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

Breastfeeding and risk classification of medications used during hospitalization for delivery: 2015 Pelotas Birth Cohort. / Classificação de risco dos medicamentos usados na internação para o parto na amamentação: coorte de nascimentos de Pelotas/2015.

OBJECTIVE: To classify the drugs used during childbirth in relation to risks in breastfeeding, by using different sources of information and determining their disagreements. METHODS: Cross-sectional study, within the 2015 Pelotas Birth Cohort. Information about the use of drugs was collected, classified and compared regarding risk according to: 1) Brazil Ministry of Health Manual (MS), 2) World Organization (WHO), 3) Newton and Hale's classification and 4) American Academy of Pediatrics (AAP). RESULTS: A total of 1,409 mothers participated, and they had used 14,673 medicines, with 143 different drugs, of which 28 showed discordant classification with regard to breastfeeding risk. These 28 drugs included the following: morphine (64%), classified by AAP and WHO as compatible and as judicious use use by MS and Newton and Hale; hyoscine (23%), classified as judicious use by MS and compatible (A) by AAP; and metoclopramide (18%), classified as compatible by MS, of effects unknown (D) by AAP, and should be avoided according to WHO. Of the total drugs, 49.7% were classified as compatible during breastfeeding. Almost all women used oxytocin (97.4%), followed by lidocaine (75%), ketoprofen (69%), cephalothin (66%) and diclofenac (65%), which were classified as compatible. CONCLUSION: There was extensive use of drugs by mothers in labor during admission, most of the drugs being classified at the same risk and almost half classified as compatible with breastfeeding. However, there was disagreement between the sources for 19.6% of the drugs analyzed, which could endanger the infant's health or leave doubts about the use of the drug or breastfeeding.

Classificação de risco dos medicamentos usados na internação para o parto na amamentação: coorte de nascimentos de Pelotas/2015 / Breastfeeding and risk classification of medications used during hospitalization for delivery: 2015 Pelotas Birth Cohort

RESUMO: Objetivo: Classificar os medicamentos usados durante o parto quanto aos riscos na amamentação, utilizando diferentes fontes e verificando suas discordâncias. Métodos: Estudo transversal inserido na coorte de nascimentos de Pelotas de 2015. Coletaram-se informações sobre o uso de medicamentos, classificando-os quanto ao risco de acordo com: manual do Ministério da Saúde (MS), Organização Mundial da Saúde (OMS), classificação de Newton e Hale e Academia Americana de Pediatria (AAP). Resultados: Participaram 1.409 mães, utilizando 14.673 medicamentos, sendo 143 fármacos diferentes, dos quais 28 tiveram classificação de risco na amamentação discordante. Entre aqueles com classificação discordante estão morfina (64%), classificada pela AAP e OMS como compatível e pelo MS e por Newton e Hale como criterioso; hioscina (23%), criterioso pelo MS e compatível (A) pela AAP; e metoclopramida (18%), compatível pelo MS, de efeitos desconhecidos (D) pela AAP e evitado de acordo com a OMS. Do total de medicamentos, 49,7% foi classificado como compatível com a amamentação. Quase a totalidade das mulheres utilizou ocitocina (97,4%), seguida de lidocaína (75%), cetoprofeno (69%), cefalotina (66%) e diclofenaco (65%), classificados como compatíveis. Conclusão: Houve amplo uso de medicamentos pelas mães durante a internação para o parto, a maioria deles classificada no mesmo grau de risco, e quase a metade classificada como compatível com a amamentação, porém houve discordância entre as fontes para 19,6% dos medicamentos analisados, o que pode colocar em risco a saúde do lactente ou deixar dúvida quanto ao uso do medicamento ou à prática da amamentação.

