Functional Recovery of Adults Following Acute COVID-19: A Systematic Review and Meta-Analysis.

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 ($peak\dot{\mathrm{V}}{\mathrm{o}}_2$) 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.

Real-world implementation of the National Early Warning Score-2 in an acute respiratory unit.

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.

Pneumococcal serotypes and risk factors in adult community-acquired pneumonia 2018-20; a multicentre UK cohort study.

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.

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.

Readmission following hospital admission for community-acquired pneumonia in England.

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.

Association between antidepressants with pneumonia and exacerbation in patients with COPD: a self-controlled case series (SCCS).

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.

Incidence of cognitive impairment and dementia after hospitalisation for pneumonia: a UK population-based matched cohort study.

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.

Impact of social deprivation on clinical outcomes of adults hospitalised with community-acquired pneumonia in England: a retrospective cohort study.

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.

Qualitative study of user perspectives and experiences of digital inhaler technology.

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.

Predicting outcome in acute respiratory admissions using patterns of National Early Warning Scores.

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.

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.

Dynamic early warning scores for predicting clinical deterioration in patients with respiratory disease.

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.

Impact of Coexisting Dementia on Inpatient Outcomes for Patients Admitted with a COPD Exacerbation.

Purpose: 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.

Non-invasive pneumococcal pneumonia due to vaccine serotypes: A systematic review and meta-analysis.

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.

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.

A low exhaled nitric oxide level excludes a short-term benefit from inhaled corticosteroids in suspected asthma: A randomized placebo-controlled trial.

BACKGROUND AND OBJECTIVE: Fractional exhaled nitric oxide (FeNO) is a non-invasive biomarker that reflects IL-4/IL-13 production and therefore represents T2 allergic inflammation. FeNO has previously been used to guide inhaled corticosteroid (ICS) treatment in asthma. The purpose of this study was to determine if a low FeNO (≤27 ppb) could be used to reliably identify patients with symptoms suggestive of asthma who would not benefit from initiating treatment with an ICS. METHODS: A total of 180 steroid-naïve adults with healthcare professional suspected asthma and an FeNO of ≤27 ppb were randomized to receive either 400 mcg of budesonide or placebo daily for 3 months. The primary outcome was the difference in the Asthma Control Questionnaire 7 (ACQ7) between treatment groups and the study was powered to determine equivalence. Secondary outcomes were the difference in FEV1 , Medical Research Council and Leicester Cough Questionnaire scores. RESULTS: One hundred and thirty-four patients (68 budesonide and 66 placebo) completed the study and were included in the analysis. The between-group mean difference in ACQ7 from baseline to the end of the study was -0.25 and the 95% CI around this difference was -0.004 to 0.495 confirming equivalence (p < 0.05). Differences in forced expiratory volume over 1 s and other secondary outcomes were also small and clinically unimportant. CONCLUSION: The results of this study suggest that steroid-naïve patients with symptoms suggestive of asthma and an FeNO ≤ 27 ppb are unlikely to benefit from initiating treatment with an ICS over 3 months. However, further research is recommended to confirm these findings before withholding ICS treatment.