Determining the impact of an artificial intelligence tool on the management of pulmonary nodules detected incidentally on CT (DOLCE) study protocol: a prospective, non-interventional multicentre UK study.

INTRODUCTION: In a small percentage of patients, pulmonary nodules found on CT scans are early lung cancers. Lung cancer detected at an early stage has a much better prognosis. The British Thoracic Society guideline on managing pulmonary nodules recommends using multivariable malignancy risk prediction models to assist in management. While these guidelines seem to be effective in clinical practice, recent data suggest that artificial intelligence (AI)-based malignant-nodule prediction solutions might outperform existing models. METHODS AND ANALYSIS: This study is a prospective, observational multicentre study to assess the clinical utility of an AI-assisted CT-based lung cancer prediction tool (LCP) for managing incidental solid and part solid pulmonary nodule patients vs standard care. Two thousand patients will be recruited from 12 different UK hospitals. The primary outcome is the difference between standard care and LCP-guided care in terms of the rate of benign nodules and patients with cancer discharged straight after the assessment of the baseline CT scan. Secondary outcomes investigate adherence to clinical guidelines, other measures of changes to clinical management, patient outcomes and cost-effectiveness. ETHICS AND DISSEMINATION: This study has been reviewed and given a favourable opinion by the South Central-Oxford C Research Ethics Committee in UK (REC reference number: 22/SC/0142).Study results will be available publicly following peer-reviewed publication in open-access journals. A patient and public involvement group workshop is planned before the study results are available to discuss best methods to disseminate the results. Study results will also be fed back to participating organisations to inform training and procurement activities. TRIAL REGISTRATION NUMBER: NCT05389774.

Risk of Mortality Following Surgery in Patients With a Previous Cardiovascular Event.

Importance: There is a lack of consensus regarding the interval of time-dependent postoperative mortality risk following acute coronary syndrome or stroke. Objective: To determine the magnitude and duration of risk associated with the time interval between a preoperative cardiovascular event and 30-day postoperative mortality. Design, Setting, and Participants: This is a longitudinal retrospective population-based cohort study. This study linked data from the Hospital Episode Statistics for National Health Service England, Myocardial Ischaemia National Audit Project and the Office for National Statistics mortality registry. All adults undergoing a National Health Service-funded noncardiac, nonneurologic surgery in England between April 1, 2007, and March 31, 2018, registered in Hospital Episode Statistics Admitted Patient Care were included. Data were analyzed from July 2021 to July 2022. Exposure: The time interval between a previous cardiovascular event (acute coronary syndrome or stroke) and surgery. Main Outcomes and Measures: The primary outcome was 30-day all-cause mortality. Secondary outcomes were postoperative mortality at 60, 90, and 365 days. Multivariable logistic regression models with restricted cubic splines were used to estimate adjusted odds ratios. Results: There were 877 430 patients with and 20 582 717 without a prior cardiovascular event (overall mean [SD] age, 53.4 [19.4] years; 11 577 157 [54%] female). Among patients with a previous cardiovascular event, the time interval associated with increased risk of postoperative mortality was surgery within 11.3 months (95% CI, 10.8-11.7), with subgroup risks of 14.2 months before elective surgery (95% CI, 13.3-15.3) and 7.3 months for emergency surgery (95% CI, 6.8-7.8). Heterogeneity in these timings was noted across many surgical specialties. The time-dependent risk intervals following stroke and myocardial infarction were similar, but the absolute risk was greater following a stroke. Regarding surgical urgency, the risk of 30-day mortality was higher in those with a prior cardiovascular event for emergency surgery (adjusted hazard ratio, 1.35; 95% CI, 1.34-1.37) and an elective procedure (adjusted hazard ratio, 1.83; 95% CI, 1.78-1.89) than those without a prior cardiovascular event. Conclusions and Relevance: In this study, surgery within 1 year of an acute coronary syndrome or stroke was associated with increased postoperative mortality before reaching a new baseline, particularly for elective surgery. This information may help clinicians and patients balance deferring the potential benefits of the surgery against the desire to avoid increased mortality from overly expeditious surgery after a recent cardiovascular event.

Effect of implementing the NEWS2 escalation protocol in a large acute NHS trust: a retrospective cohort analysis of mortality, workload and ability of early warning score to predict death within 24 hours.

