Management by objectives and its impact on specialist prescription quality at discharge and in external consultations.

OBJECTIVE: To verify that implementing a policy of management by objectives, based on collaboration between hospital pharmacy, primary care and specialised medical managers, improves prescription quality indicators in specialised care and reduces unwanted "induced" prescriptions (i.e. those issued by specialists, hospital doctors or the patients themselves) in primary care. METHOD: A four year quasi-experimental controlled intervention study on prescription at discharge and in outpatient hospital consultations was conducted. In hospital A, a quality cycle was applied: assessment, identifying improvement opportunities, implementing corrective actions and re-assessment. However, it was not applied in control hospital B. The indicators chosen were the percentage of generic medicines prescribed, the percentage of prescriptions for new therapies with no added value and the percentage of prescriptions for ACE inhibitors recommended. RESULTS: In hospital A, an increase in indicators 1 and 3 has been observed, both being statistically significant, between the last year of intervention and the year previous to intervention. Hospital A managed to reduce indicator 2 to 4.5%, while this indicator increased in hospital B to 8.8%. Furthermore, a statistically significant difference in indicators between the two hospitals has been registered. CONCLUSION: Pay-for-Performance programs in prescription practices of hospital physicians are effective actions to improve quality indicators of medication use.

Prospective, randomised study to compare empirical treatment versus targeted treatment on the basis of the urine antigen results in hospitalised patients with community-acquired pneumonia.

BACKGROUND: Recommendations for diagnostic testing in hospitalised patients with community-acquired pneumonia remain controversial. The aim of the present study was to evaluate the impact of a therapeutic strategy based on the microbiological results provided by urinary antigen tests for Streptococcus pneumoniae and Legionella pneumophila. METHODS: For a 2-year period, hospitalised patients with community-acquired pneumonia were randomly assigned to receive either empirical treatment, according to international guidelines, or targeted treatment, on the basis of the results from antigen tests. Outcome parameters, monetary costs and antibiotic exposure levels were compared. RESULTS: Out of 194 enrolled patients, 177 were available for randomisation; 89 were assigned to empirical treatment and 88 were assigned to targeted treatment. Targeted treatment was associated with a slightly higher overall cost (euro 1657.00 vs euro 1617.20, p=0.28), reduction in the incidence of adverse events (9% vs 18%, p=0.12) and lower exposure to broad-spectrum antimicrobials (154.4 vs 183.3 defined daily doses per 100 patient days). No statistically significant differences in other outcome parameters were observed. Oral antibiotic treatment was started according to the results of antigen tests in 25 patients assigned to targeted treatment; these patients showed a statistically significant higher risk of clinical relapse as compared with the remaining population (12% vs 3%, p=0.04). CONCLUSIONS: The routine implementation of urine antigen detection tests does not carry substantial outcome-related or economic benefits to hospitalised patients with community-acquired pneumonia. Narrowing the antibiotic treatment according to the urine antigen results may in fact be associated with a higher risk of clinical relapse.

[Stability of a lipid emulsion in formulations for total parenteral nutrition]. / Estabilidad de una emulsión de lípidos en mezclas para nutrición parenteral total.

The complex nature of "all in one" formulas for TPN, makes it difficult to ensure the stability of the lipid emulsions in these preparations. Despite the fact that studies on this issue are increasing, official guidelines on maximum acceptable particle size and the methods to control it are still lacking. The objective of this study was to assess the stability of a lipid emulsion in four standard mixtures also containing amino acids, glucose or F-G-X, electrolytes and vitamins or trace elements. Lipid stability was assessed visually through electronic counts and microphotographs. The pH of mixtures ranges between 5.3 and 5.9, not changing with time nor storage temperature. Visual observation showed a possible rupture of the emulsion in one mixture after storing 96 hours at room temperature, but not when stored at 4 degrees C. Mean diameter of fat particles did not change. The percentage of droplets having a diameters under 1.2 micron was higher than 90%, although particles greater than 6 micron appeared in all mixtures. Micrographic observation revealed the presence of aggregates with a diameter greater than 8 microns in one mixture. According to the results obtained, one of the mixtures may be considered physically unstable. The clinical viability of this mixture and of the other three stable mixtures, depends on the limits considered acceptable regarding particle size. Due to the slight composition differences of the mixtures studied, it is difficult to explain the difference in behavior observed. Therefore, it would be adviceable to study standard "all in one" mixtures of known stability, while waiting for more conclusive studies to be performed, especially in the case of critical mixtures.

