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Ayushman Gupta,1 Tricia M McKeever,1,2 John P Hutchinson,3 Charlotte E Bolton1 1NIHR Nottingham BRC Respiratory Theme, Translational Medical Sciences, School of Medicine, University of Nottingham, Nottingham, UK; 2Division of Epidemiology and Public Health, School of Medicine, University of Nottingham, Nottingham, UK; 3Respiratory Medicine, Sherwood Forest Hospitals NHS Foundation Trust, Sutton-in-Ashfield, UKCorrespondence: Charlotte E Bolton, B22, NIHR Nottingham BRC respiratory theme, Translational Medical Sciences, School of Medicine, University of Nottingham, Clinical Sciences Building, City Hospital Campus, Hucknall road, Nottingham, NG5 1PB, UK, Email Charlotte.bolton@nottingham.ac.ukPurpose: People with COPD are at a higher risk of cognitive dysfunction than the general population. However, the additional impact of dementia amongst such patients is not well understood, particularly in those admitted with a COPD exacerbation. We assessed the impact of coexisting dementia on inpatient mortality and length of stay (LOS) in patients admitted to hospital with a COPD exacerbation, using the United States based National Inpatient Sample database.Patients and Methods: Patients aged over 40 years and hospitalised with a primary diagnosis of COPD exacerbation from 2011 to 2015 were included. Cases were grouped into patients with and without dementia. Multivariable logistic regression analysis, stratified by age, was used to assess risk of inpatient deaths. Cox regression was carried out to compare death rates and competing risk analysis gave estimates of discharge rates with time to death a competing variable.Results: A total of 576,381 patients were included into the analysis, of which 35,372 (6.1%) had co-existent dementia. There were 6413 (1.1%) deaths recorded. The odds of inpatient death were significantly greater in younger patients with dementia (41– 64 years) [OR (95% CI) dementia vs without: 1.75 (1.04– 2.92), p=0.03]. Cases with dementia also had a higher inpatient mortality rate in the first 4 days [HR (95% CI) dementia vs without: 1.23 (1.08– 1.41), p=0.002] and a longer LOS [sub-hazard ratio (95% CI) dementia vs without: 0.93 (0.92– 0.94), p< 0.001].Conclusion: Dementia as a comorbidity is associated with worse outcomes based on inpatient deaths and LOS in patients admitted with COPD exacerbations.Keywords: chronic obstructive pulmonary disease, exacerbation, morbidity, length of stay

Ayushman Gupta, 1 Leah R Jayes, 2 Steve Holmes, 3 Opinder Sahota, 4 Melissa Canavan, 5 Sarah L Elkin, 6 Kelvin Lim, 7 Anna C Murphy, 8 Sally Singh, 9, 10 Elizabeth A Towlson, 11 Helen Ward, 12 Jane Scullion, 9 Tricia M McKeever, 2 Charlotte E Bolton 1 1NIHR Nottingham BRC Respiratory Theme, School of Medicine, University of Nottingham, City Hospital Campus, Nottingham, UK; 2Division of Epidemiology and Public Health, School of Medicine, University of Nottingham, City Hospital Campus, Nottingham, UK; 3General Practitioner, Park Medical Partnership, Shepton Mallet, UK; 4Department of Geriatric Medicine, Nottingham University Hospitals Trust, Nottingham, UK; 5Department of Respiratory, Respiratory Care Solutions, Leeds, UK; 6Department of Pharmacy, Imperial Healthcare NHS Trust, St Mary’s Hospital, London, UK; 7Eastwood Primary Care Centre, Eastwood, Nottingham, UK; 8Department of Pharmacy, University Hospitals of Leicester NHS Trust, Leicester, UK; 9Department of Respiratory Science, University Hospitals of Leicester NHS Trust, Leicester, UK; 10Department of Respiratory Science, University of Leicester, Leicester, UK; 11Respiratory Nurse, Saxon Cross Surgery, Stapleford, Nottingham, UK; 12Faculty of Medicine, The Royal Wolverhampton NHS Trust, West Midlands, UKCorrespondence: Ayushman GuptaNIHR Nottingham BRC Respiratory Theme, School of Medicine, University of Nottingham, Clinical Sciences Building, City Hospital Campus, Hucknall Road, Nottingham NG5 1PB, UKEmail ayushman.gupta@nottingham.ac.ukIntroduction: 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.Keywords: COPD, fracture risk, osteoporosis, bone health

Ali Hakamy,1,2 Tricia M McKeever,2 Michael C Steiner,3 C Michael Roberts,4 Sally J Singh,3 Charlotte E Bolton1 1Nottingham Respiratory Research Unit, NIHR Nottingham Biomedical Research Centre, 2Division of Epidemiology and Public Health, School of Medicine, University of Nottingham, Nottingham, 3Leicester Respiratory Biomedical Research Unit, Institute for Lung Health, University Hospitals of Leicester NHS Trust, Leicester, 4Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK Abstract: Our aim was to evaluate the use and impact of the practice walk test on enrolment, completion, and clinical functional response to pulmonary rehabilitation (PR) using the 2015 UK National Chronic Obstructive Pulmonary Disease (COPD) Pulmonary Rehabilitation audit data. Patients were assessed according to whether a baseline practice walk test was performed or not. Study outcomes included use of the practice walk test, baseline and change in incremental shuttle walk test distance (ISWD) or 6-minute walk test distance (6MWD), and enrolment to and completion of PR program. Of 7,355 patients, only 1,666 (22.6%) had a baseline practice test. At baseline, the practice walk test group walked further as compared to the no practice walk test group: ISWD, 17.9 m [95% confidence interval (CI) 8.2–27.5 m] and 6MWD, 34.8 m (95% CI 24.7–44.9 m). The practice walk test group were 2.2 times (95% CI 1.8–2.6) more likely to enroll and 17% (95% CI 1.03–1.34) more likely to complete PR. Although the change in ISWD and 6MWD with PR was lower in the practice walk test group, they walked further at discharge assessment. Only 22.6% of the patients in the 2015 National PR audit had a practice walk test at assessment. Those who did had better enrolment, completion, and better baseline walking distance, from which the prescription is set. Keywords: pulmonary rehabilitation, COPD, functional performance test, functional exercise test

