Citations

Background Non–vitamin K antagonist oral anticoagulants (NOACs) are indicated for stroke prevention in atrial fibrillation (AF) but require lower doses in certain patients. We sought to describe the frequency, appropriateness (according to Food and Drug Administration labeling), and outcomes of patients prescribed reduced doses of NOACs in community practice. Methods and Results We analyzed data from the ORBIT‐AF II (The Outcomes Registry for Better Informed Treatment of Atrial Fibrillation II) registry, a prospective, national, observational registry of AF patients. Among 7925 AF patients receiving NOACs, we assessed patterns of use of reduced NOAC doses and associated cardiovascular and bleeding outcomes at median follow‐up of 1 year. Overall, 6636 patients (84%) received a NOAC at standard dose, which was consistent with US Food and Drug Administration labeling in 6376 (96%). Reduced NOAC dose was prescribed to 1289 (16% overall), which was consistent with Food and Drug Administration labeling in only 555 patients (43%). Compared with those whose NOAC dose was appropriately reduced, patients receiving inappropriate dose reductions were younger (median age 79 versus 84, P <0.0001) and had lower ORBIT bleeding risk scores (26% ≥4 versus 45%, P <0.0001). Compared with those appropriately receiving standard dosing, patients receiving inappropriately reduced‐dose NOACs had higher unadjusted rates of thromboembolic events (2.11 versus 1.35 events per 100 patient years, hazard ratio 1.56, 95% confidence interval 0.92‐2.67) and death (6.77 versus 2.60, hazard ratio 2.61, 95% confidence interval 1.86‐3.67). After adjustment, outcomes were not significantly different but tended to favor patients dosed appropriately. Conclusions The majority of dose reductions of NOACs in AF are inconsistent with US Food and Drug Administration recommendations. There appear to be opportunities to improve current NOAC dosing in community practice. Clinical Trial Registration URL: http://www.clinicaltrials.gov . Unique identifier: NCT01701817.

While superficial (cutaneous/subcutaneous) solitary fibrous tumor (SFT) have been described, definitive diagnosis is difficult due to overlapping features with other tumors. We describe the largest series to date of superficial SFT. For inclusion, SFT had to arise in dermis or subcutis. Twenty-six cases were identified. Patients ranged from 16 to 80 years (mean, 47 y) with a marked female predominance (19 F; 7 M). Tumors involved the head (11), thigh (7), back (3), shoulder (2), upper arm (1), ankle (1), and great toe (1). Mean size was 2.9 cm (range, 1.0 to 7.0 cm). The majority (n=19) had typical histologic features (cellular SFT) with irregular fascicles of spindled cells, staghorn-like blood vessels, and variable amounts of collagen. Necrosis was evident in 3 cases (all <25%). Mitotic activity ranged from 0 to 10 mitotic figures/10 high-power fields (mean, 2 mitotic figures/10 high-power fields). Seventeen of the 18 were positive for STAT6, whereas 21/22 expressed CD34. All were low risk (23/23) by proposed criteria (Demicco and colleagues), including 2 cases with malignant histology. Three could not be risk stratified due to lack of information on tumor size. Follow-up, available on 7 cases, showed no recurrence/metastasis (mean follow-up, 100 mo; range, 2 to 241 mo). Cutaneous SFT are more common in women and most often involve the head. They are usually low risk by proposed criteria and appear to behave in an indolent manner, though larger studies are needed to confirm this. Recognition that SFT may present as a superficial mass will avoid misclassification as other CD34-positive neoplasms that frequently arise in the skin and subcutaneous tissue.

Background. There is little published literature regarding the impact of age on outcomes amongst hospitalized HHT (hereditary hemorrhagic telangiectasia) patients. Methods. The Nationwide Inpatient Sample (NIS) was used to obtain data on all hospital discharges occurring in HHT patients from 2000 to 2012. The association between admission age and HHT-related complications and outcomes were studied. Results. 10293 hospitalizations in HHT patients from 2000 to 2012 were included. Patients > 50 accounted for 77% of all admissions with 30% of admissions occurring in the 51–65 age group. Bleeding related complications were the most frequent (62.7%, n=6455 hospitalizations), followed by cardiovascular (41%, n=4216), neurological (12.4%, n=1276), and hepatobiliary (6.4%, n=660) complications. Patients older than 50 accounted for 83% of bleeding events, 90% of cardiovascular events, 58% of neurologic events, and 81% of hepatobiliary events. The vast majority (83%) of medical and surgical procedures were performed in those older than 50 years of age. Older patients also experienced higher rates of death. Conclusion. Aging has significant adverse impacts on rates of hospitalization, complications, and outcomes amongst HHT patients in the United States. Except for neurologic complications, the vast majority of this disease burden is borne by patients older than 50 years.

