Unmet clinical needs in the management of advanced melanoma: findings from a survey of oncologists.

Advanced melanoma is a life-threatening cancer with limited life expectancy. The recent introduction of new targeted systemic therapies has provided clinicians with the means to potentially extend survival for the first time. However, the chance of cure remains very low and treatment-induced toxicity is well described. This qualitative study was undertaken to evaluate clinicians' assessment regarding the key concerns in managing advanced melanoma following the introduction of these new treatments. Three hundred and forty-three oncologists were surveyed online between August and November 2012 (in 11 countries) and March and April 2013 (in an additional country). Analysis of free-text responses identified 23 clinical issues of concern across all countries. Of these, the most common clinical concerns were drug toxicity and tolerability, followed by limited treatment effectiveness and limited treatment options. These results suggest that despite the promise of the two new agents in the field, clinicians are still concerned about the limitations of current treatment options, recognising that there remains a significant unmet need in the treatment of advanced melanoma.

Treatment patterns in advanced melanoma: findings from a survey of European oncologists.

With the emergence of new therapies, established patterns of treating advanced melanoma are changing. The aim of this study was to understand how advanced melanoma is treated in clinical practice in Europe following the introduction of ipilimumab and vemurafenib. An online survey was conducted between August and November 2012 with 150 oncologists and dermatologists, from France, Germany, Italy, Spain and the U.K.; respondents reported treating the majority of patients with one or two lines of therapy. For BRAF mutant melanoma, the most frequently used first-line treatments were vemurafenib and dacarbazine. For BRAF wild-type melanoma, the most frequently used first-line treatment was dacarbazine. There was no single preferred agent for the second-line treatment of BRAF mutant or BRAF wild-type disease. Most sequencing from first- to second-line was from conventional dacarbazine to newer agents such as ipilimumab and vemurafenib. The treatment of advanced melanoma is rapidly evolving due to the introduction of new agents. This study presents an early insight into access to the new agents, ipilimumab and vemurafenib, and clinical practice in several European countries.

Patient safety events reported in general practice: a taxonomy.

OBJECTIVE: To develop a taxonomy describing patient safety events in general practice from reports submitted by a random representative sample of general practitioners (GPs), and to determine proportions of reported event types. DESIGN: 433 reports received by the Threats to Australian Patient Safety (TAPS) study were analysed by three investigating GPs, classifying event types contained. Agreement between investigators was recorded as the taxonomy developed. SETTING AND PARTICIPANTS: 84 volunteers from a random sample of 320 GPs, previously shown to be representative of 4666 GPs in New South Wales, Australia. MAIN OUTCOME MEASURES: Taxonomy, agreement of investigators coding, proportions of error types. RESULTS: A three-level taxonomy resulted. At the first level, errors relating to the processes of healthcare (type 1; n = 365 (69.5%)) were more common than those relating to deficiencies in the knowledge and skills of health professionals (type 2; n = 160 (30.5%)). At the second level, five type 1 themes were identified: healthcare systems (n = 112 (21.3%)); investigations (n = 65 (12.4%)); medications (n = 107 (20.4%)); other treatments (n = 13 (2.5%)); and communication (n = 68 (12.9%)). Two type 2 themes were identified: diagnosis (n = 62 (11.8%)) and management (n = 98 (18.7%)). The third level comprised 35 descriptors of the themes. Good inter-coder agreement was demonstrated with an overall kappa score of 0.66. A least two out of three investigators independently agreed on event classification in 92% of cases. CONCLUSIONS: The proposed taxonomy for reported events in general practice provides a comprehensible tool for clinicians describing threats to patient safety, and could be built into reporting systems to remove difficulties arising from coder interpretation of events.

A Phase II study of 3-aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP) and gemcitabine in advanced pancreatic carcinoma. A trial of the Princess Margaret hospital Phase II consortium.

3-Aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP, Triapine, Vion Pharmaceuticals, New Haven, CT) is an inhibitor of the M2 subunit of ribonucleotide reductase (RR). Preclinical testing demonstrates synergy between 3-AP and gemcitabine. Phase I studies of the combination have suggested tolerability and some initial evidence of efficacy. Therefore, a phase II study of gemcitabine plus 3-AP in advanced pancreatic carcinoma was undertaken. In this two-step phase II trial, patients with advanced pancreatic adenocarcinoma who had not received prior chemotherapy for advanced disease were treated with 3-AP 105 mg/m(2) given over 2 h. Four hours after the 3-AP infusion was completed, gemcitabine 1,000 mg/m(2) was given over 30 min. Both drugs were given on days 1, 8 and 15 of a 28-day cycle.Twenty-six patients were enrolled to the study. One patient withdrew consent prior to receiving any treatment and is excluded from all further analyses. Four patients discontinued treatment due to adverse effects. Grade 3/4 hematological adverse events included neutropenia, thrombocytopenia, lymphopenia, leukopenia and anemia and the most frequent non-hematological adverse events were fatigue and pain. No objective responses were observed. Eleven patients had stable disease (SD). In five of these eleven patients, SD lasted for more than 6 months. The median time to progression was 4.1 months and the 6 month progression-free survival rate was 29%. The median survival was 9.0 months with a 1-year survival of 28.0%. The combination of 3-AP and gemcitabine is associated with moderate toxicity in patients with advanced pancreatic cancer. This two-stage trial was stopped after stage I due to lack of antitumour activity. On the basis of this clinical trial, the combination of gemcitabine and 3-AP at this dose and schedule does not warrant further study in this patient population.

