bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exploring professionals' understanding, interpretation and implementation of the ‘appropriate medical treatment test’ in the 2007 amendment of the Mental Health Act 1983
Authors: Perry Benjamin I. , Champaneri Nina , Griffiths Frances , Paul Moli , Islam Zoebia , Rugkåsa Jorun , Burns Tom , Tyrer Peter , Crawford Michael , Deb Shoumitro , Singh Swaran P. 
Published: February 2017

BackgroundThe appropriate medical treatment test (ATT), included in the Mental Health Act (MHA) (1983, as amended 2007), aims to ensure that detention only occurs when treatment with the purpose of alleviating a mental disorder is available.AimsAs part of the Assessing the Impact of the Mental Health Act (AMEND) project, this qualitative study aimed to assess professionals' understanding of the ATT, and its impact on clinical practice.MethodForty-one professionals from a variety of mental health subspecialties were interviewed. Interviews were coded related to project aims, and themes were generated in an inductive process.ResultsWe found that clinicians are often wholly relied upon for the ATT. Considered treatment varied depending on the patient's age rather than diagnosis. The ATT has had little impact on clinical practice.ConclusionsOur findings suggest the need to review training and support for professionals involved in MHA assessments, with better-defined roles. This may enable professionals to implement the ATT as its designers intended.
Phase II trial of a 3-hour infusion of paclitaxel in previously untreated patients with advanced non-small-cell lung cancer.
Authors: Millward M J , Bishop J F , Friedlander M , Levi J A , Goldstein D , Olver I N , Smith J G , Toner G C , Rischin D , Bell D R 
Published: February 2017

PURPOSE To determine the antitumor activity and toxicity of paclitaxel administered as a 3-hour infusion in patients with advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS Fifty-one patients with advanced measurable or assessable NSCLC and performance status 0 to 2 who had not received prior chemotherapy were treated with paclitaxel 175 mg/m2 over 3 hours with premedication. Cycles were repeated every 3 weeks for a maximum of nine cycles. Most patients had prior radiotherapy (57%), extrathoracic metastatic disease (65%), and measurable disease (75%). Twenty-two percent had previously untreated stage III disease. RESULTS The objective response rate was five of 51 (10%; 95% confidence interval, 3% to 21%). No subgroup with a higher response rate could be identified. There were no complete responses (CRs) and all responses lasted less than 5 months. Treatment was well tolerated with brief World Health Organization (WHO) grade IV neutropenia in only 16% of patients. Grade III/IV myalgia/athralgia occurred in 22% of patients. No significant hypersensitivity reactions occurred. CONCLUSION The antitumor activity of this dose and schedule appears inferior to that reported in previously published phase II trials in NSCLC that used higher doses of paclitaxel infused over 24 hours, although confidence intervals for response overlap. Determining the optimal dose and schedule for using paclitaxel in NSCLC requires further investigation, and these results should caution against using shorter infusions outside appropriate clinical trials.
Geographic variation in patient surveillance after colon cancer surgery.
Authors: Johnson F E , McKirgan L W , Coplin M A , Vernava A M , Longo W E , Wade T P , Virgo K S 
Published: February 2017

PURPOSE Considerable variation among surgeons exists in the current practice of patient surveillance after colon cancer treatment. We evaluated whether geographic factors are responsible for this observed variation. METHODS Profiles of hypothetical patients and a detailed questionnaire based on the profiles were mailed to 2,733 members of two national surgical societies. The influence of the geographic location of the respondents on practice patterns were assessed in two ways. Repeated-measures analysis of variance was used to compare the practice patterns among 19 large metropolitan statistical areas (MSAs) and chi 2 analysis was used to determine whether these patterns differed by MSA population size. RESULTS Seven of nine commonly used surveillance modalities were ordered significantly more frequently with increasing tumor-node-metastasis (TNM) stage and significantly less frequently with year postsurgery among the 995 respondents with assessable responses, but MSA population size and geographic location of physicians generally had no effect on documented practice variability. The remaining two modalities (bone scan and computed tomography [CT]) were used so infrequently as to preclude meaningful analysis. CONCLUSION Surveillance after potentially curative colon cancer surgery for otherwise healthy patients is not significantly affected by the geographic location of the surgeon who performs the surveillance testing and only modestly affected by the population size of the MSA in which he/she practices. These data should help in the design of prospective trials of this topic.
Outcome of high-dose therapy and autologous transplantation in non-Hodgkin's lymphoma based on the presence of tumor in the marrow or infused hematopoietic harvest.
Authors: Sharp J G , Kessinger A , Mann S , Crouse D A , Armitage J O , Bierman P , Weisenburger D D 
Published: February 2017

