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Objectives Changes of routine disease management associated with COVID-19 lockdown might have potentially affected the clinical course of juvenile idiopathic arthritis (JIA). Aim of our study was to assess the rate of disease flare before and during COVID-19 lockdown to investigate its impact on disease course in JIA children. Methods A single-center retrospective study was conducted, including patients presenting inactive JIA between September 1st , 2018 and March 9th , 2019 (group A) and between September 1st , 2019 and March 9th , 2020 (group B). For each patient, demographic and clinical data were collected. The rate of JIA flare from March 10th , 2019 to June 30th , 2019 for group A and from March 10th , 2020 to June 30th , 2020 for group B was compared. Results Group A included 126 patients and group B 124 patients. Statistical analysis did not show significant differences among the two cohorts with respect to age, sex, age of JIA onset, JIA subtype, co-occurrence of uveitis, ANA positivity and past or ongoing medications. The rate of disease flare during lockdown at time of first COVID-19 pandemic wave, was significantly higher in comparison to the previous year (16.9% vs 6.3%, p=0.009). Conclusion Our study showed that COVID-19 lockdown was associated with a higher rate of joint inflammation in JIA children. This finding has a considerable clinical implication, since restrictive measures may be necessary in order to contain pandemics. Our data highlight the need for rearrangement in the home and healthcare management of JIA children during lockdowns.

Neuroprognostication following diffuse axonal injury (DAI) has historically relied on neuroimaging techniques with lower spatial resolution and contrast than techniques currently available in clinical practice. Since the initial studies of DAI classification and prognosis in the 1980s and 1990s, advances in neuroimaging have improved detection of brainstem microbleeds, a hallmark feature of Grade 3 DAI that has traditionally been associated with poor neurologic outcome. Here, we report clinical and radiologic data from two patients with severe traumatic brain injury and grade 3 DAI who recovered functional independence and returned to work within 4 months of injury. Importantly, both patients were scanned using 3 Tesla MRI protocols that included susceptibility-weighted imaging (SWI), a technique that provides enhanced sensitivity for detecting brainstem microbleeds. These observations highlight the importance of developing approaches to DAI classification and prognosis that better align with contemporary neuroimaging capabilities.

This article characterizes 2 cases of longitudinally extensive transverse myelitis (LETM) that did not respond to immunotherapy and were diagnosed by biopsy as primary central nervous system (CNS) malignancies. Diffuse H3 K27M-mutant glioma is a recently described entity with very few cases of isolated spinal disease described in adults. Primitive neuroectodermal tumor is similarly uncommon in the spinal cord. Malignancies should be considered in patients who fail to improve with immunomodulatory therapy. We believe the experiences of our center will raise awareness about that point, broaden the existing understanding of the diagnostic approach to LETM, and highlight the need for additional studies.

PURPOSE: Ethnic disparities in childhood cancer survivor (CCS) mental health have been identified, although prior survivorship research has focused predominantly on non-Hispanic/Latinx (H/L) white survivors. METHODS: This study examined the association of acculturation with depressive symptoms and wellbeing among 582 young adult H/L CCS recruited to a population-based study of CCS in Southern California. RESULTS: In multivariable regression models adjusted for covariates, greater identification with both the Hispanic and Anglo cultures was positively associated with wellbeing (p = 0.007 and p

The coronavirus disease 2019 (COVID-19) pandemic likely affected youth with type 1 diabetes (T1D). We used electronic health record-extracted data to compare continuous glucose monitoring (CGM) metrics during 1 year of the pandemic with those of the previous year. The sample comprised CGM users, aged 1 to

INTRODUCTION: Black patients have a higher incidence of heart failure (HF) and worse outcomes than white patients. Guidelines recommend palliative care for patients with advanced HF, but no studies have examined outcomes in a black patient cohort. METHODS: This is a post hoc analysis of the Palliative Care in Heart Failure trial, which randomized patients to usual care plus a palliative care intervention (UC+PAL) or usual care (UC). Quality of life (QoL) was measured using Kansas City Cardiomyopathy Questionnaire (KCCQ) and Functional Assessment of Chronic Illness Therapy-Palliative Care scale (FACIT-Pal). RESULTS: Black patients represented 41% of the 148 patients. At six months, QoL improved more in UC+PAL than UC for both racial subgroups. The difference was greater for black than white patients (difference: KCCQ 10.8 vs. 2.5; FACIT-Pal: 14.8 vs. 3.9). However, the findings were not statistically significant. CONCLUSIONS: Larger studies are needed to assess the benefits of palliative care for black patients with HF. ClinicalTrials.gov Identifier: NCT01589601.

Objective We aimed to explore the impact of telehealth in the setting of COVID-19 on patient access to ambulatory rheumatologic care at our academic public health system and to determine whether telemedicine visits had a beneficial impact on access to our rheumatology ambulatory clinics. Methods We compared completed, no-show, and cancellation rates between in-person clinic visits and telemedicine appointments over a 10-week time period before Ohio's initial executive order responding to COVID-19 (premandate period) and a 10-week time period afterward (postmandate period). Scheduling and appointment data were retrospectively extracted from the medical center's electronic health record. Results During the premandate period, when all visits were in-person, the total number of completed visits was 930. The percentages of cancellations, no-shows, and completed appointments of all appointment activities were 31.43%, 13.12%, and 55.46%, respectively. During the postmandate period, when telemedicine visits were added, the overall total number of completed visits was 1038. The percentages of cancellations, no-shows, and completed appointments of all appointment activities were 53.45%, 13.91%, and 32.64%, respectively, for in-person appointments and 0.12%, 8.48%, and 91.39%, respectively, for telemedicine appointments. Conclusion Telemedicine during the COVID-19 pandemic resulted in higher rates of completed appointments and lower rates of missed appointments in the rheumatology outpatient clinic compared with in-person visits during and prior to the pandemic.

BACKGROUND: National Consensus Project for quality palliative care guidelines emphasizes the importance of a comprehensive assessment of all care domains, including physical, psychosocial, and spiritual aspects of care, for seriously ill patients. However, less is known about how real-world practice compares with this guideline. OBJECTIVE: To describe clinicians' assessment practices and factors influencing their approach. DESIGN: This is a two-part web-based survey of palliative care clinicians from five academic groups in the United States. RESULTS: Nineteen out of 25 invited clinicians (physicians, nurse practitioners, and physician assistants) completed the survey. A majority (62%) reported that, although some elements of assessment were mandatory, their usual practice was to tailor the focus of the consultation. Time limitations and workload received the highest mean scores as reasons for tailored assessment (6.1 on a 0–9 importance scale), followed by beliefs that comprehensive assessment is unnecessary (4.8) and absence of the full interdisciplinary team (4.4). All participants cited symptom acuity, and 91% cited reason for consult as factors influencing a tailored approach. Among domains “always” assessed, physical symptoms were reported most commonly (81%) and spiritual and cultural factors least commonly (24% and 19%, respectively). Although a majority of clinicians reported usually tailoring their consultations, mean importance scores for almost all assessment elements were high (range 3.9–8.8, mean 7.1); however, there was some variation based on reason for consult. Spiritual elements received lower importance scores relative to other elements (5.0 vs. 7.4 mean score for all others). CONCLUSION: Although clinicians placed high importance on most elements included in comprehensive palliative care, in practice they often tailored their consultations, and the perceived relative importance of domains shifted depending upon the type of consultation.