Michelle E John,1 John R Cockcroft,2 Tricia M McKeever,3 William R Coward,1 Dennis J Shale,2 Simon R Johnson,1 Jim G Thornton,4 Timothy W Harrison,1 Alan J Knox,1 Charlotte E Bolton1 1Nottingham Respiratory Research Unit, School of Medicine, University of Nottingham, Nottingham, UK; 2Wales Heart Research Institute, Cardiff University, Cardiff, UK; 3Division of Epidemiology and Public Health, 4Clinical Trials Unit and Department of Obstetrics and Gynaecology, School of Medicine, University of Nottingham, Nottingham, UK Background: There is excess cardiovascular mortality in patients with chronic obstructive pulmonary disease. Aortic stiffness, an independent predictor of cardiovascular risk, and systemic and airway inflammation are increased in patients with the disease. Statins modulate aortic stiffness and have anti-inflammatory properties. A proof-of-principle, double-blind, randomized trial determined if 6 weeks of simvastatin 20 mg once daily reduced aortic stiffness and systemic and airway inflammation in patients with chronic obstructive pulmonary disease.Methods: Stable patients (n=70) were randomized to simvastatin (active) or placebo. Pre-treatment and post-treatment aortic stiffness, blood pressure, spirometry, and circulating and airway inflammatory mediators and lipids were measured. A predefined subgroup analysis was performed where baseline aortic pulse wave velocity (PWV) was >10 m/sec.Results: Total cholesterol dropped in the active group. There was no significant change in aortic PWV between the active group and the placebo group (-0.7 m/sec, P=0.24). In those with aortic stiffness >10 m/sec (n=22), aortic PWV improved in the active group compared with the placebo group (-2.8 m/sec, P=0.03). Neither systemic nor airway inflammatory markers changed. Conclusion: There was a nonsignificant improvement in aortic PWV in those taking simvastatin 20 mg compared with placebo, but in those with higher baseline aortic stiffness (a higher risk group) a significant and clinically relevant reduction in PWV was shown. Keywords: chronic obstructive pulmonary disease, arterial stiffness, statins

Rationale: Previous studies have raised concern that women with asthma have increased risks of adverse obstetric and pediatric complications, but these have generally been underpowered.Objectives: To quantify risks of major adverse pregnancy outcomes and obstetric complications in women with and without asthma.Methods: We extracted information on 281,019 pregnancies from the Health Improvement Network database between 1988 and 2004. We analyzed the data using logistic regression.Measurements and Main Results: In 37,585 pregnancies of women with asthma compared with 243,434 pregnancies of women without asthma, risks of stillbirth and therapeutic abortion were similar; however, the risk of miscarriage was slightly higher (odds ratio [OR], 1.10; 95% confidence interval [CI], 1.06-1.13). Risks of most obstetric complications (placental abruption, placental insufficiency, placenta previa, preeclampsia, hypertension, gestational diabetes, thyroid disorders in pregnancy, and assisted delivery) were not higher in pregnancies of women with asthma compared with those without asthma, with the exception of increases in antepartum (OR, 1.20; 95% CI, 1.08-1.34) or postpartum (OR, 1.38; 95% CI, 1.21-1.57) hemorrhage, anemia (OR, 1.06; 95% CI, 1.01-1.12), depression (OR, 1.52; 95% CI, 1.36-1.69), and caesarean section (OR, 1.11; 95% CI, 1.07-1.16). Risks of miscarriage, depression, and caesarean section increased moderately in women with more severe asthma and previous asthma exacerbations.Conclusions: We found some increased risks in women with asthma that need to be considered in the future; however, our results indicate that women with asthma have similar reproductive risks compared with women without asthma in the general population for most of the range of outcomes studied. [ABSTRACT FROM AUTHOR]

Rationale: Oxidative stress may increase the risk of asthma, contribute to asthma progression, and decrease lung function. Previous research suggests that use of acetaminophen, which is hypothesized to reduce antioxidant capacity in the lung, is associated with an increased risk of asthma. We hypothesized that acetaminophen use may also be associated with chronic obstructive pulmonary disease (COPD) and decreased lung function.Objectives: To investigate the associations between use of pain medication, particularly acetaminophen, and asthma, COPD, and FEV1 in adults.Methods: A cross-sectional analysis using the Third National Health and Nutrition Examination Survey.Measurement and Main Results: Increased use of acetaminophen had a positive, dose-dependent association with COPD (adjusted odds ratio for increasing category of intake, 1.16; 95% confidence interval [CI], 1.09-1.24; p value for trend < 0.001) and an inverse association with lung function (daily user compared with never users, -54.0 ml; 95% CI, -90.3 to -17.7, adjusted). Neither of these associations was explained by overlap between COPD and asthma occurrence. We confirmed a dose-response association of acetaminophen use and asthma (adjusted odds ratio, 1.20; 95% CI, 1.12-1.28; p value for trend < 0.001).Conclusions: This study provides further evidence that use of acetaminophen is associated with an increased risk of asthma and COPD, and with decreased lung function. [ABSTRACT FROM AUTHOR]

Although people with diabetes have decreased lung function, the dose-response relation between measures of glucose control and lung function in nondiabetic people is not known. The authors used data from the Third National Health and Nutrition Examination Survey (1988-1994) to investigate the relation between glucose tolerance test response and other measures of glucose homeostasis and lung function in an adult population without a clinical diagnosis of diabetes. Plasma glucose level 2 hours after oral administration of 75 g of glucose was inversely related to forced expiratory volume in 1 second (FEV(1)), with a difference of -144.7 ml (95% confidence interval: -231.9, -57.4) for persons in the highest quintile of postchallenge glucose compared with the lowest. Similar inverse associations with FEV(1) were found for other measures of glucose autoregulation. Lung function did not appear to be related to fasting glucose level. Similar associations were seen for forced vital capacity (FVC) but not for the FEV(1):FVC ratio. In the total study population, persons with previously diagnosed diabetes had an FEV(1) 119.1 ml (95% confidence interval: -161.5, -76.6) lower than persons without diabetes. This effect was greater in those with poorly controlled diabetes. These findings suggest that impaired glucose autoregulation is associated with impaired lung function. [ABSTRACT FROM AUTHOR]

