Hospital variation of outcomes in status epilepticus.

OBJECTIVE: Understanding factors driving variation in status epilepticus outcomes would be critical to improve care. We evaluated the degree to which patient and hospital characteristics explained hospital-to-hospital variability in intubation and postacute outcomes. METHODS: This was a retrospective cohort study of Medicare beneficiaries admitted with status epilepticus between 2009 and 2019. Outcomes included intubation, discharge to a facility, and 30- and 90-day readmissions and mortality. Multilevel models calculated percent variation in each outcome due to hospital-to-hospital differences. RESULTS: We included 29 150 beneficiaries. The median age was 68 years (interquartile range [IQR] = 57-78), and 18 084 (62%) were eligible for Medicare due to disability. The median (IQR) percentages of each outcome across hospitals were: 30-day mortality 25% (0%-38%), any 30-day readmission 14% (0%-25%), 30-day status epilepticus readmission 0% (0%-3%), 30-day facility stay 40% (25%-53%), and intubation 46% (20%-61%). However, after accounting for many hospitals with small sample size, hospital-to-hospital differences accounted for 2%-6% of variation in all unadjusted outcomes, and approximately 1%-5% (maximally 8% for 30-day readmission for status epilepticus) after adjusting for patient, hospitalization, and/or hospital characteristics. Although many characteristics significantly predicted outcomes, the largest effect size was cardiac arrest predicting death (odds ratio = 10.1, 95% confidence interval = 8.8-11.7), whereas hospital characteristics (e.g., staffing, accreditation, volume, setting, services) all had lesser effects. SIGNIFICANCE: Hospital-to-hospital variation explained little variation in studied outcomes. Rather, certain patient characteristics (e.g., cardiac arrest) had greater effects. Interventions to improve outcomes after status epilepticus may be better focused on individual or prehospital factors, rather than at the inpatient systems level.

Changes in the Use of Brand Name and Generic Medications and Total Prescription Cost Among Medicare Beneficiaries With Epilepsy.

OBJECTIVE: To characterize trends in antiseizure medication (ASM) fills and total prescription costs in people with epilepsy. METHODS: This was a retrospective cohort study of beneficiaries with epilepsy (ASM, plus International Classification of Diseases codes) in a 20% random Medicare sample, with continuous Fee-For-Service coverage (Parts A, B, and D) in 2008-2018. We summed the number of pill days and costs (adjusted to 2018 dollars) per person-year for each ASM. ASMs were categorized into brand versus generic, first- versus newer-generation, and enzyme-inducers versus non-inducers. RESULTS: There were 77,000-133,000 beneficiaries with epilepsy per year. The most common ASM was phenytoin in 2008, which shifted to levetiracetam in 2018 (2008: phenytoin 25%, levetiracetam 14%; 2018: phenytoin 9%, levetiracetam 27%). Brand name (2008: 56%; 2018: 14%), first-generation (2008: 55%; 2018: 32%), and enzyme-inducing ASMs (2008: 44%; 2018: 24%) each decreased over time as a proportion of pill days. The number of brand pill days per person-year initially decreased (e.g. 2008: 250; 2009: 121; 2010: 96), but then plateaued (2013-2018: between 66-69) given a notable increase in lacosamide pill days per person (2008: 0; 2018: 20). Total brand name costs per year initially decreased 2008-2010 (2008: $150 million; 2010: $72 million) but then increased after 2010 (2018: $256 million). In 2018 brand name ASMs represented 79% of costs despite representing only 14% of pill days, a one-year pill supply became 277% more expensive for brand name but 42% less expensive for generic medications over time (2008: brand ∼$2,800 versus generic ∼$800; 2018: brand ∼$10,700 versus generic ∼$460), and many common brand name ASMs cost approximately ten-fold more per pill day than their generic equivalents. CONCLUSIONS: First-generation and enzyme-inducing ASMs waned from 2008 to 2018. While brand name ASMs initially waned translating into lower costs and potentially higher value care, after 2010 brand name costs markedly increased due to increasing use of lacosamide plus a 277% increase in per-pill cost of brand name ASMs. Brand name ASMs represented a small minority of prescriptions, but the large majority of costs.

Polypharmacy composition and patient- and provider-related variation in patients with epilepsy.

