An "On Demand" canakinumab regimen for treating children with Colchicine-Resistant familial Mediterranean fever - A multicentre study.

OBJECTIVES: Canakinumab, a human monoclonal antibody targeted at interleukin-1 beta, has demonstrated safety and efficacy in preventing familial Mediterranean fever (FMF) attacks among individuals with colchicine-resistant (crFMF). The manufacturer orders prescribe monthly subcutaneous injections. However, a subset of our patients is treated with an "canakinumab on demand " (COD) strategy, with wider intervals between drug administrations. Therefore, we aimed to compare disease activity and drug safety between COD and "canakinumab fixed frequency" (CFF) policies. METHODS: This retrospective study collected data from three Israeli paediatric rheumatology centres, of children with crFMF who were treated with canakinumab. Epidemiological and clinical parameters, cumulative drug dosages, and adverse events were compared between children treated by both policies. RESULTS: Twenty-five (49 %) children were treated according to COD policy and 26 according to CFF policy. Demographic parameters and most of the disease features did not differ significantly between the groups. Both groups showed significant reduction in attacks after canakinumab introduction. The median number (interquartile range) of attacks per month did not differ significantly between the COD and CFF groups (0.33 (0.08, 0.58) and 0.13 (0, 0.5), respectively, p = 0.485 (even though, per definition, COD patients presumably had an attack before receiving the second canakinumab dose). The mean monthly dose was lower for the COD than the CFF group (1.13 ± 1.13 vs. 3.16 ± 1.46 mg/kg, p < 0.001). Adverse events were similar between the groups. CONCLUSION: For individuals with crFMF, COD compared to CFF policy can achieve similar efficacy and safety, with a lower accumulated canakinumab dose, rendering it less immunosuppressive and less expensive.

Safety and Immunogenicity Following the Second and Third Doses of the BNT162b2 mRNA COVID-19 Vaccine in Adolescents with Juvenile-Onset Autoimmune Inflammatory Rheumatic Diseases: A Prospective Multicentre Study.

BACKGROUND: To explore the long-term safety and dynamics of the immune response induced by the second and third doses of the BNT162b2 mRNA COVID-19 vaccine in adolescents with juvenile-onset autoimmune inflammatory rheumatic diseases (AIIRDs) compared with healthy controls. METHODS: This international prospective study included adolescents with AIIRDs and controls vaccinated with two (AIIRDs n = 124; controls n = 80) or three (AIIRDs n = 64; controls n = 30) doses of the BNT162b2 vaccine, evaluated for vaccine side-effects, disease activity, COVID-19 breakthrough infection rates and severity, and anti-spike S1/S2 IgG antibody titers in a sample from both groups. RESULTS: The vaccination safety profile was favorable, with most patients reporting mild or no side-effects. The rheumatic disease remained stable at 98% and 100% after the second and third doses, respectively. The two-dose vaccine induced comparable seropositivity rates among patients (91%) and controls (100%), (p = 0.55), which declined within 6 months to 87% and 100%, respectively (p = 0.3) and increased to 100% in both groups after the third vaccine dose. The overall post-vaccination COVID-19 infection rate was comparable between patients and controls, 47.6% (n = 59) and 35% (n = 28), respectively; p = 0.5278, with most infections occurring during the Omicron surge. In relation to the last vaccination, time-to-COVID-19 infection was similar between patients and controls, at a median of 5.5 vs. 5.2 months, respectively (log-rank p = 0.1555). CONCLUSION: The safety profile of three doses of the BNT162b2 mRNA vaccine was excellent, with adequate humoral response and similar efficacy among patients and controls. These results support the recommendation for vaccinating adolescents with juvenile-onset AIIRDs against COVID-19.

Infantile Takayasu: clinical features and long-term outcome.

OBJECTIVES: Takayasu arteritis (TAK) is a large-vessel vasculitis rarely reported in children and infants. Most articles on paediatric TAK have not focused on infants. We present the largest case series of infantile TAK, aiming to identify its demographic and clinical characteristics and compare them with existing data on older children. METHODS: We conducted an international multicentre retrospective cohort study. Epidemiological and clinical data were collected from patients' charts from six rheumatology centres. All patients met both the EULAR/PReS 2008 criteria and the 1990 ACR/EULAR criteria and were diagnosed with TAK at age <5 years. RESULTS: Twelve patients were included (50% female). Median age of symptom onset was 11 months, with a diagnostic delay of 4 months. The most common symptoms at presentation were hypertension, blood pressure differences between limbs, and fever. The most commonly involved arteries were the abdominal aorta and renal artery. Medications included steroids, conventional and biologic DMARDs, and other immunosuppressive therapies. Half of the patients received biologic agents, of which infliximab had the highest complete remission rate (40%). Other medications resulting in complete remission were CYC (40%) and MTX (38%). Invasive procedures were required for 58% of patients. The most common complications were cardiac (50%), stroke (42%), and serious infections (33%). No patients died. CONCLUSION: This study presents the largest series of infantile TAK. Compared with other reported series on older children, infants with TAK have more severe disease and were more likely to receive biologic agents, develop complications, and require invasive interventions.

Adherence of caregivers of children to advice provided by a National Poison Information Center.