OBJECTIVES: To describe the inpatient population, establish patterns in admission and mortality over a 4-year period in different cohorts and assess the prognostic ability and workload implications of introducing the National Early Warning Score 2 (NEWS2) and associated escalation protocol. DESIGN: Retrospective cohort analyses of medical and surgical inpatient admissions. SETTING: Large teaching hospital with tertiary inpatient care and a major trauma centre employing an electronic observations platform, initially with a local early warning score, followed by NEWS2 introduction in June 2019. PARTICIPANTS: 332 682 adult patients were admitted between 1 January 2016 and 31 December 2019. OUTCOME MEASURES: Mortality, workload and ability of early warning score to predict death within 24 hours. RESULTS: Admissions rose by 19% from 76 055 in 2016 to 90 587 in 2019. Total bed days rose by 10% from 433 382 to 477 485. Mortality fell from 3.7% to 3.1% and was significantly lower in patients discharged from a surgical specialty, 1.0%-1.2% (p<0.001). Total observations recorded increased by 14% from 1 976 872 in 2016 to 2 249 118 in 2019. 65% of observations were attributable to patients under medical specialties, 34% to patients under surgical specialties. Recorded escalations to the registrar were stable from January 2016 to May 2019 but trebled following the introduction of NEWS2 in June 2019. CONCLUSIONS: There was an increase in hospital inpatient activity between 2016 and 2019, associated with a reduction in mortality and percentage of observations calculated as reaching threshold NEWS2 score of 7 for escalation to the registrar. The introduction of the NEWS2, with a higher sensitivity and lower specificity, when allied to its escalation protocol, was associated with a significant increase in actual recorded escalations to the registrar. This was more marked in the surgical population and would support refining threshold scores based on admission characteristics when developing the next iteration of NEWS.

Effects of tobacco smoking on recurrent hospitalisation with pneumonia: a population-based cohort study.

The incidence of and risk factors for recurrent hospitalisation for pneumonia were investigated using data from Hospital Episode Statistics, linked to a UK primary care database. Within 90 days and 1 year of follow-up, 1733 (3.1%) and 5064 (9.0%), developed recurrent pneumonia respectively. Smoking status at the time of hospitalisation with index pneumonia was associated with the risk of readmission with recurrent pneumonia within a year of discharge: current versus never smokers: adjusted subhazard ratio (sHR) 1.42, 95% CI 1.32 to 1.53, p<0.001, and ex smokers versus never smokers: adjusted sHR 1.24, 95% CI 1.15 to 1.34, p<0.001. Other independent risk factors associated with recurrent pneumonia were age, gender, deprivation and underlying comorbidities.

Factors associated with survival in small cell lung cancer: an analysis of real-world national audit, chemotherapy and radiotherapy data.

BACKGROUND: The mainstay of treatment for small cell lung cancer (SCLC) involves platinum doublet chemotherapy but the optimal duration, 4 vs. 6 cycles, is not known. Concurrent thoracic radiotherapy followed by prophylactic cranial irradiation (PCI) is recommended for fit individuals with limited stage. However, outside of clinical trials, the efficacy of sequential thoracic radiotherapy and PCI for extensive stage is uncertain. METHODS: This retrospective, observational, cohort study used English national lung cancer data to determine the factors associated with survival for all people diagnosed with SCLC. More precisely, for individuals who received chemotherapy, we examined survival by the chemotherapy duration, thoracic radiotherapy dose and the use of PCI. RESULTS: In total 6,438 people were diagnosed with SCLC. We identified that male sex (OR 0.7; 95% CI: 0.62-0.80), increasing age (P=0.01) greater comorbidity (P≤0.01), extensive stage (OR 0.21; 95% CI: 0.19-0.25) and worse performance status (PS2 vs. PS0 adjusted OR 0.38 95% CI: 0.31-0.48) were associated with reduced 1-year survival. Receipt of chemotherapy augmented survival. We analysed data for 1,761 people who had received chemotherapy. Thoracic radiotherapy (≥30 Gy for extensive stage and ≥40 Gy for limited stage) and PCI were independently associated with better survival (P≤0.01 for each), but 6 cycles of chemotherapy instead of 4 was not (limited stage adjusted OR 0.97; 95% CI: 0.48-1.97) extensive stage adjusted OR 1.34; 95% CI: 0.81-2.21). CONCLUSIONS: Extending chemotherapy beyond 4 cycles to 6 does not augment survival. Appropriately prescribed thoracic radiotherapy and PCI can prolong survival in both limited and extensive stage SCLC.

