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BackgroundAn electronic diary embedded in a mobile device to monitor lifestyle can be as effective as traditional methods. However, the efficacy of self-monitoring multiple behaviors for dietary intake has not been well studied in people with diabetes. ObjectiveThis study aimed to compare the effect of using technology-assisted self-monitoring versus paper diaries on changes in dietary intake. MethodsThis is a secondary analysis of data collected from 39 people with type 2 diabetes as part of a 3-month pilot clinical trial. Changes in energy intake and the contribution of total fat intake and total carbohydrate intake to total calories (%) from baseline to after intervention (3 months) were evaluated. ResultsIn total, 26 (67%) of the 39 participants preferred mobile diaries over paper diaries. Participants in the mobile diary group showed slightly higher self-monitoring adherence. Linear mixed modeling results indicated a significant overall decrease in total energy intake (P=.005), dietary fat intake (P=.01), and carbohydrate intake (P=.08) from baseline to 3 months. No significant group differences were detected (P>.05). ConclusionsThe implementation of a 3-month, multiple-behavior, self-monitoring intervention in Diabetes Self-Management Education programs has resulted in successful reduction in dietary intake (energy, fat, and carbohydrate), whichever self-monitoring method is chosen by participants according to their preferences. Long-term studies are needed to confirm our findings on dietary intake and examine other behavioral and disease outcomes that require monitoring.

Disparities in maternal health outcomes are striking. Historical and biased clinical support tools have potential to exacerbate inequities. In 2022, NewYork-Presbyterian, with ?25,000 annual births, and our academic partners, Columbia and Weill Cornell, launched a program to better understand practice patterns and clinician attitudes toward a vaginal birth after cesarean (VBAC) calculator, which predicts VBAC success. This article summarizes the program, focusing on the VBAC calculator utilization survey, which measured provider awareness of the revised calculator and key factors considered in patient counseling. Our preliminary findings warrant future research and education on the calculator's implications for counseling and outcomes.

Abstract Objective Pediatric rheumatology faces a looming supply-demand crisis. While strategies have been proposed to address the supply shortfall, investigation into the increased demand for pediatric rheumatic care has been limited. Herein, we analyze new patient visits to a large tertiary care pediatric rheumatology center to identify emerging trends in referrals and areas for potential intervention to meet this increased demand. Methods All patients referred to and seen by the University of Alabama at Birmingham Pediatric Rheumatology Division between January 2019 and December 2021 for a new patient evaluation were identified. Patient data was retrospectively abstracted, de-identified, and analyzed to develop trends in referrals and frequency of rheumatic disease, non-rheumatic disease, and specific diagnoses. Results During the study period, 2638 patients were referred to and seen in by the pediatric rheumatology division. Six hundred and ten patients (23.1%) were diagnosed with rheumatic disease. The most common rheumatic disease was juvenile idiopathic arthritis (JIA) at 45.6%, followed by primary Raynaud phenomenon (7.4%), recurrent fever syndromes (6.9%), vasculitides (6.7%), and inflammatory eye disease (6.2%). Of the 2028 patients (76.9%) diagnosed with a non-rheumatic condition, benign musculoskeletal pain was the most common (61.8%), followed by a combination of somatic conditions (11.6%), and non-inflammatory rash (7.7%). Conclusion In this analysis of new patient referrals to a large pediatric rheumatology center, the majority of patients were diagnosed with a non-rheumatic condition. As a worsening supply-demand gap threatens the field of pediatric rheumatology, increased emphasis should be placed on reducing non-rheumatic disease referrals.

Abstract Background Nurses are well positioned to promote sexual health but are not adequately prepared in their nursing programs to engage families on this topic and often lack the knowledge and confidence necessary to counsel families about sexual health communication. The purpose of this study was to determine how facilitating a parent-based sexual health intervention would impact nursing students’ attitudes and intentions about sexual health education and parent communication counseling. Methods Using an embedded mixed-methods design, which integrated a quasi-experimental framework, we examined the impact of participation in a parent-based sexual health intervention among 126 baccalaureate nursing students enrolled in a community/public health nursing clinical course. Independent t-tests, chi-squared tests, and the Mann-Whitney U test were used to compare intervention and control groups at baseline. Multiple linear regression was used to compare the groups for pre-post changes. Qualitative content analysis was used to analyze exit interview transcripts. Results We found statistically significant differences in nursing students’ confidence to teach sexual health (p =

