Citations

AbstractValosin‐containing protein (VCP)‐associated multisystem proteinopathy (MSP) is a rare genetic disorder with abnormalities in the autophagy pathway leading to various combinations of myopathy, bone diseases, and neurodegeneration. Ninety percent of patients with VCP‐associated MSP have myopathy, but there is no consensus‐based guideline. The goal of this working group was to develop a best practice set of provisional recommendations for VCP myopathy which can be easily implemented across the globe. As an initiative by Cure VCP Disease Inc., a patient advocacy organization, an online survey was initially conducted to identify the practice gaps in VCP myopathy. All prior published literature on VCP myopathy was reviewed to better understand the different aspects of management of VCP myopathy, and several working group sessions were conducted involving international experts to develop this provisional recommendation. VCP myopathy has a heterogeneous clinical phenotype and should be considered in patients with limb‐girdle muscular dystrophy phenotype, or any myopathy with an autosomal dominant pattern of inheritance. Genetic testing is the only definitive way to diagnose VCP myopathy, and single‐variant testing in the case of a known familial VCP variant, or multi‐gene panel sequencing in undifferentiated cases can be considered. Muscle biopsy is important in cases of diagnostic uncertainty or lack of a definitive pathogenic genetic variant since rimmed vacuoles (present in ~40% cases) are considered a hallmark of VCP myopathy. Electrodiagnostic studies and magnetic resonance imaging can also help rule out disease mimics. Standardized management of VCP myopathy will optimize patient care and help future research initiatives.

Introduction: Health promotion programs focused on cardiovascular disease are underutilized with im/migrants. The one-time referral to group-based interventions model ignores (1) the complex sociocultural influences on behavior change and (2) the socio-historical context of migration, racialization of immigrants and refugees, and the roles these play in differential social integration of refugees. One solution may be to apply community-based participatory research (CBPR) and Public Health Critical Race Praxis (PHCRP) to social network interventions with opinion leaders. Yet, these interventions are challenging to scale. There is a critical need to understand how to scale community-driven social network interventions to effectively address cardiovascular disease inequities resulting from systemic racism experienced by im/migrant populations. Developed using CBPR and informed by PHCRP, this work builds upon Healthy Immigrant Community (HIC), a collaborative effort between Latinx and Somali im/migrant partners and Rochester Healthy Community Partnership. Our aim is to explore opinion leader recruitment, their characteristics, and expectations for HIC scale-up. Qualitative Hypothesis: Learning more about the opinion leaders’ background and experience in the Healthy Immigrant Community social network intervention will prepare us for a future efficacy study. Methods: We conducted a process evaluation by: (1) interviewing community partners who recruited opinion leaders (n=8) and (2) conducting three pre-intervention focus groups with opinion leaders (Latinx n=4; Somali women n=8; Somali men n=8). We used PHCRP to deductively form codes yet allowed for new ideas that arose from the data by inductively generating additional codes. Results: Interview participants described their decision-making process, qualities considered, recruitment strategies, and expectations for an implementation study. Focus group participants discussed their personal motivations for participation, how they hoped the study would help their community, and the barriers to health they experience because of structural determinism (macro-level forces that sustain inequities). Conclusions: This work will enhance our ability to translate HIC to other communities by expanding our knowledge of opinion leader characteristics that are important in a community-driven, social network intervention. Because social network interventions have been demonstrated to cause positive behavior change, further adapting these interventions in a community setting would be expected to provide a more effective approach compared to individually targeted behavior change strategies. Additionally, selecting OLs is neither time nor resource intensive and could enhance organizational strategies for implementing health promotion programming.

