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David R. Morrison

Other affiliations: McGill University
Bio: David R. Morrison is an academic researcher from Jewish General Hospital. The author has contributed to research in topics: Medicine & Mendelian randomization. The author has an hindex of 9, co-authored 16 publications receiving 305 citations. Previous affiliations of David R. Morrison include McGill University.

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Journal ArticleDOI
TL;DR: In this article, a two-sample Mendelian randomization (MR) study was conducted to identify circulating proteins influencing Coronavirus Disease 2019 (COVID-19) susceptibility and severity, rapidly scanning hundreds of circulating proteins while reducing bias due to reverse causation and confounding.
Abstract: To identify circulating proteins influencing Coronavirus Disease 2019 (COVID-19) susceptibility and severity, we undertook a two-sample Mendelian randomization (MR) study, rapidly scanning hundreds of circulating proteins while reducing bias due to reverse causation and confounding. In up to 14,134 cases and 1.2 million controls, we found that an s.d. increase in OAS1 levels was associated with reduced COVID-19 death or ventilation (odds ratio (OR) = 0.54, P = 7 × 10−8), hospitalization (OR = 0.61, P = 8 × 10−8) and susceptibility (OR = 0.78, P = 8 × 10−6). Measuring OAS1 levels in 504 individuals, we found that higher plasma OAS1 levels in a non-infectious state were associated with reduced COVID-19 susceptibility and severity. Further analyses suggested that a Neanderthal isoform of OAS1 in individuals of European ancestry affords this protection. Thus, evidence from MR and a case–control study support a protective role for OAS1 in COVID-19 adverse outcomes. Available pharmacological agents that increase OAS1 levels could be prioritized for drug development. A variant of the OAS1 gene, which encodes an enzyme that is critical for the innate immune response to viral infections, is associated with decreased risk of death in patients with COVID-19.

156 citations

Journal ArticleDOI
TL;DR: System-wide interventions may be more effective to improve the use of VTE prophylaxis than relying on individual providers' prescribing behaviors and publication bias, as well as the occurrence of symptomatic VTE, asymptomatic V TE, and safety outcomes such as bleeding.
Abstract: Blood clots which are classified as deep vein thrombosis (DVT) in the legs and pulmonary embolism (PE) in the lungs, together known as venous thromboembolism (VTE), are potential complications of surgical and medical hospitalization. These complications extend hospital stay and are a leading cause of long-term disability and/or death for patients in hospital. Risk factors for VTE include surgery, acute medical illness, cancer and cancer therapy, trauma, immobilization, central venous catheters, previous history of VTE, older age and obesity. Prevention of venous thromboembolism has been ranked as the number one strategy to improve patient safety in hospitals. Graduated compression stockings, sequential compression devices, and anticoagulant medications, such as low molecular weight heparin, are safe and can prevent blood clotting in patients at risk of these complications, but they are underused. Our review included 55 studies (8 randomised controlled trials and 47 non-randomized studies). One of the non-randomized studies reported data in patient-days and could not be quantitatively analyzed with the others. The 54 remaining studies eligible for inclusion in our quantitative synthesis enrolled a total of 78,343 participants. and showed that alerts, such as computer reminders and stickers on patient charts, increased the number of patients who received prophylaxis by 13%. Education and alerts were associated with increases in the prescription of appropriate prophylaxis, and multifaceted interventions were associated with increases in the prescription of any prophylaxis and appropriate prophylaxis. Multifaceted interventions had the largest effect. It was also shown that multifaceted interventions which included an alert may be more effective at improving rates of prophylaxis than those without an alert.

