The usefulness of Olanzapine plasma concentrations in monitoring treatment efficacy and metabolic disturbances in first-episode psychosis.

INTRODUCTION: The role of Olanzapine therapeutic drug monitoring is controversial. The present study explores the associations of Olanzapine plasma concentrations with clinical response and metabolic side effects in first episode psychosis (FEP) after 2 months of treatment. METHODS: Forty-seven patients were included. Improvement in clinical symptomatology was assessed using the PANSS. Metabolic assessment included weight, blood pressure, waist circumference, blood glucose, total cholesterol, high-density lipoprotein, low-density lipoprotein, and triglycerides. RESULTS: The Olanzapine plasma concentrations after 2 months of treatment were positively correlated with weight gain (r = 0.49, p = 0.003), and a concentration > 23.28 ng/mL was identified as a positive predictor of weight gain (≥ 7%). The Olanzapine concentration to dose (C/D) ratio was positively correlated with the percentage of improvement in the total PANSS (r = 0.46, p = 0.004), and a C/D ratio > 2.12 was identified as a positive predictor of a good response (percentage of improvement > 30%) after 2 months of treatment. We also identified several factors that could alter Olanzapine pharmacokinetics: gender (p = 0.03), diagnosis (p = 0.05), smoking habit (p = 0.05), and co-medications such as valproic acid (p = 0.05) and anxiolytics (p = 0.01). DISCUSSION: In conclusion, our results suggest that therapeutic drug monitoring of Olanzapine could be helpful to evaluate therapeutic efficacy and metabolic dysfunction in FEP patients treated with Olanzapine.

Relación entre niveles plasmáticos de efavirenz y alteraciones lipémicas / Efavirenz plasma levels and dyslipidemia

El objetivo del presente trabajo es evaluar si existe relación entre los niveles plasmáticos de efavirenz y la aparición de dislipemia como hipercolesterolemia, hipretrigliceridemia o aumento de LDL-c.Se realizaron niveles plasmáticos de efavirenz a los pacientes en tratamiento con este fármaco desde septiembre de 2012 hasta junio de 2015. Se registraron los parámetros lipídicos correspondientes a cada analítica. Las determinaciones de efavirenz se realizaron mediante cromatografía líquida de alta eficacia. Los datos se manejaron mediante el programa Quick Statistics Calculator y Excel 2007.Los niveles plasmáticos de efavirenz superiores a 4.000 ng/ml se asocian en nuestro estudio con una mayor frecuencia de niveles de colesterol superiores a 200 mg/dl.Este estudio puede ser de utilidad para aquellas zonas en las que usen pautas de tratamiento con este fármaco de manera frecuente. (AU)

The aim of this study is to evaluate if there is a relationship between plasma levels of efavirenz and the occurrence of dyslipidemia such as hypercholesterolemia, hypretrigiceridemia or increased LDL-c.Plasma levels of efavirenz were performed to patients under treatment with this drug during the period from September 2012 to June 2015. Lipid parameters corresponding to each analytical were recorded. Determinations of efavirenz were analyzed by high performance liquid chromatography. Data were managed using the Quick Statistics Calculator and Excel 2007 program.Plasma levels of efavirenz higher than 4,000 ng/ml were associated, in our study, with a higher frequency of cholesterol levels higher than 200 mg/dl.This study may be useful to those areas where treatment guidelines with this drug are used on a frequent basis. (AU)

Determinación cualitativa de anidulafungina en líquidos de diálisis con administración intraperitoneal / Qualitative determination of anidulafungin in dialysis fluids with intraperitoneal administration

La infección fúngica peritoneal es poco frecuente pero supone una elevada mortalidad. A pesar de que la principal recomendación es la retirada de catéter cuando se sospecha que es éste el foco de infección, hay ocasiones en las se requiere considerar otras opciones. La administración de anidulafungina intraperitoneal es una técnica sobre la que hay pocos estudios. Presentamos un caso clínico en el que administramos anidulafungina intraperitoneal y analizamos mediante técnica cualitativa la presencia del antifúngico en distintas muestras. Además, calculamos el porcentaje de reducción de anidulafungina entre el líquido de diálisis en el que la diluimos y este mismo tras permanecer 8 horas en la cavidad peritoneal. (AU)

