[Hospital admission and mortality causes of HIV patients in a third level hospital]. / Diagnóstico al alta y causas de mortalidad de pacientes VIH+ ingresados en un hospital de tercer nivel.

OBJECTIVE: The aim of this study is to describe the HIV population admitted to a tertiary level hospital and analyze hospital admission and mortality causes during hospitalization. METHODS: Observational, retrospective study carried out in a third level Hospital. Inclusion criteria: Patients ≥18 years with a prescription of ART and diagnosis of HIV known or discovered during admission. It was accepted hospital ward discharge diagnose as hospitalization causes. Clinical, analytical outcomes as well as causes of mortality were collected. RESULTS: Among 162 hospitalized HIV infected, 128 met the inclusion criteria, 8 of those were diagnosed as naive HIV patients. 79.7% were male; Age 50.29 ± 9.81 years. The main reasons for hospital admissions (38.3%) were certain infectious and parasitic diseases (ICD-10 Classification) and more specifically human immunodeficiency virus [HIV] disease represented 24,1% of whole hospitalizations. Mortality rates of ≥18 years HIV patients that were admitted to hospital during 2016-2017 were the 13.52%. The main causes of death were certain infectious and parasitic diseases followed by malignancies. CONCLUSIONS: Our results emphasize the need of intensifying the HIV early diagnosis as well as Pneumocystis jirovecii primary prophylaxis. Insist on ART adherence from infectology follow-up appointment and pharmacy care consultations, educate clinics on ART treatment prescription during hospital admission as well as requesting viral and CD4 lymphocytes loads to every HIV admitted patients.

Effectiveness of 12 week ledipasvir/sofosbuvir and predictors of treatment failure in patients with hepatitis C.

OBJECTIVE: The efficacy of ledipasvir/sofosbuvir (LDV/SOF) have been demonstrated in randomized controlled trials, however,there is an unmet need for real-world effectiveness data. It is important to gather data regarding potential predictors of treatment failure with (LDV/SOF). Predictors of sustained virologic response (SVR) to all-oral HCV regimens can inform nuanced treatment decisions. The objectives of this study were to evaluate the effectiveness of LDV/SOF, SVR12 as main endpoint and SVR24 as second endpoint, and identify predictors of treatment failure. METHODS: Retrospective and observational study carried out from April 2015 to January 2016. Inclusion criteria: patients with HCV infection treated with LDV/SOF for 12 weeks during study period. The patients that were treated during 24 weeks were excluded as well as those treated with peg-interferon. Binary logistic regression was used to predict what variable was associated with treatment failure. RESULTS: A total of 122 patients were analyzed achieving SVR12 91.80% (112/122) of them. The patients with HCV genotype (GT) 1a or GT1b or GT4 achieved SVR12. Only one pre-treated non-cirrhotic HCV GT1 patients relapsed to treatment. The lowest SVR12 were obtained for GT3, 43.75%, (7/16). Everybody that got SVR12 achieved SVR24. None of the variables analyzed significantly influenced the SVR12, except GT (p=0.001). Almost all the relapses occurred in GT3. CONCLUSIONS: LDV/SOF combination has been very effective to treat GT1 and GT4 infected patients, however, has constituted a suboptimal therapeutic option for those patients infected with GT3, regardless of the rest of the variables analyzed.

Direct-acting antiviral agents in patients with hepatitis C genotype 1-4 infections in a tertiary hospital.

OBJECTIVE: Hepatitis C virus (HCV) infection is a major cause of chronic liver disease. Six different genotypes (GT) of HCV (genotypes 1-6) have been identified. The genotype is clinically relevant since the majority of current direct antiviral agents (DAA´s) do not have pangenotypic efficacy. The purpose of this study was to describe the clinical characteristics of real world patients and evaluate the effectiveness of different treatment regimens. METHODS: Retrospective and observational study carried out in a third level hospital. Study period: January 2015-January 2016. Inclusion criteria: HCV patients of any genotype treated with either DAAs ± rivabirin (RBV) or DAAs + RBV + pegilated interferon (Peg-IFN) regimens for 12 weeks. Exclusion criteria: patients without adequate clinical or analytical information available for further analysis. Patients treated for 24 weeks were excluded. The main endpoint was sustained virologic response 12 weeks after the end of treatment (SVR12), and secondary endpoint was SVR24. RESULTS: A total of 515 patients were included (aged 55.52±8.97 years). GT1: patients treated with simeprevir + sofosbuvir (SIM + SOF), ledipavir (LDV)/SOF and paritaprevir/ritonavir/ombitasvir + dasabuvir (PTV/r/OBV + DSV) ± RBV had a SVR12 of 93.59% (190/203), 98.82% (N=84/85), 94.28% (66/70), respectively. Regarding daclatasvir (DCV) + SOF and SIM + DCV, everybody (19/19) and 87.5% (7/8) got SVR12, respectively. GT2: 71.42% (N=10/14) of patients achieved SVR12, concretely, SOF + RBV had a SVR12 75% (N=6/8). GT3: 43.75% (N=7/16), 90% (N=9/10) and 95% (N=19/20) of patients treated with LDV/SOF, LDV/SOF + RBV and SOF + DCV obtained SVR12, respectively. GT4: patients treated with LDV/SOF, SIM + SOF and PTV/r/OBV ± RBV had a SVR12 rate of 100% (21/21), 91.67% (22/24) and 92% (23/25), respectively. All patients that got SVR12 achieved SVR24. CONCLUSIONS: Our study confirmed the efficacy data reported in clinical trials in a cohort of patients with GT1-4 and a wide range of basal characteristics.