Background/aimManaging reactive hypoglycaemia (RH) poses challenges due to limited and often ineffective treatment options. We report a case series and draw on this to propose a stepwise treatment approach consisting of lifestyle modifications, metformin, GLP-1 analogues, and the use of flash glucose monitoring technology.MethodA retrospective review was conducted to analyse the management of 11 cases presenting with recurrent RH symptoms.ResultTwo patients experienced successful resolution of symptoms through lifestyle modifications. Metformin alone was effective in treating seven out of nine patients who received pharmacological treatment. Two patients with previous upper gastrointestinal surgery showed a partial response to metformin and benefited further from additional long-acting GLP-1 analogue. Pharmacological intervention led to significant reductions in insulin and C-peptide levels in repeat mixed meal tolerance tests (P-values 0.043 for insulin and 0.006 for C-peptide). Finally, flash glucose monitoring technology was useful in early detection and preventing episodes of hypoglycaemia in one of these patients with persistent symptoms.ConclusionThese findings highlight the potential efficacy of escalated treatment strategies for RH, including the use of metformin, GLP-1 analogues, and flash glucose monitoring technology.

Abstract Background Depressive symptoms are a significant psychological complication of stroke, impacting both survivors and informal caregivers of survivors. Randomized controlled trials are needed to determine optimal non-pharmacological strategies to prevent or ameliorate depressive symptoms in stroke survivors and their informal caregivers. Methods A prospective, randomized, parallel-group, single-center, feasibility study. Participants were assigned to a 4-week meditation intervention or expressive writing control group. The intervention comprised four facilitator-led group meditation sessions, one session per week and building upon prior session(s). Descriptive statistics were used to examine the proportion of eligible individuals who enrolled, retention and adherence rates, and the proportion of questionnaires completed. Data were collected at baseline, immediately after the 4-week intervention period, and 4 and 8 weeks after the intervention period. Secondary analysis tested for changes in symptoms of depression (Center for Epidemiologic Studies-Depression [CES-D]), anxiety [State-Trait Anxiety Inventory for Adults (STAI)], and pain (Brief Pain Inventory-Short Form) in the intervention group via paired t tests. Linear mixed models were used to compare longitudinal changes in the measures between the groups. Intervention and trial design acceptability were preliminary explored. Results Seventy-one (77%) individuals enrolled and 26 (37%) completed the study (baseline and 8-week post-intervention visits completed). Forty-two (66%) participants completed baseline and immediate post-intervention visits. Mean questionnaire completion rate was 95%. The median meditation group session attendance rate for the intervention group was 75.0%, and the mean attendance rate was 55%. Non-significant reductions in CES-D scores were found. Paired t tests for stroke survivors indicated a significant reduction from baseline through week 8 in BPI-sf severity scores (p = 0.0270). Repeated measures analysis with linear mixed models for informal caregivers indicated a significant reduction in in STAI-Trait scores (F [3,16.2] = 3.28, p = 0.0479) and paired t test showed a significant reduction from baseline to week 4 in STAI-Trait scores (mean = − 9.1250, 95% CI [− 16.8060 to 1.4440], p = 0.0262). No between-group differences were found. Conclusions Future trials will require strategies to optimize retention and adherence before definitive efficacy testing of the meditation intervention. Trial registration: ClinicalTrials.gov Identifier: NCT03239132. Registration date: 03/08/2017

Abstract Background Laparoscopic (LSC) Heller myotomy (HM) is considered the standard procedure for the treatment of achalasia. Robotic platforms, established over the last years, provide important advantages to surgeons, such as binocular 3-dimensional vision and improvement of fine motor control. However, whether perioperative outcomes and long-term results of robotic-assisted laparoscopic (RAL) HM are similar or even superior to LSC technique, especially concerning long-term follow-up, is still debated. Therefore, the aim of the present study was to evaluate intra- and postoperative results as well as long-term quality of life after RAL compared to LSC surgery for achalasia in a single high-volume visceral surgery center. Methods Between August 2007 and April 2020, 43 patients undergoing minimally invasive HM for achalasia in a single high-volume Swiss visceral surgery center, were included in the present study. Intra- and postoperative outcome parameters were collected and evaluated, and a long-term follow-up was performed using the gastroesophageal-reflux disease health-related quality of life (GERD-Hr-QuoL) questionnaire. Results A total of 11 patients undergoing RAL and 32 undergoing LSC HM were analyzed. Baseline demographics and clinical characteristics were similar. A trend (p = 0.052) towards a higher number of patients with ASA III score treated with RAL was detectable. Operation time was marginally, but significantly, shorter in LSC (140 min, IQR: 136–150) than in RAL (150 min, IQR: 150–187, p = 0.047). Postoperative complications graded Clavien-Dindo ≥ 3 were only observed in one patient in each group. Length of hospital stay was similar in both groups (LSC: 11 days, IQR: 10–13 vs. RAL: 11 days, IQR: 10–14, p = 0.712). Long-term follow-up (LSC: median 89 months, vs. RAL: median 28 months, p = 0.001) showed comparable results and patients from both groups expressed similar levels of satisfaction (p = 0.181). Conclusions LSC and RAL HM show similar peri- and postoperative results and a high quality of life, even in long-term (> 24 months) follow-up. Prospective, randomized, controlled multicenter trials are needed to overcome difficulties associated to small sample sizes in a rare condition and to confirm the equality or demonstrate the superiority of robotic-assisted procedures for achalasia. Meanwhile, the choice of the treatment technique could be left to the operating surgeon’s preferences.

