Black Cohosh Interactions with Prescription Medications Associated with Serotonin Toxicity and Rhabdomyolysis: A Case Report.

BACKGROUND: Serotonin toxicity is a well-described phenomenon that is commonly attributed to a variety of drug-drug combinations. Some unregulated herbal supplements have been implicated in the onset of serotonin toxicity, however, there is currently minimal literature available on the potential for black cohosh to contribute to rhabdomyolysis and serotonin toxicity, in spite of its known serotonergic properties. CASE REPORT: A middle-aged woman presented to the emergency department with serotonin toxicity and rhabdomyolysis shortly after taking black cohosh supplements in the setting of long-term dual antidepressant use. The serotonin toxicity and rhabdomyolysis resolved with IV fluids, benzodiazepines, and discontinuation of the offending drugs. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Patients are sometimes not aware of how over-the-counter supplements might interact with their prescription medications. Female patients taking black cohosh to manage hot flashes and menopausal symptoms could be at risk for developing rhabdomyolysis and serotonin toxicity if they are also taking other serotonergic agents.

Trends and predictors of decompressive craniectomy in acute ischemic stroke, 2011-2020.

INTRODUCTION: Rates of decompressive craniectomy (DC) in acute ischemic stroke (AIS) have been reported to decline over time, attributed to an increase in endovascular therapy (EVT) preventing the development of malignant cerebral edema. We sought to characterize trends in DC in AIS between 2011 and 2020. MATERIAL AND METHODS: We performed a retrospective observational study of U.S. AIS hospitalizations using the National Inpatient Sample, 2011 to 2020. We calculated rates of DC per 10,000 AIS among all AIS hospitalizations, as well as AIS hospitalizations undergoing invasive mechanical ventilation (IMV). A logistic regression to determine predictors of DC was performed. RESULTS: Of ∼4.4 million AIS hospitalizations, 0.5 % underwent DC; of ∼300,000 AIS with IMV, 5.8 % underwent DC. From 2011 to 2020, the rate of DC increased from 37.4 to 59.1 per 10,000 AIS (p < 0.001). The rate of DC in patients undergoing IMV remained stable at ∼550 per 10,000 (p = 0.088). The most important factors predicting DC were age (OR 4.88, 95 % CI 4.53-5.25), hospital stroke volume (OR 2.61, 95 % CI 2.17-3.14), hospital teaching status (OR 1.54, 95 % CI 1.36-1.75), and transfer status (OR 1.53, 95 % CI 1.41-1.66); EVT status did not predict DC. CONCLUSIONS: The rate of DC in AIS has increased between 2011 and 2020. Our findings are contrary to prior reports of decreasing DC rates over time. Increasing EVT rates do not seem to be preventing the occurrence of DC. Future research should focus on the decision-making process for both clinicians and surrogates regarding DC with consideration of long-term outcomes.

National Cost Estimates of Invasive Mechanical Ventilation and Tracheostomy in Acute Stroke, 2008-2017.

BACKGROUND: Patients with stroke receiving invasive mechanical ventilation (IMV) and tracheostomy incur intense treatment and long hospitalizations. We aimed to evaluate US hospitalization costs for patients with stroke requiring IMV, tracheostomy, or no ventilation. METHODS: We performed a retrospective observational study of US hospitalizations for acute ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage receiving IMV, tracheostomy, or none using the National Inpatient Sample, 2008 to 2017. We calculated hospitalization costs using cost-to-charge ratios adjusted to 2017 US dollars for inpatients with stroke by ventilation status (no IMV, IMV alone, tracheostomy). RESULTS: Of an estimated 5.2 million (95% CI, 5.1-5.3) acute stroke hospitalizations, 2008 to 2017; 9.4% received IMV alone and 1.4% received tracheostomy. Length of stay for patients without IMV was shorter (median, 4 days; interquartile range [IQR], 2-6) compared with IMV alone (median, 6 days; [IQR, 2-13]), and tracheostomy (median, 25 days; [IQR, 18-36]; P<0.001). Mortality for patients without IMV was 3.2% compared with 51.2% for IMV alone and 9.8% for tracheostomy (P<0.001). Median hospitalization costs for patients without IMV was $9503 (IQR, $6544-$14 963), compared with $23 774 (IQR, $10 900-$47 735) for IMV alone and $95 380 (IQR, $63 921-$144 019) for tracheostomy. Tracheostomy placement in ≤7 days had lower costs compared with placement in >7 days (median, $71 470 [IQR, $47 863-$108 250] versus $102 979 [IQR, $69 563-$152 543]; P<0.001). Each day awaiting tracheostomy was associated with a 2.9% cost increase (95% CI, 2.6%-3.1%). US hospitalization costs for patients with acute stroke were $8.7 billion/y (95% CI, $8.5-$8.9 billion). For IMV alone, costs were $1.8 billion/y (95% CI, $1.7-$1.9 billion) and for tracheostomy $824 million/y (95% CI, $789.7-$858.3 million). CONCLUSIONS: Patients with acute stroke who undergo tracheostomy account for 1.4% of stroke admissions and 9.5% of US stroke hospitalization costs. Future research should focus on the added value to society and patients of IMV and tracheostomy, in particular after 7 days for the latter procedure given the increased costs incurred and poor outcomes in stroke.

