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)

Chronic Pain Treatment With Cannabidiol in Kidney Transplant Patients in Uruguay.

BACKGROUND: Chronic pain is a major therapeutic problem in kidney transplant patients owing to nephrotoxicity associated with nonsteroidal antiiflammatory drugs. Benefits in chronic pain treatment with cannabidiol (CBD) have been reported. This study assesses the effect, safety, and possible drug interactions in kidney transplant patients treated with CBD for chronic pain. METHODS: We assessed patients who asked to receive CBD for pain treatment. Doses were increased from 50 to 150 mg twice a day for 3 weeks. Creatinine, blood count, liver function, liver enzymes, and drug levels were determined every 48 hours the first week and then once a week thereafter. RESULTS: We assessed 7 patients with a mean age of 64.5 years (range, 58-75 years). CBD initial dose was 100 mg/d, CBD dose reduction to 50 mg/d has been done on day 4 to patient 1 for persistent nausea. Tacrolimus dose reduction in patient 3 was undertaken on days 4, 7, and 21 owing to persisting elevated levels (even before CBD) and itching, and on day 21 in patient 5. Tacrolimus levels decreased in patient 2 but were normal in the control 1 week later. Patients on cyclosporine were stable. Adverse effects were nausea, dry mouth, dizziness, drowsiness, and intermittent episodes of heat. CBD dose decrease was required in 2 patients. Two patients had total pain improvement, 4 had a partial response in the first 15 days, and in 1 there was no change. CONCLUSIONS: During this follow-up, CBD was well-tolerated, and there were no severe adverse effects. Plasma levels of tacrolimus were variable. Therefore, longer follow-up is required.

Week 96 results of the randomized, multicentre Maraviroc Switch (MARCH) study.

OBJECTIVES: The Maraviroc Switch (MARCH) study week 48 data demonstrated that maraviroc, a chemokine receptor-5 (CCR5) inhibitor, was a safe and effective switch for the ritonavir-boosted protease inhibitor (PI/r) component of a two nucleos(t)ide reverse transcriptase inhibitor [N(t)RTI] plus PI/r-based antiretroviral regimen in patients with R5-tropic virus. Here we report the durability of this finding. METHODS: MARCH, an international, multicentre, randomized, 96-week open-label switch study, enrolled HIV-1-infected adults with R5-tropic virus who were stable (> 24 weeks) and virologically suppressed [plasma viral load (pVL) < 50 HIV-1 RNA copies/mL]. Participants were randomized to continue their current PI/r-based regimen (PI/r) or to switch to MVC plus two N(t)RTIs (MVC) (1:2 randomization). The primary endpoint was the difference in the proportion with pVL < 200 copies/mL at 96 weeks. The switch arm was defined as noninferior if the lower limit of the 95% confidence interval (CI) for the difference was < -12% in the intention-to-treat (ITT) population. Safety endpoints (the difference in the mean change from baseline or a comparison of proportions) were analysed as key secondary endpoints. RESULTS: Eighty-two (PI/r) and 156 (MVC) participants were randomized and included in the ITT analysis; 71 (87%) and 130 (83%) were in follow-up and on therapy at week 96. At week 96, 89.0% and 90.4% in the PI/r and MVC arms, respectively, had pVL < 50 copies/mL (95% CI -6.6, 10.2). Moreover, in those switching away from PI/r, there were significant reductions in mean total cholesterol (differences 0.31 mmol/L; P = 0.02) and triglycerides (difference 0.44 mmol/L; P < 0.001). Changes in CD4 T-cell count, renal function, and serious and nonserious adverse events were similar in the two arms. CONCLUSIONS: MVC as a switch for a PI/r is safe and effective at maintaining virological suppression while having significant lipid benefits over 96 weeks.

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.

Amiloidosis primaria / Primary amyloidosis

No disponible

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.

Tratamiento de linfoma difuso de células B mediastínico durante el embarazo / No disponible

No disponible

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.

Embolismo pulmonar biliar no traumático fatal tras colecistitis litiásica / No disponible

No disponible

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.