Lung cancer stage-shift following a symptom awareness campaign.

BACKGROUND: Lung cancer outcomes in the UK are worse than in many other developed nations. Symptom awareness campaigns aim to diagnose patients at an earlier stage to improve cancer outcomes. METHODS: An early diagnosis campaign for lung cancer commenced in Leeds, UK in 2011 comprising public and primary-care facing components. Rates of community referral for chest X-ray and lung cancer stage (TNM seventh edition) at presentation were collected from 2008 to 2015. Linear trends were assessed by χ2 test for trend in proportions. Headline figures are presented for the 3 years pre-campaign (2008-2010) and the three most recent years for which data are available during the campaign (2013-2015). FINDINGS: Community-ordered chest X-ray rates per year increased from 18 909 in 2008-2010 to 34 194 in 2013-2015 (80.8% increase). A significant stage shift towards earlier stage lung cancer was seen (χ2(1)=32.2, p<0.0001). There was an 8.8 percentage point increase in the proportion of patients diagnosed with stage I/II lung cancer (26.5% pre-campaign vs 35.3% during campaign) and a 9.3% reduction in the absolute number of patients diagnosed with stage III/IV disease (1254 pre-campaign vs 1137 during campaign). INTERPRETATION: This is the largest described lung cancer stage-shift in association with a symptom awareness campaign. A causal link between the campaign and stage-shift cannot be proven but appears plausible. Limitations of the analysis include a lack of contemporary control population.

Optimising water treatment practices for the removal of Anabaena circinalis and its associated metabolites, geosmin and saxitoxins.

The cyanobacterium Anabaena circinalis has the ability to co-produce geosmin and saxitoxins, compounds which can compromise the quality of drinking water. This study provides pertinent information in optimising water treatment practices for the removal of geosmin and saxitoxins. In particular, it demonstrates that pre-oxidation using potassium permanganate could be applied at the head of water treatment plants without releasing intracellular geosmin and saxitoxins from A. circinalis. Furthermore, powdered activated carbon (PAC) was shown to be an effective treatment barrier for the removal of extracellular (dissolved) geosmin and saxitoxins, with similar adsorption trends of both compounds. The relative removal of the saxitoxins compared with geosmin was determined to be 0.84 +/- 0.27, which implies that saxitoxin removal with PAC can be estimated to be approximately 60 to 100% of the removal of geosmin under equivalent conditions. Chlorine was shown to be effective for the oxidation of the saxitoxins with CT values of approximately 30 mg min l(-1) required for greater than 90% destruction of the saxitoxins.

Risk of malignancy in pulmonary nodules: A validation study of four prediction models.

OBJECTIVES: Clinical prediction models assess the likelihood of malignancy in pulmonary nodules detected by computed tomography (CT). This study aimed to validate four such models in a UK population of patients with pulmonary nodules. Three models used clinical and CT characteristics to predict risk (Mayo Clinic, Veterans Association, Brock University) with a fourth model (Herder et al. [4]) additionally incorporating (18)Fluorine-Fluorodeoxyglucose (FDG) avidity on positron emission tomography-computed tomography (PET-CT). MATERIALS AND METHODS: The likelihood of malignancy was calculated for patients with pulmonary nodules (4-30mm diameter) and data used to calculate the area under the receiver operating characteristic curve (AUC) for each model. The models were used in a restricted cohort of patients based on each model's exclusion criteria and in the total cohort of all patients. RESULTS: Two hundred and forty-four patients were studied, of whom 139 underwent FDG PET-CT. Ninety-nine (40.6%) patients were subsequently confirmed to have malignant nodules (33.2% primary lung cancer, 7.4% metastatic disease). The Mayo and Brock models performed similarly (AUC 0.895 and 0.902 respectively) and both were significantly better than the Veterans Association model (AUC 0.735, p<0.001 and p=0.002 respectively). In patients undergoing FDG PET-CT, the Herder model had significantly higher accuracy than the other three models (AUC 0.924). When the models were tested on all patients in the cohort (i.e. including those outside the original model inclusion criteria) AUC values were reduced, yet remained high especially for the Herder model (AUC 0.916). For sub-centimetre nodules, AUC values for the Mayo and Brock models were 0.788 and 0.852 respectively. CONCLUSIONS: The Mayo and Brock models showed good accuracy for determining likelihood of malignancy in nodules detected on CT scan. In patients undergoing FDG PET-CT for nodule evaluation, the highest accuracy was seen for the model described by Herder et al. incorporating FDG avidity.

