Correction: Pulsed moxifloxacin for the prevention of exacerbations of chronic obstructive pulmonary disease: a randomized controlled trial

BACKGROUND: Acute exacerbations contribute to the morbidity and mortality associated with chronic obstructive pulmonary disease (COPD). This proof-of-concept study evaluates whether intermittent pulsed moxifloxacin treatment could reduce the frequency of these exacerbations. METHODS: Stable patients with COPD were randomized in a double-blind, placebo-controlled trial to receive moxifloxacin 400 mg PO once daily (N = 573) or placebo (N = 584) once a day for 5 days. Treatment was repeated every 8 weeks for a total of six courses. Patients were repeatedly assessed clinically and microbiologically during the 48-week treatment period, and for a further 24 weeks' follow-up. RESULTS: At 48 weeks the odds ratio (OR) for suffering an exacerbation favoured moxifloxacin: per-protocol (PP) population (N = 738, OR 0.75, 95% confidence interval (CI) 0.565-0.994, p = 0.046), intent-to-treat (ITT) population (N = 1149, OR 0.81, 95% CI 0.645-1.008, p = 0.059), and a post-hoc analysis of per-protocol (PP) patients with purulent/mucopurulent sputum production at baseline (N = 323, OR 0.55, 95% CI 0.36-0.84, p = 0.006).There were no significant differences between moxifloxacin and placebo in any pre-specified efficacy subgroup analyses or in hospitalization rates, mortality rates, lung function or changes in St George's Respiratory Questionnaire (SGRQ) total scores. There was, however, a significant difference in favour of moxifloxacin in the SGRQ symptom domain (ITT: -8.2 vs -3.8, p = 0.009; PP: -8.8 vs -4.4, p = 0.006). Moxifloxacin treatment was not associated with consistent changes in moxifloxacin susceptibility. There were more treatment-emergent, drug related adverse events with moxifloxacin vs placebo (p < 0.001) largely due to gastrointestinal events (4.7% vs 0.7%). CONCLUSIONS: Intermittent pulsed therapy with moxifloxacin reduced the odds of exacerbation by 20% in the ITT population, by 25% among the PP population and by 45% in PP patients with purulent/mucopurulent sputum at baseline. There were no unexpected adverse events and there was no evidence of resistance development. TRIAL REGISTRATION: ClinicalTrials.gov number, NCT00473460 (ClincalTrials.gov)

HLA-A and HLA-DRB1 amino acid polymorphisms are associated with susceptibility and protection to pulmonary tuberculosis in a Greek population

Background: Pulmonary tuberculosis remains the single deadliest infectious disease causing high mortality in humans leading to 1.4. million deaths annually. Inherited genetic factors may explain why some people resist infection more successfully than others. Methods: The polymorphisms of HLA-class I (-A, -B) and class II (-DRB1, -DQB1) genes have been evaluated using DNA-based typing in a population of 86 non-immunosuppressed, unrelated Greek patients with PTb and 46 healthy unrelated people without a history of PTb, who were all tested purified protein derivative positive (&amp;gt;14. mm). Results: The HLA-A R114 and HLA-DRβN37 residues are associated with susceptibility. They operate independently from each other and their effect is detected when the population is evaluated for their concurrent presence (A R114 positive or DRβN37 positive or A R114 and DRβN37 positive). Furthermore the HLA-A S77 appears to have a protective role, however in the presence of the DRβN37, the A-S77 does not exert its protective effect. Conclusion: The HLA residues A-S77, A-R114 and DRβN37 in combination with PTb antigenic elements possibly modulate T-cell responses against MTb that lead to either protection or susceptibility. The HLA-A and -DRB1-dependent T-cell networks may interact among themselves and influence each other resulting in different PTb phenotypes. © 2012 American Society for Histocompatibility and Immunogenetics

