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.

Spontaneous Hypothermia As an Indicator of Early Diffuse Anoxic Brain Injury in Post-Cardiac Arrest Patients.

OBJECTIVES: To determine the association between spontaneous hypothermia (SH), defined as initial post-resuscitation core body temperature less than 34°C, and diffuse anoxic brain injury (DABI) on initial CT scan of the head (CTH) in post-cardiac arrest patients. DESIGN SETTING AND PARTICIPANTS: This was a retrospective, observational cohort study. This study was performed at the University of Rochester Medical Center Strong Memorial Hospital. All in-hospital and out-of-hospital cardiac arrest patients with return of spontaneous circulation admitted between January 1, 2022, and October 31, 2022, were included. MAIN OUTCOMES AND MEASURES: The primary outcomes were the odds of DABI on initial CTH for patients with SH compared with patients without SH post-cardiac arrest using a multivariable logistic regression controlling for patient covariates including basic demographics and arrest features. DABI on initial CTH was measured qualitatively and quantitatively using neuroradiologist interpretation and calculated gray-white matter ratio of the basal ganglia, respectively. Secondary outcome measures included length of stay (LOS), inpatient mortality, and those who underwent withdrawal of life-sustaining therapy (WOLST) or progression to brain death. RESULTS: Out of the observed 150 cases of cardiac arrest, 31 patients (21%) had SH. Of the 128 patients who had an initial CTH performed, 27 (21%) had DABI. The adjusted odds ratio of DABI on initial CTH associated with SH was 3.55 (95% CI, 1.08-11.64; p = 0.036) and 2.18 (95% CI, 0.69-6.91; p = 0.182) when DABI was measured qualitatively and quantitatively, respectively, after controlling for multiple covariates. There was a difference observed in LOS between the groups (3 vs. 10 d; p = 0.0005) and this was driven by early WOLST. CONCLUSIONS AND REVELANCE: Patients presenting with SH after cardiac arrest may be at greater risk of early DABI on initial CTH compared with those with higher body temperatures in the post-arrest period. Recognition of early SH may help to risk stratify post-cardiac arrest patients at highest risk of DABI.

Impact of the COVID-19 Pandemic on Inpatient Utilization for Acute Neurologic Disease.

Background and Objective: The initial months of the Corona Virus 2019 (COVID-19) pandemic resulted in decreased hospitalizations. We aimed to describe differences in hospitalizations and related procedures across neurologic disease. Methods: In our retrospective observational study using the California State Inpatient Database and state-wide population-level estimates, we calculated neurologic hospitalization rates for a control period from January 2019 to February 2020 and a COVID-19 pandemic period from March to December 2020. We calculated incident rate ratios (IRR) for neurologic hospitalizations using negative binomial regression and compared relevant procedure rates over time. Results: Population-based neurologic hospitalization rates were 29.1 per 100,000 (95% CI 26.9-31.3) in April 2020 compared to 43.6 per 100,000 (95% CI 40.4-46.7) in January 2020. Overall, the pandemic period had 13% lower incidence of neurologic hospitalizations per month (IRR 0.87, 95% CI 0.86-0.89). The smallest decreases were in neurotrauma (IRR 0.92, 95% CI 0.89-0.95) and neuro-oncologic cases (IRR 0.93, 95% CI 0.87-0.99). Headache admissions experienced the greatest decline (IRR 0.62, 95% CI 0.58-0.66). For ischemic stroke, greater rates of endovascular thrombectomy (5.6% vs 5.0%; P < .001) were observed in the pandemic. Among all neurologic disease, greater rates of gastrostomy (4.0% vs 3.5%; P < .001), intubation/mechanical ventilation (14.3% vs 12.9%, P < .001), and tracheostomy (1.4 vs 1.2%; P < .001) were observed during the pandemic. Conclusions: During the first months of the COVID-19 pandemic there were fewer hospitalizations to varying degrees for all neurologic diagnoses. Rates of procedures indicating severe disease increased. Further study is needed to determine the impact on triage, patient outcomes, and cost consequences.

Association of Do-Not-Resuscitate orders and in-hospital mortality among patients undergoing cranial neurosurgery.

