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To determine whether multimorbidity is associated with treatment changes and achieving target disease activity thresholds in patients with active rheumatoid arthritis (RA).We conducted a retrospective cohort study of adults with active RA within the Rheumatology Informatics System for Effectiveness (RISE) registry. Multimorbidity was measured using RxRisk, a medication-based index of chronic disease. We used multivariable logistic regression models to assess the associations of multimorbidity with the odds of initiating a new disease-modifying antirheumatic drug (DMARD) in active RA, and among those initiating a new DMARD, the odds of achieving low disease activity or remission.We identified 15,626 patients using the Routine Assessment of Patient Index Data 3 (RAPID3) cohort and 5,733 patients using the Clinical Disease Activity Index (CDAI) cohort. All patients had active RA, of which 1,558 (RAPID3) and 834 (CDAI) initiated a new DMARD and had follow-up disease activity measures. Patients were middle aged, female, and predominantly White, and on average received medications from 6 to 7 RxRisk categories. Multimorbidity was not associated with new DMARD initiation in active RA. However, a greater burden of multimorbidity was associated with lower odds of achieving treatment targets (per 1-unit RxRisk: RAPID3 cohort odds ratio [OR] 0.95 [95% confidence interval (95% CI) 0.91, 0.98]; CDAI cohort OR 0.94 [95% CI 0.90, 0.99]). Those with the highest burden of multimorbidity had the lowest odds of achieving target RA disease activity (RAPID3 cohort OR 0.54 [95% CI 0.34, 0.85]; CDAI cohort OR 0.65 [95% CI 0.37, 1.15]).These findings from a large, real-world registry illustrate the potential impact of multimorbidity on treatment response and indicate that a more holistic management approach targeting multimorbidity may be needed to optimize RA disease control in these patients.

BackgroundO’Donnell-Luria-Rodan syndrome (ODLURO) is an autosomal-dominant neurodevelopmental disorder caused by pathogenic, mostly truncating variants in KMT2E. It was first described by O’Donnell-Luria et al in 2019 in a cohort of 38 patients. Clinical features encompass macrocephaly, mild intellectual disability (ID), autism spectrum disorder (ASD) susceptibility and seizure susceptibility.MethodsAffected individuals were ascertained at paediatric and genetic centres in various countries by diagnostic chromosome microarray or exome/genome sequencing. Patients were collected into a case cohort and were systematically phenotyped where possible.ResultsWe report 18 additional patients from 17 families with genetically confirmed ODLURO. We identified 15 different heterozygous likely pathogenic or pathogenic sequence variants (14 novel) and two partial microdeletions of KMT2E. We confirm and refine the phenotypic spectrum of the KMT2E-related neurodevelopmental disorder, especially concerning cognitive development, with rather mild ID and macrocephaly with subtle facial features in most patients. We observe a high prevalence of ASD in our cohort (41%), while seizures are present in only two patients. We extend the phenotypic spectrum by sleep disturbances.ConclusionOur study, bringing the total of known patients with ODLURO to more than 60 within 2 years of the first publication, suggests an unexpectedly high relative frequency of this syndrome worldwide. It seems likely that ODLURO, although just recently described, is among the more common single-gene aetiologies of neurodevelopmental delay and ASD. We present the second systematic case series of patients with ODLURO, further refining the mutational and phenotypic spectrum of this not-so-rare syndrome.

Introduction A long dwell time is associated with higher inferior vena cava (IVC) filter retrieval complication rates. Manufacturers advise that “excessive force should not be used” during filter retrieval; however, the term “excessive” is subjective and is likely to lead to variability amongst operators. The aims of this study were to 1) ascertain what interventional radiologists consider to be excessive force during filter retrieval and 2) to understand the variability in interventional radiologists’ perception of force. Methods The authors recruited interventional radiologists to perform a benchtop simulated filter retrieval. Participants were invited to pull on a modified force tester attached to a Gunther Tulip filter retrieval set (GTRS). The participants were asked to pull as if they were retrieving an IVC filter and stop when they felt it was clinically unsafe to apply greater force. They were then asked to replicate forces of 10N and 50N, respectively. Each of the three tasks was completed three times. Data were obtained on the clinical experience of the participants with specific questions focusing on their filter retrieval practices. Results The range of maximum forces applied during filter retrieval varied between 0.8 and 79.8N. When asked to replicate 10N and 50N, for attempt-1, the median forces produced were 23.5N and 38.1N, respectively. A trend analysis showed that those who overestimate 10N are more likely to apply a greater overall maximum force (rs = 0.622; P Conclusion There is wide variation in what interventional radiologists consider to be the maximum safe force to apply during IVC filter retrieval. Implications for practice Manufacturers and operators should consider methods in which only a safe range of forces can be applied during an IVC filter retrieval. Operators may wish to undertake ‘personal’ force calibration as part of training in interventional radiology.

Purpose The purpose of this study was to design, develop, and test geographic information systems (GIS) analytic methods for quantifying and characterizing catchment populations across all sites served by a radiology global health organization. Methods The analysis included populations served by 78 low-resource medical facilities in 32 countries partnered with radiology nonprofit organization, RAD-AID International. Three constraints were used to approximate patient catchment areas: (1) 1-hour driving time, (2) 1-hour walking time, and (3) 10-mile circular radius. GIS calculated populations within each constraint using publicly available geospatial input databases, including a global digital elevation model, population and land cover data, and road locations from OpenStreetMap. Demographic and health data from the World Health Organization were incorporated to provide further characteristics of covered populations. Results The total populations served by all RAD-AID sites as measured by driving time, walking time, and 10-mile radius were 189,241,193 (47.8% female), 26,190,117 (48.7% female), and 110,884,095 (48.1% female), respectively. For individual locations, median population within 1-hour driving time was 1,795,977 (range: 8,742-30,630,800), with an average life expectancy of 68.4 ± 5.8 years. Median child mortality before age 5 was 3.8% (range: 0.9%-8.3%), and median prevalence of human immunodeficiency virus infection was 3.1% (range: 0.7%-10.9%). Conclusion In this study, GIS provided a robust multisite analysis for estimating the potential global population reached by an international radiology outreach organization with targeted individual site measurements. Given heightened needs to accurately characterize global outreach populations, this GIS-based approach may be useful for analysis, outreach planning, and resource allocation among global health organizations.

Background: Despite advances in surgery and pharmacotherapy, there remains significant residual ischemic risk after coronary artery bypass grafting surgery. Methods: In REDUCE-IT (Reduction of Cardiovascular Events With Icosapent Ethyl–Intervention Trial), a multicenter, placebo-controlled, double-blind trial, statin-treated patients with controlled low-density lipoprotein cholesterol and mild to moderate hypertriglyceridemia were randomized to 4 g daily of icosapent ethyl or placebo. They experienced a 25% reduction in risk of a primary efficacy end point (composite of cardiovascular death, myocardial infarction, stroke, coronary revascularization, or hospitalization for unstable angina) and a 26% reduction in risk of a key secondary efficacy end point (composite of cardiovascular death, myocardial infarction, or stroke) when compared with placebo. The current analysis reports on the subgroup of patients from the trial with a history of coronary artery bypass grafting. Results: Of the 8179 patients randomized in REDUCE-IT, a total of 1837 (22.5%) had a history of coronary artery bypass grafting, with 897 patients randomized to icosapent ethyl and 940 to placebo. Baseline characteristics were similar between treatment groups. Randomization to icosapent ethyl was associated with a significant reduction in the primary end point (hazard ratio [HR], 0.76 [95% CI, 0.63–0.92]; P =0.004), in the key secondary end point (HR, 0.69 [95% CI, 0.56–0.87]; P =0.001), and in total (first plus subsequent or recurrent) ischemic events (rate ratio, 0.64 [95% CI, 0.50–0.81]; P =0.0002) compared with placebo. This yielded an absolute risk reduction of 6.2% (95% CI, 2.3%–10.2%) in first events, with a number needed to treat of 16 (95% CI, 10–44) during a median follow-up time of 4.8 years. Safety findings were similar to the overall study: beyond an increased rate of atrial fibrillation/flutter requiring hospitalization for at least 24 hours (5.0% vs 3.1%; P =0.03) and a nonsignificant increase in bleeding, occurrences of adverse events were comparable between groups. Conclusions: In REDUCE-IT patients with a history of coronary artery bypass grafting, treatment with icosapent ethyl was associated with significant reductions in first and recurrent ischemic events. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01492361.

