Treatment with ibritumomab tiuxetan radioimmunotherapy in patients with rituximab-refractory follicular non-Hodgkin's lymphoma.

PURPOSE: Rituximab is commonly used as a single agent or in combination therapy for non-Hodgkin's lymphoma (NHL). Ibritumomab tiuxetan radioimmunotherapy targets the same antigen as rituximab and has demonstrated efficacy in rituximab-na?ve NHL. This study evaluated ibritumomab tiuxetan in the treatment of rituximab-refractory follicular NHL. PATIENTS AND METHODS: Eligible patients were refractory to rituximab; this was defined as no objective response to rituximab (375 mg/m(2) weekly for 4 weeks) or time to progression (TTP) of < or = 6 months. The ibritumomab tiuxetan treatment regimen consisted of pretreatment with rituximab (250 mg/m(2) intravenously on days 1 and 8) to deplete peripheral blood B cells, then yttrium-90 ibritumomab tiuxetan (0.4 mCi/kg; maximum, 32 mCi) intravenously on day 8, administered on an outpatient basis. An imaging/dosimetry dose of indium-111 ibritumomab tiuxetan (5 mCi) was injected after rituximab (day 1) in 28 patients. RESULTS: Fifty-seven patients were treated. The median age was 54 years, 74% had tumors > or = 5 cm, and all were extensively pretreated (median, four prior therapies; range, one to nine). The estimated radiation-absorbed doses to healthy organs were below the study-defined limit in all patients studied with dosimetry. The overall response rate for the 54 patients with follicular NHL was 74% (15% complete responses and 59% partial responses). The Kaplan-Meier-estimated TTP was 6.8 months (range, 1.1 to > or = 25.9 months) for all patients and 8.7 months for responders. Adverse events were primarily hematologic; the incidence of grade 4 neutropenia, thrombocytopenia, and anemia was 35%, 9%, and 4%, respectively. CONCLUSION: Ibritumomab tiuxetan radioimmunotherapy is effective in rituximab-refractory patients. The only significant toxicity is hematologic.     

A comparative study of HER2/neu amplification and overexpression using fluorescencein situ hybridization (FISH) and immunohistochemistry (IHC) in 101 breast cancer patients

The HER2/neu protooncogene is expressed in the breast, ovarian, gastric and prostatic tumors. Studies done in a number of laboratories have demostrated that 25%–30% of breast cancer contain overexpression of HER2/neu gene. A comparative analysis of the amplification and overexpression of HER2/neu using fluorescencein situ hybridization (FISH) and immunohistochemistry (IHC) was performed to determine the correlation between both techniques. In this study, FISH with HER2/neu probe (Path Vysion) is compared to immunohistochemistry (rabbit anti-human c-erbB-2-DAKO) in a series of 101 prospective human breast cancer specimens. Among 25 patients with score of IHC 3+, 23 (92%) were detected amplified by FISH and in two cases we found overexpression (3+) but without gene amplification. Out of 46 cases with 2+ by IHC, we found 43 not amplified, two moderately amplified (<10 copies) and one highly amplified (>10 copies) (6.5%). No patient with IHC O or 1+, presented amplification of HER2/neu. A good correlation between both techniques was found. FISH technique should have clinical utillity overoat in cases with 2+.     

嘈杂语噪声下汉语整句识别的同质性研究

目的 获得嘈杂语噪声背景下汉语短句识别率一信噪比(Performance-Intensity,P-I)函数的斜率和50%的得分所对应的信噪比(记为SNR50),并对所有短句的同质性进行评估和调整.方法 采用16张(每张20句)新编嘈杂语噪声下汉语普通话短句识别表作为测试材料.选取年龄为21～25岁之间、听力/言语发育正常且日常以汉语普通话为交流方式的48名受试者按"随机区组设计"在-1、-4、-7、-10 dB四种信噪比条件下进行言语识别率的心理声学测量.使用Statistica7.0软件进行P-I函数拟合和统计分析.结果 320句语句在嘈杂语噪声下的言语识别P-I函数曲线的阈值呈正态分布,斜率呈不规则分布.剔除P-I函数强健性增长(斜率＞55%/dB)的语句,并保留阈值变异度在±2σ内的语句,精选出同质性良好的240句.结论 逐个调整每句的SNR以实现同质性,可为编制"等言语识别阈级"的句表奠定扎实的心理声学基础.     

