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In biomedical research, cluster analysis is often performed to identify patient subgroups based on patients' characteristics or traits. In the model-based clustering for identifying patient subgroups, mixture models have played a fundamental role in modeling. While there is an increasing interest in using mixture modeling for identifying patient subgroups, little work has been done in selecting the predictors that are associated with the class assignment. In this study, we develop and compare two approaches to perform variable selection in the context of a mixture model to identify important predictors that are associated with the class assignment. These two approaches are the one-step approach and the stepwise approach. The former refers to an approach in which clustering and variable selection are performed simultaneously in one overall model, whereas the latter refers to an approach in which clustering and variable selection are performed in two sequential steps. We considered both shrinkage prior and spike-and-slab prior to select the importance of variables. Markov chain Monte Carlo algorithms are developed to estimate the posterior distribution of the model parameters. Practical applications and simulation studies are carried out to evaluate the clustering and variable selection performance of the proposed models.

In clinical and epidemiological studies, there is a growing interest in studying the heterogeneity among patients based on longitudinal characteristics to identify subtypes of the study population. Compared to clustering a single longitudinal marker, simultaneously clustering multiple longitudinal markers allow additional information to be incorporated into the clustering process, which reveals co-existing longitudinal patterns and generates deeper biological insight. In the current study, we propose a Bayesian consensus clustering (BCC) model for multivariate longitudinal data. Instead of arriving at a single overall clustering, the proposed model allows each marker to follow marker-specific local clustering and these local clusterings are aggregated to find a global (consensus) clustering. To estimate the posterior distribution of model parameters, a Gibbs sampling algorithm is proposed. We apply our proposed model to the primary biliary cirrhosis study to identify patient subtypes that may be associated with their prognosis. We also perform simulation studies to compare the clustering performance between the proposed model and existing models under several scenarios. The results demonstrate that the proposed BCC model serves as a useful tool for clustering multivariate longitudinal data.

Objective: To systematically evaluate the effectiveness of mindfulness-based interventions (MBIs) on rumination among patients with depression and their efficacy across countries and year of publication and control conditions. Methods: Web of Science Core Collection, Medline, BIOSIS Citation Index, KCI-Korean Journal Database, SciELO Citation Index, PubMed, Cochrane Library, and Embase were searched to include randomized controlled trials of MBIs for depressive rumination that met the criteria. The Rumination Scale was used as the primary outcome indicator; Depression, mindfulness, and anxiety indexes were selected as the secondary outcome indicators. An evaluation of bias risk was conducted to identify possible sources of bias based on methodological and clinical factors. RevMan5.3 software was used to perform a meta-analysis of the extracted data. Results: Nineteen studies with 1138 patients were included. Meta-analysis showed that MBIs could significantly reduce rumination levels in patients with depression (standardized mean difference (SMD) = −0.46; 95% confidence interval (CI): −0.58, −0.34; p < 0.001), notably improve depression (SMD = −0.58; 95% CI: −0.83, −0.32; p < 0.001), enhance mindfulness ability (SMD = 0.95; 95% CI: 0.57, 1.32; p < 0.001), and reduce the anxiety of patients with depression (SMD = −0.45, 95% CI: −0.62, −0.27; p < 0.001). MBIs conducted in Asia improved rumination better than studies in Europe and North America (SMD = −2.05 95% CI: −4.08, −0.01; p < 0.001) but had no greater effect than behavior activation on depression. The interventions carried out in the past 5 years were significantly better than earlier studies in improving mindfulness levels (SMD = 2.74; 95% CI: 0.81, 4.66; p = 0.005). Conclusions: MBIs are effective in the treatment of depression as they produce pleasant improvement in rumination and depression, decrease the degree of anxiety, and enhance mindfulness levels compared to controls. In newer forms of MBIs, regional differences need to be considered when designing the intervention program. More large, high-quality randomized controlled studies are needed to confirm the conclusion that the effectiveness of MBIs has differences in terms of the trial area and year of publication.

