Mathieu Nendaz

Clinical prediction rules for pulmonary embolism: a systematic review and meta-analysis.

Summary.  Background: Pretest probability assessment is necessary to identify patients in whom pulmonary embolism (PE) can be safely ruled out by a negative D‐dimer without further investigations. Objective: Review and compare the performance of available clinical prediction rules (CPRs) for PE probability assessment. Patients/methods: We identified studies that evaluated a CPR in patients with suspected PE from Embase, Medline and the Cochrane database. We determined the 95% confidence intervals (CIs) of prevalence of PE in the various clinical probability categories of each CPR. Statistical heterogeneity was tested. Results: We identified 9 CPR and included 29 studies representing 31215 patients. Pooled prevalence of PE for three‐level scores (low, intermediate or high clinical probability) was: low, 6% (95% CI, 4–8), intermediate, 23% (95% CI, 18–28) and high, 49% (95% CI, 43–56) for the Wells score; low, 13% (95% CI, 8–19), intermediate, 35% (95% CI, 31–38) and high, 71% (95% CI, 50–89) for the Geneva score; low, 9% (95% CI, 8–11), intermediate, 26% (95% CI, 24–28) and high, 76% (95% CI, 69–82) for the revised Geneva score. Pooled prevalence for two‐level scores (PE likely or PE unlikely) was 8% (95% CI,6–11) and 34% (95% CI,29–40) for the Wells score, and 6% (95% CI, 3–9) and 23% (95% CI, 11–36) for the Charlotte rule. Conclusion: Available CPR for assessing clinical probability of PE show similar accuracy. Existing scores are, however, not equivalent and the choice among various prediction rules and classification schemes (three‐ versus two‐level) must be guided by local prevalence of PE, type of patients considered (outpatients or inpatients) and type of D‐dimer assay applied.

β-Lactam Monotherapy vs β-Lactam-Macrolide Combination Treatment in Moderately Severe Community-Acquired Pneumonia A Randomized Noninferiority Trial

IMPORTANCE The clinical benefit of adding a macrolide to a β-lactam for empirical treatment of moderately severe community-acquired pneumonia remains controversial. OBJECTIVE To test noninferiority of a β-lactam alone compared with a β-lactam and macrolide combination in moderately severe community-acquired pneumonia. DESIGN, SETTING, AND PARTICIPANTS Open-label, multicenter, noninferiority, randomized trial conducted from January 13, 2009, through January 31, 2013, in 580 immunocompetent adult patients hospitalized in 6 acute care hospitals in Switzerland for moderately severe community-acquired pneumonia. Follow-up extended to 90 days. Outcome assessors were masked to treatment allocation. INTERVENTIONS Patients were treated with a β-lactam and a macrolide (combination arm) or with a β-lactam alone (monotherapy arm). Legionella pneumophila infection was systematically searched and treated by addition of a macrolide to the monotherapy arm. MAIN OUTCOMES AND MEASURES Proportion of patients not reaching clinical stability (heart rate <100/min, systolic blood pressure >90 mm Hg, temperature <38.0°C, respiratory rate <24/min, and oxygen saturation >90% on room air) at day 7. RESULTS After 7 days of treatment, 120 of 291 patients (41.2%) in the monotherapy arm vs 97 of 289 (33.6%) in the combination arm had not reached clinical stability (7.6% difference, P = .07). The upper limit of the 1-sided 90% CI was 13.0%, exceeding the predefined noninferiority boundary of 8%. Patients infected with atypical pathogens (hazard ratio [HR], 0.33; 95% CI, 0.13-0.85) or with Pneumonia Severity Index (PSI) category IV pneumonia (HR, 0.81; 95% CI, 0.59-1.10) were less likely to reach clinical stability with monotherapy, whereas patients not infected with atypical pathogens (HR, 0.99; 95% CI, 0.80-1.22) or with PSI category I to III pneumonia (HR, 1.06; 95% CI, 0.82-1.36) had equivalent outcomes in the 2 arms. There were more 30-day readmissions in the monotherapy arm (7.9% vs 3.1%, P = .01). Mortality, intensive care unit admission, complications, length of stay, and recurrence of pneumonia within 90 days did not differ between the 2 arms. CONCLUSIONS AND RELEVANCE We did not find noninferiority of β-lactam monotherapy in patients hospitalized for moderately severe community-acquired pneumonia. Patients infected with atypical pathogens or with PSI category IV pneumonia had delayed clinical stability with monotherapy. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00818610.

