Jean-Luc Bosson

A comparison of low-molecular-weight heparin with unfractionated heparin for acute pulmonary embolism

BACKGROUNDnLow-molecular-weight heparin appears to be at least as effective and safe as standard, unfractionated heparin for the treatment of deep-vein thrombosis, but only limited data are available on the use of low-molecular-weight heparin to treat acute symptomatic pulmonary embolism.nnnMETHODSnWe randomly assigned 612 patients with symptomatic pulmonary embolism who did not require thrombolytic therapy or embolectomy to either subcutaneous low-molecular-weight heparin (tinzaparin) given once daily in a fixed dose or adjusted-dose, intravenous unfractionated heparin. Oral anticoagulant therapy was begun between the first and the third day and was given for at least three months. We compared the treatments at day 8 and day 90 with respect to a combined end point of recurrent thromboembolism, major bleeding, and death.nnnRESULTSnIn the first eight days of treatment, 9 of 308 patients assigned to receive unfractionated heparin (2.9 percent) reached at least one of the end points, as compared,with 9 of 304 patients assigned to low-molecular-weight heparin (3.0 percent; absolute difference, 0.1 percentage point; 95 percent confidence interval, -2.7 to 2.6). By day 90, 22 patients assigned to unfractionated heparin (7.1 percent) and 18 patients assigned to low-molecular-weight heparin (5.9 percent) had reached at least one end point (P=0.54; absolute difference, 1.2 percentage points; 95 percent confidence interval, -2.7 to 5.1). The risk of major bleeding was similar in the two treatment groups throughout the study.nnnCONCLUSIONSnUnder the conditions of this study, initial subcutaneous therapy with the low-molecular-weight heparin tinzaparin appeared to be as effective and safe as intravenous unfractionated heparin in patients with acute pulmonary embolism.

Six Months vs Extended Oral Anticoagulation After a First Episode of Pulmonary Embolism: The PADIS-PE Randomized Clinical Trial

IMPORTANCEnThe optimal duration of anticoagulation after a first episode of unprovoked pulmonary embolism is uncertain.nnnOBJECTIVESnTo determine the benefits and harms of an additional 18-month treatment with warfarin vs placebo, after an initial 6-month nonrandomized treatment period on a vitamin K antagonist.nnnDESIGN, SETTING, AND PARTICIPANTSnRandomized, double-blind trial (treatment period, 18 months; median follow-up, 24 months); 371 adult patients who had experienced a first episode of symptomatic unprovoked pulmonary embolism (ie, with no major risk factor for thrombosis) and had been treated initially for 6 uninterrupted months with a vitamin K antagonist were randomized and followed up between July 2007 and September 2014 in 14 French centers.nnnINTERVENTIONSnWarfarin or placebo for 18 months.nnnMAIN OUTCOMES AND MEASURESnThe primary outcome was the composite of recurrent venous thromboembolism or major bleeding at 18 months after randomization. Secondary outcomes were the composite at 42 months (treatment period plus 24-month follow-up), as well as each component of the composite, and death unrelated to pulmonary embolism or major bleeding, at 18 and 42 months.nnnRESULTSnAfter randomization, 4 patients were lost to follow-up, all after month 18, and 1 withdrew due to an adverse event. During the 18-month treatment period, the primary outcome occurred in 6 of 184 patients (3.3%) in the warfarin group and in 25 of 187 (13.5%) in the placebo group (hazard ratio [HR], 0.22; 95% CI, 0.09-0.55; Pu2009=u2009.001). Recurrent venous thromboembolism occurred in 3 patients in the warfarin group and 25 patients in the placebo group (HR, 0.15; 95% CI, 0.05-0.43); major bleeding occurred in 4 patients in the warfarin group and in 1 patient in the placebo group (HR, 3.96; 95% CI, 0.44 to 35.89). During the 42-month entire study period (including the study treatment and follow-up periods), the composite outcome occurred in 33 patients (20.8%) in the warfarin group and in 42 (24.0%) in the placebo group (HR, 0.75; 95% CI, 0.47-1.18). Rates of recurrent venous thromboembolism, major bleeding, and unrelated death did not differ between groups.nnnCONCLUSIONS AND RELEVANCEnAmong patients with a first episode of unprovoked pulmonary embolism who received 6 months of anticoagulant treatment, an additional 18 months of treatment with warfarin reduced the composite outcome of recurrent venous thrombosis and major bleeding compared with placebo. However, benefit was not maintained after discontinuation of anticoagulation therapy.nnnTRIAL REGISTRATIONnclinicaltrials.gov Identifier: NCT00740883.