Association of Postoperative Delirium and Parkinson Disease After Common United States Surgical Procedures.

INTRODUCTION: To determine the association of Parkinson disease (PD) and postoperative delirium following common surgical procedures. METHODS: We performed a retrospective database analysis of the National Inpatient Sample. We used a matched sample of patients with and without PD who underwent any of ten common surgical procedures in the US, 2005-2014. Primary outcome measure was postoperative delirium for patients with and without PD. Secondary measures included disposition, length of stay, and hospital costs. RESULTS: There were 3,235,866 patients receiving any of the ten most common operative procedures, 2005-2014. There were 35,743 patients with and without PD matched based on age, sex, elective admission status, Charlson Comorbidity index, and presence of dementia. Median age was 77 y (interquartile range 72-82), median Charlson Comorbidity index was 1 (standard deviation 0-2), 46.6% were female, and 46.8% were admitted electively. The three most common operative procedures were hip arthroplasty (28.5%), knee arthroplasty (16.1%), and percutaneous coronary angioplasty (14.9%). Postoperative delirium was present in 1519 patients with PD compared to 828 matched patients without PD (4.2% versus 2.3%; P < 0.001). The adjusted odds ratio of postoperative delirium for PD compared to the matched cohort without PD was 1.88 (95% confidence interval 1.73-2.05). Those undergoing spinal fusion (adjusted odds ratio 2.99, 95% confidence interval 2.06-4.38) had the greatest odds of delirium. For patients with PD, adjusted length of stay, adjusted hospital costs, and adjusted odds of postacute care facility discharge were greater compared to the matched cohort without PD. CONCLUSIONS: Patients with PD are more likely to develop postoperative delirium and have a more complicated postoperative course with longer length of stay and greater hospitalization costs.

Hospital Discharge and Readmissions Before and During the COVID-19 Pandemic for California Acute Stroke Inpatients.

BACKGROUND: Acute stroke therapy and rehabilitation declined during the COVID-19 pandemic. We characterized changes in acute stroke disposition and readmissions during the pandemic. METHODS: We used the California State Inpatient Database in this retrospective observational study of ischemic and hemorrhagic stroke. We compared discharge disposition across a pre-pandemic period (January 2019 to February 2020) to a pandemic period (March to December 2020) using cumulative incidence functions (CIF), and re-admission rates using chi-squared. RESULTS: There were 63,120 and 40,003 stroke hospitalizations in the pre-pandemic and pandemic periods, respectively. Pre-pandemic, the most common disposition was home [46%], followed by skilled nursing facility (SNF) [23%], and acute rehabilitation [13%]. During the pandemic, there were more home discharges [51%, subdistribution hazard ratio 1.17, 95% CI 1.15-1.19], decreased SNF discharges [17%, subdistribution hazard ratio 0.70, 95% CI 0.68-0.72], and acute rehabilitation discharges were unchanged [CIF, p<0.001]. Home discharges increased with increasing age, with an increase of 8.2% for those ≥85 years. SNF discharges decreased in a similar distribution by age. Thirty-day readmission rates were 12.7 per 100 hospitalizations pre-pandemic compared to 11.6 per 100 hospitalizations during the pandemic [p<0.001]. Home discharge readmission rates were unchanged between periods. Readmission rates for discharges to SNF (18.4 vs. 16.7 per 100 hospitalizations, p=0.003) and acute rehabilitation decreased (11.3 vs. 10.1 per 100 hospitalizations, p=0.034). CONCLUSIONS: During the pandemic a greater proportion of patients were discharged home, with no change in readmission rates. Research is needed to evaluate the impact on quality and financing of post-hospital stroke care.