ABSTRACT: Objective: To classify the drugs used during childbirth in relation to risks in breastfeeding, by using different sources of information and determining their disagreements. Methods: Cross-sectional study, within the 2015 Pelotas Birth Cohort. Information about the use of drugs was collected, classified and compared regarding risk according to: 1) Brazil Ministry of Health Manual (MS), 2) World Organization (WHO), 3) Newton and Hale's classification and 4) American Academy of Pediatrics (AAP). Results: A total of 1,409 mothers participated, and they had used 14,673 medicines, with 143 different drugs, of which 28 showed discordant classification with regard to breastfeeding risk. These 28 drugs included the following: morphine (64%), classified by AAP and WHO as compatible and as judicious use use by MS and Newton and Hale; hyoscine (23%), classified as judicious use by MS and compatible (A) by AAP; and metoclopramide (18%), classified as compatible by MS, of effects unknown (D) by AAP, and should be avoided according to WHO. Of the total drugs, 49.7% were classified as compatible during breastfeeding. Almost all women used oxytocin (97.4%), followed by lidocaine (75%), ketoprofen (69%), cephalothin (66%) and diclofenac (65%), which were classified as compatible. Conclusion: There was extensive use of drugs by mothers in labor during admission, most of the drugs being classified at the same risk and almost half classified as compatible with breastfeeding. However, there was disagreement between the sources for 19.6% of the drugs analyzed, which could endanger the infant's health or leave doubts about the use of the drug or breastfeeding.

Access and use of medicines by elderly individuals with dementia

The objective is to reveal the difficulties concerning the access and use of medicines by elderly individuals with dementia, reported by their caregivers. This qualitative study applied the participant observation method during pharmaceutical appointments performed in a specialized geriatrics service of the University Hospital of Brasília. Caregivers reported facing difficulties regarding the itinerary for medicines access in public pharmacies, as well as the high cost of these technologies in private establishments. Psychiatric symptoms, cognitive deficits, behavioral changes, apraxia, dysphagia, among other clinical manifestations of dementia syndromes, incapacitates the elderly for self-responsibility concerningthe use of drugs, which accentuates the complexity of medicines administration within the care process. In conclusion, it is fundamental to recognize caregivers' role in promoting the rational use of medicines, and so this theme should be highlighted within the pharmaceutical services context.

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)

Continuum Cardiovascular 25 anos - Evolução de um Modelo Etiofisiopatológico / Cardiovascular Continuum 25 years – The Evolution of an Etiopathophysiology Model

O conceito de continuum cardiovascular foi elaborado por Dzau e Braunwald e difundido entre cardiologistas como modelo etiofisiopatológico que direciona o desenvolvimento de medidas intervencionistas na prevenção das doenças cardiovasculares. Após workshop realizado em 1989, foi possível reunir questões resolvidas e não resolvidas sobre fatores relacionados à terapia e proteção cardiovascular, resultando na primeira publicação por Dzau e Braunwald, em 1991. O avanço nos estudos da biologia molecular e celular permitiu entendimento do papel da disfunção endotelial no estresse oxidativo e do óxido nítrico na doença aterosclerótica coronariana (DAC),concedendo prêmio Nobel aos autores Ferid Murad, Robert Furchgott e Louis Ignarro. Em 2006, uma segunda publicação, também liderada por Dzau, consolidou o modelo clássico do continuum cardiovascular, no qual fatores de risco para DAC se associam e desencadeiam cascata progressiva de eventos levando aos estágios finais da doença cardiovascular. A partir da observação da existência de doenças isquêmicas do miocárdio em populações com baixa incidência de aterosclerose coronariana, estudos comprovaram que a doença isquêmica não está apenas associada à aterosclerose, mas também ao envelhecimento vascular. Este achado levou à publicação do terceiro artigo de O’Rourke em 2010, que apresentou um modelo adicional: continuum do envelhecimento vascular. Aevolução desse modelo possibilitou o enfoque não apenas em tratamentos preventivos dos fatores de risco da DAC, mas também na busca de terapias capazes de prevenir dano endotelial causado pelo envelhecimento vascular e de modular o estresse oxidativo. Esta revisão tem por objetivo reunir os principais estudos que embasam a evolução do modelo continuum cadiovascular em 25 anos...