Inhibitor of apoptosis proteins (IAPs) regulate apoptosis and modulate NF‐κB signaling thereby driving expression of genes involved in immune/inflammatory responses. The orally available IAP antagonist Debio 1143 has potential to enhance tumor response to chemoradiotherapy and/or immunotherapy. Patients with pre‐operative squamous cell carcinomas of the head and neck (SCCHN) received: Debio 1143 monotherapy (200 mg/day [D]1–15 +/‐ 2); Debio 1143 (200 mg/day D1–15 +/‐ 2) plus cisplatin (40 mg/m2 D 1 and 8); cisplatin alone (40 mg/m2 D 1 and 8; EudraCT: 2014‐004655‐31). Pharmacokinetic/pharmacodynamic effects were assessed in plasma and resected tumors. Primary end point; effect of Debio 1143 on cellular IAP‐1 (cIAP‐1). Levels of cIAP‐1/‐2, X‐linked inhibitor of apoptosis protein (XIAP), tumor infiltrating lymphocytes (TILs), including CD8+ T cells, programmed cell death protein 1 (PD‐1), PD‐ligand 1 (PD‐L1), and gene expression were also analyzed. Twenty‐three of 26 patients completed treatment. In the Debio 1143 monotherapy cohort (n = 13), mean tumor concentrations of Debio 1143 were 18‐fold (maximum 55.2‐fold) greater than in plasma, exceeding the half‐maximal inhibitory concentration for cIAPs and XIAP by 100 to 1000‐fold, with significant engagement/degradation of cIAP‐1 (p

Background: Palliative care (PC) services expanded rapidly to meet the needs of coronavirus disease 2019 (COVID-19) patients, yet little is known about which patients were referred for PC consultation during the pandemic. Objective: Examine factors predictive of PC consultation for COVID-19 patients. Design: Retrospective cohort study of COVID-19 patients discharged from four hospitals (March 1–June 30, 2020). Exposures: Patient demographic, socioeconomic, and clinical factors and hospital-level characteristics. Outcome Measurement: Inpatient PC consultation. Results: Of 4319 hospitalized COVID-19 patients, 581 (14%) received PC consultation. Increasing age, serious illness (cancer, chronic obstructive pulmonary disease, and dementia), greater illness severity, and admission to the quaternary hospital were associated with receipt of PC consultation. There was no association between PC consultation and race/ethnicity, household crowding, insurance status, or hospital-factors, including inpatient, emergency department, and intensive care unit census. Conclusions: Although site variation existed, the highest acuity patients were most likely to receive PC consultation without racial/ethnic or socioeconomic disparities.

Objective: To assess the impact of initiation of closed-loop control (CLC) on glycemic metrics in older adults with type 1 diabetes (T1D) in the real world. Methods: Retrospective analysis of electronic health records from a single tertiary diabetes center of older adults prescribed CLC between January and December 2020. Results: Forty-eight patients (mean age 70 ± 4 years, T1D duration 42 ± 14 years) were prescribed CLC and 39/48 started on the CLC. Among the CLC starters, 97.5% and 95% were prior pump and continuous glucose monitoring (CGM) users, respectively. CGM metrics showed an increase in time-in-range (62% ± 13% to 76% ± 9%; P 180 mg/dL (30% ± 11% to 20% ± 9%; P

CONTEXT: Considering that SCI is the main cause of neurogenic bladder, in Brazil, studies and statistical data on the number of people with neurogenic bladder are practically non-existent. To ascertain the prevalence of neurogenic bladder among users of SARAH Network hospitals with traumatic and non-traumatic spinal cord injury. METHODS: Data collection form from electronic medical records to characterize the sample. The variables were related to sociodemographic data such as age, care unit, and date of admission; and to clinical data, such as main diagnosis, neurogenic bladder diagnosis. In the cases of traumatic spinal cord injury, the ASIA Impairment Scale (AIS) was considered. The statistical tests were Mann–Whitney, for two independent samples, and Pearson's Chi-squared, for the categorical variables. FINDINGS: The sample included 954 participants. The prevalence of neurogenic bladder was 94.65%, of which 67% had a traumatic spinal cord injury diagnosis and 69.32% were male. Mean age of the participants was 46.12 years old (SD = 15.78 years). CONCLUSION/CLINICAL RELEVANCE: The prevalence of neurogenic bladder found in the sample was 94.65%. The analysis showed that participants with TSCI are more afflicted by lower urinary tract dysfunction than those with NTSCI. TSCI was more prevalent among males and NTSCI was more prevalent among females. This was a pioneering study on the prevalence of neurogenic bladder in SCI in Brazil. However, further studies will be necessary to corroborate the data found here. The development of a database with national data is indispensable to obtain more reliable results that could provide a basis for public healthcare policies for the prevention and rehabilitation of people with SCI in Brazil.

Objective: Parent–child interaction therapy (PCIT) is an evidence-based approach for children aged 2–7 years with disruptive behavior problems. This study examined the effectiveness of PCIT with and without concurrent pharmacotherapy. Methods: A convenience sample was collected from a retrospective chart review of preschool-aged children treated with PCIT at the Mayo Clinic Young Child Clinic between 2016 and 2020. Quantitative and qualitative data were abstracted from all patients. The sample was divided into two groups based on psychotropic medications status (medicated and unmedicated) at the initiation of PCIT. Effectiveness of treatment was assessed with the change in Eyberg Child Behavior Inventory (ECBI) score. The change over time in ECBI score was compared between the two PCIT groups with and without concurrent pharmacotherapy using a linear mixed model. Results: Of the 62 youth, 38.71% were females. Mean age was 4.71 ± 1.17 years. The mean baseline ECBI score was 148.74 ± 30.86, indicating clinically significant disruptive behaviors. The mean number of PCIT sessions was 6.59 ± 3.82. There was no statistically significant difference in ECBI scores between the two groups at pre-PCIT (medication group: 149.68, standard error [SE] = 11.61 vs. unmedicated group: 147.92, SE = 10.93, p = 0.8904) and at post-PCIT (medication group: 116.27 [SE = 11.89] vs. unmedicated group: 128.86 [SE = 11.57], p = 0.3464). There was a statistically significant improvement in ECBI scores for both groups after completing therapy (medication group = −33.41 [−22.32%], SE = 6.27, p

Identification of anthracycline-induced muscle loss is critical for maintaining health in adolescent and young adult (AYA) cancer patients. We used routine chest computed tomography (CT) scans to investigate changes in skeletal muscle of 16 AYA sarcoma patients at thoracic vertebrae 4 (T4) after anthracycline treatment. CT images were examined at three time points (prechemotherapy, postchemotherapy, and 1 year). Significant changes in total skeletal muscle index and density were seen after chemotherapy (p = 0.021 and p = 0.016, respectively) and at 1 year versus baseline (both p

