Background: Tumour hypoxia is a recognised cause of radiotherapy treatment resistance in head and neck squamous cell carcinoma (HNSCC). Current positron emission tomography-based hypoxia imaging techniques are not routinely available in many centres. We investigated if an alternative technique called oxygen-enhanced magnetic resonance imaging (OE-MRI) could be performed in HNSCC. Method(s): A volumetric OE-MRI protocol for dynamic T1 relaxation time mapping was implemented on 1.5-T clinical scanners. Participants were scanned breathing room air and during high-flow oxygen administration. Oxygen-induced changes in T1 times (DELTAT1) and R2* rates (DELTAR2*) were measured in malignant tissue and healthy organs. Unequal variance t-test was used. Patients were surveyed on their experience of the OE-MRI protocol. Result(s): Fifteen patients with HNSCC (median age 59 years, range 38 to 76) and 10 non-HNSCC subjects (median age 46.5 years, range 32 to 62) were scanned; the OE-MRI acquisition took less than 10 min and was well tolerated. Fifteen histologically confirmed primary tumours and 41 malignant nodal masses were identified. Median (range) of DELTAT1 times and hypoxic fraction estimates for primary tumours were -3.5% (-7.0 to -0.3%) and 30.7% (6.5 to 78.6%) respectively. Radiotherapy-responsive and radiotherapy-resistant primary tumours had mean estimated hypoxic fractions of 36.8% (95% confidence interval CI] 17.4 to 56.2%) and 59.0% (95% CI 44.6 to 73.3%), respectively (p = 0.111). Conclusion(s): We present a well-tolerated implementation of dynamic, volumetric OE-MRI of the head and neck region allowing discernment of differing oxygen responses within biopsy-confirmed HNSCC. Trial registration: ClinicalTrials.gov, NCT04724096. Registered on 26 January 2021. Relevance statement: MRI of tumour hypoxia in head and neck cancer using routine clinical equipment is feasible and well tolerated and allows estimates of tumour hypoxic fractions in less than ten minutes. Key points: * Oxygen-enhanced MRI (OE-MRI) can estimate tumour hypoxic fractions in ten-minute scanning. * OE-MRI may be incorporable into routine clinical tumour imaging. * OE-MRI has the potential to predict outcomes after radiotherapy treatment. Graphical Abstract: (Figure presented.)Copyright © The Author(s) 2024.

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: 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: 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, pCONCLUSION: 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. Copyright © Author(s) (or their employer(s)) 2023.

BACKGROUND: With higher valency pneumococcal vaccines on the horizon and new adult immunisation strategies under discussion, we aimed to evaluate the contribution of individual pneumococcal serotypes to the burden of pneumococcal community-acquired pneumonia (CAP). Over 10 years, trends in pneumococcal pneumonia epidemiology in adults hospitalised with CAP were assessed. The risk factors and severity associated with serotype 3 were examined., METHODS: We conducted a prospective cohort study of adults hospitalised with CAP between September 2013 and May 2023. Pneumococcal serotypes were identified using a serotype-specific 24-valent urinary-antigen assay. Trends in the proportion of CAP due to pneumococcus and causative serotypes were compared prepandemic and postpandemic. Risk factors and severity of serotype 3 pneumonia were compared with other serotypes using logistic regression., RESULTS: Of 5186 patients with CAP, 2193 (42.2%) had pneumococcal pneumonia. The proportion of CAP due to pneumococcus increased across all ages between 2013 and 2023 (36.4%-66.9%, p: Of 5186 patients with CAP, 2193 (42.2%) had pneumococcal pneumonia. The proportion of CAP due to pneumococcus increased across all ages between 2013 and 2023 (36.4%-66.9%, p: Of 5186 patients with CAP, 2193 (42.2%) had pneumococcal pneumonia. The proportion of CAP due to pneumococcus increased across all ages between 2013 and 2023 (36.4%-66.9%, pINTERPRETATION: Serotype 3 is the predominant serotype in adult pneumococcal CAP and has been increasing despite a mature infant pneumococcal immunisation programme, consistent with a lack of herd protection for this serotype. Copyright © Author(s) (or their employer(s)) 2024.

BACKGROUND: Hydroxychloroquine and chloroquine have been proposed as treatments for coronavirus disease 2019 (Covid-19) on the basis of in vitro activity and data from uncontrolled studies and small, randomized trials., METHODS: In this randomized, controlled, open-label platform trial comparing a range of possible treatments with usual care in patients hospitalized with Covid-19, we randomly assigned 1561 patients to receive hydroxychloroquine and 3155 to receive usual care. The primary outcome was 28-day mortality., RESULTS: The enrollment of patients in the hydroxychloroquine group was closed on June 5, 2020, after an interim analysis determined that there was a lack of efficacy. Death within 28 days occurred in 421 patients (27.0%) in the hydroxychloroquine group and in 790 (25.0%) in the usual-care group (rate ratio, 1.09; 95% confidence interval CI], 0.97 to 1.23; P = 0.15). Consistent results were seen in all prespecified subgroups of patients. The results suggest that patients in the hydroxychloroquine group were less likely to be discharged from the hospital alive within 28 days than those in the usual-care group (59.6% vs. 62.9%; rate ratio, 0.90; 95% CI, 0.83 to 0.98). Among the patients who were not undergoing mechanical ventilation at baseline, those in the hydroxychloroquine group had a higher frequency of invasive mechanical ventilation or death (30.7% vs. 26.9%; risk ratio, 1.14; 95% CI, 1.03 to 1.27). There was a small numerical excess of cardiac deaths (0.4 percentage points) but no difference in the incidence of new major cardiac arrhythmia among the patients who received hydroxychloroquine., CONCLUSIONS: Among patients hospitalized with Covid-19, those who received hydroxychloroquine did not have a lower incidence of death at 28 days than those who received usual care. (Funded by UK Research and Innovation and National Institute for Health Research and others; RECOVERY ISRCTN number, ISRCTN50189673; ClinicalTrials.gov number, NCT04381936.). Copyright © 2020 Massachusetts Medical Society.

