Adults with first-time nephrotic syndrome had increased risk for thromboembolic events, higher near time of diagnosis.

SOURCE CITATION: Vestergaard SV, Birn H, Darvalics B, et al. Risk of arterial thromboembolism, venous thromboembolism, and bleeding in patients with nephrotic syndrome: a population-based cohort study. Am J Med. 2022;135:615-25.e9. 34979093.

Adherence to apixaban for extended thromboprophylaxis after major abdominal or pelvic surgery for cancer: A prospective cohort study.

BACKGROUND: Due to lack of data, direct oral anticoagulants are not considered by guidelines for venous thromboembolism (VTE) prophylaxis after cancer surgery. Adherence to low-molecular-weight heparin injections in this setting is sometimes poor. AIM: Analysis of adherence to oral apixaban for extended thromboprophylaxis. METHODS: Consecutive patients discharged after major surgery for abdominal/pelvic cancer and considered eligible for extended prophylaxis were offered apixaban 2.5 mg twice daily. Primary outcomes were adherence metrics-proportion of prescriptions filled, persistence (not prematurely discontinued), proportion of days covered (PDC) based on apixaban pill counts, and modified Morisky medication adherence scale at Days 28-30. Secondary outcomes were bleeding, VTE, and serious adverse events until Day 90. RESULTS: We included 53 patients, 51 were analyzed. Of 45 patients with prescriptions all had it filled (95% confidence interval [CI], 92%-100%). Persistence was 98% (95% CI, 90%-100%). PDC was ≥80% for 48 patients (94%; 95% CI, 84%-99%). We found good adherence (0/6 answers "yes") in 75% and moderate (1/6 answers "yes") in 25%. No major bleed or VTE occurred while on apixaban. CONCLUSION: Our results support good adherence with apixaban for VTE prophylaxis up to 28 days after major abdominal or pelvic cancer surgery.

Learning From Clinical Supervisor Practice Variability: Exploring Medical Resident and Fellow Experiences and Interpretations.

PURPOSE: Clinical practice variability is characterized by 2 or more clinicians making different treatment decisions despite encountering a similar case. This study explores how medical residents and fellows experience and interpret intersupervisor clinical practice variability and how these variations influence learning. METHOD: Seventeen senior residents or fellows in internal medicine, hematology, or thrombosis medicine (postgraduate year 3 or above) participated in semistructured interviews after a clinical rotation in thrombosis medicine from December 2019 to March 2021. Data collection and analysis occurred iteratively and concurrently in a manner consistent with constructivist grounded theory. Variation theory was used to guide the development of some interview questions. A central tenet of this theory is that learning occurs by experiencing 3 sequential patterns of variation: contrast, generalization, and fusion. Participants were recruited purposively with respect to specialty until theoretical sufficiency was reached. RESULTS: Clinical practice variability was experienced by all participants. Residents and fellows attributed practice variability to intrinsic differences among supervisors; interinstitutional differences; selection and interpretation of evidence; patient preferences, priorities, and fears; and their own participation in the decision-making process. Clinical practice variability helped residents and fellows discern key features of cases that influenced decision-making (contrast), group similar cases so that the appropriate evidence could be applied (generalization), and develop attitudes consistent with providing individualized patient care (fusion). Observing practice variability was more helpful for fifth- and sixth-year residents and less helpful for third- and fourth-year residents. CONCLUSIONS: Clinical practice variability helped residents and fellows discern critical aspects, group similar patients, and practice individualized medicine. Future research should characterize how clinical practice variability influences learning across the spectrum of training, how supervisors could encourage learning from practice variability, and how curricula could be modified to allow learners greater opportunity to reflect on and consolidate the practice differences they observe.

Prothrombin complex concentrate for emergency surgery in patients on oral Xa-inhibitors.

