Effectiveness of GenoType MTBDRsl in excluding TB drug resistance in a clinical trial.

OBJECTIVES: To assess the performance of the GenoType MTBDRsl v1, a line-probe assay (LPA), to exclude baseline resistance to fluoroquinolones (FQs) and second-line injectables (SLIs) in the Standard Treatment Regimen of Anti-tuberculosis Drugs for Patients With MDR-TB 1 (STREAM 1) trial.METHODS: Direct sputum MTBDRsl results in the site laboratories were compared to indirect phenotypic drug susceptibility testing (pDST) results in the central laboratory, with DNA sequencing as a reference standard.RESULTS: Of 413 multidrug-resistant TB (MDR-TB) patients tested using MTBDRsl and pDST, 389 (94.2%) were FQ-susceptible and 7 (1.7%) FQ-resistant, while 17 (4.1%) had an inconclusive MTBDRsl result. For SLI, 372 (90.1%) were susceptible, 5 (1.2%) resistant and 36 (8.7%) inconclusive. There were 9 (2.3%) FQ discordant pDST/MTBDRsl results, of which 3 revealed a mutation and 5 (1.3%) SLI discordant pDST/MTBDRsl results, none of which were mutants on sequencing. Among the 17 FQ- and SLI MTBDRsl-inconclusive samples, sequencing showed 1 FQ- and zero SLI-resistant results, similar to frequencies among the conclusive MTBDRsl. The majority of inconclusive MTBDRsl results were associated with low bacillary load samples (acid-fast bacilli smear-negative or scantily positive) compared to conclusive results (P < 0.001).CONCLUSION: MTBDRsl can facilitate the rapid exclusion of FQ and SLI resistances for enrolment in clinical trials.

Energy expenditure of rugby players during a 14-day in-season period, measured using doubly labelled water.

Criterion data for total energy expenditure (TEE) in elite rugby are lacking, which prediction equations may not reflect accurately. This study quantified TEE of 27 elite male rugby league (RL) and rugby union (RU) players (U16, U20, U24 age groups) during a 14-day in-season period using doubly labelled water (DLW). Measured TEE was also compared to estimated, using prediction equations. Resting metabolic rate (RMR) was measured using indirect calorimetry, and physical activity level (PAL) estimated (TEE:RMR). Differences in measured TEE were unclear by code and age (RL 4369 ± 979; RU 4365 ± 1122; U16, 4010 ± 744; U20, 4414 ± 688; U24, 4761 ± 1523 Kcal day- 1). Differences in PAL (overall mean 2.0 ± 0.4) were unclear. Very likely differences were observed in RMR by code (RL 2366 ± 296; RU 2123 ± 269 Kcal day- 1). Differences in relative RMR between U20 and U24 were very likely (U16, 27 ± 4; U20, 23 ± 3; U24, 26 ± 5 Kcal kg- 1 day- 1). Differences were observed between measured and estimated TEE, using Schofield, Cunningham and Harris-Benedict equations for U16 (187 ± 614, unclear; - 489 ± 564, likely and - 90 ± 579, unclear Kcal day- 1), U20 (- 449 ± 698, likely; - 785 ± 650, very likely and - 452 ± 684, likely Kcal day- 1) and U24 players (- 428 ± 1292; - 605 ± 1493 and - 461 ± 1314 Kcal day- 1, all unclear). Rugby players have high TEE, which should be acknowledged. Large inter-player variability in TEE was observed demonstrating heterogeneity within groups, thus published equations may not appropriately estimate TEE.

The Reliability of a Pre-Loaded Treadmill Time-Trial in Moderate Normobaric Hypoxia.

The purpose of this study was to assess the reliability of a pre-loaded 1 500-m treadmill time trial, conducted in moderate normobaric hypoxia. 8 trained runners/triathletes (24±3 years, 73.2±8.1 kg, 182.5±6.5 cm, altitude specific V˙O2max: 52.9±5.5 ml·kg(-1)·min(-1)) completed 3 trials (the first as a familiarisation), involving 2, 15-min running bouts at 45% and 65% V˙O2max, respectively, and a 1 500-m time trial in moderate normobaric hypoxia equivalent to a simulated altitude of 2 500 m (FiO2~15%). Heart rate, arterial oxygen saturation, skeletal muscle and cerebral tissue oxygenation (StO2), expired gas ( V˙O2 and V˙CO2), and ratings of perceived exertion were monitored. Running performance (Trial 1: 352.7±40; Trial 2: 353.9±38.2 s) demonstrated a low CV (0.9%) and high ICC (1). All physiological variables demonstrated a global CV≤4.2%, and ICC≥0.87, with the exception of muscle (CV 10.4%; ICC 0.70) and cerebral (CV 4.1%; ICC 0.82) StO2. These data demonstrate good reliability of the majority of physiological variables and indicate that a pre-loaded 1 500-m time trial conducted in moderate normobaric hypoxia is a highly reliable test of performance.

