Serpentine supravenous hyperpigmentation induced by chemotherapy: a systematic review.

Serpentine supravenous hyperpigmentation (SSH) describes increased skin pigmentation that develops in the area immediately overlying the vessels through which chemotherapeutic drugs are administered. While SSH can be cosmetically distressing and there are no definitive management options, the literature is severely limited and the variations in clinical presentation, risk factors, and histopathology of SSH across patients are not well understood. We aimed to systematically summarize characteristics from current available data, and thus improve SSH awareness and management. A literature search was conducted in PubMed using specific eligibility criteria through the end of December 2022. Included articles focused on patients who experienced SSH after chemotherapy infusion. Study quality was assessed using a modified Oxford Centre for Evidence-Based Medicine quality rating scheme. Of the 41 articles identified by literature search, 24 met eligibility criteria. Two additional articles were identified through the reference sections of retrieved articles, for 26 articles total. All articles were case reports, representing 28 patients total. Locations of SSH were mostly in the forearm near the site of injection (85%), and the most common associated symptom was erythema. Histopathologic analysis was available for half of cases, the majority of which were inflammatory in nature. The most common inflammatory pattern observed was a vacuolar/lichenoid interface dermatitis. Duration of SSH ranged from days to > 1 year after the chemotherapy was stopped. Six (21%) patients were managed with topical steroids and oral vasodilators, six (21%) patients switched to central venous infusion rather than peripheral infusion, five (18%) patients received only supportive care, three (11%) patients received venous washing with chemotherapy, three (11%) patients stopped chemotherapy, and one (4%) patient reduced the chemotherapy dosage. Ten (36%) patients attained complete resolution, seven (25%) had SSH that was near resolution/fading, and three (11%) had persistent hyperpigmentation. Although SSH often spontaneously resolves once the chemotherapeutic agent is stopped, it can persist in some patients and cause significant distress. As the literature is severely limited and there are no definitive treatments, additional research using more standardized definitions and methods of assessments is necessary to improve characterization of SSH and evaluate potential interventions.

Accuracy of Medical Student Measurements of CT Right-to-Left Ventricular Diameter in Patients with Acute Pulmonary Embolism.

Objectives: Acute pulmonary embolism (PE) is a common disease, necessitating risk stratification to determine management. A right ventricle (RV) to left ventricle (LV) diameter ratio ≥1.0 on computed tomography pulmonary angiography (CTPA) suggests RV strain, which may indicate a worse prognosis. Two prior studies showed that residents with brief training by a radiologist could accurately measure RV/LV ratio. We assessed whether medical students could accurately measure RV dilatation. Methods: We conducted a post hoc analysis of a retrospective cohort study of adults undergoing management for acute PE at 21 community emergency departments across Kaiser Permanente Northern California from 2013 to 2015. We created a sample, stratified to contain an equal number of patients from each of the 5 PE Severity Index classes. Four medical students measured RV and LV diameter on CTPA after training from an emergency medicine physician and an interventional radiologist. We used Cohen's kappa statistics, Bland-Altman plots, and Pearson correlation coefficients to assess interrater reliability. Results: Of the 108 CTPAs reviewed, 79 (73%) showed RV dilatation and 29 (27%) did not. The kappa statistic for the presence of RV dilatation of the medical students compared to the radiologist showed moderate agreement for 3 medical students (kappa (95% CI): 0.46 (0.21-0.70), 0.49 (0.31-0.68), 0.50 (0.32-0.68)) and fair agreement for 1 medical student (kappa (95% CI): 0.29 (0.10-0.47)). The average interrater differences in RV/LV ratio between a radiologist and each of the 4 medical students were -0.04, -0.05, 0.04, and 0.24. Pearson correlation coefficients were 0.87, 0.80, 0.74, and 0.78, respectively, indicating moderate correlation (P < .001 for all). Conclusion: Medical students were able to identify RV dilatation on CTPA in moderate agreement with that of a radiologist. Further study is needed to determine whether medical student accuracy could improve with additional training.

Patient-reported Primary Care Video and Telephone Telemedicine Preference Shifts During the COVID-19 Pandemic.

