Rachel Warren’s research while affiliated with St. Michael's Hospital and other places

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Publications (30)


Figure 1. Flow diagram illustrating the individual steps involved in the updated PRISMA-NMA process.
Updating the PRISMA reporting guideline for network meta-analysis: a scoping review
  • Preprint
  • File available

February 2025

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30 Reads

Areti Angeliki Veroniki

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Daniella Rangira

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STANDFIRST This scoping review represents the initial step in updating the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) extension for network meta-analysis (NMA) to improve the usability and relevance of systematic reviews with NMA for diverse audiences. The update will address gaps in reporting, such as documenting methods for assessing NMA homogeneity and transitivity, defining intervention nodes, and considering advances in statistical modeling. It will align with PRISMA 2020 and incorporate input from diverse knowledge users, including patients and the public. This scoping review included 61 studies, comprising 23 guidance documents and 38 overviews of reviews evaluating the completeness of reporting and methodological quality of published NMAs. We identified 37 additional NMA items for inclusion in the next step—the Delphi survey. Building on a 2014 scoping review by our team, we incorporated recent studies to inform the PRISMA-NMA update, adhering to established standards for guideline development. SUMMARY POINTS Network meta-analyses (NMAs) are increasingly prominent in evidence synthesis, but their methodological transparency and reporting completeness remain inconsistent, which affects the reliability of results. This scoping review highlights the need to update PRISMA-NMA to address evolving methodologies (e.g., component NMA) and reporting challenges to improve accessibility and utility of NMA findings. The review underscores progress and gaps in NMA reporting since the 2015 PRISMA-NMA extension, focusing on synthesis methods, homogeneity, consistency and transitivity assessments, and network geometry. Key recommendations, such as defining pre-specified nodes, specifying statistical methods, and addressing competing interests, were often overlooked in NMA reporting, but addressing these gaps could enhance transparency, reproducibility, and trust in NMA results.

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PRISMA flow diagram
Interventions on gender equity in the workplace: a scoping review

April 2024

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353 Reads

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3 Citations

BMC Medicine

Background Various studies have demonstrated gender disparities in workplace settings and the need for further intervention. This study identifies and examines evidence from randomized controlled trials (RCTs) on interventions examining gender equity in workplace or volunteer settings. An additional aim was to determine whether interventions considered intersection of gender and other variables, including PROGRESS-Plus equity variables (e.g., race/ethnicity). Methods Scoping review conducted using the JBI guide. Literature was searched in MEDLINE, Embase, PsycINFO, CINAHL, Web of Science, ERIC, Index to Legal Periodicals and Books, PAIS Index, Policy Index File, and the Canadian Business & Current Affairs Database from inception to May 9, 2022, with an updated search on October 17, 2022. Results were reported using Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension to scoping reviews (PRISMA-ScR), Sex and Gender Equity in Research (SAGER) guidance, Strengthening the Integration of Intersectionality Theory in Health Inequality Analysis (SIITHIA) checklist, and Guidance for Reporting Involvement of Patients and the Public (GRIPP) version 2 checklist. All employment or volunteer sectors settings were included. Included interventions were designed to promote workplace gender equity that targeted: (a) individuals, (b) organizations, or (c) systems. Any comparator was eligible. Outcomes measures included any gender equity related outcome, whether it was measuring intervention effectiveness (as defined by included studies) or implementation. Data analyses were descriptive in nature. As recommended in the JBI guide to scoping reviews, only high-level content analysis was conducted to categorize the interventions, which were reported using a previously published framework. Results We screened 8855 citations, 803 grey literature sources, and 663 full-text articles, resulting in 24 unique RCTs and one companion report that met inclusion criteria. Most studies (91.7%) failed to report how they established sex or gender. Twenty-three of 24 (95.8%) studies reported at least one PROGRESS-Plus variable: typically sex or gender or occupation. Two RCTs (8.3%) identified a non-binary gender identity. None of the RCTs reported on relationships between gender and other characteristics (e.g., disability, age, etc.). We identified 24 gender equity promoting interventions in the workplace that were evaluated and categorized into one or more of the following themes: (i) quantifying gender impacts; (ii) behavioural or systemic changes; (iii) career flexibility; (iv) increased visibility, recognition, and representation; (v) creating opportunities for development, mentorship, and sponsorship; and (vi) financial support. Of these interventions, 20/24 (83.3%) had positive conclusion statements for their primary outcomes (e.g., improved academic productivity, increased self-esteem) across heterogeneous outcomes. Conclusions There is a paucity of literature on interventions to promote workplace gender equity. While some interventions elicited positive conclusions across a variety of outcomes, standardized outcome measures considering specific contexts and cultures are required. Few PROGRESS-Plus items were reported. Non-binary gender identities and issues related to intersectionality were not adequately considered. Future research should provide consistent and contemporary definitions of gender and sex. Trial registration Open Science Framework https://osf.io/x8yae.