Adequacy of endobronchial ultrasound transbronchial needle aspiration samples in the subtyping of non-small cell lung cancer.

INTRODUCTION: The histological subtyping of non small cell lung cancer (NSCLC) is important in the selection of the optimal treatment for patients with advanced disease. There are now important differences in the chemotherapy regimens used for squamous and non-squamous cancers. Non-squamous cancers (particularly adenocarcinomas) are also suitable for targeted therapy if the epidermal growth factor receptor (EGFR) genetic mutation is present. Diagnosis is frequently made by fine needle aspiration from lymph node metastases. We have evaluated the adequacy of material obtained by EBUS-TBNA for subtyping of NSCLC. METHODS: All EBUS-TBNA procedures performed at Leeds Teaching Hospitals between February 2009 and November 2011 were analysed. Data was collected on the indication, final cytological diagnosis and whether EGFR mutation testing was possible. We analysed the data to establish our rate of NSCLC-NOS diagnoses and to determine the technical success of EGFR testing. RESULTS: Data from 391 procedures was analysed. The indication was staging of malignancy in 345 patients and suspected non-malignant disease in 48 patients. Malignant disease was diagnosed in 204 patients (53.7%), small cell 43, squamous cell 64, adenocarcinoma 40, adenosquamous 2, large cell 12, NSCLC-NOS 31 and malignant disease of non-lung primary 12. EBUS-TBNA identified 149 patients with NCSLC. Subtyping could be obtained in 118 (79.2%). The number of patients with a diagnosis of NSCLC NOS on EBUS-TBNA was 31 (20.8%, 95% CI 15-28%). Of the 204 specimens with a malignant diagnosis immunohistochemistry was performed in 149 (73.0%). It was not performed in 52 (25.5%) cases and there was insufficient material available in 3 (1.5%) cases. EGFR testing was requested in 36 patients. Our test success rate for EGFR mutation testing on EBUS-TBNA samples was 88.8% (95%CI 74.7-95.6%). CONCLUSION: EBUS-TBNA samples when made into cell blocks and subjected to a panel of immunohistochemical stains returned adequate tissue for cytological analysis in over 97% of cases, with an NOS rate of 20.8%. We have also shown that cytology specimens are adequate for EGFR mutation testing in over 88% of cases. We conclude that EBUS-TBNA is an accurate diagnostic test both for determining NSCLC subtype and performing EGFR mutation analysis to tailor treatment in lung cancer patients.

In-vitro characterisation of the nebulised dose during non-invasive ventilation.

OBJECTIVES: Non-invasive ventilation (NIV) with nebulised bronchodilators helps some patients to maintain effective ventilation. However, the position of the nebuliser in the ventilation circuit may affect lung delivery. METHODS: We placed the nebuliser proximal (A) and distal (B) to a breathing simulator in a standard NIV circuit with inspiratory (I) and expiratory (E) pressures of 20 and 5 cm H(2)O, 1 : 3 I : E ratio, 15 breaths/min and a tidal volume of 500 ml. Five milligrams of terbutaline solution was nebulised using an Aeroneb Pro (AERO) and a Sidestream (SIDE) nebuliser. The fate of the nebulised dose was determined and the aerodynamic droplet characteristics were measured using a cooled Next Generation Impactor. KEY FINDINGS: More terbutaline was entrained on the inhalation filter in position A than in position B (P < 0.001) for both nebulisers. These amounts were greater (P < 0.001) for AERO than SIDE due to a smaller (P < 0.001) residual volume. The mean (SD) fine particle doses for AEROA, AEROB, SIDEA and SIDEB were 1.31 (0.2), 1.13 (0.14), 0.56 (0.03) and 0.39 (0.13) mg. These amounts from AEROA were significantly greater (P < 0.001) than those of the other three methods. CONCLUSIONS: The results highlight the differences between nebulisers and the influence on the placement of the nebuliser in the NIV circuit.