13 research outputs found
What is translational research? Background, concepts, and a definition
No full textAuthor version made available here in accordance with publisher copyright policy.This discussion paper aims to offer an overview and working definition of translational research, appropriate to health. Methods: Using scholarly and applied literature, the paper first identifies key challenges in achieving evidence-based policy and practice. It highlights international policy interest in new approaches to evidence translation and the barriers to achieving sound evidence translation. The paper offers an explicit definition of translational research and explains why it is important to have such a definition. It then elaborates on this definition by identifying and exploring seven distinctive research practices that could be associated with translational research. Findings and conclusions: Translational research is research with a sense of place. Its defining feature is excellence in evidence for a specific context or sphere of action, whether that is health policy for the World Health Organisation or service design for a local non-government organisation. If research is to be translated at all, it needs to be meaningful to many specific contexts, including small and regional contexts. The best promise that translational research offers is of exciting new techniques to achieve rigour and systemacy for such localised ‘real world’ policy, service and practice contexts
Helicobacter pylori and the management of gastro-oesophageal reflux disease
No full textThis thesis is centred on the current controversy and possible links between H. pylori and GORD and whether the infection should be eradicated in those requiring long PPIs. The thesis combines three methodologies: systematic reviews to ascertain current knowledge, qualitative research to ascertain the perceptions of GPs regarding this link, and, a cross sectional survey of patients on long term PPIs, including an evaluation of their H. pylori status. The field work was done in Northern England. The findings were:1) Patients with oesophagitis or reflux were less likely to have H. pylori infection. 2) The eradication of H. pylori in patients with duodenal ulcer did not influence the presence or absence of oesophagitis afterwards. The view that eradication provokes oesophagitis was not substantiated. 3) The effect of H. pylori eradication in patients with reflux oesophagitis,without peptic ulcer, was uncertain. 4) GPs held diverse views to justify variations in PPI prescribing. They did not consider a link between H. pylori and GORD and rarely prescribed eradication therapy to such patients. 5) 1. 73% of the population was on long term PPIs, rates varying six fold between practices. Reflux disease was associated with a third of this prescribing. 111 6) Over 66% of patients on long term PPIs had had an upper Gl investigation. However, practices varied widely in their use of endoscopy (33%-82%).7) Virtually all patients on long term PPIs still had ongoing symptoms. 31% were positive for H. pylori and in them, reflux symptoms and quality of life measures were better than those who tested negative. Conclusions A potential link between H. pylori and GORD did not impinge upon decision making in general practice. Current knowledge does not substantiate the view that H. pylori eradication provokes reflux oesophagitis but there are insufficient data about the effect of eradication in patients treated solely for reflux. The widespread variations in PPI prescribing and investigation rates could not be correlated with epidemiological or practice characteristics but it was ascertained that the rate of long term PPI usage was three times than previously determined. Virtually all patients had ongoing symptoms despite PPI use and reflux symptoms and QoL measures were worse in those patients who tested negative. This research does not definitively answer the question whether H. pylori should be eradicated in patients on long term PPIs. However,should this be considered necessary, the size of this task is quantified. Future research centred on therapy in this category of patients is required for a definitive answer
Epidemiology, practice of ventilation and outcome for patients at increased risk of postoperative pulmonary complications: LAS VEGAS - an observational study in 29 countries.
No full textDo we need gastric acid?