Introduction Renal Doppler resistive index (RI) and pulsatility index (PI) values are potentially more sensitive at detecting renal abnormalities when compared to standard laboratory indices in patients with HIV/AIDS. To the best of our knowledge, there are no published research articles on renal Doppler indices and their correlation with laboratory indices of HIV sero-positive adult individuals. This study aimed to assess the renal function of HIV-sero-positive adults using RI and PI, and correlating these indices against laboratory values. Methods A prospective cross-sectional study was conducted from July 2019 to April 2020. A purposive sampling method was employed and included 396 HIV sero-positive adult individuals. Sampling for the renal RI and PI was performed at the level of the inter-lober arteries, in between the medullary pyramids. An RI value above 0.70 and a PI value above 1.56 were consider abnormal. Serum creatine and urea together with evidence of proteinuria were recorded at the time of scanning. Results Forty-three (10.9%) men had an abnormal RI, 32 (8.1%) had abnormal PI, five (2.5%) had abnormal creatinine, two (1%) abnormal urea and eight (4.1%) with proteinuria. In women, 29 (7.3%) had abnormal RI, 22 (5.6%) abnormal PI, four (2%) abnormal creatinine and urea and six (3%) had proteinuria. There was a statistically significant weak positive correlation between RI and PI and serum creatinine and urea (r > 0.2, P Conclusion The proportion of patients with abnormal RI and PI was higher than the proportion of participants with abnormal serum urea, creatinine and proteinuria. Renal Doppler indices could be used be used in the early assessment of renal function in HIV sero-positive adults individuals. Implications for practice Serum creatinine and urea are routinely used to evaluate renal function in patients with HIV/AIDS. Findings from this initial study show that RI and PI could be used detecting early renal abnormalities when compared to standard laboratory values.

Rheumatoid arthritis (RA) and its treatments are associated with an increased risk of infection, but it remains unclear whether these factors have an impact on the risk or severity of COVID-19. The present study was undertaken to assess the risk and severity of COVID-19 in a US Department of Veterans Affairs (VA) cohort of patients with RA and those without RA.A matched cohort study using national VA data was conducted. Patients diagnosed as having RA were identified among nondeceased individuals who were active in the VA health care system as of January 1, 2020 and who had received care in a VA medical center in 2019; patients for whom no RA diagnostic code was indicated were matched to the RA patients (1:1) by age, sex, and VA site (non-RA controls). Patients diagnosed as having COVID-19 and those with severe COVID-19 (defined as requiring hospitalization or leading to death) were ascertained from a national VA COVID-19 surveillance database through December 10, 2020. Multivariable Cox models were used to compare the risk of COVID-19 and COVID-19 hospitalization or death between RA patients and non-RA controls, after adjusting for demographic characteristics, comorbidities, health care utilization and access, and county-level COVID-19 incidence rates.This VA cohort of RA patients and non-RA controls (n = 33,886 subjects per group) predominantly comprised male patients (84.5%), and the mean age was 67.8 years. During follow-up, 1,503 patients in the cohort were diagnosed as having COVID-19; among them, 388 patients had severe COVID-19 (hospitalization or death), while in 228 patients, the deaths were not related to COVID-19. In the multivariable model, RA was associated with a higher risk of COVID-19 (adjusted hazard ratio [HR] 1.25 [95% confidence interval (95% CI) 1.13-1.39]) and a higher risk of COVID-19 hospitalization or death (adjusted HR 1.35 [95% CI 1.10-1.66]) as compared to non-RA controls. Use of disease-modifying antirheumatic drugs and prednisone, as well as self-reported Black race, self-reported Hispanic ethnicity, and presence of several chronic conditions, but not seropositivity for RA autoantibodies, were each associated with risk of COVID-19 and severe COVID-19 (hospitalization or death).Patients with RA are at higher risk of developing COVID-19 and severe COVID-19 (leading to hospitalization or death) compared to those without RA. With a risk of COVID-19 that approaches that of other recognized chronic conditions, these findings suggest that RA patients should be prioritized for COVID-19 prevention and management strategies.

We describe a computer-assisted program for conducting well-body assessments of children with neurodevelopmental disabilities attending a private special education school. Classroom instructors completed daily assessments to detect the presence of bodily injuries and other skin trauma, determine the need for medical treatment, and monitor healing status. Evaluations performed with the classroom instructors revealed that they implemented the program with high integrity and rated several procedural components favorably. Compared to “paper form” data recording, clinicians and supervisors judged the computer-assisted program to track student injuries more thoroughly and record student injuries more accurately. The importance of health monitoring among persons with neurodevelopmental disabilities, advantages of technology-based assessment methods, and practice considerations are discussed.

BACKGROUND: Clinical vestibular technology is rapidly evolving to improve objective assessments of vestibular function. Understanding the reliability and expected score ranges of emerging clinical vestibular tools is important to gauge how these tools should be used as clinical endpoints. OBJECTIVE: The objective of this study was to evaluate inter-rater and test-retest reliability intraclass correlation coefficients (ICCs) of four vestibular tools and to determine expected ranges of scores through smallest real difference (SRD) measures. METHODS: Sixty healthy graduate students completed two 1-hour sessions, at most a week apart, consisting of two video head-impulse tests (vHIT), computerized dynamic visual acuity (cDVA) tests, and a smartphone-assisted bucket test (SA-SVV). Thirty students were tested by different testers at each session (inter-rater) and 30 by the same tester (test-retest). ICCs and SRDs were calculated for both conditions. RESULTS: Most measures fell within the moderate ICC range (0.50–0.75). ICCs were higher for cDVA in the inter-rater subgroup and higher for vHITs in the test-retest subgroup. CONCLUSIONS: Measures from the four tools evaluated were moderately reliable. There may be a tester effect on reliabilities, specifically vHITs. Further research should repeat these analyses in a patient population and explore methodological differences between vHIT systems.

The hormone oxytocin is commonly administered during childbirth to initiate and strengthen uterine contractions and prevent postpartum hemorrhage. However, patients have wide variation in the oxytocin dose required for a clinical response. To begin to uncover the mechanisms underlying this variability, we screened the 11 most prevalent missense genetic variants in the oxytocin receptor (OXTR) gene. We found that five variants, V45L, P108A, L206V, V281M, and E339K, significantly altered oxytocin-induced Ca2+ signaling or β-arrestin recruitment and proceeded to assess the effects of these variants on OXTR trafficking to the cell membrane, desensitization, and internalization. The variants P108A and L206V increased OXTR localization to the cell membrane, whereas V281M and E339K caused OXTR to be retained inside the cell. We examined how the variants altered the balance between OXTR activation and desensitization, which is critical for appropriate oxytocin dosing. The E339K variant impaired OXTR activation, internalization, and desensitization to roughly equal extents. In contrast, V281M decreased OXTR activation but had no effect on internalization and desensitization. V45L and P108A did not alter OXTR activation but did impair β-arrestin recruitment, internalization, and desensitization. Molecular dynamics simulations predicted that V45L and P108A prevent extension of the first intracellular loop of OXTR, thus inhibiting β-arrestin binding. Overall, our data suggest mechanisms by which OXTR genetic variants could alter clinical response to oxytocin.

Chronic kidney disease (CKD) and end stage renal disease (ESRD) are increasingly frequent and devastating conditions that have driven a surge in the need for kidney transplantation. A stark shortage of organs has fueled interest in generating viable replacement tissues ex vivo for transplantation. One promising approach has been self-organizing organoids, which mimic developmental processes and yield multicellular, organ-specific tissues. However, a recognized roadblock to this approach is that many organoid cell types fail to acquire full maturity and function. Here, we comprehensively assess the vasculature in two distinct kidney organoid models as well as in explanted embryonic kidneys. Using a variety of methods, we show that while organoids can develop a wide range of kidney cell types, as previously shown, endothelial cells (ECs) initially arise but then rapidly regress over time in culture. Vasculature of cultured embryonic kidneys exhibit similar regression. By contrast, engraftment of kidney organoids under the kidney capsule results in the formation of a stable, perfused vasculature that integrates into the organoid. This work demonstrates that kidney organoids offer a promising model system to define the complexities of vascular-nephron interactions, but the establishment and maintenance of a vascular network present unique challenges when grown ex vivo.

OBJECTIVE The present study was undertaken to evaluate whether the rate of incident chronic opioid use is higher in obese patients with rheumatoid arthritis (RA). METHODS Participants with RA in the FORWARD databank were asked about their use of weak and strong opioid medications on semiannual surveys. Incident chronic opioid use was defined as new reported use extending over 2 contiguous surveys (~7-12 months). Cox proportional hazards models were used to evaluate associations between body mass index (BMI) at enrollment and incident chronic opioid use (overall use and strong opioid use). Models adjusted for demographics, smoking, disease duration, RA treatments, household income, and education level. The predicted 5-year cumulative incidence was calculated from Cox models. RESULTS Among 19,794 participants, 2,802 experienced an incident episode of chronic opioid use over 93,254 person-years of follow-up. Higher BMI was associated with higher risk of chronic opioid use. Severe obesity (BMI >35 kg/m2 ) was associated with a higher risk of overall use (adjusted hazard ratio [HRadj ] 1.74 [95% confidence interval (95% CI) 1.72-2.04], P < 0.0001) and strong opioid use (HRadj 2.11 [95% CI 1.64-2.71], P < 0.001) compared to normal BMI. This association was partially explained by greater comorbidity, pain, and disability in obese groups. The attributable risk for obesity was 15% of overall opioid use and 24% of strong opioid use. CONCLUSION Obesity is associated with a substantially higher risk of incident chronic opioid use. Approximately 1 in 4 cases of incident use of strong opioids may be attributable to obesity, suggesting a major public health impact. Interventions to prevent or reduce obesity could have an important impact on the use of opioids.