Peritoneal fungal infection is rare but involves high mortality. Although the main recommendation is catheter removal when it is suspected that this is the focus of infection, there are occasions when other options are required.There are few references about administration of intraperitoneal anidulafungin. We present a clinical case in which we administer intraperitoneal anidulafungin and analyze the presence of this antifungal in different samples using a qualitative technique. In addition, we calculate the percentage reduction of anidulafungin between the dialysis fluid in which we diluted it and this fluid after remain 8 hours in the peritoneal cavity. (AU)

Tenofovir disoproxil fumarate/emtricitabine plus ritonavir-boosted lopinavir or cobicistat-boosted elvitegravir as a single-tablet regimen for HIV post-exposure prophylaxis.

Objectives: To assess HIV-1 post-exposure prophylaxis (PEP) non-completion at day 28, comparing ritonavir-boosted lopinavir versus cobicistat-boosted elvitegravir as a single-tablet regimen (STR), using tenofovir disoproxil fumarate/emtricitabine with both of these therapies. Methods: A prospective, open, randomized clinical trial was performed. Individuals attending the emergency room due to potential sexual exposure to HIV and who met criteria for PEP were randomized 1:3 into two groups receiving either 400/100 mg of lopinavir/ritonavir (n = 38) or 150/150 mg of elvitegravir/cobicistat (n = 119), with both groups also receiving 245/200 mg of tenofovir disoproxil fumarate/emtricitabine. Five follow-up visits were scheduled at days 1, 10, 28, 90 and 180. The primary endpoint was PEP non-completion at day 28. Secondary endpoints were adherence, adverse effects and rate of seroconversions. Clinical trials.gov number: NCT08431173. Results: Median age was 32 years and 95% were males. PEP non-completion at day 28 was 36% (n = 57), with a trend to be higher in the lopinavir/ritonavir arm [lopinavir/ritonavir 47% (n = 18) versus elvitegravir/cobicistat 33% (n = 39), P = 0.10]. We performed a modified ITT analysis including only those patients who attended on day 1. PEP non-completion in this subgroup was higher in the lopinavir/ritonavir arm than in the elvitegravir/cobicistat arm (33% versus 15%, respectively, P = 0.04). Poor adherence was significantly higher in the lopinavir/ritonavir arm versus the elvitegravir/cobicistat arm (47% versus 9%, respectively, P < 0.0001). Adverse events were reported by 73 patients (59%), and were significantly more common in the lopinavir/ritonavir arm (90% versus 49%, P = 0.0001). A seroconversion was observed in the elvitegravir/cobicistat arm in a patient with multiple exposures before and after PEP. Conclusions: A higher PEP non-completion, poor adherence and adverse events were observed in patients allocated to the lopinavir/ritonavir arm, suggesting that STR elvitegravir/cobicistat is a well-tolerated antiretroviral for PEP.

Programa de atención farmacéutica integrada en pacientes con enfermedades crónicas / Integrated pharmaceutical care programme in patients with chronic diseases

Objetivo: Valorar si un programa de atención farmacéutica integrada (PAFI) en pacientes crónicos mejora la evolución clínica, la calidad de vida de los pacientes y disminuye el consumo de recursos sanitarios. Material y métodos Ensayo clínico, paralelo, abierto y multicéntrico de un PAFI en pacientes con insuficiencia cardiaca (IC) y/o enfermedad pulmonar obstructiva crónica (EPOC) en 8 áreas de salud de Cataluña. Al paciente en intervención le realizaban seguimiento farmacoterapéutico los farmacéuticos de hospital, atención primaria y farmacia comunitaria. Al control, seguimiento habitual. Todos los pacientes fueron seguidos 12 meses y se les realizó un test de calidad de vida al inicio y final del seguimiento. Resultados Participaron 8 hospitales, 8 centros de atención primaria y 109 farmacias comunitarias. Finalizaron el estudio 238 pacientes con un porcentaje de pérdidas del 2,9%. No hubo diferencias significativas en reingresos, visitas al médico o urgencias. Se detectaron 50 problemas relacionados con medicamentos (PRM) en 37 pacientes, siendo estadísticamente significativa la diferencia de PRM entre el grupo intervención y control en pacientes con IC y casi significativa en pacientes con EPOC. El 36% de los PRM fueron moderados-graves. El 94% PRM fueron evitables y el farmacéutico los resolvió en el 90% de los casos. No hubo diferencias entre la calidad de vida al inicio y final del estudio ni en el consumo de recursos sanitarios. Conclusiones Los programas de atención farmacéutica integrada permiten la mejora de la calidad asistencial al paciente, no obstante es necesaria la utilización de registros electrónicos que faciliten la comunicación entre niveles asistenciales (AU)

