Functional, neuroplastic and biomechanical changes induced by early Hand-Arm Bimanual Intensive Therapy Including Lower Extremities (e-HABIT-ILE) in pre-school children with unilateral cerebral palsy: study protocol of a randomized control trial.

BACKGROUND: Cerebral palsy (CP) causes motor, cognitive and sensory impairment at different extents. Many recent rehabilitation developments (therapies) have focused solely on the upper extremities (UE), although the lower extremities (LE) are commonly affected. Hand-arm Bimanual Intensive Therapy Including Lower Extremities (HABIT-ILE) applies the concepts of motor skill learning and intensive training to both the UE and LE. It involves constant stimulation of the UE and LE, for several hours each day over a 2-week period. The effects of HABIT-ILE have never been evaluated in a large sample of young children. Furthermore, understanding of functional, neuroplastic and biomechanical changes in infants with CP is lacking. The aim of this study is to carry out a multi-center randomized controlled trial (RCT) to evaluate the effects of HABIT-ILE in pre-school children with unilateral CP on functional, neuroplastic and biomechanical parameters. METHODS: This multi-center, 3-country study will include 50 pre-school children with CP aged 1-4 years. The RCT will compare the effect of 50 h (two weeks) of HABIT-ILE versus usual motor activity, including regular rehabilitation. HABIT-ILE will be delivered in a day-camp setting, with structured activities and functional tasks that will be continuously progressed in terms of difficulty. Assessments will be performed at 3 intervals: baseline (T0), two weeks later and 3 months later. Primary outcomes will be the Assisting Hand Assessment; secondary outcomes include the Melbourne Assessment-2, executive function assessments, questionnaires ACTIVLIM-CP, Pediatric Evaluation of Disability Inventory, Young Children's Participation and Environment Measure, Measure of the Process of Care, Canadian Occupational Performance Measure, as well as neuroimaging and kinematics measures. DISCUSSION: We expect that HABIT-ILE will induce functional, neuroplastic and biomechanical changes as a result of the intense, activity-based rehabilitation process and these changes will impact the whole developmental curve of each child, improving functional ability, activity and participation in the short-, mid- and long-term. Name of the registry: Changes Induced by Early HABIT-ILE in Pre-school Children With Uni- and Bilateral Cerebral Palsy (EarlyHABIT-ILE). TRIAL REGISTRATION: Trial registration number: NCT04020354-Registration date on the International Clinical Trials Registry Platform (ICTRP): November 20th, 2018; Registration date on NIH Clinical Trials Registry: July 16th, 2019.

Ohmic contact engineering in few-layer black phosphorus: approaching the quantum limit.

Achieving good quality Ohmic contacts to van der Waals materials is a challenge, since at the interface between metal and van der Waals material different conditions can occur, ranging from the presence of a large energy barrier between the two materials to the metallization of the layered material below the contacts. In black phosphorus (bP), a further challenge is its high reactivity to oxygen and moisture, since the presence of uncontrolled oxidation can substantially change the behavior of the contacts. Here we study three of the most commonly used metals as contacts to bP, chromium, titanium, and nickel, and investigate their influence on contact resistance against the variability between different flakes and different samples. We investigate the gate dependence of the current-voltage characteristics of field-effect transistors fabricated with these metals on bP, observing good linearity in the accumulation regime for all metals investigated. Using the transfer length method, from an analysis of ten devices, both at room temperature and at low temperature, Ni results to provide the lowest contact resistance to bP and minimum scattering between different devices. Moreover, we observe that our best devices approach the quantum limit for contact resistance both for Ni and for Ti contacts.

Oxybutynin as a treatment for generalized hyperhidrosis: a randomized, placebo-controlled trial.

