Autonomic Parameter and Stress Profile Predict Secondary Ischemic Events After Transient Ischemic Attack or Minor Stroke.

Background and Purpose- Traditional risk factors for ischemic stroke are body stressors that are related to autonomic autonomic system (ANS) dysfunction. The value of ABCD2 score (age, blood pressure, clinical features, duration of symptoms, diabetes) to predict ischemic stroke after transient ischemic attack is compromised by the inclusion of a limited number of stressors. We aimed to assess whether markers of ANS function and stress could predict the occurrence of secondary ischemic events after transient ischemic attack or minor stroke. Methods- This is a prospective cohort study in which 201 patients were recruited within 48 hours after initial transient ischemic attack or minor stroke and followed for 90 days to assess the development of secondary ischemic events. ABCD2 score, heart rate variability (HRV) parameters as markers of ANS function, and psychological stress were assessed. Logistic regression and area under the curve (AUC) were used to assess the models' predictive ability. Results- Morning high frequency (HF) HRV power and changes in HF HRV from morning to afternoon (daytime HF changes) were the most useful HRV predictors for both ischemic events (AUC=0.61 and 0.70) and ischemic stroke (AUC=0.62 and 0.72). Compared with ABCD2 score, 2 HRV-based stress models showed higher predictive ability for ischemic events (AUC=0.82 versus 0.63, 0.76 versus 0.63; P<0.05) and ischemic stroke (AUC=0.87 versus 0.64, 0.82 versus 0.64; P<0.05). Conclusions- Assessing the effects of stress on the ANS may be an innovative way to stratify the risk of ischemic events after transient ischemic attack or minor stroke. New risk stratification by assessing the dynamic features of ANS dysfunction and stress may help identify high-risk sub-populations that may benefit from added management.

Scholarly training objectives and requirements for paediatric residents in Canada.

In the absence of national standards for scholarly requirements, paediatric resident training varies significantly across Canadian programs. This variability may contribute to significant differences in trainee experiences and productivity. A panel of coordinators of paediatric resident research programs from across Canada met in 2014, to share experiences and identify barriers to successful resident scholarly activity. A survey of all programs was completed in 2015. A scoping review and series of meetings led to the development of a proposed list of expectations, timelines for successful completion and consequences for not completing a scholarly project. We propose a harmonized list of scholarly competencies and activities for paediatric residents in Canada to accomplish before completing their training. We also propose that programs implement standardized timelines and consequences in the event that a resident does not meet their program's scholarly expectations.

Glucose control and autonomic response during acute stress in youth with type 1 diabetes: A pilot study.

BACKGROUND: Type 1 diabetes (T1D) is a chronic source of metabolic and neuropsychological stress, which may eventually lead to autonomic neuropathy and other complications related to micro- and macro-vasculopathies. We aimed to investigate the relationship between T1D chronic stress and autonomic response to acute stress testing that was expected being affected by chronic stress. METHODS: Twenty youths with confirmed diagnosis of T1D were assessed. Chronic stress assessment included hemoglobin A1c (HbA1c) ≥7.5%, psychological stress assessed by perceived stress scale (PSS), hypoglycemic events, and proinflammatory cytokines. The acute stress testing used standardized stress video games. Autonomic response to acute stress was assessed by the amplitude and direction of changes in heart rate variability. Analyses determined correlations between changes in parasympathetic nervous system during stress testing and chronic diabetes stressors. RESULTS: A strong correlation was found between the amplitude of high frequency (HF) changes and HbA1c values (ρ = 0.74, P < .001). Youths with HbA1c ≥7.5% showed a larger amplitude of HF changes during acute stress (49% vs 16%, P < .001) and a higher PSS score (22.5 vs 19.0, P = .003), compared to those with HbA1c <7.5%. Additionally, among youths with HbA1c ≥7.5%, those with positive changes in HF had a lower level of IL-8 than those with negative changes (5.40 vs 7.85 pg/mL, P = .009). CONCLUSIONS: Study findings support the need for better understanding the health effects of stress-related autonomic dysfunction in youth with T1D.

