ORCID Profile
0000-0002-3249-1508
Current Organisation
Oxford University Hospitals NHS Foundation Trust
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Publisher: Springer Science and Business Media LLC
Date: 19-04-2016
Publisher: Wiley
Date: 12-06-2017
DOI: 10.1111/AAS.12917
Abstract: In this statistical analysis plan, we aim to provide details of the pre-defined statistical analyses of the Stress Ulcer Prophylaxis in the Intensive Care Unit (SUP-ICU) trial. The aim of the SUP-ICU trial is to assess benefits and harms of stress ulcer prophylaxis with a proton pump inhibitor in adult patients in the intensive care unit (ICU). The SUP-ICU trial is an investigator-initiated, international, multicentre, randomised, blinded, parallel-group trial of intravenously pantoprazole 40 mg once daily vs. placebo in 3350 acutely ill adult ICU patients at risk of gastrointestinal bleeding. The primary outcome measure is 90-day mortality. Secondary outcomes include the proportion of patients with clinically important gastrointestinal bleeding, pneumonia, Clostridium difficile infection or myocardial ischaemia, days alive without life support, serious adverse reactions, 1-year mortality, and a health economic analysis. Two formal interim analyses will be performed. The statistical analyses will be conducted according to the outlined pre-defined statistical analysis plan. The primary analysis will be a logistic regression analysis adjusted for stratification variables comparing the two intervention groups in the intention-to-treat population. In a secondary analysis, we will additionally adjust the primary outcome for potential random differences in baseline characteristics. The conclusion will be based on the intention-to-treat population. Stress ulcer prophylaxis is standard of care in ICUs worldwide, but has never been tested in large high-quality randomised placebo-controlled trials. The SUP-ICU trial will provide important high-quality data on the balance between the benefits and harms of stress ulcer prophylaxis in adult critically ill patients.
Publisher: Wiley
Date: 16-04-2015
DOI: 10.1111/AAS.12508
Abstract: Stress ulcer prophylaxis (SUP) may decrease the incidence of gastrointestinal bleeding in patients in the intensive care unit (ICU), but the risk of infection may be increased. In this study, we aimed to describe SUP practices in adult ICUs. We hypothesised that patient selection for SUP varies both within and between countries. Adult ICUs were invited to participate in the survey. We registered country, type of hospital, type and size of ICU, preferred SUP agent, presence of local guideline, reported indications for SUP, criteria for discontinuing SUP, and concerns about adverse effects. Fisher's exact test was used to assess differences between groups. Ninety-seven adult ICUs in 11 countries participated (eight European). All but one ICU used SUP, and 64% (62/97) reported having a guideline for the use of SUP. Proton pump inhibitors were the most common SUP agent, used in 66% of ICUs (64/97), and H2-receptor antagonists were used 31% (30/97) of the units. Twenty-three different indications for SUP were reported, the most frequent being mechanical ventilation. All patients were prescribed SUP in 26% (25/97) of the ICUs. Adequate enteral feeding was the most frequent reason for discontinuing SUP, but 19% (18/97) continued SUP upon ICU discharge. The majority expressed concern about nosocomial pneumonia and Clostridium difficile infection with the use of SUP. In this international survey, most participating ICUs reported using SUP, primarily proton pump inhibitors, but many did not have a guideline indications varied considerably and concern existed about infectious complications.