Summary Background & aims Mixed oil intravenous lipid emulsion (MO ILE) that contains 30% soybean oil (SO), 30% medium chain triglycerides, 25% olive oil and 15% fish oil can benefit hospitalized patients receiving parenteral nutrition (PN) but there are very few studies on its long-term use. Our goal was to evaluate the clinical outcomes of adults receiving home PN (HPN) with MO versus those receiving SO ILE over a 2-year period. Method This is a retrospective analysis of data collected prospectively from a cohort of patients recorded in the Canadian HPN Registry over a 2-year period. HPN patients from academic programs across Canada were entered in the Registry according to a validated protocol. For this study, demographic, nutritional, laboratory and clinical data were extracted from January 1st 2015, when MO lipid emulsion became available in Canada, to July 24th 2019. Clinical data for each patient included: number of hospitalizations, number of hospitalizations related to HPN and number of hospitalization days related to HPN, over a year; incidence of line sepsis per 1000 catheter days and mortality. Data are presented as median (1st, 3rd quartile) for continuous variables and frequency (percentage) for categorical variables. Comparisons between groups were performed using two sample t-test or Wilcoxon Rank Sum tests for continuous variables and Chi-square tests or Fisher's exact tests for categorical variables. Univariate and multiple linear regressions were also carried out. Statistical significance is set at a p-value Results A total of 120 patients were included (MO n = 68, SO n = 52). Significant differences at baseline between the two groups were a higher use of Hickman line (62.12% vs 42%, p = 0.038) and more western Canada based hospital care with MO (75% vs 42.31%, p = 0.0002). The MO group had significantly more hospitalizations (p = 0.001), more hospitalizations related to HPN (p = 0.012) and more hospitalization days related to HPN (p = 0.016) per patient per year compared to SO patients. There was no significant difference between groups for line sepsis per 1000 catheter days (MO: 0.05 (0.0, 1.0) vs SO: 0.0 (0.0, 0.22), p = 0.053) or mortality. All other variables, including biochemical variables, were similar between groups. In a multiple regression analysis, the following factors were significantly associated with a greater number of hospitalizations per patient per year: use of MO, high blood glucose from the last recorded value and having died by the end of the study period. Conclusion This 2-year prospective cohort study suggests an increased risk of hospitalization in HPN patients receiving MO lipid emulsion. The long-term effect of using MO lipid emulsion in HPN patients should be further evaluated using a large randomized controlled trial. The study was registered in clinicaltrials.gov (NCT02299466).

In many clinical studies, researchers are interested in parsimonious models that simultaneously achieve consistent variable selection and optimal prediction. The resulting parsimonious models will facilitate meaningful biological interpretation and scientific findings. Variable selection via Bayesian inference has been receiving significant advancement in recent years. Despite its increasing popularity, there is limited practical guidance for implementing these Bayesian approaches and evaluating their comparative performance in clinical datasets. In this paper, we review several commonly used Bayesian approaches to variable selection, with emphasis on application and implementation through R software. These approaches can be roughly categorized into four classes: namely the Bayesian model selection, spike-and-slab priors, shrinkage priors, and the hybrid of both. To evaluate their variable selection performance under various scenarios, we compare these four classes of approaches using real and simulated datasets. These results provide practical guidance to researchers who are interested in applying Bayesian approaches for the purpose of variable selection.

Rationale: Sleep study interpretation in children needs to be based on age-specific normal values. Although several studies have reported normal cardiorespiratory parameters during sleep in childre...

The lung clearance index (LCI) is a measure of pulmonary function. Variable feasibility (50-80%) in preschool children has been reported. There are limited studies exploring its relationship to respiratory symptoms and how it predicts persistent wheeze. We aimed to assess the association with respiratory symptoms in preschool-aged children with LCI and determine its utility in predicting persistent wheeze.LCI was measured in a subcohort of the CHILD Cohort Study at age 3 years using SFAt age 3 years, 69% (234/340) had feasible LCI. Excluding two children with missing data, 232 participants were categorized as follows: 33 (14%) 3RW; 28 (12%) 3RC; 17 (7%) IS; and 154 (66%) NCS. LCI z-score at age 3 years was highest in children with 3RW compared to 3RC (mean (SD): 1.14 (1.56) vs. 0.09 (0.95), p .01), IS (mean (SD): -0.14 (0.59), p .01), and NCS (mean (SD): -0.08 (1.06), p .01). LCI z-score at age 3 was predictive of persistent wheeze at age 5 (PW) (AUROC: 0.87).LCI at age 3 was strongly associated with recurrent wheeze at age 3, and predictive of its persistence to age 5.

Objective To explore relationship among self‐injury behavior, experiential avoidance, cognitive fusion, anxiety, and depression in Chinese adolescent patients with nonsuicidal self‐injury (NSSI). Methods Cognitive fusion questionnaire (CFQ), Acceptance and Action Questionnaire—2nd edition (AAQ‐II), adolescent nonsuicidal self‐injury behavior questionnaire (ANSAQ), Hamilton Anxiety Scale (HAMA), and Hamilton Depression Scale (HAMD) were used as research tools to investigate 120 subjects with NSSI and 130 healthy controls. Results The scores of CFQ and AAQ‐II in the NSSI group were significantly higher than those in the healthy control group (p, This study investigated the incidence of postoperative delirium in elderly patients after hip fracture surgery, and to identify risk factors for such, as part of developing a risk stratification index (RSI) system to predict a patient's risk of postoperative delirium.