Figure 1 Study selection flow.
Figure 2 Geographic locations of included studies.
Figure 3 Publication status of included studies. on February 18, 2023 by guest. Protected by copyright.
Global evidence of gender equity in academic health research: a scoping review

February 2023

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300 Reads

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16 Citations

BMJ Open

Objectives To chart the global literature on gender equity in academic health research. Design Scoping review. Participants Quantitative studies were eligible if they examined gender equity within academic institutions including health researchers. Primary and secondary outcome measures Outcomes related to equity across gender and other social identities in academia: (1) faculty workforce: representation of all genders in university/faculty departments, academic rank or position and salary; (2) service: teaching obligations and administrative/non-teaching activities; (3) recruitment and hiring data: number of applicants by gender, interviews and new hires for various rank; (4) promotion: opportunities for promotion and time to progress through academic ranks; (5) academic leadership: type of leadership positions, opportunities for leadership promotion or training, opportunities to supervise/mentor and support for leadership bids; (6) scholarly output or productivity: number/type of publications and presentations, position of authorship, number/value of grants or awards and intellectual property ownership; (7) contextual factors of universities; (8) infrastructure; (9) knowledge and technology translation activities; (10) availability of maternity/paternity/parental/family leave; (11) collaboration activities/opportunities for collaboration; (12) qualitative considerations: perceptions around promotion, finances and support. Results Literature search yielded 94 798 citations; 4753 full-text articles were screened, and 562 studies were included. Most studies originated from North America (462/562, 82.2%). Few studies (27/562, 4.8%) reported race and fewer reported sex/gender (which were used interchangeably in most studies) other than male/female (11/562, 2.0%). Only one study provided data on religion. No other PROGRESS-PLUS variables were reported. A total of 2996 outcomes were reported, with most studies examining academic output (371/562, 66.0%). Conclusions Reviewed literature suggest a lack in analytic approaches that consider genders beyond the binary categories of man and woman, additional social identities (race, religion, social capital and disability) and an intersectionality lens examining the interconnection of multiple social identities in understanding discrimination and disadvantage. All of these are necessary to tailor strategies that promote gender equity. Trial registration number Open Science Framework: https://osf.io/8wk7e/ .


Study, participant and outcome characteristics
Evidence synthesis characteristics
Treatment options evaluated in systematic reviews
Comparative-effectiveness research of COVID-19 treatment: a rapid scoping review

June 2022

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128 Reads

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10 Citations

BMJ Open

Objectives The COVID-19 pandemic has stimulated growing research on treatment options. We aim to provide an overview of the characteristics of studies evaluating COVID-19 treatment. Design Rapid scoping review Data sources Medline, Embase and biorxiv/medrxiv from inception to 15 May 2021. Setting Hospital and community care. Participants COVID-19 patients of all ages. Interventions COVID-19 treatment. Results The literature search identified 616 relevant primary studies of which 188 were randomised controlled trials and 299 relevant evidence syntheses. The studies and evidence syntheses were conducted in 51 and 39 countries, respectively. Most studies enrolled patients admitted to acute care hospitals (84%), included on average 169 participants, with an average age of 60 years, study duration of 28 days, number of effect outcomes of four and number of harm outcomes of one. The most common primary outcome was death (32%). The included studies evaluated 214 treatment options. The most common treatments were tocilizumab (11%), hydroxychloroquine (9%) and convalescent plasma (7%). The most common therapeutic categories were non-steroidal immunosuppressants (18%), steroids (15%) and antivirals (14%). The most common therapeutic categories involving multiple drugs were antimalarials/antibiotics (16%), steroids/non-steroidal immunosuppressants (9%) and antimalarials/antivirals/antivirals (7%). The most common treatments evaluated in systematic reviews were hydroxychloroquine (11%), remdesivir (8%), tocilizumab (7%) and steroids (7%). The evaluated treatment was in favour 50% and 36% of the evaluations, according to the conclusion of the authors of primary studies and evidence syntheses, respectively. Conclusions This rapid scoping review characterised a growing body of comparative-effectiveness primary studies and evidence syntheses. The results suggest future studies should focus on children, elderly ≥65 years of age, patients with mild symptoms, outpatient treatment, multimechanism therapies, harms and active comparators. The results also suggest that future living evidence synthesis and network meta-analysis would provide additional information for decision-makers on managing COVID-19.


