Carolyne J Montgomery

Recently, many new approaches, study designs, and statistical and analytical methods have emerged for studying gene-environment interactions (G×Es) in large-scale studies of human populations. There are opportunities in this field, particularly with respect to the incorporation of -omics and next-generation sequencing data and continual improvement in measures of environmental exposures implicated in complex disease outcomes. In a workshop called "Current Challenges and New Opportunities for Gene-Environment Interaction Studies of Complex Diseases," held October 17-18, 2014, by the National Institute of Environmental Health Sciences and the National Cancer Institute in conjunction with the annual American Society of Human Genetics meeting, participants explored new approaches and tools that have been developed in recent years for G×E discovery...

There are inadequate age-specific data to support the use of current self-report pain scales in 3- and 4-year-old children. Most preschool-aged children also lack the necessary cognitive development to use standard scales. We aimed to evaluate the validity and feasibility of 2 novel simplified scales (Simplified Faces Pain Scale, S-FPS; Simplified Concrete Ordinal Scale, S-COS) for preschool-aged children. These simplified scales used a 2-step self-report method: children were first asked whether they have pain (yes/no); only if yes, then pain intensity was self-reported using a 3-point scale with visual aids signifying mild/moderate/severe...

BACKGROUND: Oral morphine has been proposed as an effective and safe alternative to codeine for after-discharge pain in children following surgery but there are few data guiding an optimum safe oral dose. AIMS: The aim of this study was to characterize the absorption pharmacokinetics of enteral morphine in order to simulate time-concentration profiles in children given common oral morphine dose regimens. METHODS: Children (2-6 years, n = 34) undergoing elective surgery and requiring opioid analgesia were randomized to receive preoperative oral morphine (100 mcg·kg(-1) , 200 mcg·kg(-1) , 300 mcg·kg(-1) )...

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BACKGROUND: Clinical indications for the perioperative use of dexmedetomidine in pediatric anesthesia are accumulating. However, in 2013, dexmedetomidine was added to the list of medications with possible risk of prolonging the QT interval and/or inducing Torsades de Pointes. Unfortunately, current evidence for dexmedetomidine-induced QT prolongation is sparse and somewhat contradictory. OBJECTIVE: The purpose of this study was to evaluate temporal changes in corrected QT interval (QTc) after a rapid bolus administration of dexmedetomidine under total intravenous anesthesia (TIVA) with a standardized propofol and remifentanil administration...

BACKGROUND: Effective pain assessment is essential during postoperative recovery. Extensive validation data are published supporting the Faces Pain Scale-Revised (FPS-R) and the Color Analog Scale (CAS) in children. Panda is a smartphone-based application containing electronic versions of these scales. OBJECTIVES: To evaluate agreement between Panda and original paper/plastic versions of the FPS-R and CAS and to determine children's preference for either Panda or original versions of these scales...

BACKGROUND AND OBJECTIVES: Currently, the majority of the surgical procedures performed in paediatric hospitals are done on a day care basis, with post-operative pain being managed by caregivers at home. Pain after discharge of these post-operative children has historically been managed with oral codeine in combination with paracetamol (acetaminophen). Codeine is an opioid, which elicits its analgesic effects via metabolism to morphine and codeine-6-glucuronide. Oral morphine is a feasible alternative for outpatient analgesia; however, the pharmacokinetics of morphine after oral administration have been previously described only sparsely, and there is little information in healthy children...

BACKGROUND: Dexmedetomidine is a highly sensitive, specific α2 adrenoceptor agonist with anxiolytic, sedative, and analgesic effects. Administration is recommended as a loading dose infused over 10 min. Clinical experience and a previous study suggested a shorter time frame might be used without causing adverse hemodynamic effects. OBJECTIVE: To determine the dexmedetomidine dose that can be given as a rapid 5 s bolus to healthy children during total intravenous anesthesia (TIVA) without causing significant hemodynamic effects...

In the ongoing debate about gender-specific (GS) vs. traditional knee implants, there is limited information about patella-specific outcomes. GS femoral component features should provide better patellar tracking, but techniques have not existed previously to test this accurately. Using novel computed tomography and radiography imaging protocols, 15 GS knees were compared to 10 traditional knees, for the 6 degrees of freedom of the patellofemoral and tibiofemoral joints throughout the range of motion, plus other geometric measures and quality of life (QOL)...

BACKGROUND: Emergence delirium (ED) refers to a variety of behavioral disturbances commonly seen in children following emergence from anesthesia. Vapor-based anesthesia with sevoflurane, the most common pediatric anesthetic technique, is associated with the highest incidence of ED. Propofol has been shown to reduce ED, but these studies have been methodologically limited. OBJECTIVE: To conduct a randomized-controlled trial comparing the incidence of ED in children following sevoflurane (SEVO) anesthesia and propofol-remifentanil total intravenous anesthesia (TIVA)...

