Predicting which children with juvenile idiopathic arthritis will not attain early remission with conventional treatment: Results from the Reacch-out cohort

Objective. To estimate the probability of early remission with conventional treatment for each child with juvenile idiopathic arthritis (JIA). Children with a low chance of remission may be candidates for initial treatment with biologics or triple disease-modifying antirheumatic drugs (DMARD). Methods. We used data from 1074 subjects in the Research in Arthritis in Canadian Children emphasizing Outcomes (ReACCh-Out) cohort. The predicted outcome was clinically inactive disease for ≥ 6 months starting within 1 year of JIA diagnosis in patients who did not receive early biologic agents or triple DMARD. Models were developed in 200 random splits of 75% of the cohort and tested on the remaining 25% of subjects, calculating expected and observed frequencies of remission and c-index values. Results. Our best Cox logistic model combining 18 clinical variables a median of 2 days after diagnosis had a c-index of 0.69 (95% CI 0.67-0.71), better than using JIA category alone (0.59, 95% CI 0.56-0.63). Children in the lowest probability decile had a 20% chance of remission and 21% attained remission; children in the highest decile had a 69% chance of remission and 73% attained remission. Compared to 5% of subjects identified by JIA category alone, the model identified 14% of subjects as low chance of remission (probability \u3c 0.25), of whom 77% failed to attain remission. Conclusion. Although the model did not meet our a priori performance threshold (c-index \u3e 0.70), it identified 3 times more subjects with low chance of remission than did JIA category alone, and it may serve as a benchmark for assessing value added by future laboratory/imaging biomarkers

A survey of national and multi-national registries and cohort studies in juvenile idiopathic arthritis: Challenges and opportunities

Background: To characterize the existing national and multi-national registries and cohort studies in juvenile idiopathic arthritis (JIA) and identify differences as well as areas of potential future collaboration. Methods: We surveyed investigators from North America, Europe, and Australia about existing JIA cohort studies and registries. We excluded cross-sectional studies. We captured information about study design, duration, location, inclusion criteria, data elements and collection methods. Results: We received survey results from 18 studies, including 11 national and 7 multi-national studies representing 37 countries in total. Study designs included inception cohorts, prevalent disease cohorts, and new treatment cohorts (several of which contribute to pharmacosurveillance activities). Despite numerous differences, the data elements collected across the studies was quite similar, with most studies collecting at least 5 of the 6 American College of Rheumatology core set variables and the data needed to calculate the 3-variable clinical juvenile disease activity score. Most studies were collecting medication initiation and discontinuation dates and were attempting to capture serious adverse events. Conclusion: There is a wide-range of large, ongoing JIA registries and cohort studies around the world. Our survey results indicate significant potential for future collaborative work using data from different studies and both combined and comparative analyses

The prevalence of systemic autoimmune rheumatic diseases in Canadian pediatric populations: administrative database estimates

CI 17.9, 29.2). SARDs were more common in females than in males across all provinces. There was a slightly higher prevalence among those living in urban compared to rural areas of Alberta (rate difference 14.4, 95 % CI 8.6, 20.1) and Saskatchewan (rate difference 13.8, 95 % CI 1.0, 26.6). Our results provide population-based prevalence estimates of pediatric SARDs in four Canadian provinces. Keywords Pediatric rheumatic diseases · Systemic autoimmune rheumatic diseases · Epidemiology · Disease prevalence Abstract To estimate systemic autoimmune rheumatic disease (SARD) prevalence using administrative data for pediatric populations in four Canadian provinces. Physician billing claims and inpatient hospitalizations from Alberta, Manitoba, Quebec, and Saskatchewan were used to define cases aged ≤18 years with a SARD diagnosis code in: one or more hospitalization, two or more physician visits within 2 years and at least 2 months apart, or one or more physician visit to a rheumatologist. Estimates ranged from 15.9/100,000 in Quebec [95 % confidence interval (95 % CI) 14.1, 18.0] to 23.0/100,000 in Manitoba (95 % Rheumatology INTERNATIONA

