bluuebunny/crossref_metadata_2025_split huggingface dataset:
Setting up a methadone maintenance clinic in a hostel in London's West End
Authors: Dunn John , Robertson David , Davis Paul , Khosrawan Babak , Christian Suneel 
Published: August 2006

Aims and MethodA satellite methadone prescribing service was set up in a hostel in London's West End. The aim was to investigate if it were feasible to engage and retain these hard-to-reach, chaotic, polydrug users in treatment. A basic needs assessment was undertaken with staff and clients at the hostel. Treatment outcomes were assessed at 16 weeks using the Maudsley Addiction Profile.ResultsAt 16 weeks 87% of the original cohort (26 out of 30) were still in treatment. There were also significant reductions in mean heroin use (from 29.7 to 14.5 out of the past 30 days, P<0.001) and in the frequency of injecting (from 25.9 to 15.9 days, P<0.001).Clinical ImplicationsThis outreach clinic offers a model for developing services to homeless people with substance misuse problems.
Psychological formulations in psychiatric care: staff views on their impact
Authors: Summers Alison 
Published: August 2006

Aims and MethodTo understand the benefits and limitations of using psychological formulations for patients with severe mental illness, a qualitative study of staff views was conducted, based on semi-structured interviews with 25 staff working in a high-dependency rehabilitation service.ResultsParticipants believed that formulations benefited care planning, staff–patient relationships, staff satisfaction and teamworking, through increasing understanding of patients, bringing together staff with different views and encouraging more creative thinking. They particularly valued meeting together to develop the formulations. Some staff accepted formulations as tentative and provisional, whereas others regarded them as statements of conviction.Clinical ImplicationsThe study suggests that using psychological formulations in the care of psychiatric patients may well be valuable, but needs further exploration.
Outpatient Oral Antibiotics for Febrile Neutropenic Cancer Patients Using a Score Predictive for Complications
Authors: Klastersky Jean , Paesmans Marianne , Georgala Aspasia , Muanza Frédérique , Plehiers Barbara , Dubreucq Laurent , Lalami Yassine , Aoun Michel , Barette Martine 
Published: August 2006

Purpose Since febrile neutropenic patients were recognized to constitute a heterogeneous population, several models have been developed for predicting the risk of serious medical complications. The Multinational Association for Supportive Care in Cancer score and its derived clinical prediction rules have been validated, but thus far there were no data about its use for simplifying therapy in predicted low-risk patients. Patients and Methods In a single institution, we followed all episodes of febrile neutropenia between January 1999 and November 2003. Those patients predicted at low risk for complications, who were not receiving antibacterials at fever onset and were eligible for treatment with oral antibiotics, were treated with ciprofloxacin and amoxicillin-clavulanate and were discharged if they were clinically stable or improving after an initial observation period. The primary end point of the study was the rate of resolution of the febrile neutropenic episode without complications, among these early discharged patients. Results Of 383 first febrile neutropenic episodes predicted at low risk of omplication, 178 patients (33 men and 145 women, mainly with solid tumors) were treated orally; they constituted the basis of our analysis. Seventy-nine patients (44%) were discharged early (with a median time to discharge of 26 hours); no complications occurred among them but three patients had to be readmitted, resulting in a success rate of 96% (95% CI, 92% to 100%). Conclusion Our study shows that oral therapy followed by early discharge was feasible in a small but significant proportion of patients selected by a strategy combining predicted low risk and medical and nonmedical criteria.
Thymidine Phosphorylase Expression Is Associated With Response to Capecitabine Plus Irinotecan in Patients With Metastatic Colorectal Cancer
Authors: Meropol Neal J. , Gold Philip J. , Diasio Robert B. , Andria Michael , Dhami Mandeep , Godfrey Thomas , Kovatich Albert J. , Lund Kirk A. , Mitchell Edith , Schwarting Roland 
Published: August 2006