INTRODUCTION: Most calls to poison information centers are from the public, pertaining to young children, and due to minor or nontoxic exposures. Rational poison center consultations can prevent unnecessary visits to emergency departments (EDs), callers' adherence to such advice is required. OBJECTIVES: Estimate adherence of callers from the public to the poison center concerning exposures of young children to the advice provided by the clinical toxicologist, estimate the number of unnecessary ED visits of these children prevented by poison center consultations. METHODS: Prospective, phone-survey cohort study. Calls from the public concerning children under 6 years old were recorded and collected, telephone follow-up was performed within two weeks. Data collected included: demographics, exposure, severity, triage advised, adherence to the advice, reasons for nonadherence, and what the caller would have done had the poison center been unavailable. The study was conducted over 3 months representing different seasons and holidays times during a 1-year period. RESULTS: 1762 callers completed the telephone follow-up; 1443 (81.9%) cases were asymptomatic at the time of call; 1452 (82.3%) were advised to remain at home, 175 (9.9%) and 137 (7.8%) were referred to community clinics and EDs, respectively; 1648 (93.5%) of callers adhered to the advice provided; highest adherence rate was among callers advised to stay home (98.3%, 1427), and 78.9% (108) and 62.1% (109) among callers referred to EDs and community clinics, respectively. Among callers advised to stay home, 491 stated that they would have referred themselves to the ED had the poison center been unavailable, an annual estimate of 4309 cases. The main parameter predicting nonadherence was calls made during night shift. CONCLUSIONS: The high adherence of callers to the poison center consultation suggests it plays an important role in preventing unnecessary ED visits of young children due to poison exposures, and may substantially reduce ED load and costs.

Oxygenation Instability Assessed by Oxygen Saturation Histograms during Supine vs Prone Position in Very Low Birthweight Infants Receiving Noninvasive Respiratory Support.

OBJECTIVE: To evaluate the effect of prone vs supine position on the oxygenation instability among very low birth weight (VLBW) infants receiving noninvasive respiratory support, as assessed by the average oxygen saturation (SpO2) histograms. STUDY DESIGN: Sixty-nine histograms from 23 VLBW infants were studied prospectively. Each infant was studied during 3 consecutive 3-hour periods of alternating positions; 12 infants started the study while prone and 11 infants started supine, by random order. Histogram classification system was used to quantify oxygenation stability and time spent in different SpO2 ranges. RESULTS: The fraction of inspired oxygen values were similar in both positions. Unstable histograms were more common in supine vs prone position (20/34 [59%] vs 10/35 [29%]; P = .02, respectively). Analyzing oxygenation stability as per position change revealed that a change from prone to supine increased oxygenation instability, and supine to prone decreased instability (P = .02). In the supine vs prone position, percent of time spent in SpO2 ≤80% and <90% was higher (5.0 ± 4.2 vs 2.4 ± 3.4 [P < .001] and 24.1 ± 13.7 vs 13.2 ± 10.0 [P < .001], respectively), and percent of time in SpO2 >94% was lower (39.7 ± 26.0 vs 52.4 ± 23.4 [P = .04]). CONCLUSIONS: Prone positioning decreased oxygenation instability and resulted in higher oxygenation among VLBW premature infants on noninvasive respiratory support. SpO2 histograms allow easy bedside assessment of oxygenation instability, and quantification of the time spent at different SpO2 ranges.

CPM Test-Retest Reliability: "Standard" vs "Single Test-Stimulus" Protocols.

OBJECTIVES: Assessment of pain inhibitory mechanisms using conditioned pain modulation (CPM) is relevant clinically in prediction of pain and analgesic efficacy. Our objective is to provide necessary estimates of intersession CPM reliability, to enable transformation of the CPM paradigm into a clinical tool. DESIGN: Two cohorts of young healthy subjects (N = 65) participated in two dual-session studies. In Study I, a Bath-Thermode CPM protocol was used, with hot water immersion and contact heat as conditioning- and test-stimuli, respectively, in a classical parallel CPM design introducing test-stimulus first, and then the conditioning- and repeated test-stimuli in parallel. Study II consisted of two CPM protocols: 1) Two-Thermodes, one for each of the stimuli, in the same parallel design as above, and 2) single test-stimulus (STS) protocol with a single administration of a contact heat test-stimulus, partially overlapped in time by a remote shorter contact heat as conditioning stimulus. Test-retest reliability was assessed within 3-7 days. RESULTS: The STS-CPM had superior reliability intraclass correlation (ICC2 ,: 1 = 0.59) over Bath-Thermode (ICC2 ,: 1 = 0.34) or Two-Thermodes (ICC2 ,: 1 = 0.21) protocols. The hand immersion conditioning pain had higher reliability than thermode pain (ICC2 ,: 1 = 0.76 vs ICC2 ,: 1 = 0.16). Conditioned test-stimulus pain scores were of good (ICC2 ,: 1 = 0.62) or fair (ICC2 ,: 1 = 0.43) reliability for the Bath-Thermode and the STS, respectively, but not for the Two-Thermodes protocol (ICC2 ,: 1 = 0.20). CONCLUSIONS: The newly developed STS-CPM paradigm was more reliable than other CPM protocols tested here, and should be further investigated for its clinical relevance. It appears that large contact size of the conditioning-stimulus and use of single rather than dual test-stimulus pain contribute to augmentation of CPM reliability.