Theresa A. Scott

Comparison of the sedating effects of levocetirizine and cetirizine: a randomized, double-blind, placebo-controlled trial

BACKGROUND Compared with placebo, levocetirizine has been found to be less sedating than cetirizine in separate trials. However, whether levocetirizine is less sedating than its parent drug cetirizine has not yet been studied in a randomized trial. OBJECTIVE To determine whether levocetirizine is less sedating than cetirizine. METHODS We conducted a randomized, double-blind, crossover, placebo-controlled trial examining sedation and allergy symptoms in patients with perennial allergic rhinitis who had previously reported significant sedation with cetirizine. Enrollment ran from January 28, 2009, to February 25, 2009. All patients completed the study by April 17, 2009. Thirty patients enrolled, and 29 patients completed the study (1 patient did not return her questionnaire). In a double-blind fashion, the 29 study participants received levocetirizine, 5 mg daily for 1 week, cetirizine, 10 mg daily for 1 week, and an equivalent placebo pill for 1 week in randomized order with washout periods before each treatment arm. At the end of each washout period and each treatment period, participants completed a 1-page questionnaire. This questionnaire included questions about sedation or sleepiness in the form of a modified Epworth Sleepiness Scale, a Likert scale measuring general or global sedation, and allergy symptoms as measured by the total rhinitis symptom score. RESULTS Sedation as measured by both the modified Epworth Sleepiness Scale and the Likert scale was not significantly different between the levocetirizine and cetirizine treatments. CONCLUSIONS In patients with a perceived history of sedation with cetirizine, most were able to tolerate levocetirizine. However, this controlled trial also suggests that many of these patients would tolerate cetirizine if given in a masked manner. Therefore, patients with a history of mild to moderate sedation with cetirizine are unlikely to experience a different sedation profile with levocetirizine.

Is cardiac catheterization necessary before initial management of patients with stable ischemic heart disease? Results from a Web-based survey of cardiologists

BACKGROUND It is unknown whether preconceived beliefs regarding the need for cardiac catheterization and revascularization in patients with stable ischemic heart disease (SIHD) would preclude a study randomizing patients with significant ischemia to a conservative strategy. Given the widespread practice of performing revascularization in patients with SIHD, we assessed the feasibility of conducting a randomized trial comparing initial invasive and conservative strategies in patients with SIHD and moderate or severe ischemia. METHODS An online survey to cardiologists queried their willingness to enroll a sample patient with frequent stable angina, >10% myocardial ischemia, and normal ejection fraction into a randomized trial with a 50% chance of being conservatively managed without cardiac catheterization. RESULTS Among 499 respondents, 57% (95% CI 53%-62%) were willing to enroll the patient. Among 207 cardiologists unwilling to enroll, 55% (95% CI 48%-61%) would be willing if they knew the patient did not have very high-risk features on stress imaging, yielding a total of 80% (95% CI 76%-83%) of cardiologists willing to enroll. No differences were observed among different types of cardiologists (interventional, invasive/noninterventional, and noninvasive). Seventy-one percent (95% CI 67%-75%) were more likely to try initial medical therapy after the publication of the Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation trial results. CONCLUSIONS Most surveyed cardiologists were willing to enroll SIHD patients with at least moderate ischemia into a trial with an initial noninvasive strategy arm. These findings support the feasibility of planning a large-scale trial to test the role of cardiac catheterization and revascularization in the initial management of SIHD patients with moderate or severe ischemia.

National rates of diarrhea-associated ambulatory visits in children.