Objectives: To assess whether an integrated pharmaceutical care programme (IPCP) improvesclinical evolution, patient quality of life, and reduces health costs in chronic patients. Material and methods: A parallel, open, and multi-centre clinical trial of an IPCP in patients with heart failure (HF) and/or chronic obstructive pulmonary disease (COPD) in 8 different health areas in Cataluña. The intervened patient was monitored for pharmacotherapeutic evolution by hospital pharmacists, primary care physicians, and community pharmacists. Controls received normal follow-up. All patients were monitored for 12 months, with quality of life tests administered at the beginning and end of follow-up. Results: We had the participation of 8 different hospitals, 8 primary care centres, and109 community pharmacies. 238 patients completed the study, with 2.9% of participants lost during the study period. There were no significant differences in terms of readmissions, visits to the doctors, or to emergency services. We detected 50 different medication-related problems(MRP) in 37 patients, with a statistically significant difference in terms of MRP between the control and treatment groups of patients with HF, and almost significant differences in COPD patients. MRP were moderate-severe in 36% of cases. MRP were avoidable in 94% of cases, and the pharmacist resolved the issue in 90% of cases. There were no differences in terms of patient quality of life or health costs between the start and end of the study. Conclusions: Integrated pharmaceutical care programs facilitate an improvement in the quality of patient care, but electronic registries are necessary to promote communication between sections of the health care network (AU)

[Integrated pharmaceutical care programme in patients with chronic diseases]. / Programa de atención farmacéutica integrada en pacientes con enfermedades crónicas.

OBJECTIVES: To assess whether an integrated pharmaceutical care programme (IPCP) improves clinical evolution, patient quality of life, and reduces health costs in chronic patients. MATERIAL AND METHODS: A parallel, open, and multi-centre clinical trial of an IPCP in patients with heart failure (HF) and/or chronic obstructive pulmonary disease (COPD) in 8 different health areas in Cataluña. The intervened patient was monitored for pharmacotherapeutic evolution by hospital pharmacists, primary care physicians, and community pharmacists. Controls received normal follow-up. All patients were monitored for 12 months, with quality of life tests administered at the beginning and end of follow-up. RESULTS: We had the participation of 8 different hospitals, 8 primary care centres, and 109 community pharmacies. 238 patients completed the study, with 2.9% of participants lost during the study period. There were no significant differences in terms of readmissions, visits to the doctors, or to emergency services. We detected 50 different medication-related problems (MRP) in 37 patients, with a statistically significant difference in terms of MRP between the control and treatment groups of patients with HF, and almost significant differences in COPD patients. MRP were moderate-severe in 36% of cases. MRP were avoidable in 94% of cases, and the pharmacist resolved the issue in 90% of cases. There were no differences in terms of patient quality of life or health costs between the start and end of the study. CONCLUSIONS: Integrated pharmaceutical care programs facilitate an improvement in the quality of patient care, but electronic registries are necessary to promote communication between sections of the health care network.

Estudio de incidencia de los errores de medicación en los procesos de utilización del medicamento: prescripción, transcripción, validación, preparación, dispensación y administración en el ámbito hospitalario / Incident study of medication errors in drug use processes: prescription, transcription, validation, preparation, dispensing and administering in the hospital environment