PURPOSE To evaluate the outcomes in 65 consecutive patients with non-Hodgkin's lymphoma (NHL) undergoing high-dose therapy (HDT) and autologous transplantation based on initial marrow involvement and the presence or absence of minimal disease in the hematopoietic harvests. PATIENTS AND METHODS Patients with any history of histologic evidence of marrow tumor underwent autologous peripheral-blood stem-cell transplantation (PSCT), whereas others underwent autologous bone marrow transplantation (ABMT). Patients who underwent ABMT were further segregated retrospectively into two groups depending on whether there was evidence by cell culture and/or Southern analysis of minimal tumor in the marrow harvest. RESULTS Comparable proportions (58% to 60%) of patients in each of the two groups (PSCT and ABMT) achieved a complete clinical remission (CR) at 100 days. For patients who achieve a CR, the actuarial relapse-free survival rate at 5 years for PSCT patients who received a tumor-negative apheresis harvest was 64%, compared with 57% for patients who received a tumor-negative bone marrow harvest and 17% for patients who received a histologically negative but minimally contaminated bone marrow harvest. Lymphoma grade and phenotype were not significant predictors of outcome. CONCLUSION The observation that survival was significantly better in the groups of patients who received tumor-negative harvests and worse for patients who received minimally contaminated harvests suggests that tumor cells, even at minimal levels, reinfused in the transplanted harvest are responsible for progression in a proportion of patients who achieve a CR following HDT, although other biologic characteristics of the tumor could also be important. A relatively good outcome can be achieved with HDT and PSCT, even in patients with a significant marrow tumor burden.
Randomized phase II trial comparing different doses of the bisphosphonate ibandronate in the treatment of hypercalcemia of malignancy.
Authors: Pecherstorfer M , Herrmann Z , Body J J , Manegold C , Degardin M , Clemens M R , Thürlimann B , Tubiana-Hulin M , Steinhauer E U , van Eijkeren M , Huss H J , Thiébaud D 
Published: February 2017

PURPOSE To evaluate the hypocalcemic effect and safety of three different doses of the bisphosphonate ibandronate in tumor-associated hypercalcemia, and to identify factors predicting response. PATIENTS AND METHODS One hundred seventy-four cancer patients with a serum calcium level greater than 2.7 mmol/L (10.8 mg/dL) were enrolled onto the trial. If hypercalcemia persisted after fluid repletion, patients were randomly assigned to treatment with 0.6 mg, 1.1 mg, and 2.0 mg of ibandronate. Response, defined as restoration of normocalcemia, was evaluated by an intent-to-treat analysis. RESULTS One hundred seventy-three (99%) patients were assessable for toxicity and 151 (87%) for efficacy. The administration of 0.6 mg (group A), 1.1 mg (group B), or 2.0 mg (group C) of ibandronate led to response rates of 44%, 52%, and 67%, respectively. Significantly more patients in group C responded than in group A (P = .0276). Of the various parameters examined, only the initial serum calcium level (P < .0001; odds ratio, 0.083) and the dose of ibandronate (P = .0162; odds ratio, 2.094) correlated with response. One hundred ninety-five adverse events (AEs) were reported, 99 classified as serious and 96 as nonserious. Three serious and sixteen nonserious AEs were considered related to ibandronate treatment. The three serious AEs were one case with thrombocytopenia, one with nausea, and one with fever. CONCLUSION Ibandronate therapy led to a dose-dependent reduction in serum calcium levels. The response to ibandronate treatment correlated negatively with the initial serum calcium level and positively with the dose administered. A dose of 2 mg was necessary to achieve a response rate comparable to that in previous studies with the bisphosphonates pamidronate and clodronate. Because the incidence of drug-associated AEs was low, a dose escalation of ibandronate can be recommended for further clinical trials.
New statistical strategy for monitoring safety and efficacy in single-arm clinical trials.
Authors: Thall P F , Simon R M , Estey E H 
Published: February 2017