Publisher: Springer Science and Business Media LLC
Date: 10-01-2018
Publisher: Springer Science and Business Media LLC
Date: 10-04-2015
DOI: 10.1007/S00134-015-3725-1
Abstract: To describe the prevalence of, risk factors for, and prognostic importance of gastrointestinal (GI) bleeding and use of acid suppressants in acutely ill adult intensive care patients. We included adults without GI bleeding who were acutely admitted to the intensive care unit (ICU) during a 7-day period. The primary outcome was clinically important GI bleeding in ICU, and the analyses included estimations of baseline risk factors and potential associations with 90-day mortality. A total of 1,034 patients in 97 ICUs in 11 countries were included. Clinically important GI bleeding occurred in 2.6 % (95 % confidence interval 1.6-3.6 %) of patients. The following variables at ICU admission were independently associated with clinically important GI bleeding: three or more co-existing diseases (odds ratio 8.9, 2.7-28.8), co-existing liver disease (7.6, 3.3-17.6), use of renal replacement therapy (6.9, 2.7-17.5), co-existing coagulopathy (5.2, 2.3-11.8), acute coagulopathy (4.2, 1.7-10.2), use of acid suppressants (3.6, 1.3-10.2) and higher organ failure score (1.4, 1.2-1.5). In ICU, 73 % (71-76 %) of patients received acid suppressants most received proton pump inhibitors. In patients with clinically important GI bleeding, crude and adjusted odds for mortality were 3.7 (1.7-8.0) and 1.7 (0.7-4.3), respectively. In ICU patients clinically important GI bleeding is rare, and acid suppressants are frequently used. Co-existing diseases, liver failure, coagulopathy and organ failures are the main risk factors for GI bleeding. Clinically important GI bleeding was not associated with increased adjusted 90-day mortality, which largely can be explained by severity of comorbidity, other organ failures and age.
Publisher: Wiley
Date: 11-09-2019
DOI: 10.1111/AAS.13459
Abstract: The aetiology and risk factors for clinically important gastrointestinal bleeding (CIB) in adult ICU patients may differ according to the onset of CIB, which could affect the balance between benefits and harms of stress ulcer prophylaxis (SUP). We assessed the time to CIB in the Stress Ulcer Prophylaxis in the Intensive Care Unit (SUP-ICU) trial. We assessed if associations between baseline characteristics including allocation to SUP and CIB changed during time in the ICU, specifically in the later (after day 2) compared to the earlier (first 2 days) period, using Cox models adjusted for SAPS II and allocation to SUP. Additionally, we described baseline characteristics and CIB episodes stratified by earlier/later/no CIB and 90-day mortality status. Clinically important gastrointestinal bleeding occurred in 110/3291 (3.3%) patients after a median of 6 (interquartile range 2-13) days 25.5% of the episodes occurred early. Higher SAPS II was consistently associated with increased risk of CIB (hazard ratio (HR) 1.03, 95% confidence interval (CI) 1.01-1.05 in the earlier period vs HR 1.02, 95% CI 1.01-1.03 in the later period P = .37) university hospital admission was associated with decreased risk of earlier CIB (HR 0.30, 95% CI 0.14-0.63) this significantly increased in the later period (to HR 0.85, 95% CI 0.53-1.37 P = .02). Patients with later compared to earlier CIB received more transfusions and had more diagnostic/therapeutic procedures for CIB. Clinically important gastrointestinal bleeding mostly occurred more than 2 days after randomization. University hospital admission was associated with significantly decreased risk of CIB in the earlier period only.
Publisher: National Institute for Health and Care Research
Date: 04-2022
Abstract: Data corrected and figures revised.
