OBJECT Postsurgical readmissions are common and vary by procedure. They are significant drivers of increased expenditures in the health care system. Reducing readmissions is a national priority that has summoned significant effort and resources. Before the impact of quality improvement efforts can be measured, baseline procedure-related 30-day all-cause readmission rates are needed. The objects of this study were to determine population-level, 30-day, all-cause readmission rates for cranial neurosurgery and identify factors associated with readmission. METHODS The authors identified patient discharge records for cranial neurosurgery and their 30-day all-cause readmissions using the Agency for Healthcare Research and Quality (AHRQ) State Inpatient Databases for California, Florida, and New York. Patients were categorized into 4 groups representing procedure indication based on ICD-9-CM diagnosis codes. Logistic regression models were developed to identify patient characteristics associated with readmissions. The main outcome measure was unplanned inpatient admission within 30 days of discharge. RESULTS A total of 43,356 patients underwent cranial neurosurgery for neoplasm (44.23%), seizure (2.80%), vascular conditions (26.04%), and trauma (26.93%). Inpatient mortality was highest for vascular admissions (19.30%) and lowest for neoplasm admissions (1.87%; p < 0.001). Thirty-day readmissions were 17.27% for the neoplasm group, 13.89% for the seizure group, 23.89% for the vascular group, and 19.82% for the trauma group (p < 0.001). Significant predictors of 30-day readmission for neoplasm were Medicaid payer (OR 1.33, 95% CI 1.15–1.54) and fluid/electrolyte disorder (OR 1.44, 95% CI 1.29–1.62); for seizure, male sex (OR 1.74, 95% CI 1.17–2.60) and index admission through the emergency department (OR 2.22, 95% CI 1.45–3.43); for vascular, Medicare payer (OR 1.21, 95% CI 1.05–1.39) and renal failure (OR 1.52, 95% CI 1.29–1.80); and for trauma, congestive heart failure (OR 1.44, 95% CI 1.16–1.80) and coagulopathy (OR 1.51, 95% CI 1.25–1.84). Many readmissions had primary diagnoses identified by the AHRQ as potentially preventable. CONCLUSIONS The frequency of 30-day readmission rates for patients undergoing cranial neurosurgery varied by diagnosis between 14% and 24%. Important patient characteristics and comorbidities that were associated with an increased readmission risk were identified. Some hospital-level characteristics appeared to be associated with a decreased readmission risk. These baseline readmission rates can be used to inform future efforts in quality improvement and readmission reduction.

A lzheimer's disease (AD) is a progressive and ultimately fatal neurodegenerative disorder characterized by cognitive and functional decline. In the brain, the microscopic hallmarks are β-amyloid-containing plaques and neurofibrillary tangles. Therapeutic options are limited. On June 7, 2021, against the strong recommendation of the Peripheral and Central Nervous System Drugs Advisory Committee, the US Food and Drug Administration (FDA) approved aducanumab as "an amyloid-directed antibody indicated for the treatment of Alzheimer's disease." 1 The usual standard for FDA approval is a determination that a drug is both safe and effective. However, aducanumab was approved under an Accelerated Approval Program that allows for earlier approval of drugs that treat serious conditions and that fill an unmet medical need, based on a surrogate end point-in this instance, based on dose-dependent reductions of β-amyloid plaques in the brain as demonstrated by amyloid imaging using positron emission tomography.

We demonstrated that hydrophobic derivatives of the nonsteroidal anti-inflammatory drug (NSAID)flufenamic acid (FA), can be formed into stable nanometer-sized prodrugs (nanoprodrugs) that inhibit the growth of glioma cells, suggesting their potential application as anticancer agent. We synthesized highly hydrophobic monomeric and dimeric prodrugs of FA via esterification and prepared nanoprodrugs using spontaneous emulsification mechanism. The nanoprodrugs were in the size range of 120 to 140 nm and physicochemically stable upon long-term storage as aqueous suspension, which is attributed to the strong hydrophobic interaction between prodrug molecules. Importantly, despite the highly hydrophobic nature and water insolubility, nanoprodrugs could be readily activated into the parent drug by porcine liver esterase, presenting a potential new strategy for novel NSAID prodrug design. The nanoprodrug inhibited the growth of U87-MG glioma cells with IC50 of 20 μM, whereas FA showed IC50 of 100 μM, suggesting that more efficient drug delivery was achieved with nanoprodrugs.

Background As the global climate changes in response to anthropogenic greenhouse gas emissions, weather and temperature are expected to become increasingly variable. Although heat sensitivity is a recognized clinical feature of multiple sclerosis (MS), a chronic demyelinating disorder of the central nervous system, few studies have examined the implications of climate change for patients with this disease. Methods and findings We conducted a retrospective cohort study of individuals with MS ages 18–64 years in a nationwide United States patient-level commercial and Medicare Advantage claims database from 2003 to 2017. We defined anomalously warm weather as any month in which local average temperatures exceeded the long-term average by ≥1.5°C. We estimated the association between anomalously warm weather and MS-related inpatient, outpatient, and emergency department visits using generalized log-linear models. From 75,395,334 individuals, we identified 106,225 with MS. The majority were women (76.6%) aged 36–55 years (59.0%). Anomalously warm weather was associated with increased risk for emergency department visits (risk ratio [RR] = 1.043, 95% CI: 1.025–1.063) and inpatient visits (RR = 1.032, 95% CI: 1.010–1.054). There was limited evidence of an association between anomalously warm weather and MS-related outpatient visits (RR = 1.010, 95% CI: 1.005–1.015). Estimates were similar for men and women, strongest among older individuals, and exhibited substantial variation by season, region, and climate zone. Limitations of the present study include the absence of key individual-level measures of socioeconomic position (i.e., race/ethnicity, occupational status, and housing quality) that may determine where individuals live—and therefore the extent of their exposure to anomalously warm weather—as well as their propensity to seek treatment for neurologic symptoms. Conclusions Our findings suggest that as global temperatures rise, individuals with MS may represent a particularly susceptible subpopulation, a finding with implications for both healthcare providers and systems.