PURPOSE Efficacy and toxicity are both important outcomes in cancer clinical trials. Nonetheless, most statistical designs for phase II trials only provide rules for evaluating treatment efficacy, and moreover only allow early stopping after fixed cohorts of patients have been treated. We illustrate a new statistical design strategy for monitoring both adverse and efficacy outcomes on a patient-by-patient basis in phase II and other single-arm clinical trials. DESIGN The new strategy is used to design a phase II trial of the experimental regimen idarubicin plus cytarabine (ara-C) plus cyclosporine for treatment of patients with intermediate-prognosis acute myelogenous leukemia (AML). The design requires a maximum of 56 patients and provides continuous monitoring boundaries to terminate the trial if the toxicity rate is unacceptably high or the complete remission (CR) rate is unacceptably low compared with the rates of these events with the standard regimen of anthracycline plus ara-C. RESULTS The design has an 88% to 91% probability of stopping the trial early with a median of 15 to 18 patients if the toxicity rate of the experimental regimen is .05 to .10 above that of the standard and there is no improvement in the CR rate. If there is a .15 improvement in the CR rate and the toxicity rate is no more than .05 above that of the standard, then there is at least an 83% probability that the trial will run to completion. CONCLUSION The proposed monitoring strategy provides a flexible, practical means to continuously monitor both safety and efficacy in single-arm cancer clinical trials. The design strategy can be implemented easily using a freely available menu-driven computer program, and provides a scientifically sound alternative to the use of ad hoc safety monitoring rules.
Phase II and pharmacologic study of docetaxel as initial chemotherapy for metastatic breast cancer.
Authors: Hudis C A , Seidman A D , Crown J P , Balmaceda C , Freilich R , Gilewski T A , Hakes T B , Currie V , Lebwohl D E , Baselga J , Raptis G , Gollub M , Robles M , Bruno R , Norton L 
Published: February 2017

PURPOSE Because docetaxel (Taxotere, RP 56976; Rhone-Poulenc Rorer, Antony, France) appeared to be active against breast cancer in phase I trials, we performed this phase II study. PATIENTS AND METHODS Thirty-seven patients with measurable disease were enrolled. Only prior hormone therapy was allowed, as was adjuvant chemotherapy completed > or = 12 months earlier. Docetaxel 100 mg/m2 was administered over 1 hour every 21 days. Diphenhydramine hydrochloride and/or corticosteroid premedication was added after hypersensitivity-like reactions (HSRs) were seen in two of the first six patients. Pharmacokinetic studies were performed during cycle 1 for correlation with toxicity. RESULTS Thirty-seven patients were assessable. Nineteen (51%) required dose reductions, usually for neutropenic fever. The median nadir WBC count was 1.4 x 10(3)/microL. HSRs were noted in 20 patients (54%). At a median cumulative dose of 297 mg/m2 (range, 99.6 to 424.5 mg/m2), 30 patients (81%) developed fluid retention, for which 11 (30%) subsequently stopped treatment. The first-cycle plasma area under the concentration-time curve (AUC) did not correlate with toxicity, although an ineligible patient with hepatic metastases (pretreatment bilirubin level 1.8 mg/dL) had an elevated AUC and died of toxicity. Responses were seen at all sites. On an intent-to-treat basis, there were two (5%) complete responses (CRs) and 18 (49%) partial responses (PRs). The overall response proportion (CRs plus PRs) was 54% (95% confidence interval, 37% to 71%). The median time to response was 12 weeks (range, 3 to 15) and the median duration was 26 weeks (range, 10 to 58+). CONCLUSION Docetaxel is active for metastatic breast cancer. Neutropenia and fluid retention are dose-limiting. The AUC did not predict toxicity, but caution is warranted when treating patients with liver dysfunction. An understanding of the pathophysiology of the fluid retention may facilitate prevention. Frequent HSR may warrant prophylactic premedication.
Outcome of extensive evaluation before adjuvant therapy in women with breast cancer and 10 or more positive axillary lymph nodes.
Authors: Crump M , Goss P E , Prince M , Girouard C 
Published: February 2017