The concept of cardiovascular continuum was devised by Dzau and Braunwald and spread among cardiologists as na etiopathophysiology model that directs the development of interventionist measures in the prevention of cardiovascular diseases. After a workshop held in 1989, it was possible to gather resolved and unresolved issues about factors related to cardiovascular therapy and protection, resulting in the first publication by Dzau and Braunwald, in 1991. Progress in the studies of molecular and cellular biology allowed understanding the role of endothelial dysfunction in oxidative stress and nitric oxide in coronary artery atherosclerosis (CAA), awarding Nobel Prize to authors Ferid Murad, Robert Furchgott and Louis Ignarro. In 2006, a second publication, also ledby Dzau, consolidated the classic model of cardiovascular continuum, in which risk factors for CAA are associated and trigger a progressive cascade of events leading to the final stages of cardiovascular disease. By observing the existence of ischemic myocardial diseases in populations with low incidence of coronary artery atherosclerosis, studies have shown that ischemic heart disease is not only associated with atherosclerosis, but also to vascular aging. This finding led to the publication of O’Rourke’s third manuscriptin 2010, which presented an additional model: vascular aging continuum. The evolution of this model allowed focusing on preventive treatments for the risk factors of CAA and the search for therapies capable of preventing endothelial damage caused by vascular aging and modulating oxidative stress. This review aims to bring together the leading studies that support the evolution of the cardiovascular continuum model over 25 years...

DRESS syndrome induced by meropenem

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Pharmacoepidemiological characterisation of zolpidem and zopiclone usage.

PURPOSE: Zolpidem and zopiclone are two widely used non-benzodiazepine hypnotics whose usage seems to be associated to pharmacodependence. However, to our knowledge, there has as yet been no published epidemiological study which has compared their abuse or dependence potential. We used a pharmacoepidemiological approach to identify and characterise zolpidem and zopiclone users in real life situations. METHODS: Regular users of zolpidem or zopiclone were identified in the database of a French regional health insurance organisation. A latent class analysis (LCA) was used to identify different subgroups of users of these two hypnotics. RESULTS: The study cohort comprised 25,168 patients who regularly used zolpidem and 21,860 who regularly used zopiclone. The results of the latent class analysis, which enables subgroups with similar patterns of response to be identified, revealed four clinical subtypes of users of zolpidem: non-problematic users, users with associations with hypnotics/anxiolytics or with associated mental disorders, and problematic users. Only three subgroups were identified for zopiclone, and LCA did not discriminate a special class of problematic users for this drug. CONCLUSION: Our analysis indicates that there is a subclass of zolpidem user suggestive of abuse; this was not the case for zopiclone. This methodology is very interesting because it allows analysis of databases and determination of a specific signature of drugs potentially leading to abuse or dependence.

Medicine use by the elderly in Goiania, Midwestern Brazil.

OBJECTIVE: To analyze the pattern of use of medications use in aged people and associate it with socioeconomic aspects and with the self-rated health. METHODS: A population-based cross-sectional design study with 934 elderly people from Goiania, Midwestern Brazil, between December 2009 and April 2010. Data were collected through a questionnaire. The dependent variable was the number of medications consumed and the independent variables were sex, marital status, education, type of residence, age, income, and self-rated health. Drugs were classified according to the Anatomical Therapeutic Chemical Classification. The inappropriate drugs for the elderly were identified according to the Beers-Fick criteria. The tests used were Chi-square and Fisher's exact test, p was considered significant when < 0.05. RESULTS: The elderly consumed 2,846 medicines (3.63 medications/person). The most commonly consumed were those which act in the cardiovascular system (38.6%). The prevalence of polypharmacy was 26.4% and self-medication was 35.7%. The most used drugs for self-medication were analgesics (30.8%), 24.6% of the elderly consumed drug considered inappropriate. Women, widows, those aged 80 or over and with worse self-rated health were more likely to practiced more polypharmacy. Most self-medication was associated with lower levels of education and worse self-rated health. CONCLUSIONS: The pattern of drug use by the elderly was similar to that found in the elderly in other regions of Brazil. The number of drugs used, the prevalence of self-medication and practice of polypharmacy and inappropriate drug use were within the national average.

Consumo de medicamentos por idosos, Goiânia, Brasil / Consumo de medicamentos por ancianos, Goiania, Brasil / Medicine use by the elderly in Goiania, Midwestern Brazil