OBJECTIVE: BCORL1, a transcriptional co-repressor, has a role in cortical migration, neuronal differentiation, maturation, and cerebellar development. We describe BCORL1 as a new genetic cause for major brain malformations. METHODS AND RESULTS: We report three patients from two unrelated families with neonatal onset intractable epilepsy and profound global developmental delay. Brain MRI of two siblings from the first family depicted hypoplastic corpus callosum and septal agenesis (ASP) in the older brother and unilateral perisylvian polymicrogyria (PMG) in the younger one. MRI of the patient from the second family demonstrated complete agenesis of corpus callosum (CC). Whole Exome Sequencing revealed a novel hemizygous variant in NM_021946.5 (BCORL1):c.796C>T (p.Pro266Ser) in the two siblings from the first family and the NM_021946.5 (BCORL1): c.3376G>A; p.Asp1126Asn variant in the patient from the second family, both variants inherited from healthy mothers. We reviewed the patients’ charts and MRIs and compared the phenotype to the other published BCORL1-related cases. Brain malformations have not been previously described in association with the BCORL1 phenotype. We discuss the potential influence of BCORL1 on brain development. CONCLUSIONS: We suggest that BCORL1 variants present with a spectrum of neurodevelopmental disorders and can lead to major brain malformations originating at different stages of fetal development. We suggest adding BCORL1 to the genetic causes of PMG, ASP, and CC dysgenesis.

The United Kingdom has one of the poorest lung cancer survival rates in Europe. In this study, to help design and evaluate a single lung cancer pathway (SCP) for Wales, existing diagnostic pathways and processes have been mapped and then modelled with a discrete event simulation. The validated models have been used to provide key performance indicators and to examine different diagnostic testing strategies. Under the current diagnostic pathways, the mean time to treatment was 72 days for surgery patients, 56 days for chemotherapy patients, and 61 days for radiotherapy patients. Our research demonstrated that by ensuring that the patient attends their first outpatient appointment within 7 days and streamlining the diagnostic tests would have the potential to remove approximately 11 days from the current lung cancer pathway resulting in a 21% increase in patients receiving treatment within the Welsh Government set target of 62 days.

Inflammatory pseudotumor is a term used to designate inflammation-rich tumefactive lesions. Following the exclusion of specific entities such as IgG4-related disease and other neoplastic entities previously included in this entity, the majority of hepatic pseudotumors show a prominent fibrohistiocytic inflammatory reaction and have been previously categorized as fibrohistiocytic variant of hepatic pseudotumor (FHVHPT). The goal of this study was to examine the clinical, radiologic, histologic, and etiologic aspects of this entity. After excluding neoplastic diseases, we identified 30 patients with FHVHPT from 3 institutions between 2009 and 2019. We extracted demographic and clinical data, liver function tests as well as culture results and radiologic information. Hematoxylin and eosin-stained slides were reviewed for pattern of inflammation as well as its cellular composition. Immunohistochemistry for IgG4 and IgG was performed in all cases. The mean age of the 30 lesions characterized as FHVHPT was 56 years (range: 23 to 79 y). Nineteen patients showed solitary lesions; 11 were multiple. The mean size of the lesion was 3.8 cm (range: 1 to 7.5 cm). On imaging, a neoplastic process or metastasis was the leading diagnostic consideration (n=15, 50%). The most common symptom was abdominal pain (n=14/30); 8 patients presented with symptoms compatible with an infectious process, including fever. The inflammatory infiltrate was dominated by lymphocytes and plasma cells, and in most cases, a prominent histiocytic infiltrate (22/30). Neutrophils were identified in 12 cases, with microabscess noted in 8. Storiform pattern of fibrosis was seen in 14/30 cases; obliterative phlebitis was not identified. Culture identified a microorganism in 4 of 9 cases evaluated. The mean IgG4 count was 9.3 per HPF (range: 0 to 51) with 9 of the 26 (35%) biopsies showing >10 IgG4 positive plasma cells per HPF. The mean IgG4 to IgG ratio was 8% (range: 8% to 46%). A hepatectomy was performed in 4 cases. On broad spectrum antibiotics (n=14) the lesions either resolved or decreased in size. Eight patients did not receive specific therapy, nevertheless, the lesion(s) resolved spontaneously in 6 cases, remained stable or decreased in size in 2 cases. Notably, none of these patients showed evidence of a hepatic recurrence. FHVHPT, a tumefactive lesion that mimics hepatic neoplasia, is histologically characterized by a fibrohistiocytic infiltrate. In the majority of patients FHVHPT represents the organizing phase of hepatic abscess and can be successfully managed with antibiotic therapy.

Background: Cocaine is a stimulant and Schedule II drug used as a local anesthetic and vasoconstrictor. Objective: This descriptive study characterized medical cocaine use in the United States. Methods: Retail drug distribution data from 2002 to 2017 were extracted for each state from the Drug Enforcement Administration, which reports on medical, research, and analytical chemistry use. The percentage of buyers (pharmacies, hospitals, and providers) was obtained. Use per state, corrected for population, was determined. Available cross-sectional data on cocaine use as reported by the Medicare and Medicaid programs for 2013-2017 and electronic medical records were examined. Results: Medical cocaine use decreased by −62.5% from 2002 to 2017. Hospitals accounted for 84.9% and practitioners for 9.9% of cocaine distribution in 2017. The number of pharmacies carrying cocaine dropped by −69.4%. The percentages of hospitals, practitioners, and pharmacies that carried cocaine in 2017 were 38.4%, 2.3%, and 0.3%, respectively. There was a 7-fold difference in 2002 (South Dakota, 76.1 mg/100 persons; Delaware, 10.1 mg/100 persons). Relative to the average state in 2017, those reporting the highest values (Montana, 20.1; North Dakota, 24.1 mg/100 persons) were significantly elevated. Cocaine use within the Medicare and Medicaid programs was negligible. Cocaine use within the Geisinger system was rare from 2002 to 2007 (

ZusammenfassungPermanentmagneterregte Synchronmaschinen werden im Bereich der Traktionsmaschinen in der Regel mit einer Rotorstaffelung ausgeführt, d. h. der Rotor wird ähnlich wie bei der Nutschrägung entlang des Blechpakets segmentweise um insgesamt eine Nutteilung am Umfang versetzt, um Parasitäreffekte wie Drehmomentwelligkeit zu reduzieren und das akustische Verhalten zu verbessern. Allerdings wird durch die Staffelung der Rotorsegmente in axialer Richtung die Hauptwellenflussverkettung der Permanentmagnete gegenüber einer ungestaffelten Maschine verringert. Daher muss in einer gestaffelten Maschine mehr Magnetmaterial eingesetzt werden als in einer ungestaffelten Maschine, um das gleiche Drehmoment zu erreichen, was sich in den Kosten niederschlägt. Darüber hinaus ist die Staffelung ein vergleichsweise aufwendiger Schritt im Fertigungsprozess, sodass sich die Produktionszeit je Maschine erhöht und letztendlich die Kosten steigen.In diesem Artikel wird der Einfluss einer Rotorpolweitenmodulation auf das Betriebsverhalten für V-förmig vergrabene Magnettopologien untersucht. Es wird bewertet, ob mithilfe dieser zusätzlichen Modifikation der Maschinengeometrie ein Antrieb ohne Staffelung ausgeführt werden kann, der die Vorgaben des Lastenhefts in Bezug auf die Drehmomentwelligkeit sowie auf das maximale Drehmoment einhält und gleichzeitig die Geräuschemissionen begrenzt. Zur vorteilhaften Gestaltung einer Rotorpolweitenmodulation wird eine Kombination der Magnetöffnungswinkel mittels eines analytischen Netzwerks identifiziert, die die für die Anregung von Pendelmomenten und Geräuschen kritischen Feldwellen des Rotors reduzieren kann. Anschließend werden die analytischen Ergebnisse mit FEM-Berechnungen validiert. Der Einfluss der Rotorpolweitenmodulation auf das Drehmomentverhalten sowie die Geräuschanregung wird mit der gestaffelten Referenzmaschine verglichen.

Background Direct mechanical thrombectomy may result in similar outcomes compared to a bridging approach with intravenous thrombolysis (IVT + MT) in acute ischemic stroke. Recent randomized controlled trials have varied in their design and noninferiority margin. Aim We sought to meta-analyze accumulated trial data to assess the difference and non-inferiority in clinical and procedural outcomes between direct mechanical thrombectomy and bridging therapy. Summary of review We conducted a systematic review of electronic databases following the preferred reporting items for systematic reviews and meta-analyses guidelines. Random effects meta-analyses were conducted for the pooled data. The primary outcome was good functional outcome at 90 days (modified Rankin scale (mRS) ≤ 2). Secondary outcomes included excellent functional outcome (mRS ≤ 1), mortality, any intracranial hemorrhage, symptomatic intracranial hemorrhage, successful reperfusion (thrombolysis in cerebral infarction ≥ 2 b), and procedure-related complications. Four randomized controlled trials comprising 1633 patients (817 direct mechanical thrombectomy, 816 bridging therapy) were included. There were no statistical differences for the 90-day good functional outcome (OR = 1.02, 95% CI 0.84–1.25, p = 0.54, I2 = 0%), and the absolute risk difference was 1% (95% CI: −4% to 5%). The lower 95% CI falls within the strictest noninferiority margin of −10% among included randomized control trials. Direct mechanical thrombectomy reduced the odds of successful reperfusion (OR = 0.76, 95% CI: 0.60–0.97, p = 0.03, I2 = 0%) and any intracranial hemorrhage (OR = 0.65, 95% CI: 0.49–0.86, p = 0.003, I2 = 38%). There was no difference in the remaining secondary outcomes. The risk of bias for all studies was low. Conclusion The combined trial data assessing direct mechanical thrombectomy versus bridging therapy showed no difference in improving good functional outcome. The wide noninferiority thresholds set by individual trials are in contrast with the clinical consensus on minimally important differences. However, our pooled analysis indicates noninferiority of direct mechanical thrombectomy with a 4% margin of confidence. The application of these findings is limited to patients presenting directly to mechanical thrombectomy-capable centers and real-world workflow times may differ against those achieved in a trial setting.

