Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 206
Filtrar
1.
BMJ Open ; 11(2): e049598, 2021 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-33622960

RESUMO

INTRODUCTION: With over 1 million units of blood transfused each year in Canada, their use has a significant clinical and economic impact on our health system. Adequate screening of blood donors is important to ensure the safety and clinical benefit of blood products. Some adverse transfusion reactions have been shown to be related to donor factors (eg, lung injury), whereas other adverse outcomes have been theoretically related to donor factors (mortality and infection). Our clinical trial will test whether male donor blood leads to a greater benefit for transfusion recipients compared with female donor blood. METHODS AND ANALYSIS: We have designed a pragmatic, double-blind, randomised trial that will allocate transfusion recipients to receive either male-only or female-only donor transfusions. We will enrol 8850 adult patients requiring at least one transfusion at four sites over an approximate 2-year period. Randomisation and allocation will occur in the blood bank prior to release of the units of blood for transfusion. Our primary outcome is mortality. An intent-to-treat analysis will be applied using all randomised and transfused patients. The principal analysis will be a survival analysis comparing the time from randomisation to death between patients allocated to male donor red blood cells (RBCs) and female donor RBCs. ETHICS AND DISSEMINATION: Approval has been obtained from research ethics boards of all involved institutions, as well as from privacy offices of Canadian Blood Services, Institute for Clinical Evaluative Science and The Ottawa Hospital Data Warehouse. Our findings will be published in peer-reviewed journals and presented at relevant stakeholder conferences and meetings. TRIAL REGISTRATION NUMBER: NCT03344887; Pre-results.

2.
J Arthroplasty ; 2021 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-33549420

RESUMO

BACKGROUND: This study aims to: 1) Determine the prevalence of preoperative anemia in arthroplasty; 2) Assess whether preoperative anemia is associated with inferior outcomes; and 3) Ascertain whether optimization in a dedicated blood management program (BMP) is associated with improved outcomes. METHODS: All primary arthroplasties performed at an academic, tertiary-care, arthroplasty center between 2012 and 2017 were reviewed. Hemoglobin level obtained in the preoperative assessment clinic was recorded. Patients with anemia were then considered for further review in BMP. Outcomes included improvement in hemoglobin level post-BMP; length of stay; perioperative transfusion; 90-day readmission, complication, and reoperation rates. The effect of preoperative anemia and the effect of treatment at the BMP on outcomes were evaluated through multivariable regression analysis controlling for relevant covariates. RESULTS: 17% of patients (932/5384) were found to have anemia; 115/357 patients who attended the BMP were no longer anemic. Thus, at time of operation, 15% of patients (817/5384) had anemia. Anemic patients were 4.09 times more likely (95% CI: 2.64-6.35) to require a transfusion; 1.42 times more likely (95% CI: 0.99-2.03) to sustain complications and had 19% longer (95% CI: 13%-26%) length of stay. Those who attended the BMP were less likely to receive a transfusion (OR = 0.32, 95% CI: 0.16-0.66), suffer from postoperative complications (OR = 0.30, 95% CI: 0.14-0.63), or require readmission compared with anemic patients not seen in the BMP (OR = 0.25, 95% CI: 0.09-0.71). CONCLUSIONS: The prevalence of anemia in this arthroplasty cohort was 15%. Preoperative, timely, optimization of anemia should be strongly considered as it is likely to reduce "anemia-associated burden" after arthroplasty.

3.
BMJ Open ; 11(2): e040212, 2021 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-33593766

RESUMO

OBJECTIVES: Current guidelines do not recommend direct oral anticoagulants (DOACs) to treat cerebral venous thrombosis (CVT) despite their benefits over standard therapy. We performed a systematic review to summarise the published experience of DOAC therapy in CVT. DATA SOURCES: MEDLINE, Embase and COCHRANE databases up to 18 November 2020. ELIGIBILITY CRITERIA: All published articles of patients with CVT treated with DOAC were included. Studies without follow-up information were excluded. DATA EXTRACTION AND SYNTHESIS: Two independent reviewers screened articles and extracted data. A risk of bias analysis was performed. PRIMARY AND SECONDARY OUTCOME MEASURES: Safety data included mortality, intracranial haemorrhage (ICH) or other adverse events. Efficacy data included recurrent CVT, recanalisation rates and disability by modified Rankin Scales (mRS). RESULTS: 33 studies met inclusion criteria. One randomised controlled trial, 5 observational cohorts and 27 case series or studies reported 279 patients treated with DOAC for CVT: 41% dabigatran, 47% rivaroxaban, 10% apixaban and 2% edoxaban, in addition to 315 patients treated with standard therapy. The observational cohorts showed a similar risk of death in DOAC and standard therapy arms (RR 2.12, 95% CI 0.29 to 15.59). New ICH was reported in 2 (0.7%) DOAC-treated patients and recurrent CVT occurred in 4 (1.5%). A favourable mRS between 0 and 2 was reported in 94% of DOAC-treated patients, more likely than standard therapy in observational cohorts (RR 1.13, 95% CI 1.02 to 1.25). CONCLUSION: The evidence for DOAC use in CVT is limited although suggests sufficient safety and efficacy despite variability in timing and dose of treatment. This systematic review highlights that further rigorous trials are needed to validate these findings and to determine optimal treatment regimens.