Province-wide Biliary Atresia Home Screening Program in British Columbia: Evaluation of First 2 Years.

BACKGROUND AND OBJECTIVES: Biliary atresia (BA), a rare newborn liver disease, is the leading cause of liver-related death in children. Early disease recognition and timely surgical Kasai hepatoportoenterostomy (KP) offers long-term survival without liver transplant. Universal BA screening in Taiwan using infant stool color cards (ISCCs) has proven effectiveness. We report our experience with infant stool color card (ISCC) BA screening in a province-wide program in British Columbia (BC). The objective of this study is to assess program performance and cost from launch April 1, 2014 to March 31, 2016. METHODS: ISCCs distributed to families upon maternity ward discharge. Parents were instructed to monitor their infant's stool color for 1 month and contacted the screening center with concerns. The number of live births, ISCC distribution, BA cases, and costs were recorded. Cases with Program screen success had both acholic stool recognition (ISCC screen success) and timely referral for BA. RESULTS: All 126 maternity units received ISCCs. Of 87,583 live births there were 6 BA cases. Of the 5 cases with ISCC Screen Success 3 had Program Screen Success. The median KP age in the program screen success and failure groups was 49 (42-52) and 116 (49-184) days, respectively. Program sensitivity was 50%, specificity 99%, positive predictive value 4%, and negative predictive value 99%. A random sample of 1054 charts at BC Children's Hospital found an ISCC distribution rate of 94%. After a phase-in period, the annual program cost was $30,033.82, and the ISCC cost per birth was $0.68. CONCLUSIONS: The screening program has high specificity and distribution with low cost. Successful program case identification had earlier age at KP. Program modifications aim to improve sensitivity. Longer-term studies will determine program impact on health outcomes.

Cardiac Autonomic Nervous System Activity in Children with Bladder and Bowel Dysfunction.

PURPOSE: Bladder and bowel dysfunction is a common reason for referral to pediatric urology. The role of the autonomic nervous system in the pathogenesis of bladder and bowel dysfunction has not been well investigated. We compared autonomic nervous system activity in children with bladder and bowel dysfunction to that in healthy controls. We hypothesized that children with dysfunction have a different autonomic profile as measured by parameters from spectral analysis of heart rate variability and impedance cardiography. MATERIALS AND METHODS: We recruited 40 children, including 25 girls, with a median age of 10 years (range 5 to 18) in whom bladder and bowel dysfunction was clinically diagnosed by a validated questionnaire and 19 healthy controls, including 9 girls, with a median age of 8 years (range 5 to 16). Cardiac autonomic activity was assessed at baseline and during voiding. The primary outcome measures were the main parameters of heart rate variability, including total power and high frequency, as well as pre-ejection period and heart rate. RESULTS: Comparison of outcomes at baseline showed significantly lower total power and high frequency heart rate variability in bladder and bowel dysfunction cases (p = 0.001 and 0.002, respectively). Children with dysfunction also showed a significantly smaller decrease in sympathetic nervous system activity during voiding (p = 0.05). CONCLUSIONS: Our results demonstrate that compared to healthy controls children with bladder and bowel dysfunction show a different cardiac autonomic profile at rest and in response to voiding. This difference may be used in future studies to further clarify the pathophysiology of bladder and bowel dysfunction, and introduce novel treatment targets to manage the condition.

Home-Based Screening for Biliary Atresia Using Infant Stool Color Cards in Canada: Quebec Feasibility Study.