Few studies have examined phthalate exposure during infancy and early life, critical windows of development. The Canadian Healthy Infant Longitudinal Development (CHILD) study, a population-based birth cohort, ascertained multiple exposures during early life. To characterize exposure to phthalates during infancy and early childhood. Environmental questionnaires were administered, and urine samples collected at 3, 12, and 36 months. In the first 1578 children, urine was analyzed for eight phthalate metabolites: mono-methyl phthalate (MMP), mono-ethyl phthalate (MEP), mono-butyl phthalate (MBP), mono-benzyl phthalate (MBzP), mono-2-ethylhexyl phthalate (MEHP), mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP), mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), and mono-3-carboxypropyl phthalate (MCPP). Geometric mean (GM) concentrations were calculated by age, together with factors that may influence concentrations. Trends with age were examined using mixed models and differences within factors examined using ANOVA. The highest urinary concentration was for the metabolite MBP at all ages (GM: 15–32 ng/mL). Concentrations of all phthalate metabolites significantly increased with age ranging from GM: 0.5–15.1 ng/mL at 3 months and 1.9–32.1 ng/mL at 36 months. Concentrations of all metabolites were higher in the lowest income categories except for MEHP at 3 months, among children with any breastfeeding at 12 months, and in urine collected on dates with warmer outdoor temperatures (>17 °C), except for MBzP at 3 months and MEHP at 3 and 12 months. No consistent differences were found by gender, study site, or maternal age. Higher phthalate metabolite concentrations were observed among children in lower income families. Examination of factors associated with income could inform interventions aimed to reduce infant phthalate exposure.

In longitudinal studies, it is often of great interest to cluster individual trajectories based on repeated measurements taken over time. Non-linear growth trajectories are often seen in practice, and the individual data can also be measured sparsely, and at irregular time points, which may complicate the modeling process. Motivated by a study of pregnant women hormone profiles, we proposed a shape invariant growth mixture model for clustering non-linear growth trajectories. Bayesian inference via Monte Carlo Markov Chain was employed to estimate the parameters of interest. We compared our model to the commonly used growth mixture model and functional clustering approach by simulation studies. Results from analyzing the real data and simulated data were presented and discussed.

Olive oil (OO)-based intravenous lipid emulsion (IVLE) may have biological advantages for nutrition and inflammation status compared with soybean oil (SO)-based IVLE. We aimed to compare prealbumin levels during infusion of OO- or SO-based IVLE in patients receiving parenteral nutrition in the acute-care setting.In this prospective, noninferiority, double blind randomized controlled efficacy trial, patients received either OO-based or SO-based IVLE after providing consent. Biochemical and nutrition parameters were collected at baseline and at 7 to 10 d after initiation of parenteral nutrition. Results are expressed as means (standard deviations).A total of 210 patients completed the study: 102 patients in the SO-based IVLE group and 108 patients in the OO-based IVLE group. Both groups had a significant increase in prealbumin levels from baseline (SO: 0.10 [0.06] versus 0.15 [0.08] g/L; P0.0001; OO: 0.11 [0.06] versus 0.16 [0.08] g/L; P0.0001), but mean changes between groups were not different (P = 0.53). OO-based IVLE was noninferior to SO-based IVLE in maintaining or increasing serum prealbumin levels, with 20% as the noninferiority margin at follow-up (least square geometric mean ratio [95% CI], 1.10 [0.83,1.47]; P = 0.50). There was a significant improvement in C-reactive protein levels from baseline within each group (SO: 83.24 [69.72] versus 53.4 [59.78] mg/dL; P0.0001; OO: 85.13 [68.14] versus 58.75 [60.11] mg/dL; P = 0.004), but mean changes between the groups were not different (P = 0.836). Mortality, length of stay, and infection rates were not different for both groups.In this study, OO-based IVLE was not inferior to SO-based IVLE in maintaining or increasing the prealbumin level. The improvement of C-reactive protein levels and other clinical outcomes were not different for both groups.

INTRODUCTION Severe gastrointestinal dysmotility disorder (GID) constitute approximately 20% of patients requiring home parenteral nutrition (HPN), whereas short-bowel syndrome (SBS) remains the most frequent indication for HPN. This study's aim was to characterize GID patients and compare clinical parameters and survival to SBS patients. Similarly, clinical comparisons between sclerodermaand nonscleroderma patients were made. METHODS Demographic and clinical data for all patients was extracted from the Canadian HPN Registry from January 1, 2003, to November 1, 2018. Kaplan-Meier method was used to estimate the unadjusted survival probability, and log-rank test was used to compare the survival probability between groups. RESULT 270 patients (52 GID and 218 SBS) were included in the analysis. For all patients, higher mortality was associated with age (hazard ratio [HR], 1.02 [1.00-1.04]; P = .05), PN dependence (HR, 1.01 [1.00-1.02]; P = .04), hospitalizations (HR, 1.21 [1.10-1.33]; P < .001), and use of immunosuppressant (HR, 1.97 [1.02-3.82]; P = .04). The 5- and 10-year actuarial survival probabilities between GID and SBS were not significantly different (5-year: 70.0% vs 59.2%; 10-year: 79.6% vs 66.2% [P = .5], respectively). There was no difference in survival between scleroderma and nonscleroderma patients (P = .67). CONCLUSION T5- and 10- year survival probabilities were similar between GID and SBS patients. The diagnosis of scleroderma had no effect on survival. Use of immunosuppressant, older age, PN dependence, and number of hospitalizations per PN duration are risk factors for mortality in both the GID and SBS groups.