4.
BMJ Open ; 11(2): e043370, 2021 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-33593782

RESUMO

INTRODUCTION: Women have historically been under-represented in randomised controlled trials (RCTs), including many landmark RCTs that established standards of care. In light of this fact, some modern researchers are calling for replication of earlier landmark trials with women only. This approach is ethically concerning, in that it would require some enrolled women to be deprived of treatments that are currently considered standard of care. OBJECTIVE: In an attempt to better understand the justification of a women-only approach to designing clinical trials, this study looks to systematically categorise the number of women-only RCTs for conditions that affect both men and women and the reasons given within the medical and philosophical literatures to perform them. METHODOLOGY: This scoping review of the literature will search, screen and select articles based on predetermined inclusion/exclusion criteria, after which a grounded theory approach will be used to synthesise the data. It is expected that there will be a variety of reasons given for why a women-only trial may be justified. Electronic databases that will be searched include MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, Cochrane Clinical Trials Register, Web of Science Proceedings, ClinicalTrials.gov, Philosopher's Index, Phil Papers, JSTOR, Periodicals Archive Online, Project MUSE and the National Reference Centre for Bioethics. SIGNIFICANCE: The scope of this study is to determine published rationales used to justify women-only randomised trials, both in the case of new trials and in the repetition of landmark trials. ETHICS AND DISSEMINATION: Research ethics board approval is not required for this study as there is no participant involvement. Results will be published as a stand-alone manuscript and will inform a larger project related to the ethics of a women-only RCT of carotid intervention for women with symptomatic high-grade carotid stenosis.

5.
Can J Anaesth ; 2021 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-33594597

RESUMO

PURPOSE: Tranexamic acid (TXA) reduces red blood cell transfusion in various orthopedic surgeries, yet the degree of practice variation in its use among anesthesiologists and surgeons has not been described. To target future knowledge transfer and implementation strategies, and to better understand determinants of variability in prophylactic TXA use, our primary objective was to evaluate the influence of surgical team members on the variability of prophylactic TXA administration. METHODS: This was a retrospective cohort study of all adult patients undergoing primary total hip arthroplasty (THA), hip fracture surgery, and spine fusion ± vertebrectomy at two Canadian hospitals between January 2014 and December 2016. We used Canadian Classification of Health Interventions procedure codes within the Discharge Abstract Database which we linked to the Ottawa Data Warehouse. We described the percentage of patients that received TXA by individual surgery, the specifics of TXA dosing, and estimated the effect of anesthesiologists and surgeons on prophylactic TXA using multivariable mixed-effects logistic regression analyses. RESULTS: In the 3,900 patients studied, TXA was most commonly used in primary THA (85%; n = 1,344/1,582), with lower use in hip fracture (23%; n = 342/1,506) and spine fusion surgery (23%; n = 186/812). The median [interquartile range] total TXA dose was 1,000 [1,000-1,000] mg, given as a bolus in 92% of cases. Anesthesiologists and surgeons added significant variability to the odds of receiving TXA in hip fracture surgery and spine fusion, but not primary THA. Most of the variability in TXA use was attributed to patient and other factors. CONCLUSION: We confirmed the routine use of TXA in primary THA, while observing lower utilization with more variability in hip fracture and spine fusion surgery. Further study is warranted to understand variations in use and the barriers to TXA implementation in a broader population of orthopedic surgical patients at high risk for transfusion.