[Rifampicin toxicity in HIV-infected patients: A study of its incidence and the risk factors]. / Toxicidad de la rifampicina en pacientes con infección VIH. Estudio de la incidencia y factores de riesgo.

OBJECTIVE: Evaluate the effect of HIV infection in the appearance of toxicity in patients treated with rifampin, analysing the involved elements in its genesis. METHODS: We realized a comparative study of the epidemiologic and clinical characteristics, and the incidence of adverse reactions to rifampin (between 1986-1993), comparing the seropositive patients treated with rifampin, during more than 3 months, with one control group, of equal number of patients, without evidence of HIV infection, taken at random, with epidemiologic characteristics (age and sex) similar to the first group and also treated with rifampin during a similar period. In the group with HIV infection, we analysed the related epidemiologic, clinical and analytic characteristics, in a way statistically significative, with the appearance of toxicity to rifampin. RESULTS: The risk of toxicity to rifampin was associated significantly to HIV infection (p < 0.01), without finding any other distinguishing characteristics among the analysed groups. Indicative parameters of advanced HIV infection: advanced clinical stage, minor level of lymphocytes CD4+, total leukocytes, total lymphocytes and quotient CD4+/CD8+, also high levels of beta 2-microglobulinemia and [correction of 2-microglobulina e] IgA, and a negative protein purified derivative test (PPD) were found statistically related with the appearance to toxicity to rifampin. Patients with number of lymphocytes CD4+ between 20-50/mm3, showed a major predisposition of suffering toxicity to rifampin. CONCLUSION: HIV infection involved a notably increase of toxicity risk to rifampin. Clinical or analytic parameters associated with advanced illness conditioned an increase of this risk, essentially among patients with number of CD4+ between 20-50/mm.

Effect of proteasome inhibitors on proliferation and apoptosis of human cutaneous melanoma-derived cell lines.

BACKGROUND: Cutaneous malignant melanoma is an aggressive type of skin cancer which causes disproportionate mortality in young and middle-aged adults. Once disseminated, melanoma can be considered an incurable disease, highly resistant to standard antineoplastic treatment, such as chemotherapy or radiation therapy. The proteasome represents a novel target for cancer therapy that can potentially be used in melanoma. OBJECTIVES: To assess the effect of four structurally different proteasome inhibitors on human cutaneous melanoma-derived cell lines. METHODS: Sixteen human cutaneous melanoma-derived cell lines which are original were obtained from patients who were treated by two of the authors. Cells were cultured, exposed to proteasome inhibitors (bortezomib, ALLN, MG-132 and epoxomicin) and then assayed for cell cycle and cell death analyses. RESULTS: Proteasome inhibitors inhibited the in vitro growth of melanoma cells, and this effect was due to a reduction in cell proliferation rate and an induction of both caspase-dependent and caspase-independent cell death. Moreover, release of apoptosis-inducing factor was observed in the presence of the broad-specificity caspase inhibitor BAF (Boc-D-fmk). In addition, the four different proteasome inhibitors induced caspase 2 processing. CONCLUSIONS: This study provides information regarding the in vitro effects of proteasome inhibitors on melanoma cell lines, and the molecular mechanisms involved. It also gives support to the future use of such inhibitors in the treatment of patients with melanoma, either administered alone or in combination with other drugs.