Seasonal Variation in Neurologic Hospitalizations in the United States.

OBJECTIVE: Certain neurologic diseases have been noted to vary by season, and this is important for understanding disease mechanisms and risk factors, but seasonality has not been systematically examined across the spectrum of neurologic disease, and methodologic guidance is also lacking. METHODS: Using nationally representative data from the National Inpatient Sample, a stratified 20% sample of all non-federal acute care hospitalizations in the United States, we calculated the monthly rate of hospitalization for 14 neurologic diseases from 2016 to 2018. For each disease, we assessed seasonality of hospitalization using chi-squared, Edward, and Walter-Elwood tests and seasonal time series regression models. Statistical tests were adjusted for multiple hypothesis testing using Bonferroni correction. RESULTS: Meningitis, encephalitis, ischemic stroke, intracerebral hemorrhage, Guillain-Barre syndrome, and multiple sclerosis had statistically significant seasonality according to multiple methods of testing. Subarachnoid hemorrhage, status epilepticus, myasthenia gravis, and epilepsy had significant seasonality according to Edwards and Walter-Elwood tests but not chi-square tests. Seasonal time series regression illustrated seasonal variation in all 14 diseases of interest, but statistical testing for seasonality within these models using the Kruskal-Wallis test only achieved statistical significance for meningitis. INTERPRETATION: Seasonal variation is present across the spectrum of acute neurologic disease, including some conditions for which seasonality has not previously been described, and can be examined using multiple different methods. ANN NEUROL 2023;93:743-751.

Adjusting for Underrepresentation Reveals Widespread Underestimation of Parkinson's Disease Symptom Burden.

BACKGROUND: Clinical research is limited by underrepresentation, but the impact of underrepresentation on patient-reported outcomes in Parkinson's disease (PD) is unknown. OBJECTIVES: To produce nationwide estimates of non-motor symptom (NMS) prevalence and PD-related quality of life (QOL) limitations while accounting for underrepresentation. METHODS: We performed a cross-sectional analysis of data from the Fox Insight (FI) study, an ongoing prospective longitudinal study of persons with self-reported PD. Using epidemiologic literature and United States (US) Census Bureau, Medicare, and National Health and Aging Trends Study data, we simulated a "virtual census" of the PD population. To compare the PD census to the FI cohort, we used logistic regression to model the odds of study participation and calculate predicted probabilities of participation for inverse probability weighting. RESULTS: There are an estimated 849,488 persons living with PD in the US. Compared to 22,465 eligible FI participants, non-participants are more likely to be older, female, and non-White; live in rural regions; have more severe PD; and have lower levels of education. When these predictors were incorporated into a multivariable regression model, predicted probability of participation was much higher for FI participants than non-participants, indicating a significant difference in the underlying populations (propensity score distance 2.62). Estimates of NMS prevalence and QOL limitation were greater when analyzed using inverse probability of participation weighting compared to unweighted means and frequencies. CONCLUSIONS: PD-related morbidity may be underestimated because of underrepresentation, and inverse probability of participation weighting can be used to give greater weight to underrepresented groups and produce more generalizable estimates. © 2023 International Parkinson and Movement Disorder Society.

Health equity integrated epilepsy care and research: A narrative review.

