Fluorouracil-Induced Hyperpigmentation Schaefer, Jordan K; Ramnath, Nithya
The New England journal of medicine,
2020-Jan-23, Letnik:
382, Številka:
4
Journal Article
Although understanding of the pathogenesis and molecular biology of primary myelofibrosis continues to improve, treatment options are limited, and several biological features remain unexplained. With ...an appropriate clinical history, exam, laboratory evaluation, and bone marrow biopsy, the diagnosis can often be established. Recent studies have better characterized prognostic factors and driver mutations in myelofibrosis, facilitated by use of next-generation sequencing. These advances have facilitated development of a management strategy that is based on both risk factors and clinical phenotype. For low-risk patients, treatment will depend on symptom severity. For patients with higher-risk disease, several treatments are available including JAK inhibitors, allogeneic hematopoietic stem cell transplant, and clinical trials using novel molecularly targeted therapies and rational drug combinations. In this review, we outline what is known about the disease pathogenesis, discuss an approach to reaching the diagnosis, review the prognosis of myelofibrosis, and detail current therapeutic strategies.
Essentials
It is not clear if patients are less adherent to low molecular weight heparin (LMWH) compared to direct oral anticoagulants (DOACs) for cancer‐associated thrombosis (CAT).
We evaluated ...medication adherence among two propensity‐matched groups of patients with CAT by comparing the proportion of days covered (PDC).
Median treatment persistence on DOACs was more than 80 days longer than LMWH.
Medication adherence was high (~95%) and was similar with LMWH compared to DOACs.
Background
Low molecular weight heparin (LMWH) and direct oral anticoagulants (DOACs) are used to treat cancer‐associated thrombosis (CAT). It is not clear if patients are less adherent to LMWH compared to DOACs.
Objectives
To compare medication persistence and adherence between LMWH and DOACs.
Patients/Methods
We analyzed Optum's de‐identified Clinformatics® Data Mart Database of privately insured adults with cancer diagnosed between January 2009 and October 2015 who were undergoing chemotherapy, immunotherapy, targeted or hormonal therapies; developed CAT; and were treated with an outpatient anticoagulant. The proportion of days covered (PDC) was calculated from the date of anticoagulant prescription until the anticoagulant was switched, stopped, or the study end. Medication adherence was defined as PDC ≥ 80%, ≥95%, and by comparing the mean PDC.
Results
Two propensity‐matched groups of 1128 patients were identified. Patient persistence was higher with DOACs compared to LMWH (median 116 days versus 34 days). With adherence defined as PDC ≥ 80%, we found no significant difference (95.6% versus 94.6% adherence with DOACs versus LMWH, P = .33). The mean difference of PDC between the two groups was also similar. With medication adherence defined as PDC ≥ 95%, adherence was evident in 73% of DOAC users and 81% of patients on LMWH (P < .001). Prescription copayments were higher on average for LMWH compared to DOACs (mean $153.61 versus 40.67; standard deviation $306.74 versus $33.11).
Conclusion
Patients remain on DOACs longer than LMWH, but medication adherence is similar with LMWH.
Direct oral factor inhibitors (DOFIs) are an attractive alternative to vitamin K antagonists (VKA) for the treatment of patients with antiphospholipid syndrome (APS). In the absence of prospective, ...randomised trial data, reports of therapeutic failures in clinical practice alert clinicians to potential limitations of DOFI therapy for this indication. Data for all cases were collected from a centralised system that contains complete medical records of all patients treated and followed at Mayo Medical Center. We present here three consecutive APS patients who had had no thromboembolism recurrence on warfarin but were switched to DOFIs. The diagnosis of APS was established according to currently recommended criteria. The three cases were as follows: A woman with primary APS developed thrombotic endocarditis with symptomatic cerebral emboli after transition to dabigatran. A second woman with primary APS experienced ischemic arterial strokes and right transverse-sigmoid sinus thrombosis after conversion to rivaroxaban. A man with secondary APS suffered porto-mesenteric venous thrombosis after switching to rivaroxaban. None of these patients had failed warfarin prior to the transition to DOFIs. Based on these three cases, we advocate caution in using DOFIs for APS patients outside of a clinical trial setting, until further data becomes available.