BACKGROUND: Opioid use after surgery is associated with increased health care utilization and costs. Although some studies show that surgical patients may later become persistent opioid users, data on the association between new persistent opioid use after surgery and health care utilization and costs are lacking. OBJECTIVE: To compare health care utilization and costs after major inpatient or METHODS: The IBM MarketScan Research databases were used to identify opioid-naive patients with major inpatient or outpatient surgeries and at least 1 year of continuous enrollment before and after this index surgery. Cohorts were stratified by new persistent opioid utilization status, setting of surgery (inpatient, outpatient), and payer (commercial, Medicare, Medicaid). Patients were considered new persistent opioid users if they had at least 1 opioid claim 4-90 days after index surgery and at least 1 opioid claim 91-180 days after index surgery. Patients with opioid prescription claims between 1 year and 15 days before their index event were excluded. Health care utilization and costs (excluding index surgery) were measured in the 1-year period after surgery. Predicted costs and cost ratios were estimated using multivariable log-linked gamma-family generalized linear models. RESULTS: In the inpatient cohorts, 827,583 commercial, 186,154 Medicare, and 104,734 Medicaid patients were included in the study, and the incidence of new persistent opioid use in these cohorts was 4.1%, 5.6%, and 7.1%, respectively. In the outpatient cohorts, 1,542,565 commercial, 390,876 Medicare, and 94,878 Medicaid patients were selected, with 2.0%, 1.5%, and 6.4% new persistent opioid use, respectively. Across all 3 payers in both surgical settings, patients with new persistent opioid use had a higher comorbidity burden and more use of concomitant medications in the baseline period. In the 1-year period after index surgery, patients with new persistent opioid use had more inpatient admissions, emergency department visits, and ambulance/paramedic service use than patients without persistent use, regardless of payer and setting. Patients with new persistent opioid use had approximately 5 times more opioid prescriptions and also had more nonopioid pharmacy claims than those without persistent use across all cohorts. After covariate adjustment, predicted 1-year total health care costs were significantly higher for patients with new persistent opioid use compared with those without persistent use for all comparisons (commercial inpatient: $29,499 vs. $11,798; Medicare inpatient: $34,455 vs. $21,313; Medicaid inpatient: $14,622 vs. $6,678; commercial outpatient: $18,751 vs. $7,517; Medicare outpatient ($26,411 vs. $13,577; Medicaid outpatient: $12,381 vs. $6,784; all P < 0.001). CONCLUSIONS: New persistent opioid use after major surgery in opioid-naive patients is associated with increased health care utilization and costs in the year after surgery across all surgical settings and payers. DISCLOSURES: Funding for this study was provided by Heron Therapeutics, which participated in analysis and interpretation of data, drafting, reviewing, and approving the publication. All authors contributed to the analysis and interpretation of the data and development of the publication and maintained control over the final content. England and Evans-Shields are employees of Heron Therapeutics. Kong, Lew, Zimmerman, and Henriques are employees of IBM Watson Health, which was compensated by Heron Therapeutics for conducting this research. Brummett is a paid consultant for Heron Therapeutics, Vertex Pharmaceuticals, and Alosa Health and provides expert testimony. He further reports receipt of research funding from MDHHS (Sub K Michigan Open), NIDA (Centralized Pain Opioid Non-Responsiveness R01 DA038261-05), NIH0DHHS-US-16 PAF 07628 (R01 NR017096-05), NIH-DHHS (P50 AR070600-05 CORT), NIH-DHHS-US (K23 DA038718-04), NIH-DHHS-US-16-PAF06270 (R01 HD088712-05), NIH-DHHS-US-17-PAF02680 (R01 DA042859-05), and UM Michigan Genomics Initiative and holds a patent for peripheral perineural dexmedetomidine. Sun reports funding from the National Institute on Drug Abuse (K08DA042314) as well as consulting fees from the Mission Lisa Foundation that are unrelated to this work.

Background and purpose Comprehensive swallow screening assessments to identify dysphagia and make early eating and drinking recommendations can be used by trained nurses. This study aimed to validate the Dysphagia Trained Nurse Assessment (DTNAx) tool in acute stroke patients. Methods Participants with diagnosed stroke were prospectively and consecutively recruited from an acute stroke unit. Following a baseline DTNAx on admission, participants underwent a speech and language therapist (SLT) bedside assessment of swallowing (speech and language therapist assessment [SLTAx]), videofluoroscopy (VFS) and a further DTNAx by the same or a different nurse. Results Forty-seven participants were recruited, of whom 22 had dysphagia. Compared to SLTAx in the identification of dysphagia, DTNAx had a sensitivity of 96.9% (95% confidence interval [CI] 83.8–99.9) and specificity of 89.5% (95% CI 75.2–97.1). Compared to VFS in the identification of aspiration, DTNAx had a sensitivity of 77.8% (95% CI 40.0–97.2) and a specificity of 81.6% (95% CI 65.7–92.3). Over 81% of the diet and fluid recommendations made by the dysphagia trained nurses were in absolute agreement compared to SLTAx. Both DTNAx and SLTAx had low diagnostic accuracy compared to the VFS-based definition of dysphagia. Conclusions Nurses trained in DTNAx showed good diagnostic accuracy in identifying dysphagia compared to SLTAx and in identifying aspiration compared to VFS. They made appropriate diet and fluid recommendations in line with SLTs in the early management of dysphagia.

OBJECTIVE The objective of this review was to identify and map the evidence for oral dietary management of ileostomies. INTRODUCTION Dietary advice is commonly provided for ileostomy management but can be inconsistent, conflicting, and inadequate. There is a lack of high-quality research investigating dietary management of ileostomies. This scoping review highlights gaps in the literature that need addressing to inform practice, and identifies dietary strategies and outcomes to be investigated in future studies. INCLUSION CRITERIA Evidence relating to the use of oral dietary strategies to manage complications and nutritional consequences associated with having an ileostomy was included. Evidence included all types of original research (ie, quantitative and qualitative methodologies, expert opinion articles, and consensus guidelines). METHODS This review followed JBI methodology for scoping reviews. A pre-determined search of 13 databases, including MEDLINE, Embase, and Web of Science, was conducted in August 2019. The search was not limited by date, but during screening, expert opinion evidence was limited to 2008 onward. Data extraction was carried out by two reviewers for each study/article using a database tool designed specifically for this review. Results are presented using a combination of tabular summaries and narrative reports. RESULTS Thirty-one research studies were included: 11 experimental (including four crossover randomized controlled trials), three pre-post design, 13 observational (12 cross-sectional, one longitudinal), and four qualitative. Forty-four expert opinion articles/guidelines were also included. In experimental studies, nine nutrient modifications and 34 individual foods/drinks were investigated. In pre-post studies, 10 nutrient modifications, 80 foods/drinks, and 11 eating-related behaviors were investigated. In observational studies, eight nutrient modifications, 94 foods/drinks, and five eating-related behaviors were reported. In qualitative studies, two nutrient modifications, 17 foods/drinks, and one eating-related behavior were reported. In expert opinion articles/guidelines, recommendations relating to 51 nutrient modifications, 339 foods/drinks, and 23 eating-related behaviors were reported. Although large numbers of individual foods and drinks were suggested to be associated with outcomes relating to ileostomy management, findings from observational studies showed these were generally reported by

We compared the characteristics of hospitalized and nonhospitalized patients who had coronavirus disease in Atlanta, Georgia, USA. We found that risk for hospitalization increased with a patient's age and number of concurrent conditions. We also found a potential association between hospitalization and high hemoglobin A1c levels in persons with diabetes.

Purpose Geographic information systems (GIS) are widely used in public health research but rarely used in radiology research. GIS can be an impactful tool in radiology global health to locate medically underserved populations and poor transportation infrastructure, characterize medical needs, and design outreach programs. Using the example of aircraft-based outreach in Alaska, we demonstrate the utility of GIS in radiological program planning for global health. Methods Multicriteria GIS evaluations were performed to create a health severity index, using life expectancy and percentage uninsured data, and an accessibility severity index, using distance from roads and health centers or hospitals. These indices were combined with population density to create a final health access severity index (HASI). A map presenting suitable hybrid airship operating areas was produced using land cover data. Alaskan health care facilities were georeferenced to create a coordinate data set. Infrastructure was obtained from OpenStreetMap. Health data were accessed from the 2017 American Community Survey and CDC US Small-area Life Expectancy Estimates Project. Results GIS analyzed 738,050 Alaskans. The health severity index identified decreased health outcomes (high or very high severity) in 285,446 (39%) Alaskans, and the accessibility severity index determined decreased access to care in 218,201 (30%). Combined, the HASI established 165,108 (22%) Alaskans as underserved with high or very high overall severity. Thirty-nine percent of Alaska land area is suitable for hybrid airship operations, including 27% of HASI high and very high severity areas. Conclusions GIS identified underserved populations for mobile radiology outreach in Alaska and may be useful for global health outreach planning and resource allocation.

