Download the Free Unbound MEDLINE PubMed App to your smartphone or tablet.
Available for iPhone, iPad, iPod touch, and Android.
- Inhaled, dual release liposomal ciprofloxacin in non-cystic fibrosis bronchiectasis (ORBIT-2): a randomised, double-blind, placebo-controlled trial. [JOURNAL ARTICLE]
- Thorax 2013 May 16.
BACKGROUND:The delivery of antipseudomonal antibiotics by inhalation to Pseudomonas aeruginosa-infected subjects with non-cystic fibrosis (CF) bronchiectasis is a logical extension of treatment strategies successfully developed in CF bronchiectasis. Dual release ciprofloxacin for inhalation (DRCFI) contains liposomal ciprofloxacin, formulated to optimise airway antibiotic delivery.
METHODS:Phase II, 24-week Australian/New Zealand multicentre, randomised, double-blind, placebo-controlled trial in 42 adult bronchiectasis subjects with ≥2 pulmonary exacerbations in the prior 12 months and ciprofloxacin-sensitive P aeruginosa at screening. Subjects received DRCFI or placebo in three treatment cycles of 28 days on/28 days off. The primary outcome was change in sputum P aeruginosa bacterial density to the end of treatment cycle 1 (day 28), analysed by modified intention to treat (mITT). Key secondary outcomes included safety and time to first pulmonary exacerbation-after reaching the pulmonary exacerbation endpoint subjects discontinued study drug although remained in the study.
RESULTS:DRCFI resulted in a mean (SD) 4.2 (3.7) log10 CFU/g reduction in P aeruginosa bacterial density at day 28 (vs -0.08 (3.8) with placebo, p=0.002). DRCFI treatment delayed time to first pulmonary exacerbation (median 134 vs 58 days, p=0.057 mITT, p=0.046 per protocol). DRCFI was well tolerated with a similar incidence of systemic adverse events to the placebo group, but fewer pulmonary adverse events.
CONCLUSIONS:Once-daily inhaled DRCFI demonstrated potent antipseudomonal microbiological efficacy in adults with non-CF bronchiectasis and ciprofloxacin-sensitive P aeruginosa. In this modest-sized phase II study, DRCFI was also well tolerated and delayed time to first pulmonary exacerbation in the per protocol population.
- Incremental value of T-SPOT.TB for diagnosis of active pulmonary tuberculosis in children in a high-burden setting: a multivariable analysis. [JOURNAL ARTICLE]
- Thorax 2013 May 14.
INTRODUCTION:Interferon γ release assays (IGRAs) are increasingly used for tuberculosis (TB) infection, but their incremental value beyond patient demographics, clinical signs and conventional tests for active disease has not been evaluated in children.
METHODS:The incremental value of T-SPOT.TB was assessed in 491 smear-negative children from two hospitals in Cape Town, South Africa. Bayesian model averaging was used to select the optimal set of patient demographics and clinical signs for predicting culture-confirmed TB. The added value of T-SPOT.TB over and above patient characteristics and conventional tests was measured using statistics such as the difference in the area under the receiver operating characteristic curve (AUC), the net reclassification improvement (NRI) and the integrated discrimination improvement (IDI).
RESULTS:Cough longer than 2 weeks, fever longer than 2 weeks, night sweats, malaise, history of household contact and HIV status were the most important predictors of culture-confirmed TB. Binary T-SPOT.TB results did not have incremental value when added to the baseline model with clinical predictors, chest radiography and the tuberculin skin test. The AUC difference was 3% (95% CI 0% to 7%). Using risk cut-offs of <10%, 10-30% and >30%, the NRI was 7% (95% CI -8% to 31%) but the CI included the null value. The IDI was 3% (95% CI 0% to 11%), meaning that the average predicted probability across all possible cut-offs improved marginally by 3%.
CONCLUSIONS:In a high-burden setting, the T-SPOT.TB did not have added value beyond clinical data and conventional tests for diagnosis of TB disease in smear-negative children.
- SKUP3 randomised controlled trial: polysomnographic results after uvulopalatopharyngoplasty in selected patients with obstructive sleep apnoea. [JOURNAL ARTICLE]
- Thorax 2013 May 5.
OBJECTIVE:To assess the 6-month efficacy of uvulopalatopharyngoplasty (UPPP) compared with expectancy in selected patients with obstructive sleep apnoea syndrome (OSAS).
DESIGN:A prospective single-centre randomised controlled trial with two parallel arms stratified by Friedman stage and body mass index (BMI).
PARTICIPANTS:65 consecutive patients with moderate to severe OSAS (apnoea-hypopnoea index (AHI) ≥15 events/h sleep), BMI <36 kg/m(2), Epworth sleepiness scale ≥8, Friedman stage I or II.
INTERVENTION:Surgical treatment with UPPP. The control group underwent UPPP after a delay of 6 months.
OUTCOMES:Changes in AHI and other polysomnography parameters at baseline compared with the 6-month follow-up.
RESULTS:All patients (32 in the intervention group and 33 in the control group) completed the trial. The mean (SD) AHI in the intervention group decreased significantly (p<0.001) by 60% from 53.3 (19.7) events/h to 21.1 (16.7) events/h . In the control group the mean AHI decreased by 11% from 52.6 (21.7) events/h to 46.8 (22.8) events/h, with a significant difference between the groups (p<0.001). The mean time in the supine position and the BMI were unchanged in both groups. Subgroup analyses for Friedman stage, BMI group and tonsil size all showed significant reductions in AHI in the intervention group compared with controls. There were no severe complications after surgery.
CONCLUSIONS:This trial demonstrates the efficacy of UPPP in treating selected patients with OSAS with a mean reduction in AHI of 60% compared with 11% in controls, a highly significant and clinically relevant difference between the groups. TRIAL REGISTRATION NUMBER: NCT01659671.
- P38 inhibition in COPD; cautious optimism. [JOURNAL ARTICLE]
- Thorax 2013 Apr 23.
- GOLD classifications and mortality in chronic obstructive pulmonary disease: the HUNT Study, Norway. [JOURNAL ARTICLE]
- Thorax 2013 Apr 23.