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WHAT IS KNOWN AND OBJECTIVE: To report five cases with a probable interaction between acenocoumarol and levofloxacin. CASE DESCRIPTION: In five patients on long-term acenocoumarol treatment who had had stable international normalized ratios for at least 6 months, sudden erratic changes in the values of these ratios were observed after 1.5-8 days of concomitant levofloxacin treatment with no other apparent cause. WHAT IS NEW AND CONCLUSIONS: Closer monitoring should be considered in patients with concomitant use of acenocoumarol and levofloxacin, especially elderly patients and those with renal dysfunction who seemed to suffer the interaction more severely.

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In total, 17 pediatric patients with hematologic malignancies (n=14) and Fanconi anemia (FA) (n=3) underwent haploidentical SCT with T-cell depletion. The patients were conditioned with reduced-intensity regimens, and CYA was used for GVHD prophylaxis. Successful engraftment occurred in 16 patients (94%). One patient failed to achieve a primary engraftment. Another patient rejected the first SCT after 10 weeks and had a successful second transplant. Of all engrafted patients, only one developed severe acute GVHD. Ten patients were alive at a median follow-up of 18 months (range, 5-62 months). The 5-years' OS was 53.8%. The three patients with FA are currently well with full-donor chimerism at 16, 6 and 5 months post transplant, respectively. The OS of 14 patients with high-risk hematologic malignancies was 47.6%. Three patients died as a result of post transplant leukemia relapse. CMV infection, GVHD and organ injury were other causes of mortality. Haploidentical SCT was found to be an alternative feasible treatment in Uruguay for patients who need allogenic transplantation but lack an HLA-identical family donor. It should be considered as an early option in FA patients before transformation or significant exposure to blood products.

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BACKGROUND & AIMS: Multiple instances of DILI in the same patient with drugs of similar structure or function as well as completely unrelated drugs are not well understood and poorly documented. We have sought evidence of the frequency and characteristics of patients who have experienced two DILI episodes due to different drugs. METHODS: All cases of DILI systematically collected in the Spanish DILI Registry between 1994 and 2009 were retrieved. Data on demographics, clinical, laboratory and pathological findings, and outcome were analyzed. RESULTS: Nine patients (mean age 67 years, four women) out of 742, 1.21%, had evidence of two DILI episodes caused by different drugs. In four cases DILI was associated with structurally related drugs and in an additional two cases the drugs had a common target. In another case, unrelated antibiotics were implicated. In only two cases, the two drugs/herbals were not related in structure or function. All but one patient exhibited hepatocellular damage. The type of damage was consistent in both DILI episodes. Four cases presented as autoimmune hepatitis (AIH) in the second episode. CONCLUSIONS: Multiple episodes of DILI in association with different drugs occur infrequently. In each individual, the type of injury was similar during the two DILI episodes, regardless of the causative drug. Second episodes of DILI are more likely to be associated with features of AIH. It remains uncertain if this is drug-induced unmasking of true AIH or DILI with autoimmune features. These cases illustrate the dilemma faced by clinicians in distinguishing these possibilities.

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Objetivos Evaluar la adherencia al tratamiento antirretroviral en la cohorte de pacientes VIH de nuestro hospital y ver su evolución a lo largo de 9 años; así como conocer el patrón individual de la adherencia con el tiempo. Métodos Estudio descriptivo de la evolución de la adherencia media anual y el porcentaje anual de pacientes con adherencias superiores al 95%, desde el 2000 al 2008. Se analizó el patrón individual de adherencia con el tiempo y se clasificó a los pacientes en adherentes consistentes, no adherentes consistentes y fluctuantes. Resultados En el análisis de 577 pacientes, la adherencia basal fue significativamente mayor en los pacientes naive respecto a los pretratados. La adherencia media anual aumentó ligeramente y se mantuvo en valores cercanos al 95%. Al igual que el porcentaje de pacientes con adherencia superior al 95%, que aumentó desde el 64% en el 2000 al 79% en 2008.En cuanto al patrón individual de adherencia con el tiempo, de los 468 pacientes analizados, la mayoría (59%) fueron adherentes consistentes, un 4% no adherente y el resto (37%) presentaban fluctuaciones en su adherencia. Conclusiones En nuestra cohorte los valores de adherencia global se mantienen con el tiempo e incluso presentan una tendencia positiva; resultado de una monitorización sistemática de la adherencia e implantación de estrategias dirigidas a mantener la adherencia (AU)

