Drug Management in End-of-Life Hospitalized Palliative Care Cancer Patients: The RHESO Cohort Study.

OBJECTIVE: Little data about the management of drugs in terminally ill palliative care cancer patients is available. The present study aimed at describing the evolution of anticancer and non-anticancer treatments (NACTs) in cancer patients in palliative care units. The second objective was to identify factors leading to the medical decision to withdraw or not NACTs. METHODS: Data from 1,091 cancer patients hospitalized in palliative care units were prospectively collected in 2010-2011, through a multicenter, observational French cohort. RESULTS: The median overall survival after admittance in palliative care units was 15 days. Specific anticancer treatments were systematically stopped in the first 24 h in palliative care units, but for 4.5% of patients. Regarding NACTs, patients were heavily treated with strong opioids (74%), corticosteroids (51%), and antidepressants (21.8%) until death. Antiulcer agents (63.4%), antibiotics (25.7%), thrombosis prevention (21.8%), antidiabetics (7.6%), and transfusions (4%) were often also continuously prescribed. In multivariate analysis, ECOG PS 4 was an independent predictor of continuous prescription of morphine and an independent predictor of discontinuation of corticosteroids, proton-pump inhibitors, antidiabetics, and preventive anticoagulant therapy. Infection symptoms independently predicted continuous prescription of paracetamol. Paralysis and cancer palpable mass independently predicted corticosteroid withdrawal. Brain metastases independently predicted antiulcer withdrawal. Hemorrhage independently predicted preventive anticoagulant withdrawal. Availability to a venous access independently predicted paracetamol and antiulcer continuous prescriptions. Co-prescriptions independently predicted continuous prescriptions (antibiotics with antiulcer, antifungals with antibiotics) or withdrawal (preventive anticoagulant with antiplatelets and antifungals). CONCLUSIONS: NACT prescription remained commonplace in terminally ill palliative cancer patients, although their benefit is questionable.

High tolerance of progressive elastic compression in peripheral arterial disease.

Background: Theoretically progressive compression stockings, which produce a higher compression at the calf than at the ankle level, improve venous return flow without exacerbating peripheral arterial insufficiency (PAD). We aimed to evaluate the short-term tolerance of elastic progressive compression stockings on peripheral arterial vascularisation in patients with symptomatic PAD and associated mild venous insufficiency. Patients and methods: Monocentric, prospective, open pilot study of 18 patients (acceptability study, 6 x 6 plan) evaluating the short-term tolerance of progressive compression stockings (18 ± 2 mmHg at calf and 8 ± 2 mmHg at ankle level) in patients with PAD (ankle brachial index ABI > 0.60 < 0.75) and chronic venous insufficiency (C1s-C4 stages of the CEAP classification). Day 15 tolerance was evaluated by a composite primary criteria comprising: no decrease > 15 % of ABI on each side, no decrease > 15 % of toe brachial index (TBI) on each side and no decrease > 25 % of the number of active plantar flexions performed while standing. Results: The proportion of men was 77.8 %, mean age was 77.3 ± 7.5 years and no patient were diabetic. At inclusion, the mean low ABI was 0.60 ± 0.04 and the mean high ABI was 0.77 ± 0.18. The mean low TBI was 0.32 ± 0.09 and the mean high TBI 0.46 ± 0.15. The mean number of active standing plantar flexions was 33.0 ± 5.0. The majority of the patients were classified in CEAP C2s and C3 classes (class 2: 16.7 %, class C2s: 27.8 %, class C3: 44.4 %, class C4: 5.6 % and class C4s: 5.6 %). Poor tolerance occurred in no patient. By day 30, no patient had worsening of their arterial and venous symptoms. No adverse events occurred during the study. Conclusions: These results suggest a high tolerance of progressive elastic stockings (18 ± 2 mmHg at calf and 8 ± 2 mmHg at ankle level) in symptomatic PAD.

Intravenous Tranexamic Acid Bolus plus Infusion Is Not More Effective than a Single Bolus in Primary Hip Arthroplasty: A Randomized Controlled Trial.

BACKGROUND: Preoperative administration of the antifibrinolytic agent tranexamic acid reduces bleeding in patients undergoing hip arthroplasty. Increased fibrinolytic activity is maintained throughout the first day postoperation. The objective of the study was to determine whether additional perioperative administration of tranexamic acid would further reduce blood loss. METHODS: This prospective, double-blind, parallel-arm, randomized, superiority study was conducted in 168 patients undergoing unilateral primary hip arthroplasty. Patients received a preoperative intravenous bolus of 1 g of tranexamic acid followed by a continuous infusion of either tranexamic acid 1 g (bolus-plus-infusion group) or placebo (bolus group) for 8 h. The primary outcome was calculated perioperative blood loss up to day 5. Erythrocyte transfusion was implemented according to a restrictive transfusion trigger strategy. RESULTS: The mean perioperative blood loss was 919 ± 338 ml in the bolus-plus-infusion group (84 patients analyzed) and 888 ± 366 ml in the bolus group (83 patients analyzed); mean difference, 30 ml (95% CI, -77 to 137; P = 0.58). Within 6 weeks postsurgery, three patients in each group (3.6%) underwent erythrocyte transfusion and two patients in the bolus group experienced distal deep-vein thrombosis. A meta-analysis combining data from this study with those of five other trials showed no incremental efficacy of additional perioperative administration of tranexamic acid. CONCLUSIONS: A preoperative bolus of tranexamic acid, associated with a restrictive transfusion trigger strategy, resulted in low erythrocyte transfusion rates in patients undergoing hip arthroplasty. Supplementary perioperative administration of tranexamic acid did not achieve any further reduction in blood loss.

Bleeding risk under selective serotonin reuptake inhibitor (SSRI) antidepressants: A meta-analysis of observational studies.

Selective serotonin reuptake inhibitors (SSRIs) have been reported to be potentially associated with an increased risk of bleeding. A meta-analysis of observational studies was conducted to quantify this risk. Case-control and cohort studies investigating bleeding risk under SSRI therapy were retrieved by searching the Medline, Pascal, Google Scholar and Scopus databases. Case-control studies were included if they reported bleeding incidents with and without the use of SSRIs and cohort studies were included if they reported the rate of bleeds among SSRI users and non-users. The main outcome was severe bleeding, whatever the site. Only data concerning SSRI belonging to the ATC class N06AB were used. For both case-control and cohort studies, we recorded the adjusted effect estimates and their 95% confidence intervals (CI). Pooled adjusted odds ratio (OR) estimates were computed for case-control and cohort studies using an inverse-variance model. Meta-analysis of the adjusted ORs of 42 observational studies showed a significant association between SSRI use and the risk of bleeding [OR 1.41 (95% CI 1.27-1.57), random effect model, p<0.0001]. The association was found for the 31 case-control studies (1,255,073 patients), with an increased risk of 41% of bleeding [OR 1.41 (95% CI 1.25-1.60)], as well as for the 11 cohort studies including 187,956 patients [OR 1.36 (95% CI 1.12-1.64)]. Subgroup analyses showed that the association remained constant whatever the characteristics of studies. This meta-analysis shows an increased risk of bleeding of at least 36% (from 12% to 64%) based on the high-level of observational studies with SSRIs use.

Prevention of venous thromboembolic events with low-molecular-weight heparin in the non-major orthopaedic setting: meta-analysis of randomized controlled trials.

PURPOSE: To assess the efficacy of low-molecular-weight heparin (LMWH) venous thromboprophylaxis in patients with transient reduced mobility in the non-major orthopaedic setting. METHODS: A meta-analysis was conducted using data from all available randomized trials comparing LMWH with placebo or no prophylactic treatment in patients with leg immobilization for fracture or soft-tissue injury of the lower limb or in patients undergoing knee arthroscopy. The primary endpoint was the incidence of major venous thromboembolic events (VTEs), including asymptomatic proximal deep-vein thrombosis, symptomatic VTEs, and VTE-related death. The Mantel-Haenszel method was used to generate the summary statistics for the overall effect of LMWH. RESULTS: Fourteen studies were included (4,726 patients). The weighted rate of major VTEs was estimated to be 2.9% (95% confidence interval [CI], 2.2% to 3.7%) without LMWH prophylaxis. Overall, a significant 68% reduction in the risk of major VTEs was observed with LMWH prophylaxis (relative risk [RR], 0.32; 95% CI, 0.20 to 0.51; P < .001). The treatment effect was not modified by the clinical setting, that is, distal lower limb injury (7 studies; 1,711 patients; RR, 0.42; 95% CI, 0.20 to 0.86) or knee arthroscopy (6 studies; 2,428 patients; RR, 0.27; 95% CI, 0.15 to 0.49). A nonsignificant 35% increase in the risk of major bleeding was observed in the LMWH prophylaxis group (RR, 1.35; 95% CI, 0.53 to 3.47). CONCLUSIONS: This meta-analysis indicates potential efficacy of LMWH in preventing thromboembolic events in patients with reduced mobility in the non-major orthopaedic setting compared with placebo or no treatment. However, the decision of whether to implement LMWH prophylaxis in each specific setting should also take into account the risk of VTEs in the absence of prophylaxis, the potential adverse effects of LMWH, and the cost. LEVEL OF EVIDENCE: Level II, meta-analysis of Level II studies or Level I studies with inconsistent results.

A framework to characterise the reproducibility of meta-analysis results with its application to direct oral anticoagulants in the acute treatment of venous thromboembolism.

The number of meta-analyses of aggregate data has dramatically increased due to the facility of obtaining data from publications and the development of free, easy-to-use, and specialised statistical software. Even when meta-analyses include the same studies, their results may vary owing to different methodological choices. Assessment of the replication of meta-analysis provides an example of the variation of effect 'naturally' observed between multiple research projects. Reproducibility of results has mostly been reported using graphical descriptive representations. A quantitative analysis of such results would enable (i) breakdown of the total observed variability with quantification of the variability generated by the replication process and (ii) identification of which variables account for this variability, such as methodological quality or the statistical analysis procedures used. These variables might explain systematic mean differences between results and dispersion of the results. To quantitatively characterise the reproducibility of meta-analysis results, a bivariate linear mixed-effects model was developed to simulate both mean results and their corresponding uncertainty. Results were assigned to several replication groups, those assessing the same studies, outcomes, treatment indication and comparisons classified in the same replication group. A nested random effect structure was used to break down the total variability within each replication group and between these groups to enable calculation of an intragroup correlation coefficient and quantification of reproducibility. Determinants of variability were investigated by modelling both mean and variance parameters using covariates. The proposed model was applied to the example of meta-analyses evaluating direct oral anticoagulants in the acute treatment of venous thromboembolism.

Replication of systematic reviews: is it to the benefit or detriment of methodological quality?

OBJECTIVES: To perform an overview of the overlap of systematic reviews (SRs) assessing direct oral anticoagulants and characterize these reviews in terms of bias and methodological quality (PROSPERO: CRD42022316273). STUDY DESIGN AND SETTING: A PubMed-indexed search was performed from inception to January 31, 2022 to identify SRs evaluating direct oral anticoagulants in patients treated for an acute venous thromboembolism. The risk of bias of these SRs was assessed according to the Risk Of Bias In Systematic reviews tool. Redundancy was defined as overlap in terms of the type of population considered, the interventions compared, and the studies included. RESULTS: A total of 144 SRs were evaluated, of which 26 (18.1%) were classified as original, 87 (60.4%) as conceptual replications, and 31 (21.5%) as excessive replications. The risk of bias was high in 19 (73.1%) of the original SRs, 65 (74.7%) of the conceptual replications, and 21 (67.7%) of the excessive replications. Compared to the original SRs, the overall methodological quality was not improved in either conceptual or excessive replications. CONCLUSION: A large number of SRs was classified as replications; a fifth constituted excessive replications. The replications showed no improvement in overall methodological quality compared to the original SRs.

Impact of wearable device-based interventions with feedback for increasing daily walking activity and physical capacities in cardiovascular patients: a systematic review and meta-analysis of randomised controlled trials.

OBJECTIVE: To systematically review randomised controlled trials (RCTs) using a wearable physical activity monitoring device as an intervention to increase daily walking activity and improve physical capacities in patients with cardiovascular disease (CVD). DESIGN: Systematic review and meta-analysis of RCTs. DATA SOURCES: PubMed, Embase and Web of Science from inception to June 2022. ELIGIBILITY CRITERIA: Randomised controlled studies including patients with CVD over 18 years of age at the end of a cardiac rehabilitation programme comparing an intervention group using a wearable physical activity monitoring device with feedback with usual care or with a control group receiving no feedback on their physical activity and reporting a change in the daily number of steps and/or a change in the distance covered in the 6-minute walk test (6-MWT) or a change in peak oxygen uptake (V̇O2peak) as endpoints. RESULTS: Sixteen RCTs were included. The intervention of wearing a physical activity monitoring device with feedback significantly improved daily number of steps compared with controls (standardised mean difference (SMD) 0.85; 95% CI (0.42; 1.27); p<0.01). The effect was greater when the duration of the intervention was less than 3 months (SMD 1.0; 95% CI (0.18; 1.82); p<0.01) than when the duration of the intervention was 3 months or longer (SMD 0.71; 95% CI (0.27; 1.16); p<0.01), but no significant interaction was found between subgroups (p=0.55). 6-MWT distance and V̇O2peak showed only small effects (SMD 0.34; 95% CI (-0.11; 0.80); p=0.02 and SMD 0.54; 95% CI (0.03; 1.03); p=0.07, respectively). CONCLUSION: The use of wearable physical activity monitoring devices appears to help patients with CVD to increase their daily walking activity and thus their physical activity, particularly in the short term. PROSPERO REGISTRATION NUMBER: CRD42022300423.

Antithrombotic therapy and cardiovascular outcomes after transcatheter aortic valve implantation in patients without indications for chronic oral anticoagulation: a systematic review and network meta-analysis of randomized controlled trials.

AIMS: As the antithrombotic regimen that may best prevent ischaemic complications along with the lowest bleeding risk offset following transcatheter aortic valve implantation (TAVI) remains unclear, we aimed to compare the safety and efficacy of antithrombotic regimens in patients without having an indication for chronic oral anticoagulation. METHODS AND RESULTS: We conducted a PROSPERO-registered (CRD42021247924) systematic review and network meta-analysis of randomized controlled trials evaluating post-TAVI antithrombotic regimens up to April 2022. We estimated the relative risk (RR) and 95% confidence intervals (95% CIs) using a random-effects model in a frequentist pairwise and network metanalytic approach. We included seven studies comprising 4006 patients with a mean weighted follow-up of 12.9 months. Risk of all-cause death was significantly reduced with dual antiplatelet therapy (DAPT) compared with low-dose rivaroxaban + 3-month single antiplatelet therapy (SAPT) (RR 0.60, 95% CI 0.41-0.88), while no significant reduction was observed with SAPT vs. DAPT (RR 1.02, 95% CI 0.67-1.58) and SAPT and DAPT compared with apixaban or edoxaban (RR 0.60, 95% CI 0.32-1.14 and RR 0.59, 95% CI 0.34-1.02, respectively). SAPT was associated with a significant reduction of life-threatening, disabling, or major bleeding compared with DAPT (RR 0.45, 95% CI 0.29-0.70), apixaban or edoxaban alone (RR 0.45, 95% CI 0.25-0.79), and low-dose rivaroxaban + 3-month SAPT (RR 0.30, 95% CI 0.16-0.57). There were no differences between the various regimens with respect to myocardial infarction, stroke, or systemic embolism. CONCLUSION: Following TAVI in patients without an indication for chronic oral anticoagulant, SAPT more than halved the risk of bleeding compared with DAPT and direct oral anticoagulant-based regimens without significant ischaemic offset.

Docetaxel-containing adjuvant chemotherapy in patients with early stage breast cancer. Consistency of effect independent of nodal and biomarker status: a meta-analysis of 14 randomized clinical trials.

The benefit of taxanes in the adjuvant setting for node-negative (N0) early breast cancer (EBC) has not yet been established. We conducted a meta-analysis of randomized adjuvant trials comparing docetaxel-containing versus non-taxane-containing regimens. The purpose of this study was to determine whether the incorporation of docetaxel improves disease-free survival (DFS) and overall survival (OS) in early stage breast cancer. Studies were retrieved by searching major databases and the proceedings of leading breast cancer conferences. We extracted hazard ratios (HRs) and 95% confidence intervals (CIs) for DFS and OS and obtained pooled estimates using an inverse-variance model. Fourteen randomized phase III studies were included (25,067 patients). The pooled HR estimate was 0.84 (95% CI 0.78-0.89; P < 0.001) favoring docetaxel for DFS and 0.86 (0.78-0.94; P < 0.001) for OS. In N0 patients (4,274 patients), the pooled HR estimate for DFS was 0.86 (0.73-1.00; P = 0.05). The HR for OS was equal to 1 (0.75-1.34). The improvement in DFS with docetaxel-containing regimens was observed across all subgroups (age, under or over 50; number of involved nodes; hormone receptor or HER2 status (including triple negative status), or administration schedule (sequential or concomitant). The addition of docetaxel to a non-taxane-containing regimen improves DFS and OS in high risk EBC patients. The benefit in DFS was seen across all subgroups regardless of nodal status, age, hormone receptor or HER2 status (including triple negative status), or administration schedule.

A randomized double-blind trial of upward progressive versus degressive compressive stockings in patients with moderate to severe chronic venous insufficiency.

BACKGROUND: The present randomized double-blind multicenter study was designed to assess the efficacy of a progressive compressive stocking (new concept with maximal pressure at calf), compared to a degressive compressive stocking graded 30 mm Hg, evaluating the improvement of lower leg symptoms of chronic venous insufficiency (CVI) in ambulatory patients with moderate to severe chronic venous disease. METHODS: Both gender outpatients presenting symptomatic moderate to severe CVI were eligible for a treatment by compressive stockings. Patients were randomly assigned to receive either degressive compressive stockings (30 mm Hg at ankle, 21 mm Hg at upper calf) or progressive compressive stockings (10 mm Hg at ankle, 23 mm Hg at upper calf). The primary outcome, evaluated after 3 months, was a composite success outcome, including improvement of pain or heavy legs without onset of either ulcer, deep or superficial vein thrombosis of the lower limbs, or pulmonary embolism. The ease of application of the compressive stockings reported by patients was one of secondary outcome. RESULTS: Overall, 401 patients (199 in the progressive compressive stocking group and 202 in the degressive compressive stocking group) were randomized by 44 angiologists in France. Among them, 66% were classified in the C3 CEAP category. The rate of success was significantly higher in the progressive compressive stocking group compared to the degressive compressive stocking group (70.0% vs 59.6%; relative risk, 1.18; 95% confidence interval, 1.02-1.37; P = .03). This was mainly due to more frequent symptom improvement in the progressive compressive stocking group. The compressive stockings were considered easy to apply by 81.3% of patients in the progressive compressive stocking group vs 49.7% of patients in the degressive compressive stocking group (P < .0001). The rate of related serious adverse events was low and similar in both groups. CONCLUSIONS: This trial has demonstrated that progressive compressive stockings are more effective than usual degressive compressive stockings in the improvement of pain and lower leg symptoms in patients with CVI. Moreover, progressive compressive stockings were easier to apply, raising no safety concern at 3 months.

Management of Cancer-Associated Thrombosis in France: A National Survey among Vascular Disease and Supportive Care Specialists.

Low molecular weight heparins (LMWHs) are recommended by international guidelines for at least 6 months in patients with cancer-associated thromboembolism (CAT). Direct oral anticoagulants (DOACs) have been proposed as an alternative to LMWH. In clinical practice, the specialists in charge of CAT have to decide which anticoagulant to prescribe. An electronic survey tool, including vignettes and questions, was sent to members of the French Society of Vascular Medicine, the French-speaking association for supportive care in oncology and the Investigation Network On Venous Thrombo-Embolism. Among the 376 respondents, LMWHs were reported as the first choice by most specialists. The prescription of DOACs within the first 3 weeks of CAT diagnosis was highly dependent on the cancer site: 5.9%, 18.6% and 24.5% in patients with locally advanced colorectal, lung and breast cancer, respectively. The determinants were mostly related to cancer (site and stage or evolution) and to anticancer treatments. For 61% of physicians, some anticancer treatments were contraindications to DOACs. However, almost 90% of physicians considered switching to DOAC after a median 3-month period of LMWHs. In daily practice, LMWHs and DOACs are now considered by specialists of CAT; the decision is mostly driven by the site of cancer. The role of anticancer treatments in the decision remains to be investigated.

Adjusted versus fixed doses of LMWHs in trauma patients: A systematic review and meta-analysis.

PURPOSE: Venous thromboembolism (VTE) causes significant morbidity and mortality in patients with traumatic injuries, despite thromboprophylaxis. To decrease both thrombotic and bleeding risks, some authors suggest adjusting the thromboprophylactic doses of low-molecular-weight heparins (LMWH), in particular according to body weight at treatment initiation or to changes in anti-factor Xa level during treatment. Our objective was to estimate in trauma patients the efficacy and safety of such adjustments, compared with the conventional strategy of fixed-dose LMWH thromboprophylaxis. SOURCE: A systematic review and a meta-analysis were conducted to identify and assess randomised control trials and observational studies with prospective enrolment that included trauma patients and compared adjustment of LMWH thromboprophylaxis versus no adjustment. The primary and secondary endpoints were VTE and bleeding, respectively. The Odds Ratio (OR) and 95% Confidence Interval (95% CI) were calculated using the Mantel-Haenszel method. PRINCIPAL FINDINGS: Nine studies were included in the meta-analysis. No significant reduction in the risk of VTE was observed with adjusted doses of LMWH compared with fixed doses when considering only randomised control trials (OR 1.02 [95% CI, 0.09 to 11.6]) or all trials (OR 0.70 [95% CI, 0.34 to 1.42]). Similarly, there was no significant difference in bleeding risk (OR 1.36, 95% CI 0.59 to 3.10). CONCLUSION: This meta-analysis shows that, to date, there is no evidence to justify adjusting LMWH doses, in agreement with the recommendations of the American College of Chest Physicians.

Failure of the Ottawa Score to Predict the Risk of Recurrent Venous Thromboembolism in Cancer Patients: The Prospective PREDICARE Cohort Study.

INTRODUCTION: Recurrent venous thromboembolism (VTE) despite curative anticoagulation is frequent in patients with cancer. Identifying patients with a high risk of recurrence could have therapeutic implications. A prospective study was designed to validate the Ottawa risk score of recurrent VTE in cancer patients. METHODS: In a prospective multicenter observational cohort, adult cancer patients with a recent diagnosis of symptomatic or incidental lower limb deep vein thrombosis or pulmonary embolism (PE) were treated with tinzaparin for 6 months. The primary endpoint was the recurrence of symptomatic or asymptomatic VTE within the first 6 months of treatment. All clinical events were centrally reviewed and adjudicated. Time-to-event outcomes were estimated by the Kalbfleisch and Prentice method to take into account the competing risk of death. A C-statistic value of > 0.70 was needed to validate the Ottawa score. RESULTS: A total of 409 patients were included and analyzed on an intention-to-treat basis. Median age was 68 years, 60.4% of patients had PE, and VTE was symptomatic in 271 patients (66.3%). The main primary sites were lung (31.3%), lower digestive tract (14.4%), and breast (13.9%) cancers. The Ottawa score was high (≥ 1) in 58% of patients. The 6-month cumulative incidence of recurrent VTE was 7.3% (95% confidence interval [CI]: 4.9-11.1) overall, and 5.0% (95% CI: 2.3-10.8) versus 9.1% (95%CI: 6.1-13.6) in the Ottawa low versus high risk groups, respectively. The C-statistic value was 0.60 (95% CI: 0.55-0.65). CONCLUSION: In this prospective cohort of patients with cancer receiving tinzaparin for VTE, the Ottawa score failed to accurately predict recurrent VTE.

Prevention of Atrial Fibrillation After Atrial Flutter Ablation With Ramipril (from the PREFACE Study).

The clinical efficacy of the inhibitors of the renin-angiotensin-aldosterone system (RAAS) as an upstream therapy for atrial fibrillation (AF) prevention is controversial. No study has itemized so far the role of RAAS inhibitors in AF prevention after atrial flutter (AFL) ablation. This trial aims to investigate the effect of ramipril compared with placebo on AF occurrence in patients hospitalized for AFL ablation without structural heart disease. The Prevention of Atrial Fibrillation by Inhibition Conversion Enzyme (ICE) After Radiofrequency Ablation of Atrial Flutter (PREFACE) trial was a prospective, multicenter, randomized, double-blind, double-dummy trial depicting the AF occurrence during a 12-month follow-up as the primary end point. A total of 198 patients hospitalized for AFL ablation were enrolled in the trial and randomized to placebo or ramipril 5 mg/day. Patients were followed up during 1 year after AFL ablation using 1-week Holter electrocardiogram at 3, 6, 9, and 12 months. The intention-to-treat population encompassed 97 patients in the ramipril group and 101 patients in the placebo group. The primary end point, such as AF occurrence during the 1-year follow-up, was not different between the 2 groups (p = 0.96). Secondary end points, including the occurrence of supraventricular arrhythmia (p = 0.50), heart failure, stroke, and death, were not different between the 2 groups. Safety outcome parameters, including serious adverse events leading to treatment disruption (p = 0.10), hypotension, impairment of renal function, and elevated serum potassium level, also were not different between the 2 groups. In conclusion, RAAS inhibition using ramipril does not reduce AF occurrence in patients facing AFL ablation during the 1-year follow-up.

Extended Anticoagulant Treatment with Full- or Reduced-Dose Apixaban in Patients with Cancer-Associated Venous Thromboembolism: Rationale and Design of the API-CAT Study.

Cancer-associated thrombosis (CT) is associated with a high risk of recurrent venous thromboembolic (VTE) events that require extended anticoagulation in patients with active cancer, putting them at risk of bleeding. The aim of the API-CAT study (NCT03692065) is to assess whether a reduced-dose regimen of apixaban (2.5 mg twice daily [bid]) is noninferior to a full-dose regimen of apixaban (5 mg bid) for the prevention of recurrent VTE in patients with active cancer who have completed ≥6 months of anticoagulant therapy for a documented index event of proximal deep-vein thrombosis and/or pulmonary embolism. API-CAT is an international, randomized, parallel-group, double-blind, noninferiority trial with blinded adjudication of outcome events. Consecutive patients are randomized to receive apixaban 2.5 or 5 mg bid for 12 months. The primary efficacy outcome is a composite of recurrent symptomatic or incidental VTE during the treatment period. The principal safety endpoint is clinically relevant bleeding, defined as a composite of major bleeding or nonmajor clinically relevant bleeding. Assuming a 12-month incidence of the primary outcome of 4% with apixaban and an upper limit of the two-sided 95% confidence interval of the hazard ratio <2.0, 1,722 patients will be randomized, assuming an up to 10% loss in total patient-years (ß = 80%; α one-sided = 0.025). This trial has the potential to demonstrate that a regimen of extended treatment for patients with CT beyond an initial 6 months, with a reduced apixaban dose, has an acceptable risk of recurrent VTE recurrence and decreases the risk of bleeding.

An epidemic of redundant meta-analyses.

BACKGROUND: Meta-analyses are widely used to strengthen available evidence and obtain more precise estimates of treatment effect than any individual trial. Paradoxically, multiplication of meta-analyses on the same topic can lead to confusion as practitioners no longer benefit from a rapid and synthetic response. This phenomenon may appear disproportionate when the number of published meta-analyses exceeds the number of original studies. OBJECTIVES: To describe an example of redundant meta-analyses published in the same area with the same randomized clinical trials (RCTs). METHODS: A systematic review was performed to identify all published meta-analyses of original RCTs that compared direct oral anticoagulants with low molecular weight heparins in cancer patients with venous thromboembolism (VTE). Forest plots were used to represent the meta-analyses results for efficacy (VTE recurrence) and safety (major bleeding) endpoints. An authors' network was constructed to explore the links between the authors of the published meta-analyses. RESULTS: In the past 3 years, four original RCTs were the subject of 20 published meta-analyses by 142 authors: five, four, and 11 meta-analyses pooled the data of two, three, and four RCTs, respectively. The results of meta-analyses were similar regarding the risks of VTE recurrence and major bleeding. The 11 meta-analyses of four RCTs were published within 6 months of the publication of the last RCT. CONCLUSIONS: The epidemic proportions of such redundant literature and authorship could be moderated by developing "living" meta-analyses and encouraging authors of new RCTs to update the corresponding meta-analysis in the same paper as their original research.

Impact of a Visual Support Dedicated to Prognosis on Symptoms of Stress of ICU Family Members: A Before-and-After Implementation Study.

Family members commonly have inaccurate expectations of patient's prognosis in ICU. Adding to classic oral information, a visual support, depicting day by day the evolution of the condition of the patient, improves the concordance in prognosis estimate between physicians and family members. The objective of this study was to evaluate the impact of this tool on symptoms of anxiety/depression of family members. DESIGN: Bicenter prospective before-and-after study. SETTING: A nonacademic and a university hospital. SUBJECTS: Relatives of consecutive patients admitted in the two ICUs. INTERVENTIONS: In the period "before," family members received classic oral information, and in the period "after," they could consult the visual support in the patient's room. The primary endpoint was the Hospital Anxiety and Depression Scale score of relatives at day 5. Secondary outcomes were the prevalence of symptoms of anxiety (Hospital Anxiety and Depression Scale anxiety subscale score > 7) and depression (Hospital Anxiety and Depression Scale depression subscale score > 7) at day 5 and Hospital Anxiety and Depression Scale score at day 90. MEASUREMENTS AND MAIN RESULTS: A total of 140 patients and their referent family members were included (77 in period before and 63 after). Characteristics of patients of the two groups were similar regarding age, reason for admission, Simplified Acute Physiology Score II at admission, and Sequential Organ Failure Assessment score at day 5. At day 5, median Hospital Anxiety and Depression Scale score was 17 (9-25) before and 15 (10-22) after the implementation of the visual support (p = 0.43). The prevalence of symptoms of anxiety and depression was similar in the two groups (66.2% and 49.4% before and 68.3% and 36.5% after [not significant], respectively). At day 90, median Hospital Anxiety and Depression Scale score was 11 before (7-16) and 9 (5-16) after the implementation of the tool (p = 0.38). CONCLUSIONS: In this study, the use of a visual support tool dedicated to prognosis did not modify the level of stress of family members.

Management of acute venous thromboembolism in patients taking antiplatelet therapy.

BACKGROUND: Concomitant anticoagulant and antiplatelet therapy increases bleeding risk, but most data are derived from patients with atrial fibrillation. Patients with venous thromboembolism (VTE) may differ. OBJECTIVE: To study the management of patients diagnosed with acute VTE while receiving antiplatelet treatment. The primary outcome was the number of patients discharged with concomitant therapy. Secondary outcomes were clinically relevant bleeding, cardiovascular events, recurrent VTE and death during follow-up, according to discharge therapy. METHODS: We performed a post-hoc analysis of patients included in two prospective registries, sharing the same case report form, from 2007 to 2017. RESULTS: Among the 1694 identified patients, 254 (15.0%) were receiving antiplatelet treatment at VTE diagnosis, of whom 61 (24.0%) were discharged with concomitant anticoagulant and antiplatelet therapy. In multivariable analysis, age ≥ 80 years-old and the use of Direct Oral Anticoagulants for VTE therapy were associated with the decision to stop the antiplatelet, while having dual anti-platelet therapy at baseline, a history of coronaropathy or peripheral arterial disease were associated with concomitant anticoagulant and antiplatelet therapy. The decision to stop antiplatelet was associated with a non-significant 46% decrease in the risk of bleeding (OR 0.54 (0.16; 1.78)), and a non-significant 68% increase in the risk of cardiovascular events (OR 1.68 (0.44; 6.46)). CONCLUSION: At acute VTE diagnosis, over 15% of patients were receiving antiplatelet agents, of whom 24% were discharged with concomitant anticoagulant and antiplatelet therapy. This therapeutic decision may be associated with a lower risk of cardiovascular events, but an increased risk of bleeding.