BACKGROUND: With the unanimous approval of the Intersectoral Global Action Plan on epilepsy and other neurological disorders by the World Health Organization in May 2022, there are strong imperatives to work towards equitable neurological care. AIMS: Using epilepsy as an entry point to other neurologic conditions, we discuss disparities faced by marginalized groups including racial/ethnic minorities, Americans living in rural communities, and Americans with low socioeconomic status. MATERIALS AND METHODS: The National Institute on Minority Health Disparities Research Framework (NIMHD) was used to conduct a narrative review through a health equity lens to create an adapted framework for epilepsy and propose approaches to working towards equitable epilepsy and neurological care. RESULTS: In this narrative review, we identified priority populations (racial and ethnic minority, rural-residing, and low socioeconomic status persons with epilepsy) and outcomes (likelihood to see a neurologist, be prescribed antiseizure medications, undergo epilepsy surgery, and be hospitalized) to explore disparities in epilepsy and guide our focused literature search using PubMed. In an adapted NIMHD framework, we examined individual, interpersonal, community, and societal level contributors to health disparities across five domains: (1) behavioral, (2) physical/built environment, (3) sociocultural, (4) environment, and (5) healthcare system. We take a health equity approach to propose initiatives that target modifiable factors that impact disparities and advocate for sustainable change for priority populations. DISCUSSION: To improve equity, healthcare providers and relevant societal stakeholders can advocate for improved care coordination, referrals for epilepsy surgery, access to care, health informatics interventions, and education (i.e., to providers, patients, and communities). More broadly, stakeholders can advocate for reforms in medical education, and in the American health insurance landscape. CONCLUSIONS: Equitable healthcare should be a priority in neurological care.

Core concepts in pharmacoepidemiology: Key biases arising in pharmacoepidemiologic studies.

Pharmacoepidemiology has an increasingly important role in informing and improving clinical practice, drug regulation, and health policy. Therefore, unrecognized biases in pharmacoepidemiologic studies can have major implications when study findings are translated to the real world. We propose a simple taxonomy for researchers to use as a starting point when thinking through some of the most pervasive biases in pharmacoepidemiology. We organize this discussion according to biases best assessed with respect to the study population (including confounding by indication, channeling bias, healthy user bias, and protopathic bias), the study design (including prevalent user bias and immortal time bias), and the data source (including misclassification bias and missing data/loss to follow up). This tutorial defines, provides a curated list of recommended references, and illustrates through relevant case examples these key biases to consider when planning, conducting, or evaluating pharmacoepidemiologic studies.

Dopamine agonists and risk of lung cancer in patients with restless legs syndrome.

PURPOSE: To examine the association between long-term use of dopamine agonists (DAs) and the risk of lung cancer in patients with restless legs syndrome (RLS). METHODS: We conducted a retrospective cohort study using Optum Clinformatics® database. We included adults ≥40 years diagnosed with RLS during the study period (1/2006-12/2016). Follow-up started with the first RLS diagnosis and ended on the earliest of: incident diagnosis of lung cancer, end of enrollment in the database or end of the study period. The exposure of interest was cumulative duration of DAs use, measured in a time-varying manner. We constructed a multivariable Cox regression model to estimate HRs and 95% CIs for the association between lung cancer and cumulative durations of DA use, adjusting for potential confounding variables. RESULTS: We identified 295 042 patients with a diagnosis of RLS. The mean age of the cohort was 62.9; 66.6% were women and 82.3% were white. The prevalence of any DA exposure was 40.3%. Compared to the reference group (no use and ≤1 year), the crude HRs for lung cancer were 1.16 (95% CI 0.99-1.36) and 1.14 (95% CI 0.86-1.51) for 1-3 years and >3 years of cumulative DA use, respectively. The adjusted HR for lung cancer was 1.05 (95% CI 0.88-1.25) for 1-3 years and 1.02 (95% CI 0.76-1.37) for >3 years of cumulative DA use, respectively. CONCLUSIONS: At typical doses for the clinical management of RLS, long-term DA use was not associated with risk of lung cancer.

Medicare Claims Data Underestimate Hallucinations in Older Adults With Dementia.

