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Diagnostic error or delay (DEOD) is common in the acute care setting and results in poor patient outcomes. Many factors contribute to DEOD, but little is known about how contributors may differ across acute care areas and professional roles. As part of a sequential exploratory mixed methods research study, we surveyed acute care clinical stakeholders about the frequency with which different factors contribute to DEOD. Survey respondents could also propose solutions in open text fields. N = 220 clinical stakeholders completed the survey. Care Team Interactions, Systems and Process, Patient, Provider, and Cognitive factors were perceived to contribute to DEOD with similar frequency. Organization and Infrastructure factors were perceived to contribute to DEOD significantly less often. Responses did not vary across acute care setting. Physicians perceived Cognitive factors to contribute to DEOD more frequently compared to those in other roles. Commonly proposed solutions included: technological solutions, organization level fixes, ensuring staff know and are encouraged to work to the full scope of their role, and cultivating a culture of collaboration and respect. Multiple factors contribute to DEOD with similar frequency across acute care areas, suggesting the need for a multi-pronged approach that can be applied across acute care areas.

Importance In patients with severe aortic valve stenosis at intermediate surgical risk, transcatheter aortic valve replacement (TAVR) with a self-expanding supra-annular valve was noninferior to surgery for all-cause mortality or disabling stroke at 2 years. Comparisons of longer-term clinical and hemodynamic outcomes in these patients are limited. Objective To report prespecified secondary 5-year outcomes from the Symptomatic Aortic Stenosis in Intermediate Risk Subjects Who Need Aortic Valve Replacement (SURTAVI) randomized clinical trial. Design, Setting, and Participants SURTAVI is a prospective randomized, unblinded clinical trial. Randomization was stratified by investigational site and need for revascularization determined by the local heart teams. Patients with severe aortic valve stenosis deemed to be at intermediate risk of 30-day surgical mortality were enrolled at 87 centers from June 19, 2012, to June 30, 2016, in Europe and North America. Analysis took place between August and October 2021. Intervention Patients were randomized to TAVR with a self-expanding, supra-annular transcatheter or a surgical bioprosthesis. Main Outcomes and Measures The prespecified secondary end points of death or disabling stroke and other adverse events and hemodynamic findings at 5 years. An independent clinical event committee adjudicated all serious adverse events and an independent echocardiographic core laboratory evaluated all echocardiograms at 5 years. Results A total of 1660 individuals underwent an attempted TAVR (n = 864) or surgical (n = 796) procedure. The mean (SD) age was 79.8 (6.2) years, 724 (43.6%) were female, and the mean (SD) Society of Thoracic Surgery Predicted Risk of Mortality score was 4.5% (1.6%). At 5 years, the rates of death or disabling stroke were similar (TAVR, 31.3% vs surgery, 30.8%; hazard ratio, 1.02 [95% CI, 0.85-1.22]; P = .85). Transprosthetic gradients remained lower (mean [SD], 8.6 [5.5] mm Hg vs 11.2 [6.0] mm Hg; P < .001) and aortic valve areas were higher (mean [SD], 2.2 [0.7] cm 2 vs 1.8 [0.6] cm 2 ; P < .001) with TAVR vs surgery. More patients had moderate/severe paravalvular leak with TAVR than surgery (11 [3.0%] vs 2 [0.7%]; risk difference, 2.37% [95% CI, 0.17%- 4.85%]; P = .05). New pacemaker implantation rates were higher for TAVR than surgery at 5 years (289 [39.1%] vs 94 [15.1%]; hazard ratio, 3.30 [95% CI, 2.61-4.17]; log-rank P < .001), as were valve reintervention rates (27 [3.5%] vs 11 [1.9%]; hazard ratio, 2.21 [95% CI, 1.10-4.45]; log-rank P = .02), although between 2 and 5 years only 6 patients who underwent TAVR and 7 who underwent surgery required a reintervention. Conclusions and Relevance Among intermediate-risk patients with symptomatic severe aortic stenosis, major clinical outcomes at 5 years were similar for TAVR and surgery. TAVR was associated with superior hemodynamic valve performance but also with more paravalvular leak and valve reinterventions.

