Abstract Background Dose reduction of non–vitamin K antagonist oral anticoagulants (NOACs) is indicated in patients with atrial fibrillation (AF) with renal impairment. Failure to reduce the dose in ...patients with severe kidney disease may increase bleeding risk, whereas dose reductions without a firm indication may decrease the effectiveness of stroke prevention. Objectives The goal of this study was to investigate NOAC dosing patterns and associated outcomes, i.e., stroke (ischemic stroke and systemic embolism) and major bleeding in patients treated in routine clinical practice. Methods Using a large U.S. administrative database, 14,865 patients with AF were identified who initiated apixaban, dabigatran, or rivaroxaban between October 1, 2010, and September 30, 2015. We examined use of a standard dose in patients with a renal indication for dose reduction (potential overdosing) and use of a reduced dose when the renal indication is not present (potential underdosing). Cox proportional hazards regression was performed in propensity score–matched cohorts to investigate the outcomes. Results Among the 1,473 patients with a renal indication for dose reduction, 43.0% were potentially overdosed, which was associated with a higher risk of major bleeding (hazard ratio: 2.19; 95% confidence interval: 1.07 to 4.46) but no statistically significant difference in stroke (3 NOACs pooled). Among the 13,392 patients with no renal indication for dose reduction, 13.3% were potentially underdosed. This underdosing was associated with a higher risk of stroke (hazard ratio: 4.87; 95% confidence interval: 1.30 to 18.26) but no statistically significant difference in major bleeding in apixaban-treated patients. There were no statistically significant relationships in dabigatran- or rivaroxaban-treated patients without a renal indication. Conclusions In routine clinical practice, prescribed NOAC doses are often inconsistent with drug labeling. These prescribing patterns may be associated with worse safety with no benefit in effectiveness in patients with severe kidney disease and worse effectiveness with no benefit in safety in apixaban-treated patients with normal or mildly impaired renal function.
Abstract Background Oral anticoagulation (OAC) with warfarin is underused for atrial fibrillation (AF). The availability of direct oral anticoagulants (DOACs) may improve overall OAC rates in AF ...patients, but a large-scale evaluation of their effects has not been conducted. Objectives This study assessed the effect of DOAC availability on overall OAC rates for nonvalvular AF. Methods Between April 1, 2008 and September 30, 2014, we identified 655,000 patients with nonvalvular AF and a CHA2 DS2 -VASc score of >1 in the National Cardiovascular Data Registry PINNACLE registry. Temporal trends in overall OAC and individual warfarin and DOAC use were analyzed. Multivariable hierarchical logistic regression identified patient factors associated with OAC and DOAC use. Practice variation of OAC and DOAC use was also assessed. Results Overall OAC rates increased from 52.4% to 60.7% among eligible AF patients (p for trend <0.01). Warfarin use decreased from 52.4% to 34.8% (p for trend <0.01), and DOAC use increased from 0% to 25.8% (p for trend <0.01). An increasing CHA2 DS2 -VASc score was associated with higher OAC use (odds ratio OR: 1.06; 95% confidence interval CI: 1.05 to 1.07), but with lower DOAC use (OR: 0.97; 95% CI: 0.96 to 0.98). Significant practice variation was present in OAC use (median odds ratio MOR: 1.52; 95% CI: 1.45 to 1.57) and in DOAC use (MOR: 3.58; 95% CI: 3.05 to 4.13). Conclusions Introduction of DOACs in routine practice was associated with improved rates of overall OAC use for AF, but significant gaps remain. In addition, there is significant practice-level variation in OAC and DOAC use.
Shah et al explore the routine use of electronic health records (EHRs) in hospitals, health systems, and physician practices. They note the rapid growth in the availability of health care data over ...the last decade. In addition to the structured data in EHRs, new methods such as natural language processing can derive meaning from unstructured data, permitting the capture of substantial clinical information embedded in clinical notes. Furthermore, the growth in the availability of registries and claims data and the linkages between all these data sources have created a big data platform in health care, vast in both size and scope. They believe that tese developments underscore the need for rigorous studies that evaluate the effects of prediction models on health care decisions and patient outcomes, including cost and quality of care.
Neuroblastoma (NBL) is an embryonal malignancy of childhood with poor outcomes for patient with high-risk disease. Multimodal treatment approaches have improved outcomes but at the cost of ...significant toxicity, and there is no durable therapeutic approach for relapsed disease. As NBL has no singular oncogenic driver, targeted therapeutic options have been limited. Galinski et al report the results of a proteomic screen of neuroblastomas and identify the nuclear export protein XPO1 as a protein that is preferentially expressed and located in neuroblast nuclei. XPO1 overexpression is associated with nuclear export of IκB and increased NF-κB activity, both of which can be abrogated in NBL cell lines with the XPO1 inhibitor Selinexor with or without the proteasome inhibitor bortezomib. This work highlights new strategies for therapeutic target identification and the novel identification of nuclear export as a targetable oncogenic pathway across malignancies.
This cohort study compares rates at which patients with type 2 diabetes received diabetes-related health services prior to and during the COVID-19 pandemic.