Current pneumococcal vaccines cover the 10 to 23 most common serotypes of the 92 presently described. However, with the increased usage of pneumococcal-serotype-based vaccines, the risk of serotype replacement and an increase in disease caused by nonvaccine serotypes remains. Serotype surveillance of pneumococcal infections relies heavily on culture techniques, which are known to be insensitive, particularly in cases of noninvasive disease. Pneumococcal-serotype-specific urine assays offer an alternative method of serotyping for both invasive and noninvasive disease. However, the assays described previously cover mainly conjugate vaccine serotypes, give little information about circulating nonvaccine serotypes, and are currently available only in one or two specialist laboratories. Our laboratory has developed a Luminex-based extended-range antigen capture assay to detect pneumococcal-serotype-specific antigens in urine samples. The assay targets 24 distinct serotypes/serogroups plus the cell wall polysaccharide (CWP) and some cross-reactive serotypes. We report that the assay is capable of detecting all the targeted serotypes and the CWP at 0.1 ng/ml, while some serotypes are detected at concentrations as low as 0.3 pg/ml. The analytical serotype specificity was determined to be 98.4% using a panel of polysaccharide-negative urine specimens spiked with nonpneumococcal bacterial antigens. We also report clinical sensitivities of 96.2% and specificities of 89.9% established using a panel of urine specimens from patients diagnosed with community-acquired pneumonia or pneumococcal disease. This assay can be extended for testing other clinical samples and has the potential to greatly improve serotype-specific surveillance in the many cases of pneumococcal disease in which a culture is never obtained. Copyright © Crown copyright 2017.

National surveillance of pneumococcal disease at the serotype level is essential to assess the effectiveness of vaccination programmes. We previously developed a highly sensitive extended-specificity multiplex immunoassay for detection of Streptococcus pneumoniae serotype-specific antigen in urine in the absence of isolates. The assay uses human mAbs that detect the 24 pneumococcal serotype/groups targeted by the pneumococcal conjugate vaccines (PCVs) and pneumococcal polysaccharide vaccine (PPV-23) plus some cross-reactive types and the pneumococcal cell-wall polysaccharide. However, the previous assay had some limitations, namely the reduced specificity of the serotype 7F, 20 and 22F assays, for which non-specific binding in urine samples was observed. Here we report on the further development and re-validation of a new version of the assay (version 2.1), which offers improved sensitivity towards serotypes 7F, 18C and 19F and increased specificity for serotypes 7F, 20 and 22F by replacement of some of the antibody clones with new clones. Using a panel of urine specimens from patients diagnosed with community-acquired pneumonia or pneumococcal disease, the overall clinical sensitivity of this version of the assay based on isolation of S. pneumoniae from a normally sterile site is 94.3 % and the clinical specificity is 93.6 %, in comparison with clinical sensitivity and specificity values of 96.2 % and 89.9 % in the previous assay. Copyright © 2020 Crown copyright.

BACKGROUND: Up to 70% of patients report ongoing symptoms 4 weeks after hospitalisation for pneumonia; the impact on primary care is poorly understood., AIM: To investigate the frequency of primary care consultations after hospitalisation for pneumonia, and the reasons for consultation., DESIGN AND SETTING: A population-based cohort study in England using a UK primary care database of anonymised medical records (Clinical Practice Research Datalink CPRD]) linked to Hospital Episode Statistics (HES)., METHOD: Adults with the first International Classification of Diseases, 10th Revision (ICD-10) code for pneumonia (J12-J18) recorded in HES between July 2002 and June 2017 were included. Primary care consultation within 30 days of discharge was identified as the recording of any medical Read code (excluding administration-related codes) in CPRD. Competing-risks regression analyses were conducted to determine the predictors of consultation and antibiotic use at consultation; death and readmission were competing events. Reasons for consultation were examined., RESULTS: Of 56 396 adults, 55.9% (n = 31 542) consulted primary care within 30 days of hospital discharge. The rate of consultation was highest within 7 days (4.7 per 100 person-days). The strongest predictor for consultation was a higher number of primary care consultations in the year before index admission (adjusted subhazard ratio sHR] 8.98, 95% confidence interval CI] = 6.42 to 12.55). The most common reason for consultation was for a respiratory disorder (40.7%, n = 12 840), 11.8% for pneumonia specifically. At consultation, 31.1% (n = 9823) received further antibiotics. Penicillins (41.6%, n = 5753/13 829) and macrolides (21.9%, n = 3029/13 829) were the most common antibiotics prescribed., CONCLUSION: Following hospitalisation for pneumonia, a significant proportion of patients consulted primary care within 30 days, highlighting the morbidity experienced by patients during recovery from pneumonia. Copyright © The Authors.

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 : 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 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. Copyright ©The authors 2023.

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

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. Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.