Pilot study of the safety and effect of adalimumab on pain, physical function, and musculoskeletal disease in mucopolysaccharidosis types I and II.

Mucopolysaccharidosis I and II are lysosomal storage disorders that, despite treatment with hematopoietic cell transplantation (HCT) and/or enzyme replacement therapy (ERT), continue to cause significant skeletal abnormalities leading to pain, stiffness, physical dysfunction, and short stature. Tumor necrosis factor - alpha (TNF-α) is elevated in individuals with MPS I and II and associated with pain and physical dysfunction. Therefore, we evaluated the safety and effects of the TNF-α inhibitor adalimumab in patients with MPS I and II in a 32-week, randomized, double blind, placebo-controlled, crossover study of adalimumab at a dose of 20 mg (weight 15-<30 kg) or 40 mg (weight ≥ 30 kg) administered subcutaneously every other week or saline placebo for 16 weeks. Participants were evaluated at baseline, week 16, and week 32 with the Children's Health Questionnaire - Parent Form 50 (CHQ-PF50), the Pediatric Pain Questionnaire (PPQ), range-of-motion (ROM) measurements, anthropometry, six-minute walk test (6MWT), hand dynamometer, and laboratory evaluations for safety. The primary outcome was safety and primary efficacy outcome was bodily pain (BP) measured by the CHQ-PF50. Two subjects, one with MPS I and one with MPS II, completed the study. Adalimumab was well tolerated and there were no serious adverse events. Standardized BP scores for age and gender were higher (i.e. less pain) at the end of the treatment versus placebo phase for both subjects. Subject #1 became unblinded during treatment due to skin erythema. Behavior measured by both CHQ-PF50 and parental report improved during treatment compared to placebo in both subjects. ROM improved by > 5° in seven of eight joints in Subject #1 and five of eight joints in Subject #2 (range 7.0° to 52.8°). There was no change in the PPQ, 6MWT, or hand dynamometer. Data from this small pilot study suggest that treatment with adalimumab is safe, tolerable, and may improve ROM, physical function, and possibly pain, in children with MPS I or II. However, additional clinical trials are needed before this therapy should be recommended as part of clinical care

White versus gray matter function as seen on neuropsychological testing following bone marrow transplant for acute leukemia in childhood

Current theory suggests that neurocognitive late effects of treatments for childhood cancer such as difficulties with attention, processing speed and visual-motor ability are the result of white matter damage. Neuroimaging studies have produced a variety of white matter findings. However, although white matter is thought to be differentially affected, previous studies have not demonstrated a discrepancy between white and gray matter function. The present study included 36 children treated for childhood leukemia with hematopoietic stem cell transplant (HCT). Their performance on neurocognitive measures traditionally thought to measure white matter was compared to performance on measures thought to measure gray matter function. Composite white and gray matter standard scores were created based on neuropsychological measures that individuals with known white or gray matter damage perform poorly. As predicted, composite white matter scores (mean = 98.1) were significantly lower (t = 2.26, p = 0.03) than composite gray matter scores (mean = 102.5). Additionally, as gray matter performance increased, the difference between gray and white matter scores increased (R = 0.353, p = 0.035). Overall, the results of this study support the current theory that white matter damage is responsible for the more subtle neurocognitive late effects resulting from treatment for childhood leukemia

Symptom Clusters, Physical Activity, and Quality of Life: A Latent Class Analysis of Children During Maintenance Therapy for Leukemia

BACKGROUND: Children undergoing treatment for acute lymphocytic leukemia (ALL) report co-occurring symptoms of fatigue, sleep disturbances, and depression as a symptom cluster. Physical activity (PA) may influence symptom severity and quality of life (QOL). OBJECTIVES: This study examined changes in symptoms and QOL during ALL maintenance in children categorized by symptom cluster and explored the influence of PA and symptoms on QOL. METHODS: Self-report of fatigue, sleep disturbance, and depression; QOL; and PA were measured at the beginning and end of maintenance in 42 children aged 3 to 18 years with ALL. Children were categorized into symptom cluster groups based on measurements at the beginning of maintenance. RESULTS: Two latent classes of symptom clusters (low and high) were identified with significant differences between groups in symptoms at both the beginning and end maintenance (P \u3c .01). Each group\u27s symptom levels did not change during maintenance. Quality-of-life was different between groups at both time points (P \u3c .01) and did not improve. Children with low symptoms and high PA at the beginning of maintenance had better QOL as treatment ended compared with the physically active high-symptom group and the inactive high-symptom group (P \u3c .01). CONCLUSIONS: Children with higher symptoms did not experience an improvement with time. Symptom and PA levels may influence QOL at the end of treatment. IMPLICATIONS FOR PRACTICE: Maintenance therapy is a long time (1.5 years) in a child\u27s life. Symptom assessment is needed early in maintenance; interventions are needed for children with high levels