OBJECTIVE: Administrative claims data are used to study the incidence and outcomes of dementia-related hallucinations, but the validity of International Classification of Diseases (ICD) codes for identifying dementia-related hallucinations is unknown. METHODS: We analyzed Medicare-linked survey data from 2 nationally representative studies of U.S. older adults (the National Health and Aging Trends Study and the Health and Retirement Study) which contain validated cognitive assessments and a screening question for hallucinations. We identified older adults who had dementia or were permanent nursing home residents, and we combined this with questionnaire responses to define dementia-related hallucinations. Using Medicare claims data, we calculated the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of ICD codes for dementia-related hallucinations overall and within prespecified strata of age, neurologic comorbidity, and health care utilization. RESULTS: We included 2,337 older adults with dementia in our cohort. Among 3,789 person-years of data, 1,249 (33.0%) had hallucations, and of these 286 had a qualifying ICD code for dementia-related hallucinations or psychosis (sensitivity 22.9%). Of 2,540 person-years of dementia without hallucinations, 284 had a diagnosis code for hallucinations (specificity 88.8%). PPV was 50.2%, and NPV was 70.1%. Sensitivity was greatest (57.0%) among those seeing a psychiatrist. Otherwise, there were no significant differences in sensitivity, specificity, PPV, or NPV by age, neurologic diagnosis, or neurologist care. CONCLUSION: Dementia-related hallucinations are poorly captured in administrative claims data, and estimates of their prevalence and outcomes using these data are likely to be biased.

Comparing LASSO and random forest models for predicting neurological dysfunction among fluoroquinolone users.

BACKGROUND: Fluoroquinolones are associated with central (CNS) and peripheral (PNS) nervous system symptoms, and predicting the risk of these outcomes may have important clinical implications. Both LASSO and random forest are appealing modeling methods, yet it is not clear which method performs better for clinical risk prediction. PURPOSE: To compare models developed using LASSO versus random forest for predicting neurological dysfunction among fluoroquinolone users. METHODS: We developed and validated risk prediction models using claims data from a commercially insured population. The study cohort included adults dispensed an oral fluoroquinolone, and outcomes were CNS and PNS dysfunction. Model predictors included demographic variables, comorbidities and medications known to be associated with neurological symptoms, and several healthcare utilization predictors. We assessed the accuracy and calibration of these models using measures including AUC, calibration curves, and Brier scores. RESULTS: The underlying cohort contained 16 533 (1.18%) individuals with CNS dysfunction and 46 995 (3.34%) individuals with PNS dysfunction during 120 days of follow-up. For CNS dysfunction, LASSO had an AUC of 0.81 (95% CI: 0.80, 0.82), while random forest had an AUC of 0.80 (95% CI: 0.80, 0.81). For PNS dysfunction, LASSO had an AUC of 0.75 (95% CI: 0.74, 0.76) versus an AUC of 0.73 (95% CI: 0.73, 0.74) for random forest. Both LASSO models had better calibration, with Brier scores 0.17 (LASSO) versus 0.20 (random forest) for CNS dysfunction and 0.20 (LASSO) versus 0.25 (random forest) for PNS dysfunction. CONCLUSIONS: LASSO outperformed random forest in predicting CNS and PNS dysfunction among fluoroquinolone users, and should be considered for modeling when the cohort is modest in size, when the number of model predictors is modest, and when predictors are primarily binary.

Selected autonomic signs and symptoms as risk markers for phenoconversion and functional dependence in prodromal Parkinson's disease.

PURPOSE: To determine whether dysautonomia can stratify individuals with other prodromal markers of Parkinson's disease (PD) for risk of phenoconversion and functional decline, which may help identify subpopulations appropriate for experimental studies. METHODS: Data were obtained from Parkinson's Progression Markers Initiative. Cohorts without PD but with at-risk features were included (hyposmia and/or rapid-eye-movement-sleep behavior disorder, LRRK2 gene mutation, GBA gene mutation). Dysautonomia measures included Scales-for-Outcomes-in-Parkinson's-Disease Autonomic (SCOPA-AUT), seven SCOPA-AUT subscales, and cardiovascular dysfunction (supine hypertension, low pulse pressure, neurogenic orthostatic hypotension). Outcome measures were phenoconversion and Schwab-and-England Activities-of-Daily-Living (SE-ADL) ≤ 70, which indicates functional dependence. Cox proportional-hazards regression was used to evaluate survival to phenoconversion/SE-ADL ≤ 70 for each dysautonomia measure. If a significant association was identified, a likelihood-ratio test was employed to evaluate whether a significant interaction existed between the measure and cohort. If so, regression analysis was repeated stratified by cohort. RESULTS: Median follow-up was 30 months. On multivariable analysis, gastrointestinal and female sexual dysfunction subscales were associated with increased risk of phenoconversion, while the cardiovascular subscale and neurogenic orthostatic hypotension were associated with increased risk of SE-ADL ≤ 70; respective hazard ratios (95% confidence intervals) were 1.13 (1.01-1.27), 3.26 (1.39-7.61), 1.87 (1.16-2.99), 5.45 (1.40-21.25). Only the association between the cardiovascular subscale and SE-ADL ≤ 70 was modified by cohort. CONCLUSIONS: Symptoms of gastrointestinal and female sexual dysfunction predict phenoconversion in individuals with other risk markers for PD, while signs and symptoms of cardiovascular dysfunction may be associated with functional decline.