A 3-y-old, intact female, American Pit Bull Terrier was presented because of acute onset of anorexia and a large subcutaneous submandibular mass that had been present for 3 wk. The submandibular mass, 2 engorged black-legged ticks on the dorsum of the neck, pyrexia, and icterus were seen on physical examination. Abnormal laboratory test results included a positive Anaplasma antibody test, severe thrombocytopenia, mild nonregenerative anemia, hyperbilirubinemia, and elevated liver enzyme activities. Cytology of the mass was interpreted as marked septic purulent inflammation with acute hemorrhage. Treatment with doxycycline for anaplasmosis was unsuccessful, and the patient died at an emergency follow-up visit 2 d after the initial presentation. Autopsy and histopathology revealed widespread metastasis of a presumptive histiocytic neoplasm with associated hemophagocytosis seen in lymph nodes (LNs), liver, and spleen. Immunohistochemistry yielded a definitive diagnosis of a CD3+/CD18+ T-cell lymphoma. In this case of canine lymphoma-associated hemophagocytic syndrome, hemophagocytes were observed as >2% of neoplastic cells in the liver, spleen, and LN histologically, a scarce or unreported finding, to our knowledge. The prognosis was grave, with a short survival time after the onset of clinical signs.

BACKGROUND: Little is known about the cognitive and neuropsychiatric profile associated with punding and hobbyism in Parkinson's disease (PD). OBJECTIVE: To compare the clinical and neuropsychological features of PD patients with punding and hobbyism to PD controls. METHODS: The Questionnaire for Impulsive‐Compulsive Disorders in Parkinson's Disease‐Rating Scale (QUIP‐RS) was used as a screening tool, and a structured interview was used to diagnose punding/hobbyism. Clinical and neuropsychological assessment was conducted with validated questionnaires/scales. RESULTS: Twenty‐one patients with PD and punding (PD + pu) were compared to 26 with hobbyism (PD + h) and 25 PD controls. PD + pu patients showed higher levels of anxiety, non‐motor symptoms and motor symptoms, and lower Frontal Assessment Battery scores. The PD + h group exhibited similar levels of anxiety and motor fluctuations to the PD + pu group. CONCLUSION: PD + pu showed increased anxiety and frontal lobe dysfunction, similar to PD + h. Hobbyism could be a prodromal phase with increased risk of leading to punding.

A muskox neonate ( Ovibos moschatus) that died of starvation was diagnosed with congenital lenticular anomalies that included spherophakia and hypermature cataract associated with probable lens-induced lymphocytic uveitis and neutrophilic keratitis. Impaired sight as a result of cataract and associated inflammation likely contributed to abandonment and starvation, although maternal death cannot be excluded definitively. Ocular lesions, such as congenital cataracts and spherophakia in neonates, may be important factors affecting survival in free-ranging animals.

Comparing first and second wave MIS-C cohorts at our quaternary pediatric institution, second wave were older, presented more frequently with shortness of breath, higher maximum troponin and N-terminal BNP, and more frequently required advanced respiratory and inotropic support. Despite increased severity in the second cohort, both cohorts had similar rates of coronary artery abnormalities, systolic dysfunction, and length of stay.

Background Comorbidities including ischemic heart disease (IHD) worsen outcomes after SARS‐CoV‐2 infections. High lipoprotein(a) [Lp(a)] concentrations are a strong risk factor for IHD and possibly for thromboembolic events. We therefore evaluated whether SARS‐CoV‐2 infections modify the risk of high Lp(a) concentrations for IHD or thromboembolic events during the first 8.5 months follow‐up of the pandemic. Method Cohort study using data from the UK Biobank during the SARS‐CoV‐2 pandemic. Baseline Lp(a) was compared between SARS‐CoV‐2 positive patients and the population controls. UK Biobank received ethical approval from the North West Multi‐Centre Research Ethics Committee (REC reference: 11/NW/0382). All participants gave written informed consent before enrolment in the study, which was conducted in accordance with the principles of the Declaration of Helsinki. Results SARS‐CoV‐2 positive patients had Lp(a) concentrations similar to the population controls. The risk for IHD increased with higher Lp(a) concentrations in both, the population controls (n = 435,104) and SARS‐CoV‐2 positive patients (n = 6,937). The causality of the findings was supported by a genetic risk score for Lp(a). A SARS‐CoV‐2 infection modified the association with a steeper increase in risk for infected patients (interaction P‐value = 0.03). Although SARS‐CoV‐2 positive patients had a 5‐times higher frequency of thromboembolic events compared to the population controls (1.53% vs. 0.31%), the risk was not influenced by Lp(a). Conclusions SARS‐CoV‐2 infections enforce the association between high Lp(a) and IHD but the risk for thromboembolic events is not influenced by Lp(a). This article is protected by copyright. All rights reserved

BACKGROUND: Fatigue has a major impact on health‐related quality of life (HR‐QOL) in Parkinson's disease (PD). OBJECTIVES: To determine whether demographic characteristics modify the relationship between fatigue and HR‐QOL. METHODS: Patients with PD in the Fox Insight study completed the Parkinson Fatigue Scale (PFS‐16) and Geriatric Depression Scale (GDS‐15). Linear regression examined the relationship between the PFS‐16 and Parkinson Disease Quality of Life, as modified by age, sex, and GDS‐15. RESULTS: A total of 1029 participants (44% female, mean age 67.4 years, and mean disease duration 4.6 years) were included in this analysis. Multivariable regression modeling demonstrated a negative effect modification for age (β = −0.07, P

Background The reported incidence of adverse reactions following Coronavirus disease 2019 (COVID‐19) convalescent plasma (CCP) transfusion has generally been lower than expected based on the incidence of transfusion reactions that have been observed in studies of conventional plasma transfusion. This raises the concern for under‐reporting of adverse events in studies of CCP that rely on passive surveillance strategies. Materials and Methods Our institution implemented a protocol to actively identify possible adverse reactions to CCP transfusion. In addition, we retrospectively reviewed the charts of inpatients who received CCP at Stanford Hospital between May 13, 2020 and January 31, 2021. We determined the incidence of adverse events following CCP transfusion. Results A total of 49 patients received CCP. Seven patients (14%) had an increased supplemental oxygen requirement within 4 h of transfusion completion, including one patient who was intubated during the transfusion. An additional 11 patients (total of 18, 37%) had increased oxygen requirements within 24 h of transfusion, including 3 patients who were intubated. Six patients (12%) fulfilled criteria for transfusion‐associated circulatory overload (TACO). Conclusion Using an active surveillance strategy, we commonly observed adverse events following the transfusion of CCP to hospitalized patients. It was not possible to definitively determine whether or not these adverse events are related to CCP transfusion. TACO was likely over‐diagnosed given overlap with the manifestations of COVID‐19. Nevertheless, these results suggest that the potential adverse effects of CCP transfusion may be underestimated by reports from passive surveillance studies.

