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.

Retrospective case-control study to evaluate hypocalcaemia as a distinguishing feature of COVID-19 compared with other infective pneumonias and its association with disease severity.

OBJECTIVES: To investigate whether calcium derangement was a specific feature of COVID-19 that distinguishes it from other infective pneumonias, and its association with disease severity. DESIGN: A retrospective observational case-control study looking at serum calcium on adult patients with COVID-19, and community-acquired pneumonia (CAP) or viral pneumonia (VP). SETTING: A district general hospital on the outskirts of London, UK. PARTICIPANTS: 506 patients with COVID-19, 95 patients with CAP and 152 patients with VP. OUTCOME MEASURES: Baseline characteristics including hypocalcaemia in patients with COVID-19, CAP and VP were detailed. For patients with COVID-19, the impact of an abnormally low calcium level on the maximum level of hospital care, as a surrogate of COVID-19 severity, was evaluated. The primary outcome of maximal level of care was based on the WHO Clinical Progression Scale for COVID-19. RESULTS: Hypocalcaemia was a specific and common clinical finding in patients with COVID-19 that distinguished it from other respiratory infections. Calcium levels were significantly lower in those with severe disease. Ordinal regression of risk estimates for categorised care levels showed that baseline hypocalcaemia was incrementally associated with OR of 2.33 (95% CI 1.5 to 3.61) for higher level of care, superior to other variables that have previously been shown to predict worse COVID-19 outcome. Serial calcium levels showed improvement by days 7-9 of admission, only in survivors of COVID-19. CONCLUSION: Hypocalcaemia is specific to COVID-19 and may help distinguish it from other infective pneumonias. Hypocalcaemia may independently predict severe disease and warrants detailed prognostic investigation. The fact that decreased serum calcium is observed at the time of clinical presentation in COVID-19, but not other infective pneumonias, suggests that its early derangement is pathophysiological and may influence the deleterious evolution of this disease. TRIAL REGISTRATION NUMBER: 20/HRA/2344.

Early prognostication of COVID-19 to guide hospitalisation versus outpatient monitoring using a point-of-test risk prediction score.

INTRODUCTION: Risk factors of adverse outcomes in COVID-19 are defined but stratification of mortality using non-laboratory measured scores, particularly at the time of prehospital SARS-CoV-2 testing, is lacking. METHODS: Multivariate regression with bootstrapping was used to identify independent mortality predictors in patients admitted to an acute hospital with a confirmed diagnosis of COVID-19. Predictions were externally validated in a large random sample of the ISARIC cohort (N=14 231) and a smaller cohort from Aintree (N=290). RESULTS: 983 patients (median age 70, IQR 53-83; in-hospital mortality 29.9%) were recruited over an 11-week study period. Through sequential modelling, a five-predictor score termed SOARS (SpO2, Obesity, Age, Respiratory rate, Stroke history) was developed to correlate COVID-19 severity across low, moderate and high strata of mortality risk. The score discriminated well for in-hospital death, with area under the receiver operating characteristic values of 0.82, 0.80 and 0.74 in the derivation, Aintree and ISARIC validation cohorts, respectively. Its predictive accuracy (calibration) in both external cohorts was consistently higher in patients with milder disease (SOARS 0-1), the same individuals who could be identified for safe outpatient monitoring. Prediction of a non-fatal outcome in this group was accompanied by high score sensitivity (99.2%) and negative predictive value (95.9%). CONCLUSION: The SOARS score uses constitutive and readily assessed individual characteristics to predict the risk of COVID-19 death. Deployment of the score could potentially inform clinical triage in preadmission settings where expedient and reliable decision-making is key. The resurgence of SARS-CoV-2 transmission provides an opportunity to further validate and update its performance.

A pilot study of a digital drainage system in pneumothorax.

UNLABELLED: Over recent years there has been increasing usage of digital systems within cardiothoracic surgery to quantify air leaks and aid in clinical decision-making regarding the removal of chest drains postoperatively. The literature suggests improved agreement on timing of removal of chest drains and a reduced length of stay of patients. It could be that such devices could be useful tools for the clinician managing cases of pneumothorax. METHODS: This pilot study recruited adults admitted under the medical team with a pneumothorax requiring a chest drain. Participants had the underwater seal device changed for a digital device (Thopaz) which allowed continuous monitoring of the air leak. Drains were removed when either there was no ongoing air leak and the lung had expanded, or surgery was deemed necessary. RESULTS: Thirteen patients with pneumothorax (four primary, nine secondary) used the device during their admission including one patient treated in the community (the device has internal suction). Data were used to aid the clinician in management of the pneumothorax including the timing of surgery/ removal of drain and commencement of suction. DISCUSSION: Digital devices appear to be safe and effective and may prove to be a useful tool in the management of pneumothorax.

An unusual cause of cyanosis in a patient with COPD.

