Risk management: the clinician's defense against liability

As Stock and LeFroy conclude, a RM program lends structure and direction to management. Consistent delivery of high-quality service requires that hundreds of individuals perform numerous roles with a value-added service orientation. Jan Carlzon, the Director of Scandinavian Airlines and the person responsible for its remarkable turnaround, has the proper perspective: "We don't seek to be one thousand percent better at any one thing. We seek to be one percent better at one thousand things." Risk management is one factor in the development of a service-oriented health care culture that leads to sustained profitability through a stable patient base. The development of a RM program for a private dental office will lay the groundwork for a higher goal; a demonstrable, verifiable quality of care throughout the practice.     

Implantation of human fetal ventral mesencephalon to the right caudate nucleus in advanced Parkinson's disease

Disaggregated ventral mesencephalic tissue from single aborted human fetuses of 11 to 18 weeks' gestation was implanted stereotaxically into a consistent striatal site in 12 patients with advanced Parkinson's disease. All were receiving optimum levodopa therapy and were examined preoperatively and at 3,6,9, and 12 months postoperatively. Immunosuppression was not used. There were significant sustained improvements at 12 months in three patients; motor fluctuations were absent in two. There were modest group improvements up to 6 months, with increased quality of "on" and "off" phases, quantity of on times, and specific improvements in contralateral upper limb bradykinesia. Preoperative levodopa requirements were reduced to a mean of 64% at 6 months and 61% at 12 months. Deterioration below baseline ratings occurred in three of nine patients who had consistent follow-up to 12 months. Grafting of midgestational human fetal tissue can lead to improvement in Parkinson's disease. Individual disease severity may be critical, and further trials are needed to identify host factors influencing outcome.     

Some problems of confidentiality in medical computing.

Patients have a right to consider that any information about themselves will be regarded as confidential, but inadvertently, and, very occasionally deliberately, that confidence may be broken. Therefore the principles on which the computer system at The London Hospital is based rest on maintaining confidentiality but at the same time using the facilities unique to the computer to the fullest extent for the benefit of patients. The system is described in outline, and a note is added of occasions when it would be desirable to suppress information on a patient and the reasons for so doing.     

Higher-dose and less frequent dendritic cell infusions with PSMA peptides in hormone-refractory metastatic prostate cancer patients

BACKGROUND: Infusion of dendritic cells (DCs) pulsed with PSMA peptides was considered possible in hormone-refractory metastatic prostate cancer patients both with or without prior treatment with a greater number of DCs and for lesser infusions than previously administered. METHODS: DCs + PSMA peptides in patients undergoing leukapheresis were administered monthly 1-4 times, at rates greater than 20 million DCs in 17 patients not previously treated, and in 11 patients previously treated. RESULTS: Three partial responders and one complete responder were noted in the 17 previously untreated persons. DCs + PSMA peptides averaged 28.5 million cells (range in millions, 21.0-42.3). All responders received 3 or 4 infusions of greater than 22 million cells (3-4 times). In the previously treated group of 11 patients, DCs infused averaged 29.3 million cells (range in millions, 20-40.5). One new responder (bone scan) was noted. Two prior responders continued. Observation times were similar. Toxicity was minimal. CONCLUSIONS: These results suggest that DCs + PSMA peptide infusions can be given with greater numbers of DCs with a lesser number of infusions (1-4 monthly) with no loss of response rates compared to those noted previously, and without increased side effects. In previously treated patients (both relapsing and nonrelapsing), adverse effects were not noted, and new responses can be anticipated to be without harmful side effects. However, the follow-up time, and number of patients in this group, were small.     

Lamivudine for the prevention of hepatitis B virus reactivation in hepatitis B s-antigen seropositive cancer patients undergoing cytotoxic chemotherapy.

PURPOSE: For cancer patients receiving cytotoxic chemotherapy, hepatitis B virus (HBV) reactivation is a well described complication resulting in varying degrees of liver damage. The objectives of this study were to assess the efficacy of the antiviral agent lamivudine in reducing the incidence of HBV reactivation and diminishing morbidity and mortality of cancer patients with chronic HBV infection during chemotherapy. PATIENTS AND METHODS: Two groups were compared in this nonrandomized study. The prophylactic lamivudine group consisted of 65 patients in a phase II study who were treated with lamivudine before and until 8 weeks after discontinuing chemotherapy. The historical controls consisted of 193 consecutive patients who underwent chemotherapy without prophylactic lamivudine. Significant prognosticators for the development of HBV reactivation were determined based on data from the controls. Potential confounding factors were identified between the two groups. The outcomes were compared. RESULTS: In the controls, lymphoma and anthracycline usage were factors identified to be associated with reactivation. The two groups were comparable in most baseline characteristics, although in the prophylactic lamivudine group, there were significantly more patients with lymphoma and receiving anthracyclines. In the prophylactic lamivudine group, there was significantly less HBV reactivation (4.6% v 24.4% in the controls; P <.001), fewer incidences of hepatitis (17.5% v 44.6%; P <.0001) that were less severe (4.8% v 18.7%; P =.0005), and less disruption of chemotherapy (15.4% v 34.6%; P =.0029). The reduction in overall mortality was not statistically different. CONCLUSION: Prophylactic lamivudine significantly reduced the incidence of HBV reactivation and the overall morbidity of cancer patients undergoing chemotherapy.     

42nd Annual Meeting of the American Society for Cell Biology,San Francisco,California, USA, 14–18 December 2002

The Annual Meeting of the American Society for Cell Biology (ASCB) is a diverse conference covering all topics in cell biology. While all of the basic biology presented at this meeting may potentially contribute to breast cancer research, there were a significant number of presentations and posters directly pertinent to this field. Here we have summarized the research that is of greatest immediate relevance to breast cancer, with particular emphasis on mammary gland development and tumorigenesis in vivo, three-dimensional in vitro models of mammary morphogenesis, alterations of signal transduction pathways in breast cancer, and global studies in expression profiling and drug screening.     

Automated assessment of time-dependent inhibition of human cytochrome P450 enzymes using liquid chromatography-tandem mass spectrometry analysis.

Increasing reports of time-dependent inhibition of cytochrome P450 (P450) suggest further emphasis on interpreting the consequences, either from a pharmacokinetic or toxicological perspective. Two automated, time-dependent inhibition assays with a liquid chromatography-tandem mass spectrometric endpoint are presented. The initial assay utilizes human liver microsomes, a single concentration of inhibitor, and a single preincubation time of 30 min. Phenacetin, diclofenac, S-mephenytoin, bufuralol, and midazolam are used as substrates for CYP1A2, 2C9, 2C19, 2D6, and 3A4, and the assay differentiates between reversible and irreversible inhibition. The second assay uses individual recombinant human P450s, six inhibitor concentrations, and three time points to accurately define kinact and KI. A good correlation is demonstrated between kinact/KI and partition ratio, indicating that both terms are related in describing the efficiency of enzyme inactivation. Despite the single preincubation time point of 30 min used in the initial assay, a good relationship has been found to exist between the unbound IC50 estimated from this initial screen and the kinact/KI ratio derived from the more extensive subsequent single P450 assay. The higher throughput human liver microsomal assay can therefore generate IC50 values that can be used to predict the pharmacokinetic impact on cotherapies from the estimated kinact/KI ratio, predicted human dose, and pharmacokinetics.