OBJECTIVES: Biliary atresia (BA) is a leading cause of liver failure and liver transplantation in pediatrics. BA manifests by 3 weeks of life with jaundice and pale stools. Delayed diagnosis and surgical intervention with Kasai portoenterostomy after 3 months of age is significantly associated with poor prognosis for native liver survival. A national Taiwan infant stool color card (SCC) screening program has entirely eliminated late Kasai portoenterostomy >90 days of age and improved native liver survival. A recent large-scale prospective cohort study in British Columbia, Canada, indicated that distribution of SCC on the maternity ward was feasible, led to high utilization rate, and was cost-effective. The aim of the present study was to assess the generalizability of this screening strategy in another Canadian jurisdiction with a different sociodemographic profile. METHODS: An SCC was distributed to families of newborns discharged at St Mary's Hospital Center, Montreal, Quebec. Families were instructed to monitor their infant's stool color for 21 days and then complete and mail the SCC to the study center. Phone surveys to families who did not return cards were used to estimate total card utilization rate. RESULTS: Two thousand two hundred forty-six infants were eligible for inclusion; 99.9% were enrolled. Mail SCC return rate was 63.3%. No cases of BA were identified. All of the 118 families who completed the phone survey reported that they had utilized the SCC. Conservative and optimistic estimates for total card utilization rates were 82% and 100%, respectively. CONCLUSIONS: The high enrollment and utilization rates in this screening study strongly support the feasibility of implementing a Canadian SCC screening program to improve outcomes of children with BA.

Sustainable childhood obesity prevention through community engagement (SCOPE) program: evaluation of the implementation phase.

Childhood obesity rates are steadily rising. Sustainable Childhood Obesity Prevention Through Community Engagement (SCOPE) is a community-based participatory action research (PAR) program aimed at preventing childhood obesity. This study aimed to describe community perspectives on, and elicit feedback about, SCOPE's first phase of implementation in two pilot cities in British Columbia, Canada. A case study was implemented using interviews and questionnaires to obtain feedback about SCOPE from two groups: SCOPE coordinators and stakeholders (i.e., individuals and organizations that were a member of the community and engaged with SCOPE coordinators). Participants were recruited via email and (or) by telephone. Coordinators completed a telephone interview. Stakeholders completed a questionnaire and (or) a telephone interview. Thematic analysis was conducted. Participants included 2 coordinators and 15 stakeholders. Participants similarly interpreted SCOPE as a program focused on raising awareness about childhood obesity prevention, while engaging multiple community sectors. Overall, participants valued the program's role in facilitating networking and partnership development, providing evidence-based resources, technical expertise, and contributing funding. Participants felt that SCOPE is sustainable. However, participants felt that barriers to achieving healthy weights among children included those related to the built environment, and social, behavioral, and economic obstacles. Perspectives on factors that facilitated and acted as barriers to SCOPE's first phase of implementation were obtained from the SCOPE communities and may be used to enhance the sustainability of SCOPE and its applicability to other BC communities.

Biofeedback for nonneuropathic daytime voiding disorders in children: a systematic review and meta-analysis of randomized controlled trials.

PURPOSE: Biofeedback has been used to treat children with symptoms of bladder dysfunction not responding to standard therapy alone. However, evidence of the effectiveness of biofeedback is scarce and is based on small studies. We conducted a systematic review of the literature to assess the effects of biofeedback as adjunctive therapy for symptoms of nonneuropathic voiding disorders in children up to age 18 years. MATERIALS AND METHODS: We searched MEDLINE(®), Embase(®) and CENTRAL on the OvidSP(®) platform as well as conference proceedings for randomized trials presented at scientific conventions, symposia and workshops through August 13, 2013. Hand searches and review of reference lists of retrieved articles were also performed. RESULTS: Five eligible studies were included in the systematic review, of which 4 (382 participants) were pooled in the meta-analysis based on available outcomes data. The overall proportion of cases with resolved incontinence at month 6 was similar in the biofeedback and control groups (OR 1.37 [95% CI 0.64 to 2.93], RD 0.07 [-0.09, 0.23]). There was also no significant difference in mean maximum urinary flow rate (mean difference 0.50 ml, range -0.56 to 1.55) or likelihood of urinary tract infection (OR 1.30 [95% CI 0.65 to 2.58]). CONCLUSIONS: Current evidence does not support the effectiveness of biofeedback in the management of children with nonneuropathic voiding disorders. More high quality, randomized controlled trials are needed to better evaluate the effect of biofeedback.