ImportanceThere is limited evidence for therapeutic options for pediatric COVID-19 outside of multisystem inflammatory syndrome in children (MIS-C).ObjectiveTo determine whether the use of steroids within 2 days of admission for non–MIS-C COVID-19 in children is associated with hospital length of stay (LOS). The secondary objective was to determine their association with intensive care unit (ICU) LOS, inflammation, and fever defervescence.Design, Setting, and ParticipantsThis cohort study analyzed data retrospectively for children (<18 years) who required hospitalization for non–MIS-C COVID-19. Data from March 2020 through September 2021 were provided by 58 hospitals in 7 countries who participate in the Society of Critical Care Medicine Discovery Viral Infection and Respiratory Illness Universal Study (VIRUS) COVID-19 registry.ExposureAdministration of steroids within 2 days of admission.Main Outcomes and MeasuresLength of stay in the hospital and ICU. Adjustment for confounders was done by mixed linear regression and propensity score matching.ResultsA total of 1163 patients met inclusion criteria and had a median (IQR) age of 7 years (0.9-14.3). Almost half of all patients (601/1163, 51.7%) were male, 33.8% (392/1163) were non-Hispanic White, and 27.9% (324/1163) were Hispanic. Of the study population, 184 patients (15.8%) received steroids within 2 days of admission, and 979 (84.2%) did not receive steroids within the first 2 days. Among 1163 patients, 658 (56.5%) required respiratory support during hospitalization. Overall, patients in the steroids group were older and had greater severity of illness, and a larger proportion required respiratory and vasoactive support. On multivariable linear regression, after controlling for treatment with remdesivir within 2 days, country, race and ethnicity, obesity and comorbidity, number of abnormal inflammatory mediators, age, bacterial or viral coinfection, and disease severity according to ICU admission within first 2 days or World Health Organization ordinal scale of 4 or higher on admission, with a random intercept for the site, early steroid treatment was not significantly associated with hospital LOS (exponentiated coefficient, 0.94; 95% CI, 0.81-1.09; P = .42). Separate analyses for patients with an LOS of 2 days or longer (n = 729), those receiving respiratory support at admission (n = 286), and propensity score–matched patients also showed no significant association between steroids and LOS. Early steroid treatment was not associated with ICU LOS, fever defervescence by day 3, or normalization of inflammatory mediators.Conclusions and RelevanceSteroid treatment within 2 days of hospital admission in a heterogeneous cohort of pediatric patients hospitalized for COVID-19 without MIS-C did not have a statistically significant association with hospital LOS.

Abstract Purpose To investigate preoperative and postoperative factors affecting functional success in anatomically successful retinal detachment surgery. Methods 75 eyes of 75 patients with rhegmatogenous retinal detachment (RRD) who underwent anatomically successful surgery, from 2014 to 2019 with more than one year follow up were included in the study. Demographic characteristics, ocular examination findings, preoperative and postoperative Spectral Domain Optic Coherence Tomography (SD-OCT) images were retrospectively evaluated. Results The mean age was 53.9 ± 17 (range: 11–85). The mean follow-up period was 36.7 ± 16 (range: 14–72) months. The mean best corrected visual acuity (BCVA) of the patients before surgery was 1.35 ± 1.24, and at postoperative 12 months was 0.66 ± 0.5 logMAR. Patients who were operated in 7 days of visual symptoms onset were found to have better visual acuity at the first and subsequent postoperative exams. Preoperative proliferative vitreoretinopathy (PVR), vitreous hemorrhage (VH) and extent of retinal detachment were found to have a negative effect on functional success at 12 months. Regeneration of the outer retinal layers had a positive effect on visual acuity at 12 months but did not significantly increase visual acuity after 12 months. Multivariate analysis showed that preoperative external limiting membrane (ELM) integrity was significantly associated with better functional outcomes. Conclusion Early intervention, presence of preoperative ELM integrity and restoration of postoperative outer retinal layers positively affected functional success. The presence of preoperative VH, PVR and the extent of retinal detachment had a negative effect on prognosis at 12 months.

AbstractIron overload is a severe general complication of hereditary anemias. Treatment with iron chelators is hampered by important side‐effects, high costs, and the lack of availability in many countries with a high prevalence of hereditary anemias. In this phase III randomized placebo‐controlled trial, we assigned adults with non‐transfusion‐dependent hereditary anemias with mild‐to‐moderate iron overload to receive esomeprazole (at a dose of 40 mg twice daily) or placebo for 12 months in a cross‐over design. The primary end point was change of liver iron content measured by MRI. A total of 30 participants were enrolled in the trial. Treatment with esomeprazole resulted in a statistically significant reduction in liver iron content that was 0.55 mg Fe/g dw larger than after treatment with placebo (95%CI [0.05 to 1.06]; p = 0.03). Median baseline liver iron content at the start of esomeprazole was 4.99 versus 4.49 mg Fe/g dw at start of placebo. Mean delta liver iron content after esomeprazole treatment was −0.57 (SD 1.20) versus −0.11 mg Fe/g dw (SD 0.75) after placebo treatment. Esomeprazole was well tolerated, reported adverse events were mild and none of the patients withdrew from the study due to side effects. In summary, esomeprazole resulted in a significant reduction in liver iron content when compared to placebo in a heterogeneous group of patients with non‐transfusion‐dependent hereditary anemias. From an international perspective this result can have major implications given the fact that proton pump inhibitors may frequently be the only realistic therapy for many patients without access to or not tolerating iron chelators.