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Procedural pain and patient-reported side effects with weekly injections of subcutaneous Methotrexate in children with rheumatic disorders

Abstract Background Despite the widespread use of subcutaneous methotrexate in treating pediatric rheumatic disorders, the amount of pain associated with the injections has not been quantified. Our study aims 1) to quantify the amount of pain associated with subcutaneous injections of methotrexate, 2) to explore predictors of pain, 3) to determine the frequency of patient-reported clinical adverse effects of methotrexate, and 4) identify coping strategies of patients and caregivers. Methods Patients aged 4–17 years with rheumatologic diseases who were receiving weekly subcutaneous methotrexate injections for at least 4 weeks were invited to participate in this prospective cohort study. They were trained to use the Faces Pain Scale – Revised (FPS-R) and Faces, Legs, Arms, Cry, Consolability (FLACC) tools to rate pain associated with the injections. All patients underwent focused interviews exploring their experiences with methotrexate injections. Results Forty-one patients consented to the study. The mean age was 11.2 years (SD = 3.9 years) and 68% were female. Most patients were diagnosed with JIA (73%). Mean duration of methotrexate therapy was 2.5 years (SD = 2.1 yrs). All but one of the patients used methotrexate 25 mg/ml solution for injection in 1 cc or 3 cc syringe with 30 gauge ½” needle. Median amount of pain was 2/10 on the FPS-R and 1/10 on the FLACC. Higher intensity of pain was significantly associated with presence of side effects (p = 0.004), but not duration of therapy (p = 0.20) or age (p = 0.24). Most participants (61%) experienced at least one adverse effect; nausea (56%) and vomiting (34%) were the most common symptoms reported. Patients and caregivers reported using ice (34%), comfort positions (51%), rewards (49%), reassurance (54%), distraction (51%), and analgesic medications (22%) to cope with the injections. Conclusion Subcutaneous injections of methotrexate are associated with a mild amount of pain. Presence of side effects may amplify the amount of perceived pain. Clinicians can apply this knowledge when counseling patients and family members about methotrexate therapy

Procedural pain and patient-reported side effects with weekly injections of subcutaneous Methotrexate in children with rheumatic disorders

Abstract Background Despite the widespread use of subcutaneous methotrexate in treating pediatric rheumatic disorders, the amount of pain associated with the injections has not been quantified. Our study aims 1) to quantify the amount of pain associated with subcutaneous injections of methotrexate, 2) to explore predictors of pain, 3) to determine the frequency of patient-reported clinical adverse effects of methotrexate, and 4) identify coping strategies of patients and caregivers. Methods Patients aged 4–17 years with rheumatologic diseases who were receiving weekly subcutaneous methotrexate injections for at least 4 weeks were invited to participate in this prospective cohort study. They were trained to use the Faces Pain Scale – Revised (FPS-R) and Faces, Legs, Arms, Cry, Consolability (FLACC) tools to rate pain associated with the injections. All patients underwent focused interviews exploring their experiences with methotrexate injections. Results Forty-one patients consented to the study. The mean age was 11.2 years (SD = 3.9 years) and 68% were female. Most patients were diagnosed with JIA (73%). Mean duration of methotrexate therapy was 2.5 years (SD = 2.1 yrs). All but one of the patients used methotrexate 25 mg/ml solution for injection in 1 cc or 3 cc syringe with 30 gauge ½” needle. Median amount of pain was 2/10 on the FPS-R and 1/10 on the FLACC. Higher intensity of pain was significantly associated with presence of side effects (p = 0.004), but not duration of therapy (p = 0.20) or age (p = 0.24). Most participants (61%) experienced at least one adverse effect; nausea (56%) and vomiting (34%) were the most common symptoms reported. Patients and caregivers reported using ice (34%), comfort positions (51%), rewards (49%), reassurance (54%), distraction (51%), and analgesic medications (22%) to cope with the injections. Conclusion Subcutaneous injections of methotrexate are associated with a mild amount of pain. Presence of side effects may amplify the amount of perceived pain. Clinicians can apply this knowledge when counseling patients and family members about methotrexate therapy