114 research outputs found

    Equivalence of 2 effective graft-versus-host disease prophylaxis regimens: Results of a prospective double-blind randomized trial

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    AbstractWe have previously demonstrated a decrease in the incidence of acute graft-versus-host disease (GVHD) with the addition of methotrexate (MTX) to cyclosporine (CSP) and prednisone (PSE) chemotherapy in patients with leukemia. We have now completed a prospective randomized trial comparing the 3-drug regimen (CSP/MTX/PSE, including 3 doses of MTX) to the standard 2-drug regimen (CSP/MTX, including 4 doses of MTX) to investigate the benefit of PSE used up front for the prevention of acute and chronic GVHD. In the trial, 193 patients were randomized and 186 were included in the final analysis. All patients received a bone marrow graft from a fully histocompatible sibling donor. The preparatory regimen consisted of fractionated total-body irradiation (fTBI) and etoposide in all but 13 patients, who received fTBI and cyclophosphamide. The patients were randomized to receive either CSP/MTX/PSE or CSP/MTX. The 2 groups were well balanced with respect to diagnosis, disease stage, age, donor-recipient sex, and parity. In an intent-to-treat analysis, the incidence of acute GVHD was 18% (95% confidence interval [CI] 12-28) for the CSP/MTX/PSE group compared with 20% (CI 10-26) for the CSP/,MTX group (P = .60), with a median follow up of 2.2 years. Overall survival was 65% for those receiving CSP/MTX/PSE and 72% for those receiving CSP/MTX (P = .10); the relapse rate was 15% for the CSP/MTX/PSE group and 12% for the CSP/MTX group (P = .83). The incidence of chronic GVHD was similar (46% versus 52%; P = .38), with a follow-up of 0.7 to 6.0 years. Of interest, 21 patients went off study due to GVHD (5 in the CSP/MTX/PSE group and 16 in the CSP/MITX group [P = .02]), and 11 patients went off study because of alveolar hemorrhage (3 in the CSP/MTX/PSE group and 8 in the CSP/MTX group [P = .22]). The addition of PSE did not result in a higher incidence of infectious complications, bacterial (66% versus 58%), viral (77% versus 66%), or fungal (20% versus 20%), in those receiving CSP/MTX/PSE versus CSP/MTX, respectively. These data suggest that the addition of PSE was associated with a somewhat lower incidence of early posttransplantation complications but did not have a positive impact on the incidence of acute or chronic GVHD or event-free or overall survival.Biol Blood Marrow Transplant 2000;6(3):254-61

    Design and feasibility testing of a novel group intervention for young women who binge drink in groups

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    BackgroundYoung women frequently drink alcohol in groups and binge drinking within these natural drinking groups is common. This study describes the design of a theoretically and empirically based group intervention to reduce binge drinking among young women. It also evaluates their engagement with the intervention and the acceptability of the study methods.MethodsFriendship groups of women aged 18ā€“35 years, who had two or more episodes of binge drinking (>6 UK units on one occasion; 48g of alcohol) in the previous 30 days, were recruited from the community. A face-to-face group intervention, based on the Health Action Process Approach, was delivered over three sessions. Components of the intervention were woven around fun activities, such as making alcohol free cocktails. Women were followed up four months after the intervention was delivered. Results The target of 24 groups (comprising 97 women) was recruited. The common pattern of drinking was infrequent, heavy drinking (mean consumption on the heaviest drinking day was UK 18.1 units). Process evaluation revealed that the intervention was delivered with high fidelity and acceptability of the study methods was high. The women engaged positively with intervention components and made group decisions about cutting down. Twenty two groups set goals to reduce their drinking, and these were translated into action plans. Retention of individuals at follow up was 87%.ConclusionsThis study successfully recruited groups of young women whose patterns of drinking place them at high risk of acute harm. This novel approach to delivering an alcohol intervention has potential to reduce binge drinking among young women. The high levels of engagement with key steps in the behavior change process suggests that the group intervention should be tested in a full randomised controlled trial

    Comparative Effectiveness of Oxaliplatin vs Nonā€“Oxaliplatin-containing Adjuvant Chemotherapy for Stage III Colon Cancer

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    The addition of oxaliplatin to adjuvant 5-fluorouracil (5-FU) improves survival of patients with stage III colon cancer in randomized clinical trials (RCTs). However, RCT participants are younger, healthier, and less racially diverse than the general cancer population. Thus, the benefit of oxaliplatin outside RCTs is uncertain

    Breast cancer metastasis to gynaecological organs: a clinico-pathological and molecular profiling study

