Identifying clinically meaningful severity categories for PROMIS pediatric measures of anxiety, mobility, fatigue, and depressive symptoms in juvenile idiopathic arthritis and childhood-onset systemic lupus erythematosus.

PURPOSE: A key limitation to widespread adoption of patient-reported outcome (PRO) measures is the lack of interpretability of scores. We aim to identify clinical severity thresholds to distinguish categories of no problems, mild, moderate, and severe along the PROMIS® Pediatric T-score metric for measures of anxiety, mobility, fatigue, and depressive symptoms for use in populations with juvenile idiopathic arthritis (JIA) and childhood-onset systemic lupus erythematosus (cSLE). METHODS: We used a modified standard setting methodology from educational testing to identify clinical severity thresholds (clinical cut scores). Using item response theory-based parameters from PROMIS item banks, we developed a series of clinical vignettes that represented different severity or ability levels along the PROMIS Pediatric T-score metric. In stakeholder workshops, participants worked individually and together to reach consensus on clinical cut scores. Median cut-score placements were taken when consensus was not reached. Focus groups were recorded and qualitative analysis was conducted to identify decision-making processes. RESULTS: Nine adolescents (age 13-17 years) with JIA (33% female) and their caregivers, five adolescents (age 14-16 years) with cSLE (100% female) and their caregivers, and 12 pediatric rheumatologists (75% female) participated in bookmarking workshops. Placement of thresholds for bookmarks was highly similar across stakeholder groups (differences from 0 to 5 points on the PROMIS t-score metric) for all but one bookmark placement. CONCLUSION: This study resulted in clinical thresholds for severity categories for PROMIS Pediatric measures of anxiety, mobility, fatigue, and depressive symptoms, providing greater interpretability of scores in JIA and cSLE populations.

Exploring the impact of paediatric localized scleroderma on health-related quality of life: focus groups with youth and caregivers.

BACKGROUND: Paediatric localized scleroderma (LS) can negatively impact health-related quality of life (HRQoL) by causing skin fibrosis, abnormal limb development, disfigurement, and side-effects from immunosuppressive treatment. Studies to date have rarely included qualitative data gathered directly from paediatric patients with LS. OBJECTIVES: To assess the impact of LS on HRQoL among affected youth and their caregivers using qualitative description. METHODS: Youth with all subtypes of LS and their caregivers were purposively sampled to participate in age-appropriate focus groups (younger children, early adolescents, adolescents). Each group started with a drawing exercise followed by in-depth discussion of topics including skin symptoms (e.g. itch, pain, tightness), functional impairment, physical appearance, family and peer relationships, and treatment burden. Focus groups were transcribed verbatim and co-coded, with adjudication of differentially applied codes. The study findings were triangulated via comparison with adult reports and published literature. RESULTS: Eleven youth aged 9-16 years and 16 caregivers participated in three focus groups each. Major identified areas of impact included uncomfortable skin symptoms, physical functioning limitations, extracutaneous manifestations, body image, bullying and teasing, unwanted questioning from others, and treatment side-effects and burden. CONCLUSIONS: This is the first qualitative study of HRQoL in LS to include all major LS subtypes. We identified domains of HRQoL impacted by LS, some of which replicate earlier findings and some of which were novel. As impact also changed with developmental stage, our findings support the need for ongoing, formal evaluation of HRQoL in children and adolescents with LS. What is already known about this topic? Paediatric localized scleroderma (LS) negatively impacts health-related quality of life (HRQoL) via skin fibrosis, musculoskeletal and other extracutaneous manifestations from the disease process, and side-effects of systemic immunosuppression. The full impact of LS and its treatment on HRQoL is incompletely understood, with only one published qualitative study of youth with LS, which was limited to facial involvement. There are no qualitative studies of HRQoL in other LS subtypes to date. What does this study add? This is the first qualitative evaluation of HRQoL in youth with LS inclusive of all disease subtypes. Our study confirms that LS affects HRQoL across multiple distinct domains, including uncomfortable skin sensations, impacts on body image, bullying and teasing from peers, unwanted intrusive questioning, physical limitations, extracutaneous manifestations and high treatment burden. These results indicate the need for ongoing clinical assessment of paediatric patients in these domains. What are the clinical implications of the work? These results support the need to care for patients with LS holistically by synthesizing cutaneous, musculoskeletal and extracutaneous disease assessments with multidimensional evaluation of psychosocial impact and adverse effects of treatments. The development of an LS-specific HRQoL measure would advance such efforts.

