Biomedical subjects
David Joske
Publications and source records attributed to David Joske.
Patient perceptions of the GP role in cancer management.
BACKGROUND: During the course of their cancer treatment, patients have to deal with a number of health professionals. We investigated patients' perceptions of the role of the general practitioner, with particular reference to GPs' ability to manage patients' cancer outside of the hospital setting. METHOD: We took a phenomenological approach, focussing on empowerment, and any central role of the GP. In depth interviews were conducted on the same haematological cancer patients over a 2 year period. Results were analysed for main themes regarding support and management of illness. RESULTS: Many patients had a long term relationship with an individual GP. They perceived GPs as providing a primarily supportive rather than treatment role outside of the hospital setting, and relied on them for clarification and reassurance. DISCUSSION: The personal, confiding relationship between the GP and cancer patient might be better exploited by specialists. Patients could feel more empowered in relation to their condition if provided with information by their GP that is more relevant and explicit. For this to occur, specialists must first provide GPs with timely and pertinent information about their cancer management.
Real-time quantitative PCR analysis can be used as a primary screen to identify patients with CML treated with imatinib who have BCR-ABL kinase domain mutations.
Mutations within the BCR-ABL kinase domain in imatinib-treated chronic myeloid leukemia (CML) are the main mechanism of acquired resistance. The early detection of mutations should provide clinical benefit by allowing early intervention. Quantitative polymerase chain reaction (RQ-PCR) results of BCR-ABL mRNA were correlated with mutation analysis in 214 patients treated with imatinib. We determined whether there was a difference in the incidence of mutations between the patients with a more than 2-fold rise in BCR-ABL and patients with stable or decreasing levels. Of the 56 patients with a more than 2-fold rise, 34 (61%) had detectable mutations (median rise, 3.0-fold; 25th-75th percentiles, 2.3-5.2). In 31 (91%) of these 34 patients, the mutation was present at the time of the rise and became detectable within 3 months in the remaining patients. Only 1 (0.6%) of 158 patients with stable or decreasing BCR-ABL levels had a detectable mutation, P less than .0001. Thus, a more than 2-fold rise identified 34 (97%) of 35 patients with a mutation. We conclude that a rise in BCR-ABL of more than 2-fold can be used as a primary indicator to test patients for BCR-ABL kinase domain mutations.
Haematological cancer patients: achieving a sense of empowerment by use of strategies to control illness.
BACKGROUND: The role that empowerment plays through involving haematological cancer patients and their families in their treatment and care is undeniable. It encompasses the implementation of various strategies to achieve a sense of empowerment. AIMS AND OBJECTIVES: This phenomenological study sought to identify core strategies used by cancer patients regardless of their illness stage and prognosis who exhibited a strong sense of empowerment in coping with their condition. DESIGN: A phenomenological approach using an in depth interviewing technique was used to identify the common factors which patients and spouses believed could enable them to achieve a measure of control in managing their illness. These measures were referred to as coping strategies. METHODS: It was decided to conduct a purposive study and re-interview seven of 12 patients who had previously participated in a pilot Haematology Shared Care project and who had developed a high level of ability in coping with their illness. At the patient's discretion, spouses were invited to participate and to contribute to the interview. Three spouses participated in the interviewing process. RESULTS: Common strategies emerged regardless of the patient's stage of illness and prognosis. Informants identified the determination to remain in control of the illness and treatment side effects, having the support of family and significant others, illness acceptance and maintaining hope as crucial to their sense of empowerment. RELEVANCE TO CLINICAL PRACTICE: It is hoped that clinicians will gain a deeper understanding of the varied and numerous strategies used by cancer patients in coping with their illness. This understanding will ensure that by encouraging these strategies, patients and their families will be supported by health professionals to achieve a greater sense of empowerment. As this and other studies have shown, working alongside health professionals contributes to empowerment for both the cancer patient and significant others in their lives.
Autologous hemopoietic stem cell transplantation in severe rheumatoid arthritis: a report from the EBMT and ABMTR.
OBJECTIVE: Since 1996, autologous hemopoietic stem cell transplantation (HSCT) has been used to treat severe rheumatoid arthritis (RA). To date, published reports have been individual cases or series containing small numbers. This study combined the worldwide experience in a single analysis. METHODS: The Autoimmune Disease Databases of the European Group for Blood and Marrow Transplantation (EBMT) and the Autologous Blood and Marrow Transplant Registry (ABMTR) were used to identify patients with RA treated with autologous HSCT. Further information relating to patient and treatment-specific variables was obtained by questionnaire. RESULTS: Seventy-six patients were registered from 15 centers. Seventy-three patients had received autologous HSCT, and in 3 patients hematopoietic stem cells (HSC) were mobilized but not transplanted. Transplanted patients (median age 42 yrs, 74% female, 86% rheumatoid factor positive) had been previously treated with a mean of 5 (range 2-9) disease modifying antirheumatic drugs (DMARD). Significant functional impairment was present, with a median Health Assessment Questionnaire (HAQ) score of 1.4 (range 1.1-2.0) and Steinbrocker score mean 2.39 (SD 0.58). The high dose treatment regimen was cyclophosphamide (CYC) alone in the majority of patients, mostly 200 mg/kg (n = 62). Seven patients received anti-thymocyte globulin (ATG) in addition to CYC, 2 patients busulfan and CYC (BuCYC), and one patient CYC with total body irradiation and ATG. One patient received fludarabine with ATG. Following treatment, one patient received bone marrow but the rest received chemotherapy and/or granulocyte colony-stimulating factor mobilized peripheral blood stem cells. The harvest was unmanipulated in 28 patients, the rest receiving some form of lymphocyte depletion, mostly through CD34+ selection. Median followup was 16 months (range 3-55). Responses were measured using the American College of Rheumatology (ACR) criteria. Forty-nine patients (67%) achieved at least ACR 50% response at some point following transplant. There was a significant reduction in the level of disability measured by the HAQ (p < 0.005). Most patients restarted DMARD within 6 months for persistent or recurrent disease activity, which provided disease control in about half the cases. Response was significantly related to seronegative RA (p = 0.02) but not to duration of disease, number of previous DMARD, presence of HLA-DR4, or removal of lymphocytes from the graft. There was no direct transplant related mortality, although one patient, treated with the BuCYC regimen, died 5 months post-transplant from infection and incidental non-small cell lung cancer. CONCLUSION: Autologous HSCT is a relatively safe form of salvage treatment in severe, resistant RA. In these open label studies significant responses were achieved in most patients, with over 50% achieving an ACR 50 or more response at 12 months. Although the procedure is not curative, recurrent or persistent disease activity may be subsequently controlled in some patients with DMARD. Clinical trials are necessary to develop this approach in patients with aggressive disease who have failed conventional treatment including anti-tumor necrosis factor agents.
