Oregon Health and Science University Hospital

=0.10, 95%CI=0.01;0.20) were significantly larger for supervised than unsupervised interventions. In conclusion, exercise, and particularly supervised exercise, effectively improves QoL and PF in patients with cancer with different demographic and clinical characteristics during and following treatment. Although effect sizes are small, there is consistent empirical evidence to support implementation of exercise as part of cancer care.

Background: Endovascular treatment with mechanical thrombectomy (MT) is beneficial for patients with acute stroke suffering a large-vessel occlusion, although treatment efficacy is highly time-dependent. We hypothesized that interhospital transfer to endovascular-capable centers would result in treatment delays and worse clinical outcomes compared with direct presentation. Methods: STRATIS (Systematic Evaluation of Patients Treated With Neurothrombectomy Devices for Acute Ischemic Stroke) was a prospective, multicenter, observational, single-arm study of real-world MT for acute stroke because of anterior-circulation large-vessel occlusion performed at 55 sites over 2 years, including 1000 patients with severe stroke and treated within 8 hours. Patients underwent MT with or without intravenous tissue plasminogen activator and were admitted to endovascular-capable centers via either interhospital transfer or direct presentation. The primary clinical outcome was functional independence (modified Rankin Score 0–2) at 90 days. We assessed (1) real-world time metrics of stroke care delivery, (2) outcome differences between direct and transfer patients undergoing MT, and (3) the potential impact of local hospital bypass. Results: A total of 984 patients were analyzed. Median onset-to-revascularization time was 202.0 minutes for direct versus 311.5 minutes for transfer patients ( P <0.001). Clinical outcomes were better in the direct group, with 60.0% (299/498) achieving functional independence compared with 52.2% (213/408) in the transfer group (odds ratio, 1.38; 95% confidence interval, 1.06–1.79; P =0.02). Likewise, excellent outcome (modified Rankin Score 0–1) was achieved in 47.4% (236/498) of direct patients versus 38.0% (155/408) of transfer patients (odds ratio, 1.47; 95% confidence interval, 1.13–1.92; P =0.005). Mortality did not differ between the 2 groups (15.1% for direct, 13.7% for transfer; P =0.55). Intravenous tissue plasminogen activator did not impact outcomes. Hypothetical bypass modeling for all transferred patients suggested that intravenous tissue plasminogen activator would be delayed by 12 minutes, but MT would be performed 91 minutes sooner if patients were routed directly to endovascular-capable centers. If bypass is limited to a 20-mile radius from onset, then intravenous tissue plasminogen activator would be delayed by 7 minutes and MT performed 94 minutes earlier. Conclusions: In this large, real-world study, interhospital transfer was associated with significant treatment delays and lower chance of good outcome. Strategies to facilitate more rapid identification of large-vessel occlusion and direct routing to endovascular-capable centers for patients with severe stroke may improve outcomes. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02239640.

This article reviews the evaluation of patients with acute limb ischemia, including assessment of temperature, appearance, and pulses, by palpation and Doppler. Strategies for treatment of viable limbs are reviewed.

BACKGROUND: The use of implementation strategies is an active and purposive approach to translate research findings into routine clinical care. The Expert Recommendations for Implementing Change (ERIC) identified and defined discrete implementation strategies, and Proctor and colleagues have made recommendations for specifying operationalization of each strategy. We use empirical data to test how the ERIC taxonomy applies to a large dissemination and implementation initiative aimed at taking cardiac prevention to scale in primary care practice. METHODS: EvidenceNOW is an Agency for Healthcare Research and Quality initiative that funded seven cooperatives across seven regions in the USA. Cooperatives implemented multi-component interventions to improve heart health and build quality improvement capacity, and used a range of implementation strategies to foster practice change. We used ERIC to identify cooperatives' implementation strategies and specified the actor, action, target, dose, temporality, justification, and expected outcome for each. We mapped and compiled a matrix of the specified ERIC strategies across the cooperatives, and used consensus to resolve mapping differences. We then grouped implementation strategies by outcomes and justifications, which led to insights regarding the use of and linkages between ERIC strategies in real-world scale-up efforts. RESULTS: Thirty-three ERIC strategies were used by cooperatives. We identified a range of revisions to the ERIC taxonomy to improve the practical application of these strategies. These proposed changes include revisions to four strategy names and 12 definitions. We suggest adding three new strategies because they encapsulate distinct actions that were not described in the existing ERIC taxonomy. In addition, we organized ERIC implementation strategies into four functional groupings based on the way we observed them being applied in practice. These groupings show how ERIC strategies are, out of necessity, interconnected, to achieve the work involved in rapidly taking evidence to scale. CONCLUSIONS: Findings of our work suggest revisions to the ERIC implementation strategies to reflect their utilization in real-work dissemination and implementation efforts. The functional groupings of the ERIC implementation strategies that emerged from on-the-ground implementers will help guide others in choosing among and linking multiple implementation strategies when planning small- and large-scale implementation efforts. TRIAL REGISTRATION: Registered as Observational Study at www.clinicaltrials.gov ( NCT02560428 ).

