Comparison of alignment efficiency of different sizes of superelastic nickel-titanium archwires in the initial phase of fixed orthodontic treatment: A single-center, double-blind randomized clinical trial.

INTRODUCTION: This 3-arm parallel, double-blind study aimed to evaluate the alignment efficiency of 3 different diameters of superelastic nickel-titanium (NiTi) archwires during the initial phase of orthodontic treatment. METHODS: Ninety-three patients with nonextraction treatment in the mandibular arch (using 0.022-in Roth prescription brackets) were randomly allocated into 3 groups: 0.012-in NiTi (group 1), 0.014-in NiTi (group 2), and 0.016-in NiTi (group 3). The alignment change was measured using the modified Little's irregularity index before archwire placement and every 4 weeks. The alignment efficiency of the 3 groups was analyzed. RESULTS: Ninety patients were analyzed (group 1: n = 29, group 2: n = 31, and group 3: n = 30; overall mean age, 16.6 years). The overall Wald test analysis revealed that wire type was not statistically significant (P = 0.91), whereas time exhibited significance as expected (P <0.001). Furthermore, the interaction between wire type and time was not significant (P = 0.93). The time-adjusted estimated difference between 0.014-in and 0.012-in was -0.49 (95% confidence interval, -2.83 to 1.85; P = 0.68). The time-adjusted estimated difference between 0.016-in and 0.012-in was -0.45 (95% confidence interval, -2.95 to 2.05; P = 0.72). No harm was observed. CONCLUSIONS: The clinical performance of 3 different sizes of NiTi archwires was similar. In addition, 0.014-in and 0.016-in NiTi archwires demonstrated better performances in aligning any irregularities because of a greater number of wire deformations in the 0.012-in group. REGISTRATION: IR.TBZMED.REC.1395.1039. PROTOCOL: The protocol was not published before trial commencement. FUNDING: None.

Suboptimal Intake of Fruits and Vegetables in Nine Selected Countries of the World Health Organization European Region.

The objective of this study was to characterize fruit and vegetable consumption in 9 selected countries of the World Health Organization (WHO) European Region. We analyzed data on fruit and vegetable intake and participant sociodemographic characteristics for 30,455 adults in 9 Eastern European and Central Asian countries via standardized STEPS survey methodology. Fruit and vegetable consumption across all countries was suboptimal, with a high percentage of populations not meeting the WHO-recommended intake of at least 5 servings (400 g) per day. Strengthened implementation of evidence-based policies to increase intake of fruit and vegetables is needed to reduce the burden of and disparities in NCDs.

Lifetime Body Weight Trajectories and Risk of Renal Cell Cancer: A Large U.S. Prospective Cohort Study.

BACKGROUND: Body mass index (BMI) is a known risk factor for renal cell cancer (RCC), but data are limited as to the effect of lifetime exposure to excess body weight. METHODS: Using the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (N = 138,614, 527 incident RCCs), we identified several anthropometric measures to capture the lifetime BMI patterns: (i) BMI at specific ages; (ii) adulthood BMI trajectories; (iii) cumulative exposure to overweight/obesity denoted as weighted years of living overweight/obese (WYO); and (iv) weight change during each age span. We conducted multivariable Cox model to quantify the association between each anthropometric metric and incident RCC. RESULTS: A higher BMI at ages 20 and 50 and at baseline was associated with a greater hazard of RCC. Compared with individuals who retained normal BMI throughout adulthood, we observed an increased hazard of RCC for BMI trajectory of progressing from normal BMI to overweight [HR, 1.49; 95% confidence interval (CI), 1.19-1.87], from normal BMI to obesity (HR, 2.22; 95% CI, 1.70-2.90), and from overweight to obesity (HR, 2.78; 95% CI, 1.81-4.27). Compared with individuals who were never overweight (WYO = 0), elevated HRs were observed among individuals who experienced low (HR, 1.31; 95% CI, 0.99-1.74), medium (HR, 1.57; 95% CI, 1.20-2.05), and high (HR, 2.10; 95% CI, 1.62-2.72) WYO tertile. Weight gain of ≥10 kg was associated with increased RCC incidence for each age span. CONCLUSIONS: Across the lifespan, being overweight/obese, weight gain, and higher cumulative exposure to excess weight were all associated with increased RCC risk. IMPACT: It is important to avoid weight gain and assess BMI from a life-course perspective to reduce RCC risk.

Infants less than or equal to 2.5 kg have increased mortality and worse motor neurodevelopmental outcomes at 2 years of age after Norwood-Sano palliation.

