Clinical phenotypes and biologic treatment use in juvenile dermatomyositis-associated calcinosis

Abstract Background Few risk factors have been identified for the development of calcinosis among patients with Juvenile Dermatomyositis, and currently no clinical phenotype has been associated with its development. We analyzed a large database of patients to further elucidate any relationships among patients with and without calcinosis. Method The CARRA legacy registry recruited pediatric rheumatology patients from 55 centers across North America from 2010 through 2014, including over 650 subjects with Juvenile Dermatomyositis. We compared the demographic characteristics, clinical disease features and treatment histories of those with and without calcinosis using univariate and multivariate logistic regression. Results Of the 631 patients included in the analysis, 84 (13%) had a current or prior history of calcinosis. These patients were statistically more likely to have longer durations of disease prior to diagnosis and treatment, have lipodystrophy and joint contractures, and to have received intravenous immune globulin or rituximab as treatments. Conclusions Calcinosis is found more often in patients with prolonged active disease, severe disease, and certain clinical features such as lipodystrophy and joint contractures. When these factors are combined with other known associations and predictors, groups of at-risk patients can be more effectively identified, treated and studied to improve overall outcomes

Outcomes for continuous subcutaneous insulin infusion users in young adults from lower socioeconomic backgrounds

OBJECTIVE: Diabetes technology is available and its efficacy and safety have been demonstrated; however, there is little evidence as to how this technology is being utilized and its effectiveness in vulnerable populations. This study evaluated differences in outcomes for young adults in the United States (U.S.) from lower socioeconomic (SES) backgrounds with type 1 diabetes (T1D) managed on continuous subcutaneous insulin infusion (CSII) versus multiple daily injections (MDI) or fixed-dose insulin (FDI). RESEARCH DESIGN METHODS AND PARTICIPANTS: Utilizing the Optum® de-identified Electronic Health Record data set between 2008 and 2018 to perform a retrospective, cohort study, we identified 805 subjects with T1D aged 18-30 years with Medicaid. We evaluated median difference in HbA1c between CSII and MDI/FDI users for 24 months. Predictors of diabetic ketoacidosis (DKA)-associated hospitalizations by CSII use were evaluated using logistic regression. RESULTS: CSII users showed statistically significant lower median HbA1c values at 24 months of follow-up compared to individuals on MDI/FDI. Non-white individuals were at lower odds of receiving treatment with CSII. Subjects on CSII were not more likely to be hospitalized for DKA compared to subjects treated with MDI/FDI. Older subjects were at lower odds of being hospitalized for DKA. Males and subjects followed by Endocrinologists were at higher odds of being hospitalized for DKA. CONCLUSIONS: Young adults with T1D from lower SES backgrounds show improved glycaemic control when in CSII compared to MDI/FDI without increases in hospitalizations for DKA

S100A8/A9 regulates CD11b expression and neutrophil recruitment during chronic tuberculosis

Neutrophil accumulation is associated with lung pathology during active tuberculosis (ATB). However, the molecular mechanism or mechanisms by which neutrophils accumulate in the lung and contribute to TB immunopathology are not fully delineated. Using the well-established mouse model of TB, our new data provide evidence that the alarmin S100A8/A9 mediates neutrophil accumulation during progression to chronic TB. Depletion of neutrophils or S100A8/A9 deficiency resulted in improved Mycobacterium tuberculosis (Mtb) control during chronic but not acute TB. Mechanistically, we demonstrate that, following Mtb infection, S100A8/A9 expression is required for upregulation of the integrin molecule CD11b specifically on neutrophils, mediating their accumulation during chronic TB disease. These findings are further substantiated by increased expression of S100A8 and S100A9 mRNA in whole blood in human TB progressors when compared with nonprogressors and rapidly decreased S100A8/A9 protein levels in the serum upon TB treatment. Furthermore, we demonstrate that S100A8/A9 serum levels along with chemokines are useful in distinguishing between ATB and asymptomatic Mtb-infected latent individuals. Thus, our results support targeting S100A8/A9 pathways as host-directed therapy for TB

Interleukin-17 limits hypoxia-inducible factor 1α and development of hypoxic granulomas during tuberculosis