BACKGROUND: Patient satisfaction is an indicator of the quality of care provided by emergency department (ED) personnel. It is this perception of satisfaction that becomes the basis for future ED choice or the recommendation of a specific ED to other potential patients. OBJECTIVE: To perform an evidence-based literature review to: 1) characterize measures of "patient satisfaction"; 2) identify factors that have been associated with overall ED patient satisfaction; 3) critique the methods used to assess patient satisfaction in the literature; and 4) address how this information can be beneficial to those reading the satisfaction literature or designing a satisfaction survey instrument. METHODS: The MEDLINE database was searched for studies addressing ED patient satisfaction, from January 1976 through July 1999, using MeSH terms and a text word search. Bibliographies of manuscripts also were searched for additional relevant articles and each clinical study was used as a search criterion in Science Citation Index, from the date of publication through July 1999. RESULTS: Multiple measures have been used to evaluate overall patient satisfaction. Sixteen studies were found associating ED patient satisfaction with service and patient factors. Most studies are observational and of these, most are cross-sectional. Hence, cause-and-effect determination of factors responsible for patient satisfaction cannot be resolved using the current literature. CONCLUSIONS: Despite considerable methodologic variability, key themes (e.g., association of satisfaction with patient information, provider-patient interpersonal factors, and perceived waiting time) emerge from review of the ED patient satisfaction literature. To standardize future investigations, clinicians and investigators should use a common definition for the state of overall patient satisfaction, e.g., when the patient's own expectations for treatment and care are met (or exceeded). This common definition should be incorporated into the instrument used to measure overall ED patient satisfaction.

OBJECTIVE: To characterize fatigue in Parkinson's disease (PD). BACKGROUND: Fatigue is a recognized problem in PD. Fatigue can be in the physical realm or in the mental realm. Fatigue has not been characterized in PD. METHODS: We characterized fatigue in 39 PD patients and 32 age-matched normal controls using five questionnaires: A. The Multidimensional Fatigue Inventory (MFI), which measures five dimensions of fatigue independently including general fatigue, physical fatigue, reduced motivation, reduced activity, and mental fatigue. B. The Fatigue Severity Inventory (FSI), which quantifies fatigue in general. C. The Profile of Mood States (POMS), which assesses six subjective subscales: tension-anxiety, depression-dejection, anger-hostility, fatigue-inertia, vigor-activity, and confusion-bewilderment. D. Center for Epidemiological Studies-Depression Scale (CES-D). E. Visual Analog linear scale of energy (VA-E). RESULTS: PD patients scored higher in all of the five dimensions of fatigue in the MFI including general fatigue, physical fatigue, reduced motivation, reduced activity, and mental fatigue (P < 0.001 except for mental fatigue P = 0.005). The severity of physical fatigue did not correlate with that of mental fatigue. PD patients scored higher on the FSI, POMS, CES-D, and scored lower on the VA-E. The scores in the FSI correlated with general fatigue, physical fatigue, reduced activity, and reduced motivation but not with mental fatigue in the MFI. Depression correlated with all dimensions of fatigue except physical fatigue in the MFI. Disease severity, as measured by Modified Hoehn and Yahr staging, did not correlate with any of the measures. CONCLUSIONS: PD patients have increased physical fatigue and mental fatigue compared to normals. Physical fatigue and mental fatigue are independent symptoms in PD that need to be assessed and treated separately.

Many hospitalists incorporate point-of-care ultrasound (POCUS) into their daily practice to answer specific diagnostic questions or to guide performance of invasive bedside procedures. However, standards for hospitalists in POCUS training and assessment are not yet established. Most internal medicine residency training programs, the major pipeline for incoming hospitalists, have only recently begun to incorporate POCUS in their curricula. The purpose of this document is to inform a broad audience on what POCUS is and how hospitalists are using it. This document is intended to provide guidance for the hospitalists who use POCUS and administrators who oversee its use. We discuss POCUS 1) applications, 2) training, 3) assessments, and 4) program management. Practicing hospitalists must continue to collaborate with their local credentialing bodies to outline requirements for POCUS use. Hospitalists should be integrally involved in decision-making processes surrounding POCUS program management.