Interferon-free treatments in patients with hepatitis C genotype 3 infection in a tertiary hospital.

OBJECTIVE: Hepatitis C virus genotype 3 represents a unique entity within HCV treatment and multiple studies have documented that HCV genotype 3 infection is associated with more rapid disease progression than other genotypes, resulting in increased risk of cirrhosis, hepatocellular carcinoma, and all-cause mortality. In the current study, we further evaluated the real-world effectiveness of 12 weeks of ledipasvir/sofosbuvir ± ribavirin (LDV/SOF ± RBV) and sofosbuvir + daclatasvir (SOF + DCV) for treatment-naive or treatment-experienced patients infected with HCV genotype 3, with or without cirrhosis. METHODS: Retrospective and observational study carried out in a third level hospital. Study period: April 2015 to January 2016. Inclusion criteria: Patients with HCV genotype-3 infection treated either with LDV/SOF ± RBV or with SOF + DCV during study period treated for 12 weeks. The patients that were treated during 24 weeks were excluded and those treated with peg-interferon. The main endpoint measured was the sustained virologic response (SVR) at 12 weeks (SVR12) and the secondary endpoint was SVR at 24 weeks (SVR24). RESULTS: During the study period, 603 patients were treated in our hospital: 71 with genotype 3. We included 46 patients who were treated with LDV/SOF ± RBV or SOF + DCV for 12 weeks. A 43.75% (7/16) of all patients treated with LDV/SOF achieved SVR12, 90% (9/10) of the patients treated with LDV/SOF+RBV achieved SVR12 and 95% (19/20) of the patients treated with SOF+DCV achieved SVR12. There was statistically significant difference (p=0.001) between LDV/SOF respect to SOF+DCV and between LDV/SOF with regard to LDV/SOF +RBV (p=0.018) used to treat HCV genotype 3 infection. CONCLUSIONS: In conclusion, in our cohort of patients, the combination of SOF + DCV followed by LDV/SOF + RBV 12 weeks were the most effective in patients with HCV genotype 3 and with cirrhosis (SVR12 90% and 80%, respectively) and in those without cirrhosis (SVR12 100% in both combinations). All patients who achieved SVR12 also achieved SVR24, regardless of the regimen received.

[Darunavir/cobicistat monotherapy. Experience in a tertiary hospital]. / Monoterapia con darunavir/cobicistat. Experiencia en un hospital de tercer nivel.

OBJECTIVE: Ritonavir-boosted protease inhibitor (IP/r) monotherapy: darunavir/ritonavir (DRV/r) or lopinavir/ritonavir (LPV/r) monotherapy is only provided in the major treatment guidelines in pretreated patients to prevent toxicity associated with nucleoside/nucleotide reverse transcriptase inhibitor (NRTI), reduce costs and simplify antiretroviral treatment. To start IP/r monotherapy, according to GESIDA guidelines 2016, patients need to meet the following criteria: absence of chronic hepatitis B, plasma viral load <50 copies/ mL for at least 6 months and absence of protease inhibitors mutations or previous virologic failures to IP/r. Currently, there are no studies that evaluate the efficacy and safety of darunavir/cobicistat (DRV/COBI) monotherapy. METHODS: This prospective study analyzed pretreated HIV patients with DRV/r monotherapy that were switched to DRV/COBI monotherapy. The aim of the study is to describe the effectiveness and safety of the DRV/COBI monotherapy. RESULTS: Seventy-eight patients were evaluated. Patients had a median of 31.29 months of DRV/r monotherapy before DRV/COBI monotherapy. Nine of the 78 patients developed "blips" (plasma viral load: 50-200 copies/ml) and four patients had plasma viral load ≥200 copies/mL. An 83.3% (65/78) of the patients remained with undetectable plasma viral load. As for safety, there were no significant differences in lipid profile, liver function (transaminases) and renal function between DRV/r and DRV/COBI monotherapy. CONCLUSIONS: DRV/COBI monotherapy seems to be effective and safe (lipid profile, liver and kidney function). However, it will be necessary to design specific studies comparing DRV/r vs DRV/COBI monotherapy to confirm these results.