Study and patient characteristics Number of studies (n = 92) % of studies
Flow diagram of included studies. Flow diagram illustrating how included studies were identified during screening of citations and full text articles
Network diagrams for primary and secondary outcomes. Illustration of networks for each network meta-analysis. Each treatment node indicates an intervention and is weighted according to the number of patients who received the particular intervention. Each edge (line connecting the nodes) is weighted according to the number of studies that directly compare the treatments it connects. Abbreviations: AFLI, aflibercept; BEVA, bevacizumab; BROL, brolucizumab; CONB, conbercept; DXM, dexamethasone; IVTA, intravitreal triamcinolone acetonide; PDT, photodynamic therapy; PLAC, placebo; RANI, ranibizumab
Forest plots of treatments versus placebo for vision gain and vision loss outcomes. Illustration of effect estimates for anti-VEGF agents compared to placebo for the outcomes of vision gain and vision loss. Abbreviations: AFLI, aflibercept; BEVA, bevacizumab; BROL, brolucizumab; CONB, conbercept; DXM, dexamethasone; IVTA, intravitreal triamcinolone acetonide; PDT, photodynamic therapy; PLAC, placebo; RANI, ranibizumab
Anti-vascular endothelial growth factor therapy for age-related macular degeneration: a systematic review and network meta-analysis

December 2021

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147 Reads

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7 Citations

Systematic Reviews

Background The comparative safety and efficacy between anti-vascular endothelial growth factor agents (anti-VEGFs) and between combined therapies for patients with neovascular age-related macular degeneration (nAMD) is unclear. We conducted a systematic review to examine the comparative safety and efficacy anti-VEGFs for adults with nAMD. Methods Studies were identified through MEDLINE, EMBASE, and Cochrane CENTRAL (inception to June 3, 2019), grey literature, and scanning reference lists. Two reviewers independently screened citations and full-text articles to identify randomized controlled trials (RCTs), extracted data, and appraised risk of bias. Pairwise random-effects meta-analysis and Bayesian network meta-analysis (NMA) were conducted. The primary outcomes were the proportion of patients experiencing moderate vision gain (≥ 15 letters on the Early Treatment Diabetic Retinopathy Study chart) and the proportion of patients experiencing moderate vision loss (≤ 15 letters). Results After screening 3647 citations and 485 potentially relevant full-text articles, 92 RCTs with 24,717 patients were included. NMA (34 RCTs, 8809 patients, 12 treatments) showed small differences among anti-VEGFs in improving the proportion of patients with moderate vision gain, with the largest for conbercept versus broluczumab (OR 0.15, 95% CrI: 0.05–0.56), conbercept versus ranibizumab (OR 0.17, 95% CrI: 0.05–0.59), conbercept versus aflibercept (OR 0.19, 95% CrI: 0.06–0.65), and conbercept versus bevacizumab (OR 0.2, 95% CrI: 0.06–0.69). In NMA (36 RCTs, 9081 patients, 13 treatments) for the proportion of patients with moderate vision loss, small differences were observed among anti-VEGFs, with the largest being for conbercept versus aflibercept (OR 0.24, 95% CrI: 0–4.29), conbercept versus brolucizumab (OR 0.24, 95% CrI: 0–4.71), conbercept versus bevacizumab (OR 0.26, 95% CrI: 0–4.65), and conbercept versus ranibizumab (OR 0.27, 95% CrI: 0–4.67). Conclusion The only observed differences were that ranibizumab, bevacizumab, aflibercept, and brolucizumab were statistically superior to conbercept in terms of the proportion of patients with nAMD who experienced moderate vision gain. However, this finding is based on indirect evidence through one small trial comparing conbercept with placebo. This does not account for drug-specific differences when assessing anatomic and functional treatment efficacy in variable dosing regimens. Systematic review registration PROSPERO registration number CRD42015022041.