Objectives: We aimed to determine the prevalence of and risk factors for nasopharyngeal and oral pneumococcal carriage in adults with community-acquired pneumonia (CAP), and the relationship between carried and disease-causing serotypes., Methods: Between 2016 and 2018, nasopharyngeal swabs, oral-fluid, and urine were collected from hospitalised adults recruited into a prospective cohort study of CAP. Pneumococcal carriage was detected by semi-quantitative real-time PCR of direct and culture-enriched nasopharyngeal swabs and culture-enriched oral-fluid. LytA and piaB positive/indeterminate samples underwent semi-quantitative serotype/serogroup-specific real-time-PCR. Serotypes in urine were identified using a 24-valent serotype-specific urinary-antigen assay., Results: We included 465 CAP patients. Nasopharyngeal carriage was detected in 34/103 (33.0%) swabbed pneumococcal pneumonia patients and oral carriage in 18/155 (12%) of sampled pneumococcal pneumonia patients. Concordance between nasopharyngeal/urine serotypes and oral/urine serotypes was 70.6% and 50% respectively. Serotypes 3 (26%, 22.2%), 8 (19.7%, 19.4%), non-typeable (11.6%, 13.9%) and 19A/F (7.5%, 8.3%) were most prevalent in urine and nasopharyngeal swabs respectively, with non-typeable (35%) and 15A/F (17%) most prevalent in oral-fluid. Pneumococcal carriage was significantly associated with pneumococcal pneumonia (nasopharyngeal adjusted odds ratio [aOR] 8.1, 95% confidence interval [CI] 3.8-17.2; oral aOR 5.5, 95% CI 2.1-13.3). All-cause CAP patients ≥65 years had lower odds of nasopharyngeal carriage (aOR 0.47, 95% CI 0.24-0.91) and current smokers had higher odds of oral carriage (aOR 2.69, 95% CI 1.10-6.60)., Conclusions: The association between nasopharyngeal carriage and pneumococcal CAP was strong. Adult carriage and disease from serotypes 8 and 19A may support direct protection of adults with PCV vaccines., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships that may be considered as potential competing interests: Wei Shen Lim reports unrestricted investigator-initiated research funding from Pfizer to WSL’s institution for an unrelated study of pneumonia in which WSL is the Chief Investigator.WSL reports research funding from NIHR for a multi-centre clinical trial of aspirin in community acquired pneumonia in which WSL is a co-applicant. WSL is Deputy Chair of the Joint Committee of Vaccination and Immunisation (JCVI)(unpaid), and unpaid Chair of the NIHR Respiratory-Translational Research Centre’s Acute Respiratory Infection National Strategy Research Group. Caroline Trotte participated in a CMV vaccine advisory board meeting in May 2022, unrelated to the topic of this paper. Seyi Eletu declares participation in a Virtual Advisory Board for a pneumococcal project organised by Sanofi Pasteur SA unrelated to the submitted work. The UK Health Security Agency (UKHSA) received monies from the University of Nottingham from an unrestricted grant from Pfizer for this work. The Vaccine Preventable Bacteria Section of UKHSA has received grants from Pfizer for investigator led research unrelated to the current project. The UKHSA provides vaccine manufacturers (GlaxoSmithKline (GSK), MSD, Pfizer) with post marketing surveillance reports on vaccine-preventable disease, including pneumococcal infections for which a cost recovery charge is made and which is unrelated to the submitted work. No other authors declare competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Delaying surgery after a major cardiovascular event might reduce adverse postoperative outcomes. The time interval represents a potentially modifiable risk factor but is not well studied., Methods: This was a longitudinal retrospective population-based cohort study, linking data from Hospital Episode Statistics for NHS England and the Myocardial Ischaemia National Audit Project. Adults undergoing noncardiac, non-neurologic surgery in 2007-2018 were included. The time interval between a preoperative cardiovascular event and surgery was the main exposure. The outcomes of interest were acute coronary syndrome (ACS), acute myocardial infarction (AMI), cerebrovascular accident (CVA) within 1 year of surgery, unplanned readmission (at 30 days and 1 year), and prolonged length of stay. Multivariable logistic regression models with restricted cubic splines were used to estimate adjusted odds ratios (aORs; age, sex, socioeconomic deprivation, and comorbidities)., Results: In total, 877 430 people had a previous cardiovascular event and 20 582 717 were without an event. CVA, ACS, and AMI in the year after elective surgery were more frequent after prior cardiovascular events (adjusted hazard ratio 2.12, 95% confidence interval [CI] 2.08-2.16). Prolonged hospital stay (aOR 1.36, 95% CI 1.35-1.38) and 30-day (aOR 1.28, 95% CI 1.25-1.30) and 1-yr (aOR 1.60, 95% CI 1.58-1.62) unplanned readmission were more common after major operations in those with a prior cardiovascular event. After adjusting for the time interval between preoperative events until surgery, elective operations within 37 months were associated with an increased risk of postoperative ACS or AMI. The risk of postoperative stroke plateaued after a 20-month interval until surgery, irrespective of surgical urgency., Conclusions: These observational data suggest increased adverse outcomes after a recent cardiovascular event can occur for up to 37 months after a major cardiovascular event., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Aim: To determine the frequency with which the National Early Warning Score-2 (NEWS-2) fails to detect physiological deterioration preceding in-hospital cardiac arrest (IHCA)., Methods: We conducted a retrospective observational study of all adult patients (age ≥ 18) who had suffered an IHCA between 1st July 2019 and 31st December 2021 in two large acute hospitals located in an urban centre (Nottingham, UK). Clinical observations and case notes were examined for the period leading up to IHCA events to determine if there was evidence of physiological deterioration which warranted an urgent patient assessment, whether NEWS-2 was triggered, and whether an urgent assessment actually took place., Results: Urgent assessment was indicated in the lead-up to 126/374 (33.7 %) IHCA cases, and NEWS-2 failed to trigger in 20 of these cases (15.9 %). An urgent assessment took place in 89/106 (84.0 %) cases where NEWS-2 was triggered, and 13/20 (65.0 %) cases where NEWS-2 was not triggered, with the difference in proportions being statistically significant (p = 0.048). Half of cases in which NEWS-2 missed a physiological deterioration were related to a new or rising oxygen requirement., Conclusions: A significant proportion of IHCA events are preceded by clinically important abnormalities in vital signs which are not detected by NEWS-2. This may be a causative factor in some failure-to-rescue events., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Data Access Statement Study data are not currently available for sharing due to ethical and institutional restrictions. Requests for data sharing should be directed to the corresponding author., (© 2024 The Author(s).)