PurposeTo evaluate the clinical activity and toxicity of capecitabine plus irinotecan as first-line therapy for patients with metastatic colorectal cancer (mCRC), and to describe the association of expression of thymidine phosphorylase (TP), thymidylate synthase (TS), and dihydropyrimidine dehydrogenase (DPD) with antitumor activity.Patients and MethodsPatients with previously untreated mCRC received irinotecan days 1 and 8 intravenously, and capecitabine days 2 to 15 orally in 21-day cycles. Doses were irinotecan 125 mg/m2and capecitabine 1,000 mg/m2bid (n = 15; cohort 1), or irinotecan 100 mg/m2and capecitabine 900 mg/m2bid (n = 52; cohort 2). Tissues from primary and metastatic sites were assessed for TP, TS, and DPD gene and protein expression.ResultsAn unacceptable level of GI toxicity in the first 15 patients led to a protocol modification in starting doses. The response rate was 45% (30 of 67 patients). Overall survival was associated with TP expression assessed by immunohistochemistry in both primary tumors (P = .045) and metastases (P = .001). Objective tumor response was associated with TP expression in primary tumors (odds ratio, 4.77; 95% CI, 1.25 to 18.18), with a similar trend in metastases (odds ratio, 8.67; 95% CI, 0.95 to 79.1). TP gene expression in primary tumors was also associated with response.ConclusionThese data indicate that capecitabine plus irinotecan is an active regimen against mCRC. The biomarker analysis (including metastatic tissue) was feasible in a multicenter setting, and provides preliminary evidence that TP expression may be a predictive marker for response.
Phase I Dose Escalation and Pharmacokinetic Study of Enzastaurin, an Oral Protein Kinase C Beta Inhibitor, in Patients With Advanced Cancer
Authors: Carducci Michael A. , Musib Luna , Kies Merrill S. , Pili Roberto , Truong Mylene , Brahmer Julie R. , Cole Patricia , Sullivan Rana , Riddle Jeanne , Schmidt Jill , Enas Nathan , Sinha Vikram , Thornton Donald E. , Herbst Roy S. 
Published: August 2006

Purpose This phase I study was conducted to determine the recommended dose of enzastaurin, an oral protein kinase C beta (PKCβ) inhibitor, for phase II trials. Secondary objectives were maximum-tolerated dose (MTD), pharmacokinetics (PK), toxicity, and response. Patients and Methods Patients at least 18 years of age with advanced cancer and an Eastern Cooperative Oncology Group performance status of 0 or 1 lower received enzastaurin orally once daily at a starting dose of 20 mg. Dose escalation proceeded using a modified Simon design. Results All 47 patients enrolled (mean age, 58 years) received at least one dose of enzastaurin, with a median of two cycles (range, one to 17 cycles). Prevalent malignancies were lung (n = 10) and head and neck cancers (n = 9). Although no MTD was identified up to 700 mg/d, 525 mg was chosen as the recommended dose, and 12 additional patients were accrued at that level. Three dose-limiting toxicities (QTc changes) occurred: one at the 700-mg dose (patient discontinued), and two in the expansion cohort at the 525-mg dose. Total analytes (enzastaurin and its metabolites) exposure increased with increasing doses up to 240 mg, and appeared to plateau at 525 and 700 mg. Grade 1 chromaturia, fatigue, and other GI toxicities were the most common, while no clinically significant grade 3/4 toxicities occurred. Two deaths, unrelated to enzastaurin, occurred. Twenty-one patients (45%) achieved stable disease (SD) for two to 16 cycles. Conclusion On the basis of plasma exposures and safety data, enzastaurin 525 mg once daily is the recommended phase II dose. Enzastaurin is well tolerated up to 700 mg/d. Evidence of early activity was seen with significant stable disease.
Prognostic Impact of Germinal Center–Associated Proteins and Chromosomal Breakpoints in Poor-Risk Diffuse Large B-Cell Lymphoma
Authors: van Imhoff Gustaaf W. , Boerma Evert-Jan G. , van der Holt Bronno , Schuuring Ed , Verdonck Leo F. , Kluin-Nelemans Hanneke C. , Kluin Philip M. 
Published: August 2006