Cerebrovascular accident and acute coronary syndrome and perioperative outcomes (CAPO) study protocol: a 10-year database linkage between Hospital Episode Statistics Admitted Patient Care, Myocardial Infarction National Audit Project and Office for National Statistics registries for time-dependent risk analysis of perioperative outcomes in English NHS hospitals.

INTRODUCTION: An increasing number of people who have a history of acute coronary syndrome or cerebrovascular accident (termed cardiovascular events) are being considered for surgery. Up-to-date evidence of the impact of these prior events is needed to inform person-centred decision making. While perioperative risk for major adverse cardiac events immediately after a cardiovascular event is known to be elevated, the duration of time after the event for which the perioperative risk is increased is not clear. METHODS AND ANALYSIS: This is an individual patient-level database linkage study of all patients in England with at least one operation between 2007 and 2017 in the Hospital Episode Statistics Admitted Patient Care database. Data will be linked to mortality data from the Office for National Statistics up to 2018, for 30-day, 90-day and 1-year mortality and to the Myocardial Ischaemia National Audit Project, a UK registry of acute coronary syndromes. The primary outcome will be the association between time from cardiovascular event to index surgery and 30-day all-cause mortality. Additional associations we will report are all unplanned readmissions, prolonged length of stay, 30-day hospital free survival and incidence of new cardiovascular events within one postoperative year. Important subgroups will be surgery specific (invasiveness, urgency and subspecialty), type of acute coronary syndrome (ST or non-ST elevation myocardial infarction) and type of cerebrovascular accident (ischaemic or haemorrhagic stroke). ETHICS AND DISSEMINATION: Ethical approval for this observational study has been obtained from East Midlands-Nottingham 1 Research Ethics Committee; REC reference: 18/EM0403. The results of the study will be made available through peer-reviewed publications and via the Health Services Research Centre of the Royal College of Anaesthetists, London.

Management of Fracture Risk in Patients with Chronic Obstructive Pulmonary Disease (COPD): Building a UK Consensus Through Healthcare Professional and Patient Engagement.

Introduction: Osteoporosis and bone fractures are common in chronic obstructive pulmonary disease (COPD) and contribute significantly to morbidity and mortality. Current national guidance on COPD management recommends addressing bone health in patients, however, does not detail how. This consensus outlines key elements of a structured approach to managing bone health and fracture risk in patients with COPD. Methods: A systematic approach incorporating multifaceted methodologies included detailed patient and healthcare professional (HCP) surveys followed by a roundtable meeting to reach a consensus on what a pathway would look like. Results: The surveys revealed that fracture risk was not always assessed despite being recognised as an important aspect of COPD management by HCPs. The majority of the patients also stated they would be receptive to discussing treatment options if found to be at risk of osteoporotic fractures. Limited time and resource allocation were identified as barriers to addressing bone health during consultations. The consensus from the roundtable meeting was that a proactive systematic approach to assessing bone health should be adopted. This should involve using fracture risk assessment tools to identify individuals at risk, investigating secondary causes of osteoporosis if a diagnosis is made and reinforcing non-pharmacological and preventative measures such as smoking cessation, keeping active and pharmacological management of osteoporosis and medicines management of corticosteroid use. Practically, prioritising patients with important additional risk factors, such as previous fragility fractures, older age and long-term oral corticosteroid use for an assessment, was felt required. Conclusion: There is a need for integrating fracture risk assessment into the COPD pathway. Developing a systematic and holistic approach to addressing bone health is key to achieving this. In tandem, opportunities to disseminate the information and educational resources are also required.

A systematic review of survival following anti-cancer treatment for small cell lung cancer.