Pilot study of the safety and effect of adalimumab on pain, physical function, and musculoskeletal disease in mucopolysaccharidosis types I and II

Mucopolysaccharidosis I and II are lysosomal storage disorders that, despite treatment with hematopoietic cell transplantation (HCT) and/or enzyme replacement therapy (ERT), continue to cause significant skeletal abnormalities leading to pain, stiffness, physical dysfunction, and short stature. Tumor necrosis factor – alpha (TNF-α) is elevated in individuals with MPS I and II and associated with pain and physical dysfunction. Therefore, we evaluated the safety and effects of the TNF-α inhibitor adalimumab in patients with MPS I and II in a 32-week, randomized, double blind, placebo-controlled, crossover study of adalimumab at a dose of 20 mg (weight 15–5° in seven of eight joints in Subject #1 and five of eight joints in Subject #2 (range 7.0° to 52.8°). There was no change in the PPQ, 6MWT, or hand dynamometer. Data from this small pilot study suggest that treatment with adalimumab is safe, tolerable, and may improve ROM, physical function, and possibly pain, in children with MPS I or II. However, additional clinical trials are needed before this therapy should be recommended as part of clinical care

Pilot study of the safety and effect of adalimumab on pain, physical function, and musculoskeletal disease in mucopolysaccharidosis types I and II.

Mucopolysaccharidosis I and II are lysosomal storage disorders that, despite treatment with hematopoietic cell transplantation (HCT) and/or enzyme replacement therapy (ERT), continue to cause significant skeletal abnormalities leading to pain, stiffness, physical dysfunction, and short stature. Tumor necrosis factor - alpha (TNF-α) is elevated in individuals with MPS I and II and associated with pain and physical dysfunction. Therefore, we evaluated the safety and effects of the TNF-α inhibitor adalimumab in patients with MPS I and II in a 32-week, randomized, double blind, placebo-controlled, crossover study of adalimumab at a dose of 20 mg (weight 15-<30 kg) or 40 mg (weight ≥ 30 kg) administered subcutaneously every other week or saline placebo for 16 weeks. Participants were evaluated at baseline, week 16, and week 32 with the Children's Health Questionnaire - Parent Form 50 (CHQ-PF50), the Pediatric Pain Questionnaire (PPQ), range-of-motion (ROM) measurements, anthropometry, six-minute walk test (6MWT), hand dynamometer, and laboratory evaluations for safety. The primary outcome was safety and primary efficacy outcome was bodily pain (BP) measured by the CHQ-PF50. Two subjects, one with MPS I and one with MPS II, completed the study. Adalimumab was well tolerated and there were no serious adverse events. Standardized BP scores for age and gender were higher (i.e. less pain) at the end of the treatment versus placebo phase for both subjects. Subject #1 became unblinded during treatment due to skin erythema. Behavior measured by both CHQ-PF50 and parental report improved during treatment compared to placebo in both subjects. ROM improved by > 5° in seven of eight joints in Subject #1 and five of eight joints in Subject #2 (range 7.0° to 52.8°). There was no change in the PPQ, 6MWT, or hand dynamometer. Data from this small pilot study suggest that treatment with adalimumab is safe, tolerable, and may improve ROM, physical function, and possibly pain, in children with MPS I or II. However, additional clinical trials are needed before this therapy should be recommended as part of clinical care

Elevated TNF-α is associated with pain and physical disability in mucopolysaccharidosis types I, II, and VI