Objectives: This study was conducted to assess an intervention that was created by a community–academic partnership to address COVID-19 health inequities. We evaluated a community-engaged bidirectional pandemic crisis and emergency risk communication (CERC) framework with immigrant and refugee populations during the COVID-19 pandemic. Methods: A 17-year community-engaged research partnership adopted a CERC framework in March 2020 to address COVID-19 prevention, testing, and socioeconomic impacts with immigrant and refugee groups in southeast Minnesota. The partnership used bidirectional communication between communication leaders and their social networks to refine messages, leverage resources, and advise policy makers. We conducted a mixed-methods evaluation for intervention acceptability, feasibility, reach, adaptation, and sustainability through multisource data, including email communications, work group notes, semistructured interviews, and focus groups. Results: The intervention reached at least 39 000 people in 9 months. It was implemented as intended and perceived efficacy was high. Frequent communication between community and academic partners allowed the team to respond rapidly to concerns and facilitated connection of community members to resources. Framework implementation also led to systems and policy changes to meet the needs of immigrant and refugee populations. Conclusions: Community-engaged CERC is feasible and sustainable and can reduce COVID-19 disparities through shared creation and dissemination of public health messages, enhanced connection to existing resources, and incorporation of community perspectives in regional pandemic mitigation policies.

Abstract Background Children with inflammatory bowel disease [IBD] are disproportionally affected by recurrent Clostridioides difficile infection [rCDI]. Although faecal microbiota transplantation [FMT] has been used with good efficacy in adults with IBD, little is known about outcomes associated with FMT in paediatric IBD. Methods We performed a retrospective review of FMT at 20 paediatric centres in the USA from March 2012 to March 2020. Children with and without IBD were compared with determined differences in the efficacy of FMT for rCDI. In addition, children with IBD with and without a successful outcome were compared with determined predictors of success. Safety data and IBD-specific outcomes were obtained. Results A total of 396 paediatric patients, including 148 with IBD, were included. Children with IBD were no less likely to have a successful first FMT then the non-IBD affected cohort [76% vs 81%, p = 0.17]. Among children with IBD, patients were more likely to have a successful FMT if they received FMT with fresh stool [p = 0.03], were without diarrhoea prior to FMT [p = 0.03], or had a shorter time from rCDI diagnosis until FMT [p = 0.04]. Children with a failed FMT were more likely to have clinically active IBD post-FMT [p = 0.002] and 19 [13%] patients had an IBD-related hospitalisation in the 3-month follow-up. Conclusions Based on the findings from this large US multicentre cohort, the efficacy of FMT for the treatment of rCDI did not differ in children with IBD. Failed FMT among children with IBD was possibly related to the presence of clinically active IBD.

OBJECTIVE To describe the impact of obesity on disease severity and outcomes of coronavirus disease 2019 (COVID-19) among hospitalized children. METHODS This retrospective cohort study from the Society of Critical Care Medicine Viral Respiratory Illness Universal Study registry included all children hospitalized with COVID-19 from March 2020 to January 2021. Obesity was defined by Centers for Disease Control and Prevention BMI or World Health Organization weight for length criteria. Critical illness definition was adapted from National Institutes of Health criteria of critical COVID. Multivariate mixed logistic and linear regression was performed to calculate the adjusted odds ratio of critical illness and the adjusted impact of obesity on hospital length of stay. RESULTS Data from 795 patients (96.4% United States) from 45 sites were analyzed, including 251 (31.5%) with obesity and 544 (68.5%) without. A higher proportion of patients with obesity were adolescents, of Hispanic ethnicity, and had other comorbidities. Those with obesity were also more likely to be diagnosed with multisystem inflammatory syndrome in children (35.7% vs 28.1%, P = .04) and had higher ICU admission rates (57% vs 44%, P < .01) with more critical illness (30.3% vs 18.3%, P < .01). Obesity had more impact on acute COVID-19 severity than on multisystem inflammatory syndrome in children presentation. The adjusted odds ratio for critical illness with obesity was 3.11 (95% confidence interval: 1.8–5.3). Patients with obesity had longer adjusted length of stay (exponentiated parameter estimate 1.3; 95% confidence interval: 1.1–1.5) compared with patients without obesity but did not have increased mortality risk due to COVID-19 (2.4% vs 1.5%, P = .38). CONCLUSION In a large, multicenter cohort, a high proportion of hospitalized children from COVID-19 had obesity as comorbidity. Furthermore, obesity had a significant independent association with critical illness.