BACKGROUND: Hyperhidrosis is a disorder that can impair quality of life. Localized treatments may be cumbersome and ineffective, and no systemic treatments have proven to be significantly beneficial. OBJECTIVES: To evaluate the effectiveness and tolerance of low-dose oxybutynin for hyperhidrosis. METHODS: We conducted a prospective, randomized, placebo-controlled trial. From June 2013 to January 2014, 62 patients with localized or generalized hyperhidrosis were enrolled. Oxybutynin was started at a dose of 2·5 mg per day and increased gradually to 7·5 mg per day. The primary outcome was defined as improvement of at least one point on the Hyperhidrosis Disease Severity Scale (HDSS). Dermatology Life Quality Index (DLQI) and tolerance were also reported. RESULTS: Most patients (83%) in our study had generalized hyperhidrosis. Oxybutynin was superior to placebo in improving the HDSS: 60% of patients treated with oxybutynin, compared with 27% of patients treated with placebo, improved at least one point on the HDSS (P = 0·009). The mean improvement in quality of life measured by DLQI was significantly better in the oxybutynin arm (6·9) than in the placebo arm (2·3). The most frequent side-effect was dry mouth, which was observed in 43% of the patients in the oxybutynin arm, compared with 11% in the placebo arm. CONCLUSIONS: Treatment with low-dose oxybutynin is effective in reducing symptoms of hyperhidrosis in generalized or localized forms. Side-effects were frequent but minor and mainly involved dry mouth.

Prothrombin G20210A mutation and lower extremity peripheral arterial disease: a systematic review and meta-analysis.

OBJECTIVE/BACKGROUND: Despite being an important risk factor for venous thromboembolism, the role of the prothrombin G20210A mutation in patients with arterial disease remains unclear. The aim of this review was to evaluate the association of prothrombin G20210A and lower extremity peripheral arterial disease (PAD). METHODS: This was a systematic review and meta-analysis of case-control studies. A systematic review of electronic databases, including MEDLINE and Embase, was conducted to assess the prevalence of prothrombin G20210A in patients with lower extremity PAD. The main outcome was the prevalence of prothrombin G20210A in patients with lower extremity PAD. The random effects model odds ratio (OR) was used as the primary outcome measure. RESULTS: The initial electronic search identified 168 relevant abstracts of which five studies evaluating 1,524 cases of PAD and 1,553 controls were included. Prothrombin G20210A was found in 70 of 1,524 patients with lower extremity PAD and 44 of 1,553 of the controls (random effects OR 1.68, 95% confidence interval [CI] 0.8-3.2). In those with critical limb ischemia (CLI), the prevalence of prothrombin G20210A was 23 of 302 compared with 31 of 1,253 of the controls (OR 3.2, 95% CI 1.6-6.1). CONCLUSION: Despite finding no significant association between lower extremity PAD and prothrombin G20210A, the meta-analysis suggests that the prevalence of prothrombin G20210A is significantly elevated in those with atherosclerotic occlusive disease of the lower extremities presenting with CLI. Well-designed prospective cohort studies evaluating the role of prothrombin G20210A as a predictor of disease progression or adverse vascular events are highly needed.

Thrombocytopenia with and without thrombosis following COVID-19 vaccination: long-term management.

Background: Since administration of COVID-19 vaccines, there has been growing evidence of thrombotic and thrombocytopenic events following vaccination. However, there remains limited data on long-term management of these adverse hematologic events. Key Clinical Question: We report on 9 patients presenting with thrombocytopenia following COVID-19 vaccination, with 4 subsequently diagnosed with vaccine-induced thrombocytopenia and thrombosis (VITT) and 5 with immune thrombocytopenia. Clinical Approach: A retrospective chart review was completed for adults >18 years of age presenting to a tertiary care center with new-onset thrombocytopenia occurring 4 to 42 days following COVID-19 vaccination. Presenting symptoms, laboratory investigations, and response to treatment are described. Conclusion: Two of 4 patients with VITT developed refractory thrombocytopenia successfully treated with intravenous immunoglobulin, corticosteroids, and plasma exchange therapy. Patients with VITT remained on anticoagulation for at least 9 months due to persistently positive diagnostic tests. Four of 5 patients with immune thrombocytopenia received intravenous immunoglobulin and corticosteroids with good recovery. Patients who received a subsequent COVID-19 mRNA vaccine had no adverse hematologic effects.

[Usefulness of preemptive anticoagulation in patients with suspected pulmonary embolism]. / Utilité d'une anticoagulation avant le diagnostic définitif d'embolie pulmonaire.