BACKGROUND: Patient perceptions of primary care telephone and video telemedicine and whether COVID-19 pandemic-related telemedicine exposure shifted patients' visit preference is unknown. OBJECTIVES: We examined patient surveys to understand the health care experience of patients seeking primary care through telemedicine and how patients expected their preferences to shift as a result of the COVID-19 pandemic. RESEARCH DESIGN/SUBJECTS: In an integrated delivery system that shifted to a "telemedicine-first" health care model during the COVID-19 pandemic, we sampled monthly and collected 1000 surveys from adults with primary care telemedicine visits scheduled through the online patient portal between 3/16/2020 and 10/31/2020. MEASURES: Participants reported their preferred primary care visit modality (telephone, video, or in-person visits) across 3 time points: before, during and (hypothetically) after the COVID-19 pandemic, and reported their general assessment of primary care visits during the pandemic. RESULTS: The majority of participants preferred in-person visits before (69%) and after the COVID-19 pandemic (57%). However, most participants reported a preference for telemedicine visits during the pandemic and continue to prefer telemedicine visits at a 12% higher rate post-pandemic. Many participants (63%) expressed interest in using telemedicine at least some of the time. Among participants reporting a recent telemedicine visit, 85% agreed that the visit addressed their health needs. CONCLUSION: As primary care visit modality preferences continue to evolve, patients anticipate that they will continue to prefer telemedicine visits, both video and telephone, at an increased rate than before the COVID-19 pandemic.

CA FIRST (California Febrile Infant Risk Stratification Tool) Algorithm Development in a Learning Health System.

Introduction There is considerable variation in the approach to infants presenting to the emergency department (ED) with fever. The authors' primary aim was to develop a robust set of algorithms using community ED data to inform modifications of broader clinical guidance. Methods The authors report the development of California Febrile Infant Risk Stratification Tool (CA FIRST) using key components of the Roseville Protocol (ROS) and American Academy of Pediatrics (AAP) Clinical Practice Guideline (CPG). Expanded guidance was derived using a retrospective analysis of a cohort of 3527 febrile infants aged 7-90 days presenting to any Kaiser Permanente Northern California ED between 2010 and 2019 who underwent a core febrile infant evaluation. Results Melding ROS and AAP CPG algorithms in infants 7-60 days old, CA FIRST Algorithms had comparable performance characteristics to ROS and AAP CPG. CA FIRST enhancements included guidance on febrile infants 61-90 days old, high-risk infants, infants with bronchiolitis, and infants who received immunizations within the prior 48 hours. This retrospective analysis revealed that of 235 febrile infants 22-90 days old with respiratory syncytial virus and 221 who had fever in the 48 hours following vaccination, there were no cases of invasive bacterial infection. Discussion CA FIRST is a set of 13 algorithms providing a thoughtful and flexible approach to the febrile infant while minimizing unnecessary interventions. Conclusions CA FIRST Algorithms empower clinicians to manage most febrile infants. Algorithms are being modified as new data become available, imparting useful and ever-current educational information within a learning health care system.

Clinical decision support to Optimize Care of patients with Atrial Fibrillation or flutter in the Emergency department: protocol of a stepped-wedge cluster randomized pragmatic trial (O'CAFÉ trial).

BACKGROUND: Management of adults with atrial fibrillation (AF) or atrial flutter in the emergency department (ED) includes rate reduction, cardioversion, and stroke prevention. Different approaches to these components of care may lead to variation in frequency of hospitalization and stroke prevention actions, with significant implications for patient experience, cost of care, and risk of complications. Standardization using evidence-based recommendations could reduce variation in management, preventable hospitalizations, and stroke risk. METHODS: We describe the rationale for our ED-based AF treatment recommendations. We also describe the development of an electronic clinical decision support system (CDSS) to deliver these recommendations to emergency physicians at the point of care. We implemented the CDSS at three pilot sites to assess feasibility and solicit user feedback. We will evaluate the impact of the CDSS on hospitalization and stroke prevention actions using a stepped-wedge cluster randomized pragmatic clinical trial across 13 community EDs in Northern California. DISCUSSION: We hypothesize that the CDSS intervention will reduce hospitalization of adults with isolated AF or atrial flutter presenting to the ED and increase anticoagulation prescription in eligible patients at the time of ED discharge and within 30 days. If our hypotheses are confirmed, the treatment protocol and CDSS could be recommended to other EDs to improve management of adults with AF or atrial flutter. TRIAL REGISTRATION: ClinicalTrials.gov NCT05009225 .  Registered on 17 August 2021.

Sodium in the skin: a summary of the physiology and a scoping review of disease associations.