Objective The objective of this study was to validate the diagnosis of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) as the primary cause of end-stage renal disease (ESRD) in the US Renal Data System (USRDS). Methods We identified patients with ESRD in the Mass General Brigham (MGB) health care system who were enrolled in the USRDS. The health records of those with AAV listed as the primary cause of ESRD in the USRDS were reviewed to confirm the diagnosis and estimate positive predictive value (PPV). Sensitivity was estimated by evaluating the primary cause of ESRD listed in the USRDS for patients with ESRD due to AAV in the MGB AAV cohort. Results We identified 89 MGB patients with ESRD due to AAV in the USRDS. Of these, 85 cases were confirmed to be true cases of AAV (PPV = 94%). Among the patients classified as having AAV, 84 (99%) had an ANCA test, which was predominantly myeloperoxidase/P-ANCA (47 [55%]); 36 (42%) had a renal biopsy, and all biopsies were supportive of the diagnosis. The majority (81 [90%]) was identified as AAV by International Classification of Diseases Ninth Revision or International Classification of Diseases 10th Revision codes for granulomatosis with polyangiitis (446.4 or M313.1). Of the 77 MGB AAV cohort patients with ESRD who were linked to the USRDS, 41 (53%) had AAV listed as the cause of ESRD; in the remainder, ESRD was attributed to nonspecific nephritis. Conclusion The diagnosis of AAV as the cause of ESRD in the USRDS has a high PPV; sensitivity was moderate. These findings support the continued use of the USRDS to study ESRD due to AAV.

Introduction The sale of tobacco products within American pharmacies has generated controversy for several decades, leading two U.S. states and 45 municipalities to adopt tobacco-free pharmacy policies. While previous research has reported cheaper cigarette prices in pharmacies, compared to other retailers, little is known about cigarette promotions in pharmacies, which are associated with increased youth smoking and unplanned cigarette purchases among adults. Aims and Methods Between May and August 2015, trained data collectors conducted store audits at 2128 tobacco retailers located within 97 U.S. counties in 40 states. Observations were made for three types of cigarette promotions: special price (e.g., $0.30 off/pack), multi-pack promotions (e.g., buy one pack, get one free), and cross-product promotions (e.g., buy a pack of cigarettes and a get free can of snus). We calculated weighted estimates of the proportion of pharmacies and other retailer types with cigarette promotions and used weighted multivariable logistic regression to compare cigarette promotions by tobacco retailer type, accounting for clustering at the county level and controlling for county-level demographic characteristics. Results Cigarette promotions were observed in 94.0% of pharmacies, more than any other retailer type (e.g., convenience stores: 82.0%, tobacco stores: 77.0%). All retailer types had lower odds of promotions for Marlboro, Newport, Camel, menthol, or any interior cigarette promotion, compared to pharmacies. Conclusions Nearly all pharmacies offered in-store cigarette promotions and pharmacies had greater odds of offering cigarette promotions than all other retailer types. Whether voluntarily or legislatively, tobacco-free pharmacies would eliminate a prevalent retail source of cigarette promotions. Implications This is the first known national study to examine prevalence of cigarette promotions in U.S. pharmacies compared to other retailer types. Nearly all pharmacies offered in-store cigarette promotions and pharmacies had greater odds of offering cigarette promotions than all other retailer types. These findings underscore the inherent contradiction of pharmacies serving both as an important component of the health care system, but also as purveyors and promotors of addictive and lethal tobacco products. Whether voluntarily or legislatively, tobacco-free pharmacy policies would eliminate a prevalent retail source of cigarette promotions.

Background Asymptomatic patients with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS‐CoV‐2) can develop hypercoagulable conditions and acute vascular events. The objective of this study is to determine whether SARS‐CoV‐2 was present in resected specimens from patients with acute bowel ischemia, but asymptomatic for Coronavirus Disease 2019 (COVID‐19) and with persistently real‐time polymerase chain reaction negative pharyngeal swab. Methods Three consecutive patients presented severe abdominal symptoms due to extensive ischemia and necrosis of the bowel, with co‐existent thrombosis of abdominal blood vessels. None had the usual manifestations of COVID‐19, and repeated pharyngeal swabs tested negative. They underwent emergency surgery with intestinal resection. Immunohistochemical testing for SARS‐CoV‐2 on resected tissue was performed. Results All tested samples were strongly positive for SARS‐CoV‐2. Conclusions This is the first case report in which patients with severe intestinal symptoms presented a marked SARS‐CoV‐2 positivity in the resected tissues, without any usual clinical manifestations of COVID‐19. These results suggest that the patients might be infected with SARS‐CoV‐2 presenting acute abdominal distress but without respiratory or constitutional symptoms.

Objective Vaccination against preventable infections is widely recommended for patients with systemic rheumatic disease. The coronavirus disease 2019 (COVID‐19) pandemic has highlighted variability in attitudes toward vaccination, particularly with the use of novel vaccine platforms. We studied attitudes toward vaccination against COVID‐19 and other preventable infections among patients with systemic rheumatic disease and compared these against the general population. Methods We surveyed patients treated at Brigham and Women’s Hospital for systemic rheumatic disease using a secure web‐based survey or paper survey in English or Spanish, from December 2020 to April 2021. We included survey questions used in the nationwide Harris Poll (October 2020 and February 2021), allowing the comparison of responses with those from the general population. Response frequencies were estimated and compared using descriptive statistics. Results Of 243 participants (25% response rate), the mean age was 56 years, 82% were women, and 33% were nonwhite. Rheumatoid arthritis (50%) and systemic lupus erythematosus (28%) were the most common diagnoses. Thirty percent had been hospitalized previously for any infection. Seventy‐six percent worried a lot or somewhat about contracting COVID‐19. Attitudes toward vaccination were very favorable, with 92% having received a flu shot in the past year and 84% desiring a COVID‐19 vaccine as soon as possible compared with 30% to 40% of Harris Poll respondents (P < 0.001). Physician recommendation to receive a vaccine and desire to avoid infection were the most common reasons for desiring vaccinations. Conclusion Vaccine acceptability, including toward COVID‐19 vaccines, was high among this population of patients with systemic rheumatic disease seen at an academic medical center cohort. Physician recommendation is a key factor for vaccine uptake.

Background Anti‐SARS‐CoV‐2 S antibodies prevent viral replication. Critically ill COVID‐19 patients show viral material in plasma, associated with a dysregulated host response. If these antibodies influence survival and viral dissemination in ICU‐COVID patients is unknown. Patients/Methods We studied the impact of anti‐SARS‐CoV‐2 S antibodies levels on survival, viral RNA‐load in plasma, and N‐antigenaemia in 92 COVID‐19 patients over ICU admission. Results Frequency of N‐antigenaemia was >2.5‐fold higher in absence of antibodies. Antibodies correlated inversely with viral RNA‐load in plasma, representing a protective factor against mortality (Adjusted HR [CI 95%], p): (S IgM [AUC ≥ 60]: 0.44 [0.22; 0.88], 0.020); (S IgG [AUC ≥ 237]: 0.31 [0.16; 0.61]

