Prolonged QTc Interval in Cancer Therapeutic Drug Development: Defining Arrhythmic Risk in Malignancy

Anticancer therapy drug development is an arduous task, taking 10 to 15 years to complete, requiring approximately 1 billion dollars, and rarely leads to Food and Drug Administration approval. Methods to predict unacceptable drug-induced toxicity, such as a prolonged QTc interval/risk of torsade de pointes, should be highly informative to quickly and accurately determine if further resources should be allocated in the continued development of an agent. Expert consensus has established guidelines to ascertain the ability of a new drug to prolong the QTc interval. Although QTc measurement is the best way to assess arrhythmic risk, it is imprecise for a variety of reasons. In addition, oncology patients have multiple risk factors for QTc prolongation at baseline. Competing interests involved in assessing arrhythmic risk of a new oncology agent include inability to precisely follow published guidelines for QTc assessment, patients' concomitant medical problems interfering with drug assessment and therefore clinical trial enrollment, patient safety concerns, general public safety concerns regarding toxicity assessment, need for discovery of more curative drug therapies, and individual patient perception of therapeutic risk vs benefit. Oncology patients are concerned about access to experimental agents, as well as early abandonment of a potentially beneficial agent because of a low estimated risk of toxicity, even if the event is catastrophic. We review the issues involved in evaluating the QTc interval-prolonging risk in new anticancer agents.     

2009年美国FDA批准新药介绍

2009年美国食品和药物管理局（FDA,http:∥www.fda.gov）共批准上市新药37种,其中包括新分子实体20个、新生物制品8个和新疫苗9个。部分药品也经欧洲药品管理局（EMEA,http:∥www.ema.europa.eu/）批准上市。按食品和药物管理局批准新药说明书首页处方资料要点,本文重点介绍了28个新治疗药物,分别简要叙述这些新分子实体和新生物制品的特性、化学结构、作用机制、生产厂家、适应证、剂量和用法、禁忌证、不良反应和黑框警告等相关信息。此外,还概述2009年批准新药研发史中涉及的重要首次事件。     

Evidence and consensus based GKJR guidelines for the treatment of juvenile idiopathic arthritis

Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease in children and adolescents. Immunomodulatory drugs are used frequently in its treatment. Using the nominal group technique (NGT) and Delphi method, we created a multidisciplinary, evidence- and consensus-based treatment guideline for JIA based on a systematic literature analysis and three consensus conferences. Conferences were headed by a professional moderator and were attended by representatives who had been nominated by their scientific societies or organizations. 15 statements regarding drug therapy, symptomatic and surgical management were generated. It is recommended that initially JIA is treated with NSAID followed by local glucocorticoids and/or methotrexate if unresponsive. Complementing literature evidence with long-standing experience of caregivers allows creating guidelines that may potentially improve the quality of care for children and adolescents with JIA.     

B cell elimination in systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is an autoimmune disorder with a worldwide distribution, potentially life-threatening with considerable morbidity. The elimination of pathogenic B cells has emerged as a rational therapeutic option. Many open label studies have reported encouraging results in which clinical and serological remission have invariably been described, often enabling the reduction of steroid and immunosuppressive treatment. However, the results from randomized controlled studies have been disappointing and several questions remain to be answered. In this review we will focus on results of B cell direct depletion in the treatment of patients with systemic lupus erythematosus.     

Combining ibuprofen and acetaminophen for acute pain management after third-molar extractions: Translating clinical research to dental practice

BackgroundEffective and safe drug therapy for the management of acute postoperative pain has relied on orally administered analgesics such as ibuprofen, naproxen and acetaminophen, or N-acetyl-p-aminophenol (APAP), as well as combination formulations containing opioids such as hydrocodone with APAP. The combination of ibuprofen and APAP has been advocated in the last few years as an alternative therapy for postoperative pain management. The authors conducted a critical analysis to evaluate the scientific evidence for using the ibuprofen-APAP combination and propose clinical treatment recommendations for its use in managing acute postoperative pain in dentistry.Types of Studies ReviewedThe authors used quantitative evidence-based reviews published by the Cochrane Collaboration to determine the relative analgesic efficacy and safety of combining ibuprofen and APAP. They found additional articles by searching the Ovid MEDLINE, PubMed and http://ClinicalTrials.gov databases.ConclusionsThe results of the quantitative systematic reviews indicated that the ibuprofen-APAP combination may be a more effective analgesic, with fewer untoward effects, than are many of the currently available opioid-containing formulations. In addition, the authors found several randomized controlled trials that also indicated that the ibuprofen-APAP combination provided greater pain relief than did ibuprofen or APAP alone after third-molar extractions. The adverse effects associated with the combination were similar to those of the individual component drugs.Practical ImplicationsCombining ibuprofen with APAP provides dentists with an additional therapeutic strategy for managing acute postoperative dental pain. This combination has been reported to provide greater analgesia without significantly increasing the adverse effects that often are associated with opioid-containing analgesic combinations. When making stepwise recommendations for the management of acute postoperative dental pain, dentists should consider including ibuprofen-APAP combination therapy.     

Mullerian agenesis associated with in-utero thalidomide exposure: A case report

Thalidomide is a well-known teratogen, which is experiencing resurgence as new uses are identified. Exposure is classically associated with limb deformities, such as: dysmelia, phocomelia, preaxial hypoplasia and polydactyly, in addition to visceral anomalies that have been documented as well. We report a case of a 38 year-old nulligravid female, who was previously evaluated for primary amenorrhea, and given the presumptive false diagnosis of an imperforate hymen. On magnetic resonance imaging (MRI) exam, she was noted to have uterovaginal agenesis. The implications of thalidomide on women’s health extend beyond external birth defects. Although, most commonly associated with limb deformities, there may also be gynecologic implications of in utero exposure. As this medication is increasingly used for various medical conditions, obstetricians/gynecologists need to remain aware of this potential mullerian teratogenic effect.     

One-Year Analysis of the Prospective Multicenter SENTRY Clinical Trial: Safety and Effectiveness of the Novate Sentry Bioconvertible Inferior Vena Cava Filter

Purpose

To prospectively assess the Sentry bioconvertible inferior vena cava (IVC) filter in patients requiring temporary protection against pulmonary embolism (PE).

Multicenter Trial of the VenaTech Convertible Vena Cava Filter

Purpose

To demonstrate rates of successful filter conversion and 6-month major device-related adverse events in subjects with converted caval filters.