Metformin and statins: a possible role in high-risk prostate cancer.

AIM AND BACKGROUND: There is increasing evidence that statins and oral anti-diabetic drugs, such as metformin, can have a favorable role in advanced prostate cancer treatment.Metformin has been shown to inhibit proliferation of tumor cells in vitro and statins inhibit carcinogenesis by suppressing angiogenesis/invasion mechanisms. However, clinical evidence on the protective effect of these drugs is still weak.The purpose of this study is to analyze if these drugs have an impact on Biochemical-Failure-Free-Survival (BFFS) and on Distant-Failure-Free-Survival (DFFS) in localized high-risk prostate cancer. MATERIAL AND METHODS: From 2002-2016, 447 patients with histologically confirmed high-risk prostate cancer were retrospectively evaluated. All patients received radiotherapy and androgen deprivation therapy. Biochemical recurrence was determined by the Phoenix criteria and metastatic patients were defined by the presence of radiological metastasis. Survival analysis was performed using the Kaplan-Meier method. RESULTS: 175 patients were treated with statins (65.3 % with a dose ≤ 20 mg/day) and 70 with metformin (75.7 % with a dose ≤ 1700 mg/day). Median follow-up was 88 months (1-194) with no differences in BFFS and DFFS between metformin and non-metformin patients (77.4 % versus 80 %, p = 0.91 and 89.4 % versus 88.7 %, p = 0.56, respectively). We did not find a statistical difference in BFFS and DFFS in patients taking higher doses of those drugs. CONCLUSION: Metformin and statins were not associated with BFFS or DFFS improvement in our analysis. However, the small number of patients treated with these drugs limits the reliability of the results and prospective studies are needed.

Extensive Nosocomial Transmission of Measles Originating in Cruise Ship Passenger, Sardinia, Italy, 2014.

We report a measles outbreak in Sardinia, Italy, that originated in a cruise ship passenger. The outbreak showed extensive nosocomial transmission (44 of 80 cases). To minimize nosocomial transmission, health care facilities should ensure that susceptible health care workers are vaccinated against measles and should implement effective infection control procedures.

Epidemiology and treatment of renal anaemia in Spain: RIKAS retrospective study.

BACKGROUND AND OBJECTIVE: Studies on the prevalence of anaemia in chronic kidney disease in adults not on dialysis (CKD-ND) and in dialysis programmes (CKD-D) in Spain are not recent or focus on certain subgroups. The aim of this study was to know the epidemiology and current treatment patterns of anaemia associated with CKD in Spain. MATERIALS AND METHODS: Multicentre, non-interventional, retrospective study with CKD-ND stage 3a-5 and CKD-D patients treated in Spain between 2015 and 2017 (RIKAS study). RESULTS: The prevalence of anaemia in CKD-ND and CKD-D in 2015 was 33.8% and 91.5%, respectively, with similar results during 2016-2017. The prevalence of systemic inflammation in anaemic patients (18.1% and 51.8% for CKD-ND and CKD-D, respectively) was higher, especially in those treated with erythropoiesis-stimulating agents (ESA), compared to the general population with CKD-ND. After 12 months of follow-up, mean ferritin and transferrin saturation index (TSI) values in anaemic patients with CKD-ND were 187.1 ng/mL and 22.2%, respectively, while in CKD-D were 254.6 ng/mL and 20.2%. In ESA-treated patients, mean values were 190.6 ng/mL and 22.0% in ND-CKD, and 255.0 ng/mL and 20.2% in D-CKD. CONCLUSIONS: The prevalence of anaemia and inflammation increased with the disease severity, being higher in D-CKD. Iron parameters in anaemic patients treated or not with ESA are insufficient according to the guidelines, so there is room for improvement in the treatment of anaemia associated with CKD.

Epidemiología y tratamiento de la anemia renal en España: estudio retrospectivo RIKAS / Epidemiology and treatment of renal anaemia in Spain: RIKAS retrospective study