BACKGROUND: Previous studies identified pre-existing DNR orders as a predictor of mortality after surgery. We sought to evaluate mortality of patients receiving cranial neurosurgery with DNR orders placed at the time of, or within 24 h of admission. METHODS: We performed a retrospective cohort study using the California State Inpatient Database, January 2018 to December 2020. We used International Classification of Diseases, 10th Revision (ICD-10) codes to identify emergent hospitalizations with principal diagnosis of brain injury, including traumatic brain injury [TBI], ischemic stroke [IS], intracerebral hemorrhage [ICH], subarachnoid hemorrhage [SAH], or malignant brain tumor [mBT]. We used procedure and Diagnosis Related Group codes to identify cranial neurosurgery. Patients with DNR were one-to-one matched to non-DNR controls based on diagnosis (exact matching), age, sex, Elixhauser comorbidity index, and organ failure (coarsened matching). The primary outcome was inpatient mortality. RESULTS: In California, 30,384 patients underwent cranial neurosurgery, 2018-2020 (n = 3,112, 10% DNR). DNR patients were older, more often female, more often White, with greater comorbidity and organ system dysfunction. There were 2,505 patients with DNR orders 1:1 matched to controls. Patients with DNR had greater inpatient mortality (56% vs. 23%, p < 0.001; Hazard Ratio 3.11, 95% CI 2.50-3.86), received tracheostomy (Odds Ratio [OR] 0.37, 95% CI 0.24-0.57) and gastrostomy less (OR 0.48, 95% CI 0.39-0.58) compared to controls. Multivariable analysis of the unmatched cohort demonstrated similar results. CONCLUSION: Patients undergoing cranial neurosurgery with early or pre-existing DNR have high inpatient mortality compared to clinically similar non-DNR patients; 1 in 2 died during their hospitalization.

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.

Effect of COVID-19 pandemic on outcomes in intracerebral hemorrhage.

OBJECTIVES: Patients with severe intracerebral hemorrhage (ICH) often suffer from impaired capacity and rely on surrogates for decision-making. Restrictions on visitors within healthcare facilities during the pandemic may have impacted care and disposition for patient with ICH. We investigated outcomes of ICH patients during the COVID-19 pandemic compared to a pre-pandemic period. MATERIALS AND METHODS: We conducted a retrospective review of ICH patients from two sources: (1) University of Rochester Get With the Guidelines database and (2) the California State Inpatient Database (SID). Patients were divided into 2019-2020 pre-pandemic and 2020 pandemic groups. We compared mortality, discharge, and comfort care/hospice. Using single-center data, we compared 30-day readmissions and follow-up functional status. RESULTS: The single-center cohort included 230 patients (n = 122 pre-pandemic, n = 108 pandemic group), and the California SID included 17,534 patients (n = 10,537 pre-pandemic, n = 6,997 pandemic group). Inpatient mortality was no different before or during the pandemic in either cohort. Length of stay was unchanged. During the pandemic, more patients were discharged to hospice in the California SID (8.4% vs. 5.9%, p<0.001). Use of comfort care was similar before and during the pandemic in the single center data. Survivors in both datasets were more likely to be discharged home vs. facility during the pandemic. Thirty-day readmissions and follow-up functional status in the single-center cohort were similar between groups. CONCLUSIONS: Using a large database, we identified more ICH patients discharged to hospice during the COVID-19 pandemic and, among survivors, more patients were discharged home rather than healthcare facility discharge during the pandemic.

Complications and outcomes of hospitalizations for patients with and without Parkinson disease.

