Alan J. Neville

Chemotherapy with mitoxantrone plus prednisone or prednisone alone for symptomatic hormone-resistant prostate cancer: a Canadian randomized trial with palliative end points.

PURPOSE To investigate the benefit of chemotherapy in patients with symptomatic hormone-resistant prostate cancer using relevant end points of palliation in a randomized controlled trial. PATIENTS AND METHODS We randomized 161 hormone-refractory patients with pain to receive mitoxantrone plus prednisone or prednisone alone (10 mg daily). Nonresponding patients on prednisone could receive mitoxantrone subsequently. The primary end point was a palliative response defined as a 2-point decrease in pain as assessed by a 6-point pain scale completed by patients (or complete loss of pain if initially 1 +) without an increase in analgesic medication and maintained for two consecutive evaluations at least 3 weeks apart. Secondary end points were a decrease of > or = 50% in use of analgesic medication without an increase in pain, duration of response, and survival. Health-related quality of life was evaluated with a series of linear analog self-assessment scales (LASA and the Prostate Cancer-Specific Quality-of-Life Instrument [PROSQOLI]), the core questionnaire of the European Organization for Research and Treatment of Cancer (EORTC), and a disease-specific module. RESULTS Palliative response was observed in 23 of 80 patients (29%; 95% confidence interval, 19% to 40%) who received mitoxantrone plus prednisone, and in 10 of 81 patients (12%; 95% confidence interval, 6% to 22%) who received prednisone alone (P = .01). An additional seven patients in each group reduced analgesic medication > or = 50% without an increase in pain. The duration of palliation was longer in patients who received chemotherapy (median, 43 and 18 weeks; P < .0001, log-rank). Eleven of 50 patients randomized to prednisone treatment responded after addition of mitoxantrone. There was no difference in overall survival. Treatment was well tolerated, except for five episodes of possible cardiac toxicity in 130 patients who received mitoxantrone. Most responding patients had an improvement in quality-of-life scales and a decrease in serum prostate-specific antigen (PSA) level. CONCLUSION Chemotherapy with mitoxantrone and prednisone provides palliation for some patients with symptomatic hormone-resistant prostate cancer.

Problem-Based Learning and Medical Education Forty Years On

Problem-based learning (PBL) has swept the world of medical education since its introduction 40 years ago, leaving a trail of unanswered or partially answered questions about its benefits. The literature is replete with systematic reviews and meta-analyses, all of which have identified some common themes; however, heterogeneity in the definition of a ‘problem-based learning curriculum’ and its delivery, coupled with different outcome measurements, has produced divergent opinions. Proponents and detractors continue to dispute the merits of the cognitive foundation of a PBL approach, but, despite this, there is evidence that graduates of PBL curricula demonstrate equivalent or superior professional competencies compared with graduates of more traditional curricula.

Bisphosphonate Associated Osteonecrosis of the Jaw

In 2003, the first reports describing osteonecrosis of the jaw (ONJ) in patients receiving bisphosphonates (BP) were published. These cases occurred in patients with cancer receiving high-dose intravenous BP; however, 5% of the cases were in patients with osteoporosis receiving low-dose bisphosphonate therapy. We present the results of a systematic review of the incidence, risk factors, diagnosis, prevention, and treatment of BP associated ONJ. We conducted a comprehensive literature search for relevant studies on BP associated ONJ in oncology and osteoporosis patients published before February 2008.All selected relevant articles were sorted by area of focus. Data for each area were abstracted by 2 independent reviewers. The results showed that the diagnosis is made clinically. Prospective data evaluating the incidence and etiologic factors are very limited. In oncology patients receiving high-dose intravenous BP, ONJ appears to be dependent on the dose and duration of therapy, with an estimated incidence of 1%–12% at 36 months of exposure. In osteoporosis patients, it is rare, with an estimated incidence < 1 case per 100,000 person-years of exposure. The incidence of ONJ in the general population is not known. Currently, there is insufficient evidence to confirm a causal link between low-dose BP use in the osteoporosis patient population and ONJ. We concluded BP associated ONJ is associated with high-dose BP therapy primarily in the oncology patient population. Prevention and treatment strategies are currently based on expert opinion and focus on maintaining good oral hygiene and conservative surgical intervention.

