Reasons for discontinuation of novel oral anticoagulant therapy in patients with atrial fibrillation

Aims: We sought to investigate the reasons for, and rates of, novel oral anticoagulant (DOAC) therapy discontinuation.Methods: This was an observational cohort study of patients with atrial fibrillation (AF) referred to a regional DOAC outpatient clinic between February 2013 and October 2017. The study population consisted of 875 consecutive patients with AF who visited the DOAC outpatient unit to initiate treatment with apixaban (N = 303), dabigatran (N = 267) or rivaroxaban (N = 305) for long-term ischemic stroke prophylaxis. All the patients came from the Leeuwarden Medical Center cardiology outpatient clinic, which offers a well structured and nurse-run DOAC unit in cooperation with the hospital's thrombosis service. This clinic operates according to the Dutch nationwide guidelines on integration of anticoagulation services.Results: Overall rate of discontinuation was 11.9 per 100 patient-years of follow-up. Discontinuation rates for apixaban, dabigatran and rivaroxaban were 8.1, 16.6 and 11.5 per 100 patient-years of follow-up.Apixaban had the lowest rate of discontinuation during the 36 month follow-up period. Dabigatran and rivaroxaban had high discontinuation rates during the 3-6 month period following DOAC therapy initiation. The main reasons for discontinuation of DOAC therapy were adverse side effects, patient-initiated discontinuation and any bleed.Limitation: This was a retrospective and non-randomized study, and our results should be interpreted in light of these observations.Conclusion: DOAC discontinuation rates varied significantly and appeared related to drug-specific side effects, patient-initiated discontinuation and bleeding. We observed longer-term administration of apixaban, suggesting that this drug is better tolerated than dabigatran or rivaroxaban

Minor bleeding in patients with atrial fibrillation using a non-vitamin K antagonist oral anticoagulant

Aims: We sought to investigate the magnitude of minor bleeding and identify risk factors for minor bleeds during non-vitamin K antagonist oral anticoagulant (NOAC) therapy.Methods: This was an observational cohort study of patients with atrial fibrillation (AF) referred to a regional NOAC outpatient clinic between February 2013 and October 2017. The study population consisted of 875 consecutive patients with AF who visited the NOAC outpatient unit to initiate treatment with apixaban (N = 303), dabigatran (N = 267) or rivaroxaban (N = 305) for long-term ischemic stroke prophylaxis. Minor bleed was defined as every overt bleeding that does not fulfil the criteria of major or non-major clinically relevant bleeding according to the International Society on Thrombosis and Haemostasis.Results: Overall rate of minor bleeds was 19.2 per 100 patient years of follow up. Bleeding rates for apixaban, dabigatran and rivaroxaban were 26, 8.3 and 23 per 100 patient-years of follow-up. Next to the type of NOAC, the main risk indicators for minor bleedings during NOAC therapy were a HAS-BLED score of 3 or higher and novel anticoagulant use (no history of vitamin K antagonist use).Limitation: This was a retrospective observational study evaluating NOAC treatment in a non-randomized setting.Conclusion: Our data showed that minor bleeds are common in novel NOAC users, especially when using apixaban and rivaroxaban. In the latter two NOACs, hematoma (bruises) and nose bleeds were more frequently observed and accounted for the difference with dabigatran. Besides type of NOAC, a higher HAS-BLED score and novel anticoagulant drug use were associated with an increased risk of minor bleeding

Observational study of administering intranasal steroid sprays by healthcare workers

OBJECTIVES: Patients with allergic rhinitis receive their information about administering intranasal corticosteroid sprays (INCS) from healthcare workers. Since the majority of patients does not administer these sprays correctly, we investigated whether healthcare workers know how to administer INCS. SETTINGS: We studied participants at their working place: pharmacy, outpatient clinic or general practitioner centre for emergencies. PARTICIPANTS: Pharmacist assistants, general practitioners, paediatricians and ear nose throat doctors. DESIGN: Observational study. All the participants demonstrated the administration technique with a spray device filled with water. PRIMARY OUTCOME: Number of steps of administration of INCS based on the established INCS protocol. SECONDARY OUTCOME: Number of five steps are labelled essential to obtain optimal distribution of the medication. RESULTS: Among the 75 participants, none performed all the steps correctly. The median of correctly performed steps in the protocol was 14 out of 29. A significantly better result was found among the pharmacist assistants. The essential steps were performed by 27 out of the 75 participants (36%). CONCLUSION: The majority of healthcare workers does not know how to administer INCS correctly. Patients could, therefore, receive incorrect and non-uniform instructions. The education of healthcare workers on how to administer INCS correctly may be an option for improvement

