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Objective To identify clusters of comorbidities in patients with rheumatoid arthritis (RA) using 4 methods and to compare to patients without RA. Methods In this retrospective, population‐based study, residents of 8 Minnesota counties with prevalent RA as of January 1, 2015 were identified. Age‐, sex‐, and county‐matched non‐RA comparators were selected from the same underlying population. Diagnostic codes were retrieved for 5 years before January 1, 2015. Using 2 codes ≥30 days apart, 44 previously defined morbidities and 11 nonoverlapping chronic disease categories based on Clinical Classifications Software were defined. Unsupervised machine learning methods of interest included hierarchical clustering, factor analysis, K‐means clustering, and network analysis. Results Two groups of 1,643 patients with and without RA (72% female; mean age 63.1 years in both groups) were studied. Clustering of comorbidities revealed strong associations among mental/behavioral comorbidities and among cardiovascular risk factors and diseases. The clusters were associated with age and sex. Differences between the 4 clustering methods were driven by comorbidities that are rare and those that were weakly associated with other comorbidities. Common comorbidities tended to group together consistently across approaches. The instability of clusters when using different random seeds or bootstrap sampling impugns the usefulness and reliability of these methods. Clusters of common comorbidities between RA and non‐RA cohorts were similar. Conclusion Despite the higher comorbidity burden in patients with RA compared to the general population, clustering comorbidities did not identify substantial differences in comorbidity patterns between the RA and non‐RA cohorts. The instability of clustering methods suggests caution when interpreting clustering using 1 method.

5579 Background: Adavosertib (AZD-1775) is a potent small molecule inhibitor of Wee-1, currently in clinical development. In a double-blind, placebo-controlled, phase 2 trial (NCT02151292), adavosertib and gemcitabine significantly prolonged progression-free survival (PFS) and overall survival (OS) in patients with recurrent platinum-resistant or platinum-refractory high grade serous ovarian cancer (HGSOV) compared to gemcitabine alone. We investigated whether plasma and intra-tumoral adavosertib concentrations correlated with survival in these patients. Methods: Adavosertib was administered orally on Days 1, 2, 8, 9, 15 and 16 at 175 mg per day, and gemcitabine was administered on Days 1, 8 and 15 at 1000 mg/m2 every 28 days. Serial blood samples were collected on Day 1 of cycle 1 after adavosertib administration. Tumor biopsies were taken 1-2 weeks after initiation of study treatments. Plasma and tumor adavosertib concentrations were determined using validated HPLC-MS/MS. Patients were divided into groups with plasma or tumor adavosertib concentrations above or below the biologically active concentration (BAC) of 125 ng/ml (Leijen et al, J Clin Onco 2016). Survival was described using the Kaplan-Meier method. Results: Among 61 HGSOV patients who received adavosertib, plasma samples were available in 47, and tumor samples were available in 31 patients. Among 25 non-HGSOV patients (exploratory cohort), plasma and tumor samples were available in 21 and 17 patients respectively. The mean maximum adavosertib concentration (Cmax) was 355.3 ± 120.9 ng/ml and 358.6 ± 117.9 ng/ml respectively. Cmax was above BAC in all patients. The mean tumor adavosertib concentration was 609.2 ± 1129.2 ng/ml (range: 0.47 – 5501 ng/ml) for HGSOV patients, and 964.2 ± 1611.2 ng/ml (range: 0.22 – 6116 ng/ml) for non-HGSOV patients. There was no correlation between Cmax and tumor adavosertib concentrations. In HGSOV, the median PFS was 5.8 months for patients with tumor concentrations above BAC, and 3.5 months for those with tumor concentrations below BAC (Hazard ratio (HR): 0.46, 95% confidence interval: 0.19 – 1.14, p = 0.06). No difference in PFS was seen in non-HGSOV patients according to tumor adavosertib concentration. Tumor adavosertib concentration did not correlate with OS. Conclusions: Although Cmax was above BAC in all patients, there was a high variability in tumor adavosertib concentrations. In HGSOV, higher tumor adavosertib concentration was associated with a trend towards improved PFS, but not OS. Our results indicate that the current adavosertib dosing regimen may not produce the desired concentrations in tumors for some patients, and further optimization may be needed.