Purpose: The objective of this study was to explore parent and child anxiety during the pandemic. Unlike previous pandemics, measures implemented to prevent the transmission of the SARS-CoV-2 virus have been much more limiting. Methods: An explanatory convergent mixed-methods design was used to describe anxiety of children 9–17 years of age and their parents during August–October 2020. Adult and child versions of State-Trait Anxiety Inventory (STAI) were used to examine levels as measured on STAI’s state-anxiety subscale. Web-based interviews with a subset of patients were conducted qualitatively to analyze anxiety-related themes. Results: A total of 188 parents and 140 children responded to the questionnaires. Mean overall anxiety scores for parents (49.17 [standard deviation: 12.247]) and children (35.43 [standard deviation: 7.894]) were higher than published norms. Parent and child anxiety were positively correlated (r = 0.36; P = 0.01). From interviews with 11 parents and 11 children; 4 major themes and 10 subthemes describing physical and emotional outcomes resulting from limited social contact, work and family role strain, and uncertainty about COVID-19 were identified. Conclusions: Parents and children reported elevated anxiety levels during the COVID-19 pandemic. Findings of this study can guide the development of strategies that mitigate the negative impact of isolation, role strain, and uncertainty related to future public health crises.

BackgroundDiabetes mellitus can lead to severe and debilitating foot complications, such as infections, ulcerations, and amputations. Despite substantial progress in diabetes care, foot disease remains a major challenge in managing this chronic condition that causes serious health complications worldwide. ObjectiveThe primary aim of this study was to examine the feasibility and usability of a telehealth program focused on preventive diabetes foot care. A secondary aim was to descriptively measure self-reported changes in diabetes knowledge, self-care, and foot care behaviors before and after participating in the program. MethodsThe study used a single-arm, pre-post design in 2 large family medical practice clinics in Texas. Participants met individually with the nurse practitioner once a month for 3 months using synchronous telehealth videoconferencing. Each participant received diabetes foot education guided by the Integrated Theory of Health Behavior Change. Feasibility was measured with rates of enrollment and program and assessment completion. Usability was measured with the Telehealth Usability Questionnaire. Diabetes knowledge, self-care, and foot care behaviors were measured with validated survey instruments at baseline, 1.5 months, and 3 months. ResultsOf 50 eligible individuals, 39 (78%) enrolled; 34 of 39 (87%) completed the first videoconference and 29 of 39 (74%) completed the second and third videoconferences. Of the 39 who consented, 37 (95%) completed the baseline assessment; 50% (17/34) of those who attended the first videoconference completed the assessment at 1.5 months, and 100% (29/29) of those who attended the subsequent videoconferences completed the final assessment. Overall, participants reported a positive attitude toward the use of telehealth, with a mean Telehealth Usability Questionnaire score of 6.24 (SD 0.98) on a 7-point scale. Diabetes knowledge increased by a mean of 15.82 (SD 16.69) points of 100 (P

ObjectivesPeriodontitis disproportionately affects different racial and ethnic populations. We have previously reported the higher levels of Porphyromonas gingivalis and lower ratios of Streptococcus cristatus to P. gingivalis may contribute to periodontal health disparities. This prospective cohort study was designed to investigate if ethnic/racial groups responded differently to non-surgical periodontal treatment and if the treatment outcomes correlated to the bacterial distribution in patients with periodontitis before treatment.MethodsThis prospective cohort pilot study was carried out in an academic setting, at the School of Dentistry, University of Texas Health Science Center at Houston. Dental plaque was collected from a total of 75 African Americans, Caucasians and Hispanics periodontitis patients in a 3-year period. Quantitation of P. gingivalis and S. cristatus was carried out using qPCR. Clinical parameters including probing depths and clinical attachment levels were determined before and after nonsurgical treatment. Data were analyzed using one-way ANOVA, the Kruskal–Wallis test, the paired samples t-test and the chi-square test.ResultsThe gains in clinical attachment levels after treatment significantly differed amongst the 3 groups–Caucasians responded most favorably, followed by African-Americans, lastly Hispanics, while numbers of P. gingivalis were highest in Hispanics, followed by African-Americans, and lowest in Caucasians (p = 0.015). However, no statistical differences were found in the numbers of S. cristatus amongst the 3 groups.ConclusionDifferential response to nonsurgical periodontal treatment and distribution of P. gingivalis are present in different ethnic/racial groups with periodontitis.