OBJECTIVE To estimate national rates of ambulatory healthcare visits due to diarrhea- and rotavirus-associated illness before the introduction of rotavirus vaccine. STUDY DESIGN Annual rates for diarrhea-associated visits in children age < 5 years were calculated for 1995-2004 using National Ambulatory Medical Care Survey, National Hospital Ambulatory Medical Care Survey, and US Census Bureau data. Rates by age, race, and time period were compared using Poisson regression. RESULTS Annual rates of outpatient and emergency department (ED) visits for 1995-2004 were 955 (95% confidence interval [CI] = 803 to 1107) and 314 (95% CI = 278 to 350)/10,000 person-years, respectively. Annual outpatient (P = .470) and ED (P = .734) visit rates remained stable from 1995 to 2004. Outpatient visits were less frequent in African Americans than Caucasians (716/10,000 person-years vs 1012/10,000 person-years; P < .05; incidence rate ratio [IRR] = 0.71; 95% CI = 0.51 to 0.99), whereas ED visits were more frequent in African Americans than Caucasians (520/10,000 person-years vs 286/10,000 person-years; P < .05; IRR = 1.83; 95% CI = 1.58 to 2.11). Approximately 29% of outpatient diarrhea-associated outpatient visits (273/10,000 person-years; 95% CI = 145 to 401) and 25% of diarrhea-associated ED visits (78/10,000 person-years; 95% CI = 64 to 83) were due to rotavirus. CONCLUSIONS Diarrhea- and rotavirus-associated illness is associated with significant healthcare utilization. Future studies are needed to investigate factors causing differences in healthcare use by race and to explore the impact of the rotavirus vaccine.

Exostoses of the external auditory canal in white-water kayakers†

Exostoses of the external auditory canal are benign bony tumors associated with frequent cold‐water exposure. Obstruction may lead to conductive hearing loss and recurrent otitis externa, requiring surgical correction when symptoms become intolerable. This study aimed to characterize the prevalence of exostoses in white‐water kayakers and identify associated risk factors and protective measures.

Diagnosis of Trichomonas vaginalis in Female Children and Adolescents Evaluated for Possible Sexual Abuse: A Comparison of the InPouch TV Culture Method and Wet Mount Microscopy

STUDY OBJECTIVE To compare the performance of wet mount microscopy and the InPouch TV culture method in diagnosing Trichomonas vaginalis in a cohort of female children and adolescents evaluated for possible sexual abuse. DESIGN A prospective study in which samples for both wet mount and InPouch TV were collected from the vaginal vault of each participant. The wet mount was examined microscopically for the presence of motile trichomonads, and the InPouch TV was analyzed in accordance with manufacturer specifications. SETTING A regional, university-affiliated sexual abuse center in Nashville, TN. PARTICIPANTS Females (N = 271) aged 10 to 17 years (inclusive) who met screening criteria for sexually transmitted infection testing in accordance with Centers for Disease Control recommendations, and who exhibited evidence of at least partial hymenal estrogenization. MAIN OUTCOME MEASURES A Trichomonas vaginalis diagnosis either via detection of motile trichomonads on wet mount or a positive InPouch TV. RESULTS The median age of the 271 participants was 13.6 years, 88% (235/268) were genital Tanner stage 4 or 5, and 66% (173/263) were Caucasian. Trichomonas vaginalis was diagnosed by either wet mount or InPouch TV in 4% (12/274) of the possible sexually transmitted infection exposures. The sensitivity of wet mount was 8/12 = 0.67 (95% confidence interval [CI]: 0.39, 0.86) and specificity was 262/262 = 1.00 (95% CI: 0.99, 1.00). The false negative rate of wet mount was 4/12 = 0.33 (95% CI: 0.14, 0.61). CONCLUSIONS A culture-based method such as InPouch TV should be considered for Trichomonas vaginalis diagnosis when evaluating children and adolescents in whom sexual abuse is a concern.

Accuracy of Perception of Body Size Among Overweight Latino Preadolescents After a 6-Month Physical Activity Skills Building Intervention

Background. Previous research has shown that overweight Latino children underestimate their body size. Erroneous perception of body size may have important health and behavioral implications and serve as a significant barrier to weight control. Objective. The aim of this study was to determine whether children’s perceptions of their body size became more accurate following a pediatric obesity intervention focused on increasing physical activity. Design/ methods. This analysis includes 61 overweight (body mass index ≥85%) Latino children (aged 8-11 years) parent—child dyads who completed a pilot randomized control trial. Results. After the intervention, 40.7% (11/27) of children in the intervention group rated their body size accurately compared with 21.2% (7/33) in the control group. The difference indicates a trend toward significance (P = .09). Conclusions. Participating in monthly physical activity skill building sessions may increase children’s accuracy in body size perception.This may be an important first step toward behavior modification.

