Use of a formal consensus development technique to produce recommendations for improving the effectiveness of adult mental health multidisciplinary team meetings.

BACKGROUND: Multidisciplinary team (MDT) meetings are the core mechanism for delivering mental health care but it is unclear which models improve care quality. The aim of the study was to agree recommendations for improving the effectiveness of adult mental health MDT meetings, based on national guidance, research evidence and experiential insights from mental health and other medical specialties. METHODS: We established an expert panel of 16 health care professionals, policy-makers and patient representatives. Five panellists had experience in a range of adult mental health services, five in heart failure services and six in cancer services. Panellists privately rated 68 potential recommendations on a scale of one to nine, and re-rated them after panel discussion using the RAND/UCLA Appropriateness Method to determine consensus. RESULTS: We obtained agreement (median ≥ 7) and low variation in extent of agreement (Mean Absolute Deviation from Median of ≤1.11) for 21 recommendations. These included the explicit agreement and auditing of MDT meeting objectives, and the documentation and monitoring of treatment plan implementation. CONCLUSIONS: Formal consensus development methods that involved learning across specialities led to feasible recommendations for improved MDT meeting effectiveness in a wide range of settings. Our findings may be used by adult mental health teams to reflect on their practice and facilitate improvement. In some other contexts, the recommendations will require modification. For example, in Child and Adolescent Mental Health Services, context-specific issues such as the role of carers should be taken into account. A limitation of the comparative approach adopted was that only five members of the panel of 16 experts were mental health specialists.

Cost effectiveness of itraconazole in the prophylaxis of invasive fungal infections.

BACKGROUND: Invasive fungal infections in neutropenic patients treated for haematological malignancies are associated with a high mortality rate and, therefore, require early treatment. As the diagnosis of invasive fungal infections is difficult, effective antifungal prophylaxis is desirable. So far, fluconazole has been the most commonly used. OBJECTIVE: To assess the cost effectiveness of itraconazole compared with both fluconazole and no prophylaxis for the prevention of invasive fungal infections in haematological patients, mean age 51 years, in Germany and The Netherlands. STUDY DESIGN: We designed a probabilistic decision model to fully incorporate the uncertainty associated with the risk estimates of acquiring an invasive fungal infection. These risk estimates were extracted from two meta-analyses, evaluating the effectiveness of fluconazole and itraconazole and no prophylaxis. The perspective of the analysis was that of the healthcare sector; only medical costs were taken into account. All costs were reported in euro, year 2004 values.Cost effectiveness was expressed as net costs per invasive fungal infection averted. No discounting was performed, as the model followed patients during their neutropenic period, which was assumed to be less than 1 year. RESULTS: According to our probabilistic decision model, the monetary benefits of averted healthcare exceed the costs of itraconazole prophylaxis under baseline assumptions (95% CI: from cost-saving to euro 5000 per invasive fungal infection averted). Compared with fluconazole, itraconazole is estimated to be both more effective and more economically favourable, with a probability of almost 98%. CONCLUSIONS: In specific groups of neutropenic patients treated for haematological malignancies, itraconazole prophylaxis could potentially reduce overall healthcare expenditure, without harming effectiveness, in settings where fluconazole is common practice in the prophylaxis of invasive fungal infections.

The debate: The trials have told us very little.

The original trials of empiric intravenous amphotericin-B in the 1980s failed to prove conclusively its efficacy in the treatment of febrile neutropenia. Despite that, all subsequent studies of the therapy of presumed, possible, probable and proven invasive aspergillosis have assumed that this drug, either as deoxycholate or in lipid-based form, is the gold standard treatment against which all newcomers should be compared. This has led to a series of further inconclusive randomized controlled trials of empiric therapy as a result of which the most we can say is that nearly all new drugs are less toxic but also no more effective than amphotericin-B deoxycholate. The toxicity of the non-lipid formulation of this drug should have led us to withdraw it from both RCTs and routine clinical practice some years ago in view of the increasing evidence of equivalent efficacy and lower toxicity of other agents including lipid amphotericin formulations.Recent studies of the use of newer diagnostic techniques (i.e., CT and serology) reinforce the need to abandon the empiric trial approach in which we have repeatedly shown lack of superiority in the treatment of an infection which most patients do not have. Even in the small number of trials of the therapy of proven or probable invasive aspergillosis, results have been inconclusive or at best confusing in trying to find a better option than amphotericin-B. The trial of voriconazole versus amphotericin-B deoxycholate for this indication is a model for study for all those interested in the difficulties of designing trials which lead to convincing results.Effective prophylaxis trials and their analyses began by following a more rational pathway, first showing convincingly that fluconazole reduced the risk of C. albicans systemic infection in transplant patients. Unfortunately the widespread faith in the ability of this drug to prevent a wider range of systemic fungal infections in a wider range of patients is simply not supported by the data from many subsequent single trials and meta-analyses. This attachment to fluconazole has been mirrored by unwillingness to accept the evidence that itraconazole is superior in prophylaxis to fluconazole which is inactive against Aspergillus spp. In this case the trials have not told us enough because we have not believed the results. Results of trials of extended range azoles such as posaconazole are interesting but there are insufficient data to claim that posaconazole is superior to itraconazole.The progress in therapy and prophylaxis of systemic fungal infection has been unsatisfactory and slow. A new approach is needed for the design of clinical trials for these indications. There is good evidence that supportive investigations should now be used routinely in clinical practice and trials to increase certainty about the presence of invasive infection, to limit unnecessary use of expensive and toxic drugs and to improve analysis of efficacy of old and new antifungal agents.

