bluuebunny/crossref_metadata_2025_split huggingface dataset:
High dose methylprednisolone therapy for the treatment of severe systemic lupus erythematosus
Authors: Parker BJ , Bruce IN 
Published: July 2007

The pharmacological armamentarium for the treatment of SLE is expanding and a number of novel therapies are currently under investigation. In spite of this, steroid therapy remains the cornerstone of treatment and intravenous methylprednisolone (IVMP) is still widely used in clinical practice. There is however surprisingly little evidence on which to define its precise role. The objective of this review was to consider the published evidence relating to the use of IVMP in SLE patients and also to identify open questions that still need to be answered with regard to its use. In acute flares, IVMP induces rapid suppression of acute inflammation. There is not however a strong evidence base to support the use of high doses compared to low IVMP doses or oral prednisolone. In maintenance regimes, secondary analyses suggest that IVMP may confer additional long-term renal survival over oral steroids as part of a cyclophosphamide regime. Therefore, in addition to the evaluation of novel therapies for SLE, better evidence to define the precise role of IVMP in SLE is still required. ( Lupus (2007) 16, 387—393)
How adult are our learners?
Authors: Norrie Peter , Dalby David 
Published: July 2007

Knowles proposed a model to describe the characteristics of adult learners. This may be summarised by a move away from highly structured teaching methods (pedagogic teaching) to more explorative and less formal ones (andragogic teaching). This paper explores whether this progression occurs across an undergraduate nursing programme. Twelve questions based upon Knowles' model were incorporated into a Likert scale questionnaire. The sample was inclusive across three cohorts of an undergraduate nursing programme ( n = 555). No significant differences were found within the sample with reference to gender or branch. Some significant differences were present with reference to age and year of study, but these suggest that students regress from the characteristics of the adult learners within these parameters. Some significant differences were present with reference to ethnicity, suggesting that some ethnic-minority students were more willing to add to learning with independent study. The research findings do not conform to predictions based upon Knowles' model. There is no evidence that students gain more of the characteristics of andragogy as they progress through their studies. Instead, there is some evidence that students become less willing to take responsibility for their learning. This should be of concern to those involved in health education.
`No worries!'
Authors: Ingram Jenny , Salmon Debra 
Published: July 2007

`No Worries!' is a nurse-led drop-in sexual health service for young people in one Primary Care Trust in South West England. The service aims to provide sexual health promotion, contraception, STI testing and a range of health promotion advice. The service was evaluated from the young people's perspectives using quantitative and qualitative methodologies. Attendance data, questionnaires and interviews explored patterns of use, effectiveness and acceptability of three clinics, two in areas of social deprivation and a third with increasing teenage conception rates. Questionnaire data were collected from 153 young people (232 clinic attendances) and 18 were interviewed (aged 14—18 years). The pattern of service use varied across the clinics, with those from the lowest socio-economic community using fewer condoms, having more pregnancy tests and STI swabs. Average age of first intercourse was 15 years, and most visited the clinic after having sex rather than before. Young people found the service accessible and they highlighted close proximity to home and school, the drop-in nature, and confidentiality, professionalism and friendliness of staff. After using the service, respondents reported that they would be more likely to practise safer sex and change their behaviour. The clinics appeared to match up to young people's expectations of the service, but did not manage to attract many boys. Young people said the service made them feel more confident, more informed about sex, aware of sexually transmitted diseases and take fewer risks.
The developmental program of human dendritic cells is operated independently of conventional myeloid and lymphoid pathways
Authors: Ishikawa Fumihiko , Niiro Hiroaki , Iino Tadafumi , Yoshida Shuro , Saito Noriyuki , Onohara Shinya , Miyamoto Toshihiro , Minagawa Hiroko , Fujii Shin-ichiro , Shultz Leonard D. , Harada Mine , Akashi Koichi 
Published: July 2007