Hearing loss mutations alter the functional properties of human P2X2 receptor channels through distinct mechanisms.

Activation of P2X2 receptor channels by extracellular ATP is thought to play important roles in cochlear adaptation to elevated sound levels and protection from overstimulation. Each subunit of a trimeric P2X2 receptor is composed of intracellular N and C termini, a large extracellular domain containing the ATP binding site and 2 transmembrane helices (TM1 and TM2) that form a cation permeable pore. Whole-exome sequencing and linkage analysis have identified 3 hP2X2 receptor mutations (V60L, D273Y, and G353R) that cause dominantly inherited progressive sensorineural hearing loss (DFNA41). Available structures of related P2X receptors suggest that these 3 mutations localize to TM1 (V60L), TM2 (G353R), or the ß-sheet linking the TMs to the extracellular ATP binding sites (D273Y). Previous studies have concluded that the V60L and G353R mutants are nonfunctional, whereas the D273Y mutant has yet to be studied. Here, we demonstrate that both V60L and G353R mutations do form functional channels, whereas the D273Y mutation prevents the expression of functional channels on the cell membrane. Our results show that the V60L mutant forms constitutively active channels that are insensitive to ATP or the antagonist suramin, suggesting uncoupling of the pore and the ligand binding domains. In contrast, the G353R mutant can be activated by ATP but exhibits alterations in sensitivity to ATP, inward rectification, and ion selectivity. Collectively, our results demonstrate that the loss of functional P2X2 receptors or distinct alterations of its functional properties lead to noise-induced hearing loss, highlighting the importance of these channels in preserving hearing.

Hepatocyte Specific gp130 Signalling Underlies APAP Induced Liver Injury.

N-acetyl-p-aminophenol (APAP)-induced liver damage is associated with upregulation of Interleukin-11 (IL11), which is thought to stimulate IL6ST (gp130)-mediated STAT3 activity in hepatocytes, as a compensatory response. However, recent studies have found IL11/IL11RA/gp130 signaling to be hepatotoxic. To investigate further the role of IL11 and gp130 in APAP liver injury, we generated two new mouse strains with conditional knockout (CKO) of either Il11 (CKOIl11) or gp130 (CKOgp130) in adult hepatocytes. Following APAP, as compared to controls, CKOgp130 mice had lesser liver damage with lower serum Alanine Transaminase (ALT) and Aspartate Aminotransferase (AST), greatly reduced serum IL11 levels (90% lower), and lesser centrilobular necrosis. Livers from APAP-injured CKOgp130 mice had lesser ERK, JNK, NOX4 activation and increased markers of regeneration (PCNA, Cyclin D1, Ki67). Experiments were repeated in CKOIl11 mice that, as compared to wild-type mice, had lower APAP-induced ALT/AST, reduced centrilobular necrosis and undetectable IL11 in serum. As seen with CKOgp130 mice, APAP-treated CKOIl11 mice had lesser ERK/JNK/NOX4 activation and greater features of regeneration. Both CKOgp130 and CKOIl11 mice had normal APAP metabolism. After APAP, CKOgp130 and CKOIl11 mice had reduced Il6, Ccl2, Ccl5, Il1ß, and Tnfα expression. These studies exclude IL11 upregulation as compensatory and establish autocrine, self-amplifying, gp130-dependent IL11 secretion from damaged hepatocytes as toxic and anti-regenerative.

IL11 is elevated in systemic sclerosis and IL11-dependent ERK signalling underlies TGFß-mediated activation of dermal fibroblasts.

