Suicide is a devastating public health problem and very few biological treatments have been found to be effective for quickly reducing the intensity of suicidal ideation (SI). We have previously ...shown that a single dose of ketamine, a glutamate N-methyl-d-aspartate (NMDA) receptor antagonist, is associated with a rapid reduction in depressive symptom severity and SI in patients with treatment-resistant depression.
We conducted a randomized, controlled trial of ketamine in patients with mood and anxiety spectrum disorders who presented with clinically significant SI (n = 24). Patients received a single infusion of ketamine or midazolam (as an active placebo) in addition to standard of care. SI measured using the Beck Scale for Suicidal Ideation (BSI) 24 h post-treatment represented the primary outcome. Secondary outcomes included the Montgomery-Asberg Depression Rating Scale--Suicidal Ideation (MADRS-SI) score at 24 h and additional measures beyond the 24-h time-point.
The intervention was well tolerated and no dropouts occurred during the primary 7-day assessment period. BSI score was not different between the treatment groups at 24 h (p = 0.32); however, a significant difference emerged at 48 h (p = 0.047). MADRS-SI score was lower in the ketamine group compared to midazolam group at 24 h (p = 0.05). The treatment effect was no longer significant at the end of the 7-day assessment period.
The current findings provide initial support for the safety and tolerability of ketamine as an intervention for SI in patients who are at elevated risk for suicidal behavior. Larger, well-powered studies are warranted.
Deep transcranial magnetic stimulation (dTMS) has been sanctioned by the United States Food and Drug Administration for treatment-resistant depression. In a retrospective cohort study, we evaluated ...response and effectiveness of dTMS in real-world practice, as an add-on treatment for resistant depression.
Forty adult outpatients suffering from depression, all taking psychiatric medications, underwent 20 dTMS treatments over a 4-6 week period. At baseline (T0), visit 10 (T1), and visit 20 (T2), the Clinical Global Impression-Severity (CGI-S) scale was administered, and the Clinical Global Impression Improvement (CGI-I) scale was completed at T1 and T2; the Hamilton Depression Rating Scale (HDRS-21) was administrated at T0 and T2 only. The patients also completed the Quick Inventory of Depressive Symptoms-Self-Report (QIDS-SR) at T0, T1, and T2.
Depressive symptoms (HDRS-21 total score) decreased significantly following treatment. The HDRS total score decreased from an average of 21.22 (±6.09) at T0, to 13.95 (±7.24) at T2. Correspondingly, at T2, 32.5% were responders to the treatment and 20% were in remission, based on the HDRS-21. Treatment was well tolerated, with a discontinuation rate of 7.5%. While depressive symptoms at baseline did not predict remission/response at T2, higher HDRS scores at T0 were associated with a larger decrease in depressive symptoms during the study.
Significant antidepressant effects were seen following 20 dTMS treatments, given as augmentation to ongoing medications in treatment-resistant depression. The findings suggest that among patients with TRD, the severity of the depressive episode (and not necessarily the number of failed antidepressant medication trials) is associated with a positive therapeutic effect of dTMS. Hence, the initial severity of the depressive episode may guide clinicians in referring patients for dTMS.
Objective
To develop standardized treatment regimens for chronic nonbacterial osteomyelitis (CNO), also known as chronic recurrent multifocal osteomyelitis (CRMO), to enable comparative effectiveness ...treatment studies.
Methods
Virtual and face‐to‐face discussions and meetings were held within the CNO/CRMO subgroup of the Childhood Arthritis and Rheumatology Research Alliance (CARRA). A literature search was conducted, and CARRA membership was surveyed to evaluate available treatment data and identify current treatment practices. Nominal group technique was used to achieve consensus on treatment plans for CNO refractory to nonsteroidal antiinflammatory drug (NSAID) monotherapy and/or with active spinal lesions.
Results
Three consensus treatment plans (CTPs) were developed for the first 12 months of therapy for CNO patients refractory to NSAID monotherapy and/or with active spinal lesions. The 3 CTPs are methotrexate or sulfasalazine, tumor necrosis factor inhibitors with optional methotrexate, and bisphosphonates. Short courses of glucocorticoids and continuation of NSAIDs are permitted for all regimens. Consensus was achieved on these CTPs among CARRA members. Consensus was also reached on subject eligibility criteria, initial evaluations that should be conducted prior to the initiation of CTPs, and data items to collect to assess treatment response.
Conclusion
Three consensus treatment plans were developed for pediatric patients with CNO refractory to NSAIDs and/or with active spinal lesions. Use of these CTPs will provide additional information on efficacy and will generate meaningful data for comparative effectiveness research in CNO.
Objective
To provide guidance on the management of Multisystem Inflammatory Syndrome in Children (MIS‐C), a condition characterized by fever, inflammation, and multiorgan dysfunction that manifests ...late in the course of severe acute respiratory syndrome coronavirus 2 (SARS–CoV‐2) infection. Recommendations are also provided for children with hyperinflammation during coronavirus disease 2019 (COVID‐19), the acute, infectious phase of SARS–CoV‐2 infection.
