Early impacts of the COVID-19 pandemic on children with pediatric rheumatic diseases.

OBJECTIVES: The experiences of children with pediatric rheumatic diseases (PRD) during the initial phase of the COVID-19 pandemic have not been well-documented. We sought to determine the effects of the COVID-19 pandemic on protective behaviors, healthcare access, medication management, and education among an international cross-sectional parental survey of children with PRDs. METHODS: The COVID-19 Global Rheumatology Alliance Patient Experience Survey was distributed online, and parents of children with parental-reported PRD, with or without COVID-19 infection, were eligible to enroll. Respondents described their child's demographics, adoptions of protective behaviors, healthcare access, changes to immunosuppression, and disruptions in schooling. RESULTS: A total of 427 children were included in the analyses. The most common rheumatic disease was juvenile idiopathic arthritis (40.7%), and most children were taking conventional synthetic diseasemodifying antirheumatic drugs (DMARDs) (54.6%) and/or biologic DMARDs (51.8%). A diagnosis of COVID-19 was reported in five children (1.2%), none of whom required hospitalization. Seventeen children (4.0%) had stopped or delayed their drugs due to concern for immunosuppression, most commonly glucocorticoids. Almost all families adopted behaviors to protect their children from COVID-19, including quarantining, reported by 96.0% of participants. In addition, 98.3% of full-time students experienced disruptions in their education, including cancelations of classes and transitions to virtual classrooms. CONCLUSION: Despite the low numbers of children with PRDs who developed COVID-19 in this cohort, most experienced significant disruptions in their daily lives, including quarantining and interruptions in their education. The drastic changes to these children's environments on their future mental and physical health and development remain unknown.

Is denosumab associated with an increased risk for infection in patients with low bone mineral density? A systematic review and meta-analysis of randomized controlled trials.

AIM: Denosumab increases bone mineral density through inhibition of the receptor activator of nuclear factor κ-Β ligand (RANKL). RANKL has known immunomodulatory effect. The largest study to date that reviewed denosumab efficacy in osteoporosis demonstrated an increased incidence of serious adverse events of infection (SAEI). We aimed to further evaluate risk of infection and SAEI in denosumab-treated patients. METHOD: PubMed, Embase, Cochrane Central Register of Controlled Trials, and Web of Science were searched for randomized controlled trials. Studies comparing denosumab 60 mg every 6 months with placebo or bisphosphonate for treatment of low bone mineral density were included. Trials were excluded for use of denosumab in cancer patients treated for skeletal-related events, immunosuppressed patient populations, or for comparison to teriparatide. Risk ratios (RR) with a 95% confidence interval (CI) were pooled using a fixed effects model, or a random effects model if heterogeneity occurred. RESULTS: Twenty-four randomized controlled trials (20 470 patients) were analyzed. An increased incidence of any infection (RR 1.11; 95% CI 1.02-1.20; P = 0.02) was observed in denosumab-treated patients compared with bisphosphonates, but not when compared with placebo. In contrast, a higher incidence of SAEI (RR 1.21; 95% CI 1.03-1.43; P = 0.02) was seen with denosumab when compared with placebo, but not compared with bisphosphonates. CONCLUSION: Denosumab-treated patients with low bone mineral density have slightly increased incidence of SAEI compared with placebo, but not when compared with bisphosphonates. Application of these results requires consideration of the entire body of data available regarding denosumab safety.

Immediate effect of the COVID-19 pandemic on patient health, health-care use, and behaviours: results from an international survey of people with rheumatic diseases.

BACKGROUND: The impact and consequences of the COVID-19 pandemic on people with rheumatic disease are unclear. We developed the COVID-19 Global Rheumatology Alliance Patient Experience Survey to assess the effects of the COVID-19 pandemic on people with rheumatic disease worldwide. METHODS: Survey questions were developed by key stakeholder groups and disseminated worldwide through social media, websites, and patient support organisations. Questions included demographics, rheumatic disease diagnosis, COVID-19 diagnosis, adoption of protective behaviours to mitigate COVID-19 exposure, medication access and changes, health-care access and communication with rheumatologists, and changes in employment or schooling. Adults age 18 years and older with inflammatory or autoimmune rheumatic diseases were eligible for inclusion. We included participants with and without a COVID-19 diagnosis. We excluded participants reporting only non-inflammatory rheumatic diseases such as fibromyalgia or osteoarthritis. FINDINGS: 12 117 responses to the survey were received between April 3 and May 8, 2020, and of these, 10 407 respondents had included appropriate age data. We included complete responses from 9300 adults with rheumatic disease (mean age 46·1 years; 8375 [90·1%] women, 893 [9·6%] men, and 32 [0·3%] participants who identified as non-binary). 6273 (67·5%) of respondents identified as White, 1565 (16·8%) as Latin American, 198 (2·1%) as Black, 190 (2·0%) as Asian, and 42 (0·5%) as Native American or Aboriginal or First Nation. The most common rheumatic disease diagnoses included rheumatoid arthritis (3636 [39·1%] of 9300), systemic lupus erythematosus (2882 [31·0%]), and Sjögren's syndrome (1290 [13·9%]). Most respondents (6921 [82·0%] of 8441) continued their antirheumatic medications as prescribed. Almost all (9266 [99·7%] of 9297) respondents adopted protective behaviours to limit SARS-CoV-2 exposure. A change in employment status occurred in 2524 (27·1%) of 9300) of respondents, with a 13·6% decrease in the number in full-time employment (from 4066 to 3514). INTERPRETATION: People with rheumatic disease maintained therapy and followed public health advice to mitigate the risks of COVID-19. Substantial employment status changes occurred, with potential implications for health-care access, medication affordability, mental health, and rheumatic disease activity. FUNDING: American College of Rheumatology.

Regional variability in fecal microbiota transplantation practices: a survey of the Southern Ontario Fecal Microbiota Transplantation Movement.

BACKGROUND: There is growing evidence that fecal microbiota transplantation (FMT) is an effective treatment for recurrent Clostridium difficile infection, but little guidance exists for implementation of FMT programs. The objective of this study is to describe the program characteristics and protocols of 9 planned or operating FMT programs in the Southern Ontario Fecal Microbiota Transplantation (SOFT) Movement, to help guide future FMT program implementation. METHODS: A 59-item survey was administered electronically to clinical leads of the SOFT Movement on June 2, 2016. The survey evaluated 7 domains: FMT program characteristics, FMT recipients, donor screening/selection, transplant manufacturing, FMT administration, good manufacturing procedures/biosafety procedures and infection-control procedures. We used descriptive statistics to analyze quantitative data. RESULTS: All 9 programs responded to the survey: 6 were active, 1 had FMT standard operating procedures developed but did not have clinical experience, and 2 were in the process of forming FMT programs. All 6 active programs performed FMT in adult patients with C. difficile infection. About 1300 FMT procedures were performed between 2003 and 2016. Five of the 6 operating programs administered the preparation via enema. Programs were driven primarily by physicians. All programs used universal FMT donors and followed Health Canada's screening guidelines, with considerable variability in screening frequency (every 3-6 mo) and modality. Locations for transplant preparation and manufacturing protocols varied across programs. Stool mass for FMT ranged from 20 g to 150 g, and transplant volume ranged from 25 mL to 300 mL. INTERPRETATION: The experience of this high-volume regional FMT network highlights current challenges in FMT program development, including a high reliance on physicians and the costly nature of donor screening. Standardization and optimization through development of regional centres of excellence for FMT donor recruitment and administration should be explored.