BACKGROUND: Peripheral nerve blocks (PNBs) are used to provide postoperative analgesia after total mastectomy. PNBs improve patient satisfaction and decrease postoperative opioid use, nausea, and vomiting. Few studies have examined whether there is racial-ethnic disparity in the use of PNBs for patients having total mastectomy. We hypothesized that non-Hispanic Asian, non-Hispanic Black, non-Hispanic patients of other races, and Hispanic patients would be less likely to receive a PNB for postoperative analgesia compared to non-Hispanic White patients having total mastectomy. Secondarily, we hypothesized that PNBs would be associated with reduced odds of major complications after total mastectomy. METHODS: We performed a retrospective cohort study using National Surgical Quality Improvement Program (NSQIP) data from 2015 to 2019. Patients were included if they underwent total mastectomy under general anesthesia. Unadjusted rates of PNB use were compared between race-ethnicity groups. Multivariable logistic regression was performed to determine whether race-ethnicity group was independently associated with receipt of a PNB for postoperative analgesia. Secondarily, we calculated crude and risk-adjusted odds ratios for major complications in patients who received a PNB. RESULTS: There were 64,103 patients who underwent total mastectomy and 4704 (7.3%) received a PNB for postoperative analgesia. Patients who received a PNB were younger, more commonly women, were less likely to have diabetes and hypertension, and had less disseminated cancer (all P < .05). In our regression analysis, the odds of receiving a PNB differed significantly by race-ethnicity group ( P < .001). Non-Hispanic Asian and non-Hispanic Black patients had reduced odds of receiving a PNB compared to non-Hispanic White patients (odds ratio [OR], 0.41; 95% confidence interval [CI], 0.33–0.49 and OR, 0.37 [0.32–0.44]), respectively. Non-Hispanic patients of other races, including American Indian, Alaskan Native, and Pacific Islander, also had reduced odds of receiving a PNB (OR, 0.73 [95% CI, 0.64–0.84]) compared to non-Hispanic White patients, as did Hispanic patients (OR, 0.62 [0.56–0.69]). Patients who received a PNB did not have reduced odds of major complications after mastectomy (crude OR, 0.83 [0.65–1.08]; P = .17 and adjusted OR, 0.85 [0.65–1.10]; P = .21). CONCLUSIONS: Significant disparity exists in the use of PNBs for postoperative analgesia in patients of different race-ethnicity who undergo total mastectomy in the United States. Continued efforts are needed to better understand the causes of disparity and to ensure equitable access to PNBs.

PURPOSE Most cases of pediatric acute leukemia occur in low- and middle-income countries, where health centers lack the tools required for accurate diagnosis and disease classification. Recent research shows the robustness of using unbiased short-read RNA sequencing to classify genomic subtypes of acute leukemia. Compared with short-read sequencing, nanopore sequencing has low capital and consumable costs, making it suitable for use in locations with limited health infrastructure. MATERIALS AND METHODS We show the feasibility of nanopore mRNA sequencing on 134 cryopreserved acute leukemia specimens (26 acute myeloid leukemia [AML], 73 B-lineage acute lymphoblastic leukemia [B-ALL], 34 T-lineage acute lymphoblastic leukemia, and one acute undifferentiated leukemia). Using multiple library preparation approaches, we generated long-read transcripts for each sample. We developed a novel composite classification approach to predict acute leukemia lineage and major B-ALL and AML molecular subtypes directly from gene expression profiles. RESULTS We demonstrate accurate classification of acute leukemia samples into AML, B-ALL, or T-lineage acute lymphoblastic leukemia (96.2% of cases are classifiable with a probability of > 0.8, with 100% accuracy) and further classification into clinically actionable genomic subtypes using shallow RNA nanopore sequencing, with 96.2% accuracy for major AML subtypes and 94.1% accuracy for major B-lineage acute lymphoblastic leukemia subtypes. CONCLUSION Transcriptional profiling of acute leukemia samples using nanopore technology for diagnostic classification is feasible and accurate, which has the potential to improve the accuracy of cancer diagnosis in low-resource settings.