BACKGROUND: It is uncertain whether prothrombin complex concentrate (PCC) improves hemostasis in patients on treatment with oral factor Xa-inhibitors (XaI) who require emergency surgery. OBJECTIVES: To evaluate whether, in patients with therapeutic levels of oral XaI, preoperative PCC prevents excessive bleeding during and after emergency surgery and is not associated with thrombotic complications. METHODS: We conducted a prospective cohort study wherein a fixed 2000 IU dose of 4-factor PCC was given to patients taking oral XaI with plasma XaI levels of at least 75 ng/mL before the emergency surgery with an expected blood loss of at least 50 mL. Patients were followed for 30 days. The primary efficacy outcome was the incidence of normal or mildly abnormal surgical hemostasis, as assessed by the surgeon; primary safety outcome was the incidence of thromboembolic events within 7 days. RESULTS: We included 20 patients, of which 50% were female, on apixaban (75%) or rivaroxaban (25%) with median XaI level of 128 ng/mL (range, 77-497 ng/mL). The median duration of surgery was 2 hours 42 minutes (range, 15 minutes to 8 hours 17 minutes). Normal or mildly abnormal hemostasis was observed in 16 patients (80%); 2 patients had moderately abnormal and 2 had severely abnormal hemostasis, 1 each of those was considered due to local or technical factors. There were 4 deaths (20%) secondary to underlying disease and 1 incidental pulmonary embolism in a patient with cancer. CONCLUSION: A fixed dose of PCC appears to control hemostasis in patients with therapeutic plasma levels of apixaban or rivaroxaban requiring emergency surgery.

What do hematology residents know about caring for older adults with cancer? A national survey of Canadian hematology residents' knowledge and interests.

INTRODUCTION: As the Canadian population ages, older adults comprise an increasing proportion of those diagnosed and treated for hematologic malignancies. A geriatric oncology curriculum has been recognized as a top priority in the care of older patients with cancer. It is not clear, however, whether hematology trainees receive training in geriatric oncology. We sought to understand residents' views and needs for a geriatric oncology curriculum during hematology residency in Canada. MATERIALS AND METHODS: We conducted a cross-sectional needs assessment of hematology trainees enrolled in a Canadian residency or advanced fellowship training program within hematology. The survey, which was piloted with three non-hematology residents to ensure user-friendliness, used a combination of Likert scale, multiple-choice, and open-ended questions. The survey comprised three sections: (1) demographic data, (2) current state of geriatric oncology training (amount, content) and (3) attitudes towards learning about geriatric oncology and preferred curriculum components and identified needs. The survey was administered by the study team and distributed electronically to program directors in June 2020. The program directors were asked to forward the survey to trainees registered within their Division of Hematology. Data were analyzed descriptively. RESULTS: Twenty-nine hematology residents participated (41.4% estimated response rate). Most respondents had not received geriatric oncology teaching (58.6%, n = 17) and have never been taught about geriatric oncology assessment tools (72.4%, n = 21) during hematology residency. Most respondents felt that their program should deliver a geriatric oncology curriculum (96.6%, n = 28). Respondents were most interested in learning about use of geriatric assessment tools for pre-treatment chemotherapy decision-making (86.2%, n = 25), prediction of chemotherapy toxicity (82.8%, n = 24), and to facilitate conversations regarding treatment initiation, continuation, or termination (79.3%, n = 23). DISCUSSION: Our study highlights the paucity of geriatric oncology training in hematology residency training programs. Our results highlight both the need and interest for a future dedicated geriatric oncology curriculum integrated into hematology training and provide guidance about which topics are most valued by trainees.

Direct oral anticoagulants after bariatric surgery-What is the evidence?

BACKGROUND: Obesity is a global epidemic and bariatric surgery is used with increasing frequency to treat its complications. The extent to which bariatric surgery alters the efficacy, safety, and pharmacokinetics of direct oral anticoagulants (DOACs) is unknown. AIMS: In this review, we summarize the evidence supporting the use of DOACs after bariatric surgery and apply our findings to resolve several clinical cases. MATERIALS & METHODS: We systematically searched MEDLINE, EMBASE, Cochrane Library, CINAHL and ClinicalTrials.gov from January 1, 2000, to June 15, 2021 for randomized and non-randomized studies evaluating the use of DOACs for any indication after bariatric surgery. Two reviewers independently screened titles, abstracts, and full-text articles. Clinical and pharmacokinetic outcomes were pooled by random-effects meta-analysis with inverse variance weighting. We used the Newcastle-Ottawa scale to assess risk of bias in non-randomized studies and assessed the certainty of evidence with GRADE. RESULTS: From 2519 records, we included 28 studies (n = 3229 patients): no randomized trials, 7 cohort studies, 6 case series, and 15 case reports. Incidence rates for arterial thromboembolism, venous thromboembolism and major bleeding were: 0.73 (95% confidence interval [CI]: 0.01-5.10), 2.45 (95% CI: 0.40-7.94), and 3.40 (95% CI: 0.80-9.36) events per 100 patient-years, respectively. The pooled proportion of peak direct oral anticoagulant drug levels within the expected range was 58% (95% CI: 39%-74%). CONCLUSION: There appears be substantial risk of DOAC malabsorption after bariatric surgery that could affect clinical outcomes, however the certainty of evidence was very low. PROSPERO: CRD42020202636.