Background Persistent symptoms including breathlessness, fatigue, and decreased exercise tolerance have been reported in patients after acute SARS-CoV-2 infection. The biological mechanisms underlying this “long COVID” syndrome remain unknown. However, autopsy studies have highlighted the key roles played by pulmonary endotheliopathy and microvascular immunothrombosis in acute COVID-19. Objectives To assess whether endothelial cell activation may be sustained in convalescent COVID-19 patients and contribute to long COVID pathogenesis. Patients and Methods Fifty patients were reviewed at a median of 68 days following SARS-CoV-2 infection. In addition to clinical workup, acute phase markers, endothelial cell (EC) activation and NETosis parameters and thrombin generation were assessed. Results Thrombin generation assays revealed significantly shorter lag times (p < .0001, 95% CI −2.57 to −1.02 min), increased endogenous thrombin potential (p = .04, 95% CI 15–416 nM/min), and peak thrombin (p < .0001, 95% CI 39–93 nM) in convalescent COVID-19 patients. These prothrombotic changes were independent of ongoing acute phase response or active NETosis. Importantly, EC biomarkers including von Willebrand factor antigen (VWF:Ag), VWF propeptide (VWFpp), and factor VIII were significantly elevated in convalescent COVID-19 compared with controls (p = .004, 95% CI 0.09–0.57 IU/ml; p = .009, 95% CI 0.06–0.5 IU/ml; p = .04, 95% CI 0.03–0.44 IU/ml, respectively). In addition, plasma soluble thrombomodulin levels were significantly elevated in convalescent COVID-19 (p = .02, 95% CI 0.01–2.7 ng/ml). Sustained endotheliopathy was more frequent in older, comorbid patients, and those requiring hospitalization. Finally, both plasma VWF:Ag and VWFpp levels correlated inversely with 6-min walk tests. Conclusions Collectively, our findings demonstrate that sustained endotheliopathy is common in convalescent COVID-19 and raise the intriguing possibility that this may contribute to long COVID pathogenesis.

In a national survey of 2074 US parents of children ≤12 years of age conducted in March 2021, 49.4% reported plans to vaccinate their child for coronavirus disease 2019 when available. Lower income and less education were associated with greater parental vaccine hesitancy/resistance; safety and lack of need were primary reasons for vaccine hesitancy/resistance.

Background Coronavirus disease 2019 (COVID‐19) occurs following infection with the potentially fatal, severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) virus. Infection can be complicated by coagulopathy, at times featuring thrombocytopenia and thrombosis alongside other coagulation abnormalities, also termed COVID‐19‐associated coagulopathy (CAC). Data concerning CAC in pregnancy are limited. Better understanding of physician experiences is essential to identify current practice patterns and knowledge gaps. Objectives To determine physician experiences and practice patterns regarding CAC in pregnancy. Methods Self‐administered survey using the RedCap online platform; supported by the ISTH Subcommittee on Women's Health Issues in Thrombosis and Hemostasis. Results Seventy‐five respondents fully or partially completed the survey. Of 1546 reported cases, disease severity was specified in 1298. Sixty‐four percent of COVID‐19 infections were mild, whereas 4% were severe. Of all cases, 1% developed CAC, with 65% classified as severe. The most frequent abnormalities included thrombocytopenia, elevated C‐reactive protein, D‐dimer, and lymphopenia. Low molecular weight heparin was the anticoagulant of choice in CAC and was provided by 77% of respondents, with 60% using standard prophylactic dosing. Thrombosis occurred in seven anticoagulated patients who were receiving standard prophylactic (four) or weight‐based (three) dosing. Disease severity and additional thrombosis risk factors dictated anticoagulation duration. Conclusion In the select population reported by our survey, CAC appears to be uncommon in pregnancy. Anticoagulation practices vary and may not reflect current guidelines. Venous thromboembolism was observed in some CAC patients despite prophylactic anticoagulation (including standard and weight‐adjusted dosing). Urgent research is required to determine appropriate anticoagulant dosing and duration in pregnant women with COVID‐19 infection.

Coagulation factor Xa (recombinant), inactivated-zhzo (andexanet alfa) is approved for reversal of life-threatening bleeding with rivaroxaban and apixaban use. Clinical decision-making to initiate reversal is reliant on dose taken and timing of last dose. In practice, timing of last dose may be unknown, and the turnaround time for drug-specific anti-factor Xa levels at some institutions may be prolonged, leaving clinicians balancing a difficult decision with limited tools. This report includes a series of 3 patients who presented to our institution with an intracranial hemorrhage and received andexanet alfa for apixaban reversal. These cases highlight the challenges clinicians are facing when using andexanet alfa for emergent rivaroxaban or apixaban reversal when the timing of last dose is unknown, or patients fall outside of the recommended timeframe for use and clinically relevant drug levels are still suspected. Based on our experiences, we encourage other institutions to evaluate their abilities to rapidly and accurately detect the presence of clinically relevant rivaroxaban and apixaban levels when utilizing andexanet alfa.

In non-endemic settings, transfusion-transmitted malaria (TTM) is rare but potentially fatal and becoming more common with globalization. We present two pediatric cases that demonstrate donor screening using questionnaires is subject to error and that TTM should be considered with fever following numerous transfusions in children, particularly sickle cell patients.

Objectives To develop and cross-validate self-administered Rapid Geriatric Assessment (SA-RGA) app against administered Rapid Geriatric Assessment (A-RGA) to identify seniors with geriatric syndromes such as frailty, sarcopenia, and anorexia of ageing who may benefit from targeted intervention. Design Prospective observational study. Setting Primary Care and Community. Participants A-RGA and SA-RGA app were administered to older adults ≥ 60 years old from December 2020 to April 2021. Measurements The RGA app screens for frailty (FRAIL), sarcopenia (SARC-F), anorexia of aging (SNAQ) and cognition (Rapid Cognitive Screen) with assisted management pathway. Patient Health Questionnaire 9 is administered for those who score positive for fatigue. The diagnostic performance of SA-RGA was compared against A-RGA as a reference by calculating the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) and positive likelihood ratio (+LR). Results 123 participants with a mean age of 71 ± 5.9 years completed both the SA-RGA and A-RGA. Questions on fatigue, 5 or more illnesses, loss of weight and falls in the past year performed better with high sensitivity, specificity, NPV and +LR than self-functional assessment where SA-RGA participants reported lower prevalence on the FRAIL scale aerobic and resistance components, and higher prevalence on the SARC-F strength and rising from a chair components. Conclusion The SA-RGA app performed well in certain domains such as assessment for weight loss, falls, number of chronic illness and fatigue. Self-functional assessment can be improved further by removing ambiguity in wordings such as “some” or “a lot” and replacing it with functional difficulty scale. SA-RGA has the potential to be incorporated in the eHEALTH platforms worldwide for early identifications of older adults at risk and to reduce health inequalities, at the same time building community resilience in the era of Covid-19 pandemic.

A 27-mo-old, spayed female mixed-breed dog was presented with left forelimb pain, which progressed to full thickness necrosis of the soft tissues of multiple limbs. Clinical imaging and postmortem examination suggested multiple large arterial thromboemboli. Histologic examination of vascular lesions revealed markedly thickened tunica intima with polypoid intraluminal projections, which partially to entirely occluded the arterial lumen. The expanded tunica intima was comprised of intimal accumulation of Alcian blue–positive matrix with scattered spindle-to-satellite cells. These cells were positive for von Willebrand factor and vimentin but negative for α–smooth muscle actin, suggesting endothelial origin. Deposition of the intimal mucoid matrix was observed in the elastic and muscular arteries associated with regional ischemic changes. Mucoid emboli, likely from fragmentation of proliferative intimal tissue, were identified in smaller vessels supplied by affected arteries. Based on these findings, we diagnosed systemic mucoid degeneration of the arterial tunica intima. Such systemic arterial degeneration characterized by deposition of mucoid matrix in the tunica intima has not been reported previously in dogs, to our knowledge, and should be distinguished from thromboembolism and other degenerative vascular diseases.