6.
Can Urol Assoc J ; 2021 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-33443481

RESUMO

INTRODUCTION: Approximately 50% of patients with non-metastatic prostate cancer are treated with radical prostatectomy. While some men will be cured with surgery alone, a substantial proportion will experience cancer recurrence. Androgen-directed therapy (ADT) is an effective adjuvant therapy for patients treated with prostate radiation. Comparatively, the efficacy of ADT in surgical patients has not been well studied. METHODS: A systematic search of MEDLINE, Embase, and the Cochrane Library from inception to July 2020 was performed. Randomized trials comparing ADT with radical prostatectomy vs. prostatectomy alone in patients with clinically localized prostate cancer were included. Neoadjuvant ADT and adjuvant ADT interventions were assessed separately. The primary outcomes were cancer recurrence-free survival (RFS) and overall survival (OS). Pathologic outcomes following neoadjuvant ADT were also evaluated. RESULTS: Fifteen randomized trials met eligibility criteria; 11 evaluated neoadjuvant ADT (n=2322) and four evaluated adjuvant ADT (n=5205). Neoadjuvant ADT (three months of treatment) did not improve RFS (hazard ratio [HR] 0.90, 95% confidence interval [CI] 0.74-1.11) or OS (HR 1.22, 95% CI 0.62-2.41). Neoadjuvant ADT significantly decreased the risk of positive surgical margins (relative risk [RR] 0.48, 95% CI 0.41-0.56) and extraprostatic tumor extension (RR 0.75, 95% CI 0.64-0.89). Adjuvant ADT improved RFS (HR 0.65, 95% CI 0.45-0.93) but did not improve OS (HR 1.02, 95% CI 0.84-1.24). CONCLUSIONS: Neoadjuvant ADT causes a pathologic downstaging of prostate tumors, but has not been found to delay cancer recurrence nor extend survival. Few studies evaluated adjuvant ADT. Trials are needed to determine the benefits and harms of intermediate or long-term adjuvant ADT for radical prostatectomy patients.

7.
BMC Surg ; 21(1): 42, 2021 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-33461529

RESUMO

BACKGROUND: Anastomotic leakage (AL) is a common and serious complication following esophagectomy. We aimed to provide an up-to-date review and critical appraisal of the efficacy and safety of all previous interventions aiming to reduce AL risk. METHODS: We searched MEDLINE and Embase from 1946 to January 2019 for randomized controlled trials (RCTs) evaluating interventions to minimize esophagogastric AL. Pooled risk ratios (RR) for AL were obtained using a random effects model. RESULTS: Two reviewers screened 441 abstracts and identified 17 RCTs eligible for inclusion; 11 studies were meta-analyzed. Omentoplasty significantly reduced the risk of AL by 78% [RR: 0.22; 95% CI: 0.10, 0.50] compared to conventional anastomosis (3 studies, n = 611 patients). Early removal of NG tube significantly reduced the risk of AL by 62% [RR: 0.38; 95% CI: 0.02, 0.65] compared to prolonged NG tube removal (2 studies, n = 293 patients); Stapled anastomosis did not significantly reduce the risk of AL [RR: 0.92; 95% CI: 0.45, 1.87] compared to hand-sewn anastomosis (6 studies, n = 1454 patients). The quality of evidence was high for omentoplasty (vs. conventional anastomosis), moderate for early NG tube removal (vs. prolonged NG tube removal), and very low for stapled anastomosis (vs. hand-sewn anastomosis). CONCLUSIONS: This is the first meta-analysis to summarize the graded quality of evidence for all RCT interventions designed to reduce the risk of AL following esophagectomy. Our findings demonstrated that omentoplasty significantly reduced the risk of AL with a high quality of evidence. Although early NG tube removal significantly reduced AL risk, there is a need for further research to strengthen the quality of evidence for this finding. Evidence profiles presented in our review may help inform the development of future clinical practice recommendations. Systematic review registration: CRD42019127181.


Assuntos
Anastomose Cirúrgica/efeitos adversos , Fístula Anastomótica/prevenção & controle , Neoplasias Esofágicas/cirurgia , Esofagectomia/efeitos adversos , Fístula Anastomótica/etiologia , Neoplasias Esofágicas/patologia , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto
8.
Transl Stroke Res ; 2021 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-33405011

RESUMO

Remote ischemic conditioning (RIC) is a promising neuroprotective therapy for ischemic stroke. Preclinical studies investigating RIC have shown RIC reduced infarct volume, but clinical trials have been equivocal. Therefore, the efficacy of RIC in reducing infarct volume and quality of current literature needs to be evaluated to identify knowledge gaps to support future clinical trials. We performed a systematic review and meta-analysis of preclinical literature involving RIC in rodent models of focal ischemia. This review was registered with PROSPERO (CRD42019145441). Eligibility criteria included rat or mice models of focal ischemia that received RIC to a limb either before, during, or after stroke. MEDLINE and Embase databases were searched from 1946 to August 2019. Risk of bias was assessed using the SYRCLE risk of bias tool along with construct validity. Seventy-two studies were included in the systematic review. RIC was shown to reduce infarct volume (SMD - 2.19; CI - 2.48 to - 1.91) when compared to stroke-only controls and no adverse events were reported with regard to RIC. Remote ischemic conditioning was shown to be most efficacious in males (SMD - 2.26; CI - 2.58 to - 1.94) and when delivered poststroke (SMD - 1.34; CI - 1.95 to - 0.73). A high risk of bias was present; thus, measures of efficacy may be exaggerated. A limitation is the poor methodological reporting of many studies, resulting in unclear construct validity. We identified several important, but under investigated topics including the efficacy of RIC in different stroke models, varied infarct sizes and location, and potential sex differences.

