Cross-Sectional Analysis of Quality of Life in Pediatric Patients with Inflammatory Bowel Disease in British Columbia, Canada.

OBJECTIVES: To evaluate quality of life (QoL) in a large cohort of pediatric patients with inflammatory bowel disease (IBD) and to identify the clinical factors that influence QoL. STUDY DESIGN: This cross-sectional study analyzes a quality improvement initiative in 351 pediatric patients with IBD in British Columbia, Canada using the self-reported Pediatric Quality of Life Inventory (PedsQL) 4.0 generic scale. The questionnaire was completed at outpatient clinic and biologic infusion appointments. Statistical analysis included the t test, ANOVA, and multilinear regressions to evaluate the relationships between clinical factors and QoL. RESULTS: Mean (SE) QoL scores (79.95 [0.84]) fell between previously described healthy and chronically ill populations. Disease activity was the most significant predictor of QoL, with patients in remission scoring similar (84.42 [0.87]) to well established healthy norms, and those with moderately or severely active disease having some of the lowest published PedsQL scores (63.13 [3.27]), lower than most other chronic pediatric conditions. Twenty-five patients with moderately or severely active disease at the time of survey completion had follow-up surveys identified 1 year later and had a significant improvement of both their disease activity (P < .005) and their PedsQL scores (follow-up survey mean 76.13 [3.11]). Additional clinical factors independently associated with poor QoL were school nonattendance (15.5% decrease in QoL, P < .001), immune-modulator selection (methotrexate conferring a 9.5% lower mean QoL score than azathioprine, P = .005), and female gender (P = .031). CONCLUSION: Pediatric patients with IBD experience a QoL significantly impacted by multiple clinical factors including current severity of IBD symptoms.

Making Sense of "Somatization": A Systematic Review of its Relationship to Pediatric Pain.

OBJECTIVES: Pain and other physical symptoms commonly co-occur in childhood. There is debate about the relevance of somatization in understanding pain. The present review critically appraised and synthesized the extant literature on the relationship between pediatric pain and somatization. METHODS: A systematic review (PROSPERO registration #95956) was conducted in Medline, PsycINFO, EMBASE, and CINAHL using search terms related to pain and somatization in children and adolescents. A total of 156 articles were eligible for inclusion in the review. For studies that measured somatization using a symptom questionnaire, descriptions of "somatization" were extracted. Data regarding the relationship between pain and somatization were extracted for studies measuring somatization using a diagnostic category (e.g., Somatic Symptom and Related Disorders [SSRDs]). RESULTS: While many studies using somatic symptom questionnaires described somatization as having a psychological component, this was not always captured in measurement tools. Pain was reported as a common symptom in patients with an SSRD diagnosis, though rates varied depending on the specific diagnosis and pain location. Rates of SSRD diagnoses among pain patients were less frequent than rates of pain amongst SSRD patients. CONCLUSIONS: SSRDs and pain commonly co-occur, though rates differ depending on diagnosis and pain location. Understanding the relationship between pain and somatization is complicated by the discrepancy between how somatization is defined and measured in questionnaire studies. A comprehensive and measurable definition of somatization is needed so researchers can better identify the shared and unique contributions of pain and somatization in pediatric populations.

Feasibility of Using a Single Heart Rate-Based Measure for Real-time Feedback in a Voluntary Deep Breathing App for Children: Data Collection and Algorithm Development.

BACKGROUND: Deep diaphragmatic breathing, also called belly breathing, is a popular behavioral intervention that helps children cope with anxiety, stress, and their experience of pain. Combining physiological monitoring with accessible mobile technology can motivate children to comply with this intervention through biofeedback and gaming. These innovative technologies have the potential to improve patient experience and compliance with strategies that reduce anxiety, change the experience of pain, and enhance self-regulation during distressing medical procedures. OBJECTIVE: The aim of this paper was to describe a simple biofeedback method for quantifying breathing compliance in a mobile smartphone app. METHODS: A smartphone app was developed that combined pulse oximetry with an animated protocol for paced deep breathing. We collected photoplethysmogram data during spontaneous and subsequently paced deep breathing in children. Two measures, synchronized respiratory sinus arrhythmia (RSAsync) and the corresponding relative synchronized inspiration/expiration heart rate ratio (HR-I:Esync), were extracted from the photoplethysmogram. RESULTS: Data collected from 80 children aged 5-17 years showed a positive RSAsync effect in all participants during paced deep breathing, with a median (IQR; range) HR-I:Esync ratio of 1.26 (1.16-1.35; 1.01-1.60) during paced deep breathing compared to 0.98 (0.96-1.02; 0.82-1.18) during spontaneous breathing (median difference 0.25, 95% CI 0.23-0.30; P<.001). The measured HR-I:Esync values appeared to be independent of age. CONCLUSIONS: An HR-I:Esync level of 1.1 was identified as an age-independent threshold for programming the breathing pattern for optimal compliance in biofeedback.

