Hospital readmission within 30 days of older adults hospitalized in a public hospital

Older adults have difficulty monitoring their drug therapy in the first thirty days following hospital discharge. This transition care period may trigger hospital readmissions. The study aims to identify the factors associated with the readmission of older adults 30 days after discharge from the perspective of drug therapy. This is a cross-sectional study and hospital admission within 30 days was defined as readmission to any hospital 30 days after discharge. The complexity of the drug therapy was established by the Medication Regimen Complexity Index (MRCI).. Readmission risks were predicted by the "Readmission Risk Score - RRS". The multivariate logistic regression was used to identify factors associated with readmission within 30 days after discharge. Two hundred fifty-five older adults were included in the study, of which 32 (12.5%) had non-elective hospital readmission. A higher number of readmissions was observed with increased RRS value, suggesting a linear gradient effect. The variables included in the final logistic regression model were the diagnosis of cancer (OR=2.9, p=0.031), pneumonia (OR=2.3, p=0.055), and High MRCI (> 16.5) following discharge (OR=1.9, p=0.119). The cancer diagnosis is positively associated with hospital readmissions of older adults within 30 days

Planejamento, síntese e avaliação biológica de candidatos a fármacos: busca de inibidores epigenéticos da Sirtuína 2 Sir2 / Design, synthesis and biological evaluation of drug candidates: search for Sirtuin 2 (Sir 2) epigenetic inhibitors

As doenças negligenciadas são causadas por agentes infecciosos e parasitários, como vírus, bactérias, protozoários e helmintos. Essas doenças são prevalentes em populações de baixa renda que vivem em países em desenvolvimento e são responsáveis por incapacitar e levar milhares de pessoas à morte. Este nome se dá pois, apesar de sua grande relevância médica, recebem pouca atenção dos governos e indústrias farmacêuticas. Dentre essas doenças podemos destacar a Doença de Chagas, doença infecciosa causada pelo parasita hemoflagelado Trypanosoma cruzi. Endêmica em 21 países, com 6 a 7 milhões de pessoas infectadas resultando em 7500 mortes por ano. A quimioterapia disponível contra essa parasitose é baseada em apenas dois medicamentos, o benznidazol e o nifurtimox, ativos principalmente na fase aguda da doença e com efeitos adversos graves que comprometem a adesão ao tratamento e, além disso, apesar dos enormes esforços na pesquisa de novos agentes antichagásicos em nível nacional e internacional, na maioria realizada academicamente, ainda não foram encontradas alternativas terapêuticas para a doença, persistindo, assim, a necessidade de descoberta e desenvolvimento de novos fármacos. O início de um planejamento de um novo fármaco se dá pela definição de um alvo bioquímico a ser utilizado na busca de moléculas que possam exercer a função de inibidores ou moduladores, conforme a atividade biológica desejada. Neste sentido, as sirtuínas 2 (Sir2) são enzimas que se mostraram essenciais para o crescimento in vitro do T. cruzi em suas formas amastigota e epimastigota. No caso de tripanossomatídeos, em geral, a superexpressão de Sir2 está relacionada à sobrevivência de formas amastigotas. Assim, essas evidências indicam que a Sir2 de tripanosomatídeos tem grande potencial como alvo biológico na busca e desenvolvimento de novos fármacos antichagásicos. O objetivo principal deste projeto foi identificar moléculas que apresentaram atividade inibitória para a sirtuína 2 de T. cruzi por meio da utilização da estratégia de Planejamento de Fármacos Baseada no Ligante - Ligand Based Drug Design (LBDD) e o desenvolvimento de análogos dos inibidores da Sir2. A modificação molecular está entre algumas das técnicas tradicionais usadas no desenvolvimento racional de um fármaco, e é usada principalmente no desenvolvimento de análogos, e busca melhorar as propriedades farmacocinéticas e/ou farmacodinâmicas de um protótipo, obter propriedades de interação semelhantes ao alvo e, em alguns casos, revelar uma atividade biológica. Com este intuito, análogos do sirtinol e da salermida foram sintetizados e uma nova rota sintética utilizando o microrreator em fluxo contínuo foi desenvolvida e apresentou rendimento superior quando comparado à síntese em bancada. A partir desta metodologia foram obtidos 20 compostos. Os ensaios in vitro contra formas amastigotas do T. cruzi indicaram que 8 compostos inibiram a atividade parasitária em mais de 50%, na dose de 10 µM, sendo que alguns destes apresentaram maior inibição parasitária quando comparados ao benznidazol, o fármaco de referência e único disponível no Brasil. Com estes resultados preliminares, novos ensaios estão sendo realizados para identificar potência e mecanismo de ação destes candidatos a agentes tripanomicidas

Neglected diseases are caused by infectious and parasitic agents such as viruses, bacteria, protozoa and helminths. These diseases are prevalent in low-income populations living in developing countries and are responsible for disabling and killing thousands of people. They get this name because, despite their great medical relevance, they end up receiving little attention from governments and pharmaceutical industries. Among these diseases, we can highlight Chagas disease, an infectious endemic disease caused by the hemoflagellate parasite Trypanosoma cruzi. This disease is endemic in 21 countries, with 6 to 7 million people infected resulting in 7,500 deaths per year. Chemotherapy is based on just two drugs, benznidazole and nifurtimox, which are mainly active in the acute phase of the disease. These drugs have adverse effects that compromise adherence, even more, considering that they are not effective from the point of view of the chronic phase of the disease. Despite the enormous efforts in researching new anti-chagasic agents at the national and international level, and mostly carried out academically, therapeutic alternatives for the disease have not yet been found, thus, the need for the discovery and development of new drugs persists. Sirtuins 2 (Sir2) are enzymes that have been shown to be essential for the in vitro growth of T. cruzi in its amastigote and epimastigote forms. In the case of trypanosomatids in general, Sir2 overexpression is related to the survival of amastigote forms. Sir2 inhibitors, such as sirtinol, have shown efficacy in leishmanicides. Thus, these evidences indicate that Sir2 from trypanosomatids can be considered as a biological target in the search and development of new anti-chagasic drugs. The beginning of a new drug planning study is the definition of a biochemical target to be used in the search for molecules that can play the role of inhibitors or modulators, according to the desired biological activity. The main objective of this project was to identify molecules that presented inhibitory activity to sirtuin 2 of T. cruzi using the Ligand Based Drug Design (LBDD) strategy of planning and the development of analogues of Sir2 inhibitors. Molecular modification is a traditional technique used in the rational development of a drug, as well as the use of natural products, combinatorial chemistry, high-throughput screening (HTS), among others. Mainly used in the development of analogues, molecular modification is applied for different purposes, among them, it seeks to improve the pharmacokinetic and/or pharmacodynamic properties of a prototype, obtain target-like interaction properties and, in some cases, reveal an activity biological. For this purpose, analogues of sirtinol and salermide were synthesized and a new synthetic route using the microreactor in continuous flow was developed and presented superior yield when compared to benchtop synthesis. From this methodology, 20 compounds were obtained. in vitro assays against amastigote forms of T. cruzi indicated that 8 compounds inhibited parasitic activity by more than 50% at a dose of 10 µM, and some of these showed greater parasitic inhibition when compared to benznidazole, the reference drug, and only available in Brazil. With these preliminary results, new assays are being carried out to identify the potency and mechanism of action of these candidate trypanocidal agents