We evaluated the impacts of COVID-19 on multi-organ and metabolic function in patients following severe hospitalised infection compared to controls. Patients (n = 21) without previous diabetes, cardiovascular or cerebrovascular disease were recruited 5-7 months post-discharge alongside controls (n = 10) with similar age, sex and body mass. Perceived fatigue was estimated (Fatigue Severity Scale) and the following were conducted: oral glucose tolerance (OGTT) alongside whole-body fuel oxidation, validated magnetic resonance imaging and spectroscopy during resting and supine controlled exercise, dual-energy X-ray absorptiometry, short physical performance battery (SPPB), intra-muscular electromyography, quadriceps strength and fatigability, and daily step-count. There was a greater insulin response (incremental area under the curve, median (inter-quartile range)) during the OGTT in patients [18,289 (12,497-27,448) mIU/min/L] versus controls [8655 (7948-11,040) mIU/min/L], P < 0.001. Blood glucose response and fasting and post-prandial fuel oxidation rates were not different. This greater insulin resistance was not explained by differences in systemic inflammation or whole-body/regional adiposity, but step-count (P = 0.07) and SPPB scores (P = 0.004) were lower in patients. Liver volume was 28% greater in patients than controls, and fat fraction adjusted liver T 1 , a measure of inflammation, was raised in patients. Patients displayed greater perceived fatigue scores, though leg muscle volume, strength, force-loss, motor unit properties and post-exercise muscle phosphocreatine resynthesis were comparable. Further, cardiac and cerebral architecture and function (at rest and on exercise) were not different. In this cross-sectional study, individuals without known previous morbidity who survived severe COVID-19 exhibited greater insulin resistance, pointing to a need for physical function intervention in recovery., (© 2024 The Author(s). Experimental Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.)

Objective: This systematic review and meta-analysis aimed to investigate the objective, functional recovery of patients more than 3 months after acute COVID-19 infection., Methods: Comprehensive database searches of EMBASE, PubMed/MEDLINE, Cochrane COVID-19 Study Register, CINAHL, and Google Scholar in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement were carried out until October 19, 2022. Data were extracted and agreed in duplicate. Data were narratively synthesized, and a series of meta-analyses were performed using the random-effects inverse variance method., Results: One-hundred six papers covering 20,063 patients who were either hospitalized or not hospitalized with acute COVID-19 who were followed-up between 3 to 24 months were included. Percentage predicted 6-minute walk distance at 3 months to <5 months was 84.3% (95% CI = 79.2-89.3; n = 21; I2 = 98.3%) and 92.5% (95% CI = 89.8-95.3; n = 9; I2 = 94.5%) at ≥11 months. Cardiopulmonary exercise testing revealed percentage predicted peak oxygen consumption rate ($peak\dot{\mathrm{V}}{\mathrm{o}}&#95;2$) at 3 months to <5 months was 77.3% (95% CI = 71.0-83.7; n = 6; I2 = 92.3%) and 95.4% (95% CI = 87.1-103.6; n = 2; I2 = 77.3%) at ≥11 months. Mean handgrip strength was greatest at ≥11 months at 31.16 kg (95% CI = 19.89-42.43; n = 2; I2 = 98.3%) of all time points. All analyses showed marked heterogeneity., Conclusion: Patients have reduced physical function more than 3 months after COVID-19 infection. Better physical function in multiple physical domains is found after a longer recovery time., Impact: Physical function as measured by the 6-minute walk test, hand grip strength, and cardiopulmonary exercise testing is reduced at 3 months after COVID-19 infection and can remain over 11 months of follow-up. This protracted recovery following acute COVID-19 infection supports the need to assess physical function at any clinical follow-up, and further research into rehabilitation programs and intervention for patients who have not recovered., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Physical Therapy Association.)

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.

Introduction: The National Early Warning Score-2 (NEWS-2) is used to detect deteriorating patients in hospital settings. We aimed to understand how NEWS-2 functions in the real-life setting of an acute respiratory unit., Methods: Clinical observations data were extracted for adult patients (age ≥18 years), admitted under the care of respiratory medicine services from July to December 2019, who had at least one recorded task relating to clinical deterioration. The timing and nature of urgent out-of-hours medical reviews (escalations) were extracted through manual review of the case notes., Results: The data set comprised 765 admission episodes (48.9% women) with a mean (SD) age of 69.3 (14.8). 8971 out of 35 991 out-of-hours observation sets (24.9%) had a NEWS-2 ≥5, and 586 of these (6.5%) led to an escalation. Out of 687 escalations, 101 (14.7%) were associated with observation sets with NEWS-2<5. Rising oxygen requirement and extreme values of individual observations were associated with an increased risk of escalation. 57.6% of escalations resulted in a change in treatment. Inpatient mortality was higher in patients who were escalated at least once, compared with those who were not escalated., Conclusions: Most observation sets with NEWS-2 scores ≥5 did not lead to a medical escalation in an acute respiratory setting out-of-hours, but more than half of escalations resulted in a change in treatment. Rising oxygen requirement is a key indicator of respiratory patient acuity which appears to influence the decision to request urgent out-of-hours medical reviews., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