OBJETIVO: Analisar o padrão de consumo de medicamentos entre idosos e sua associação com aspectos socioeconômicos e autopercepção de saúde. MÉTODOS: Estudo de base populacional e delineamento transversal com 934 idosos de Goiânia, GO, Brasil, entre dezembro de 2009 e abril de 2010. Os dados foram coletados por meio de questionário. As variáveis estudadas foram: número de medicamentos consumidos, sexo, estado civil, escolaridade, tipo de moradia, idade, renda e autopercepção de saúde. Os medicamentos foram classificados segundo o Anatomical Therapeutic and Chemical Classification. Os medicamentos impróprios para idosos foram identificados segundo o Critério de Beers-Fick. Os testes utilizados foram Qui-quadrado (X²) e exato de Fisher e p foi considerado significativo quando < 0,05. RESULTADOS: Os idosos consumiam 2.846 medicamentos (3,63 medicamentos/idoso). Os mais usuais atuavam no aparelho cardiovascular (38,6%). A prevalência de polifarmácia foi de 26,4% e da automedicação de 35,7%. Os medicamentos mais ingeridos por automedicação foram os analgésicos (30,8%); 24,6% dos idosos consumia medicamento considerado impróprio. Mulheres, viúvos, idosos com 80 anos ou mais e com pior autopercepção de saúde praticavam mais a polifarmácia. A maior prática da automedicação esteve associada com menor escolaridade e pior autopercepção de saúde. CONCLUSÕES: O padrão do consumo de medicamentos por idosos foi semelhante ao encontrado em idosos de outras regiões do Brasil. O número de medicamentos usados, a prevalência das práticas da polifarmácia e automedicação e consumo de medicamentos impróprios estiveram dentro da média nacional.

OBJECTIVE: To analyze the pattern of use of medications use in aged people and associate it with socioeconomic aspects and with the self-rated health. METHODS: A population-based cross-sectional design study with 934 elderly people from Goiania, Midwestern Brazil, between December 2009 and April 2010. Data were collected through a questionnaire. The dependent variable was the number of medications consumed and the independent variables were sex, marital status, education, type of residence, age, income, and self-rated health. Drugs were classified according to the Anatomical Therapeutic Chemical Classification. The inappropriate drugs for the elderly were identified according to the Beers-Fick criteria. The tests used were Chi-square and Fisher's exact test, p was considered significant when < 0.05. RESULTS: The elderly consumed 2,846 medicines (3.63 medications/person). The most commonly consumed were those which act in the cardiovascular system (38.6%). The prevalence of polypharmacy was 26.4% and self-medication was 35.7%. The most used drugs for self-medication were analgesics (30.8%), 24.6% of the elderly consumed drug considered inappropriate. Women, widows, those aged 80 or over and with worse self-rated health were more likely to practiced more polypharmacy. Most self-medication was associated with lower levels of education and worse self-rated health. CONCLUSIONS: The pattern of drug use by the elderly was similar to that found in the elderly in other regions of Brazil. The number of drugs used, the prevalence of self-medication and practice of polypharmacy and inappropriate drug use were within the national average.

OBJETIVO: Analizar el patrón de consumo de medicamentos entre ancianos y su asociación con aspectos socioeconómicos y autopercepción de salud. MÉTODOS: Estudio de base poblacional y delineamiento transversal con 934 ancianos de Goiania, GO, Brasil, entre diciembre de 2009 y abril de 2010. Los datos fueron colectados por medio de cuestionario. Las variables estudiadas fueron: número de medicamentos consumidos, sexo, estado civil, escolaridad, tipo de vivienda, edad, renta y autopercepción de la salud. Los medicamentos fueron clasificados de acuerdo al Anatomical Therapeutic and Chemical Classification. Los medicamentos inadecuados para ancianos se identificaron según el Criterio de Beers-Fick. Las pruebas utilizadas fueron Chi-cuadrado (X2) y exacto de Fisher y el p fue considerado significativo al ser <0,05. RESULTADOS: Los ancianos consumían 2.846 medicamentos (3,63 medicamentos/anciano). Los más consumidos actuaban en el sistema cardiovascular (38,6%). La prevalencia de polifarmacia fue de 26,4% y de la automedicación de 35,7%. Los medicamentos más consumidos por automedicación fueron los analgésicos (30,8%), 24,6% de los ancianos consumía medicamento considerado inadecuado. Mujeres, viudos, ancianos con 80 años o más y con peor autorpercepción de salud practicaban más la polifarmacia. La mayor práctica de automedicación estuvo asociada con menor escolaridad y peor autopercepción de salud. CONCLUSIONES: El patrón de consumo de medicamentos por ancianos fue semejante al encontrado en ancianos de otras regiones de Brasil. El número de medicamentos usados, la prevalencia de las prácticas de polifarmacia y automedicación y consumo de medicamentos inadecuados estuvieron dentro del promedio nacional.