Objective: To examine complications and outcomes of hospitalizations for common indications for hospitalization among patients with Parkinson disease (PD). Methods: We identified and selected the ten most common indications for hospitalization among individuals ≥65 years of age using principal diagnoses from the California State Inpatient Database, 2018-2020. Patients with comorbid PD were identified using secondary diagnosis codes and matched one-to-one to patients without PD based on principal diagnosis (exact matching), age, gender, race and ethnicity, and Elixhauser comorbidity index (coarsened exact matching). We identified potentially preventable complications based on the absence of present on admission indicators among secondary diagnoses. In the matched cohort, we compared inpatient complications, early Do-Not-Resuscitate (DNR) orders (placed within 24 h of admission), use of life-sustaining therapies, new nursing facility requirement on discharge, and death or hospice discharge for patients with and without PD. Results: We identified 35,457 patients with PD among the ten leading indications for hospitalization in older adults who were matched one-to-one to patients without PD (n = 70,914 in total). Comorbid PD was associated with an increased odds of developing aspiration pneumonia (OR 1.17 95% CI 1.02-1.35) and delirium (OR 1.11 95% CI 1.02-1.22) during admission. Patients with PD had greater odds of early DNR orders [placed within 24 h of admission] (OR 1.34 95% CI 1.29-1.39). While there was no difference in the odds of mechanical ventilation (OR 1.04 95% CI 0.98-1.11), patients with PD demonstrated greater odds of tracheostomy (OR 1.41 95% CI 1.12-1.77) and gastrostomy placement (OR 2.00 95% CI 1.82-2.20). PD was associated with greater odds of new nursing facility requirement upon discharge (OR 1.58 95% CI 1.53-1.64). Patients with PD were more likely to die as a result of their hospitalization (OR 1.11 95% CI 1.06-1.16). Conclusion: Patients with PD are at greater risk of developing aspiration pneumonia and delirium as a complication of their hospitalization. While patients with PD more often have early DNR orders, they have greater utilization of life-sustaining therapies and experience worse outcomes of their hospitalization including new nursing facility requirement upon discharge and greater mortality.

Institutional Variability in Representation of Women and Racial and Ethnic Minority Groups Among Medical School Faculty.

Importance: Bolstering the ranks of women and underrepresented groups in medicine (URM) among medical faculty can help address ongoing health care disparities and therefore constitutes a critical public health need. There are increasing proportions of URM faculty, but comparisons of these changes with shifts in regional populations are lacking. Objective: To quantify the representation of women and URM and assess changes and variability in representation by individual US medical schools. Design, Setting, and Participants: This retrospective cross-sectional study assessed US medical school faculty rosters for women and URM, including American Indian and Alaska Native, Black, Hispanic, and Native Hawaiian or other Pacific Islander faculty. US allopathic medical schools participating in the Association of American Medical Colleges (AAMC) Faculty Administrative Management Online User System from 1990 to 2019 (updated December 31 for each year), were included. Faculty data were analyzed from yearly cross-sections updated as of December 31 for each year from 1990 to 2019. For census data, decennial census data were used for years 1990, 2000, and 2010. Intercensal estimates were used for all other years from 1990 to 2019. Main Outcomes and Measures: Trends and variability in representation quotient (RQ), defined as representation of a group within an institution's faculty compared to its respective US county. Results: There were 121 AAMC member institutions (72 076 faculty) in 1990, which increased to 144 institutions (184 577 faculty) in 2019. The median RQ of women faculty increased from 0.42 (IQR, 0.37-0.46) to 0.80 (IQR, 0.74-0.89) (slope, +1.4% per year; P < .001). The median RQ of Black faculty increased from 0.10 (IQR, 0.06-0.22) to 0.22 (IQR, 0.14-0.41) (slope, +0.5% per year; P < .001), but remained low. In contrast, the median RQ of Hispanic faculty decreased from 0.44 (IQR, 0.19-1.22) to 0.34 (IQR, 0.23-0.62) (slope, -1.7% per year; P < .001) between 1990 and 2019. Absolute total change in RQ of URM showed an increase; however, the 30-year slope did not differ from zero (+0.1% per year; P = .052). Although RQ of women faculty increased for most institutions (127 [88.2%]), large variability in URM faculty trends were observed (57 institutions [39.6%] with increased RQ and 10 institutions [6.9%] with decreased RQ). Nearly one-quarter of institutions shifted from the top to bottom 50th percentile institutional ranking by URM RQ with county vs national comparisons. Conclusions and Relevance: The findings of this cross-sectional study suggest that representation of women in academic medicine improved with time, while URM overall experienced only modest increases with wide variability across institutions. Among URM, the Hispanic population has lost representational ground. County-based population comparisons provide new insights into institutional variation in representation among medical school faculty.