AbstractTwo distinct dendritic cell (DC) subsets, conventional DCs (cDCs) and plasmacytoid DCs (pDCs), have been shown to develop via either the myeloid or the lymphoid pathway in murine hematopoiesis. Lineage-specific phenotypes or functions of “myeloid” and “lymphoid” DCs, however, still remain elusive. Furthermore, such analysis has been particularly difficult in humans, due to lack of an assay system appropriate for the analysis of human stem and progenitor cell differentiation. Here, using a highly efficient xenotransplantation model, we extensively analyze the origin and the molecular signature of human DCs. Purified human common myeloid progenitors (CMPs) and common lymphoid progenitors (CLPs) were intravenously transplanted into nonobese diabetic–severe combined immunodeficiency (NOD-scid)/IL2rγnull newborn mice. CMPs and CLPs displayed significant expansion in the xenogeneic host, and human cDC and pDC progeny were isolatable. Strikingly, each human DC subset possessed indistinguishable expression patterns of surface phenotype and gene transcripts regardless of their CMP or CLP origin, even at the genome-wide level. Thus, cDC and pDC normally develop after cells have committed to the myeloid or the lymphoid lineage in human hematopoiesis, while their transcriptional signatures are well preserved irrespective of their lineage origin. We propose that human DCs use unique and flexible developmental programs that cannot be categorized into the conventional myeloid or lymphoid pathway.
Combination Therapy With Gefitinib and Rofecoxib in Patients With Platinum-Pretreated Relapsed Non–Small-Cell Lung Cancer
Authors: O'Byrne Kenneth J. , Danson Sarah , Dunlop David , Botwood Nick , Taguchi Fumiko , Carbone David , Ranson Malcolm 
Published: July 2007

Purpose In non–small-cell lung cancer (NSCLC), the epidermal growth factor receptor (EGFR) and cyclooxygenase-2 (COX-2) play major roles in tumorigenesis. This phase I/II study evaluated combined therapy with the EGFR tyrosine kinase inhibitor (TKI) gefitinib and the COX-2 inhibitor rofecoxib in platinum-pretreated, relapsed, metastatic NSCLC (n = 45). Patients and Methods Gefitinib 250 mg/d was combined with rofecoxib (dose escalated from 12.5 to 25 to 50 mg/d through three cohorts, each n = 6). Because the rofecoxib maximum-tolerated dose was not reached, the 50 mg/d cohort was expanded for efficacy evaluation (n = 33). Results Among the 42 assessable patients, there was one complete response (CR) and two partial responses (PRs) and 12 patients with stable disease (SD); disease control rate was 35.7% (95% CI, 21.6% to 52.0%). Median time to tumor progression was 55 days (95% CI, 47 to 70 days), and median survival was 144 days (95% CI, 103 to 190 days). In a pilot study, matrix-assisted laser desorption/ionization (MALDI) proteomics analysis of baseline serum samples could distinguish patients with an objective response from those with SD or progressive disease (PD), and those with disease control (CR, PR, and SD) from those with PD. The regimen was generally well tolerated, with predictable toxicities including skin rash and diarrhea. Conclusion Gefitinib combined with rofecoxib provided disease control equivalent to that expected with single-agent gefitinib and was generally well tolerated. Baseline serum proteomics may help identify those patients most likely to benefit from EGFR TKIs.
Magnetic Resonance Imaging of the Axial Skeleton for Detecting Bone Metastases in Patients With High-Risk Prostate Cancer: Diagnostic and Cost-Effectiveness and Comparison With Current Detection Strategies
Authors: Lecouvet Frédéric E. , Geukens Daphné , Stainier Annabelle , Jamar François , Jamart Jacques , d'Othée Bertrand Janne , Therasse Patrick , Berg Bruno Vande , Tombal Bertrand 
Published: July 2007

Purpose To evaluate the diagnostic performance, costs, and impact on therapy of one-step magnetic resonance imaging (MRI) of the axial skeleton (MRIas) for detecting bone metastases in patients with high-risk prostate cancer (PCa). Patients and Methods Sixty-six consecutive patients with high-risk PCa prospectively underwent MRIas in addition to the standard sequential work-up (SW) of bone metastases (technetium-99m bone scintigraphy [BS] completed with targeted x-rays [TXR] in patients with equivocal BS findings and with MRI obtained on request [MRIor] in patients with inconclusive BS/TXR findings). Panel review of initial and 6-month follow-up MRI findings, BS/TXR, and all available baseline and follow-up clinical and biologic data were used as the best valuable comparator to define metastatic status. Diagnostic effectiveness of MRIas alone was compared with each step of the SW. Impact of MRIas screening on patient management and costs was evaluated. Results On the basis of the best valuable comparator, 41 patients (62%) had bone metastases. Sensitivities were 46% for BS alone, 63% for BS/TXR, 83% for BS/TXR/MRIor, and 100% for MRIas; the corresponding specificities were 32%, 64%, 100%, and 88%, respectively. MRIas was significantly more sensitive than any other approach (P < .05, McNemar). MRIas identified metastases in seven (30%) of 23 patients considered negative and eight (47%) of 17 patients considered equivocal by other strategies, which altered the initially planned therapy. Economic impact was variable among countries, depending on reimbursement rates. Conclusion MRIas is more sensitive than the current SW of radiographically identified bone metastases in high-risk PCa patients, which impacts the clinical management of a significant proportion of patients.
Parental Grief After Losing a Child to Cancer: Impact of Professional and Social Support on Long-Term Outcomes
Authors: Kreicbergs Ulrika C. , Lannen Patrizia , Onelov Erik , Wolfe Joanne 
Published: July 2007