OBJECTIVES: We conducted a systematic review and meta-analysis of survival following treatment recommended by the European Society of Medical Oncology for SCLC in order to determine a benchmark for novel therapies to be compared with. MATERIALS AND METHODS: Randomized controlled trials and observational studies reporting overall survival following chemotherapy for SCLC were included. We calculated survival at 30 and 90-days along with 1-year, 2-year and median. RESULTS: We identified 160 for inclusion. There were minimal 30-day deaths. Survival was 99 % (95 %CI 98.0-99.0 %, I233.9 %, n = 77) and 90 % (95 %CI 89.0-92.0 %, I279.5 %, n = 73) at 90 days for limited (LD-SCLC) and extensive stage (ED-SCLC) respectively. The median survival for LD-SCLC was 18.1 months (95 %CI 17.0-19.1 %, I277.3 %, n = 110) and early thoracic radiotherapy (thoracic radiotherapy 18.4 months (95 %CI 17.3-19.5, I278.4 %, n = 100)) vs no radiotherapy 11.7 months (95 %CI 9.1-14.3, n = 10), prophylactic cranial irradiation (PCI 19.7 months vs No PCI 13.0 months (95 %CI 18.5-21.0, I275.7 %, n = 78 and 95 %CI 10.5-16.6, I281.1 %, n = 15 respectively)) and better performance status (PS0-1 22.5 months vs PS0-4 15.3 months (95 %CI 18.7-26.1, I272.4 %, n = 11 and 95 %CI 11.5-19.1 I277.9 %, n = 13)) augmented this. For ED-SCLC the median survival was 9.6 months (95 %CI 8.9-10.3 %, I295.2 %, n = 103) and this improved when irinotecan + cisplatin was used, however studies that used this combination were mostly conducted in Asian populations where survival was better. Survival was not improved with the addition of thoracic radiotherapy or PCI. Survival for both stages of cancer was better in modern studies and Asian cohorts. It was poorer for studies administering carboplatin + etoposide but this regimen was used in studies that had fewer patient selection criteria. CONCLUSION: Early thoracic radiotherapy and PCI should be offered to people with LD-SCLC in accordance with guideline recommendations. The benefit of the aforementioned therapies to treat ED-SCLC and the use of chemotherapy in people with poor PS is less clear.

Effect of tobacco smoking on the risk of developing community acquired pneumonia: A systematic review and meta-analysis.

AIM: To summarise and quantify the effect of tobacco smoking on the risk of developing community acquired pneumonia (CAP) in adults. METHODS: We systematically searched MEDLINE, Embase, CINAHL, PsychINFO and Web of Science, from inception to October 2017, to identify case-control and cohort studies and reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) checklist. The review protocol was registered with the PROSPERO database (CRD42018093943). Study quality was assessed by the Newcastle-Ottawa Scale. Pooled odds ratios (ORs) or hazard ratios (HRs) were estimated using a random-effects model. RESULTS: Of 647 studies identified, 27 studies were included (n = 460,592 participants) in the systematic review. Most of the included studies were of moderate quality with a median score of six (IQR 6-7). Meta-analysis showed that current smokers (pooled OR 2.17, 95% CI 1.70-2.76, n = 13 studies; pooled HR 1.52, 95% CI 1.13-2.04, n = 7 studies) and ex-smokers (pooled OR 1.49, 95% CI 1.26-1.75, n = 8 studies; pooled HR 1.18, 95% CI 0.91-1.52, n = 6 studies) were more likely to develop CAP compared to never smokers. Although the association between passive smoking and risk of CAP in adults of all ages was not statistically significant (pooled OR 1.13, 95% CI 0.94-1.36, n = 5 studies), passive smoking in adults aged ≥65 years was associated with a 64% increased risk of CAP (pooled OR 1.64; 95% CI 1.17-2.30, n = 2 studies). Dose-response analyses of data from five studies revealed a significant trend; current smokers who smoked higher amount of tobacco had a higher risk of CAP. CONCLUSION: Tobacco smoke exposure is significantly associated with the development of CAP in current smokers and ex-smokers. Adults aged > 65 years who are passive smokers are also at higher risk of CAP. For current smokers, a significant dose-response relationship is evident.

Prevalence of tobacco use in healthcare workers: A systematic review and meta-analysis.

OBJECTIVES: To estimate tobacco use prevalence in healthcare workers (HCW) by country income level, occupation and sex, and compare the estimates with the prevalence in the general population. METHODS: We systematically searched five databases; Medline, EMBASE, CINHAL Plus, CAB Abstracts, and LILACS for original studies published between 2000 and March 2016 without language restriction. All primary studies that reported tobacco use in any category of HCW were included. Study extraction and quality assessment were conducted independently by three reviewers, using a standardised data extraction and quality appraisal form. We performed random effect meta-analyses to obtain prevalence estimates by World Bank (WB) country income level, sex, and occupation. Data on prevalence of tobacco use in the general population were obtained from the World Health Organisation (WHO) Global Health Observatory website. The review protocol registration number on PROSPERO is CRD42016041231. RESULTS: 229 studies met our inclusion criteria, representing 457,415 HCW and 63 countries: 29 high-income countries (HIC), 21 upper-middle-income countries (UMIC), and 13 lower-middle-and-low-income countries (LMLIC). The overall pooled prevalence of tobacco use in HCW was 21%, 31% in males and 17% in females. Highest estimates were in male doctors in UMIC and LMLIC, 35% and 45%, and female nurses in HIC and UMIC, 21% and 25%. Heterogeneity was high (I2 > 90%). Country level comparison suggest that in HIC male HCW tend to have lower prevalence compared with males in the general population while in females the estimates were similar. Male and female HCW in UMIC and LMLIC tend to have similar or higher prevalence rates relative to their counterparts in the general population. CONCLUSIONS: HCW continue to use tobacco at high rates. Tackling HCW tobacco use requires urgent action as they are at the front line for tackling tobacco use in their patients.

