Relação entre benefício e risco em interações medicamentosas nas prescrições médicas de um hospital universitário no estado de São Paulo / Benefit-risk relationship in drug interactions in prescriptions from a university hospital in the state of São Paulo / Relación beneficio-riesgo en interacciones medicamentosas en prescripciones de un hospital universitario del estado de São Paulo

Objetivo: Avaliar interações medicamentosas (IM), em que os riscos se so- brepõem aos benefícios (nível I) ou os benefícios se sobrepõem aos riscos (nível II); a partir da análise retrospectiva de prescrições médicas em um Hospital Universitário no estado de São Paulo, Brasil. Métodos: Foram analisadas 19762 prescrições médicas des- tinadas à farmácia do hospital, de janeiro a setembro de 2009; com o auxílio de programas sobre IM, para categorizar IM de nível I e II. Resultados: Na análise 26,53% apresentaram IM, em que 23,64% foram classificadas em nível I e 76,35% em nível II. Dentre as IM com maior frequência no nível I, estavam: ácido acetilsalicílico (AAS) e clopidogrel, AAS e heparina, captopril e espironolactona, digoxina e hidroclorotiazida. Houve uma redução em percentual de IM de nível I, comparando janeiro representado por 26,5% e setembro representado por 18,4%. Já nas IM de nível II, tem-se as seguintes associações com maior frequência: AAS e propranolol, AAS e insulina regular humana, AAS e ate- nolol, AAS e enalapril, AAS e carvedilol. Conclusão: A atuação dos farmacêuticos cola- borou à redução de IM de nível I, devido à intervenção por meio de comunicação estabe- lecida com os prescritores; sinalizando a importância da equipe interprofissional em saúde.

Objective: To evaluate drug interactions (MI), in which risks outweigh the benefits (level I) or benefits outweigh the risks (level II); from the retrospective analysis of medical prescriptions in a University Hospital in the state of São Paulo, Brazil. Methods: 19,762 prescriptions destined to the hospital pharmacy were analyzed, from January to September 2009; with the help of programs on MI, to categorize level I and II MI. Results: In the analysis 26.53% presented MI, in which 23.64% were classified in level I and 76.35% in level II. Among the most frequent level I MI were: acetylsalicylic acid (ASA) and clopidogrel, ASA and heparin, captopril and spironolactone, digoxin and hydrochlorothiazide. There was a reduction in the percentage of level I MI, comparing January, which accounted for 26.5%, and September, which accounted for 18.4%. As for level II MI, the following associations were more frequent: ASA and propranolol, ASA and regular human insulin, ASA and atenolol, ASA and enalapril, ASA and carvedilol. Conclusion: The role of pharmacists collaborated to the reduction of level I MI, due to the intervention by means of communication established with the prescribers; signaling the importance of the interprofessional health team.

Objetivo: Evaluar las interacciones medicamentosas (IM), en las que los riesgos superan a los beneficios (nivel I) o los beneficios superan a los riesgos (nivel II); a partir del análisis retrospectivo de las prescripciones médicas en un Hospital Universitario del estado de São Paulo, Brasil. Métodos: Se analizaron 19.762 prescripciones destinadas a la farmacia del hospital, de enero a septiembre de 2009; con la ayuda de programas sobre IM, para categorizar los IM de nivel I y II. Resultados: En el análisis el 26,53% presentaron IM, en el que el 23,64% se clasificaron en nivel I y el 76,35% en nivel II. Entre los IM de nivel I más frecuentes estaban: ácido acetilsalicílico (AAS) y clopidogrel, AAS y heparina, captopril y espironolactona, digoxina e hidroclorotiazida. Hubo una reducción del porcentaje de IM de nivel I, comparando enero, que supuso el 26,5%, y septiembre, que supuso el 18,4%. En cuanto a los IM de nivel II, fueron más frecuentes las siguientes asociaciones: AAS y propranolol, AAS e insulina humana regular, AAS y atenolol, AAS y enalapril, AAS y carvedilol. Conclusiones: El papel de los farmacéuticos colaboró a la reducción de las IM de nivel I, debido a la intervención mediante la comunicación establecida con los prescriptores; señalando la importancia del equipo sanitario interprofesional.