Reversal of Advanced Directives in Neurologic Emergencies.

Objective: Patients with advanced directives or Medical Orders for Life-Sustaining Treatment (MOLST), including "Do Not Resuscitate" (DNR) and/or "Do Not Intubate" (DNI), may be candidates for procedural interventions when presenting with acute neurologic emergencies. Such interventions may limit morbidity and mortality, but typically they require MOLST reversal. We investigated outcomes of patients with MOLST reversal for treatment of neurologic emergencies. Methods: We conducted a retrospective chart review from July 1, 2019 to April 30, 2021 of patients with MOLST reversal treated in our NeuroMedicine Intensive Care Unit. Variables collected include neurologic disease, MOLST reversal decision maker, procedural interventions, and outcomes. Results: Twenty-seven patients (18 female, median age 78 years (IQR 73-85 years), median baseline modified Rankin score 1 [IQR 0-2.5] were identified with MOLST reversal. The most common pre-procedural MOLST was DNR/DNI (n=22, 81%), and 93% (n=25) pre-procedural MOLSTs were completed by the patient. MOLSTs were reversed by surrogates in n=23 cases (85%). The median time from MOLST completion to MOLST reversal was 603 days (IQR 45 days to 4 years). The most common neurologic emergency was ischemic stroke (n=14, 52%). Most patients died (n=14, 52%), 26% (n=7) were discharged to skilled nursing, and 22% (n=6) returned to home or assisted living. Conclusions: In neurologic emergencies, urgent shared decision making is needed to ensure goal-concordant care, which may result in reversal of existing advanced directives. Outcomes of patients with MOLST reversal were heterogeneous, emphasizing the importance of deliberate patient-centered care weighing the risks and benefits of each intervention.

Brain Histopathology of Adult Decedents After Extracorporeal Membrane Oxygenation.

OBJECTIVE: To test the hypothesis that brain injury is more common and varied in patients receiving extracorporeal membrane oxygenation (ECMO) than radiographically observed, we described neuropathology findings of ECMO decedents and associated clinical factors from 3 institutions. METHODS: We conducted a retrospective multicenter observational study of brain autopsies from adult ECMO recipients. Pathology findings were examined for correlation with demographics, clinical data, ECMO characteristics, and outcomes. RESULTS: Forty-three decedents (n = 13 female, median age 47 years) received autopsies after undergoing ECMO for acute respiratory distress syndrome (n = 14), cardiogenic shock (n = 14), and cardiac arrest (n = 15). Median duration of ECMO was 140 hours, most decedents (n = 40) received anticoagulants; 60% (n = 26) underwent venoarterial ECMO, and 40% (n = 17) underwent venovenous ECMO. Neuropathology was found in 35 decedents (81%), including microhemorrhages (37%), macrohemorrhages (35%), infarctions (47%), and hypoxic-ischemic brain injury (n = 17, 40%). Most pathology occurred in frontal neocortices (n = 43 occurrences), basal ganglia (n = 33), and cerebellum (n = 26). Decedents with hemorrhage were older (median age 57 vs 38 years, p = 0.01); those with hypoxic brain injury had higher Sequential Organ Failure Assessment scores (8.0 vs 2.0, p = 0.04); and those with infarction had lower peak Paco2 (53 vs 61 mm Hg, p = 0.04). Six of 9 patients with normal neuroimaging results were found to have pathology on autopsy. The majority underwent withdrawal of life-sustaining therapy (n = 32, 74%), and 2 of 8 patients with normal brain autopsy underwent withdrawal of life-sustaining therapy for suspected neurologic injury. CONCLUSION: Neuropathological findings after ECMO are common, varied, and associated with various clinical factors. Further study on underlying mechanisms is warranted and may guide ECMO management.

Difficult Discharges to Skilled Nursing Facilities Attributed to Multiple Sclerosis Medications: An Observational Study.