Figure 1 Study flow. RCT, randomised controlled trial.
Summary study characteristics Study characteristic Total no of trials included (n=19)* (%) No of studies with cn-AMD (n=12) (%) No of studies with DMO (n=3) (%) No of studies with RVO-MO (n=2) (%) No of studies with m-CNV (n=2) (%)
Comparison of monthly versus as needed anti-VEGF treatment regimens in cn-AMD patients
Anti-vascular endothelial growth factor treatment for retinal conditions: a systematic review and meta-analysis

May 2019

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292 Reads

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74 Citations

BMJ Open

Objectives To evaluate the comparative effectiveness and safety of intravitreal bevacizumab, ranibizumab and aflibercept for patients with choroidal neovascular age-related macular degeneration (cn-AMD), diabetic macular oedema (DMO), macular oedema due to retinal vein occlusion (RVO-MO) and myopic choroidal neovascularisation (m-CNV). Design Systematic review and random-effects meta-analysis. Methods Multiple databases were searched from inception to 17 August 2017. Eligible head-to-head randomised controlled trials (RCTs) comparing the (anti-VEGF) drugs in adult patients aged ≥18 years with the retinal conditions of interest. Two reviewers independently screened studies, extracted data and assessed risk of bias. Results 19 RCTs involving 7459 patients with cn-AMD (n=12), DMO (n=3), RVO-MO (n=2) and m-CNV (n=2) were included. Vision gain was not significantly different in patients with cn-AMD, DMO, RVO-MO and m-CNV treated with bevacizumab versus ranibizumab. Similarly, vision gain was not significantly different between cn-AMD patients treated with aflibercept versus ranibizumab. Patients with DMO treated with aflibercept experienced significantly higher vision gain at 12 months than patients receiving ranibizumab or bevacizumab; however, this difference was not significant at 24 months. Rates of systemic serious harms were similar across anti-VEGF agents. Posthoc analyses revealed that an as-needed treatment regimen (6–9 injections per year) was associated with a mortality increase of 1.8% (risk ratio: 2.0 [1.2 to 3.5], 2 RCTs, 1795 patients) compared with monthly treatment in cn-AMD patients. Conclusions Intravitreal bevacizumab was a reasonable alternative to ranibizumab and aflibercept in patients with cn-AMD, DMO, RVO-MO and m-CNV. The only exception was for patients with DME and low visual acuity (<69 early treatment diabetic retinopathy study [ETDRS] letters), where treatment with aflibercept was associated with significantly higher vision gain (≥15 ETDRS letters) than bevacizumab or ranibizumab at 12 months; but the significant effects were not maintained at 24 months. The choice of anti-VEGF drugs may depend on the specific retinal condition, baseline visual acuity and treatment regimen. PROSPERO registration number CRD 42015022041 .


Table 4 | Summary of main results using randomised controlled trials only and intention to treat sample: meta-analyses and network meta-analyses
Efficacy, effectiveness, and safety of herpes zoster vaccines in adults aged 50 and older: Systematic review and network meta-analysis