A large and growing body of research suggests that the skin plays an important role in regulating total body sodium, challenging traditional models of sodium homeostasis that focused exclusively on blood pressure and the kidney. In addition, skin sodium may help to prevent water loss and facilitate macrophage-driven antimicrobial host defence, but may also trigger immune dysregulation via upregulation of proinflammatory markers and downregulation of anti-inflammatory processes. We performed a systematic search of PubMed for published literature on skin sodium and disease outcomes and found that skin sodium concentration is increased in patients with cardiometabolic conditions including hypertension, diabetes and end-stage renal disease; autoimmune conditions including multiple sclerosis and systemic sclerosis; and dermatological conditions including atopic dermatitis, psoriasis and lipoedema. Several patient characteristics are associated with increased skin sodium concentration including older age and male sex. Animal evidence suggests that increased salt intake results in higher skin sodium levels; however, there are conflicting results from small trials in humans. Additionally, limited data suggest that pharmaceuticals such as diuretics and sodium-glucose co-transporter-2 inhibitors approved for diabetes, as well as haemodialysis may reduce skin sodium levels. In summary, emerging research supports an important role for skin sodium in physiological processes related to osmoregulation and immunity. With the advent of new noninvasive magnetic resonance imaging measurement techniques and continued research on skin sodium, it may emerge as a marker of immune-mediated disease activity or a potential therapeutic target.

Using AAP Guidelines for Managing Febrile Infants Without C-Reactive Protein and Procalcitonin.

BACKGROUND AND OBJECTIVES: In 2021, the American Academy of Pediatrics (AAP) published the Clinical Practice Guideline (CPG) for management of well-appearing, febrile infants 8 to 60 days old. For older infants, the guideline relies on several inflammatory markers, including tests not rapidly available in many settings like C-reactive protein (CRP) and procalcitonin (PCT). This study describes the performance of the AAP CPG for detecting invasive bacterial infections (IBI) without using CRP and PCT. METHODS: This retrospective cohort study included infants aged 8 to 60 days old presenting to Kaiser Permanente Northern California emergency departments between 2010 and 2019 with temperatures ≥38°C who met AAP CPG inclusion criteria and underwent complete blood counts, blood cultures, and urinalyses. Performance characteristics for detecting IBI were calculated for each age group. RESULTS: Among 1433 eligible infants, there were 57 (4.0%) bacteremia and 9 (0.6%) bacterial meningitis cases. Using absolute neutrophil count >5200/mm3 and temperature >38.5°C as inflammatory markers, 3 (5%) infants with IBI were misidentified. Sensitivities and specificities for detecting infants with IBIs in each age group were: 8 to 21 days: 100% (95% confidence interval [CI] 83.9%-100%) and 0% (95% CI 0%-1.4%); 22 to 28 days: 88.9% (95% CI 51.8%-99.7%) and 40.4% (95% CI 33.2%- 48.1%); and 29 to 60 days: 93.3% (95% CI 77.9%-99.2%) and 32.1% (95% CI 29.1%- 35.3%). Invasive interventions were recommended for 100% of infants aged 8 to 21 days; 58% to 100% of infants aged 22 to 28 days; and 0% to 69% of infants aged 29 to 60 days. CONCLUSIONS: When CRP and PCT are not available, the AAP CPG detected IBI in young, febrile infants with high sensitivity but low specificity.

Higher intensity of 72-h noninvasive cardiac test referral does not improve short-term outcomes among emergency department patients with chest pain.

BACKGROUND: It is unclear whether referral for cardiac noninvasive testing (NIT) following emergency department (ED) chest pain encounters improves short-term outcomes. METHODS: This was a retrospective cohort study of patients presenting with chest pain, without ST-elevation myocardial infarction or myocardial injury by serum troponin testing, between 2013 and 2019 to 21 EDs within an integrated health care system. We examined the association between NIT referral (within 72 h of the ED encounter) and a primary outcome of 60-day major adverse cardiac events (MACE). Secondary outcomes were 60-day MACE without coronary revascularization (MACE-CR) and 60-day all-cause mortality. To account for confounding by indication for NIT, we grouped patient encounters into ranked tertiles of NIT referral intensity based on the likelihood of 72-h NIT referral associated with the initially assigned emergency physician, relative to local peers and within discrete time periods. Associations between NIT referral-intensity tertile and outcomes were assessed using risk-adjusted multivariable logistic regression. RESULTS: Among 210,948 eligible patient encounters, 72-h NIT referral frequency was 11.9%, 18.3%, and 25.9% in low, intermediate, and high NIT referral-intensity encounters, respectively. Compared with the low referral-intensity tertile, there was a higher risk of 60-day MACE within the high referral-intensity tertile (odds ratio [OR] = 1.11, 95% confidence interval [CI] = 1.04 to 1.17) due to more coronary revascularizations without corresponding differences in MACE-CR or all-cause mortality. In analyses stratified by patients' estimated risk (HEART score; 50.5% lower risk, 38.7% moderate risk, 10.8% higher risk), the difference in 60-day MACE was primarily attributable to moderate-risk encounters (OR = 1.15, 95% CI = 1.08 to 1.24), with no differences among either lower- (OR = 1.10, 95% CI = 0.92 to 1.31) or higher- (OR = 1.01, 95% CI = 0.90 to 1.14) risk encounters. CONCLUSION: Higher referral intensity for 72-h NIT was associated with higher risk of coronary revascularization but no difference in adverse events within 60 days. These findings further call into question the urgency of NIT among ED patients without objective evidence of myocardial injury.