Running effective meetings: a primer for doctors.

This paper uses a series of exercises and practical examples to assist individuals and groups of doctors in training to gain skills in a critical area of management: conducting and participating in effective meetings. Through this paper, readers will be shown how to recognise and manage situations as they occur in meetings to work towards appropriate outcomes. By understanding the elements of conducting a meeting from preparation through to follow up, doctors will be able to conduct and participate more effectively in meetings that arise in their workplaces.

Conflict management: a primer for doctors in training.

Conflict in the health arena is a growing concern and is well recognised for doctors in training. Its most extreme expression, workplace violence is on the increase. There is evidence that many conflicts remain unsatisfactorily resolved or unresolved, and result in ongoing issues for staff morale. This paper describes the nature of conflict in the health care system and identifies the difference between conflict and disagreement. Using a conflict resolution model, strategies for dealing with conflict as it arises are explored and tips are provided on how to effectively manage conflict to a satisfactory resolution for all parties.

Co-morbidity in general practice.

BACKGROUND: Co-morbidity, or the presence of more than one clinical condition, is gaining increased attention in epidemiological and health services research. However, the clinical relevance of co-morbidity has yet to be defined. In general practice, few studies have been conducted into co-morbidity, either at a single health care encounter, an episode of care, or for a defined time period. AIMS: To describe the major co-morbidity cluster profiles recorded by general practitioners. Another aim of this study is to describe the common clusters of co-prescribing. METHODS AND RESULTS: Twelve month data from patients attending 156 GPs from 95 practices around a six month period of January to June 2003 were analysed. This represented 840,961 encounters from about 200,000 individual patients at these participating practices. Co-morbidity and co-prescribing cluster profiles are represented by problems managed and reasons for prescribing for the top 10 presentations and top 10 prescribed drugs in the study period. CONCLUSIONS: By analysing the 10 most prevalent problems and 10 most prevalent drugs prescribed in consultations in a community sample, other co-morbidities that are particular to general practice, for example hypertension and lipid disorders, can be uncovered. Whether these clusters are causally related or occur by chance requires further analysis.

The relationship between physician cost and functional status in the elderly.

OBJECTIVE: To explore the relationship between functional status and physician cost (general practitioner/specialist) in an elderly population. DESIGN, SETTING AND PARTICIPANTS: A longitudinal study involving 328 patients aged 65 years or over admitted to medical and surgical wards of a Sydney metropolitan hospital over a 10-month period. MAIN OUTCOME MEASURES: Two predictive cost models were developed using multiple linear regression analyses. Nine predictors were modelled including functional status (Short Form 36; SF-36) and major diagnostic categories. These models were then applied to the Australian SF-36 norms to produce a profile of cost by level of functioning. RESULTS: After adjusting for potential confounders, five variables were found to be predictive of general practitioner cost at a 5% significance level. Females and age were positively associated, whereas case note mention of post-discharge services and high SF-36 vitality and role emotional scores were negatively predictive. For specialist cost, five variables were statistically significant. The SF-36 domains of physical functioning and mental health were positively associated. Higher vitality, role emotional scores and case note mention of post-discharge services were negatively associated. CONCLUSIONS: Cost models can be used to highlight the differences between general practitioner and specialist attendances, guide future physician care of the aged, and facilitate informed decision making.

Functional status and health service planning.

Functional status indicators have been proposed as instruments to aid health service planning for patients. This study examines functional status at three points surrounding an acute health episode: admission, discharge and 3 months post discharge from a community hospital. The aim of the study is to determine the most appropriate time to measure functional status to assist health service planning. A longitudinal cohort study was conducted at Manly Hospital, Australia. Four hundred patients aged 65 years and over representing a 10% random sample of all hospital admissions in a 10-month period were interviewed on admission, discharge and 3 months post discharge. Repeated measure multiple analysis of variance identified a decline in functional status between admission and discharge. At 3 months post discharge functional status had improved to levels higher than admission. Functional status assessment at discharge can assist consumers, clinicians, health planners and health insurers to make effective decisions to maximize health outcomes.

Standardising health outcome measurements in general practice.