Part-time physician faculty in a pediatrics department: a study of equity in compensation and academic advancement.

Purpose To assess equity in compensation and academic advancement in an academic pediatrics department in which a large proportion of the physician faculty hold part-time appointments. Method The authors analyzed anonymized data from Vanderbilt University School of Medicine Department of Pediatrics databases for physician faculty (faculty with MD or MD/PhD degrees) employed during July 1, 2007 to June 30, 2008. The primary outcomes were total compensation and years at assistant professor rank. They compared compensation and years at junior rank by part-time versus full-time status, controlling for gender, rank, track, years since first appointment as an assistant professor, and clinical productivity. Results Of the 119 physician faculty in the department, 112 met inclusion criteria. Among those 112 faculty, 23 (21%) were part-time and 89 (79%) were full-time faculty. Part-time faculty were more likely than full-time faculty to be women (74% versus 28%, P < .001) and married (100% versus 84%, P = .042). Analyses accounting for gender, years since first appointment, rank, clinical productivity, and track did not demonstrate significant differences in compensation by part-time versus full-time status. In other adjusted analyses, faculty with part-time appointments spent an average of 2.48 more years as an assistant professor than did faculty with full-time appointments. Conclusions Overall group differences in total compensation were not apparent in this department, but physician faculty with part-time appointments spent more time at the rank of assistant professor. This study provides a model for determining and analyzing compensation and effort to ensure equity and transparency across faculty.

Reproducibility of intracardiac and transpulmonary biomarkers in the evaluation of pulmonary hypertension

Intracardiac and transpulmonary levels of natriuretic peptides (NPs) and cyclic guanosine monophosphate (cGMP) provide insight into the pathophysiology of pulmonary hypertension (PH) secondary to left-heart failure but have not been evaluated in established or suspected pulmonary arterial hypertension (PAH). Demonstrating adequate reproducibility of these markers is an important precursor to further study. We hypothesized that the reproducibility of intracardiac and transpulmonary NPs and cGMP is similar to the reproducibility of these markers sampled from the peripheral venous circulation. In outpatients undergoing right-heart catheterization for PH, blood samples were obtained from a peripheral venous site, superior vena cava, inferior vena cava, coronary sinus, pulmonary artery, and pulmonary capillary wedge position. At each site, a repeat sample was collected approximately 60 seconds after the initial measurement. Reproducibility was assessed using the slope of the regression line between initial and follow-up levels. We enrolled 10 patients: Six had PAH, two had pulmonary venous hypertension, and two had normal pulmonary pressure. At all sites, the slopes of the regression lines for BNP were close to identity. BNP was generally more reproducible than NT-pro-BNP. For the NPs and cGMP, reproducibility at intracardiac and transpulmonary sites was similar to the peripheral venous site. Reproducibility of NPs was not influenced by PH severity, access site, or time between measurements. The two patients with the highest transpulmonary pressure gradients had high transpulmonary BNP uptake, but their transpulmonary cGMP gradients were negative. In patients evaluated for PH, reproducibility of NPs and cGMP at intracardiac and transpulmonary sites is high and is comparable to that of peripheral venous measurements.