Objectives: In infants with single-ventricle congenital heart disease, prematurity and low weight at the time of the Norwood operation are risk factors for mortality. Reports assessing outcomes (including neurodevelopment) post Norwood palliation in infants ≤2.5 kg are limited. Methods: All infants who underwent a Norwood-Sano procedure between 2004 and 2019 were identified. Infants ≤2.5 kg at the time of the operation (cases) were matched 3:1 with infants >3.0 kg (comparisons) for year of surgery and cardiac diagnosis. Demographic and perioperative characteristics, survival, and functional and neurodevelopmental outcomes were compared. Results: Twenty-seven cases (mean ± standard deviation: weight 2.2 ± 0.3 kg and age 15.6 ± 14.1 days at surgery) and 81 comparisons (3.5 ± 0.4 kg and age 10.9 ± 7.9 days at surgery) were identified. Post-Norwood, cases had a longer time to lactate ≤2 mmol/L (33.1 ± 27.5 vs 17.9 ± 12.2 hours, P < .001), longer duration of ventilation (30.5 ± 24.5 vs 18.6 ± 17.5 days, P = .005), greater need for dialysis (48.1% vs 19.8%, P = .007), and greater need for extracorporeal membrane oxygenation support (29.6% vs 12.3%, P = .004). Cases had significantly greater postoperative (in-hospital) (25.9% vs 1.2%, P < .001) and 2-year (59.2% vs 11.1%, P < .001) mortality. Neurodevelopmental assessment showed the following for cases versus comparisons, respectively: cognitive delay (18.2% vs 7.9%, P = .272), language delay (18.2% vs 11.1%, P = .505), and motor delay (27.3% vs 14.3%, P = .013). Conclusions: Infants ≤2.5 kg at Norwood-Sano palliation have significantly increased postoperative morbidity and mortality up to 2-year follow-up. Neurodevelopmental motor outcomes were worse in these infants. Additional studies are warranted to assess the outcome of alternative medical and interventional treatment plans in this patient population.

Maternal co-exposure to mercury and perfluoroalkyl acid isomers and their associations with child neurodevelopment in a Canadian birth cohort.

BACKGROUND: Perfluoroalkyl acids (PFAAs) within the broader class of per- and polyfluoroalkyl substances (PFAS) are present in human serum as isomer mixtures, but epidemiological studies have yet to address isomer-specific associations with child development and behavior. OBJECTIVES: To examine associations between prenatal exposure to 25 PFAAs, including perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA) isomers, and child neurodevelopment among 490 mother-child pairs in a prospective Canadian birth cohort, the Alberta Pregnancy Outcomes and Nutrition (APrON) study. To consider the influence of a classic neurotoxicant, total mercury (THg), based on its likelihood of co-exposure with PFAAs from common dietary sources. METHODS: Maternal blood samples were collected in the second trimester and child neurodevelopment was assessed at 2 years of age using the Bayley Scales of Infant and Toddler Development, 3rd Edition (Bayley-III). Linear or curvilinear multiple regression models were used to examine associations between exposures and neurodevelopment outcomes. RESULTS: Select PFAAs were associated with lower Cognitive composite scores, including perfluoroheptanoate (PFHpA) (ß = -0.88, 95% confidence interval (CI): -1.7, -0.06) and perfluorododecanoate (PFDoA) (ß = -2.0, 95% CI: -3.9, -0.01). Non-linear relationships revealed associations of total PFOS (ß = -4.4, 95% CI: -8.3, -0.43), and linear-PFOS (ß = -4.0, 95% CI: -7.5, -0.57) and 1m-PFOS (ß = -1.8, 95% CI: -3.3, -0.24) isomers with lower Language composite scores. Although there was no effect modification, including THg interaction terms in PFAA models revealed negative associations between perfluorononanoate (PFNA) and Motor (ß = -3.3, 95% CI: -6.2, -0.33) and Social-Emotional (ß = -3.0, 95% CI: -5.6, -0.40) composite scores. DISCUSSION: These findings reinforce previous reports of adverse effects of maternal PFAA exposure during pregnancy on child neurodevelopment. The unique hazards posed from isomers of PFOS justify isomer-specific analysis in future studies. To control for possible confounding, mercury co-exposure may be considered in studies of PFAAs.

Infants' gut microbiome data: A Bayesian Marginal Zero-inflated Negative Binomial regression model for multivariate analyses of count data.