Management and Outcomes of Adults Diagnosed with Acute Pulmonary Embolism in Primary Care: Community-Based Retrospective Cohort Study.

BACKGROUND: The management and outcomes of patients diagnosed with acute pulmonary embolism in primary care have not been characterized. OBJECTIVE: To describe 30-day outcomes stratified by initial site-of-care decisions DESIGN: Multicenter retrospective cohort study PARTICIPANTS: Adults diagnosed with acute pulmonary embolism in primary care in a large, diverse community-based US health system (2013-2019) MAIN MEASURES: The primary outcome was a composite of 30-day serious adverse events (recurrent venous thromboembolism, major bleeding, and all-cause mortality). The secondary outcome was 7-day pulmonary embolism-related hospitalization, either initial or delayed. KEY RESULTS: Among 652 patient encounters (from 646 patients), median age was 64 years; 51.5% were male and 70.7% identified as non-Hispanic white. Overall, 134 cases (20.6%) were sent home from primary care and 518 cases (79.4%) were initially referred to the emergency department (ED) or hospital. Among the referred, 196 (37.8%) were discharged home from the ED without events. Eight patients (1.2%; 95% CI 0.5-2.4%) experienced a 30-day serious adverse event: 4 venous thromboemboli (0.6%), 1 major bleed (0.2%), and 3 deaths (0.5%). Seven of these patients were initially hospitalized, and 1 had been sent home from primary care. All 3 deaths occurred in patients with known metastatic cancer initially referred to the ED, hospitalized, then enrolled in hospice following discharge. Overall, 328 patients (50.3%) were hospitalized within 7 days: 322 at the time of the index diagnosis and 6 following initial outpatient management (4 clinic-only and 2 clinic-plus-ED patients). CONCLUSIONS: Patients diagnosed with acute pulmonary embolism in this primary care setting uncommonly experienced 30-day adverse events, regardless of initial site-of-care decisions. Over 20% were managed comprehensively by primary care. Delayed 7-day pulmonary embolism-related hospitalization was rare among the 51% treated as outpatients. Primary care management of acute pulmonary embolism appears to be safe and could have implications for cost-effectiveness and patient care experience.

Graded Coronary Risk Stratification for Emergency Department Patients With Chest Pain: A Controlled Cohort Study.

Background Resource utilization among emergency department (ED) patients with possible coronary chest pain is highly variable. Methods and Results Controlled cohort study amongst 21 EDs of an integrated healthcare system examining the implementation of a graded coronary risk stratification algorithm (RISTRA-ACS [risk stratification for acute coronary syndrome]). Thirteen EDs had access to RISTRA-ACS within the electronic health record (RISTRA sites) beginning in month 24 of a 48-month study period (January 2016 to December 2019); the remaining 8 EDs served as contemporaneous controls. Study participants had a chief complaint of chest pain and serum troponin measurement in the ED. The primary outcome was index visit resource utilization (observation unit or hospital admission, or 7-day objective cardiac testing). Secondary outcomes were 30-day objective cardiac testing, 60-day major adverse cardiac events (MACE), and 60-day MACE-CR (MACE excluding coronary revascularization). Difference-in-differences analyses controlled for secular trends with stratification by estimated risk and adjustment for risk factors, ED physician and facility. A total of 154 914 encounters were included. Relative to control sites, 30-day objective cardiac testing decreased at RISTRA sites among patients with low (≤2%) estimated 60-day MACE risk (-2.5%, 95% CI -3.7 to -1.2%, P<0.001) and increased among patients with non-low (>2%) estimated risk (+2.8%, 95% CI +0.6 to +4.9%, P=0.014), without significant overall change (-1.0%, 95% CI -2.1 to 0.1%, P=0.079). There were no statistically significant differences in index visit resource utilization, 60-day MACE or 60-day MACE-CR. Conclusions Implementation of RISTRA-ACS was associated with better allocation of 30-day objective cardiac testing and no change in index visit resource utilization or 60-day MACE. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT03286179.

