Hepatitis C virus infection and the role of a pharmaceutical care program.

PURPOSE: The design, implementation, and assessment of a comprehensive pharmaceutical care program (CPCP) for hepatitis C virus (HCV)-infected patients treated with direct-acting antivirals (DAA) are described. SUMMARY: The advent of DAA regimens has caused the evolution of the role of hospital pharmacists, leading to the development of more specialized models of pharmaceutical care. Three clinical pharmacists were incorporated into the pharmacy department of a general tertiary teaching hospital in Madrid, Spain, with the aim of developing and implementing a CPCP for HCV-infected patients. Pharmacists were responsible for proposing standards and local guidelines to physicians, monitoring adherence to guidelines, managing drug interactions and adverse drug events (ADEs), providing patient education, and evaluating health outcomes and costs. Implementation steps included (1) estimation of the healthcare demand and pharmacy resources, (2) definition of the workflow of the CPCP, (3) definition of the treatment care plan, for which tools were developed to support pharmaceutical validation, detection, and management of ADEs and drug-drug interactions, and (4) program assessment in terms of safety and cost-effectiveness. The pharmacists' interventions performed, severity of errors intercepted, and patients' satisfaction with the CPCP were also assessed. This CPCP demonstrates that the involvement of the pharmacist throughout the care plan prevents harmful medication errors in this population (0.1 per patient) and prompts significant cost savings (€1.2 million for 1,930 treated patients). CONCLUSION: The implementation of a CPCP developed by hospital pharmacists for patients treated with DAA for HCV infection is an effective approach for preventing harmful medication errors and improving cost- effectiveness.

[Parathyroid carcinoma: diagnosis by a femur fracture]. / Carcinoma de paratiroides: diagnóstico por fractura de fémur.

BACKGROUND: Carcinoma of the parathyroid gland (PC) described by De Quervain since 1909, it represents the least common neoplasm, with an incidence of 1,25/10,000,000 peoples. It has been reported approximately 1,000 cases of CP in world literature. There are two series in Mexico, one of eight patients and other with four cases. Because CP is functionally active, its early clinical behavior is similar to that of parathyroid benign neoplasms. CLINICAL CASE: A 66-year-old female with history of thighbone pain and spontaneous femoral fracture, osteolytic lesions, hypercalcemia, elevated levels of alkaline phosphatase and parathyroid hormone detected; the scintigraphy showed a functioning tumor located in upper mediastinum. By hemithyroidectomy in block, the tumor was resected. Histopathological study reported parathyroid carcinoma. DISCUSSION: PC is the least common neoplasia, in patients with parathyroid hormone levels greater than 1,000 pg/ml and hypercalcemia upper of 14 mg/dl this disease should be suspected.

ANTECEDENTES: El carcinoma de las glándulas paratiroides (CP) descrito por De Quervain en 1909 representa la neoplasia menos frecuente, siendo su incidencia de 1.25/10,000,000 personas. Se han reportado aproximadamente 1,000 casos de carcinoma paratiroideo en la literatura mundial. En México existen dos series, una de ocho pacientes y otra de cuatro, además de tres reportes de casos aislados. Dado que el CP es funcionalmente activo el comportamiento clínico inicial es similar a las neoplasias paratiroideas benignas. CASO CLÍNICO: Femenino de 66 años de edad con dolor óseo en muslo y fractura espontánea de fémur, en la que se detectaron lesiones osteolíticas, hipercalcemia, niveles elevados de fosfatasa alcalina y de paratohormona; con gammagrama que mostró un tumor funcionante localizado en mediastino superior, fue sometida a extirpación en bloque con hemitiroidectomía derecha con tumor de la glándula paratiroides. El estudio histopatológico reportó CP. DISCUSIÓN: El CP representa la neoplasia menos común; en pacientes con niveles de paratohormona mayores de 1,000 pg/ml e hipercalcemia mayor de 14 mg/dl debe sospecharse dicha patología.

Decreased INR after acenocoumarol, ombitasvir/paritaprevir/ritonavir and dasabuvir co-administration.