Patterns of transfusion burden in an unselected population of patients with myelodysplastic syndromes:A population-based study

BACKGROUND: Ineffective hematopoiesis in patients with myelodysplastic syndromes (MDS) often results in transfusion dependence. The burden of frequent transfusions in the real-world MDS population is largely unknown.STUDY DESIGN AND METHODS: An observational, retrospective, population-based study, using the HemoBase registry, was performed including all patients diagnosed with MDS between 2005 and 2017 in Friesland, a province in the Netherlands with approximately 650,000 inhabitants. Detailed clinical information was collected from the electronic health records. Transfusion burden was classified according to the International Working Group 2018 criteria: not transfusion dependent, low (LTB), or high transfusion burden (HTB). Univariate and multivariable regression analyses were performed.RESULTS: Of 292 patients, 136 (46.6%) had a HTB of ≥8 units/16 weeks and 17 (5.8%) had a LTB of 3-7 units/16 weeks. This was present in all types of MDS patients, but patients aged 75-84 years (odds ratio [OR] 4.02, 95% confidence interval [CI]: 1.84-8.82), high-risk MDS patients (OR 2.88, 95% CI: 1.08-7.68) and MDS-EB-2 patients (OR 7.07, 95% CI: 2.17-22.90) were particularly at risk for a HTB.DISCUSSION: This study provides a reliable estimate of the transfusion burden in real-world MDS patients, with almost half of the patients having a HTB. A HTB was observed in all MDS subtypes and both low- and high-risk MDS. Therefore, we conclude that the entire MDS population might benefit from novel agents that reduce the transfusion need and that might have beneficial effects on patient outcomes and healthcare utilization outcomes.</p

Costs of minor bleeds in atrial fibrillation patients using a non-vitamin K antagonist oral anticoagulant

BACKGROUND: A very common side effect of non-vitamin K antagonist oral anticoagulant (NOAC) is (minor) bleeding. Data about impact and costs of minor bleeds in NOAC therapy is still limited or not present in current literature. In this patient orientated study, we aim to provide an estimate of the costs of minor bleeds in patients with atrial fibrillation (AF) treated with a NOAC. METHODS: A retrospective observational cohort study was conducted. Patients with AF and on NOAC therapy were included. Data was obtained by questionnaires and information from electronic patient records. Reference prices were used to calculate the costs per patient. Furthermore, cost of minor bleeds per patient is compared with literature-based costs of minor and major bleeding. RESULTS: 139 patients were included. A total of 94 minor bleed were reported by 71 patients. The sum of minor bleeding costs from societal perspective were €9,851.49, or on average €70,87 (95% CI €54,37 - €85,68) per patient with AF. The biggest cost drivers were rectal and vaginal bleeds, epistaxis was most commonly reported. CONCLUSION: Total costs of minor bleeds from a societal perspective, in AF patients using NOACs, are non trivial and exceed the costs presented in existing literature

Comorbidities and malignancies negatively affect survival in myelodysplastic syndromes:A population-based study

Population-based studies that contain detailed clinical data on patients with myelodysplastic syndrome (MDS) are scarce. This study focused on the real-world overall survival (OS) of MDS patients in association with comorbidities, specifically malignancies. An observational population-based study using the HemoBase registry was performed, including all patients with MDS diagnosed between 2005 and 2017 in Friesland, a Dutch province. Detailed information about diagnosis, patient characteristics, previous treatment of malignancies, and comorbidities according to the Charlson Comorbidity Index (CCI) was collected from electronic health records. Patients were followed up until June 2019. Kaplan-Meier plots and Cox regression analyses were used to study survival differences. In the 291 patients diagnosed with MDS, the median OS was 25.3 months (95% confidence interval [CI], 20.3-30.2). OS was significantly better for patients with CCI score <4, age <65 years, female sex, and low-risk MDS. Fifty-seven patients (20%) had encountered a prior malignancy (excluding nonmelanoma skin cancer), and a majority (38 patients; 67%) were therapy related. Both therapy-related and secondary MDSs were associated with worse OS (hazard ratio, 1.51; 95% CI, 1.02-2.23 and 1.58; 95% CI, 0.95-2.65, respectively), as compared with de novo MDS patients (P = .04). Patients in remission at time of MDS diagnosis had a similar median OS compared with patients with de novo MDS (25.5 vs 28.3 months). This population-based study involving all newly diagnosed MDS patients over a 13-year period in Friesland showed that multiple comorbidities, including previous malignancies, are associated with shorter OS. OS was not related to the use of radiotherapy or chemotherapy