October 2018

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633 Reads

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121 Citations

The BMJ

Objective To compare the efficacy, effectiveness, and safety of the herpes zoster live attenuated vaccine with the herpes zoster adjuvant recombinant subunit vaccine or placebo for adults aged 50 and older. Design Systematic review with bayesian meta-analysis and network meta-analysis. Data sources Medline, Embase, and Cochrane Library (inception to January 2017), grey literature, and reference lists of included studies. Eligibility criteria for study selection Experimental, quasi-experimental, and observational studies that compared the live attenuated vaccine with the adjuvant recombinant subunit vaccine, placebo, or no vaccine in adults aged 50 and older. Relevant outcomes were incidence of herpes zoster (primary outcome), herpes zoster ophthalmicus, post-herpetic neuralgia, quality of life, adverse events, and death. Results 27 studies (22 randomised controlled trials) including 2 044 504 patients, along with 18 companion reports, were included after screening 2037 titles and abstracts, followed by 175 full text articles. Network meta-analysis of five randomised controlled trials found no statistically significant differences between the live attenuated vaccine and placebo for incidence of laboratory confirmed herpes zoster. The adjuvant recombinant subunit vaccine, however, was statistically superior to both the live attenuated vaccine (vaccine efficacy 85%, 95% credible interval 31% to 98%) and placebo (94%, 79% to 98%). Network meta-analysis of 11 randomised controlled trials showed the adjuvant recombinant subunit vaccine to be associated with statistically more adverse events at injection sites than the live attenuated vaccine (relative risk 1.79, 95% credible interval 1.05 to 2.34; risk difference 30%, 95% credible interval 2% to 51%) and placebo (5.63, 3.57 to 7.29 and 53%, 30% to 73%, respectively). Network meta-analysis of nine randomised controlled trials showed the adjuvant recombinant subunit vaccine to be associated with statistically more systemic adverse events than placebo (2.28, 1.45 to 3.65 and 20%, 6% to 40%, respectively). Conclusions Using the adjuvant recombinant subunit vaccine might prevent more cases of herpes zoster than using the live attenuated vaccine, but the adjuvant recombinant subunit vaccine also carries a greater risk of adverse events at injection sites. Protocol registration Prospero CRD42017056389.


Fig. 1 Study flow diagram 
Table 1 Document characteristics
Fig. 2 Wordcloud of social media sources mined in the documents 
Table 4 Utility and challenges of social media listening Utility and challenges of social media listening Count (%) Utility of social media listening for pharmacovigilance
Steps typically involved in social media data processing flow
Utility of social media and crowd-intelligence data for pharmacovigilance: A scoping review

June 2018

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438 Reads

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70 Citations

BMC Medical Informatics and Decision Making

Background: A scoping review to characterize the literature on the use of conversations in social media as a potential source of data for detecting adverse events (AEs) related to health products. Methods: Our specific research questions were (1) What social media listening platforms exist to detect adverse events related to health products, and what are their capabilities and characteristics? (2) What is the validity and reliability of data from social media for detecting these adverse events? MEDLINE, EMBASE, Cochrane Library, and relevant websites were searched from inception to May 2016. Any type of document (e.g., manuscripts, reports) that described the use of social media data for detecting health product AEs was included. Two reviewers independently screened citations and full-texts, and one reviewer and one verifier performed data abstraction. Descriptive synthesis was conducted. Results: After screening 3631 citations and 321 full-texts, 70 unique documents with 7 companion reports available from 2001 to 2016 were included. Forty-six documents (66%) described an automated or semi-automated information extraction system to detect health product AEs from social media conversations (in the developmental phase). Seven pre-existing information extraction systems to mine social media data were identified in eight documents. Nineteen documents compared AEs reported in social media data with validated data and found consistent AE discovery in all except two documents. None of the documents reported the validity and reliability of the overall system, but some reported on the performance of individual steps in processing the data. The validity and reliability results were found for the following steps in the data processing pipeline: data de-identification (n = 1), concept identification (n = 3), concept normalization (n = 2), and relation extraction (n = 8). The methods varied widely, and some approaches yielded better results than others. Conclusions: Our results suggest that the use of social media conversations for pharmacovigilance is in its infancy. Although social media data has the potential to supplement data from regulatory agency databases; is able to capture less frequently reported AEs; and can identify AEs earlier than official alerts or regulatory changes, the utility and validity of the data source remains under-studied. Trial registration: Open Science Framework ( https://osf.io/kv9hu/ ).




Citations (19)


... Other reviews also identified limitations of the current literature, as it lacks consistency in defining sex and gender as well as data by year, suggesting a need for systematic reviews based on funder reports [16,22]. They highlight that it is insightful and beneficial when funders publish success rates by sex, race, and ethnicity, as displayed in the National Institutes of Health Data Book via NIH RePORTER [23]. ...

Reference:

Gastroenterology Training and Career in Women: Challenges and Opportunities
Global evidence of gender equity in academic health research: a scoping review

BMJ Open

... The CAL ® tool was chosen due to its prior use by some of our team members. 18 The results of the database searches were imported into the CAL ® tool, without removing duplicates. The CAL ® tool learns from the results of manual screening by reviewers to identify and rank titles and abstracts most likely to meet the inclusion criteria. ...