A randomized controlled trial of an intervention for infants' behavioral sleep problems.

BACKGROUND: Infant behavioral sleep problems are common, with potential negative consequences. We conducted a randomized controlled trial to assess effects of a sleep intervention comprising a two-hour group teaching session and four support calls over 2 weeks. Our primary outcomes were reduced numbers of nightly wakes or parent report of sleep problem severity. Secondary outcomes included improvement in parental depression, fatigue, sleep, and parent cognitions about infant sleep. METHODS: Two hundred thirty five families of six-to-eight month-old infants were randomly allocated to intervention (n = 117) or to control teaching sessions (n = 118) where parents received instruction on infant safety. Outcome measures were observed at baseline and at 6 weeks post intervention. Nightly observation was based on actigraphy and sleep diaries over six days. Secondary outcomes were derived from the Multidimensional Assessment of Fatigue Scale, Center for Epidemiologic Studies Depression Measure, Pittsburgh Sleep Quality Index, and Maternal (parental) Cognitions about Infant Sleep Questionnaire. RESULTS: One hundred eight intervention and 107 control families provided six-week follow-up information with complete actigraphy data for 96 in each group: 96.9% of intervention and 97.9% of control infants had an average of 2 or more nightly wakes, a risk difference of -0.2% (95% CI: -1.32, 0.91). 4% of intervention and 14% of control infants had parent-assessed severe sleep problems: relative risk 0.3, a risk difference of -10% (CI: 0.11, 0.84-16.8 to -2.2). Relative to controls, intervention parents reported improved baseline-adjusted parental depression (CI: -3.7 to -0.4), fatigue (CI: -5.74 to -1.68), sleep quality (CI: -1.5 to -0.2), and sleep cognitions: doubts (CI: -2.0 to -0.6), feeding (CI: - 2.1 to - 0.7), anger (CI: - 1.8 to - 0.4) and setting limits (CI: -3.5 to -1.5). CONCLUSIONS: The intervention improved caregivers' assessments of infant sleep problem severity and parental depression, fatigue, sleep, and sleep cognitions compared with controls. TRIAL REGISTRATION: ISRCTN42169337 , NCT00877162.

Surgical suite to pediatric intensive care unit handover protocol: implementation process and long-term sustainability.

The article reports the long-term sustainability of a standardized transfer protocol from cardiac surgical suite to the pediatric intensive care unit. Using rapid process improvement technique, the original mean defect rate per handover decreased from 13.2 to 0 and 0.3, 12, and 24 months postimplementation, respectively. This study stresses the importance of long-term assessment to control for possible observation biases; it also illustrates a successful implementation strategy that used video recording to engage staff in identifying solutions to the observed defects.

Care delivery in youth with type 2 diabetes - are we meeting clinical practice guidelines?

BACKGROUND: Studies indicate high rates of treatment failure and early onset diabetes-related complications in youth-onset type 2 diabetes (T2D). We aim to describe the quality of care provided to children and youth with T2D. METHODS: This prospective cohort study used administrative datasets to describe individuals aged 10-24 yr diagnosed with T2D at <20 yr of age (488 individuals; 2111 person-years). The primary outcome was being 'at goal' for adherence to Canadian clinical practice guidelines (CPGs). This was defined as having either optimal [three diabetes-related physician visits/year, three hemoglobin A1C (A1C) tests/year, and all recommended screening tests for complications (i.e., retinopathy, nephropathy)] or good (two diabetes-related physician visits/year, two A1C tests/year, and at least two screening tests) adherence to CPGs. Descriptive statistics and logistic regression modeling were used. RESULTS: Sixty eight percentage person-years had poor adherence to CPGs (<2 physician visits and A1c tests/year and no screening tests). Only 29% and 25% were at goal for adherence in the 15-19 and 20-24 yr age groups, respectively. There was a 52% decreased odds of being at goal for adherence 4 yr after diagnosis of T2D (p < 0.001). For every year increase in age at diagnosis, there was a 5% decreased odds of being at goal (p = 0.04). CONCLUSIONS: Youth with T2D are not receiving high quality care, and older youth and young adults are particularly at risk. Future research is needed to understand the effectiveness of care in the context of poor adherence as well as patient, physician, and health system factors that might improve adherence.