RATIONALE: Obstructive sleep apnea is a risk factor for mortality, but its diagnostic metric-the apnea-hypopnea index-is a poor risk predictor. The apnea-hypopnea index does not capture the range of physiological variability within and between patients, such as degree of hypoxemia and sleep fragmentation, that reflect differences in pathophysiological contributions of airway collapsibility, chemoreceptive negative feedback loop gain, and arousal threshold. OBJECTIVES: To test whether respiratory event duration, a heritable sleep apnea trait reflective of arousal threshold, predicts all-cause mortality. METHODS: Mortality risk as a function of event duration was estimated by Cox proportional hazards in the Sleep Heart Health Study, a prospective community-based cohort. Gender-specific hazard ratios were also calculated. MEASUREMENTS AND MAIN RESULTS: Among 5,712 participants, 1,290 deaths occurred over 11 years of follow-up. After adjusting for demographic factors (mean age, 63 yr; 52% female), apnea-hypopnea index (mean, 13.8; SD, 15.0), smoking, and prevalent cardiometabolic disease, individuals with the shortest-duration events had a significant hazard ratio for all-cause mortality of 1.31 (95% confidence interval, 1.11-1.54). This relationship was observed in both men and women and was strongest in those with moderate sleep apnea (hazard ratio, 1.59; 95% confidence interval, 1.11-2.28). CONCLUSIONS: Short respiratory event duration, a marker for low arousal threshold, predicts mortality in men and women. Individuals with shorter respiratory events may be predisposed to increased ventilatory instability and/or have augmented autonomic nervous system responses that increase the likelihood of adverse health outcomes, underscoring the importance of assessing physiological variation in obstructive sleep apnea.

OBJECTIVE: To assess the long-term effects of a prepackaged, nutritionally complete, prepared meal plan compared with a usual-care diet (UCD) on weight loss and cardiovascular risk factors in overweight and obese persons. DESIGN: In this randomized multicenter study, 302 persons with hypertension and dyslipidemia (n = 183) or with type 2 diabetes mellitus (n = 119) were randomized to the nutrient-fortified prepared meal plan (approximately 22% energy from fat, 58% from carbohydrate, and 20% from protein) or to a macronutrient-equivalent UCD. MAIN OUTCOME MEASURES: The primary outcome measure was weight change. Secondary measures were changes in blood pressure or plasma lipid, lipoprotein, glucose, or glycosylated hemoglobin levels; quality of life; nutrient intake; and dietary compliance. RESULTS: After 1 year, weight change in the hypertension/dyslipidemia group was -5.8+/-6.8 kg with the prepared meal plan vs -1.7+/-6.5 kg with the UCD plan (P<.001); for the type 2 diabetes mellitus group, the change was -3.0+/-5.4 kg with the prepared meal plan vs -1.0+/-3.8 kg with the UCD plan (P<.001) (data given as mean +/- SD). In both groups, both interventions improved blood pressure, total and low-density lipoprotein cholesterol levels, glycosylated hemoglobin level, and quality of life (P<.02); in the diabetic group, the glucose level was reduced (P<.001). Compared with those in the UCD group, participants with hypertension/dyslipidemia in the prepared meal plan group showed greater improvements in total (P<.01) and high-density lipoprotein (P<.03) cholesterol levels, systolic blood pressure (P<.03), and glucose level (P<.03); in participants with type 2 diabetes mellitus, there were greater improvements in glucose (P =.046) and glycosylated hemoglobin (P<.02) levels. The prepared meal plan group also showed greater improvements in quality of life (P<.05) and compliance (P<.001) than the UCD group. CONCLUSIONS: Long-term dietary interventions induced significant weight loss and improved cardiovascular risk in high-risk patients. The prepared meal plan simultaneously provided the simplicity and nutrient composition necessary to maintain long-term compliance and to reduce cardiovascular risk.

OBJECTIVE: To determine the accuracy and repeatability of ear-based, bladder, oral, and axillary temperature methods. DESIGN: Prospective, descriptive comparison of the accuracy of four temperature methods in relation to pulmonary artery temperature and the repeatability of each method. SETTING: Critical care units of a university teaching hospital. PATIENTS: Convenience sample of 38 adult patients with indwelling pulmonary artery thermistor catheters. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Ear-based estimates of core temperature with an infrared thermometer and pulmonary artery, bladder, oral, and axillary temperatures with thermistor-based instruments were made every 20 mins for 4 hrs. Mean offsets (+/- SD) from pulmonary artery temperature for each method were as follows: ear-based 0.07 +/- 0.41 degrees C; bladder 0.03 +/- 0.23 degrees C; oral 0.05 +/- 0.26 degrees C; and axillary -0.68 +/- 0.57 degrees C. The accuracy of each method varied with the level of pulmonary artery temperature. Repeated measurements with all four methods had mean SD values within +/- 0.2 degrees C. CONCLUSIONS: Infrared ear thermometry provided a relatively close estimate of pulmonary artery core temperature, although with more variability than bladder or oral methods, while axillary readings were substantially lower than the pulmonary artery temperature and highly variable.