Background Persisting atopic dermatitis (AD) is known to be associated with more serious allergic diseases at later ages; however, making an accurate diagnosis during infancy is challenging. We assessed the diagnostic performance of questionnaire-based AD measures with criteria-based in-person clinical assessments at age 1 year and evaluated the ability of these diagnostic methods to predict asthma, allergic rhinitis and food allergies at age 5 years. Methods Data relate to 3014 children participating in the Canadian Healthy Infant Longitudinal Development (CHILD) Study who were directly observed in a clinical assessment by an experienced healthcare professional using the UK Working Party criteria. The majority (2221; 73.7%) of these children also provided multiple other methods of AD ascertainment: a parent reporting a characteristic rash on a questionnaire, a parent reporting the diagnosis provided by an external physician and a combination of these two reports. Results Relative to the direct clinical assessment, the area under the Receiver Operating Characteristic curve for a parental report of a characteristic rash, reported physician diagnosis and a combination of both were, respectively, 0.60, 0.69 and 0.70. The strongest predictor of asthma at 5 years was AD determined by criteria-based in-person clinical assessment followed by the combination of parental and physician report. Conclusions These findings suggest that questionnaire data cannot accurately substitute for assessment by experienced healthcare professionals using validated criteria for diagnosis of atopic dermatitis. Combining the parental report with diagnosis by a family physician might sometimes be appropriate (eg to avoid costs of a clinical assessment).

BackgroundThe care of infants with recurrent wheezing relies largely on clinical assessment. The lung clearance index (LCI), a measure of ventilation inhomogeneity, is a sensitive marker of early airway disease in children with cystic fibrosis, but its utility has not been explored in infants with recurrent wheezing.ObjectiveTo assess ventilation inhomogeneity using LCI among infants with a history of recurrent wheezing compared with healthy controls.MethodsThis is a case–control study, including 37 infants with recurrent wheezing recruited from outpatient clinics, and 113 healthy infants from a longitudinal birth cohort, the Canadian Healthy Infant Longitudinal Development study. All infants, at a time of clinical stability, underwent functional assessment including multiple breath washout, forced expiratory flows and body plethysmography.ResultsLCI z-score values among infants with recurrent wheeze were 0.84 units (95% CI 0.41 to 1.26) higher than healthy infants (mean (95% CI): 0.26 (−0.11 to 0.63) vs −0.58 (−0.79 to 0.36), p1.64 z-scores). Elevated exhaled nitric oxide, but not symptoms, was associated with abnormal LCI values in infants with recurrent wheeze (p=0.05).ConclusionsVentilation inhomogeneity is present in clinically stable infants with recurrent wheezing.

Objective To quantify changes in motor function, sensation, and lower extremity quality of life following anterior lateral thigh free flap (ALT) resection. Methods This mixed methods study contained both a prospective cohort arm (n = 20) and retrospective cross-sectional arm (n = 20). In both arms, patients underwent formal motor and sensation testing of the ipsilateral and contralateral thigh by sphygmomanometry and monofilament testing. In the prospective arm, data was collected preoperatively and at the 6-month and 1-year follow-up visits. In the retrospective arm, consecutive patients with a minimum of 6-month postoperative follow-up were enrolled. Results Postoperatively, 82% of participants endorsed some degree of numbness and tingling at the donor site. On monofilament testing, patients from the prospective arm showed decreased sensibility of the midthigh at both the 6- and 12-month assessment (P < 0.01). Two-point discrimination scores were moderately correlated with the cross-sectional surface area of the flap. Donor thighs demonstrated a similar peak isometric quadriceps contraction (retrospective [retro]: 47 ± 24 mmHg, prospective [pro]: 90 ± 36 mmHg) to the unoperated thighs (retro: 43 mmHg ± 22, pro: 69 ± 35.3 mmHg, P = 0.49). When stratified by perforator anatomy, no significant differences were noted. Subjective donor site morbidity measured with the lower extremity function scale demonstrated no statistically significant difference between the preoperative and 12-month postoperative assessment. Conclusion The ALT flap offers minimal donor site morbidity. Reduced sensibility of the ALT flap is a common complaint among patients. Quadriceps strength is not significantly affected by an ALT free flap harvest. Level of Evidence 4. Laryngoscope, 2017