Objetivo: Determinar la incidencia global y por etapas de los errores de medicación en 6 hospitales de Cataluña, así como los tipos de error y las consecuencias. Método: Diseño prospectivo, cuya variable global es el error de medicación. Se han excluido los errores potenciales. En cada hospital se estudiaron los ingresados en 2 unidades hasta 300 pacientes y se observaron 1.500 administraciones. Se aplicó la taxonomía del National Coordinating Council for Medication Error Reporting and Prevention. El error de prescripción se detectó mediante la revisión de las prescripciones, en la que se comprobaron paciente, medicamento, adherencia a protocolos, interacciones, contraindicaciones, omisión, duplicidad terapéutica, dosis, frecuencia, vía y falta de seguimiento. En la transcripción/validación se comprobó la coincidencia con la orden médica original. En la dispensación, antes de enviar los carros de unidosis, se revisó el contenido de los cajetines, y se contrastó con el listado generado informáticamente. En planta, los observadores comprobaron transcripción, preparación y administración. En todos los procesos se registraron los datos en una hoja específica. La concordancia entre revisores fue moderada (kappa = 0,525). Resultados: Se detectaron 16,94 errores por 100 pacientes-día y 0,98 por paciente: 16 % en prescripción, 27 % en transcripción/validación, 48 % en dispensación y 9 % en administración. El 84,47 % pertenecía a la categoría B (no se alcanzó al paciente), y menos del 0,5 % causaron daño. La población, de 65 años de media, se distribuyó en una relación varón/mujer de 60/40. Los principales grupos terapéuticos fueron: agentes contra la úlcera péptica y el reflujo gastroesofágico, antitrombóticos, y otros analgésicos y antipiréticos, en los que predominaba la forma farmacéutica (..) (AU)

Objective: To determine both the global Incident, and the Incident for stages of medication errors in six Catalonian hospitals, the types of error and the consequences. Method: A prospective design, with the global variable of the medication error. Potential errors have been excluded. The patients admitted to each hospital were studied in 2 groups of up to 300 patients and 1,500 administrations were observed. The NCCMERP taxonomy was applied. The prescription error was detected through the review of prescriptions, checking the patient, medication, adherence to protocols, interactions, contraindications, omission, duplicated therapy, doses, frequency, method, and lack of follow-up. During the transcription/validation, it was verified that the prescription matched the original order. In the dispensing process, the content of the drawers was checked, comparing it to the computer generated list, before sending out the single dose trolley. The transcription, preparation and administration were observed on the wards. The information for all the procedures was registered in a specific data sheet. There was moderate concordance amongst the inspectors (kappa = 0.525). Results: 16.94 errors were detected per 100 patients-day and 0.98 errors per patient: 16 % in prescription, 27 % in transcription/validation, 48 % in dispensing, and 9 % in administration. 84.47 % were category B errors (they did not reach the patient), and < 0.5 % of the errors were harmful. The population, with an average age of 65, had a male/female ratio of 60/40. The principal therapeutic groups were: agents against peptic ulcer and GERD, antithrombotic agents, and other analgesics and antipyretics, (..) (AU)

[Incident study of medication errors in drug use processes: prescription, transcription, validation, preparation, dispensing and administering in the hospital environment]. / Estudio de incidencia de los errores de medicación en los procesos de utilización del medicamento: prescripción, transcripción, validación, preparación, dispensación y administración en el ámbito hospitalario.

OBJECTIVE: To determine both the global Incident, and the Incident for stages of medication errors in six Catalonian hospitals, the types of error and the consequences. METHOD: A prospective design, with the global variable of the medication error. Potential errors have been excluded. The patients admitted to each hospital were studied in 2 groups of up to 300 patients and 1,500 administrations were observed. The NCCMERP taxonomy was applied. The prescription error was detected through the review of prescriptions, checking the patient, medication, adherence to protocols, interactions, contraindications, omission, duplicated therapy, doses, frequency, method, and lack of follow-up. During the transcription/validation, it was verified that the prescription matched the original order. In the dispensing process, the content of the drawers was checked, comparing it to the computer generated list, before sending out the single dose trolley. The transcription, preparation and administration were observed on the wards. The information for all the procedures was registered in a specific data sheet. There was moderate concordance amongst the inspectors (kappa = 0.525). RESULTS: 16.94 errors were detected per 100 patients-day and 0.98 errors per patient: 16 % in prescription, 27 % in transcription/validation, 48 % in dispensing, and 9 % in administration. 84.47 % were category B errors (they did not reach the patient), and < 0.5 % of the errors were harmful. The population, with an average age of 65, had a male/female ratio of 60/40. The principal therapeutic groups were: agents against peptic ulcer and GERD, antithrombotic agents, and other analgesics and antipyretics, principally in a solid oral drug form (58 %). The medications per patient-day were 5.5 and the units of medication were on average 11.21, varying greatly among the institutions. The adjustment of 10 units made the results more uniform. In all the stages, omission was the most frequent error. DISCUSSION: The different methods used and different areas of the investigations make comparisons difficult. This is evident in the harmful errors, the proportion of which is affected by the detection procedure. The number of mistakes avoided during the execution of this project demonstrates the need to improve the planning of the work systems and to establish safety measures.