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., Competing Interests: Competing interests: FG reports grant funding from NIHR and Innovate UK, consultancy fees from Polarean and has shares in Optellum; SJ has received grant funding from GRAIL, consultancy fees/ honoraria from AstraZeneca and Chiesi, stock options in Optellum Ltd and his spouse is employed by AstraZeneca; RL is funded by the Royal Marsden NIHR BRC, Royal Marsden Cancer charity and SBRI (including QURE.AI). RL’s institution receives compensation for time spent in a secondment role for the lung health check program and as a National Specialty Lead for the National Institute of Health and Care Research. He has received research funding from CRUK, Innovate UK (cofunded by GE Healthcare, Roche and Optellum), SBRI, RM Partners Cancer Alliance and NIHR (coapplicant in grants with Optellum). He has received honoraria from CRUK; WM has received honoraria from Amgen; AN declares grants from Department of Health’s NIHR Biomedical Research Centre's funding scheme and GRAIL, consulting fees from Aidence BV, Faculty Science LTD and MSD; Support for attending meetings from Takeda Limited; Advisory Board participation for Aidence BV and Faculty Science Ltd; JR has received support for travel and accommodation from BTOG, ERS, CRUK, EORTC, ESMO and NCRI; RT has received honoraria from Olympus Medical; DRB has grant from NHS Digital and had received honoraria from MSD and AstraZeneca; DC, FM, JW are Optellum employees and have share options in Optellum. The remaining authors declare no conflicts of interests., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To assess whether antidepressant prescriptions are associated with an increased risk of pneumonia and chronic obstructive pulmonary disease (COPD) exacerbation., Methods: A self-controlled case series was performed to investigate the rates of pneumonia and COPD exacerbation during periods of being exposed to antidepressants compared with non-exposed periods. Patients with COPD with pneumonia or COPD exacerbation and at least one prescription of antidepressant were ascertained from The Health Improvement Network in the UK. Incidence rate ratios (IRR) and 95% CI were calculated for both outcomes., Results: Of 31 253 patients with COPD with at least one antidepressant prescription, 1969 patients had pneumonia and 18 483 had a COPD exacerbation. The 90-day risk period following antidepressant prescription was associated with a 79% increased risk of pneumonia (age-adjusted IRR 1.79, 95% CI 1.54 to 2.07). These associations then disappeared once antidepressants were discontinued. There was a 16% (age-adjusted IRR 1.16, 95% CI 1.13 to 1.20) increased risk of COPD exacerbation within the 90 days following antidepressant prescription. This risk persisted and slightly increased in the remainder period ((age-adjusted IRR 1.38, 95% CI 1.34 to 1.41), but diminished after patients discounted the treatment., Conclusion: Antidepressants were associated with an increased risk of both pneumonia and exacerbation in patients with COPD, with the risks diminished on stopping the treatment. These findings suggest a close monitoring of antidepressant prescription side effects and consideration of non-pharmacological interventions., Competing Interests: Competing interests: All authors have completed the International Committee of Medical Journal Editors (ICMJE) Form for Disclosure of Potential Conflicts of Interest (available on request from the corresponding author) and declare that the following: CEB reports grants from BLF Early COPD Study—various pharma, grants from Pfizer, grants from GSK, other from Chiesi, outside the submitted work; and no financial relationship with any organisation that might have an interest in the submitted work in the previous three years, no other relationship or activity that could appear to have influenced the submitted work., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Higher-valency pneumococcal vaccines are anticipated. We aimed to describe serotype distribution and risk factors for vaccine-serotype community-acquired pneumonia (CAP) in the two years pre-SARS-CoV-2 pandemic., Methods: We conducted a prospective cohort study of adults hospitalised with CAP at three UK sites between 2018 and 2020. Pneumococcal serotypes were identified using a 24-valent urinary-antigen assay and blood cultures. Risk factors associated with vaccine-type pneumonia caused by serotypes in the 13-, 15- and 20-valent pneumococcal conjugate vaccines (PCV13, PCV15, PCV20) and 23-valent pneumococcal polysaccharide vaccine (PPV23) were determined from multivariable analysis., Findings: Of 1921 adults hospitalised with CAP, 781 (40.7%, 95% confidence intervals (CI) 38.5-42.9%) had pneumococcal pneumonia. A single PCV13-serotype was detected in 242 (31.0%, 95% CI 27.8-34.3%) pneumococcal CAP patients, mostly serotype 3 (171/242, 70.7%, 95% CI 64.5-76.0%). The additional two PCV15-serotypes were detected in 31 patients (4%, 95% CI 2.8-5.6%), and PCV20-non13-serotypes in 192 (24.6%), with serotype 8 most prevalent (123/192, 64.1%, 95% CI 57.1-70.5%). Compared to PCV13-serotype CAP, people with PCV20-non13 CAP were younger (median age 62 versus 72 years, p < 0.001) and less likely to be male (44% versus 61%, p = 0.01). PPV23-non13-serotypes were found in 252 (32.3%, 95% CI 29.1-35.6%) pneumococcal CAP patients., Interpretation: Despite mature infant pneumococcal programmes, the burden of PCV13-serotype pneumonia remains high in older adults, mainly due to serotype 3. PCV20-non13-serotype pneumonia is more likely in younger people with fewer pneumococcal risk factors., Funding: Unrestricted investigator-initiated research grant from Pfizer, United Kingdom; support from National Institute for Health Research (NIHR) Biomedical Research Centre, Nottingham., Competing Interests: WSL reports unrestricted investigator-initiated research funding from Pfizer to WSL's institution. WSL is Chair of COVID-19 Immunisation, Joint Committee of Vaccination and Immunisation (JCVI) (unpaid), is an unpaid expert panel member for NICE COVID-19 Guidelines, and is an unpaid member of the NHSE Specialist Commissioning Group for Covid-19 therapeutics. University of Nottingham paid costs to Liverpool University Foundation Hospital Trust for the completion of the field work; NF is an honorary member of LUHFT and of the department that received this funding. NF is PI on grants from Wellcome, MRC, EDTCP and Gates Foundation and is a co-investigator on awards from Seqirus CSl and from GSK for studies unrelated to this work, participates on 3 Data Safety Monitoring Boards for NIHR and MRC funded research trials in relation to pneumococcal challenge models outside the submitted work, and serves on the pneumococcal subcommittee of the JCVI UK. CT participated in a CMV vaccine advisory board meeting in May 2022, unrelated to the topic of this paper. SE declares participation in a Virtual Advisory Board for a pneumococcal project organised by Sanofi Pasteur SA unrelated to the submitted work. The UK Health Security Agency (UKHSA) received monies from the University of Nottingham from an unrestricted grant from Pfizer for this work. The Vaccine Preventable Bacteria Section of UKHSA has received grants from Pfizer for investigator led research unrelated to the current project. The UKHSA provides vaccine manufacturers (GlaxoSmithKline (GSK), MSD, Pfizer) with post marketing surveillance reports on vaccine-preventable disease, including pneumococcal infections for which a cost recovery charge is made and which is unrelated to the submitted work. No other authors declare competing interests., (© 2023 The Authors.)

