OBJECTIVES: Validated assessment tools are required to support competency-based education. We aimed to assess the reliability and validity of the Gastrointestinal Endoscopy Competency Assessment Tool for Pediatric Colonoscopy (GiECATKIDS), an instrument developed by 41 North American experts using Delphi methodology. METHODS: GiECATKIDS consists of a 7-item global rating scale (GRS) and an 18-item checklist (CL). An attending physician assessed 104 colonoscopies performed at 3 North American hospitals by 56 endoscopists, including 25 novices (procedures), 21 intermediates (50-250), and 10 advanced endoscopists ( > 500). Another observer rated procedures to assess interrater reliability using intraclass correlation coefficient (ICC). Test-retest reliability was measured with ICC comparing endoscopists' first and second procedure scores. Discriminative validity was examined by comparing experience level with scores. Concurrent validity was assessed by correlating scores with colonoscopy experience, cecal and terminal ileal intubation rates, and physician global assessment. RESULTS: Interrater reliability of the GiECATKIDS was high (total: ICC = 0.88; GRS: ICC = 0.79; CL: ICC = 0.89). Test-retest reliability was excellent (total: ICC = 0.94; GRS: ICC = 0.94; CL: ICC = 0.84). GiECATKIDS total, GRS, and CL scores differed significantly among novice, intermediate, and advanced endoscopists (P < 0.001). There was a significant positive correlation (P < 0.001) between scores and number of previous colonoscopies (total: rho = 0.91, GRS: rho = 0.92, CL: rho = 0.84), cecal intubation rate (total: rho = 0.82, GRS: rho = 0.85, CL: rho = 0.77), ileal intubation rate (total: rho = 0.82, GRS: rho = 0.82, CL: rho = 0.80), and physician global assessment (total: rho = 0.95, GRS: rho = 0.94, CL: rho = 0.89).
CONCLUSIONS: The GiECATKIDS demonstrates strong reliability and validity as a measure of performance of pediatric colonoscopy that can be used to support training and assessment.
OBJECTIVE: To report outcomes associated with the administration of granulocyte colony-stimulating factor (G-CSF) to women with chronic neutropenia during pregnancy. METHODS: We conducted an observational study of women of childbearing potential with congenital, cyclic, idiopathic, or autoimmune neutropenia enrolled in the Severe Chronic Neutropenia International Registry to determine outcomes of pregnancies, without and with chronic G-CSF therapy, 1999-2014. Treatment decisions were made by the patients' personal physicians. A research nurse conducted telephone interviews of all enrolled U.S. women of childbearing potential using a standard questionnaire. Comparisons used Fisher's exact test analysis and Student's t test.
RESULTS: One hundred seven women reported 224 pregnancies, 124 without G-CSF therapy and 100 on chronic G-CSF therapy (median dose 1.0 micrograms/kg per day, range 0.02-8.6 micrograms/kg per day). There were no significant differences in adverse events between the groups considering all pregnancies or individual mothers, for example, spontaneous terminations (all pregnancies: no G-CSF in 27/124, G-CSF in 13/100; P=.11, Fisher's exact test), preterm labors (all pregnancies, no G-CSF in 9/124, G-CSF in 2/100, P=.12). A study with at least 300 per group would be needed to detect a difference in these events with 80% statistical power (alpha=0.05). Four newborns of mothers with idiopathic or autoimmune neutropenia not on G-CSF (4/101) had life-threatening infections, whereas there were no similar events (0/90) in the treated group, but this difference was also not statistically significant (P=.124). Adverse events in the neonates were similar for the two groups.
CONCLUSION: This observational study showed no significant adverse effects of administration of G-CSF to women with severe chronic neutropenia during pregnancy. LEVEL OF EVIDENCE: III.
Could home sexually transmitted infection specimen collection with e-prescription be a cost-effective strategy for clinical trials and clinical care
BACKGROUND: Results of a recent demonstration project evaluating feasibility, acceptability, and cost of a Web-based sexually transmitted infection (STI) testing and e-prescription treatment program (eSTI) suggest that this approach could be a feasible alternative to clinic-based testing and treatment, but the results need to be confirmed by a randomized comparative effectiveness trial.
METHODS: We modeled a decision tree comparing (1) cost of eSTI screening using a home collection kit and an e-prescription for uncomplicated treatment versus (2) hypothetical costs derived from the literature for referral to standard clinic-based STI screening and treatment. Primary outcome was number of STIs detected. Analyses were conducted from the clinical trial perspective and the health care system perspective.