Children with cochlear implants who live in monolingual and bilingual homes.

OBJECTIVE: To determine if exposure to a second language impacts the ability of children with cochlear implants to develop spoken English skills. STUDY DESIGN: Matched-pairs comparison of postoperative speech perception and speech/language data of children from monolingual and bilingual homes with cochlear implants. SETTING: Tertiary medical facility. SUBJECTS: Twelve matched pairs of children with unilateral cochlear implants who reside in monolingual or in bilingual homes. Pairs were matched for age of implantation, cochlear anatomy, educational setting, and device type. All subjects received their implant before the age of 6 years. INTERVENTION: Subjects participated in routine speech perception and speech and language assessments at various postimplantation time intervals. MAIN OUTCOME MEASURES: Matched-pairs t tests and mixed-model analyses were used to evaluate and compare scores obtained by the 2 groups on the Peabody Picture Vocabulary Test, The MacArthur-Bates Communicative Development Inventory: Words and Gestures, The Oral and Written Language Scales, The Infant-Toddler Meaningful Auditory Integration Scale, and the Student Oral Language Observation Matrix. RESULTS: No significant differences were found between the scores of children living in bilingual homes when compared with the scores obtained by children living in monolingual homes at any interval tested. CONCLUSION: This study supports the belief that exposure to a second language at home does not impair primary language acquisition for some young children with cochlear implants. The study suggests that some children with cochlear implants can learn multiple spoken languages and that parents of such children do not need to avoid using a minority language with their child who has a cochlear implant.     

Cost-Utility Analysis of Rimonabant in the Treatment of Obesity

Objective:  To estimate the incremental cost-utility ratio (ICUR) of rimonabant 20 mg/day in the treatment of obesity from a third-party payer's perspective.
Methods:  Pooled data from three randomized clinical trials were used to develop a decision tree with five treatment alternatives: 1- and 2-year treatment with rimonabant, 2-year placebo, 1-year rimonabant followed by 1-year placebo, and no treatment. All alternatives, except no treatment, were accompanied by lifestyle interventions. Treatment benefits included gains in quality-adjusted life-years (QALYs) and reduced incidence of type-2 diabetes mellitus and coronary heart disease (CHD). Drug acquisition cost was based on the average wholesale price of a comparator drug minus 15%. One-way and probabilistic sensitivity analyses were conducted to assess the stability of the base-case results.
Results:  One-year rimonabant and 1-year rimonabant followed by placebo were extendedly dominated. Rimonabant for 2 years showed an average weight reduction of 8.49 kg, a body mass index reduction of 2.98 kg/m² and reduced waist circumference by 8.24 cm (placebo: 3.55 kg, 1.22 kg/m², 4.18 cm). Two-year rimonabant was associated with a relative reduction in the 5-year incidence of CHD by 7.15% and of diabetes by 9.28%. Incremental benefits (costs) were 0.0984 QALYs ($5209) compared to no treatment and 0.0581 QALYs ($4182) compared to placebo, producing ICURs of $52,936/QALY (95% confidence interval $39K–$69K) and $71,973/QALY ($51K–$98K), respectively.
Conclusions:  Rimonabant combined with lifestyle interventions has the potential to decrease the rate of obesity-related comorbidities and improve health-related quality of life, albeit at considerable cost.     

Factors influencing the participation of gastroenterologists and hepatologists in clinical research

Background  

Although clinical research is integral to the advancement of medical knowledge, physicians face a variety of obstacles to their participation as investigators in clinical trials. We examined factors that influence the participation of gastroenterologists and hepatologists in clinical research.     

Role of socioeconomic indicators in the prediction of all causes and coronary heart disease mortality in over 12,000 men – The Italian RIFLE pooling project