9.
Crit Care Med ; 49(2): 311-323, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33332817

RESUMO

OBJECTIVES: In many jurisdictions, ethical concerns require surrogate humane endpoints to replace death in small animal models of acute lung injury. Heterogenous selection and reporting of surrogate endpoints render interpretation and generalizability of findings between studies difficult. We aimed to establish expert-guided consensus among preclinical scientists and laboratory animal veterinarians on selection and reporting of surrogate endpoints, monitoring of these models, and the use of analgesia. DESIGN: A three-round consensus process, using modified Delphi methodology, with researchers who use small animal models of acute lung injury and laboratory animal veterinarians who provide care for these animals. Statements on the selection and reporting of surrogate endpoints, monitoring, and analgesia were generated through a systematic search of MEDLINE and Embase. Participants were asked to suggest any additional potential statements for evaluation. SETTING: A web-based survey of participants representing the two stakeholder groups (researchers, laboratory animal veterinarians). Statements were rated on level of evidence and strength of support by participants. A final face-to-face meeting was then held to discuss results. SUBJECTS: None. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Forty-two statements were evaluated, and 29 were rated as important, with varying strength of evidence. The majority of evidence was based on rodent models of acute lung injury. Endpoints with strong support and evidence included temperature changes and body weight loss. Behavioral signs and respiratory distress also received support but were associated with lower levels of evidence. Participants strongly agreed that analgesia affects outcomes in these models and that none may be necessary following nonsurgical induction of acute lung injury. Finally, participants strongly supported transparent reporting of surrogate endpoints. A prototype composite score was also developed based on participant feedback. CONCLUSIONS: We provide a preliminary framework that researchers and animal welfare committees may adapt for their needs. We have identified knowledge gaps that future research should address.

10.
BMJ Open ; 10(12): e042413, 2020 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-33268434

RESUMO

INTRODUCTION: Chronic rhinosinusitis (CRS) is common, with a Canadian prevalence of 5%, and associated with significant morbidity. Understandably, CRS impairs workplace productivity but that productivity substantially increases following surgical treatment. CRS with nasal polyps (CRSwNP), the most common type of CRS, is usually treated with a combination of medications and endoscopic sinus surgery (ESS). Historically, surgical treatment has only been performed in the operating room at a cost of about $C3500. However, recent studies have shown that a de-escalated procedure, endoscopic polypectomy performed in clinic (EPIC), can provide an improvement in patient symptoms to levels equal to those for ESS. Moreover, EPIC has additional proposed advantages including shorter recovery time, significantly lower cost to the healthcare system and shorter wait time for the patient. There is currently insufficient evidence to draw conclusions about the superiority of polypectomy or ESS for the management of CRSwNP. METHODS AND ANALYSIS: We designed a multicentre, open-label, randomised controlled trial to evaluate whether EPIC was non-inferior to the current clinical standard, ESS for the treatment of CRSwNP. The primary outcome is the Sinonasal Outcome Test-22 score measured at baseline and at 3 months after surgery. Other outcomes include peak nasal inspiratory flow, quality of life measured by the EuroQoL 5 Dimensions 5 Levels questionnaire and work impairment using the Work Productivity and Activity Impairment Questionnaire.We aim to recruit 140 patients from sites across Canada. Participants will be randomly assigned to EPIC or ESS and followed up for 3 months in clinic after the procedure. Additionally, participants will enter a 5-year long-term follow-up period. ETHICS AND DISSEMINATION: This study was approved by the Ottawa Health Sciences Network Research Ethics Board for all sites in Ontario, Canada (study number CTO0801). Sites located outside of Ontario obtained approval from their local/institutional research ethics board. TRIAL REGISTRATION NUMBER: NCT02975310.