The usefulness of anticoagulation in patients with suspected non-massive pulmonary embolism (PE) is uncertain. We recently published a decision analysis model suggesting a benefit for preemptive anticoagulation in patients with an intermediate or high probability of PE, even with short diagnostic delays (0-3 h). In case of a low probability of PE, the decision to treat or not could partly rely on the expected diagnostic delay. Once the diagnosis is confirmed, achieving rapidly therapeutic anticoagulation levels decreases future thrombotic complications.

D-dimer testing: A narrative review.

D-dimer containing species are soluble fibrin degradation products derived from plasmin-mediated degradation of cross-linked fibrin, i.e., 'D-dimer'. D-dimer can hence be considered a biomarker of in vivo activation of both coagulation and fibrinolysis, the leading clinical application in daily practice of which is ruling out venous thromboembolism (VTE). D-dimer has been further evaluated for assessing the risk of VTE recurrence and helping define optimal duration of anticoagulation treatment in VTE, for diagnosing disseminated intravascular coagulation (DIC), and for screening those at enhanced risk of VTE. D-dimer assays should however be performed as intended by regulatory agencies, as their use outside these indications might make them a laboratory-developed test (LDT). This narrative review is aimed at: (1) reviewing the definition of D-dimer, (2) discussing preanalytical variables affecting D-dimer measurement, (3) reviewing and comparing the assays performance and some postanalytical variables (e.g., different units and age-adjusted cutoffs), and (4) discussing the interest of D-dimer measurement across different clinical settings, including pregnancy, cancer, and coronavirus disease 2019 (COVID-19).

Prognostic value of the Geneva prediction rule in patients in whom pulmonary embolism is ruled out.

OBJECTIVES: The prognosis of patients in whom pulmonary embolism (PE) is suspected but ruled out is poorly understood. We evaluated whether the initial assessment of clinical probability of PE could help to predict the prognosis for these patients. DESIGN: Retrospective analysis of data obtained during a prospective multicentre management study. SETTING: Six general and teaching hospitals in Belgium, France and Switzerland. SUBJECTS: In 1334 patients in whom PE was ruled out, 3-month mortality data were available (hospital readmission status was unknown for three patients) and clinical probability was evaluated with the revised Geneva score (RGS). MAIN OUTCOME MEASURES: Three-month mortality and readmission rates. RESULTS: Three-month mortality and readmissions rates were 3% and 19%, respectively and differed significantly depending on the RGS-determined PE probability group (P<0.001). When compared with patients presenting with a low probability, the risk of death after 3 months was higher in cases of intermediate or high RGS-based probability {odds ratio: 8.7 [95% confidence interval (CI): 2.7-28.5] and 22.6 (95%CI: 2.1-241.2), respectively}. The readmission risk increased with PE probability group (P<0.001). The main causes of death were cancer, respiratory failure and cardiovascular failure. In total, 86% of patients with low RGS-based probability were alive and had not been readmitted to hospital, whereas other patients had a twofold increased risk of death or readmission during the 3-month follow-up. The simplified Geneva score, calculated a posteriori, gave similar results. CONCLUSIONS: Initial assessment of clinical probability may help to stratify prognosis of patients in whom PE has been ruled out. Patients with a low probability of PE have a good prognosis. Whether patients with higher probability might benefit from more vigilant care should be evaluated.

A 4He vector zero-field optically pumped magnetometer operated in the Earth-field.

Low intrinsic noise, high bandwidth, and high accuracy vector magnetometers are key components for many ground or space geophysical applications. Here, we report the design and the test of a 4He vector optically pumped magnetometer specifically dedicated to these needs. It is based on a parametric resonance magnetometer architecture operated in the Earth magnetic field with closed-loop compensation of the three components of the magnetic field. It provides offset-free vector measurements in a ±70 µT range with a DC to 1 kHz bandwidth. We demonstrate a vector sensitivity up to 130 fT/√Hz, which is about ten times better than the best available fluxgate magnetometers currently available for the same targeted applications.

Diagnosis and management of congenital thrombophilia in the era of direct oral anticoagulants.