Improving Medical Education in Hematology and Transfusion Medicine in Canada: Standards and Limitations.

The paradigm of medical education is evolving with the introduction of competency-based medical education (CBME) and it is crucial that residency programs adapt. In this paper, we provide an overview of the current status of medical education in Hematology in Canada including models of training, assessment methods, anticipated challenges, and the effects of the COVID-19 pandemic. We will also discuss additional training that can be pursued after a Hematology residency, with a particular focus On Transfusion Medicine as it was one of the first programs to implement a competency-based curriculum. Finally, we explore the future directions of medical education in Hematology and Transfusion Medicine.

Management of major bleeds in patients with immune thrombocytopenia.

BACKGROUND: A standard approach to the recognition and management of major bleeding in immune thrombocytopenia (ITP) is lacking. METHODS: Retrospective cohort study of ITP patients presenting to the emergency department (ED) with severe thrombocytopenia (platelet count <20 × 109 /L) and bleeding in four academic hospitals from 2008 to 2016. We defined a major ITP bleed as a bleed at a critical site or causing hemodynamic instability. RESULTS: We identified 112 ITP patients (n = 141 visits) who presented to the ED with platelets <20 × 109 /L and bleeding. Twenty--nine patients (26%) had 32 ED visits with major bleeds. Risk factors for major bleeds were older age (odds ratio [OR] 1.03, 95% confidence interval [CI] 1.01-1.06), male sex (OR 3.25, 95% CI 1.22-9.32), and more prior ITP therapies (OR 1.42, 95% CI 1.10-1.87). Acute treatment of major bleeds required a median of three treatments (interquartile range [IQR] 2--4), which included intravenous immune globulin (91% of visits), corticosteroids (78% of visits), and platelet transfusions (75% of visits). Three patients (10%) died, nine (31%) developed recurrent bleeds, one (3%) developed arterial thrombosis, and one (3%) had permanent neurological disability. Six patients presented with minor bleeding and subsequently developed a major bleed after a median of 2 days (IQR 1-3). All six patients had oral purpura and four of six had gross hematuria preceding the major bleed. CONCLUSIONS: Major ITP bleeds are associated with significant morbidity and mortality. Oral purpura and hematuria often preceded major bleeds. Further research is needed to refine the definition of a major ITP bleed and develop evidence-based treatment strategies.

First-Line Therapy for Immune Thrombocytopenia.

Immune thrombocytopenia (ITP) is an autoimmune disease affecting blood platelets that causes thrombocytopenia and an increased risk of bleeding. First-line therapy is indicated for patients with bleeding complications or who are at increased risk of bleeding, and the decision to initiate therapy depends not only on the platelet count, but also on other endpoints including quality of life. The choice of first-line therapy depends primarily on how quickly a platelet count response is required, with intravenous immune globulin providing the more rapid response, followed by high-dose dexamethasone and prednisone. In this narrative review, we discuss key issues with first-line therapy in ITP including when to initiate therapy, treatment options and special considerations for children. Evidence-based guidelines are lacking for the emergency management of patients with ITP who present with significant bleeding; we provide our approach to this critical situation.

High-dose dexamethasone compared with prednisone for previously untreated primary immune thrombocytopenia: a systematic review and meta-analysis.