Readmission Following Hospitalization for Traumatic Brain Injury: A Nationwide Study.

OBJECTIVE: To determine whether sociodemographic and clinical factors were associated with nonelective readmission within 30 days of hospitalization for traumatic brain injury (TBI). Secondary objectives were to examine the effects of TBI severity on readmission and characterize primary reasons for readmission. SETTING: Hospitalized patients in the United States, using the 2014 Nationwide Readmission Database. PARTICIPANTS: All patients hospitalized with a primary diagnosis of TBI between January 1, 2014, and November 30, 2014. We excluded patients (1) with a missing or invalid length of stay or admission date, (2) who were nonresidents, and 3) who died during their index hospitalization. DESIGN: Observational study; cohort study. MAIN MEASURES: Survey weighting was used to compute national estimates of TBI hospitalization and nonelective 30-day readmission. Associations between sociodemographic and clinical factors with readmission were assessed using unconditional logistic regression with and without adjustment for suspected confounders. RESULTS: There were 135 542 individuals who were hospitalized for TBI; 8.9% of patients were readmitted within 30 days of discharge. Age (strongest association for 65-74 years vs 18-24 years: adjusted odds ratio [AOR], 2.57; 95% CI: 2.02-3.27), documentation of a fall (AOR, 1.24; 95% CI: 1.13-1.35), and intentional self-injury (AOR, 3.13; 95% CI: 1.88-5.21) at the index admission were positively associated with readmission. Conversely, history of a motor vehicle (AOR, 0.69; 95% CI: 0.62-0.78) or cycling (AOR, 0.56; 95% CI: 0.40-0.77) accident was negatively associated with readmission. Females were also less likely to be readmitted following hospitalization for a TBI (AOR, 0.87; 95% CI: 0.82-0.92). CONCLUSIONS: Many sociodemographic and clinical factors were found to be associated with acute readmission following hospitalizations for TBI. Future studies are needed to determine the extent to which readmissions following TBI hospitalizations are preventable.

Claims-Based Frailty and Outcomes: Applying an Aging Measure to Older Adults with Parkinson's Disease.

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.

Pharmacosafety of fluoroquinolone and macrolide antibiotics in the clinical care of patients with myasthenia gravis.

INTRODUCTION/AIMS: Anecdotal case reports have suggested a potential association of fluoroquinolones and macrolides with myasthenia gravis (MG) exacerbation, prompting warnings against the use of these drugs in this population. However, large-scale and reliable population-based data that demonstrate this association are lacking. This study aims to examine the association between outpatient treatment with fluoroquinolones or macrolides and MG-related hospitalization. METHODS: A retrospective cohort study consisting of adult MG patients was conducted using a large de-identified healthcare claims database. Antibiotic prescription claims were identified, and MG-related hospitalizations were assessed at 15, 30, and 90 days after the date of prescription. We used mixed effects survival regression with log-logistic distribution and independent covariance matrix to estimate odds ratios (ORs) of hospitalization for each potentially exacerbating antibiotic using beta-lactam as the reference and adjusting for covariates. RESULTS: Among 1556 MG patients receiving 894 fluoroquinolone prescriptions, 729 macrolide prescriptions, and 1608 beta-lactam prescriptions during the study period, there was no difference in 15, 30, or 90-day odds of MG-related hospitalization between fluoroquinolone or macrolide users compared to prescribed beta-lactams. However, estimates were higher for fluoroquinolones than macrolides, even after covariate adjustment (adjusted OR [aOR] 4.60, 95% confidence interval [CI] 0.55-38.57 for fluoroquinolones and OR 0.56, 95% CI 0.32-0.97 for macrolides, respectively, at 15 days). DISCUSSION: Fluoroquinolone and macrolide antibiotics are prescribed frequently to patients with MG. While statistical imprecision precludes a definitive conclusion, elevated ORs for fluoroquinolones raise the possibility of an underpowered association that merits further investigation.