Hepatotoxicity of nevirapine in virologically suppressed patients according to gender and CD4 cell counts.

OBJECTIVES: A warning advising a higher risk of hepatotoxicity in antiretroviral-naive patients starting a nevirapine-containing combination antiretroviral therapy (NcART) has been issued by health authorities. It is unclear whether this higher risk also applies to stable virologically suppressed patients starting NcART. METHODS: We performed a meta-analysis of published randomized studies including virologically suppressed patients who switched to NcART with a follow-up >or=3 months. CD4 cell cell counts were classified as high (HCD4) (400 cells/microL for males and 250 cells/microL for females) or low (LCD4). The main endpoint was hepatotoxicity within the first 3 months. RESULTS: Four studies with a pooled total of 410 patients were included. The risk of hepatotoxicity within the first 3 months was 2% and 4% in the LCD4 and HCD4 groups, respectively, with a combined odds ratio of 1.46 [95% confidence interval (CI) 0.43-4.98; P=0.54]. The risk of hepatotoxicity at any point during the study was similar in both groups, with a combined hazard ratio of 0.8 (95% CI 0.3-2.5; P=0.80). CONCLUSIONS: In our study, virologically suppressed patients switching to nevirapine did not have a significantly higher risk of hepatotoxicity or rash when stratified by gender and CD4 cell count, although small differences may have gone undetected because of the sample size limitation.

A randomized trial comparing the efficacy and tolerability of two HAART strategies at two years in antiretroviral naive patients.

BACKGROUND: The use of HAART combining 2 nucleoside analogues reverse transcriptase inhibitors (NRTIs) plus one protease inhibitor (PI) or 2 NRTIs + 1 non-nucleoside reverse transcriptase inhibitor (NNRTI) has shown comparable efficacy. The study was designed to compare long term (2 years) effectiveness of two antiretroviral (ARV) treatment strategies in patients not previously treated: starting with a nelfinavir based HAART switching to nevirapine in case of failure or side effects or the reverse sequence. METHODS: This multicenter, randomized, open label clinical trial enrolled ARV-naïve HIV patients with CD4 counts below 500 cells/mm3. They were randomly assigned to start ddI + d4T + nelfinavir (switching to ZDV + 3TC + NEV in case of failure or toxicity) (PI-NEV arm) or ddI + d4T + nevirapine, switching to ZDV + 3TC + NFV in case of failure or toxicity (NEV-PI arm). The primary study endpoint was the Kaplan-Meier estimates of the time to failure after switching to second regimen if necessary (considering failure as two consecutive plasma HIV-1 RNA determinations above 200 copies/mL, death, a new category C event or toxicity leading to treatment discontinuation of the second regimen) after a minimum follow-up of two years. RESULTS: A total of 137 patients were evaluable (67 and 70 in the PI-NEV and NEV-PI arms respectively). Baseline characteristics did not differ among groups. Kaplan-Meier estimates of time to failure did not show differences between the two arms neither in the on-treatment (OT) analysis (log rank test, p = 0.81) nor in the intent-to-treat (ITT) analysis (p = 0.58). At 24 months, the estimated proportion of patients free of failure were 72% and 66% respectively in the PI-NEV and NEV-PI arms OT analysis (p = 0.54) and 73% and 64% in the PI-NEV and NEV-PI arms in the ITT analysis (p = 0.49). The difference in the median in CD4+ lymphocyte count at 24 months was not significantly different in the two groups: 393 and 307 CD4 cells/mm3 in the PI-NEV and NEV-PI arms respectively (p = 0.167). The incidence of adverse events (AEs) in the two arms was very similar: 50 (75%) in the PI-NEV and 54 (70%) in the NEV-PI group, as it was for grade 3-4 AEs leading to drug switching. CONCLUSION: At two years both treatments strategies (PI-NEV vs NEV-PI) had a high and comparable efficacy and were generally well tolerated.