Introduction: Readmission rates following hospital admission with community-acquired pneumonia (CAP) have increased in the UK over the past decade. The aim of this work was to describe the cohort of patients with emergency 30-day readmission following hospitalisation for CAP in England and explore the reasons for this., Methods: A retrospective analysis of cases from the British Thoracic Society national adult CAP audit admitted to hospitals in England with CAP between 1 December 2018 and 31 January 2019 was performed. Cases were linked with corresponding patient level data from Hospital Episode statistics, providing data on the primary diagnosis treated during readmission and mortality. Analyses were performed describing the cohort of patients readmitted within 30 days, reasons for readmission and comparing those readmitted and primarily treated for pneumonia with other diagnoses., Results: Of 8136 cases who survived an index admission with CAP, 1304 (15.7%) were readmitted as an emergency within 30 days of discharge. The main problems treated on readmission were pneumonia in 516 (39.6%) patients and other respiratory disorders in 284 (21.8%). Readmission with pneumonia compared with all other diagnoses was associated with significant inpatient mortality (15.9% vs 6.5%; aOR 2.76, 95% CI 1.86 to 4.09, p<0.001). A diagnosis of hospital-acquired infection was more frequent in readmissions treated for pneumonia than other diagnoses (22.1% vs 3.9%, p<0.001)., Conclusion: Pneumonia is the most common condition treated on readmission following hospitalisation with CAP and carries a higher mortality than both the index admission or readmission due to other diagnoses. Strategies to reduce readmissions due to pneumonia are required., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Survivors of common infections may develop cognitive impairment or dementia; however, the risk of these conditions in people hospitalised with pneumonia is not well established., Methods: A matched cohort study was conducted using Hospital Episode Statistics (HES) data linked to the Clinical Practice Research Database (CPRD). Adults with the first International Classification of Diseases (10th Revision) code for pneumonia recorded in the HES between 1 July 2002 and 30 June 2017 were included, and up to four controls without hospitalisation for pneumonia in the CPRD were matched by sex, age and practice. Cognitive impairment and dementia incidence rates were calculated and survival analysis was performed comparing those hospitalised with pneumonia to the general population., Results: The incidence rates of cognitive impairment and dementia were 18 (95% CI 17.3-18.7) and 13.2 (95% CI 13-13.5) per 1000 person-years among persons previously hospitalised with pneumonia and the matched cohort respectively. People previously hospitalised with pneumonia had 53% higher incidence of cognitive impairment and dementia (adjusted hazard ratio (aHR) 1.53, 95% CI 1.46-1.61) than their matched cohort. The highest incidence was observed within 1 year of hospitalisation for pneumonia compared to the general population (aHR 1.89, 95% CI 1.75-2.05). Age modified the effect of hospitalisation for pneumonia on cognitive impairment and dementia such that the size of effect was stronger in people between 45 and 60 years old (p-value for interaction <0.0001)., Conclusion: Cognitive impairment and dementia are more likely to be diagnosed in people who have been hospitalised for pneumonia, especially in the first year after discharge, than in the general population., Competing Interests: Conflict of interest: C.V. Chalitsios, V. Baskaran, R.H. Harwood and T.M. McKeever declare no competing interests. W.S. Lim reports grants from National Institute for Health Research and Pfizer outside the submitted work. W.S. Lim is the Chair of COVID-19 Immunisation (unpaid) and the National Lead of British Thoracic Society community-acquired pneumonia audit programme (unpaid)., (Copyright ©The authors 2023.)

Electronic monitoring devices (EMDs) have been trialled in interventions to improve inhaled corticosteroid adherence and clinical outcomes. This study sought to understand the perceptions and experiences of EMD end-users. Participants recruited into a six-month EMD study were invited to a semi-structured interview. Interviews were audio-recorded, transcribed verbatim and analysed using the framework approach. Twenty-eight participants (68% female, median age 47) were interviewed. Individuals described feeling responsible for their asthma control. Recent attacks motivated a desire to maintain control. Study participation led to increased awareness of asthma status and medication use. Several individuals were open to integrating digital monitoring data with other mHealth inputs, perceiving the potential to enhance communication with clinicians and empower self-management. Openness to data sharing was tied to expectations of transparent data use. Data supported integrating beliefs and habit formation to achieve behaviour change. There was a willingness for an integrated, platform-based approach to digital self-management., (© 2022. The Author(s).)