Abstract Aims The objective of this study is to longitudinally assess sociodemographic and psychological correlates of increased alcohol use during the coronavirus disease of 2019 (COVID-19) period among adolescents and young adults. Methods Pre-COVID period is defined as the 1-year period on or before 31 March 2020, and during-COVID period is defined as the period from 1st April 2020 to 30 March 2021. Univariable logistic regression models are used to evaluate the association of demographic characteristics, Area Deprivation Index (ADI), rurality, changes in Patient Health Questionnaire (PHQ-9) and Generalized Anxiety Disorder (GAD-7) scale severity, and the risk of increased alcohol consumption (binge drinking, number of drinks and drinking regularity) from pre-COVID to during-COVID period. Results and conclusion Our study found that worsened anxiety symptoms, older age, being in college and current cigarette smoking status were associated with increased alcohol use among youth during the pandemic year. Socioeconomic position (measured by ADI) and rural status were not found to be associated with increased alcohol use among adolescents and young adults.

Background: Ovarian cancer has the highest mortality of all gynecologic malignancies, howeverthere is no proven effective screening for ovarian cancer. Evidence suggests that epithelial ovarian cancer begins in the fallopian tubes. Prophylactic bilateral total salpingectomy has been shown to reduce the risk of epithelial ovarian cancer and is now recommended to be considered at the time of sterilization procedures. There are limited well designed clinical trials that compare the safety and feasibility of total salpingectomy to that of traditional partial salpingectomy for tubal sterilization in obstetrics. We thus conducted a randomized controlled trial to assess the safety of bilateral total salpingectomy at the time of cesarean delivery. Methods: We conducted a non-inferiority randomized controlled trial at the Mayo Clinic, Rochester, Minnesota. Women age 21 years and older who were undergoing cesarean delivery and desired concomitant sterilization were enrolled between May 17, 2017 and July 16, 2018. Stratified randomization was performed based on number of previous cesarean deliveries and their Basal Metabolic Index, into a bilateral total salpingectomy (BTS) group and bilateral partial salpingectomy (BPS) group. All salpingectomies were performed using clamps and suture. The primary outcome was to compare the mean peri-operative hemoglobin change for both groups. Secondary objectives included sterilization completion time, postoperative length of stay, estimated blood loss, postoperative pain and adverse events. Results: Of the 111 women screened, 40 were enrolled and randomized. Of these, 38 underwent the assigned procedure (18 BTS, 20 BPS). No difference in Mean ± SD hemoglobin drop between groups (1.4 ± 0.7 g/dL for the BPS group and 1.8 ± 1.0 g/dL for the BTS group, p = 0.08), however the point estimate of –0.4 is very close to the non-inferiority margin of –0.5, and the CI widely exceeds the non-inferiority margin (95% CI –0.99, 0.17). Therefore non-inferiority was not shown. Mean time to completion of sterilization procedure was significantly longer in the BTS group (16.3 ± 5.6 minutes for the BTS group vs 5.1 ± 1.6 minutes for the BPS group, p < 0.01). No significant differences for other outcome measures. Conclusions: Bilateral total salpingectomy is not non-inferior to tradiational bilateral partial salpingectomy with regards to postoperative hemoglobin drop, and is associated with a small increase in operative time. There, however, was no difference in adverse events, postoperative length of stay and postoperative pain between the two groups. This information may be helpful when counseling patients.

