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This trial showed that the addition of abdominopelvic CT to routine measures in patients with unprovoked venous thrombosis did not detect additional occult cancers. The incidence of cancer in first unprovoked venous thrombosis was 4%, not 10% as had been previously reported. Venous thromboembolism, which comprises deep-vein thrombosis and pulmonary embolism, is the third most common cardiovascular disorder. 1 – 3 It is classified as provoked when it is associated with a transient risk factor (e.g., trauma, surgery, prolonged immobility, or pregnancy or the puerperium) and as unprovoked when it is associated with neither a strong transient risk factor nor overt cancer. Unprovoked venous thromboembolism may be the earliest sign of cancer 4 , 5 ; up to 10% of patients with unprovoked venous thromboembolism receive a diagnosis of cancer in the year after their diagnosis of venous thromboembolism. 6 More than 60% of occult cancers are . . .

Patients receiving cancer treatment who had an intermediate-to-high risk of venous thromboembolism were randomly assigned to apixaban or placebo for 6 months. VTE was noted in 4.2% of patients receiving apixaban and 10.2% of those receiving placebo, a significant difference. Major bleeding occurred in 3.5% of patients with apixaban and in 1.8% with placebo.

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. 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. 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. ECS did not prevent PTS after a first proximal DVT, hence our findings do not support routine wearing of ECS after DVT. Canadian Institutes of Health Research.

Little is known about the risk of venous thrombosis following kidney transplant. To determine this we estimated the risk of thromboembolic events (TEs) in a cohort of consecutive patients who underwent kidney transplantation at a single tertiary care center over an 11-year period and calculated standardized incidence ratios (SIRs) for a first TE in kidney transplant recipients compared with the general population. We then performed a nested case–control study and compared patients with and without TEs to identify risk factors for thrombosis. Among 913 kidney transplant recipients (KTRs), 68 patients developed these events. The SIR for TEs in KTRs compared with the general population was 7.9 over the duration of follow-up. The risk was particularly higher in the first post-transplant year (SIR 26.1) but remained elevated afterward (SIR 5.2). Hospitalization, use of sirolimus, low hemoglobin level, and use of renin–angiotensin system inhibitors were independently associated with these events. When cases of TEs that occurred during hospitalization were excluded, the risk of these events remained elevated. The risk of TEs in KTRs was eightfold higher than in the general population but not fully explained by the increased risk associated with hospitalization. Our results underscore the important risk of thrombosis in patients who received a kidney transplant, making vigilance mandatory especially during hospitalization.

A 26-year-old black woman underwent evaluation in the emergency department after two weeks of worsening nausea, vomiting and fatigue. Her medical history included having had malaria at eight years of age, for which she had received treatment in Eritrea. A complete review of systems was unremarkable aside from a two-day history of a mild bitemporal headache. The patient stated no recent changes in her dietary habits or bowel movements. She did not take any medication or over-the-counter products, and she had never used illicit drugs. She had no history of venous thromboembolism. Laboratory investigations in the emergency department showed normocytic anemia, with hemoglobin 57 [normal 120-152] g/L, mild thrombocytopenia and normal leukocyte count and differential. The presence of schistocytes and fragmented cells supported a diagnosis of microangiopathic hemolytic anemia. At this point, our differential diagnosis included thrombotic thrombocytopenic purpura/hemolytic uremic syndrome given the presence of thrombocytopenia and the findings consistent with microangiopathic hemolytic anemia on the peripheral blood smear.