The Its Not JUST Idiopathic pulmonary fibrosis Study (INJUSTIS): description of the protocol for a multicentre prospective observational cohort study identifying biomarkers of progressive fibrotic lung disease.

Introduction: The Its Not JUST Idiopathic pulmonary fibrosis Study (INJUSTIS) is a multicentre, prospective, observational cohort study. The aims of this study are to identify genetic, serum and other biomarkers that may identify specific molecular mechanisms, reflecting disease endotypes that are shared among patients with progressive pulmonary fibrosis regardless of aetiology. Furthermore, it is anticipated that these biomarkers will help predict fibrotic activity that may identify patterns of disease behaviour with greater accuracy than current clinical phenotyping. Methods and analysis: 200 participants with the multidisciplinary team confirmed fibrotic lung disease (50 each of rheumatoid-interstitial lung disease (ILD), asbestosis, chronic hypersensitivity pneumonitis and unclassifiable ILD) and 50 idiopathic pulmonary fibrosis participants, recruited as positive controls, will be followed up for 2 years. Participants will have blood samples, lung function tests, quality of life questionnaires and a subgroup will be offered bronchoscopy. Participants will also be given the option of undertaking blinded home handheld spirometry for the first 3 months of the study. The primary end point will be identification of a biomarker that predicts disease progression, defined as 10% relative change in forced vital capacity (FVC) or death at 12 months. Ethics and dissemination: The trial has received ethical approval from the National Research Ethics Committee Nottingham (18/EM/0139). All participants must provide written informed consent. The trial will be overseen by the INJUSTIS steering group that will include a patient representative, and an independent chairperson. The results from this study will be submitted for publication in peer-reviewed journals and disseminated at regional and national conferences. Trial registration number: NCT03670576.

Predicting fracture risk in patients with chronic obstructive pulmonary disease: a UK-based population-based cohort study.

OBJECTIVE: To assess the incidence of hip fracture and all major osteoporotic fractures (MOF) in patients with chronic obstructive pulmonary disease (COPD) compared with non-COPD patients and to evaluate the use and performance of fracture risk prediction tools in patients with COPD. To assess the prevalence and incidence of osteoporosis. DESIGN: Population-based cohort study. SETTING: UK General Practice health records from The Health Improvement Network database. PARTICIPANTS: Patients with an incident COPD diagnosis from 2004 to 2015 and non-COPD patients matched by age, sex and general practice were studied. OUTCOMES: Incidence of fracture (hip alone and all MOF); accuracy of fracture risk prediction tools in COPD; and prevalence and incidence of coded osteoporosis. METHODS: Cox proportional hazards models were used to assess the incidence rates of osteoporosis, hip fracture and MOF (hip, proximal humerus, forearm and clinical vertebral fractures). The discriminatory accuracies (area under the receiver operating characteristic [ROC] curve) of fracture risk prediction tools (FRAX and QFracture) in COPD were assessed. RESULTS: Patients with COPD (n=80 874) were at an increased risk of fracture (both hip alone and all MOF) compared with non-COPD patients (n=308 999), but this was largely mediated through oral corticosteroid use, body mass index and smoking. Retrospectively calculated ROC values for MOF in COPD were as follows: FRAX: 71.4% (95% CI 70.6% to 72.2%), QFracture: 61.4% (95% CI 60.5% to 62.3%) and for hip fracture alone, both 76.1% (95% CI 74.9% to 77.2%). Prevalence of coded osteoporosis was greater for patients (5.7%) compared with non-COPD patients (3.9%), p<0.001. The incidence of osteoporosis was increased in patients with COPD (n=73 084) compared with non-COPD patients (n=264 544) (adjusted hazard ratio, 1.13, 95% CI 1.05 to 1.22). CONCLUSION: Patients with COPD are at an increased risk of fractures and osteoporosis. Despite this, there is no systematic assessment of fracture risk in clinical practice. Fracture risk tools identify those at high risk of fracture in patients with COPD.