BACKGROUND: The costs of multiple sclerosis (MS) disease-modifying therapies (DMTs) and certain symptomatic treatments (ie, dalfampridine [DFP]) are high. Consolidated billing models require that medication costs be covered by skilled nursing facilities (SNFs) after hospitalization. As a result, patients may experience suboptimal discharge, off of medication or without rehabilitation. METHODS: To characterize the frequency with which MS pharmaceutical costs lead to suboptimal discharge, we performed a retrospective chart review of admissions to a large academic medical center from January 2013 to December 2017 among patients with MS on DMT and/or DFP with SNF rehabilitation recommendations. We quantified the burden of suboptimal discharge due to medication discontinuation, limited medication supplies, or forgone rehabilitation. RESULTS: Among 169 admissions of patients with MS with discharge recommendations for SNF rehabilitation, there were 57 (33.7%) admissions across 49 patients with MS on DMT/DFP. Overall, 39 (68%) of 57 admissions (71% of patients) experienced a suboptimal discharge. Overall, 29 (65%) discontinued DMT/DFP, 9 (16%) took their remaining home supply of medications during rehabilitation (including 5 admissions also affected by a discontinuation), and 6 (11%) were discharged home to remain on DMT. Among those discharged to rehabilitation, discharge to a hospital-owned SNF was associated with a routine discharge with no lapse in medication (n = 11/15 vs 7/36, P < .001). CONCLUSIONS: High costs of MS medications in conjunction with SNF consolidated payment models result in misaligned incentives and often lead to medication discontinuation or other suboptimal discharge for patients with MS.

Autosomal dominant mitochondrial membrane protein-associated neurodegeneration (MPAN).

BACKGROUND: Mitochondrial membrane protein-associated neurodegeneration (MPAN) is caused by pathogenic sequence variants in C19orf12. Autosomal recessive inheritance has been demonstrated. We present evidence of autosomal dominant MPAN and propose a mechanism to explain these cases. METHODS: Two large families with apparently dominant MPAN were investigated; additional singleton cases of MPAN were identified. Gene sequencing and multiplex ligation-dependent probe amplification were used to characterize the causative sequence variants in C19orf12. Post-mortem brain from affected subjects was examined. RESULTS: In two multi-generation non-consanguineous families, we identified different nonsense sequence variations in C19orf12 that segregate with the MPAN phenotype. Brain pathology was similar to that of autosomal recessive MPAN. We additionally identified a preponderance of cases with single heterozygous pathogenic sequence variants, including two with de novo changes. CONCLUSIONS: We present three lines of clinical evidence to demonstrate that MPAN can manifest as a result of only one pathogenic C19orf12 sequence variant. We propose that truncated C19orf12 proteins, resulting from nonsense variants in the final exon in our autosomal dominant cohort, impair function of the normal protein produced from the non-mutated allele via a dominant negative mechanism and cause loss of function. These findings impact the clinical diagnostic evaluation and counseling.

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.

Post-acute care discharge delays for neurology inpatients: Opportunity to improve patient flow.

BACKGROUND: Hospital stays for patients discharged to post-acute care are longer and more costly than routine discharges. Issues disrupting patient flow from hospital to post-acute care facilities are an underrecognized strain on hospital resources. We sought to quantify the burden of medically unnecessary hospital days for inpatients with neurologic illness and planned discharge to post-acute care facilities. METHODS: We conducted a retrospective evaluation of hospital discharge delays for patients with neurologic disease and plans for discharge to post-acute care. We identified 100 sequential hospital admissions to an academic neurology inpatient service that were medically ready for discharge from December 4, 2017, to January 25, 2018. For each patient, we quantified the number of medically unnecessary hospital days, or all days in the hospital following the determination of medical discharge readiness. RESULTS: Among 100 patients medically ready for discharge with plans for post-acute care disposition (47 female, mean age 72.5 years, mean length of stay 12.3 days), 50 patients were planned for discharge to skilled nursing, 37 to acute rehabilitation, 10 to hospice/palliative care, and 3 to other facilities. There was a total of 1,226 patient-days, and 480 patient-days (39%) occurred following medical readiness for discharge. Medically unnecessary days ranged from 0 to 80 days per patient (mean 4.8, median 2.5, interquartile range 1-5 days). CONCLUSION: Unnecessary hospital days represent a large burden for patients with neurologic illness requiring post-acute care on discharge. These discharge delays present an opportunity to improve hospital-wide patient flow.