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    Breast cancer metastasis to gynaecological organs is an understudied pattern of tumour spread. We explored clinico-pathological and molecular features of these metastases to better understand whether this pattern of dissemination is organotropic or a consequence of wider metastatic dissemination. Primary and metastatic tumours from 54 breast cancer patients with gynaecological metastases were analysed using immunohistochemistry, DNA copy-number profiling, and targeted sequencing of 386 cancer-related genes. The median age of primary tumour diagnosis amongst patients with gynaecological metastases was significantly younger compared to a general breast cancer population (46.5 versus 60ā€‰years; p < 0.0001). Median age at metastatic diagnosis was 54.4, time to progression was 4.8ā€‰years (range 0-20ā€‰years), and survival following a diagnosis of metastasis was 1.95ā€‰years (range 0-18ā€‰years). Patients had an average of five involved sites (most frequently ovary, fallopian tube, omentum/peritoneum), with fewer instances of spread to the lungs, liver, or brain. Invasive lobular histology and luminal A-like phenotype were over-represented in this group (42.8 and 87.5%, respectively) and most patients had involved axillary lymph nodes (p < 0.001). Primary tumours frequently co-expressed oestrogen receptor cofactors (GATA3, FOXA1) and harboured amplifications at 8p12, 8q24, and 11q13. In terms of phenotype conversion, oestrogen receptor status was generally maintained in metastases, FOXA1 increased, and expression of progesterone receptor, androgen receptor, and GATA3 decreased. ESR1 and novel AR mutations were identified. Metastasis to gynaecological organs is a complication frequently affecting young women with invasive lobular carcinoma and luminal A-like breast cancer, and hence may be driven by sustained hormonal signalling. Molecular analyses reveal a spectrum of factors that could contribute to de novo or acquired resistance to therapy and disease progression.Jamie R Kutasovic, Amy E McCart Reed, Renique Males, Sarah Sim, Jodi M Saunus ... Liana Dedina ... et al

    Procjena utjecaja modernizacije i novih tehnoloŔkih procesa na izloženost buci u aluminijskoj industriji

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    The aim of this study was to assess to which extent modernisation of an aluminium production complex reduced occupational noise hazard for jobs with the highest potential of exposure. Periodical measurements of noise level were taken at the same workplaces using the same method, before and after modernisation of all plants. The results were compared with the recommended standard. After modernisation, the noise was significantly reduced in all sections of all plants. The greatest reduction was measured in the foundry. After modernisation, the portion of workplaces with excessive noise level dropped significantly (chi-square=21.315; p<0.0001) from 78.4 % to 13 %. Noise remained a problem in ingot casting and dross skimming section. In the anode plant, noise remained a problem in the green mill section where noise intensities generated by mills and vibrocompactors varied from 95 dB(A) to 102 dB(A). In the electrolysis plant, the portion of workplaces with extensive noise dropped from 77.8 % to 39.3 % after modernisation (p=0.0019). Noise remains to be a problem at the anode covering section where levels rise up to 100 dB(A). The modernisation of the factory has considerably reduced the noise level in the working environment of all plants, but it can not be reduced completely.Cilj je rada procijeniti utjecaj modernizacije tehnoloÅ”kog procesa proizvodnje aluminija na prisutnost i razinu buke Å”tetne za zdravlje radnika u radnom okoliÅ”u. U tu svrhu uspoređivani su rezultati periodičkih mjerenja razine buke prije i nakon modernizacije. Mjerenja intenziteta buke provedena su na istim radnim mjestima i istom metodom tijekom radnih smjena i uspoređeni s važećim nacionalnim standardom. Nakon modernizacije tvornice u svim odjelima proizvodnih pogona značajno se smanjila razina buke, kao i broj radnih mjesta na kojima su radnici izloženi prekomjernoj buci. Najbolji rezultati postignuti su u ljevaonici, gdje se broj radnih mjesta s prekomjernom razinom buke, tj. razinom buke viÅ”om od 90 dB(A) smanjio sa 78.4 % na 13 %. Na radnim mjestima gdje se izlijevaju ingoti i skida Å”ljaka buka je i dalje prekomjerna. U pogonu anoda prekomjerna je buka i dalje prisutna pri proizvodnji sirovih anoda, gdje razina buke zbog rada mlinova i vibrokompresora varira od 95 dB(A) do 102 dB(A). U pogonu elektrolize buka viÅ”a od 100 dB(A) izmjerena je pri zasipanju anoda. Iako je modernizacijom tvornice i unaprjeđenjem tehnoloÅ”kog procesa značajno reducirana razina buke, nije ju moguće u cijelosti ukloniti

    Clinical benefit of a precision medicine based approach for guiding treatment of refractory cancers

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    Patients and methods: Patients with metastatic solid tumors who had progressed on at least one line of standard of care therapy were referred to the Indiana University Health Precision Genomics Program. Tumor samples were submitted for DNA & RNA next-generation sequencing, fluorescence in situ hybridization, and immunohistochemistry for actionable targets. A multi-disciplinary tumor board reviewed all results. For each patient, the ratio of progression-free survival (PFS) of the genomically guided line of therapy divided by the PFS of their prior line was calculated. Patients whose PFS ratio was ā‰„ 1.3 were deemed to have a meaningful improvement in PFS. Results: From April 2014-October 2015, 168 patients were evaluated and 101 patients achieved adequate clinical follow-up for analysis. 19 of 44 (43.2%) patients treated with genomically guided therapy attained a PFS ratio ā‰„ 1.3 vs. 3 of 57 (5.3%) treated with non-genomically guided therapy (p < 0.0001). Similarly, overall PFS ratios (irrespective of cutoff) were higher for patients with genomically guided therapy vs non-genomically guided therapy (p = 0.05). Further, patients treated with genomically guided therapy had a superior median PFS compared to those treated with non-genomically guided therapy (86 days vs. 49 days, p = 0.005, H.R. = 0.55, 95% C.I.:0.37-0.84). Conclusion: Patients with refractory metastatic cancer who receive genomically guided therapy have improved PFS ratios and longer median PFS compared to patients who do not receive genomically guided therapy
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