Direct oral anticoagulants (DOAC)s are often preferred to other anticoagulants as they are more practical and do not require routine laboratory monitoring. Less is known about their use in congenital thrombophilia. Efficacy of DOACs in congenital thrombophilia, effect of DOACs and other anticoagulants on diagnostic tests as well as efficacy and safety of anticoagulant use in this population is still a matter of debate. In this review we intended to analyze the potential pitfalls of testing for thrombophilia in patients using DOACs and vitamin K antagonists (VKA)s as well as to suggest strategies to improve diagnostic accuracy in this setting. We also reviewed the literature for evidence regarding the safety and efficacy of DOACs in patients with congenital thrombophilia. Some evidence was found supporting the use of DOACs in low risk thrombophilia, although evidence for their use in high risk thrombophilia is limited to small series and case reports. Our findings support the generation of better evidence to support DOAC use for congenital thrombophilia, especially in the high risk subgroups.

2008 SOR guidelines for the prevention and treatment of thrombosis associated with central venous catheters in patients with cancer: report from the working group.

BACKGROUND: In view of the lack of recommendations on central venous catheter (CVC)-associated thrombosis in cancer patients, we established guidelines according to the well-standardized Standards, Options and Recommendations methodology. MATERIAL AND METHODS: A literature review (1990-2007) on CVC-associated thrombosis was carried out. The guidelines were developed on the basis of the corresponding levels of evidence derived from analysis of the 36 of 175 publications selected. They were then peer reviewed by 65 independent experts. RESULTS: For the prevention of CVC-associated thrombosis, the distal tip of the CVC should be placed at the junction between the superior cava vein and right atrium; anticoagulants are not recommended. Treatment of CVC-associated thrombosis should be based on the prolonged use of low-molecular weight heparins. Maintenance of the catheter is justified if it is mandatory, functional, in the right position, and not infected, with a favorable clinical evolution under close monitoring; anticoagulant treatment should then be continued as long as the catheter is present. CONCLUSIONS: Several rigorous studies do not support the use of anticoagulants for the prevention of CVC-associated thrombosis. Treatment of CVC-associated thrombosis relies on the same principles as those applied in the treatment of established thrombosis in cancer patients.

[Diagnosis of pulmonary embolism]. / Diagnostic de l'embolie pulmonaire.

The diagnosis of pulmonary embolism (PE) is nowadays based on the sequential use of several diagnostic tests rather than on a single test. These diagnostic strategies are safe and have been prospectively validated. The first step after identifying patients with suspicion of PE is to establish the pre-test clinical probability. Several scores are available in order to make a standardised and reproducible assessment of the clinical probability, and therefore represent precious diagnostic tools. Indeed, clinical probability guides further investigations. Indeed, in patients with a low or an intermediate clinical probability or an "unlikely" probability, PE can be safely ruled out by negative D-dimers in approximately one third of outpatients without additional imaging. In case of positive D-dimers and a high clinical probability or a "likely" clinical probability, CT pulmonary angiography is now the recommended imaging technique. However, lower limb venous compression ultrasound and ventilation/perfusion scans remain useful in patients with contra-indications to CT, mainly those with renal insufficiency. Finally, some novel diagnostic tests seem promising. For example, V/Q SPECT has arisen as a highly accurate test and a potential alternative to CTPA. However, prospective management outcome studies are still lacking and are warranted before its implementation in routine clinical practice.

Venous thromboembolism risk stratification for patients with lower limb trauma and cast or brace immobilization.

BACKGROUND: Thromboprophylaxis for patients with non-surgical isolated lower-limb trauma requiring immobilization is a matter of debate. Our aim was to develop and validate a clinical risk- stratification model based on Trauma, Immobilization and Patients' characteristics (the TIP score). METHODS: The TIP score criteria and the cut-off were selected by a consensus of international experts (n = 27) using the Delphi method. Retrospective validation was performed in a population-based case-control study (MEGA study). The potential score's impact in anticoagulant treatment was assessed in a prospective single-center observational cohort study. FINDINGS: After four successive rounds, 30 items constituting the TIP score were selected: thirteen items for trauma, three for immobilization and 14 for patient characteristics were selected, each rated on a scale of 1 to 3. In the validation database, the TIP score had an AUC of 0·77 (95% CI 0.70 to 0.85). Using the cut-off proposed by the experts (≥5) and assuming a prevalence of 1·8%, the TIP scores had a sensitivity, specificity and negative predictive values of 89·9%, 30·7% and 99·4% respectively. In the prospective cohort, 84·2% (165/196) of all the patients concerned who presented at the emergency department had a low VTE risk not requiring thromboprophylaxis according to their TIP scores. The 3-month rate of symptomatic VTE was 1/196 [95% CI 0.1-2.8] this patient was in the sub-group TIP score ≥5. CONCLUSION: For patients with non-surgical lower-limb trauma and orthopedic immobilization, the TIP score allows an individual VTE risk-assessment and shows promising results in guiding thromboprophylaxis.