OBJECTIVE: To describe polypharmacy composition, and the degree to which patients versus providers contribute to variation in medication fills, in people with epilepsy. METHODS: We performed a retrospective study of Medicare beneficiaries with epilepsy (antiseizure medication plus diagnostic codes) in 2014 (N = 78,048). We described total number of medications and prescribers, and specific medications. Multilevel models evaluated the percentage of variation in two outcomes (1. number of medications per patient-provider dyad, and 2. whether a medication was filled within thirty days of a visit) due to patient-to-patient differences versus provider-to-provider differences. RESULTS: Patients filled a median of 12 (interquartile range [IQR] 8-17) medications, from median of 5 (IQR 3-7) prescribers. Twenty-two percent filled an opioid, and 61% filled at least three central nervous system medications. Levetiracetam was the most common medication (40%), followed by hydrocodone/acetaminophen (27%). The strongest predictor of medications per patient was Charlson comorbidity index (7.5 [95% confidence interval (CI) 7.2-7.8] additional medications for index 8+ versus 0). Provider-to-provider variation explained 36% of variation in number of medications per patient, whereas patient-to-patient variation explained only 2% of variation. Provider-to-provider variation explained 57% of variation in whether a patient filled a medication within 30 days of a visit, whereas patient-to-patient variation explained only 30% of variation. CONCLUSION: Patients with epilepsy fill a large number of medications from a large number of providers, including high-risk medications. Variation in medication fills was substantially more related to provider-to-provider rather than patient-to-patient variation. The better understanding of drivers of high-prescribing practices may reduce avoidable medication-related harms.

Clinical characteristics and outcomes of nonurothelial cell carcinoma of the bladder: Results from the National Cancer Data Base.

OBJECTIVES: To determine the clinical characteristics, treatment patterns, and outcomes of patients with nonurothelial cell bladder cancer (NUBC) in the United States. METHODS: A total of 163,683 patients with bladder cancer from 1998 to 2014 in the National Cancer Data Base were identified. Of all, 153,262 had urothelial cell (UC) carcinoma (93.6%) and 10,421 had NUBC (6.4%) further classified as: squamous cell carcinoma (SC, 2.4%), adenocarcinoma (AC, 1.7%), neuroendocrine (NE, 1.3%), micropapillary (MP, a UC variant histology, 0.3%), lymphoid/haematopoietic (LH, 0.3%), and sarcoma/mesenchymal (SM, 0.3%). Analyses were run on the entire cohort, those with non-muscle-invasive disease (T0-1, N0, M0), muscle-invasive disease (MIBC, T2-4A, N0, M0), and metastatic disease (T4B or N+ or M+). Clinical characteristics and treatment received (surgery, chemotherapy, and radiation) were reported by histologic subtype. Survival analysis was performed via Kaplan-Meier estimates and Cox proportional hazards models. RESULTS: Patients with NE, SC, MP, and AC were more likely to be diagnosed with metastatic disease (11.5% for UC vs. 40%, 31.3%, 17.8%, and 30.6%, respectively, P<0.001). Patients with NUBC were also more likely to have MIBC compared to UC (43% vs. 32.5%, respectively). For all patients, those with UC may be less likely to undergo cystectomy, chemotherapy, and radiation therapy (P<0.001). For all patients, NUBC, with the exception of LH, SM, and MP, was associated with inferior survival compared to UC (P<0.001). CONCLUSIONS: This encompassing clinical characterization and prognosis of NUBC patients in the United States shows NUBC patients have significantly different disease characteristics compared to those with UC, and present with more advanced disease, receive more treatment, and overall have inferior outcomes. Further work is needed to help improve outcomes for these patients.

Time-resolved spectroscopy using a chopper wheel as a fast shutter.

Widely available, small form-factor, fiber-coupled spectrometers typically have a minimum exposure time measured in milliseconds, and thus cannot be used directly for time-resolved measurements at the microsecond level. Spectroscopy at these faster time scales is typically done with an intensified charge coupled device (CCD) system where the image intensifier acts as a "fast" electronic shutter for the slower CCD array. In this paper, we describe simple modifications to a commercially available chopper wheel system to allow it to be used as a "fast" mechanical shutter for gating a fiber-coupled spectrometer to achieve microsecond-scale time-resolved optical measurements of a periodically pulsed light source. With the chopper wheel synchronized to the pulsing of the light source, the time resolution can be set to a small fraction of the pulse period by using a chopper wheel with narrow slots separated by wide spokes. Different methods of synchronizing the chopper wheel and pulsing of the light sources are explored. The capability of the chopper wheel system is illustrated with time-resolved measurements of pulsed plasmas.

Electron-impact excitation out of the metastable levels of krypton.

We have measured the electron-impact excitation cross sections out of the two metastable levels of Kr into the ten levels of the 4p(5)5p configuration. For a common 4p(5)5p final level, the peak excitation cross sections out of the two individual 4p(5)5s metastable levels are found to differ by 1 to 2 orders of magnitude. This is explained by the special features of the electronic structure of the two configurations involved. The peak cross sections are 10 to 1600 times larger than the corresponding peak cross sections out of the ground state.