Hepatotoxicity in HIV-1-infected patients receiving nevirapine-containing antiretroviral therapy.

OBJECTIVES: To assess the incidence and risk factors for hepatotoxicity associated with nevirapine. DESIGN: A prospective cohort study in a teaching and referral hospital involving all consecutive patients who were prescribed a nevirapine-containing antiretroviral regimen between September 1997 and May 2000. METHOD: Cutaneous and hepatic adverse reactions and clinical hepatitis were assessed. Blood analysis including plasma HIV-1 RNA CD4 cell counts, liver chemistry tests, and serology for hepatitis B and C viruses. Hepatotoxicity was defined as an increase of at least threefold in serum alanine aminotransferase or aspartate aminotransferase levels compared with baseline values. RESULTS: Of a total of 610 patients, 82 (13.4%) were antiretroviral naive when commencing nevirapine, and 46.2 and 8.9% were coinfected with hepatitis C and B viruses, respectively. Median duration of exposure to nevirapine was 8.7 months (interquartile range 3.4--14.3). Hepatotoxicity developed in 76 (12.5%), an incidence of 13.1/100 person-years. Kaplan--Meier estimated incidence of hepatotoxicity at 3, 6 and 12 months was 3.7, 9.7 and 20.1%, respectively. In seven (1.1%) patients, hepatotoxicity was associated with clinical hepatitis, which was reversible upon discontinuation of therapy. Multivariate analysis identified the duration of prior exposure to antiretroviral drugs, hepatitis C virus, and higher baseline levels of alanine aminotransferase as independent risk factors for hepatotoxicity. CONCLUSIONS: Hepatotoxicity but not clinical hepatitis was common in HIV-1-infected patients receiving nevirapine-containing regimens and the incidence steadily increased over time. Prolonged exposure to any antiretroviral therapy, coinfection with hepatitis C virus and abnormal baseline levels of alanine aminotransferase identified patients at a higher risk.

The use of evidence in pharmacovigilance. Case reports as the reference source for drug withdrawals.

OBJECTIVE: Withdrawal of a drug from the market for safety reasons is a serious and sometimes complex decision. The scientific evidence supporting drug withdrawals in the past years is critically appraised. METHODS: With data provided by the Spanish Medicines Agency, all drugs withdrawn from the Spanish market for safety reasons from January 1990 to December 1999 were identified. The adverse drug reactions (ADRs) were classified by the year of withdrawal, by the organ/system affected and by the alleged type of reaction (Rawlins and Thompson classification). A systematic review of the literature was performed. RESULTS: A total of 22 drugs were withdrawn from the market due to safety reasons. In 18 of 22 cases (82%), the evidence supporting the drug withdrawal came from individual case reports, cases series or the combination of data provided by randomised clinical trials and case reports. Hepatic (eight cases) and cardiac (five cases) reactions accounted for 59% (13 of 22) of the total withdrawals. In 10 of 22 (45%) cases, drug withdrawal was clearly due to type-B reactions. Only four withdrawals were based on evidence from observational studies including a comparison group. CONCLUSION: Case reports are the main source of information used to withdraw a drug from the market for safety reasons. It is necessary to improve the quality of evidence supporting the withdrawal process of drugs linked to unexpected and severe ADRs. The use of large databases to perform cohort or nested case-control analyses is the most efficient and reliable method to study type-A class effect ADRs. The implementation of such databases in different countries could increase the quality of the information on ADRs by allowing researchers to conduct efficiently these type of studies.

Dose-finding study of once-daily indinavir/ritonavir plus zidovudine and lamivudine in HIV-infected patients.