Lethal and sub-lethal effects of faecal deltamethrin residues on dung-feeding insects.

Endectocides administered to livestock to facilitate pest and parasite control may be excreted in the faeces at concentrations that are toxic to coprophagous insects, including species of ecological importance. Although much research has focused on the effects of macrocyclic lactones, relatively less attention has been given to any similar impacts of the widely used pyrethroid insecticides. Here, the effects of faecal residues of the pyrethroid deltamethrin after application to Holstein-Friesian cattle in a proprietary pour-on formulation are examined. Freshly dropped dung was collected 1, 3, 5 and 7 days after treatment and from an untreated control group. In laboratory bioasssays, female Lucilia sericata (Diptera: Calliphoridae) blow flies matured significantly smaller egg batches and had a lower percentage of eggs hatch after feeding on dung collected for up to 5 days after treatment, compared with flies feeding on dung from untreated cattle. In the field, artificial dung pats were constructed from the collected dung and left on pastureland for 7 days before being retrieved and searched for insects. Significantly more adult Diptera emerged from the faeces of untreated cattle than from the dung of treated cattle collected on days 1 and 3 after treatment. Adult Coleoptera were found in lower numbers in the dung of treated animals compared with control dung, suggesting a repellent effect. The results indicate that deltamethrin residues in cattle faeces have a range of lethal and sub-lethal effects on dung-feeding insects for up to a week after treatment, but that the precise duration and nature of toxicity varies depending on the sensitivity of the insect in question.

An unusual case of duodenal obstruction-gangliocytic paraganglioma.

Gangliocytic paragangliomas are rare tumors located in the gastrointestinal tract that are considered to be benign. They are composed of spindle-shaped cells, epithelioid cells, and ganglion-like cells. They usually present with abdominal pain, and/or gastrointestinal bleeding, and occasionally with obstructive jaundice. We report a case of obstruction in a 17-year-old female, which on histology was found to be a gangliocytic paraganglioma, with an extremely unusual presentation. Intraoperatively, the patient was found to have local tumor extension and regional lymph node invasion, and so she underwent a pylorus-preserving pancreaticoduodenectomy, with local lymph node clearance. We discuss the management of this unusual case and review the literature.

How much do medical students know about infection control?

Changes in undergraduate medical training mean that students have direct patient contact from an early stage of their training. This study aimed to assess the knowledge of third-year medical students at the University of Birmingham Medical School, UK on infection control policy and procedures. A semi-structured questionnaire was distributed to medical students. Out of 322 students, 156 returned completed questionnaires (48%). Results showed that 58% of medical students did not know the correct indications for using alcoholic hand gel, 35% did not know the correct use of gloves, and 50% did not know the exclusion period after an episode of diarrhoea and vomiting. Sixty-four percent of medical students reported formal teaching on hand hygiene, 12% reported informal teaching, 19% reported both types of teaching and 5% reported no hand hygiene teaching at all. Forty-nine percent of medical students thought that there was insufficient emphasis on infection control in their course. These results raised concerns about medical students' knowledge about infection control. The University is currently reviewing the need for a more structured model for the teaching and assessment of infection control.

Interactions between components of the essential oil of Melaleuca alternifolia.