Purpose Outcome of diffuse large B-cell lymphoma (DLBCL) with a germinal center B-cell (GCB) expression profile is superior to that of non-GCB DLBCL. This conclusion is mainly derived from patients with mixed international prognostic index (IPI) risk profiles treated with CHOP-like therapy (cyclophosphamide, doxorubicin, vincristine, and prednisone). We wondered whether the prognostic impact of the expression profile would hold out in a homogeneous cohort of poor-risk DLBCL patients treated with high-dose sequential therapy (HDT) and autologous stem-cell transplantation (ASCT) as first-line therapy. Patients and Methods DLBCL from 66 newly diagnosed poor-risk patients, treated in two sequential prospective Dutch Hemato-Oncology Association (HOVON) trials, were studied retrospectively for expression of CD10, bcl6, MUM1/IRF4, bcl2, Ki67, and CD21+ follicular dendritic cells (FDC) by immunohistochemistry, and for the breakpoints of BCL2, BCL6, and MYC by fluorescent in situ hybridization (FISH). Lymphomas with any follicular component were excluded. Results A GCB immunophenotype profile was found in 58% and non-GCB immunophenotype profile in 42% of the tumors. Clinical characteristics of both groups were similar. Complete response (CR) rate was higher in patients with CD10+ tumors (58% v 30%; P = .03). A GCB immunophenotype profile, its constituting markers CD10 more than 30% and MUM1 less than 70%, and bcl2 less than 10% were each associated with a better overall survival (OS). FDC networks, equally present in GCB and non-GCB tumors, had superior CR (73% v 31%; P = .01), but disease-free survival rates were lower and there was no difference in OS rates. None of the breakpoints had a prognostic impact on outcome. Conclusion Also in patients with poor-risk DLBCL treated with HDT and ASCT, the GCB immunophenotype and bcl2 expression retained a major impact on survival.
Phase I/II Study of Docetaxel, Cisplatin, and Concomitant Boost Radiation for Locally Advanced Squamous Cell Cancer of the Head and Neck
Authors: Tsao Anne S. , Garden Adam S. , Kies Merrill S. , Morrison William , Feng Lei , Lee J. Jack , Khuri Fadlo , Zinner Ralph , Myers Jeffery , Papadimitrakopoulou Vassiliki , Lewin Jan , Clayman Gary L. , Ang K. Kian , Glisson Bonnie S. 
Published: August 2006

Purpose To investigate the feasibility of combining concomitant boost accelerated radiation with docetaxel and cisplatin and assess the regimen's toxicity, locoregional control rate, and survival in patients with locally advanced head and neck cancer (HNSCC). Patients and Methods Patients with stage III-IV HNSCC were eligible. Phase I included two schedules of docetaxel and cisplatin: arm 1, once per week during weeks 1 to 4; arm 2, every 21 days for weeks 1 and 4. Radiation consisted of 72 Gy in 42 fractions over 6 weeks (concomitant boost). Results Twenty patients were enrolled in phase I. The arm 1 maximum-tolerated dose (MTD) was defined at docetaxel 15 mg/m2 and cisplatin 20 mg/m2 based on prolonged mucositis in 29% of patients. The initial dose level in arm 2 was above the MTD. In total, 52 patients were treated using the arm 1 regimen in phase II. Acute toxicity included grade 3 mucositis and dermatitis in 81% and 44% of patients. The 2-year locoregional control rate was 71%. The 2-year progression-free and overall survival rates were 61% and 65%. Median survival was 37.8 months. Late effects included feeding tube dependence in 17% of patients alive and free of disease. Conclusion Locoregional control, survival, and acute toxicity with this regimen were comparable with other trials utilizing taxanes and/or platins and concomitant conventional or altered fractionation radiation. Our data suggest that chemotherapy added to concomitant boost fractionation may increase rates of long-term feeding tube dependence. Phase III trials are needed to assess the contribution of concomitant boost fractionation to chemoradiotherapy.
Impact of a Multi-Disciplinary Patient Education Session on Accrual to a Difficult Clinical Trial: The Toronto Experience With the Surgical Prostatectomy Versus Interstitial Radiation Intervention Trial
Authors: Wallace Kris , Fleshner Neil , Jewett Michael , Basiuk Joan , Crook Juanita 
Published: August 2006

