20-Year Risks of Breast-Cancer Recurrence after Stopping Endocrine Therapy at 5 Years

The administration of endocrine therapy for 5 years substantially reduces recurrence rates during and after treatment in women with early-stage, estrogen-receptor (ER)-positive breast cancer. Extending such therapy beyond 5 years offers further protection but has additional side effects. Obtaining data on the absolute risk of subsequent distant recurrence if therapy stops at 5 years could help determine whether to extend treatment

English for Academic Purposes at Swedish universities: Teachers\u27 objectives and practices

In a parallel-language environment the use of textbooks in English in courses otherwise in the local language is naturalized and not widely discussed or questioned. The aim of this study was to elicit the attitudes and syllabus infrastructure that underlie the practice. A large-scale survey was carried out and answers were obtained from over 20% of teachers at Swedish universities. Results confirmed that a majority regarded English as important during and/or after university studies and showed that they considered the use of English-language textbooks as providing a useful opportunity for incidental language learning. In strong contrast to the Situation in a content and language integrated learning environment, only a small minority of courses were reported to have any specified learning outcome related to English. Open answers showed awareness of the benefits and risks of parallel-language practices, but no interest in making aims explicit. In our view, there is no contradiction between incidental learning and explicit aims, and course aims which remain implicit make rational planning and constructive alignment more difficult. They also inhibit discussion of appropriate methodology

In vitro membrane penetration of modified peptide nucleic acid (PNA)

Efficient cellular uptake is crucial for the success of any drug directed towards targets inside cells. Peptide nucleic acid (PNA), a DNA analog with a promising potential as a gene-directed drug, has been shown to display slow membrane penetration in cell cultures. We here used liposomes as an in vitro model of cell membranes to investigate the effect on penetration of a PNA molecule colvalently modified with a lipophilic group, an adamantyl moiety. The adamantyl attachment was found to increase the membrane-penetration rate of PNA three-fold, as compared to corresponding unmodified PNA. From the penetration behaviour of a number of small and large molecules we could conclude that passive diffusion is the mechanism for liposome-membrane passage. Flow linear dichroism (LD) of the modified PNA in presence of rod-shaped micelles, together with octanol-water distribution experiments. showed that the adamantyl-modified PNA is amphiphilic; the driving force behind the observed increased membrane-penetration rate appears to be an accumulation of the PNA in the lipid double layer

Assessment of problematic severe asthma in children

Assessment of problematic severe asthma in children should be performed in a step-wise manner to ensure an optimal approach. A four-step assessment scheme is proposed. First, a full diagnostic work-up is performed to exclude other diseases which mimic asthma. Secondly, a multi-disciplinary assessment is performed to identify issues that may need attention, including comorbidities. Thirdly, the pattern of inflammation is assessed, and finally steroid responsiveness is documented. Based upon these four steps an optimal individualised treatment plan is developed. In this article the many gaps in our current knowledge in all these steps are highlighted, and recommendations for current clinical practice and future research are made. The lack of good data and the heterogeneity of problematic severe asthma still limit our ability to optimise the management on an individual basis in this small, but challenging group of patients

Clinical Evidence for Topotecan-Paclitaxel Non\u2013Cross-Resistance in Ovarian Cancer

Purpose: A large, randomized study comparing the efficacy and safety of topotecan versus paclitaxel in patients with relapsed epithelial ovarian cancer showed that these two compounds have similar activity. In this study, a number of patients crossed over to the alternative drug as third-line therapy, ie, from paclitaxel to topotecan and vice versa. We therefore were able to assess the degree of non\u2013cross-resistance between these two compounds. Patients and Methods: Patients who had progressed after one platinum-based regimen were randomized to either topotecan (1.5 mg/m2/d) 3 5 every 21 days (n 5 112) or paclitaxel (175 mg/m2 over 3 hours) every 21 days (n 5 114). A total of 110 patients received crossover therapy with the alternative drug (61 topotecan, 49 paclitaxel) as third-line therapy. Results: Response rates to third-line cross-over therapy were 13.1% (8 of 61 topotecan) and 10.2% (5 of 49 paclitaxel; P 5 .638). Seven patients who responded to third-line topotecan and four patients who responded to paclitaxel had failed to respond to their second-line treatment. Median time to progression (from the start of third-line therapy) was 9 weeks in both groups, and median survival was 40 and 48 weeks for patients who were receiving topotecan or paclitaxel, respectively. The principal toxicity was myelosuppression; grade 4 neutropenia was more frequent with topotecan (81.4% of patients) than with paclitaxel (22.9% of patients). Conclusion: Topotecan and paclitaxel have similar activity as second-line therapies with regard to response rates and progression-free and overall survival. We demonstrated that the two drugs have a degree of non\u2013cross-resistance. Thus, there is a good rationale for incorporating these drugs into future first-line regimens