A diagnostic challenge: acute generalized exanthematous pustulosis or pustular psoriasis due to terbinafine.

A 72-year-old man developed a generalized erythematous pustular eruption 11 weeks after commencing terbinafine. Clinically and histologically, the appearance was that of acute generalized exanthematous pustulosis (AGEP), and the disease was managed with topical preparations. Initial improvement was marred by relapse of acute pustulosis, now more in keeping with terbinafine-induced pustular psoriasis (PP), which was successfully treated with acitretin. This case highlights the difficulty of differentiating between AGEP and PP.

Robotic radical trachelectomy for preservation of fertility in early cervical cancer: case series and description of technique.

STUDY OBJECTIVE: To present a case series of robotic radical trachelectomy for preservation of fertility in early cervical cancer. DESIGN: Descriptive study. DESIGN: Canadian Task Force Classification III. SETTING: Tertiary referral center. PATIENTS: Women with early cervical cancer who wish to maintain fertility potential. INTERVENTIONS: Robotic radical trachelectomy with bilateral pelvic lymphadenectomy. The procedure also uses a cervical cerclage and permits preservation of the ascending branches of the uterine arteries to the uterus. MEASUREMENTS AND MAIN RESULTS: Report of the technique, and operative and immediate postoperative complications. To date, 6 women have undergone robotic radical trachelectomy, with preservation of the uterine arteries in all patients. One patient underwent completion hysterectomy when the frozen section of the trachelectomy margin revealed inability to clear the cancer. Five women have maintained their fertility potential after the procedure. CONCLUSION: Robotic radical trachelectomy is a feasible technique that permits radical removal of the cervix. Improved visualization with the robot and fine dissection permissible with the instrument facilitate this procedure.

Relationship of perception of radon as a health risk and willingness to engage in radon testing and mitigation.

PURPOSE/OBJECTIVES: To gather data on radon levels and determine correlations among subjects' characteristics, willingness to test for radon, and perceptions of radon as a health risk. DESIGN: Descriptive correlational. SETTING: Rural DeKalb County in northern Illinois. SAMPLE: 473 respondents from a group of 1,620 randomly selected county residences. METHODS: Participants were surveyed via telephone using the Community Radon Program questionnaire. Radon measurements were taken with home radon test kits. MAIN RESEARCH VARIABLES: Gender, income, age, educational level, smoking status, race, home ownership, willingness to test for radon, and radon risk perception. FINDINGS: Most participants were familiar with radon but did not view it as an immediate health hazard and would not have screened for radon on their own. 88% of the radon measurements exceeded the U.S. Environmental Protection Agency's moderate risk potential level, and 53% exceeded the action level (i.e., 4 pCi/L). CONCLUSIONS: Perception of radon as a health risk was correlated positively with planning to conduct further radon testing and to employ radon mitigation methods. More research is needed on people's willingness to obtain radon emission levels and the cancer rates in areas that have high potential for radon. IMPLICATIONS FOR NURSING: According to the environmental literature, the effect of household radon emissions on the development of lung cancer is as great a health risk as secondhand smoke. Virtually no nursing literature on the subject has been published. As the primary source of health information in many rural counties, nurses, especially public health nurses, are at the forefront in public health educational efforts. Nurses are the most likely healthcare professionals to enter patients' homes and can play a significant role in disseminating information about radon as a potential carcinogen.

Low exhaled nitric oxide and a polymorphism in the NOS I gene is associated with acute chest syndrome.