COVID-19 mRNA vaccines (BNT162b2 [Pfizer-BioNTech] and mRNA-1273 [Moderna]) are effective at preventing COVID-19-associated hospitalization (1-3). However, how well mRNA vaccines protect against the most severe outcomes of these hospitalizations, including invasive mechanical ventilation (IMV) or death is uncertain. Using a case-control design, mRNA vaccine effectiveness (VE) against COVID-19-associated IMV and in-hospital death was evaluated among adults aged ≥18 years hospitalized at 21 U.S. medical centers during March 11, 2021-January 24, 2022. During this period, the most commonly circulating variants of SARS-CoV-2, the virus that causes COVID-19, were B.1.1.7 (Alpha), B.1.617.2 (Delta), and B.1.1.529 (Omicron). Previous vaccination (2 or 3 versus 0 vaccine doses before illness onset) in prospectively enrolled COVID-19 case-patients who received IMV or died within 28 days of hospitalization was compared with that among hospitalized control patients without COVID-19. Among 1,440 COVID-19 case-patients who received IMV or died, 307 (21%) had received 2 or 3 vaccine doses before illness onset. Among 6,104 control-patients, 4,020 (66%) had received 2 or 3 vaccine doses. Among the 1,440 case-patients who received IMV or died, those who were vaccinated were older (median age = 69 years), more likely to be immunocompromised* (40%), and had more chronic medical conditions compared with unvaccinated case-patients (median age = 55 years; immunocompromised = 10%; p<0.001 for both). VE against IMV or in-hospital death was 90% (95% CI = 88%-91%) overall, including 88% (95% CI = 86%-90%) for 2 doses and 94% (95% CI = 91%-96%) for 3 doses, and 94% (95% CI = 88%-97%) for 3 doses during the Omicron-predominant period. COVID-19 mRNA vaccines are highly effective in preventing COVID-19-associated death and respiratory failure treated with IMV. CDC recommends that all persons eligible for vaccination get vaccinated and stay up to date with COVID-19 vaccination (4).