BackgroundChildren and adults with the lysosomal storage diseases mucopolysaccharidosis (MPS) types I, II and VI live shortened lives permeated by chronic pain and physical disability. Current treatments do not alleviate these problems. Thus there is a critical need to understand the mechanism of chronic pain and disability in MPS in order to improve the way we treat patients. A potential target is inflammation.HypothesisWe hypothesized that excessive inflammation mediated by the tumor necrosis factor-α (TNF-α) inflammatory pathway is the fundamental cause of much of the chronic pain and physical disability in MPS.Methods55 patients with MPS I, II, or VI were enrolled over the course of a 5-year prospective longitudinal natural history study and evaluated annually for 2-5years. 51 healthy controls were enrolled in a separate cross-sectional study of bone and energy metabolism. TNF-α was measured by ELISA. Pain and physical disability were measured by the Children's Health Questionnaire - Parent Form 50 (CHQ-PF50). Differences in log-transformed TNF-α levels and associations with CHQ domains were evaluated using a linear mixed effects model with random intercept.ResultsTNF-α levels were measured in 48 MPS (age: 5-17years; 35% female) and 51 controls (age: 8-17years; 53% female). Among MPS, 22 (46%) were treated with hematopoietic cell transplantation (HCT) alone, 24 (50%) with enzyme replacement therapy (ERT) alone, and 2 (4%) with both HCT and ERT. TNF-α levels are higher in MPS compared to healthy controls (p<0.001). Higher TNF-α levels are associated with increased pain and decreased physical function, social limitations due to physical health, and physical summary score (all p<0.05). TNF-α levels were not significantly associated with the general health score. TNF-α levels did not change significantly over time in MPS.ConclusionsHigher TNF-α levels are implicated in the pain and decreased physical function present in individuals with MPS despite treatment with ERT and/or HCT, suggesting that TNF-a inhibition could potentially be a useful adjunctive therapy. Further investigation into the role of TNF-α inhibition in MPS to decrease pain and improve physical function is indicated

Diverse Parents’ Perception of the Impact of COVID-19 on Their Families’ Experience of Food Security

This study aimed to examine how the COVID-19 pandemic impacted food insecurity and to identify food assistance interventions that should be sustained post-COVID-19, as recommended by racially/ethnically diverse caregivers from multiple food security statuses. Qualitative interviews were conducted virtually with mothers (n = 40) during March-May 2021 in the Twin Cities, Minnesota. Study results suggest that emergency interventions developed during COVID-19 (e.g. Pandemic EBT, SNAP expansions) have been beneficial in improving families’ access to food. However, more research is needed to understand the various barriers that exist in making food more accessible for families most at risk of experiencing food insecurity.</p

The dose of behavioral interventions to prevent and treat childhood obesity: a systematic review and meta-regression

Abstract Background A better understanding of the optimal “dose” of behavioral interventions to affect change in weight-related outcomes is a critical topic for childhood obesity intervention research. The objective of this review was to quantify the relationship between dose and outcome in behavioral trials targeting childhood obesity to guide future intervention development. Methods A systematic review and meta-regression included randomized controlled trials published between 1990 and June 2017 that tested a behavioral intervention for obesity among children 2–18 years old. Searches were conducted among PubMed (Web-based), Cumulative Index to Nursing and Allied Health Literature (EBSCO platform), PsycINFO (Ovid platform) and EMBASE (Ovid Platform). Two coders independently reviewed and abstracted each included study. Dose was extracted as intended intervention duration, number of sessions, and length of sessions. Standardized effect sizes were calculated from change in weight-related outcome (e.g., BMI-Z score). Results Of the 258 studies identified, 133 had sufficient data to be included in the meta-regression. Average intended total contact (# sessions x length of sessions) was 27.7 (SD 32.2) hours and average duration was 26.0 (SD 23.4) weeks. When controlling for study covariates, a random-effects meta-regression revealed no significant association between contact hours, intended duration or their interaction and effect size. Conclusions This systematic review identified wide variation in the dose of behavioral interventions to prevent and treat pediatric obesity, but was unable to detect a clear relationship between dose and weight-related outcomes. There is insufficient evidence to provide quantitative guidance for future intervention development. One limitation of this review was the ability to uniformly quantify dose due to a wide range of reporting strategies. Future trials should report dose intended, delivered, and received to facilitate quantitative evaluation of optimal dose. Trial registrations The protocol was registered on PROSPERO (Registration # CRD42016036124 )

Additional file 1: of The dose of behavioral interventions to prevent and treat childhood obesity: a systematic review and meta-regression

Figure S1. Forest plot demonstrating a visual representation of the variability in standardized effect size. Table S1. Dose of behavioral intervention and intervention characteristics by study and a full reference list of all studies reviewed. Table provides details of all articles reviewed in this meta-regression. Table S2. Meta-regression evaluating the relationship between dose and standardized effect size stratified by study characteristics. (PDF 1938 kb