AIMS: This study compared the antimicrobial activity of Melaleuca alternifolia (tea tree) oil with that of some of its components, both individually and in two-component combinations. METHODS AND RESULTS: Minimum inhibitory concentration and time-kill assays revealed that terpinen-4-ol, the principal active component of tea tree oil, was more active on its own than when present in tea tree oil. Combinations of terpinen-4-ol and either gamma-terpinene or p-cymene produced similar activities to tea tree oil. Concentration-dependent reductions in terpinen-4-ol activity and solubility also occurred in the presence of gamma-terpinene. CONCLUSION: Non-oxygenated terpenes in tea tree oil appear to reduce terpinen-4-ol efficacy by lowering its aqueous solubility. SIGNIFICANCE AND IMPACT OF THE STUDY: These findings explain why tea tree oil can be less active in vitro than terpinen-4-ol alone and further suggest that the presence of a non-aqueous phase in tea tree oil formulations may limit the microbial availability of its active components.

The outer membrane of Pseudomonas aeruginosa NCTC 6749 contributes to its tolerance to the essential oil of Melaleuca alternifolia (tea tree oil).

Pseudomonas aeruginosa is less susceptible to the antimicrobial properties of tea tree oil than many bacteria and its tolerance is considered to be due to its outer membrane. Polymyxin B nonapeptide (PMBN), which has no antibacterial action, was used to permeabilize the outer membrane. The addition of PMBN to Ps. aeruginosa NCTC 6749 markedly increased this organism's susceptibility to tea tree oil and to its normally inert hydrocarbons, p-cymene and gamma-terpinene.

The mode of antimicrobial action of the essential oil of Melaleuca alternifolia (tea tree oil).

The essential oil of Melaleuca alternifolia (tea tree) exhibits broad-spectrum antimicrobial activity. Its mode of action against the Gram-negative bacterium Escherichia coli AG100, the Gram-positive bacterium Staphylococcus aureus NCTC 8325, and the yeast Candida albicans has been investigated using a range of methods. We report that exposing these organisms to minimum inhibitory and minimum bactericidal/fungicidal concentrations of tea tree oil inhibited respiration and increased the permeability of bacterial cytoplasmic and yeast plasma membranes as indicated by uptake of propidium iodide. In the case of E. coli and Staph. aureus, tea tree oil also caused potassium ion leakage. Differences in the susceptibility of the test organisms to tea tree oil were also observed and these are interpreted in terms of variations in the rate of monoterpene penetration through cell wall and cell membrane structures. The ability of tea tree oil to disrupt the permeability barrier of cell membrane structures and the accompanying loss of chemiosmotic control is the most likely source of its lethal action at minimum inhibitory levels.

Tea tree oil causes K+ leakage and inhibits respiration in Escherichia coli.

Concentrations of tea tree oil (TTO) which inhibit or decrease growth of Escherichia coli also inhibit glucose-dependent respiration and stimulate the leakage of intracellular K+. Stationary phase cells are more tolerant to these TTO effects than exponential phase cells.

Redistribution of pulmonary blood flow during unilateral hypoxia in prone and supine dogs.

We used fluorescent-labeled microspheres in pentobarbital-anesthetized dogs to study the effects of unilateral alveolar hypoxia on the pulmonary blood flow distribution. The left lung was ventilated with inspired O2 fraction of 1.0, 0.09, or 0.03 in random order; the right lung was ventilated with inspired O2 fraction of 1.0. The lungs were removed, cleared of blood, dried at total lung capacity, then cubed to obtain approximately 1,500 small pieces of lung ( approximately 1.7 cm3). The coefficient of variation of flow increased (P < 0.001) in the hypoxic lung but was unchanged in the hyperoxic lung. Most (70-80%) variance in flow in the hyperoxic lung was attributable to structure, in contrast to only 30-40% of the variance in flow in the hypoxic lung (P < 0.001). When adjusted for the change in total flow to each lung, 90-95% of the variance in the hyperoxic lung was attributable to structure compared with 70-80% in the hypoxic lung (P < 0.001). The hilar-to-peripheral gradient, adjusted for change in total flow, decreased in the hypoxic lung (P = 0.005) but did not change in the hyperoxic lung. We conclude that hypoxic vasoconstriction alters the regional distribution of flow in the hypoxic, but not in the hyperoxic, lung.