Obstructive sleep apnea (OSA) is a common disorder estimated at 1–5% in the school-aged children. With the obesity prevalence reaching staggering rates globally, OSA in obese adolescents is estimated to be 4–5-folds higher than their lean peers. There is a paucity of data regarding obesity-related OSA in children 6 years and less. This is particularly relevant as OSA is associated with neurocognitive deficits. The aim of this study is to evaluate the prevalence of OSA among obese toddlers and preschool children and further to determine what other factors may be associated with the presence of OSA. A retrospective study involving children ≤6 years, identified from two Canadian pediatric tertiary care centers who had an in-lab polysomnography (PSG). Obesity was defined by a BMI of > 95th percentile for age and gender or a z-score of > 2. OSA was diagnosed if the obstructive apnea-hypopnea index (OAHI) was greater than 2 events per hour. There were 60 participants included; the mean age was 4.4 years (standard deviation [SD] ± 1.7), mean BMI z-score was 3.0 (SD ± 1.2). Of these, 22/60 (36.6%) had OSA. Compared with the non-OSA group, the OSA group had a higher Epworth sleepiness score (p = 0.03) and were more likely to snore (p = 0.01). Young obese children should be assessed for OSA. A history of snoring and daytime sleepiness may be useful indicators to facilitate triage for a PSG, especially in resource-limited settings.

Cervical cancer is the 2nd most common malignant tumour in women worldwide. Previous research studies have given little attention to its prognostic factors in the rapidly growing Asian American population. In the present study, we explored prognostic factors in Asian and white American patients with cervical cancer, considering competing risks. The study included 58,780 patients with cervical cancer, of whom 54,827 were white and 3953 were Asian American, and for all of whom complete clinical information was available in the U.S. Surveillance, Epidemiology, and End Results database. Death from cervical cancer was considered to be the event of interest, and deaths from other causes were defined as competing risks. The cumulative incidence function and the Fine&ndash, Gray method were applied for univariate and multivariate analysis respectively. We found that, for all patients (white and Asian American combined), the cumulative incidence function was associated with several factors, such as age at diagnosis, figo (F&eacute, d&eacute, ration internationale de Gyn&eacute, cologie et d&rsquo, Obst&eacute, trique) stage, registry area, and lymph node metastasis. Similar results were found when considering white patients only. However, for Asian American patients, registry area was not associated with the cumulative incidence function, but the other factors (for example, figo stage) remained statistically significant. Similarly, in multivariate analyses, we found that age at diagnosis, figo stage, lymph node metastasis, tumour histology, treatment method, and race were all associated with prognosis. Survival status differs for white and Asian American patients with cervical cancer. Our results could guide the treatment of, and facilitate prognostic judgments about, white and Asian American patients with cervical cancer.

Background Narcolepsy is a sleep disorder with no cure with onset typically during adolescence. Caring for an adolescent with a lifelong medical condition can negatively impact family structure, cohesion, relationships, and overall functioning. The primary objective of this study was to evaluate family functioning in a cohort of adolescents with narcolepsy using the PedsQL Family Impact Module. The secondary objective was to compare family functioning in adolescents with narcolepsy to adolescents with chronic pain based on published data. Methods This was a cross-sectional study of adolescents (aged 10 to 18 years) with narcolepsy. The narcolepsy group was recruited from The Hospital for Sick Children in Toronto, Canada. Family functioning was assessed by the PedsQL family impact module total scores, which was completed by the patient’s caregiver. The PedsQL family impact module yields a total scale which encompasses parent health-related quality of life, daily activities, family relationships, communication, and worry subscales. Lower scores suggest poorer family functioning. Secondary data analyses were used to compare participants’ family functioning to a cohort of adolescents with chronic pain. Results Thirty adolescents with narcolepsy participated (mean age=13.8 ± 2.2 years, 76.7% male). Family functioning was impaired in this cohort of adolescents with narcolepsy and similar to adolescents with chronic pain (64.0 ± 19.8 versus 64.7 ± 19.5; P=0.849). Conclusion Family functioning is impaired in adolescents with narcolepsy. Clinical teams should assess family functioning at routine clinic visits by asking about concerns and challenges related to caring for an adolescent with narcolepsy and providing resources and support as needed.