Diagnostic utility of concentrated Mus m 1 allergen extract in humans

There is growing evidence that the mouse allergen is a major causative factor for allergic rhinitis, conjunctivitis, and asthma in children and adults of urban and rural populations.1 Furthermore, exposure to mice by laboratory animal workers is associated with a high risk of developing occupational allergies.2 Our Allergy practice at Vanderbilt University has recognized a number of patients with poorly controlled allergies to the mice that they work with. This clinical observation prompted an investigation for a better diagnostic and therapeutic option for our patients. The major mouse allergens belong to the lipocalin family of proteins that are synthesized in the mouse liver and secreted in the urine. The major mouse allergen is known as Mus m 1 in the allergen nomenclature. Although detectable in serum and pelt extracts, Mus m 1 concentration is 10 times greater in mouse urine than serum.3 Yet, currently the only commercially available mouse extracts are mouse epithelial extracts which contain varying low concentrations of the major mouse allergen Mus m 1 (0.5–8 µg/mL).4 We hypothesized that a highly concentrated major mouse allergen extract suitable for mouse allergy testing in humans could be isolated from mouse urine. The purpose of the study was to develop a new method for preparing mouse urine allergen extract and assess its diagnostic properties in humans. Volunteers underwent skin prick testing and intranasal challenge with the mouse urine extract to determine the diagnostic performance. To our knowledge, this is the first study to determine the diagnostic performance of mouse urine extract. We asked ALK-Abello Laboratory (Round Rock, TX) to prepare a new mouse urine extract to use in our investigation. Mouse urine collected from male laboratory mice was stored frozen until tested for Mus m 1 (Indoor Biotechnologies, Charlottesville, NC). Urine, containing 2,000 to 3,000 µg/mL of Mus m 1 was dialyzed using 0.4% phenol in normal saline, and then diluted to a concentration of 100 µg/ml. The final extract contained 100 µg/mL of Mus m 1 in 50% glycerin, 0.9% NaCl and 0.4% phenol. Qualitative analysis of protein content in the new mouse urine extract and the commercial mouse epithelial extract (ALK-Abello) were analyzed by reversed-phase liquid chromatography-tandem mass spectrometry.5 Thirty nine healthy individuals (32 women, 7 men, age 18–60 years) with a history of mouse exposure were recruited from Vanderbilt University by means of mass e-mail and advertisement. Volunteers consented verbally and in writing to the protocol that was approved by the Vanderbilt University Committee for the Protection of Human Subjects. An Investigational New Drug agreement with the U.S. Food and Drug Administration for the use of mouse urine extract for skin testing and nasal provocations in humans was in place prior to initiation of the study. Subjects discontinued any medications that could interfere with testing at least 5 days prior to the study. Patients completed a questionnaire to assess mouse-related allergic symptoms and exposure. Volunteers then underwent skin prick testing with common aeroallergens (cat and dog hair, mixed mites, German cockroach, alternaria, cladosporium, Bermuda grass, Johnson grass, pecan pollen, oak, cedar, ragweed, mixed lambs quarter) and the commercial mouse epithelial extract (ALK-Abello). Subsequently, volunteers underwent titrated skin prick testing to the new mouse urine extract. Normal saline was added to the mouse urine extract containing 100 µg/mL of Mus m 1 to produce concentrations of extract ranging from 0.33 µg/mL to 100 µg/mL. Skin prick testing to the new mouse urine extract started at 0.33 µg/mL if positive to the commercial mouse epithelial extract or 1 µg/mL if the subject was negative to the commercial mouse epithelial extract in prior testing. Regardless of the starting point, the dose was then increased by ½ log increments until the subject was considered positive or reached the maximum concentration of 100 µg/mL. Allergy testing was performed using standard guidelines and was considered positive if the wheal was ≥3 mm than negative control at 15 min post-exposure.6 Intradermal testing was not done. In addition, all volunteers, regardless of symptoms, underwent nasal challenge to the new mouse urine extract using the procedure described by Bousquet and colleagues.7 The starting point for the nasal challenge depended on the titrated skin test results and clinical symptoms to mice, as evaluated by the mouse symptom and exposure survey. Each challenge was 0.1mL of full strength mouse extract diluted with 0.9% NaCl beginning with glycerin control followed by increases in concentration of mouse allergen extract until a positive challenge or maximum dose (100 µg/mL) was reached. A positive challenge was determined by using a 13-point symptom score of