Influence of age on the cost-effectiveness of diagnostic strategies for suspected pulmonary embolism

Summary.  Background: Age has a marked effect on the diagnostic yield of D‐dimer measurement and lower limb compression ultrasonography (CUS) in patients with suspected pulmonary embolism (PE), suggesting that specific diagnostic strategies may be needed in elderly patients. Objective: To evaluate the cost‐effectiveness of including D‐dimer and CUS in the workup of PE, with particular attention to patient age. Subjects and methods: We analyzed data from two recent outcome studies that enrolled 1721 consecutive outpatients with suspected PE. Both studies used a sequential diagnostic strategy that included assessment of clinical probability, D‐dimer measurement, CUS, and helical computed tomography (hCT). A decision analysis model was created for analyzing cost‐effectiveness according to six classes of age. The main outcome measures were 3‐month quality‐adjusted expected survival and costs per patient managed. Results: All strategies were equally safe, with variations in the 3‐month survival never exceeding 0.5% as compared to the most effective strategy. D‐dimer measurement was highly cost‐saving under the age of 80 years. Above 80 years, the cost‐sparing effect of D‐dimer was diminished, but not completely abolished. Inclusion of CUS increased the costs of diagnostic strategies irrespective of age. Results were unchanged over a wide range of the variables of interest (costs, sensitivity, and specificity of the tests). Conclusions: Diagnostic strategies using D‐dimer are less expensive. The cost‐sparing effect of D‐dimer is reduced but not abolished above 80 years, suggesting that adapting specific diagnostic strategies in elderly outpatients is not mandatory. CUS is costly, and only marginally improves the safety of diagnostic strategies for PE.

Promoting diagnostic problem representation.

Purpose  Problem representation, as mediated by semantic qualifiers (SQs), has been associated with better diagnostic outcomes. The purpose of this study was to assess the effect of training medical students to use semantic abstractions as a means of building problem representations.

Preventing stroke recurrence in patients with patent foramen ovale: Antithrombotic therapy, foramen closure, or therapeutic abstention? A decision analytic perspective

Emphasis on the role of patent foramen ovale as a potential risk factor for ischemic paradoxical stroke has recently increased. Current therapeutic options for secondary stroke prevention include long-term antithrombotic therapies and invasive closure of the defect, but selective indications have not been evaluated. Therefore we developed a Markov-based decision analysis model for a hypothetical cohort of patients 55 years of age with presumed paradoxical embolism, measuring for each therapy the risks of stroke recurrence, treatment-related complications, and death after 5 years and the quality-adjusted life-years. Over a wide range of stroke risk recurrence (0.8% per year to 7% per year), the gain provided by closure of the defect exceeded the one obtained by other therapeutic options. When the risk exceeded 0.8% per year and 1.4% per year, respectively, this was also verified for anticoagulation and antiplatelet therapies compared with therapeutic abstention. Therapeutic abstention was the preferred strategy under 0.8% per year. Sensitivity analyses identified key parameters influencing the choice of therapy. These included estimates of stroke recurrence, bleeding rates, surgery-related case fatality rates, and age. Considering the risks of treatment and the devastating consequences of a recurrent stroke, our model suggests that if the estimated risk of paradoxical stroke recurrence is > 0.8% per year, therapeutic abstention becomes the worst option. Above this threshold secondary stroke prevention with anticoagulation therapy or surgical closure of the defect is the preferred strategy, and assessment of both the risk of stroke recurrence and the risk related to therapeutic options should guide individual therapeutic decision making.

Validation of a risk score identifying patients with acute pulmonary embolism, who are at low risk of clinical adverse outcome

A clinical predictive model that accurately identifies patients with pulmonary embolism who are at low risk of adverse medical outcomes may be useful for management decisions, such as outpatient treatment. We aimed to externally validate a previously derived prognostic score identifying emergency ward patients with acute pulmonary embolism at low risk of 3-month complications. One hundred and ninety-nine consecutive patients with proven pulmonary embolism were included from the emergency centres of three teaching and general hospitals. Adverse outcomes, such as death, major bleed, or recurrent venous thromboembolism, were recorded during a 3-month follow-up. We retrospectively computed the prognostic score for each patient and determined its predictive accuracy at different threshold values. The overall 3-month risk of adverse event after the diagnosis of pulmonary embolism was 9.5%. At a threshold of 2 points, eight patients with scores at or below the cut-off (5%; 95% CI 2.6-9.6) and 11 patients with scores above this cut-off (27.5%; 95% CI 16.1-42.8) presented a complication. The negative predictive value for an adverse out-come was 95.0% (95% CI 90.4-97.4). The receiver operating characteristic curve derived from the score distribution had an area of 0.77 (95% CI 0.65-0.89). This compared favourably with the characteristics of the derivation study. We conclude that the Geneva risk score has an acceptable predictive accuracy to identify patients with pulmonary embolism at low risk for 3-month adverse outcomes. Whether this score remains accurate and useful in clinical practice should be determined in a prospective multicentre validation study.