Introduction: Socioeconomic deprivation has been associated with an increased incidence of infection and poorer clinical outcomes during influenza pandemics and the COVID-19 pandemic. The aim of this study was to determine the relationship between deprivation and adverse clinical outcomes following hospital admission with community-acquired pneumonia (CAP), specifically 30-day all-cause mortality and non-elective hospital readmission., Methods: Data from the British Thoracic Society national CAP audit on patients admitted to hospital with CAP in England between 1 December 2018 and 31 January 2019 were linked to patient-level Hospital Episode Statistics data and Index of Multiple Deprivation (IMD) scores. Multivariable logistic regression models were used to examine the association between deprivation and (a) 30-day mortality and (b) 30-day readmission with p values for trend reported. Age was examined as a potential effect modifier on the effect of IMD quintile on mortality and subsequent subanalysis in those <65 and ≥65 years was performed., Results: Of 9165 adults admitted with CAP, 24.7% (n=2263) were in the most deprived quintile. No significant trend between deprivation and mortality was observed (p trend=0.38); however, the association between deprivation and mortality differed by age group. In adults aged<65 years, 30-day mortality was highest in the most deprived and lowest in the least deprived quintiles (4.4% vs 2.5%, aOR 1.83, 95% CI 0.84 to 4.0) with a significant trend across groups (p trend=0.04). Thirty-day readmission was highest in the most deprived quintile (17.1%) with a significant p trend across groups (p trend 0.003). Age-adjusted odds of readmission were highest in the most deprived compared with the least deprived (aOR 1.41, 95% CI 1.16 to 1.73)., Conclusions: In adults aged<65 years hospitalised with CAP in England, mortality varied inversely with indices of social deprivation. There was also a significant association between deprivation and 30-day readmission. Strategies are required to decrease health inequalities in pneumonia mortality and hospital readmissions associated with deprivation., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

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., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Aims: Accurately predicting risk of patient deterioration is vital. Altered physiology in chronic disease affects the prognostic ability of vital signs based early warning score systems. We aimed to assess the potential of early warning score patterns to improve outcome prediction in patients with respiratory disease., Methods: Patients admitted under respiratory medicine between April 2015 and March 2017 had their National Early Warning Score 2 (NEWS2) calculated retrospectively from vital sign observations. Prediction models (including temporal patterns) were constructed and assessed for ability to predict death within 24 hours using all observations collected not meeting exclusion criteria. The best performing model was tested on a validation cohort of admissions from April 2017 to March 2019., Results: The derivation cohort comprised 7,487 admissions and the validation cohort included 8,739 admissions. Adding the maximum score in the preceding 24 hours to the most recently recorded NEWS2 improved area under the receiver operating characteristic curve for death in 24 hours from 0.888 (95% confidence interval (CI) 0.881-0.895) to 0.902 (95% CI 0.895-0.909) in the overall respiratory population., Conclusion: Combining the most recently recorded score and the maximum NEWS2 score from the preceding 24 hours demonstrated greater accuracy than using snapshot NEWS2. This simple inclusion of a scoring pattern should be considered in future iterations of early warning scoring systems., (© Royal College of Physicians 2022. All rights reserved.)

Background: The National Early Warning Score-2 (NEWS-2) is used to detect patient deterioration in UK hospitals but fails to take account of the detailed granularity or temporal trends in clinical observations. We used data-driven methods to develop dynamic early warning scores (DEWS) to address these deficiencies, and tested their accuracy in patients with respiratory disease for predicting (1) death or intensive care unit admission, occurring within 24 h (D/ICU), and (2) clinically significant deterioration requiring urgent intervention, occurring within 4 h (CSD)., Methods: Clinical observations data were extracted from electronic records for 31,590 respiratory in-patient episodes from April 2015 to December 2020 at a large acute NHS Trust. The timing of D/ICU was extracted for all episodes. 1100 in-patient episodes were annotated manually to record the timing of CSD, defined as a specific event requiring a change in treatment. Time series features were entered into logistic regression models to derive DEWS for each of the clinical outcomes. Area under the receiver operating characteristic curve (AUROC) was the primary measure of model accuracy., Results: AUROC (95% confidence interval) for predicting D/ICU was 0.857 (0.852-0.862) for NEWS-2 and 0.906 (0.899-0.914) for DEWS in the validation data. AUROC for predicting CSD was 0.829 (0.817-0.842) for NEWS-2 and 0.877 (0.862-0.892) for DEWS. NEWS-2 ≥ 5 had sensitivity of 88.2% and specificity of 54.2% for predicting CSD, while DEWS ≥ 0.021 had higher sensitivity of 93.6% and approximately the same specificity of 54.3% for the same outcome. Using these cut-offs, 315 out of 347 (90.8%) CSD events were detected by both NEWS-2 and DEWS, at the time of the event or within the previous 4 h; 12 (3.5%) were detected by DEWS but not by NEWS-2, while 4 (1.2%) were detected by NEWS-2 but not by DEWS; 16 (4.6%) were not detected by either scoring system., Conclusion: We have developed DEWS that display greater accuracy than NEWS-2 for predicting clinical deterioration events in patients with respiratory disease. Prospective validation studies are required to assess whether DEWS can be used to reduce missed deteriorations and false alarms in real-life clinical settings., (© 2022. The Author(s).)