Mycobacterium tuberculosis (Mtb) is a global health threat, compounded by the emergence of drug-resistant strains. A hallmark of pulmonary tuberculosis (TB) is the formation of hypoxic necrotic granulomas, which upon disintegration, release infectious Mtb. Furthermore, hypoxic necrotic granulomas are associated with increased disease severity and provide a niche for drug-resistant Mtb. However, the host immune responses that promote the development of hypoxic TB granulomas are not well described. Using a necrotic Mtb mouse model, we show that loss of Mtb virulence factors, such as phenolic glycolipids, decreases the production of the proinflammatory cytokine IL-17 (also referred to as IL-17A). IL-17 production negatively regulates the development of hypoxic TB granulomas by limiting the expression of the transcription factor hypoxia-inducible factor 1α (HIF1α). In human TB patients, HIF1α mRNA expression is increased. Through genotyping and association analyses in human samples, we identified a link between the single nucleotide polymorphism rs2275913 in the IL-17 promoter (-197G/G), which is associated with decreased IL-17 production upon stimulation with Mtb cell wall. Together, our data highlight a potentially novel role for IL-17 in limiting the development of hypoxic necrotic granulomas and reducing disease severity in TB

Predicting postoperative troponin in patients undergoing elective hip or knee arthroplasty: A comparison of five cardiac risk prediction tools

BACKGROUND: Elderly patients undergoing hip or knee arthroplasty are at a risk for myocardial injury after noncardiac surgery (MINS). We evaluated the ability of five common cardiac risk scores, alone or combined with baseline high-sensitivity cardiac troponin I (hs-cTnI), in predicting MINS and postoperative day 2 (POD2) hs-cTnI levels in patients undergoing elective total hip or knee arthroplasty. METHODS: This study is ancillary to the Genetics-InFormatics Trial (GIFT) of Warfarin Therapy to Prevent Deep Venous Thrombosis, which enrolled patients 65 years and older undergoing elective total hip or knee arthroplasty. The five cardiac risk scores evaluated were the atherosclerotic cardiovascular disease calculator (ASCVD), the Framingham risk score (FRS), the American College of Surgeon\u27s National Surgical Quality Improvement Program (ACS-NSQIP) calculator, the revised cardiac risk index (RCRI), and the reconstructed RCRI (R-RCRI). RESULTS: None of the scores predicted MINS in women. Among men, the ASCVD ( CONCLUSION: In elderly patients undergoing elective hip or knee arthroplasty, several of the scores modestly predicted MINS in men and correlated with POD2 hs-cTnI

The Role of Interprofessional Education in the Development of Healthcare Professionals’ Team Skills

Purpose: Interprofessional education (IPE) across the health professions learning continuum is suggested to prepare health professionals for interprofessional collaborative practice (IPCP) through development of necessary attitudes, knowledge, behaviors, and skills. The purpose of this study was to investigate the flow-on effects of previous IPE experiences across the learning continuum on existing IPCP skills and behaviors in healthcare professionals. Methods: A retrospective observational study design was used to survey a convenience sample of healthcare professionals working in IPCP clinics about their self-reported team and collaboration skills via the pre-existing Team Skills Scale (TSS) and Self-Assessed Collaborative Skills (SACS) tools. Additional survey items were created by the research team based on self-reported prior IPE exposure, timing of initial IPE exposure, and number of IPE exposures. Sixty-three participants completed the survey (28% response rate). Results: No statistically significant differences were found between groups across all categories of IPE exposure. Non-significant trends suggest higher team and collaboration skills are related to earlier and cumulative IPE exposures throughout learning and professional development. Conclusion: IPE as a broad definition is not sufficient to detect significant relationships with healthcare professionals’ IPCP skills. Future studies should investigate the longitudinal effectiveness of specific IPE interventions on distal IPCP skills and account for other contributing factors

Effect of cognitive fluctuation on neuropsychological performance in aging and dementia