Surgeons are privileged to offer treatments that often cure disease. Optimizing comfort for those who cannot be cured is also a core part of every clinician's duty: surveys repeatedly tell us that when death is approaching, people value quality of life above length of survival. Recognizing when someone is dying can be difficult. Tools exist to help; it is worth noting that emergency presentation with life-threatening symptoms can be a marker of poor prognosis. Clear, effective communication is crucial: understanding the patient's perspective and expectations is vital before attempting to offer information that allows future care planning. Judicious use of surgery combined with careful prescribing will optimize comfort, allowing the patient to live as well as possible for as long as possible. Anticipatory prescribing includes opioid, anti-emetic, anti-secretory and sedative medication. Attention should also be given to care of the bereaved. Generalists should understand when to refer to specialist palliative care and remember that reflecting on care when someone has died can be beneficial for professional wellbeing.

Contains fulltext : 235277.pdf (Publisher’s version ) (Closed access) BACKGROUND: Balancing the risks of recurrent ischaemic stroke and intracranial haemorrhage is important for patients treated with antithrombotic therapy after ischaemic stroke or transient ischaemic attack. However, existing predictive models offer insufficient performance, particularly for assessing the risk of intracranial haemorrhage. We aimed to develop new risk scores incorporating clinical variables and cerebral microbleeds, an MRI biomarker of intracranial haemorrhage and ischaemic stroke risk. METHODS: We did a pooled analysis of individual-patient data from the Microbleeds International Collaborative Network (MICON), which includes 38 hospital-based prospective cohort studies from 18 countries. All studies recruited participants with previous ischaemic stroke or transient ischaemic attack, acquired baseline MRI allowing quantification of cerebral microbleeds, and followed-up participants for ischaemic stroke and intracranial haemorrhage. Participants not taking antithrombotic drugs were excluded. We developed Cox regression models to predict the 5-year risks of intracranial haemorrhage and ischaemic stroke, selecting candidate predictors on biological relevance and simplifying models using backward elimination. We derived integer risk scores for clinical use. We assessed model performance in internal validation, adjusted for optimism using bootstrapping. The study is registered on PROSPERO, CRD42016036602. FINDINGS: The included studies recruited participants between Aug 28, 2001, and Feb 4, 2018. 15 766 participants had follow-up for intracranial haemorrhage, and 15 784 for ischaemic stroke. Over a median follow-up of 2 years, 184 intracranial haemorrhages and 1048 ischaemic strokes were reported. The risk models we developed included cerebral microbleed burden and simple clinical variables. Optimism-adjusted c indices were 0·73 (95% CI 0·69-0·77) with a calibration slope of 0·94 (0·81-1·06) for the intracranial haemorrhage model and 0·63 (0·62-0·65) with a calibration slope of 0·97 (0·87-1·07) for the ischaemic stroke model. There was good agreement between predicted and observed risk for both models. INTERPRETATION: The MICON risk scores, incorporating clinical variables and cerebral microbleeds, offer predictive value for the long-term risks of intracranial haemorrhage and ischaemic stroke in patients prescribed antithrombotic therapy for secondary stroke prevention; external validation is warranted. FUNDING: British Heart Foundation and Stroke Association.

Aim This study aimed to investigate the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection on all types of acute cardiac admissions (ACAs) and cardiac mortality in Malta. Methods Number, characteristics and delay to presentation of ACAs to our institution during the study period (28 February–30 April 2020) were compared with the corresponding 2019 period. Non-parametric correlation analyses between daily SARS-CoV-2 cases in Malta, Italy and the UK and daily ACAs were performed. Differences in cardiac death distribution (community vs. in-hospital) during the two periods were analysed. Results There was a significant decline in daily ACAs in 2020 (median 3 [IQR 3]) vs. 2019 (median 5 [IQR 4]), p

Despite strong evidence of heritability and growing discovery of genetic markers for major mental illness, little is known about how gene expression in the brain differs across psychiatric diagnoses, or how known genetic risk factors shape these differences. Here we investigate expressed genes and gene transcripts in postmortem subgenual anterior cingulate cortex (sgACC), a key component of limbic circuits linked to mental illness. RNA obtained postmortem from 200 donors diagnosed with bipolar disorder, schizophrenia, major depression, or no psychiatric disorder was deeply sequenced to quantify expression of over 85,000 gene transcripts, many of which were rare. Case–control comparisons detected modest expression differences that were correlated across disorders. Case–case comparisons revealed greater expression differences, with some transcripts showing opposing patterns of expression between diagnostic groups, relative to controls. The ~250 rare transcripts that were differentially-expressed in one or more disorder groups were enriched for genes involved in synapse formation, cell junctions, and heterotrimeric G-protein complexes. Common genetic variants were associated with transcript expression (eQTL) or relative abundance of alternatively spliced transcripts (sQTL). Common genetic variants previously associated with disease risk were especially enriched for sQTLs, which together accounted for disproportionate fractions of diagnosis-specific heritability. Genetic risk factors that shape the brain transcriptome may contribute to diagnostic differences between broad classes of mental illness.

Immune checkpoint inhibitors (ICIs) are becoming the standard of care treatment for many malignancies. ICIs are associated with a unique spectrum of immune-related adverse events (irAEs) due to the blockade of inhibitory signals of immune activation. The main objective of this study is to review the characteristic histological features and pathologic differential diagnosis of ICI-related injury of the gastrointestinal (GI) tract and hepatobiliary system. Diarrhea and hepatitis are some of the more common irAEs. The pathology of ICI-related injury is both diverse and largely non-specific, with various site-specific findings to become familiar with. Early and accurate recognition of an irAE is important in order to initiate proper management. This generally includes withdrawal of ICI therapy, and possibly the administration of a corticosteroid or other immunosuppressives depending on the severity of injury.

Key Points Question What genetic variants are associated with juvenile amyotrophic lateral sclerosis (ALS)? Findings In this family-based genetic study, exome sequencing was performed in 3 patients diagnosed with juvenile ALS and failure to thrive; this identified de novo variants in SPTLC1 (p.Ala20Ser in 2 patients and p.Ser331Tyr in 1 patient). Variants in SPTLC1 are a known cause of hereditary sensory and autonomic neuropathy, type 1A, and these data extend the phenotype associated with this gene. Meaning De novo variants in the SPTLC1 gene are associated with juvenile ALS, a fatal neurological disorder., This genetic association study identifies genetic variants associated with juvenile amyotrophic lateral sclerosis., Importance Juvenile amyotrophic lateral sclerosis (ALS) is a rare form of ALS characterized by age of symptom onset less than 25 years and a variable presentation. Objective To identify the genetic variants associated with juvenile ALS. Design, Setting, and Participants In this multicenter family-based genetic study, trio whole-exome sequencing was performed to identify the disease-associated gene in a case series of unrelated patients diagnosed with juvenile ALS and severe growth retardation. The patients and their family members were enrolled at academic hospitals and a government research facility between March 1, 2016, and March 13, 2020, and were observed until October 1, 2020. Whole-exome sequencing was also performed in a series of patients with juvenile ALS. A total of 66 patients with juvenile ALS and 6258 adult patients with ALS participated in the study. Patients were selected for the study based on their diagnosis, and all eligible participants were enrolled in the study. None of the participants had a family history of neurological disorders, suggesting de novo variants as the underlying genetic mechanism. Main Outcomes and Measures De novo variants present only in the index case and not in unaffected family members. Results Trio whole-exome sequencing was performed in 3 patients diagnosed with juvenile ALS and their parents. An additional 63 patients with juvenile ALS and 6258 adult patients with ALS were subsequently screened for variants in the SPTLC1 gene. De novo variants in SPTLC1 (p.Ala20Ser in 2 patients and p.Ser331Tyr in 1 patient) were identified in 3 unrelated patients diagnosed with juvenile ALS and failure to thrive. A fourth variant (p.Leu39del) was identified in a patient with juvenile ALS where parental DNA was unavailable. Variants in this gene have been previously shown to be associated with autosomal-dominant hereditary sensory autonomic neuropathy, type 1A, by disrupting an essential enzyme complex in the sphingolipid synthesis pathway. Conclusions and Relevance These data broaden the phenotype associated with SPTLC1 and suggest that patients presenting with juvenile ALS should be screened for variants in this gene.