OBJECTIVES: Interleukin 11 (IL11) is highly upregulated in skin and lung fibroblasts from patients with systemic sclerosis (SSc). Here we tested whether IL11 is mechanistically linked with activation of human dermal fibroblasts (HDFs) from patients with SSc or controls. METHODS: We measured serum IL11 levels in volunteers and patients with early diffuse SSc and manipulated IL11 signalling in HDFs using gain- and loss-of-function approaches that we combined with molecular and cellular phenotyping. RESULTS: In patients with SSc, serum IL11 levels are elevated as compared with healthy controls. All transforming growth factor beta (TGFß) isoforms induced IL11 secretion from HDFs, which highly express IL11 receptor α-subunit and the glycoprotein 130 (gp130) co-receptor, suggestive of an autocrine loop of IL11 activity in HDFs. IL11 stimulated ERK activation in HDFs and resulted in HDF-to-myofibroblast transformation and extracellular matrix secretion. The pro-fibrotic action of IL11 in HDFs appeared unrelated to STAT3 activity, independent of TGFß upregulation and was not associated with phosphorylation of SMAD2/3. Inhibition of IL11 signalling using either a neutralizing antibody against IL11 or siRNA against IL11RA reduced TGFß-induced HDF proliferation, matrix production and cell migration, which was phenocopied by pharmacological inhibition of ERK. CONCLUSIONS: These data reveal that autocrine IL11-dependent ERK activity alone or downstream of TGFß stimulation promotes fibrosis phenotypes in dermal fibroblasts and suggest IL11 as a potential therapeutic target in SSc.

Widespread Translational Control of Fibrosis in the Human Heart by RNA-Binding Proteins.

BACKGROUND: Fibrosis is a common pathology in many cardiac disorders and is driven by the activation of resident fibroblasts. The global posttranscriptional mechanisms underlying fibroblast-to-myofibroblast conversion in the heart have not been explored. METHODS: Genome-wide changes of RNA transcription and translation during human cardiac fibroblast activation were monitored with RNA sequencing and ribosome profiling. We then used RNA-binding protein-based analyses to identify translational regulators of fibrogenic genes. The integration with cardiac ribosome occupancy levels of 30 dilated cardiomyopathy patients demonstrates that these posttranscriptional mechanisms are also active in the diseased fibrotic human heart. RESULTS: We generated nucleotide-resolution translatome data during the transforming growth factor ß1-driven cellular transition of human cardiac fibroblasts to myofibroblasts. This identified dynamic changes of RNA transcription and translation at several time points during the fibrotic response, revealing transient and early-responder genes. Remarkably, about one-third of all changes in gene expression in activated fibroblasts are subject to translational regulation, and dynamic variation in ribosome occupancy affects protein abundance independent of RNA levels. Targets of RNA-binding proteins were strongly enriched in posttranscriptionally regulated genes, suggesting genes such as MBNL2 can act as translational activators or repressors. Ribosome occupancy in the hearts of patients with dilated cardiomyopathy suggested the same posttranscriptional regulatory network was underlying cardiac fibrosis. Key network hubs include RNA-binding proteins such as Pumilio RNA binding family member 2 (PUM2) and Quaking (QKI) that work in concert to regulate the translation of target transcripts in human diseased hearts. Furthermore, silencing of both PUM2 and QKI inhibits the transition of fibroblasts toward profibrotic myofibroblasts in response to transforming growth factor ß1. CONCLUSIONS: We reveal widespread translational effects of transforming growth factor ß1 and define novel posttranscriptional regulatory networks that control the fibroblast-to-myofibroblast transition. These networks are active in human heart disease, and silencing of hub genes limits fibroblast activation. Our findings show the central importance of translational control in fibrosis and highlight novel pathogenic mechanisms in heart failure.

3D Printed Microfluidic Devices for Solid-Phase Extraction and On-Chip Fluorescent Labeling of Preterm Birth Risk Biomarkers.

