The impact of endoscopist performance and patient factors on distal adenoma detection and colorectal cancer incidence.

BACKGROUND: High quality endoscopy is key for detecting and removing precursor lesions to colorectal cancer (CRC). Adenoma detection rates (ADRs) measure endoscopist performance. Improving other components of examinations could increase adenoma detection. AIMS: To investigate how endoscopist performance at flexible sigmoidoscopy (FS) affects adenoma detection and CRC incidence. METHODS: Among 34,139 participants receiving FS screening by the main endoscopist at one of 13 centres in the UK FS Screening Trial, median follow-up was 17 years. Factors examined included family history of CRC, bowel preparation quality, insertion and withdrawal time, bowel segment reached, patient pain and ADR. Odds ratios (OR) for distal adenoma detection were estimated by logistic regression. Hazard ratios (HR) for distal CRC incidence were estimated by Cox regression. RESULTS: At screening, 4,104 participants had distal adenomas detected and 168 participants developed distal CRC during follow-up. In multivariable models, a family history of CRC (yes vs. no: OR 1.40, 95%CI 1.21-1.62), good or adequate bowel preparation quality (vs. excellent: OR 0.84, 95%CI 0.74-0.95; OR 0.56, 95%CI 0.49-0.65, respectively) and longer insertion and withdrawal times (≥ 4.00 vs. < 2.00 min: OR 1.96, 95%CI 1.68-2.29; OR 32.79, 95%CI 28.22-38.11, respectively) were associated with adenoma detection. Being screened by endoscopists with low or intermediate ADRs, compared to high ADRs, was positively associated with CRC incidence (multivariable: HR 4.71, 95%CI 2.65-8.38; HR 2.16, 95%CI 1.22-3.81, respectively). CONCLUSIONS: Bowel preparation quality and longer insertion and withdrawal time are key for improving distal adenoma detection. Higher ADRs were associated with a lower risk of distal CRC.

Physiological effects of titrated oxygen via nasal high-flow cannulae in COPD exacerbations: A randomized controlled cross-over trial.

BACKGROUND AND OBJECTIVE: Increased arterial carbon dioxide tension (PaCO2 ) is an important complication of acute exacerbations of COPD. The effects of nasal high-flow cannulae (NHF) on PaCO2 in patients with COPD exacerbations, and whether this therapy should be used in this clinical situation, are less certain. We aimed to investigate the effect of NHF on PaCO2 in patients admitted to hospital with a COPD exacerbation. METHODS: We performed a single-centre randomized controlled cross-over trial in 24 hospital inpatients with acute exacerbations of COPD receiving oxygen via standard nasal prongs (SNPs). Patients received both supplemental oxygen via NHF (35 L/min) and SNP for 30 min each, with oxygen titrated to maintain the patient's baseline oxygen saturation, measured by pulse oximetry (SpO2 ). Interventions were administered in random order with a minimum 15-min washout between interventions. The primary outcome was difference in transcutaneous carbon dioxide tension (PtCO2 ) at 30 min adjusted for time zero. RESULTS: The difference in PtCO2 adjusted for time zero was lower after 30 min for NHF compared with SNP (-1.4 mm Hg (95% CI: -2.2 to -0.6), P = 0.001). There was no difference in SpO2 at 30 min (-0.02% (95% CI: -0.8 to 0.7), P = 0.96). The reduction in respiratory rate for NHF at 30 min was not statistically significant (-2.0 breaths/min (95% CI: -4.5 to 0.4), P = 0.099). CONCLUSION: Short-term use of NHF results in a small reduction in PtCO2 compared with SNP in patients with acute exacerbations of COPD, but whether this is clinically significant is uncertain.

RCT of the effect of berryfruit polyphenolic cultivar extract in mild steroid-naive asthma: a cross-over, placebo-controlled study.

OBJECTIVE: There is preclinical evidence that consumption of berryfruit extract may reduce chronic airways inflammation and modify airway remodelling in allergen-induced models of lung inflammation. We investigated the effect of berryfruit extract on the fractional expired nitric oxide (FeNO), a biomarker of eosinophilic airways inflammation, in adults with steroid-naïve asthma. DESIGN: Randomised placebo-controlled cross-over double-blind trial. SETTING: Single-centre community-based trial. PARTICIPANTS: 28 steroid-naïve mild asthmatics with Feno >40 ppb, of whom 25 completed both study interventions. INTERVENTIONS: Participants were randomised to receive, according to the cross-over design, 100 mg berryfruit polyphenolic extract (BFPE) or placebo for 4 weeks, with a 4-week washout period between the interventions. PRIMARY OUTCOME MEASURE: The primary outcome variable was FeNO at 4 weeks, analysed by a mixed linear model, with a random effect for participant and baseline FeNo as a covariate. RESULTS: The mean (SD) natural logarithm transformed (ln) FeNO after 4 weeks of treatment for the BFPE and placebo groups was 4.28 (0.47) and 4.22 (0.47), respectively. The paired change from baseline mean (SD) BFPE minus placebo ln FeNO was -0.03 (0.39), N=25. The mixed linear model estimate, with baseline covariate adjustment, difference in ln FeNO, was -0.002 (95% CI -0.15 to 0.14), p=0.98. This is equivalent to a ratio of geometric mean FeNO of 1.0 (95% CI 0.86 to 1.15). CONCLUSIONS: In steroid-naïve participants with mild asthma and elevated FeNO, there was no effect of BFPE on FeNO, a biomarker of eosinophilic airways inflammation. Caution is required in the extrapolation of apparent benefit in murine models of lung eosinophilia to clinical efficacy in patients with asthma. TRIAL REGISTRATION NUMBER: ANZCTR: 12613000451707; Results.

Randomised, double-blind, placebo-controlled, cross-over single dose study of the bronchodilator duration of action of combination fluticasone furoate/vilanterol inhaler in adult asthma.

BACKGROUND: Fluticasone furoate (FF)/vilanterol (VI) is a once-daily maintenance treatment for asthma and chronic obstructive pulmonary disease. The duration of bronchodilation beyond 24 h has not been determined previously. METHODS: Adults aged 18-65 (n = 32), with asthma and reversibility to salbutamol (≥15% and ≥200 mL increase in forced expiratory volume in 1 s [FEV1]) participated in a double-blind, placebo-controlled, crossover study. Patients were admitted to a clinical trials unit for 72 h, and inhaled, in random order, placebo or FF/VI 100/25 mcg via ELLIPTA dry powder inhaler on two occasions 7-14 days apart. FEV1 was measured at baseline, 15 and 30 min, 1, 2, 4, 12, 24, 36, 48, 60, and 72 h. The differences in change in FEV1 from baseline between treatments and corresponding two-sided 95% confidence intervals (CI) were calculated at each time point. FINDINGS: FF/VI produced a rapid onset of bronchodilation (adjusted mean difference in change from baseline in FEV1 versus placebo at 15 min, 252 mL [95% CI 182-322]). Maximum bronchodilation was observed at 12 h (adjusted mean difference in the change from baseline in FEV1, 383 mL [95% CI 285-481]). Bronchodilation was maintained throughout the 72-h assessment period (adjusted mean difference in the change in FEV1 from baseline at 72 h, 108 mL (95% CI 15-200]). FF/VI was well tolerated and no serious side effects were reported. INTERPRETATION: A single dose of FF/VI 100/25 mcg showed evidence of a 72-h bronchodilator duration of action in adults with asthma.