103 citations

Journal ArticleDOI
TL;DR: In this paper, a 2-sample Mendelian randomization (MR) was used to assess evidence supporting a causal effect of circulating 25-hydroxy vitamin D (25OHD) levels on COVID-19 susceptibility and severity.
Abstract: Background Increased vitamin D levels, as reflected by 25-hydroxy vitamin D (25OHD) measurements, have been proposed to protect against COVID-19 based on in vitro, observational, and ecological studies. However, vitamin D levels are associated with many confounding variables, and thus associations described to date may not be causal. Vitamin D Mendelian randomization (MR) studies have provided results that are concordant with large-scale vitamin D randomized trials. Here, we used 2-sample MR to assess evidence supporting a causal effect of circulating 25OHD levels on COVID-19 susceptibility and severity. Methods and findings Genetic variants strongly associated with 25OHD levels in a genome-wide association study (GWAS) of 443,734 participants of European ancestry (including 401,460 from the UK Biobank) were used as instrumental variables. GWASs of COVID-19 susceptibility, hospitalization, and severe disease from the COVID-19 Host Genetics Initiative were used as outcome GWASs. These included up to 14,134 individuals with COVID-19, and up to 1,284,876 without COVID-19, from up to 11 countries. SARS-CoV-2 positivity was determined by laboratory testing or medical chart review. Population controls without COVID-19 were also included in the control groups for all outcomes, including hospitalization and severe disease. Analyses were restricted to individuals of European descent when possible. Using inverse-weighted MR, genetically increased 25OHD levels by 1 standard deviation on the logarithmic scale had no significant association with COVID-19 susceptibility (odds ratio [OR] = 0.95; 95% CI 0.84, 1.08; p = 0.44), hospitalization (OR = 1.09; 95% CI: 0.89, 1.33; p = 0.41), and severe disease (OR = 0.97; 95% CI: 0.77, 1.22; p = 0.77). We used an additional 6 meta-analytic methods, as well as conducting sensitivity analyses after removal of variants at risk of horizontal pleiotropy, and obtained similar results. These results may be limited by weak instrument bias in some analyses. Further, our results do not apply to individuals with vitamin D deficiency. Conclusions In this 2-sample MR study, we did not observe evidence to support an association between 25OHD levels and COVID-19 susceptibility, severity, or hospitalization. Hence, vitamin D supplementation as a means of protecting against worsened COVID-19 outcomes is not supported by genetic evidence. Other therapeutic or preventative avenues should be given higher priority for COVID-19 randomized controlled trials.

69 citations

Journal ArticleDOI
TL;DR: In conclusion, ECS do not reduce leg pain in patients with acute proximal DVT, and results were similar in an analysis restricted to patients who reported wearing stockings every day.
Abstract: Acute deep venous thrombosis (DVT) causes leg pain. Elastic compression stockings (ECS) have potential to relieve DVT-related leg pain by diminishing the diameter of distended veins and increasing venous blood flow. It was our objective to determine whether ECS reduce leg pain in patients with acute DVT. We performed a secondary analysis of the SOX Trial, a multicentre randomised placebo controlled trial of active ECS versus placebo ECS to prevent the post-thrombotic syndrome.The study was performed in 24 hospital centres in Canada and the U.S. and included 803 patients with a first episode of acute proximal DVT. Patients were randomised to receive active ECS (knee length, 30–40 mm Hg graduated pressure) or placebo ECS (manufactured to look identical to active ECS, but lacking therapeutic compression). Study outcome was leg pain severity assessed on an 11-point numerical pain rating scale (0, no pain; 10, worst possible pain) at baseline, 14, 30 and 60 days after randomisation. Mean age was 55 years and 60% were male. In active ECS patients (n=409), mean (SD) pain severity at baseline and at 60 days were 5.18 (3.29) and 1.39 (2.19), respectively, and in placebo ECS patients (n=394) were 5.38 (3.29) and 1.13 (1.86), respectively. There were no significant differences in pain scores between groups at any assessment point, and no evidence for subgroup interaction by age, sex or anatomical extent of DVT. Results were similar in an analysis restricted to patients who reported wearing stockings every day. In conclusion, ECS do not reduce leg pain in patients with acute proximal DVT.

51 citations

Journal ArticleDOI
TL;DR: The effects of system-wide interventions designed to increase the implementation of thromboprophylaxis and decrease the incidence of VTE in hospitalized adult medical and surgical patients at risk for VTE are assessed, focusing on RCTs only.
Abstract: Background Venous thromboembolism (VTE) is a leading cause of morbidity and mortality in hospitalized patients. While numerous randomized controlled trials (RCTs) have shown that the appropriate use of thromboprophylaxis in hospitalized patients at risk for VTE is safe, effective, and cost‐effective, thromboprophylaxis remains underused or inappropriately used. Our previous review suggested that system‐wide interventions, such as education, alerts, and multifaceted interventions were more effective at improving the prescribing of thromboprophylaxis than relying on individual providers’ behaviors. However, 47 of the 55 included studies in our previous review were observational in design. Thus, an update to our systematic review, focused on the higher level of evidence of RCTs only, was warranted.