Solid-phase extraction (SPE) is a general preconcentration method for sample preparation that can be performed on a variety of specimens. The miniaturization of SPE within a 3D printed microfluidic device further allows for fast and simple extraction of analytes while also enabling integration of SPE with other sample preparation and separation methods. Here, we present the development and application of a reversed-phase lauryl methacrylate-based monolith, formed in 3D printed microfluidic devices, which can selectively retain peptides and proteins. The effectiveness of these SPE monoliths and 3D printed microfluidic devices was tested using a panel of nine preterm birth biomarkers of varying hydrophobicities and ranging in mass from 2 to 470 kDa. The biomarkers were selectively retained, fluorescently labeled, and eluted separately from the excess fluorescent label in 3D printed microfluidic systems. These are the first results demonstrating microfluidic analysis processes on a complete panel of preterm birth biomarkers, an important step toward developing a miniaturized, fully integrated analysis system.

FURIN Inhibition Reduces Vascular Remodeling and Atherosclerotic Lesion Progression in Mice.

Objective- Atherosclerotic coronary artery disease is the leading cause of death worldwide, and current treatment options are insufficient. Using systems-level network cluster analyses on a large coronary artery disease case-control cohort, we previously identified PCSK3 (proprotein convertase subtilisin/kexin family member 3; FURIN) as a member of several coronary artery disease-associated pathways. Thus, our objective is to determine the role of FURIN in atherosclerosis. Approach and Results- In vitro, FURIN inhibitor treatment resulted in reduced monocyte migration and reduced macrophage and vascular endothelial cell inflammatory and cytokine gene expression. In vivo, administration of an irreversible inhibitor of FURIN, α-1-PDX (α1-antitrypsin Portland), to hyperlipidemic Ldlr-/- mice resulted in lower atherosclerotic lesion area and a specific reduction in severe lesions. Significantly lower lesional macrophage and collagen area, as well as systemic inflammatory markers, were observed. MMP2 (matrix metallopeptidase 2), an effector of endothelial function and atherosclerotic lesion progression, and a FURIN substrate was significantly reduced in the aorta of inhibitor-treated mice. To determine FURIN's role in vascular endothelial function, we administered α-1-PDX to Apoe-/- mice harboring a wire injury in the common carotid artery. We observed significantly decreased carotid intimal thickness and lower plaque cellularity, smooth muscle cell, macrophage, and inflammatory marker content, suggesting protection against vascular remodeling. Overexpression of FURIN in this model resulted in a significant 67% increase in intimal plaque thickness, confirming that FURIN levels directly correlate with atherosclerosis. Conclusions- We show that systemic inhibition of FURIN in mice decreases vascular remodeling and atherosclerosis. FURIN-mediated modulation of MMP2 activity may contribute to the atheroprotection observed in these mice.

Trends in Interhospital Transfers and Mechanical Thrombectomy for United States Acute Ischemic Stroke Inpatients.

OBJECTIVE: Stroke care in the US is increasingly regionalized. Many patients undergo interhospital transfer to access specialized, time-sensitive interventions such as mechanical thrombectomy. METHODS: Using a stratified survey design of the US Nationwide Inpatient Sample (2009-2014) we examined trends in interhospital transfers for ischemic stroke resulting in mechanical thrombectomy. International Classification of Disease-Ninth Revision (ICD-9) codes were used to identify stroke admissions and inpatient procedures within endovascular-capable hospitals. Regression analysis was used to identify factors associated with patient outcomes. RESULTS: From 2009-2014, 772,437 ischemic stroke admissions were identified. Stroke admissions that arrived via interhospital transfer increased from 12.5% to 16.8%, 2009-2014 (P-trend < .001). Transfers receiving thrombectomy increased from 4.0% to 5.2%, 2009-2014 (P-trend = .016), while those receiving tissue plasminogen activator increased from 16.0% to 20.0%, 2009-2014 (P-trend < .001). One in 4 patients receiving thrombectomy were transferred from another acute care facility (n = 6,014 of 24,861). Compared to patients arriving via the hospital "front door" receiving mechanical thrombectomy, those arriving via transfer were more often from rural areas and received by teaching hospitals with greater frequency of thrombectomy. Those arriving via interhospital transfer undergoing thrombectomy had greater odds of symptomatic intracranial hemorrhage (adjusted odds ratio [AOR] 1.19, 95% CI: 1.01-1.42) versus "front door" arrivals. There were no differences in inpatient mortality (AOR 1.11, 95% CI: .93-1.33). CONCLUSIONS: From 2009 to 2014, interhospital stroke transfers to endovascular-capable hospitals increased by one-third. For every ∼15 additional transfers over the time period one additional patient received thrombectomy. Optimization of transfers presents an opportunity to increase access to thrombectomy.