Antecedentes y objetivo: Los estudios sobre la prevalencia de anemia en enfermedad renal crónica (ERC) en adultos no en diálisis (ERC-ND) y en programa de diálisis (ERC-D) en España no son recientes, o se centran en ciertos subgrupos. El objetivo fue conocer la epidemiología y los patrones actuales de tratamiento de la anemia asociada a la ERC en España. Materiales y métodos: Estudio multicéntrico, no intervencionista, retrospectivo con pacientes ERC-ND estadios 3a-5 y ERC-D, atendidos en España entre 2015 y 2017 (estudio RIKAS). Resultados: La prevalencia de anemia en ERC-ND y ERC-D en 2015 fue del 33,8 y del 91,5%, respectivamente, con resultados similares durante 2016-2017. La prevalencia de inflamación sistémica en pacientes anémicos (18,1 y 51,8% para ERC-ND y ERC-D, respectivamente) fue superior, especialmente en aquellos tratados con agentes estimuladores de eritropoyesis (AEE), respecto a la población general con ERC-ND. Tras 12meses de seguimiento, los valores medios de ferritina y del índice de saturación de transferrina (IST) en pacientes anémicos con ERC-ND fueron de 187,1ng/ml y del 22,2%, respectivamente, mientras que en ERC-D fueron de 254,6ng/ml y del 20,2%. En pacientes tratados con AEE, los valores medios fueron de 190,6ng/ml y del 22,0% en ERC-ND, y de 255,0ng/ml y del 20,2% en ERC-D. Conclusiones: La prevalencia de anemia y de inflamación aumentan con la severidad de la enfermedad, siendo mayores en ERC-D. Los parámetros férricos en pacientes anémicos tratados o no con AEE son insuficientes según las guías, por lo que existe un margen de mejora para el tratamiento de la anemia asociada a la ERC. (AU)

Background and objective: Studies on the prevalence of anaemia in chronic kidney disease (CKD) in adults not on dialysis (CKD-ND) and in dialysis programmes (CKD-D) in Spain are not recent or focus on certain subgroups. The aim of this study was to know the epidemiology and current treatment patterns of anaemia associated with CKD in Spain. Materials and methods: Multicentre, non-interventional, retrospective study with CKD-ND stage 3a-5 and CKD-D patients treated in Spain between 2015 and 2017 (RIKAS study). Results: The prevalence of anaemia in CKD-ND and CKD-D in 2015 was 33.8% and 91.5%, respectively, with similar results during 2016-2017. The prevalence of systemic inflammation in anaemic patients (18.1% and 51.8% for CKD-ND and CKD-D, respectively) was higher, especially in those treated with erythropoiesis-stimulating agents (ESA), compared to the general population with CKD-ND. After 12months of follow-up, mean ferritin and transferrin saturation index (TSI) values in anaemic patients with CKD-ND were 187.1ng/ml and 22.2%, respectively, while in CKD-D were 254.6ng/ml and 20.2%. In ESA-treated patients, mean values were 190.6ng/ml and 22.0% in ND-CKD, and 255.0ng/ml and 20.2% in D-CKD. Conclusions: The prevalence of anaemia and inflammation increased with disease severity, being higher in D-CKD. Iron parameters in anaemic patients treated or not with ESA are insufficient according to the guidelines, so there is room for improvement in the treatment of anaemia associated with CKD. (AU)

Clozapine toxicity due to a multiple drug interaction: a case report.

INTRODUCTION: We report the case of a multiple drug interaction involving clozapine, antifungals and oral contraceptives, which resulted in an increased clozapine plasma level, pericarditis with pericardial effusion and eosinophilia in a young Caucasian woman. These symptoms and signs disappeared a few days after discontinuation of clozapine. At present, we are not aware of reports of clozapine-antifungals interaction, whereas there is only one other case report on the interaction between oral contraceptives and clozapine. The purpose of this case report is to show the risk of potentially serious adverse effects stemming from drug interactions involving medications routinely used in clinical practice. CASE PRESENTATION: A 29-year-old Caucasian woman diagnosed with a schizoaffective disorder was admitted to a psychiatric unit for acute psychosis (hallucinations, delusions and catatonic behavior). She denied smoking tobacco products and was on long-term oral contraceptives. During the first month of hospitalization she was treated with antipsychotics and for 1 week she took simultaneously fluconazole and miconazole gel, after being diagnosed with oral candidiasis. On the last day of antifungals treatment, 29 days after admission, clozapine was started with resolution of psychotic symptoms. After 3 weeks, her clozapine plasma level had increased to 542 ng/mL and eosinophilia was observed. She complained of nausea, vomiting and palpitations; echocardiography showed echocardiographic abnormalities and pericardial effusion. Oral contraceptives were discontinued and after 1 week clozapine was interrupted, with a complete resolution of side effects and pericardial effusion within 4 days. CONCLUSIONS: Clozapine is metabolized by cytochrome P450. The use of inhibitors or other substrates of cytochrome P450, such as antifungals and oral contraceptives, can cause long-lasting interactions and clozapine toxicity. The Naranjo algorithm shows clozapine is a definite cause of pericarditis (score 9) and both clozapine-antifungals and clozapine-contraceptives interactions resulted probable (score 5) in Drug Interaction Probability Scale. A good knowledge on drugs that act as substrates, inhibitors or inducers of cytochrome P450 is mandatory. When those drugs are used in patients taking clozapine, blood level monitoring of clozapine should be recommended, since a lower dose of clozapine might be required to prevent clozapine toxicity.