A qualitative study exploring perspectives towards rational use of medicines in Pakistan's Malaria Control Program (MCP)

Malaria is one of the most important global public health problems threatening the health of the population owing to prevailing socio-economic conditions and epidemiological reasons in Pakistan. This qualitative study has focused on the perspectives held towards the rational use of medicine intervention among malaria control program officials. Eight semi-structured interviews with all officials working for the malaria control program in Islamabad were conducted. The interviews, which were audio-taped and transcribed verbatim, were evaluated by thematic content analysis and by all authors. All respondents agreed on successful implementation of the malaria control program in Pakistan for controlling malaria by improving diagnostic and treatment facilities and promoting rational case management through training of prescribers. However, funding is still the major challenge faced by the program for its future implementation.

A malária é um dos mais importantes problemas sanitários globais, que ameaça a saúde população devido às condições socioeconômicas e por razões epidemiológicas no Paquistão. Este estudo qualitativo focou-se nas perspectivas no sentido do uso racional da intervenção médica entre os funcionários do programa de controle da malária. Oito entrevistas semiestruturas com todos os funcionários que trabalham no programa de controle da malária foram conduzidas em Islamabad. As entrevistas, que eram gravadas e transcritas, foram avaliadas por análise temática do conteúdo e por todos os autores. Todos os respondentes concordaram com o êxito da implementação do programa de controle da malária no Paquistão por meio do aprimoramento do diagnóstico e de facilidades do tratamento, promovendo a gestão racional por meio do treinamento dos prescritores. Entretanto, o financiamento é, ainda, o principal desafio enfrentado para a implementação futura do programa.

The quality of prescription drug utilization five years after the 2003 Bam earthquake.

PURPOSE: Few reports considering drug use among earthquake survivors exist. The present study aims to examine the Bam earthquake's impact on prescribing patterns and drug use among residents five years post-disaster. DESIGN/METHODOLOGY/APPROACH: In this study, 297,104 prescriptions, issued by general practitioners in Bam city in 2008, were investigated for drugs/prescriptions, drug name, drug category, using WHO appropriate general practice prescribing indicators. FINDINGS: Mean drugs per prescription was 3.1. Drugs affecting the central nervous system were the most frequently used among Bam residents, representing 25.1 per cent, followed by antimicrobials, respiratory, cardiovascular and gastrointestinal tract drugs. Benzodiazepines were the most frequently used central nervous system drugs (15.8 per cent) followed by narcotic analgesics and tricyclic antidepressants. Penicillins (6.4 per cent) and cephalosporines (2.3 per cent) were the most frequently used antimicrobial drugs. ORIGINALITY/VALUE: Results emphasize increased drug use for psychological disturbances and the need for strategies to improve mental health among disaster survivors.

Rational use of antioxidants in solid oral pharmaceutical preparations

Antioxidants are currently used as efficient excipients that delay or inhibit the oxidation process of molecules. Excipients are often associated with adverse reactions. Stability studies can guide the search for solutions that minimize or delay the processes of degradation. The ability to predict oxidation reactions in different drugs is important. Methods: This study was conducted to assess the rational use of butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), sodium metabisulfite (SMB), propyl gallate (PG) and cysteine (CYS) in tablet formulations of simvastatin and ketoconazole. These antioxidants were evaluated according to stability parameters and the relationship between efficiency of the antioxidant and chemical structure of the drugs. Results were compared with DPPH tests and computational simulations. BHT was most efficient regarding simvastatin stability, and the most effective BHT concentrations for maintaining stability were 0.5 and 0.1%. In relation to ketoconazole, SMB was most efficient for maintaining content and dissolution profile. The evaluation by DPPH showed that the largest percentage of absorbance reduction was observed for PG, while SMB proved most efficient and had lower consumption of DPPH. The same pattern was observed, albeit with lower efficiency, for the other lipophilic antioxidants such as BHT and BHA. The results of the molecular modeling study demonstrated that electronic properties obtained were correlated with antioxidant activity in solution, being useful for the rational development of liquid pharmaceutical formulations but not for solid oral formulations. This study demonstrated the importance of considering stability parameters and molecular modeling to elucidate the chemical phenomena involved in antioxidant activity, being useful for the rational use of antioxidants in the development of pharmaceutical formulations.

