Determining the feasibility of calculating pancreatic cancer risk scores for people with new-onset diabetes in primary care (DEFEND PRIME): study protocol.

INTRODUCTION: Worldwide, pancreatic cancer has a poor prognosis. Early diagnosis may improve survival by enabling curative treatment. Statistical and machine learning diagnostic prediction models using risk factors such as patient demographics and blood tests are being developed for clinical use to improve early diagnosis. One example is the Enriching New-onset Diabetes for Pancreatic Cancer (ENDPAC) model, which employs patients' age, blood glucose and weight changes to provide pancreatic cancer risk scores. These values are routinely collected in primary care in the UK. Primary care's central role in cancer diagnosis makes it an ideal setting to implement ENDPAC but it has yet to be used in clinical settings. This study aims to determine the feasibility of applying ENDPAC to data held by UK primary care practices. METHODS AND ANALYSIS: This will be a multicentre observational study with a cohort design, determining the feasibility of applying ENDPAC in UK primary care. We will develop software to search, extract and process anonymised data from 20 primary care providers' electronic patient record management systems on participants aged 50+ years, with a glycated haemoglobin (HbA1c) test result of ≥48 mmol/mol (6.5%) and no previous abnormal HbA1c results. Software to calculate ENDPAC scores will be developed, and descriptive statistics used to summarise the cohort's demographics and assess data quality. Findings will inform the development of a future UK clinical trial to test ENDPAC's effectiveness for the early detection of pancreatic cancer. ETHICS AND DISSEMINATION: This project has been reviewed by the University of Surrey University Ethics Committee and received a favourable ethical opinion (FHMS 22-23151 EGA). Study findings will be presented at scientific meetings and published in international peer-reviewed journals. Participating primary care practices, clinical leads and policy makers will be provided with summaries of the findings.

Detection of COVID-19 by quantitative analysis of carbonyl compounds in exhaled breath.

COVID-19 has caused a worldwide pandemic, creating an urgent need for early detection methods. Breath analysis has shown great potential as a non-invasive and rapid means for COVID-19 detection. The objective of this study is to detect patients infected with SARS-CoV-2 and even the possibility to screen between different SARS-CoV-2 variants by analysis of carbonyl compounds in breath. Carbonyl compounds in exhaled breath are metabolites related to inflammation and oxidative stress induced by diseases. This study included a cohort of COVID-19 positive and negative subjects confirmed by reverse transcription polymerase chain reaction between March and December 2021. Carbonyl compounds in exhaled breath were captured using a microfabricated silicon microreactor and analyzed by ultra-high-performance liquid chromatography-mass spectrometry (UHPLC-MS). A total of 321 subjects were enrolled in this study. Of these, 141 (85 males, 60.3%) (mean ± SD age: 52 ± 15 years) were COVID-19 (55 during the alpha wave and 86 during the delta wave) positive and 180 (90 males, 50%) (mean ± SD age: 45 ± 15 years) were negative. Panels of a total of 34 ketones and aldehydes in all breath samples were identified for detection of COVID-19 positive patients. Logistic regression models indicated high accuracy/sensitivity/specificity for alpha wave (98.4%/96.4%/100%), for delta wave (88.3%/93.0%/84.6%) and for all COVID-19 positive patients (94.7%/90.1%/98.3%). The results indicate that COVID-19 positive patients can be detected by analysis of carbonyl compounds in exhaled breath. The technology for analysis of carbonyl compounds in exhaled breath has great potential for rapid screening and detection of COVID-19 and for other infectious respiratory diseases in future pandemics.

Decreasing Admissions but Increasing Readmissions for Mental Health in-Patient Treatment in Scotland, UK.

We have analysed mental health data for in-patient admissions from 1997 to 2021 in Scotland. The number of patient admissions for mental health patients is declining despite population numbers increasing. This is driven by the adult population; child and adolescent numbers are consistent. We find that mental health in-patients are more likely to be from deprived areas: 33 % of patients are from the most deprived areas, compared to only 11 % from the least deprived. The average length of stay for a mental health in-patient is decreasing, with a rise in stays lasting less than a day. The number of mental health patients who have been readmitted within a month fell from 1997 to 2011, then increased to 2021. Despite the average stay length decreasing, the number of overall readmissions is increasing, suggesting patients are having more, shorter stays.

A feasibility study on exhaled breath analysis using UV spectroscopy to detect COVID-19.