Incidence and predictors of venous thromboembolism recurrence after a first isolated distal deep vein thrombosis

Isolated distal deep vein thrombosis (iDDVT) (i.e. without proximal DVT or pulmonary embolism) represents half of all cases of lower limb DVT. Its clinical significance and management are controversial. Data on long‐term follow‐up are scarce, especially concerning risk and predictors of venous thromboembolism (VTE) recurrence.

Antipsychotic drugs and risk of pulmonary embolism.

Antipsychotic drugs (APs) expose users to several adverse effects. Some reports describe an increased risk of venous thromboembolism for particular drugs in this family.

Computerized physician order entry system combined with on‐ward pharmacist: analysis of pharmacists' interventions

RATIONALE, AIMS AND OBJECTIVESnTo analyse pharmacists interventions in a setting where a computerized physician order entry system (CPOE) is in use and a pharmacist works on the ward.nnnMETHODnA prospective cohort study was conducted in seven wards of a French teaching hospital using CPOE along with the presence of a full-time on-ward pharmacy resident. We documented the characteristics of pharmacists interventions communicated to physicians during the medication order validation process whenever a drug-related problem was identified. Independent predictors of the physicians acceptance of the pharmacists intervention were assessed using multiple logistic regression analysis.nnnRESULTSnThe 448 pharmacists interventions concerned: non-conformity to guidelines or contraindications (22%), too high doses (19%), drug interactions (15%) and improper administration (15%). The interventions consisted of changes in drug choice (41%), dose adjustment (23%), drug monitoring (19%) and optimization of administration (17%). Interventions were communicated via the CPOE in 57% of cases and 43% orally. The rate of physicians acceptance was 79.2%. In multivariate analysis, acceptance was significantly associated with the physicians status [higher for residents vs. seniors: OR = 7.23, CI 95 (2.37-22.10), P < 0.01], method of communication [higher for oral vs. computer communication: OR = 12.5, CI 95 (4.16-37.57), P < 0.01] and type of recommendation [higher for drug monitoring vs. drug choice recommendations: OR = 10.32, CI 95 (3.20-33.29), P < 0.01].nnnCONCLUSIONSnWhen a clinical pharmacist is present on a ward in which a CPOE is in use, the pharmacists interventions are well accepted by physicians. Specific predictors of the acceptance by physicians emerge, but further research as to the impact of CPOE on pharmacist-physician communication is needed.

Flapless implant surgery using an image-guided system. A 1- to 4-year retrospective multicenter comparative clinical study.

PURPOSEnThe aim of this retrospective multicenter clinical study was to compare the survival rate of dental implants placed with two different surgical procedures: (1) a flapless surgical procedure using an image-guided system (IGS flapless protocol) and (2) the conventional technique (open flap without IGS) with a computed tomography scan.nnnMATERIALS AND METHODSnBetween 2001 and 2004, 552 implants were placed in 169 patients by six practitioners who used both protocols to restore completely and partially edentulous arches: 271 of them were placed with the IGS flapless protocol (test group) and 281 with the conventional procedure (control group). Each implant was categorized as survival or failure after 1 to 4 years of follow-up after prosthesis implantation. A preoperative classification was used to evaluate the anatomic features of each case. There was initially no possible comparison between these two groups because of the indication bias relative to the retrospective clinical study data characteristics. After a classic logistic regression analysis, propensity scores were used to reduce this bias: prognosis variables were included in a regression logistic model to define the probability for each implant to be treated with the IGS flapless protocol. Implants showing the same probability were categorized into three classes. The implants were then compared with each other within the same class.nnnRESULTSnAfter the follow-up period, the cumulative survival rate was 98.57% in the control group and 96.30% in the test group. Whatever the statistical method used, no statistical differences between the two protocols were shown. Transmucosal implant placement showed a survival rate of 97%. Even though the initial conditions were less favorable, the survival rate in the test group was comparable with the standard protocol group.nnnCONCLUSIONnPassing an implant through the gum does not interfere with osseointegration. The IGS flapless procedure makes it possible to use the flapless procedure, even though anatomic conditions were initially unfavorable.