Abnormalities of nitric oxide metabolism have been implicated in the pathogenesis of acute chest syndrome in subjects with sickle cell anemia. It is not known whether exhaled nitric oxide levels (FE(NO)) are abnormal in children with a history of the acute chest syndrome (ACS). We compared FE(NO), plasma nitric oxide metabolites (NO(x)), serum arginine and citrulline levels, and the number of AAT repeats in intron 20 of NOS I in subjects with sickle cell disease (SCD) and a history of at least one episode of ACS (ACS(+), n = 13), subjects with SCD and no prior history of ACS (ACS(-), n = 7), and healthy children (HC, n = 6). Mean +/- SD FE(NO) (ppb) was lower in ACS(+) than in ACS(-) and HC: (10.4 +/- 4.3 versus 23.4 +/- 6.1 p = 0.002] and 30.4 +/- 15.8 [p = 0.0001], respectively). Plasma NO(x) (microM) were similar in all three groups (37.3 +/- 19.4, 33.0 +/- 13.2, 44.7 +/- 7.8, respectively). Arginine and citrulline levels (microM) did not differ between ACS(+) and ACS(-) groups. Spirometric data revealed a mildly diminished FEV(1) and FVC in ACS(+) that was statistically different from HC but not ACS(-): (FEV(1) as % of predicted for ACS(+), ACS(-), and HC; 83 +/- 17 versus 87 +/- 16 versus 102 +/- 16, respectively, p < 0.05 between ACS(+) and HC). The level of FE(NO) was significantly associated with the sum of AAT repeats in intron 20 of NOS I gene alleles. The correlation coefficient (r) was 0.62 (p < 0.005). We conclude that FE(NO) levels are significantly reduced in subjects who have a history of ACS and that the FE(NO) levels are significantly correlated with the number of NOS I AAT repeats. FE(NO) is a sensitive marker and may be a predictor of ACS prone children.

Exhaled nitric oxide as an indicator of severity of asthmatic inflammation.

Traditional assessment of severity of asthma relies on an evaluation of signs and symptoms and pulmonary function tests. These pulmonary function tests, such as peak expiratory flow rates, forced vital capacity, and forced expiratory flow rates, are indirect measures of airway caliber only, and not inflammation. Since asthma is an inflammatory disease, a measure of the degree of inflammation would be helpful in quantitating severity and titrating of anti-inflammatory therapy. A noninvasive method for measuring pulmonary inflammation would therefore be helpful to assist the emergency physician in initial treatment and assist in titration of anti-inflammatory therapy during repeat visits. Exhaled nitric oxide (NO) assays are convenient and practical and may fulfill this role. In this review, we discuss the role of NO in asthmatic inflammation and the role that exhaled NO values may play in the emergency management of asthma.

FE(NO): relationship to exhalation rates and online versus bag collection in healthy adolescents.

Measurement of exhaled nitric oxide (FE(NO)) is a noninvasive and practical method for assessing airway inflammation. We conducted this investigation to determine the most appropriate flow rate for FE(NO) measurement and to obtain normal values for FE(NO). We determined which expiratory flow was easy to sustain, generated reproducible values, and provided good correlation between offline and online measurements. Thirty-two healthy subjects (15- 18 yr old) underwent spirometry and FE(NO) measurements, using a chemiluminescent NO analyzer at expiratory flow rates of 46, 31, 23, 15, 10, 7, 5, and 4 ml/s. The major findings were as follows: (1) FE(NO) increased as flow rates decreased, with strong correlation between FE(NO) values and flow rates at the four highest flows (0. 85- 0.93, p < 0.001); (2) there were no significant differences and good agreement between offline bag and online FE(NO) values for the four highest flows (p < 0.09-0.83); (3) online FE(NO) values increased with age 15-17 yr at all flow rates, but decreased at age 18 yr; and (4) using multiple regression, significant predictors of FE(NO) were flow, body surface area, age, and FEF(25-75). On the basis of these results, we provide FE(NO) values for healthy adolescents and propose that the ideal flow rate for children is between 30 and 50 ml/s.

Exhaled nitric oxide measurements in childhood asthma: techniques and interpretation.

In this review, we outline the role of nitric oxide in airway inflammation in children with asthma. We also discuss the various methods reported for measuring exhaled nitric oxide and provide some insight as to the pros and cons and pitfalls of these techniques. Guidelines for measurements of exhaled nitric oxide based on our experience are provided, as well as suggestions for the use of this technique as a new "airway inflammation test."

The effect of short-term administration of theophylline on erythropoietin levels in healthy adults.

A previous study demonstrated suppression of erythropoietin production in patients treated with long-term theophylline. This effect could exacerbate anemia of prematurity in neonates receiving this drug for apnea of prematurity. In this pilot project we evaluated the effect of short-term theophylline administration on serum erythropoietin in healthy adults. Six subjects were given a bolus followed by a continuous infusion of theophylline targeted to achieve a serum level of at least 10 micrograms/ml, followed by oral theophylline for 36 hours. Serum erythropoietin and theophylline levels were measured before, during, and after drug infusion. Complete hemograms were performed before and after completion of the infusion. No significant changes in serum erythropoietin levels were seen at any time (F = 1.57, p = 0.12). Hematologic values also remained unaltered. We conclude that short-term administration of theophylline is unlikely to have any effect on serum erythropoietin levels in healthy adults.