The infants' gut microbiome is dynamic in nature. Literature has shown high inter-individual variability of gut microbial composition in the early years of infancy compared to adulthood. Although next-generation sequencing technologies are rapidly evolving, several statistical analysis aspects need to be addressed to capture the variability and dynamic nature of the infants' gut microbiome. In this study, we proposed a Bayesian Marginal Zero-inflated Negative Binomial (BAMZINB) model, addressing complexities associated with zero-inflation and multivariate structure of the infants' gut microbiome data. Here, we simulated 32 scenarios to compare the performance of BAMZINB with glmFit and BhGLM as the two other widely similar methods in the literature in handling zero-inflation, over-dispersion, and multivariate structure of the infants' gut microbiome. Then, we showed the performance of the BAMZINB approach on a real dataset using SKOT cohort (I and II) studies. Our simulation results showed that the BAMZINB model performed as well as those two methods in estimating the average abundance difference and had a better fit for almost all scenarios when the signal and sample size were large. Applying BAMZINB on SKOT cohorts showed remarkable changes in the average absolute abundance of specific bacteria from 9 to 18 months for infants of healthy and obese mothers. In conclusion, we recommend using the BAMZINB approach for infants' gut microbiome data taking zero-inflation and over-dispersion properties into account in multivariate analysis when comparing the average abundance difference.

Geographically weighted linear combination test for gene-set analysis of a continuous spatial phenotype as applied to intratumor heterogeneity.

Background: The impact of gene-sets on a spatial phenotype is not necessarily uniform across different locations of cancer tissue. This study introduces a computational platform, GWLCT, for combining gene set analysis with spatial data modeling to provide a new statistical test for location-specific association of phenotypes and molecular pathways in spatial single-cell RNA-seq data collected from an input tumor sample. Methods: The main advantage of GWLCT consists of an analysis beyond global significance, allowing the association between the gene-set and the phenotype to vary across the tumor space. At each location, the most significant linear combination is found using a geographically weighted shrunken covariance matrix and kernel function. Whether a fixed or adaptive bandwidth is determined based on a cross-validation cross procedure. Our proposed method is compared to the global version of linear combination test (LCT), bulk and random-forest based gene-set enrichment analyses using data created by the Visium Spatial Gene Expression technique on an invasive breast cancer tissue sample, as well as 144 different simulation scenarios. Results: In an illustrative example, the new geographically weighted linear combination test, GWLCT, identifies the cancer hallmark gene-sets that are significantly associated at each location with the five spatially continuous phenotypic contexts in the tumors defined by different well-known markers of cancer-associated fibroblasts. Scan statistics revealed clustering in the number of significant gene-sets. A spatial heatmap of combined significance over all selected gene-sets is also produced. Extensive simulation studies demonstrate that our proposed approach outperforms other methods in the considered scenarios, especially when the spatial association increases. Conclusion: Our proposed approach considers the spatial covariance of gene expression to detect the most significant gene-sets affecting a continuous phenotype. It reveals spatially detailed information in tissue space and can thus play a key role in understanding the contextual heterogeneity of cancer cells.

Exploring educational inequalities in hypertension control, salt knowledge and awareness, and patient advice: insights from the WHO STEPS surveys of adults from nine Eastern European and Central Asian countries.

OBJECTIVE: To inform strategies aimed at improving blood pressure (BP) control and reducing salt intake, we assessed educational inequalities in high blood pressure (HBP) awareness, treatment and control; physician's advice on salt reduction; and salt knowledge, perceptions and consumption behaviours in Eastern Europe and Central Asia. DESIGN: Data were collected in cross-sectional, population-based nationally representative surveys, using a multi-stage clustered sampling design. Five HBP awareness, treatment and control categories were created from measured BP and hypertension medication use. Education and other variables were self-reported. Weighted multinomial mixed-effects regression models, adjusted for confounders, were used to assess differences across education categories. SETTINGS: Nine Eastern European and Central Asian countries (Armenia, Azerbaijan, Belarus, Georgia, Kyrgyzstan, Republic of Moldova, Tajikistan, Turkey and Uzbekistan). PARTICIPANTS: Nationally representative samples of 30 455 adults aged 25-65 years. RESULTS: HBP awareness, treatment and control varied substantially by education. The coverage of physician's advice on salt was less frequent among participants with lower education, and those with untreated HBP or unaware of their HBP. The education gradient was evident in salt knowledge and perceptions of salt intake but not in salt consumption behaviours. Improved salt knowledge and perceptions were more prevalent among participants who received physician's advice on salt reduction. CONCLUSIONS: There is a strong education gradient in HBP awareness, treatment and control as well as salt knowledge and perceived intake. Enhancements in public and patient knowledge and awareness of HBP and its risk factors targeting socio-economically disadvantaged groups are urgently needed to alleviate the growing HBP burden in low- and middle-income countries.