PURPOSE To evaluate the effect of extensive screening of women with high-risk, node-positive breast cancer on the detection of occult metastatic disease and patient eligibility for a randomized trial of the addition of high-dose chemotherapy and autologous bone marrow support (ABMT) to standard adjuvant therapy. PATIENTS AND METHODS Women with resected T1-3N1,2 primary breast cancer and > or = 10 positive axillary lymph nodes referred for possible trial participation were evaluated for this report. All had normal chest x-ray, bone scan, and liver ultrasound performed by the referring physician. Those who provided informed consent for the randomized trial were further evaluated according to protocol with computed tomographic (CT) scans of the head, chest, abdomen, and pelvis and bilateral bone marrow biopsies; those with metastatic disease detected by any of these tests were excluded from study registration. RESULTS Forty-four women were evaluated between February 1993 and April 1995. Fourteen did not undergo further protocol staging because of refusal to participate or the presence of metastatic disease on clinical assessment or review of outside radiologic studies. The remaining 30 underwent additional investigations, and seven (23%; 95% confidence interval [CI], 12% to 41%) had metastases detected by CT scanning (four patients) or bone marrow biopsy (three patients) not detected by routine screening. CONCLUSION Although the number of patients evaluated is small, these data suggest that some of the improvement in outcome of women with > or = 10 positive axillary lymph nodes who receive ABMT as part of adjuvant chemotherapy in phase II trials may be from the exclusion of patients with occult metastatic disease. The importance of these exclusions can only be determined by ongoing, randomized controlled trials.
Phase I study of paclitaxel in combination with cyclophosphamide and granulocyte colony-stimulating factor in metastatic breast cancer patients.
Authors: Tolcher A W , Cowan K H , Noone M H , Denicoff A M , Kohler D R , Goldspiel B R , Barnes C S , McCabe M , Gossard M R , Zujewski J , O'Shaughnessy J A 
Published: February 2017

PURPOSE In vitro data suggest that prolonged exposure to paclitaxel enhances breast cancer cytotoxicity. Our objective in this phase I study was to determine the tolerability of paclitaxel administered by 72-hour continuous intravenous (i.v.) infusion (CIVI) in combination with high-dose cyclophosphamide and granulocyte colony-stimulating factor (G-CSF) in the ambulatory setting to metastatic breast cancer patients. PATIENTS AND METHODS Paclitaxel was administered over 72 hours by CIVI and cyclophosphamide was given daily by i.v. bolus on days 1, 2, and 3, followed by G-CSF every 21 days. The availability of ambulatory infusion pumps and paclitaxel-compatible tubing permitted outpatient administration. RESULTS Fifty-five patients with metastatic breast cancer who had been previously treated with a median of two prior chemotherapy regimens were entered onto the study. Dose-limiting toxicity of grade 4 neutropenia for longer than 5 days and grade 4 thrombocytopenia occurred in three of five patients treated with paclitaxel 160 mg/m2 CIVI and cyclophosphamide 3,300 mg/m2 followed by G-CSF. The maximum-tolerated dose (MTD) was paclitaxel 160 mg/m2 CIVI and cyclophosphamide 2,700 mg/m2 in divided doses with G-CSF. Nonhematologic toxicities were moderate and included diarrhea, mucositis, and arthalgias. Although hemorrhagic cystitis developed in six patients, recurrence was prevented with i.v. and oral mesna, which permitted continued outpatient delivery. One hundred seventy-four cycles were safely administered in the ambulatory setting using infusional pumps and tubing. Objective responses occurred in 23 (one complete and 22 partial) of 42 patients with bidimensionally measurable disease (55%; 95% confidence interval, 38% to 70%), with a response rate of 73% (11 of 15) seen at the highest dose levels. CONCLUSION Paclitaxel by 72-hour CIVI with daily cyclophosphamide followed by G-CSF can be administered safely in the ambulatory setting, has acceptable toxicity, and is an active regimen in the treatment of metastatic breast cancer.
In vivo purging of bone marrow in children with poor-risk neuroblastoma for marrow collection and autologous bone marrow transplantation.
Authors: Saarinen U M , Wikström S , Mäkipernaa A , Lanning M , Perkkiö M , Hovi L , Rapola J , Sariola H 
Published: February 2017