Desenvolvimento de inibidores duais de histona desacetilase 6 (HDAC6) e tirosina quinase (TQ) com vistas ao tratamento do câncer / Design of histone deacetylase 6 (HDAC6) and tyrosine kinase (TK) dual inhibitors for cancer treatment

Câncer é a denominação atribuída a um conjunto de doenças que são responsáveis pela segunda maior causa de morte no Brasil e no mundo. A quimioterapia figura entre uma das estratégias utilizadas para o tratamento e cura do câncer, sendo amplamente empregada em estratégias terapêuticas isoladas, ou em associação à radioterapia e cirurgia. A enzima histona desacetilase 6 (HDAC6) é responsável por desacetilar a cadeia lateral de N-acetillisinas em -tubulinas, desempanhando papel crítico na dinâmica do citoesqueleto celular, estando superexpressa em uma série de neoplasias. Neste sentido, na última década os receptores tirosina quinase (TQ) foram os principais alvos de fármacos aprovados para o tratamento do câncer e de doenças autoimunes e continuam atraindo a atenção de grupos de pesquisa dada a exorbitante diversidade do quinoma humano. É sabido que a monoterapia seja com inibidores de HDAC, seja com inibidores TQ, apresenta problemas de toxicidade, reações adversas, ineficácia, resistência e/ou recidiva. Diversos estudos relatam o desenvolvimento de inibidores duais de HDAC-TQ, almejando tanto a simplificação do tratamento, quanto sinergismo terapêutico e redução de efeitos adversos. Assim, o presente trabalho apresenta o planejamento, síntese e avaliação da citotoxicidade de inibidores duais, potencialmente seletivos para HDAC6 e receptores TQ. No total, 23 compostos foram sintetizados entre 2 a 4 etapas. Todos os compostos finais foram caracterizados por RMN (1H e 13C) e espectrometria de massas de alta resolução (HRMS). A citotoxicidade foi determinada pelo ensaio de MTT, em linhagens derivadas de tumores sólidos (HCT116 e MCF-7) e hematológicos (Jurkat e Namalwa). Os compostos apresentaram citotoxicidade em concentrações micro e nanomolares em todas as linhagens testadas, sendo que a linhagem MCF-7 foi a mais resistente à ação dos compostos, e as linhagens hematológicas foram as mais sensíveis. Os inibidores 4d-f foram os mais ativos na triagem por MTT, com IC50 iguais a 20, 30 e 50 nM, respectivamente, em células Jurkat. Estudos mecanísticos do efeito citotóxico indicaram que os compostos 4d-f exercem atividade de forma tempo-dependente, e majoritariamente por ação antiproliferativa, embora estímulos apoptóticos também tenham sido observados nos estudos. Simulações de ancoramento molecular (docking) e de relação entre as estruturas químicas dos compostos e suas respectivas atividades biológicas (REA) permitiram identificar padrões moleculares, propriedades físico-químicas e eletrônicas que potencialmente possuem relação com a atividade biológica dos compostos, permitindo futuras otimizações do arcabouço molecular desta série de compostos. Tomados em conjunto, os resultados deste trabalho revelam o potencial terapêutico de inibidores duais de HDAC6-TQ. Notadamente, os compostos apresentados aqui podem ser os primeiros potenciais inibidores duais de HDAC6-TQ a serem reportados na literatura

Cancer is the name of a series of diseases that are the second main cause of death in Brazil and worldwide. Chemotherapy is one of the main strategies to treat and cure cancer, and has been widely applied as a single therapeutic agent, and in association with radiotherapy and surgery. Histone deacetylase 6 (HDAC6) deacetylates N-acetyllysine side chains of tubulin, playing crucial role on cytoskeletal dynamics, and could be overexpressed in several cancers. Tyrosine kinase receptors (TK) have been the main targets of FDA-approved drugs through the last decade for both cancer and autoimmune diseases, and have been attracting special attention of research groups due to the exorbitant diversity of the human kinome. It is known that either HDAC or TK single therapy have toxicity issues, adverse effects, inefficacy, resistance and/or recidive. Therefore, many studies report the design of HDAC-TK dual inhibitors aiming simpler treatments, synergism of action and side effects reduction. Herein, the design, synthesis and cytotoxic evaluation of dual and selective HDAC6-TK inhibitors are presented. A total of 23 compounds were designed and synthesized through 2 to 4 steps. All final compounds were characterized by 1H/13C NMR and high-resolution mass spectrometry (HRMS). The cytotoxicity of compounds was determined by MTT assay for both solid (HCT116 and MCF-7 cells) and hematological cancers (Jurkat and Namalwa cells). Compounds exhibited micro and nanomolar ranges of cytotoxicity for all cell lines tested. MCF-7 cells were the most resistant against the treatment, and hematological cells were more susceptible to the cytotoxic effect of the compounds. Compounds 4d-f were the most actives in the MTT screening against Jurkat cells (IC50 = 20, 30 and 50 nM, respectively). Mechanistic studies regarding the cytotoxic effects of 4d-f indicated that the compounds induced cell death in a time-dependent manner mainly via cytostatic activity even though apoptotic stimuli were observed also. Molecular docking and structure-activity relationships (SARs) allowed the identification of molecular patterns, and physicochemical and electronic properties that potentially modulate the biological activity of these compounds, allowing further optimizations of the molecular scaffold for these series of compounds. Taken together, the results of this study reveal the therapeutic potential of HDAC6-TK dual inhibitors. Noteworthy, the compounds reported herein could be the first HDAC6-TK dual inhibitors ever reported in literature

Avaliação do tratamento quimioterápico paliativo com o esquema LDE- paclitaxel em pacientes portadores de metástases ósseas por neoplasia maligna / Evaluation of palliative chemotherapy treatment with the LDEpaclitaxel regimen in patients with bone metastases from malignant neoplas