Evaluating the Prevalence and Factors Associated With an Optimal Neurodevelopmental Outcome in 4- to 6-Year-Old Children With Fontan Circulation.

BACKGROUND: We sought to evaluate the prevalence and factors associated with "optimal" neurodevelopmental outcomes in 4- to 6-year-old children with Fontan circulation. METHODS: Patients followed through the Western Canadian Complex Pediatric Therapies Follow-Up Program, and born between September 1996 and December 2015, were included. Optimal neurodevelopmental outcome was defined as full-scale intelligence quotient; visual-motor integration; adaptive behaviour assessment system-general adaptive composite scores of ≥ 80 each; and the absence of chronic motor disability, permanent hearing loss, visual impairment, and seizure disorder. Multivariable regression models and decision algorithms evaluated variables associated with optimal outcomes. RESULTS: The Fontan procedure was completed on 225 children, with neurodevelopmental outcome data available for 205 (mean [standard deviation]) age at Fontan 3.4 (0.9) years, 37% female). Optimal neurodevelopmental outcome was identified in 55% (112 of 205). Factors independently associated with optimal neurodevelopmental outcome were female sex (odds ratio [OR], 2.1; 95% confidence interval [CI] 1.1-4.1), years of maternal schooling (OR, 1.2 [1.1-1.4]), age at Fontan (years) (OR, 0.97 [0.94-1.0]), need for concomitant atrioventricular valve (AVV) intervention (OR, 0.4 [0.2-1.0]), and time (hours) for lactate to be ≤ 2 mmol/L (OR, 0.9 [0.8-1.0]). Of those with Fontan completion < 3.25 years, without concomitant AVV intervention and lactate normalization within 8 hours post-Fontan, 87% (27 of 31) had optimal neurodevelopmental outcomes. CONCLUSIONS: Optimal neurodevelopmental outcome was present in more than one-half of 4- to 6-year-old children with Fontan circulation in this cohort study, with important associated factors identified, including potentially modifiable factors such as younger age at Fontan surgery and lack of concomitant AVV intervention.

Geostatistical Modeling and Heterogeneity Analysis of Tumor Molecular Landscape.

Intratumor heterogeneity (ITH) is associated with therapeutic resistance and poor prognosis in cancer patients, and attributed to genetic, epigenetic, and microenvironmental factors. We developed a new computational platform, GATHER, for geostatistical modeling of single cell RNA-seq data to synthesize high-resolution and continuous gene expression landscapes of a given tumor sample. Such landscapes allow GATHER to map the enriched regions of pathways of interest in the tumor space and identify genes that have spatial differential expressions at locations representing specific phenotypic contexts using measures based on optimal transport. GATHER provides new applications of spatial entropy measures for quantification and objective characterization of ITH. It includes new tools for insightful visualization of spatial transcriptomic phenomena. We illustrate the capabilities of GATHER using real data from breast cancer tumor to study hallmarks of cancer in the phenotypic contexts defined by cancer associated fibroblasts.

An updated reference for age-sex-specific birth weight percentiles stratified for ethnicity based on data from all live birth infants between 2005 and 2014 in Alberta, Canada.

OBJECTIVE: This study aims to update the current reference for sex-specific birth weight percentiles by gestational age, overall and for specific ethnic groups, based on data from all singleton live-birth deliveries from 2005 to 2014 in Alberta, Canada. METHODS: Infant and maternal information were captured in the Alberta Vital Statistics-Births Database for 473,115 singleton infants born to 311,800 women between January 1, 2005 and December 31, 2014. Within each sex, and each sex-ethnic group, birth weights were modelled by gestational age using generalized additive models and natural cubic splines. Crude and corrected estimates for birth weight percentiles including cut-off values for large for gestational age (LGA) and small for gestational age (SGA) were calculated by sex and sex-ethnic group, and gestational age for singleton live births. RESULTS: LGA and SGA cut-offs were lower for females than for males for all gestational ages. The SGA and LGA percentiles were greater for both male and female very preterm infants in Alberta compared to previous national references. Ethnicity-specific LGA and SGA cut-offs for term Chinese and preterm and at-term South Asian infants were consistently lower than those for both the general population in Alberta and the previous national reference. South Asian infants had lower birth weights at almost all gestational ages compared with the other groups. CONCLUSION: The updated birth weight percentiles presented in this study highlight the differences in SGA and LGA cut-offs among infants from South Asian, Chinese, and the general population, which may be important for clinical perinatal care.