RESULTS: The eSTI strategy detected 75 infections, and the clinic referral strategy detected 45 infections. Total cost of eSTI was $94,938 ($1266/STI detected) from the clinical trial perspective and $96,088 ($1281/STI detected) from the health care system perspective. Total cost of clinic referral was $87,367 ($1941/STI detected) from the clinical trial perspective and $71,668 ($1593/STI detected) from the health care system perspective.
CONCLUSIONS: Results indicate that eSTI will likely be more cost-effective (lower cost/STI detected) than clinic-based STI screening, both in the context of clinical trials and in routine clinical care. Although our results are promising, they are based on a demonstration project and estimates from other small studies. A comparative effectiveness research trial is needed to determine actual cost and impact of the eSTI system on identification and treatment of new infections and prevention of their sequelae.
PURPOSE OF REVIEW: Mutations in the gene for neutrophil elastase, ELANE, cause cyclic neutropenia (CyN) and severe congenital neutropenia (SCN). This study summarized data from the Severe Chronic Neutropenia International Registry (SCNIR) on genotype-phenotype relationships of ELANE mutations to important clinical outcomes. We also summarize findings for ELANE mutations not observed in SCNIR patients.
RECENT FINDINGS: There were 307 SCNIR patients with 104 distinctive ELANE mutations who were followed longitudinally for up to 27 years. The ELANE mutations were diverse; there were 65 single amino acid substitutions; 61 of these mutations (94%) were 'probably' or 'possibly damaging' by PolyPhen-2 analysis, and one of the 'benign' mutations was associated with two cases of acute myeloid leukemia (AML). All frame-shift mutations (19/19) were associated with the SCN. The pattern of mutations in the SCN versus CyN was significantly different (P < 10), but some mutations were observed in both groups (overlapping mutations). The cumulative incidence of severe adverse events, that is, myelodysplasia, AML, stem cell transplantation, or deaths was significantly greater for patients with SCN versus those with CyN or overlapping mutations. Specific mutations (i.e. G214R or C151Y) had a high risk for evolution to AML.
SUMMARY: Sequencing is useful for predicting outcomes of ELANE-associated neutropenia.
PURPOSE OF REVIEW: A single case of sustained HIV control in the absence of antiretroviral therapy or HIV-specific immune responses ensued following 18 months of combination antiretroviral therapy initiated at 30 h of age in a perinatally HIV-infected child (the Mississippi child). This case provides proof-of-concept that delay in HIV viremic rebound may ensue following very early treatment (VET) in perinatal infection, likely through marked reduction of latent replication-competent HIV reservoirs.
RECENT FINDINGS: The latent HIV reservoir remains the critical barrier to remission. Several studies indicate that the earlier effective combination antiretroviral therapy is initiated, the smaller the size of the HIV reservoir. The unique ability of perinatally infected neonates to initiate VET at the time of birth maximizes the potential benefits of limiting latent reservoir size and permitting reservoir decay, likely lengthening the duration of remission and limiting the capacity for re-establishment of viremia.
SUMMARY: This article covers the rationale and feasibility of VET to achieve sustained virologic remission in perinatal infection. Recent studies highlighting the effects of VET on biomarkers of HIV persistence in perinatal HIV infection are reviewed as well as implications and challenges for cure research in pediatric populations.
Case report of an 11-year-old premenarchal female with a history of constipation, sickle cell trait, and obesity who presented to the emergency department with 5 days of abdominal pain.
Cryptochromes (CRYs) are flavoproteins important for the molecular clocks of animals. The Drosophila cryptochrome (dCRY) is a circadian photoreceptor, whereas mouse cryptochromes (mCRY1 and mCRY2) are essential negative elements of circadian clock transcriptional feedback loops. It has been proposed that reduction/oxidation (redox) reactions are important for dCRY light responsiveness and mCRY1 transcriptional inhibition. We therefore evaluated the role of redox in light-dependent activation of dCRY and in mCRY1 transcriptional inhibition in Drosophila Schneider 2 cells. Using site-directed mutagenesis, three of the four conserved flavin binding residues in dCRY were found to be essential for light responses, whereas three of the four corresponding residues in mCRY1 did not abolish transcriptional responses. Two tryptophan residues in dCRY are critical for its function and are likely involved in an intramolecular redox reaction. The corresponding tryptophan residues do not play a redox-mediated role in mCRY1 function. The data provide a multistep redox model for the light-dependent activities of dCRY and suggest that such a model does not apply to mCRY1 transcriptional responses.
The molecular dissection of the mammalian circadian clock continues to yield exciting and important discoveries. Here we review the recent progress in the field, highlighting work on the central clock mechanism itself, the photopigments involved in the entrainment of the central clock by light, and the signals that entrain peripheral oscillators.