Introdução: Pacientes com câncer em estádios avançados e metástases ósseas frequentemente não apresentam condições clínicas para a realização de esquemas quimioterápicos convencionais subsequentes, restringindo as opções de tratamento. Anteriormente, demonstramos que nanopartículas artificiais lipídicas (LDE), semelhantes à lipoproteína de baixa densidade (LDL) rica em colesterol, são captadas por tecidos malignos, e quando associadas aos quimioterápicos, após injeção pela via endovenosa, reduz drasticamente a toxicidade do tratamento. Os objetivos deste presente estudo foram avaliar a resposta clínica ao tratamento quimioterápico com paclitaxel (PTX) associado à LDE; avaliar as toxicidades clínicas e laboratorial, e a capacidade da associação LDE-PTX em reduzir a dor oncológica relacionada às metástases ósseas em pacientes com carcinoma de mama, próstata e pulmão, previamente tratados e não elegíveis para tratamento quimioterápico convencional subsequente. Métodos: Dezoito pacientes (8 com câncer de mama, 5 de próstata e 5 de pulmão) com metástases ósseas foram incluídos. O tratamento consistiu no esquema LDE-PTX na dose convencional do PTX (175 mg/m2 de superfície corpórea de 3/3 semanas) e os pacientes foram avaliados por resposta clínica, redução da dor óssea, uso de medicamentos opióides, e ocorrência de fraturas ósseas patológicas. Resultados: No total, 104 ciclos de quimioterapia foram realizados, e nenhum paciente apresentou toxicidade clínica, laboratorial, assim como não houve fraturas patológicas. Dos 18 pacientes incluídos, 9 tiveram sobrevida livre de progressão de doença 6 meses. Houve em todos os pacientes redução da dor óssea, permitindo substituição da medicação opióide por analgésico não opióide. Conclusão: A melhora significativa na dor óssea sem que tenha ocorrido toxicidade do tratamento, e o tempo de não progressão de doença 6 meses na metade dos pacientes sugere que esses pacientes tenham se beneficiado consistentemente do tratamento com a LDE-PTX. Portanto, a LDE-PTX pode tornar- se uma opção terapêutica interessante em pacientes com carcinomas de próstata, mama ou pulmão em estágios avançados e sem condições clínicas de se submeterem a outros esquemas quimioterápicos convencionais

Introduction: Patients with advanced cancer and bone metastases usually do not have clinical conditions to perform additional conventional chemotherapy regimens, restricting treatment options. Previously, we showed that lipid core nanoparticles (LDE), similar to cholesterol-rich low-density lipoprotein (LDL), are taken up by malignant tissues, and when associated to chemotherapy, after endovenous injection, it drastically decreases the toxicity of the treatment. The objectives of this study were to evaluate the clinical response to chemotherapy treatment with paclitaxel (PTX) associated with LDE; to evaluate the clinical and laboratorial toxicities, and the ability of the LDE-PTX to reduce cancer pain related to bone metastases in patients with breast, prostate or lung carcinoma, previously treated and not eligible for subsequent conventional chemotherapy treatment. Methods: Eighteen patients (8 with breast cancer, 5 with prostate and 5 with lung) with bone metastases were included. Treatment consisted of the LDE-PTX regimen at a conventional dose of PTX (175 mg/m2 body surface area, 3/3 weeks) and patients were evaluated for clinical response, reduction in bone pain, use of opioid medications, and the occurrence of pathological bone fractures. Results: In total, 104 chemotherapy cycles were performed, and none of the patients showed clinical or laboratorial toxicities, as well as there were no pathological fractures. Of the 18 patients evaluated, 9 had progression-fee survival 6 months. Patients had decrease in bone pain allowing replacement of opioid medication by another non-opioid analgesic. Conclusion: Significant improvement in bone pain without treatment toxicity, and time to disease progression of 6 months in half of the patients suggest that these patients have consistently benefited with LDE-PTX treatment. Therefore, LDE-PTX may become an interesting therapeutic option in patients with advanced stage of prostate, breast or lung carcinomas and without clinical conditions to undergo other conventional chemotherapy regimens

Profile of pharmaceutical interventions of a pharmacotherapeutic follow-up model for diabetic patients in a community pharmacy

Abstract The insertion of Pharmaceutical Care in Primary Health Care (PHC) improves patients' clinical outcomes and quality of life. Pharmacotherapeutic follow-up can contribute to the management of chronic diseases such as diabetes, promoting better glycemic control and adherence to therapy. This study aimed to assess the Drug-therapy Problems (DTPs) and Pharmacist Interventions (PIs) on the pharmacotherapeutic management in patients with type 2 diabetes mellitus (T2DM) in a community pharmacy. A quantitative, retrospective, and cross-sectional study was conducted in a Pharmaceutical Care Program within the PHC in Juiz de Fora (Minas Gerais, Brazil). Inclusion criteria were patients with T2DM above 18, who attended at least three pharmaceutical consultations between July 2016 and October 2018 and presented two or more glycated hemoglobin tests. The study group (n = 17) was largely composed of women (65%), elderly (76%), sedentary (72%), and obese people (52%). The resolution was achieved in 79% of the DTPs identified (n = 115). Most of DTPs were related to administration and adherence to pharmacotherapy (46%). 60% of the 437 PIs involved the provision of information and counseling. In other words, accessible interventions lead to high resolvability. Therefore, clinical actuation of pharmacists could improve the prognosis in diabetes treatment

Development and validation of a reversed-phase HPLC method for quantification of 1'-acetoxychavicol acetate content in a nanostructured lipid carrier formulation

Abstract 1'-acetoxychavicol acetate (ACA)-loaded nanostructured lipid carriers (NLCs) were formulated for prostate cancer therapy and to determine the optimal therapeutic dose, we developed a rapid, specific, and accurate reversed-phase high-performance liquid chromatography (RP-HPLC) method to quantify the ACA content in NLCs. The method was validated according to International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) guidelines. Chromatographic separation of ACA from the lipid components was performed with an Agilent 1220 Infinity LC system and ultraviolet detector using an Agilent Poroshell C18 column (4.6 x 250.0 mm). The mobile phase consisted of acetonitrile and water (80:20 [v/v]) with a flow rate of 0.8 mL/min in isocratic mode. Linearity of the standard curve was assessed at an ACA concentration range of 5-200 µg/mL, and a 1/x weighted linear regression was adopted for the calibration curve. The calculated limits of detection and quantification were 0.59 µg/mL and 1.79 µg/mL, respectively. The mean percent recovery of ACA was 100.02% (relative SD, 2%), and the coefficients of variation for intraday and interday assays were within the values required by the ICH. We also demonstrated robustness of the method by altering the mobile phase ratio and flow rate. Furthermore, we proved specificity of the method for ACA by comparing chromatograms of the blank NLC and ACA-NLC. Hence, we effectively used this validated method to determine the drug-loading capacity and entrapment efficiency of the NLCs.