RéSUMé: OBJECTIFS: L'objectif de cette étude est d'actualiser la référence actuelle pour les percentiles de poids à la naissance spécifique au sexe par l'âge gestationnel, globalement et pour des groupes ethniques spécifiques, basé sur les données de tous les accouchements de naissances vivante uniques entre 2005 et 2014 en Alberta, au Canada. MéTHODES: L'information infantile et maternelle ont été capturées dans les statistiques de l'état civil ­ base de données sur les naissances, en Alberta, pour 473 115 nourrissons uniques nés de 311 800 femmes entre le 1er janvier 2005 et le 31 décembre 2014. Dans chaque sexe, et dans chaque groupe sexe-ethnique, les poids de naissances ont été modélisés par l'âge gestationnel grâce à l'utilisation de modèles additifs généralisés et de splines cubiques naturelles. Des estimations grossières et corrigées pour les percentiles de poids à la naissance, y compris les valeurs seuils pours les nourrissons gros pour l'âge gestationnel (GAG) et petits pour l'âge gestationnel (PAG), ont été calculées par sexe et groupe sexe-ethnique, et par l'âge gestationnel pour les naissances vivantes uniques. RéSULTATS: Les critères pour GAG et PAG étaient plus bas pour les femelles que pour les mâles pour tous les âges gestationnels. Les percentiles pour PAG et GAG étaient plus élevés pour les nourrissons mâles et femelles nés très prématurés en Alberta en comparaison avec les références nationales précédentes. Les critères pour GAG et PAG spécifiques à l'ethnicité chinoise, pour les nourrissons nés à termes, et sud-asiatiques, pour les nourrissons nés avant et à termes, étaient régulièrement plus basses que ceux de la population générale en Alberta et de la référence nationale précédente. Les nourrissons sud-asiatiques avaient des poids de naissances plus basses à presque tous les âges gestationnels en comparaison avec les autres groupes. CONCLUSION: Les percentiles de poids à la naissance actualisés présentés dans cette étude mettent en évidence les différences de PAG et GAG entre les nourrissons sud-asiatiques, chinoises et de la population générale, qui peuvent êtres importantes pour les soins cliniques périnatales.

Music Use for Sedation in Critically ill Children (MUSiCC trial): a pilot randomized controlled trial.

OBJECTIVE: To demonstrate feasibility of a music medicine intervention trial in pediatric intensive care and to obtain information on sedation and analgesia dose variation to plan a larger trial. MATERIAL AND METHODS: Pilot randomized controlled trial (RCT) was conducted at the Stollery Children's Hospital general and cardiac intensive care units (PICU/PCICU). The study included children 1 month to 16 years of age on mechanical ventilation and receiving sedation drugs. Patients were randomized in a 1:1:1 ratio to music, noise cancellation or control. The music group received classical music for 30 min three times/day using headphones. The noise cancellation group received the same intervention but with no music. The control group received usual care. RESULTS: A total of 60 patients were included. Average enrollment rate was 4.8 patients/month, with a consent rate of 69%. Protocol adherence was achieved with patients receiving > 80% of the interventions. Overall mean (SD) daily Sedation Intensity Score was 52.4 (30.3) with a mean (SD) sedation frequency of 9.75 (7.21) PRN doses per day. There was a small but statistically significant decrease in heart rate at the beginning of the music intervention. There were no study related adverse events. Eighty-eight percent of the parents thought the headphones were comfortable; 73% described their child more settled during the intervention. CONCLUSIONS: This pilot RCT has demonstrated the feasibility of a music medicine intervention in critically ill children. The study has also provided the necessary information to plan a larger trial.

Reduced myocardial blood flow reserve in kidney transplant candidates may hamper risk stratification.