Introduction The effects of drospirenone-containing combined oral contraceptives (COCs) on the risk of venous thromboembolism (VTE) remain controversial due to the challenge in distinguishing between first-time users and restarters, and their different underlying VTE risks, in healthcare databases. Objectives The aim of this study was to describe the challenge of studying the risk of VTE among first-time users of drospirenone-containing COCs in a healthcare database and assess the risk among first-time users and restarters. Methods We used data from the Clinical Practice Research Datalink to construct two cohorts. The first-time user cohort included all women aged 16–45 years who received a first ever prescription of drospirenone- or levonorgestrel-containing COCs between May 2002 and March 2015. The restarter cohort included those who were restarting a COC after a period of non-use of ≥6 months. Cox proportional hazards models adjusted for high dimensional propensity scores were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Results The final cohorts included 55,139 first-time users (3582 drospirenone and 51,557 levonorgestrel) and 162,959 restarters (23,191 drospirenone and 139,768 levonorgestrel). The adjusted HR of VTE associated with drospirenone versus levonorgestrel was 3.19 (95% CI 1.12–9.08) for first-time users and 1.96 (95% CI 1.12–3.41) for restarters. Conclusions We found an elevated risk of VTE associated with drospirenone-containing COCs in comparison with levonorgestrel-containing COCs in both cohorts. While left truncation of healthcare databases is a concern for the identification of first-time users, the use of a more explicit cohort of restarters suggests a doubling of VTE risk with drospirenone-containing COCs.

Patients with venous thromboembolism (VTE) often have comorbidities that require use of antiplatelets. However, evidence on the effects of concomitant use of direct oral anticoagulants (DOACs) and antiplatelets in this high‐risk population is scarce. Our international, multi‐database cohort study assessed the real‐world effectiveness and safety of concomitant use of DOACs and antiplatelets among patients with VTE. We assembled two population‐based cohorts using administrative health care databases from Québec and Germany. We included patients with incident VTE who initiated treatment with a DOAC or a vitamin K antagonist (VKA), while being exposed to antiplatelets (acetylsalicylic acid, clopidogrel, ticagrelor, prasugrel, dipyridamole). The study period spanned from 2012 to 2016 (Québec) or 2019 (Germany). Concomitant use of DOACs and antiplatelets was compared with concomitant use of VKAs and antiplatelets, using inverse probability of treatment weighting to balance exposure groups. Cox proportional hazards models estimated site‐specific hazard ratios (HRs) and 95% confidence intervals (CIs) of major bleeding, all‐cause mortality (primary outcomes), and recurrent VTE (secondary outcome). Site‐specific estimates were meta‐analyzed using random‐effects models. Overall, 4971 patients with VTE initiated concomitant use of a DOAC (n = 2289) or a VKA (n = 2682) and antiplatelets. Compared with concomitant use of VKAs and antiplatelets, concomitant use of DOACs and antiplatelets was associated with similar risks of major bleeding (HR, 0.81; 95% CI, 0.46‐1.45), all‐cause mortality (HR, 1.25; 95% CI, 0.87‐1.79), and recurrent VTE (HR, 0.96; 95% CI, 0.40‐2.27). Among patients with VTE using antiplatelets, there were no major differences in effectiveness and safety between DOACs and VKAs.

Indirect evidence suggests that prolonged treatment with warfarin might be associated with a decreased incidence of urogenital cancer. We aimed to assess this association in a large population-based study. Beneficiaries of Saskatchewan Health who were eligible for prescription drug benefits and aged 50 years or over with no history of cancer since 1967 were enrolled into a nested, matched case-control study. 19 412 new cases of urogenital cancer diagnosed between Jan 1, 1981, and Dec 31, 2002, were identified by use of information from the Saskatchewan Cancer Agency registry. For each case, six controls, totalling 116 470, who were matched for age, sex, and time of diagnosis were selected randomly. Conditional logistic regression analysis was used to calculate adjusted incidence rates of urogenital cancer in relation to warfarin use. Compared with men who never used warfarin, men with 4 years of warfarin use had an adjusted incidence rate of 0·80 (95% CI [0·65–0·99]). For warfarin use 76–100% of the time, the adjusted rate ratios were 0·80 (0·66–0·96) during year 2 preceding diagnosis of prostate cancer, 0·76 (0·62–0·94) during year 3, and 0·67 (0·53–0·86) during year 4. No significant association was found between warfarin and risk of other urogenital cancers. Our results suggest that warfarin has an antitumour effect that is specific to prostate cancer. Further investigation, with more complete assessment of confounders and that addresses the effect of warfarin on mortality of prostate cancer, is warranted.