A new method for determining the minimum inhibitory concentration of essential oils.

A new microdilution method has been developed for determining the minimum inhibitory concentration (MIC) of oil-based compounds. The redox dye resazurin was used to determine the MIC of a sample of the essential oil of Melaleuca alternifolia (tea tree) for a range of Gram-positive and -negative bacteria. Use of 0.15% (w/v) agar as a stabilizer overcame the problem of adequate contact between the oil and the test bacteria and obviated the need to employ a chemical emulsifier. A rapid version of the assay was also developed for use as a screening method. A comparison of visual and photometric reading of the microtitre plates showed that results could be assessed without instrumentation; moreover, if the rapid assay format was used, rigorous asepsis was not necessary. Accuracy of the resazurin method was confirmed by plate counting from microwells and MIC values were compared with results obtained using an agar dilution assay. The MIC results obtained by the resazurin method were slightly lower than those obtained by agar dilution.

The 're-do' chest wall deformity correction.

BACKGROUND: A small percentage of patients who undergo surgical correction of a chest wall deformity will have results so unsatisfactory that a second procedure, the so-called "re-do," will be required. CONCLUSIONS: The literature contains very little information regarding the technique and results of these procedures. Based on experience with 18 "re-do" procedures, the authors believe that recurrent deformities should be surgically corrected. Although this is a somewhat diverse group based on age at the first and second procedure, type of original operative procedure, and interval between the procedures, the operative approach is standard, and the results are predictable.

Significance of chest trauma in children.

Chest trauma in children is a marker of injury severity and is associated with a high mortality rate. This retrospective study of 1,356 trauma patients from a private pediatric hospital over a 2.5-year period identified 82 patients with chest injuries and a mortality rate of 22%. Results of Injury Severity Score, Glasgow Coma Scale, and Revised Trauma Score all indicated that children with chest injuries sustained more severe injuries. The presence of any extrathoracic injury was associated with a higher mortality (29%) than chest injury alone (4.3%). The type of extrathoracic injury was important, with head and neck injuries resulting in the highest mortality. Specific chest injuries, such as rib fractures and pulmonary contusions, were not related to increased mortality unless there was an associated extrathoracic injury. Many reports have shown a high mortality associated with chest trauma. This study suggests that it is the associated extrathoracic injury, rather than the chest injury itself, that is the real cause of the high mortality.

A combined hospital experience with fundoplication and gastric emptying procedure for gastroesophageal reflux in children.

BACKGROUND: Operative treatment of symptomatic gastroesophageal reflux (GER), often together with neurologic feeding disorders, is very common in infancy and childhood. Delayed gastric emptying (DGE) has been observed frequently in association with GER in children. STUDY DESIGN: A retrospective review was performed on 1,200 consecutive patients 18 years of age and younger operated upon for symptomatic GER or neurologic feeding disorders, or both, at two pediatric surgery centers in widely separated geographic areas in the United States of America, to compare the results after fundoplication with or without a gastric emptying procedure (GEP). RESULTS: Operations included gastroesophageal fundoplication (GEF) alone (871 patients), GEF plus GEP (286 patients), reoperative GEF plus GEP (30 patients), and GEP alone (13 patients). Thus, 27 percent of the total and 40 percent of the last 494 children with reflux had a GEP. Delayed gastric emptying with retention of more than 60 percent of an isotope meal appropriate for age at 90 minutes was present in 241 of the 451 children with reflux studied. Major neurologic disorders were present in 219 (25 percent) of 871 children who underwent GEF alone and in 247 (75 percent) of 329 children who had a GEP. All patients operated upon from both hospitals were relieved of recurrent emesis, and those with failure to thrive showed significant weight gain; pulmonary symptoms were relieved in 94 percent. Recurrent GER developed in 47 (5.2 percent) of 901 children who had GEF alone, but in only four (1.2 percent) of 329 patients who had a GEP. CONCLUSIONS: The excellent clinical results with low morbidity in this largest reported clinical experience with GEP in childhood suggest that a GEP should be combined with GEF for symptomatic children who have both GER and DGE. Minimal investigative studies are necessary for most neurologically impaired children who require a feeding gastrostomy.