Background: Cognitive fluctuations are spontaneous alterations in cognition, attention, and arousal. Fluctuations are a core feature of dementia with Lewy bodies, but the impact of fluctuations in healthy brain aging and Alzheimer disease ( AD) are unknown. Methods: Research participants (n = 511, age 78.1 +/- 8 years, education 14.9 +/- 3 years) enrolled in a longitudinal study of memory and aging at the Washington University Alzheimer Disease Research Center were assessed for the presence and severity of dementia with the Clinical Dementia Rating (CDR) and a neuropsychological test battery. Informant assessments of fluctuations with the Mayo Fluctuations Questionnaire and daytime level of alertness with the Mayo Sleep Questionnaire were completed. Results: After controlling for age and alertness level, participants with cognitive fluctuations ( 3 or 4 individual symptoms) were 4.6 times more likely to have dementia (95% confidence interval: 2.05, 10.40). Participants who presented with disorganized, illogical thinking were 7.8 times more likely to be rated CDR >0. The risk of being rated CDR 0.5 among those with fluctuations was 13.4 times higher than among those without fluctuations. The risk of being rated CDR 1 increased 34-fold among participants with fluctuations. Compared with participants without fluctuations, the presence of cognitive fluctuations corresponds to a decrease in performance across individual neuropsychological tests as well as composite scores. Conclusions: Cognitive fluctuations occur in Alzheimer disease and, when present, significantly affect both clinical rating of dementia severity and neuropsychological performance. Assessment of fluctuations should be considered in the evaluation of patients for cognitive disorders. Neurology (R) 2010; 74: 210-21

Exploring Treatment for Depression in Parkinson’s Patients: A Cross-Sectional Analysis

Depression is a highly prevalent, often underrecognized and undertreated comorbidity of Parkinson’s disease closely correlated to health-related quality of life. National trends in depression care for patients with Parkinson’s disease are not well documented. This paper identifies a cohort of patients with Parkinson’s disease from nationally representative survey data and analyzes trends in depression care. Using data from the 2005–2006 through 2015–2016 waves of the National Health and Nutrition Examination Survey (NHANES), individuals were classified as Parkinson’s patients by reported medication use. PHQ-9 scores were used to identify individuals screening positive for depression. A composite treatment variable examined the reported use of mental health services and antidepressant medication. Survey participants with probable PD screened positive for depression, reported the use of antidepressant medication, and reported visits to mental health services more frequently than the control group. Survey participants with PD who screened positive for depression were more likely to report limitations in physical functioning due to an emotional problem than controls. While depression is highly prevalent among individuals with Parkinson’s disease, they are more likely to receive any treatment. Further research is required to investigate differences in patterns of treatment, contributing factors of emotions to limitations in physical functioning, and appropriate interventions

Characterization of combined endoscopies and aerodigestive care: An analysis of utilization and financial feasibility.

BackgroundAerodigestive care is one model of multi-disciplinary care, which is a valuable tool for both providers and patients. Aerodigestive care models are associated with improved outcomes, reduced anesthesia exposure, reduction in hospital admissions, and fewer days of missed work or school. This is the first study to explore national usage and cost trends in combined endoscopy utilization to identify gaps in care and the potential for financial resource optimization.MethodsData from the Healthcare Cost and Utilization Project (HCUP) Kid's Inpatient Sample (KID) was used from 2016 and 2019. Diagnoses and procedures were identified using ICD-10 codes, for patients with hospital length of stay less than 1 day. Demographic data were identified, and survey-weighted means and proportions were computed. Bivariate comparisons were made using Rao Scott Chi-Square tests. National estimates of charges were computed with discharge weights, developed using the American Hospital Association (AHA) universe.Key resultsWhite, high-income patients, and those at urban teaching hospitals received the greatest proportion of combined endoscopic procedures. The cost/charges associated with combined endoscopies are less than for separate gastrointestinal (GI) or airway only endoscopies combined. However, combined procedures comprise a smaller share of national aggregate cost.ConclusionsNational utilization trends highlight racial and socioeconomic disparities and suggest differences in access based on hospital characteristics, despite the reduced cost/charges of the combined procedure. For patients with a need for combined aerodigestive procedures, there appears to be a cost-savings opportunity to increase efforts for combined procedures at the level of the clinician or hospital