Factors influencing treatment selection and 30-day mortality after chemotherapy for people with small-cell lung cancer: An analysis of national audit data.

BACKGROUND: Thirty-day mortality after treatment for lung cancer is a measure of unsuccessful outcome and where treatment should have been avoided. Guidelines recommend offering chemotherapy to individuals with small-cell lung cancer (SCLC) who have poorer performance status (PS) because of its high initial response rate. However, this comes with an increased risk of toxicity and early death. We quantified real-world 30-day mortality in SCLC after chemotherapy, established the factors associated with this and compared these with the factors that influence receipt of chemotherapy. METHODS: We used linked national English data sets to define the factors associated with both receiving chemotherapy and 30-day mortality after chemotherapy. RESULTS: We identified 3715 people diagnosed with SCLC, of which 2235 (60.2%) received chemotherapy. There were 174 (7.8%) deaths within 30 days of chemotherapy. The adjusted odds of receiving chemotherapy decreased with older age, worsening PS and increasing comorbidities. Thirty-day mortality was independently associated with poor PS [PS 2 vs PS 0, adjusted odds ratio (OR) 3.75, 95% confidence interval (CI) 1.71-8.25] and stage (extensive vs limited adjusted OR 1.68, 95% CI 1.03-2.74) but in contrast was not associated with increasing age. Both chemotherapy administration and 30-day mortality varied by hospital network. CONCLUSIONS: To reduce variation in chemotherapy administration, predictors of 30-day mortality could be used as an adjunct to improve suboptimal patient selection. We have quantified 30-day mortality risk by the two independently associated factors, PS and stage, so that patients and clinicians can make better informed decisions about the potential risk of early death after chemotherapy.

A survey of tobacco dependence treatment guidelines content in 61 countries.

AIMS: To assess tobacco dependence treatment guidelines content in accordance with Article 14 of the World Health Organization (WHO) Framework Convention on Tobacco Control (FCTC) and its guidelines, and association between content and country income level. DESIGN: Cross-sectional study. SETTING: On-line survey from March to July 2016. PARTICIPANTS: Contacts in 77 countries, including 68 FCTC Parties, six Signatories and three non-Parties which had indicated having guidelines in previous surveys, or had not been surveyed before. MEASUREMENTS: A nine-item questionnaire on guidelines content, key recommendations, writing and dissemination. FINDINGS: We received responses from contacts in 63 countries (82%); 61 had guidelines. The majority are for doctors (93%), primary care (92%) and nurses (75%). All recommend brief advice, 82% recording tobacco use in medical notes, 98% nicotine replacement therapy (NRT), 61% quitlines, 31% text messaging and 87% intensive specialist support, and 54% stress the importance of health-care workers not using tobacco. Only 57% have a dissemination strategy, and 62% have not been updated for 5 or more years. Compared with high-income countries, quitlines are less likely to be recommended in upper middle-income countries guidelines [odds ratio (OR) = 0.15, 95% confidence interval (CI) = 0.04-0.61] and intensive specialist support in lower middle-income countries guidelines (OR = 0.01, 95% CI = 0.00-0.20). Guidelines updating is associated positively with country income level (P = 0.027). CONCLUSIONS: Although most tobacco dependence treatment guidelines in the 61 countries assessed in 2016 follow the World Health Organization's Framework Convention on Tobacco Control Article 14 recommendations and do not differ significantly by income level, improvements are needed in keeping guidelines up-to-date, applying good writing practices and developing a dissemination strategy.

Early Respiratory Bacterial Detection and Antistaphylococcal Antibiotic Prophylaxis in Young Children with Cystic Fibrosis.

