A. Gray Ellrodt

The Relation between Systematic Reviews and Practice Guidelines

Systemic Review Series Series Editors: Cynthia Mulrow, MD, MSc Deborah Cook, MD, MSc Historically, implicit clinical policies rested primarily with individual practitioners, protected under the rubric of the art of medicine and modulated by knowledge, experience, and heuristics [1]. Dissemination of information through peer-reviewed publications and traditional continuing medical education represent two major, albeit somewhat passive and indirect, attempts to inform clinical practice. The promulgation of explicit clinical policy embodied in practice guidelines has recently heightened awareness of the determinants of medical decision making [2]. Practice guidelines have been developed to improve the process of health care and health outcomes, decrease practice variation, and optimize resource utilization [3, 4]. Described as systematically developed statements to assist practitioner and patient decisions about appropriate health care for specific clinical circumstances [5], guidelines attempt to distill a large body of medical expertise into a convenient, readily usable format. Practice guidelines based on the synthesis of the best, most recent evidence can help practitioners keep current with the literature and help them assimilate evidence into practice [6, 7]. The term guideline is used loosely to describe documents with different purposes, such as regulation of hospital admissions, use of tests and technology, transfer of seriously ill patients [8], and training programs [9]. Sporting such names as practice policies, practice parameters, and clinical indicators [10, 11], other decision aids further expand this lexicon. Clinical practice guidelines represent specific decision nodes that can be linked together to form clinical pathways or algorithms. Clinical pathways organize, sequence, and time the care given to a typical, uncomplicated patient [4, 12], whereas clinical algorithms are a set of more complex instructions for addressing a particular issue in which decisions and their consequences are expressed in conditional, branching logic [13]. This article focuses on the relation between systematic reviews and practice guidelines: how the development of guidelines can benefit from systematic reviews, and how systematic reviews can be used to help implement guidelines. Methods for Developing Guidelines: An Overview Methods used to develop guidelines differ according to the stakeholders involved, the degree of reliance on formal literature reviews, the extent to which expert opinion prevails, and the process by which the ultimate recommendations are expressed [11]. A multidisciplinary team may result in a holistic approach and wider endorsement of the final product [7]. Group processes commonly used to generate clinical recommendations include informal peer committees, nominal group techniques [14], the Delphi method [15], and expert or nonexpert consensus conferences. These strategies are not mutually exclusive, and their advantages and disadvantages have been summarized elsewhere [16]. One method for guideline development is outlined in the (Figure 1). Whether guidelines are created by local health providers, regional or national professional bodies, payers, or purchasers, the resources available may also determine the focus and methods. Few studies have compared the process, products, and health outcomes of these different approaches to developing recommendations [17]. Figure 1. One approach to developing guidelines and pathways on the basis of summaries of the relevant research evidence Selecting the clinical problem to be addressed by a guideline involves considering the prevalence of the problem, the clinical and economic burden it imposes, the resources available for its care, the availability of evidence for both existing care and improved care, and the likelihood of influencing practice [18, 19]. The next steps involve learning about current clinical practice as a baseline for change, defining the goals of the guidelines, and searching for the relevant research evidence (Figure 1). Because a guideline based on an incomplete or biased evaluation of the literature can lead to inappropriate recommendations, the search for relevant research should be comprehensive, research should be selected by using explicit criteria, and the validity of the results should be judged in a rigorous and reproducible fashion. Guideline and pathway developers ideally search for, select, critique, and combine data in a manner analogous to that used for a systematic review. In addition to incorporating evidence and acknowledging its absence, creating clinical recommendations requires making value judgments about preferred courses of action. Some guidelines lay out choices and are distinctively influenced by patient preferences. Consider the difference in this regard between offering men with prostate cancer the choice of conservative management or radical prostatectomy (which builds patient preference into the decision) and assuming that all patients without advance directives who sustain a cardiac arrest want cardiopulmonary resuscitation (which does not). Guideline documents ideally indicate how disagreements were handled and how information was synthesized (for example, by a qualitative pooling of opinion, a quantitative approach such as meta-analysis or decision analysis, or some combination of methods [19]). If guideline developers do not indicate how they identified and summarized the evidence and integrated different values, clinicians cannot adequately evaluate the rigor of the guidelines and the extent to which research evidence supports the recommendations [20, 21]. Recent guidelines for the diagnosis and treatment of idiopathic thrombocytopenic purpura [22] described the literature, emphasized the paucity of evidence and the limitations of opinion-based recommendations, and issued recommendations on the basis of clear documentation of the strength and variance of opinion [23]. The Role of Research Evidence in Practice Guideline Development Guideline developers who want to incorporate research evidence into their clinical recommendations recognize the challenges of exhaustively searching the literature. For many common conditions, the volume of clinically useful literature is considerable. For other conditions, data may be sparse. Because guideline development is often limited by the difficulty of locating and appraising primary research, searching for and conducting systematic reviews is important. Accordingly, both primary research and integrative articles are potentially useful to guideline developers (Figure 1). Systematic reviews are the most common type of integrative article. Their authors have searched for, selected, and synthesized (either qualitatively or quantitatively) evidence on specific clinical questions. Economic analyses quantitatively compare the costs and consequences of alternate courses of action. Decision analyses present the probability of various outcomes in terms of the values of expected benefits and harms of key decisions. Although clinical recommendations may emerge from these documents, their content is typically structured in a research report format. In contrast, practice guidelines are more often presented in a framework congruent with decision making; they suggest or support specific clinical recommendations but may reflect the scope of information contained in systematic reviews, economic analyses, and decision analyses. For example, the American College of Physicians guidelines for magnetic resonance imaging of the brain and spine [24] were produced after a systematic review of neuroimaging with magnetic resonance imaging [25], and the guideline developers acknowledged the absence of studies comparing magnetic resonance imaging with other technologies. Relevant reviews are sometimes published after rather than before guidelines are developed. Such was the case with the 1994 clinical practice guideline on unstable angina by the Agency for Health Care Policy and Research [26], whose expert panel recommended that patients with unstable angina who are receiving aspirin should be treated with heparin for 2 to 5 days unless heparin is contraindicated. Two years later, a supporting meta-analysis showed a 33% reduction in risk for myocardial infarction or death in patients who had unstable angina and received aspirin plus heparin compared with those who received aspirin alone [27]. The scope of guidelines may reflect the particular interests of the guideline developers. The Colleges guidelines for the medical treatment of stroke prevention [28] clearly incorporate the results of a concurrently published systematic review [29] but are not explicit about cost-effectiveness issues (such as the rationale for choosing aspirin rather than ticlopidine). Other guidelines, such as those created by the American Heart Association for carotid endarterectomy [30], comprehensively summarize research and address economic issues more directly. Examples of How To Use Systematic Reviews for Building Practice Guidelines and Clinical Pathways As an alternate or complementary approach to formally summarizing primary research, guideline and pathway developers can use previously published systematic reviews that summarize the relevant primary studies. For the management of bleeding esophageal varices, approximately 200 randomized trials of pharmacologic, mechanical, and surgical interventions could be considered, as could a more manageable number of systematic reviews of these topics. For example, systematic reviews of primary prevention of variceal gastrointestinal hemorrhage indicate that -blockade and sclerotherapy reduce bleeding and mortality rates [31-33]. Systematic reviews also indicate the following. First, for control of acute bleeding, vasopressin is superior to no treatment but somatostatin is more effective than vasopressin [34, 35]. Second, although emergency sclerotherapy controls bleeding and