Clinical characteristics of COVID-19 patients evaluated in the emergency department: A retrospective cohort study of 801 cases.

BACKGROUND: Coronavirus disease 2019 (COVID-19), the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has extracted devastating tolls. Despite its pervasiveness, robust information on disease characteristics in the emergency department (ED) and how that information predicts clinical course remain limited. METHODS: We conducted a retrospective cohort study of the first ED visit from SARS-CoV-2-positive patients in our health system, from February 21, 2020 to April 5, 2020. We reviewed each patient's ED visit(s) and included the first visit with symptoms consistent with COVID-19. We collected demographic, clinical, and treatment variables from electronic health records and structured manual chart review. We used multivariable logistic regression to examine the association between patient characteristics and 2 primary outcomes: a critical outcome and hospitalization from index visit. Our critical outcome was defined as death or advanced respiratory support (high flow nasal cannula or greater) within 21 days. RESULTS: Of the first 1030 encounters, 801 met our inclusion criteria: 15% were over age 75 years, 47% were female, and 24% were non-Hispanic white. We found 161 (20%) had a critical outcome and 393 (49%) were hospitalized. Independent predictors of a critical outcome included a history of hypertension, abnormal chest x-ray, elevated neutrophil to lymphocyte ratio, elevated blood urea nitrogen (BUN), measured fever, and abnormal respiratory vital signs (respiratory rate, oxygen saturation). Independent predictors of hospitalization included abnormal pulmonary auscultation, elevated BUN, measured fever, and abnormal respiratory vital signs. CONCLUSIONS: In this large, diverse study of ED patients with COVID-19, we have identified numerous clinical characteristics that have independent associations with critical illness and hospitalization.

Prospective Validation and Comparative Analysis of Coronary Risk Stratification Strategies Among Emergency Department Patients With Chest Pain.

Background Coronary risk stratification is recommended for emergency department patients with chest pain. Many protocols are designed as "rule-out" binary classification strategies, while others use graded-risk stratification. The comparative performance of competing approaches at varying levels of risk tolerance has not been widely reported. Methods and Results This is a prospective cohort study of adult patients with chest pain presenting between January 2018 and December 2019 to 13 medical center emergency departments within an integrated healthcare delivery system. Using an electronic clinical decision support interface, we externally validated and assessed the net benefit (at varying risk thresholds) of several coronary risk scores (History, ECG, Age, Risk Factors, and Troponin [HEART] score, HEART pathway, Emergency Department Assessment of Chest Pain Score Accelerated Diagnostic Protocol), troponin-only strategies (fourth-generation assay), unstructured physician gestalt, and a novel risk algorithm (RISTRA-ACS). The primary outcome was 60-day major adverse cardiac event defined as myocardial infarction, cardiac arrest, cardiogenic shock, coronary revascularization, or all-cause mortality. There were 13 192 patient encounters included with a 60-day major adverse cardiac event incidence of 3.7%. RISTRA-ACS and HEART pathway had the lowest negative likelihood ratios (0.06, 95% CI, 0.03-0.10 and 0.07, 95% CI, 0.04-0.11, respectively) and the greatest net benefit across a range of low-risk thresholds. RISTRA-ACS demonstrated the highest discrimination for 60-day major adverse cardiac event (area under the receiver operating characteristic curve 0.92, 95% CI, 0.91-0.94, P<0.0001). Conclusions RISTRA-ACS and HEART pathway were the optimal rule-out approaches, while RISTRA-ACS was the best-performing graded-risk approach. RISTRA-ACS offers promise as a versatile single approach to emergency department coronary risk stratification. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT03286179.

Computed Tomography Use in Children With Minor Head Trauma Presenting to 21 Community Emergency Departments Within an Integrated Health-Care System.