The relationship of socioeconomic indicators (education, occupation and residence) to short-term all cause mortality and coronary heart disease (CHD) mortality was evaluated in an Italian population sample. Socioeconomic indicators (education, occupational level and residence) and major CHD risk factors were measured in 12,361 males aged 40–69 years; mortality data by cause were collected for the next 6 years. All cause and CHD mortality risk ratio (RR) in the different educational and occupational levels and residence were computed by Cox proportional hazards models. After 6 years 385 men died, of whom 105 were coronary fatalities. No association with educational level was found for all cause mortality (RR: 1.00 high, 0.71 medium, 0.77 low) and for CHD mortality (RR: 1.00 high, 0.39 intermediate, 0.71 low). Occupational level was significantly associated (p < 0.031) with all cause mortality (RR: 1.00 high-intermediate, 1.27 low). Urban vs. rural residence (RR: 1.00) showed a RR for all cause mortality of 1.33 (p < 0.011). Adjustment for bio-behavioral risk factors did not change the above results; only mortality for CHD of urban vs. rural residents increased (RR: 1.94, p = 0.004). In conclusion the negative association of mortality with occupational level, albeit not with education, indicates that occupation is a better indicator of socioeconomic status in Italy. Status incongruity as well as residence in an urban environment could be risk conditions for total and CHD mortality.     

Frequency of RAS and p53 Mutations in Acute Promyelocytic Leukemias

The frequency of RAS and p53 mutations was investigated in 30 acute promyelocytic leukemias by single strand conformation polymorphism analysis and direct sequencing of ge-nomic DNA. Only two cases bore N-RAS codon 12 mutations and none had p53 mutations responsible for aminoacid substitutions. It would, therefore, seem that neither RAS nor p53 are involved in acute promyelocytic leukemogenesis.     

Prognostic impact of bulky mediastinal lymph nodes (N2>2.5 cm) in patients with locally advanced non-small-cell lung cancer (LA-NSCLC) treated with platinum-based induction chemotherapy

A group of 70 patients with locally advanced non-small-cell lung cancer (LA-NSCLC), treated in different phase II-III trials with platinum-based chemotherapy in two institutions, have been evaluated to identify potential baseline prognostic factors predicting their survival. The eligibility criteria were patients with stage IIIA (N2)-IIIB, Eastern Cooperative Oncology Group performance status 0.1 and less than 5% weight loss. All 37 patients with stage IIIA(N2) were treated with platinum-based induction chemotherapy followed by surgery plus radiotherapy if no progression was observed. The other 33 patients with stage IIIB were treated with platinum-based induction chemotherapy followed by conventional fractionation radiotherapy if no progression was observed. The overall response rate to induction chemotherapy was 40%. Median survival of the 70 patients was 13 months, with a 4-year survival of 15%. At univariate analysis, two prognostic factors correlated with survival: partial or complete response to induction chemotherapy (P<0.00001) and bulky mediastinal lymph nodes (N2>2.5 cm) (P=0.03). At multivariate analysis, only the response to induction chemotherapy retained statistical significance (P=0.00001). Randomized well-balanced prospective trials considering initially mediastinal N2 node size are needed to clearly establish the role of chemotherapy, surgery and radiotherapy in LA-NSCLC.     

The growth-restricted fetus: risk of mortality by each additional week of expectant management

Objective: To compare fetal/infant mortality risk associated with each additional week of expectant management with the infant mortality risk of immediate delivery in growth-restricted pregnancies.

Methods: A retrospective cohort study was conducted of singleton, nonanomalous pregnancies from the 2005–2008 California Birth Registry comparing pregnancies affected and unaffected by growth restriction, defined using birth weights as a proxy for fetal growth restriction (FGR). Birth weights were subdivided as greater than the 90th percentile, between the 10th percentile and 90th percentile, and less than the 10th percentile. Cases greater than the 90th percentile were excluded from analysis. Cases less than the 10th percentile were considered to have FGR and were further subcategorized into <10th percentile, <5th percentile, and <3rd percentile. We compared the risk of infant death at each gestational age week against a composite risk representing the mortality risk of one additional week of expectant management.

Results: We identified 1,641,000 births, of which 110,748 (6.7%) were less than 10th percentile. The risk of stillbirth increased with gestational age with the risk of stillbirth at each week of gestation inversely proportional to growth percentile. The risks of fetal and infant mortality with expectant management outweighed the risk of infant death for all FGR categories analyzed beginning at 38 weeks. However, the absolute risks differed by growth percentiles, with the highest risks of infant death and stillbirth in the <3rd percentile cohort. At 39 weeks, absolute risks were low, although the number needed to deliver to prevent 1 death ranged from 413 for <3rd percentile to 2667 in unaffected pregnancies.

Conclusion: At 38 weeks, the mortality risk of expectant management for one additional week exceeds the risk of delivery across all growth-restricted cohorts, despite variation in absolute risk by degree of growth restriction.