Health-Related Quality of Life in Men With Metastatic Prostate Cancer Treated With Prednisone Alone or Mitoxantrone and Prednisone

PURPOSE A combination of mitoxantrone plus prednisone is preferable to prednisone alone for reduction of pain in men with metastatic, hormone-resistant, prostate cancer. The purpose of this study was to assess the effects of these treatments on health-related quality of life (HQL). PATIENTS AND METHODS Men with metastatic prostate cancer (n = 161) were randomized to receive either daily prednisone alone or mitoxantrone (every 3 weeks) plus prednisone. Those who received prednisone alone could have mitoxantrone added after 6 weeks if there was no improvement in pain. HQL was assessed before treatment initiation and then every 3 weeks using the European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire C30 (EORTC QLQ-C30) and the Quality of Life Module-Prostate 14 (QOLM-P14), a trial-specific module developed for this study. An intent-to-treat analysis was used to determine the mean duration of HQL improvement and differences in improvement duration between groups of patients. RESULTS At 6 weeks, both groups showed improvement in several HQL domains, and only physical functioning and pain were better in the mitoxantrone-plus-prednisone group than in the prednisone-alone group. After 6 weeks, patients taking prednisone showed no improvement in HQL scores, whereas those taking mitoxantrone plus prednisone showed significant improvements in global quality of life (P =.009), four functioning domains, and nine symptoms (.001 < P <. 01), and the improvement (> 10 units on a scale of 0 to100) lasted longer than in the prednisone-alone group (.004 < P <.05). The addition of mitoxantrone to prednisone after failure of prednisone alone was associated with improvements in pain, pain impact, pain relief, insomnia, and global quality of life (.001 < P <.003). CONCLUSION Treatment with mitoxantrone plus prednisone was associated with greater and longer-lasting improvement in several HQL domains and symptoms than treatment with prednisone alone.

Use of palliative end points to evaluate the effects of mitoxantrone and low-dose prednisone in patients with hormonally resistant prostate cancer.

PURPOSE This phase II study was designed to assess the effects of mitoxantrone with prednisone in patients with metastatic prostate cancer who had progressed on hormonal therapy. The methods of assessment included quality-of-life analyses, pain indices, analgesic scores, and the National Prostatic Cancer Project (NPCP) criteria. PATIENTS AND METHODS Patients received mitoxantrone 12 mg/m2 intravenously every 3 weeks plus prednisone 10 mg orally daily. All had a castrate serum testosterone and Eastern Cooperation Oncology Group (ECOG) performance status < or = 3, and had not received prior chemotherapy. Every 3 weeks, analgesic intake was scored, and a present pain intensity (PPI) record and visual analog scale (VAS) describing pain were collected. Every 6 weeks, the European Organization for Research and Treatment of Cancer (EORTC) core quality-of-life questionnaire plus a prostate-specific module were completed. A palliative response was defined as a decrease in analgesic score by > or = 50% or a decrease in PPI by > or = two integers without any increase in the other. RESULTS Twenty-seven patients were entered onto the study. Nine of 25 (36%) assessable patients achieved a palliative response maintained for > or = two cycles (range, two to eight or more). Improvements in mean PPI and VAS pain scores after each cycle of therapy (P < .05) were seen. Quality-of-life analysis showed improvements in social and emotional functioning, and in pain and anorexia. Using NPCP criteria, one patient achieved a partial response (PR) and 12 had stable disease; one of seven patients with measurable disease had a PR. No serious nonhematologic toxicity was experienced, and there were no episodes of febrile neutropenia. CONCLUSION Mitoxantrone with low-dose prednisone is a well-tolerated treatment regimen that has some beneficial effects on disease-related symptoms and quality of life for patients with advanced prostate cancer.