46 citations


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Journal ArticleDOI
TL;DR: A model of budget impact, in the perspective of the Italian NHS, is built from the data related to cases of major surgical orthopedic procedures and a meta-analysis on the pivotal RCT, which aims to measure the differential effects in terms of prevention of VTE, showing that the financial impact of the NOA in the prophylaxis of major Orthopedic surgery is not particularly relevant.
Abstract: Venous thromboembolism (VTE) is defined as the obstruction, partial or complete, of one or more veins of deep circulation. It is a condition that can lead to a deterioration in his state of health until death, manifesting as deep vein thrombosis (DVT) or pulmonary embolism (PE). The major orthopedic surgery and the surgical oncology are frequently associated with thromboembolic complications, because of conditions that are often critical in these patients. It is estimated that in Italy DVT has an incidence that varies between 50 and 150 new cases per 100,000 population, while the prevalence would be between 2.5 and 5%. In the absence of thromboprophylaxis, the orthopedic surgery lead to a high increased risk of VTE. In elective hip replacement, in the absence of prophylaxis, the incidence of DVT and of fatal PE is about 50% and 2% respectively. In elective knee arthroplasty the risk of venous thromboembolic complications is even higher. It is estimated that 56.2% of the costs of prophylaxis with Low Molecular Weight Heparin (LMWH) in patients undergoing major orthopedic surgery are attributable to the cost of drugs (about € 200), followed (with 44.8%) by the cost of administration (approximately € 159). The average total cost/day was estimated at € 8 per patient. In Italy, it has been estimated an annual cost for new cases between 215 and 260 million €. The clinical advantages of the New Oral Anticoagulants (NOA) appear to be substantially clear, the major concern with regard to their reimbursement is therefore linked to the financial impact, due to the higher cost per day of the NOA compared with LMWH. To this end, it was built a model of budget impact, in the perspective of the Italian NHS, from the data related to cases of major surgical orthopedic procedures and a meta-analysis on the pivotal RCT, which aims to measure the differential effects in terms of prevention of VTE. The results show that the financial impact of the NOA in the prophylaxis of major orthopedic surgery is not particularly relevant. In fact, the major pharmaceutical costs that, at national level, amount to € 10.8 mil. (€ 15.2 mil. in the case of prolonged prophylaxis in knee operations) would be more than offset by savings in terms of fewer treatments of VTE, which is based on the assumption of more than 4,000 cases, up to about 6,600 in hypothesis best efficacy.

507 citations

Journal ArticleDOI
01 Sep 2015-BMJ Open
TL;DR: This theory-led analysis suggests that interventions which contribute to normative restructuring of practice, modifying peer group norms and expectations and relational restructuring, reinforcing modifiedpeer group norms by emphasising the expectations of an external reference group offer the best chances of success.
Abstract: Objectives Translating research evidence into routine clinical practice is notoriously difficult. Behavioural interventions are often used to change practice, although their success is variable and the characteristics of more successful interventions are unclear. We aimed to establish the characteristics of successful behaviour change interventions in healthcare. Design We carried out a systematic overview of systematic reviews on the effectiveness of behaviour change interventions with a theory-led analysis using the constructs of normalisation process theory (NPT). MEDLINE, CINAHL, PsychINFO and the Cochrane Library were searched electronically from inception to July 2015. Setting Primary and secondary care. Participants Participants were any patients and healthcare professionals in systematic reviews who met the inclusion criteria of having examined the effectiveness of professional interventions in improving professional practice and/or patient outcomes. Interventions Professional interventions as defined by the Cochrane Effective Practice and Organisation of Care Review Group. Primary and secondary outcome measures Success of each intervention in changing practice or patient outcomes, and their mechanisms of action. Reviews were coded as to the interventions included, how successful they had been and which NPT constructs its component interventions covered. Results Searches identified 4724 articles, 67 of which met the inclusion criteria. Interventions fell into three main categories: persuasive; educational and informational; and action and monitoring. Interventions focusing on action or education (eg, Audit and Feedback, Reminders, Educational Outreach) acted on the NPT constructs of Collective Action and Reflexive Monitoring, and reviews using them tended to report more positive outcomes. Conclusions This theory-led analysis suggests that interventions which contribute to normative restructuring of practice, modifying peer group norms and expectations (eg, educational outreach) and relational restructuring, reinforcing modified peer group norms by emphasising the expectations of an external reference group (eg, Reminders, Audit and Feedback), offer the best chances of success. Combining such interventions is most likely to change behaviour.

347 citations

Journal ArticleDOI
TL;DR: Practical clinical guidance on the prevention and treatment of obstetric-associated VTE based on existing guidelines and consensus expert opinion based on available literature where guidelines are lacking is provided.
Abstract: Venous thromboembolism (VTE), which may manifest as pulmonary embolism (PE) or deep vein thrombosis (DVT), is a serious and potentially fatal condition. Treatment and prevention of obstetric-related VTE is complicated by the need to consider fetal, as well as maternal, wellbeing when making management decisions. Although absolute VTE rates in this population are low, obstetric-associated VTE is an important cause of maternal morbidity and mortality. This manuscript, initiated by the Anticoagulation Forum, provides practical clinical guidance on the prevention and treatment of obstetric-associated VTE based on existing guidelines and consensus expert opinion based on available literature where guidelines are lacking.

280 citations

Journal ArticleDOI
TL;DR: The European Society for Vascular Surgery (ESVS) 2021 Clinical Practice Guidelines on the Management of Venous Thrombosis as discussed by the authors have been published for the management of venous thrombotic vessels.

240 citations