Cost analysis of a medication dispensing service in community pharmacy in Brazil

This study was aimed to calculate in detail the costs of a medication dispensing service in community pharmacy in Brazil. Descriptive and retrospective analysis with a cost analysis based on mixed costing; absorption costing and time-driven activity based-costing, considering year 2018 and both public and private health system perspectives within a one-year time horizon to estimates costs related to implement and to deploy the service, costs per patient and costs per activity of process (US$ 1 = R$ 3.8310 in October, 2018). Total costs of dispensing service ranged from US$ 24,451.61 to US$ 37,914.48. Costs per patient ranged from US$ 2.43 to US$ 3.77. Costs per activity of the process ranged from US$ 0.39 in pharmacotherapy assessment to US$ 2.46 in pharmaceutical interview. This provides evidence to deploy and implement a structured medication dispensing service in community pharmacy in Brazil with a view to optimize the usage of medicines.

Pharmacotherapy for methamphetamine/amphetamine use disorder-a systematic review and meta-analysis.

AIMS: Addiction to methamphetamine/amphetamine (MA/A) is a major public health problem. Currently there are no pharmacotherapies for MA/A use disorder that have been approved for use by the US Food and Drug Administration or the European Medicines Agency. We reviewed the effectiveness of pharmacotherapy for MA/A use disorder to assess the quality, publication bias and overall strength of the evidence. METHODS: Systematic review and meta-analysis. We searched multiple data sources (MEDLINE, PsycINFO and Cochrane Library) to April 2019 for systematic reviews (SRs) and randomized controlled trials (RCTs). Included studies recruited adults who had MA/A use disorder; sample sizes ranged from 19 to 229 participants. Outcomes of interest were abstinence, defined as 3 or more consecutive weeks with negative urine drug screens (UDS); overall use, analyzed as the proportion of MA/A negative UDS specimens; and treatment retention. One SR of pharmacotherapies for MA/A use disorder and 17 additional RCTs met our inclusion criteria encompassing 17 different drugs (antidepressants, antipsychotics, psychostimulants, anticonvulsants and opioid antagonists). We combined the findings of trials with comparable interventions and outcome measures in random-effects meta-analyses. We assessed quality, publication bias and the strength of evidence for each outcome using standardized criteria. RESULTS: There was low-strength evidence from two RCTs that methylphenidate may reduce MA/A use: 6.5 versus 2.8% MA/A-negative UDS in one study (n = 34, P = 0.008) and 23 versus 16% in another study (n = 54, P = 0.047). Antidepressants as a class had no statistically significant effect on abstinence or retention on the basis of moderate strength evidence. Studies of anticonvulsants, antipsychotics (aripiprazole), opioid antagonists (naltrexone), varenicline and atomoxetine provided either low-strength or insufficient evidence of no effect on the outcomes of interest. Many of the studies had high or unclear risk of bias. CONCLUSIONS: On the basis of low- to moderate-strength evidence, most medications evaluated for methamphetamine/amphetamine use disorder have not shown a statistically significant benefit. However, there is low-strength evidence that methylphenidate may reduce use.

DrPOCS: Drug Repositioning Based on Projection Onto Convex Sets.

Drug repositioning, i.e., identifying new indications for known drugs, has attracted a lot of attentions recently and is becoming an effective strategy in drug development. In literature, several computational approaches have been proposed to identify potential indications of old drugs based on various types of data sources. In this paper, by formulating the drug-disease associations as a low-rank matrix, we propose a novel method, namely DrPOCS, to identify candidate indications of old drugs based on projection onto convex sets (POCS). With the integration of drug structure and disease phenotype information, DrPOCS predicts potential associations between drugs and diseases with matrix completion. Benchmarking results demonstrate that our proposed approach outperforms popular existing approaches with high accuracy. In addition, a number of novel predicted indications are validated with various types of evidences, indicating the predictive power of our proposed approach.

Schizophrenia: effects of aripiprazole in metabolic syndrome

Schizophrenia, in general, is characterized by severe and disabling mental alterations, characterized by the impairment of one's mental, behavioral and social activities, developing certain clinical symptoms, relevant to the diagnosis. The drugs used for the reversion of the symptoms cause several adverse effects that affect the patient's health and well-being, such as motor, endocrine and cardiovascular damages. For a long time, little was known about the origin and the treatment of schizophrenia, which has become a curiosity for science, originating countless researches and theories that are background for several treatments. It is known that alterations in dopaminergic pathways are related to the development of the symptoms of the disease, and evaluating these symptoms, the diagnosis is made and the treatment is initiated. The insertion of new drugs with different characteristics and mechanisms tends to be an advance in the treatment of schizophrenia, as well as reducing the occurence of adverse effects or not worsening already existing cases. Aripiprazole is an innovative atypical antipsychotic employed in the pharmacotherapy of schizophrenia, which tends to attenuate the symptoms, inducing few adverse effects compared to other drugs that are already used, and promotes better quality of life to patients.

Grading the potential safety risk of medications used in hospital care / Clasificación de los grupos de medicamentos según su nivel de riesgo en el ámbito hospitalario

Objective: The aim of this study was to stratify medications used in hospital care according to their potential risk. Method: The RAND/UCLA Appropriateness Method was used. Anatomical Therapeutic Chemical subgroups were classified according to their potential risk. A literature search, bulletins, and alerts issued by patient safety organizations were used to identify the potential safety risk of these subgroups. Nine experts in patient/medication safety were selected to score the subgroups for their appropriateness in the classification. Two evaluation rounds were conducted: the first by email and the second by a panel meeting. Results: A total of 298 Anatomical Therapeutic Chemical subgroups were evaluated. They were classified into three scenarios (low, medium, and high risk). In the first round, 266 subgroups were classified as appropriate to the assigned scenario, 32 were classified as uncertain, and none were classified as inappropriate. In the second round, all subgroups were classified as appropriate. The most frequent subgroups in the low-risk scenario belonged to group A "Alimentary tract and metabolism" (44%); the most frequent in the medium-risk scenario belonged to group J "Antiinfectives for systemic use" (32%); and the most frequent in the high-risk scenario belonged to group L "Antineoplastic and immunomodulating agents" (29%) and group N "Nervous system" (26%). Conclusions: Based on the RAND/UCLA appropriateness method, Anatomical Therapeutic Chemical subgroups used in hospital care were classified according to their potential risk (low, medium, or high). These lists can be incorporated into a risk-scoring tool for future patient/medication safety studies (AU)

