Cardiovascular events among recipients of hematopoietic stem cell transplantation-A systematic review and meta-analysis.

Cardiovascular diseases are an emerging cause of mortality and morbidity in survivors of hematopoietic stem cell transplantation (HSCT); however, the incidence of cardiovascular events (CVEs) in this population is not well described. This systematic review summarizes the evidence on the incidence of CVEs in HSCT recipients. Medline and Embase were searched from inception to December 2020. Inclusion criteria were cohort studies and phase 3 randomized controlled trials that reported CVEs among adults who underwent HSCT for hematological malignancies. After reviewing 8386 citations, 57 studies were included. The incidence of CVEs at 100 days was 0.19 (95% CI: 0.17-0.21) per 100 person-days after autologous HSCT and 0.06 (95% CI: 0.05-0.07) per 100 person-days after allogeneic HSCT. This higher incidence after autologous HSCT was driven by reports of arrhythmia from one population-based study in patients with multiple myeloma. The incidence of long-term CVEs was 3.98 (95% CI; 3.44-4.63) per 1000 person-years in survivors of autologous HSCT and 3.06 (95% CI; 2.69-3.48) per 1000 person-years in survivors of allogeneic HSCT. CVEs remain an important but under-reported cause of morbidity and mortality in recipients of HSCT. Future studies are required to better understand the incidence and risk factors for CVEs in HSCT recipients.

Resumption of anticoagulant therapy after anticoagulant-related gastrointestinal bleeding: A systematic review and meta-analysis.

INTRODUCTION: Oral anticoagulation (OAC) is permanently discontinued in up to 50% of patients following a gastrointestinal (GI) bleed. A previous meta-analysis showed a reduced risk of thromboembolism and death, and a non-statistically significant increased risk of re-bleeding associated with resumption. We conducted an updated meta-analysis to determine the risks of recurrent GI bleeding, thromboembolism, and death in patients who resumed OAC compared to those who did not. MATERIALS AND METHODS: We searched EMBASE, MEDLINE, and the Cochrane Central Register of Controlled Trials for new references from January 2014 to September 2017. Randomized controlled trials and observational studies involving adults with OAC-related GI bleeding were included. Risk of bias was assessed using the Cochrane Collaboration's ROBINS-I tool. Pooled relative risk (RR) ratios were calculated using a random-effects model. RESULTS: We identified 12 observational studies involving 3098 patients. There was an increased risk of recurrent GI bleeding (RR 1.91, 95% CI 1.47-2.48, I2 = 0%, 11 studies), and a reduced risk of thromboembolism (RR 0.30, 95% CI 0.13-0.68, I2 = 59.8%, 9 studies) and death (RR 0.51, 95% CI 0.38-0.70, I2 = 71.8%, 8 studies) in patients who resumed OAC compared to those who did not. Eleven studies were judged to be at serious risk of bias due to confounding. CONCLUSIONS: Resuming OAC after OAC-related GI bleeding appears to be associated with an increase in recurrent GI bleeding, but a reduction in thromboembolism and death. Further prospective data are needed to identify patients for whom the net clinical benefit favours OAC resumption and the optimal timing of resumption.

McMaster RARE-Bestpractices clinical practice guideline on diagnosis and management of the catastrophic antiphospholipid syndrome.

Background The McMaster RARE-Bestpractices project group selected the catastrophic antiphospholipid syndrome (CAPS) for a pilot exercise in guideline development for a rare disease. Objectives The objectives of this exercise were to provide a proof of principle that guidelines can be developed for rare diseases and assist in clinical decision making for CAPS. Patients/Methods The GIN-McMaster Guideline Development checklist and GRADE methodology were followed throughout the guideline process. The CAPS guideline was coordinated by a steering committee, and the guideline panel was formed with representation from all relevant stakeholder groups. Systematic reviews were performed for the key questions. To supplement the published evidence, we piloted novel methods, including use of an expert-based evidence elicitation process and ad hoc analysis of registry data. Results This paper describes the CAPS guideline recommendations, including evidence appraisal and discussion of special circumstances and implementation barriers identified by the panel. Many of these recommendations are conditional, because of subgroup considerations in this heterogeneous disease, as well as variability in patient values and preferences. Conclusions The CAPS clinical practice guideline initiative met the objective of the successful development of a clinical practice guideline in a rare disease using GRADE methodology. We expect that clinicians caring for patients with suspected CAPS will find the guideline useful in assisting with diagnosis and management of this rare disease.

Audit of provincial IVIG Request Forms and efficacy documentation in four Ontario tertiary care centres.

OBJECTIVE: Retrospective audit of IVIG Request Forms in four Ontario tertiary care centres: to determine the case mix of new IVIG requests, to authenticate information provided, and to determine documentation of clinical efficacy. AIMS: To understand contributors to increases in IVIG utilisation and to determine whether IVIG is being used and monitored appropriately. INTRODUCTION: Intravenous immunoglobulin (IVIG) use in Canada is high compared with other developed countries. We performed a retrospective audit of new IVIG Request Forms across four tertiary care centres in Ontario, one with an active surveillance programme, to determine the case mix, authenticate information provided and assess documentation of efficacy. METHODS: Consecutive adult patients with a first-time IVIG request in 2014 were included. The ordering physician specialty, form completeness, documentation of diagnostic criteria for the medical condition and indication for IVIG use and documentation of efficacy were assessed by form and chart review. RESULTS: Of 178 patients, the most common indications for IVIG were immune thrombocytopenia (24.2%) and secondary immune deficiency (20.2%). The most frequent prescribers were haematologists (37.6%) and neurologists (10.7%). Other conditions not listed on the form represented 24.2% of cases, with most not indicated in current guidelines. A total of 32.6% of cases overall lacked verification of diagnostic criteria and 51.7% lacked verification for IVIG utilisation criteria, with the number of cases meeting criteria based on documentation being higher at the active surveillance site (P = 0.005). A total of 19.1% of cases had a discrepancy between the indication written on the form and the documented clinical diagnosis. A total of 18.7% of clinic notes following IVIG had no mention of efficacy. CONCLUSION: Our audit demonstrates a lack of compliance with IVIG Request Form requirements, a lack of documentation of diagnostic criteria and efficacy, and suggests inappropriate use of IVIG. Current implementation of the form may not be sufficient as a strategy for improving appropriate IVIG use.