How to Prevent Stroke Recurrence in Patients with Patent Foramen ovale: Anticoagulants, Antiaggregants, Foramen Closure, or Nothing?

Several studies found a significant association between patent foramen ovale (PFO), interatrial septal aneurysm, and patients less than 60 years of age presenting with acute stroke and without any identified coexisting mechanism explaining the acute event. Paradoxical embolism from a venous source through a right-to-left shunt is usually incriminated, but the definite proof for paradoxical embolism is often lacking, with screening for deep-venous thrombosis leading to variable estimates. Despite these controversies, the-possibility of paradoxical embolism in patients with cryptogenic stroke and PFO is commonly retained as the cause of the neurological deficit. Moreover, there are now definite studies documenting that these patients are at risk of recurrence. The aim of the present paper is to review the literature on the risks of stroke recurrence in patients with atrial septal defects, and to weigh the risks and benefits of the different therapeutic options currently available to prevent stroke recurrence. These options include chronic oral anticoagulant or antiplatelet therapy, and more invasive procedures such as surgical closure or transcatheter closure of the defect. Finally, using the principles of decision analysis, the authors suggest tentative practical therapeutic recommendations that might be helpful to clinicians in daily practice.

Prevention of stroke recurrence with presumed paradoxical embolism

Abstract Paradoxical cerebral embolism (PCE) through a patent foramen ovale (PFO) should be considered as a cause of ischemic stroke, particularly in young patients without an altenative cause for stroke. PCE is even more important that it is potentially treatable. However, PCE remains often presumed because it rests upon the rarely demonstrated findings of a deep venous thrombosis and a thrombus lodged in the PFO. Recent studies have shown a rather low stroke recurrence rate in patients with PFO and stroke but suggest that some subgroups of patients with a higher stroke recurrence risk exist according clinical, echocardiographical and radiological characteristics. For these subgroups, it seems that a more invasive treatment should be required. There are four therapeutic options; antiaggregants, anticoagulation, transcatheter closure of PFO, and surgical closure of PFO. However, these treatments have yet to be evaluated in clinical trials.

Interprofessional Collaboration on an Internal Medicine Ward: Role Perceptions and Expectations among Nurses and Residents

Background Effective interprofessional collaboration requires that team members share common perceptions and expectations of each others roles. Objective Describe and compare residents’ and nurses’ perceptions and expectations of their own and each other’s professional roles in the context of an Internal Medicine ward. Methods A convenience sample of 14 residents and 14 nurses volunteers from the General Internal Medicine Division at the University Hospitals of Geneva, Switzerland, were interviewed to explore their perceptions and expectations of residents’ and nurses’ professional roles, for their own and the other profession. Interviews were analysed using thematic content analysis. The same respondents also filled a questionnaire asking their own intended actions and the expected actions from the other professional in response to 11 clinical scenarios. Results Three main themes emerged from the interviews: patient management, clinical reasoning and decision-making processes, and roles in the team. Nurses and residents shared general perceptions about patient management. However, there was a lack of shared perceptions and expectations regarding nurses’ autonomy in patient management, nurses’ participation in the decision-making process, professional interdependence, and residents’ implication in teamwork. Results from the clinical scenarios showed that nurses’ intended actions differed from residents’ expectations mainly regarding autonomy in patient management. Correlation between residents’ expectations and nurses’ intended actions was 0.56 (p = 0.08), while correlation between nurses’ expectations and residents’ intended actions was 0.80 (p<0.001). Conclusions There are discordant perceptions and unmet expectations among nurses and residents about each other’s roles, including several aspects related to the decision-making process. Interprofessional education should foster a shared vision of each other’s roles and clarify the boundaries of autonomy of each profession.

Diagnostic errors and flaws in clinical reasoning: mechanisms and prevention in practice

Diagnostic errors account for more than 8% of adverse events in medicine and up to 30% of malpractice claims. Mechanisms of errors may be related to the working environment but cognitive issues are involved in about 75% of the cases, either alone or in association with system failures. The majority of cognitive errors are not related to knowledge deficiency but to flaws in data collection, data integration, and data verification that may lead to premature diagnostic closure. This paper reviews some aspects of the literature on cognitive psychology that help us to understand reasoning processes and knowledge organisation and summarises biases related to clinical reasoning. It reviews the strategies described to prevent cognitive diagnostic errors. Many approaches propose awareness and reflective practice during daily activities, but the improvement of the quality of training at the pre-graduate, postgraduate and continuous levels, by using evidence-based education, should also be considered. Several conditions must be fulfilled to increase the understanding, the prevention, and the correction of diagnostic errors related to clinical reasoning: physicians must be willing to understand their own reasoning and decision processes; training efforts should be provided during the whole continuum of a clinicians career; and the involvement of medical schools, teaching hospitals, and medical societies in medical education research should be increased to improve evidence about error prevention.