Atualmente, antioxidantes são usados como excipientes eficientes, que retardam ou inibem o processo de oxidação de moléculas. Excipientes são frequentemente associados a efeitos adversos. Estudos de estabilidade podem ajudar na busca por possíveis soluções para minimizar ou retardar os processos de degradação. A habilidade de prever as reações de oxidação em diferentes fármacos é importante. O estudo foi conduzido com o objetivo de avaliar o uso racional de hidroxianisol butilado (BHA), hidroxitolueno butilado (BHT), metabissulfito sódico (SMB), galato de propila (PG) e cisteína (CYS) em formulações de comprimidos de sinvastatina e cetoconazol. Eles foram avaliados por parâmetros de estabilidade e pela relação entre a eficiência dos antioxidantes e a estrutura química do fármaco. Os resultados foram comparados com testes de DPPH e simulações em computador. BHT foi mais eficiente com relação a estabilidade da sinvastatina e às concentrações mais eficientes para manutenção de estabilidade foram 0,5 e 0,1%. Com relação ao cetoconazol, SMB foi mais eficiente em manter o conteúdo e o perfil de dissolução. A avaliação por DPPH mostrou que o maior percentual de redução de absorção foi observado para PG, enquanto que SMB mostrou ser mais eficiente e consumir menos DPPH. A mesma tendência foi observada com menos eficiência em todos os outros antioxidantes lipofílicos como o BHT e BHA. Os resultados do estudo de modelagem molecular demonstraram que as propriedades eletrônicas obtidas podem ser correlacionadas com a atividade antioxidante em solução, sendo útil para o desenvolvimento racional de formulações farmacêuticas líquidas, mas não para formulações sólidas orais. Este estudo demonstrou a importância de considerar parâmetros de estabilidade e modelagem molecular para elucidar os fenômenos químicos envolvidos na atividade antioxidante, sendo úteis para o uso racional de antioxidantes no desenvolvimento de formulações farmacêuticas.

Results of a retrospective database analysis of drug utilization and costs for treatment of chronic hepatitis B virus infection in the northern Netherlands between 2000 and 2006.

OBJECTIVES: The main aims of this work were to describe patterns of medication use in the treatment of chronic hepatitis B virus (HBV) infection in patients in the northern part of the Netherlands and to compare these practices with established guidelines. In addition, the duration of use and the costs of these treatments were investigated. METHODS: We selected subjects from the University of Groningen's IADB.nl database; by 2006, the database provided information about drug utilization from 55 community pharmacies in the northern Netherlands and included a population of 528,911 individuals, of which 49% were male. Eligible subjects had received >or=1 prescription for drugs used to treat chronic HBV infection (ie, lamivudine, pegylated interferon-alpha2a, pegylated interferon-alpha2b, adefovir, tenofovir, and entecavir) between the years 2000 and 2006. The annual prevalence and cumulative incidence of HBV treatment per 1000 people covered in the database were calculated and stratified by sex. Kaplan-Meier survival analysis was used to analyze the duration of use. Drug costs in the treatment were calculated for all patients or per patient, and by drugs used per subperiod (2000-2003 and 2004-2006). Treatments for hepatitis C virus and HIV were excluded from the analyses. RESULTS: From the database, we identified 59 patients (46 male, 13 female), aged 25 to 60 years, who received >or=1 prescription for a medication to treat chronic HBV infection between 2000 and 2006. The overall prevalence of people using chronic treatments for HBV was between 0.03 and 0.06 per 1000 during the years of the study. The cumulative incidence of treatment was approximately 0.01 per 1000 per year (ranging from a high of 0.021 in 2000 to a low of 0.009 in 2006). When stratified by sex, there were more male than female subjects who received medications for HBV. Lamivudine was the most commonly prescribed drug, followed by adefovir and pegylated interferon-alpha2b. In 2000 and 2001, lamivudine was the only medication prescribed for the treatment of chronic HBV. From 2002 to 2006, the prescription rate for lamivudine dropped from 90% to 61%. In contrast, the prescription rate for adefovir increased from 4% in 2003 to 36% in 2006. Pegylated interferon-alpha2b remained stable at 8% to 11% between 2002 and 2006. Twenty-five percent of patients had stopped HBV treatment by the end of 1 year. Fifty-five percent had stopped by 3 years. Seventy-seven percent of patients received their first HBV prescription from a medical specialist. Per patient, the cost of drug therapy was highest with adefovir. From 2004 to 2006, the cost of adefovir therapy accounted for 49% of total expenditures for the treatment of chronic HBV (equivalent to euro128,037; as of January 2010, euro1.00 = US $1.43). The second and third most expensive drugs were tenofovir and pegylated interferon-alpha2b (euro33,700 and euro33,250, respectively). Costs incurred per patient increased over the years of the study period. CONCLUSIONS: The overall prevalence and cumulative incidence of patients with treatments for chronic HBV were relatively low in the northern part of the Netherlands between 2000 and 2006. The prescribing and utilization patterns were in agreement with international and Dutch guidelines. Given the low numbers of prescriptions, the costs also remained relatively low.