BACKGROUND: Outcome measures are gaining importance especially in areas such as divisions of general practice. The plethora of outcome measurements and the rhetoric surrounding this may make it difficult for doctors to decide the place of such measures in daily practice. An understanding of outcomes and their indicators is emerging as an essential requirement for good practice. OBJECTIVE: The aim of this paper is to propose a practical framework for describing health outcome measurements that may be applied to general practice. METHODS: This paper outlines the key features of outcomes measurements and proposes a model for understanding health outcome indicators using a set of indicators relevant to clinical practice. RESULTS: Pertinent to developing outcome terminology for use with patients in general practice are the four key features: a clear description of the indicator utility in practice comparability between practices endurance over time. CONCLUSION: To have reliability and validity and be able to deliver outcomes with practical and clinical significance, we need to be sure that the instruments we use are precisely defined. It is also important that the meaning is universally understood by all who might want to use the instruments. The product should also have cultural applicability beyond English. In clinical practice, the definition of the instrument aims not only to give the general practitioner a clear understanding of what is being measured but how it is used and the implications for its future use.

Guidelines for every person.

Guidelines, it is assumed in health care circles, have worth. In the ideal health care system they may offer everything from medical certainty to legal protection. They have the potential to save practitioners from the trauma of indecision and at the same time protect them from the consequences of wrong decisions. In this paper, I discuss the impact of guidelines on general practitioners and consumers. Both groups are at the effector end where guidelines should have maximal impact. It is primarily medical practitioners and their constituents in the long run that have to make guidelines work. Theoretical questions about the essential worth of guidelines for consumers and general practitioners are explored, as well as the more practical issues of utility of guidelines. My hypothesis is that guidelines may be conceptually worthwhile, but as yet are of unproven utility. This argument is traced through the literature surrounding the involvement of general practitioners and consumers in guideline development, implementation, review and relevance. From this information a new role for guidelines which is cogniscent of the needs and circumstances of the end users is postulated. Guidelines can become the basis for the principles of sound clinical practice which allow for the unique individual circumstances of clinical practice whilst also providing a consolidated basis for this practice.

Translocations and deletions of 5q13.1 in myelodysplasia and acute myelogenous leukemia: evidence for a novel critical locus.

Acquired partial and complete deletions of chromosome 5 (5q-, -5) are common cytogenetic anomalies associated with myelodysplasia (MDS) and acute myeloid leukemia (AML). A critical region of consistent loss at 5q31.1 (in > 90% of cases) has led us and others to postulate the presence of a key negative regulator(s) of leukemogenesis. Although the interstitial deletion limits vary among patients, del(5) (q13q33) and del(5)(q13q35) constitute major subsets. Furthermore, it is not rare to encounter deletions, translocations, or paracentric inversions involving 5q11 to 5q13, which indicates inactivation or disruption of important gene(s) at that locus. In this report, we have localized a novel locus at 5q13.1 to a 2.0-Mb interval between the anonymous markers D5S672 and GATA-P1804. This locus resided within the region of loss in 12 of 27 patients with anomalies of chromosome 5; one of these cases had apparent retention of both alleles of all the telomeric loci. Fluorescence in situ hybridization (FISH) studies demonstrate that the AML cell line ML3 is disrupted at 5q13.1 by a translocation involving chromosome 3, with apparent retention of the entire chromosome 5 sequence. Our results suggest that this novel proximal locus encodes a critical gene that may be deleted or disrupted in a subset of MDS/AML patients with chromosome 5 anomalies.

The reliability and validity of work measurement in Australian general practice consultations.

OBJECTIVES: To examine the reliability of relative work value assessment in general practice consultations and to determine whether different methods of assessing work produce consistent rankings. DESIGN: Cross-sectional observational assessment of general practice consulations. SETTING: General practices in Victoria between October 1991 and October 1992. PARTICIPANTS: 686 patients attending one of 58 general practitioners (GPs) drawn from a random, stratified sample. METHODS: Each participating GP had one day of consultations videotaped. They rated the work value of each consultation by using a magnitude estimation scale relative to a reference vignette. Three GP observers independently applied the same scale to the videotaped consultations. After three months, the observers applied a second measurement of work value, a compensation scale (also relative to the reference vignette), to the videotaped consultations. Duration of consultation was the third rating method. MAIN OUTCOME MEASURES: The reliability of work value assessment for each scale. Consultation rank order correlation coefficients among all rating methods. RESULTS: Observer reliability was high for both scales. Practising GPs showed lower levels of reliability in assessing the work value of their consultations. Strong positive correlations were found for consultation rankings among the observer scales and duration of the consultation. The duration of the consultation emerged as an important predictor of consultation work value. CONCLUSIONS: Scaling methods appear to be of little value to the practising GP in reliably assessing the relative work value of their consultations; training in the use of these scales may improve their reliability. However, the duration of consultation may be a reasonable proxy for relative work value assessment in general practice consultations.

Locums. A guide on how to use them.

This article outlines a range of issues that should be resolved with each locum before placement in a general practice. It also provides some measures by which the service provided to the practice can be evaluated. Through a series of checklists, general practitioners can prepare their practice for locums and assess the impact of the service.