Lisa K. Moores

Simplification of the pulmonary embolism severity index for prognostication in patients with acute symptomatic pulmonary embolism.

BACKGROUND The Pulmonary Embolism Severity Index (PESI) estimates the risk of 30-day mortality in patients with acute pulmonary embolism (PE). We constructed a simplified version of the PESI. METHODS The study retrospectively developed a simplified PESI clinical prediction rule for estimating the risk of 30-day mortality in a derivation cohort of Spanish outpatients. Simplified and original PESI performances were compared in the derivation cohort. The simplified PESI underwent retrospective external validation in an independent multinational cohort (Registro Informatizado de la Enfermedad Tromboembólica [RIETE] cohort) of outpatients. RESULTS In the derivation data set, univariate logistic regression of the original 11 PESI variables led to the removal of variables that did not reach statistical significance and subsequently produced the simplified PESI that contained the variables of age, cancer, chronic cardiopulmonary disease, heart rate, systolic blood pressure, and oxyhemoglobin saturation levels. The prognostic accuracy of the original and simplified PESI scores did not differ (area under the curve, 0.75 [95% confidence interval (CI), 0.69-0.80]). The 305 of 995 patients (30.7%) who were classified as low risk by the simplified PESI had a 30-day mortality of 1.0% (95% CI, 0.0%-2.1%) compared with 10.9% (8.5%-13.2%) in the high-risk group. In the RIETE validation cohort, 2569 of 7106 patients (36.2%) who were classified as low risk by the simplified PESI had a 30-day mortality of 1.1% (95% CI, 0.7%-1.5%) compared with 8.9% (8.1%-9.8%) in the high-risk group. CONCLUSION The simplified PESI has similar prognostic accuracy and clinical utility and greater ease of use compared with the original PESI.

Treatment and prevention of heparin-induced thrombocytopenia: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines.

BACKGROUND Heparin-induced thrombocytopenia (HIT) is an antibody-mediated adverse drug reaction that can lead to devastating thromboembolic complications, including pulmonary embolism, ischemic limb necrosis necessitating limb amputation, acute myocardial infarction, and stroke. METHODS The methods of this guideline follow the Methodology for the Development of Antithrombotic Therapy and Prevention of Thrombosis Guidelines: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines in this supplement. RESULTS Among the key recommendations for this article are the following: For patients receiving heparin in whom clinicians consider the risk of HIT to be > 1%, we suggest that platelet count monitoring be performed every 2 or 3 days from day 4 to day 14 (or until heparin is stopped, whichever occurs first) (Grade 2C). For patients receiving heparin in whom clinicians consider the risk of HIT to be < 1%, we suggest that platelet counts not be monitored (Grade 2C). In patients with HIT with thrombosis (HITT) or isolated HIT who have normal renal function, we suggest the use of argatroban or lepirudin or danaparoid over other nonheparin anticoagulants (Grade 2C). In patients with HITT and renal insufficiency, we suggest the use of argatroban over other nonheparin anticoagulants (Grade 2C). In patients with acute HIT or subacute HIT who require urgent cardiac surgery, we suggest the use of bivalirudin over other nonheparin anticoagulants or heparin plus antiplatelet agents (Grade 2C). CONCLUSIONS Further studies evaluating the role of fondaparinux and the new oral anticoagulants in the treatment of HIT are needed.

Meta-analysis: outcomes in patients with suspected pulmonary embolism managed with computed tomographic pulmonary angiography.

