[Systematic review of the implementation and evaluation of Pharmaceutical Care in hospitalised patients(Pharmaceutical Care implementation in hospitalised patients. Systematic review)]. / Revision sistemática sobre la implantación y la evaluación del seguimiento farmacoterapéutico en pacientes hospitalizados.

INTRODUCTION: The persistent morbidity and mortality related to pharmaceutical treatment for hospitalised patients mean that it is necessary to identify scientific criteria for implementing and evaluating Pharmaceutical Care (phC) on the hospital setting. OBJECTIVE: The purpose of the study is to perform a systematic literature review in order to locate, select and analyse studies on implementing and evaluating phC in hospitalised patients. MATERIAL AND METHODS: We searched for articles having to do with clinical pharmacy (CP) and phC published between 1990 and 2006, using a restricted search technique combining all descriptors. The databases we searched were Medline, Embase-Drug & Pharmacology and Cochrane Library. We selected original articles and reviews in English or Spanish describing a phC and clinical pharmacy programme having a participating pharmacist and used in hospitalised patients. RESULTS: We located 66 publications, of which 49 (74.2%) were included and 17 (25.8%) were excluded. We selected 15 (22.7%) on integrating CP and phC in the hospital environment, 18 (27.3%) on implementing phC and 16 (24.2%) relating to evaluating phC programmes. CONCLUSIONS: In the listed studies, pharmacists have managed to incorporate phC programmes in pharmacy divisions' treatment activities. Joining efforts in order to unify CP and phC criteria should be a plan for a common future in this profession. Patients under care should obtain concrete health benefits from phC use, and hospitals should recognise that they create beneficial effects at a reasonable cost.

[Approach to establishing and evaluating clinical relevance of drug interactions in HIV patients: 2009 update]. / Aproximación para establecer y evaluar la relevancia clínica de las interacciones medicamentosas en pacientes infectados con virus de la inmunodeficiencia humana: actualización 2009.

OBJECTIVE: To update information on drug interactions in patients with HIV/AIDS. METHOD: PubMed was used to review English and Spanish articles published between 1 July 2007 and 30 April 2009 on antiretroviral drug interactions in humans. The search included a review of interactions between commonly-used medications in patients with HIV/AIDS and references from articles considered to be relevant. RESULTS: 52 new interactions were identified having to do with CYP3A4 metabolism and competition for intestinal absorption. New pharmacokinetic interactions were identified for medications that were already on the market, and we report interactions for drugs that were recently introduced: Tipranavir, Fosamprenavir, Darunavir, Raltegravir, Maraviroc and Etravirine. CONCLUSIONS: There is evidence of 52 new interactions between medications using metabolic routes in the CYP450 enzymatic system, and an explanation is given for others in the intestinal absorption process.

[Negative results related to drugs required in hospitalisation]. / Resultados negativos asociados con medicamentos como causa de ingreso hospitalario.

OBJECTIVE: To assess the prevalence of negative clinical outcomes associated with medication as a cause of hospital admission and to determine their characteristics (types, categories, avoidability, severity and the drug groups involved.) To determine possible risk factors related to the appearance of this problem. METHOD: An observational study carried out over a three month period in a department of the university hospital, 163 patients were selected at random. The information obtained from the patient interview, the revision of clinical records and clinical sessions were used to then identify negative clinical outcomes using the Dader method. RESULTS: In 27 cases (16.6 %; 95 % confidence interval [CI], 1.6 to 23.0), negative clinical outcomes associated with medication were considered to be the main cause of hospital admission. The most frequent negative clinical outcomes associated with medication were untreated health problems, non-quantitative ineffectiveness and quantitative safety problems respectively. The overall prevalence of preventable admissions due to negative clinical outcomes associated with medication was 88.9 %; (95 % CI, 71.9 to 96.1 %.) With regards to severity, 74.1 % (95 % CI, 55.3 to 86.1 %) of the total admissions were moderate. The most common drugs implicated in hospital admissions were: antibacterial for systemic use, cardiovascular and non steroidal anti-inflammatory agents. Apart from age, no other factors were found for hospital admissions due to negative results associated with medication. CONCLUSIONS: Negative clinical outcomes associated with medication as cause of hospital admission are a prevalent problem and most of them are avoidable with pharmacotherapeutic follow-up.