Background The introduction of non-vitamin K antagonist oral anticoagulants (NOACs) has been a major advance for stroke prevention in atrial fibrillation (AF). Patients and clinicians now have a ...choice between different NOACs, but there is no direct comparative effectiveness evidence to guide decision-making. We aimed to compare the effectiveness and safety of dabigatran, rivaroxaban, and apixaban in clinical practice. Methods Using a large US administrative claims database, we created three one-to-one propensity-score-matched cohorts of patients with nonvalvular AF who were users of dabigatran, rivaroxaban, or apixaban between October 1, 2010 and February 28, 2015 (rivaroxaban vs dabigatran, n = 31,574; apixaban vs dabigatran, n = 13,084; and apixaban vs rivaroxaban, n = 13,130). The primary outcomes were stroke and systemic embolism (effectiveness) and major bleeding (safety) that occurred during treatment. Cox proportional hazards models were used to compare outcomes in propensity-score-matched cohorts. Results We found no differences between the three NOACs in the risk of stroke or systemic embolism (hazard ratio HR, 1.00; 95% CI, 0.75-1.32 for rivaroxaban vs dabigatran; HR, 0.82; 95% CI, 0.51-1.31 for apixaban vs dabigatran; and HR, 1.05; 95% CI, 0.64-1.72 for apixaban vs rivaroxaban). Apixaban was associated with a lower risk of major bleeding (HR, 0.50; 95% CI, 0.36-0.70; P < .001 vs dabigatran and HR, 0.39; 95% CI, 0.28-0.54; P < .001 vs rivaroxaban). Rivaroxaban was associated with an increased risk of major bleeding (HR, 1.30; 95% CI, 1.10-1.53; P < .01) and intracranial bleeding (HR, 1.79; 95% CI, 1.12-2.86; P < .05) compared with dabigatran. Conclusions Dabigatran, rivaroxaban, and apixaban appear to have similar effectiveness, although apixaban may be associated with a lower bleeding risk and rivaroxaban may be associated with an elevated bleeding risk.
Donor lymphocyte infusion (DLI) is an important treatment modality in the management of relapsed hematological malignancies after allogeneic hematopoietic cell transplantation (allo-HCT). Donor T ...lymphocytes can be used in a therapeutic, pre-emptive or prophylactic manner in an attempt to stimulate a graft versus leukemia (GVL) effect and eradicate residual disease or even prevent relapse in a high-risk setting. DLIs are not without complications, however, graft versus host disease (GVHD) in particular. Data to date is limited to retrospective and small prospective studies. This review summarizes the available literature on approaches to managing relapse, dosing and timing of DLI, complications and potential future therapies.
Osteoporosis Choice, an encounter decision aid, can engage patients and clinicians in shared decision making about osteoporosis treatment. Its effectiveness compared to the routine provision to ...clinicians of the patient's estimated risk of fracture using the FRAX calculator is unknown.
Patient-level, randomized, three-arm trial enrolling women over 50 with osteopenia or osteoporosis eligible for treatment with bisphosphonates, where the use of Osteoporosis Choice was compared to FRAX only and to usual care to determine impact on patient knowledge, decisional conflict, involvement in the decision-making process, decision to start and adherence to bisphosphonates.
We enrolled 79 women in the three arms. Because FRAX estimation alone and usual care produced similar results, we grouped them for analysis. Compared to these, use of Osteoporosis Choice increased patient knowledge (median score 6 vs. 4, p = .01), improved understanding of fracture risk and risk reduction with bisphosphonates (p = .01 and p<.0001, respectively), had no effect on decision conflict, and increased patient engagement in the decision making process (OPTION scores 57% vs. 43%, p = .001). Encounters with the decision aid were 0.8 minutes longer (range: 33 minutes shorter to 3.0 minutes longer). There were twice as many patients receiving and filling prescriptions in the decision aid arm (83% vs. 40%, p = .07); medication adherence at 6 months was no different across arms.
Supporting both patients and clinicians during the clinical encounter with the Osteoporosis Choice decision aid efficiently improves treatment decision making when compared to usual care with or without clinical decision support with FRAX results.
clinical trials.gov NCT00949611.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background & Aims Direct oral anticoagulant (DOAC) agents increase the risk of gastrointestinal (GI) bleeding. We investigated which DOAC had the most favorable GI safety profile and compared ...differences among these drugs in age-related risk of GI bleeding. Methods We conducted a retrospective, propensity-matched study using administrative claims data from the OptumLabs Data Warehouse of privately insured individuals and Medicare Advantage enrollees. We created 3 propensity-matched cohorts of patients with nonvalve atrial fibrillation with incident exposure to dabigatran, rivaroxaban, or apixaban from October 1, 2010 through February 28, 2015. We compared data on rivaroxaban vs dabigatran for 31,574 patients, data on apixaban vs dabigatran for 13,084 patients, and data on apixaban vs rivaroxaban for 13,130 patients. Cox proportional hazards models, stratified by age, were used to estimate rates of total GI bleeding. Results Baseline characteristics were well balanced among sub-cohorts. GI bleeding occurred more frequently in patients given rivaroxaban than dabigatran (hazard ratio HR, 1.20; 95% confidence interval CI, 1.00−1.45). Apixaban was associated with a lower risk of GI bleeding than dabigatran (HR, 0.39; 95% CI, 0.27−0.58; P < .001) or rivaroxaban (HR, 0.33; 95% CI, 0.22−0.49; P < .001). Rates of events for all DOACs increased among patients 75 years or older. Apixaban had a lower risk of association with GI bleeding in the very elderly than dabigatran (HR, 0.45; 95% CI, 0.29−0.71) or rivaroxaban (HR, 0.39; 95% CI, 0.25−0.61). Median times to GI bleeding were <90 days for apixaban and rivaroxaban and <120 days for dabigatran. Conclusions In a population-based study of patients receiving DOAC agents, we found apixaban had the most favorable GI safety profile and rivaroxaban least favorable. GI bleeding events among patient taking DOACs increased with age; the risk was greatest among persons ersons as old. Apixaban had the most favorable GI safety profile among all age groups.
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