OBJECTIVE. To determine the association of inhalant exposures with rheumatoid arthritis (RA)–related autoantibodies and severity in US veterans. METHODS. Participants in the Veterans Affairs Rheumatoid Arthritis (VARA) registry were mailed surveys assessing occupational, agricultural, and military inhalant exposures. Demographic characteristics, disease activity, functional status, and extraarticular features were obtained from the VARA registry, while HLA–DRB1 shared epitope (SE) status, anti–cyclic citrullinated peptide (anti-CCP) antibodies, and rheumatoid factor (RF) were measured using banked DNA/serum from enrollment. Associations between inhalant exposures and RA-related factors (autoantibodies, severity, and extraarticular features) were assessed using multivariable linear and logistic regression models adjusted for age, sex, race, and tobacco use and stratified by SE status. Adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated. RESULTS. Questionnaires were returned by 797 of 1,566 participants (50.9%). Survey respondents were older, more often White or male, and less frequently smokers, and had lower disease activity compared to nonrespondents. Anti-CCP positivity was more common among veterans exposed to burn pits (OR 1.66 [95% CI 1.02, 2.69]) and military waste disposal (OR 1.74 [95% CI 1.04, 2.93]) independent of other factors. Among participants who were positive for SE alleles, burn pit exposure (OR 5.69 [95% CI 2.73, 11.87]) and military waste disposal exposure (OR 5.05 [95% CI 2.42, 10.54]) were numerically more strongly associated with anti-CCP positivity. Several inhalant exposures were associated with the presence of chronic lung disease, but not with the presence of RF or the level of disease activity. CONCLUSION. Military burn pit exposure and military waste disposal exposure were independently associated with the presence of anti-CCP antibodies in RA patients. These findings are consistent with emerging evidence that various inhalant exposures influence autoantibody expression and RA risk.

PurposeRheumatoid arthritis (RA) is associated with a higher risk of diabetes mellitus (DM). Our aim was to determine associations between inflammatory disease activity (including evaluation of specific cytokines and chemokines) and incident DM.MethodsParticipants were adults with physician-confirmed RA from Veteran’s Affairs Rheumatoid Arthritis Registry. Disease activity and clinical assessments occur longitudinally as part of clinical care. Thirty cytokines and chemokines were measured in banked serum obtained at the time of enrolment. Cytokine/chemokine values were log-adjusted and standardised (per SD). Incident DM was defined based on validated algorithms using diagnostic codes and medications. Multivariable Cox proportional hazard models evaluated associations between clinical factors and incident DM. Independent associations between cytokines/chemokines and incident DM were assessed adjusting for age, sex, race, smoking, body mass index (BMI) and medication use at baseline.ResultsAmong 1866 patients with RA without prevalent DM at enrolment, there were 130 incident cases over 9223 person-years of follow-up. High Disease Activity Score (DAS28)-C reactive protein (CRP), obese BMI, older age and male sex were associated with greater risk for incident DM while current smoking and methotrexate use were protective. Patients using methotrexate were at lower risk. Several cytokines/chemokines evaluated were independently associated (per 1 SD) with DM incidence including interleukin(IL)-1, IL-6 and select macrophage-derived cytokines/chemokines (HR range 1.11–1.26). These associations were independent of the DAS28-CRP.ConclusionsHigher disease activity and elevated levels of cytokines/chemokines are associated with a higher risk of incident DM in patients with RA. Future study may help to determine if targeted treatments in at-risk individuals could prevent the development of DM.

Background and Purpose: The causes of recurrent ischemic stroke despite anticoagulation for atrial fibrillation are uncertain but might include small vessel occlusion. We investigated whether magnetic resonance imaging markers of cerebral small vessel disease (SVD) are associated with ischemic stroke risk during follow-up in patients anticoagulated for atrial fibrillation after recent ischemic stroke or transient ischemic attack. Methods: We analyzed data from a prospective multicenter inception cohort study of ischemic stroke or transient ischemic attack anticoagulated for atrial fibrillation (CROMIS-2 [Clinical Relevance of Microbleeds in Stroke Study]). We rated markers of SVD on baseline brain magnetic resonance imaging: basal ganglia perivascular spaces (number ≥11); cerebral microbleeds (number ≥1); lacunes (number ≥1); and white matter hyperintensities (periventricular Fazekas grade 3 or deep white matter Fazekas grade ≥2). We investigated the associations of SVD presence (defined as presence of ≥1 SVD marker) and severity (composite SVD score) with the risk of ischemic stroke during follow-up using a Cox proportional hazards model adjusted for congestive heart failure, hypertension, age >75, diabetes, stroke, vascular disease, age 65–74, female score. Results: We included 1419 patients (mean age: 75.8 years [SD, 10.4]; 42.1% female). The ischemic stroke rate during follow-up in patients with any SVD was 2.20 per 100-patient years (95% CI, 1.60–3.02), compared with 0.98 per 100 patient-years (95% CI, 0.59–1.62) in those without SVD ( P =0.008). After adjusting for congestive heart failure, hypertension, age >75, diabetes, stroke, vascular disease, age 65–74, female score, SVD presence remained significantly associated with ischemic stroke during follow-up (hazard ratio, 1.89 [95% CI, 1.01–3.53]; P =0.046); the risk of recurrent ischemic stroke increased with SVD score (hazard ratio per point increase, 1.33 [95% CI, 1.04–1.70]; P =0.023). Conclusions: In patients anticoagulated for atrial fibrillation after ischemic stroke or transient ischemic attack, magnetic resonance imaging markers of SVD are associated with an increased risk of ischemic stroke during follow-up; improved stroke prevention treatments are required in this population. Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02513316.

Remote ischaemic per-conditioning (RIC) is neuroprotective in experimental ischaemic stroke. Several neurohumoral, vascular and inflammatory mediators are implicated. The effect of RIC on plasma biomarkers was assessed using clinical data from the REmote ischaemic Conditioning After Stroke Trial (RECAST-1).RECAST-1 was a pilot sham-controlled blinded trial in 26 patients with ischaemic stroke, randomized to receive four 5-min cycles of RIC within 24 h of ictus. Plasma taken pre-intervention, immediately post-intervention and on day 4 was analysed for nitric oxide (nitrate/nitrite) using chemiluminescence and all other biomarkers by multiplex analysis. Biomarkers were correlated with clinical outcome (day 90 National Institutes of Health Stroke Scale, modified Rankin Scale, Barthel index).Remote ischaemic per-conditioning reduced serum amyloid protein (SAP) and tissue necrosis factor α (TNF-α) levels from pre- to post-intervention (n = 13, two-way ANOVA, p 0.05). Overall (n = 26), increases in SAP pre- to post-intervention and pre-intervention to day 4 were moderately correlated with worse day 90 clinical outcomes. No consistent significant changes over time, or by treatment, or correlations with outcome were seen for other biomarkers.Remote ischaemic per-conditioning reduced SAP and TNF-α levels from pre- to post-intervention. Increases in plasma levels of SAP were associated with worse clinical outcomes after ischaemic stroke. Larger studies assessing biomarkers and the safety and efficacy of RIC in acute ischaemic stroke are warranted to further understand these relationships.

Purpose We analyzed multi-institutional data to understand the relationship of ACR Diagnostic Radiology In-Training Examination (DXIT) scores to ABR Core examination performance. Methods We collected DXIT rank scores and ABR Core examination outcomes and scores for anonymized residents from 12 different diagnostic radiology residency programs taking the ABR Core examination between 2013 and 2019. DXIT scores were grouped into quintiles based on rank score for residency year 1 (R1), residency year 2 (R2), and residency year 3 (R3) residents. Core outcome was scored as fail when conditionally passed or failed. Core performance was grouped using SD from the mean and measured by the percent of residents with scores below the mean. Differences between DXIT score quintiles for Core outcome and Core performance were statistically evaluated. Results DXIT and Core outcome data were available for 446 residents. The Core examination failure rate for the lowest quintile R1, R2, and R3 DXIT scores was 20.3%, 34.2%, and 38.0%, respectively. Core performance improved with higher R3 DXIT quintiles. Only 2 of 229 residents with R3 DXIT score ≥ 50th percentile failed the Core examination, with both failing residents having R2 DXIT scores in the lowest quintile. Conclusions DXIT scores are useful evaluation metrics to identify a subgroup of residents at significantly higher risk for Core examination failure and another subgroup of residents at significantly lower risk for Core examination failure, with increasing predictive power with advancing residency year. These scores enable identification of approximately one-half of R3 residents whose risk of Core examination failure is negligible.

Background and Objectives Homebound older adults and their caregivers have not historically been engaged as advisors in patient-centered outcomes research. This study aimed to understand the attitudes of homebound older adults and their caregivers toward research and participation as research advisors. Research Design and Methods Descriptive thematic analysis of semistructured interviews conducted with 30 homebound older adults and caregivers recruited from home-based medical care practices. Interview questions addressed opinions on research and preferences for engaging as research advisors. Results Of 30 participants, 22 were female, 17 were people of color, and 11 had Medicaid. Two themes emerged related to perceptions of research overall: (a) utility of research and (b) relevance of research. Overall, participants reported positive attitudes toward research and felt that research could affect people like them. Three themes emerged related to participating as research advisors: (a) motivators, (b) barriers, and (c) preferences. Participants were open to engaging in a variety of activities as research advisors. Most participants were motivated by helping others. Common barriers included time constraints and caregiving responsibilities, and physical barriers for homebound individuals. Participants also reported fears such as lacking the skills or expertise to contribute as advisors. Many were willing to participate if these barriers were accommodated and shared their communication preferences. Discussion and Implications Diverse homebound older adults and caregivers are willing to be engaged as research advisors and provided information to inform future engagement strategies. Findings can inform efforts to meet new age-inclusive requirements of the National Institutes of Health.