Humanistic burden of pediatric type 1 diabetes on children and informal caregivers: systematic literature reviews.

BACKGROUND: Diagnosis of children with type 1 diabetes (T1D) imposes an unprecedented burden on children and their caregivers. OBJECTIVE: To assess the burden of T1D on children and their informal caregivers, both after a recent diagnosis or after a longer duration of disease. METHODS: A series of systematic literature reviews were performed to explore the burden of T1D on children with the disease and their primary informal caregivers, based on the time of diagnosis. After the extraction of the qualitative and quantitative data from the included studies, two literature-based conceptual frameworks were developed: on the burden of pediatric T1D on children, and on informal caregivers. A third conceptual framework on the shared burden of pediatric T1D on both children and informal caregivers as part of the same family unit was also developed. RESULTS: The review of literature has identified a series of factors that affect the quality of life of children with T1D and their informal caregivers, with a direct impact on physical, emotional, and social outcomes. Generally, female patients and older adolescents experience more worry and stress that affects their quality of life. Other categories of factors affecting the child's and caregiver's burden include social, emotional, and physical factors, treatment-related and disease-related factors, as well as their coping abilities. Anxiety, depression, stress, and worry were commonly found among children and caregivers, starting with the diagnosis of T1D and continuing over time in relation to new challenges pertaining to aging or the disease duration. CONCLUSION: T1D causes a significant burden to affected children and their caregivers, both independently and through transactional interaction within the family unit. Disease burden can be reduced by strengthening individuals for the benefit of the whole family.

Association between electroencephalogram alpha-band oscillations and executive and processing functions in patients with cerebral small vessel diseases.

Electroencephalogram (EEG) alpha-band oscillations may reflect executive and processing function in patients with cerebral small vessel disease (CSVD). We aimed to assess such association and its relationship with CSVD severity, and to identify specific alpha-band parameters and the cut-off values for cognitive screening. We analysed the dispersion of amplitude-frequency characteristics of EEG alpha-band and different alpha-band parameters (PFα , ΔPFα , PPα , NCL) in different brain locations. We also assessed patients' executive and processing functions using verbal fluency test (VFT) and color trails test (CTT), and CSVD severity using total burden and Fazekas scores. 129 patients were recruited in the study. After adjusting for age, gender and education, PFα(F3), PFα(F4) and NCL were significantly associated with VFT-composite performance (p < 0.05). CTT-1 time and error were associated with PFα(F3), PFα(F4), ΔPFα(O1;F3) and CSVD severity (p < 0.05), whereas CTT-2 time was only associated with CSVD severity. Moreover, the correlations between alpha-band oscillations and cognitive function were higher in low than in high disease-severity group (ρ: -0.58 vs. -0.38, p < 0.05). The AUC of selected alpha-band parameters were higher than 0.8 for VFT and CTT. Specific alpha-band parameters in the frontal lobe were identified to correspond to executive and processing function. Assessing EEG alpha-band oscillations may assist in screening cognitive impairment.

Adherence to clinical practice guidelines in the management of children, youth, and young adults with type 1 diabetes--a prospective population cohort study.