BACKGROUND: Strategies for treatment of HIV need to be considered in terms of combining potency, safety, and convenience of dosage. However, regimens including once-daily protease inhibitors are not yet available. We have performed a pilot study to determine an indinavir/ritonavir (IND/RTV) regimen for once-daily dosing, by monitoring plasma levels. METHODS: Antiretroviral-naive HIV-infected adults were eligible. Therapy was zidovudine/lamivudine 1 pill twice daily plus IND/RIT (liquid formulation) 800/100 mg twice daily with food. At 4-week intervals, plasma levels were measured and dosage of IND/RIT switched to 1000/100 mg daily and then 800/200 mg daily. If 12-hour minimum concentrations (Cmin12h) of IND were too low (<0.1 microg/ml) with IND/RIT 1000/100 mg once daily in the first half of the patients, it was planned to switch directly to 800/200 mg once daily in the other half. RESULTS: In all, 27 patients were recruited. Mean baseline CD4+ lymphocyte count was 107 x 106/L (range, 4-623 x 106/L). Eleven patients (40%) discontinued the study medication within the first 4 weeks due to clinical progression (n = 3) or grade 1-2 RTV related side effects (n = 8). Nine patients (group A) switched from 800/100 mg twice daily to 1000/100 mg once daily and then to 800/200 mg once daily. Seven patients (group B) switched directly to 800/200 mg once daily. At week 32, viral load was <5 copies/ml in 15 of 16 patients (94%). RTV levels were always <2.1 microg/ml. The mean and 95% confidence interval for IND Cmin and Cmax in microg/ml was: using IND/RTV 800/100 mg twice daily (n = 16) 1.4 (0.5-2.3) and 6.7 (4.4-9.1), respectively; using IND/RTV 1000/100 mg once daily (n = 9) 0.18 (0-0.41) and 8.6 (3.3-14), respectively; and using 800/200 mg once daily (n = 16) 0.38 (0-0.9), and 7.5 (0.8-14.8). For all 16 patients who received IND/RTV 800/100 mg twice daily, the Cmin value for IND was >/=0.1 microg/ml. Conversely, IND Cmin was <0.1 microg/ml in 4 of 9 receiving 1000/100 mg once daily but in only 1 of 16 receiving 800/200 mg once daily. CONCLUSION: Once-daily regimen of IND/RIT is feasible and deserves further evaluation in larger randomized trials. Liquid formulation of RIT was not well tolerated by our antiretroviral-naive patients despite lower than suggested doses.

Methodological and political issues in clinical pharmacology research by the year 2000.

Parallel groups in a large, multicenter, phase III "pivotal" randomized clinical trial (RCT) with clinically relevant end-points are seen by the medical community as the "gold standard" of clinical research. However, there are limitations, some methodological and others political. The main one is the external validity of the method because a treatment, as studied in RCTs, does not necessarily reflect how it is used in clinical practice. Also, the method, as it stands, is not really predictive of the success in a particular patient of a certain intervention studied in a trial. To overcome these methodological drawbacks, different options have been implemented. The most important ones are: (1) the performance of pragmatic RCTs intended to address effectiveness rather than efficacy; (2) meta-analysis; and (3) the use of observational studies, with or without a comparison group. Recent experience has shown that type-A adverse drug reactions (ADRs) related to a specific class of drugs have been successfully characterized throughout cohort- or population-based case-control studies, whereas the evidence linking a specific drug entity to a type-B ADR, apparently severe enough to withdraw the drug from the market, has come mainly from case reports or case series. Other limitations of the RCT are more of a political nature. These large "pivotal" trials are mostly sponsored by the pharmaceutical industry, and to guarantee the scientific and ethical integrity of data produced, they are performed following standard operating procedures (SOPs) and good clinical practice (GCP) guidelines. Sometimes industry is not interested in sponsoring trials; thus, RCTs performed are in practice highly biased because of their potential economical profits. Furthermore, applying SOPs and GCPs is expensive and difficult to implement, and it is hard to find funding in public institutions. As a result, there is an urgent need to create a network of independent, skilled groups interested in sponsoring and performing institutional RCTs following "user friendly" GCP when the profits are low, but scientific interest high.

[Detection of opportunities for improvement of the quality of parenteral nutrition in patients subjected to gastrointestinal surgery]. / Detección de oportunidades de mejora en el soporte nutricional por vía parenteral en pacientes sometidos a cirugía gastrointestinal.