Relationship between type of unprovoked venous thromboembolism and cancer location: An individual patient data meta-analysis.

BACKGROUND: Unprovoked venous thromboembolism (VTE) may be the first manifestation of an underlying cancer. We aimed to assess the period prevalence of occult cancer detection stratified by VTE location (deep vein thrombosis [DVT], pulmonary embolism [PE] or both) and the anatomical relationship between occult cancer and VTE. METHODS: Post-hoc analysis of a systematic review and individual patient data meta-analysis of adults with unprovoked VTE with at least 12 months of follow-up. Cancer types were grouped according to thoracic, abdomino-pelvic, or other locations. RESULTS: A total of 2300 patients were eligible including 1218 with DVT only (53%), 719 with PE only (31%), and 363 with both PE and DVT (16%). The pooled 12-month period prevalence of cancer in DVT only, PE only, and DVT + PE was 5.6% (95% CI, 4.4 to 7.2), 4.3% (95% CI, 2.7 to 6.9), and 5.6% (95% CI, 1.7 to 15.5), respectively. Most occult cancers were located in the abdomen (68.4%). The proportion of patients with an abdomino-pelvic cancer was not different in patients with DVT + PE (81%; 95% CI, 54 to 96) than in those with DVT (68%; 95% CI, 57 to 78) or PE alone (65%; 95% CI, 48 to 79). CONCLUSION: The 12-month prevalence of occult cancer was similar in patients with DVT only, PE only, or both. Most cancers were located in the abdomen, and there was no relationship between VTE type and cancer location.

Comparison of the revised Geneva score with the Wells rule for assessing clinical probability of pulmonary embolism.

BACKGROUND: The revised Geneva score, a standardized clinical decision rule in the diagnosis of pulmonary embolism (PE), was recently developed. The Wells clinical decision is widely used but lacks full standardization, as it includes subjective clinician's judgement. We have compared the performance of the revised Geneva score with the Wells rule, and their usefulness for ruling out PE in combination with D-dimer measurement. METHODS: In 300 consecutive patients, the clinical probability of PE was assessed prospectively by the Wells rule and retrospectively using the revised Geneva score. Patients comprised a random sample from a single center, participating in a large prospective multicenter diagnostic study. The predictive accuracy of both scores was compared by area under the curve (AUC) of receiver operating characteristic (ROC) curves. RESULTS: The overall prevalence of PE was 16%. The prevalence of PE in the low-probability, intermediate-probability and high-probability categories as classified by the revised Geneva score was similar to that of the original derivation set. The performance of the revised Geneva score as measured by the AUC in a ROC analysis did not differ statistically from the Wells rule. After 3 months of follow-up, no patient classified into the low or intermediate clinical probability category by the revised Geneva score and a normal D-dimer result was subsequently diagnosed with acute venous thromboembolism. CONCLUSIONS: This study suggests that the performance of the revised Geneva score is equivalent to that of the Wells rule. In addition, it seems safe to exclude PE in patients by the combination of a low or intermediate clinical probability by the revised Geneva score and a normal D-dimer level. Prospective clinical outcome studies are needed to confirm this latter finding.

[Clinical probability of PE: should we use a clinical prediction rule?]. / Apport de la clinique : faut-il utiliser un score ?