OBJECTIVE: To describe adherence to clinical practice guidelines for the treatment of childhood type 1 diabetes and identify associated patient and system level factors. STUDY DESIGN: This prospective cohort study used population-based administrative data to describe individuals aged 1-24 years who had been diagnosed with type 1 diabetes at <20 years of age (1472 unique individuals and 5883 person-years over a 7-year period) living in British Columbia, Canada. The outcome measure was proportion 'at goal,' which was defined as having optimal adherence (3 diabetes-related physician visits/year, 3 hemoglobin A1c (HbA1c) tests/year, 1 glucagon prescription dispensed/year, and appropriate screening for diabetes-related comorbidity [ie, hypothyroidism] and complications [ie, retinopathy and nephropathy]), or good adherence to guidelines (2 diabetes-related physician visits/year, 2 HbA1c tests/year, and appropriate screening for diabetes-related comorbidity and complications). Statistical methods included descriptive statistics and logistic regression modeling. RESULTS: Fifty-four percent person-years had poor adherence to guidelines (<2 diabetes-related physician visits and HbA1c tests/year) and 7.4% had optimal adherence. The proportion of person-years at goal was higher in females vs males (41.0% vs 37.6%; P = .007). Individuals 4-years post-diagnosis of diabetes were 78% less likely to be at goal compared with the year of diagnosis (P < .0001). CONCLUSIONS: The treatment of pediatric type 1 diabetes likely does not meet national and international standards. Future studies should explore facilitators and barriers to adherence to guidelines among health care providers, patients, and families, and whether adherence to guidelines is associated with glycemic control.

Antidepressant use among survivors of childhood, adolescent and young adult cancer: a report of the Childhood, Adolescent and Young Adult Cancer Survivor (CAYACS) Research Program.

BACKGROUND: Although survivors of childhood, adolescent, and young adult (AYA) cancer are at risk for late psychological sequelae, it is unclear if they are more likely to be prescription antidepressant users than their peers. PROCEDURE: All 5-year survivors of childhood or AYA cancer diagnosed before age 25 years in British Columbia from 1970 to 1995 were identified. Those with complete follow-up in the provincial health insurance registry from 2001 to 2004 were included (n = 2,389). A birth-cohort and gender-matched set of population controls 10 times the size of the survivor group was randomly selected (n = 23,890). All prescriptions filled between 2001 and 2004 were identified through linkage to the provincial prescription drug administrative database. Logistic regression analyses determined the impact of cancer survivorship on the likelihood of ever filling an antidepressant prescription. RESULTS: After adjusting for sociodemographic factors, survivors of childhood and AYA cancer were more likely to have filled an antidepressant prescription compared to controls (OR 1.21, 95% CI 1.09-1.35). Cancer survivors had an increased likelihood of using all categories of antidepressants, and of using drugs from two or more antidepressant categories, compared to peers (OR 1.31, 95% CI 1.11-1.55 [≥2 antidepressant categories]). Treatment was not a significant predictor of antidepressant use. Female survivors, those in young adulthood and those more than 20 years post-treatment had increased antidepressant use. CONCLUSIONS: Survivors of childhood and AYA cancer are more likely to fill antidepressant prescriptions compared to peer controls. This may indirectly reflect an increased underlying prevalence of mental health conditions among survivors.

Associations between Autonomic Function and Cognitive Performance among Patients with Cerebral Small Vessel Disease.

Data linking heart rate variability (HRV) and cognitive status remains controversial and scarce, particularly in cerebral small vessel disease (CSVD) patients. Whether the association between HRV and cognitive performance exists in CSVD patients is unclear. Hence, we aimed to investigate the association between HRV and cognitive performance in patients with CSVD. This cross-sectional study was conducted among 117 CSVD patients. All patients underwent HRV assessment and global cognitive evaluation by the Mini-Mental-State Examination (MMSE) and Montreal Cognitive Assessment (MoCA). Multivariable analyses were performed to evaluate the association between HRV and cognitive status. The mean age of study population was 59.5 ± 11.8 years and 39.3% were female. After adjusting for confounding factors, a higher high frequency (HF) norm was independently associated with better MMSE scores (ß = 0.051; 95% confidence interval (CI): 0.012~0.090; p = 0.011) and MoCA scores (ß = 0.061; 95% CI: 0.017~0.105; p = 0.007), while a higher low frequency (LF)/HF ratio was independently associated with worse MMSE scores (ß = -0.492; 95% CI: -0.893~-0.092; p = 0.017) and MoCA scores (ß = -0.691; 95% CI: -1.134~-0.248; p = 0.003). The HF norm was positively associated with global cognitive performance, whereas the LF/HF ratio was negatively associated with global cognitive performance among CSVD patients. Further study of the relationship between autonomic function and cognitive performance is warranted.