Study ObjectivesTo evaluate the association between depressive symptoms, sleep patterns (duration and quality), excessive daytime sleepiness (EDS), and physical activity (PA) in adolescents with narcolepsy.MethodsThis cross-sectional study included adolescents (ages 10–18 years) with narcolepsy attending a tertiary care facility (The Hospital for Sick Children, Toronto, Canada). Adolescents with narcolepsy completed questionnaires evaluating depressive symptoms (Children’s Depression Inventory-2nd edition [CDI-2]), sleep quality (Pittsburgh Sleep Quality Index), EDS (Epworth Sleepiness Scale), and PA (Godin Leisure-Time Exercise Questionnaire). Wrist-based actigraphy was worn by adolescents for 1 week to measure total sleep time (over 24 hr) and sleep efficiency percentage.ResultsThirty adolescents with narcolepsy (mean age = 13.8 ± 2.2 years, 76.7% male) participated. In this cohort of adolescents with narcolepsy, 23.3% had CDI-2 total scores in the elevated range. Greater CDI-2 total scores were associated with poor sleep quality (ρ = 0.571; p = 0.02), EDS (ρ = 0.360; p = 0.05), and lower self-reported PA levels (ρ = −0.512; p < 0.01).ConclusionsAdolescents with narcolepsy report experiencing depressive symptoms, which are associated with poor sleep quality, EDS, and low PA levels. Strategies to improve nocturnal sleep quality and symptoms of EDS as well as promoting increased PA levels in adolescents with narcolepsy may provide an opportunity to improve depressive symptoms in this population. Multidisciplinary care with mental health and sleep specialists for adolescents with narcolepsy is needed.

BACKGROUND Pulmonary function testing is commonly performed for diagnosis and clinical management of respiratory diseases. It is important to use appropriate reference equations from healthy subjects for interpretation of data from infants with lung disease. This study aimed to determine if published reference equations were similar to forced flow measures and plethysmographic infant pulmonary function testing data collected in the Canadian Healthy Infant Longitudinal Development (CHILD) Study. METHODS Reference equations for five pulmonary function variables (FEV0.5 , FVC, FEF25-75 , FEV0.5 /FVC ratio and plethysmography (FRCpleth )) were developed using data from the nSpire system. New reference equations developed using healthy data from the CHILD Study were compared to previously published reference equations for forced flow and plethysmographic measures. RESULTS The current analysis included 131 infants (on 181 test occasions) with forced flow measures and 161 infants (on 246 test occasions) with plethysmography measures, aged 3-24 months. Age and length were major determinants of both forced flow and plethysmography measures. In addition, ethnicity (Caucasian vs non-Caucasian) was significantly associated with FEV0.5 /FVC and FEF25-75 measures. We found that the published reference equations based on custom-built equipment or commercially available systems provided poor fit to our current pulmonary function testing data, resulting in placing a large proportion of our healthy population outside the normal ranges. CONCLUSIONS Our current data support the need for population and device specific reference data for infant pulmonary function studies. By deriving new equipment-specific reference equations for our healthy population, we provide normative data to other centers utilizing this equipment.

Supplemental Material for Shape invariant mixture model for clustering non-linear longitudinal growth trajectories by Zihang Lu and Wendy Lou in Statistical Methods in Medical Research

Multiple breath inert gas washout (MBW) measurements in infants are performed supine and often obtained under sedation and thus are combined with other lung function tests such as raised volume rapid thoracoabdominal compression (RVRTC). In this study, we sought to determine the effects of RVRTC maneuvers on MBW measures. Compared with tests performed prior to RVRTC, MBW measured after RVRTC was associated with a small reduction in functional residual capacity and a more pronounced decrease in cumulative expired volume in both healthy children and children with obstructive lung disease (cystic fibrosis or recurrent wheeze) indicating a more efficient washout after the raised volume maneuvers. Lung Clearance Index (LCI) decreased significantly in infants with respiratory disease (change in LCI of -0.24 units post RVRTC; standard error (SE) ± 0.07 units; P = 0.0004), but not in healthy infants (change in LCI of -0.08 units; SE ± 0.11 units; P = 0.44). As the RVRTC maneuver affects MBW measurements in infants, the timing of testing procedures needs to be standardized in longitudinal studies.

There is conflicting data regarding the independent associations of obstructive sleep apnea (OSA) with metabolic risk in obese youth. Previous studies have not consistently addressed central adiposity, specifically elevated waist to height ratio (WHtR), which is associated with metabolic risk independent of body mass index. The objective of this study was to determine the independent effects of the obstructive apnea-hypopnea index (OAHI) and associated indices of nocturnal hypoxia on metabolic function in obese youth after adjusting for WHtR. Subjects had standardized anthropometric measurements. Fasting blood included insulin, glucose, glycated hemoglobin, alanine transferase, and aspartate transaminase. Insulin resistance was quantified with the homeostatic model assessment. Overnight polysomnography determined the OAHI and nocturnal oxygenation indices. Of the 75 recruited subjects, 23% were diagnosed with OSA. Adjusting for age, gender, and WHtR in multivariable linear regression models, a higher oxygen desaturation index was associated with a higher fasting insulin (coefficient [standard error] = 48.076 [11.255], p