Left ventricular performance in septic shock: Reversible segmental and global abnormalities

Left ventricular dysfunction has been implicated in the pathogenesis of septic shock, but little is known about its natural history, cause, and prognostic significance. Left ventricular performance was assessed by serial radionuclide and hemodynamic studies in 35 patients with culture-proven septic shock. The mean age (+/- S.D.) of the group was 64 +/- 18 years; 16 of the subjects were women, and 15 had antecedent heart disease. On the first study, the left ventricular stroke work index was depressed in 33 (94%) patients, and nineteen (54%) had a left ventricular ejection fraction less than 0.48. Twenty-two (63%) of the patients had segmental and four had generalized wall motion abnormalities. Conventional hemodynamic parameters were of no value in predicting the patients who had a depressed left ventricular ejection fraction or segmental abnormalities. Patients with underlying heart disease had a much higher frequency (87%) of segmental dysfunction than those without underlying heart disease (45%; p = 0.016), but no differences were noted in the left ventricular ejection fraction or left ventricular stroke work index of these two groups. Segmental abnormalities and low ejection fractions were seen more often in patients with a large left ventricular end-diastolic volume index. Only five subjects had a systemic vascular resistance index greater than 2580 dynes X sec X cm-5 per m2, and the correlation between systemic vascular resistance index and left ventricular ejection fraction was poor. No difference was found in the mean coronary perfusion pressure of those with segmental abnormalities and those with normal wall motion.(ABSTRACT TRUNCATED AT 250 WORDS)

Right ventricular performance in septic shock: A combined radionuclide and hemodynamic study

