Treatment Rationale Study Design for the MetLung Trial: A Randomized,Double-Blind Phase III Study of Onartuzumab (MetMAb) in Combination With Erlotinib Versus Erlotinib Alone in Patients Who Have Received Standard Chemotherapy for Stage IIIB or IV Met-Positive Non–Small-Cell Lung Cancer

We present the treatment rationale and study design of the MetLung phase III study. This study will investigate onartuzumab (MetMAb) in combination with erlotinib compared with erlotinib alone, as second- or third-line treatment, in patients with advanced non–small-cell lung cancer (NSCLC) who are Met-positive by immunohistochemistry. Approximately 490 patients (245 per treatment arm) will receive erlotinib (150 mg oral daily) plus onartuzumab or placebo (15 mg/kg intravenous every 3 weeks) until disease progression, unacceptable toxicity, patient or physician decision to discontinue, or death. The efficacy objectives of this study are to compare overall survival (OS) (primary endpoint), progression-free survival, and response rates between the 2 treatment arms. In addition, safety, quality of life, pharmacokinetics, and translational research will be investigated across treatment arms. If the primary objective (OS) is achieved, this study will provide robust results toward an alternative treatment option for patients with Met-positive second- or third-line NSCLC.     

Transmission of hepatitis C virus by occupational percutaneous injuries in South Korea

Korea is an endemic area of hepatitis. Hepatitis C virus (HCV) infections caused by occupational percutaneous injuries are a serious problem for healthcare workers and there has been a gradual increase in the number of HCV infections. We therefore determined the transmission rate of HCV after occupational percutaneous injury. This was a retrospective cohort study reviewing all occupational blood exposure reports made between January 1, 2004, and December 31, 2008, at a university-affiliated acute care hospital. Over the 5-year study period, there were 1,516 accidents of occupational exposure to blood; of these, 327 (21.6%) were to the blood of HCV-infected patients and 3 (0.9%) healthcare workers became infected with HCV (95% CI 0.6-8.8). In Korea, although the bloodborne accidents leading to exposure to HCV occurred frequently (21.6%), the transmission rate was very low (0.92%).     

Two cases of atrial flutter with fetal hydrops: successful fetal drug therapy.

We describe two cases of fetal atrial flutter associated with severe fetal hydrops which were unresponsive to digoxin but were successfully treated with flecainide acetate. Two cases of fetal atrial flutter were identified in fetuses with severe fetal hydrops on 3rd trimester ultrasonogram(28 weeks'' gestation and 30 weeks'' gestation). Following failed digoxin monotherapy, flecainide acetate was added to digoxin. On the 7th day and 13th day after combined therapy, fetal heart rate converted to normal sinus rhythm without recurrence. Our cases showed that the combined therapy of digoxin and flecainide acetate can effectively treat fetal atrial flutter associated with fetal hydrops unresponsive to digoxin monotherapy.     

Immunohistochemical and ultrastructural studies of the various nuclei of the trigeminal complex in the human newborn.

The various nuclei of the trigeminal complex were studied by immunohistochemical (enkephalin localization) and ultrastructural means in the brainstems of eight newborn human babies that died within 24 h after birth. Positive enkephalin neurons were detected in the chief sensory and spinal trigeminal nuclei as well as in some fibers of the trigeminal nerve. Ultrastructurally, two morphologically distinct types of neuron were observed, respectively, in the motor nucleus, the spinal nucleus and the mesencephalic nucleus of the trigeminal complex, whereas three morphologically distinct types of neuron were observed in the chief sensory nucleus. "Glomerulus" formation was a frequently observed feature in the chief sensory nucleus. In the spinal nucleus, rolls of synaptic terminals stacking up one on top of another and synapsing onto the final synaptic element were very much in evidence. Axosomatic, axodendritic, dendrodendritic and dendroaxonic synapses were demonstrated in all the different nuclear areas of the trigeminal complex but axoaxonic synapses were absent in the mesencephalic nucleus. Some of the findings in the present human study were similar to those reported in the rats and cats.     

Protection of leukotriene receptor antagonist against aspirin-induced bronchospasm in asthmatics

Purpose

Leukotriene receptor antagonists (LTRAs) are used to treat aspirin-intolerant asthma (AIA); however, the protective effects of long-term LTRA administration against aspirin-induced bronchospasm have not been evaluated.