The determination of the clinical pretest probability using clinical prediction models is an important step in the assessment of patients with suspected pulmonary embolism (PE). It helps establish which test or sequence of tests can effectively corroborate or safely rule out PE. For example, it has been demonstrated that it is safe to withhold anticoagulant therapy in patients with negative d-dimer results and low pretest probability at initial presentation. Clinical probability will also increase the diagnostic yield of ventilation perfusion lung scan. Compared with clinical gestalt, clinical prediction rules provide a standardized and more reproducible estimate of a patient's probability of having a PE. Clinical prediction models combine aspects of the history and physical examination to categorize a patient's probability of having a disease. The models classify patients as having a low, moderate, or high likelihood of having PE. Clinical prediction models have been validated and are well established for the diagnosis of PE in symptomatic patients. They allow all physicians, whatever their expertise, to reliably determine the clinical pretest probability of PE, and thus safely manage their patients using diagnostic and therapeutic algorithms.

[A bilateral diaphragmatic paralysis due to Parsonage and Turner syndrome--its evolution over eight years]. / Paralysie diaphragmatique bilatérale imputable à un syndrome de Parsonage-Turner. Evolution à huit ans.

The diaphragmatic paralysis is a rare disease whose causes and evolving forms are numerous. We report the development to eight years of paralysis diaphragmatic bilateral attributed to a Parsonage-Turner syndrome: the lack of recovery is proved by respiratory functional follow-up. The therapeutic possibilities, limited, are discussed.

Treatment algorithm in cancer-associated thrombosis: Canadian expert consensus.

Management of anticoagulant therapy for the treatment of venous thromboembolism (vte) in cancer patients is complex because of an increased risk of recurrent vte and major bleeding complications in those patients relative to the general population. Subgroups of patients with cancer also show variation in their risk for recurrent vte and adverse bleeding events. Accordingly, a committee of 10 Canadian clinical experts developed the consensus risk- stratification treatment algorithm presented here to provide guidance on tailoring anticoagulant treatment choices for the acute and extended treatment of symptomatic and incidental vte, to prevent recurrent vte, and to minimize the bleeding risk in patients with cancer. During a 1-day live meeting, a systematic review of the literature was performed, and a draft treatment algorithm was developed. The treatment algorithm was refined through the use of a Web-based platform and a series of online teleconferences. Clinicians using this treatment algorithm should consider the bleeding risk, the type of cancer, and the potential for drug-drug interactions in addition to informed patient preference in determining the most appropriate treatment for patients with cancer-associated thrombosis. Anticoagulant therapy should be regularly reassessed as the patient's cancer status and management change over time.

Ruling out pulmonary embolism across different subgroups of patients and healthcare settings: protocol for a systematic review and individual patient data meta-analysis (IPDMA).

BACKGROUND: Diagnosing pulmonary embolism in suspected patients is notoriously difficult as signs and symptoms are non-specific. Different diagnostic strategies have been developed, usually combining clinical probability assessment with D-dimer testing. However, their predictive performance differs across different healthcare settings, patient subgroups, and clinical presentation, which are currently not accounted for in the available diagnostic approaches. METHODS: This is a protocol for a large diagnostic individual patient data meta-analysis (IPDMA) of currently available diagnostic studies in the field of pulmonary embolism. We searched MEDLINE (search date January 1, 1995, till August 25, 2016) to retrieve all primary diagnostic studies that had evaluated diagnostic strategies for pulmonary embolism. Two authors independently screened titles, abstracts, and subsequently full-text articles for eligibility from 3145 individual studies. A total of 40 studies were deemed eligible for inclusion into our IPDMA set, and principal investigators from these studies were invited to participate in a meeting at the 2017 conference from the International Society on Thrombosis and Haemostasis. All authors agreed on data sharing and participation into this project. The process of data collection of available datasets as well as potential identification of additional new datasets based upon personal contacts and an updated search will be finalized early 2018. The aim is to evaluate diagnostic strategies across three research domains: (i) the optimal diagnostic approach for different healthcare settings, (ii) influence of comorbidity on the predictive performance of each diagnostic strategy, and (iii) optimize and tailor the efficiency and safety of ruling out PE across a broad spectrum of patients with a new, patient-tailored clinical decision model that combines clinical items with quantitative D-dimer testing. DISCUSSION: This pre-planned individual patient data meta-analysis aims to contribute in resolving remaining diagnostic challenges of time-efficient diagnosis of pulmonary embolism by tailoring available diagnostic strategies for different healthcare settings and comorbidity. SYSTEMATIC REVIEW REGISTRATION: Prospero trial registration: ID 89366.

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

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.