Effect of position-specific single-point mutations and biophysical characterization of amyloidogenic peptide fragments identified from lattice corneal dystrophy patients.

Corneal stromal dystrophies are a group of genetic disorders that may be caused by mutations in the transforming growth factor ß-induced (TGFBI) gene which results in the aggregation and deposition of mutant proteins in various layers of the cornea. The type of amino acid substitution dictates the age of onset, anatomical location of the deposits, morphological features of deposits (amyloid, amorphous powder or a mixture of both forms) and the severity of disease presentation. It has been suggested that abnormal turnover and aberrant proteolytic processing of the mutant proteins result in the accumulation of insoluble protein deposits. Using mass spectrometry, we identified increased abundance of a 32 amino acid-long peptide in the 4th fasciclin-like domain-1 (FAS-1) domain of transforming growth factor ß-induced protein (amino acid 611-642) in the amyloid deposits of the patients with lattice corneal dystrophies (LCD). In vitro studies demonstrated that the peptide readily formed amyloid fibrils under physiological conditions. Clinically relevant substitution (M619K, N622K, N622H, G623R and H626R) of the truncated peptide resulted in profound changes in the kinetics of amyloid formation, thermal stability of the amyloid fibrils and cytotoxicity of fibrillar aggregates, depending on the position and the type of the amino acid substitution. The results suggest that reduction in the overall net charge, nature and position of cationic residue substitution determines the amyloid aggregation propensity and thermal stability of amyloid fibrils.

Incidental Findings in Radiographic Imaging for Inpatients with Acute Ischemic Stroke.

BACKGROUND: Incidental findings on radiographic diagnostic imaging are a growing concern in the medical field. Little is known about the incidence and spectrum of incidental findings uncovered during stroke evaluations. METHODS AND RESULTS: A random sample of 200 acute ischemic stroke admissions at an academic medical center was reviewed to better understand the incidence and spectrum of incidental findings on radiographic imaging studies obtained for a stroke evaluation. Among 200 stroke patients, 53 (26.5%) were found to have one or more incidental findings on radiographic imaging. Over 651 imaging studies, 69 incidental findings were uncovered, or 11 incidental findings per 100 imaging studies. Incidental findings were most commonly discovered within computerized tomography angiograms of the head and neck (n = 41 from of 176 studies). The most commonly identified incidental findings included thyroid nodules (n = 12), sinus disease (n = 11), pulmonary nodules (n = 10), and intracranial/cervical artery aneurysms (n = 5). CONCLUSIONS: Incidental findings are commonly found in patients undergoing an evaluation for acute ischemic stroke, some of which may be clinically relevant. Vascular neurologists and other clinicians caring for stroke patients may benefit from guidance on the management of expected incidental findings.

Variability in Gastrostomy Tube Placement for Intracerebral Hemorrhage Patients at US Hospitals.

OBJECTIVE: We sought to characterize the variability among US hospitals with regard to gastrostomy tube placement for inpatients with intracerebral hemorrhage (ICH). METHODS: Using the Nationwide Inpatient Sample, we examined variations in the annual rate of gastrostomy tube placement from 2002 to 2011 for ICH patients admitted to hospitals with 30 or more annual ICH admissions. We then directly compared, among these hospitals, their individual frequencies of gastrostomy tube placement for ICH patients over the same time period. To quantify variability among hospitals, we used multilevel multivariable regression models accounting for a hospital random effect, adjusted for patient-level and hospital-level factors predictors of placement. RESULTS: Gastrostomy tube placement rates did not significantly change from 2002 to 2011 (9.8 to 8.7 per 100 admissions; P trend = .57). Among 690 hospitals with 38,080 ICH hospitalizations during this period, 10.4% of patients had a gastrostomy tube placed (n = 3976). Variation in the rate of placement among individual hospitals was large, from 0% to 34.4% (interquartile range 5.7%-13.6%). For a regression model controlling for patient and hospital covariates, the median odds ratio was 1.36 (95% confidence interval 1.28-1.44), indicating that if a patient moved from one hospital to another with a higher intrinsic propensity of placement, there was a 1.36-fold median increase in the odds of receiving a gastrostomy tube, independent of patient and hospital factors. CONCLUSIONS: Variation in gastrostomy tube placement rates across hospitals is large and may in part reflect differences in local practice patterns or patient and surrogate preferences.