Management of infection prophylaxis in Dutch patients with myelodysplastic syndromes, a web-based case vignette questionnaire:the MINDSET study

OBJECTIVES: Infections are a major cause of morbidity and mortality in patients with myelodysplastic syndromes (MDS). The objective of the MINDSET study was to evaluate haematologists' management of infection prevention in MDS patients using a case vignette study and to assess the availability of guidelines. METHODS: We conducted a web-based, nationwide survey amongst haematologists in the Netherlands between September and December 2021. The survey included a set of case vignettes. Additionally, the availability of protocols was evaluated. RESULTS: Sixty responses were obtained (23.6%). These responses were well distributed across hospital types as well as level of experience. No protocols regarding infection prophylaxis specifically for MDS patients were received. In the case vignette of a 75-year-old MDS patient, respondents would primarily prescribe infection prophylaxis in case of recurrent infections (96.7%) and neutropenia (75.0% for absolute neutrophil count [ANC]<0.2x10^9/L and 53.3% for ANC<0.5x10^9/L), especially in combination with hypomethylating agents (80.0%), lenalidomide (66.7%) or chemotherapy (51.7%). Respondents would predominantly choose antibacterial agents (85.0%), followed by antifungal agents (71.7%). CONCLUSIONS: This study showed diverse reasons and considerations of haematologists regarding whether to prescribe infection prophylaxis in MDS patients. Given the seriousness of infections in MDS patients, patient-tailored recommendations might be valuable in clinical decision-making. This article is protected by copyright. All rights reserved

Proton-pump inhibitors are associated with a reduced risk for bleeding and perforated gastroduodenal ulcers attributable to non-steroidal anti-inflammatory drugs: a nested case-control study

Treatment with non-steroidal anti-inflammatory drugs (NSAIDs) is hampered by gastrointestinal ulcer complications, such as ulcer bleeding and perforation. The efficacy of proton-pump inhibitors in the primary prevention of ulcer complications arising from the use of NSAIDs remains unproven. Selective cyclooxygenase-2 (COX-2) inhibitors reduce the risk for ulcer complications, but not completely in high-risk patients. This study determines which patients are especially at risk for NSAID ulcer complications and investigates the effectiveness of different preventive strategies in daily clinical practice. With the use of a nested case-control design, a large cohort of NSAID users was followed for 26 months. Cases were patients with NSAID ulcer complications necessitating hospitalisation; matched controls were selected from the remaining cohort of NSAID users who did not have NSAID ulcer complications. During the observational period, 104 incident cases were identified from a cohort of 51,903 NSAID users with 10,402 patient years of NSAID exposure (incidence 1% per year of NSAID use, age at diagnosis 70.4 ± 16.7 years (mean ± SD), 55.8% women), and 284 matched controls. Cases were characterised by serious, especially cardiovascular, co-morbidity. In-hospital mortality associated with NSAID ulcer complications was 10.6% (incidence 21.2 per 100,000 NSAID users). Concomitant proton-pump inhibitors (but not selective COX-2 inhibitors) were associated with a reduced risk for NSAID ulcer complications (the adjusted odds ratio 0.33; 95% confidence interval 0.17 to 0.67; p = 0.002). Especially at risk for NSAID ulcer complications are elderly patients with cardiovascular co-morbidity. Proton-pump inhibitors are associated with a reduced risk for NSAID ulcer complications

Administration of benralizumab in a patient with severe asthma admitted to the intensive care unit with COVID-19 pneumonia:Case report

A patient with severe asthma on benralizumab therapy was admitted to the intensive care unit (ICU) for a coronavirus disease 2019 (COVID-19) infection. At the end of the 8 week benralizumab dosing interval, discussion arose as to whether benralizumab should be administered or if treatment should be discontinued, due to the lack of experience with benralizumab in this situation. Severe broncho-obstruction developed, and the next injection of benralizumab was administered during ICU admission without detrimental symptoms. With this case report, we would like to share our experience with the safe administration of benralizumab during COVID-19 pneumonia, guiding doctors in future decision making