Outcomes for Inpatients with Normal Findings on Whole-leg Ultrasonography: A Prospective Study

BACKGROUNDnUltrasonography is used routinely for ruling out suspected deep vein thrombosis in hospitalized patients, although most evidence supporting this strategy is derived from the outpatient setting. This study aimed to estimate the rate of venous thromboembolism when anticoagulant therapy was withheld from inpatients with normal findings on whole-leg ultrasonography.nnnMETHODSnAs part of a prospective multicenter cohort study, 1926 medical and surgical inpatients with clinically suspected deep vein thrombosis during their stay were enrolled. Ultrasonography of all lower extremities was performed by board-certified vascular medicine physicians using a standardized examination protocol. Deep vein thrombosis was detected in 395 patients (20%). Anticoagulant therapy was withheld from patients with normal findings, and 523 of them were randomly selected for follow-up. The main outcome measure was 3-month incidence of symptomatic venous thromboembolism.nnnRESULTSnA total of 513 patients with normal findings on ultrasonography successfully completed 3 months of follow-up, 9 patients were lost to follow-up, and 1 patient received anticoagulant therapy during follow-up. Three patients (0.6%) experienced nonfatal symptomatic venous thromboembolic events confirmed by objective testing. The cause of death was judged to be possibly related to pulmonary embolism for 7 other patients (1.3%). Overall, the 3-month rate of venous thromboembolism was 1.9% (10/513; 95% confidence interval, 0.9-3.5).nnnCONCLUSIONnAlthough withholding anticoagulant therapy after a single negative whole-leg ultrasonography seems to be safe, up to 3.5% of inpatients may nevertheless develop venous thromboembolism in the next 3 months. Further study is warranted to determine whether this strategy is equivalent to serial compression ultrasonography limited to proximal veins.

Short- and medium-term duplex sonography follow-up of deep venous thrombosis of the lower limbs

We conducted this study to assess the progression or regression of venous thrombi during and after treatment and to search for criteria of embolism risk.

Chronic Infection and Venous Thromboembolic Disease.

Venous thromboembolic disease often arises as a complication of another pathological condition and/or triggering event. Infectious diseases result from both the direct action of the pathogens themselves and their effect on the immune system. The resulting inflammatory process and the coagulation and fibrinolysis processes share common pathways, explaining why infection is associated with thrombosis. In this brief overview, besides certain chronic infectious diseases, we also consider some acute infections, as the mechanisms are likely to be similar, particularly in the initial infective stage or the more acute episodes of a chronic infection. The infectious agent can be viral, bacterial, fungal, or parasitic. However, the literature on the link between infections and venous thromboembolism (VTE) is uneven, favoring infections that are found in more developed countries where physicians have access to VTE diagnostic tools. Thus, large epidemiological studies in this field are restricted to a limited number of the common chronic infectious diseases such as tuberculosis, while for other infections, particularly parasitic and fungal infections, the link with VTE is only evoked in a few scattered case reports.

How best to use and evaluate Patient Information Leaflets given during a consultation: a systematic review of literature reviews

In the past, several authors have attempted to review randomized clinical trials (RCT) evaluating the impact of Patient Information Leaflets (PILs) used during a consultation and draw some general conclusions. However, this proved difficult because the clinical situations, size and quality of RCTs were too heterogeneous to pool relevant data.