Detection of BCR-ABL mutations in patients with CML treated with imatinib is virtually always accompanied by clinical resistance, and mutations in the ATP phosphate-binding loop (P-loop) are associated with a poor prognosis.
Imatinib-treated chronic myeloid leukemia (CML) patients with acquired resistance commonly have detectable BCR-ABL kinase domain mutations. It is unclear whether patients who remain sensitive to imatinib also have a significant incidence of mutations. We evaluated 144 patients treated with imatinib for BCR-ABL kinase domain mutations by direct sequencing of 40 accelerated phase (AP), 64 late chronic phase (> or = 12 months from diagnosis, late-CP), and 40 early-CP patients. Mutations were detected in 27 patients at 17 different residues, 13 (33%) of 40 in AP, 14 (22%) of 64 in late-CP, and 0 of 40 in early-CP. Acquired resistance was evident in 24 (89%) of 27 patients with mutations. Twelve (92%) of 13 patients with mutations in the adenosine triphosphate (ATP) binding loop (P-loop) died (median survival of 4.5 months after the mutation was detected). In contrast, only 3 (21%) of 14 patients with mutations outside the P-loop died (median follow-up of 11 months). As the detection of mutations was strongly associated with imatinib resistance, we analyzed features that predicted for their detection. Patients who commenced imatinib more than 4 years from diagnosis had a significantly higher incidence of mutations (18 [41%] of 44) compared with those treated within 4 years (9 [9%] of 100), P <.0001. Lack of a major cytogenetic response (MCR) was also associated with a higher likelihood of detecting a mutation; 19 (38%) of 50 patients without a MCR had mutations compared with 8 (8.5%) of 94 with an MCR, P <.0001. In conclusion, the detection of kinase domain mutations using a direct sequencing technique was almost always associated with imatinib resistance, and patients with mutations in the P-loop had a particularly poor prognosis.
A pilot randomized trial comparing CD34-selected versus unmanipulated hemopoietic stem cell transplantation for severe, refractory rheumatoid arthritis.
OBJECTIVE: Evidence from animal studies, case reports, and phase I studies suggests that hemopoietic stem cell transplantation (HSCT) can be effective in the treatment of rheumatoid arthritis (RA). It is unclear, however, if depletion of T cells in the stem cell product infused after high-dose chemotherapy is beneficial in prolonging responses by reducing the number of infused autoreactive T cells. This pilot multicenter, randomized trial was undertaken to obtain feasibility data on whether CD34 selection (as a form of T cell depletion) of an autologous stem cell graft is of benefit in the HSCT procedure in patients with severe, refractory RA. METHODS: Thirty-three patients with severe RA who had been treated unsuccessfully with methotrexate and at least 1 other disease-modifying agent were enrolled in the trial. The patients received high-dose immunosuppressive treatment with 200 mg/kg cyclophosphamide followed by an infusion of autologous stem cells that were CD34 selected or unmanipulated. Safety, efficacy (based on American College of Rheumatology [ACR] response criteria), and time to recurrence of disease were assessed on a monthly basis for up to 12 months. RESULTS: All patients were living at the end of the study, with no major unexpected toxicities. Overall, on an intent-to-treat basis, ACR 20% response (ACR20) was achieved in 70% of the patients. An ACR70 response was attained in 27.7% of the 18 patients who had received CD34-selected cells and 53.3% of the 15 who had received unmanipulated cells (P = 0.20). The median time to disease recurrence was 147 days in the CD34-selected cell group and 201 days in the unmanipulated cell group (P = 0.28). There was no relationship between CD4 lymphopenia and response, but 72% of rheumatoid factor (RF)-positive patients had an increase in RF titer prior to recurrence of disease. CONCLUSION: HSCT can be performed safely in patients with RA, and initial results indicate significant responses in patients with severe, treatment-resistant disease. Similar outcomes were observed in patients undergoing HSCT with unmanipulated cells and those receiving CD34-selected cells. Larger studies are needed to confirm these findings.
Palliative care and haematological malignancy: a case study.
There is now substantial evidence that patients with haematological malignancies are not referred to the palliative system. Findings from the in-depth qualitative analysis of a successful case study are presented as a paradigmatic example of creative solutions that are available to begin to address this issue of inequity of access. The data provides important insights on the factors that facilitated timely referral to the palliative system, factors that facilitated the opportunity to die at home, a description of important elements of the dying experience, and the outcome of the palliative care experience for the carer. The opportunity for a satisfying dying experience can be afforded to haematology patients. This case study highlights some aspects that need to be considered during the development of palliative services for these diagnostic groups.