Context Is it safe to withhold anticoagulation in adults with suspected pulmonary embolism (PE) and negative results on spiral computed tomographic pulmonary angiography (CTPA)? Contribution This meta-analysis summarized data from 23 studies that reported rates of thromboembolism among patients with suspected PE who did not receive anticoagulation after negative results on CTPA. Among 4657 patients, the 3-month risks for a thromboembolic event and fatal PE were 1.4% and 0.51%, respectively. Cautions Studies used early-generation CT technology and different diagnostic algorithms for thromboembolism. Implications Withholding anticoagulation from patients with low to moderate probability of PE and negative results on CTPA appears reasonable. The Editors Pulmonary embolism (PE) remains a major cause of morbidity and mortality (1). The limitations of clinical examination in establishing a diagnosis of PE, as well as the perils of unnecessary anticoagulation and untreated clots, mandate use of judicious objective diagnostic testing in the evaluation of this disorder. Spiral computed tomographic pulmonary angiography (CTPA) has become an integral part of the diagnostic evaluation for suspected PE, given its widespread availability, ease of acquisition, favorable performance characteristics (2), and utility in revealing alternative diagnoses (3, 4). Researchers have been cautiously optimistic that CTPA may be useful as a definitive study to exclude PE (5). However, CTPA is often applied as part of an algorithmic screening approach that includes other diagnostic tests, including pretest prediction models, d-dimer testing, lower-extremity compression ultrasonography, and lung scintigraphy (3, 6-13). Many of these algorithms recommend conventional pulmonary angiography (CPA) as the gold standard (14). Although screening algorithms are reported to have good efficacy, they remain cumbersome to apply (15) and may be considerably underused in clinical practice (16). Some recent investigations suggest that CTPA merits consideration as a definitive diagnostic study (17-19). However, many authors remain unconvinced that negative CTPA results alone can reliably exclude clinically significant pulmonary emboli (20, 21). Bates and Ginsberg (20) have proposed that acceptance of CTPA as a definitive study would require establishment of its interobserver and intraobserver variability and study characteristics, determination of its accuracy, and an assessment of outcomes after anticoagulation is withheld because of a negative test result. The first 2 criteria have been evaluated (21, 22). In the current study, we performed a systematic review of the literature and conducted a meta-analysis of eligible studies to determine the safety and efficacy of withholding systemic anticoagulation after negative results on CTPA for PE. Methods We searched MEDLINE (1966 to March 2004) and EMBASE (1974 to 2004) using the terms pulmonary embolism, computed x-ray tomography, CTPA, angiography, sensitivity and specificity, prognosis, and recurrence. We augmented our search by reviewing the reference lists of retrieved articles and review articles, our personal files, and reference lists of related articles in our files. Our medical librarian performed an independent search to ensure completeness. The search was not limited to the English language, but only published reports were included (Figure 1). Figure 1. Flow diagram of study selection. Study Identification and Eligibility We attempted to identify all published studies that examined the rate of subsequent symptomatic venous thromboembolism (VTE) in patients who did not receive anticoagulation after negative or indeterminate CTPA results. To be included in the analysis, studies had to 1) have a consecutive sample or a well-defined reason for a selected sample (for example, inclusion of only patients with underlying cardiopulmonary disease or those referred to specialty centers); 2) define the diagnostic strategy used to confirm or exclude VTE; 3) withhold anticoagulation or clearly state the reason for administering anticoagulation when VTE was excluded (patients who received anticoagulation were excluded from the final analysis); 4) have a minimum of 3 months of follow-up; and 5) report subsequent symptomatic VTE events and the means of confirmation. Study Quality Two reviewers independently rated each studys quality. Because there are no validated tools for quality assessment of outcome studies, we adapted the McMaster criteria for evaluating the validity of studies about prognosis (23). Studies were assessed for presence of 9 features: description of patient sample characteristics, description of inclusion and exclusion criteria, potential selection bias, length of follow-up, completeness of follow-up, description of patients lost to follow-up, description of reasons for incomplete follow-up, definition of outcomes at the start of the study, and objectivity of outcomes. The intraclass correlation coefficient for agreement between the 2 raters on overall quality rating for all included studies was 0.85 (P< 0.001). Disagreements were resolved by consensus. In addition to abstracted data on patients, CTPA performance, and outcomes, we recorded the number of patients who had initial nondiagnostic CTPA results and follow-up of these patients if reported. Patients who received anticoagulation despite initial negative results on CTPA were excluded from the final analysis. Although some studies included a longer follow-up period, we limited our analysis to the first 3 months after negative results on CTPA because events after 3 months are likely to be new rather than recurrences. Statistical Analysis The rates of subsequent VTE events and fatal PE were calculated from the abstracted numbers for each study. Extracted outcomes were the proportion of individuals with negative results on CTPA who subsequently experienced pulmonary emboli, fatal or otherwise. These data were combined by using an approximation to the inverse variance approach, effectively weighting each study according to its sample size (24). The 95% CI for each study and for the overall effect was calculated by using exact binomial methods. Heterogeneity was assessed visually with Galbraith plots (25). Publication bias was assessed visually by using funnel plots and by statistically using the method of Egger and colleagues (26). The sensitivity of our results to potential publication bias was assessed by using the methods of Duval and Tweedie (27). We performed sensitivity analyses, assessing the effects of type of study (prospective vs. retrospective), year of study, whether patients were consecutive or selected, generation of computed tomography (CT) scanner, the thickness of CT cuts, caudocranial image acquisition, view box interpretation, and the prevalence of PE. Role of the Funding Source No funding was received in support of this review. Results We identified 640 abstracts in our search. Most were excluded because they did not include outcome data on patients not treated with anticoagulants (Figure 1). Among the 27 remaining articles, 4 were excluded: 3 had insufficient follow-up data (4, 28, 29) and 1 reported duplicate data (30) that were presented as part of the final report of a prospective study (31). Therefore, 23 articles were included in our analysis (3, 6, 11-13, 15, 17-19, 31-44). One of these (33) included 35 patients from another study (32). Qualitative Review The 23 studies included 15 prospective and 8 retrospective trials (Table). Study samples ranged from 54 to 1512, averaging 403 patients. Seventeen of the included studies examined consecutive patients, and 6 included selected patient samples. Overall, the mean prevalence of PE was 19.8% (range, 13% to 42%). Three studies (34, 37, 38) enrolled only patients in whom PE had been excluded and therefore did not report on prevalence in the sample. Nine of the studies included images obtained in the caudocranial direction, and 15 interpreted images on view box stations. The average CT scanner thickness was 2.1 mm (range, 2 to 5 mm). Ten prospective studies used CTPA with other diagnostic methods as part of a predetermined algorithm (3, 6, 11-13, 31-33, 35, 40). Pretest probability was used in 6 studies (6, 12, 13, 31, 32, 35), lung scintigraphy in 5 (11, 12, 31, 32, 35), lower-extremity compression ultrasonography in 6 (3, 13, 31-33, 40), and d-dimer testing in 4 (6, 11, 33, 40). Fourteen studies (3, 12, 13, 15, 17-19, 31, 33, 36, 37, 39, 41, 43) used objective imaging to confirm subsequent VTE events, while only 6 (3, 13, 15, 18, 34, 39) used autopsy confirmation or central adjudication to confirm fatal events. Table. Data Extracted from Individual Studies Twenty-one of the studies included a small proportion of patients (n= 492) who received anticoagulation despite negative results on CTPA. The reasons for anticoagulation included presence of deep venous thrombosis on concomitant ultrasonography (n= 70), chronic VTE (n= 68), and cardiac arrhythmias or other cardiac abnormalities (n= 204). Four patients had positive results on another test (ventilationperfusion scanning or CPA) that suggested PE, while 65 patients (13%) were listed as having nonthromboembolic disorders. The reason for anticoagulation was not stated in 63 patients. Only 18 patients received anticoagulation because of persistent high clinical suspicion of PE despite negative results on CTPA. These patients were not included in our analysis of outcomes. Overall quality ratings ranged from 3 to 9 (Appendix Table). Common quality problems included inadequately clear inclusion and exclusion criteria in 6 studies, potential selection bias in 16 studies, incomplete follow-up in 13 studies, inadequate description of the patients lost to follow-up in 14 studies, inadequate description of the reason for incomplete follow-up in 7 studies, and problems with the objectivity of outcome assessment in 9 studies. Appendix