OBJECTIVE: With a vaccine effectiveness of 95% for preventing coronavirus disease 2019 (COVID-19), Pfizer-BioNTech BNT162b2 (BNT162b2) was the first vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to be approved. However, immunosuppressive therapy was an exclusion criterion in the phase 3 trial that led to approval. Thus, extrapolation of the trial results to patients with rheumatic diseases treated with immunosuppressive drugs warrants caution.METHODS: Patients with systemic lupus erythematosus (SLE; n = 61) and rheumatoid arthritis (RA; n = 73) were included from the COPANARD (Corona Pandemic Autoimmune Rheumatic Disease) cohort, followed since the beginning of the COVID-19 pandemic. Patients received the BNT162b2 vaccine between December 2020 and April 2021. All patients had total antibodies against SARS-CoV-2 measured before vaccination and 1 week after the second vaccination (VITROS Immunodiagnostic Products).RESULTS: Of 134 patients (median age, 70 years), 77% were able to mount a detectable serological response to the vaccine. Among patients treated with rituximab, only 24% had detectable anti-SARS-CoV-2 antibodies in their serum after vaccination. The time since the last rituximab treatment did not seem to influence the vaccine response. No significant difference was observed between patients with RA or SLE when adjusting for treatment, and no correlation between antibody levels and age was detected (r = -0.12; P = 0.18).CONCLUSION: Antibody measurements against SARS-CoV-2 in patients with RA and SLE after two doses of the BNT162b2 vaccine demonstrated that 23% of patients could not mount a detectable serological response to the vaccine. B cell-depleting therapy (BCDT) is of specific concern, and our findings call for particular attention to the patients receiving BCDT.

Objective: Patients with chronic rheumatic diseases (CRDs), such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA), require special attention during the COVID-19 pandemic as they are considered at risk of severe infections. Our objective was to assess the seroprevalence of SARS–CoV-2 in patients with SLE and RA and to assess patient behavior, disease-related symptoms, and mental health. Methods: More than 900 participants were included: 405 patients with RA or SLE (CRD patients) and 513 blood donors. All participants had blood SARS–CoV-2 total antibodies measured (sensitivity 96.7%, specificity 99.5%) and answered a questionnaire concerning behavior, anxiety, and symptoms of depression (Patient Health Questionnaire 9). The CRD patients were further asked about physical activity, adherence to medication, and disease-related symptoms. Results: CRD patients had a significantly lower seroprevalence of SARS–CoV-2 antibodies (n = 1 of 365, 0.3%) compared to blood donors (n = 10 of 513, 1.9%; P = 0.03). Almost 60% of patients were unable to exercise as usual, and increased pain and disease activity was experienced by 34% and 24% of patients, respectively. Almost 10% of patients reduced or discontinued their immunosuppressive treatments at their own initiative. Symptoms of moderate depression were present in 19% of patients compared to 6.8% of blood donors (P < 0.001). Conclusion: Low seroprevalence in patients with CRDs indicates successful mitigation of exposure to SARS–CoV-2. However, this mitigation appears to occur at the expense of physical activity, experience of increased pain, disease activity, and symptoms of depression. There is a need for care providers to be aware of these negative side effects and for further studies to investigate the possible long-term consequences.

Objective: Menopause is associated with an increased prevalence of sleep difficulties. We evaluated the economic burden of sleep disturbances among working midlife women. Methods: This retrospective, longitudinal cohort study collected data from the US Study of Women's Health Across the Nation (SWAN) database of women age 42-52 years at enrollment. We assessed the association between sleep disturbances (trouble falling asleep, waking early, or nocturnal awakenings) and workplace productivity (employment [yes/no] and work hours/wk) for women who were employed at the baseline visit and had ≥1 follow-up visit. We estimated overall economic burden by multiplying changes in productivity by median age-specific hourly US wages. Each woman's data were compared from visit to visit and were excluded after the first observed unemployment. Regression analysis was used to estimate associations between changes in sleep and changes in workplace productivity while controlling for relevant characteristics that varied over time. Results: The analysis included 2,489 working women (19,707 visits); 31% became unemployed during follow-up. Risk of unemployment was 31% higher for women with versus without new-onset sleep disturbances (P = 0.0474). Onset of sleep disturbances was associated with a 0.44-0.57 hours/wk reduction in work time (not significant). Using the more conservative reduction (0.44 h), sleep problems were associated with an annual loss of $517 to $524 per woman and $2.2 billion/yr in lost productivity among women age 42-64 nationwide. Conclusions: New-onset sleep problems in midlife women are associated with significant increases in risk of unemployment and ∼$2 billion/yr in lost productivity nationwide. Video Summary:.

Introduction Varenicline is the most efficacious drug for smoking cessation; saliva varenicline concentrations can be useful for the evaluation of adherence in smoking cessation trials. Saliva is a useful noninvasive matrix for mail-in specimen collection, if stable. We investigated the stability of varenicline in saliva at different storage temperatures simulating the time it takes to mail in a sample. Methods We evaluated the concentrations of varenicline, nicotine, cotinine, 3′-hydroxycotinine, and 3′-hydroxycotinine/cotinine (3HC/COT) ratio in quality control saliva samples (and after repeated freezing and thawing), and in smokers’ saliva samples, stored for up to 21 days at room temperature (~25°C), 4°C, and −80°C. Results In saliva quality control samples, concentrations of varenicline, nicotine, cotinine, 3′-hydroxycotinine, and 3HC/COT remained unchanged and showed little within-sample variation (CV ≤ 5.5%) for up to 21 days at the three storage temperatures; they were also not altered after three thaw-freeze cycles. In smokers’ saliva, a significant main effect of storage duration, but not temperature, was observed for varenicline, cotinine, and 3′-hydroxycotinine, but not for nicotine or the 3HC/COT ratio. However, these changes were within analytical (i.e., equipment) variation resulting in little within-sample variation (CV ≤ 5.8%) for all analytes in smokers’ saliva. Conclusions Varenicline, the other analytes, and the 3HC/COT ratio remained stable in saliva during storage for 21 days at all temperatures tested and after repeated freezing and thawing with only minor changes in concentration over time. These findings support the potential use of mail-in approach for saliva samples in varenicline smoking cessation clinical trials. Implications Assessing saliva varenicline concentrations can be useful for the evaluation of adherence in smoking cessation trials. Saliva is a noninvasive matrix suitable for mail-in specimen collection. This is the first investigation of stability of varenicline in saliva. Varenicline, nicotine, cotinine, 3′-hydroxycotinine, and 3HC/COT were stable in saliva for up to 21 days at room temperature (~25°C), 4°C, and −80°C, supporting the use of a mail-in approach for saliva specimen in smoking cessation trials.