Purpose Random assignment to clinical trials involving different treatment modalities can be difficult. We describe our experience with the Surgical Prostatectomy Versus Interstitial Radiation Intervention Trial (SPIRIT; ACOSOG Z0070 NCIC PR10), a randomized trial for early-stage prostate cancer comparing radical prostatectomy (RP), and brachytherapy (BT). A multidisciplinary educational session was developed to improve patient understanding of treatment options and to facilitate accrual. Patients and Methods Prostate cancer referrals were screened and men who met favorable risk criteria (T1c/T2a, prostate-specific antigen [PSA] < 10 ng/mL, Gleason ≤ 6) were invited to a structured education session before a specialty consultation. Men and their partners viewed the SPIRIT informed-consent video and heard from a cancer patient who described his participation in a randomized trial. Then, a urologist and radiation oncologist together compared and contrasted RP and BT to establish the rationale for the trial. Results In May 2002, SPIRIT opened for accrual and was endorsed by the University Health Network urologists and radiation oncologists. The first 27 eligible patients were approached about SPIRIT, consulted both specialties, and viewed an educational video. No patients consented. The multidisciplinary education session was then introduced. Forty-seven education sessions with 263 patients resulted in 34 consents. Of 203 patients who were suitable for the study but declined random assignment, 62 chose surgery, 94 chose brachytherapy, three patients chose external radiotherapy, and 11 chose no treatment. Consent rates for eligible and suitable patients were one in six. Conclusion Men who understand their treatment options and trial rationale as presented jointly by representative specialists from competing treatment modalities may be better equipped to make an informed decision and are more likely to consent to random assignment.
Phase III Study of Craniospinal Radiation Therapy Followed by Adjuvant Chemotherapy for Newly Diagnosed Average-Risk Medulloblastoma
Authors: Packer Roger J. , Gajjar Amar , Vezina Gilbert , Rorke-Adams Lucy , Burger Peter C. , Robertson Patricia L. , Bayer Lisa , LaFond Deborah , Donahue Bernadine R. , Marymont MaryAnne H. , Muraszko Karin , Langston James , Sposto Richard 
Published: August 2006

Purpose To determine the event-free survival (EFS) and overall survival of children with average-risk medulloblastoma and treated with reduced-dose craniospinal radiotherapy (CSRT) and one of two postradiotherapy chemotherapies. Methods Four hundred twenty-one patients between 3 years and 21 years of age with nondisseminated medulloblastoma (MB) were prospectively randomly assigned to treatment with 23.4 Gy of CSRT, 55.8 Gy of posterior fossa RT, plus one of two adjuvant chemotherapy regimens: lomustine (CCNU), cisplatin, and vincristine; or cyclophosphamide, cisplatin, and vincristine. Results Forty-two of 421 patients enrolled were excluded from analysis. Sixty-six of the remaining 379 patients had incompletely assessable postoperative studies. Five-year EFS and survival for the cohort of 379 patients was 81% ± 2.1% and 86% ± 9%, respectively (median follow-up over 5 years). EFS was unaffected by sex, race, age, treatment regimen, brainstem involvement, or excessive anaplasia. EFS was detrimentally affected by neuroradiographic unassessability. Patients with areas of frank dissemination had a 5-year EFS of 36% ± 15%. Sixty-seven percent of progressions had some component of dissemination. There were seven second malignancies. Infections occurred more frequently on the cyclophosphamide arm and electrolyte abnormalities were more common on the CCNU regimen. Conclusion This study discloses an encouraging EFS rate for children with nondisseminated MB treated with reduced-dose craniospinal radiation and chemotherapy. Additional, careful, step-wise reductions in CSRT in adequately staged patients may be possible.
Six-Month Androgen Suppression Plus Radiation Therapy Compared With Radiation Therapy Alone for Men With Prostate Cancer and a Rapidly Increasing Pretreatment Prostate-Specific Antigen Level
Authors: D'Amico Anthony V. , Loffredo Marian , Renshaw Andrew A. , Loffredo Brittany , Chen Ming-Hui 
Published: August 2006

Purpose We evaluated whether treatment with 6 months of androgen-suppression therapy (AST) and radiation therapy (RT) compared with RT was associated with the time to prostate-specific antigen (PSA) recurrence, prostate cancer–specific mortality (PCSM), and all-cause mortality (ACM) in men with a pretreatment PSA velocity more than 2 ng/mL/yr. Patients and Methods The study cohort comprised 241 men with clinically localized or locally advanced prostate cancer treated with RT and AST or RT from 1989 to 2002. Cox regression and Gray's formulation were used to assess whether treatment was associated significantly with the time to PSA recurrence or ACM and PCSM, respectively, adjusting for known prognostic factors. Results Despite the significantly longer median follow-up, younger age at diagnosis, higher proportion of Gleason score 7 to 10, and advanced T-category cancers, significantly lower estimates of PSA recurrence (P < .001), PCSM (P = .007), and ACM (P < .001) were observed in men who were treated using RT and AST compared with RT. Treatment with RT and AST compared with RT was associated with a longer time to PSA recurrence (adjusted hazard ratio [HR], 0.22; 95% CI, 0.14 to 0.35; P < .001), PCSM (HR, 0.23, 95% CI, 0.09 to 0.64; P = .005), and ACM (HR, 0.30; 95% CI, 0.16 to 0.58; P < .001). Conclusion Treatment using 6 months of AST and RT compared with RT in men with a pretreatment PSA velocity greater than 2 ng/mL/yr was associated with a longer time to PSA recurrence, PCSM, and ACM.
Cost-Effectiveness Analysis of Computerized Tomography in the Routine Follow-Up of Patients After Primary Treatment for Hodgkin’s Disease
Authors: Guadagnolo Beverly A. , Punglia Rinaa S. , Kuntz Karen M. , Mauch Peter M. , Ng Andrea K. 
Published: August 2006