Publisher: Wiley
Date: 19-07-2019
DOI: 10.1111/AAS.13436
Abstract: The long-term effects of stress ulcer prophylaxis with pantoprazole are unknown in ICU patients. We report 1-year mortality outcome in the Stress Ulcer Prophylaxis in the Intensive Care Unit (SUP-ICU) trial. In the SUP-ICU trial, acutely admitted adult ICU patients at risk of gastrointestinal bleeding were randomised to intravenous pantoprazole 40 mg vs placebo (saline) once daily during their ICU stay. We assessed mortality at 1 year and did sensitivity analyses according to the trial protocol and statistical analysis plan. A total of 3261 of the 3291 patients with available data (99.1%) were followed up at 1 year after randomisation 1635 were allocated to pantoprazole and 1626 to placebo. At 1 year after randomisation, 610 of 1635 patients (37.3%) had died in the pantoprazole group as compared with 601 of 1626 (37.0%) in the placebo group (relative risk, 1.01 95% confidence interval 0.92-1.10). The results were consistent in the sensitivity analysis adjusted for baseline risk factors and in those of the per-protocol population. We did not observe heterogeneity in the effect of pantoprazole vs placebo on 1-year mortality in the predefined subgroups, that is, patients with and without shock, mechanical ventilation, liver disease, coagulopathy, high disease severity (SAPS II > 53) or in medical vs surgical ICU patients. We did not observe a difference in 1-year mortality among acutely admitted adult ICU patients with risk factors for gastrointestinal bleeding allocated to stress ulcer prophylaxis with pantoprazole or placebo during the ICU stay. (The SUP-ICU trial was funded by Innovation Fund Denmark and others ClinicalTrials.gov number, NCT02467621).
Publisher: Elsevier BV
Date: 04-2023
Publisher: Informa UK Limited
Date: 09-08-2018
DOI: 10.1080/10803548.2017.1336299
Abstract: Musculoskeletal symptoms related to using traditional computer workstations are common. Quantitative methods for measuring muscle stress and strain are needed to improve ergonomics of workstations. We hypothesize that infrared thermography (IRT) is suited for this purpose. This hypothesis was evaluated by estimating muscle activity in upright and traditional working postures with IRT and surface electromyography (sEMG). IRT and sEMG measurements were conducted in 14 female participants with both working postures. First, measurements with the traditional posture were performed. Later, participants had 1 month to adjust to the upright working posture before repeating the measurements. IRT images were acquired before and after a full working day, with sEMG recordings being conducted throughout the measurement days. Participants evaluated their neck pain severity using neck disability index (NDI) questionnaires before the first and after the second measurement day. Spatial variation in upper back temperature was higher (p = 0.008) when working in traditional posture and the upright working posture reduced (p < 0.05) upper back muscle activity. The NDI was significantly lower (p = 0.003) after working in the upright posture. IRT was found suitable for evaluating muscle activity and upright working posture to reduce the NDI and muscle activity in the upper back.
Publisher: SAGE Publications
Date: 02-04-2022
Abstract: Acute kidney injury is common in critical illness. In patients with severe acute kidney injury, renal replacement therapy is needed to prevent harm from metabolic and electrolyte disturbances and fluid overload. In the UK, continuous renal replacement therapy (CRRT) is the preferred modality, which requires anticoagulation. Over the last decade, conventional systemic heparin anticoagulation has started being replaced by regional citrate anticoagulation for CRRT, which is now used in approximately 50% of ICUs. This shift towards regional citrate anticoagulation for CRRT is occurring with little evidence of safety or longer term effectiveness. Renal replacement anticoagulant management (RRAM) is an observational comparative effectiveness study, utilising existing data sources to address the clinical and cost-effectiveness of the change to regional citrate anticoagulation for CRRT in UK ICUs. The study will use data from approximately 85,000 patients who were treated in adult, general ICUs participating in the case mix programme national clinical audit between 1 April 2009 and 31 March 2017. A survey of health service providers’ anticoagulation practices will be combined with treatment and hospital outcome data from the case mix programme and linked with long-term outcomes from the Civil Registrations (deaths), Hospital Episodes Statistics for England, Patient Episodes Data for Wales, and the UK Renal Registry datasets. The primary clinical effectiveness outcome is all-cause mortality at 90-days. The study will incorporate an economic evaluation with micro-costing of both regional citrate anticoagulation and systemic heparin anticoagulation. Study registration: NCT03545750