Abstract Background Health system science (HSS) encompasses both core and cross-cutting domains that emphasize the complex interplay of care delivery, finances, teamwork, and clinical practice that impact care quality and safety in health care. Although HSS skills are required during residency training for physicians, current HSS didactics have less emphasis on hands-on practice and experiential learning. Medical simulation can allow for experiential participation and reflection in a controlled environment. Our goal was to develop and pilot three simulation scenarios as part of an educational module for resident physicians that incorporated core and cross-cutting HSS domains. Methods Each scenario included a brief didactic, an interactive simulation in small-group breakout rooms, and a structured debriefing. The case scenario topics consisted of educational leadership, quality and safety, and implementation science. Learners from four residency programs (psychiatry, emergency medicine, orthopedics, ophthalmology) participated January – March 2021. Results A total of 95 resident physicians received our curricular module, and nearly all (95%) participants who completed a post-session survey reported perceived learning gains. Emotional reactions to the session were positive especially regarding the interactive role-play format. Recommendations for improvement included participation from non-physician professions and tailoring of scenarios for specific disciplines/role. Knowledge transfer included use of multiple stakeholder perspectives and effective negotiation by considering power/social structures. Conclusions The simulation-based scenarios can be feasibly applied for learner groups across different residency training programs. Simulations were conducted in a virtual learning environment, but future work can include in-person and actor-based simulations to further enhance emotional reactions and the reality of the case scenarios.

(1) Background: Some severe COVID-19 patients develop hyperinflammatory cytokine storm syndrome (CSS). We assessed the efficacy of anakinra added to standard of care (SoC) in hospitalized COVID-19 CSS patients. (2) Methods: In this single-center, randomized, double-blind, placebo-controlled trial (NCT04362111), we recruited adult hospitalized patients with SARS-CoV-2 infection, evidence of pneumonia, new/increasing oxygen requirement, ferritin ≥ 700 ng/mL, and at least three of the following indicators: D-dimer ≥ 500 ng/mL, platelet count < 130,000/mm3, WBC < 3500/mm3 or lymphocyte count < 1000/mm3, AST or ALT > 2X the upper limit of normal (ULN), LDH > 2X ULN, C-reactive protein > 100 mg/L. Patients were randomized (1:1) to SoC plus anakinra (100 mg subcutaneously every 6 h for 10 days) or placebo. All received dexamethasone. The primary outcome was survival and hospital discharge without need for intubation/mechanical ventilation. The data were analyzed according to the modified intention-to-treat approach. (3) Results: Between August 2020 and January 2021, 32 patients were recruited, of which 15 were assigned to the anakinra group, and 17 to the placebo group. Two patients receiving the placebo withdrew within 48 h and were excluded. The mean age was 63 years (SD 10.3), 20 (67%) patients were men, and 20 (67%) were White. At Day 10, one (7%) patient receiving anakinra and two (13%) patients receiving the placebo had died (p = 1.0). At hospital discharge, four (27%) patients receiving anakinra and four (27%) patients receiving the placebo had died. The IL-6 level at enrollment was predictive of death (p < 0.01); anakinra use was associated with decreases in CXCL9 levels. (4) Conclusions: Anakinra added to dexamethasone did not significantly impact the survival of COVID-19 pneumonia patients with CSS. Additional studies are needed to assess patient selection and the efficacy, timing, and duration of anakinra treatment for COVID-19 CSS.

Warburgia salutaris (pepperbark tree) is an endangered species greatly valued in South Africa for use in traditional medicine. In one of the few remaining W. salutaris conserved sites, the Kruger National Park (KNP), fruit production is extremely low, with a relatively low proportion of juveniles in the population. This study aimed firstly, to understand the reproductive ecology of W. salutaris and, secondly, to investigate factors that may contribute to the limited fruit (and seed) output in KNP by comparing results from KNP with a reproductively successful orchard in Eston, KwaZulu-Natal Province. In the first part of the study, potential pollinators were observed and collected for further analysis; four pollination treatments (i.e. autonomous self-, geitonogamous self-, cross- and natural pollination) were set-up to elucidate the breeding system; pollen viability was assessed; and pollen tube growth for self-, cross- and natural pollination was compared. In the second part of the study, fruit production and maturation was assessed; seed dispersers were identified; and germination success of seeds from natural and cultivated populations were compared. Pollination trials revealed that W. salutaris is likely self-incompatible as self-pollinated flowers in neither KNP nor Eston resulted in mature fruit. In addition, the majority of flowers that began to form fruit in the natural-bagged treatment (i.e. naturally pollinated flowers bagged to protect from seed predation) were aborted. Pollen viability was high across both the KNP sub-populations and Eston, while percentage pollen tube occurrence for self- and cross-pollination was higher in Eston than KNP. Mature KNP fruit were only present on three trees in one sub-population during the two-year study period. Ceratitis cosyra, the marula fly, was the only seed predator in W. salutaris fruit, and 20% of collected KNP fruit were affected by seed predation. Frugivore observations in a supplemental population at Leshiba Mountain Retreat (Limpopo Province) revealed that baboons (Papio ursinus) and vervet monkeys (Chlorocebus aethiops pygerythrus) eat W. salutaris fruit (but not the exocarp) and possibly orally discard the seeds at a later stage. Seeds from KNP fruit were viable and had the highest percentage germination, followed by Eston, and Leshiba. Overall, W. salutaris has many floral visitors, with Lepidoptera the most likely pollinators, pollen viability is high, and seeds that are produced germinate successfully. Therefore, the impaired reproductive output in KNP appears to be in the high occurrence of aborted fruit, supporting the hypothesis that the species relies on clonal reproduction and resprouting to persist in KNP. However, long-term reliance on clonal reproduction may impair the ability to reproduce sexually, which is ultimately necessary to establish genetically diverse genets that can adapt to environmental changes.