Watch a video presentation of this article Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the United States and in other industrialized nations. Its increase in prevalence and severity correlates with the rise in obesity and the metabolic syndrome, and NAFLD now represents a leading indication for liver transplantation in the United States.1 The rising clinical and economic burden of NAFLD has highlighted the need for a streamlined approach to prevention, diagnosis, and treatment of the disease. In this review, we will summarize updated guideline and guidance recommendations for the management of adult NAFLD; highlight key difference between US, Asian, and European recommendations; and provide key updates. In 2012, the American Association for the Study of Liver Diseases (AASLD), the American College of Gastroenterology, and the American Gastroenterological Association published a joint practice guideline on NAFLD.2 The diagnosis of NAFLD currently requires: (1) evidence of hepatic steatosis (HS) by imaging or histology, (2) no significant alcohol consumption, (3) no competing causes of HS, and (4) no coexisting causes of chronic liver disease. Research efforts have led to significant progress in our understanding of the disease. An updated practice guidance, based on expert consensus rather than by systematic review of the literature, was published by AASLD in 2018 to help clinicians navigate the most recent evidence into clinical practice.3 The guidance should be used in conjunction with the graded recommendations from previously published guidelines. One notable change in guidance is a stronger emphasis on assessment for metabolic risk factors in patients with incidental findings of HS and normal liver chemistries but lacking liver-related symptoms. Growing evidence supports that patients with NAFLD have increased cardiovascular morbidity and mortality.4 Moreover, advanced liver fibrosis is associated with increasing number of metabolic comorbidities.5 Thus, early identification and treatment of individual components of the metabolic syndrome are critical in preventing both cardiovascular and liver-related mortality. The importance of identifying and staging the degree of fibrosis in patients with NAFLD is underscored in the updated guidance because it is thought to be the main driver of overall and liver-related mortality.6 In the original guideline, NAFLD fibrosis score was the only recommended tool to assess fibrosis noninvasively because imaging modalities were not yet readily available in the United States. Fibrosis-4 score (FIB-4), ultrasound-based elastography, and magnetic resonance elastography have now been added to the arsenal of clinically useful tools to assess fibrosis staging. Accessibility to advanced imaging tools vary across institutions, and no guidance is provided for the optimal sequence of diagnostic testing. More recently, a consensus of international experts proposed changing the name of NAFLD to metabolic (dysfunction)-associated fatty liver disease (MAFLD).7 The paradigm shift to MAFLD would reflect the underlying pathogenesis, eliminate the “negative” nomenclature, and allow for the coexistence of other chronic liver diseases, including alcoholic liver disease. One concern of the use of MAFLD would be an inclusive definition that would not specifically address the population with nonalcoholic steatohepatitis (NASH) who are at highest risk for complications. Future research and guidelines will likely address this ongoing conversation within the field currently. In today’s increasingly globalized world, awareness of international differences in the approach to NAFLD is important to provide high-quality care to patients of all backgrounds. The European Association for the Study of the Liver (EASL), in a joint effort with the European Association for the Study of Diabetes and European Association for the Study of Obesity, published a NAFLD clinical practice guideline in 2016.8 The Asia-Pacific Working Party on NAFLD published its guideline in 2017.9, 10 Both the European and Asian guidelines use the grading of recommendation assessment, development, and evaluation (GRADE) approach to rate the quality of evidence and the strength of each recommendation. Although many similarities exist across guidelines, there are several key areas of divergence that will be outlined later (Table 1). All society guidelines characterize NAFLD by the presence of HS in the absence of significant alcohol consumption. However, there is no international consensus as to the amount of alcohol considered “significant.” The Asian guideline has the most conservative alcohol threshold and mirrors the exclusion criteria for alcohol use defined in the National Institutes of Health Nonalcoholic Steatohepatitis Research Network database protocol. It is important to keep in mind that alcohol thresholds are oversimplified because the duration of significant alcohol exposure, drinking pattern, and individual susceptibility all play a role in alcohol-induced liver injury. All societies recommend against systematic screening for NAFLD in the general population. AASLD currently recommends against screening even in high-risk populations because of the lack of effective drug treatment, cost-effectiveness analysis, and unclear long-term benefits to screening. A “high index of suspicion” for NAFLD is advised in patients with type 2 diabetes. The European guideline acknowledges the lack of validated cost-utility studies and the need to be cognizant of regional variations in available health care resources but recommends that all patients with obesity or the metabolic syndrome be screened for NAFLD because of the prognostic implications of progressive disease. The Asian guidelines state that screening may be considered in at-risk groups, such as patients with diabetes and obesity. Lean NAFLD is prevalent in Asia, where almost a quarter of patients with NAFLD are not obese.11 Thus, insulin resistance (IR) and altered body fat distribution rather than body mass index per se may be better indicators of NAFLD in such patients. In patients without diabetes, the homeostatic model assessment for IR (HOMA-IR) provides an acceptable estimate of IR. Ultrasound remains the first-line assessment for HS because of its wide availability and low cost. However, it is less reliable when HS is <20%12 and raises concerns of underestimating the prevalence of NAFLD. Magnetic resonance imaging–derived proton density fat fraction is highly sensitive but is not widely available outside of research settings. Controlled attenuation parameter is available with the FibroScan system and may be more sensitive than ultrasound. Its point-of-care nature makes it appealing as a tool to monitor disease progression and treatment response, but more studies are needed to assess its validity. Liver histology remains the gold standard for differentiating steatohepatitis from simple steatosis and for assessing fibrosis staging. Due to its invasive nature and associated costs, all guidelines agree that liver biopsy should be considered only in select individuals. The American and European guidelines agree that patients with NAFLD and suspicion for advanced fibrosis should have a liver biopsy to confirm findings because this would have prognostic implications and lead to management changes. The Asian guidelines differ in that they recommend biopsy only if the presence and/or the severity of coexisting chronic liver disease cannot be excluded or if assessment of fibrosis using noninvasive testing is inconclusive. All guidelines agree that noninvasive tools should be used to stratify patients as low or high risk for advanced fibrosis, but a preferred sequence of testing is not provided in the American and Asian guidelines. The European guideline provides a proposed diagnostic algorithm with suggestions to guide referral to hepatology. In addition, it provides a proposed follow-up strategy to monitor for disease progression with the caveat that optimal follow-up has yet to be determined. The identification of NASH is clinically important because it indicates an increased risk for fibrosis progression and the need for aggressive treatment and closer follow-up. There are currently no acceptable noninvasive modalities to differentiate between bland steatosis and steatohepatitis. The presence of the metabolic syndrome increases the risk for steatohepatitis, and the US guidelines suggest performing liver biopsy in these patients. However, because most patients with NAFLD have at least one component of the metabolic syndrome, such an approach is clinically impractical. Furthermore, without the availability of a US Food and Drug Administration (FDA)–approved pharmacological therapy for NASH, many clinicians remain hesitant to proceed with biopsy. Once NASH is diagnosed, therapies recommended by the AASLD guidelines include vitamin E for patients with advanced fibrosis and without diabetes mellitus (DM) and pioglitazone, a thiazolidinedione that may be used in patients with NASH and diabetes. More recently, liraglutide, a glucagon-like peptide-1 receptor agonist, was shown to be of benefit in patients with NASH and DM. Pharmacological therapy for NASH is an area of significant ongoing investigation. Hepatocellular carcinoma (HCC) related to NAFLD is of growing concern, particularly because it can occur in the absence of cirrhosis.13 Obesity, type 2 diabetes, advanced age, male sex, and certain gene polymorphisms are associated with increased risk for HCC. However, the mortality benefit and cost-effectiveness of surveillance for HCC in patients with noncirrhotic NAFLD is yet to be determined and is not recommended at this time by any of the guidelines. Early recognition and intervention are key to improving clinical outcomes and reducing the economic and health care burden of NAFLD. Despite this, widespread awareness of NAFLD in the primary care setting is lacking and remains underdiagnosed in real-world settings.14, 15 Once drugs specifically targeting NAFLD obtain FDA approval, there will most likely be a surge of interest in NAFLD by the key health care stakeholders: patients, providers, payors, and policymakers. NAFLD is a fast-moving field, and current guidelines will soon be outdated. Future guideline updates should outline a practical strategy for the identification of high-risk patients with NAFLD who would benefit most from hepatology referral and targeted therapy (Fig. 1). There remains a pressing need to establish the optimal assessment of steatosis, steatohepatitis, and fibrosis in a cost-effective and minimally invasive manner.