No full textEvidence from comparative anatomy and physiology studies indicates that gastric acid secretion developed during the evolution of vertebrates approximately 350 million years ago. The cellular mechanisms that produce gastric acid have been conserved over the millennia and therefore proton pump inhibitors have pharmacological effects in almost all relevant species. These observations suggest that gastric acid provides an important selective advantage; however, in modern-day humans the need for gastric acid can be questioned in light of the widespread use of safe and effective pharmacologic acid suppression. The Kandahar Working Group addressed questions concerning the need, production and effects of gastric acid, specifically: (1) motility in the upper gastrointestinal (GI) tract; (2) neuroendocrine factors; (3) digestive and mucosal processes; (4) microbiology, and (5) central processes and psychological involvement. We addressed each topic with the individual models available to answer our questions including animal versus human studies, pharmacologic, surgical as well as pathophysiologic states of acid suppression
Sex difference and intra-operative tidal volume: Insights from the LAS VEGAS study
No full textBACKGROUND: One key element of lung-protective ventilation is the use of a low tidal volume (VT). A sex difference in use of low tidal volume ventilation (LTVV) has been described in critically ill ICU patients.OBJECTIVES: The aim of this study was to determine whether a sex difference in use of LTVV also exists in operating room patients, and if present what factors drive this difference.DESIGN, PATIENTS AND SETTING: This is a posthoc analysis of LAS VEGAS, a 1-week worldwide observational study in adults requiring intra-operative ventilation during general anaesthesia for surgery in 146 hospitals in 29 countries.MAIN OUTCOME MEASURES: Women and men were compared with respect to use of LTVV, defined as VT of 8 ml kg-1 or less predicted bodyweight (PBW). A VT was deemed 'default' if the set VT was a round number. A mediation analysis assessed which factors may explain the sex difference in use of LTVV during intra-operative ventilation.RESULTS: This analysis includes 9864 patients, of whom 5425 (55%) were women. A default VT was often set, both in women and men; mode VT was 500 ml. Median [IQR] VT was higher in women than in men (8.6 [7.7 to 9.6] vs. 7.6 [6.8 to 8.4] ml kg-1 PBW, P < 0.001). Compared with men, women were twice as likely not to receive LTVV [68.8 vs. 36.0%; relative risk ratio 2.1 (95% CI 1.9 to 2.1), P < 0.001]. In the mediation analysis, patients' height and actual body weight (ABW) explained 81 and 18% of the sex difference in use of LTVV, respectively; it was not explained by the use of a default VT.CONCLUSION: In this worldwide cohort of patients receiving intra-operative ventilation during general anaesthesia for surgery, women received a higher VT than men during intra-operative ventilation. The risk for a female not to receive LTVV during surgery was double that of males. Height and ABW were the two mediators of the sex difference in use of LTVV.TRIAL REGISTRATION: The study was registered at Clinicaltrials.gov, NCT01601223
The Association of Intraoperative driving pressure with postoperative pulmonary complications in open versus closed abdominal surgery patients – a posthoc propensity score–weighted cohort analysis of the LAS VEGAS study
No full textBackground: It is uncertain whether the association of the intraoperative driving pressure (ΔP) with postoperative pulmonary complications (PPCs) depends on the surgical approach during abdominal surgery. Our primary objective was to determine and compare the association of time–weighted average ΔP (ΔP TW) with PPCs. We also tested the association of ΔP TW with intraoperative adverse events. Methods: Posthoc retrospective propensity score–weighted cohort analysis of patients undergoing open or closed abdominal surgery in the ‘Local ASsessment of Ventilatory management during General Anaesthesia for Surgery’ (LAS VEGAS) study, that included patients in 146 hospitals across 29 countries. The primary endpoint was a composite of PPCs. The secondary endpoint was a composite of intraoperative adverse events. Results: The analysis included 1128 and 906 patients undergoing open or closed abdominal surgery, respectively. The PPC rate was 5%. ΔP was lower in open abdominal surgery patients, but ΔP TW was not different between groups. The association of ΔP TW with PPCs was significant in both groups and had a higher risk ratio in closed compared to open abdominal surgery patients (1.11 [95%CI 1.10 to 1.20], P < 0.001 versus 1.05 [95%CI 1.05 to 1.05], P < 0.001; risk difference 0.05 [95%CI 0.04 to 0.06], P < 0.001). The association of ΔP TW with intraoperative adverse events was also significant in both groups but had higher odds ratio in closed compared to open abdominal surgery patients (1.13 [95%CI 1.12– to 1.14], P < 0.001 versus 1.07 [95%CI 1.05 to 1.10], P < 0.001; risk difference 0.05 [95%CI 0.030.07], P < 0.001). Conclusions: ΔP is associated with PPC and intraoperative adverse events in abdominal surgery, both in open and closed abdominal surgery. Trial registration: LAS VEGAS was registered at clinicaltrials.gov (trial identifier NCT01601223)