Objective The objective of this study is to evaluate pediatric patients using existing macrophage activation syndrome (MAS) and hemophagocytic lymphohistiocytosis (HLH) scoring systems to determine how these systems identify patients with cytokine storm syndrome (CSS) in the setting of a multisystem inflammatory syndrome in children (MIS‐C) and active coronavirus disease 2019 (COVID‐19) infection. Methods Hospitalized pediatric patients with MIS‐C and active COVID‐19 infection at a single institution were identified. Infectious data, clinical findings, and laboratory values were collected, and patients were stratified by disease severity. Eight historically used scoring systems for MAS, HLH, and CSS were examined in the cohort of patients with MIS‐C and pediatric COVID‐19. Results The HLH‐2004 criteria and HScore did not identify any patients as having CSS on admission, with only one patient with COVID‐19 meeting criteria at peak disease severity. The 2016 systemic juvenile idiopathic arthritis (sJIA)/MAS criteria, ferritin/erythrocyte sedimentation rate (ESR) ratio, and COVID‐19 CSS Quick Score most frequently identified CSS in this population and distinguished between COVID‐19 and MIS‐C hyperinflammation. The 2019 MAS/sJIA (MS) score and the COVID‐19–associated hyperinflammatory syndrome (cHIS) criteria were less likely to identify CSS, as the MS score overestimated CSS and the cHIS resulted in similar scores regardless of severity or disease type. The Caricchio COVID‐Cytokine Storm (COVID‐CS) criteria identified patients with COVID‐19 frequently but was less useful in MIS‐C because of its COVID‐19‐specific criteria. Conclusion MIS‐C and pediatric COVID‐19 result in relatively unique CSSs and patterns of inflammation. Existing scoring systems for CSSs likely do not capture the full breadth of this disease process in MIS‐C and pediatric COVID‐19.

Primary motor cortex (M1) consists of a stack of interconnected but distinct layers (L1-L6) which affect motor control through large-scale networks. However, the brain-wide functional influence of each layer is poorly understood. We sought to expand our knowledge of these layers’ circuitry by combining Cre-driver mouse lines, optogenetics, fMRI, and electrophysiology. Neuronal activities initiated in Drd3 neurons (within L2/3) were mainly confined within M1, while stimulation of Scnn1a, Rbp4, and Ntsr1 neurons (within L4, L5, and L6, respectively) evoked distinct responses in M1 and motor-related subcortical regions, including striatum and motor thalamus. We also found that fMRI responses from targeted stimulations correlated with both local field potentials (LFPs) and spike changes. This study represents a step forward in our understanding of how different layers of primary motor cortex are embedded in brain-wide circuitry.

Cytokine storm syndrome (CSS) is a serious and potentially life-threatening condition caused by severe systemic inflammation, immune activation, and a positive feedback loop of cytokine release. Typically triggered by systemic infection, malignancy, monogenic or rheumatic disease, similar patterns of hyper-inflammation have been seen in patients undergoing cardiopulmonary bypass (CPB) and in patients treated with extracorporeal membrane oxygenation (ECMO). Typical treatments used for the prevention and treatment of CPB/ECMO-induced hyper-inflammation have not been shown to be substantially effective. Two patients suffering from ECMO-related CSS were identified by their severe hyper-inflammatory profile and life-threatening sequelae of vasodilatory shock and respiratory failure. Anakinra, an interleukin-1 receptor antagonist, was employed as specific cytokine-directed therapy for the treatment of CSS in these two patients to good effect, with significant improvement in hyper-inflammation and cardiorespiratory status. The use of cytokine-directed therapies in CPB/ECMO-related CSS has great potential to improve the treatment and outcomes of this serious condition.