Background The coronavirus disease 2019 (COVID‐19) pandemic has highlighted the importance of using information and communication technology (ICT) to address daily and healthcare needs. The barriers for older adults in the United States to learn a new technology to go online during the pandemic remain to be studied. Methods Using data from the 2019–2020 National Health and Aging Trends Study (NHATS), a nationally representative survey of older Medicare beneficiaries aged 65 years and older in the United States, we used multivariable logistic regression models to identify sociodemographic and clinical factors associated with learning a new technology to go online during the COVID‐19 pandemic. Results Our sample represented 23,547,688 older adults nationally, of which the majority (60.2%) increased ICT use during the COVID‐19 pandemic. However, most older adults (71.8%) did not report learning a new technology to go online. Those who did not learn a new technology to go online had less of an increase in ICT use than those who learned either with help or by themselves (50.7% vs. 78.4% or 89.2% respectively, p

Community-acquired bacterial meningitis (CABM) morbidity and mortality remains high in those infected. Rapid diagnosis and treatment is paramount to reducing mortality and improving outcome. This retrospective cohort study aims to assess the time from presentation to diagnosis and treatment of vaccine preventable CABM as well as identify possible factors associated with delays in diagnosis and antibiotic administration. A retrospective chart review was conducted of individuals who presented to Columbia University Irving Medical Center (CUIMC), Children’s Hospital of New York (CHONY), Mount Sinai Medical Center, and Weill Cornell Medical Center with BM due to Haemophilus influenzae type B, Streptococcus pneumoniae, and Neisseria meningitidis between January 1, 2012 and December 31, 2017. Diagnosis was delayed by more than 8 hours in 13 patients (36.1%) and 5 individuals (13.9%) had a delay of 4 hours or more from presentation to the administration of antibiotics with appropriate CNS coverage. All of these patients were also initially misdiagnosed at an outpatient clinic, outside hospital, or emergency department. This retrospective study identified febrile and/or viral infections not otherwise specified and otitis media as the most common misdiagnoses underlying delays from presentation to diagnosis and to antibiotic treatment in those with BM.

Background Convalescent plasma (CP) therapy for coronavirus disease (COVID‐19) provides virus‐neutralizing antibodies that may ameliorate the outcome of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infections. The effectiveness of CP likely depends on its antiviral neutralizing potency and is determined using in vitro neutralizing antibody assays. Study design and methods We evaluated abilities of three immunoassays for anti‐spike antibodies (EUROimmun, Ortho, Roche), a pseudotype‐based neutralization assay, and two assays that quantify ACE2 binding of spike protein (GenScript and hemagglutination test [HAT]‐based assay) to predict neutralizing antibody titers in 113 CP donations. Assay outputs were analyzed through linear regression and calculation of sensitivities and specificities by receiver operator characteristic (ROC) analysis. Results Median values of plasma samples containing neutralizing antibodies produced conversion factors for assay unitage of ×6.5 (pseudotype), ×19 (GenScript), ×3.4 (HAT assay), ×0.08 (EUROimmun), ×1.64 (Roche), and ×0.10 (Ortho). All selected assays were sufficient in identifying the high titer donations based on ROC analysis; area over curve ranged from 91.7% for HAT and GenScript assay to 95.6% for pseudotype assay. However, their ability to predict the actual neutralizing antibody levels varied substantially as shown by linear regression correlation values (from 0.27 for Ortho to 0.61 for pseudotype assay). Discussion Overall, the study data demonstrate that all selected assays were effective in identifying donations with high neutralizing antibody levels and are potentially suitable as surrogate assays for donation selection for CP therapy.

Background The coronavirus disease 2019 pandemic was caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although the predominant clinical presentation is a respiratory disease, neurological manifestations are being recognized increasingly. Case report We report 2 children aged 9 years old who developed acute disseminated encephalomyelitis-like disease associated with SARS-CoV-2. Seizures and encephalopathy were the main central nervous system symptoms. The cerebrospinal fluid analysis performed within the first week of disease onset showed elevated protein in both children with normal cell count and no evidence of infection including negative SARS-CoV-2 by antibody and polymerase chain reaction. Brain magnetic resonance imaging revealed T2A, fluid-attenuated inversion recovery cortical and subcortical hyperintensity without restricted diffusion consistent with acute disseminated encephalomyelitis-like disease. They received methylprednisolone followed by therapeutic plasma exchange. One of them showed complete clinical improvement and resolution in magnetic resonance imaging findings. The other developed laminar necrosis in brain magnetic resonance imaging and showed significant clinical improvement after therapeutic plasma exchange. He was positive for positive SARS-CoV-2 antibody in cerebrospinal fluid on day 55 of admission. They were both positive for SARS-CoV-2 antibodies in serum after 2 weeks. Conclusions Our two cases highlight the occurrence of acute disseminated encephalomyelitis-like disease as a postinfectious/immune-mediated complication of SARS-CoV-2 infection.

Eight of 9 juvenile raccoons at a rehabilitation center died without obvious prior clinical signs. Gross changes were unremarkable except for mildly distended intestines. Microscopically, crypt loss, distension, necrosis, and regeneration with intranuclear viral inclusions were observed in the small intestine, with marked lymphoid depletion and necrosis in Peyer patches and mesenteric lymph nodes. Immunohistochemistry with a canine parvovirus antibody showed intensive signals of parvoviral antigens in the crypts and lymphoid germinal centers. Metagenomic sequencing allowed assembly of a complete parvoviral genome with >99% identity to canine parvovirus 2a, as well as Salmonella enterica subsp. enterica. Also, S. enterica subsp. enterica serovar Thompson with multiple antimicrobial resistance was isolated from the intestinal contents. Concurrent infection with parvovirus and Salmonella should be included as a differential diagnosis in raccoons with sudden death.

The goal of this study was to characterize trajectories of continuous glucose monitoring (CGM) use in youth 5–12 weeks after starting CGM and examine what factors differentiate between the trajectory groups. Parent–youth dyads completed assessments before starting CGM. Days of CGM use between weeks 5 and 12 were accessed through cloud-based data repository. Three patterns of use were observed among 96 youth (mean age 13.4 ± 2.75 years; 75% white): sustained high, declining, and sustained low. Youth in the sustained low and declining groups were more likely than those in the sustained high group to use a receiver (versus smart phone). There were no differences between the trajectory groups with respect to age, race, ethnicity, income, or insulin regimen. Future research should examine trajectory groups for a longer follow-up period and identify baseline factors that reliably predict which youth will have low or declining CGM use over time.

Background: Electronic health records (EHRs) may help enable reliable, rapid data management for many uses, such as facilitating communication of advance care planning (ACP). However, issues with validity and accuracy of EHRs hinder the use of ACP information for practical applications. Design: We present a cross-sectional pilot study of 433 older adults with cancer from three large health care systems, participating in an ongoing multisite pragmatic trial (4UH3AG060626-02). We compared data extracted from dedicated structured EHR fields for ACP to a chart review of corresponding ACP documentation contained in the medical chart. Results: Structured ACP data existed for 43.2% of patients and varied by site (25.7% −48.9%). Of the identified structured ACP data elements, 59.2% of recorded elements were correct, 23.7% were incorrect, and 17.1% were duplicates with heterogeneity across sites. Conclusion: Structured ACP data in EHRs were frequently incorrect. This represents a problem for patients and their families, as well as quality improvement and research efforts. Clinical Trials Registration: NCT03609177.

