A Predictive Model for Thiamine Responsive Disorders Among Infants and Young Children: Results from a Prospective Cohort Study in Lao People's Democratic Republic.

OBJECTIVE: To develop a predictive model for thiamine responsive disorders (TRDs) among infants and young children hospitalized with signs or symptoms suggestive of thiamine deficiency disorders (TDDs) based on response to therapeutic thiamine in a high-risk setting. STUDY DESIGN: Children aged 21 days to <18 months hospitalized with signs or symptoms suggestive of TDD in northern Lao People's Democratic Republic were treated with parenteral thiamine (100 mg daily) for ≥3 days in addition to routine care. Physical examinations and recovery assessments were conducted frequently for 72 hours after thiamine was initiated. Individual case reports were independently reviewed by three pediatricians who assigned a TRD status (TRD or non-TRD), which served as the dependent variable in logistic regression models to identify predictors of TRD. Model performance was quantified by empirical area under the receiver operating characteristic curve. RESULTS: A total of 449 children (median [Q1, Q3] 2.9 [1.7, 5.7] months old; 70.3% exclusively/predominantly breastfed) were enrolled; 60.8% had a TRD. Among 52 candidate variables, those most predictive of TRD were exclusive/predominant breastfeeding, hoarse voice/loss of voice, cyanosis, no eye contact, and no diarrhea in the previous 2 weeks. The area under the receiver operating characteristic curve (95% CI) was 0.82 (0.78, 0.86). CONCLUSIONS: In this study, the majority of children with signs or symptoms of TDD responded favorably to thiamine. While five specific features were predictive of TRD, the high prevalence of TRD suggests that thiamine should be administered to all infants and children presenting with any signs or symptoms consistent with TDD in similar high-risk settings. The usefulness of the predictive model in other contexts warrants further exploration and refinement. TRIAL REGISTRATION: Clinicaltrials.gov NCT03626337.

Repeated attacks of hereditary angioedema in pediatric female.

A 16-year-old female presented to an outpatient clinic with a 13-year history of recurrent episodes of abdominal pain, vomiting and mild cutaneous swelling, either spontaneously or following minor trauma. The episodes occurred every 1-2 months. There was no family history of a similar complaint or hereditary angio-oedema (HAE). At the age of 16, evaluation confirmed the diagnosis of HAE type II, characterised by low C4 levels and reduced C1 esterase inhibitor function. The patient was prescribed tranexamic acid 1 g twice daily as well as C1 esterase inhibitor used as rescue medication during symptomatic episodes. This case report emphasises the importance of considering a diagnosis of HAE in patients with recurrent, unexplained abdominal pain, even in the absence of a positive family history of HAE.Abbreviations: ANA Antinuclear antibodies; C1-INH C1-inhibitor; CBC Complete blood count; FMF Familial Mediterranean fever; HAE Hereditary angioedema; IBD Inflammatory bowel diseases; SDP Solvent detergent-treated plasma; SLE Lupus erythematosus.

Treatment of vitamin D deficiency in children.

INTRODUCTION: Vitamin D deficiency affects from 10% to 50% in various pediatric population groups and causes life-threatening hypocalcemia in infants, crippling rickets in infants and children, and increased risk of subsequent adult metabolic and neurologic problems. AREAS COVERED: An English language literature search of PubMed was performed since 1940 as were the authors' personal literature collections. References identified in the reviewed literature are considered. DIAGNOSIS: The diagnosis of vitamin D deficiency is based on serum 25-hydroxyvitamin D levels. Clinical features of rickets include bone deformities and elevated alkaline phosphatase. Most children and adolescents who are biochemically vitamin D deficient do not have specific symptoms or signs of deficiency. PREVENTION: Prevention of vitamin D deficiency is via exposure to sunshine, food and beverage fortification, and dietary supplementation. TREATMENT: Effective treatment of vitamin D deficiency is via oral or injectable administration of vitamin D. Dosing and duration of vitamin D therapy have been described for healthy children and for children with underlying medical conditions, but recommendations vary. EXPERT OPINION: Further investigation is needed to determine long-term non-skeletal effects of childhood vitamin D deficiency, benefits of supplementation in asymptomatic individuals with biochemical vitamin D deficiency, and appropriate screening for vitamin D deficiency in asymptomatic children and adolescents.

Craving Sweet Success: A Recipe for Developing a Global Health Education Consortium (or Any Consortium, for That Matter).