ABSTRACT Background Multiple System Atrophy is a rare neurodegenerative disease with alpha‐synuclein aggregation in glial cytoplasmic inclusions and either predominant olivopontocerebellar atrophy or striatonigral degeneration, leading to dysautonomia, parkinsonism, and cerebellar ataxia. One prior genome‐wide association study in mainly clinically diagnosed patients with Multiple System Atrophy failed to identify genetic variants predisposing for the disease. Objective Since the clinical diagnosis of Multiple System Atrophy yields a high rate of misdiagnosis when compared to the neuropathological gold standard, we studied only autopsy‐confirmed cases. Methods We studied common genetic variations in Multiple System Atrophy cases (N = 731) and controls (N = 2898). Results The most strongly disease‐associated markers were rs16859966 on chromosome 3, rs7013955 on chromosome 8, and rs116607983 on chromosome 4 with P ‐values below 5 × 10 −6 , all of which were supported by at least one additional genotyped and several imputed single nucleotide polymorphisms. The genes closest to the chromosome 3 locus are ZIC1 and ZIC4 encoding the zinc finger proteins of cerebellum 1 and 4 (ZIC1 and ZIC4). Interpretation Since mutations of ZIC1 and ZIC4 and paraneoplastic autoantibodies directed against ZIC4 are associated with severe cerebellar dysfunction, we conducted immunohistochemical analyses in brain tissue of the frontal cortex and the cerebellum from 24 Multiple System Atrophy patients. Strong immunohistochemical expression of ZIC4 was detected in a subset of neurons of the dentate nucleus in all healthy controls and in patients with striatonigral degeneration, whereas ZIC4‐immunoreactive neurons were significantly reduced inpatients with olivopontocerebellar atrophy. These findings point to a potential ZIC4‐mediated vulnerability of neurons in Multiple System Atrophy. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society

Abstract Background: Associations between candidate germline genetic variants and treatment outcome of oxaliplatin, a drug commonly used for patients with colorectal cancer, have been reported but not robustly established. This study aimed to construct polygenic hazard scores (PHSs) as predictive markers for oxaliplatin treatment outcome by using a supervised principal component approach (PCA). Methods: Genome-wide association analysis for overall survival, including interaction terms (SNP*treatment type) was carried out using two phase III trials, 3,098 resected stage III colon cancer (rCC) patients of NCCTG N0147 and 506 metastatic colorectal cancer (mCRC) patients of NCCTG N9741, separately. SNPs showing interaction with genome-wide significance (P < 5 × 10–8) were selected for PCA to derive a PHS. PHS interaction with treatment was included in Cox regression models to predict outcome. Replication of prediction models was performed in an independent cohort, DACHS. Results: The two PHSs based on the first two principal components of selected SNPs (15SNPs for rCC and 13SNPs for mCRC) were used to construct interaction terms with treatment type and included in models adjusted for clinical covariables. However, in the DACHS study, the addition of the two PHS terms to clinical models did not improve the prediction error in either patients with rCC or mCRC. PHS interaction was also not replicated. Conclusions: The PHSs derived using principal components efficiently combined multiple predictive SNPs for estimating likelihood of benefit from oxaliplatin versus other treatment but could not be replicated. Impact: These results highlight the potential but also challenges in generating evidence for a predictive polygenic score for oxaliplatin efficacy.