WHAT IS KNOWN AND OBJECTIVE: Limited data are available on co-administration of acenocoumarol with direct-acting antiviral agents for chronic hepatitis C virus infection. CASE SUMMARY: We report a case of a patient who required a significant increase in acenocoumarol weekly dose probably due to an interaction with ombitasvir/paritaprevir/ritonavir and/or dasabuvir. A causality assessment of the drug-drug interaction leading to a reduced INR was conducted according to the Naranjo algorithm. A score of 6 suggested that the adverse drug reaction was probable. WHAT IS NEW AND CONCLUSION: Because of possible INR abnormalities during the concomitant use of acenocoumarol, ombitasvir/paritaprevir/ritonavir and dasabuvir, clinicians should closely monitor INR values.

Optimisation of antithrombotic therapy in patients with acute coronary syndrome to reduce bleeding episodes.

AIM: The aim of the study was to evaluate the effectiveness of a multidisciplinary intervention to reduce the risk of bleeding associated with antithrombotic drugs in patients with acute coronary syndrome (ACS). METHODS: We designed a pre-post quasi-experimental intervention study using retrospective cohorts. The first cohort was analysed to detect correctable measures contributing to bleeding (PRE: January-July 2010). Second, a bundle of interventions was implemented and third, a second cohort of patients was evaluated to investigate the impact of our measures in bleeding reduction (POST: September 2011-February 2012). RESULTS: A total of 677 patients were included (377 in PRE and 300 in POST). The bundle of interventions was: Overdose avoidance measures: the percentage of patients overdosed was reduced by 66.3% (p < 0.001). Institutional protocol update to include the latest recommendations regarding bleeding prevention: In POST, the percentage of patients treated with fondaparinux increased (2.4% vs. 50.7%; p < 0.001). In PRE, 11 patients were treated with the combination of abciximab and bivalirudin; whereas in POST, only one patient received the combination (p = 0.016). Mandatory measurement of body weight: the percentage of patients with unknown body weight was reduced by 35% (p = 0.0001). In POST, the total bleeding rate was reduced by 29.2% (31.6% in PRE vs. 22.4%, p < 0.05, OR: 0.62; 95% CI: 0.44-0.88). It was necessary to implement the interventions in 11 patients to prevent one bleeding episode (95% CI: 7-39). CONCLUSION: The multidisciplinary programme has been effective in reducing bleeding episodes. The interventions were effective in reducing antithrombotic drugs overdosage, incorporating the use of fondaparinux to the NSTE-ACS therapeutic arsenal, limiting the use of bivalirudin with abciximab and obtaining body weight for most patients.

Veterinary education in the area of food safety (including animal health, food pathogens and surveillance of foodborne diseases).

The animal foodstuffs industry has changed in recent decades as a result of factors such as: human population growth and longer life expectancy, increasing urbanisation and migration, emerging zoonotic infectious diseases and foodborne diseases (FBDs), food security problems, technological advances in animal production systems, globalisation of trade and environmental changes. The Millennium Development Goals and the 'One Health' paradigm provide global guidelines on efficiently addressing the issues of consumer product safety, food security and risks associated with zoonoses. Professionals involved in the supply chain must therefore play an active role, based on knowledge and skills that meet current market requirements. Accordingly, it is necessary for the veterinary medicine curriculum, both undergraduate and postgraduate, to incorporate these skills. This article analyses the approach that veterinary education should adopt in relation to food safety, with an emphasis on animal health, food pathogens and FBD surveillance.

Effects of pregnancy on insulin receptor in liver, skeletal muscle and adipose tissue of rats.

The mechanism responsible for insulin resistance during pregnancy remains unclear. Considerable evidence indicates that the insulin receptor plays an important role in insulin sensitivity. It seems possible that the hormonal milieu during gestation could have an effect on the insulin receptor. In the present study, measurements of tyrosine phosphorylation and protein content of the insulin receptor and expression of its gene in liver, skeletal muscle and adipose tissue indicate that during pregnancy significant changes occur in these parameters. We found that at the end of early gestation (day 10), muscle and adipose tissue are very sensitive to insulin action because the amount, phosphorylation and gene expression of insulin receptor is higher than in late gestation (days 15-20), while the tissue which is most sensitive to insulin action in late gestation is the liver. Our hypothesis is that these results are connected with changes in the concentrations of estradiol and progesterone observed during pregnancy. In conclusion, our previous and present findings seem to demonstrate that the different concentrations of gestational hormones play an important role in insulin sensitivity in this period and that each tissue responds in the most appropriate manner to guarantee the gestation in its entirety.

