Adrienne Cheung

Antivirals for treatment of influenza: a systematic review and meta-analysis of observational studies.

BACKGROUND Systematic reviews of randomized, controlled trials in patients with influenza suggest a lack of evidence about the effects of antiviral therapy on several patient-important outcomes of influenza. PURPOSE To systematically review observational studies for benefits and harms of oseltamivir, zanamivir, amantadine, or rimantadine in the treatment of influenza. DATA SOURCES MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, CINAHL, SIGLE, the Chinese Biomedical Literature Database, Panteleimon, and LILACS up to November 2010; contact with pharmaceutical companies; and reference lists. STUDY SELECTION Observational studies in any language that compared single antiviral therapy with no therapy or other antiviral therapy, or that had no comparator, for influenza or influenza-like illness. DATA EXTRACTION Two independent investigators extracted data. Confidence in the estimates of the obtained effects (quality of evidence) was assessed by using the Grading of Recommendations Assessment, Development, and Evaluation approach. DATA SYNTHESIS 74 studies fulfilled the inclusion criteria. Meta-analyses of the few studies providing effects with adjustment for confounders suggest that, in high-risk populations, oral oseltamivir may reduce mortality (odds ratio, 0.23 [95% CI, 0.13 to 0.43]; low-quality evidence), hospitalization (odds ratio, 0.75 [CI, 0.66 to 0.89]; low-quality evidence), and duration of symptoms (33 hours [CI, 21 to 45 hours]; very low-quality evidence) compared with no treatment. Earlier treatment with oseltamivir was generally associated with better outcomes. Inhaled zanamivir may lead to shorter symptom duration (23 hours [CI, 17 to 28 hours]; moderate-quality evidence) and fewer hospitalizations (odds ratio, 0.66 [CI, 0.37 to 1.18]) but more complications than no treatment. Direct comparison of oral oseltamivir and inhaled zanamivir suggests no important differences in key outcomes. Data from 1 study suggest that oral amantadine may reduce mortality and pneumonia associated with influenza A. No included study evaluated rimantadine. LIMITATIONS Mortality was assessed in high-risk patients, and generalizability is limited. The overall body of evidence is limited by risk for confounding and selection, reporting, and publication bias. CONCLUSION Therapy with oral oseltamivir and inhaled zanamivir may provide a net benefit over no treatment of influenza. However, as with the randomized trials, the confidence in the estimates of the effects for decision making is low to very low. PRIMARY FUNDING SOURCES: World Health Organization and McMaster University.

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).

Antivirals for influenza: a summary of a systematic review and meta-analysis of observational studies

Despite the use of antivirals to treat patients with severe influenza, questions remain with respect to effects and safety. Although a recent systematic review has provided some indication of benefit, the analysis is limited by the quality of the available evidence from randomized controlled trials. To supplement the existing information, the authors conducted a systematic review of observational studies of antiviral treatment for influenza. This report summarises the findings of that review. Similar to the randomised trials, the confidence in the estimates of the effects for decision‐making is low to very low primarily due to the risk of selection and publication bias in the observational studies. From these observational studies, the summary estimates suggest that oseltamivir may reduce mortality, hospitalisation and duration of symptoms compared with no treatment. Inhaled zanamivir may also reduce symptom duration and hospitalisations, but patients may experience more complications compared with no treatment. Earlier treatment with antivirals is generally associated with better outcomes than later treatment. Further high‐quality evidence is needed to inform treatment guidelines because of the overall low to very low quality of evidence.

Decision-Making about Healthcare Related Tests and Diagnostic Strategies: User Testing of GRADE Evidence Tables

Objective To develop guidance on what information to include and how to present it in tables summarizing the evidence from systematic reviews of test accuracy following the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Methods To design and refine the evidence tables, we used an iterative process based on the analysis of data from four rounds of discussions, feedback and user testing. During the final round, we conducted one-on-one user testing with target end users. We presented a number of alternative formats of evidence tables to participants and obtained information about users’ understanding and preferences. Results More than 150 users participated in initial discussions and provided their formal and informal feedback. 20 users completed one-on-one user testing interviews. Almost all participants preferred summarizing the results of systematic reviews of test accuracy in tabular format rather than plain text. Users generally preferred less complex tables but found presenting sensitivity and specificity estimates only as too simplistic. Users found the presentation of test accuracy for several values of prevalence initially confusing but modifying table layout and adding sample clinical scenarios for each prevalence reduced this confusion. Providing information about clinical consequences of testing result was viewed as not feasible for authors of systematic reviews. Conclusion We present the current formats for tables presenting test accuracy following the GRADE approach. These tables can be developed using GRADEpro guidelines development tool (www.guidelinedevelopment.org or www.gradepro.org) and are being further developed into electronic interactive tables that will suit the needs of different end users. The formatting of these tables, and how they influence result interpretation and decision-making will be further evaluated in a randomized trial.

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.

058 Assessment of the Evidence for Diagnostic Tests and Strategies: A Systematic Review of Available Tools

Background The challenges facing guideline developers when making recommendations about diagnostic tests and strategies (DTS) are considerably different when compared to treatment recommendations. Objectives To identify, describe and compare all available instruments, checklists, critical appraisal tools, and indices designed for assessing the quality of evidence (QoE) or strength of recommendations (SoR) dealing with diagnostic tests and strategies. Methods We conducted a comprehensive systematic search of the literature including state of the art diagnostic guidelines, methods papers and diagnostic systematic reviews. Results We identified 45 tools and modifications of existing tools to assess the QoE and SoR of DTS. Most tools acknowledge the importance of assessing the QoE and SoR separately. Most tools include individual quality criteria and study design but no tool rates all quality criteria suggested by the GRADE working group. Only two tools explicitly consider factors that increase the confidence in the evidence. When moving from evidence to recommendations, patient values and preferences and resources were rarely considered. Discussion There is confusion about the terminology that describes the various factors that influence the QoE and SoR. The criteria for evaluating the QoE and moving from evidence to recommendations are incomplete for most guideline development frameworks that we evaluated. Implications for Guideline Developers/Users The GRADE approach is the most complete approach encompassing all factors but users will benefit from a better description of the evidence to recommendation framework in GRADE and clarification of issues that relate to laboratory validity parameters.