Combinations of prognostic tools for identification of high-risk normotensive patients with acute symptomatic pulmonary embolism

Background In haemodynamically stable patients with acute symptomatic pulmonary embolism (PE), studies have not evaluated the usefulness of combining the measurement of cardiac troponin, transthoracic echocardiogram (TTE), and lower extremity complete compression ultrasound (CCUS) testing for predicting the risk of PE-related death. Methods The study assessed the ability of three diagnostic tests (cardiac troponin I (cTnI), echocardiogram, and CCUS) to prognosticate the primary outcome of PE-related mortality during 30 days of follow-up after a diagnosis of PE by objective testing. Results Of 591 normotensive patients diagnosed with PE, the primary outcome occurred in 37 patients (6.3%; 95% CI 4.3% to 8.2%). Patients with right ventricular dysfunction (RVD) by TTE and concomitant deep vein thrombosis (DVT) by CCUS had a PE-related mortality of 19.6%, compared with 17.1% of patients with elevated cTnI and concomitant DVT and 15.2% of patients with elevated cTnI and RVD. The use of any two-test strategy had a higher specificity and positive predictive value compared with the use of any test by itself. A combined three-test strategy did not further improve prognostication. For a subgroup analysis of high-risk patients, according to the pulmonary embolism severity index (classes IV and V), positive predictive values of the two-test strategies for PE-related mortality were 25.0%, 24.4% and 20.7%, respectively. Conclusions In haemodynamically stable patients with acute symptomatic PE, a combination of echocardiography (or troponin testing) and CCUS improved prognostication compared with the use of any test by itself for the identification of those at high risk of PE-related death.