PURPOSE: Neoadjuvant chemotherapy for breast cancer provides critical information about tumor response; how best to leverage this for predicting recurrence-free survival (RFS) is not established. The I-SPY 1 TRIAL (Investigation of Serial Studies to Predict Your Therapeutic Response With Imaging and Molecular Analysis) was a multicenter breast cancer study integrating clinical, imaging, and genomic data to evaluate pathologic response, RFS, and their relationship and predictability based on tumor biomarkers...

Small RNAs--including piRNAs, miRNAs, and endogenous siRNAs--bind Argonaute proteins to form RNA silencing complexes that target coding genes, transposons, and aberrant RNAs. To assess the requirements for endogenous siRNA formation and activity in Caenorhabditis elegans, we developed a GFP-based sensor for the endogenous siRNA 22G siR-1, one of a set of abundant siRNAs processed from a precursor RNA mapping to the X chromosome, the X-cluster. Silencing of the sensor is also dependent on the partially complementary, unlinked 26G siR-O7 siRNA...

Neoadjuvant chemotherapy for breast cancer allows individual tumor response to be assessed depending on molecular subtype, and to judge the impact of response to therapy on recurrence-free survival (RFS). The multicenter I-SPY 1 TRIAL evaluated patients with ≥ 3 cm tumors by using early imaging and molecular signatures, with outcomes of pathologic complete response (pCR) and RFS. The current analysis was performed using data from patients who had molecular profiles and did not receive trastuzumab. The various molecular classifiers tested were highly correlated...

Argonaute-associated siRNAs and Piwi-associated piRNAs have overlapping roles in silencing mobile genetic elements in animals. In Caenorhabditis elegans, mutator (mut) class genes mediate siRNA-guided repression of transposons as well as exogenous RNAi, but their roles in endogenous RNA silencing pathways are not well-understood. To characterize the endogenous small RNAs dependent on mut class genes, small RNA populations from a null allele of mut-16 as well as a regulatory mut-16(mg461) allele that disables only somatic RNAi were subjected to deep sequencing...

PURPOSE: Patient questionnaires are popular tools for assessing and improving service quality, especially as administrators are increasingly expected to consider the patient's voice in their decision making. Despite web-based questionnaire advantages, they have not been previously compared to telephone questionnaires for assessing quality. The purpose of this paper is to compare telephone questionnaire administration with a web-based version. DESIGN/METHODOLOGY/APPROACH: Day surgery patients from a tertiary pediatric hospital completed a telephone interview and a web-based questionnaire with identical questions...

BACKGROUND: The number of fluctuations of skin conductance per second (NFSC) has been shown to correlate with induced pain and self-report pain scales. This study aimed to evaluate the validity and feasibility of NFSC as an objective measurement of nociception intensity in school-aged children after surgery. METHODS: After approval by the research ethics board and obtaining consent, 100 subjects participated in this prospective observational study. Preoperatively, NFSC was measured for 60 s at rest and during response to a self-report pain scale (numeric rating scale [NRS], Faces Pain Scale-Revised) and anxiety scoring (NRS)...

INTRODUCTION: This study aimed to determine the age-specific bolus dose of remifentanil (ED(50)) to facilitate tracheal intubation without the use of neuromuscular blocking agents. METHODS: ASA 1-2 subjects were recruited into three groups of 0-3 months (group I), 4-12 months (group II), and 1-3 years (group III) of age. A sequential up-and-down design determined the remifentanil bolus dose, which was initially started at 3 mcg x kg(-1) and adjusted in 1 mcg x kg(-1) increments (range 1-6 mcg x kg(-1))...

PURPOSE: The purpose of this study was to compare clinical and health-related quality-of-life (HRQL) outcomes within a group of patients treated for pectus excavatum (PE). METHODS: A retrospective 3-year review of patients undergoing Nuss or Ravitch correction of PE was performed. Health-related quality-of-life assessment was performed using the Child Health Questionnaire (CHQ-CF87) and the 17-item Pectus Excavatum Evaluation Questionnaire, and results were compared between groups and with age-matched CHQ-CF87 normative data...

This brief report describes the process of developing a valid and reliable questionnaire for quality measurement of pediatric day surgery care from the families' perspective. Questionnaire items were generated through a literature search and interviews with clinicians and parents. A computer-assisted telephone interview was used to administer the questionnaire to 448 parents within 72 hours of patient discharge. Tests of reliability and validity were administered, and questionnaire items were improved or omitted based on the results...

OBJECTIVE: To evaluate the effect of treatment with the dipeptidyl peptidase (DPP)-4 inhibitor vildagliptin on insulin sensitivity and beta-cell function in subjects with impaired fasting glucose (IFG). RESEARCH DESIGN AND METHODS: A total of 22 subjects with IFG (11 female and 11 male, mean +/- SD age 59.6 +/- 11.5 years) were treated orally with 100 mg vildagliptin once daily in a single-blind study. Subjects received placebo for 2 weeks (run-in) followed by vildagliptin for 6 weeks (treatment) and then placebo for 2 weeks (washout)...