Purpose It is still uncertain whether or not parents can ever come to terms with the loss of a child and whether professional or social support facilitate the long-term grief process. Methods A Swedish population-based study, which sent an anonymous, mail-in questionnaire to parents who had lost a child to a malignancy 4 to 9 years earlier, gained the participation of 449 (80%) of 561 parents. Parents were asked whether, and to what extent, they had worked through their grief. Questions were also asked regarding those who provided parents with support. We examined candidate factors to determine their associations with greater likelihood of working through parental grief. Results Overall, most parents (74%) stated that they had worked through their grief “a lot” or “completely” at the time of the follow-up. Parents who had shared their problems with others during the child's illness (fathers: relative risk [RR], 3.0; 95% CI, 1.8 to 5.0; mothers: RR 1.9; 95% CI, 1.2 to 2.8) and who had access to psychological support during the last month of their child's life (fathers: RR 1.4; 95% CI, 1.0 to 1.8; mothers: RR 1.3; 95% CI, 1.1 to 1.6) were more likely to have worked through their grief. In cases where health care staff offered parents counseling during the child's last month, the parents were more likely to have worked through their grief (fathers: RR 1.5; 95% CI, 1.2 to 1.8; mothers; RR 1.2; 95% CI, 1.1 to 1.4). Conclusion Most parents eventually work through the grief associated with losing a child to cancer. In the long term, sharing the emotional burden with others facilitates the grieving process.
Bone Marrow Transplantation Generates Immature Oocytes and Rescues Long-Term Fertility in a Preclinical Mouse Model of Chemotherapy-Induced Premature Ovarian Failure
Authors: Lee Ho-Joon , Selesniemi Kaisa , Niikura Yuichi , Niikura Teruko , Klein Rachael , Dombkowski David M. , Tilly Jonathan L. 
Published: July 2007

Purpose Although early menopause frequently occurs in female cancer patients after chemotherapy (CTx), bone marrow (BM) transplantation (BMT) has been linked to an unexplained return of ovarian function and fertility in some survivors. Studies modeling this in mice have shown that BMT generates donor-derived oocytes in CTx-treated recipients. However, a subsequent report claimed that ovulated eggs are not derived from BM and that BM-derived oocytes reported previously are misidentified immune cells. This study was conducted to further clarify the impact of BMT on female reproductive function after CTx using a preclinical mouse model. Methods Female mice were administered CTx followed by BMT using coat color-mismatched female donors. After housing with males, the number of pregnancies and offspring genotype were recorded. For cell tracking, BM from germline-specific green fluorescent protein-transgenic mice was transplanted into CTx-treated wild-type recipients. Immune cells were sorted from blood and analyzed for germline markers. Results BMT rescued long-term fertility in CTx-treated females, but all offspring were derived from the recipient germline. Cell tracking showed that donor-derived oocytes were generated in ovaries of recipients after BMT, and two lines of evidence dispelled the claim that these oocytes are misidentified immune cells. Conclusion These data from a preclinical mouse model validate a testable clinical strategy for preserving or resurrecting ovarian function and fertility in female cancer patients after CTx, thus aligning with recommendations of the 2005 National Cancer Institute Breast Cancer Progress Review Group and President's Cancer Panel to prioritize research efforts aimed at improving the quality of life in cancer survivors.
Clinical Benefit With Docetaxel Plus Fluorouracil and Cisplatin Compared With Cisplatin and Fluorouracil in a Phase III Trial of Advanced Gastric or Gastroesophageal Adenocarcinoma: The V-325 Study Group
Authors: Ajani Jaffer A. , Moiseyenko Vladimir M. , Tjulandin Sergei , Majlis Alejandro , Constenla Manuel , Boni Corrado , Rodrigues Adriano , Fodor Miguel , Chao Yee , Voznyi Edouard , Marabotti Cindy , Van Cutsem Eric 
Published: July 2007

