Nancy Lloyd

Strategies to enhance venous thromboprophylaxis in hospitalized medical patients (SENTRY): a pilot cluster randomized trial

BackgroundVenous thromboembolism (VTE) is a common preventable cause of mortality in hospitalized medical patients. Despite rigorous randomized trials generating strong recommendations for anticoagulant use to prevent VTE, nearly 40% of medical patients receive inappropriate thromboprophylaxis. Knowledge-translation strategies are needed to bridge this gap.MethodsWe conducted a 16-week pilot cluster randomized controlled trial (RCT) to determine the proportion of medical patients that were appropriately managed for thromboprophylaxis (according to the American College of Chest Physician guidelines) within 24 hours of admission, through the use of a multicomponent knowledge-translation intervention. Our primary goal was to determine the feasibility of conducting this study on a larger scale. The intervention comprised clinician education, a paper-based VTE risk assessment algorithm, printed physicians’ orders, and audit and feedback sessions. Medical wards at six hospitals (representing clusters) in Ontario, Canada were included; three were randomized to the multicomponent intervention and three to usual care (i.e., no active strategies for thromboprophylaxis in place). Blinding was not used.ResultsA total of 2,611 patients (1,154 in the intervention and 1,457 in the control group) were eligible and included in the analysis. This multicomponent intervention did not lead to a significant difference in appropriate VTE prophylaxis rates between intervention and control hospitals (appropriate management rate odds ratio = 0.80; 95% confidence interval: 0.50, 1.28; p = 0.36; intra-class correlation coefficient: 0.022), and thus was not considered feasible. Major barriers to effective knowledge translation were poor attendance by clinical staff at education and feedback sessions, difficulty locating preprinted orders, and lack of involvement by clinical and administrative leaders. We identified several factors that may increase uptake of a VTE prophylaxis strategy, including local champions, support from clinical and administrative leaders, mandatory use, and a simple, clinically relevant risk assessment tool.ConclusionsHospitals allocated to our multicomponent intervention did not have a higher rate of medical inpatients appropriately managed for thromboprophylaxis than did hospitals that were not allocated to this strategy.

The Use of Chemotherapy in Patients with Advanced Malignant Pleural Mesothelioma: A Systematic Review and Practice Guideline

Background: This clinical practice guideline, based on a systematic review, was developed to determine which chemotherapeutic agents (or combinations of agents) show the highest response rates, improved survival, quality of life, or symptom control in patients with advanced malignant pleural mesothelioma. Methods: A thorough systematic search of the literature was conducted for published articles and conference proceedings for applicable abstracts. Relevant trials, published as articles and abstracts, were selected and assessed. External feedback was obtained from Ontario clinicians, and the guideline was approved by the provincial Lung Cancer Disease Site Group. Results: One hundred nineteen studies were eligible, including eight randomized trials and 111 phase II trials. The pooled response rates from phase II trials suggest that response rates with combination chemotherapy are higher than with single agents. Data from the largest randomized controlled trial demonstrated that chemotherapy with cisplatin and pemetrexed significantly improves response rates (41% versus 17%, p < 0.001), time to progression (5.7 months versus 3.9 months, p = 0.001), and overall survival (median, 12.1 months versus 9.3 months, hazard ratio = 0.77, p = 0.020) in comparison to single-agent cisplatin. A second trial demonstrated cisplatin and raltitrexed significantly improved median survival compared to single-agent cisplatin (11.4 months versus 8.8 months; hazard ratio = 0.76, p = 0.0483). Overall response rate (24% versus 14%, p = 0.056) was greater in the combination treatment arm, but this difference was not statistically significant. Conclusions: There is good evidence to recommend chemotherapy with pemetrexed and cisplatin for adult patients with symptomatic advanced malignant pleural mesothelioma. Such treatment should be administered with supplementation of vitamin B12 and folic acid. If pemetrexed is not available, cisplatin plus raltitrexed is a reasonable alternative.

