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5.3 years (interquartile range, 3.1-7.4 years). Normalization of FC within 12 months of diagnosis was confirmed in 43.5% of patients. Patients with normalized levels of FC had a significantly lower risk of composite disease progression (hazard ratio [HR], 0.36; 95% CI, 0.24-0.53; P less then .001). They also had a lower risk of reaching any of the separate progression endpoints (progression in Montreal behavior or new perianal disease HR, 0.22; 95% CI, 0.11-0.45; P less then .001; hospitalization HR, 0.33; 95% CI, 0.21-0.53; P less then .001; surgery HR, 0.39; 95% CI, 0.19-0.78; P = .008) CONCLUSIONS Normalization of FC within 12 months of diagnosis is associated with a reduced risk of progression of CD. Inflammatory bowel diseases (IBD) often require multidisciplinary care with tight coordination among providers. Provider connectedness, a measure of the relationship among providers, is an important aspect of care coordination that has been linked to higher quality care. We aimed to assess variation in provider connectedness among medical centers, and to understand the association between this established measure of care coordination and outcomes of patients with IBD. We conducted a national cohort study of 32,949 IBD patients with IBD from 2005 to 2014. We used network analysis to examine provider connectedness, defined using network properties that measure the strength of the collaborative relationship, team cohesiveness, and between-facility collaborations. https://www.selleckchem.com/products/reacp53.html We used multilevel modeling to examine variations in provider connectedness and association with patient outcomes. There was wide variation in provider connectedness among facilities in complexity, rural designation, and volume of patients with IBion and quality of care. Data evaluating efficacy of different doses of swallowed topical corticosteroids (STC) in the long-term management of eosinophilic esophagitis (EoE) are lacking. We assessed long-term effectiveness and safety of different STC doses for adults with EoE after achievement of histological remission. We performed a retrospective multicenter study at five EoE referral centers (US and Switzerland). We analyzed data on 82 patients with EoE in histological remission and ongoing STC treatment with therapeutic adherence of ≥75% (58 males; mean age at diagnosis, 37.2±14.4 years). Patients were followed for a median of 2.2 years (interquartile range [IQR], 1.0-3.8 years). We collected data from 217 follow-up endoscopy visits. The primary endpoint was time to histological relapse. Histological relapse occurred in 67% of patients. Relapse rates were comparable in patients taking low dose (≤0.5 mg per day, n = 58) and high dose STC (>0.5 mg per day, n = 24) with 72 vs 54% (ns). However, histological relapse occurred significantly earlier with low dose STC (1.0 vs 1.8 years, P = .030). There was no difference regarding rates of and time to stricture formation for low vs high dose STC. Esophageal candidiasis was observed in 6% of patients (5% for low dose, 8% for high dose, ns). No dysplasia or mucosal atrophy was detected. Histological relapse frequently occurs in EoE despite ongoing STC treatment regardless of STC doses. However, relapse develops later in patients on high dose STC without an increase in side-effects. Doses higher than 0.5 mg/day may be considered for EoE maintenance treatment, but advantage over lower doses appears to be small. Histological relapse frequently occurs in EoE despite ongoing STC treatment regardless of STC doses. However, relapse develops later in patients on high dose STC without an increase in side-effects. Doses higher than 0.5 mg/day may be considered for EoE maintenance treatment, but advantage over lower doses appears to be small.This editorial summarizes the content of the current themed issue of J Pharm Tox Methods derived from the 2019 Annual Safety Pharmacology Society (SPS) meeting held in Barcelona, Spain, and reflects on 20 years of innovation in the elaboration of methods for evaluating adversity, particularly during the nonclinical research phase. Given the success of safety pharmacology (SP) in the last 20 years, we propose that the rubric for SP method invention and validation be examined in more detail to explore whether it may have wider relevance to the drug discovery process. Articles arising from the Barcelona meeting are summarized here. They reflect current areas of controversy and innovation in SP. Not for the first time in recent years, the suitability of the No Observable Adverse Effect Level (NOAEL) as a variable in SP was considered in an article derived from a survey of SPS members. It was found from the survey and concluded from the analysis that the NOAEL is not necessary for assessing the safety of a New Chemical Entity (NCE). The meeting included scientific content from more than 190 abstracts (reproduced in the current volume of J Pharm Tox Methods). The impact of the INSPIRE program on the educational endeavor of SP, cardiovascular SP with regard to hERG and advances in CiPA and stem cells assays, the use of the echocardiogram in SP, the applicability of deep learning methods in SP and toxicology studies, the role of biomarkers in renal SP studies, and advances in CNS SP are highlighted in this issue of the Journal. This continued innovation reflects a rubric in SP that identifies problems, seeks solutions and, importantly, validates the solutions. If there is a lesson to be learned from the 20 years of annual SP methods themed issues it is that drug discovery efforts may benefit from a more rigorous validation process for discovery methods, using positive and negative controls for validation, as is done in SP method validation. The purpose of this study was to assess clinical characteristics and risk factors for mortality of patients with coronavirus disease 2019 (COVID-19) from Mexico, given that it currently is in active community transmission. Multivariate logistic regression model and Kaplan-Meier survival curves were fitted to study odds of death of characteristics and comorbidities in patients with COVID-19 in Mexico. Age, sex, and the most frequent comorbidities diabetes, obesity, and hypertension were significantly associated to the risk of death by COVID-19 (P<.0001). Smoking habit was not identified as a risk factor for death. Less-frequent comorbidities such as chronic obstructive pulmonary disease, chronic kidney disease, and patients with immunosuppressed conditions also showed a significant risk for death (P<.0001). Hospitalized patients and those with pneumonia had serious risks for mortality (P<.0001), and more attention to specific conditions might be considered during clinical admission. A more vulnerable positive patient is depicted by a male patient, older than 41years, which increases their risk with more prevalent comorbidities such as diabetes, hypertension, and obesity.
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