For-Profit Hospital Status and Carotid Artery Stent Utilization in US Hospitals Performing Carotid Revascularization.

BACKGROUND AND PURPOSE: Carotid artery stenting may be an economically attractive procedure for hospitals and physicians. We sought to identify the association of hospital ownership (nonprofit versus for-profit) on carotid artery stenting (CAS) versus carotid endarterectomy utilization in US hospitals. METHODS: Using the Nationwide Inpatient Sample admissions for cerebrovascular disease from 2008 to 2011, we identified all private, nonfederal US hospitals performing at least 20 carotid revascularization procedures annually, including carotid artery stenting (International Classification of Diseases-Ninth Revision 00.63) or carotid endarterectomy (International Classification of Diseases-Ninth Revision 38.12). We used a multilevel multivariable logistic regression controlling for patient demographics, comorbidities, and hospital characteristics, to assess the effect of hospital ownership on CAS use. RESULTS: Across 723 hospitals (600 nonprofit, 123 for-profit), 66 731 carotid revascularization admissions were identified. Approximately 1 in 5 (n=11 641; 17.4%) revascularizations received CAS. The mean CAS rate among nonprofit hospitals was 17.5 per 100 revascularizations (median, 11.5; interquartile range, 5.2-24.5), and the mean CAS rate among for-profit hospitals was 24.2 per 100 revascularizations (median, 16.0; interquartile range, 6.7-33.3; P<0.001). Adjusting for patient and hospital characteristics, for-profit hospital designation was associated with greater odds of CAS (adjusted odds ratio, 1.45; 95% confidence interval, 1.07-1.98). CONCLUSIONS: For-profit hospital ownership is associated with a higher rate of CAS compared to nonprofit hospitals in those receiving carotid revascularization. Further research is needed to understand the individual- and system-level factors driving this difference.

Timing of Percutaneous Endoscopic Gastrostomy for Acute Ischemic Stroke: An Observational Study From the US Nationwide Inpatient Sample.

BACKGROUND AND PURPOSE: Stroke guidelines recommend time-limited trials of nasogastric feeding prior to percutaneous endoscopic gastrostomy (PEG) tube placement. We sought to describe timing of PEG placement and identify factors associated with early PEG for acute ischemic stroke. METHODS: We designed a retrospective observational study to examine time to PEG for ischemic stroke admissions in the Nationwide Inpatient Sample, 2001 to 2011. We defined early PEG placement as 1 to 7 days from admission. Using multivariable regression analysis, we identified the effects of patient and hospital characteristics on PEG timing. RESULTS: We identified 34 623 admissions receiving a PEG from 2001 to 2011, 53% of which received the PEG 1 to 7 days from admission. Among hospitals placing ≥10 PEG tubes, median time to PEG for individual hospitals ranged from 3 days to over 3 weeks (interquartile range 6-8.5 days). Older adult age groups were associated with early PEG (≥85 years versus 18-54 years: adjusted odds ratio 1.68, 95% confidence interval 1.50-1.87). Those receiving a PEG and tracheostomy were more likely to receive the PEG beyond 7 days, and these patients were more often younger compared with PEG only recipients. Those admitted to high-volume hospitals were more likely to receive their PEG early (≥350 versus <150 hospitalizations; adjusted odds ratio 1.26, 95% confidence interval 1.17-1.35). CONCLUSIONS: More than half of the PEG recipients received their surgical feeding tube within 7 days of admission. The oldest old, who may benefit most from time-limited trials of nasogastric feeding for ≥2 to 3 weeks, were most likely to receive a PEG within 7 days.

Forgiven but not Relieved: US Physician Workforce Consequences of Changes to Public Service Loan Forgiveness.