RATIONALE: Consensus is lacking regarding antistaphylococcal antibiotic prophylaxis use for young children with cystic fibrosis. Prophylaxis is recommended in the United Kingdom, but it is recommended against in the United States. OBJECTIVES: To test the hypothesis that antistaphylococcal antibiotic prophylaxis is associated with a decreased risk of Staphylococcus aureus acquisition but no increased risk of Pseudomonas aeruginosa acquisition. METHODS: We undertook a longitudinal observational study of children with cystic fibrosis who were recruited from birth (or from their first registry entry in the period) and followed until the age of 4 years (1,500 d) using 2000-2009 data from the UK Cystic Fibrosis Trust and Cystic Fibrosis Foundation registries. Children were excluded if they had a positive culture result for S. aureus or P. aeruginosa, or if they were receiving inhaled antibiotics, at the first encounter. Time to first S. aureus and P. aeruginosa detection in the UK/U.S. cohorts was compared using a Cox proportional hazards model. A UK-based analysis compared the same for those receiving flucloxacillin with those who received no prophylaxis. We included the following covariates: sex, age at registry entry, dornase alfa use, genotype, and center size. RESULTS: The primary analysis comprised 1,074 UK and 3,677 U.S. children. The risk of first detection was greater in U.S. children than in UK children for S. aureus (hazard ratio [HR], 5.79; 95% confidence interval [CI], 4.85, 6.90; P < 0.001) and P. aeruginosa (HR, 1.92; 95% CI, 1.65, 2.24; P < 0.001). In the UK analysis, we compared 278 children receiving flucloxacillin and 306 receiving no prophylaxis. Flucloxacillin was not associated with a reduced risk of S. aureus detection (HR, 1.22; 95% CI, 0.74, 2.0; P = 0.43), but it was associated with an increased risk of P. aeruginosa detection (HR, 2.53; 95% CI, 1.71, 3.74; P < 0.001). None of the covariates significantly affected the risk estimate in either analysis. CONCLUSIONS: The risk of first detection of S. aureus and P. aeruginosa was greater in the United States than in the United Kingdom. In the United Kingdom, the risk of first P. aeruginosa detection was increased among those receiving flucloxacillin compared with those who received no prophylaxis. These observational findings should be examined in randomized controlled trials.

The recording and characteristics of pulmonary rehabilitation in patients with COPD using The Health Information Network (THIN) primary care database.

Pulmonary rehabilitation is recommended for patients with COPD to improve physical function, breathlessness and quality of life. Using The Health Information Network (THIN) primary care database in UK, we compared the demographic and clinical parameters of patients with COPD in relation to coding of pulmonary rehabilitation, and to investigate whether there is a survival benefit from pulmonary rehabilitation. We identified patients with COPD, diagnosed from 2004 and extracted information on demographics, pulmonary rehabilitation and clinical parameters using the relevant Read codes. Thirty six thousand one hundred and eighty nine patients diagnosed with COPD were included with a mean (SD) age of 67 (11) years, 53% were male and only 9.8% had a code related to either being assessed, referred, or completing pulmonary rehabilitation ever. Younger age at diagnosis, better socioeconomic status, worse dyspnoea score, current smoking, and higher comorbidities level are more likely to have a record of pulmonary rehabilitation. Of those with a recorded MRC of 3 or worse, only 2057 (21%) had a code of pulmonary rehabilitation. Survival analysis revealed that patients with coding for pulmonary rehabilitation were 22% (95% CI 0.69-0.88) less likely to die than those who had no coding. In UK THIN records, a substantial proportion of eligible patients with COPD have not had a coded pulmonary rehabilitation record. Survival was improved in those with PR record but coding for other COPD treatments were also better in this group. GP practices need to improve the coding for PR to highlight any unmet need locally. CHRONIC LUNG DISEASE: ROLLING OUT THE REHAB: Analysis of recent UK data suggests that more patients with chronic lung disease could benefit from lung rehabilitation programmes. During pulmonary rehabilitation (PR), patients with chronic obstructive pulmonary disease (COPD) work with specialists to learn exercises and optimise breathing techniques. The programmes are recommended under current guidelines, particularly for patients with a high breathlessness score. Despite this, when Charlotte Bolton and co-workers at the University of Nottingham analysed 36,189 patient primary care records gathered since 2004, they found only 9.8% of COPD patients had ever had a coded record of being assessed, referred for, or undertaken PR. Those patients who completed PR were 22% less likely to die that those who didn't, although appeared they had also received better overall COPD care. Current smokers, those suffering from co-morbidities and younger patients were more likely to receive PR than other patient groups.

Progress in implementation of WHO FCTC Article 14 and its guidelines: a survey of tobacco dependence treatment provision in 142 countries.