INTRODUCTION: Decreasing unnecessary cranial computed tomography (CT) use in pediatric head trauma patients remains important for emergency departments (EDs) across the US. Our study evaluated CT use in children with minor blunt head trauma in 21 community EDs within an integrated health-care system. METHODS: We studied all children younger than 18 years old presenting to 21 community EDs between 2016 through 2018 with acute minor blunt head trauma, defined by an algorithm of ED chief complaints and diagnoses. We excluded patients with traumatic brain injuries diagnosed in the prior year, a CT within 24 hours prior to the ED visit, or an ED Glasgow Coma Scale score of less than 14. RESULTS: Among 39,792 pediatric minor head trauma ED visits, the aggregate CT use proportion across all EDs was 12.9% [95% confidence interval (CI), 12.6-13.3%; facility-level range, 5.4-21.6%]. The 7 facilities that had previously received a clinical decision support system intervention implementing the Pediatric Emergency Care Applied Research Network rules during 2013 through 2014 had an aggregate mean CT ordering rate of 11.2% (95% CI, 10.7-11.7%; facility-level range, 5.4-14.3%) compared to 14.1% (95% CI, 13.6-14.5%; facility-level range, 7.3-21.6%) for the nonintervention facilities. CONCLUSION: CT use for children with minor blunt head trauma in the community EDs of an integrated health-care system was low and stable across facilities from 2016 through 2018. This may be indicative of the safe stewardship of resources in the system, including the absence of financial or medicolegal incentives to scan very low-risk patients as well the availability of resources for close patient follow-up.

"Outpatient Management" of Pulmonary Embolism Defined in the Primary Literature: A Narrative Review.

PURPOSE: The evidence for the effectiveness of outpatient treatment of low-risk patients with acute pulmonary embolism (PE) continues to mount. However, lack of definitional clarity may hinder understanding of this emerging management strategy and impede translation into clinical practice. We describe the range of definitions provided in the primary outpatient PE literature. METHODS: We undertook a narrative review of the English-language medical literature indexed in PubMed and Embase through the end of 2019. We identified studies of outpatient treatment of patients with acute PE. RESULTS: Fifty-one studies met our criteria. All studies provided some degree of definition of "outpatient," even if implicit or broad. Forty-six studies (90%) reported 1 or 2 sites of patient discharge (or departure) to home: emergency department (ED)/ambulatory care unit (n = 31), inpatient ward (n = 13), and secondary care clinic (n = 8). Of the 31 ED-based studies, 9 (29%) delimited duration of care (from < 24 to < 48 hours). All inpatient studies placed an outer boundary on the time to discharge within their definition of outpatient care. CONCLUSION: Definitions of outpatient care in the PE literature vary considerably. The sites, duration, and intensity of care involved in outpatient PE management prior to home discharge range from comprehensive specialty clinic care to an ED evaluation, sometimes coupled with 1 to 5 days of additional inpatient care. Research on the outpatient management of acute PE would benefit from greater definitional clarity as clinicians, departments, and health systems seek to translate this research into real-world clinical practice.

Does double-blind peer review impact gender authorship trends? An evaluation of two leading neurosurgical journals from 2010 to 2019.

OBJECTIVE: Publications are key for advancement within academia. Although women are underrepresented in academic neurosurgery, the rates of women entering residency, achieving board certification, and publishing papers are increasing. The goal of this study was to assess the current status of women in academic neurosurgery publications. Specifically, this study sought to 1) survey female authorship rates in the Journal of Neurosurgery (JNS [not including JNS: Spine or JNS: Pediatrics]) and Neurosurgery from 2010 to 2019; 2) analyze whether double-blind peer review (started in Neurosurgery in 2011) altered female authorship rates relative to single-blind review (JNS); and 3) evaluate how female authorship rates compared with the number of women entering neurosurgery residency and obtaining neurosurgery board certification. METHODS: Genders of the first and last authors for JNS and Neurosurgery articles from 2010 to 2019 were obtained. Data were also gathered on the number and percentage of women entering neurosurgery residency and women obtaining American Board of Neurological Surgeons (ABNS) certification between 2010 and 2019. RESULTS: Women accounted for 13.4% (n = 570) of first authors and 6.8% (n = 240) of last authors in JNS and Neurosurgery publications. No difference in rates of women publishing existed between the two journals (first authors: 13.0% JNS vs 13.9% Neurosurgery, p = 0.29; last authors: 7.3% JNS vs 6.0% Neurosurgery, p = 0.25). No difference existed between women first or last authors in Neurosurgery before and after initiation of double-blind review (p = 0.066). Significant concordance existed between the gender of first and last authors: in publications with a woman last author, the odds of the first author being a woman was increased by twofold (OR 2.14 [95% CI 1.43-3.13], p = 0.0001). Women represented a lower proportion of authors of invited papers (8.6% of first authors and 3.1% of last authors were women) compared with noninvited papers (14.1% of first authors and 7.4% of last authors were women) (first authors: OR 0.576 [95% CI 0.410-0.794], p = 0.0004; last authors: OR 0.407 [95% CI 0.198-0.751], p = 0.001). The proportion of women US last authors (7.4%) mirrors the percentage of board-certified women neurosurgeons (5.4% in 2010 and 6.8% in 2019), while the percentage of women US first authors (14.3%) is less than that for women entering neurosurgical residency (11.2% in 2009 and 23.6% in 2018). CONCLUSIONS: This is the first report of female authorship in the neurosurgical literature. The authors found that single- versus double-blind peer review did not impact female authorship rates at two top neurosurgical journals.