Faculty Development Seminars Based on the One‐Minute Preceptor Improve Feedback in the Ambulatory Setting

OBJECTIVE: While several models of medical student instruction in the ambulatory setting exist, few have been formally studied. We wished to assess the impact of a faculty development workshop based on the One-Minute Preceptor model on the amount and quality of feedback in the outpatient setting.DESIGN: Ambulatory teaching behaviors were studied during consecutive outpatient precepting sessions before and after 3 faculty development workshops. Student-teacher interactions were assessed using audiotapes of teaching encounters coded through qualitative techniques, and surveys of teacher, learner, and patient satisfaction.SETTING: Ambulatory internal medicine clinic in a tertiary care medical center.PATIENTS/PARTICIPANTS: Nine board-certified internist faculty preceptors and 44 third-year medical students.INTERVENTIONS: Three 90-minute faculty development seminars based on the One-Minute Preceptor teaching model.MEASUREMENTS AND MAIN RESULTS: Ninety-four encounters with 18,577 utterances were recorded, half before and half after the seminars. After the workshops, the proportion of utterances that contained feedback increased from 17% to 22% (P=.09) and was more likely to be specific (9% vs 15%; P=.02). After the workshops, teachers reported that the learning encounters were more successful (P=.03) and that they were better at letting the students reach their own conclusions (P=.001), at evaluating the learners (P=.03), and at creating plans for post-encounter learning (P=.02). The workshops had no effect on the duration of the student-teacher encounter or on student or patient satisfaction with the encounters.CONCLUSIONS: Brief, interactive, faculty development workshops based on the One-Minute Preceptor model of clinical teaching resulted in modest improvements in the quality of feedback delivered in the ambulatory setting.

Pulmonary Embolism Severity Index and troponin testing for the selection of low‐risk patients with acute symptomatic pulmonary embolism

Summary.  Background: The combination of the Pulmonary Embolism Severity Index (PESI) and troponin testing could help physicians identify appropriate patients with acute pulmonary embolism (PE) for early hospital discharge. Methods: This prospective cohort study included a total of 567 patients from a single center registry with objectively confirmed acute symptomatic PE. On the basis of the PESI, each patient was classified into one of five classes (I–V). At the time of hospital admission, patients had troponin I (cTnI) levels measured. The endpoint of the study was all‐cause mortality within 30 days after diagnosis. We calculated the mortality rates in four patient groups: group 1, PESI class I–II plus cTnI < 0.1 ng mL−1; group 2, PESI classes III–V plus cTnI < 0.1 ng mL−1; group 3, PESI classes I–II plus cTnI ≥ 0.1 ng mL−1; and group 4, PESI classes III–V plus cTnI ≥ 0.1 ng mL−1. Results: The study cohort had a 30‐day mortality of 10% [95% confidence interval (CI), 7.6–12.5%]. Mortality rates in the four groups were 1.3%, 14.2%, 0% and 15.4%, respectively. Compared with non‐elevated cTnl, the low‐risk PESI had a higher negative predictive value (NPV) (98.9% vs. 90.8%) and negative likelihood ratio (NLR) (0.1 vs. 0.9) for predicting mortality. The addition of non‐elevated cTnI to low‐risk PESI did not improve the NPV or the NLR compared with either test alone. Conclusions: Compared with cTnl testing, PESI classification more accurately identified patients with PE who are at low risk of all‐cause death within 30 days of presentation.