Irinotecan plus gemcitabine vs irinotecan for the second-line treatment of patients with advanced non-small-cell lung cancer pretreated with docetaxel and cisplatin: a multicentre, randomised, phase II study

To compare irinotecan (CPT-11) + gemcitabine vs CPT-11 alone as second-line treatment for patients with advanced non-small cell lung cancer (NSCLC) progressing after docetaxel-cisplatinum- based therapy. A total of 147 evaluable, pretreated patients, with NSCLC, received either gemcitabine (1000 mg m(-2), days 1 and 8) + CPT-11 (300 mg m(-2), day 8) (Group A, n = 76) or CPT-11 (300 mg m(-2), day 1) (Group B, n = 71), every 3 weeks. All patients were evaluable for response and toxicity. The objective response rate was 18.4% (95% CI: 9.71-27.14%) and 4.2% (95% CI: 0-8.90%) (P = 0.009) for groups A and B, respectively. No significant differences between the two groups in terms of the median duration of response, time to tumour progression, overall survival and 1-year survival were observed. The CPT-11/gemcitabine regimen significantly improved the patients’ quality of life (’general mood today’ (P = 0.014), ‘coughing’ (P = 0.003) and ‘intensity of symptoms’ (P = 0.034)) compared with CPT-11. More cycles had to be delayed (P = 0.001) and required prophylactic growth factor support (P = 0.001) in Group A than B. Three (3.9%) patients in Group A and eight (11.3%) in Group B developed febrile neutropenia (P = 0.09); one patient died of sepsis in each group. Three additional (Group A, n = 1; Group B, n 2) treatment-related deaths were observed. Grade 3-4 haematologic toxicity was comparable in the two groups except anaemia (P = 0.03 in favour of CPT-11). Other nonhaematologic toxicities were mild and similar in the two groups. CPT-11 + gemcitabine resulted in a higher response rate and better control of disease-related symptoms than CPT-11 alone, but without any improvement in the overall survival

Vinorelbine plus cisplatin versus docetaxel plus gemcitabine in advanced non-small-cell lung cancer: A phase III randomized trial

Purpose To compare the activity and tolerability of docetaxel/gemcitabine (DG) and vinorelbine/cisplatin (VC) combinations in chemotherapy-naive non-small-cell lung cancer (NSCLC) patients. Patients and Methods Patients with advanced NSCLC were randomly assigned to receive either DG (gemcitabine 1,000 mg/m(2) [days 1 and 8] plus docetaxel 100 mg/m(2) [day 8]) or VC (vinorelbine 30 mg/m(2) [days 1 and 8] plus cisplatin 80 mg/m(2) [day 8]) and prophylactic recombinant human granulocyte colony-stimulating factor (150 mu g/m(2) subcutaneously [day 9 through 15]) every 3 weeks. Results A total of 413 randomly assigned patients were analyzed for response and toxicity (DG, n = 197; VC, In = 192). Median survival was 9.0 and 9.7 months (P = .965) for DG and VC arms, respectively; the corresponding 1-year survival rates were 34.3% and 40.8%, respectively. Overall response rate was 30% (95% CI, 23.9% to 36.3%) and 39.2% (95% CI, 32.5% to 45.9%; P = .053) for DG and VC, respectively. Toxicity was as follows (DG v VC): grade 2 to 4 anemia, 34% v 55% (P = .0001); grade 3 to 4 neutropenia, 16% v 37% (P = .0001); febrile neutropenia, 6% v 11% (P = .009); and grade 3 to 4 nausea and vomiting, 1% v 15% (P = .003). Nephrotoxicity occurred in 8% and ototoxicity in 2% of VC-treated patients. There were five and six treatment-related deaths in the DG and VC arms, respectively. Quality of life was improved in DG but not in VC patients. Conclusion Although the two regimens produced comparable overall survival, the DG regimen had a better toxicity profile. Therefore, DG could be used in the first-line setting of advanced NSCLC, especially for patients who cannot tolerate cisplatin