11.
J Urol ; : 101097JU0000000000001517, 2020 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-33347776

RESUMO

BACKGROUND: Surgeons induce renal hypothermia during partial nephrectomy to preserve kidney function, without strong evidence of benefit. This trial examined the effectiveness and safety of renal hypothermia during partial nephrectomy. METHODS: We conducted a parallel randomized controlled trial of hypothermia versus no hypothermia (control group) during partial nephrectomy at six academic hospitals. Eligible patients had a planned open partial nephrectomy for the treatment of a renal tumor. During surgery, after clamping the renal hilum, patients were randomized to the intervention or control arm in a 1:1 ratio using permuted blocks of variable lengths (2 and 4), stratified by institution, using a computer-based program. Surgeons and study coordinators were masked to treatment allocation until the renal hilum was clamped. Overall glomerular filtration rates were determined before, and 1-year after, surgery. The primary outcome was measured glomerular filtration rate (mGFR) assessed by the plasma clearance of 99mTc-DTPA. The trial (NCT01529658) was designed with 90% power to detect a minimal clinically important difference in mGFR of 10ml/min/1.73m2 at a 5% significance level. FINDINGS: Of the 184 patients randomized, hypothermia and control patients had similar baseline mean mGFR (87.1 vs 81.0 ml/min/1.73m2). One hundred and sixty-one (79 hypothermia, 82 control) were alive with primary outcome data 1-year after surgery. The change in mGFR 1-year after surgery was -6.6 ml/min/1.73m2 in the hypothermia group and -7.8 mL/min/1.73m2 in the control group (mean difference 1.2 mL/min/1.73m2, 95% CI -3.3 to 5.6). Operated-kidney change in mGFR was similar between groups (-5.8 vs -6.3 mL/min/1.73m2; mean difference 0.5 mL/min/1.73m2, 95% CI -2.9 to 3.8). No clinically significant difference in the mGFR was observed when patients were stratified by pre-planned subgroups. Renal hypothermia did not impact the secondary outcomes of surgical complications and patient reported quality of life. INTERPRETATION: Renal hypothermia during partial nephrectomy does not preserve kidney function in patients with normal or mildly impaired renal function.

12.
J Clin Epidemiol ; 132: 106-115, 2020 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-33338563

RESUMO

OBJECTIVES: Despite clear evidence showing that many clinical trials fail or are delayed because of poor patient recruitment, there is surprisingly little empirically supported guidance for trialists seeking to optimize their trial recruitment strategies. We propose that the challenges of recruitment can be better understood and addressed by thinking of research participation as one or more behaviors, subject to the same forces as other human behaviors. In this article, we describe an adaptable, behavioral theory-driven approach for designing pretrial surveys of the barriers and drivers relevant to trial participation. Instead of proposing a single survey instrument intended to be used uniformly across many situations, we propose that tailored surveys be informed by a common comprehensive, theory-guided development approach that ensures all domains potentially guiding participation are considered. STUDY DESIGN AND SETTING: We used the Theoretical Domains Framework (TDF), which organizes over 100 constructs known to be associated with behavior and behavior change into 14 domains that describe determinants of professional and patient health behaviors, to inform the development of tailored surveys about barriers to and drivers of clinical trial participation. After searching the literature for barriers and drivers to trial recruitment relevant to each of the TDF domains, we developed separate surveys for members of two national health charities (Canadian Breast Cancer Network, Huntington Society of Canada) to exemplify how the approach can be adapted across settings. We conducted think-aloud interviews with members of each group to maximize the clarity and usability of the surveys, elicited opinions about which barriers/drivers were relevant for each patient group, and identified additional barriers/drivers. Interviews proceeded iteratively with changes incorporated into subsequent interviews. Here, we describe our two target patient groups, as well as our process of modifying, adding, and deleting barrier/driver items for each group and across theoretical domains. RESULTS: We interviewed 8 women with a history of breast cancer from the Canadian Breast Cancer Network (48-65 year old) and 11 Huntington Disease community members (9 women) from the Huntington Society of Canada (26-70 year old). After the iterative development interviews, the breast cancer group had identified 38 barriers/drivers thought relevant to their participation in clinical trials across 12 TDF domains. The Huntington group identified 47 items across 13 TDF domains. CONCLUSION: Our patient-focused and theory-guided approach was able to identify a more comprehensive range of barriers to and drivers of trial participation than existing published tools. Our approach is also more broadly adaptable than such tools, in that it uses a theoretical framework and in-depth piloting to generate a set of items tailored to each specific clinical area, rather than a single set of items intended to be applicable to all situations. This theory-guided approach also enables more specific recruitment strategies to be developed once domain-specific barriers are known, potentially optimizing participation for a given trial and helping build a cumulative evidence of barriers/drivers and strategies for addressing them.

