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28 results on '"Kirkham, Aidan M."'

6. Implementation and Adherence-Supporting Strategies to Improve Healthcare Provider Prescription of and Patient Adherence to Guideline-Recommended Cardiovascular Medications for Atherosclerotic Occlusive Disease: Protocol for Two Systematic Reviews and Meta-Analyses of Randomized Trials (Preprint)

Author

Kirkham, Aidan M, primary, Fergusson, Dean A, additional, Presseau, Justin, additional, McIsaac, Daniel I, additional, Shorr, Risa, additional, and Roberts, Derek J, additional

Published
2024
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26. Persistence of CRISPR/Cas9gene edited hematopoietic stem cells following transplantation: A systematic review and meta‐analysis of preclinical studies

Author

Maganti, Harinad B., Bailey, Adrian J. M., Kirkham, Aidan M., Shorr, Risa, Pineault, Nicolas, and Allan, David S.

Abstract

Gene editing blood‐derived cells is an attractive approach to cure selected monogenic diseases but remains experimental. A systematic search of preclinical controlled studies is needed to determine the persistence of edited cells following reinfusion. All studies identified in our systematic search (to 20 October 2020) examining the use of CRISPR/Cas9 gene editing in blood‐derived cells for transplantation were included. Meta‐analysis was performed to determine the engraftment and persistence of gene edited cells. A total of 3538 preclinical studies were identified with 15 published articles meeting eligibility for meta‐analysis. These in vivo animal studies examined editing of hemoglobin to correct sickle cell disease (eight studies), inducing resistance to acquired immunodeficiency syndrome (two studies), and six other monogenic disorders (single studies). CRISPR‐Cas9 edited hematopoietic stem and progenitor cells demonstrated equivalent early engraftment compared to controls in meta‐analysis but persistence of gene‐edited cells was reduced at later time points and in secondary transplant recipients. Subgroup analysis in studies targeting the hemoglobin gene revealed a significant reduction in the persistence of gene‐edited cells whether homology‐directed repair or nonhomologous end‐joining were used. No adverse side effects were reported. Significant heterogeneity in study design and outcome reporting was observed and the potential for bias was identified in all studies. CRISPR‐Cas9 gene edited cells engraft similarly to unedited hematopoietic cells. Persistence of gene edited cells, however, remains a challenge and improved methods of targeting hematopoietic stem cells are needed. Reducing heterogeneity and potential risk of bias will hasten the development of informative clinical trials. Among 15 studies identified in our systematic search of the literature, meta‐analysis of 21 animal cohorts that examined long‐term persistence of transplanted hematopoietic stem cells that underwent CRISPR/Cas9 gene editing revealed a decline over time.

Published
2021
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27. A Meta-Analysis to Derive Population-Based Quality Benchmarks of the Incidence of Surgical Site Infection after Lower Limb Revascularization Surgery

Author

Kirkham, Aidan M., Candeliere, Jasmine, Stelfox, Henry T., Nagpal, Sudhir K., Dubois, Luc, MacFadden, Derek R., McIsaac, Daniel I., and Roberts, Derek J.

Abstract

The reported incidence of surgical site infection (SSI) after lower limb revascularization surgery varies. We conducted a systematic review and meta-analysis of population-based studies reporting the incidence of SSI in adults who underwent these surgeries in high-income countries to derive SSI quality benchmarks.

Published
2023
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28. Evidence for clinician underprescription of and patient non-adherence to guideline-recommended cardiovascular medications among adults with peripheral artery disease: protocol for a systematic review and meta-analysis.

Author

de Launay D, Paquet M, Kirkham AM, Graham ID, Fergusson DA, Nagpal SK, Shorr R, Grimshaw JM, and Roberts DJ

Subjects
Humans, Cardiovascular Agents therapeutic use, Research Design, Platelet Aggregation Inhibitors therapeutic use, Hydroxymethylglutaryl-CoA Reductase Inhibitors therapeutic use, Practice Guidelines as Topic, Practice Patterns, Physicians' statistics & numerical data, Adult, Antihypertensive Agents therapeutic use, Meta-Analysis as Topic, Peripheral Arterial Disease drug therapy, Systematic Reviews as Topic, Medication Adherence statistics & numerical data
Abstract

Introduction: International guidelines recommend that adults with peripheral artery disease (PAD) be prescribed antiplatelet, statin and antihypertensive medications. However, it is unclear how often people with PAD are underprescribed these drugs, which characteristics predict clinician underprescription of and patient non-adherence to guideline-recommended cardiovascular medications, and whether underprescription and non-adherence are associated with adverse health and health system outcomes., Methods and Analysis: We will search MEDLINE, EMBASE and Evidence-Based Medicine Reviews from 2006 onwards. Two investigators will independently review abstracts and full-text studies. We will include studies that enrolled adults and reported the incidence and/or prevalence of clinician underprescription of or patient non-adherence to guideline-recommended cardiovascular medications among people with PAD; adjusted risk factors for underprescription of/non-adherence to these medications; and adjusted associations between underprescription/non-adherence to these medications and outcomes. Outcomes will include mortality, major adverse cardiac and limb events (including revascularisation procedures and amputations), other reported morbidities, healthcare resource use and costs. Two investigators will independently extract data and evaluate study risk of bias. We will calculate summary estimates of the incidence and prevalence of clinician underprescription/patient non-adherence across studies. We will also conduct subgroup meta-analyses and meta-regression to determine if estimates vary by country, characteristics of the patients and treating clinicians, population-based versus non-population-based design, and study risks of bias. Finally, we will calculate pooled adjusted risk factors for underprescription/non-adherence and adjusted associations between underprescription/non-adherence and outcomes. We will use Grading of Recommendations, Assessment, Development and Evaluation to determine estimate certainty., Ethics and Dissemination: Ethics approval is not required as we are studying published data. This systematic review will synthesise existing evidence regarding clinician underprescription of and patient non-adherence to guideline-recommended cardiovascular medications in adults with PAD. Results will be used to identify evidence-care gaps and inform where interventions may be required to improve clinician prescribing and patient adherence to prescribed medications., Prospero Registration Number: CRD42022362801., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Published
2024
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