Purpose To estimate the clinical benefits and cost effectiveness of computed tomography (CT) in the follow-up of patients with complete response (CR) after treatment for Hodgkin’s disease (HD). Patients and Methods We developed a decision-analytic model to evaluate follow-up strategies for two hypothetical cohorts of 25-year-old patients with stage I-II or stage III-IV HD, treated with doxorubicin, bleomycin, vinblastine, and dacarbazine-based chemotherapy with or without radiation therapy, respectively. We compared three strategies for observing asymptomatic patients after CR: routine annual CT for 10 years, annual CT for 5 years, or follow-up with non-CT modalities only. We used Markov models to calculate life expectancy, quality-adjusted life expectancy, and lifetime costs. Baseline probabilities, transition probabilities, and utilities were derived from published studies. Cost data were derived from the Medicare fee schedule and medical literature. We performed sensitivity analyses by varying baseline estimates. Results Annual CT follow-up is associated with minimal survival benefit. With adjustments for quality of life, we found a decrement in quality-adjusted life expectancy for early-stage patients followed with CT compared with non-CT modalities. Sensitivity analyses showed annual CT for 5 years becomes more effective than non-CT follow-up if the specificity of CT is 80% or more or if the disutility associated with a false-positive CT result is less than 0.01 quality-adjusted life years (QALYs). For advanced-stage patients, annual CT for 5 years is associated with a very small quality-adjusted survival gain over non-CT follow-up with an incremental cost-effectiveness ratio of $9,042,300/QALY. Conclusion Our analysis suggests that routine CT should not be used in the surveillance of asymptomatic patients in CR after treatment for HD.
Increased Epidermal Growth Factor Receptor Gene Copy Number Is Associated With Poor Prognosis in Head and Neck Squamous Cell Carcinomas
Authors: Chung Christine H. , Ely Kim , McGavran Loris , Varella-Garcia Marileila , Parker Joel , Parker Natalie , Jarrett Carolyn , Carter Jesse , Murphy Barbara A. , Netterville James , Burkey Brian B. , Sinard Robert , Cmelak Anthony , Levy Shawn , Yarbrough Wendell G. , Slebos Robbert J.C. , Hirsch Fred R. 
Published: August 2006

PurposeHigh epidermal growth factor receptor (EGFR) gene copy number is associated with poor prognosis in lung cancer, but such findings have not been reported for HNSCC. A better understanding of the EGFR pathway may improve the use of EGFR inhibitors in HNSCC.Patients and MethodsEGFR status was analyzed in 86 tumor samples from 82 HNSCC patients by fluorescent in situ hybridization (FISH) to determine EGFR gene copy number, by polymerase chain reaction and direct sequencing for activating mutations, and by DNA microarray and immunohistochemistry for RNA and protein expression. The results were associated with patient characteristics and clinical end points.ResultsForty-three (58%) of 75 samples with FISH results demonstrated EGFR high polysomy and/or gene amplification (FISH positive). The FISH-positive group did not differ from the FISH-negative group with respect to age, sex, race, tumor grade, subsites and stage, or EGFR expression by analyses of RNA or protein. No activating EGFR mutations were found. However, the FISH-positive group was associated with worse progression-free and overall survival (P < .05 and P < .01, respectively; log-rank test). When microarray data were interrogated using the FISH results as a supervising parameter, ECop (which is known to coamplify with EGFR and regulate nuclear factor-kappa B transcriptional activity) had higher expression in FISH-positive tumors.ConclusionHigh EGFR gene copy number by FISH is frequent in HNSCC and is a poor prognostic indicator. Additional investigation is indicated to determine the biologic significance and implications for EGFR inhibitor therapies in HNSCC.