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Performance of the Pulmonary Embolism Rule-out Criteria (the PERC rule) combined with low clinical probability in high prevalence population.

PERC rule was created to rule out pulmonary embolism (PE) without further exams, with residual PE risk<2%. Its safety is currently not confirmed in high PE prevalence populations even when combined with low clinical probability assessed by revised Geneva score (RGS). As PERC rule and RGS are 2 similar explicit rules with many redundant criteria, we hypothesized that the combination of PERC rule with gestalt clinical probability could resolve this limitation.

METHODS: We collected prospectively documented clinical gestalt assessments and retrospectively calculated PERC rules and RGS from a prospective study of PE suspected patients. We analyzed performance of combinations of negative PERC with low clinical probability assessed by both methods in high overall PE prevalence population.

RESULTS: Among the final study population (n=959), the overall PE prevalence was 29.8%. Seventy-four patients (7.7%) were classified as PERC negative and among them, 4 patients (5.4%) had final diagnosis of PE. When negative PERC was combined with low pretest probability assessed by RGS or gestalt assessment, PE prevalence was respectively 6.2% and 0%. This last combination reaches threshold target of 2% and unnecessary exams could easily have been avoided in this subgroup (6%). However, it confidence interval was still wide (0%; CI 0-5).

CONCLUSIONS: PERC rule combined with low gestalt probability seems to identify a group of patients for whom PE could easily be ruled out without additional test. A larger study is needed to confirm this result and to ensure safety.

Superficial vein thrombosis and recurrent venous thromboembolism: a pooled analysis of two observational studies.

The management strategies of symptomatic isolated superficial-vein thrombosis (SVT) (without concomitant deep-vein thrombosis [DVT] or pulmonary embolism [PE]) have yet to achieve widespread consensus. Concerns have been raised regarding the usefulness of prescribing anticoagulant treatments to all patients with isolated SVT. Determining the isolated SVT sub-groups who have the highest risks of venous thromboembolic (VTE) recurrence (composite of DVT, PE and new SVT) may facilitate identifying patients likely to benefit from anticoagulant treatment.

Design and methods:  We performed a pooled-analysis on individual data from two observational, multicenter, prospective studies, to determine predictors for VTE recurrence and their impact in an unselected population of symptomatic isolated SVT patients.

Results:  1,074 cases of symptomatic isolated SVT were followed-up at three months. VTE recurrence was observed in 3.9% of the patients. 16.2% of the patients did not receive anticoagulants; 0.6% experienced a VTE recurrence. Cancer, personal history of VTE and a sapheno-femoral/popliteal involvement significantly increased the risk of subsequent VTE or DVT/PE in univariate analyses. Only male sex significantly increased the risk of VTE or DVT/PE recurrence in multivariate analyses. 12% of the patients had cancer or a sapheno-femoral junction involvement and were at higher risk of DVT/PE recurrence than patients without those characteristics (4.7% vs. 1.9%, p=0.06).

Conclusion:  In patients with symptomatic SVT, only male sex significantly and independently increased the risk of VTE recurrence. Patients with cancer or a sapheno-femoral junction involvement defined a population at high risk for deep VTE recurrence. Some SVT might be safely managed without anticoagulants. © 2012 International Society on Thrombosis and Haemostasis.

Prognostic significance of multidetector computed tomography in normotensive patients with pulmonary embolism: rationale, methodology and reproducibility for the PROTECT study.

The PROTECT study is designed to assess the prognostic significance of multidetector computed tomography (MDCT) findings in normotensive outpatients with pulmonary embolism (PE). MDCT assesses right ventricular dysfunction (RVD) by measuring the ratio of the right-to-left ventricular short axis diameters.

The study uses 30-day all-cause mortality as the primary outcome. The study determined inter- and intraobserver reproducibility of CT findings of RVD. According to the local radiologists' measurements, 44 % of patients (42/96) showed RVD (defined as a ratio of the RV to the LV short axis greater than 0.9). The intraclass correlation was good (0.773, CI 95 %, 0.678-0.842). For interobserver reproducibility, the weighted kappa measurement was 0.730. Intraobserver reproducibility was very good (0.932, 95 % CI, 0.880-0.962).

The PROTECT study is designed to show the prognostic significance of MDCT for PE. Inter- and intraobserver agreement of interpretation of RVD were good.