Objetivo: Estratificar los medicamentos utilizados en el ámbito hospitalario según el riesgo de provocar daño al paciente. Método: Se utilizó la metodología RAND/UCLA para clasificar los subgrupos terapéuticos del código Anatómica, Terapéutica, Química según el riesgo de provocar daño al paciente. Para ello se realizó una revisión de la evidencia disponible en publicaciones, boletines y alertas de organismos de seguridad del paciente. A continuación se seleccionaron nueve expertos en seguridad del paciente/medicamento para evaluar la clasificación de los subgrupos terapéuticos: una primera ronda de evaluación por vía telemática y una segunda ronda en una reunión presencial en la que se presentaron y discutieron los resultados de la primera. Resultados: Se evaluaron 298 subgrupos terapéuticos. Se clasificaron en tres escenarios (riesgo bajo, medio y alto). En la primera ronda se clasificaron 266 subgrupos como adecuados al escenario asignado, 32 subgrupos fueron clasificados como inciertos y ninguno fue clasificado como inapropiado. En la segunda ronda, todos los subgrupos fueron clasificados como adecuados. Los subgrupos más frecuentes en el escenario de riesgo bajo pertenecieron al Grupo A: "Tracto alimentario y metabolismo" (44%), en el de riesgo medio al Grupo J: "Antiinfecciosos para uso sistémico" (32%), y en el de riesgo alto al Grupo L: "Agentes antineoplásicos e inmunomoduladores" (29%) y al Grupo N: "Sistema nervioso" (26%). Conclusiones: La metodología RAND/UCLA ha permitido estratificar los subgrupos utilizados en el ámbito hospitalario según el riesgo potencial de provocar daño al paciente. Esta estratificación puede servir como herramienta para futuros estudios de seguridad en la utilización de medicamentos (AU)

Desenvolvimento e validação de indicadores para avaliação da qualidade do acompanhamento farmacoterapêutico / Development and validation of indicators for quality assessment of medication management

Um dos elementos para melhoria da qualidade dos serviços farmacêuticos clínicos é medir a qualidade do cuidado prestado e os indicadores podem ser usados nesta avaliação. O presente trabalho teve como objetivos identificar estudos sobre indicadores de qualidade para serviços farmacêuticos clínicos e desenvolver e validar um instrumento de indicadores para avaliação dos serviços de acompanhamento farmacoterapêutico prestados para pacientes ambulatoriais. Para tanto, uma busca abrangente da literatura foi conduzida nas bases de dados PubMed/Medline, Scopus, Lilacs e DOAJ por esses estudos. Os instrumentos apresentados pelos estudos foram avaliados em relação à qualidade das propriedades psicométricas. A seguir, foi desenvolvido um instrumento de indicadores-chave de desempenho. O grupo de pesquisa estabeleceu sete indicadores possíveis para avaliação de especialistas da área através de duas rodadas da técnica Delphi para validação de conteúdo. Ainda, farmacêuticos foram convidados a participar por meio de um questionário para validação de construto e confiabilidade do instrumento. A busca bibliográfica identificou 3.276 registros, dos quais 12 estudos completaram os critérios de inclusão. No geral, o maior número de estudos foi baseado em pesquisas para avaliar a satisfação dos pacientes e usou a revisão da literatura combinada com opinião de especialistas para o desenvolvimento do instrumento. Todos os estudos apresentaram algumas propriedades psicométricas do instrumento. A consistência interna e a validade de conteúdo foram os critérios mais relatados dos estudos, e nenhum deles apresentou o critério de estabilidade. Onze (68,8%) especialistas participaram da primeira rodada da técnica Delphi e nove (81,8%) especialistas completaram as 2 rodadas. Um novo indicador foi desenvolvido após a avaliação do painel de especialistas na primeira rodada. No geral, a validade de conteúdo e construto foi alcançada para o instrumento final. Os resultados desta tese apontam que os instrumentos dos estudos identificados na revisão sistemática apresentaram propriedades psicométricas, porém de forma incompleta ou não satisfatória. Ainda, um instrumento com seis indicadores foi desenvolvido e validado para o Serviço de Acompanhamento Farmacoterapêutico prestado para pacientes ambulatoriais

One of the elements of quality improvement of medication management services is measuring the quality of care and key performance indicators (KPIs) can be used in this assessment. The study is aimed to identify quality indicators instruments in pharmaceutical care services and to develop and validate KPI instrument for medication management services provided for outpatients. For this, comprehensive literature search was performed in databases PubMed/Medline, Scopus, and Lilacs. The psychometric quality of the instruments was determined. In addition, a key performance indicators instrument was developed. A working group established 7 possible KPIs for assessment of the expert panel through an internet based 2-round Delphi approach. An internet questionnaire was developed for pharmacists in order to construct validity and reliability of the instrument. The literature search yielded 3,276 records, of which 12 studies satisfied the inclusion criteria. Overall, the greatest number of studies were based surveys to assess patients' satisfaction and used literature review combined with expert's opinion for the instrument development. All studies presented some psychometrics properties of the instrument. Internal consistency and content validity were the most reported criteria of the studies and none of them presented stability. Eleven (68.8%) experts participated in the Delphi round 1 and nine (81.8%) experts completed the 2 Delphi rounds. A new KPI was develop after expert panel assessment in the first round. Overall, content and construct validity were reached for final instrument. The results of this thesis point out that instrument of the studies identified in the systematic review presented some psychometrics properties, but did not describe them satisfactorily. In addition, a set of six key performance indicators was developed and validated for medication management services provided for outpatients

Perfil de pacientes con fibromialgia que acuden a los centros de atención primaria en Terrassa / Profile of patients with fibromyalgia being treated in primary care centers in Terrassa, a city in northeastern Spain