Publisher: National Institute for Health and Care Research
Date: 02-2022
DOI: 10.3310/ZXHI9396
Abstract: In the UK, 10% of admissions to intensive care units receive continuous renal replacement therapy with regional citrate anticoagulation replacing systemic heparin anticoagulation over the last decade. Regional citrate anticoagulation is now used in 50% of intensive care units, despite little evidence of safety or effectiveness. The aim of the Renal Replacement Anticoagulant Management study was to evaluate the clinical and health economic impacts of intensive care units moving from systemic heparin anticoagulation to regional citrate anticoagulation for continuous renal replacement therapy. This was an observational comparative effectiveness study. The setting was NHS adult general intensive care units in England and Wales. Participants were adults receiving continuous renal replacement therapy in an intensive care unit participating in the Intensive Care National Audit & Research Centre Case Mix Programme national clinical audit between 1 April 2009 and 31 March 2017. Exposure – continuous renal replacement therapy in an intensive care unit after completion of transition to regional citrate anticoagulation. Comparator – continuous renal replacement therapy in an intensive care unit before starting transition to regional citrate anticoagulation or had not transitioned. Primary effectiveness – all-cause mortality at 90 days. Primary economic – incremental net monetary benefit at 1 year. Secondary outcomes – mortality at hospital discharge, 30 days and 1 year days of renal, cardiovascular and advanced respiratory support in intensive care unit length of stay in intensive care unit and hospital bleeding and thromboembolic events prevalence of end-stage renal disease at 1 year and estimated lifetime incremental net monetary benefit. In idual patient data from the Intensive Care National Audit & Research Centre Case Mix Programme were linked with the UK Renal Registry, Hospital Episode Statistics (for England), Patient Episodes Data for Wales and Civil Registrations (Deaths) data sets, and combined with identified periods of systemic heparin anticoagulation and regional citrate anticoagulation (survey of intensive care units). Staff time and consumables were obtained from micro-costing. Continuous renal replacement therapy system failures were estimated from the Post-Intensive Care Risk-adjusted Alerting and Monitoring data set. EuroQol-3 Dimensions, three-level version, health-related quality of life was obtained from the Intensive Care Outcomes Network study. Out of the 188 (94.9%) units that responded to the survey, 182 (96.8%) use continuous renal replacement therapy. After linkage, data were available from 69,001 patients across 181 intensive care units (60,416 during periods of systemic heparin anticoagulation use and 8585 during regional citrate anticoagulation use). The change to regional citrate anticoagulation was not associated with a step change in 90-day mortality (odds ratio 0.98, 95% confidence interval 0.89 to 1.08). Secondary outcomes showed step increases in days of renal support (difference in means 0.53 days, 95% confidence interval 0.28 to 0.79 days), advanced cardiovascular support (difference in means 0.23 days, 95% confidence interval 0.09 to 0.38 days) and advanced respiratory support (difference in means, 0.53 days, 95% CI 0.03 to 1.03 days) with a trend toward fewer bleeding episodes (odds ratio 0.90, 95% confidence interval 0.76 to 1.06) with transition to regional citrate anticoagulation. The micro-costing study indicated that regional citrate anticoagulation was more expensive and was associated with an estimated incremental net monetary loss (step change) of –£2376 (95% confidence interval –£3841 to –£911). The estimated likelihood of cost-effectiveness at 1 year was less than 0.1%. Lack of patient-level treatment data means that the results represent average effects of changing to regional citrate anticoagulation in intensive care units. Administrative data are subject to variation in data quality over time, which may contribute to observed trends. The introduction of regional citrate anticoagulation has not improved outcomes for patients and is likely to have substantially increased costs. This study demonstrates the feasibility of evaluating effects of changes in practice using routinely collected data. (1) Prioritise other changes in clinical practice for evaluation and (2) methodological research to understand potential implications of trends in data quality. This trial is registered as ClinicalTrials.gov NCT03545750. This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment Vol. 26, No. 13. See the NIHR Journals Library website for further project information.
Publisher: Massachusetts Medical Society
Date: 06-12-2018
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Mark Borthwick.