Introduction: Little is known about the variations in pathology visibility (PV) and their corresponding radiation dose values for neonatal chest radiography, between and within hospitals. Large variations in PV could influence the diagnostic outcome and the variations in radiation dose could affect the risk to patients. The aim of this study is to compare the PV and radiation dose for standard neonatal chest radiography protocols among a series of public hospitals.\ud \ud Methods: A Gammex 610 neonatal chest phantom was used to simulate the chest region of neonates. Radiographic acquisitions were conducted on 17 X-ray machines located in eight hospitals, utilising their current neonatal chest radiography protocols. Six qualified radiographers assessed PV visually using a relative visual grading analysis (VGA). Signal to noise ratios (SNR) and contrast to noise ratios (CNR) were measured as a measure of image quality (IQ). Incident air kerma (IAK) was measured using a solid-state dosimeter. \ud \ud Results: PV and radiation dose varied substantially between and within hospitals. For PV, the mean (range) VGA scores, between and within the hospitals, were 2.69 (2.00 to 3.50) and 2.73 (2.33 to 3.33), respectively. For IAK, the mean (range), between and within the hospitals, were 24.45 (8.11 to 49.94) µGy and 34.86 (22.26 to 49.94) µGy, respectively. \ud \ud Conclusion: Between and within participating hospitals there was wide variation in the visibility of simulated pathology and radiation dose (IAK). \ud \ud Implications for practice: X-ray units with lower PV and higher doses require optimisation of their standard clinical protocols. Institutions which can offer acceptable levels of PV but with lower radiation doses should help facilitate national optimisation processes.

Ineffective communication is commonly listed as a root cause of sentinel events and other adverse events in the health care setting. The psychological safety of all employees is considered to be a factor that promotes effective communication. Recently, leaders of a radiology department learned that many of the frontline staff did not feel they were being treated respectfully by radiologists during routine interactions. On a baseline survey, only 48% of technologists, reading room assistants, and child life specialists rated their interactions with radiologists as very good or excellent. An improvement team was formed, representing radiologists, technologists, reading room assistants, and child life specialists throughout the department. The improvement team launched a series of interventions with a goal of increasing the percentage of interactions rated as very good or excellent from 48% to 90%. The improvement team focused interventions on three topics: in-person interactions, telephone interactions, and trainee interactions. By the time of this publication, the median percentage of interactions rated as very good or excellent improved to 75%, with a maximum surveyed value of 90%.Online supplemental material is available for this article.©RSNA, 2020.

Current presentation The patient is right-handed, in early 50s and carries the diagnoses of generalised tonic-clonic seizures, spastic quadriparesis and severe learning disability. Generalised tonic-clonic seizures, the only reported seizure type, occur every few weeks. Current antiseizure drugs include valproate, clonazepam, levetiracetam and lacosamide. Both the patient’s condition and treatment have changed little over the past 11 years for which electronic records are available in the clinic. At best, the patient mobilises with aids and communicates through simple gestures with very limited understanding. The patient attends the clinic with elderly mother and two carers. ### Would you try to review the syndromic diagnosis or try to establish a cause? Guidelines advocate classifying a person’s seizure and epilepsy types, the epilepsy syndrome as well as the underlying cause.1 Reviewing the diagnosis is particularly important when seizures are treatment-resistant.2 From this perspective, the patient’s history of intellectual disability may be particularly important. Although diagnostic yield is higher in children, even among adults with intellectual disability and epilepsy of unknown cause, broad genetic testing may lead to diagnosis in over a quarter of those first tested.3 The patient’s DNA had been previously collected, with appropriate assent, as part of a long-running epilepsy genetics research programme at our centre. The ‘epilepsy plus’ disease category, defined as epilepsy with concomitant intellectual disability, autism spectrum disorder, structural abnormality or unexplained cognitive decline, became available through Genomics England (GEL) in the 100 000 Genomes Project.4 In 2017, the patient’s sample and current diagnoses were entered for analysis. To anticipate identification of possible clinically relevant findings, we performed screening for stop gain variants in the SCN1A gene region (chr2:165 989 160-166 128 013). This process within the GEL research environment identified the variant c.3796 G>T:p.Glu1266Ter (NM_001165963) in our patient. ### How would you approach this finding? Variants in SCN1A , encoding the alpha subunit of type 1 voltage-gated sodium channel, are associated with a wide range of epilepsies, which may be inherited or arise de …

A singleton fetus was referred to fetal magnetic resonance imaging (MRI) at 25 weeks due to mild ventriculomegaly and an abnormal fetal echocardiogram showing cardiomegaly, right ventricular hypertrophy and tricuspid insufficiency. Patchy areas of ischemic infarction, extensive subacute and chronic hemorrhage not respecting vascular territories, encephaloclastic cysts and closed lip schizencephaly were identified. Cataract was detected postnatally. The anomalies were caused by a pathogenic mutation (c.353 G>A; p.G118D) in the COL4A1 gene. The phenotype seen in this case, i.e. small vessel cerebral disease with or without ocular anomalies caused by COL4A1 mutations, is likely an underrecognized cause of perinatal stroke. The pattern of abnormalities reported herein should prompt strong consideration for diagnosis and molecular testing.

ObjectivesTo compare the onset and trajectory of multimorbidity between individuals with and without rheumatoid arthritis (RA).MethodsA matched, retrospective cohort study was completed in a large, US commercial insurance database (MarketScan) from 2006 to 2015. Using validated algorithms, patients with RA (overall and incident) were age-matched and sex-matched to patients without RA. Diagnostic codes for 44 preidentified chronic conditions were selected to determine the presence (≥2 conditions) and burden (count) of multimorbidity. Cross-sectional comparisons were completed using the overall RA cohort and conditional logistic and negative binomial regression models. Trajectories of multimorbidity were assessed within the incident RA subcohort using generalised estimating equations.ResultsThe overall cohort (n=277 782) and incident subcohort (n=61 124) were female predominant (76.5%, 74.1%) with a mean age of 55.6 years and 54.5 years, respectively. The cross-sectional prevalence (OR 2.29, 95% CI 2.25 to 2.34) and burden (ratio of conditions 1.68, 95% CI 1.66 to 1.70) of multimorbidity were significantly higher in RA than non-RA in the overall cohort. Within the incident RA cohort, patients with RA had more chronic conditions than non-RA (β 1.13, 95% CI 1.10 to 1.17), and the rate of accruing chronic conditions was significantly higher in RA compared with non-RA (RA × follow-up year, β 0.21, 95% CI 0.20 to 0.21, pConclusionsMultimorbidity is highly prevalent in RA and progresses more rapidly in patients with RA than in patients without RA during and immediately following RA onset. Therefore, multimorbidity should be aggressively identified and targeted early in the RA disease course.

Hereditary hemorrhagic telangiectasia (HHT; also known as Osler-Weber-Rendu syndrome) is an inherited vascular disorder with a spectrum of clinical manifestations depending on lesion distribution. Epistaxis, mucocutaneous telangiectasia, and gastrointestinal bleeding are most common. Patients with pulmonary arteriovenous malformations are at serious risk of cerebral embolic stroke and abscess due to paradoxical embolism, indicating the need for early diagnosis and intervention. Herein, we report a 14-year-old boy who presented to his pediatrician's office with hypoxemia and personal history of epistaxis, family history of HHT, and radiologic workup demonstrating pulmonary and cerebral arteriovenous malformations. He was diagnosed with HHT and treated by endovascular embolization.

Background/Objective We assessed the predictive value, validity, and responsiveness of the multi-biomarker disease activity (MBDA) score in rheumatoid arthritis (RA) patients initiating methotrexate. Methods We examined data from a 16-week, open-label study of methotrexate in RA. Disease activity was assessed and the MBDA score was calculated using serum that was collected and banked from baseline and week 16. Multivariable logistic regression models assessed whether MBDA scores predicted treatment response. Pearson correlations assessed the convergent validity and external responsiveness of the MBDA score with other measures of RA disease activity. Internal responsiveness was assessed by calculating standardized response means (SRMs). Results A total of 130 patients initiated the study, with follow-up MBDA scores available on 95 patients. Baseline MBDA scores did not predict ACR response or achieving low disease activity. Higher baseline DAS28-ESR scores were significantly associated with an ACR20 response (odds ratio 1.89 per unit, 95% CI 1.20–2.96) but not ACR50, ACR70, or low disease activity. The MBDA score moderate-to-weakly correlated with the DAS28-ESR and ESR at baseline and week 16, with weak-to-very weak correlations with patient global and function. Change in MBDA scores moderately correlated with changes in DAS28-ESR and ESR, while weakly correlating with changes in patient global and function. The DAS28-ESR (SRM 1.31) demonstrated greater responsiveness following methotrexate treatment than the MBDA score (SRM 0.71). Conclusions MBDA scores did not predict treatment response to methotrexate. The MBDA score weak-to-moderately correlated with baseline and post-treatment disease activity measures and was less responsive to methotrexate-related improvement than the DAS28-ESR.