Background: The effects of spinal anesthesia as compared with general anesthesia on the ability to walk in older adults undergoing surgery for hip fracture have not been well studied. Methods: We conducted a pragmatic, randomized superiority trial to evaluate spinal anesthesia as compared with general anesthesia in previously ambulatory patients 50 years of age or older who were undergoing surgery for hip fracture at 46 U.S. and Canadian hospitals. Patients were randomly assigned in a 1:1 ratio to receive spinal or general anesthesia. The primary outcome was a composite of death or an inability to walk approximately 10 ft (3 m) independently or with a walker or cane at 60 days after randomization. Secondary outcomes included death within 60 days, delirium, time to discharge, and ambulation at 60 days. Results: A total of 1600 patients were enrolled; 795 were assigned to receive spinal anesthesia and 805 to receive general anesthesia. The mean age was 78 years, and 67.0% of the patients were women. A total of 666 patients (83.8%) assigned to spinal anesthesia and 769 patients (95.5%) assigned to general anesthesia received their assigned anesthesia. Among patients in the modified intention-to-treat population for whom data were available, the composite primary outcome occurred in 132 of 712 patients (18.5%) in the spinal anesthesia group and 132 of 733 (18.0%) in the general anesthesia group (relative risk, 1.03; 95% confidence interval [CI], 0.84 to 1.27; P = 0.83). An inability to walk independently at 60 days was reported in 104 of 684 patients (15.2%) and 101 of 702 patients (14.4%), respectively (relative risk, 1.06; 95% CI, 0.82 to 1.36), and death within 60 days occurred in 30 of 768 (3.9%) and 32 of 784 (4.1%), respectively (relative risk, 0.97; 95% CI, 0.59 to 1.57). Delirium occurred in 130 of 633 patients (20.5%) in the spinal anesthesia group and in 124 of 629 (19.7%) in the general anesthesia group (relative risk, 1.04; 95% CI, 0.84 to 1.30). Conclusions: Spinal anesthesia for hip-fracture surgery in older adults was not superior to general anesthesia with respect to survival and recovery of ambulation at 60 days. The incidence of postoperative delirium was similar with the two types of anesthesia. (Funded by the Patient-Centered Outcomes Research Institute; REGAIN ClinicalTrials.gov number, NCT02507505.).

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has led to personal protective equipment (PPE) shortages, requiring mask reuse or improvisation. We provide a review of medical-grade facial protection (surgical masks, N95 respirators and face shields) for healthcare workers, the safety and efficacy of decontamination methods, and the utility of alternative strategies in emergency shortages or resource-scarce settings. METHODS: We conducted a scoping review of PubMed and grey literature related to facial protection and potential adaptation strategies in the setting of PPE shortages (January 2000 to March 2020). Limitations included few COVID-19-specific studies and exclusion of non-English language articles. We conducted a narrative synthesis of the evidence based on relevant healthcare settings to increase practical utility in decision-making. RESULTS: We retrieved 5462 peer-reviewed articles and 41 grey literature records. In total, we included 67 records which met inclusion criteria. Compared with surgical masks, N95 respirators perform better in laboratory testing, may provide superior protection in inpatient settings and perform equivalently in outpatient settings. Surgical mask and N95 respirator conservation strategies include extended use, reuse or decontamination, but these strategies may result in inferior protection. Limited evidence suggests that reused and improvised masks should be used when medical-grade protection is unavailable. CONCLUSION: The COVID-19 pandemic has led to critical shortages of medical-grade PPE. Alternative forms of facial protection offer inferior protection. More robust evidence is required on different types of medical-grade facial protection. As research on COVID-19 advances, investigators should continue to examine the impact on alternatives of medical-grade facial protection.