Application of the SCORE and Wilson-Grundy methods for the assessment of cardiovascular risk in community pharmacies.

BACKGROUND: The assessment and follow-up of patients with risk factors, or with cardiovascular disease (CVD), involves estimating and monitoring their CVD risk (CVDR). There are different opinions about the most appropriate method for this. OBJECTIVE: To compare the SCORE system and the Wilson-Grundy system (based on Framingham's study). METHODS: A descriptive, observational study over 15 days in six pharmacies, with patients aged between 25 and 74 years, and with a prescription for medications related to hypertension, dyslipidaemia, CVD prevention or type-2 diabetes. Results of patients' absolute CVDR were assessed and compared using the SCORE system and the Wilson-Grundy method, adapted for Spain. The Chi-square test was used to compare proportions, and the Student t-test was used to compare mean values, including odds ratios (OR) and 95% confidence intervals (95%CI). RESULT: A total of 257 patients [165 women, 92 men; mean (SD) age, 60.9 (10.8) years; percentage of previous medical history of hypertension (70.0%), dyslipidaemia (42.4%), type-2 diabetes (19.5%) and CVD (22.6%)] participated. With the CVDR assessed with SCORE, the distribution was as follows: low 35.8%, intermediate 21.0% and high 43.2%. The corresponding values using the Wilson-Grundy system was low 60.7%, intermediate 8.2% and high 31.1%. CONCLUSION: The cardiovascular risk of patients that attend community pharmacies with prescriptions for cardiovascular medications is significantly higher when assessed using the SCORE system than with the Wilson-Grundy method.

[Approach to evaluating the clinical relevance of drug interactions in HIV-infected patients]. / Interacciones medicamentosas en pacientes infectados con el VIH: aprocimación para establecer y evaluar su relevancia clínica.

OBJECTIVE: To systematize information about drug interactions in HIV/AIDS, and to test a proposal to identify and evaluate drug interactions considered clinically relevant highlight those associated to pharmacokinetic mechanism. METHOD: We performed a MEDLINE search of the literature published in English and Spanish from January 1995 to June 2007 on antiretroviral drug interactions in humans. Search terms were drug interactions and antiretroviral agents (or drugs) in title/abstract field. So, we searched for clinically relevant drug interactions of specific drugs commonly administered to patients with HIV, and we reviewed references cited in relevant articles. Finally, we followed a proposal to evaluate and use the clinical relevance complemented with a classification based on severity and probability of its occurrence. RESULTS: A total of 378 articles were achieved, among then we acquire the full text of 296. We presented the type and mechanism of drug interactions in HIV-infected patients. We evaluate and use the clinical relevance of drug interactions. Among pharmacokinetic interactions considered clinically relevant, approximately to 80% was related to changes in systemic clearance [due to induction or inhibition of systemic metabolic activity of cytochrome P450 3A4 (CYP3A4)]; and 15% with changes in bioavailability [(due to changes in gastrointestinal pH, presystemic metabolism or activity of the glicoprotein -P (Gp-P)]. CONCLUSIONS: Among patients with HIV/AIDS, most of the pharmacokinetic interactions of clinical relevance are attributed to inhibition or induction of hepatic systemic metabolic activity, mainly of CYP3A4.

Free software to analyse the clinical relevance of drug interactions with antiretroviral agents (SIMARV®) in patients with HIV/AIDS.