For patients on warfarin for mechanical heart valve replacement, the 2020 American College of Cardiology and American Heart Association Guidelines recommend only adding aspirin in patients with a ...specific indication for antiplatelet therapy. This contrasts with prior guidelines, which recommended concomitant aspirin therapy. We sought to assess the prevalence of guideline-discordant aspirin use among patients on warfarin for mechanical heart valve replacement and to compare adverse event rates among patients with and without concomitant aspirin.
Patients on warfarin for mechanical heart valve replacement were identified from the Michigan Anticoagulation Quality Improvement Initiative registry. Patients with myocardial infarction, percutaneous coronary intervention, or coronary artery bypass within the past 12 months were excluded. Patients were divided into 2 groups based on aspirin use. Patient characteristics and bleeding and thromboembolic outcomes were compared.
Four hundred forty-four patients met the inclusion criteria, with 341 (76.8%) on concomitant aspirin. The aspirin group was older (50.6 vs 46.3 years, P = .028) and had more hypertension (57.8% vs 46.6%, P = .046) but other patient characteristics were similar. The aspirin group had a higher rate of bleeding events (28.3 vs 13.3 per 100 patient-years, P < .001) and bleed-related emergency department visits (11.8 vs 2.9 per 100 patient-years, P = .001) compared with the non-aspirin group. There was no observed difference in rates of ischemic stroke (0.56 vs 0.48 per 100 patient-years, P = .89).
A significant proportion of patients on warfarin for mechanical heart valve replacement are on guideline-discordant aspirin. Aspirin deprescribing in select patients may safely reduce bleeding events.
Symptoms suggestive of deep vein thrombosis (DVT) are extremely common in clinical practice, but unfortunately nonspecific. In both ambulatory and inpatient settings, clinicians are often tasked with ...evaluating these concerns. Here, we review the most recent advances in biomarkers and imaging to diagnose lower extremity DVT.
The modified Wells score remains the most supported clinical decision rule for risk stratifying patients. In uncomplicated patients, the D-dimer can be utilized with risk stratification to reasonably exclude lower extremity DVT in some patients. Although numerous biomarkers have been explored, soluble P-selectin has the most promise as a novel marker for DVT. Imaging will be required for many patients and ultrasound is the primary modality. Nuclear medicine techniques are under development, and computed tomography (CT) and magnetic resonance venography are reasonable alternatives in select patients.
D-dimer is the only clinically applied biomarker for DVT diagnosis, with soluble P-selectin a promising novel biomarker. Recent studies have identified several other potential biomarkers. Ultrasound remains the imaging modality of choice, but CT, MRI, or nuclear medicine tests can be considered in select scenarios.
The novel oral anticoagulants or direct oral anticoagulants (DOAC) are becoming more common in clinical practice for the prevention of stroke in non-valvular atrial fibrillation (NVAF). The ...availability of several agents with similar efficacy and safety for stroke prevention in NVAF patients offers more selection, but at the same time requires certain knowledge to make a good choice. This comparative analysis provides an appraisal of the respective clinical trials and highlights much of what remains unknown about four FDA-approved agents: dabigatran, apixaban, rivaroxaban, and edoxaban. It details how the DOACs compare to warfarin and to one another summarizes pharmacologic and pharmacodynamic properties, and drug interactions from the stand point of practical consequences of these findings. Common misconceptions and reservations are addressed. The practical application of this data is intended to help choosing the most appropriate agent for individual NVAF patient.
Patients with cancer are at high risk of developing arterial and venous thromboembolism (VTE). They constitute 15% to 20% of the patients diagnosed with VTE. Depending on the type of tumor, cancer ...therapy, and presence of other risk factors, 1% to 25% of patients with cancer will develop thrombosis. The decision to start patients with cancer on primary thromboprophylaxis depends on patient preference, balancing risk of bleeding versus risk of thrombosis, cost, and adequate organ function. Currently, guidelines recommend against the use of routine primary thromboprophylaxis in unselected ambulatory patients with cancer. Validated risk assessment models can accurately identify patients at highest risk for cancer-associated thrombosis (CAT). This review summarizes the recently updated NCCN Guidelines for CAT primary prophylaxis, with a primarily focus on VTE prevention. Two main clinical questions that providers commonly encounter will also be addressed: which patients with cancer should receive primary thromboprophylaxis (both surgical and medical oncology patients) and how to safely choose between different anticoagulation agents.
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