BACKGROUND AND PURPOSE: EmboTrap is a novel stent retriever designed to achieve rapid and substantial flow restoration in acute ischemic stroke secondary to large-vessel occlusions. Here, we evaluated EmboTrap's safety and efficacy compared with established stent retrievers. METHODS: ARISE II (Analysis of Revascularization in Ischemic Stroke With EmboTrap) was a single-arm, prospective, multicenter study, comparing the EmboTrap device to a composite performance goal criterion derived using a Bayesian meta-analysis from the pivotal SWIFT (Solitaire device) and TREVO 2 (Trevo device) trials. Patients at 11 US and 8 European sites were eligible for inclusion if they had large-vessel occlusions and moderate-to-severe neurological deficits within 8 hours of symptom onset. The primary efficacy end point was achievement of modified Thrombolysis in Cerebral Ischemia (mTICI) reperfusion scores of ≥2b within 3 EmboTrap passes as adjudicated by the core laboratory. The primary safety end point was a composite of symptomatic intracerebral hemorrhage and serious adverse device effects. Secondary end points included functional independence (modified Rankin Scale, 0-2) and all-cause mortality at 90 days. RESULTS: value, <0.0001), and mTICI 2c/3 was 65%. After all interventions, mTICI 2c/3 was achieved in 76%, and mTICI ≥2b was 92.5%. The rate of first pass (mTICI ≥2b following a single pass) was 51.5%. The primary safety end point composite rate of symptomatic intracerebral hemorrhage or serious adverse device effects was 5.3%. Functional independence and all-cause mortality at 90 days were 67% and 9%, respectively. CONCLUSIONS: The EmboTrap stent-retriever mechanical thrombectomy device demonstrated high rates of substantial reperfusion and functional independence in patients with acute ischemic stroke secondary to large-vessel occlusions. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT02488915.

BACKGROUND: In vitro and observational epidemiological studies suggest that vitamin D may play a role in cancer prevention. However, the relationship between vitamin D and ovarian cancer is uncertain, with observational studies generating conflicting findings. A potential limitation of observational studies is inadequate control of confounding. To overcome this problem, we used Mendelian randomization (MR) to evaluate the association between single nucleotide polymorphisms (SNPs) associated with circulating 25-hydroxyvitamin D [25(OH)D] concentration and risk of ovarian cancer. METHODS: We employed SNPs with well-established associations with 25(OH)D concentration as instrumental variables for MR: rs7944926 (DHCR7), rs12794714 (CYP2R1) and rs2282679 (GC). We included 31 719 women of European ancestry (10 065 cases, 21 654 controls) from the Ovarian Cancer Association Consortium, who were genotyped using customized Illumina Infinium iSelect (iCOGS) arrays. A two-sample (summary data) MR approach was used and analyses were performed separately for all ovarian cancer (10 065 cases) and for high-grade serous ovarian cancer (4121 cases). RESULTS: The odds ratio for epithelial ovarian cancer risk (10 065 cases) estimated by combining the individual SNP associations using inverse variance weighting was 1.27 (95% confidence interval: 1.06 to 1.51) per 20 nmol/L decrease in 25(OH)D concentration. The estimated odds ratio for high-grade serous epithelial ovarian cancer (4121 cases) was 1.54 (1.19, 2.01). CONCLUSIONS: Genetically lowered 25-hydroxyvitamin D concentrations were associated with higher ovarian cancer susceptibility in Europeans. These findings suggest that increasing plasma vitamin D levels may reduce risk of ovarian cancer.

PROBLEM: The extravillous trophoblasts (EVT) express HLA-C and HLA-G, but HLA-E and HLA-F are the subject of conflicting reports. In this study, we define the HLA expression profile during active EVT placental implantation, pregnancy development, and parturition. METHOD OF STUDY: Immunohistochemistry, q-PCR, and Western blot were used to investigate HLA-C, HLA-E, and HLA-F placental expression across gestation from the early first trimester, late first trimester, second trimester (n=10 in each), preterm gestation (n=6) to elective term cesarean section and term vaginal deliveries (n=12, 38-41 weeks). EVT explants and Swan71 cells were used to assess HLA-C and HLA-F during active EVT migration. RESULTS: HLA-G, HLA-C, and HLA-F were expressed by 1st-trimester EVT and became intracellular and weaker as gestation progressed. HLA-E was only expressed in 1st-trimester placenta. HLA-F and HLA-C mRNA and protein expression levels showed a significant increase in the fetal villous mesenchyme across gestation. HLA-C levels increased with labor. We detected a 100-kDa HLA-F band in early pregnancy suggesting dimer formation on the EVT surface. These results were confirmed in EVT outgrowths and Swan71 trophoblast which showed that HLA-F and HLA-G are increased on the cell surface of migrating EVT, while HLA-C was internalized. CONCLUSION: Expression of HLA-F and HLA-G on the cell surface of actively migrating EVT supports their specific role in early EVT invasion and interactions with uterine natural killer cells. HLA-C's limited expression to the proliferative EVT suggests a protective role in the earliest events of implantation but not in active EVT invasion. We also show for the first time that HLA-C may be involved in parturition.