Annual Prevalence of Use of Potentially Inappropriate Medications for Treatment of Affective Disorders in Parkinson's Disease.

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.

Low continuation of antipsychotic therapy in Parkinson disease - intolerance, ineffectiveness, or inertia?

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.

A nationwide analysis of maternal morbidity and acute postpartum readmissions in women with epilepsy.

OBJECTIVE: To compare maternal delivery hospitalization characteristics and postpartum outcomes in women with epilepsy (WWE) versus women without common neurological comorbidities. METHODS: We performed a retrospective cohort analysis of index characterizations and short-term postpartum rehospitalizations after viable delivery within the 2015-2017 National Readmissions Database using International Classification of Diseases, Tenth Revision codes. Wald chi-squared testing compared baseline demographic, hospital and clinical characteristics and postpartum complications between WWE and controls. Multivariable logistic regression models examined odds of nonelective readmissions within 30 and 90 days for WWE compared to controls (alpha = 0.05). RESULTS: A total of 38,518 WWE and 8,136,335 controls had a qualifying index admission for delivery. Baseline differences were most pronounced in Medicare/Medicaid insurance (WWE: 58.2%, controls: 43%, p < 0.0001), alcohol/substance abuse (WWE: 8.3%, controls: 2.5%, p < 0.0001), psychotic disorders (WWE: 1.2%, controls 0.1%, p < 0.0001), and mood disorder (WWE: 15.5%, controls: 3.7%, p < 0.0001). At the time of delivery, WWE were more likely to have edema, proteinuria, and hypertensive disorders (WWE: 19%, controls: 12.9%, p < 0.0001); a history of recurrent pregnancy loss (WWE: 1%, controls: 0.4%, p < 0.0001); preterm labor (WWE: 7.3%, controls: 4.8%, p < 0.0001), or presence of any Center for Disease Control severe maternal morbidity indicator (WWE: 3.2%, controls: 0.6%, p < 0.0001; AOR 5.16, 95% CI 4.70-5.67, p < 0.0001). A higher proportion of WWE were readmitted within 30 days (WWE: 2.4%, controls: 1.1%) and 90 days (WWE: 3.7%, controls: 1.6%). After adjusting for covariates, the odds of postpartum nonelective readmissions within 30 days (AOR 1.86, 95% CI 1.66-2.08, p-value <0.0001) and 90 days (AOR 2.04, 95% CI 1.83-2.28, p-value <0.0001) were higher in WWE versus controls. INTERPRETATION: Women with epilepsy experienced critical obstetric complications and a higher risk of severe maternal morbidity indicators at the time of delivery. Although relatively low, nonelective short-term readmissions after delivery were higher in WWE than women without epilepsy or other common neurological comorbidities. Further research is needed to address multidisciplinary care inconsistencies, improve maternal outcomes, and provide evidence-based guidelines.

Inconsistent reporting of drug-drug interactions for hormonal contraception and antiepileptic drugs - Implications for reproductive health for women with epilepsy.