Comparative-effectiveness research of COVID-19 treatment: a rapid scoping review

BMJ Open

... Incubation of HUVECs with the conditioned medium from hypoxia-exposed ARPE-19 cells led to enhanced cell viability and migration. Based on the anti-angiogenic mechanism, anti-VEGF therapies for AMD have been developed 29 . Furthermore, anti-angiogenic genomic therapeutics have recently been proposed as potential treatment strategies 30 . ...

Anti-vascular endothelial growth factor therapy for age-related macular degeneration: a systematic review and network meta-analysis

Systematic Reviews

... However, no head-to-head comparative RCT studies have been conducted on aflibercept and bevacizumab. Only an indirect comparison is available from a network meta-analysis, which suggests a mean difference between bevacizumab and aflibercept of 0.02 letters [14]. To date, no randomized prospective comparative trials of these three drugs have been performed. ...

Anti-vascular endothelial growth factor treatment for retinal conditions: a systematic review and meta-analysis

BMJ Open

... Therefore, the adverse events following RZV vaccination have attracted substantial attention from the research community. A network meta-analysis of randomized controlled trials revealed that the association between adverse events and RZV was statistically stronger than that with ZVL or placebo [12]. Hence, the Centers for Disease Control and Prevention (CDC) and Food and Drug Administration (FDA) initiated the passive safety monitoring of the recombinant zoster vaccine after it was authorized for marketing in the United States. ...

Efficacy, effectiveness, and safety of herpes zoster vaccines in adults aged 50 and older: Systematic review and network meta-analysis

The BMJ

... Results were qualitatively analyzed and presented under common themes (AA, SK, and HV). We used a descriptive analysis, via charting of results, of our study findings, using a predeveloped data collection instrument founded on the authors' experiences and a literature review [15,16]. We have detailed this instrument in Multimedia Appendix 2. ...

Utility of social media and crowd-intelligence data for pharmacovigilance: A scoping review

BMC Medical Informatics and Decision Making

... road to sort out litigation in healthcare is complex compared to the experience of high-income countries but needs to be addressed if CS use is to be reduced in a sustainable manner. 37 The disagreement regarding the association between financial incentives and surgical deliveries is not surprising. This association is relevant for physicians paid in a fee-for-practice model. ...

[Supplementary File 8] Evaluative reports on medical malpractice policies in obstetrics: A rapid scoping review

... 37 For example, in a rapid scoping review on medical malpractice, the scope was narrowed to the last 10 years and only included evidence published in English. 38 Narrowing the breadth of the question may limit the generalisability of the findings. It should be noted that overly stringent inclusion criteria can result in a failure to consider equity, different socioeconomic groups or disadvantaged populations. ...

Evaluative reports on medical malpractice policies in obstetrics: A rapid scoping review

Systematic Reviews

... AAD and aortic aneurysm are both representative aortic diseases, but the pathology decisively differs between them; AAD is triggered by the emergence of an intimal tear followed by extraordinary blood flow into the media, creating acute dissection of the downstream media of the aortic wall accompanied by severe tissue destruction, intensive inflammation, and strong pain 1,42 . Aortic aneurysm, on the other hand, is generally slowly formed as a result of focal atherosclerotic degeneration of the aortic wall with a chronic time course and is not accompanied by drastic histologic destruction 43,44 . AAD often progresses dramatically and generates 2 channels for blood flow, leading to direct exposure of an enormous area of the media to the shear stress of blood flow. ...

Screening for abdominal aortic aneurysm in asymptomatic adults
  • Citing Article
  • December 2016

Journal of Vascular Surgery

... A systematic review regarding the comparative efficacy and safety of the anti-VEGF drugs was planned in response to a query from the Canadian Drug Safety and Effectiveness Network, for which a preliminary report was prepared to inform listing recommendations. 16 17 The report included a meta-analysis of pairwise comparisons of the anti-VEGF drugs for individual retinal conditions, as well as a network meta-analysis to evaluate the anti-VEGF drugs in cn-AMD patients. This paper summarises results of the meta-analysis; a separate paper is underway for the network meta-analysis results. ...

Anti–Vascular Endothelial Growth Factor Drugs for the Treatment of Retinal Conditions
  • Citing Article
  • May 2016