Objectives

We investigated the efficacy of a 12-week treatment with a LTRA in protecting against aspirin-induced asthma in AIA patients.

Methods

Fifty-two adult patients with AIA underwent an aspirin challenge test just before administration of montelukast (10 mg/day) and just after 12 weeks of treatment. The protective effect was assessed as the disappearance of aspirin-induced bronchospasm after 12 weeks of treatment. The results were compared according to the patients'' clinical and physiological parameters.

Results

The decline in FEV1 following aspirin challenge was significantly reduced from 28.6±1.9% to 10.2±1.7% (P=0.0001) after 12 weeks of montelukast treatment. However, 14 subjects (30%) still showed a positive response (>15% decline in FEV1) to aspirin challenge. Grouping the subjects into good and poor responders according to post-treatment responses revealed that the pretreatment aspirin-induced FEV1 decline was significantly greater in the poor responders and that the triggering dose of aspirin and the induction time for a positive response were lower and shorter, respectively, in the poor responders. Histories of aspirin hypersensitivity and sinusitis were more prevalent among the poor responders than among the good responders.

Conclusions

Twelve weeks of treatment with montelukast protected against aspirin-induced bronchospasm in 70% of the AIA cases. A poor response was associated with more severe aspirin-induced bronchospasms before treatment and a history of aspirin hypersensitivity or sinusitis.

Clinical implications

A severe response to aspirin challenge may be a predictor of poor responsiveness to leukotriene antagonist treatment.     

自适应动态范围优化技术临床应用效果探讨

目的比较宽动态范围压缩线路(wide dynamic range compression,WDRC)助听器和自适应动态范围优化线路(adaptive dynamic range opti mization,ADRO)助听器的助听性能。方法选择具有2年以上WDRC线路助听器配戴史的中重度感音神经性听力损失青年人9名(13耳),分别配戴WDRC线路助听器和ADRO线路助听器,经8周适应期后,通过问卷调查和言语识别率测试对不同压缩线路助听器的助听效果进行评估。结果问卷调查结果显示,受试者配戴WDRC线路助听器在适宜交谈的安静环境(EC)、具有背景噪声的环境(BN)、存在回响和混响的环境(RV)、令人厌恶的或突然的声音(AV)的聆听困难度(不适度)的得分分别为20.2%、33.5%、45.6%、38.9%;配戴ADRO线路助听器在EC、BN、RV、AV的聆听困难度(不适度)的得分分别为17.9%、35.4%、53.6%、46.9%。言语识别率测试结果则显示,无论是处于安静环境或噪声环境,针对不同强度的声音信号,受试者配戴ADRO线路助听器所记录的言语识别率较配戴WDRC线路助听器所记录的言语识别率平均可提高8%~10%(P值均<0.05)。结论自适应动态范围优化线路助听器的助听性能优于宽动态范围压缩线路助听器。     

Identifying futility in a paediatric critical care setting: a prospective observational study.

AIMS: To determine the extent of futile care provided to critically ill children admitted to a paediatric intensive care setting. METHODS: Prospective evaluation of consecutive admissions to a 20 bedded multidisciplinary paediatric intensive care unit of a North London teaching hospital over a nine month period. Three previously defined criteria for futility were used: (1) imminent demise futility (those with a mortality risk greater than 90% using the Paediatric Risk of Mortality (PRISM II) score); (2) lethal condition futility (those with conditions incompatible with long term survival); and (3) qualitative futility (those with unacceptable quality of life and high morbidity). RESULTS: A total of 662 children accounting for 3409 patient bed days were studied. Thirty four patients fulfilled at least one of the criteria for futility, and used a total of 104 bed days (3%). Only 33 (0.9%) bed days were used by patients with mortality risk greater than 90%, 60 (1.8%) by patients with poor long term prognosis, and 16 (0.5%) by those with poor quality of life. Nineteen of 34 patients died; withdrawal of treatment was the mode of death in 15 (79%). CONCLUSIONS: Cost containment initiatives focusing on futility in the paediatric intensive care unit setting are unlikely to be successful as only relatively small amounts of resources were used in providing futile care. Paediatricians are recognising futility early and may have taken ethically appropriate measures to limit care that is futile.