Drug compendia are the source of safety prescribing information. We assessed the reporting concordance of drug-drug interactions between hormonal contraception and antiepileptic drugs (AEDs) among eight leading international drug compendia. Antiepileptic drugs reported to interact with ≥1 form of hormonal contraception were reviewed. Scaled concordance was quantified using linearly weighted percent agreement (wPA). Differences in interaction severity rankings between hormonal contraception forms were evaluated using the Wilcoxon signed-rank test. There was high agreement among compendia for interactions of combined hormonal contraception interactions with AEDs (wPA = 0.82-0.84), especially potent enzyme-inducing AEDs (wPA = 0.89). However, concordance was reduced for AED interactions with progestin-only contraception (wPA = 0.69-0.81). Extreme interaction reporting discrepancies were found for less potent enzyme-inducing AEDs. The greatest variability in interaction reporting was observed for injectable and intrauterine contraception (wPA = 0.69 and 0.70, respectively), which are the only hormonal contraception options currently classified as not interacting with enzyme-inducing AEDs. Drug-drug interaction reporting variability can have major clinical implications and highlights critical knowledge gaps in the care of women with epilepsy of childbearing age. Further research on AED-contraceptive interactions is needed to standardize compendia reporting and enhance evidence-based clinical guidelines for women with epilepsy.

Comparative neurological safety of fluoroquinolones versus therapeutic alternatives.

BACKGROUND: Fluoroquinolones, one of the most commonly prescribed antibiotic classes, have been implicated in cases of central nervous system (CNS) and peripheral nervous system (PNS) adverse events, which highlights the need for epidemiologic studies of the neurological safety of fluoroquinolones. PURPOSE: To evaluate the safety of fluoroquinolones with regard to risk of diagnosed neurological dysfunction. METHODS: We conducted a propensity score-matched inception cohort study using claims data from a commercially insured population. Our study included adults prescribed an oral fluoroquinolone or comparator antibiotic between January 2000 and September 2015 for acute bacterial sinusitis, acute bacterial exacerbation of chronic bronchitis, uncomplicated urinary tract infection, or acute bronchitis. Our outcomes were CNS dysfunction, and four separate but complementary PNS dysfunction outcomes. Cox proportional hazards models were estimated after matching on propensity scores fitted using the variables age, sex, epilepsy, hereditary peripheral neuropathy, renal dysfunction, diabetes, gabapentinoid use, statin use, isoniazid use, and chemotherapy use. RESULTS: Our cohort contained 976 568 individuals exposed to a fluoroquinolone antibiotic matched 1:1 with a comparator. Matching produced balance (standardized mean difference <0.1) on all variables included in the propensity score. The hazard ratio associated with fluoroquinolone exposure was 1.08 (95% confidence interval 1.05-1.11) for CNS dysfunction, and 1.09 (95% CI 1.07-1.11) for the most commonly occurring PNS dysfunction outcome. CONCLUSIONS: Fluoroquinolone antibiotic use was associated with the development of neurological dysfunction versus comparator antibiotic use in the adult population.

Neurodegenerative disease is associated with increased incidence of epilepsy: a population based study of older adults.

OBJECTIVE: To determine the incidence of epilepsy among Medicare beneficiaries with a new diagnosis of Alzheimer dementia (AD) or Parkinson disease (PD). METHODS: Retrospective cohort study of Medicare beneficiaries with an incident diagnosis of AD or PD in the year 2009. The 5-year incidence of epilepsy was examined by sociodemographic characteristics, comorbidities and neurodegenerative disease status. Cox regression models examined the association of neurodegenerative disease with incident epilepsy, adjusting for demographic characteristics and medical comorbidities. RESULTS: We identified 178,593 individuals with incident AD and 104,157 individuals with incident PD among 34,054,293 Medicare beneficiaries with complete data in 2009. Epilepsy was diagnosed in 4.45% (7,956) of AD patients and 4.81% (5,010) of PD patients between 2009 and 2014, approximately twice as frequently as in the control sample. Minority race/ethnicity was associated with increased risk of incident epilepsy. Among individuals with AD and PD, stroke was associated with increased epilepsy risk. Traumatic brain injury (TBI) was associated with increased epilepsy risk for individuals with PD. Depression was also associated with incident epilepsy (AD adjusted hazard ratio (AHR): 1.23 (1.17-1.29), PD AHR: 1.45 (1.37-1.54)). In PD only, a history of hip fracture (AHR, 1.35 (1.17-1.57)) and diabetes (AHR, 1.11 (1.05-1.18) were also associated with increased risk of epilepsy. CONCLUSION: Incident epilepsy is more frequently diagnosed among neurodegenerative disease patients, particularly when preceded by a diagnosis of depression, TBI or stroke. Further studies into the differences in epilepsy risk between these two populations may help elucidate different mechanisms of epileptogenesis.