13.
BMC Gastroenterol ; 20(1): 372, 2020 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-33167889

RESUMO

BACKGROUND: Inflammatory bowel disease (IBD) is a debilitating chronic disease with limited treatment options. Resistant starches may represent a novel treatment for IBD. However, its efficacy and safety remain unclear. Our objective was to perform a systematic review to summarize the preclinical and clinical effects of resistant starch, which may help guide future studies. METHODS: Medline, EMBASE, and the Cochrane Central Register were searched. Included studies investigated the use of resistant starch therapy in in vivo animal models of IBD or human patients with IBD. Articles were screened, and data extracted, independently and in duplicate. The primary outcomes were clinical remission (clinical) and bowel mucosal damage (preclinical). RESULTS: 21 preclinical (n = 989 animals) and seven clinical (n = 164 patients) studies met eligibility. Preclinically, resistant starch was associated with a significant reduction in bowel mucosal damage compared to placebo (standardized mean difference - 1.83, 95% CI - 2.45 to - 1.20). Clinically, five studies reported data on clinical remission but clinical and methodological heterogeneity precluded pooling. In all five, a positive effect was seen in patients who consumed resistant starch supplemented diets. The majority of studies in both the preclinical and clinical settings were at a high or unclear risk of bias due to poor methodological reporting. CONCLUSIONS: Our review demonstrates that resistant starch is associated with reduced histology damage in animal studies, and improvements in clinical remission in IBD patients. These results need to be tempered by the risk of bias of included studies. Rigorously designed preclinical and clinical studies are warranted. Trial registration The review protocols were registered on PROSPERO (preclinical: CRD42019130896; clinical: CRD42019129513).

14.
F1000Res ; 9: 485, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33123348

RESUMO

Background: The process of translating preclinical findings into a clinical setting takes decades. Previous studies have suggested that only 5-10% of the most promising preclinical studies are successfully translated into viable clinical applications. The underlying determinants of this low success rate (e.g. poor experimental design, suboptimal animal models, poor reporting) have not been examined in an empirical manner. Our study aims to determine the contemporary success rate of preclinical-to-clinical translation, and subsequently determine if an association between preclinical study design and translational success/failure exists. Methods: Established systematic review methodology will be used with regards to the literature search, article screening and study selection process. Preclinical, basic science studies published in high impact basic science journals between 1995 and 2015 will be included. Included studies will focus on publicly available interventions with potential clinical promise. The primary outcome will be successful clinical translation of promising therapies - defined as the conduct of at least one Phase II trial (or greater) with a positive finding. A case-control study will then be performed to evaluate the association between elements of preclinical study design and reporting and the likelihood of successful translation. Discussion: This study will provide a comprehensive analysis of the therapeutic translation from the laboratory bench to the bedside. Importantly, any association between factors of study design and the success of translation will be identified. These findings may inform future research teams attempting preclinical-to-clinical translation. Results will be disseminated to identified knowledge users that fund/support preclinical research.

15.
Res Involv Engagem ; 6: 61, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33072399

RESUMO

Aim: Though patient engagement in clinical research is growing, recent reports suggest few clinical trials report on such activities. To address this gap, we describe our approach to patient engagement in the development of a clinical trial protocol to assess a new immunotherapy for blood cancer (chimeric antigen receptor T-cell therapy, CAR-T cell therapy). Methods: Our team developed a clinical trial protocol by working with patient partners from inception. Two patient partners with lived blood cancer experience were identified through referrals from our team's professional network and patient organization contacts. Our patient partners were onboarded to the team and engaged in several studies conducted to develop the clinical trial protocol, including a systematic review of the existing literature on the therapy, patient interviews and a survey to obtain perspectives on barriers and enablers to participating in the trial, an early economic analysis, and a retrospective cohort study. Results: Engaging patient partners enhanced our research in ways that would not have otherwise occurred. By selecting patient important outcomes for data collection, our partners helped flag that quality of life and health utility measures have not been reported in previous CAR-T cell therapy trials for blood cancer. Our partners also co-developed a non-technical summary of the systematic review that summarized results in an accessible manner. Our patient partners reviewed interview and survey questions, to improve the language and appropriateness; provided recruitment suggestions; and provided a patient perspective on the results, thereby confirming the importance of findings. Input was also obtained on costs for the early economic analysis. Our patient partners identified costs that may be a burden to both patients and caregivers during a trial and helped to confirm that the overall structure of the economic model reflected the patient care pathway. Our patient partners also shared their diagnosis and treatment stories, which helped to provide the research team with insight into this experience. Conclusions: Contributions by our patient partners were invaluable to each component study, as well as the overall development of the trial protocol. We plan to use this approach in the future in order to meaningfully engage patients in the development of other clinical trials; we also hope that by reporting our methods this will help other research teams to do the same. Trial registration: Affiliated with the development of NCT03765177.