We analyzed urine samples from 191 cats for bacteriuria with an automated urine sediment analyzer (Idexx SediVue Dx), combined with image review by an observer, and compared to bacteriologic culture results. Sixty-nine samples were unambiguously assigned to be free of bacteria by the instrument and the observer, and no bacterial growth was detected. Twenty-seven samples were unambiguously assigned to have bacteriuria; 24 of these 27 samples were culture-positive. For these samples, bacteriuria was predicted with a sensitivity of 100% and a specificity of 96%. A clear assignment was not possible for 95 samples, 81 of which were culture-negative. Specificity dropped to 45% when all samples were considered. Using the automated leukocyte count to predict bacteriuria, sensitivity was 82% and specificity was 75%. Automated sediment analysis is faster and less observer-dependent than sediment analysis under a microscope, but accurate detection of bacteriuria remains difficult in a large proportion of samples. Bacteriuria was significantly associated with leukocyte count; the leukocyte count was >5/high power field in 82% of culture-positive samples.

Low‐dose methotrexate (MTX) is an immunosuppressant used to treat inflammatory bowel disease (IBD). SLCO1B1 genetic variation has been associated with delayed MTX clearance and increased toxicity. The purpose of this study was to evaluate the association between SLCO1B1 genetic variation and MTX‐induced nausea in children with IBD. We performed a single center retrospective chart analysis of 278 patients who were prescribed MTX for IBD. Two hundred two patients had banked DNA and were genotyped for three SLCO1B1 single nucleotide polymorphisms (SNPs; rs4149056, rs2306283, and rs11045819). Diplotypes were determined by combining the SNPs into *1, *4, *5, *14, *15, and *37 alleles. Incidence of nausea was abstracted from clinician notes. Prescriptions and demographics were extracted from the medical record. The cohort was 69.8% boys, 89.1% White, and 87.6% had a diagnosis of Crohn’s disease with a mean age of 16.0 (± 3.8) years. MTX‐induced nausea was noted in 34% of the cohort. MTX‐induced nausea was associated with the number of reduced‐function *15 alleles (p = 0.034) and occurred 2.26 times more often in patients with at least one *15 allele who did not initiate MTX treatment with concomitant ondansetron (p = 0.034). MTX‐induced nausea was significantly independently associated with SLCO1B1 diplotype (p = 0.006) after controlling for MTX dose group and concomitant ondansetron. Our data demonstrate that the SLCO1B1 *15 allele is associated with MTX‐induced nausea in pediatric patients with IBD. Additionally, *15 allele carriers could benefit from a dose reduction of MTX to reduce exposure and treatment initiation with concomitant ondansetron to reduce nausea.

The coronavirus disease 2019 (COVID‐19) pandemic has induced considerable psychological distress in healthcare workers, increasing the risk of burnout. This research aimed to investigate sociodemographic, work‐related, COVID‐19‐related, and psychological factors associated with emotional exhaustion (the core component of burnout) among healthcare professionals during the first wave of the COVID‐19 pandemic in Italy. A cross‐sectional study was conducted to assess risk (e.g. perceived risk and fear of contagion, stress) and protective factors (e.g. job satisfaction, resilience) for emotional exhaustion among 616 hospital staff. Women, nurses, shift workers, those with a permanent contract, and frontline workers reported significantly higher levels of emotional exhaustion compared to others. Significant risk factors predicting emotional exhaustion were prolonged use of personal protective equipment, increased work pressure, lack of support, and prolonged working hours; psychologically protective factors were resilience and job satisfaction, while perceived stress was found to be a significant psychological risk factor. Organizational interventions should focus on these factors to prevent the onset of burnout.

Background Consistent with fulminant endothelial cell activation, elevated plasma von Willebrand factor (VWF) antigen levels have been reported in patients with COVID‐19. The multimeric size and function of VWF are normally regulated through A Disintegrin And Metalloprotease with ThrombSpondin Motif type 1 motif, member 13 (ADAMTS‐13)‐‐mediated proteolysis. Objectives This study investigated the hypothesis that ADAMTS‐13 regulation of VWF multimer distribution may be impaired in severe acute respiratory syndrome‐coronavirus‐2 (SARS‐CoV‐2) infection contributing to the observed microvascular thrombosis. Patients and Methods Patients with COVID‐19 (n = 23) were recruited from the Beaumont Hospital Intensive Care Unit (ICU) in Dublin. Plasma VWF antigen, multimer distribution, ADAMTS‐13 activity, and known inhibitors thereof were assessed. Results We observed markedly increased VWF collagen‐binding activity in patients with severe COVID‐19 compared to controls (median 509.1 versus 94.3 IU/dl). Conversely, plasma ADAMTS‐13 activity was significantly reduced (median 68.2 IU/dl). In keeping with an increase in VWF:ADAMTS‐13 ratio, abnormalities in VWF multimer distribution were common in patients with COVID‐19, with reductions in high molecular weight VWF multimers. Terminal sialylation regulates VWF susceptibility to proteolysis by ADAMTS‐13 and other proteases. We observed that both N‐ and O‐linked sialylation were altered in severe COVID‐19. Furthermore, plasma levels of the ADAMTS‐13 inhibitors interleukin‐6, thrombospondin‐1, and platelet factor 4 were significantly elevated. Conclusions These findings support the hypothesis that SARS‐CoV‐2 is associated with profound quantitative and qualitative increases in plasma VWF levels, and a multifactorial down‐regulation in ADAMTS‐13 function. Further studies will be required to determine whether therapeutic interventions to correct ADAMTS‐13‐VWF multimer dysfunction may be useful in COVID‐microvascular thrombosis and angiopathy.

The impact of continuous glucose monitoring (CGM) on glycemic control in young adults with type 1 diabetes (T1D) is controversial. Data from 888 young adults with T1D were reviewed (ages 18–30 years, 52% female, glycated hemoglobin [HbA1c] 8.1% ± 1.5%). Prescription of CGM was recorded for 54% of young adults; 66% were pump users, 46% on insulin injections and carbohydrate (carb) counting, and 32% on insulin doses without carb counting (P ≤ 0.001). HbA1c was lower in young adults with CGM versus no CGM (7.7% ± 1.3% vs. 8.2% ± 1.7%, P ≤ 0.001). Difference in HbA1c between CGM versus no CGM was greater in young adults noncarb counting (7.9% ± 1.4% vs. 8.9% ± 2.3%, P = 0.002) than carb counting (7.7% ± 1.5% vs. 8.2% ± 1.7%, P = 0.0008), or pump users (7.6 ± 1.2 vs. 7.9 ± 1.1, P = 0.01). Prescription of CGM was higher with increasing complexity of insulin regimens; however, impact of CGM was greatest with simpler insulin administration methods. Further studies are needed to clarify this association.