[Effectiveness of plerixafor in patients undergoing mobilization autologous haematopoietic progenitor cell]. / Efectividad de plerixafor en pacientes sometidos a movilización de progenitores hematopoyéticos para autotrasplante.

OBJECTIVE: To evaluate effectiveness of treatment with plerixafor in patients undergoing posterior mobilization for hematopoietic transplant at our hospital. METHODS: Retrospective study of all patients who until September 2012, received plerixafor in their scheme of mobilization into peripheral blood hematopoietic progenitors. We reviewed the medical records and records of drug dispensing outpatient consultation. Effectiveness variables used were: CD34/kg in apheresis product obtained, and day dose received colony stimulating factor (G-CSF) and Plerixafor. Each patient was compared to the effectiveness of the drug results with those obtained earlier mobilization schemes where Plerixafor not used, if present. Data were analyzed using IBM SPSS v19. RESULTS: A total of 24 patients received plerixafor in our hospital. Diagnoses were distributed: 15 NHL, 6 patients with multiple myeloma, 2 Hodgkin's disease, and one metastatic choriocarcinoma. The effectiveness outcomes were no plerixafor mobilization (n = 18): 5 patients were mobilized with G-CSGF only, 13 with G-CSF and chemotherapy. The G-CSF dose / day was mcg 931.1 (± 179.5) for 9.5 days (± 4.7). The average product obtained CD34/kg in cells was 0.2 (± 0.5). No patient received sufficient product (≥ 2 x 106 cells/kg) for subsequent autologous transplantation. 100% of the demonstrations failed. Mobilization with plerixafor (n = 24): 13 patients were mobilized with GCSGF only, 11 with G-CSF and chemotherapy. The G-CSF dose/ day and averaged Plerixafor mcg 885.1 (± 240.1) and 19.8 (± 4.4), respectively, administered for 8.9 (± 5.1) and 1 , 5 (± 0.6) days, respectively. The average product obtained in CD34/kg was 2.3 x 106 cells (± 1.7) (p = 0.014 in relation to the demonstrations without Plerixafor). Only 12.5% (n = 3) patients were unable to undergo autologous transplant. CONCLUSIONS: In our patients, plerixafor has proven effective in mobilizing hematopoietic progenitors for autologous back.

Objetivo: Evaluar efectividad del tratamiento con plerixafor en pacientes sometidos a movilización para posterior autotrasplante de progenitores hematopoyéticos en nuestro hospital. Métodos: Estudio retrospectivo de todos los pacientes que hasta septiembre 2012, recibieron plerixafor en su esquema de movilización de progenitores hematopoyéticos a sangre periférica. Se revisaron las historias clínicas y los registros de dispensación de medicamentos de la consulta de pacientes externos. Las variables de efectividad utilizadas fueron: CD34/kg en producto de aféresis obtenidas, dosis y días recibidos de factor estimulante de colonias (G-CSF) y de plerixafor. Para cada paciente se comparó los resultados de efectividad del fármaco con los obtenidos para anteriores esquemas de movilización en los que no se utilizó plerixafor, en caso de tenerlos. Los datos se analizaron mediante IBM spss v19. Resultados: Un total de 24 pacientes recibieron plerixafor en nuestro hospital. Los diagnósticos se distribuyeron: 15 linfoma no Hodgkin , 6 pacientes con mieloma múltiple, 2 enfermedad de Hodgkin, y 1 coriocarcinoma diseminado. Los resultados de efectividad fueron: Movilización sin plerixafor (n = 18): 5 pacientes se movilizaron sólo con G-CSGF, 13 con G-CSF y quimioterapia. La dosis de G-CSF /día fue de 931,1 mcg (± 179,5), durante 9,5 días (± 4,7). El promedio de CD34/kg en producto obtenido fue de 0,2 células (± 0,5). Ningún paciente obtuvo producto suficiente (≥?2 x 106 células/kg) para el posterior autotrasplante. El 100 % de las movilizaciones fracasaron. Movilización con plerixafor (n = 24): 13 pacientes se movilizaron sólo con G-CSGF, 11 con G-CSF y quimioterapia. La dosis de G-CSF /día y de plerixafor promedio fue de 885,1 mcg (± 240,1) y 19,8 (± 4,4), respectivamente, administrados durante 8,9 (± 5,1) y 1,5 (± 0,6) días, respectivamente. El promedio de CD34/kg en producto obtenido fue de 2,3x106 células (±1,7) (p = 0,014, en relación a las movilizaciones sin plerixafor). Sólo el 12,5% (n = 3) pacientes no pudieron someterse a autotrasplante. Conclusiones: En nuestros pacientes, plerixafor ha demostrado ser efectivo en la movilización de progenitores hematopoyéticos para posterior autotrasplante.