The Afromontane and Afroalpine areas constitute some of the main biodiversity hotspots of Africa. They are particularly rich in plant endemics, but the biogeographic origins and evolutionary processes leading to this outstanding diversity are poorly understood. We performed phylogenomic and biogeographic analyses of one of the most species-rich plant genera in these mountains, Helichrysum (Compositae-Gnaphalieae). Most previous studies have focused on Afroalpine elements of Eurasian origin, and the southern African origin of Helichrysum provides an interesting counterexample. We obtained a comprehensive nuclear dataset from 304 species (≈50% of the genus) using target-enrichment with the Compositae1061 probe set. Summary-coalescent and concatenation approaches combined with paralog recovery yielded congruent, well-resolved phylogenies. Ancestral range estimations revealed that Helichrysum originated in arid southern Africa, whereas the southern African grasslands were the source of most lineages that dispersed within and outside Africa. Colonization of the tropical Afromontane and Afroalpine areas occurred repeatedly throughout the Miocene–Pliocene. This timing coincides with mountain uplift and the onset of glacial cycles, which together may have facilitated both speciation and intermountain gene flow, contributing to the evolution of the Afroalpine flora.

ObjectiveMacrophage activation syndrome (MAS) is a life-threatening, potentially fatal condition associated with systemic juvenile idiopathic arthritis (sJIA). Interleukin-1 (IL-1) is a key cytokine in the pathogenesis of sJIA MAS. Many cases of MAS are medically refractory to traditional doses of biologic cytokine inhibitors and may require increased dosing. When MAS occurs in the setting of sJIA treated with the IL-1 receptor antagonist (IL-1Ra), anakinra, increased anakinra dosing may be beneficial. Increased dosing of another IL-1 inhibitor, canakinumab, a monoclonal antibody to IL-1β, has not been reported to treat refractory MAS in the setting of sJIA.MethodsRetrospective data collection extracted from the electronic medical record focused on canakinumab usage and dosing in 8 children with sJIA who developed MAS at a single academic center from 2011 to 2020.ResultsEight sJIA children (five girls) with median age 8.5 years (range, 0.9–14.2 years) were included in the present study. Five children developed MAS at disease onset and three during ongoing canakinumab therapy. MAS resolved in all eight children with canakinumab treatment. When the canakinumab dosing was insufficient or MAS developed during canakinumab therapy, the dosing was temporally up-titrated (four patients, maximum 300 mg per dose) without observed side effects.ConclusionThis report provides evidence for the efficacy and safety of short-term increased doses (2–3-times normal) of canakinumab in treating sJIA associated MAS. Further study of the efficacy and safety of increased doses of canakinumab for treatment of MAS in children with sJIA is warranted.

Objective Determine the pharmacokinetics (PK) and exposure–response of hydroxychloroquine (HCQ) and desethylhydroxychloroquine (DHCQ) in paediatric SLE (pSLE).Methods We conducted an exploratory phase 2, direct-to-family trial. Children enrolled in the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry with a diagnosis of pSLE were eligible if they were receiving HCQ as standard of care for ≥3 months. Biological samples were collected at up to four visits over a 6-month period. At each visit, plasma was obtained to measure the concentrations of HCQ and DHCQ, as well as cytokines. HCQ and DHCQ plasma PK data were analysed using a population PK modelling approach.Results Twenty-five subjects provided a total of 88 plasma concentrations for PK analysis. There was a poor linear fit between HCQ concentrations and total body weight (R2=0.03). There was a decline in both interferon (IFN)-alpha and IFN-gamma with higher concentrations of HCQ and DHCQ. Volume of distribution for HCQ in plasma was higher in children compared with published values in adults (73 000 L vs 44 000 L), but clearance values in children were similar to adults.Conclusions We report the first population PK model for HCQ and DHCQ in children using data from a novel direct-to-family clinical trial. We observed high interindividual variability in HCQ PK and found that weight-based dosing for HCQ is poorly correlated with drug concentrations, suggesting the need to use therapeutic drug monitoring to individualise dosing. Furthermore, our results suggest that the current weight-based dosing paradigm for HCQ may result in suboptimal drug exposures, particularly for children with obesity. Accordingly, additional studies of HCQ are needed in pSLE to determine the optimal drug concentration and dosing to reduce disease activity and improve outcomes.Trial registration number NCT04358302.