Objective To examine the relationship of posttraumatic stress disorder (PTSD) with earlier treatment discontinuation and medication adherence in US veterans with rheumatoid arthritis (RA). Methods Veterans Affairs (VA) administrative data (2005-2014) were used to define unique dispensing episodes of methotrexate (MTX) and tumor necrosis factor inhibitors (TNFi) for veterans with RA. Diagnosis codes were used to categorize patients into mutually exclusive groups: PTSD (with/without depression/anxiety), depression/anxiety without PTSD, and neither psychiatric diagnosis. Multivariable Cox proportional hazards models were used to evaluate associations between psychiatric diagnoses and time to disease-modifying antirheumatic drug discontinuation (lapse in refill >90 days). Multivariable logistic regression was used to examine associations of diagnoses with medication nonadherence (proportion of days covered Results There were 15 081 dispensing episodes of MTX and 8412 dispensing episodes of TNFi. PTSD was independently associated with a greater likelihood of earlier discontinuation of both MTX (hazard ratio [HR] 1.15 [1.10-1.21]) and TNFi (HR 1.20 [1.13-1.28]). Depression/anxiety had a comparable risk of discontinuation for both MTX (HR 1.14 [1.10-1.19]) and TNFi (HR 1.16 [1.10-1.22]). Depression/anxiety, but not PTSD, was associated with higher odds of MTX (odds ratio [OR] 1.12 [1.03-1.22]) and TNFi (OR 1.14 [1.02-1.27]) nonadherence. Conclusion Veterans with RA and comorbid PTSD, depression, or anxiety had poor persistence of MTX and TNFi therapies. These results suggest that earlier discontinuation and low adherence to therapy among patients with RA with these psychiatric comorbidities may contribute to worse disease outcomes. Mechanisms by which these comorbidities contribute to lower adherence deserve further investigation and may lead to targeted interventions to improve disease outcomes.

Introduction Untreated hyperthyroidism is associated with accelerated bone turnover, low bone mineral density (BMD) and increased susceptibility to fragility fractures. Although treatment appears to improve or even reverse some of these adverse skeletal effects, there is limited guidance on routine BMD assessment in hyperthyroid patients following treatment. By using Mendelian randomization (MR) analysis, we aimed to assess the causal association of hyperthyroid thyroid states with BMD and fractures using the UK Biobank. Methods This MR analysis included data from 473 818 participants (women: 54% of the total sample, the median age of 58.0 years (IQR = 50-63 years), median body mass index (BMI) of 26.70 (IQR + 24.11-29.82 kg/m2 ) as part of the UK Biobank study. The study outcomes were heel BMD assessed by quantitative ultrasound of the heel and self-reported fractures. Beta-weighted genetic risk score analysis was performed using 19 single nucleotide polymorphisms (SNPs) for Graves' disease, 9 SNPs for hyperthyroidism and 11 SNPs for autoimmune thyroiditis. Since the unadjusted risk score MR is equivalent to the inverse-variance weighted method, the genetic risk score analysis was adjusted for age, gender and BMI. Sensitivity analyses were conducted using the Mendelian randomization-Egger (MR-Egger) and the inverse-variance weighted estimate methods. Replication analysis was performed using the GEnetic Factors for Osteoporosis (GEFOS) consortium data. Results MR analysis using beta-weighted genetic risk score showed no association of genetic risk for Graves' disease (Beta = -0.01, P-value = .10), autoimmune thyroiditis (Beta = -0.006 P-value = .25) and hyperthyroidism (Beta = -0.009, P-value = .18) with heel ultrasound BMD. MR-Egger and inverse-variance MR methods in UK Biobank and GEFOS consortium confirmed these findings. The genetic risk for these hyperthyroid conditions was not associated with an increased risk of fractures. Conclusion Our study shows that excess genetic risk for Graves' autoimmune thyroiditis and hyperthyroidism does not increase the risk for low BMD and is not associated fractures in the Caucasian population. Our findings do not support routine screening for osteoporosis following definitive treatment of hyperthyroid states.

Background Interest into the health, disease, and performance impact of exogenous ketone bodies has rapidly expanded due to their multifaceted physiological and signaling properties but limiting our understanding is the isolated analyses of individual types and dose/dosing protocols. Methods Thirteen recreational male distance runners (24.8 ± 9.6 years, 72.5 ± 8.3 kg, VO2max 60.1 ± 5.4 ml/kg/min) participated in this randomized, double-blind, crossover design study. The first two sessions consisted of a 5-km running time trial familiarization and a VO2max test. During subsequent trials, subjects were randomly assigned to one (KS1: 22.1 g) or two (KS2: 44.2 g) doses of beta-hydroxybutyrate (βHB) and medium chain triglycerides (MCTs) or flavor matched placebo (PLA). Blood R-βHB, glucose, and lactate concentrations were measured at baseline (0-min), post-supplement (30 and 60 min), post-exercise (+ 0 min, + 15 min). Time, heart rate (HR), rating of perceived exertion (RPE), affect, respiratory exchange ratio, oxygen consumption (VO2), carbon dioxide production, and ventilation were measured during exercise. Cognitive performance was evaluated prior to and post-exercise. Results KS significantly increased R-βHB, with more potent and prolonged elevations in KS2, illustrating an administrative and dosing effect. R-βHB was significantly decreased in KS1 compared to KS2 illustrating a dosing and exercise interaction effect. Blood glucose elevated post-exercise but was unchanged across groups. Blood lactate significantly increased post-exercise but was augmented by KS administration. Gaseous exchange, respiration, HR, affect, RPE, and exercise performance was unaltered with KS administration. However, clear responders and none-responders were indicated. KS2 significantly augmented cognitive function in pre-exercise conditions, while exercise increased cognitive performance for KS1 and PLA to pre-exercise KS2 levels. Conclusion Novel βHB + MCT formulation had a dosing effect on R-βHB and cognitive performance, an administrative response on blood lactate, while not influencing gaseous exchange, respiration, HR, affect, RPE, and exercise performance.

Drinking alcohol during pregnancy can cause fetal alcohol spectrum disorders, including birth defects, behavioral disorders, and impaired cognitive development (1). Little is known about the co-use of other substances by females who drink during pregnancy. CDC used 2015-2018 data from the National Survey on Drug Use and Health (NSDUH) to estimate the overall and trimester-specific prevalence of self-reported drinking in the past 12 months, current drinking, and binge drinking, overall and by trimester, and the co-use of other substances among pregnant females aged 12-44 years. Past drinking (12 months) was reported by 64.7% of pregnant respondents. Current drinking (at least one drink in the past 30 days) was reported by 19.6% of respondents who were in their first trimester of pregnancy and 4.7% of respondents who were in their second or third trimester. Binge drinking (consuming four or more drinks on at least one occasion in the past 30 days) was reported by 10.5% of first trimester respondents and 1.4% of second or third trimester respondents. Overall, 38.2% of pregnant respondents who reported current drinking also reported current use of one or more other substances. The substances used most with alcohol were tobacco and marijuana. Self-reported drinking prevalence was substantially lower among second or third trimester respondents than among first trimester respondents. The American College of Obstetricians and Gynecologists (ACOG) recommends alcohol use and substance use disorders screening for all females seeking obstetric-gynecologic care and counseling patients that there is no known safe level of alcohol use during pregnancy (2).

Purpose We analyzed multi-institutional data to understand the relationship of US Medical Licensing Examination (USMLE) Step scores to ABR Core examination performance to identify Step score tiers that stratify radiology residents into different Core performance groups. Methods We collected USMLE Step scores and ABR Core examination outcomes and scores for anonymized residents from 13 different diagnostic radiology residency programs taking the ABR Core examination between 2013 and 2019. USMLE scores were grouped into noniles using z scores and then aggregated into three tiers based on similar Core examination pass-or-fail outcomes. Core performance was grouped using standard deviation from the mean and then measured by the percent of residents with scores below the mean. Differences between Step tiers for Core outcome and Core performance were statistically evaluated (P Results Differences in Step 1 terciles Core failure rates (45.9%, 11.9%, and 3.0%, from lowest to highest Step tiers; n = 416) and below-mean Core performance (83.8%, 54.1%, and 21.1%, respectively; n = 402) were significant. Differences in Step 2 groups Core failure rates (30.0%, 10.6%, and 2.0%, from lowest to highest Step tiers; n = 387) and below-mean Core performance (80.0%, 43.7%, and 14.0%, respectively; n = 380) were significant. Step 2 results modified Core outcome and performance predictions for residents in Step 1 terciles of varying statistical significance. Conclusions Tiered scoring of USMLE Step results has value in predicting radiology resident performance on the ABR Core examination; effective stratification of radiology resident applicants can be done without reporting numerical Step scores.

Remote ischaemic conditioning (RIC) is achieved by repeated transient ischaemia of a distant organ/limb and is neuroprotective in experimental ischaemic stroke. However, the optimal time and methods of administration are unclear. Systematic review identified relevant preclinical studies; two authors independently extracted data on infarct volume, neurological deficit, RIC method (administration time, site, cycle number, length of limb occlusion (dose)), species and quality. Data were analysed using random effects models; results expressed as standardised mean difference (SMD). In 57 publications incorporating 99 experiments (1406 rats, 101 mice, 14 monkeys), RIC reduced lesion volume in transient (SMD −2.0; 95% CI −2.38, −1.61; p