Elevado consumo de benzodiacepinas en mujeres ancianas asignadas a centros de salud urbanos de atención primaria / Increased benzodiazepine use in elderly women attending urgan primary health care centers

Objetivo. Determinar la prevalencia globaldel consumo crónico de benzodiacepinasy sus análogos en atención primaria.Diseño. Estudio transversal observacional.Emplazamiento. Centros de salud del Serviciode Atención Primaria Reus-Altebrat.Participantes. Pacientes con edad superiora 15 años, en tratamiento prolongadocon benzodiacepinas o sus análogos.Mediciones. Las variables analizadas fueron laedad, el sexo, el tipo de centro de salud (ruralo urbano), la benzodiacepina o el análogoadministrados y la duración del tratamiento.Resultados. Habían utilizado unabenzodiacepina o un análogo de formaprolongada 6.885 pacientes. El 70,9% eranmujeres, el 73,4% tenía 65 años o más, y el73% estaba adscrito a un centro urbano. Laprevalencia global fue del 6,9%, mayor entrelas mujeres que entre los varones (9,7% y 4%,respectivamente), y aumentó con la edadhasta un 27,3% entre los pacientes de 75 omás años. En los resultados estratificados seobservó que el consumo crónico era superiorentre las mujeres de 75 o más años de edadadscritas a centros de salud urbanos, conuna prevalencia del 35,7%.Conclusiones. Un porcentaje elevado de lapoblación, que comprende a los pacientesmás frágiles, está siendo tratado conbenzodiacepinas o análogos, lo que no seajusta a las recomendaciones de las guíasde práctica clínica

Objective. To determine the overallprevalence of the chronic use ofbenzodiazepines and similar drugsin primary care.Design. Observational, cross-sectional study.Setting. Healthcare centres of the Reus-Altebrat Primary Care Service,Tarragona,Spain.Participants. Patients older than 15 years, onprolonged treatment with benzodiazepinesor similar drugs.Measurements. The variables studied wereage, sex, type of healthcare centre (rural orurban), benzodiazepine, or similar drugadministered and duration of treatment.Results. There were 6885 patients who wereon prolonged benzodiazepine or similardrug treatment, of which 70.9% werefemale, 73.4% were 65 years or older, and73% attended an urban centre. The overallprevalence was 6.9%, and was higher amongwomen than men (9.7% and 4%,respectively), and increased with age up to27.3% among patients of 75 years or more.The stratified results showed that chronicconsumption was higher among women75 years of age or older attached to urbanhealthcare centres, with a prevalence of35.7%.Conclusions. A high percentage of ourpopulation, which includes the most fragilepatients, use benzodiazepines or a similardrug in a way that is not consistent withthe recommendations of clinical practiceguidelines

Expert and consumer evaluation of patient medication leaflets provided in U.S. pharmacies.

OBJECTIVE: Evaluate the distribution and quality of patient medication leaflets provided in U.S. pharmacies. DESIGN: Observational. SETTING: United States. PARTICIPANTS: 384 randomly selected community pharmacies in 44 states. INTERVENTIONS: Professional shoppers (acting as patients) presented four new prescriptions to study pharmacies. MAIN OUTCOME MEASURES: Medication leaflets obtained by shoppers were evaluated by expert and consumer raters using criteria specified in federal law mandating distribution of useful written information to 95% of individuals receiving new prescriptions by 2006. RESULTS: Leaflets were provided by pharmacies with 89% of 1,536 prescriptions presented by professional shoppers posing as patients. Leaflet quality varied: 95% of leaflets received high ratings on accuracy, but only 19% received high ratings on the specificity of directions. Fewer than 10% of all leaflets met quality criteria regarding contraindications, precautions, and how to avoid harm. One fourth of all leaflets had poor print size, according to the shoppers. CONCLUSION: Additional efforts are needed to meet federally mandated information distribution and quality goals by 2006.