Abstract Background Celecoxib and low-dose aspirin might decrease risk of breast cancer recurrence. Methods In the Canadian Cancer Trials Group MA.27, postmenopausal hormone receptor–positive breast cancer patients were randomly assigned (2 × 2) to adjuvant exemestane or anastrozole, and celecoxib or placebo. Low-dose aspirin of 81 mg or less was a stratification factor. Due to concerns about cardiac toxicity, celecoxib use was stopped in December 2004, while stratification by aspirin use was removed through protocol amendment. We examined the effects of celecoxib and low-dose aspirin on event-free survival (EFS), defined as time from random assignment to time of locoregional or distant disease recurrence, new primary breast cancer, or death from any cause; distant disease–free survival (DDFS); and overall survival (OS). All statistical tests were two-sided. Results Random assignment to celecoxib (n = 811, 50.0%) or placebo (n = 811, 50.0%) was discontinued after 18 months (n = 1622). At a median of 4.1 years’ follow-up, among 1622 patients, 186 (11.5%) patients had an EFS event: 80 (4.9%) had distant relapse, and 125 (7.7%) died from any cause. Celecoxib did not statistically significantly impact EFS, DDFS, or OS in univariate analysis (respectively, P = .92, P = .55, and P = .56) or multivariable analysis (respectively, P = .74, P = .60, and P = .76). Low-dose aspirin use (aspirin users n = 476, 21.5%; non–aspirin users n = 1733, 78.5%) was associated in univariate analyses with worse EFS (hazard ratio [HR] = 1.48, 95% confidence interval [CI] = 1.12 to 1.96, P = 0.006) and worse OS (HR = 1.87, 95% CI = 1.35 to 2.61, P < .001). After adjusting for baseline characteristics and treatment arm, aspirin use showed no statistical association with EFS (P = .08) and DDFS (P = .82), but was associated with statistically worse OS (HR = 1.67, 95% CI = 1.13 to 2.49, P = .01). Conclusion Random assignment to short-term (≤18 months) celecoxib as well as use of low-dose aspirin showed no effect on DDFS and EFS in multivariable analysis. Low-dose aspirin increased “all-cause” mortality, presumably because of higher preexisting cardiovascular risks.

Abstract We have identified a new eosinophil major basic protein gene family member in the mouse and have given it the designation murine major basic protein-2 (mMBP-2). The gene was initially characterized as a unique expressed sequence tag (EST) clone having significant identity to the previously recognized member of this gene family, mMBP-1. The EST was used to screen and isolate mMBP-2 from a bone marrow cDNA library. In addition, a genomic clone of mMBP-2 was isolated and this gene was shown to be physically linked to within 100 kb of mMBP-1 on the central region of mouse chromosome 2. Progressive similarity alignment of the deduced mMBP-2 open reading frame demonstrates the apparent conservation of the “pre-pro-mature” protein structure found in the other known mammalian MBPs. Mature mMBP-2 maintains the cationic nature associated with these proteins with a predicted pI of 9.95. However, unlike the human MBPs, which display a three orders of magnitude charge difference [hMBP-1 (pI11.4) vs. hMBP-2 (pI8.7)], mMBP-2 is only slightly less cationic than mMBP-1 (pI 10.5). Expression studies demonstrate that transcription of the mMBP-2 gene parallels mMBP-1 and is confined to hematopoietic compartments engaged in eosinophilopoiesis. Moreover, using mMBP-1 knockout mice and immunohistochemistry with an antisera that recognizes both mMBP-1 and -2, we demonstrate that mMBP-2 protein expression is restricted to eosinophil lineage-committed cells. J. Leukoc. Biol. 67: 567–576; 2000.

We aimed to study cost-effectiveness of seizure evaluation of children with epilepsy in the emergency department (ED). We reviewed epilepsy patients seen at our ED for 1 year. Age, laboratory and neuroimaging results, treatment, disposition, and usefulness of the visit (need for hospitalization, clinical improvement) were analyzed. We identified 330 patients, aged 23 days–21 years, 190 (57.5%) had blood tests, 45 (13.6%) urinalysis, 2 (0.6%) cerebrospinal fluid testing, and 44 neuroimaging studies (13.3%). Tests’ positive yield were 41%, 11%, 0%, and 4.5%, respectively. One-third of patients (n = 122) were treated with antiepileptic drugs. Other treatments were administered to 44 (13.3%). One hundred eighteen patients (35.7%) were admitted to our hospital, 208 (63%) discharged to home. Two hundred eight visits were useful (63%). One-third of visits did not provide useful patient care. Their visits were expensive and not very cost-effective. Investment in patient education could decrease unnecessary ED visits.