[Stability of pantoprazole in parenteral nutrition units]. / Estabilidad de pantoprazol en unidades para nutrición parenteral.

INTRODUCTION: Pantoprazole is a weak base (pka approximately equal to 4) with its stability in aqueous solution dependent on pH. Keeping in mind that the pH of the parenteral nutrition units (PNU) can range between 6.0 and 6.5 and since pantoprazole seems to be the most stable proton pump inhibitor (PPI) for pH acid, we want to assess the possibility of adding it to PNU with the aim of simplifying its administration to patients. METHODS: Using high performance liquid chromatographic (HPLC) to measure pantoprazole content in PNU at different time intervals. RESULTS: The chromatographic determination of pantoprazole concentration reflected a rapid and progressive aging of the sample. After 24 h the quantity of drug detected in the PNU was below 50% of the total added. CONCLUSIONS: In view of these results, we therefore do not suggest this as a suitable vehicle for pantoprazole administration as it could put patients at risk of being under-dosed and therefore exposing them to potential unknown side effects of the different drug degradation products.

[Comparison of high-resolution liquid chromatography versus microparticle enzyme immunoassay for the measurement of sirolimus levels in renal transplantation]. / Comparación de la cromatografía líquida de alta resolución frente al enzimoinmunoensayo de micropartículas para la determinación de sirolimus en trasplante renal.

OBJECTIVE: To compare sirolimus levels measured in whole blood using two analytical techniques: high-resolution liquid chromatography and microparticle enzyme immunoassay, and to evaluate whether hemoglobin, hematocrit, and time from kidney transplantation influence results obtained using the immune-enzymatic technique. METHOD: A retrospective, observational study in which all transplanted patients with at least one measurement of sirolimus levels using high-resolution liquid chromatography or microparticle enzyme immunoassay from October 2004 to May 2005 were consecutively included. For statistical comparisons simple linear regression, ANCOVA, intra-class correlation coefficient, and the method of agreement limits were all used. RESULTS: Ninety-one patients were assessed for a total of 307 measurements (median: 2, inter-quartile range: 1-4, range: 1-15) of sirolimus levels. The straight-line equation using the linear regression analysis was as follows: MEIA = 0.70 (95% CI: 0.39-1.01) + 1.14 (95% CI: 1.10-1.17) x HPLC/UV. The intra-class correlation coefficient between both measurements was 0.955 (95% CI 0.944-0.964). Mean overestimation using enzyme immunoassay was 24.8% +/- 19.4%. Difference in means between both measurements was 1.9 +/- 1.3 ng/mL. Agreement limits were established between -0.8 ng/mL (95% CI: -1.05; -0.55) and +4.6 ng/mL (95% CI: 4.35; 4.85). Factors such as post-transplant time, hemoglobin, and hematocrit did not influence overestimates obtained using enzyme immunoassays. These results were not influenced by non-independence in measurements. CONCLUSIONS: Despite enzyme immunoassay overestimates in establishing sirolimus levels in whole blood, its correlation with chromatography is acceptable. Added to its benefits versus chromatographic techniques, this renders enzyme immunoassay a good alternative for the measurement of sirolimus levels in whole blood.

[Infliximab in rheumatoid arthritis-use in a third level hospital]. / Infliximab en artritis reumatoide. Utilización en un hospital de tercer nivel.

OBJECTIVES: To study the conditions of infliximab use in rheumatoid arthritis, as well as the effectiveness and adverse effects of this therapy, and to perform an economic assessment of infliximab therapy in a third-level hospital. MATERIAL AND METHODS: A retrospective study was performed including patients treated with infliximab from January 2001 to March 2003. RESULTS: Twenty-five percent of patients received doses greater than 3 mg/kg, and 12% of them at intervals shorter than 8 weeks; 78% also received methotrexate concurrently. Adverse effects reported were similar in type to those described in the pro-duct's data sheet. Regarding therapy effectiveness, objective para-meters were seen to improve, less so the remaining parameters. Therapy cost was 5.6% of day hospital costs. CONCLUSIONS: Anti-TNF drugs are a relevant alternative in the treatment of rheumatoid arthritis because of their effectiveness-safety profile, but understanding their frame of use and following recommendations issued by scientific societies are important considerations.