More than a decade ago, two faculty met at a conference. Each talked about how they were charged with leading global health education efforts at their institutions and longed to have an opportunity to share resources and learn from each other. After reaching out to a few other Midwestern colleagues and finding a date, the first Midwest Consortium of Global Child Health Educators meeting was held in Madison, WI. Now, after a dozen annual meetings, more than 30 articles, chapters, abstracts, and workshops, as well as the creating, piloting, and sharing of several widely used curricula in global health education, the founding consortium members share the practical steps for faculty looking to form similar regional consortia around shared interests. In this article, the authors provide a recipe for the successful formation of an academic consortium based on the lessons learned from their experience. [Pediatr Ann. 2023;52(9):e351-e356.].

Assessment of comorbid symptoms in pediatric autonomic dysfunction.

PURPOSE: Pediatric patients with autonomic dysfunction and orthostatic intolerance (OI) often present with co-existing symptoms and signs that might or might not directly relate to the autonomic nervous system. Our objective was to identify validated screening instruments to characterize these comorbidities and their impact on youth functioning. METHODS: The Pediatric Assembly of the American Autonomic Society reviewed the current state of practice for identifying symptom comorbidities in youth with OI. The assembly includes physicians, physician-scientists, scientists, advanced practice providers, psychologists, and a statistician with expertise in pediatric disorders of OI. A total of 26 representatives from the various specialties engaged in iterative meetings to: (1) identify and then develop consensus on the symptoms to be assessed, (2) establish committees to review the literature for screening measures by member expertise, and (3) delineate the specific criteria for systematically evaluating the measures and for making measure recommendations by symptom domains. RESULTS: We review the measures evaluated and recommend one measure per system/concern so that assessment results from unrelated clinical centers are comparable. We have created a repository to apprise investigators of validated, vetted assessment tools to enhance comparisons across cohorts of youth with autonomic dysfunction and OI. CONCLUSION: This effort can facilitate collaboration among clinical settings to advance the science and clinical treatment of these youth. This effort is essential to improving management of these vulnerable patients as well as to comparing research findings from different centers.

Creating a data dictionary for pediatric autonomic disorders.

PURPOSE: Whether evaluating patients clinically, documenting care in the electronic health record, performing research, or communicating with administrative agencies, the use of a common set of terms and definitions is vital to ensure appropriate use of language. At a 2017 meeting of the Pediatric Section of the American Autonomic Society, it was determined that an autonomic data dictionary comprising aspects of evaluation and management of pediatric patients with autonomic disorders would be an important resource for multiple stakeholders. METHODS: Our group created the list of terms for the dictionary. Definitions were prioritized to be obtained from established sources with which to harmonize. Some definitions needed mild modification from original sources. The next tier of sources included published consensus statements, followed by Internet sources. In the absence of appropriate sources, we created a definition. RESULTS: A total of 589 terms were listed and defined in the dictionary. Terms were organized by Signs/Symptoms, Triggers, Co-morbid Disorders, Family History, Medications, Medical Devices, Physical Examination Findings, Testing, and Diagnoses. CONCLUSION: Creation of this data dictionary becomes the foundation of future clinical care and investigative research in pediatric autonomic disorders, and can be used as a building block for a subsequent adult autonomic data dictionary.

Serum 1,25-dihydroxyvitamin D levels in the diagnosis and pathogenesis of nutritional rickets - a multivariable re-analysis of a case-control study.

BACKGROUND: A multivariable logistic regression model resulting from a case-control study of nutritional rickets in Nigerian children suggested that higher levels of serum 25(OH)D may be required to prevent nutritional rickets in populations with low-calcium intakes. OBJECTIVES: This current study evaluates if adding serum 1,25-dihydroxyvitamin D [1,25(OH)2D] to that model shows that increased levels of serum 1,25(OH)2D are independently associated with risk of children on low-calcium diets having nutritional rickets. METHODS: Multivariable logistic regression analysis was used to model the association between serum 1,25(OH)2D and risk of having nutritional rickets in cases (n = 108) and controls (n = 115) after adjusting for age, sex, weight-for age z-score, religion, phosphorus intake and age began walking and the interaction between serum 25(OH)D and dietary calcium intake (Full Model). RESULTS: Serum 1,25(OH)2D levels were significantly higher (320 pmol/L vs. 280 pmol/L) (P = 0.002), and 25(OH)D levels were lower (33 nmol/L vs. 52 nmol/L) (P < 0.0001) in children with rickets than in control children. Serum calcium levels were lower in children with rickets (1.9 mmol/L) than in control children (2.2 mmol/L) (P < 0.001). Dietary calcium intakes were similarly low in both groups (212 mg/d) (P = 0.973). In the multivariable logistic model, 1,25(OH)2D was independently associated with risk of having rickets [coefficient = 0.007 (95% confidence limits: 0.002-0.011)] after adjusting for all variables in the Full Model. CONCLUSIONS: Results confirmed theoretical models that in children with low dietary calcium intake, 1,25(OH)2D serum concentrations are higher in children with rickets than in children without rickets. The difference in 1,25(OH)2D levels is consistent with the hypothesis that children with rickets have lower serum calcium concentrations which prompt the elevation of PTH levels resulting in an elevation of 1,25(OH)2D levels. These results support the need for additional studies to identify dietary and environmental risks for nutritional rickets.

