Monoclonal antibodies (mAbs) targeting calcitonin gene‐related peptide (CGRP) signaling are being explored as prophylactic treatments for migraine. Erenumab (AMG 334) is the first potent, selective, and competitive human mAb antagonist of CGRP receptor. We report data from two phase I studies assessing safety, pharmacokinetics (PK), pharmacodynamics single multiple administrations erenumab in healthy subjects patients with The results indicate that PK profile nonlinear 1 mg to 70 linear...

Capsaicin-induced dermal blood flow (CIDBF) is a validated biomarker used to evaluate the target engagement of potential calcitonin gene-related peptide-blocking therapeutics for migraine. To characterize pharmacokinetics (PK) and quantify inhibitory effects erenumab (AMG 334) on CIDBF, CIDBF data were pooled from single- multiple-dose study in healthy migraine subjects. Repeated capsaicin challenges DBF measurements performed serum concentrations determined. A population analysis was...

In the setting of breast cancer screening, 5-9% needle core biopsies are diagnosed as lesions uncertain malignant potential (B3). The management these is potentially problematic data on their outcome remains limited. our study, we aim to assess screen-detected B3 in a large series validate previous studies and characterize detected after diagnosis. Therefore, results 1,025 women screened over 7-year period (1999-2006) two different regions UK with diagnoses who underwent surgical excision...

Gaining full benefits from osteoporosis medications requires long-term treatment. Investigating the real-world persistence of women receiving in UK, we found that most patients stop treatment within a year. To prevent osteoporotic fragility fractures, must be improved. Persistence with therapies has historically been poor. treat this chronic and progressive disease, it is essential receive benefit these medications. We estimated compliance large sample postmenopausal UK. Data were obtained...

To provide updated evidence of the outcome breast lesions uncertain malignant potential (B3) and suspicious malignancy (B4) diagnosed on needle core biopsy (NCB) analyse different types intraductal epithelial atypia.One-hundred forty-nine B3 26 B4 NCBs over a 2-year period (2007-2008) were compared with those previous (1998-2000). The proportion diagnoses increased from 3.1% to 4.5%, positive predictive value (PPV) decreased 25% 10%. Increased diagnosis radial scar reductions in PPV lobular...

Abstract Ectopic varices are defined as portosystemic venous collaterals occurring in the gastrointestinal tract outside of cardio‐esophageal region. Duodenal not routinely encountered by pediatric gastroenterologists. At time this case report, there no consensus guidelines on management bleeding duodenal patients. This is a 14‐year‐old young woman with history multi‐visceral transplantation due to short gut syndrome. The patient had developed near her transplant anastomosis, which were...

Introduction:The aim was to compare the accuracy of standard supplementary views and GE digital breast tomosynthesis (DBT) for assessment soft tissue mammographic abnormalities.Methods: Women recalled further abnormalities were recruited received (typically spot compression views) two-view DBT.The added value DBT in process determined by analysing data collected prospectively unblinded radiologists working up cases.Following anonymisation cases, there also a retrospective multireader...

To assess whether vacuum-assisted excision (VAE) is a safe alternative to surgery in the treatment of breast lesions uncertain malignant potential (B3) which no atypia present on needle core biopsy (NCB). Forty two VAE procedures were performed for B3 lesions. Twenty four (57%) papillary Eighteen (43%) radial scars. Two patients (4.7%) upgraded carcinoma at VAE. with went develop cancer same (at 24 and 41 months post VAE). No developed scar group. Eight (19%) had - carcinoma, scars missed...

Evolocumab binds PCSK9, increasing low-density lipoprotein cholesterol (LDL-C) receptors and lowering LDL-C. Target-mediated evolocumab elimination is attributable to PCSK9 binding. As circulating LDL-C levels are primarily regulated by the liver, we compared pharmacokinetics, pharmacodynamics, safety in individuals with without hepatic impairment. An open-label, parallel-group study evaluated pharmacokinetics of hepatic-impaired (Child-Pugh Class A or B) healthy adults. Participants were...

Sonographic measurement of fetal humeral soft tissue thickness (STT) was performed in 93 women with gestational diabetes mellitus during the third trimester. STT measurements revealed accelerated growth large for age infants at 31 wk gestation. This new proved to be most accurate predictor excessive size compared other standard ultrasound parameters (sensitivity 82%, specificity 95%, positive predictive value 90%). Asymmetrical more evident utero. Humeral may distinguish fetuses truncal...

Several studies have shown that darbepoetin alfa, an erythropoiesis-stimulating agent (ESA), can reduce transfusions and increase hemoglobin (Hb) levels in patients with chemotherapy-induced anemia (CIA). Recent safety concerns, however, prompted changes to ESA product information. In the European Union United States, therapy initiation for CIA is now recommended at a Hb level ≤10 g/dL. The present exploratory analysis examined how this may impact patient care. Data from phase 3 randomized...

Drug-disease interactions involving therapeutic proteins that target cytokines and potentially impact cytochrome P450 (CYP) enzymes have been of increased interest to drug regulatory agencies industry sponsors in recent years. This parallel-group open-label study evaluated the effects monoclonal antibody denosumab, an inhibitor cytokine RANKL, on pharmacokinetics probe CYP3A4 substrate midazolam postmenopausal women with osteoporosis. The a 2 mg oral dose was days 1 16. Subjects Group A...

The effects of cholesterol-lowering drugs, including those that reduce cholesterol synthesis (statins) and absorption (ezetimibe), on are well understood. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors a novel class drugs robustly LDL-cholesterol (LDL-C), but little is known about their synthesis. We evaluated how treatment with evolocumab, fully human monoclonal IgG2 antibody to PCSK9, affects markers by measuring these in patients from an evolocumab clinical trial. At 2...

Objective: To compare the accuracy of standard supplementary views and GE digital breast tomosynthesis (DBT) for assessment soft-tissue mammographic abnormalities. Methods: Women recalled further abnormalities were recruited received (typically spot compression views) two-view DBT. The added value DBT in process was determined by analysing data collected prospectively radiologists working up cases. Following anonymization cases, there also a retrospective multireader review. readers first...

CHOP (cyclophosphamide, doxorubicin, vincristine, prednisolone) ± rituximab [(±R)CHOP] is the current standard of care for aggressive non-Hodgkin lymphoma (NHL). Anemia resulting from chemotherapy can be treated with erythropoiesis-stimulating agents (ESAs). As part observational IMPACT NHL study, data were collected on ESA use and anemia-related outcomes in 1829 adults receiving (±R)CHOP-14 or (±R)CHOP-21. Overall, 33% patients anemic during chemotherapy. Older age, lower baseline...