Publication Non Grata: The Challenge of Publishing Non-COVID-19 Research in the COVID Era.

OBJECTIVES: We aimed to determine publication trends in leading clinical research journals (impact factor >20) during the rise of the coronavirus disease 2019 (COVID-19) pandemic and to check for an increase in publication times of non-COVID-19 original research articles. METHODS: We collected publication data from five print-based medical journals and one online journal--JAMA: The Journal of the American Medical Association, The Lancet (Lancet), The New England Journal of Medicine, Annals of Internal Medicine, The BMJ (BMJ), and BMC Medicine (BMC Med)--for the December 2019 through May 2020 period. We categorized each article as either "COVID-19-related" or "non-COVID-19-related". When available, we further extracted data on submission-to-acceptance dates and acceptance-to-publication dates for original research articles for the January through July 2019 and January through July 2020 periods. We compared the time from submission to publication for non-COVID-19 original research articles during the two periods and tested for statistical significance with a one-tailed Wilcoxon rank-sum test. RESULTS: We found that non-COVID-19-related articles began decreasing in volume as COVID-19-related articles increased. In BMJ and Lancet, the COVID-19-related articles began overtaking the non-COVID-19-related articles in number during April and May 2020. However, COVID-19-related primary research articles only began consistently appearing in journal issues during May 2020. Only BMJ and BMC Med publicly recorded complete data regarding their publication timelines. After removing outliers, we found that the mean time from submission to publication for articles published in BMJ from January through July 2019 was 204 days (median: 194 days; IQR: 163-236), and from January through July 2020 was 223 days (median: 218 days; IQR: 177-261) (p=0.04). In BMC Med, the mean time from submission to publication from February through July 2019 was 153 days (median: 150 days; IQR: 123-181), and from February through July 2020 was 163 days (median: 157 days; IQR: 132-191) (p=0.06).  Conclusion: We discovered a steadily increasing trend in the percentage of COVID-19-related articles and a concomitant decreasing trend in the percentage of non-COVID-19-related articles published in high-impact print journals during the period from December 2019 through May 2020. For non-COVID-19-related articles published in BMJ, we found a statistically significant increase upon comparing the submission-to-publication times for the period from January through July 2020 with the submission-to-publication times for the period from January through July 2019.

Automated Retrospective Calculation of the EDACS and HEART Scores in a Multicenter Prospective Cohort of Emergency Department Chest Pain Patients.

OBJECTIVES: Coronary risk scores are commonly applied to emergency department patients with undifferentiated chest pain. Two prominent risk score-based protocols are the Emergency Department Assessment of Chest pain Score Accelerated Diagnostic Protocol (EDACS-ADP) and the History, ECG, Age, Risk factors, and Troponin (HEART) pathway. Since prospective documentation of these risk determinations can be challenging to obtain, quality improvement projects could benefit from automated retrospective risk score classification methodologies. METHODS: EDACS-ADP and HEART pathway data elements were prospectively collected using a Web-based electronic clinical decision support (eCDS) tool over a 24-month period (2018-2019) among patients presenting with chest pain to 13 EDs within an integrated health system. Data elements were also extracted and processed electronically (retrospectively) from the electronic health record (EHR) for the same patients. The primary outcome was agreement between the prospective/eCDS and retrospective/EHR data sets on dichotomous risk protocol classification, as assessed by kappa statistics (ĸ). RESULTS: There were 12,110 eligible eCDS uses during the study period, of which 66 and 47% were low-risk encounters by EDACS-ADP and HEART pathway, respectively. Agreement on low-risk status was acceptable for EDACS-ADP (ĸ = 0.73, 95% confidence interval [CI] = 0.72 to 0.75) and HEART pathway (ĸ = 0.69, 95% CI = 0.68 to 0.70) and for the continuous scores (interclass correlation coefficients = 0.87 and 0.84 for EDACS and HEART, respectively). CONCLUSIONS: Automated retrospective determination of low risk status by either the EDACS-ADP or the HEART pathway provides acceptable agreement compared to prospective score calculations, providing a feasible risk adjustment option for use in large data set analyses.