To quantify changes in motor function, sensation, and lower extremity quality of life following anterior lateral thigh free flap (ALT) resection.This mixed methods study contained both a prospective cohort arm (n = 20) and retrospective cross-sectional arm (n = 20). In both arms, patients underwent formal motor and sensation testing of the ipsilateral and contralateral thigh by sphygmomanometry and monofilament testing. In the prospective arm, data was collected preoperatively and at the 6-month and 1-year follow-up visits. In the retrospective arm, consecutive patients with a minimum of 6-month postoperative follow-up were enrolled.Postoperatively, 82% of participants endorsed some degree of numbness and tingling at the donor site. On monofilament testing, patients from the prospective arm showed decreased sensibility of the midthigh at both the 6- and 12-month assessment (P0.01). Two-point discrimination scores were moderately correlated with the cross-sectional surface area of the flap. Donor thighs demonstrated a similar peak isometric quadriceps contraction (retrospective [retro]: 47 ± 24 mmHg, prospective [pro]: 90 ± 36 mmHg) to the unoperated thighs (retro: 43 mmHg ± 22, pro: 69 ± 35.3 mmHg, P = 0.49). When stratified by perforator anatomy, no significant differences were noted. Subjective donor site morbidity measured with the lower extremity function scale demonstrated no statistically significant difference between the preoperative and 12-month postoperative assessment.The ALT flap offers minimal donor site morbidity. Reduced sensibility of the ALT flap is a common complaint among patients. Quadriceps strength is not significantly affected by an ALT free flap harvest.4. Laryngoscope, 128:1057-1061, 2018.

The impact of breastfeeding on respiratory health is uncertain, particularly when the mother has asthma. We examined the association of breastfeeding and wheezing in the first year of life.We studied 2773 infants from the Canadian Healthy Infant Longitudinal Development (CHILD) birth cohort. Caregivers reported on infant feeding and wheezing episodes at 3, 6 and 12 months. Breastfeeding was classified as exclusive, partial (supplemented with formula or complementary foods) or none.Overall, 21% of mothers had asthma, 46% breastfed for at least 12 months and 21% of infants experienced wheezing. Among mothers with asthma, breastfeeding was inversely associated with infant wheezing, independent of maternal smoking, education and other risk factors (adjusted rate ratio (aRR) 0.52; 95% CI 0.35–0.77 for ≥12 versus Breastfeeding appears to confer protection against wheezing in a dose-dependent manner among infants born to mothers with asthma.

Background Pulmonary function testing has been recommended as an adjunct to symptom monitoring for assessment of asthma control. Lung clearance index (LCI) measures ventilation inhomogeneity and is thought to represent changes in the small airways. It has been proposed as a useful early marker of airway disease in asthmatic subjects, and determining it is feasible in preschool children. This study aims to assess whether LCI remains elevated in symptomatically controlled asthmatic children with a history of severe asthma, compared with healthy controls. A secondary aim was to determine whether the results were consistent across the preschool and school‐aged populations. Methods Using a case‐control design, we compared 33 children with currently well‐controlled symptoms who had a history of severe asthma, to 45 healthy controls (age 3‐15 years) matched by age, height, and sex. We performed multiple breath washout tests using sulfur hexafluoride as a tracer gas, to determine their LCI and Scond values. Results In the overall study, LCI z‐score values were on average 0.86 units (95% confidence interval: 0.24‐1.47, P = 0.01, t‐test) higher in children with a history of severe asthma with current well‐controlled symptoms compared with healthy controls. In addition, within the subgroup of preschool children (age ≤ 6), the asthmatic had significantly higher LCI z‐score values than their healthy controls peers (mean (SD), 0.57 (2.18) vs −1.10 (1.00), P = 0.03, t‐test). Twenty‐seven percent (27%; 9/33) of subjects had an LCI value greater than the upper limit of our healthy controls despite being symptom controlled. Amongst preschool children, 5 (42%; 5/12) of the asthmatic children had abnormal LCI at the individual level. Conclusions LCI is elevated in children with asthma, which may be driven by differences in the preschool population. LCI may be useful in defining preschool asthma endotypes with persistent ventilation inhomogeneity despite symptomatic control.