Complex interactive multimodal intervention to improve personalized stress management among healthcare workers in China: A knowledge translation protocol.

Objectives: Numerous stress management interventions have been implemented in the workplace, but few are adapted to the healthcare setting. Due to the nature of their jobs, healthcare workers (HCWs) may find it difficult to adopt recommended stress management strategies. We present the protocol for a 12-week personalized stress management intervention among HCWs to change their behavior as well as improve physiological/psychological outcomes. Methods: It is a pragmatic quasi-experimental study involving stressed HCWs from two general hospitals in Wuhan, China. The intervention group will receive a complex interactive multimodal intervention, including advanced education via mobile connection, participation in a web-based social network, tailored feedback, and the support of a nurse coach, while the control group will engage in self-guided stress management. Results: The primary outcome is centered on behavioral measures, namely improvements in stress management practice frequency after a 12-week intervention. The secondary outcomes are the changes in stress-related physiological indices (i.e. high frequency variability and normalized unit assessed by Holter) and psychological indicators (scores on the Perceived Stress Scale and Depression, Anxiety, Stress Scale) following 12 weeks of treatment. Conclusion: The knowledge translation intervention builds on a body of work defining the role of individualized instruction and feedback intervention, as well as group intervention through WeChat social network and personalized coaching. We believe this novel intervention will help HCWs promote their stress management awareness and skills, and ultimately benefit their long-term health. Trial Registration: ClinicalTrials.gov., NCT05239065. Registered 14 February 2022-Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT05239065.

Preemptive use of high-dose fluticasone for virus-induced wheezing in young children.

BACKGROUND: Although virus-induced wheezing is common in preschool-age children, optimal management remains elusive. We examined the efficacy and safety of preemptive treatment with high-dose fluticasone in reducing the severity of recurrent virus-induced wheezing in children. METHODS: We randomly assigned 129 children who were 1 to 6 years of age to receive 750 microg of fluticasone propionate (ex-valve [manufacturer-measured] dose) or placebo twice daily, beginning at the onset of an upper respiratory tract infection and continuing for a maximum of 10 days, over a period of 6 to 12 months. The primary outcome was rescue oral corticosteroid use. Secondary outcomes included symptoms, use of beta(2)-agonists, acute care visits, hospitalizations, discontinuation of the study drug, change in growth and bone mineral density, basal cortisol level, and adverse events. RESULTS: Over a median period of 40 weeks, 8% of upper respiratory tract infections in the fluticasone group led to treatment with rescue systemic corticosteroids, as compared with 18% in the placebo group (odds ratio, 0.49; 95% confidence interval [CI], 0.30 to 0.83). Children who were treated with fluticasone, as compared with those who were given placebo, had smaller mean (+/-SD) gains from baseline in height (6.23+/-2.62 cm [unadjusted value]; z score, -0.19 +/-0.42 vs. 6.56+/-2.90 cm [unadjusted value]; z score, 0.00+/-0.48; difference between groups in z score from baseline to end point, -0.24 [95% CI, -0.40 to -0.08]) and in weight (1.53+/-1.17 kg [unadjusted value]; z score, -0.15+/-0.48 vs. 2.17+/-1.79 kg [unadjusted value]; z score, 0.11+/-0.43; difference between groups in z score from baseline to end point, -0.26 [95% CI, -0.41 to -0.09]). There were no significant differences between the groups in basal cortisol level, bone mineral density, or adverse events. CONCLUSIONS: In preschool-age children with moderate-to-severe virus-induced wheezing, preemptive treatment with high-dose fluticasone as compared with placebo reduced the use of rescue oral corticosteroids. Treatment with fluticasone was associated with a smaller gain in height and weight. Given the potential for overuse, this preventive approach should not be adopted in clinical practice until long-term adverse effects are clarified. (ClinicalTrials.gov number, NCT00238927.)