THE IMPACT OF DIFFERENT BCG STRAINS ON OUTCOME IN A LARGE COHORT OF T1G3 PATIENTS TREATED WITH BCG

There are few RCT\u2019s comparing different BCG strains. As a consequence, there is limited information available on the difference in their efficacy in the treatment of patients with NMIBC. A trial from 1995 showed that an induction course BCG RIVM significantly reduced the number of recurrences compared to an induction course of BCG Tice [Vegt et al, J Urol 1995]. A recently published trial [Rentsch et al, Eur Urol 2014] also found an induction course of BCG Connaught to be significantly better in the reduction of recurrences than an induction course of BCG Tice. We retrospectively compared the outcomes after BCG Connaught and BCG Tice in a large study cohort of high risk NMIBC patients, and looked at recurrence, progression and cancer specific survival (CSS)

Breast cancer survival in the US and Europe: A CONCORD high-resolution study.

Breast cancer survival is reportedly higher in the US than in Europe. The first worldwide study (CONCORD) found wide international differences in age-standardized survival. The aim of this study is to explain these survival differences. Population-based data on stage at diagnosis, diagnostic procedures, treatment and follow-up were collected for about 20,000 women diagnosed with breast cancer aged 15-99 years during 1996-98 in 7 US states and 12 European countries. Age-standardized net survival and the excess hazard of death up to 5 years after diagnosis were estimated by jurisdiction (registry, country, European region), age and stage with flexible parametric models. Breast cancers were generally less advanced in the US than in Europe. Stage also varied less between US states than between European jurisdictions. Early, node-negative tumors were more frequent in the US (39%) than in Europe (32%), while locally advanced tumors were twice as frequent in Europe (8%), and metastatic tumors of similar frequency (5-6%). Net survival in Northern, Western and Southern Europe (81-84%) was similar to that in the US (84%), but lower in Eastern Europe (69%). For the first 3 years after diagnosis the mean excess hazard was higher in Eastern Europe than elsewhere: the difference was most marked for women aged 70-99 years, and mainly confined to women with locally advanced or metastatic tumors. Differences in breast cancer survival between Europe and the US in the late 1990s were mainly explained by lower survival in Eastern Europe, where low healthcare expenditure may have constrained the quality of treatment

Overview of the randomized trials of radiotherapy in ductal carcinoma in situ of the breast.

Individual patient data were available for all four of the randomized trials that began before 1995, and that compared adjuvant radiotherapy vs no radiotherapy following breast-conserving surgery for ductal carcinoma in situ (DCIS). A total of 3729 women were eligible for analysis. Radiotherapy reduced the absolute 10-year risk of any ipsilateral breast event (ie, either recurrent DCIS or invasive cancer) by 15.2% (SE 1.6%, 12.9% vs 28.1% 2 P <.00001), and it was effective regardless of the age at diagnosis, extent of breast-conserving surgery, use of tamoxifen, method of DCIS detection, margin status, focality, grade, comedonecrosis, architecture, or tumor size. The proportional reduction in ipsilateral breast events was greater in older than in younger women (2P < .0004 for difference between proportional reductions; 10-year absolute risks: 18.5% vs 29.1% at ages <50 years, 10.8% vs 27.8% at ages ≥ 50 years) but did not differ significantly according to any other available factor. Even for women with negative margins and small low-grade tumors, the absolute reduction in the 10-year risk of ipsilateral breast events was 18.0% (SE 5.5, 12.1% vs 30.1%, 2P = .002). After 10 years of follow-up, there was, however, no significant effect on breast cancer mortality, mortality from causes other than breast cancer, or all-cause mortality.Journal ArticleResearch Support, Non-U.S. Gov'tReviewinfo:eu-repo/semantics/publishe