Background: Depression is frequently reported in patients with Chronic Obstructive Pulmonary Disease (COPD). However, there is little information available on the incidence of depression following a COPD diagnosis., Objective: To determine the incidence of a new diagnosis of depression or antidepressant prescription in people with and without a COPD diagnosis., Methods: A matched cohort study was conducted using The Health Improvement Network database. Patients with confirmed COPD diagnosis were matched to up to four subjects without a COPD diagnosis by age, sex and GP practice. Cox proportional hazards models were used to assess the incidence rates of depression and antidepressant prescription., Results: 44,362 patients with COPD and 124,140 subjects without COPD were included. The incidence rate of depression per 1000 person-years following COPD diagnosis was greater (11.4; 95% CI: 10.9-11.8) compared to subjects without COPD (5.7; 95% CI: 5.5-5.8) (p < 0.001). Patients with COPD were 42% more likely to have an incident depression (adjusted hazard ratio [aHR]: 1.42; 95% CI: 1.32-1.53; p < 0.001), and 40% more likely to be prescribed an antidepressant (aHR: 1.40; 95% CI: 1.35-1.45; p < 0.001). The incidence to either depression or antidepressant prescription was also greater for patients with COPD (aHR: 1.41; 95% CI: 1.36-1.46; p < 0.001). Patients with COPD and worse breathlessness had a higher risk of incident depression compared to patients with less breathlessness., Conclusion: Healthcare providers managing patients with COPD should be alert to the existence of depression and aware of its symptoms and consequences., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Concerns have been raised over the association between bisphosphonates and atypical fractures in subtrochanteric and femoral shaft regions, but the potential risk of these fractures due to bisphosphonate use in asthma has not been examined., Introduction: Bisphosphonates are used as first-line treatment for osteoporosis; however, concerns have been raised over their association with atypical subtrochanteric (ST) and femoral shaft (FS) fractures. The potential risk of atypical ST/FS fractures from bisphosphonate use in asthma has not been examined., Methods: A nested case-control study was conducted using linked data from the Clinical Practice Research Datalink (CPRD) and Hospital Episode Statistics (HES) databases. Using an asthma cohort, we identified patients with atypical ST/FS fractures and sex, age, and practice-matched controls. Conditional logistic regression was used to determine the association between bisphosphonate exposure and atypical ST/FS fractures., Results: From a cohort of 69,074 people with asthma, 67 patients with atypical ST/FS fractures and 260 matched control subjects were identified. Of the case patients, 40.3% had received bisphosphonates as compared with 14.2% of the controls corresponding to an adjusted odds ratio (aOR) of 4.42 (95%CI, 2.98 to 8.53). The duration of use influenced the risk with long-term users to be at a greater risk (> 5 years vs no exposure; aOR = 7.67; 95%CI, 1.75 to 33.91). Drug withdrawal was associated with diminished odds of atypical ST/FS fractures., Conclusion: Regular review of bisphosphonates should occur in patients with asthma. The risks and benefits of bisphosphonate therapy should be carefully considered in consultation with the patient. To improve AFF prevention, early signs which may warrant imaging, such as prodromal thigh pain, should be discussed., (© 2021. International Osteoporosis Foundation and National Osteoporosis Foundation.)

Background: Non-invasive pneumococcal pneumonia causes significant morbidity and mortality in older adults. Understanding pneumococcal sero-epidemiology in adults ≥50 years is necessary to inform vaccination policies and the updating of pneumococcal vaccines., Methods: We conducted a systematic review and random-effects meta-analysis to determine the proportion of community-acquired pneumonia (CAP) in people ≥50 years due to pneumococcus and the proportion caused by pneumococcal vaccine serotypes. We searched MEDLINE, EMBASE and PubMed from 1 January 1990 to 30 March 2021. Heterogeneity was explored by subgroup analysis according to a) patient group (stratified versus age) and depth of testing, b) detection/serotyping method, and c) continent. The protocol is registered with PROSPERO (CRD42020192002)., Findings: Twenty-eight studies were included (34,216 patients). In the period 1-5 years after introduction of childhood PCV10/13 immunisation, 18% of CAP cases (95% CI 13-24%) were attributable to pneumococcus, with 49% (43-54%) of pneumococcal CAP due to PCV13 serotypes. The estimated proportion of pneumococcal CAP was highest in one study that used 24-valent serotype-specific urinary-antigen detection (ss-UAD)(30% [28-31%]), followed by studies based on diagnostic serology (28% [24-33%]), PCR (26% [15-37%]), ss-UAD14 (17% [13-22%]), and culture alone (14% [10-19%]). A higher estimate was observed in Europe (26% [21-30%] than North America (11% [9-12%]( p <0·001). PCV13-serotype estimates were also influenced by serotyping methods., Interpretation: Non-invasive pneumococcal CAP and vaccine-type pneumococcal CAP remains a burden in older adults despite widespread introduction of pneumococcal infant immunisation. Studies heavily reliant on ss-UADs restricted to vaccine-type serotypes may overestimate the proportion of potentially vaccine-preventable pneumococcal pneumonia. Sero-epidemiological data from low-income countries are lacking., Competing Interests: WSL reports unrestricted investigator-initiated research funding from Pfizer from 2016 to present for an unrelated multi-centre study in pneumonia in which he is the CI, and research funding for unrelated clinical trials in the fields of COVID-19, tuberculosis and community-acquired pneumonia. WSL also declares unpaid roles as the Joint Committee on Vaccination and Immunisation (JCVI) UK Chair of COVID-19 Immunisation, and National Lead of the British Thoracic Society community acquired pneumonia audit programme. LL's salary is funded by the National Institute for Health Research (NIHR) Nottingham Biomedical Research Centre, UK. HL declares voluntary, unpaid membership of the National Confidential Enquiry into Patient Outcome and Death specialist advisory group for Community Acquired Pneumonia. TM and BL declare no competing interests., (© 2022 The Authors.)

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., Competing Interests: Competing interests: WSL reports grants from National Institute for Health Research and Pfizer outside the submitted work., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Inhaled corticosteroids (ICS), prednisolone and antibiotics all play a crucial role in the management of respiratory diseases. The aim of this study was to analyse whether the declaration of the COVID-19 pandemic affected prescribing rates, as public health measures were implemented to reduce transmission of SARS-CoV-2. Monthly practise-level prescribing data published by NHS Digital were analysed. At the point, the COVID-19 outbreak was declared a pandemic, ICS prescriptions rose significantly. This was followed by a decrease in ICS and prednisolone prescribing in the following months. There was no difference in the antibiotic prescribing trend., (© The Author(s) 2021. Published by Oxford University Press on behalf of Faculty of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)