Thiamine deficiency disorders in women and children.

Thiamine (vitamin B1) is available in common foods such as the outer husk of rice and is necessary for normal cardiovascular, neurological and metabolic processes. Thiamine deficiency is common in many parts of Asia and Africa, affecting up to a third or more of children and women of child-bearing age. The diagnosis is based on clinical suspicion, especially when noting heart failure in infants, encephalopathy in patients of any age, and peripheral neuropathy in older children and adults. Blood tests for whole-blood thiamine diphosphate (the quantity of biologically active thiamine present) and erythrocyte transketolase activity (the functional impact of thiamine) are not always readily available in areas where thiamine deficiency is common. Treatment is safe and effective, although dosing guidelines vary widely; 50 mg daily for 5 days is probably effective for treating acute thiamine deficiency disorders, and ongoing adequate thiamine intake is also needed. Prevention efforts depend on local and regional circumstances, including dietary diversification, food fortification, and/or supplementation of children and women at risk.Abbreviations: HIC: high-income countries; LMIC: low- and middle-income countries; MRI: magnetic resonance imaging; TDD: thiamine deficiency disorders.

Infant and Maternal Vitamin D Supplementation: Clinician Perspectives and Practices.

INTRODUCTION: Rates of infant vitamin D supplementation fall short of guideline recommendations. We explored this discrepancy from the clinician perspective as they advise and affect this important intervention to prevent rickets. We compared infant and high-dose maternal vitamin D supplementation prescribing attitudes and practices between infant-only clinicians (IC) and clinicians who care for mothers and infants (MIC). METHODS: We surveyed clinicians in departments of family medicine, obstetrics/gynecology, primary care pediatrics, neonatology, newborn nursery, and members of vitamin D and rickets working groups and a social media group for lactation medicine providers about their perspectives and practices regarding vitamin D supplementation. RESULTS: 360 clinician survey responses were analyzed. In current practice, IC were more likely than MIC to recommend vitamin D supplementation to exclusively (P < .001) and partially breastfed infants (P = .005). MIC were more likely than IC to discuss infant and high-dose maternal supplementation options and let the parents/caregivers choose (34.7%, 22.0%, P = .009). If supplementing the mother with high-dose vitamin D or the infant directly each provided adequate vitamin D in the infant, MIC were more likely than IC to think that supplementation of the mother would be preferred by parents/caregivers (63.0%, 45.2%, P = .003), improve adherence (66.5%, 49.4%, P = .006), and promote breastfeeding (54.7%, 36.5%, P = .001); they were also more likely to recommend supplementation of the mother (17.7%, 8.9%, P = .04). CONCLUSIONS: MIC are more likely than IC to embrace high-dose maternal vitamin D supplementation to provide adequate vitamin D for infants. This highlights an opportunity for further education of clinicians about this option.

Opportunities for Antimicrobial Stewardship in Caring for Febrile Pediatric Inpatients in Abu Dhabi.

Antimicrobial stewardship programs seek to improve patient outcomes, reduce cost, and hinder development of antimicrobial resistance. Collection of inpatient antimicrobial use data is foundational to these programs, and decisions to initiate and discontinue antibiotics are potentially amenable to improvement. In order to better understand our current practices and with a view toward improved antimicrobial stewardship, we reviewed charts of previously healthy children to age 16 years hospitalized with fever (without an evident localized source) and/or other findings suggestive of serious bacterial infection. Of 105 patients (18% 0-2 months of age, 42% 3-12 months, 25% 2-5 years), 100 (95%) received antibiotics, 72% for more than 2 days. Of 98 patients with negative body fluid cultures, 23 received antibiotics for 2 days or less, and 70 received antimicrobial therapy for more than 2 days. Focusing on selective initiation and earlier discontinuation of antimicrobial therapy in hospitalized children might reduce unnecessary antibiotic use.