Prognostic significance of multidetector CT in normotensive patients with pulmonary embolism: results of the protect study

Background In patients with acute pulmonary embolism (PE), rapid and accurate risk assessment is paramount in selecting the appropriate treatment strategy. The prognostic value of right ventricular dysfunction (RVD) assessed by multidetector CT (MDCT) in normotensive patients with PE has lacked adequate validation. Methods The study defined MDCT-assessed RVD as a ratio of the RV to the left ventricle short axis diameter greater than 0.9. Outcomes assessed through 30 days after the diagnosis of PE included all-cause mortality and ‘complicated course’, which consisted of death from any cause, haemodynamic collapse or recurrent PE. Results MDCT detected RVD in 533 (63%) of the 848 enrolled patients. Those with RVD on MDCT more frequently had echocardiographic RVD (31%) than those without RVD on MDCT (9.2%) (p<0.001). Patients with RVD on MDCT had significantly higher brain natriuretic peptide (269±447 vs 180±457 pg/ml, p<0.001) and troponin (0.10±0.43 vs 0.03±0.24 ng/ml, p=0.001) levels in comparison with those without RVD on MDCT. During follow-up, death occurred in 25 patients with and in 13 patients without RVD on MDCT (4.7% vs 4.3%; p=0.93). Those with and those without RVD on MDCT had a similar frequency of complicated course (3.9% vs 2.3%; p=0.30). Conclusions The PROgnosTic valuE of CT study showed a relationship between RVD assessed by MDCT and other markers of cardiac dysfunction around the time of PE diagnosis, but did not demonstrate an association between MDCT–RVD and prognosis.

The shock index and the simplified PESI for identification of low-risk patients with acute pulmonary embolism

We compared the test characteristics of the shock index (SI) and the simplified pulmonary embolism severity index (sPESI) for predicting 30-day outcomes in a cohort of 1,206 patients with objectively confirmed pulmonary embolism (PE). The primary outcome of the study was all-cause mortality. The secondary outcome was nonfatal symptomatic recurrent venous thromboembolism (VTE) or nonfatal major bleeding. Overall, 119 (9.9%) out of 1,206 patients died (95% CI 8.2–11.5%) during the first month of follow-up. The sPESI classified fewer patients as low-risk (369 (31%) out of 1,206 patients, 95% CI 28–33%) compared to the SI (1,024 (85%) out of 1,206 patients, 95% CI 83–87%) (p<0.001). Low-risk patients based on the sPESI had a lower 30-day mortality than those based on the SI (1.6% (95% CI 0.3–2.9%) versus 8.3% (95% CI 6.6–10.0%)), while the 30-day rate of nonfatal recurrent VTE or major bleeding was similar (2.2% (95%CI 0.7–3.6%) versus 3.3% (95%CI 2.2–4.4%)). The net reclassification improvement with the sPESI was 13.4% (p = 0.07). The integrated discrimination improvement was estimated as 1.8% (p<0.001). The sPESI quantified the prognosis of patients with PE better than the SI.

SMOKING AND POSTOPERATIVE PULMONARY COMPLICATIONS: An Evidence-Based Review of the Recent Literature

Postoperative pulmonary complications (PPC) lead to significant morbidity after both thoracic and non-thoracic surgical procedures. The role of smoking as an independent risk factor is controversial, though recent level III and IV studies suggest that it may indeed be significant. In addition, the role and timing of pre-operative smoking cessation is not clear. Although some studies suggest that abstinence too soon prior to operation may actually increase the risk of PPC, it still appears that aggressive counseling for smoking cessation prior to any elective procedure is the best overall course of action.

The Science of Continuing Medical Education: Terms, Tools, and Gaps: Effectiveness of Continuing Medical Education: American College of Chest Physicians Evidence-Based Educational Guidelines

BACKGROUND By its synthesis of a selected portion of the continuing medical education (CME) literature, the evidence-based practice center (EPC) review discovered several major issues in primary study design and in the systematic review process of CME studies. Through this process, the review speaks to the need for clarity in designing, reporting and synthesizing CME trials and provides an opportunity to advance the research agenda in this field. METHODS The evidence-based guideline (EBG) committee reviewed the methods section of the EPC report and these guidelines in detail, commenting on the search and review process and on the nature of the primary literature and the definitions used within it, comparing these to other published standardized measures. RESULTS Although the EBG committee noted much strength in the EPC review, limitations of the primary literature and the review methodology were identified and defined. These strengths and limitations hold implications for further research in this area. CONCLUSIONS Noting these limitations and in order to move the field forward, the EBG committee proposes a standard nomenclature of terms in common use in CME; a more rigorous process of searching, distilling, and synthesizing the primary literature in this area; and a common format on which to base the development and description of future trials of CME interventions.