Purpose For patients with advanced gastric or gastroesophageal cancer (AGGEC) providing clinical benefit with improved palliation is highly desirable. However, a prospective evaluation of clinical benefit in AGGEC patients has never before been reported in a phase III setting. Patients and Methods In a multinational trial (V325), 445 patients were randomly assigned and treated with either docetaxel plus cisplatin and fluorouracil (DCF) or cisplatin and fluorouracil (CF). Clinical benefit was prospectively evaluated in this trial as a secondary end point. The primary measure for clinical benefit analysis was time to definitive worsening by one or more categories of Karnofsky performance status (KPS). Secondary clinical benefit end points included time to 5% definitive weight loss, time to definitive worsening of appetite by one grade, pain-free survival (defined as time to first appearance of pain), and time to first cancer pain-related opioid intake. Clinical benefit assessments were recorded at each clinic visit. Results Clinical benefit assessments were performed in more than 75% of patients throughout V325. DCF significantly prolonged time to definitive worsening of KPS compared with CF (median, 6.1 v 4.8 months; hazard ratio, 1.38; 95% CI, 1.08 to 1.76; log-rank P = .009). Although time to definitive weight loss and time to definitive worsening of appetite favored DCF, the results were not statistically significant. Pain-free survival and time to first cancer pain-related opioid intake were comparable. Conclusion To our knowledge, V325 is the first phase III trial to report clinical benefit in AGGEC patients. Clinical benefit was assessed beyond protocol-specific chemotherapy. The addition of D to CF not only significantly improved clinical benefit but also improved quality of life, time to progression, and overall survival compared with CF.
Expression of Epiregulin and Amphiregulin and K-ras Mutation Status Predict Disease Control in Metastatic Colorectal Cancer Patients Treated With Cetuximab
Authors: Khambata-Ford Shirin , Garrett Christopher R. , Meropol Neal J. , Basik Mark , Harbison Christopher T. , Wu Shujian , Wong Tai W. , Huang Xin , Takimoto Chris H. , Godwin Andrew K. , Tan Benjamin R. , Krishnamurthi Smitha S. , Burris Howard A. , Poplin Elizabeth A. , Hidalgo Manuel , Baselga Jose , Clark Edwin A. , Mauro David J. 
Published: July 2007

Purpose The antiepidermal growth factor receptor (EGFR) antibody cetuximab shows activity in multiple epithelial tumor types; however, responses are seen in only a subset of patients. This study was conducted to identify markers that are associated with disease control in patients treated with cetuximab. Patients and Methods One hundred ten patients with metastatic colorectal cancer were enrolled onto a cetuximab monotherapy trial. Transcriptional profiling was conducted on RNA from mandatory pretreatment metastatic biopsies to identify genes whose expression correlates with best clinical responses. EGFR and K-ras mutation analyses and EGFR gene copy number analyses were performed on DNA from pretreatment biopsies. Results Gene expression profiles showed that patients with tumors that express high levels of the EGFR ligands epiregulin and amphiregulin are more likely to have disease control with cetuximab (EREG, P = .000015; AREG, P = .000025). Additionally, patients whose tumors do not have K-ras mutations have a significantly higher disease control rate than patients with K-ras mutations (P = .0003). Furthermore, patients with tumors that have high expression of EREG or AREG also have significantly longer progression-free survival (PFS) than patients with low expression (EREG: P = .0002, hazard ratio [HR] = 0.47, and median PFS, 103.5 v 57 days, respectively; AREG: P < .0001, HR = 0.44, and median PFS, 115.5 v 57 days, respectively). Conclusion Patients with tumors that have high gene expression levels of epiregulin and amphiregulin and patients with wild-type K-ras are more likely to have disease control on cetuximab treatment. The identified markers could be developed further to select patients for cetuximab therapy.
Prospective Study of Rituximab in Chemotherapy-Dependent Human Immunodeficiency Virus–Associated Multicentric Castleman's Disease: ANRS 117 CastlemaB Trial
Authors: Gérard Laurence , Bérezné Alice , Galicier Lionel , Meignin Véronique , Obadia Martine , De Castro Nathalie , Jacomet Christine , Verdon Renaud , Madelaine-Chambrin Isabelle , Boulanger Emmanuelle , Chevret Sylvie , Agbalika Felix , Oksenhendler Eric 
Published: July 2007