We present a case of acquired methaemoglobinaemia related to the prolonged use of dapsone in a patient with chronic hypoxia. The patient was initially successfully treated for infective exacerbation of chronic obstructive pulmonary disease (COPD). However, he remained persistently hypoxic on pulse oximetry despite a normal PaO2 on arterial blood gas sampling. His fraction of methaemoglobin (FMetHb) was found to be elevated at 13%. After cessation of dapsone, his clinical cyanosis recuperated, his exercise tolerance and functional capacity improved and his FMetHb normalised to 1%.

Seasonal variability and meteorological factors: retrospective study of the incidence of pulmonary embolism from a large United kingdom teaching hospital.

BACKGROUND: Seasonal variations in the incidence of pulmonary embolism (PE) have been reported. It has been suggested that changes in meteorological factors may explain this variation. Previous studies have provided inconsistent results, possibly as a result of a small number of observations, in some studies and confounding factors. OBJECTIVE: To investigate whether there is a seasonal variation in the incidence of idiopathic PE and to investigate its relationship with atmospheric pressure, humidity, and temperature. METHODS: A large retrospective study was conducted. All confirmed cases of PE at our institution over a 9-year period were included, except for those patients with a major risk factor for PE. Meteorological data were obtained from a local weather station. Days when there was at least one episode of PE (event day) were compared with days when there were no episodes of PE (non-event day). RESULTS: There were a total of 640 episodes of PE. There was a statistically significant lower percentage of event days in spring (13.8%), compared with the rest of the year (18.3%) (P = .003). The incidence of PE was related to decreased atmospheric pressure and increased temperature. For atmospheric pressure the relationship was most significant for the mean atmospheric pressure for the 2 days preceding clinical presentation with PE (P = .02). For temperature the relationship was most significant for the mean temperature for the 5 days preceding clinical presentation with PE (P = .04). CONCLUSIONS: The results confirm the presence of seasonal variations in episodes of idiopathic PE and an association between decreased atmospheric pressure and increased temperature.

Modified Th2 responses at high-dose exposures to allergen: using an occupational model.

RATIONALE: The relationships between allergen exposures and allergy and asthma are complex. High exposure levels to cat allergen are associated with IgG- and IgG(4)-specific antibody responses without sensitization or risk of asthma, a process described as a "modified Th2 response." Attenuation of risk of allergy and asthma at high exposure levels has been reported in longitudinal studies of both childhood and occupational asthma. OBJECTIVES: To investigate, using an occupational model, the relationships among estimated exposure to aeroallergens, the production of specific IgE, IgG and IgG(4) antibodies, and the prevalence of associated symptoms. METHODS: Cross-sectional survey of employees exposed to rats at work on six pharmaceutical sites across the United Kingdom. A total of 689 (89%) provided a blood sample and completed a questionnaire. MEASUREMENTS AND MAIN RESULTS: At highest exposure to rats, there was an attenuation of the exposure response for sensitization and symptoms. In contrast, the frequency of individuals producing high quantities of specific IgG and IgG(4) increased with exposure intensity. Ratios of IgG(4)/IgE were highest in those handling the greatest number of rats. Risk of developing work-related chest symptoms was lower for those who produced both specific IgE and IgG(4) compared to those with specific IgE only. CONCLUSIONS: High exposure to rats is associated with lower rates of specific IgE and symptoms but an increased frequency of high specific IgG and IgG(4) production. Specific IgG(4) produced together with specific IgE may reduce the risk of developing work-related chest symptoms compared with when specific IgE is produced alone.

HLA associations with occupational sensitization to rat lipocalin allergens: a model for other animal allergies?

BACKGROUND: Laboratory animal allergy is a common occupational health problem affecting between 11% and 44% of exposed researchers. Allergy to rats and mice is most common, probably because these are the animals most frequently used. OBJECTIVE: We hypothesized that HLA class II molecules, involved in the presentation of allergen to the T cell and likely candidates for controlling the immune response, might be associated with sensitization to rat urinary proteins among laboratory animal handlers. METHODS: We undertook a cross-sectional study of 741 employees at 6 pharmaceutical sites across the United Kingdom who had contact at work with laboratory rats. In all, 109 cases with specific sensitization to rat proteins and 397 referents were HLA-typed for DRB1 and DQB1 loci. Amino acid analyses of significantly associated HLA molecules were carried out. RESULTS: HLA-DR7 was associated with sensitization (odds ratio [OR], 1.82; CI, 1.12-2.97), respiratory symptoms at work (OR, 2.96; CI, 1.64-5.37) and, most strongly, sensitization with symptoms (OR, 3.81; CI, 1.90-7.65). HLA-DR3 was protective against sensitization (OR, 0.55; CI, 0.31-0.97). Amino acid analyses of these 2 molecules indicated a biologically plausible explanation for the associations. CONCLUSION: HLA phenotype is an important determinant of individual susceptibility to sensitization and asthma among laboratory animal workers. Similar mechanisms might apply in other animal allergies.