16.
Pilot Feasibility Stud ; 6: 159, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33110622

RESUMO

Background: The vast majority of children undergoing cardiac surgery have low vitamin D levels post-operative, which may contribute to greater illness severity and worse clinical outcomes. Prior to the initiation of a large phase III clinical trial focused on clinical outcomes, studies are required to evaluate the feasibility of the study protocol, including whether the proposed dosing regimen can safely prevent post-operative vitamin D deficiency in this high-risk population. Methods: We conducted a two-arm, double-blind dose evaluation randomized controlled trial in children requiring cardiopulmonary bypass for congenital heart disease. Pre-operatively, participants were randomized to receive cholecalciferol representing usual care (< 1 year = 400 IU/day, > 1 year = 600 IU/day) or a higher dose approximating the Institute of Medicine tolerable upper intake level (< 1 year = 1600 IU/day, > 1 year = 2400 IU/day). The feasibility outcomes were post-operative vitamin D status (primary), vitamin D-related adverse events, accrual rate, study withdrawal rate, blinding, and protocol non-adherence. Results: Forty-six children were randomized, and five withdrew prior to surgery, leaving 41 children (21 high dose, 20 usual care) in the final analysis. The high dose group had higher 25-hydroxyvitamin D concentrations both intraoperatively (mean difference + 25.9 nmol/L; 95% CI 8.3-43.5) and post-operatively (mean difference + 17.2 nmol/L; 95% CI 5.5-29.0). Fewer participants receiving high-dose supplementation had post-operative serum 25-hydroxyvitamin D concentrations under 50 nmol/L, compared with usual care (RR 0.31, 95% CI 0.11-0.87). Post-operative vitamin D status was associated with the treatment arm and the number of doses received. There were no cases of hypercalcemia, and no significant adverse events related to vitamin D. While only 75% of the target sample size was recruited (limited funding), the consent rate (83%), accrual rate (1.5 per site month), number of withdrawals (11%), and ability to maintain blinding support feasibility of a larger trial. Conclusions: Pre-operative daily high-dose supplementation improved vitamin D status pre-operatively and at time of pediatric ICU admission. The protocol for a more definitive trial should limit enrollment of children with at least 30 days between randomization and surgery to allow adequate duration of supplementation or consider a loading dose. Trial registration: ClinicalTrials.gov, NCT01838447. Registered on April 24, 2013.

17.
J Bone Joint Surg Am ; 102(21S Suppl 1): 114-124, 2020 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-32870618

RESUMO

BACKGROUND: Our objective was to identify combination tests used to diagnose chronic periprosthetic joint infection (PJI) and develop a stepwise decision-making tool to facilitate diagnosis. METHODS: We conducted a systematic review of existing combinations of serum, synovial, and tissue-based tests for diagnosing chronic PJI after hip or knee replacement. This work is an extension of our systematic review of single tests, from which we chose eligible studies that also described the diagnostic performance of combination tests. RESULTS: Thirty-seven eligible articles described the performance of 56 combination tests, of which 8 combinations had at least 2 studies informing both sensitivity and specificity. We also identified 5 types of combination tests: (1) a type-I Boolean combination, which uses Boolean logic (AND, OR) and usually increases specificity at the cost of sensitivity; (2) a type-II Boolean combination, which usually increases sensitivity at the cost of specificity; (3) a triage-conditional rule, in which the value of 1 test serves to triage the use of another test; (4) an arithmetic operation on the values of 2 tests; and (5) a model-based prediction rule based on a fitted model applied to biomarker values. CONCLUSIONS: Clinicians can initiate their diagnostic process with a type-II Boolean combination of serum C-reactive protein (CRP) and interleukin-6 (IL-6). False negatives of the combination can be minimized when the threshold is chosen to reach 90% to 95% sensitivity for each test. Once a joint infection is suspected on the basis of serum testing, joint aspiration should be performed. If joint aspiration yields a wet tap, a leukocyte esterase (LER) strip is highly recommended for point-of-care testing, with a reading of ++ or greater indicating PJI; a reading below ++ should be followed by one of the laboratory-based synovial tests. If joint aspiration yields a dry tap, clinicians should rely on preoperative tissue culture and histological analysis for diagnosis. Combinations based on triage-conditional, arithmetic, and model-based prediction rules require further research. LEVEL OF EVIDENCE: Diagnostic Level III. See Instructions for Authors for a complete description of levels of evidence.