BACKGROUND: Highly active antiretroviral therapy has extended the expected lifespan of patients with HIV/AIDS. However, the therapeutic benefits of some drugs used simultaneously with highly active antiretroviral therapy may be adversely affected by drug interactions. OBJECTIVE: The goal was to design and develop a free software to facilitate analysis, assessment, and clinical decision making according to the clinical relevance of drug interactions in patients with HIV/AIDS. METHODS: A comprehensive Medline/PubMed database search of drug interactions was performed. Articles that recognized any drug interactions in HIV disease were selected. The publications accessed were limited to human studies in English or Spanish, with full texts retrieved. Drug interactions were analyzed, assessed, and grouped into four levels of clinical relevance according to gravity and probability. Software to systematize the information regarding drug interactions and their clinical relevance was designed and developed. RESULTS: Overall, 952 different references were retrieved and 446 selected; in addition, 67 articles were selected from the citation lists of identified articles. A total of 2119 pairs of drug interactions were identified; of this group, 2006 (94.7%) were drug-drug interactions, 1982 (93.5%) had an identified pharmacokinetic mechanism, and 1409 (66.5%) were mediated by enzyme inhibition. In terms of clinical relevance, 1285 (60.6%) drug interactions were clinically significant in patients with HIV (levels 1 and 2). With this information, a software program that facilitates identification and assessment of the clinical relevance of antiretroviral drug interactions (SIMARV®) was developed. CONCLUSIONS: A free software package with information on 2119 pairs of antiretroviral drug interactions was designed and developed that could facilitate analysis, assessment, and clinical decision making according to the clinical relevance of drug interactions in patients with HIV/AIDS.

Morbidity and mortality associated with pharmacotherapy. Evolution and current concept of drug-related problems.

Medicines are a great contribution to the rising life expectancy in XX century. But a lot of drug safety problems were reported since 1960's. More recently, ineffectiveness is also being considered as a problem. Since 1975, the term 'drug-related problem' (DRP) is being used for several definition and purposes. This has led to a number of different DRP classifications. The aim of the present review is to gather different positions, definitions and classifications of DRP. And to present a more modern concept, which is also named as pharmacotherapy failure, corresponding to negative clinical outcomes resulting from the use or the lack of use of medicines. Those pharmacotherapy failures include necessity, effectiveness and safety problems.

Structural process and implementation programs of pharmaceutical care in different countries.

Pharmaceutical care started in the nineties in the United States and has rapidly extended in many other countries. Although there are different trends, such as clinical pharmacy services, cognitive services, medication management, medication review, they all share the same philosophy and objectives, namely "the responsible provision of drug therapy for the purpose of achieving definite outcomes that improve a patient's quality of life". To attain these objectives, a pharmaceutical care process has to be followed point-by-point in order to detect possible medication-related problems. Furthermore, pharmacists have to work together with patients, and ultimately with physicians to establish a care plan. This methodology requires basic skills of documentation and communication and therefore, it is important to establish implementation programs aimed at community-, hospital-, and consultant pharmacists, and to consider PC as a basic element of University teaching programs and postgraduate studies. Moreover, there are still barriers that hinder the provision of this service and have to be overcome. In this article, we have revised the implementation process and the existing projects in many countries and we conclude that despite the enormous amount of work, there is still much to be done from sides of Administration and pharmacists themselves.

Apparent nitrogen balance and 3-methylhistidine urinary excretion in intravenously fed children with trauma and infection.

This study was designed to compare and evaluate the effects of two isocaloric parenteral nutrition infusions, FreAmine and F080, differing in their amino acid composition, on the apparent nitrogen balance and urinary excretion of 3-methylhistidine in children with trauma (n = 27) or grave infection (n = 24). Trauma patients at the beginning of parenteral nutrition showed a more negative nitrogen balance than infected children, but in all children the apparent nitrogen balance increased to become positive and the 3-methylhistidine urinary excretion dropped. No differences related to the amino acid composition of the parenteral nutrition solutions were found. Apparent nitrogen balance and 3-methylhistidine excretion were correlated in all study groups irrespective of urine sample time. The enriched branched chain amino acid solution used for parenteral nutrition of trauma and infected children did not show a better effect than the non-enriched one in terms of muscle catabolism and nitrogen balance. The use of adequate nutritional support including both amino acids and energy source is of major importance in children recovering from trauma and infection.