The nutritional support team must justify its role by proving that it provides an adequate quality control and supervises the administration of the nutritional support to avoid its inappropriate use. The measures based on the process reported on the improvement opportunities while those based on the results allow an evaluation of the quality. The objective of this study is to present the results of a systematic search for improvement opportunities in two fundamental activities of the nutritional support team: the evaluation of the patient needs, and the adequation of the caloric supply to these needs. The data corresponding to nutritional support and nutritional assessment of 217 patients who initiated central parenteral nutrition during the perioperative surgery period for a laparotomy were registered between January of 1996 and June of 1997. These data were used to calculate 8 selected quality indicators to report on the quality of the activities subject to the evaluation. Moreover, the initial and final values of the nutritional assessment parameters of a sub-group of patients were compared with the aim of obtaining a measure of the result of parenteral nutrition. The final average levels of albumin, prealbumin, transferin, and the Nutritional Prognostic Index were significantly better than the initial data in the subgroup in which these data were available. The analysis of the process indicators allowed the detection of the need to reduce the caloric supply in relation to the protein supply and to promote the use of programs with a caloric supply that was better adjusted to the BMI and/or the patients' weight. It was also shown that it is necessary to increase the number of patients assessed from a nutritional point of view at the beginning and at the end of parenteral nutrition.

Topical heparin for the treatment of acute superficial phlebitis secondary to indwelling intravenous catheter. A double-blind, randomized, placebo-controlled trial.

OBJECTIVE: To assess the clinical efficacy of a topical gel containing 1000 IU x g(-1) of heparin, applied three times daily for a maximal period of 7 days to patients with acute superficial phlebitis secondary to indwelling intravenous catheter. METHODS: A Double-blind, randomized, placebo-controlled study was conducted in one of the internal medicine wards of a tertiary General Hospital in Barcelona, Spain. Inpatients of both genders over 18 years of age that developed superficial phlebitis and gave informed consent were included in the study. The sample size estimation was 132 patients. Sixty-six patients were allocated to each group. There were five protocol deviations and 24 withdrawals in the intervention group, and one protocol deviation and 25 withdrawals in the control group. Consequently, 37 patients in the intervention group and 40 in the control group completed the trial. The main outcome measure was the disappearance of the symptoms and signs of superficial phlebitis. Clinical course, investigator's global impression and adverse events were also recorded. RESULTS: According to the intention-to-treat analysis, after treatment for 7 days superficial phlebitis healed in 27 of the 61 patients (44.3%) who received topical heparin, and in 17 of the 65 patients (26.1%) receiving placebo, giving a relative risk [95% confidence interval (CI)] of 1.69 (1.03-2.78). This indicates that six patients (95% CI, 3-72) have to be treated in order to induce one additional healing. The clinical course and the overall clinical impression were similar in both groups. One patient treated with topical heparin developed mild urticaria. CONCLUSION: Topical heparin is safe and effective for the treatment of superficial phlebitis secondary to indwelling intravenous catheter.

[Omeprazole: a new treatment for paranasal sinus polyps in Widal syndrome. Preliminary study]. / Omeprazol: un nuevo tratamiento de la poliposis nasosinusal en el síndrome de Widal. Estudio preliminar.

A preliminary report is made of the potential therapeutic effect of omeprazol in reducing nasosinusal polyps. This study is based on the empirical observation of nasal airflow improvement in patients suffering from nasosinusal polyposis after administering omeprazol. Different phases of the study suggested that patients with Widal's syndrome benefited the most. Based on the results of this study, we have undertaken a randomized, parallel, double-blind, placebo-controlled clinical trial.

[Drug interactions in chronic prescription]. / Interacciones farmacológicas en la prescripción crónica.

OBJECTIVE: Application of computerized program for detection of potential drug interactions (PDI) in chronic prescriptions in four primary care centers. To evaluate the clinical significance of PDI identified according to clinical criterions. DESIGN: An observational crossover study. SETTING: Clutat Vella health district (City of Barcelona). MEASUREMENTS AND RESULTS: Using information of Consejo General de Colegios Oficiales de Farmaceuticos databases and the chronic prescriptions database of the primary care centers, computerized drug-interaction system have been developed for detection of PDI in patients. A panel of primary care physicians and clinical pharmacists developed criteria that were used to evaluate the clinical significance of PDI. 9840 Cards of Authorized Prescription (CAP) were analyzed, 36108 medicaments and 42877 drugs. A total of 2140 patients were involved for a total of 3406 PDI, 21.75% of patients with CAP. Clinical signification for the panel was found in 40.07% of these 3406 PIF; 3.78% were suggest to avoid the association drugs. CONCLUSIONS: The incidence of PDI with clinical signification are lower than other studies of the literature; it suggest a appropriate knowledge of drug prescription. The application of computerized program make much more easy the detection of adverse drug interactions in chronic prescription.