Mortality outcomes in patients receiving direct oral anticoagulants: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Direct oral anticoagulants (DOACs) are widely used as an alternative for warfarin. However, the impact of DOACs on mortality outcomes compared with warfarin remains unclear. OBJECTIVE: To estimate the mortality outcomes in patients treated with DOACs vs. warfarin (or another vitamin K antagonist). METHODS: MEDLINE, EMBASE and CENTRAL databases (inception to September 2014), conference abstracts and www.clinicaltrials.gov, were searched, without language restriction. Studies were selected if there were phase III, randomized trials comparing DOACs with warfarin in patients with non-valvular atrial fibrillation or venous thromboembolism. RESULTS: Thirteen randomized controlled trials involving 102 707 adult patients were included in the analysis. The case-fatality rate of major bleeding was 7.57% (95% CI, 6.53-8.68; I(2) = 0%) in patients taking DOACs and 11.04% (95% CI, 9.16-13.07; I(2) = 33.3%) in patients taking warfarin. The rate of fatal bleeding in adult patients receiving DOACs was 0.16 per 100 patient-years (95% CI, 0.12-0.20; I(2) = 36.5%). When compared with warfarin, DOACs were associated with significant reductions in fatal bleeding (RR, 0.53; 95% CI, 0.43-0.64; I(2) = 0%), cardiovascular mortality (RR, 0.88; 95% CI, 0.82-0.94; I(2) = 0%) and all-cause mortality (RR, 0.91; 95% CI, 0.87-0.96; I(2) = 0%). CONCLUSIONS: The use of DOACs compared with warfarin is associated with a lower rate of fatal bleeding, case-fatality rate of major bleeding, cardiovascular mortality and all-cause mortality.

Hemodialysis for the treatment of dabigatran-associated bleeding: a case report and systematic review.

BACKGROUND: Dabigatran, a direct thrombin inhibitor, is effective for the treatment of venous thromboembolism and the prevention of stroke and systemic embolism resulting from atrial fibrillation. The most effective way of reversing the anticoagulant effect of dabigatran in patients who have bleeding complications is unknown. OBJECTIVES: To document the clinical outcomes of patients undergoing renal replacement therapy (RRT) for dabigatran-associated bleeding. METHODS: We searched MEDLINE and EMBASE up to May 2015. Articles were selected if the patients presented with dabigatran-associated bleeding, underwent RRT for dabigatran removal, and reported an effect on bleeding. RESULTS: The search yielded 22 studies representing 35 unique patient cases. The median patient age was 74.1 years (range, 56-94 years). Thirteen patients (37.1%) were female, and 32 (91.4%) patients received dabigatran for atrial fibrillation. Twenty-three patients (65.7%) underwent intermittent hemodialysis, 10 patients (28.6%) underwent continuous RRT (CRRT), and two patients underwent both intermittent hemodialysis and CRRT. Following RRT, there were significant reductions in dabigatran concentrations (P = 0.001). Rebound of the dabigatran concentration was reported in 12 (57.1%) patients following cessation of RRT. Hemostasis was reportedly achieved in 24 patients (70.6%), and 10 patients (29.4%) died because of bleeding. CONCLUSIONS: In patients with dabigatran-associated bleeding, RRT appears to be effective in reducing dabigatran concentrations, and in case reports this has been associated with a reduction in the duration and/or severity of bleeding. However, a rebound in concentrations may be seen following withdrawal of RRT, suggesting that a prolonged course of RRT may be more effective.

A systematic review of definitions and reporting of bleeding outcome measures in haemophilia.

INTRODUCTION: Bleeding frequency is an important outcome commonly used in haemophilia studies. There is a variation in practice in how bleeding is measured and defined. AIM: The primary objective of this study was to determine how investigators define and report bleeding outcome measures. METHODS: MEDLINE, EMBASE and the CENTRAL were searched from January 1990 to January 2014. We retrieved all published studies that included patients with haemophilia A or B and reported some measures of bleeding. Two reviewers independently performed title and abstract screening, full-text review and data abstraction of the identified studies. RESULTS: A total of 118 studies fulfilled the inclusion criteria. Study designs were randomized controlled trials (RCT; 14%), cohort (68%), cross-sectional (5%) and others design (11%). The median duration of follow-up (Q1, Q3) was 20 (7.9, 50) months. We found 10 different bleeding outcomes reported [absolute number of bleeding 60 (50.8%) studies, annualized bleeding rate 60 (50.8%) studies, bleed per month 10 (8.5%) studies and others 11 (9.3%) studies]. Of these, 32 (27%) studies reported only mean or median without dispersion and 33 (28%) studies did not report any measures of central tendency (dispersion). CONCLUSIONS: There is substantial variation in definitions and measures of bleeding outcomes in the haemophilia literature. This creates difficulty and limitations in comparing the outcomes between studies and in performing meta-analysis. The haemophilia research community needs to develop a consensus on a clear definition of bleeding and how to address the limitations associated with variations in measures of bleeding between centres and studies.