Lysine restricted diet for pyridoxine-dependent epilepsy: first evidence and future trials.

OBJECTIVE: To evaluate the efficacy and safety of dietary lysine restriction as an adjunct to pyridoxine therapy on biochemical parameters, seizure control, and developmental/cognitive outcomes in children with pyridoxine-dependent epilepsy (PDE) caused by antiquitin (ATQ) deficiency. METHODS: In this observational study, seven children with confirmed ATQ deficiency were started on dietary lysine restriction with regular nutritional monitoring. Biochemical outcomes were evaluated using pipecolic acid and α-aminoadipic semialdehyde (AASA) levels in body fluids; developmental/cognitive outcomes were evaluated using age-appropriate tests and parental observations. RESULTS: Lysine restriction was well tolerated with good compliance; no adverse events were reported. Reduction in biomarker levels (measurement of the last value before and first value after initiation of dietary lysine restriction) ranged from 20 to 67% for plasma pipecolic acid, 13 to 72% for urinary AASA, 45% for plasma AASA and 42% for plasma P6C. For the 1 patient in whom data were available and who showed clinical deterioration upon interruption of diet, cerebrospinal fluid levels decreased by 87.2% for pipecolic acid and 81.7% for AASA. Improvement in age-appropriate skills was observed in 4 out of 5 patients showing pre-diet delays, and seizure control was maintained or improved in 6 out 7 children. CONCLUSIONS: This observational study provides Level 4 evidence that lysine restriction is well tolerated with significant decrease of potentially neurotoxic biomarkers in different body compartments, and with the potential to improve developmental outcomes in children with PDE caused by ATQ deficiency. To generate a strong level of evidence before this potentially burdensome dietary therapy becomes the mainstay treatment, we have established: an international PDE consortium to conduct future studies with an all-inclusive integrated study design; a website containing up-to-date information on PDE; a methodological toolbox; and an online registry to facilitate the participation of interested physicians, scientists, and families in PDE research.

Validation of classification algorithms for childhood diabetes identified from administrative data.

OBJECTIVE: Type 1 diabetes is the most common form of diabetes among children; however, the proportion of cases of childhood type 2 diabetes is increasing. In Canada, the National Diabetes Surveillance System (NDSS) uses administrative health data to describe trends in the epidemiology of diabetes, but does not specify diabetes type. The objective of this study was to validate algorithms to classify diabetes type in children <20 yr identified using the NDSS methodology. PATIENTS AND METHODS: We applied the NDSS case definition to children living in British Columbia between 1 April 1996 and 31 March 2007. Through an iterative process, four potential classification algorithms were developed based on demographic characteristics and drug-utilization patterns. Each algorithm was then validated against a gold standard clinical database. RESULTS: Algorithms based primarily on an age rule (i.e., age <10 at diagnosis categorized type 1 diabetes) were most sensitive in the identification of type 1 diabetes; algorithms with restrictions on drug utilization (i.e., no prescriptions for insulin ± glucose monitoring strips categorized type 2 diabetes) were most sensitive for identifying type 2 diabetes. One algorithm was identified as having the optimal balance of sensitivity (Sn) and specificity (Sp) for the identification of both type 1 (Sn: 98.6%; Sp: 78.2%; PPV: 97.8%) and type 2 diabetes (Sn: 83.2%; Sp: 97.5%; PPV: 73.7%). CONCLUSIONS: Demographic characteristics in combination with drug-utilization patterns can be used to differentiate diabetes type among cases of pediatric diabetes identified within administrative health databases. Validation of similar algorithms in other regions is warranted.