Background: Infant lung function (IPFT) is used to monitor early lung disease. Techniques include raised-volume rapid thoracoabdominal compression (RVRTC), body plethysmography (pleth), & multiple breath washout (MBW). Little data is available on the relative feasibility of these tests. Objectives: To evaluate and compare the feasibility of different IPFTs, both at a single test occasion and longitudinally. Methods: Subjects recruited into a birth cohort study (CHILD), were invited to an early (3-9 months), mid (9-18 months) & late infancy (18-24 months) test. Most declined the early & attended a mid or late infancy visit (Table 1). MBW (by SF 6 , mass spectrometry Innovision ApS, Denmark) was performed, then pleth & RVRTC (nSpire Infant Pulmonary Lab, Longmont, USA). All tests were performed to ATS/ERS standards, with ≥2 successful trials per test. Results: 768 families were approached, 500 were interested & 231 attended at least one IPFT visit with 191 attending a follow-up. Longitudinal (≥ 2 visits) acceptable data was attained for MBW in 120 subjects, pleth in 95 and RVRTC in 63. Results for achieving acceptable data at each test occasion are described in Table 1. Conclusion: Obtaining IPFT data is challenging in cohort studies. Success in obtaining longitudinal data is best achieved using MBW methodology.

Obstructive sleep apnea and intermittent nocturnal oxygen desaturations are highly prevalent in children with sickle cell disease and have been reported to contribute to associated morbidity, including vasoocclusive disease. Hydroxyurea (HU) is increasingly used to treat children with sickle cell disease and has been shown to decrease the number and severity of vasoocclusive crises. Although there has been an increase in the use of HU, the impact of HU on the prevalence of obstructive sleep apnea and nocturnal hypoxia are not well documented.To evaluate whether the use of HU is associated with a decreased frequency of obstructive sleep apnea and higher nocturnal and awake oxygen saturations (SaO2) in children with sickle cell disease.This was a retrospective, cross-sectional review of children with sickle cell disease referred to the sleep laboratory at the Hospital for Sick Children, Toronto, Canada. Polysomnogram data in children with sickle cell disease receiving HU therapy were compared with those not prescribed HU.Children with sickle cell disease receiving HU therapy (HU group, n = 37) were matched with children not receiving HU (no-HU group, n = 104). Obstructive sleep apnea was diagnosed in 14 of 37 (38%) and 54 of 104 (52%) in the HU group and no-HU groups, respectively (P = 0.14). The median obstructive apnea-hypopnea index was 0.9 and 1.9 events/h in the HU group and the no-HU group, respectively (P = 0.28). The HU group compared with the no-HU group had a significantly higher median awake SaO2 (98.6 and 96.2%, respectively; P 0.0001), a significantly higher median sleep SaO2 (98.4 and 96.1%, respectively; P 0.001), and a significantly higher nadir SaO2 while asleep (91.4 and 85.0%, respectively; P = 0.0002).In children with sickle cell disease, the use of HU was associated with an increase in awake and nocturnal SaO2, despite there being no difference in the frequency of obstructive sleep apnea and the severity of the obstructive apnea-hypopnea index. Improving nocturnal SaO2 may be an important mechanism of action of HU therapy. The use of HU to improve nocturnal saturations across the severity spectrum of sickle cell disease may be beneficial in decreasing morbidities related to sickle cell disease.

Multiple breath inert gas washout (MBW) measurements in infants are performed supine and often obtained under sedation and thus are combined with other lung function tests such as raised volume rapid thoracoabdominal compression (RVRTC). In this study, we sought to determine the effects of RVRTC maneuvers on MBW measures. Compared with tests performed prior to RVRTC, MBW measured after RVRTC was associated with a small reduction in functional residual capacity and a more pronounced decrease in cumulative expired volume in both healthy children and children with obstructive lung disease (cystic fibrosis or recurrent wheeze) indicating a more efficient washout after the raised volume maneuvers. Lung Clearance Index (LCI) decreased significantly in infants with respiratory disease (change in LCI of -0.24 units post RVRTC; standard error (SE) ± 0.07 units; P = 0.0004), but not in healthy infants (change in LCI of -0.08 units; SE ± 0.11 units; P = 0.44). As the RVRTC maneuver affects MBW measurements in infants, the timing of testing procedures needs to be standardized in longitudinal studies.

To evaluate five methods in the estimation on the rate of case fatality during the epidemics of diseases based on the summarizing data. Case fatality rates, derived from the simulation data, 2003 SARS epidemic data in Hong Kong, Singapore Beijing and the 2013 H7N9 epidemic data in mainland China were analyzed, using these 5 methods. Results from the simulation analysis discovered that the relative errors and the standard deviations of the Chen [7, 8] (method 3), Chen [9] (method 4)were minor with high accuracy. Data from the analysis on 2003 SARS epidemic was noticed that the estimation from method 3, 4 in Hong Kong and Singapore both showing high veracities. Since the case fatality rate reported in Beijing was not a constant value, method 5 showed low accuracy even though it was close to the final case fatality rate. Data from the 2013 H7N9 epidemic showed that the estimations of method 1, 2, 3, 4 were all higher than that in the method 5, suggesting that method 3, 4 could be used to estimate the case fatality rates of epidemics more precisely.