BACKGROUND: Vasodilator nuclear stress testing is frequently ordered for risk stratification prior to kidney transplantation. Since 82Rb-positron emission tomography-computed tomography can measure myocardial blood flow (MBF), the response to vasodilator stress can be verified rendering the results of the scan more reliable. METHODS: We reviewed the MBF response to dipyridamole infusion in 328 patients with end-stage kidney disease (ESKD) prior to transplant (188 hemodialysis-HD, 120 peritoneal dialysis-PD, and 20 pre-dialysis patients-CKD5) and in 100 controls with normal kidney function. A stress/rest MBF ratio ≥ 2 was considered an adequate response to dipyridamole. Coronary artery calcium (CAC) was measured on CT. RESULTS: Inadequate MBF response was seen in 36%-HD, 21%-PD, 45%-CKD5 vs. 23%-controls (p = 0.006). Univariable predictors of poor MBF response in ESKD patients were age, diabetes mellitus, and CAC (all p < 0.03) while serum hemoglobin was borderline significant (p = 0.052). Multivariable predictors of a poor MBF response were age (p = 0.002) and lower serum hemoglobin (p = 0.014). Ischemia was identified in 8% of ESKD patients and 24% of controls (p < 0.001). CONCLUSIONS: ESKD patients are less likely to respond appropriately to vasodilator stress compared to patients with normal renal function and had a lower incidence of ischemia despite a high pre-test probability of disease. Physicians performing vasodilator stress without MBF measurement should be aware of the high probability of a false negative response.

Health-related quality of life after pediatric heart transplantation in early childhood.

BACKGROUND: There is limited information about HRQL after pediatric heart transplantation at a young age. METHODS: Prospective follow-up study of children who received a heart transplant at age ≤4 years. HRQL was assessed using the PedsQLTM 4.0 at age 4.5 years. This cohort was compared with healthy children, children with CHD, and with chronic conditions. Peri-operative factors associated with HRQL were also explored. RESULTS: Of 66 eligible patients, 15 (23%) died prior to the HRQL assessment and 2 (3%) were lost to follow-up, leaving 49 patients. Indication for transplantation was CHD in 27 (55%) and CMP in 22 (45%). Median age (IQR) at transplant was 9 (5-31) months. HRQL was significantly lower in transplanted children compared to population norms (65.3 vs 87.3, P < .0001), children with chronic conditions (65.3 vs 76.1, P = .001), and children with CHD (65.3 vs 81.1, P < .0001). Transplanted children with CHD had lower HRQL than those with a prior diagnosis of CMP (59.5 vs 72.5, P-value = .020). Higher creatinine pretransplant and higher lactate post-operatively were associated with lower HRQL. CONCLUSION: Children after heart transplant had significantly lower HRQL, as reported by their parents, than the normative population, children with chronic conditions, and children with CHD.

Pre-school neurocognitive and functional outcomes after liver transplant in children with early onset urea cycle disorders, maple syrup urine disease, and propionic acidemia: An inception cohort matched-comparison study.

BACKGROUND: Urea cycle disorders (UCD) and organic acid disorders classically present in the neonatal period. In those who survive, developmental delay is common with continued risk of regression. Liver transplantation improves the biochemical abnormality and patient survival is good. We report the neurocognitive and functional outcomes post-transplant for nine UCD, three maple syrup urine disease, and one propionic acidemia patient. METHODS: Thirteen inborn errors of metabolism (IEM) patients were individually one-to-two matched to 26 non-IEM patients. All patients received liver transplant. Wilcoxon rank sum test was used to compare full-scale intelligence-quotient (FSIQ) and Adaptive Behavior Assessment System-II General Adaptive Composite (GAC) at age 4.5 years. Dichotomous outcomes were reported as percentages. RESULTS: FSIQ and GAC median [IQR] was 75 [54, 82.5] and 62.0 [47.5, 83] in IEM compared with 94.5 [79.8, 103.5] and 88.0 [74.3, 97.5] in matched patients (P-value <.001), respectively. Of IEM patients, 6 (46%) had intellectual disability (FSIQ and GAC <70), 5 (39%) had autism spectrum disorder, and 1/13 (8%) had cerebral palsy, compared to 1/26 (4%), 0, 0, and 0% of matched patients, respectively. In the subgroup of nine with UCDs, FSIQ (64[54, 79]), and GAC (56[45, 75]) were lower than matched patients (100.5 [98.5, 101] and 95 [86.5, 99.5]), P = .005 and .003, respectively. CONCLUSION: This study evaluated FSIQ and GAC at age 4.5 years through a case-comparison between IEM and matched non-IEM patients post-liver transplantation. The neurocognitive and functional outcomes remained poor in IEM patients, particularly in UCD. This information should be included when counselling parents regarding post-transplant outcome.

Outcomes of Preterm Infants With Congenital Heart Defects After Early Surgery: Defining Risk Factors at Different Time Points During Hospitalization.