Objetivo. Realizar una amplia caracterización clínica y epidemiológica de nuestra población afectada de fibromialgia. Pacientes, material y método. Estudio observacional a lo largo de 2 años realizado en 3 centros de atención primaria de Terrassa. Muestra de 235 personas diagnosticadas de fibromialgia visitadas en consultas de atención primaria o de reumatología a las que se ofrece la asistencia al programa multidisciplinar y aceptan completar los datos iniciales del programa. Las mediciones principales fueron: datos sociodemográficos; hábitos tóxicos y ejercicio físico; comorbilidades; tratamientos para la fibromialgia; cuestionario de impacto de la fibromialgia (FIQ); escala hospitalaria de ansiedad-depresión (HADS), y cuestionario de funcionalidad familiar (APGAR familiar). Principales resultados. El 97,8% son mujeres; edad media, 54,6 años. Predominio de pacientes con estudios primarios y en situación de baja laboral. El 94% tienen comorbilidad asociada y solo el 3% no consumen ningún fármaco para su patología, a la vez que hay un elevado consumo de fármacos sin evidencia de efectividad en la fibromialgia. La mayoría puntúan como nivel moderado en el cuestionario de Impacto de la fibromialgia (FIQ); tienen patología ansiosa y/o depresiva probable en el 63 y el 53%, respectivamente, según la Escala hospitalaria de ansiedad y depresión (HADS) y soporte familiar correcto en el 62%, según el test APGAR familiar. Conclusiones. Se confirman como datos principales y coincidiendo con la bibliografía la gran prevalencia de la fibromialgia en mujeres, con elevada comorbilidad especialmente psiquiátrica-psicológica, con moderado impacto de la enfermedad y con importante consumo de fármacos sin eficacia demostrada (AU)

Objective. To perform an extensive clinical and epidemiological characterization of our fibromyalgia patients. Patients, material, and method. Two-year observational study in 3 primary care centers in Terrassa, Spain. We recruited a sample of 235 individuals diagnosed with fibromyalgia being treated in primary care or rheumatology clinics who, when offered inclusion in a multidisciplinary program, agreed to provide the initial data we requested. The main measures were sociodemographic data, unhealthy habits and physical activity, comorbidities, treatment for fibromyalgia, Fibromyalgia Impact Questionnaire (FIQ), Hospital Anxiety and Depression Scale (HADS), and a family functioning scale (family APGAR). Main results. In all, 97.8% were women and the average age was 54.6 years. Most of the patients had a primary school education and the majority was on sick leave. Ninety-four percent had associated comorbidity and only 3% were not taking any medication for their disease. Many were taking drugs with no proven efficacy in fibromyalgia. The majority had intermediate scores on the FIQ, the HADS showed that 63% and 53% had an anxious and/or probable depressive disorder, respectively, and, according to the family APGAR score, 62% received proper family support. Conclusions. In agreement with the literature, the major findings in our fibromyalgia patients were a marked predominance of women, a high incidence of comorbidities-mainly psychiatric disorders-a moderate impact of the disease and widespread use of drugs with no demonstrated efficacy (AU)

Medicamentos en el embarazo. Clasificaciones teratogénicas y otras fuentes de información / Medications in pregnancy. Teratogenic classifications and other sources of information

Las clasificaciones de riesgo teratogénico disponibles han resultado ambiguas y a menudo difíciles de interpretar. No se dispone de guías clínicas basadas en la evidencia para la valoración del riesgo/beneficio en la toma de decisiones en el tratamiento con fármacos en el embarazo. Los estudios disponibles en humanos son limitados y como mucho muestran una asociación entre el fármaco y el efecto indeseable. Se han hecho precisos cambios en las fichas técnicas para mejorar la información sobre el uso de medicamentos en el embarazo, pero no es suficiente. Se ha mejorado la calidad de los estudios en mujeres embarazadas, pero se requiere cierta formación en epidemiología y estadística para interpretarlos. La selección del fármaco más seguro ha de ser personalizada a la situación clínica de la paciente, valorando el riesgo/beneficio del medicamento y de la enfermedad no tratada (AU)

The available teratogenic risk classifications are ambiguous and are often difficult to interpret. There are no evidence-based clinical guidelines on risk/benefit assessment to help with decision-making when drug treatment is considered in pregnancy. Studies available in humans are limited, and at best may show an association between the drug and the undesirable effect. Specific changes have been made in the data sheets to improve information on the use of medicines in pregnancy, but it is not enough. The quality of studies in pregnant women has improved, but some training in epidemiology and statistics is required to interpret them. A personalised selection of the safest drug must take into account the risk/benefit ratio of the drug as well as and the expected outcome of an untreated disease (AU)

Supervivencia de cáncer gástrico en el occidente de Honduras, estudio piloto: 2002-2012 / Survival of Gastric Cancer in Western Honduras Pilot study: 2002-2012

Antecedentes: El cáncer gástrico es la segunda causa de muerte por cáncer globalmente. En Honduras la incidencia en la década pasada fue de 39 y 21 por 100,000 habitantes para hombres y mujeres, respectivamente. En 2008 IARC (GLOBOCAN) colocó a Honduras como el país con más alta incidencia de cáncer gástrico en Latinoamérica. Objetivo: Determinar la supervivencia en pacientes diagnosticados con cáncer gástrico en el occidente de Honduras entre los años 2002-2012. Métodos: Se diseñó un es- tudio de cohorte retrospectivo de pacientes diagnosticados con cáncer gástrico en el Hospital de Occidente (2002-2012). Una muestra de 144 pacientes fue seleccionada de un total de 490 para obtener un nivel de confianza de 95%. La recolección de datos se obtuvo mediante autopsia verbal. Se analizaron los factores pronósticos de supervivencia mediante modelos de razón de riesgos proporcio - nales de Cox (CI:95%) Resultados: La relación hombre/mujer fue 2.8:1. La media de edad fue 63.29 años. La supervivencia global a cinco años fue 9.39%. Entre los pacientes que recibieron terapia dual (cirugía y quimioterapia), se encontró un aumento estadísti- camente significativo de la supervivencia (10.42%,p=0.048). Entre la localizaci ón proximal (28.95%) y distal (56.58%) se observó diferencia estadísticamente significativa (p=0.03). No hubo diferencia estadísticamente significativa entre hallazgos macroscópicos (Borrmann) y microscópicos (Lauren). Discusión: Este estudio representa el primer esfuerzo para estimar la supervivencia de cáncer gástrico en Honduras. La supervivencia podría estar ligada a la localización de la lesión primaria y al tipo de tratamiento. Se espera desarrollar estudios con mayor cobertura, para responder a estas preguntas...(AU)

Diseño, validación y aplicación clínica de un cuestionario de conocimiento (ConocEAP) de los pacientes con enfermedad arterial periférica / Design, validation and clinical application of a knowledge questionnaire (ConocEAP) in patients with peripheral arterial disease