PURPOSE To evaluate the following prospectively in poor-risk neuroblastoma (NBL) patients: (1) the feasibility and efficacy of in vivo purging of bone marrow; and (2) the outcome after autologous bone marrow transplantation (ABMT) when immunologically tumor-free, unpurged autografts were used. PATIENTS AND METHODS Twenty-three children with poor-risk NBL were evaluated during induction chemotherapy by repeat bone marrow examinations, including aspirate, biopsy, and an immunofluorescence method using the anti-GD2 monoclonal antibody 3A7. Nineteen patients completed the program with surgery with or without local irradiation followed by ABMT. RESULTS Autologous bone marrow grafts, both immunologically and cytologically clean, were obtained and used in 19 of 23 children. The overall 4-year disease-free survival of the 19 grafted children was 53%, with a toxic death rate of 16% and a posttransplant relapse rate of 37%. According to the in vivo purging efficacy of the 18 children with initial marrow disease, the following three groups were formed: patients with (1) perfect in vivo purging (n = 5); (2) eventually successful in vivo purging (n = 8); and (3) unsuccesful in vivo purging (n = 5). The 4-year DFS was 100%, 67%, and 0%, respectively (P < 0.001). The five patients with unsuccessful in vivo purging failed because of resistant/progressive bulky disease. CONCLUSION In patients with poor-risk NBL, in vivo purging of bone marrow by conventional chemotherapy is feasible, can be monitored, and the purging efficacy during the first 3 months after diagnosis is a strong prognostic factor reflecting tumor responsiveness to therapy. Autografting with immunologically clean, unpurged marrows gives a DFS well comparable to previous studies using ex vivo purging.
Biweekly intensified ambulatory chronomodulated chemotherapy with oxaliplatin, fluorouracil, and leucovorin in patients with metastatic colorectal cancer.
Authors: Bertheault-Cvitkovic F , Jami A , Ithzaki M , Brummer P D , Brienza S , Adam R , Kunstlinger F , Bismuth H , Misset J L , Lévi F 
Published: February 2017

PURPOSE This study sought to determine the feasibility and antitumor efficacy of an intensified three-drug chronomodulated regimen with maximum delivery at 4:00 AM for fluorouracil (5-FU)-leucovorin (folinic acid [FA]) and at 4:00 PM for oxaliplatin (I-OHP). PATIENTS AND METHODS Fifty patients with metastatic colorectal cancer were enrolled in the trial. The first treatment course consisted of daily administration of 5-FU (700 mg/m2/d), FA (300 mg/m2/d), and L-OHP (25 mg/m2/d) for 4 days with a multichannel programmable pump. Courses were repeated every 14 days, with 5-FU escalation by 100 mg/m2/d if toxicity was less than grade 2. RESULTS World Health Organization (WHO)-modified grade 3 or 4 diarrhea (40% of patients and 7% of courses) or stomatitis (28% of patients and 4% of courses) or grade 2 cumulative peripheral sensitive neuropathy (28% of patients) were dose-limiting. Median 5-FU and L-OHP dose-intensities (DIs), were increased by 32% and 18%, respectively, as compared with our previous 5 days on-16 days off schedule. The overall objective response rate was 48% (95% confidence limits [CL], 34% to 62%), being 40% (24% to 57%) in 37 previously treated patients and 69% (48% to 90%) in 13 chemotherapy-naive patients. A 5-FU DI > 1,400 mg/m2/wk over four courses was associated with a near doubling of the response rate. Residual metastases were surgically removed in 13 patients (26%). Median progression-free survival and survival durations were 9.3 months (95% CL, 6.6 to 11.2) and 17.8 months (95% CL, 14.1 to 21.4), respectively. CONCLUSION This highly effective fully ambulatory outpatient regimen deserves further testing in randomized trials both in chemotherapy-naive patients and before surgery to remove metastases.