Background: Compared with those born at term gestation, infants with complex congenital heart defects (CCHD) who were delivered before 37 weeks gestational age and received neonatal open-heart surgery (OHS) have poorer neurodevelopmental outcomes in early childhood. We aimed to describe the growth, disability, functional, and neurodevelopmental outcomes in early childhood of preterm infants with CCHD after neonatal OHS. Prediction models were evaluated at various timepoints during hospitalization which could be useful in the management of these infants. Study Design: We studied all preterm infants with CCHD who received OHS within 6 weeks of corrected age between 1996 and 2016. The Western Canadian Complex Pediatric Therapies Follow-up Program completed multidisciplinary comprehensive neurodevelopmental assessments at 2-year corrected age at the referral-site follow-up clinics. We collected demographic and acute-care clinical data, standardized age-appropriate outcome measures including physical growth with calculated z-scores; disabilities including cerebral palsy, visual impairment, permanent hearing loss; adaptive function (Adaptive Behavior Assessment System-II); and cognitive, language, and motor skills (Bayley Scales of Infant and Toddler Development-III). Multiple variable logistic or linear regressions determined predictors displayed as Odds Ratio (OR) or Effect Size (ES) with 95% confidence intervals. Results: Of 115 preterm infants (34 ± 2 weeks gestation, 2,339 ± 637 g, 64% males) with CCHD and OHS, there were 11(10%) deaths before first discharge and 21(18%) deaths by 2-years. Seven (6%) neonates had cerebral injuries, 7 had necrotizing enterocolitis; none had retinopathy of prematurity. Among 94 survivors, 9% had cerebral palsy and 6% had permanent hearing loss, with worse outcomes in those with syndromic diagnoses. Significant predictors of mortality included birth weight z-score [OR 0.28(0.11,0.72), P = 0.008], single-ventricle anatomy [OR 5.92(1.31,26.80), P = 0.021], post-operative ventilation days [OR 1.06(1.02,1.09), P = 0.007], and cardiopulmonary resuscitation [OR 11.58 (1.97,68.24), P = 0.007]; for adverse functional outcome in those without syndromic diagnoses, birth weight 2,000-2,499 g [ES -11.60(-18.67, -4.53), P = 0.002], post-conceptual age [ES -0.11(-0.22,0.00), P = 0.044], post-operative lowest pH [ES 6.75(1.25,12.25), P = 0.017], and sepsis [ES -9.70(-17.74, -1.66), P = 0.050]. Conclusions: Our findings suggest preterm neonates with CCHD and early OHS had significant mortality and morbidity at 2-years and were at risk for cerebral palsy and adverse neurodevelopment. This information may be important for management, parental counseling and the decision-making process.

Longitudinal linear combination test for gene set analysis.

BACKGROUND: Although microarray studies have greatly contributed to recent genetic advances, lack of replication has been a continuing concern in this area. Complex study designs have the potential to address this concern, though they remain undervalued by investigators due to the lack of proper analysis methods. The primary challenge in the analysis of complex microarray study data is handling the correlation structure within data while also dealing with the combination of large number of genetic measurements and small number of subjects that are ubiquitous even in standard microarray studies. Motivated by the lack of available methods for analysis of repeatedly measured phenotypic or transcriptomic data, herein we develop a longitudinal linear combination test (LLCT). RESULTS: LLCT is a two-step method to analyze multiple longitudinal phenotypes when there is high dimensionality in response and/or explanatory variables. Alternating between calculating within-subjects and between-subjects variations in two steps, LLCT examines if the maximum possible correlation between a linear combination of the time trends and a linear combination of the predictors given by the gene expressions is statistically significant. A generalization of this method can handle family-based study designs when the subjects are not independent. This method is also applicable to time-course microarray, with the ability to identify gene sets that exhibit significantly different expression patterns over time. Based on the results from a simulation study, LLCT outperformed its alternative: pathway analysis via regression. LLCT was shown to be very powerful in the analysis of large gene sets even when the sample size is small. CONCLUSIONS: This self-contained pathway analysis method is applicable to a wide range of longitudinal genomics, proteomics, metabolomics (OMICS) data, allows adjusting for potentially time-dependent covariates and works well with unbalanced and incomplete data. An important potential application of this method could be time-course linkage of OMICS, an attractive possibility for future genetic researchers. AVAILABILITY: R package of LLCT is available at: https://github.com/its-likeli-jeff/LLCT.

Clinical Features, Treatment, Prognosis, and Mortality in Paraquat Poisonings: A Hospital-Based Study in Iran.