Abstract Background Parents play a pivotal role in adolescent sexual health and Human Papillomavirus (HPV) vaccination. Nurses are on the frontlines of healthcare and play a critical role in promoting HPV vaccination and parent-child sexual health communication. We enhanced the Families Talking Together (FTT) parent-based sexual health curriculum to include adolescent vaccinations herein, FTT + HPV, and trained student nurses to provide a strong HPV vaccination and parent-child sexual health communication endorsement. Methods Using a randomized attention-controlled trial design, we examined the efficacy of FTT + HPV among 519 parents and their 11–14 year old youth recruited from medically underserved communities between 2015 and 2018. Participants were recruited from 22 after-school programs (e.g., Boys and Girls Clubs) and 19 charter schools. For parents, we examined protective factors including parent-child sexual health communication and parental involvement. For youth, we examined sexual health knowledge, parent-child sexual health communication, and parent-child connectedness. To assess HPV vaccination initiation and completion, we searched IMMTRAC immunization registry records for 85% of youth and used parental report for youth without registry records. Group differences were calculated using the estimated mean difference at one- and six months post-intervention with significance set at the p

Abstract Importance Active pediatric COVID-19 pneumonia and MIS-C are two disease processes requiring rapid diagnosis and different treatment protocols. Objective To distinguish active pediatric COVID-19 pneumonia and MIS-C using presenting signs and symptoms, patient characteristics, and laboratory values. Design Patients diagnosed and hospitalized with active COVID-19 pneumonia or MIS-C at Children’s of Alabama Hospital in Birmingham, AL from April 1 through September 1, 2020 were identified retrospectively. Active COVID-19 and MIS-C cases were defined using diagnostic codes and verified for accuracy using current US Centers for Disease Control case definitions. All clinical notes were reviewed for documentation of COVID-19 pneumonia or MIS-C, and clinical notes and electronic medical records were reviewed for patient demographics, presenting signs and symptoms, prior exposure to or testing for the SARS-CoV-2 virus, laboratory data, imaging, treatment modalities and response to treatment. Findings 111 patients were identified, with 74 classified as mild COVID-19, 8 patients as moderate COVID-19, 8 patients as severe COVID-19, 10 as mild MIS-C and 11 as severe MIS-C. All groups had a male predominance, with Black and Hispanic patients overrepresented as compared to the demographics of Alabama. Most MIS-C patients were healthy at baseline, with most COVID-19 patients having at least one underlying illness. Fever, rash, conjunctivitis, and gastrointestinal symptoms were predominant in the MIS-C population whereas COVID-19 patients presented with predominantly respiratory symptoms. The two groups were similar in duration of symptomatic prodrome and exposure history to the SARS-CoV-2 virus, but MIS-C patients had a longer duration between presentation and exposure history. COVID-19 patients were more likely to have a positive SAR-CoV-2 PCR and to require respiratory support on admission. MIS-C patients had lower sodium levels, higher levels of C-reactive protein, erythrocyte sedimentation rate, d-dimer and procalcitonin. COVID-19 patients had higher lactate dehydrogenase levels on admission. MIS-C patients had coronary artery changes on echocardiography more often than COVID-19 patients. Conclusions and relevance This study is one of the first to directly compare COVID-19 and MIS-C in the pediatric population. The significant differences found between symptoms at presentation, demographics, and laboratory findings will aide health-care providers in distinguishing the two disease entities.

Abstract Background Myasthenia gravis (MG) is a rare autoimmune disease mainly mediated by autoantibodies against the acetylcholine receptor (AChR) at the neuromuscular junction. The thymus is the effector organ, and its removal alleviates the symptoms of the disease. In the early-onset form of MG, the thymus displays functional and morphological abnormalities such as B cell infiltration leading to follicular hyperplasia, and the production of AChR antibodies. Type-I interferon (IFN-I), especially IFN-β, is the orchestrator of thymic changes observed in MG. As Dicer and miR-29 subtypes play a role in modulating the IFN-I signalization in mouse thymus, we investigated their expression in MG thymus. Methods The expression of DICER and miR-29 subtypes were thoroughly investigated by RT-PCR in human control and MG thymuses, and in thymic epithelial cells (TECs). Using miR-29a/b-1-deficient mice, with lower miR-29a/b-1 expression, we investigated their susceptibility to experimental autoimmune MG (EAMG) as compared to wild-type mice. Results DICER mRNA and all miR-29 subtypes were down-regulated in the thymus of MG patients and DICER expression was correlated with the lower expression of miR-29a-3p. A decreased expression of miR-29 subtypes was similarly observed in MG TECs; a decrease also induced in TECs upon IFN-β treatment. We demonstrated that miR-29a/b-1-deficient mice were more susceptible to EAMG without higher levels of anti-AChR IgG subtypes. In the thymus, if no B cell infiltration was observed, an increased expression of Ifn-β associated with Baff expression and the differentiation of Th17 cells associated with increased expression of Il-6, Il-17a and Il-21 and decreased Tgf-β1 mRNA were demonstrated in miR-29a/b-1-deficient EAMG mice. Conclusions It is not clear if the decreased expression of miR-29 subtypes in human MG is a consequence or a causative factor of thymic inflammation. However, our results from the EAMG mouse model indicated that a reduction in miR-29a/b1 may contribute to the pathophysiological process involved in MG by favoring the increased expression of IFN-β and the emergence of pro-inflammatory Th17 cells.