Seguimiento de pacientes con transplante renal + ciclosporina genérica mediante monitoreo C2 en la CCSS / Pursuit of patients with renal transplant + gneric cyclosporin by means of monitoreo C2 in the Caja Costarricense de Seguro Social

En atención a acuerdo a Junta Diectiva, se realizó un seguimiento durante los primeros 6 meses de evolución a todos los pacientes con transplante renal realizados en un periodo de 12 meses (febrero/marzo 2003-febrero 2004). Este se implementó como un Estudio de Utilización de Medicamentos (EUM) y muestra información de una serie no controlada de pacientes; su realización fue oportunamente comunicada a los comités Etico Científico de cada hospital, al CONIS y al CECI-CENDEISSS. En concordancia con los Protocolos de Transplante Renal de los hospitales nacionales donde éstos se realizaron, se registró información de los pacientes que recibieron 94 transplantes de riñón durante el periodo. Se realizó un 1º transplante a 83 pacients, un 2º a 10 pacients y un 3º a 1 paciente; la mayoría de órganos provino de donadores vivos relacionados (53 por ciento), seguido por donadores cadavéricos (37 por ciento) y vivo no relacionado (10 por ciento). Se inició el seguimento con niveles sanguíneos de ciclosporina (2) en 78 pacientes transplantados se obtuvo un registro de 81 por ciento de las determinaciones esperadas. El perfi de los niveles C2 reportados y creatinina estuvieron dentro del rango recomendado. Al final del periodo de observación, 76 (81 por ciento) de todos los tranplantes ralizados estaban funcionantes y, en general, los pacientes se encontraban en buenas condiciones generales; entre éstos, 69 pacientes (91 por ciento) estaban con ciclosporina genérica. Se registró un total de 23 casos (24 por ciento) de rechazo de injerto renal, de los cuales se rescataron exitosamente 20 pacientes (87 por ciento) con los recursos disponibles en la CCSS. En total se perdieron 18 injertos (19 por ciento) por diversas causas: 7 pacientes fallecieron por razones ajenas al transplante, 9 transplantectomías: 8 trombosis y 1 Necrosis tubular Aguda, y 2 rechazos (1 provocado por abandono del control y tratamiento y 1 que no pudo ser rescatado). Como parte del abordaje inmunosupresor con ciclosporina genérica para pacientes con transplante renal, esta serie mostró una sobrevida a 6 meses del 95.8 por ciento, con buena evolución en 69 beneficiados. En conclusión, los resultados obtendios con el presente EUM muestan que el uso de ciclosporina (genérica) como parte de la intervención inmunosupresora, contribuyó al éxito de los transplantes de riñón, tal como se esperaba según la información científica disponible.

Patterns of drug use among the community-dwelling old-old population in Israel.

BACKGROUND: Due to multiple chronic illness and disability, the elderly consume a disproportionately large share of medications. OBJECTIVES: To assess the patterns and determinants of drug use among the community dwelling old-old population. METHODS: The study population included 1,369 old-old persons from the baseline data of the Cross-Sectional and Longitudinal Aging Study (CALAS), which is based on a national random stratified sample of the Israeli Jewish population aged 75-94 years. RESULTS: The mean number of drugs used by the study population was 3.3, and only 12.5% did not consume any drugs, Multivariate linear regression analysis showed that women used significantly more drugs than men, and that those born in Europe took significantly more drugs than those born in Israel and Asia-Africa. The number of medical conditions was the strongest predictor of drug use. Hospitalizations during the last year and frequent visits to family physician were also significant factors related to drug use. All variables combined explained 40% of the variance in drug use by the old-old. The most commonly used therapeutic groups were cardiovascular drugs (53%), psychotropic drugs (31%), analgesics (30%), and gastrointestinal drugs (28%). CONCLUSIONS: Our data indicate that in addition to the association of drug use with health status and healthcare utilization, the number and type of drugs taken vary with gender and place of birth.