Background: Optimum management of carotid stenosis, both symptomatic (sx) and asymptomatic (asx), remains controversial despite clinical trials evaluating Carotid Endarterectomy (CEA) and Carotid Stenting (CAS). Objective: We compared attitudes in management of carotid stenosis between experts in Europe (EU), and North America (NA). Methods: From April 2011 to July 2012, a 3-round, email-Delphi survey was sent to members of the European Stroke Organisation (n=390) and to a list of NA stroke neurologists developed at the University of Texas at Houston Stroke Program (n=289). Those completing the survey were shown all responses broken down by EU/NA after each of the first 2 survey rounds. Continent specific consensus was defined a priori to be > 80% agreement. Results: 100 (15%, of which 73% EU) participated in all 3-Delphi rounds, 19% of all EU vs 9% NA (χ2=11.62, p=0.0007): 76% male; 69% treating between 1-8 new cases of carotid stenosis per month. In the final round, EU reached consensus in 7/11 statements (3 reached in phase-I), while NA did in 4/11 (1 reached in phase-I).Ninety-percent of EU vs 70% of NA (χ2=8.09, p=0.017) disagreed that CAS and CEA are equivalent treatments for sx carotid stenosis, and stated that CEA is superior. There remains a significant difference between EU and NA when considering ipsilateral stroke and death < 30 days as primary outcome (χ2=12.18, p=0.007). Sixty-nine-percent of NA agreed that there is a stronger indication for CAS over CEA in patients < 65 years for sx carotid stenosis whereas 55% of EU (χ2=11.39, p=0.023) disagreed with the statement. When asked how likely they would recommend CEA for an asx carotid stenosis, 81% of EU and 80% of NA said ‘sometimes’. When asked how likely they would recommend CAS for an asx carotid stenosis, 62% of NA said ‘sometimes’ vs 60% of EU said ‘never’(χ2=3.54, p=0.06). Conclusion: There are several clear differences in attitudes regarding the management of carotid stenosis between EU and NA: EU has a stronger attitude towards superiority of CEA while in NA there is more equipoise between the two treatments. Areas of lack of consensus may provide direction for future clinical trials.

Abstract Objectives To investigate the associations of the common MUC5B promoter variant with timing of RA-associated interstitial lung disease (RA-ILD) and RA onset. Methods We identified patients with RA meeting 2010 ACR/EULAR criteria and available genotype information in the Mass General Brigham Biobank, a multihospital biospecimen and clinical data collection research study. We determined RA-ILD presence by reviewing all RA patients who had CT imaging, lung biopsy or autopsy results. We determined the dates of RA and RA-ILD diagnoses by manual records review. We examined the associations of the MUC5B promoter variant (G&gt;T at rs35705950) with RA-ILD, RA-ILD occurring before or within 2 years of RA diagnosis and RA diagnosis at age &gt;55 years. We used multivariable logistic regression to estimate odds ratios (ORs) for each outcome by MUC5B promoter variant status, adjusting for potential confounders including genetic ancestry and smoking. Results We identified 1005 RA patients with available genotype data for rs35705950 (mean age 45 years, 79% female, 81% European ancestry). The MUC5B promoter variant was present in 155 (15.4%) and was associated with RA-ILD [multivariable OR 3.34 (95% CI 1.97, 5.60)], RA-ILD before or within 2 years of RA diagnosis [OR 4.01 (95% CI 1.78, 8.80)] and RA onset after age 55 years [OR 1.52 (95% CI 1.08, 2.12)]. Conclusions The common MUC5B promoter variant was associated with RA-ILD onset earlier in the RA disease course and older age of RA onset. These findings suggest that the MUC5B promoter variant may impact RA-ILD risk early in the RA disease course, particularly in patients with older-onset RA.

AbstractAmidst the COVID‐19 pandemic and social uprisings demanding social and racial equity worldwide, there is an increasing demand for health justice training for health workers. However, there are scant evidence‐based assessments of the impact of such courses. Between 2010 and 2020, SocMed—a 501(c)3 non‐profit social justice organization—offered two distinct courses about health equity, the social determinants of health, and social medicine to health workers through the University of Minnesota in Minneapolis, Minnesota and Saint Mary Hospital Lacor in Gulu, Uganda. This study assesses the immediate impact of the SocMed curriculum on participants measured by a pre‐course and post‐course survey. In Minnesota, paired pre‐course and post‐course survey responses (mean n = 69; SD = 23) spanned years 2016–2019, while Uganda paired pre‐course and post‐course survey responses (mean n = 64; SD = 21) spanned years 2012–2013 and 2017–2019. Findings indicate that the course improved participants’ knowledge in all 24 of the topics in the Minnesota course and 42 of 44 topics in the Uganda course (significant at p < 0.05).