INTRODUCCIÓN: Existe mucha desinformación en la población general y en los pacientes vasculares en particular sobre la enfermedad arterial periférica (EAP). Su adecuado conocimiento puede mejorar el autocuidado y la adherencia al tratamiento en los pacientes que la padecen. OBJETIVO: Desarrollar, validar e implementar un cuestionario que evalúe el conocimiento de los pacientes con EAP sobre su enfermedad y determinar las características clínicas y sociodemográficas que influyen en dicho conocimiento. MATERIAL Y MÉTODO: Se diseñó un cuestionario autoadministrado denominado ConocEAP, con 24 ítems de respuesta dicotómica estructurado en 5 áreas: conocimientos generales (4 ítems), factores de riesgo (6), régimen terapéutico (10), farmacoterapia (2) y signos de alarma (2). Se analizó su validez racional, de contenido mediante valoración de expertos y se implementó un pretest cognitivo. Se administró a 120 pacientes hospitalizados por EAP. La fiabilidad se analizó mediante alfa de Cronbach. RESULTADOS: Edad de los encuestados 72 °æ 13 a˜nos, 79% varones. El conocimiento global de la enfermedad fue del 60,5%. El régimen terapéutico y los signos de alarma fueron las áreas de mayor desconocimiento, y los factores de riesgo y farmacoterapia las que tuvieron mayor número de aciertos. El sexo femenino y un nivel de estudios superior se asocian a mayor conocimiento. Respecto al conocimiento de los factores de riesgo, no hubo diferencias significativas entre los pacientes que los presentaban y los que no. CONCLUSIONES: El diagnóstico de EAP no va ligado a un incremento del conocimiento sobre la enfermedad. El cuestionario ConocEAP es una herramienta válida y fiable que permite identificar el nivel de conocimiento de cada paciente y ofrece la oportunidad de individualizar las intervenciones educativas

INTRODUCTION: Peripheral artery disease (PAD) is largely unrecognised, but adequate knowledge can improve self-care and compliance in PAD patients. OBJECTIVE: To develop, validate and implement a questionnaire to assess the knowledge PAD patients have about their disease and to determine the clinical and sociodemographic characteristics determining that knowledge. MATERIAL AND METHOD: A self-administered questionnaire called ConocEAP was designed. It had 24 dichotomous response items structured into 5 areas: general knowledge (4 items), risk factors (6), therapeutics (10), pharmacotherapy (2), and warning signs (2). Rational validity was analysed by expert assessment and a cognitive pre-test was also implemented. It was administered to 120 patients admitted to hospital due to PAD. Reliability was analysed using Cronbach's alpha. RESULTS: The mean age was 72 °æ 13 years, with 79% males. Overall knowledge of the disease was 60.5%. Therapeutic regimen and warning signs were the areas of less knowledge, and risk factors and pharmacotherapy those with the highest number of correct answers. Female sex and higher education levels are associated with greater knowledge. There was no significant difference between patients as regards knowledge of risk factors, whether they had them or not. CONCLUSIONS: Diagnosis of PAD is not related to a greater knowledge about the disease. ConocEAP questionnaire is a valid and reliable tool, able to identify the level of knowledge of each patient and provides the opportunity to individualise educational interventions

Adenosine monophosphate-activated protein kinase-based classification of diabetes pharmacotherapy.

The current classification of both diabetes and antidiabetes medication is complex, preventing a treating physician from choosing the most appropriate treatment for an individual patient, sometimes resulting in patient-drug mismatch. We propose a novel, simple systematic classification of drugs, based on their effect on adenosine monophosphate-activated protein kinase (AMPK). AMPK is the master regular of energy metabolism, an energy sensor, activated when cellular energy levels are low, resulting in activation of catabolic process, and inactivation of anabolic process, having a beneficial effect on glycemia in diabetes. This listing of drugs makes it easier for students and practitioners to analyze drug profiles and match them with patient requirements. It also facilitates choice of rational combinations, with complementary modes of action. Drugs are classified as stimulators, inhibitors, mixed action, possible action, and no action on AMPK activity. Metformin and glitazones are pure stimulators of AMPK. Incretin-based therapies have a mixed action on AMPK. Sulfonylureas either inhibit AMPK or have no effect on AMPK. Glycemic efficacy of alpha-glucosidase inhibitors, sodium glucose co-transporter-2 inhibitor, colesevelam, and bromocriptine may also involve AMPK activation, which warrants further evaluation. Berberine, salicylates, and resveratrol are newer promising agents in the management of diabetes, having well-documented evidence of AMPK stimulation medicated glycemic efficacy. Hence, AMPK-based classification of antidiabetes medications provides a holistic unifying understanding of pharmacotherapy in diabetes. This classification is flexible with a scope for inclusion of promising agents of future.

Prognostic factors affecting survival in metastatic soft tissue sarcoma: an analysis of 110 patients

Background: Data on treatment outcome and prognostic factors in patients with metastatic soft tissue sarcoma (STS) are limited in the literature. Methods: A total of 119 patients with metastatic STS treated between June 2003 and December 2012 were analyzed for treatment outcome and prognostic factors. Results: Median age was 37 years (range 2-72 years) with a male to female ratio of 1.5:1. Most common histologic subtypes were synovial sarcoma (36 %) and leiomyosarcoma (16 %). Median tumor size was 12 cm (range 1.6-30 cm). Twenty-four (20 %) patients were treated with multimodality therapy and 80 % patients received systemic chemotherapy alone. At a median follow- up of 10 months (range 1-66 months), the 2-year EFS and OS were 10 and 19 %, respectively, with a median EFS and OS of 6 and 10 months, respectively. Univariate analysis identified albumin B4 g/dl (p = 0.001), histologic subtypes other than synovial sarcoma (p = 0.02), non-extremity tumors (p = 0.03) and single modality treatment (p = 0.03) as factors predicting poor EFS; however, for OS, hemoglobin B10 g/dl (p = 0.02), tumor size[10 cm (p = 0.01) and single modality treatment (p = 0.04) were identified as poor prognostic factors. Multivariate analysis identified only serum albumin B4 g/dl (p = 0.002, HR 0.47, 95 % CI 0.29-0.75) associated with poor EFS; however, for OS, hemoglobin B10 g/dl (p = 0.009, HR 0.49, 95 % CI 0.29-0.83), tumor size[10 cm (p = 0.003, HR 2.11, 95 % CI 1.28-3.47) and single modality treatment (p = 0.01, HR 0.47, 95 % CI 0.25-0.86) emerged as poor prognostic factors. Conclusions: Serum albumin, tumor size, hemoglobin and treatment modality affect survival in metastatic STS (AU)

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Examining systemic steroid Use in older inflammatory bowel disease patients using hurdle models: a cohort study.