SARS-CoV-2 and its variants continue to infect hundreds of thousands every day despite the rollout of effective vaccines. Therefore, it is essential to understand the levels of protection that these vaccines provide in the face of emerging variants. Here, we report two demographically balanced cohorts of BNT162b2 vaccine recipients and COVID-19 patients, from which we evaluate neutralizing antibody titers against SARS-CoV-2 as well as the B.1.1.7 (alpha) and B.1.351 (beta) variants. We show that both B.1.1.7 and B.1.351 are less well neutralized by serum from vaccinated individuals, and that B.1.351, but not B.1.1.7, is less well neutralized by convalescent serum. We also find that the levels of variant-specific anti-spike antibodies are proportional to neutralizing activities. Together, our results demonstrate the escape of the emerging SARS-CoV-2 variants from neutralization by serum antibodies, which may lead to reduced protection from re-infection or increased risk of vaccine breakthrough.

The May 1986 Mt. Hood climbing disaster presented Portland area hospitals the opportunity to initiate a trial of extracorporeal rewarming using cardiopulmonary bypass in ten severely hypothermic patients (two survivors). The data from this experience as well as others previously reported can yield prognostic indicators of survival in cases of accidental hypothermia. These are demonstrated to include: the presence of underlying medical illness, duration of cold exposure, initial core temperature, mental status, the presence of spontaneous respirations, presenting cardiac rate and rhythm, and arterial oxygen tension. Profound hyperkalemia and markedly elevated serum ammonia levels indicate cell lysis; significant hypofibrinogenemia suggests intravascular thrombosis and each laboratory marker predicts a dire outcome. The treatment of choice for severe accidental hypothermia is felt to be rapid core rewarming on cardiopulmonary bypass.

Importance: Financial toxicity (FT), unintended and unanticipated financial burden experienced by cancer patients undergoing cancer care, is associated with negative consequences and increased risk of mortality. Older patients (≥70 years) with cancer are at risk for FT, yet data are limited on FT and whether oncologists discuss FT with their patients. Objective: To examine the prevalence of FT in older adults with advanced cancer, its association with health-related quality of life (HRQoL), and cost conversations between oncologists and patients. Design, Setting, and Participants: This cross-sectional secondary analysis was performed on baseline data from the Improving Communication in Older Cancer Patients and Their Caregivers study, a cluster randomized trial from 31 community oncology practices across the US that was conducted from October 29, 2014, to April 28, 2017. Participants included 536 patients with advanced cancer who answered 3 questions regarding financial toxicity. Data were analyzed from September 1, 2019, to May 1, 2020. Exposure: Older patients undergoing cancer care treatments. Main Outcomes and Measures: The main outcome looked at FT and its association with HRQoL. Three questions were used to identify patients 70 years or older experiencing FT. Multivariable linear regression models were used to assess the independent associations of FT with HRQoL. A single audio-recorded clinic transcript was analyzed within 4 weeks of enrollment for patients with FT. The framework method was used to identify frequency and themes related to cost conversations. Results: This study evaluated 536 patients 70 years or older with advanced cancer. Ninety-eight patients (18.3%) reported FT; mean (SD) age was 76.4 (5.4) years; 59 (60.2%) were female, 14 (14.3%) were Black/African American, 91 (92.9%) were not employed, and 29 (29.6%) had Medicare as their sole insurance coverage. On multivariate regression analyses, FT was associated with higher levels of depression (β = 0.81; 95% CI, 0.15-1.48), anxiety (β = 1.67; 95% CI, 0.74-2.61), and distress (β = 0.73; 95% CI, 0.08-1.39) and lower HRQoL (β = -5.30; 95% CI, -8.92 to -1.69). Among those who reported FT, 49% had a conversation with their health care professional about costs. Most conversations (79%) were initiated by oncologists or patients. Four themes were generated from cost conversations: statements regarding cost of care, ability to afford medical prescriptions, indirect consequences associated with inability to work and provide for family, and cost burden in nontreatment domains. Conclusions and Relevance: In this study, among older adults with advanced cancer, FT is associated with worse HRQoL. Almost half of conversations among patients reporting FT demonstrated costs are being actively discussed. Resources and interventions are needed to manage FT.