Venous thromboembolism (VTE) represents an important cause of maternal morbidity and mortality. Estimates of bleeding associated with therapeutic‐dose anticoagulation are variable. We describe the frequency of bleeding in pregnant women receiving therapeutic anticoagulation for VTE by means of a systematic review of the literature. Medical Literature Analysis and Retrieval System, Embase, Scopus, Web of Science, and ClinicalTrials.gov were searched. Databases were searched from inception to February 27, 2022. There was no language or geographic location restriction. The search yielded 2773 articles with 2212 unique citations. Studies were included if they described pregnant women treated for an acute VTE with therapeutic‐dose anticoagulation and a defined bleeding outcome was reported. Five studies met inclusion criteria. Included studies were judged to have a serious to critical risk of bias using the Risk of Bias in Nonrandomized Studies of Intervention tool. The rate of bleeding, as defined by respective studies, ranged between 2.9% and 30.0%. Two studies included control groups, one of which found no significant difference in the risk of bleeding between groups, while the other found a significantly increased bleeding risk associated with therapeutic anticoagulation. Among pregnant women anticoagulated for VTE, the reported bleeding risk is variable. The ability to draw definite conclusions is limited by the scarcity and low quality of the studies, the small number of included patients, and the heterogeneity of bleeding definitions used. Large‐scale studies with standardized bleeding definitions are required to provide acute bleeding estimates and optimize the care of these patients. PROSPERO, CRD42021276771.

Introduction Hyperglycaemia is common during hospitalization; glycaemic targets in non‐critical care settings have not been well studied. We assessed associations between inpatient glycaemic control and adverse events. Methods We conducted a retrospective cohort study on non‐critically ill medical patients hospitalized in a tertiary care hospital between 2015 and 2018. Mean glycaemia during the first four days of hospitalization was categorized as 4.0–7.0 mmol/L, 7.1–10.0 mmol/L and >10.0 mmol/L. The primary outcome was a composite of adverse events including mortality, infections, acute kidney injury, thromboembolic and cardiovascular events. The secondary outcome was hypoglycaemia, defined as any glycaemia <4.0 mmol/L. Logistic regression was used to assess adverse events, and a Cox proportional hazards model was used to estimate hypoglycaemia risk. Results Our cohort included 1,368 patients, of whom 407 (29.8%) experienced an adverse event. We did not find associations between glycaemia of 4.0–7.0 mmol/L (adjusted odds ratio [OR]: 0.88, 95% confidence interval [CI]: 0.63–1.23) or glycaemia of >10.0 mmol/L (adjusted OR: 0.98, 95% CI: 0.75–1.28) and the occurrence of adverse events, compared to a glycaemia of 7.1–10.0 mmol/L. Glycaemia of >10.0 mmol/L was associated with an increased risk of hypoglycaemia (adjusted hazard ratio [HR]: 1.72, 95% CI: 1.21–2.45). Hypoglycaemia was associated with adverse events (adjusted OR 1.85, 95% CI 1.31–2.60). Conclusions Neither glycaemia of 4.0–7.0 mmol/L nor glycaemia of >10.0mmol/L during non‐critical care hospitalization was associated with increased adverse events. Glycaemia of >10.0 mmol/L was associated with increased hypoglycaemia, likely due to aggressive glucose lowering. These findings highlight the need for further studies to discern optimal inpatient glycaemic targets. Few studies have assessed the association between various glycaemic targets and adverse outcomes during hospitalization. Our study assessed whether glycaemia levels (ie 4.0–7.0 mmol/L, 7.1–10.0 mmol/L and >10 mmol/L) during early hospitalization is associated with an increased risk of adverse events and hypoglycaemia. Our results showed that the glycaemic targets defined in our study were not associated with an increased risk of adverse events during hospitalization; however, hypoglycaemia (ie <4.0 mmol/L) was associated with an increased risk of adverse events during hospitalization.