BACKGROUND: Interpreting clinical guideline adherence and the appropriateness of medication regimens requires consideration of individual patient and caregiver factors. Factors leading to initiation of a medication may differ from those determining continued use. We believe this is the case for systemic steroid therapy in inflammatory bowel disease (IBD), resulting in a need to apply methods that separately consider factors associated with initiation and duration of therapy. To evaluate the relationship between patient characteristics and the frequency and duration of incident steroid use we apply a 2-part hurdle model to Medicare data. We do so in older patients with tumor necrosis factor antagonist (anti-TNFs) contraindications, as they are of special interest for compliance with Medicare-adopted, quality metrics calling for anti-TNFs and nonbiologic immune therapies to reduce steroid utilization. Many older patients have contraindications to anti-TNFs. However, nonbiologics cause adverse events that are concerning in older adults, limiting their use in this population and increasing reliance on systemic steroids. METHODS: We used a national Medicare sample for 2006-2009 including patients with 12 months or greater of Parts A and B and 6 months or greater of Part D coverage, IBD confirmed with at least 2 claims for ICD-9CM 555.xx or 556.xx, anti-TNF contraindications and without contraindications to nonbiologic agents. We applied a negative binomial-logit hurdle model to examine patient characteristics associated with systemic steroid utilization. RESULTS: Among the 1,216 IBD patients without baseline steroid use, 21% used systemic steroids. Odds of receiving systemic steroids were greater in those younger, rural, and those receiving other agents. Available patient characteristics failed to predict longer steroid treatment duration. CONCLUSIONS: Our study identified differences in predictors of frequency and duration of medication use and suggests the utility of two-part models to examine drug utilization patterns. Applying such a model to Medicare data, we determined that despite medical consensus that systemic steroid use should be minimized, its use was substantial. Findings indicate anticipated difficulties in implementing recently adopted quality measures to avoid systemic steroids.

Medication regimen complexity in adults and the elderly in a primary healthcare setting: determination of high and low complexities / Complejidad del regimen de medicación en adultos y ancianos en un centro de cuidados primaries: determinación de la complejidad alta y baja

Background: The complexity of a medication regimen is related to the multiple characteristics of the prescribed regimen and can negatively influence the health outcomes of patients. Objective: To propose cut-off points in the complexity of pharmacotherapy to distinguish between patients with low and high complexities seen in a primary health care (PHC) setting to enable prioritization of patient management. Methods: This is a cross-sectional study, which included 517 adult and elderly patients, analyzing different cut-off points to define the strata of low and high pharmacotherapy complexities based on percentiles of the population evaluated. Data collection began with the solicitation of prescriptions, followed by a questionnaire that was administered by an interviewer. The complexity of a medication regimen was estimated from the Medication Regimen Complexity Index (MRCI). High complexity pharmacotherapy scores were analyzed from patient profiles, the use of health services, and pharmacotherapy. The criteria for subject inclusion in the sample population were as follows: inhabitant of the area covered by the municipality, 18 years or older, and being prescribed at least one drug during the collection period. Exclusion criteria at the time of collection were the use of any medication whose prescription was not available. All medications were accessed through the Primary Healthcare Service (PHS). Results: The median total pharmacotherapy complexity score was 8.5. High MRCI scores were correlated with age, medications taken with in the Brazilian PHS, having at least one potential drug-related problem, receiving up to eight years of schooling, number of medications and polypharmacy (five or more medicines), number of medical conditions, number of medical appointments, and number of cardiovascular diseases and endocrine metabolic diseases. We suggest different complexity tracks according to age (e.g., adult or elderly) that consider the pharmacotherapy and population coverage characteristics as high complexity limits. For the elderly patients, the tracks were as follows: MRCI≥25.4, MRCI≥20.9, MRCI≥17.5, MRCI≥15.7, MRCI≥14.0, and MRCI≥13.0. For adult patients, the limits of high complexity were MRCI≥25.1; MRCI ≥ 23.8; MRCI≥21.0; MRCI≥17.0; MRCI≥16.5; and MRCI≥15.5. Conclusion: The medication regimen complexity is associated with the patient's illness profile and problems with the use of drugs; therefore, the proposed scores can be useful in prioritizing patients for clinical care by pharmacists and other health professionals (AU)

Antecedentes: La complejidad de un régimen de medicación se relaciona con las múltiples características del régimen prescrito que pueden influenciar negativamente los resultados en salud de los pacientes. Objetivo: Proponer puntos de corte en la complejidad de la farmacoterapia para diferenciar entre pacientes de baja y alta complejidad que permita la priorización de la gestión de los pacientes entre los atendidos en un centro de cuidados primarios. Métodos: Este es un estudio transversal que incluyó 517 adultos y ancianos analizando diferentes puntos de corte para definir los estratos de alta y baja complejidad de la farmacoterapia basándose en los percentiles de la población evaluada. La recogida de datos comenzó con la solicitud de las prescripciones, seguida de un cuestionario administrado por un entrevistador. La complejidad de la medicación se estimó mediante el Medication Regimen Complexity Index (MRCI). En las farmacoterapias de alta complejidad se analizó los perfiles de los pacientes, el uso de servicios de salud, y la farmacoterapia. Los criterios para la inclusión de la muestra fueron: habitantes del área cubierta por el municipio, 18 años o más, y tener prescrito al menos un medicamento durante el periodo de recogida de datos. Los criterios de exclusión durante la recogida de datos fue el uso de algún medicamento que no estaba disponible. Todos los medicamentos eran del Servicio de Cuidados Primarios (PHS). Resultados: La mediana total de puntuación de complejidad de la farmacoterapia fue de 8,5. Las puntuaciones altas del MRCI se correlacionaban con la edad, medicamentos tomados del PHS, tener al menos una interacción potencial medicamento-medicamento, tener más de 8 años de escolaridad, numero de medicamentos, polimedicación (cinco o más medicamentos), número de problemas de salud, número de visitas al médico, y numero de enfermedades cardiovasculares o metabólicas. Sugerimos diferentes tramos de complejidad de acuerdo a la edad (e.g. adultos o ancianos) que tienen en cuenta las características de la población y la farmacoterapia como límites de alta complejidad. Para los ancianos los tramos eran: MRCI≥25,4, MRCI≥20,9, MRCI≥17,5, MRCI≥15,7, MRCI≥14,0, y MRCI≥13,0. Para los pacientes adultos los límites de complejidad eran: MRCI≥25,1; MRCI ≥ 23,8; MRCI≥21,0; MRCI≥17,0; MRCI≥16,5; y MRCI≥15,5. Conclusión: La complejidad del régimen de medicación se asocia con el perfil de enfermedad del paciente y sus problemas de uso de medicamentos; por tanto, los limites propuestos pueden ser útiles para priorizar pacientes en cuidados clínicos de los farmacéuticos u otros profesionales de la salud (AU)