The effects of food restriction on maternal endocrine adaptations in pregnant rats.

The aim of this study was to characterize hemodynamic, electrolytic and endocrine alterations produced by food restriction (50%) in pregnant rats for the purpose of evaluating the importance of these parameters on the plasma volume expansion and fetal growth. One hundred seventy six pregnant rats were divided into two groups, a control group (C) with an ad libitum diet and another with a restricted diet (U) (50% by weight of the diet of the control group). On days 5, 10, 15 and 20 of pregnancy, the weight of the mother, water intake, urine output, urine and plasma sodium concentration, plasma potassium concentration, blood pressure and heart rate, osmolality, plasma renin activity (PRA) and vasopressin were recorded. The number and weight of the fetuses were determined on days 15 and 20 of gestation. Food restriction results in inadequate weight gain in the mother and retardation of fetal growth. Water and sodium balance (p< or =0.001) were decreased in U group and basal PRA (p< or =0.001) was increased in U group. Food restriction did not significantly alter urine sodium excretion, plasma osmolality, plasma sodium and potassium values, blood pressure and basal vasopressin values. We conclude that the higher values of PRA, described in food restriction situations during pregnancy, seem to be caused by the adaptation to low sodium intake.

Role of 17-beta-estradiol and progesterone on glucose homeostasis: effects of food restriction (50%) in pregnant and non pregnant rats.

The role of 17-beta-estradiol and progesterone on glucose homeostasis was examined in pregnant and non pregnant rats with or without food restriction (50%). Blood glucose and insulin levels were significantly decreased in food restricted pregnant (PM) compared with control pregnant (PC) and in food restricted non pregnant (M) compared with non pregnant control (C). The plasmatic level of progesterone was similar in PC and PM, while the plasmatic level of 17-beta-estradiol was significantly decreased in PM compared with PC at 15 and 20 days. In spite of food restriction, the changes in the insulin/glucose ratio throughout gestation were similar in PC and PM. A positive and significant relation between 17-beta-estradiol and the level of insulin at day 5 of gestation, and a negative and significant relation between the level of 17-beta-estradiol and level of insulin at day 15 of gestation were found in PC. A negative and significant relation between the levels of progesterone and the levels of insulin at day 5 of gestation, at day 10 this relation is positive and significative, and at day 15 a positive and significant relation exists between levels of 17-beta-estradiol and levels of insulin were found in PM. These results suggest that 17-beta-estradiol acts directly on beta-cells to control insulin secretion. Food restriction does not alter the changes in the sensitivity of tissues to the insulin action, and does modify the action of 17-beta-estradiol and progesterone on beta-cell.

Prothymosin alpha is phosphorylated by casein kinase-2.

Prothymosin alpha (ProT alpha) is a 12.5 kDa acidic polypeptide that is considered to have a nuclear function related to cell proliferation. Inspection of its amino acid sequence revealed the presence of sequences that may serve as targets for phosphorylation by casein kinase-2 (CK-2). ProT alpha isolated from calf thymocytes was phosphorylated in vitro by CK-2. The phosphorylation sites are Ser and Thr residues located among the first 14 amino acid residues in the ProT alpha sequence. Another site that is theoretically suitable for phosphorylation by CK-2, at the C-terminus of the polypeptide, is not, in fact, phosphorylated. Thymosin alpha 1 (T alpha 1), a peptide whose sequence corresponds to the first 28 amino acids of ProT alpha, is also phosphorylated by CK-2 at the same phosphorylation sites as ProT alpha. In cultured splenic lymphocytes ProT alpha was phosphorylated at Thr residues located at positions 7, 12 and/or 13. Based on these observations we conclude that CK-2, or another cellular kinase with similar sequence specificity, is responsible for phosphorylation of ProT alpha in vivo.