Involvement of glucocorticoids in the stimulation of rat kidney phosphoenolpyruvate carboxykinase activity after liver intoxication by carbon tetrachloride.

The enhancement of rat kidney cortex phosphoenolpyruvate carboxykinase activity during acute liver intoxication by carbon tetrachloride (CCl4) did not appear to be related to metabolic acidosis. Blood glucocorticoids were higher in CCl4-treated animals than in controls. Adrenalectomy fully counteracted the stimulation of renal phosphoenolpyruvate carboxykinase activity and gluconeogenic capacity brought about by CCl4 administration. It is concluded that glucocorticoids are involved in the renal response to acute liver intoxication by CCl4.

Dissociation between renal gluconeogenesis and ammoniagenesis after acute liver intoxication.

Renal glucose and ammonia production as well as phosphoenolpyruvate carboxykinase and phosphate-dependent glutaminase activities were measured for acute liver intoxication. Gluconeogenesis and phosphoenolpyruvate carboxykinase activity increased, whereas ammonia production and phosphate-dependent glutaminase showed no changes with respect to the controls. The dissociation between gluconeogenesis and ammoniagenesis may be explained by the differential effect on the enzymes in these conditions.

Influences of postnatal age and dietary nucleotides on plasma fatty acids in the weanling rat.

Dietary nucleotides seem to play a number of physiologic roles during early life. They are improved in the maintenance of the immune system, intestinal maturation, and lipid metabolism. Nucleotides affect the conversion of essential fatty acids into their long-chain polyunsaturated (PUFA) derivatives in both preterm and at-term newborn infants. This work examines the effect of postnatal age and dietary nucleotides on the fatty acid composition of total plasma lipids and lipid fractions in the rat. Weanling rats (21 days old) were divided into three groups. The first group was killed, and the other two groups were fed a standard semipurified diet, and the same diet supplemented with 250 mg each of CMP, UMP, AMP, GMP, and IMP per 100 g of diet for 4 weeks. Advancing postnatal age led to an increase of total plasma fatty acids, especially saturated, and PUFA of the n-6 series, whereas PUFA of the n-3 series decreased. The fatty acid profile of plasma phospholipids (PL) exhibited minor changes, although there was a tendency to show lower levels of saturates and PUFA of the n-3 series and increased levels of PUFA of the n-6 series. Cholesteryl esters showed a response similar to that of PL, although the increase in arachidonic acid (20:4n-6) was significant. For triglycerides, linoleic acid (18:2n-6) and monounsaturates increased their levels, whereas saturates decreased. Dietary nucleotides mediated a significant increase in total plasma fatty acids, namely monounsaturated fatty acids and PUFA of both n-6 and n-3 series as compared with the control group. The relative fatty acid composition of PL and cholesteryl esters was mostly unaffected.(ABSTRACT TRUNCATED AT 250 WORDS)

Differences in the serum amino acid pattern of injured and infected children promoted by two parenteral nutrition solutions.

The effects of two parenteral nutrition (PN) amino acid solutions (FreAmine II and F080) on the serum amino acid levels of 51 children, 27 affected by multiple trauma and 24 by bacterial sepsis, and aged from 1 month to 12 years, were studied. Serum amino acids were determined on day 1 immediately before administrating PN, and on day 5 during PN. Trauma patients on F080 exhibited higher levels of alanine, aspartate, asparagine, leucine, isoleucine, valine, total branched-chain amino acids (BCAA) and total essential amino acids than those on FreAmine II; in contrast septic children showed similar levels of serum amino acids on both PN solutions. BCAA were lower in septics than in trauma patients, probably as a consequence of an increased utilization of these amino acids in sepsis because of the higher organ protein synthesis typical of this situation. The phenylalanine/tyrosine ratio was found elevated both in septic and trauma children, but it decreased after PN in the latter when using an enriched BCAA solution. Utilization of this solution, partly corrects the metabolic disturbances induced by stress, but the metabolical responses induced either by sepsis or trauma are partially different which may have important implications for patient care.