Associations of intraoperative end–tidal CO2 levels with postoperative outcome–secondary analysis of a worldwide observational study
No full textBackground: Patients receiving intraoperative ventilation during general anesthesia often have low end–tidal CO2 (etCO2). We examined the association of intraoperative etCO2 levels with the occurrence of postoperative pulmonary complications (PPCs) in a conveniently–sized international, prospective study named ‘Local ASsessment of Ventilatory management during General Anesthesia for Surgery’ (LAS VEGAS). Methods: Patients at high risk of PPCs were categorized as ‘low etCO2’ or ‘normal to high etCO2’ patients, using a cut–off of 35 mmHg. The primary endpoint was a composite of previously defined PPCs; the individual PPCs served as secondary endpoints. The need for unplanned oxygen was defined as mild PPCs and severe PPCs included pneumonia, respiratory failure, acute respiratory distress syndrome, barotrauma, and new invasive ventilation. We performed propensity score matching and LOESS regression to evaluate the relationship between the lowest etCO2 and PPCs. Results: The analysis included 1843 (74 %) ‘low etCO2’ patients and 648 (26 %) ‘normal to high etCO2’ patients. There was no difference in the occurrence of PPCs between ‘low etCO2’ and ‘normal to high etCO2’ patients (20 % vs. 19 %; RR 1.00 [95 %–confidence interval 0.94 to 1.06]; P = 0.84). The proportion of severe PPCs among total occurring PPCs, were higher in ‘low etCO2’ patients compared to ‘normal to high etCO2’ patients (35 % vs. 18 %; RR 1.16 [1.08 to 1.25]; P < 0.001). Propensity score matching did not change these findings. LOESS plot showed an inverse relationship of intraoperative etCO2 levels with the occurrence of PPCs. Conclusions: In this cohort of patients at high risk of PPCs, the overall occurrence of PPCs was not different between ‘low etCO2’ patients and ‘normal to high etCO2’ patients, but severe PPCs occurred more often in ‘low etCO2’, with an inverse dose–dependent relationship between intraoperative etCO2 levels and PPCs. Funding: This analysis was performed without additional funding. LAS VEGAS was partially funded and endorsed by the European Society of Anesthesiology and Intensive Care (ESAIC) and the Amsterdam University Medical Centers, location ‘AMC’. Registration: LAS VEGAS was registered at Clinicaltrials.gov (NCT01601223), first posted on May 17, 2012
Association of preoperative smoking with the occurrence of postoperative pulmonary complications: A post hoc analysis of an observational study in 29 countries
No full textIntroduction: While smoking has been consistently identified as a significant contributor to postoperative complications, the existing literature on its association with postoperative pulmonary complications remains conflicting. Aim: We examined the association of preoperative smoking with the occurrence of postoperative pulmonary complications (PPCs). Methods: Post hoc analysis of an observational study in 146 hospitals across 29 countries. We included patients at increased risk of PPCs, according to the Assess Respiratory Risk in Surgical Patients in Catalonia (ARISCAT) score (≥ 26 points). The primary endpoint was the occurrence of one or more predefined PPCs in the first five postoperative days, including unplanned postoperative need for supplementary oxygen, respiratory failure, unplanned need for invasive ventilation, ARDS, pneumonia and pneumothorax. Secondary endpoints included length of hospital stay and in–hospital mortality. We performed propensity score matching to correct for factors with a known association with postoperative outcomes. Results: Out of 2632 patients, 531 (20.2 %) patients were smokers and 2102 (79.8 %) non-smokers. At five days after surgery, 101 (19.0 %) smokers versus 404 (19.2) non–smokers had developed one or more PPCs (P = 0.95). Respiratory failure was more common in smokers (5.1 %) than non–smokers (3.0 %) (P = 0.02), while rates of other PPCs like need for supplementary oxygen, invasive ventilation, ARDS, pneumonia, or pneumothorax did not differ between the groups. Length of hospital stay and mortality was not different between groups. Propensity score matching did not change the findings. Conclusion: The occurrence of PPCs in smokers is not different from non–smokers. Funding: This analysis was performed without additional funding. LAS VEGAS was partially funded and endorsed by the European Society of Anaesthesiology through their Clinical Trial Network and the Amsterdam University Medical Centers, Amsterdam, The Netherlands. Registration: LAS VEGAS was registered at Clinicaltrials.gov (NCT01601223). Prior presentation: Preliminary study results have been presented at the Euroanaesthesia 2024 International Congress, in Munich, Germany