The Use of Triangulation in Qualitative Research

Triangulation refers to the use of multiple methods or data sources in qualitative research to develop a comprehensive understanding of phenomena (Patton, 1999). Triangulation also has been viewed as a qualitative research strategy to test validity through the convergence of information from different sources. Denzin (1978) and Patton (1999) identified four types of triangulation: (a) method triangulation, (b) investigator triangulation, (c) theory triangulation, and (d) data source triangulation. The current article will present the four types of triangulation followed by a discussion of the use of focus groups (FGs) and in-depth individual (IDI) interviews as an example of data source triangulation in qualitative inquiry.

The problem-based learning tutor: Teacher? Facilitator? Evaluator?

Despite the structural heterogeneity of problem-based learning (PBL) curricula, most PBL schools have embraced self-directed learning, emphasizing the use of small-group discussion and integration of the basic medical sciences with clinical problems. Self-directed learning is but one of the many terms such as discovery method or study-centred education adopted by authors since Dewey to describe an educational approach that places the learner in control of his or her learning (Knowles, 1975). The putative bene® ts of self-directed learning include enhanced opportunities to elaborate one’s knowledge through active involvement and verbalization, enhanced motivation through an increase in relevance and personal control, and the practice of skills needed in lifelong learning (Schmidt, 1983). In this educational milieu, the role of the `teacher’ requires revision; new skills are required of the teaching faculty so that they are willing and competent to allow students to take an active role in guiding their own learning and in teaching one another (Barrows & Tamblyn, 1980). This review explores the literature that has developed around the de® nition of the teacher or tutor role in `facilitating’ the learning of students in a PBL setting. Several controversies have arisen over the optimal role of the faculty person in facilitating a PBL tutorial group, including level of participation, content knowledge and involvement in student evaluation. While it appears that there is probably no completely satisfactory resolution of these controversies, from a review of the frequently con icting pieces of evidence, an attempt will be made to synthesize from the literature a coherent picture of an effective tutor in the PBL setting.

The value of basic science in clinical diagnosis.

Background The role of basic science knowledge in clinical diagnosis is unclear. There has been no experimental demonstration of its value in helping students recall and organize clinical information. This study examines how causal knowledge may lead to better recall and diagnostic skill over time. Method Undergraduate medical students learned either four neurological or rheumatic disorders. One group learned a basic science explanation for the symptoms. The other learned epidemiological information. Both were then tested with the same set of clinical cases immediately after learning and one week later. Results On immediate test, there was no difference in accuracy (70% for both groups). However, one week later, performance in the epidemiology group dropped to 51%; the basic science group only dropped to 62%. Conclusions Basic science knowledge relating causal knowledge to disease symptoms can improve diagnostic accuracy after a delay.

Economic evaluation of chemotherapy with mitoxantrone plus prednisone for symptomatic hormone-resistant prostate cancer: based on a Canadian randomized trial with palliative end points.

PURPOSE To evaluate the economic consequences of the use of chemotherapy in patients with symptomatic hormone-resistant prostate cancer (HRPC) in the context of a previously published Canadian open-label, phase III, randomized trial with palliative end points. PATIENTS AND METHODS The trial randomized 161 patients to initial treatment with mitoxantrone and prednisone (M + P) or to prednisone alone (P) and showed better palliation with M + P. There was no significant difference in survival. A detailed retrospective chart review was performed of resources used from randomization until death of 114 of 161 patients enrolled at the three largest centers: these included hospital admissions, outpatient visits, investigations, therapies (which included all chemotherapy and radiation), and palliative care. Cancer center and community hospital costs were calculated by using the hotel approximation method and case costing from the Ontario Case Cost Project, respectively. Cost-utility analysis was performed by transforming the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 global quality-of-life item measured every 3 weeks on trial to an estimate of utility, and extending the last known value through to death or last follow-up. RESULTS The mean total cost until death or last follow-up by intention-to-treat was M + P CDN

Assessment steers learning down the right road: Impact of progress testing on licensing examination performance

27,300; P CDN