Twenty-five patients with septic shock underwent simultaneous radionuclide ventriculography and right heart catheterization to clarify the role of the right ventricle in this syndrome. A depressed right ventricular ejection fraction (less than 38%) was present in 13 patients and was found in patients with elevated cardiac output (4 of 6 patients) and with normal or low cardiac output (9 of 19 patients). Right ventricular dysfunction was seen with or without acute respiratory failure. In eight patients, a depressed right ventricular ejection fraction was seen in combination with an abnormal left ventricular ejection fraction (less than 48%), but in five patients, right ventricular ejection fraction impairment occurred with normal left ventricular ejection fraction. There was no significant correlation between abnormal right ventricular afterload and depressed right ventricular ejection fraction. No clinical or hemodynamic finding could be used to identify patients with diminished right ventricular ejection fraction. On follow-up study in 17 surviving patients, right ventricular ejection fraction improved in 6 and was unchanged in 11. Improvement in right ventricular ejection fraction occurred more frequently in patients without pulmonary hypertension or respiratory distress. The results suggest that right ventricular dysfunction in septic shock may be more common than previously suspected. It may be caused by abnormalities in right ventricular afterload in some patients and depressed myocardial contractility in others. The findings are of therapeutic importance since interventions that diminish right ventricular afterload and increase right ventricular contractility would be appropriate in patients with septic shock and right ventricular dysfunction.

Selecting the best triage rule for patients hospitalized with chest pain

PURPOSE During an observational study, we investigated the potential benefits and risks of the use of admission and early transfer triage rules in 498 patients hospitalized with chest pain. PATIENTS AND METHODS Appropriateness of triage decisions was measured using explicit and implicit judgments. RESULTS Application of an admission triage rule (partially based on the Brush electrocardiographic criteria) would have increased coronary care unit (CCU) admissions by 3%, whereas application of a triage rule 24 hours after admission would have reduced bed utilization by 860 intermediate care and 82 CCU bed-days per year when compared with actual patient triage. Although 9.5% of patients who underwent triage according to the early transfer triage rule would have experienced a minor complication after transfer, the medical care of none would have been adversely affected. CONCLUSION Our results show that application of a triage rule 24 hours after admission may have the potential to shorten length of stay in the CCU and intermediate care unit without significantly compromising patient care. However, use of the admission triage rule would have increased CCU bed utilization. The failure of the admission triage rule to improve bed utilization illustrates the potential hazards of ignoring patient complications, interventions, and co-morbidity when predicting the efficacy of a triage rule.

Severe Neutropenia Associated with Sustained-Release Procainamide

Neutropenia is a rare complication of procainamide therapy. However, over a period of 20 months, 8 patients developed severe neutropenia while taking a sustained-release preparation of the drug. Seven patients presented with fever and constitutional symptoms and one patient was asymptomatic. Bone marrow examinations showed myeloid aplasia or maturation arrest in 5 patients and myeloid hyperplasia in 1. Neutropenia resolved within 30 days of drug withdrawal, and all patients survived. A case-control study showed a significant association between sustained-release procainamide therapy and severe neutropenia in 5 of 114 patients (4.4%) recovering from open-heart surgery (Mantel-Haenszel chi square = 13.84; p less than 0.001). Thus, life-threatening neutropenia may be common with sustained-release procainamide preparations.

Early Step-Down Transfer of Low-Risk Patients with Chest Pain: A Controlled Interventional Trial

OBJECTIVE To determine whether providing private practitioners with triage criteria for their low-risk chest pain patients would safely enhance bed utilization efficiency in coronary and intermediate care units. DESIGN Prospective, controlled, interventional trial using an alternate month study design. SETTING A large teaching community hospital. PATIENTS Cohort of 404 low-risk patients with chest pain for whom a diagnosis of myocardial infarction has been excluded and who have not sustained complications, required interventions, or developed unstable comorbidity. INTERVENTIONS During intervention months, private practitioners caring for low-risk patients in the coronary and intermediate care units were contacted 24 hours after admission. Physicians were informed that the transfer of low-risk patients to nonmonitored beds could probably be done safely, based on the results of a pilot study. The practitioner had the option of agreeing to or deferring patient transfer. During control months, physicians were not contacted in this way. MEASUREMENTS AND MAIN RESULTS Use of the triage criteria by private practitioners reduced lengths of stay in the intermediate and coronary care units by 36% and 53%, respectively. Bed availability increased by 744 intermediate and 372 coronary care unit bed-days per year. Charges decreased by

Hypothermia and sepsis.

2.6 million per year and profits improved by

Peripherally Inserted Central Catheters in General Medicine

390,000 per year. There were not significant differences in complications between control and intervention patients and in no case (95% CI, 0% to 1.6%) did the triage criteria adversely affect quality of care. CONCLUSIONS The early transfer triage criteria may be a safe and efficacious decision aid for improving bed utilization in intermediate and coronary care units. In addition, this study shows the feasibility of and potential benefits from applying practice guidelines at a community hospital.

Prospective Evaluation of a Clinical Guideline Recommending Hospital Length of Stay in Upper Gastrointestinal Tract Hemorrhage

Excerpt To the editor: TheAnnalshas shown continued interest in hypothermia (1-3). Most recently, Morris and colleagues (3) have reported that hypothermia does not alter the hemodynamic characteris...