Radiotherapy fractionation for the palliation of uncomplicated painful bone metastases – an evidence-based practice guideline

AbstractBackgroundThis practice guideline was developed to provide recommendations to clinicians in Ontario on the preferred standard radiotherapy fractionation schedule for the treatment of painful bone metastases.MethodsA systematic review and meta-analysis was performed and published elsewhere. The Supportive Care Guidelines Group, a multidisciplinary guideline development panel, formulated clinical recommendations based on their interpretation of the evidence. In addition to evidence from clinical trials, the panel also considered patient convenience and ease of administration of palliative radiotherapy. External review of the draft report by Ontario practitioners was obtained through a mailed survey, and final approval was obtained from the Practice Guidelines Coordinating Committee.ResultsMeta-analysis did not detect a significant difference in complete or overall pain relief between single treatment and multifraction palliative radiotherapy for bone metastases. Fifty-nine Ontario practitioners responded to the mailed survey (return rate 62%). Forty-two percent also returned written comments. Eighty-three percent of respondents agreed with the interpretation of the evidence and 75% agreed that the report should be approved as a practice guideline. Minor revisions were made based on feedback from the external reviewers and the Practice Guidelines Coordinating Committee. The Practice Guidelines Coordinating Committee approved the final practice guideline report.ConclusionFor adult patients with single or multiple radiographically confirmed bone metastases of any histology corresponding to painful areas in previously non-irradiated areas without pathologic fractures or spinal cord/cauda equine compression, we conclude that:• Where the treatment objective is pain relief, a single 8 Gy treatment, prescribed to the appropriate target volume, is recommended as the standard dose-fractionation schedule for the treatment of symptomatic and uncomplicated bone metastases. Several factors frequently considered in clinical practice when applying this evidence such as the effect of primary histology, anatomical site of treatment, risk of pathological fracture, soft tissue disease and cord compression, use of antiemetics, and the role of retreatment are discussed as qualifying statements.Our systematic review and meta-analysis provided high quality evidence for the key recommendation in this clinical practice guideline. Qualifying statements addressing factors that should be considered when applying this recommendation in clinical practice facilitate its clinical application. The rigorous development and approval process result in a final document that is strongly endorsed by practitioners as a practice guideline.

Clinical practice guideline on the optimal radiotherapeutic management of brain metastases.

BackgroundAn evidence-based clinical practice guideline on the optimal radiotherapeutic management of single and multiple brain metastases was developed.MethodsA systematic review and meta-analysis was performed. The Supportive Care Guidelines Group formulated clinical recommendations based on their interpretation of the evidence. External review of the report by Ontario practitioners was obtained through a mailed survey, and final approval was obtained from Cancer Care Ontarios Practice Guidelines Coordinating Committee (PGCC).ResultsOne hundred and nine Ontario practitioners responded to the survey (return rate 44%). Ninety-six percent of respondents agreed with the interpretation of the evidence, and 92% agreed that the report should be approved. Minor revisions were made based on feedback from external reviewers and the PGCC. The PGCC approved the final practice guideline report.ConclusionsFor adult patients with a clinical and radiographic diagnosis of brain metastases (single or multiple) we conclude that,• Surgical excision should be considered for patients with good performance status, minimal or no evidence of extracranial disease, and a surgically accessible single brain metastasis.• Postoperative whole brain radiotherapy (WBRT) should be considered to reduce the risk of tumour recurrence for patients who have undergone resection of a single brain metastasis.• Radiosurgery boost with WBRT may improve survival in select patients with unresectable single brain metastases.• The whole brain should be irradiated for multiple brain metastases. Standard dose-fractionation schedules are 3000 cGy in 10 fractions or 2000 cGy in 5 fractions.• Radiosensitizers are not recommended outside research studies.• In select patients, radiosurgery may be considered as boost therapy with WBRT to improve local tumour control. Radiosurgery boost may improve survival in select patients.• Chemotherapy as primary therapy or chemotherapy with WBRT remains experimental.• Supportive care is an option but there is a lack of Level 1 evidence as to which subsets of patients should be managed with supportive care alone.Qualifying statements addressing factors to consider when applying these recommendations are provided in the full report. The rigorous development, external review and approval process has resulted in a practice guideline that is strongly endorsed by Ontario practitioners.

Systematic reviews and meta-analyses of benefits and harms of cryotherapy, LEEP, and cold knife conization to treat cervical intraepithelial neoplasia

Cervical intraepithelial neoplasia (CIN) stage 2–3 is a premalignant lesion that can progress to cervical cancer in 10–20 years if untreated.