The neurosurgery applicant's "arms race": analysis of medical student publication in the Neurosurgery Residency Match.

OBJECTIVE: Neurosurgery is consistently one of the most competitive specialties for resident applicants. The emphasis on research in neurosurgery has led to an increasing number of publications by applicants seeking a successful residency match. The authors sought to produce a comprehensive analysis of research produced by neurosurgical applicants and to establish baseline data of neurosurgery applicant research productivity given the increased emphasis on research output for successful residency match. METHODS: A retrospective review of publication volume for all neurosurgery interns in 2009, 2011, 2014, 2016, and 2018 was performed using PubMed and Google Scholar. Missing data rates were 11% (2009), 9% (2011), and < 5% (all others). The National Resident Matching Program report "Charting Outcomes in the Match" (ChOM) was interrogated for total research products (i.e., abstracts, presentations, and publications). The publication rates of interns at top 40 programs, students from top 20 medical schools, MD/PhD applicants, and applicants based on location of residency program and medical school were compared statistically against all others. RESULTS: Total publications per neurosurgery intern (mean ± SD) based on PubMed and Google Scholar were 5.5 ± 0.6 in 2018 (1.7 ± 0.3, 2009; 2.1 ± 0.3, 2011; 2.6 ± 0.4, 2014; 3.8 ± 0.4, 2016), compared to 18.3 research products based on ChOM. In 2018, the mean numbers of publications were as follows: neurosurgery-specific publications per intern, 4.3 ± 0.6; first/last author publications, 2.1 ± 0.3; neurosurgical first/last author publications, 1.6 ± 0.2; basic science publications, 1.5 ± 0.2; and clinical research publications, 4.0 ± 0.5. Mean publication numbers among interns at top 40 programs were significantly higher than those of all other programs in every category (p < 0.001). Except for mean number of basic science publications (p = 0.1), the mean number of publications was higher for interns who attended a top 20 medical school than for those who did not (p < 0.05). Applicants with PhD degrees produced statistically more research in all categories (p < 0.05) except neurosurgery-specific (p = 0.07) and clinical research (p = 0.3). While there was no statistical difference in publication volume based on the geographical location of the residency program, students from medical schools in the Western US produced more research than all other regions (p < 0.01). Finally, research productivity did not correlate with likelihood of medical students staying at their home institution for residency. CONCLUSIONS: The authors found that the temporal trend toward increased total research products over time in neurosurgery applicants was driven mostly by increased nonindexed research (abstracts, presentations, chapters) rather than by increased peer-reviewed publications. While we also identified applicant-specific factors (MD/PhDs and applicants from the Western US) and an outcome (matching at research-focused institutions) associated with increased applicant publications, further work will be needed to determine the emphasis that programs and applicants will need to place on these publications.

Development of a broad toxicological screening technique for urine using ultra-performance liquid chromatography and time-of-flight mass spectrometry.

Withdrawal of the support for the REMEDi HS drug profiling system has necessitated its replacement within our laboratories with an alternative broad toxicological screening technique. To this end, a novel method, based on ultra-performance liquid chromatography (UPLC) and time-of-flight (TOF) mass spectrometry, was developed for the routine analysis of urine samples. Identification was achieved by comparison of acquired data to libraries containing more than 300 common drugs and metabolites, and was based on a combination of retention time, exact mass and fragmentation patterns. Validation data for the method is presented and comprised an evaluation of the following parameters: precision; transferability of the methodology between the six collaborating laboratories; specificity; extraction recovery and stability of processed samples; matrix effects and sensitivity. This paper presents the benefits of supplementary fragmentation data with particular regard to increasing specificity and confidence of identification and its usefulness with overdosed samples. The utility of the method was assessed by the parallel analysis of 30 authentic urine samples using the REMEDi HS and UPLC-TOF. The latter provided enhanced detection, leading to the identification of twice as many drugs. Furthermore it did not miss any compounds that were identified by REMEDi HS. The UPLC-TOF findings were further verified by a combination of data from three other conventional screening techniques, i.e., GC-MS, HPLC-DAD and UPLC-MS/MS.