Purpose Single-agent chemotherapy is usually effective in HIV-associated multicentric Castleman's disease (MCD). However, in most patients, chemotherapy cannot be discontinued. Patients and Methods To evaluate the efficacy of four weekly rituximab infusions (375 mg/m2) after discontinuation of chemotherapy in HIV-associated MCD, 24 patients were enrolled onto a prospective open-label trial. Results At study entry, the median time from MCD diagnosis was 21 months. All patients had stable disease on chemotherapy and were dependent on chemotherapy for a median time of 13 months. The median CD4 cell count was 270 × 106/L, and the plasma HIV RNA was less than 50 copies/mL in 18 patients. One patient died with progressive disease at day 15, and 23 patients completed the four cycles of rituximab. Sustained remission (SR) off treatment at day 60 (primary end point) was achieved in 22 patients (92%). From day 60 to day 365, one patient died with acute respiratory failure of undetermined origin, and four patients experienced relapse. Seventeen patients (71%) were alive in SR at day 365 without specific treatment, and the overall survival rate was 92% (95% CI, 71% to 98%). Rituximab was well tolerated, and the majority of adverse events were mild to moderate infections. Mild exacerbation of Kaposi's sarcoma (KS) lesions was observed in eight of 12 patients with previous KS. Conclusion Rituximab was both effective and safe in HIV-infected patients with chemotherapy-dependent MCD.
Efficacy and Tolerability of Temozolomide in an Alternating Weekly Regimen in Patients With Recurrent Glioma
Authors: Wick Antje , Felsberg Jörg , Steinbach Joachim P. , Herrlinger Ulrich , Platten Michael , Blaschke Britta , Meyermann Richard , Reifenberger Guido , Weller Michael , Wick Wolfgang 
Published: July 2007

Purpose Evaluation of toxicity and efficacy of an alternating weekly regimen of temozolomide administered 1 week on and 1 week off in patients with recurrent glioma. Patients and Methods Ninety adult patients with recurrent gliomas accrued in one center received chemotherapy with temozolomide at 150 mg/m2/d (days 1 through 7 and 15 through 21 every 4 weeks) with individual dose adjustments according to hematologic toxicity. Results A total of 906 treatment weeks were delivered. Grade 4 hematotoxicity according to the Common Terminology Criteria for Adverse Events (CTCAE; version 3.0) was observed in 24 treatment weeks (2.6%). CTCAE grade 4 lymphopenia eventually developed in 11 patients (12%). There were neither cumulative lymphopenias nor opportunistic infections. The progression-free survival (PFS) rate at 6 months for glioblastoma patients was 43.8%. The median PFS in these patients was 24 weeks (95% CI, 17 to 26 weeks), the median survival time from diagnosis of progression was 38 weeks (95% CI, 30 to 46 weeks), and the 1-year survival rate from progression was 23%. O6-methylguanine DNA methyltransferase (MGMT) gene promoter methylation in the tumor tissue was not associated with longer PFS (log-rank P = .37). Conclusion These data imply that the alternating weekly schedule is feasible, safe, and effective and clearly warrants investigation in randomized studies. Compared with more protracted low-dose temozolomide schedules, the 1-week-on/1-week-off schedule may be less toxic. We provide preliminary evidence that this dose-dense schedule is also active in patients with tumors lacking MGMT gene promoter methylation.
PIEPOC: A New Prognostic Index for Advanced Epithelial Ovarian Cancer—Japan Multinational Trial Organization OC01-01
Authors: Teramukai Satoshi , Ochiai Kazunori , Tada Harue , Fukushima Masanori 
Published: July 2007

Purpose The purpose of this study was to construct a simple and powerful prognostic index (PI) of epithelial ovarian cancer, the PIEPOC. Patients and Methods In a retrospective review, data from 768 women with stage III or IV epithelial ovarian cancer from 24 institutions in Japan were evaluated for clinical features predictive of overall survival. A PI and risk groups to predict overall survival after initial surgery were developed using the proportional hazards regression model. Results Of six factors, the four prognostic factors that remained independently significant in the analysis of a training sample (538 randomly selected patients) were age, performance status (PS), histologic cell type, and residual tumor size. From the regression function, we derived a PI = 1 (if age 70 and above) + 1 (if PS 1 or 2) + 2 (if PS 3 or 4) + 1 (if mucinous or clear-cell) + 2 (if residual size 0.1 cm and above). Patients were classified into three risk groups (PIEPOC): low risk (PI 0-2), intermediate risk (PI 3), and high risk (PI 4-6). The PIEPOC was equally predictive in a validation sample (n = 230), identifying three groups (5-year survival: 0.67 in low, 0.43 in intermediate, 0.17 in high risk). Conclusion Our proposed PI, the PIEPOC, was predictive in our patient population and may have utility in clinical practice. Prospective studies would be needed to confirm the prognostic predictive ability of the PIEPOC for patients with advanced epithelial ovarian cancer.