Survival and Health Care Use After Deep Brain Stimulation for Parkinson's Disease.

OBJECTIVES: To compare long-term survival of Parkinson's disease (PD) patients with deep brain stimulation (DBS) to matched controls, and examine whether DBS was associated with differences in injurious falls, long-term care, and home care. METHODS: Using administrative health data (Ontario, Canada), we examined DBS outcomes within a cohort of individuals diagnosed with PD between 1997 and 2012. Patients receiving DBS were matched with non-DBS controls by age, sex, PD diagnosis date, time with PD, and a propensity score. Survival between groups was compared using the log-rank test and marginal Cox proportional hazards regression. Cumulative incidence function curves and marginal subdistribution hazard models were used to assess effects of DBS on falls, long-term care admission, and home care use, with death as a competing risk. RESULTS: There were 260 DBS recipients matched with 551 controls. Patients undergoing DBS did not experience a significant survival advantage compared to controls (log-rank test p = 0.50; HR: 0.89, 95% CI: 0.65-1.22). Among patients <65 years of age, DBS recipients had a significantly reduced risk of death (HR: 0.49, 95% CI: 0.28-0.84). Patients receiving DBS were more likely than controls to receive care for falls (HR: 1.56, 95% CI: 1.19-2.05) and home care (HR: 1.59, 95% CI: 1.32-1.90), while long-term care admission was similar between groups. CONCLUSIONS: Receiving DBS may increase survival for younger PD patients who undergo DBS. Future studies should examine whether survival benefits may be attributed to effects on PD or the absence of comorbidities that influence mortality.

Statins for the Prevention of Post-Stroke Seizure and Epilepsy Development: A Systematic Review and Meta-Analysis.

OBJECTIVES: Cerebrovascular disease is the leading cause of seizures and incident epilepsy of known etiology in older adults. Statins have increasingly garnered attention as a potential preventive strategy due to their pleiotropic effects beyond lipid-lowering, which may include neuroprotective and anti-epileptogenic properties. We aim to assess the evidence on statin use for prevention of post-stroke early-onset seizures and post-stroke epilepsy. MATERIALS AND METHODS: We conducted a systematic review and meta-analysis in accordance with PRISMA guidelines, which was prospectively registered with PROSPERO (CRD42019144916). PubMed and Embase were searched from database inception to 05/2020 for English-language, full-text studies examining the association between statin use in adults and development of early-onset seizures (≤7 days post-stroke) or post-stroke epilepsy. Pooled analyses were based on random-effects models using the inverse-variance method. RESULTS: Of 182 citations identified, 175 were excluded due to duplication or ineligibility. The 7 eligible publications were all cohort studies from East Asia or South America, with a total of 53,579 patients. Pre-stroke statin use was not associated with post-stroke epilepsy (3 studies pooled: OR 1.14, CI 0.91-1.42). However, post-stroke statin use was associated with lower risk of both early-onset seizures (3 studies pooled: OR 0.36, CI 0.25-0.53), and post-stroke epilepsy (6 studies pooled: OR 0.64, CI 0.46-0.88). CONCLUSIONS: Review of 7 cohort studies suggested post-stroke, but not pre-stroke, statin use may be associated with reduced risk of early-onset seizures and post-stroke epilepsy. Further research is warranted to validate these findings in broader populations and better parse the temporal components of the associations.

Visual Impairment Is More Common in Parkinson's Disease and Is a Risk Factor for Poor Health Outcomes.

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.