18.
Transfus Med Rev ; 2020 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-32994103

RESUMO

Perioperative bleeding is a major indication for red blood cell (RBC) transfusion, yet transfusion data in many major noncardiac surgeries are lacking and do not reflect recent blood conservation efforts. We aim to describe transfusion practices in noncardiac surgeries at high risk for RBC transfusion. We completed a retrospective cohort study to evaluate adult patients undergoing major noncardiac surgery at 5 Canadian hospitals between January 2014 and December 2016. We used Canadian Classification of Health Interventions procedure codes within the Discharge Abstract Database, which we linked to transfusion and laboratory databases. We studied all patients undergoing a major noncardiac surgery at ≥5% risk of perioperative RBC transfusion. For each surgery, we characterized the percentage of patients exposed to an RBC transfusion, the mean/median number of RBC units transfused, and platelet and plasma exposure. We identified 85 noncardiac surgeries with an RBC transfusion rate ≥5%, representing 25,607 patient admissions. The baseline RBC transfusion rate was 16%, ranging from 5% to 49% among individual surgeries. Of those transfused, the median (Q1, Q3) number of RBCs transfused was 2 U (1, 3 U); 39% received 1 U RBC, 36% received 2 U RBC, and 8% were transfused ≥5 U RBC. Platelet and plasma transfusions were overall low. In the era of blood conservation, we described transfusion practices in major noncardiac surgeries at high risk for RBC transfusion, which has implications for patient consent, preoperative surgical planning, and blood bank inventory management.

19.
BMJ Open ; 10(9): e041776, 2020 09 21.
Artigo em Inglês | MEDLINE | ID: mdl-32958496

RESUMO

INTRODUCTION: Reversible cerebral vasoconstriction syndrome (RCVS) is characterised by severe, recurrent thunderclap headaches (TCHs) and vasoconstriction of cerebral arteries that resolve within 3 months. Abnormalities on non-contrast CT (NCCT) such as ischaemic strokes, intracerebral haemorrhage and subarachnoid haemorrhages are frequently observed on brain imaging of patients with RCVS though their prevalence varies considerably between studies. The aim of this systematic review and meta-analysis is to estimate the prevalence of NCCT abnormalities seen on neuroimaging of adult patients with RCVS. METHODS AND ANALYSIS: We will search the Medline, Embase and the Cochrane Library databases for studies on the prevalence of NCCT abnormalities on neuroimaging of patients with RCVS. Search results will be screened for eligibility by title and abstract. Suitable studies will be fully reviewed and relevant data extracted using a data abstraction form. The studies will be assessed for methodological quality, risk of bias and heterogeneity. Prevalence estimates across studies will be pooled using a random-effects model and subgroup analysis will be performed to assess the impact of age, sex, publication year and study design on prevalence of vascular lesions. Sensitivity analysis will be used to investigate the robustness of the findings. This protocol has been devised using the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols 2015 checklist. ETHICS AND DISSEMINATION: Formal ethics is not required as primary data will not be collected. The findings of this study will be disseminated through a peer-reviewed publication and conference presentations. TRIAL REGISTRATION NUMBER: CRD42020190637.

20.
BMJ Open ; 10(9): e037124, 2020 09 13.
Artigo em Inglês | MEDLINE | ID: mdl-32928855

RESUMO

INTRODUCTION: Cervical artery dissection, including carotid and vertebral artery dissection, is an important cause of stroke in the young. Risk of developing cervical artery dissection has been associated with physical activity in various forms and has been presumed to be related to minor trauma and mechanical stretching of the cervical arteries. This systematic review will aim to synthesise data on the risk of recurrent cervical artery dissection after an initial dissection. This information may be applied to further understand the natural history of this disease, and potentially to help direct evidence-based discussions on safe return to activity after dissection. METHODS AND ANALYSIS: A broad search of multiple electronic databases (Medline, Embase, Cochrane Central Register of Controlled Trials and Web of Science) will be conducted to identify studies published as of 13 November 2019, examining all-comers with cervical artery dissection observed over time. Studies will be screened by two independent reviewers in a two-level process to determine eligibility for inclusion. Data will be pooled from eligible articles and the main outcome of recurrent cervical artery dissection at 5 years will be determined using quantitative analysis. ETHICS AND DISSEMINATION: Ethics approval is not necessary as no primary data are being collected. The information will be disseminated in the form of a systematic review article which will be submitted to a peer-reviewed medical journal. PROSPERO REGISTRATION NUMBER: CRD42020166105.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA