Summary Background Post-thrombotic syndrome (PTS) is a common and burdensome complication of deep venous thrombosis (DVT). Previous trials suggesting benefit of elastic compression stockings (ECS) to ...prevent PTS were small, single-centre studies without placebo control. We aimed to assess the efficacy of ECS, compared with placebo stockings, for the prevention of PTS. Methods We did a multicentre randomised placebo-controlled trial of active versus placebo ECS used for 2 years to prevent PTS after a first proximal DVT in centres in Canada and the USA. Patients were randomly assigned to study groups with a web-based randomisation system. Patients presenting with a first symptomatic, proximal DVT were potentially eligible to participate. They were excluded if the use of compression stockings was contraindicated, they had an expected lifespan of less than 6 months, geographical inaccessibility precluded return for follow-up visits, they were unable to apply stockings, or they received thrombolytic therapy for the initial treatment of acute DVT. The primary outcome was PTS diagnosed at 6 months or later using Ginsberg's criteria (leg pain and swelling of ≥1 month duration). We used a modified intention to treat Cox regression analysis, supplemented by a prespecified per-protocol analysis of patients who reported frequent use of their allocated treatment. This study is registered with ClinicalTrials.gov , number NCT00143598 , and Current Controlled Trials, number ISRCTN71334751. Findings From 2004 to 2010, 410 patients were randomly assigned to receive active ECS and 396 placebo ECS. The cumulative incidence of PTS was 14·2% in active ECS versus 12·7% in placebo ECS (hazard ratio adjusted for centre 1·13, 95% CI 0·73–1·76; p=0·58). Results were similar in a prespecified per-protocol analysis of patients who reported frequent use of stockings. Interpretation ECS did not prevent PTS after a first proximal DVT, hence our findings do not support routine wearing of ECS after DVT. Funding Canadian Institutes of Health Research.
Summary Background Thrombophilias are common disorders that increase the risk of pregnancy-associated venous thromboembolism and pregnancy loss and can also increase the risk of placenta-mediated ...pregnancy complications (severe pre-eclampsia, small-for-gestational-age infants, and placental abruption). We postulated that antepartum dalteparin would reduce these complications in pregnant women with thrombophilia. Methods In this open-label randomised trial undertaken in 36 tertiary care centres in five countries, we enrolled consenting pregnant women with thrombophilia at increased risk of venous thromboembolism or with previous placenta-mediated pregnancy complications. Eligible participants were randomly allocated in a 1:1 ratio to either antepartum prophylactic dose dalteparin (5000 international units once daily up to 20 weeks' gestation, and twice daily thereafter until at least 37 weeks' gestation) or to no antepartum dalteparin (control group). Randomisation was done by a web-based randomisation system, and was stratified by country and gestational age at randomisation day with a permuted block design (block sizes 4 and 8). At randomisation, site pharmacists (or delegates) received a randomisation number and treatment allocation (by fax and/or e-mail) from the central web randomisation system and then dispensed study drug to the local coordinator. Patients and study personnel were not masked to treatment assignment, but the outcome adjudicators were masked. The primary composite outcome was independently adjudicated severe or early-onset pre-eclampsia, small-for-gestational-age infant (birthweight <10th percentile), pregnancy loss, or venous thromboembolism. We did intention-to-treat and on-treatment analyses. This trial is registered with ClinicalTrials.gov , number NCT00967382 , and with Current Controlled Trials, number ISRCTN87441504. Findings Between Feb 28, 2000, and Sept 14, 2012, 292 women consented to participate and were randomly assigned to the two groups. Three women were excluded after randomisation because of ineligibility (two in the antepartum dalteparin group and one in the control group), leaving 146 women assigned to antepartum dalteparin and 143 assigned to no antepartum dalteparin. Some patients crossed over to the other group during treatment, and therefore for on-treatment and safety analysis there were 143 patients in the dalteparin group and 141 in the no dalteparin group. Dalteparin did not reduce the incidence of the primary composite outcome in both intention-to-treat analysis (dalteparin 25/146 17·1%; 95% CI 11·4–24·2% vs no dalteparin 27/143 18·9%; 95% CI 12·8–26·3%; risk difference −1·8% 95% CI −10·6% to 7·1%)) and on-treatment analysis (dalteparin 28/143 19·6% vs no dalteparin 24/141 17·0%; risk difference +2·6% 95% CI −6·4 to 11·6%). In safety analysis, the occurrence of major bleeding did not differ between the two groups. However, minor bleeding was more common in the dalteparin group (28/143 19·6%) than in the no dalteparin group (13/141 9·2%; risk difference 10·4%, 95% CI 2·3–18·4; p=0·01). Interpretation Antepartum prophylactic dalteparin does not reduce the occurrence of venous thromboembolism, pregnancy loss, or placenta-mediated pregnancy complications in pregnant women with thrombophilia at high risk of these complications and is associated with an increased risk of minor bleeding. Funding Canadian Institutes of Health Research, Heart and Stroke Foundation of Canada, and Pharmacia and UpJohn.
2020 was a year like no other for Arctic research, and ArcticNet’s Arctic Change conference was no exception. Held every three years in different Canadian locations, the international conference ...shifted to a virtual setting with the global COVID-19 pandemic, with 1600 attendees tuning in online from across Canada and around the world. This year included 327 Northern participants, the most representative Arctic Change conference yet. The heart of any conference is the people, and the connections participants make with each other. Going virtual meant giving up the in-person visits, but not the interactions or networking opportunities. Participants watched more than 346 presentations, joined in live question and answer sessions and online chats with panelists and speakers, connected to each other on the virtual conference platform, and more than 5207 streamed the plenaries together. During the week, sessions and conference events were viewed more than 25000 times. The ArcticNet Students’ Association held their annual student day with over 300 participants, finding innovative ways to keep the social spirit of past conferences, holding a virtual trivia night to cap off a busy day of student-focused programming.
Protein C (PC) deficiency increases the risk of venous thrombosis (VT) among members of Kindred Vermont II but fails to fully account for the inheritance pattern. A genome scan of the pedigree ...supported the presence of a prothrombotic gene on chromosome 11q23 (nominal P < .0001), with weaker support on chromosomes 10p12 (P < .0003) and 18p11.2-q11 (P < .0007). Resequencing of 109 genes in the linkage regions identified 5030 variants in a sample of 20 kindred members. Of 16 single nucleotide polymorphisms in 6 genes tested in the larger family set, only single nucleotide polymorphisms in cell adhesion molecule 1 (CADM1) associated with VT. Among the 8 CADM1 single nucleotide polymorphisms genotyped in the complete sample, rs6589488 was most strongly supported (P < .000007), but the association was limited to the PC-deficient subset of the sample (P < .000001). Haplotype analysis narrowed the region containing the causative variant to the coding region of the CADM1 gene. CADM1 gene expression analyzed in blood outgrowth endothelial cells cultured from family members was decreased compared with control subjects, lending phenotypic support to this conclusion. Finally, we have for the first time demonstrated CADM1 in endothelial cells, where it appears to be selectively involved in endothelial cell migration, suggesting a role in endothelial barrier repair.
We compared the spatiotemporal variability of temperatures and precipitation with that of the magnitude and timing of maximum daily spring flows in the geographically adjacent L’Assomption River ...(agricultural) and Matawin River (forested) watersheds during the period from 1932 to 2013. With regard to spatial variability, fall, winter, and spring temperatures as well as total precipitation are higher in the agricultural watershed than in the forested one. The magnitude of maximum daily spring flows is also higher in the first watershed as compared with the second, owing to substantial runoff, given that the amount of snow that gives rise to these flows is not significantly different in the two watersheds. These flows occur early in the season in the agricultural watershed because of the relatively high temperatures. With regard to temporal variability, minimum temperatures increased over time in both watersheds. Maximum temperatures in the fall only increased in the agricultural watershed. The amount of spring rain increased over time in both watersheds, whereas total precipitation increased significantly in the agricultural watershed only. However, the amount of snow decreased in the forested watershed. The magnitude of maximum daily spring flows increased over time in the forested watershed.
Patients with Kawasaki disease can develop life-altering coronary arterial abnormalities, particularly in those resistant to intravenous immunoglobulin (IVIg) therapy. We tested the tumor necrosis ...factor α receptor antagonist etanercept for reducing both IVIg resistance and coronary artery (CA) disease progression.
In a double-blind multicenter trial, patients with Kawasaki disease received either etanercept (0.8 mg/kg;
= 100) or placebo (
= 101) subcutaneously starting immediately after IVIg infusion. IVIg resistance was the primary outcome with prespecified subgroup analyses according to age, sex, and race. Secondary outcomes included echocardiographic CA measures within subgroups defined by coronary dilation (
score >2.5) at baseline. We used generalized estimating equations to analyze
score change and a prespecified algorithm for change in absolute diameters.
IVIg resistance occurred in 22% (placebo) and 13% (etanercept) of patients (
= .10). Etanercept reduced IVIg resistance in patients >1 year of age (
= .03). In the entire population, 46 (23%) had a coronary
score >2.5 at baseline. Etanercept reduced coronary
score change in those with and without baseline dilation (
= .04 and
= .001); no improvement occurred in the analogous placebo groups. Etanercept (
= 22) reduced dilation progression compared with placebo (
= 24) by algorithm in those with baseline dilation (
= .03). No difference in the safety profile occurred between etanercept and placebo.
Etanercept showed no significant benefit in IVIg resistance in the entire population. However, preplanned analyses showed benefit in patients >1 year. Importantly, etanercept appeared to ameliorate CA dilation, particularly in patients with baseline abnormalities.
PDF