Preparation of amorphous boron nitride and its conversion to a turbostratic, tubular form.

Amorphous boron nitride, BN, is obtained from the reaction of B-trichloroborazine, (BCINH)(3), with cesium metal. The amorphous product is converted to a turbostratic form upon heating to 1100 degrees C. Scanning electron microscopy reveals a previously unreported morphology composed of hollow tubular structures. The largest of these appear to be approximately 3 micrometers in external diameter and 50 to 100 micrometers in length. Transmission electron microscopy and selected-area electron diffraction also indicate the tube walls to be turbostratic in nature. The mechanism by which the tubes form is not known, although apparent sites of incipient tube growth have been observed.

The effect of tube gastrostomy on gastroesophageal reflux in patients with esophageal atresia.

Gastroesophageal reflux (GER) occurs frequently in infants with esophageal atresia (EA). The definitive management is primary repair and often includes tube gastrostomy. The recent finding of lower esophageal sphincter (LES) pressure changes with tube gastrostomy suggests that GER might be related to gastrostomy rather than EA per se. To evaluate this thesis, two populations of patients from different children's hospitals were reviewed: EA with and without routine gastrostomy. The two populations were similar with respect to number of infants, associated anomalies, distribution in the Waterston classification, morbidity, and mortality. One hundred sixteen patients were studied. Of the 66 survivors who underwent gastrostomy and repair of EA, 30 were found to have GER (45.5%) and 12 required fundoplication (18.2%). Of 31 surviving patients who underwent repair of EA without gastrostomy, 11 had GER (35.5%) and four required fundoplication (12.9%). These data suggest that tube gastrostomy does not significantly contribute to the GER associated with EA.

Validation of a colorimetric method for determination of atmospheric formaldehyde.

Aqueous formaldehyde was stabilized in pH 7 phosphate buffer with excess sodium bisulfite of fixed and known concentration. The 5,5'-dithiobis(2-nitrobenzoic acid) (DTNB) procedure described previously was used to determine excess bisulfite colorimetrically. The slope of the calibration line (absorbance at 412 nm vs. formaldehyde concentration) is -0.350 A.U./ug CH2O/mL (correlation coefficient: 0.9995). The precision of the method at the 95% confidence level is indicated by the mean percentage relative error (1.81 +/- 1.67) and mean percentage standard error (0.42 +/- 0.39). Gaseous formaldehyde of known concentrations (ppm) in air was absorbed from air samples in pH 7 buffer and determined by the DTNB method. For the determination of formaldehyde in air, the precision and accuracy were demonstrated at the 95% confidence level by the mean percentage relative error (5.04 +/- 3.2), the mean percentage standard error (1.72 +/- 1.0), the mean percentage recovery (99.9 +/- 2.7), and the mean percentage absolute error (1.86 +/- 1.6). The graphic comparison of air concentration found vs. air concentration calculated shows a slope of 0.993 ppmfound/ppmcalcd (correlation coefficient: 0.9993).

Voiding abnormalities in children: methods of evaluation and results of treatment.

Recent advances in technology have fueled interest in the field of urodynamics and have made possible accurate diagnosis of voiding abnormalities in children. A thorough understanding of the underlying physiology and institution of the appropriate pharmacologic agents and/or teaching techniques results in correction of the underlying problems in 90% of the cases. Symptoms, techniques of diagnosis, therapeutic regimens, and results of therapy are presented.