A 23-subject feasibility study is reported to assess how UV absorbance measurements on exhaled breath samples collected from silicon microreactors can be used to detect COVID-19. The silicon microreactor technology chemoselectively preconcentrates exhaled carbonyl volatile organic compounds and subsequent methanol elution provides samples for analysis. The underlying scientific rationale that viral infection will induce an increase in exhaled carbonyls appears to be supported by the results of the feasibility study. The data indicate statistically significant differences in measured UV absorbance values between healthy and symptomatic COVID-19 positive subjects in the wavelength range from 235 nm to 305 nm. Factors such as subject age were noted as potential confounding variables.

The Impact of COVID-19 on Mental Health Services in Scotland, UK.

There is a global emergency in relation to mental health (MH) and healthcare. In the UK each year, 1 in 4 people will experience MH problems. Healthcare services are increasingly oversubscribed, and COVID-19 has deepened the healthcare gap. We investigated the effect of COVID-19 on waiting times for MH services in Scotland. We used national registers of MH services provided by Public Health Scotland. The results show that waiting times for adults and children increased drastically during the pandemic. This was seen nationally and across most of the administrative regions of Scotland. We find, however, that child and adolescent services were comparatively less impacted by the pandemic than adult services. This is potentially due to prioritisation of paediatric patients, or due to an increasing demand on adult services triggered by the pandemic itself.

Differential Functional Responses of Neutrophil Subsets in Severe COVID-19 Patients.

Neutrophils play a significant role in determining disease severity following SARS-CoV-2 infection. Gene and protein expression defines several neutrophil clusters in COVID-19, including the emergence of low density neutrophils (LDN) that are associated with severe disease. The functional capabilities of these neutrophil clusters and correlation with gene and protein expression are unknown. To define host defense and immunosuppressive functions of normal density neutrophils (NDN) and LDN from COVID-19 patients, we recruited 64 patients with severe COVID-19 and 26 healthy donors (HD). Phagocytosis, respiratory burst activity, degranulation, neutrophil extracellular trap (NET) formation, and T-cell suppression in those neutrophil subsets were measured. NDN from severe/critical COVID-19 patients showed evidence of priming with enhanced phagocytosis, respiratory burst activity, and degranulation of secretory vesicles and gelatinase and specific granules, while NET formation was similar to HD NDN. COVID LDN response was impaired except for enhanced NET formation. A subset of COVID LDN with intermediate CD16 expression (CD16Int LDN) promoted T cell proliferation to a level similar to HD NDN, while COVID NDN and the CD16Hi LDN failed to stimulate T-cell activation. All 3 COVID-19 neutrophil populations suppressed stimulation of IFN-γ production, compared to HD NDN. We conclude that NDN and LDN from COVID-19 patients possess complementary functional capabilities that may act cooperatively to determine disease severity. We predict that global neutrophil responses that induce COVID-19 ARDS will vary depending on the proportion of neutrophil subsets.

A specific low-density neutrophil population correlates with hypercoagulation and disease severity in hospitalized COVID-19 patients.

SARS coronavirus 2 (SARS-CoV-2) is a novel viral pathogen that causes a clinical disease called coronavirus disease 2019 (COVID-19). Although most COVID-19 cases are asymptomatic or involve mild upper respiratory tract symptoms, a significant number of patients develop severe or critical disease. Patients with severe COVID-19 commonly present with viral pneumonia that may progress to life-threatening acute respiratory distress syndrome (ARDS). Patients with COVID-19 are also predisposed to venous and arterial thromboses that are associated with a poorer prognosis. The present study identified the emergence of a low-density inflammatory neutrophil (LDN) population expressing intermediate levels of CD16 (CD16Int) in patients with COVID-19. These cells demonstrated proinflammatory gene signatures, activated platelets, spontaneously formed neutrophil extracellular traps, and enhanced phagocytic capacity and cytokine production. Strikingly, CD16Int neutrophils were also the major immune cells within the bronchoalveolar lavage fluid, exhibiting increased CXCR3 but loss of CD44 and CD38 expression. The percentage of circulating CD16Int LDNs was associated with D-dimer, ferritin, and systemic IL-6 and TNF-α levels and changed over time with altered disease status. Our data suggest that the CD16Int LDN subset contributes to COVID-19-associated coagulopathy, systemic inflammation, and ARDS. The frequency of that LDN subset in the circulation could serve as an adjunct clinical marker to monitor disease status and progression.