Physical Symptoms, Distress, and Functional Disability in Youth With Chronic Orthostatic Intolerance.

OBJECTIVE: Youth with chronic orthostatic intolerance (OI) can experience significant physical, social, and academic functional debilitation. Previous studies have indicated associations among symptom severity, psychosocial factors, and functional disability. However, empirically tested models explaining how different medical and psychosocial factors may contribute to functional disability are lacking. The current cross-sectional study aimed to evaluate mediation, moderation, and additive models of the effect of physical symptoms and psychological distress on functional disability. METHODS: One hundred and sixty-five youth (13-22 years old) undergoing medical evaluation of chronic OI symptoms completed measures of autonomic dysfunction symptom severity, depressive and anxiety symptoms, and functional disability. Models were evaluated using tests of indirect effects and linear and logistic regression analyses. RESULTS: Results supported the mediation and additive effects models for depressive symptoms. Mediation, moderation, and additive models for hypothesized effects of anxiety symptoms were not supported. CONCLUSIONS: Results provide preliminary support for models in which OI symptoms affect functional debility via their effects on mood and in which depressive symptoms have unique and additive effects on functioning. Findings lay the foundation for longitudinal and experimental evaluation of biopsychosocial models of functional disability in youth with chronic OI and related conditions. Implications include the importance of a biopsychosocial conceptualization of OI symptoms and debility as a complex interplay of factors rather than as a purely physiological or psychological process.

Excessive Postural Tachycardia and Postural Orthostatic Tachycardia Syndrome in Youth: Associations With Distress, Impairment, Health Behaviors, and Medication Recommendations.

Among adolescents with fatigue and postural dizziness, it is unclear how health behaviors and emotional distress relate to the presence of excessive postural tachycardia. We prospectively evaluated adolescents aged 13-22 years presenting with symptoms suggestive of autonomic dysfunction between September 2017 and December 2018. Patients underwent standard 10-minute, 70-degree head-up tilt testing. Clinician diagnoses and recommendations were recorded from the medical record. Patients completed validated self-report measures of lifestyle factors, autonomic symptoms, depression, anxiety, and functional disability. Of 179 patients, 58 were diagnosed with postural orthostatic tachycardia syndrome and 59 had excessive postural tachycardia, with 90.5% concordance between the 2 groups. Presence of excessive postural tachycardia was associated with greater baseline fluid intake and likelihood of medication prescription in their treatment plan. Medication findings were replicated for postural orthostatic tachycardia syndrome diagnosis. Presence of excessive postural tachycardia or postural orthostatic tachycardia syndrome did not differentiate patients on perceived symptom severity, emotional distress, disability, or health behaviors but did appear to determine treatment recommendations.

Nutritional rickets - Vitamin D and beyond.

Vitamin D deficiency has been considered to be the cause of nutritional rickets for most of the past century. During the past two decades, however, it has become clear that nutritional rickets may be caused by vitamin D deficiency or by dietary insufficiency of calcium. The combined deficiencies of calcium and vitamin D interact, and several other factors are also relevant in the pathogenesis of nutritional rickets.

Inpatient pediatric chaplain service utilization among children with chronic, non-cancer diseases.

Despite the broad importance of pediatric spiritual care, most research focuses on oncologic and palliative care contexts. We aim to describe the utilization of pediatric chaplain services by children hospitalized for non-cancer chronic illnesses and to identify factors that predict utilization of chaplain services. Among 629 patients with 915 admissions, we found chaplain services were utilized in 5.0% of admissions. Utilization was similar between religiously affiliated patients (7.5%, 95%CI [5.3-10.6%]) and un-affiliated patients (6.4%, [3.6-11.0%]). Christian patients (7.3% [5.1-10.5%]) demonstrated similar utilization as non-Christian patients (7.0% [4.3-11.2%]). Utilization was significantly higher among patients with LOS >2 days (10.8% [7.9-14.6%]), compared to LOS ≤2 (1.7% [0.9-3.1%]). These results may represent an addressable gap in spiritual care, and they highlight an opportunity for pediatric chaplains to play a larger role in the holistic care of hospitalized children with chronic diseases, regardless of religious affiliation.