Methods
The Task Force was composed of 9 pediatric rheumatologists and 2 adult rheumatologists, 2 pediatric cardiologists, 2 pediatric infectious disease specialists, and 1 pediatric critical care physician. Preliminary statements addressing clinical questions related to MIS‐C and hyperinflammation in COVID‐19 were developed based on evidence reports. Consensus was built through a modified Delphi process that involved anonymous voting and webinar discussion. A 9‐point scale was used to determine the appropriateness of each statement (median scores of 1–3 for inappropriate, 4–6 for uncertain, and 7–9 for appropriate). Consensus was rated as low, moderate, or high based on dispersion of the votes. Approved guidance statements were those that were classified as appropriate with moderate or high levels of consensus, which were prespecified before voting.
Results
The first version of the guidance was approved in June 2020, and consisted of 40 final guidance statements accompanied by a flow diagram depicting the diagnostic pathway for MIS‐C. The document was revised in November 2020, and a new flow diagram with recommendations for initial immunomodulatory treatment of MIS‐C was added.
Conclusion
Our understanding of SARS–CoV‐2–related syndromes in the pediatric population continues to evolve. This guidance document reflects currently available evidence coupled with expert opinion, and will be revised as further evidence becomes available.
Objective
To provide guidance on the management of multisystem inflammatory syndrome in children (MIS‐C), a condition characterized by fever, inflammation, and multiorgan dysfunction that manifests ...late in the course of severe acute respiratory syndrome coronavirus 2 (SARS–CoV‐2) infection, and to provide recommendations for children with hyperinflammation during coronavirus disease 2019 (COVID‐19), the acute, infectious phase of SARS–CoV‐2 infection.
Methods
A multidisciplinary task force was convened by the American College of Rheumatology (ACR) to provide guidance on the management of MIS‐C associated with SARS–CoV‐2 and hyperinflammation in COVID‐19. The task force was composed of 9 pediatric rheumatologists, 2 adult rheumatologists, 2 pediatric cardiologists, 2 pediatric infectious disease specialists, and 1 pediatric critical care physician. Preliminary statements addressing clinical questions related to MIS‐C and hyperinflammation in COVID‐19 were developed based on evidence reports. Consensus was built through a modified Delphi process that involved 2 rounds of anonymous voting and 2 webinars. A 9‐point scale was used to determine the appropriateness of each statement (median scores of 1–3 for inappropriate, 4–6 for uncertain, and 7–9 for appropriate), and consensus was rated as low, moderate, or high based on dispersion of the votes along the numeric scale. Approved guidance statements were those that were classified as appropriate with moderate or high levels of consensus, as prespecified prior to voting.
Results
The ACR task force approved a total of 128 guidance statements addressing the management of MIS‐C and hyperinflammation in pediatric COVID‐19. These statements were refined into 40 final clinical guidance statements, accompanied by a flow diagram depicting the diagnostic pathway for MIS‐C.
Conclusion
Our understanding of SARS–CoV‐2–related syndromes in the pediatric population continues to evolve. The guidance provided in this “living document” reflects currently available evidence, coupled with expert opinion, and will be revised as further evidence becomes available.
Objective
To provide guidance on the management of Multisystem Inflammatory Syndrome in Children (MIS‐C), a condition characterized by fever, inflammation, and multiorgan dysfunction that manifests ...late in the course of SARS–CoV‐2 infection. Recommendations are also provided for children with hyperinflammation during COVID‐19, the acute, infectious phase of SARS–CoV‐2 infection.
Methods
The Task Force is composed of 9 pediatric rheumatologists and 2 adult rheumatologists, 2 pediatric cardiologists, 2 pediatric infectious disease specialists, and 1 pediatric critical care physician. Preliminary statements addressing clinical questions related to MIS‐C and hyperinflammation in COVID‐19 were developed based on evidence reports. Consensus was built through a modified Delphi process that involved anonymous voting and webinar discussion. A 9‐point scale was used to determine the appropriateness of each statement (median scores of 1–3 for inappropriate, 4–6 for uncertain, and 7–9 for appropriate). Consensus was rated as low, moderate, or high based on dispersion of the votes. Approved guidance statements were those that were classified as appropriate with moderate or high levels of consensus, which were prespecified before voting.
Results
The guidance was approved in June 2020 and updated in November 2020 and October 2021, and consists of 41 final guidance statements accompanied by flow diagrams depicting the diagnostic pathway for MIS‐C and recommendations for initial immunomodulatory treatment of MIS‐C.
Conclusion
Our understanding of SARS–CoV‐2–related syndromes in the pediatric population continues to evolve. This guidance document reflects currently available evidence coupled with expert opinion, and will be revised as further evidence becomes available.