AIMS: To (1) estimate the number of Parties to the Framework Convention on Tobacco Control (FCTC) providing tobacco dependence treatment in accordance with the recommendations of Article 14 and its guidelines; (2) assess association between provision and countries' income level; and (3) assess progress over time. DESIGN: Cross-sectional study. SETTING: Online survey from December 2014 to July 2015. PARTICIPANTS: Contacts in 172 countries were surveyed, representing 169 of the 180 FCTC Parties at the time of the survey. MEASUREMENTS: A 26-item questionnaire based on the Article 14 recommendations including tobacco treatment infrastructure and cessation support systems. Progress over time was assessed for those countries that also participated in our 2012 survey and did not change country income level classification. FINDINGS: We received responses from contacts in 142 countries, an 83% response rate. Overall, 54% of respondents reported that their country had an officially identified person responsible for tobacco dependence treatment, 32% an official national treatment strategy, 40% official national treatment guidelines, 25% a clearly identified budget for treatment, 17% text messaging, 23% free national quitlines and 26% specialized treatment services. Most measures were associated positively and significantly with countries' income level (P < 0.001). Measures not associated significantly with income level included mandatory recording of tobacco use (30% of countries), offering help to health-care workers (HCW) to stop using tobacco (44%), brief advice integrated into existing services (44%), and training HCW to give brief advice (81%). Reporting having an officially identified person responsible for tobacco cessation was the only measure with a statistically significant improvement over time (P = 0.0351). CONCLUSION: Fewer than half of countries that are Parties to the Framework Convention on Tobacco Control have implemented the recommendations of Article 14 and its guidelines, and for most measures, provision was greater the higher the country's income. There was little improvement in treatment provision between 2012 and 2015 in all countries.

Targeted Sequencing of Lung Function Loci in Chronic Obstructive Pulmonary Disease Cases and Controls.

Chronic obstructive pulmonary disease (COPD) is the third leading cause of death worldwide; smoking is the main risk factor for COPD, but genetic factors are also relevant contributors. Genome-wide association studies (GWAS) of the lung function measures used in the diagnosis of COPD have identified a number of loci, however association signals are often broad and collectively these loci only explain a small proportion of the heritability. In order to examine the association with COPD risk of genetic variants down to low allele frequencies, to aid fine-mapping of association signals and to explain more of the missing heritability, we undertook a targeted sequencing study in 300 COPD cases and 300 smoking controls for 26 loci previously reported to be associated with lung function. We used a pooled sequencing approach, with 12 pools of 25 individuals each, enabling high depth (30x) coverage per sample to be achieved. This pooled design maximised sample size and therefore power, but led to challenges during variant-calling since sequencing error rates and minor allele frequencies for rare variants can be very similar. For this reason we employed a rigorous quality control pipeline for variant detection which included the use of 3 independent calling algorithms. In order to avoid false positive associations we also developed tests to detect variants with potential batch effects and removed them before undertaking association testing. We tested for the effects of single variants and the combined effect of rare variants within a locus. We followed up the top signals with data available (only 67% of collapsing methods signals) in 4,249 COPD cases and 11,916 smoking controls from UK Biobank. We provide suggestive evidence for the combined effect of rare variants on COPD risk in TNXB and in sliding windows within MECOM and upstream of HHIP. These findings can lead to an improved understanding of the molecular pathways involved in the development of COPD.

Surgical lung biopsy for the diagnosis of interstitial lung disease in England: 1997-2008.

International guidelines and new targeted therapies for idiopathic pulmonary fibrosis have increased the need for accurate diagnosis of interstitial lung disease (ILD), which may lead to more surgical lung biopsies. This study aimed to assess the risk of this procedure in patients from the UK.We used Hospital Episodes Statistics data from 1997 to 2008 to assess the frequency of surgical lung biopsy for ILD in England, UK. We identified cardiothoracic surgical patients using International Classification of Diseases revision 10 codes for ILD and Office of Population Censuses and Surveys Classification of Interventions and Procedures version 4 codes for surgical lung biopsy. We excluded those with lung resections or lung cancer. We estimated in-hospital, 30-day and 90-day mortality following the procedure, and linked to cause of death using data from the UK Office of National Statistics.We identified 2820 patients with ILD undergoing surgical lung biopsy during the 12-year period. The number of biopsies increased over the time period studied. In-hospital, 30-day and 90-day mortality were 1.7%, 2.4% and 3.9%, respectively. Male sex, increasing age, increasing comorbidity and open surgery were risk factors for mortality.Surgical lung biopsy for ILD has a similar mortality to lobectomy for lung cancer, and clinicians and patients should understand the likely risks involved.