Objectives To evaluate antiretroviral treatment adherence in the HIV patient cohort of our hospital and observe their evolution over a 9-year period; also to determine the individual pattern of adherence over time. Methods Descriptive study of the evolution of average annual adherence and the annual percentage of adherent patients greater than 95% from 2000 to 2008. We analysed the individual pattern of adherence over time and patients were classified into consistently adherent, consistently non-adherent, and fluctuating. Results In the analysis of 577 patients, baseline adherence was significantly greater in naïve patients with respect to those who were pre-treated. Average annual adherence increased slightly and stayed at values around 95%. As with the percentage of patients with adherence greater than 95%, which increased from 64% in 2000 to 79% in 2008.In terms of the individual pattern of adherence over time, of the 468 patients analysed, the majority (59%) were consistently adherent, 4% non-adherent, and the rest (37%) fluctuated in their adherence. Conclusions In our cohort the overall adherence values maintained themselves over time and even show a positive trend, likely the result of systematic monitoring of adherence and implementation strategies to maintain adherence (AU)

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OBJECTIVES: To evaluate antiretroviral treatment adherence in the HIV patient cohort of our hospital and observe their evolution over a 9-year period; also to determine the individual pattern of adherence over time. METHODS: Descriptive study of the evolution of average annual adherence and the annual percentage of adherent patients greater than 95% from 2000 to 2008. We analysed the individual pattern of adherence over time and patients were classified into consistently adherent, consistently non-adherent, and fluctuating. RESULTS: In the analysis of 577 patients, baseline adherence was significantly greater in naïve patients with respect to those who were pre-treated. Average annual adherence increased slightly and stayed at values around 95%. As with the percentage of patients with adherence greater than 95%, which increased from 64% in 2000 to 79% in 2008. In terms of the individual pattern of adherence over time, of the 468 patients analysed, the majority (59%) were consistently adherent, 4% non-adherent, and the rest (37%) fluctuated in their adherence. CONCLUSIONS: In our cohort the overall adherence values maintained themselves over time and even show a positive trend, likely the result of systematic monitoring of adherence and implementation strategies to maintain adherence.

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Objetivo: determinar si la utilización en nuestro medio delprograma de cribado de HCC establecido –alfa-fetoproteína (AFP)y ecografia semestral– en pacientes con hepatopatía crónica permitedetectar pacientes en estadios precoces de la enfermedad.Material y métodos: Diseño experimental: estudio retrospectivo.Criterios diagnósticos de HCC: 2 o más técnicas de imagencon lesión hipervascular mayor de 2 cm o 1 técnica de imagencon lesión hipervascular mayor de 2 cm asociado a AFPmayor de 400 ng/ml. Pacientes: 85 pacientes diagnosticados deHCC en el Hospital Donostia entre los años 2003 y 2005. Datosanalizados: información demográfica (sexo, edad), factores deriesgo (alcohol, virus de hepatitis, hemocromatosis, otras enfermedadesasociadas), e información clínica (etiología de la hepatopatía,estadio de Child-Pugh, determinación de AFP, hallazgos radiológicos,criterios de resecabilidad, tratamiento recibido,evolución). Se divide la muestra en dos grupos según hubieran seguidoo no un programa de cribado.Resultados: el 70% de los pacientes del grupo de cribado sediagnostican en estadio precoz frente al 26,7% del grupo de nocribado (p < 0,05). Trece pacientes no pueden recibir tratamientocurativo a pesar del diagnóstico en fase precoz (9 en el grupo decribado y 4 en el de no cribado). La sensibilidad global del cribadoen nuestra serie es del 95%.Conclusiones: en nuestro medio, el programa de cribado dehepatocarcinoma es eficaz en términos de aplicación de tratamientoscurativos(AU9