Association of preoperative smoking with the occurrence of postoperative pulmonary complications: A post hoc analysis of an observational study in 29 countries
No full textIntroduction: While smoking has been consistently identified as a significant contributor to postoperative complications, the existing literature on its association with postoperative pulmonary complications remains conflicting. Aim: We examined the association of preoperative smoking with the occurrence of postoperative pulmonary complications (PPCs). Methods: Post hoc analysis of an observational study in 146 hospitals across 29 countries. We included patients at increased risk of PPCs, according to the Assess Respiratory Risk in Surgical Patients in Catalonia (ARISCAT) score (≥ 26 points). The primary endpoint was the occurrence of one or more predefined PPCs in the first five postoperative days, including unplanned postoperative need for supplementary oxygen, respiratory failure, unplanned need for invasive ventilation, ARDS, pneumonia and pneumothorax. Secondary endpoints included length of hospital stay and in–hospital mortality. We performed propensity score matching to correct for factors with a known association with postoperative outcomes. Results: Out of 2632 patients, 531 (20.2 %) patients were smokers and 2102 (79.8 %) non-smokers. At five days after surgery, 101 (19.0 %) smokers versus 404 (19.2) non–smokers had developed one or more PPCs (P = 0.95). Respiratory failure was more common in smokers (5.1 %) than non–smokers (3.0 %) (P = 0.02), while rates of other PPCs like need for supplementary oxygen, invasive ventilation, ARDS, pneumonia, or pneumothorax did not differ between the groups. Length of hospital stay and mortality was not different between groups. Propensity score matching did not change the findings. Conclusion: The occurrence of PPCs in smokers is not different from non–smokers. Funding: This analysis was performed without additional funding. LAS VEGAS was partially funded and endorsed by the European Society of Anaesthesiology through their Clinical Trial Network and the Amsterdam University Medical Centers, Amsterdam, The Netherlands. Registration: LAS VEGAS was registered at Clinicaltrials.gov (NCT01601223). Prior presentation: Preliminary study results have been presented at the Euroanaesthesia 2024 International Congress, in Munich, Germany
Sex dependence of postoperative pulmonary complications – A post hoc unmatched and matched analysis of LAS VEGAS
No full textStudy objective: Male sex has inconsistently been associated with the development of postoperative pulmonary complications (PPCs). These studies were different in size, design, population and preoperative risk. We reanalysed the database of 'Local ASsessment of Ventilatory management during General Anaesthesia for Surgery study' (LAS VEGAS) to evaluate differences between females and males with respect to PPCs. Design, setting and patients: Post hoc unmatched and matched analysis of LAS VEGAS, an international observational study in patients undergoing intraoperative ventilation under general anaesthesia for surgery in 146 hospitals across 29 countries. The primary endpoint was a composite of PPCs in the first 5 postoperative days. Individual PPCs, hospital length of stay and mortality were secondary endpoints. Propensity score matching was used to create a similar cohort regarding type of surgery and epidemiological factors with a known association with development of PPCs. Main results: The unmatched cohort consisted of 9697 patients; 5342 (55.1%) females and 4355 (44.9%) males. The matched cohort consisted of 6154 patients; 3077 (50.0%) females and 3077 (50.0%) males. The incidence in PPCs was neither significant between females and males in the unmatched cohort (10.0 vs 10.7%; odds ratio (OR) 0.93 [0.81-1.06]; P = 0.255), nor in the matched cohort (10.5 vs 10.0%; OR 1.05 [0.89-1.25]; P = 0.556). New invasive ventilation occurred less often in females in the unmatched cohort. Hospital length of stay and mortality were similar between females and males in both cohorts. Conclusions: In this conveniently-sized worldwide cohort of patients receiving intraoperative ventilation under general anaesthesia for surgery, the PPC incidence was not significantly different between sexes. Registration: LAS VEGAS was registered at clinicaltrial.gov (study identifier NCT01601223)