sneezing, pruritis, rhinorrhea, nasal blockage and ocular symptoms.8 Each symptom was graded by the participant and accumulated to give a total score for each incremental challenge, including the glycerin control.9 The nasal challenge was considered positive if the subject had a non65 cumulative symptom score of ≥5. All participants tolerated the experiments well. The primary statistical objective was to compare the results of the titrated skin prick testing and nasal challenge of the new mouse urine extract. The sensitivity, specificity, positive predictive value and negative predictive value of the titrated skin prick test were calculated using 95% confidence intervals for each of these values by employing the Wilson score-test-based method for calculating confidence intervals for binomial probabilities and R (www.r-project.org) software. Qualitative reversed-phase liquid chromatography-tandem mass spectrometry analysis of the mouse urine extract revealed approximately 26 mouse urine proteins and a minute amount of albumin. In contrast, the commercial mouse epithelial extract contained more than 267 proteins including high amounts of albumin, diverse bioactive proteins including heat shock proteins and other poorly characterized proteins with only small quantities of mouse urine proteins. The mouse exposure and symptom survey was completed by 39 volunteers. These volunteers were exposed to mice on average 14 hours per week. Ninety two percent of participants (36/39) handled mice as laboratory workers. Self diagnosis of allergy to mouse and other aeroallergens based on nasal, ocular, respiratory and skin symptoms was reported by 23/39 (59%) and 29/39 individuals (74%), respectively. Thirty seven had interpretable skin prick testing (2 individuals had dermatographism). Among these 37 patients, 28 (76%) had a positive test with at least one aeroallergen, 13 (35%) with the mouse epithelial extract, and 9 (24%) with the mouse urine extract. Nasal challenge with the mouse urine extract was completed in 35 participants. Two volunteers were excluded from the study because they developed reaction to glycerin control either on skin testing or nasal challenge. Out of the 9 subjects with positive skin test to the mouse urine extract, 8 reported symptoms on the survey, and 7 were positive to nasal challenge using mouse urine extract. All subjects with negative mouse symptom questionnaires had negative nasal challenges. The sensitivity of the new mouse urine extract was 70% (7/10), specificity 92% (23/25), positive predictive value 78% (7/9), and negative predictive value 88% (23/26). The most important characteristics of allergen extracts used for diagnostic challenges and immunotherapy include chemical purity and predictable concentration of the specific antigen. We describe a new mouse urine extract that has a greater concentration of the major mouse allergen Mus m 1 and chemical purity than the commercially available mouse epithelial extract. The urine extract contains mostly mouse urine proteins, whereas the epithelial extract is a mixture of albumin, nonspecific proteins including heat shock proteins with a small amount of Mus m 1. However, despite the improved purity, the mouse urine extract did not demonstrate a clear improvement in diagnostic performance over the previously published data of the diagnostic performance of the mouse epithelial extract.4 Comparative performance is revealed in table 1. Table 1 Comparative Performance of Mouse Urine Extract to Mouse Epithelia Extract These results may suggest that Mus m 1 is not the only allergen causing clinical symptoms to mice. There are studies suggesting that serum albumin may also play an etiologic role in mouse allergy in humans.10 Serum albumin is abundantly present in the mouse epithelial extract. Perhaps, the optimal diagnostic method for mouse allergy should include testing with both Mus m 1 and albumin proteins. Importantly, it is also possible, that the reaction to the highly impure epithelial extract is mediated by both IgE and non-IgE mediated inflammatory pathways, thus only in part assessing a true allergic response to mouse. Thus, we describe a new mouse allergen extract containing pure and highly concentrated mouse urine protein that is suitable for diagnostic purposes in humans. Therefore, in our opinion, despite comparable diagnostic efficacy, the newly described urine extract could be superior to the epithelial extract as a diagnostic and research tool for mouse allergy in humans. Furthermore, if we assume that human allergy to mice is similar to cat and dog in which there is a dose dependent response to the major allergen in immunotherapy, then in the future this new extract could be used to develop desensitization methods based on dose of major allergen.11,12 This could give laboratory workers as well as children and adults with severe allergy and asthma to mice an option for relief that was previously never available.