A study of the proteins responsible for stimulating B-CLL-specific T-cell responses by autologous dendritic cells pulsed with tumour cell lysate.

We have previously shown that autologous dendritic cells (DCs) pulsed with tumour cell lysate and cultured with autologous T cells from patients with B-cell chronic lymphocytic leukaemia (B-CLL) stimulate significant increases in proliferation, IFN-gamma secretion and specific HLA class II-restricted cytotoxicity to B-CLL targets. In this study, normal and tumour cell lysates were analysed by reducing SDS-PAGE, and protein bands of interest eluted from the polyacrylamide gel by electroelution. The eluted protein fractions and whole-cell lysate were then pulsed onto autologous DCs and cocultured with autologous T cells. Finally, the stimulatory fractions were sequenced. B-CLL cell lysates revealed protein bands at 65, 42, 35 and 25 kDa, while normal B-cell lysates only showed a single protein band at 65 kDa. Both the 65 kDa band and 42 kDa bands were capable of stimulating comparable amounts of IFN-gamma secretion and specific cytotoxicity as whole lysate, while the other protein bands were not. Sequencing of the 65 kDa fraction showed a dominant peptide that matched human serum albumin, while sequencing the 42 kDa fraction showed three dominant peptides which matched human actin and another unidentified protein. The significance of these findings remains unclear.

Determinants of treatment plan implementation in multidisciplinary team meetings for patients with chronic diseases: a mixed-methods study.

OBJECTIVE: Multidisciplinary team (MDT) meetings are assumed to produce better decisions and are extensively used to manage chronic disease in the National Health Service (NHS). However, evidence for their effectiveness is mixed. Our objective was to investigate determinants of MDT effectiveness by examining factors influencing the implementation of MDT treatment plans. This is a proxy measure of effectiveness, because it lies on the pathway to improvements in health, and reflects team decision making which has taken account of clinical and non-clinical information. Additionally, this measure can be compared across MDTs for different conditions. METHODS: We undertook a prospective mixed-methods study of 12 MDTs in London and North Thames. Data were collected by observation of 370 MDT meetings, interviews with 53 MDT members, and from 2654 patient medical records. We examined the influence of patient-related factors (disease, age, sex, deprivation, whether their preferences and other clinical/health behaviours were mentioned) and MDT features (as measured using the 'Team Climate Inventory' and skill mix) on the implementation of MDT treatment plans. RESULTS: The adjusted odds (or likelihood) of implementation was reduced by 25% for each additional professional group represented at the MDT meeting. Implementation was more likely in MDTs with clear goals and processes and a good 'Team Climate' (adjusted OR 1.96; 95% CI 1.15 to 3.31 for a unit increase in Team Climate Inventory (TCI) score). Implementation varied by disease category, with the lowest adjusted odds of implementation in mental health teams. Implementation was also lower for patients living in more deprived areas (adjusted odds of implementation for patients in the most compared with least deprived areas was 0.60, 95% CI 0.39 to 0.91). CONCLUSIONS: Greater multidisciplinarity is not necessarily associated with more effective decision making. Explicit goals and procedures are also crucial. Decision implementation should be routinely monitored to ensure the equitable provision of care.

Curability of patients with acute myeloid leukemia who did not undergo transplantation in first remission.

PURPOSE: The aims of this study were to quantify the prospects of salvage treatment of patients who did not undergo transplantation in first complete remission (CR1) and to assess the contribution of allograft in second complete remission (CR2) with respect to major risk groups. This evaluation can inform the decision whether to offer a transplant in CR1. PATIENTS AND METHODS: Of 8,909 patients who entered the Medical Research Council AML10, AML12, and AML15 trials, 1,271 of 3,919 patients age 16 to 49 years who did not receive a transplant in CR1 relapsed. Of these patients, 19% are alive beyond 5 years compared with 7% of patients who relapsed after an allograft in CR1. Overall survival and the contribution of a transplant in CR2 were assessed overall and by cytogenetic risk group by using Mantel-Byar analysis. RESULTS: Fifty-five percent of patients who relapsed entered CR2. This percentage varied by risk group as follows: favorable (82%), intermediate (54%), adverse (27%), and unknown (53%), which resulted in 5-year survivals of 32%, 17%, 7%, and 23%, respectively. Sixty-seven percent of remitters received an allotransplant that delivered superior survival compared with patients who did not receive a stem-cell transplant (42% v 16%). A more-stringent assessment of a transplant by using delayed-entry (Mantel-Byar) analysis confirmed the benefit of transplant overall and within intermediate and adverse risk groups but not the favorable subgroup. CONCLUSION: Successful salvage treatment of patients who do not undergo transplantation in CR1 and relapse can be achieved in 19% of patients, which is improved by a transplant except in favorable risk disease. This result suggests that, for intermediate-risk patients in particular, equivalent overall survival can be achieved by delaying transplantation until after relapse, which would require many fewer transplants.