BACKGROUND: Whether high-dose dexamethasone has long-term efficacy and safety in previously untreated patients with immune thrombocytopenia is unclear. We did a systematic review and a meta-analysis of randomised trials to establish the effect of high-dose dexamethasone compared with prednisone for long-term platelet count response. METHODS: We searched MEDLINE, Embase, Cumulative Index of Nursing and Allied Health Literature, and the Cochrane Library Database for papers published from 1970 to July, 2016, and abstracts from American Society of Hematology annual meetings published from 2004 to 2015 for randomised trials comparing different corticosteroid regimens for patients with previously untreated immune thrombocytopenia who achieved a platelet count response. Trials that compared corticosteroids exclusively with other interventions were excluded. The primary endpoint was overall (platelets >30 × 109/L) and complete (platelets >100 × 109/L) platelet count response at 6 months with high-dose dexamethasone compared with standard-dose prednisone. Children and adults were analysed separately. Estimates of effect were pooled with a random-effects model. FINDINGS: Nine randomised trials (n=1138) were included. Of those, five (n=533) compared one to three cycles of dexamethasone (40 mg per day for 4 days) with prednisone (1 mg per kg) for 14-28 days followed by dose tapering in adults. We found no difference in overall platelet count response at 6 months (pooled proportions 54% vs 43%, relative risk [RR] 1·16, 95% CI 0·79-1·71; p=0·44). At 14 days, overall platelet count response was higher with dexamethasone (79% vs 59%, RR 1·22, 95% CI 1·00-1·49; p=0·048). The dexamethasone group had fewer reported toxicities. Long-term response rates were similar when the data were analysed by cumulative corticosteroid dose over the course of treatment. No difference in initial platelet count response was observed with different high-dose corticosteroid regimens in children. INTERPRETATION: In adults with previously untreated immune thrombocytopenia, high-dose dexamethasone did not improve durable platelet count responses compared with standard-dose prednisone. High-dose dexamethasone might be preferred over prednisone for patients with severe immune thrombocytopenia who require a rapid rise in platelet count. FUNDING: Canadian Institutes of Health Research, and Canadian Blood Services, and Health Canada.

Inadequate documentation of urinary tract infection symptoms in the medical chart.

We evaluated symptom documentation for 312 inpatients with bacteriuria by comparing information found in the chart with that obtained prospectively from the medical and nursing team caring for the patient. There was only moderate agreement (κ = 0.55), and only 77% of symptomatic patients had any symptom documented in the chart.

A Controlled Quasi-Experimental Study of an Educational Intervention to Reduce the Unnecessary Use of Antimicrobials For Asymptomatic Bacteriuria.

BACKGROUND: Asymptomatic bacteriuria (ABU) should only be treated in cases of pregnancy or in-patients undergoing urologic procedures; however, unnecessary treatment of ABU is common in clinical practice. OBJECTIVE: To identify risk factors for unnecessary treatment and to assess the impact of an educational intervention focused on these risk factors on treatment of ABU. DESIGN: Quasi-experimental study with a control group. SETTING: Two tertiary teaching adult care hospitals. PARTICIPANTS: Consecutive patients with positive urine cultures between January 30th and April 17th, 2012 (baseline) and January 30th and April 30th, 2013 (intervention). INTERVENTION: In January 2013, a multifaceted educational intervention based on risk factors identified during the baseline period was provided to medical residents (monthly) on one clinical teaching unit (CTU) at one hospital site, with the CTU of the other hospital serving as the control. RESULTS: During the baseline period, 160/341 (46.9%) positive urine cultures were obtained from asymptomatic patients at the two hospitals, and 94/160 (58.8%) were inappropriately treated with antibiotics. Risk factors for inappropriate use included: female gender (OR 2.1, 95% CI 1.1-4.3), absence of a catheter (OR 2.5, 1.2-5), bacteriuria versus candiduria (OR 10.6, 3.8-29.4), pyuria (OR 2.0, 1.1-3.8), and positive nitrites (OR 2.2, 1.1-4.5). In 2013, only 2/24 (8%) of ABU patients were inappropriately treated on the intervention CTU as compared to 14/29 (52%) on the control CTU (OR 0.10; 95% CI 0.02-0.49). A reduction was also observed as compared to baseline on the intervention CTU (OR 0.1, 0.02-0.7) with no significant change noted on the control CTU (OR 0.47, 0.13-1.7). CONCLUSIONS: A multifaceted educational intervention geared towards medical residents with a focus on identified risk factors for inappropriate management of ABU was effective in reducing unnecessary antibiotic use.