Changes in the fatty acid composition of plasma and red blood cell membrane during the first hours of life in human neonates.

The objective of this work was to examine the changes in the fatty acid profiles of plasma lipid fractions and red blood cell membrane phospholipids in newborn infants during the first 6-8 h of life. Methyl esters of fatty acids from plasma free fatty acids and phospholipids and from membrane phosphatidylethanolamine, phosphatidylcholine and sphingomyelin for cord blood (n = 20) and venous blood (n = 19) were analyzed by GLC. Important changes were observed in plasma fatty acids. Palmitic and palmitoleic acid increased from birth to 6-8 h of age for both free fatty acids and phospholipids. Palmitic acid also increased in membrane phosphatidylcholine and phosphatidylethanolamine. In the former, stearic acid declined whereas oleic and docosatetraenoic acids increased. Phosphatidylethanolamine and sphingomyelin were less affected than phosphatidylcholine probably because the internal location of the two first fractions in erythrocyte membrane. Polyunsaturated fatty acids dropped slightly during the first hours of life in most lipid fractions. This may be a consequence of the interruption of placental fatty acid supply and the limited capacity of the newborn to desaturate their essential fatty acid tissue stores.

Dietary long-chain polyunsaturated fatty acids modify heart, kidney, and lung fatty acid composition in weanling rats.

The fatty acid composition of heart, kidney, and lung was studied in weanling rats fed three diets differing in their polyunsaturated fatty acid content for 0, 2, and 4 wk. The first group had a 10% w/w fat semipurified diet which consisted of a mixture of olive oil (62.5%), soybean oil (11.1%), and refined coconut oil (26.4%) and provided 18:1n-9, 18:2n-6, and 18:3n-3 in similar amounts to a maternal human milk (diet HO). The second group received 7% of HO fat and 3% fish oil (0.4% 20:4n-6 and 5% 22:6n-3 of total fatty acids) (diet FO), and the third group was fed 7% HO fat, 1.5% of the same fish oil, and 1.5% of a purified pig brain phospholipid concentrate (0.6% 20:4n-6 and 3.5% 22:6n-3 of total fatty acids) (diet FO + BPL). The experimental diets increased tissue monounsaturated fatty acids in comparison with rats at weaning. Tissue lipid content of 20:4n-6 was increased and 22:6n-3 decreased in Group HO compared with weanling rats, whereas opposite changes were observed in Group FO. Feeding diet FO + BPL increased 22:6n:3 in tissue lipids compared with diet HO, and increased 20:4n-6 content in relation to diet FO. Our results indicate that rat heart, kidney, and lung are highly responsive to dietary n-3 and n-6 long-chain polyunsaturated fatty acids during postnatal life.

[The effect of dietary supplementation with long-chain polyunsaturated fatty acids of the n-3 and n-6 series and with vitamin E on the plasma fatty acid profile]. / Efecto de la suplementación a la dieta de ácidos grasos poliinsaturados de cadena larga de las series n-3 y n-6 y de vitamina E sobre el perfil de ácidos grasos del plasma.