Objectives: Quality and safety improvement are global priorities. In the last two decades, the United States has introduced several payment reforms to improve patient safety. The Agency for Healthcare Research and Quality (AHRQ) developed tools to identify preventable inpatient adverse events using administrative data, patient safety indicators (PSIs). The aim of this study was to assess changes in national patient safety trends that corresponded to U.S. pay-for-performance reforms.Methods: This is a retrospective, longitudinal analysis to estimate temporal changes in 13 AHRQ's PSIs. National inpatient sample from the AHRQ and estimates were weighted to represent a national sample. We analyzed PSI trends, Center for Medicaid and Medicare Services payment policy changes, and Inpatient Prospective Payment System regulations and notices between 2000 and 2013.Results: Of the 13 PSIs studied, 10 had an overall decrease in rates and 3 had an increase. Joinpoint analysis showed that 12 of 13 PSIs had decreasing or stable trends in the last 5 years of the study. Central-line blood stream infections had the greatest annual decrease (−31.1 annual percent change between 2006 and 2013), whereas postoperative respiratory failure had the smallest decrease (−3.5 annual percent change between 2005 and 2013). With the exception of postoperative hip fracture, significant decreases in trends preceded federal payment reform initiatives.Conclusions: National in-hospital patient safety has significantly improved between 2000 and 2015, as measured by PSIs. In this study, improvements in PSI trends often proceeded policies targeting patient safety events, suggesting that intense public discourses targeting patient safety may drive national policy reforms and that these improved trends may be sustained by the Center for Medicare and Medicaid Services policies that followed.

In a recent study published by De Ruysscher et al. (1), the use of prophylactic cranial irradiation (PCI) significantly reduced the rate of symptomatic brain metastasis development in patients with stage 3 non-small-cell lung cancer (NSCLC) at 2 years. Patients with WHO performance status 0-2 undergoing chemoradiotherapy with or without surgery for their stage 3 disease were randomized to an observation arm or a treatment arm that underwent PCI (36 Gy in 18 fractions, 30 Gy in 12 fractions, or 30 Gy in 10 fractions). Symptomatic brain metastases occurred at 2 years in 27.2% in the observed patients and 7.0% in the treated patients for a number needed to treat of 4.95 to prevent a case of symptomatic brain metastasis. The intervention improved time to develop symptomatic brain metastases, but not brain metastasis-free survival or, importantly, overall survival (OS). More patients in the intervention arm developed neurologic toxicity, most significantly complaining of grade 1 and 2 headaches, cognitive changes (19% with PCI, 3% without) and memory difficulties (30% with PCI, 8% without); the latter two changes persisted well beyond the 2-year primary endpoint. These results lead us to ask: after multiple studies, why hasn't PCI led to meaningful changes in OS, and how should we weigh the demonstrated neurocognitive effects if recommending this palliative treatment to patients? Brain metastases are an unfortunately common complication of Stage 3 NSCLC, occurring in about 30% of patients at 2 years (2). Because CNS progression

In this population-based study, certain accountability measures proposed for use as value-based payment modifiers show higher RAR in neurosurgery patients compared with other surgical patients and were subsequently associated with poor outcomes. Our results indicate that for quality improvement efforts, the current AHRQ risk-adjustment models should be viewed in clinically meaningful stratified subgroups: for profiling and pay-for-performance applications, additional factors should be included in the risk-adjustment models. Further evaluation of PSIs in additional high-risk surgeries is needed to better inform the use of these metrics.

Background Glioblastoma (GBM) treatment requires access to complex medical services, and the Patient Protection and Affordable Care Act (ACA) sought to expand access to health care, including complex oncologic care. Whether implementation of the ACA was subsequently associated with changes in one-year survival in GBM is not known. Methods A retrospective cohort study was performed using the Surveillance, Epidemiology and End Results Database. We identified patients with the primary diagnosis of GBM between 2008 and 2016. A multivariable adjusted Cox proportional hazards model was developed using patient and clinical characteristics to determine the main outcome: one-year cumulative probability of death by state expansion status. Results A total of 25,784 patients and 14,355 deaths at one year were identified and included in the analysis, 49.7% were older than 65 at diagnosis. Overall one-year cumulative probability of death for GBM patients in non-expansion versus expansion states did not significantly worsen over the two time periods (2008-2010: HR 1.11 [95% CI 1.04 – 1.19], 2014-2016: HR 1.18 [95% CI 1.09 – 1.27]). In GBM patients younger than age 65 at diagnosis, there was a non-significant trend toward poorer one-year cumulative probability of death in non-expansion versus expansion states (2008-2010: HR 1.09 [95% CI 0.97 – 1.22], 2014-2016: HR 1.23 [95% CI 1.09 – 1.40]). Conclusions No differences were found over time in survival for GBM patients in expansion versus non-expansion states. Further study may reveal whether GBM patients diagnosed under the age of 65 in expansion states experienced improvements in one-year survival.