Aim: to evaluate whether the current surveillance programs(ultrasonography and alpha-fetoprotein testing every six months)are successful in detecting patients in the early stages.Material and methods: the health records of all patientsdiagnosed with hepatocellular carcinoma in Donostia Hospitalbetween 2003 and 2005 were reviewed retrospectively. Eightyfivepatients (11 women and 74 men) were included in the studyand demographic data, risk factors and clinical data were obtained.Patients were split into two groups according to whether ornot they had been included in a surveillance program.Results: seventy per cent of patients of the surveillance groupis diagnosed in early stage opposite to 26.7% of patients in nosurveillance group (p < 0.05). Thirteen patients cannot receivecurative treatment in spite of the diagnosis in early stage (9 in thesurveillance group and 4 in the no surveillance group. The globalsensibility of the surveillance program in our series is 95%.Conclusions: current hepatocellular carcinoma surveillanceprograms, which comprise six-monthly ultrasonography and alpha-fetoprotein tests, are highly sensitive and effective. These programsresult in the detection of hepatocellular carcinoma in itsearly-stages, when potentially curative treatment may be offered(AU)

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AIM: to evaluate whether the current surveillance programs (ultrasonography and alpha-fetoprotein testing every six months) are successful in detecting patients in the early stages. MATERIAL AND METHODS: the health records of all patients diagnosed with hepatocellular carcinoma in Donostia Hospital between 2003 and 2005 were reviewed retrospectively. Eighty-five patients (11 women and 74 men) were included in the study and demographic data, risk factors and clinical data were obtained. Patients were split into two groups according to whether or not they had been included in a surveillance program. RESULTS: seventy per cent of patients of the surveillance group is diagnosed in early stage opposite to 26.7% of patients in no surveillance group (p < 0.05). Thirteen patients cannot receive curative treatment in spite of the diagnosis in early stage (9 in the surveillance group and 4 in the no surveillance group. The global sensibility of the surveillance program in our series is 95%. CONCLUSIONS: current hepatocellular carcinoma surveillance programs, which comprise six-monthly ultrasonography and alpha-fetoprotein tests, are highly sensitive and effective. These programs result in the detection of hepatocellular carcinoma in its early-stages, when potentially curative treatment may be offered.

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Objetivo: Valorar la evolución en el diagnóstico y tratamientodel carcinoma oculto de mama que se presenta comometástasis ganglionar.Pacientes y método: Trece mujeres diagnosticadas y tratadaspor haber presentado metástasis ganglionar de un carcinomade mama, sin localizar el foco primario.Resultados: Las 10 pacientes a las que se pudo aplicar cirugíaconservadora y radioterapia, evolucionaron favorablemente.Las tres que sólo recibieron hormonoterapia presentaronmastitis carcinomatosa a los pocos años.Conclusiones: Aunque la mamografía sigue siendo la exploraciónprincipal, la RNM y el PET ayudan a localizar algunoscarcinomas ocultos. Se confirma que el tratamiento consistenteen una linfadenectomía y radioterapia de la mama, esel de elección en la mayoría de los casos, frente a la cirugía radicalclásica(AU)

Objective: To evaluate the evolution in the diagnosis andtreatment of the occult breast carcinomas presented asmetastatic lymph node.Patients and methods: Thirteen women diagnosed andtreated of lymph node metastasis of breast cancer without primaryfocus localization.Results: Ten patients were treated with conservativesurgery and radiotherapy of the breast, presenting afavourable evolution. The 3 women that were treated onlywith hormonotherapy, had carcinomatous mastitis after fewyears.Conclusions: Mammography is still the gold standard testto study breast cancer. RNM and PET can help to localize occultbreast cancer. Lymphadenectomy and radiotherapy of thebreast is a good treatment in most cases, opposite to the classicalradical mastectomy(AU)