Dietary supplement with long-chain polyunsaturated fatty acids from the series n-3 and n-5 appears to be advisable in the nutritional repletion of a variety of conditions. It must be associated with the addition of a sufficient amount of an anti-oxidant to prevent the oxidative degradation of such fatty acids. The purpose of this study was to appraise the effect of the dietary addition of long-chain polyunsaturated fatty acids from the series n-3 and n-5 and of Vitamin E on the fatty acid profile of the plasma, and its lipidic fractions. Five groups of weaning rats were fed for a month as follows: Group A, a semipurified diet with 10% of fat [18:1(n-9) 40%; 18:2(n-6) 12%; 18:3(n-3) 1.2%]; Groups B and C, a semipurified diet with 7% of fat A and 3% of a marine oil concentrate; Groups D and E, a semipurified diet with 7% of fat A, 1.5% of a marine oil concentrate and 1.5% of a phospholipid concentrate of animal origin. Groups B and D were supplemented with 0.5 g of Vitamin E per kilogram of fat. The results obtained suggest that dietary supplement is necessary with long-chain polyunsaturated fatty acids from both the n-3 and n-5 series in order to maintain plasmatic levels of 20:4(n-6) and of 22:6(n-3) in the face of the tissular inability to produce them from their dietary precursors [18:2(n-6) and 18:3)], along with Vitamin E to prevent the oxidative malnutrition of these fatty acids.

Common health problems management uncertainties in heart failure: a qualitative study.

BACKGROUND: Medicine review with follow up quantitative studies conducted on heart failure (HF) outpatients detected health problems that were frequently treated insufficiently: hyperuricemia, gastric injury prevention, anemia, and diabetes mellitus. OBJECTIVE: The aim of this qualitative study was to explore experiences in the pharmacological management of these health problems, and to contribute with strategies to overcome the identified obstacles. METHODS: The internal medicine specialists and cardiologists of a tertiary hospital HF clinic underwent in-depth semi-structured interviews and a constant comparative approach was used. RESULTS: Interviewees highlighted there is a lack of guidelines concerning the treatment of asymptomatic hyperuricemia in HF, thus in routine practice it is often not treated. Interviewees said that preventive strategies to avoid gastric injury in at-risk patients taking prophylactic low-dose aspirin are needed, but the most appropriate strategy is not well defined. Interviewees thought that structural support is needed for the management of HF patients with anemia, and proper clinic pathways should be created to identify which service patients should be referred to. The same lack of communication with other services appeared with diabetes mellitus. CONCLUSION: HF specialists demand a closer interaction with other specialists for a comprehensive approach to these polymedicated patients with multiple co-morbidities. And suggest that specific recommendations in HF guidelines to manage these co-morbidities specifically in HF would be helpful to shed light upon the existing confusing evidence.

[Effect of pharmaceutical follow-up in patients with secondary hyperparathyroidism treated with cinacalcet]. / Efecto del seguimiento farmacoterapéutico en pacientes con hiperparatiroidismo secundario tratados con cinacalcet.

OBJECTIVES: To assess the effect of pharmaceutical intervention in the identification of drug-related problems, to improve desired clinical outcomes, and to evaluate the effectiveness of cinacalcet in achieving clinical outcomes recommended by the KDOQI Clinical Guidelines. METHOD: Quasi-experimental pre-post intervention study. Patients with Secondary Hyperparathyroidism due to Chronic Kidney Disease, aged ≥18 years and under treatment with cinacalcet were recruited at the hospital outpatient pharmacy between 2007 and 2009. Dáder follow-up method and SMAQ and Moriski questionnaires were used to verify adherence at the first interview. Then, the pharmacist analyzed each case and designed an adequate intervention. Clinical parameters were consulted in the hospital laboratory data base. RESULTS: Thirty four patients were included, 29 drug-related problems were found before pharmacist intervention, and among these, non-adherence was the most common (15). After the intervention, 9 drug-related problems remained, which means that 68.9% of them were resolved (P<0.001), reaching an adherence of 80%. Parathyroid hormone, calcium and calcium-phosphorus product serum levels decreased significantly after 3 months of treatment (P<0.001, <0.001 and 0.045, respectively), achieving the KDOQI Clinical Guideline recommendations. CONCLUSION: These results suggest that this simple and easy-to-apply intervention was effective in preventing and resolving drug-related problems in these patients. Moreover, it improved patient adherence and confirmed that cinacalcet treatment is effective for achieving the clinical outcomes recommended by KDOQI clinical guidelines.