Public Service Loan Forgiveness (PSLF) was established in 2007 for public sector and nonprofit enterprise employees to pursue educational loan forgiveness. Under PSLF, graduates are offered complete loan forgiveness after 120 qualifying monthly payments while employed at public or nonprofit institutions, including payments made during residency for physicians. In response to concerns that PSLF will heavily subsidize lawyers, doctors, and other professionals, the President's 2017 budget proposes limiting maximum forgiveness. Using data from the Association of American Medical Colleges Graduation Questionnaire (n = 55,905; response rate of 80 %), we found that intended participation in PSLF among medical school graduates grew 20 % per year since 2010. Future primary care physicians intend to use PSLF more than programs that were historically designed to promote primary care, such as the National Health Service Corp (NHSC). The federal government's projected cost of PSLF will reach over $316 million for 2014 graduates (net present value), approximately seven times the annual contributions from the NHSC. The proposed cap will reduce the total anticipated forgiveness by nearly two-thirds and substantially reduce subsidies for physicians. More targeted measures of loan forgiveness could be considered, such as making forgiveness contingent on pursuing specialties that society needs or practicing in shortage areas.

Tackling causes and costs of ED presentation for American football injuries: a population-level study.

BACKGROUND: American tackle football is the most popular high-energy impact sport in the United States, with approximately 9 million participants competing annually. Previous epidemiologic studies of football-related injuries have generally focused on specific geographic areas or pediatric age groups. Our study sought to examine patient characteristics and outcomes, including hospital charges, among athletes presenting for emergency department (ED) treatment of football-related injury across all age groups in a large nationally representative data set. METHODS: Patients presenting for ED treatment of injuries sustained playing American tackle football (identified using International Classification of Diseases, Ninth Revision, Clinical Modification code E007.0) from 2010 to 2011 were studied in the Nationwide Emergency Department Sample. Patient-specific injuries were identified using the primary International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis code and categorized by type and anatomical region. Standard descriptive methods examined patient demographics, diagnosis categories, and ED and inpatient outcomes and charges. RESULTS: During the study period 397363 football players presented for ED treatment, 95.8% of whom were male. Sprains/strains (25.6%), limb fractures (20.7%), and head injuries (including traumatic brain injury; 17.5%) represented the most presenting injuries. Overall, 97.9% of patients underwent routine ED discharge with 1.1% admitted directly and fewer than 11 patients in the 2-year study period dying prior to discharge. The proportion of admitted patients who required surgical interventions was 15.7%, of which 89.9% were orthopedic, 4.7% neurologic, and 2.6% abdominal. Among individuals admitted to inpatient care, mean hospital length of stay was 2.4days (95% confidence interval, 2.2-2.6) and 95.6% underwent routine discharge home. The mean total charge for all patients was $1941 (95% confidence interval, $1890-$1992) with substantial injury type-specific variability. Overall, at the US population, estimated total charges of $771299862 were incurred over the 2-year period. CONCLUSION: In this nationally representative sample, most ED-treated injuries associated with football were not acutely life threatening and very few required major therapeutic intervention. This study provides a cross-sectional overview of ED presentation for acute football-related injury across age groups at the population level in recent years. Longitudinal studies may be warranted to examine associations between the patterns of injury observed in this study and long-term outcomes among American tackle football players.

Traumatic brain injury in the elderly: morbidity and mortality trends and risk factors.

An estimated 1.7 million people sustain a traumatic brain injury (TBI) annually in the United States. We sought to examine factors contributing to mortality among TBI patients aged ≥65 y in the United States. TBI data from the Nationwide Inpatient Sample were combined from 2000-2010. Patients were stratified by age, sex, mechanism of injury, payer status, comorbidity, injury severity, and other factors. Odds of death were explored using an adjusted multivariable logistic regression. A total of 950,132 TBI-related hospitalizations and 107,666 TBI-related deaths occurred among adults aged ≥65 y from 2000-2010. The most common mechanism of injury was falling, and falls were more common among the oldest age groups. Logistic regression analysis showed highest odds of death among male patients, those whose mechanism of injury was motor vehicle related, patients with three or more comorbidities, and patients who were designated as self-paying.