Treatment of acute iliofemoral deep vein thrombosis.

OBJECTIVE: The objective of this systematic review and meta-analysis was to compare the efficacy of three available treatments for acute iliofemoral deep vein thrombosis (DVT): systemic anticoagulation, surgical thrombectomy, and catheter-directed thrombolysis.

METHODS: We searched electronic databases (MEDLINE, EMBASE, Cochrane CENTRAL, Web of Science, and Scopus) and sought additional references from experts. Eligible studies enrolled participants with acute iliofemoral DVT and measured the outcomes of interest. Reviewers working independently in duplicate extracted study characteristics, quality, and outcome data (death, pulmonary embolism, local complications, hemorrhagic complications, postthrombotic syndrome, pain, quality of life, and surrogate markers of venous function such as valve competence and patency). We pooled relative risks (RRs) from each study using the random effects model and estimated the 95% confidence intervals (CIs). Bayesian indirect comparison techniques were used to compare thrombectomy to catheter-directed thrombolysis.

RESULTS: We found 15 unique studies that fulfilled eligibility criteria. When compared to systemic anticoagulation, thrombectomy was associated with a statistically significant reduction in the risk of developing postthrombotic syndrome (RR, 0.67; 95% CI, 0.52-0.87), venous reflux (RR, 0.68; 95% CI, 0.46-0.99), and a trend for reduction in the risk of venous obstruction (RR, 0.84; 95% CI, 0.60-1.19). When compared to systemic anticoagulation, pharmacologic catheter-directed thrombolysis was associated with statistically significant reduction in the risk of postthrombotic syndrome (RR, 0.19; 95% CI, 0.07-0.48), venous obstruction (RR, 0.38; 95% CI, 0.18-0.37), and a trend for reduction in the risk of venous reflux (RR, 0.39; 95% CI, 0.16-1.00). Overall, the quality of evidence was low; downgraded due to the observational nature of the majority of studies, lack of comparability of study cohorts at baseline, loss to follow-up, imprecision, and indirectness of outcomes (surrogacy). There were insufficient data to compare the outcomes of thrombectomy to catheter-directed thrombolysis.

CONCLUSIONS: Low-quality evidence suggests that surgical thrombectomy decreases the incidence of postthrombotic syndrome and venous reflux. Catheter-directed pharmacologic thrombolysis decreases the incidence of postthrombotic syndrome and venous obstruction.

Challenges with current inhaled treatments for chronic Pseudomonas aeruginosa infection in patients with cystic fibrosis.

Pseudomonas aeruginosa (Pa) is the predominant pathogen infecting the airways of patients with cystic fibrosis (CF). Initial colonization is usually transient and associated with non-mucoid strains, which can be eradicated if identified early. This strategy can prevent, or at least delay, chronic Pa infection, which eventually develops in the majority of patients by their late teens or early adulthood.

This article discusses the management and latest treatment developments of Pa lung infection in patients with CF, with a focus on nebulized antibiotic therapy.

Methods: PubMed was searched to identify English language articles published up until August 2011 using combinations of the following key words: 'antibiotics', 'chronic', 'cystic fibrosis', 'eradication', 'exacerbations', 'guidelines', 'inhaled', 'intravenous', 'lung infection', 'burden', 'adherence', 'patient segregation', 'pseudomonas aeruginosa' and 'resistance'.

Findings: Antibiotics form a central part of the treatment regimens for chronic Pa lung infection. Current treatment guidelines recommend that patients with chronic pulmonary infection with Pa should receive long-term inhaled anti-pseudomonal therapy to preserve lung function, and to reduce the frequency of pulmonary exacerbations and hospital admissions. While antibiotic resistance seems to increase with frequent antibiotic use, this does not appear to impact on clinical outcome. Negative aspects of therapy include the time needed for drug administration and subsequent cleaning of the equipment. These factors cause a significant treatment burden and impact on adherence. The availability of more convenient formulations and delivery vehicles for anti-pseudomonal antibiotics may help overcome some of these challenges.

Conclusions: Current challenges in the management of CF patients with chronic Pa lung infection are numerous. The availability of novel anti-pseudomonal antibiotic formulations/devices is anticipated to improve treatment adherence in patients with CF, and could improve clinical outcomes. Thus, there is hope for improved survival in individuals with CF suffering from chronic pulmonary infection with Pa.

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