Clinico-pathologic characteristics of patients with hepatic lymphoma diagnosed using image-guided liver biopsy techniques.

Primary hepatic lymphoma is a rare presentation of a common disease. Diagnosis is difficult due to the risks of liver biopsy. We report the clinico-pathologic features of this presentation and specifically the utility of image-guided biopsy as a safe method of diagnosis. We retrospectively studied patients diagnosed with 'hepatic lymphoma' at a single center. Twenty-two patients fulfilled the criteria. Median age was 53 years (range 29-87). Nine patients were human immunodeficiency virus (HIV)-positive. The most frequent mode of presentation was with B-symptoms (15/22). All procedures were successful at obtaining diagnostic material with no complications. Six patients had synchronous bone marrow involvement. Nineteen patients received chemotherapy (10 had dose reductions) with an overall response rate of 74%. After a median follow-up of 19 months, 12 patients had died; the median overall survival (OS) was 4 months. Grade 3 or 4 aspartate transaminase (AST) abnormality was associated with very poor outcome. The OS of patients with hepatic lymphoma is poor. However, a response to modern induction therapies may predict a better outcome. The optimal dose adjustment of chemotherapy in this setting is unclear. In patients without readily accessible tissue, an image-guided core biopsy of hepatic lesions is a safe procedure with high diagnostic yield.

A comparison of low-dose cytarabine and hydroxyurea with or without all-trans retinoic acid for acute myeloid leukemia and high-risk myelodysplastic syndrome in patients not considered fit for intensive treatment.

BACKGROUND: The survival of older patients with acute myeloid leukemia has not improved. Few clinical trials have been available for older patients who are not considered fit for an intensive chemotherapy approach. METHODS: Between December 1998 and November 2003, as part of National Cancer Research Institute Acute Myeloid Leukemia 14 Trial, 217 patients, who were deemed unfit for intensive chemotherapy were randomized to receive low-dose cytarabine (Ara-C) (20 mg twice daily for 10 days) or hydroxyurea with or without all-trans retinoic acid (ATRA). RESULTS: Low-dose ara-C produced a better remission rate (18% vs 1%; odds ratio [OR], 0.15; 95% confidence interval [95% CI], 0.06-0.37; P = .00006) and better overall survival (OR, 0.60; 95% CI, 0.44-0.81; P = .0009), which was accounted for by the achievement of complete remission (CR) (duration of CR: 80 weeks vs 10 weeks for patients with no CR). Patients who had adverse cytogenetics did not benefit. ATRA had no effect. Toxicity scores or supportive care requirements did not differ between the treatment arms. CONCLUSIONS: Older, less fit patients have a poor outcome, and few trials have been conducted in this patient group. Low-dose ara-C treatment was superior to best supportive care and hydroxyurea because it had greater success in achieving CR, and it could represent standard care against which new treatments may be compared in this patient group.

Hematology in the United kingdom.

This article is the first in a series of features comparing and contrasting aspects of oncology care delivery in non-US settings. The Journal of Oncology Practice will occasionally publish similar pieces in anticipation of discovering best practices from international health care systems. Dr Prentice's contribution is based on his presentation to the Committee on Practice of the American Society of Hematology at their December 2005 meeting.

A feasibility study of simultaneous administration of gemtuzumab ozogamicin with intensive chemotherapy in induction and consolidation in younger patients with acute myeloid leukemia.

The feasibility of combining gemtuzumab ozogamicin (GO) with intensive chemotherapy as first-line treatment of acute myeloid leukemia (AML) was assessed in 72 patients, aged 17 to 59 years, as a prelude to the United Kingdom Medical Research Council (MRC) AML15 trial. Sixty-four patients received induction chemotherapy (DAT [daunorubicin, ara-C, thioguanine], DA [daunorubicin, ara-C], or FLAG-Ida [fludarabine, ara-C, G-CSF, idarubicin]) with GO on day 1. It was possible to give GO 3 mg/m2 with course 1, but 6 mg/m2 with course 1 or GO in a dose of 3 mg/m2 with consecutive courses was not feasible because of hepatotoxicity and delayed hematopoietic recovery. Thirty-one patients who were treated in consolidation with MACE (amsacrine, ara-C, etoposide) or HidAC (HidAC) and GO (3 mg/m2), and 23 in induction and consolidation, tolerated GO (3 mg/m2) well. Grade 4 liver toxicity and sinusoidal obstructive syndrome was more common in thioguanine-containing schedules (P =.007). Remission with course 1 was seen in 86% of patients. DA or FLAG-Ida with GO in induction achieved complete remission in 91% of patients and 78% of these patients are in continuous complete remission at 8 months. GO given with induction (DA or FLAG-Ida) and consolidation (MACE or HidAC) was well tolerated. These schedules are now being compared in the MRC AML15 trial in patients younger than 60 years.