Abstract Background Neurological involvement has been reported in up to 80% of adults with Primary Sjogren’s syndrome (pSS) with psychiatric abnormalities including anxiety, depression, and cognitive dysfunction being common. Psychosis due to pSS has been reported in adult patients but has never been previously reported in the adolescent/pediatric literature. Here we describe for the first time four cases of adolescent Sjogren’s syndrome that presented with psychotic symptoms. Rituximab treatment was followed by improvement of psychiatric symptoms in all patients. Case presentation 1: 16 year old female without significant past medical history presented to the emergency department with 4 days of abnormal behavior, tremors, insomnia, polyphagia, polyuria, and suicidal ideation. 2: 16 year old female with a 4 year history of severe anxiety, OCD, and tic disorder treated with fluoxetine with partial benefit presented with an abrupt and severe worsening of anxiety, OCD and new auditory hallucinations. 3: 19 year old female without significant past medical history presented with a 3 day history of progressively altered behavior, incoherent speech, insomnia, headache, and tangential thoughts. 4: 17 year old female without significant past medical history presented with new onset suicidal ideation, paranoia, confusion, and emotional lability. Conclusion Psychosis is more common in autoimmune disease than previously known. To our knowledge, the four teenage women described above are the first reported patients with adolescent pSS manifesting as psychosis. pSS should be considered in the differential diagnosis of young patients with new psychiatric disorders, even in the absence of sicca symptoms. Psychiatric symptoms improved with rituximab infusions in all 4 of our patients, which suggests rituximab may be an effective treatment option that should be considered early after the diagnosis of pSS-associated psychiatric disturbance.

Hemophagocytic lymphohistiocytosis (HLH) is a syndrome resulting from uncontrolled hyper-inflammation, excessive immune system activation, and elevated levels of inflammatory cytokines. HLH can be caused by the inability to downregulate activated macrophages by natural killer (NK) and CD8 cytotoxic T cells through a process reliant on perforin and granzyme B to initiate apoptosis. Homozygous genetic mutations in this process result in primary HLH (pHLH), a disorder that can lead to multi-system organ failure and death in infancy. Heterozygous, dominant-negative, or monoallelic hypomorphic mutations in these same genes can cause a similar syndrome in the presence of an immune trigger, leading to secondary HLH (sHLH). A genetic mutation in a potential novel HLH-associated gene, dedicator of cytokinesis 2 (DOCK2), was identified in a patient with recurrent episodes of sHLH and hyperinflammation in the setting of frequent central line infections. He required baseline immune suppression for the prevention of sHLH, with increased anti-cytokine therapies and corticosteroids in response to flares and infections. Using a foamy-virus approach, the patient’s DOCK2 mutation and wild-type (WT) control DOCK2 cDNA were separately transduced into a human NK-92 cell line. The NK-cell populations were stimulated with NK-sensitive K562 erythroleukemia target cells in vitro and degranulation and cytolysis were measured using CD107a expression and live/dead fixable cell dead reagent, respectively. Compared to WT, the patient’s DOCK2 mutation was found to cause significantly decreased NK cell function, degranulation, and cytotoxicity. This study speaks to the importance of DOCK2 and similar genes in the pathogenesis of sHLH, with implications for its diagnosis and treatment.

Background: Multisystem inflammatory syndrome in children (MIS-C) is a severe, postinfectious manifestation of coronavirus disease 2019 (COVID-19) in the pediatric population. The disease is manifested by hyperinflammation and can result in cardiac dysfunction, coronary changes, and end-organ damage. Adequate timely treatment can prevent poor outcomes in the short term, but long-term data is lacking. Methods: A large single center MIS-C cohort was followed longitudinally after treatment with intravenous immunoglobulin (IVIG) ± glucocorticoids to determine the natural history of the disease and to describe improvement in laboratory markers and cardiac outcomes. Patient were stratified by disease severity and compared. Results: 137 patients were identified with demographics similar to previously described cohorts. Regardless of disease severity, when adequately treated, initial lab abnormalities rapidly improved by the 6–8 month follow-up period, with some resolved in as little as 1–2 weeks. Similarly, cardiac abnormalities improved quickly after treatment; all abnormalities resolved in this cohort by 1–2 months post-hospitalization. Conclusions: Although MIS-C is a serious sequela of COVID-19, when identified quickly and treated aggressively, laboratory abnormalities, coronary dilatation, and systolic dysfunction rapidly improve with minimal long-term morbidity or mortality.