Treatment of Creatine Transporter (SLC6A8) Deficiency With Oral S-Adenosyl Methionine as Adjunct to L-arginine, Glycine, and Creatine Supplements.

BACKGROUND: Creatine transporter (SLC6A8) deficiency is an X-linked inborn error of metabolism characterized by cerebral creatine deficiency, behavioral problems, seizures, hypotonia, and intellectual developmental disability. A third of patients are amenable to treatment with high-dose oral creatine, glycine, and L-arginine supplementation. METHODS: Given the limited treatment response, we initiated an open-label observational study to evaluate the effect of adjunct S-adenosyl methionine to further enhance intracerebral creatine synthesis. RESULTS: Significant and reproducible issues with sleep and behavior were noted in both male patients on a dose of 50/mg/kg. One of the two patients stopped S-adenosyl methionine and did not come for any follow-up. A safe and tolerable dose (17 mg/kg/day) was identified in the other patient. On magnetic resonance spectroscopy, this 8-year-old male did not show an increase in intracerebral creatine. However, significant improvement in speech/language skills, muscle mass were observed as well as in personal outcomes as defined by the family in activities related to communication and decision making. DISCUSSION: Further research is needed to assess the potential of S-adenosyl methionine as an adjunctive therapy for creatine transporter deficiency patients and to define the optimal dose. Our study also illustrates the importance of pathophysiology-based treatment, individualized outcome assessment, and patient/family participation in rare diseases research.

Mitochondrial carbonic anhydrase VA deficiency resulting from CA5A alterations presents with hyperammonemia in early childhood.

Four children in three unrelated families (one consanguineous) presented with lethargy, hyperlactatemia, and hyperammonemia of unexplained origin during the neonatal period and early childhood. We identified and validated three different CA5A alterations, including a homozygous missense mutation (c.697T>C) in two siblings, a homozygous splice site mutation (c.555G>A) leading to skipping of exon 4, and a homozygous 4 kb deletion of exon 6. The deleterious nature of the homozygous mutation c.697T>C (p.Ser233Pro) was demonstrated by reduced enzymatic activity and increased temperature sensitivity. Carbonic anhydrase VA (CA-VA) was absent in liver in the child with the homozygous exon 6 deletion. The metabolite profiles in the affected individuals fit CA-VA deficiency, showing evidence of impaired provision of bicarbonate to the four enzymes that participate in key pathways in intermediary metabolism: carbamoylphosphate synthetase 1 (urea cycle), pyruvate carboxylase (anaplerosis, gluconeogenesis), propionyl-CoA carboxylase, and 3-methylcrotonyl-CoA carboxylase (branched chain amino acids catabolism). In the three children who were administered carglumic acid, hyperammonemia resolved. CA-VA deficiency should therefore be added to urea cycle defects, organic acidurias, and pyruvate carboxylase deficiency as a treatable condition in the differential diagnosis of hyperammonemia in the neonate and young child.

Guanidinoacetate methyltransferase (GAMT) deficiency: outcomes in 48 individuals and recommendations for diagnosis, treatment and monitoring.

We collected data on 48 patients from 38 families with guanidinoacetate methyltransferase (GAMT) deficiency. Global developmental delay/intellectual disability (DD/ID) with speech/language delay and behavioral problems as the most affected domains was present in 44 participants, with additional epilepsy present in 35 and movement disorder in 13. Treatment regimens included various combinations/dosages of creatine-monohydrate, l-ornithine, sodium benzoate and protein/arginine restricted diets. The median age at treatment initiation was 25.5 and 39 months in patients with mild and moderate DD/ID, respectively, and 11 years in patients with severe DD/ID. Increase of cerebral creatine and decrease of plasma/CSF guanidinoacetate levels were achieved by supplementation with creatine-monohydrate combined with high dosages of l-ornithine and/or an arginine-restricted diet (250 mg/kg/d l-arginine). Therapy was associated with improvement or stabilization of symptoms in all of the symptomatic cases. The 4 patients treated younger than 9 months had normal or almost normal developmental outcomes. One with inconsistent compliance had a borderline IQ at age 8.6 years. An observational GAMT database will be essential to identify the best treatment to reduce plasma guanidinoacetate levels and improve long-term outcomes.