The effect of Helicobacter pylori infection on gastric acid secretion in man

Helicobacter pylori (H pylori) infection is the commonest chronic bacterial infection world-wide. The work carried out in this thesis has sought to explore the effect of the infection on gastric secretory function in man. We developed a new test of gastric acid secretion using the substance gastrin releasing peptide (GRP) as the stimulus. Acid secretion measured in response to intravenous infusion of GRP reflects the combined functional response of the antrum and body of the stomach. It activates both stimulatory and inhibitory controls of acid secretion and in these respects it simulates the response to eating. The reproducibility of the GRP test was assessed and was found to be high for both gastrin and acid secretion. Using this new tool we studied acid secretion in a variety of subjects with and without H pylori infection. We have found that GRP stimulated acid secretion is increased six fold in DU patients with the infection compared to H pylori negative healthy volunteers (true normals). This exaggerated acid response is likely to represent a key pathophysiological defect which underlies DU disease. We have demonstrated for the first time that eradication of H pylori infection leads to normalisation of basal and GRP stimulated acid secretion in DU patients. These novel findings have shed considerable light on the understanding of the pathophysiology of DU disease and the role of H pylori infection in it. We have also shown for the first time that GRP stimulated acid secretion is increased two to three fold in H pylori positive healthy volunteers compared to true normals. This secretory abnormality also fully resolves following eradication of the infection. Since half the world's population is colonised with H pylori, it is essential that all future gastric secretory studies ensure that their control subjects are negative for the infection. The presence of the secretory abnormality in healthy volunteers may also be of relevance to other upper Gl diseases such as reflux disease. We proceeded to investigate the mechanism of the exaggerated acid response to GRP in DU patients and presented evidence compatible with this being due to impaired inhibitory control of acid secretion. We proceeded to examine the effect of the most commonly prescribed medication for dyspepsia, i.e. ranitidine, on acid secretion in healthy volunteers with and without H pylori infection. We showed that a two month course of ranitidine leads to a doubling of basal acid output and a 68% increase in GRP stimulated acid output two days after withdrawing treatment. This rebound acid hypersecretion is not associated with any significant change in gastrin concentrations and fully resolves within ten days of stopping ranitidine. These findings may offer an explanation for the common clinical problem of rapid resurgence of dyspeptic symptoms following discontinuation of acid suppressive therapy. Finally, we used the GRP test to study acid secretion in patients with non ulcer dyspepsia (NUD) and H pylori infection. We showed that a significant proportion of NUD patients had an exaggerated acid response to GRP similar to DU patients i.e. they displayed the DU diathesis. This raises the exciting possibility that this group of NUD patients may also be cured by eradication of their H pylori infection

Burnout among surgeons before and during the SARS-CoV-2 pandemic: an international survey

Background: SARS-CoV-2 pandemic has had many significant impacts within the surgical realm, and surgeons have been obligated to reconsider almost every aspect of daily clinical practice. Methods: This is a cross-sectional study reported in compliance with the CHERRIES guidelines and conducted through an online platform from June 14th to July 15th, 2020. The primary outcome was the burden of burnout during the pandemic indicated by the validated Shirom-Melamed Burnout Measure. Results: Nine hundred fifty-four surgeons completed the survey. The median length of practice was 10 years; 78.2% included were male with a median age of 37 years old, 39.5% were consultants, 68.9% were general surgeons, and 55.7% were affiliated with an academic institution. Overall, there was a significant increase in the mean burnout score during the pandemic; longer years of practice and older age were significantly associated with less burnout. There were significant reductions in the median number of outpatient visits, operated cases, on-call hours, emergency visits, and research work, so, 48.2% of respondents felt that the training resources were insufficient. The majority (81.3%) of respondents reported that their hospitals were included in the management of COVID-19, 66.5% felt their roles had been minimized; 41% were asked to assist in non-surgical medical practices, and 37.6% of respondents were included in COVID-19 management. Conclusions: There was a significant burnout among trainees. Almost all aspects of clinical and research activities were affected with a significant reduction in the volume of research, outpatient clinic visits, surgical procedures, on-call hours, and emergency cases hindering the training. Trial registration: The study was registered on clicaltrials.gov "NCT04433286" on 16/06/2020

SARS-CoV-2 vaccination modelling for safe surgery to save lives: data from an international prospective cohort study

Background: Preoperative SARS-CoV-2 vaccination could support safer elective surgery. Vaccine numbers are limited so this study aimed to inform their prioritization by modelling. Methods: The primary outcome was the number needed to vaccinate (NNV) to prevent one COVID-19-related death in 1 year. NNVs were based on postoperative SARS-CoV-2 rates and mortality in an international cohort study (surgical patients), and community SARS-CoV-2 incidence and case fatality data (general population). NNV estimates were stratified by age (18-49, 50-69, 70 or more years) and type of surgery. Best- and worst-case scenarios were used to describe uncertainty. Results: NNVs were more favourable in surgical patients than the general population. The most favourable NNVs were in patients aged 70 years or more needing cancer surgery (351; best case 196, worst case 816) or non-cancer surgery (733; best case 407, worst case 1664). Both exceeded the NNV in the general population (1840; best case 1196, worst case 3066). NNVs for surgical patients remained favourable at a range of SARS-CoV-2 incidence rates in sensitivity analysis modelling. Globally, prioritizing preoperative vaccination of patients needing elective surgery ahead of the general population could prevent an additional 58 687 (best case 115 007, worst case 20 177) COVID-19-related deaths in 1 year. Conclusion: As global roll out of SARS-CoV-2 vaccination proceeds, patients needing elective surgery should be prioritized ahead of the general population

Characteristics and outcomes of COVID-19 patients admitted to hospital with and without respiratory symptoms

Background: COVID-19 is primarily known as a respiratory illness; however, many patients present to hospital without respiratory symptoms. The association between non-respiratory presentations of COVID-19 and outcomes remains unclear. We investigated risk factors and clinical outcomes in patients with no respiratory symptoms (NRS) and respiratory symptoms (RS) at hospital admission. Methods: This study describes clinical features, physiological parameters, and outcomes of hospitalised COVID-19 patients, stratified by the presence or absence of respiratory symptoms at hospital admission. RS patients had one or more of: cough, shortness of breath, sore throat, runny nose or wheezing; while NRS patients did not. Results: Of 178,640 patients in the study, 86.4 % presented with RS, while 13.6 % had NRS. NRS patients were older (median age: NRS: 74 vs RS: 65) and less likely to be admitted to the ICU (NRS: 36.7 % vs RS: 37.5 %). NRS patients had a higher crude in-hospital case-fatality ratio (NRS 41.1 % vs. RS 32.0 %), but a lower risk of death after adjusting for confounders (HR 0.88 [0.83-0.93]). Conclusion: Approximately one in seven COVID-19 patients presented at hospital admission without respiratory symptoms. These patients were older, had lower ICU admission rates, and had a lower risk of in-hospital mortality after adjusting for confounders