Systematic reviews and meta‐analyses of the accuracy of HPV tests, visual inspection with acetic acid, cytology, and colposcopy

Cervical cancer screening is offered to women to identify and treat cervical intraepithelial neoplasia (CIN).

Decision making about healthcare-related tests and diagnostic test strategies. Paper 3: a systematic review shows limitations in most tools designed to assess quality and develop recommendations

OBJECTIVES The objective of this study was to identify and describe critical appraisal tools designed for assessing the quality of evidence (QoE) and/or strength of recommendations (SoRs) related to health care-related tests and diagnostic strategies (HCTDSs). STUDY DESIGN AND SETTING We conducted a systematic review to identify tools applied in guidelines, methodological articles, and systematic reviews to assess HCTDS. RESULTS We screened 5,534 titles and abstracts, 1,004 full-text articles, and abstracted data from 330 references. We identified 29 tools and 14 modifications of existing tools for assessing QoE and SoR. Twenty-three out of 29 tools acknowledge the importance of assessing the QoE and SoR separately, but in 8, the SoR is based solely on QoE. When making decisions about the use of tests, patient values and preferences and impact on resource utilization were considered in 6 and 8 tools, respectively. There is also confusion about the terminology that describes the various factors that influence the QoE and SoR. CONCLUSION Although at least one approach includes all relevant criteria for assessing QoE and determining SoR, more detailed guidance about how to operationalize these assessments and make related judgments will be beneficial. There is a need for a better description of the framework for using evidence to make decisions and develop recommendations about HCTDS.

Decision making about healthcare-related tests and diagnostic test strategies. Paper 4: International guidelines show variability in their approaches

OBJECTIVES The objective of the study was to describe and compare current practices in developing guidelines about the use of healthcare-related tests and diagnostic strategies (HCTDS). STUDY DESIGN AND SETTING We sampled 37 public health and clinical practice guidelines about HCTDS from various sources without language restrictions. RESULTS Detailed descriptions of the systems used to assess the quality of evidence and develop recommendations were challenging to find within guidelines. We observed much variability among and within organizations with respect to how they develop recommendations about HCTDS. Twenty-four percent of the guidelines did not consider health benefits and harms but based decisions solely on test accuracy. We did not identify guidelines that described the main potential care pathways involving tests for a healthcare problem. In addition, we did not identify guidelines that systematically assessed, described, and referenced the evidence that linked test accuracy and patient-important outcomes. CONCLUSION There is considerable variability among the processes used and factors considered in developing recommendations about the use of tests. This variability may be the cause for the disagreement we observed in recommendations about testing for the same condition.

041 MAKING RECOMMENDATIONS ABOUT DIAGNOSTIC TESTS AND STRATEGIES: WHAT DO EXPERTS SAY?

Background Current practices in developing guidelines about the use of diagnostic tests and strategies (DTS) are out of step with the conceptual discussion among experts. Objectives Identify the essential factors to consider when making recommendations about DTS. Methods We conducted semi-structured in-depth interviews with experts in assessing evidence and producing guidelines about DTS. Results We interviewed 23 international experts. Although diagnostic test accuracy (DTA) was the factor most commonly considered by organisations when developing recommendations, experts agreed that DTA is never sufficient and may be misleading. Experts identified the following additional essential factors in making decisions about DTS: resource implications, complications, inconclusive results, additional benefits of the test, diagnostic/therapeutic impact, safety, feasibility, ethical, legal, and organisational considerations, patients’ and societies’ values and preferences and the link between the test results and patient important outcomes. Because direct evidence on DTS’s effects on patient outcomes and resource implications is frequently unavailable, most experts agreed that decision analysis and mathematical modelling will be useful, but their opinion varied about the extent of details needed. Discussion Formal decision modelling can be a useful framework for organising the clinical, cost, and preference data relevant to the use of diagnostic tests. Although it requires resources, it is useful for integrating these factors into decision making, identifying evidence gaps, and high priority research areas. Implications Developing guidelines about the use of DTS requires considering factors beyond solely DTA but implementing this demand is challenging. Further development and testing of a framework that can guide this process is needed.