Omitting Radiotherapy after Breast-Conserving Surgery in Luminal A Breast Cancer.

BACKGROUND: Adjuvant radiotherapy is prescribed after breast-conserving surgery to reduce the risk of local recurrence. However, radiotherapy is inconvenient, costly, and associated with both short-term and long-term side effects. Clinicopathologic factors alone are of limited use in the identification of women at low risk for local recurrence in whom radiotherapy can be omitted. Molecularly defined intrinsic subtypes of breast cancer can provide additional prognostic information. METHODS: We performed a prospective cohort study involving women who were at least 55 years of age, had undergone breast-conserving surgery for T1N0 (tumor size <2 cm and node negative), grade 1 or 2, luminal A-subtype breast cancer (defined as estrogen receptor positivity of ≥1%, progesterone receptor positivity of >20%, negative human epidermal growth factor receptor 2, and Ki67 index of ≤13.25%), and had received adjuvant endocrine therapy. Patients who met the clinical eligibility criteria were registered, and Ki67 immunohistochemical analysis was performed centrally. Patients with a Ki67 index of 13.25% or less were enrolled and did not receive radiotherapy. The primary outcome was local recurrence in the ipsilateral breast. In consultation with radiation oncologists and patients with breast cancer, we determined that if the upper boundary of the two-sided 90% confidence interval for the cumulative incidence at 5 years was less than 5%, this would represent an acceptable risk of local recurrence at 5 years. RESULTS: Of 740 registered patients, 500 eligible patients were enrolled. At 5 years after enrollment, recurrence was reported in 2.3% of the patients (90% confidence interval [CI], 1.3 to 3.8; 95% CI, 1.2 to 4.1), a result that met the prespecified boundary. Breast cancer occurred in the contralateral breast in 1.9% of the patients (90% CI, 1.1 to 3.2), and recurrence of any type was observed in 2.7% (90% CI, 1.6 to 4.1). CONCLUSIONS: Among women who were at least 55 years of age and had T1N0, grade 1 or 2, luminal A breast cancer that were treated with breast-conserving surgery and endocrine therapy alone, the incidence of local recurrence at 5 years was low with the omission of radiotherapy. (Funded by the Canadian Cancer Society and the Canadian Breast Cancer Foundation; LUMINA ClinicalTrials.gov number, NCT01791829.).

Evaluating the Outcomes and Trainee Performance of a Canadian Medical Imaging Clinician Investigator Program.

Purpose: To measure the research productivity of trainees from the University of Toronto's Medical Imaging Clinician Investigator Program (MI-CIP) and comparing it with the research productivity of trainees from MI-non-CIP and General Surgery (GSx) Clinician Investigator Program. Methods: We identified residents who completed an MI-CIP, MI-non-CIP and GSx-CIP from 2006-2016. In each group of trainees, we assessed 3 research productivity outcomes with non-parametric tests before residency and at 7 years post-CIP completion/post-graduation. Research productivity outcomes include the number of total publications, the number of first-author publications, and the publication's average journal impact factor (IF). Results: We identified 11 MI-CIP trainees (male/female: 9 [82%]/2 [18%]), 74 MI-non-CIP trainees (46 [62%]/28 [38%]) and 41 GSx-CIP trainees (23 [56%]/18 [44%]). MI-CIP trainees had statistically significant higher research productivity than MI-non-CIP in all measured outcomes. The median (interquartile range, IQR) number of total publications of MI-CIP vs MI-non-CIP trainees was 5.0 (8.0) vs 1.0 (2.0) before residency and 6.0 (10.0) vs .0 (2.0) at 7 years post-CIP completion/post-graduation. The median (IQR) first-author publications of MI-CIP vs MI-non-CIP trainees was 2.0 (3.0) vs .0 (1.0) before residency and 2.0 (4.0) vs (.0) (1.0) at 7 years post-CIP completion/post-graduation. The median (IQR) average journal IF of MI-CIP vs MI-non-CIP trainees was 3.2 (2.0) vs .3 (2.4) before residency and 3.9 (3.2) vs .0 (2.6) at 7 years post-CIP completion/post-graduation. Between MI-CIP and GSx-CIP trainees, there were no significant differences in research productivity in all measured outcomes. Conclusion: MI-CIP trainees actively conducted research after graduation. These trainees demonstrated early research engagement before residency. The similar research productivity of MI-CIP vs GSx-CIP trainees shows initial success of MI-CIP trainees.

Surgical waitlist management: Perspectives from surgeons on surgical prioritization at a paediatric hospital.

Globally exacerbated surgical waitlists have provided the opportunity to reflect on prioritization and resource allocation decisions. The unique circumstances of paediatric surgery and consequences of surgical delay prompted the study reported in this paper. As part of a larger project to attend to prioritization in our surgical waitlists, we conducted a Quality Improvement study, the purpose of which is to understand surgeon's perspectives regarding the ethical and practical realities of surgical prioritization at our institution. The study comprises semi-structured interviews with nine full-time paediatric surgeons from a variety of subspecialties conducted at our institution, which is a tertiary paediatric hospital with ten surgical subspecialties in a publicly funded healthcare system. Participants articulated how they prioritize their waitlists, and how they understand ethical prioritization. These findings resonate with the growing public concern for ethical practice in healthcare delivery and transparency in prioritization and resource allocation practices. Specifically, more transparency, consistency, and support is required in prioritization practices. This work highlights the importance of institutional dialogue regarding surgical case prioritization. Because quality improvement work is necessarily site-specific, concrete generalizations cannot be offered. However, the insights gleaned from these interviews and the process by which they were gleaned are a valuable knowledge-sharing resource for any institution that is interested in ongoing quality improvement work. The objectives here were to clarify the goals of prioritization within the institution, improve prioritization practices, and make them more ethical and transparent.

Vitamin C Urinary Loss and Deficiency in Human Immunodeficiency Virus (HIV): Cross-sectional Study of Vitamin C Renal Leak in Women With HIV.

BACKGROUND: Reduced plasma vitamin C (vitC) concentrations in human immunodeficiency virus (HIV) may result from abnormal urinary excretion: a renal leak. VitC renal leak indicates underlying nutritional dysregulation independent of diet. We hypothesized that increased renal leak prevalence in HIV would be associated with deficient vitC concentrations. METHODS: We conducted an outpatient cross-sectional study of 96 women (40 HIV [PWH] and 56 without HIV [PWOH]) at the National Institutes of Health and Georgetown University. Renal leak was defined as abnormal urinary vitC excretion at fasting plasma concentrations <43.2µM, 2 SDs below vitC renal threshold in healthy women. To determine the primary outcome of renal leak prevalence, matched urine and plasma samples were collected the morning after overnight fast. Secondary outcomes assessed group differences in mean plasma vitC concentrations and prevalence of vitC deficiency. Exploratory outcomes assessed clinical parameters associated with renal leak. VitC was measured by high-performance liquid chromatography with coulometric electrochemical detection. RESULTS: PWH had significantly higher renal leak prevalence (73%vs14%; OR (odds ratio):16; P<.001), lower mean plasma vitC concentrations (14µMvs50µM; P<.001), and higher prevalence of vitC deficiency (43%vs7%; OR:10; P<.001) compared with PWOH, unchanged by adjustments for confounding factors. Significant predictors of renal leak included antiretroviral therapy (ART), Black race, older age, and metabolic comorbidities but not viral load or CD4 count. When compared with other chronic disease cohorts, PWH had the highest prevalence of renal leak and vitC deficiency (P<.001). CONCLUSIONS: High prevalence of vitC renal leak in HIV was associated with vitC deficiency, ART use, and race/ethnicity differences.

Patient reported symptom burden amongst immigrant and Canadian long-term resident women undergoing breast cancer surgery.

PURPOSE: Immigrants are susceptible to marginalization due to social isolation, economic disadvantage and systemic bias. Our goal was to compare symptom burden between immigrant and long-term resident women undergoing breast cancer surgery in Ontario, Canada. METHODS: A population-level retrospective cohort-study using administrative databases was conducted. Women who underwent surgery for newly diagnosed breast cancer and were treated at regional cancer centers between 2010 and 2016 were included. The primary outcome was a moderate or severe (≥ 4) symptom score on the Edmonton Symptom Assessment System Scale (ESAS). RESULTS: There were 12,250 (87.2%) long-term Canadian residents and 1,806(12.8%) immigrants. Immigrants were younger (mean age 53 vs. 61 years); had a higher proportion residing in a lowest income quintile neighbourhood (22.2% vs 15.4%); were less often on a primary-care physician roster (83.7% vs. 90.4%); and were less often diagnosed with Stage I/II disease (80.9% vs. 84.6%) (all p < 0.01). The proportion of women with scores ≥ 4 was significantly higher amongst immigrant women for 7/9 symptom categories; with the largest differences for depression (24.9% vs. 20.2%, p < 0.01) and pain (28.0% vs. 22.4%, p < 0.01). On multivariable regression analysis, immigration status was associated with scores ≥ 4 for pain (OR 1.13, 95% CI 1.02-1.23). There was an association between moderate/severe pain and region of origin, but not length of stay in Canada or immigration class. CONCLUSIONS: This is the first study comparing symptom burden amongst immigrant and non-immigrant women with breast cancer at a population-level. Immigrant women with breast cancer undergoing surgery were found to have a higher burden of pain.

Vitamin E Induces Liver Iron Depletion and Alters Iron Regulation in Mice.

BACKGROUND: Vitamin E (vit E) is an essential nutrient that functions as a lipophilic antioxidant and is used clinically to treat nonalcoholic fatty liver disease, where it suppresses oxidative damage and impedes the progression of steatosis and fibrosis. Mice lacking a critical liver iron-trafficking protein also manifest steatosis because of iron-mediated oxidative damage and are protected from liver disease by oral vit E supplements. OBJECTIVES: We aimed to examine the role of dietary vit E supplementation in modulating iron-sensing regulatory systems and nonheme iron levels in mouse liver. METHODS: C57Bl/6 male mice, aged 6 wk, were fed purified diets containing normal amounts of iron and either control (45 mg/kg) or elevated (450 mg/kg) levels of 2R-α-tocopherol (vit E) for 18 d. Mouse plasma and liver were analyzed for nonheme iron, levels and activity of iron homeostatic proteins, and markers of oxidative stress. We compared means ± SD for iron and oxidative stress parameters between mice fed the control diet and those fed the vit E diet. RESULTS: The Vit E-fed mice exhibited lower levels of liver nonheme iron (38% reduction, P < 0.0001) and ferritin (74% reduction, P < 0.01) than control-fed mice. The levels of liver mRNA for transferrin receptor 1 and divalent metal transporter 1 were reduced to 42% and 57% of the control, respectively. The mRNA levels for targets of nuclear factor erythroid 2-related factor (Nrf2), a major regulator of the oxidative stress response and iron-responsive genes, were also suppressed in vit E livers. Hepcidin, an iron regulatory hormone, levels were lower in the plasma (P < 0.05), and ferroportin (FPN), the iron exporter regulated by hepcidin, was expressed at higher levels in the liver (P < 0.05). CONCLUSIONS: Oral vit E supplementation in mice can lead to depletion of liver iron stores by suppressing the iron- and redox-sensing transcription factor Nrf2, leading to enhanced iron efflux through liver FPN. Iron depletion may indirectly enhance the antioxidative effects of vit E.

Vitamin C Urinary Loss in Fabry Disease: Clinical and Genomic Characteristics of Vitamin C Renal Leak.

BACKGROUND: Reduced plasma vitamin C concentrations in chronic diseases may result from abnormal urinary excretion of vitamin C: a renal leak. We hypothesized that vitamin C renal leak may be associated with disease-mediated renal dysregulation, resulting in aberrant vitamin C renal reabsorption and increased urinary loss. OBJECTIVES: We investigated the prevalence, clinical characteristics, and genomic associations of vitamin C renal leak in Fabry disease, an X-linked lysosomal disease associated with renal tubular dysfunction and low plasma vitamin C concentrations. METHODS: We conducted a non-randomized cross-sectional cohort study of men aged 24-42 y, with Fabry disease (n = 34) and controls without acute or chronic disease (n = 33). To match anticipated plasma vitamin C concentrations, controls were placed on a low-vitamin C diet 3 wk before inpatient admission. To determine the primary outcome of vitamin C renal leak prevalence, subjects were fasted overnight, and matched urine and fasting plasma vitamin C measurements were obtained the following morning. Vitamin C renal leak was defined as presence of urinary vitamin C at plasma concentrations below 38 µM. Exploratory outcomes assessed the association between renal leak and clinical parameters, and genomic associations with renal leak using single nucleotide polymorphisms (SNPs) in the vitamin C transporter SLC23A1. RESULTS: Compared with controls, the Fabry cohort had 16-fold higher odds of renal leak (6% vs. 52%; OR: 16; 95% CI: 3.30, 162; P < 0.001). Renal leak was associated with higher protein creatinine ratio (P < 0.01) and lower hemoglobin (P = 0.002), but not estimated glomerular filtration rate (P = 0.54). Renal leak, but not plasma vitamin C, was associated with a nonsynonymous single nucleotide polymorphism in vitamin C transporter SLC23A1 (OR: 15; 95% CI: 1.6, 777; P = 0.01). CONCLUSIONS: Increased prevalence of renal leak in adult men with Fabry disease may result from dysregulated vitamin C renal physiology and is associated with abnormal clinical outcomes and genomic variation.

Red Blood Cell Vitamin C Concentration and Its Effect on Deformability in Pediatric Sickle Cell Disease.

Red cell rigidity is common in sickle cell disease (SCD). The contribution of oxidative stress on deformability remains unknown. This study investigated red blood cell (RBC) vitamin C concentrations in pediatric SCD (n=43) compared with healthy controls ( n =23) and developed a protocol to raise RBC vitamin C concentrations to measure the effect on deformability. Sickle cell RBC vitamin C concentrations seem low (20.5 µM, SD: 16.2 vs. 51.7 µM, SD: 15.8; P <0.0001). Vitamin C can be successfully loaded into sickle cell RBCs but seems to have minimal effect on deformability. Future studies are needed to understand the clinical implications of vitamin C deficiency in pediatric SCD.

High-dose ascorbic acid synergizes with anti-PD1 in a lymphoma mouse model.

Major efforts are underway to identify agents that can potentiate effects of immune checkpoint inhibition. Here, we show that ascorbic acid (AA) treatment caused genomewide demethylation and enhanced expression of endogenous retroviral elements in lymphoma cells. AA also increased 5-hydroxymethylcytosine (5hmC) levels of CD8+ T cells and enhanced their cytotoxic activity in a lymphoma coculture system. High-dose AA treatment synergized with anti-PD1 therapy in a syngeneic lymphoma mouse model, resulting in marked inhibition of tumor growth compared with either agent alone. Analysis of the intratumoral epigenome revealed increased 5hmC with AA treatment, consistent with in vitro findings. Analysis of the tumor immune microenvironment revealed that AA strikingly increased intratumoral infiltration of CD8+ T cells and macrophages, suggesting enhanced tumor immune recognition. The combination treatment markedly enhanced intratumoral infiltration of macrophages and CD8+ T lymphocytes, granzyme B production by cytotoxic cells (cytotoxic T cells and natural killer cells), and interleukin 12 production by antigen-presenting cells compared with single-agent anti-PD1. These data indicate that AA potentiates anti-PD1 checkpoint inhibition through synergistic mechanisms. The study provides compelling rationale for testing combinations of high-dose AA and anti-PD1 agents in patients with aggressive B cell lymphoma as well as in preclinical models of other malignancies.

Use of population-based electronic databases for the identification of patients with synchronous colorectal cancer and liver metastases potentially eligible for a surgical trial.

BACKGROUND: Some population-based recruitment methods, such as registries and databases, have been used to increase enrolment in clinical trials by identifying eligible participants based on baseline characteristics; however; these methods have not been tested in surgical trials, in which accrual occurs before surgery. We evaluated the use of population-based electronic databases to identify patients who potentially could be accrued to the Simultaneous Resection of Colorectal Cancer with Synchronous Liver Metastases (RESECT) trial and compared it to the traditional methods used to accrue patients (e.g., multidisciplinary rounds, letters to community surgeons) for that same trial during the same period. METHODS: An electronic database (ePath) was interrogated every 2 weeks for patients diagnosed with colorectal cancer from Feb. 1, 2017, to Mar. 30, 2019. A radiologic image database (OneView) was reviewed to identify those with liver metastases (level 1 screening). Reports were interrogated to identify potentially eligible patients for the RESECT trial (level 2 screening). A hepatobiliary surgeon reviewed radiology images to identify eligible patients for the trial (level 3 screening). The primary outcome was patient eligibility for the ongoing RESECT trial. RESULTS: The population-based method identified 90 (11.2%) of 803 patients diagnosed with colorectal cancer over the study period. Among the 90 patients, level 2 screening identified 60 (67%) potentially eligible patients for the RESECT trial. Of the 90 patients, 18 (20%) were eligible after radiographic image review (level 3 screening). Traditional accrual methods identified 38 patients with liver metastases, 27 (71%) of whom were identified as potentially eligible on level 2 screening, and 14 (37%) of whom were deemed to be eligible on level 3 screening. Twenty-six patients were identified by both methods. Twelve patients were identified by population-based methods alone, and 8 patients by traditional methods alone. Six eligible patients were identified by both methods. Baseline characteristics were similar between the 2 groups. CONCLUSION: A population-based electronic database method of patient accrual was able to identify eligible participants for the RESECT trial. However, optimal accrual likely requires the use of traditional methods as well.

Collective self-understanding: A linguistic style analysis of naturally occurring text data.

Understanding what groups stand for is integral to a diverse array of social processes, ranging from understanding political conflicts to organisational behaviour to promoting public health behaviours. Traditionally, researchers rely on self-report methods such as interviews and surveys to assess groups' collective self-understandings. Here, we demonstrate the value of using naturally occurring online textual data to map the similarities and differences between real-world groups' collective self-understandings. We use machine learning algorithms to assess similarities between 15 diverse online groups' linguistic style, and then use multidimensional scaling to map the groups in two-dimensonal space (N=1,779,098 Reddit comments). We then use agglomerative and k-means clustering techniques to assess how the 15 groups cluster, finding there are four behaviourally distinct group types - vocational, collective action (comprising political and ethnic/religious identities), relational and stigmatised groups, with stigmatised groups having a less distinctive behavioural profile than the other group types. Study 2 is a secondary data analysis where we find strong relationships between the coordinates of each group in multidimensional space and the groups' values. In Study 3, we demonstrate how this approach can be used to track the development of groups' collective self-understandings over time. Using transgender Reddit data (N= 1,095,620 comments) as a proof-of-concept, we track the gradual politicisation of the transgender group over the past decade. The automaticity of this methodology renders it advantageous for monitoring multiple online groups simultaneously. This approach has implications for both governmental agencies and social researchers more generally. Future research avenues and applications are discussed.

Important questions for the malignant hematologist to consider when designing or evaluating a study with patient-reported outcome measures (PROMs).

Patient-reported outcome measures (PROMs), which are measures of symptom burden, health-related quality of life (HRQoL), and therapy effectiveness have become increasingly important in clinical research. They are unique in that they are reported directly from the patient, without clinician interpretation, thereby avoiding clinician bias. With an increased focus on the patient at the center of health care, PROMs have been increasingly incorporated into clinical research, systematic reviews, and clinical guidelines. Despite the recognition of the importance of including PROMs into clinical haematologic cancer research, barriers have prevented their integration into cancer research. This review highlights the value of including PROMs into clinical haematologic cancer research and addresses the methodological challenges in using and evaluating PROMs. We propose important questions for the malignant haematologist to consider when designing or evaluating a study that includes PROMs.

Simultaneous resection for synchronous colorectal cancer liver metastases: A feasibility clinical trial.

BACKGROUND AND OBJECTIVES: We tested the feasibility of a simultaneous resection clinical trial in patients with synchronous colorectal cancer liver metastases to obtain the necessary information to plan a randomized trial. METHODS: Multicenter feasibility single-arm trial enrolling patients with synchronous colorectal cancer liver metastases eligible for simultaneous resection. Prespecified criteria for feasibility were: proportion of eligible patients enrolled ≥66%, and the proportion of enrolled patients who completed simultaneous resection ≥75%. The prespecified 90-day major postoperative complication rate was 30%. RESULTS: Of 61 eligible patients from February 2017 to August 2019, 41 were enrolled (67%; 95% confidence interval [CI], 55%-78%), 32 underwent simultaneous resection (78%; 95% CI, 63%-88%). Four patients were not enrolled due to the surgeon's preference, three were due to the complexity of resection (right hepatectomy and low anterior resection). Intraoperative complications during liver resection (n = 4) and progression of disease (n = 4) were the main reasons for not undergoing simultaneous resection. The 90-day incidence of major complications was 41% (95% CI, 16%-58%) and the 90-day postoperative mortality was 6% (95% CI, 1.7%-20%). CONCLUSION: According to prespecified criteria, enrolling patients with synchronous colorectal cancer liver metastases to a trial of simultaneous resection is feasible; however, it is associated with higher than anticipated 90-day postoperative complications.

Conciliation and meta-contrast are important for understanding how people assign group memberships during conflict situations.

Pietraszewski misrepresents both the nature of behaviour in conflict and the ability of psychology to theorise the relational properties of group designation. At the behavioural level, he focusses exclusively on "attack," when consolation/care in conflict is equally present and important. At the theoretical level, he ignores existing psychological work on how group perception is shaped by the meta-contrast principle.

Physician Suicide Prevention and the Ethics and Role of a Healing Community: an American College of Physicians Policy Paper.

Suicide is a major global public health issue, and in recent years, there has been increasing recognition of the problem of physician suicide. This American College of Physicians policy paper examines, from the perspective of ethics, the issues that arise when individuals and institutions respond to physician suicides and when they engage in broader efforts aimed at physician suicide prevention. Emphasizing the medical profession as a unique moral community characterized by ethical and professional commitments of service to patients, each other, and society, this paper offers guidance regarding physician suicide and the role of a healing community. The response to an individual physician suicide should be characterized by respect and concern for those who are grieving, the creation of a supportive environment for suicide loss survivors, and careful communication about the event. Because suicide is a complex problem, actions aimed at preventing suicide must occur at the individual, interpersonal, community, and societal levels. The medical community has an obligation to foster a culture that supports education, screening, and access to mental health treatment, beginning at the earliest stages of medical training.

Assessment of Day-7 Postexposure Testing of Asymptomatic Contacts of COVID-19 Patients to Evaluate Early Release from Quarantine - Vermont, May-November 2020.

On May 8, 2020, the Vermont Department of Health (VDH) issued a Health Update* recommending shortening the duration of quarantine for persons exposed to SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19). Exposed persons who were in quarantine could be tested by polymerase chain reaction (PCR) on or after quarantine day 7. Those who had remained asymptomatic throughout quarantine and who received a negative SARS-CoV-2 PCR test result on or after day 7 could end quarantine. This policy was based on a report suggesting that symptom onset occurs within this time frame in approximately three quarters of COVID-19 cases (1) and on consultation of the Vermont Health Commissioner with the U.S. Surgeon General. VDH implemented this policy to minimize restrictions on state residents, recognizing that some reduction could occur in the prevention benefit of quarantine to contain the spread of SARS-CoV-2. State-run SARS-CoV-2 testing sites were made available to increase access to no-cost testing and facilitate implementation of this policy. During August 1-December 1, among persons seeking testing at a VDH SARS-CoV-2 testing site, 36% stated that their reason for seeking testing was to end quarantine early (VDH, unpublished data, December 7, 2020), indicating that persons were aware of and following the policy and using the testing services provided. To assess the effectiveness of this policy, VDH analyzed testing data for contacts of persons with a COVID-19 diagnosis. During May 8-November 16, VDH identified 8,798 exposed contacts of COVID-19 patients; 3,983 (45%) had sought testing within 14 days of their exposure, with day 0 defined as the date of last exposure noted in the case investigation record. Among these persons, 2,200 (55%) who received testing on days 7-10 were included in this analysis; 977 (44.9%) of these contacts had a specimen collected for testing on day 7. Among these, 34 (3%) had test results that were positive, 940 (96%) had results that were negative, and three (<1%) had results that were indeterminate (Table). Among the 34 contacts who received a positive SARS-CoV-2 PCR test result on day 7 after exposure, 12 (35%) were asymptomatic. The remaining 22 contacts with positive test results were symptomatic at the time of testing; approximately one half had developed symptoms on days 4-7 after exposure. Among the 940 contacts who received negative test results on specimens collected on day 7 after exposure, 154 (16%) had a subsequent test within the next 7 days (i.e., days 8-14); among these, 152 (99%) had tests that remained negative, and two (1%) had results that were indeterminate.

Integrating Sleep Knowledge Into the Anesthesiology Curriculum.

There is common ground between the specialties of anesthesiology and sleep medicine. Traditional sleep medicine curriculum for anesthesiology trainees has revolved around the discussion of obstructive sleep apnea (OSA) and its perioperative management. However, it is time to include a broader scope of sleep medicine-related topics that overlap these specialties into the core anesthesia residency curriculum. Five main core competency domains are proposed, including SLeep physiology; Evaluation of sleep health; Evaluation for sleep disorders and clinical implications; Professional and academic roles; and WELLness (SLEEP WELL). The range of topics include not only the basics of the physiology of sleep and sleep-disordered breathing (eg, OSA and central sleep apnea) but also insomnia, sleep-related movement disorders (eg, restless legs syndrome), and disorders of daytime hypersomnolence (eg, narcolepsy) in the perioperative and chronic pain settings. Awareness of these topics is relevant to the scope of knowledge of anesthesiologists as perioperative physicians as well as to optimal sleep health and physician wellness and increase consideration among current anesthesiology trainees for the value of dual credentialing in both these specialties.

Effect of Vitamin C, Thiamine, and Hydrocortisone on Ventilator- and Vasopressor-Free Days in Patients With Sepsis: The VICTAS Randomized Clinical Trial.

Importance: Sepsis is a common syndrome with substantial morbidity and mortality. A combination of vitamin C, thiamine, and corticosteroids has been proposed as a potential treatment for patients with sepsis. Objective: To determine whether a combination of vitamin C, thiamine, and hydrocortisone every 6 hours increases ventilator- and vasopressor-free days compared with placebo in patients with sepsis. Design, Setting, and Participants: Multicenter, randomized, double-blind, adaptive-sample-size, placebo-controlled trial conducted in adult patients with sepsis-induced respiratory and/or cardiovascular dysfunction. Participants were enrolled in the emergency departments or intensive care units at 43 hospitals in the United States between August 2018 and July 2019. After enrollment of 501 participants, funding was withheld, leading to an administrative termination of the trial. All study-related follow-up was completed by January 2020. Interventions: Participants were randomized to receive intravenous vitamin C (1.5 g), thiamine (100 mg), and hydrocortisone (50 mg) every 6 hours (n = 252) or matching placebo (n = 249) for 96 hours or until discharge from the intensive care unit or death. Participants could be treated with open-label corticosteroids by the clinical team, with study hydrocortisone or matching placebo withheld if the total daily dose was greater or equal to the equivalent of 200 mg of hydrocortisone. Main Outcomes and Measures: The primary outcome was the number of consecutive ventilator- and vasopressor-free days in the first 30 days following the day of randomization. The key secondary outcome was 30-day mortality. Results: Among 501 participants randomized (median age, 62 [interquartile range {IQR}, 50-70] years; 46% female; 30% Black; median Acute Physiology and Chronic Health Evaluation II score, 27 [IQR, 20.8-33.0]; median Sequential Organ Failure Assessment score, 9 [IQR, 7-12]), all completed the trial. Open-label corticosteroids were prescribed to 33% and 32% of the intervention and control groups, respectively. Ventilator- and vasopressor-free days were a median of 25 days (IQR, 0-29 days) in the intervention group and 26 days (IQR, 0-28 days) in the placebo group, with a median difference of -1 day (95% CI, -4 to 2 days; P = .85). Thirty-day mortality was 22% in the intervention group and 24% in the placebo group. Conclusions and Relevance: Among critically ill patients with sepsis, treatment with vitamin C, thiamine, and hydrocortisone, compared with placebo, did not significantly increase ventilator- and vasopressor-free days within 30 days. However, the trial was terminated early for administrative reasons and may have been underpowered to detect a clinically important difference. Trial Registration: ClinicalTrials.gov Identifier: NCT03509350.

ASIA: Automated Social Identity Assessment using linguistic style.

The various group and category memberships that we hold are at the heart of who we are. They have been shown to affect our thoughts, emotions, behavior, and social relations in a variety of social contexts, and have more recently been linked to our mental and physical well-being. Questions remain, however, over the dynamics between different group memberships and the ways in which we cognitively and emotionally acquire these. In particular, current assessment methods are missing that can be applied to naturally occurring data, such as online interactions, to better understand the dynamics and impact of group memberships in naturalistic settings. To provide researchers with a method for assessing specific group memberships of interest, we have developed ASIA (Automated Social Identity Assessment), an analytical protocol that uses linguistic style indicators in text to infer which group membership is salient in a given moment, accompanied by an in-depth open-source Jupyter Notebook tutorial ( https://github.com/Identity-lab/Tutorial-on-salient-social-Identity-detection-model ). Here, we first discuss the challenges in the study of salient group memberships, and how ASIA can address some of these. We then demonstrate how our analytical protocol can be used to create a method for assessing which of two specific group memberships-parents and feminists-is salient using online forum data, and how the quality (validity) of the measurement and its interpretation can be tested using two further corpora as well as an experimental study. We conclude by discussing future developments in the field.