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OBJECTIVE: To describe the implementation, functioning and results of a prospective automated system monitoring clinically relevant interactions in hospitalised patients in a 400-bed hospital for the period between 1 January 2005 and 31 March 2006. METHOD: We created a computer programme in Access(R) 97 that checks, twice daily, the drug treatments of all of the patients admitted to the hospital in order to search for the 198 pairs of drugs previously selected from: a validated tertiary source (Hansten PD, Horn JR. Hansten and Horn's Drug Interactions Analysis and Management. St. Louis, MO: Facts and Comparisons; 2001 and updates), most relevant primary sources, expert opinions and alerts from the Spanish Agency of Medicines and Health Products. The clinical pharmacist will assess the drug-drug interaction (DDI) taking into account the timeline sequence, dose, administration route, management opportunities, patient diagnosis, clinical relevance, etc. If necessary, the doctor is contacted by phone and/or letter to inform him/her of the type of interaction, the mechanism and possible management. The programme files the following variables every day: interaction, sex, age, service, number of drugs, pharmaceutical intervention and doctor response. RESULTS: Clinically relevant drug interactions were detected in 3% of patients during their stay in hospital. These patients were an average of 10 years older and received an average of four drugs more than other patients. A total of 538 interactions were detected in 15 months. Forty-three of 198 possible DDls appeared at some time. The pharmacist intervened on 126 (23%) occasions. The doctor accepted the recommendation on at least 66 (52%) occasions. Fourteen drugs were responsible for 91% of the interactions reported. CONCLUSIONS: The patients with interactions are older and receive more drugs. The prior intervention of the pharmacist eliminated 77% of unnecessary alerts.

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OBJECTIVES: To analyze the influence on adherence and clinical outcome of the replacement of a previous antiretroviral therapy to a simplified approach using zidovudine, lamivudine, and abacavir (Trizivir) and to assess its economic impact. METHODS: A retrospective study of 75 pretreated, HIV-infected adult patients who received Trizivir from May 2001 to December 2002. Adherence was assessed by dispensation records or medication counting, CD4 lymphocyte counts, and viral load before and six months after medication change was analyzed; finally, the cost of each therapy was assessed in order to calculate the economic impact of medication change. RESULTS: Mean adherence significantly increased a 2.5% after medication change; 16 more patients reached optimal adherence, with an NNT (number of patients requiring therapy change in order to obtain one more adherent) of 4.7. The number of patients with undetectable viral load remained almost similar, and mean CD4 cell counts stayed above 500 cells/mm3 in both periods of time. A great variability in incremental costs was seen, due to the varying costs of the previous treatments, and the influence of five intensification therapies using Trizivir. However, when only simplification regimens were analyzed such variability was reduced, and even became favorable in selected cases. CONCLUSIONS: Changing to a simplification therapy using Trizivir resulted in improved adherence, similar clinical outcomes, and a varying economic impact depending on previous antiretroviral therapy costs.

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Se presenta el caso de una mujer de 57 años de edad, sin antecedentes de cáncer familiar y con antecedente traumático hace 4 años, que consulta por presentar una tumoración palpable en CSI de mama derecha de 4 cm de diámetro. La mamografía mostró un nódulo polilobulado de márgenes parcialmente mal definidos de características mamográficas de malignidad. Se realizó exéresis quirúrgica con el diagnóstico histológico definitivo de fibromatosis mamaria. A pesar de la tumorectomía, la lesión recidivó, realizándose una mastectomía simple a los 36 meses del diagnóstico inicial.Se comentan los hallazgos histológicos y las características de la lesión, y se plantea la importancia de una actitud quirúrgica agresiva para evitar la recidiva. (AU)

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The synthesis of new 1,3-phenylene derivatives and their preliminary evaluation as antivirals (Herpes simplex 1, HSV-1) whose antiherpetic activity can be related with the inhibition of the interaction of the origin binding protein (OBP) with the DNA are presented. The new compounds are adjusted to a previously defined common structural model, consisting of a central aromatic system, which presents two side chains of different lengths in relative position 1, 3; these chains are made up of atomic groups characterized by the alternation of positive and negative centers, situating differently substituted rings, preferably aromatic, at the ends of both chains. Some of these derivatives, such as N,N''-(4-methoxy-1,3-phenylene)bis[N'-(4-nitrophenyl)urea] (2c) or (1,3-phenylene)bis[N-(p-tolyl)aminosulfonyl] (11b), show antiherpetic activity related to the proposed mechanism.

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