OBJECTIVE: The aim of the present study was to evaluate the demographics, clinical characteristics, fatal dose, the efficacy of treatments, and prognosis in paraquat (PQ) poisoning in the Kerman Province of Iran. METHODS: This analytical cross-sectional study was conducted on 126 PQ poisoned patients who were referred to Afzalipour Hospital during 2006-2015. Demographic variables such as age and gender, signs and symptoms of poisoning, the estimated ingested dosage of PQ, and clinical outcome were extracted from medical records. Patients were compared and categorized into two groups considering the outcome: survivors and nonsurvivors. Patients with nonoral exposures, combined drug exposures, PQ exposures more than 24 h before the presentation, and critical underlying diseases were not included in the study. FINDINGS: Our results indicated that the mean dose of PQ used by all patients was 2358 mg, which was reported as 1846 and 2812 mg in females and males, respectively. Moreover, the results showed that the highest mortality rate was in patients with respiratory distress, followed by oral ulceration and excess salivation. In all PQ-poisoned patients, the dose of greater than approximately 2250 mg predicted death with 86.2% specificity and 75.7% sensitivity. CONCLUSION: Based on the results of the present study, the mortality rate in PQ-poisoned patients depended on the dose of poison, blood sugar level, and aspartate transaminase levels. Our results suggest that these parameters have excellent prognostic value for the prediction of mortality.

Determining Risk Factors for Gastric and Esophageal Cancers between 2009-2015 in East-Azarbayjan, Iran Using Parametric Survival Models

Background: Esophageal cancer (EC) and Gastric cancer (GC) have been identified as two of the most common cancers in the northeastern regions of Iran. The increasing rates of these types of cancers requires attention. This study aims to assess the potential risk factors for these two cancers and then determine shared risk factors between them in a population of Iranian patients using parametric survival models. Methods: This retrospective cohort study was conducted using 127 patients with EC and 184 patients with GC in East Azarbaijan, Iran who were diagnosed and registered during the years 2009-2010 in Iran's National Cancer Control Registration Program and were followed for five years. Parametric survival models were used to find the risk factors of the patients. Akaike Information Criteria was used to identify the best parametric model in this study. Interaction analysis was used to determine shared risk factors between EC and GC. Results: The mean (±standard deviation) age of diagnoses for EC and GC were 66.92(±11.95) and 66.5(±11.5) respectively. The survival time ranges of GC patients was (0.07-70.33) and the survival time ranges were from 0.10 to 69.03 months for EC patients. Multivariable Log- logistic model showed that being married (OR=2.25, 95% CI: 1.33 - 3.81) for EC patients and Esophagectomy surgery for EC (OR: 1.62, 95% CI: 1.04 ­ 2.55) and GC (OR: 1.60, 95% CI: 1.02 ­ 2.53) had significant effects on survival. Age at the time of diagnosis, job status, and Esophagectomy surgery were statistically comparable regarding their magnitude of effect on survival of two cancers (all Ps>0.05). Conclusion: Esophagectomy surgery and being married were important risk factors in EC and GC. The log-logistic model was the most appropriate statistical approach to identify significant risk factors on survival of both cancers.

The Persian Version of Fertility Adjustment Scale: Psychometric Properties.

BACKGROUND: Infertility is a common clinical problem. Psychological adjustment to infertility refers to changing the viewpoint and attitude of an infertile person toward infertility problems, treatments and possible outcomes. The present study aims to prepare a valid and reliable scale for assessing the psychological adjustment to infertility, by determining the cultural adaptation, validity and reliability of the Persian version of the Fertility Adjustment Scale. MATERIALS AND METHODS: This is a cross-sectional study performed to localize and validate the Fertility Adjustment Scale, in which 40 infertile women and 40 healthy subjects (fertile or having children) were detected by a gynecologist and the subjects who completed the Fertility Adjustment Scale (FAS) questionnaire were recruited. This study had four steps: in the first step, the literature was reviewed, in the second step, the scale was translated, in the third step, the content and construct validity indicators were calculated, and in the fourth step, reliability of the scale was validated. RESULTS: The mean (± SE and range) of fertility adjustment total scores in the infertile group and the control group were 43.2 (1.2 and 27-57) and 42.3 (1.5 and 18-57), respectively (P=0.623). The content validity was good according to Content Validity Index score (0.7-0.8). A two-component structure was extracted from factor analysis which approximately justifies 52.0% of the cumulative variations. A Cronbach's alpha value of 0.68 showed moderate reliability. CONCLUSION: The results of this study revealed that the infertility adjustment scale is a useful tool for the analysis of psychological reactions towards infertility problems and evaluation of the consequences of treating this social-clinical problem.