The impact of the COVID-19 pandemic on new diagnoses of recurrent fevers and autoinflammatory diseases is largely unknown. The Childhood Arthritis and Rheumatology Research Alliance (CARRA) PFAPA/AID ...Working Group aimed to investigate the impact of the COVID-19 pandemic on the number of pediatric patients evaluated for recurrent fevers and autoinflammatory diseases in North America. The absolute number of new outpatient visits and the proportion of these visits attributed to recurrent fever diagnoses during the pre-pandemic period (1 March 2019-29 February 2020) and the first year of the COVID-19 pandemic (1 March 2020-28 February 2021) were examined. Data were collected from 27 sites in the United States and Canada. Our results showed an increase in the absolute number of new visits for recurrent fever evaluations in 21 of 27 sites during the COVID-19 pandemic compared to the pre-pandemic period. The increase was observed across different geographic regions in North America. Additionally, the proportion of new visits to these centers for recurrent fever in relation to all new patient evaluations was significantly higher during the first year of the pandemic, increasing from 7.8% before the pandemic to 10.9% during the pandemic year (
< 0.001). Our findings showed that the first year of the COVID-19 pandemic was associated with a higher number of evaluations by pediatric subspecialists for recurrent fevers. Further research is needed to understand the reasons behind these findings and to explore non-infectious triggers for recurrent fevers in children.
Background/Purpose. Understanding the practices of pediatric rheumatologists in diagnosing and treating chronic nonbacterial osteomyelitis (CNO) can provide important information to guide the ...development of consensus treatment plans. The objectives of this study were to determine physicians’ approaches to (1) diagnosing and monitoring CNO, (2) ordering a bone biopsy, and (3) making treatment decisions. Methods. A survey was distributed among members of the Childhood Arthritis and Rheumatology Research Alliance using a web-based questionnaire. Results. 121 of 277 (41%) attending physician members completed the survey. Plain radiographs (89%) were most commonly used followed by regional MRI (78%), bone scintigraphy (43%), and whole-body MRI (36%). The top three reasons for performing a biopsy were constitutional findings (66%), unifocal bone lesions (64%), and nocturnal bone pain (45%). Nearly all responders (95%) prescribed nonsteroidal anti-inflammatory drugs (NSAIDs) as initial therapy. For patients who failed NSAID treatment, methotrexate (67%), tumor necrosis factor inhibitors (65%), and bisphosphonates (46%) were the next most commonly used treatments. The presence of a spinal lesion increased the use of bisphosphonate treatment. Conclusion. The diagnostic approach and disease activity monitoring for CNO varied among surveyed physicians. Our survey findings provided important background for the development of consensus treatment plans for CNO.
To (1) estimate the health-related quality of life (HRQOL) of children with childhood-onset systemic lupus erythematosus (cSLE) and compare it to that of normative cohorts; (2) assess the ...relationship of HRQOL with cSLE disease activity and damage; and (3) determine the effects of changes of disease activity on HRQOL.
Patients with cSLE (n = 98) followed every 3 months completed HRQOL measures, the Pediatric Quality of Life Inventory Generic Core scale (PedsQL-GC), the Rheumatology Module (PedsQL-RM), and the Child Health Questionnaire (CHQ). The British Isles Lupus Activity Group Index (BILAG) was used to measure organ-system-specific disease activity. Physicians rated the course of cSLE between visits.
At baseline, mean (standard deviation, SD) score parent report of the PedsQL-GC and the PedsQL-RM was 75 (17) and 79 (14), respectively; the mean (SD) of the CHQ physical summary score (CHQ-PHS) was 49 (7) and that of the CHQ psychological summary score was 42 (12). Higher BILAG scores, especially in the general, musculoskeletal, neurological, and vascular, but not the mucocutaneous, renal, cardiovascular, or hematological BILAG domains, were associated with a significantly lower HRQOL. Patients with damage had lower HRQOL than those without damage. All HRQOL measures included were at most modestly responsive to clinically important changes with cSLE.
HRQOL with cSLE is significantly lower than that reported in healthy populations. Organ-specific involvement with cSLE has a differential effect on HRQOL. Higher disease activity and damage are associated with significantly lower HRQOL as measured by the PedsQL-RM and the CHQ-PHS, and worsening of cSLE leads to a further decline.
Systemic autoinflammatory diseases (SAIDs) are characterized by unprovoked exaggerated inflammation on a continuum from benign recurrent oral ulceration to life-threatening strokes or amyloidosis, ...with renal failure as a potential sequela. The ability to discriminate these diagnoses rests on the genetic and mechanistic defect of each disorder, considering potential overlapping autoinflammation, autoimmunity, and immune deficiency. A comprehensive and strategic genetic investigation influences management as well as the consequential expected prognoses in these subsets of rare diseases. The ever-expanding therapeutic armamentarium reflects international collaborations, which will hasten genetic discovery and consensus-driven treatment.
PDF