BACKGROUND: Anemia is common in critically ill patients and may be exacerbated through phlebotomy-associated iatrogenic blood loss. Differences in phlebotomy practice across patient demographic characteristics, clinical features, and practice environments are unclear. This investigation provides a comprehensive description of contemporary phlebotomy practices for critically ill adults. METHODS: This is an observational cohort study of adults ≥18 years of age requiring intensive care unit (ICU) admission between January 1, 2019, and December 31, 2019, at a large academic medical center. Descriptive statistics were utilized to summarize all phlebotomy episodes throughout hospitalization, with each phlebotomy episode defined by unique peripheral venous, central venous, or arterial accesses for laboratory draws, exclusive of finger sticks. Secondarily, financial costs of phlebotomy and the relationships between phlebotomy practices, hemoglobin concentrations, and red blood cell (RBC) transfusions were evaluated. RESULTS: A total of 6194 patients were included: 59% were men with a median (interquartile range) age of 66 (54–76) years and median ICU and hospital durations of 2.1 (1.4–3.9) and 7.1 (4.3–11.8) days, respectively. The median number of unique laboratory draws was 41 (18–88) throughout hospitalization, with a median volume of 232 (121–442) mL, corresponding to 5.2 (2.6–8.8) draws and 29 (19–43) mL per day. Waste (ie, discard) volume was responsible for 10.8% of total phlebotomy volume. Surgical patients had a higher number of phlebotomy episodes and greater total phlebotomy volumes compared to nonsurgical patients. Phlebotomy practices differed across ICU types, with the greatest frequency of laboratory draws in the cardiac surgical ICU and the greatest daily phlebotomy volume in the medical ICU. Across hospitalization, ICU environments had the greatest frequency and volumes of laboratory draws, with the least intensive phlebotomy practice observed in the general hospital wards. Patients in the highest quartile of cumulative blood drawn experienced the longest hospitalizations, lowest nadir hemoglobin concentrations, and greatest RBC transfusion utilization. Differences in phlebotomy practice were limited across patient age, gender, and race. Hemoglobin concentrations declined during hospitalization, congruent with intensity of phlebotomy practice. Each 100 mL of phlebotomy volume during hospitalization was associated with a 1.15 (95% confidence interval [CI], 1.14–1.17; P < .001) multiplicative increase in RBC units transfused in adjusted analyses. Estimated annual phlebotomy costs exceeded $15 million (approximately $2500 per patient admission). CONCLUSIONS: Phlebotomy continues to be a major source of blood loss in hospitalized patients with critical illness, and more intensive phlebotomy practices are associated with lower hemoglobin concentrations and greater transfusion utilization.

Rationale: Immunoglobulin (Ig) G4–related disease (IgG4-RD) reportedly has a strong relationship with adult-onset asthma and periocular xanthogranuloma (AAPOX) and may be linked to sclerosing mucoepidermoid carcinoma (MEC). We present a rare case of IgG4-RD and AAPOX occurring in a patient with resected eosinophilic or oncocytic MEC. Patient concerns: A 52-year-old woman was referred to our rheumatology clinic in 2020 to be evaluated for suspected IgG4-RD. Diagnoses: The patient had diagnoses of periorbital xanthelasmas, worsening glucocorticoid-dependent chronic rhinosinusitis and adult-onset asthma, and cervical lymphadenopathy persisting 2 years after resection of a low-grade MEC of a minor salivary gland. Interventions: Because the patient’s symptomatic relief was glucocorticoid dependent, IgG4-RD was suspected, and she was referred to our medical center. Her amylase and lipase levels were elevated. Serum IgG4 levels were initially within normal limits, but IgG4-RD was diagnosed because of the presence of lymphadenopathy and evidence of pancreatitis, which was shown on positron emission tomography/computed tomography. Furthermore, the IgG4 levels later increased without explanation. After the patient began combination therapy with a glucocorticoid (prednisone) and methotrexate, her symptoms improved but recurred when the daily oral glucocorticoid dosage decreased below 10 mg. An excisional biopsy of her right submandibular gland in 2021 yielded results consistent with IgG4-RD. In addition, AAPOX was diagnosed, given the presence of periocular edema and plaques, adult-onset asthma, and rhinosinusitis. Outcome: The patient was carcinoma free at last follow-up and was receiving medication to treat the other conditions. Lessons: The diagnosis of these 3 concomitant, uncommon entities required approximately 7 years of medical investigations. Clinicians should know that IgG4-RD, AAPOX, and MEC may occur together.

Abstract OBJECTIVEDespite longstanding and recurrent calls for effective implicit bias (IB) education in health professions education as one mechanism to reduce ongoing racism and health disparities, evidence-based IB curricula for neonatal-perinatal medicine (NPM) are limited. We aim to determine the key IB curricular elements for teaching NPM fellows, advanced practice providers, and attending physicians. STUDY DESIGNA modified Delphi study was performed with content experts in IB and health disparities who had educational relationships to those working and training in the neonatal intensive care unit. RESULTThree Delphi rounds were conducted. Experts reached consensus on a variety of items for inclusion in an IB curriculum, including educational goals, learning objectives, teaching strategies, and educator principles.CONCLUSIONEssential IB curricular components for the field of neonatal medicine were defined using rigorous consensus building methodology.