 1.0) kg. Adjusted for age at the time of each measurement, the number of measurements, age at discharge from the first-stage operation, sex, diagnosis, postoperative arrhythmia, postoperative complications, and discharge antibiotic therapy, each 100-g increase in weight was associated with an odds ratio of transplant-free interstage survival of 1.03 (95% confidence limit, 1.01, 1.05)., Conclusions: After first-stage single-ventricle palliation, interstage weight gain is significantly associated with transplant-free interstage survival., (Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Objectives: To evaluate the efficacy and safety of lorazepam in reducing psychological distress and chemotherapy-induced nausea and vomiting., Methodology: It was a prospective interventional study with seventy patients for a period of 1 year. In which, patients' anxiety, distress and status of nausea, and vomiting were assessed in the first four chemotherapy cycles before drug intervention. During the subsequent chemotherapy cycles, the outcomes of the intervention were reassessed along with patient's quality of life (QOL)., Results: Out of seventy patients, 62 showed improvement in their distress level after the drug intervention and patient counseling. Lorazepam along with other antiemetic drugs reduced chemotherapy-induced delayed nausea and vomiting. During the course of the study, 15 patients experienced drowsiness as an adverse reaction to lorazepam. The overall QOL of the population was also improved with lorazepam., Conclusion: Lorazepam along with patient counseling can improve patient's psychological distress and thus their QOL. The off-labeled use of lorazepam can be utilized for controlling chemotherapy-induced nausea vomiting., Competing Interests: There are no conflicts of interest.

Objective: Psychological distress is common among Parkinson disease (PD) patients. Screening tools, such as the Brief Symptom Inventory-18 (BSI-18), help clinicians to identify and manage PD patients with psychiatric symptoms. The objective of this study is to test the factor structure of the BSI-18 in PD patients., Methods: Analysis was conducted on PD patients who had initial visits at a movement disorders center from 2004 to 2015. Univariate analysis was used to describe the distribution of socio-demographic and clinical characteristics. The BSI-18 was used to determine the prevalence of clinically significant psychological distress. Confirmatory factor analyses (CFA) treating BSI-18 items as ordered categorical data were conducted. Five competing models were tested. Multiple fit indices, parsimony, and past theory were used to select the final model., Results: In the study sample (n=1067), 18.7%, 22.5%, 15.4%, and 15.0% of patients had BSI-18 T-scores indicative of clinically significant global psychological distress, somatization, depression, and anxiety, respectively. Of the competing models, the final model chosen was the second-order three-factor structure with somatization, depression, and anxiety loaded on psychological distress., Conclusion: The original proposed factor structure of the BSI-18 was validated in this patient population. Consequently, this study confirms the construct validity of the BSI-18 for screening of psychological distress in PD patients. Findings highlight somatization as a particularly important component of psychological distress in PD patients., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Hospital readmissions are common and costly. Our goal was to determine the association between depressive symptoms and readmission within 30 days following hospital discharge in older adults., Methods: We analyzed data from a study of 789 persons aged 65 years or older admitted to a 20-bed acute care for elders (ACE) hospital unit from May 2009 to July 2011. Depressive symptoms were recorded within 24-hours of admission to the hospital unit, using the Center for Epidemiologic Studies -Depression (CES-D) Scale. The primary outcome was readmission to hospital within 30 days of discharge., Results: The mean age was 77 years; 66% were female, 72% were White, and 59% were unmarried. On average, older patients reported 2.6 comorbid conditions. Sixteen percent were classified with high depressive symptoms (CES-D ≥ 16). The readmission rate within 30 days was 15%. Older patients with high depressive symptoms had more than 1.6 times the odds (OR 1.66; 95% CI: 1.01-2.74) of being readmitted within 30-days, as compared to those with low depressive symptoms (CES-D < 16), after adjustment for age, race/ethnicity, sex, marital status and comorbid conditions., Conclusion: High depressive symptoms increased the risk of hospital readmission within 30 days of discharge after adjusting for relevant covariates. In-hospital screening for depressive symptoms may identify older persons at risk for recurrent hospital admissions.

The yeast Mcm1 protein is a member of the MADS box family of transcription factors that interacts with several cofactors to differentially regulate genes involved in cell-type determination, mating, cell cycle control and arginine metabolism. Residues 18 to 96 of the protein, which form the core DNA-binding domain of Mcm1, are sufficient to carry out many Mcm1-dependent functions. However, deletion of residues 2 to 17, which form the nonessential N-terminal (NT) arm, confers a salt-sensitive phenotype, suggesting that the NT arm is required for the activation of salt response genes. We used a strategy that combined information from the mutational analysis of the Mcm1-binding site with microarray expression data under salt stress conditions to identify a new subset of Mcm1-regulated genes. Northern blot analysis showed that the transcript levels of several genes encoding associated with the cell wall, especially YGP1, decrease significantly upon deletion of the Mcm1 NT arm. Deletion of the Mcm1 NT arm results in a calcofluor white-sensitive phenotype, which is often associated with defects in transcription of cell wall genes. In addition, the deletion makes cells sensitive to CaCl2 and alkaline pH. We found that the defect caused by removal of the NT arm is not due to changes in Mcm1 protein level, stability, DNA-binding affinity, or DNA bending. This suggests that residues 2 to 17 of Mcm1 may be involved in recruiting a cofactor to the promoters of these genes to activate transcription.