Avaliação de medicamentos potencialmente inapropriados e da polifarmácia em pacientes idosos em um hospital universitário / Evaluation of potentially inappropriate medications and polypharmacy in elderly patients at a university hospital

Introdução: O Brasil, assim como outros países, vem alterando seu perfil demográfico elevando o número de pessoas idosas, o que repercute em mudanças não só para sociedade, mas também para saúde pública. Este grupo de pacientes é mais vulnerável devido à fisiologia inerente ao envelhecimento, logo se tornam mais propensos ao uso de medicamentos que podem causar outros problemas de saúde. Essa probabilidade de risco é uma preocupação atual e levou a criação de métodos que norteiam os prescritores para adequarem suas terapêuticas neste grupo de pacientes. Um destes métodos é o critério de Beers, que é atualizado periodicamente trazendo uma lista de medicamentos potencialmente inapropriados (MPIs) para idosos. Objetivo: Avaliar a prescrição de pacientes idosos internados no Hospital Universitário da Universidade Federal de Juiz de Fora (HU-UFJF/Ebserh) quanto à prevalência do uso de MPI e polifarmácia, no período de julho a agosto de 2019. Material e Métodos: Estudo observacional descritivo e retrospectivo, cujos dados foram coletados de prontuários pacientes idosos com idade igual ou superior a 65 anos para obtenção dos resultados que foram avaliados estatisticamente. Resultados: Foram avaliados 187 prontuários, e observada prevalência de 80,2% da prescrição de MPIs, sendo os mais prevalentes omeprazol e benzodiazepínicos. A maioria dos pacientes tiveram polifarmácia (95,7%). Conclusão: Os resultados convergem com base no critério de Beers, para necessidade de adequar a terapia de pacientes idosos. É necessário também avaliar os benefícios e alternativas quanto aos MPIs mais prevalentes, além de realizar estudos observacionais sobre possíveis efeitos adversos que possam ser consequência do uso desses medicamentos, com objetivo de aperfeiçoar a terapia farmacológica e aprimorar a farmacoeconomia, melhorando assim a qualidade de vida dos pacientes idosos.

Introduction: Brazil, like other countries, has been changing its demographic profile, increasing the number of elderly people, which reflects in changes not only for society, but also for public health. This group of patients is more vulnerable due to the inherent physiology of aging, so they become more likely to use medications that can cause other health problems. This risk probability is a current concern and has led to the creation of methods that guide prescribers to adapt their therapies in this group of patients. One of these methods is the Beers criterion, which is periodically updated with a list of potentially inappropriate medications (PIM) for the elderly. Objective: To evaluate the prescription of elderly patients hospitalized at the University Hospital of Juiz de Fora (HU-UFJF/Ebserh) regarding the prevalence of the use of PIM and polypharmacy, from July to August 2019. Material and Methods: Descriptive and retrospective observational study, whose data were collected from medical records of elderly patients aged 65 years or older to obtain the results that were statistically evaluated. Results: A total of 187 medical records were evaluated, and a prevalence of 80.2% of the prescription of PIMs was observed, the most prevalent being omeprazol and benzodiazepines. Most patients had polypharmacy (95.7%). Conclusion: The results converge, based on the Beers criterion, for the need to suit the therapy of elderly patients. It is also necessary to evaluate the benefits and alternatives regarding the most prevalent PIMs, in addition to conducting observational studies on possible adverse effects that may be a consequence of the use of these medications, aiming to refine pharmacological therapy and improve pharmacoeconomics, thus improving quality of life of elderly patients.

Prescription de l'oxygène dans le service d'urgence d'un hôpital de référence de Mahajanga

Introduction : L'oxygène est un médicament. Une prescription non appropriée peut occasionner une insuffisance ou un excès d'apport source de dépenses hospitalières dans les pays en développement. L'objectif était d'évaluer la prescription de l'oxygénothérapie dans un service d'urgence et de soins intensifs et d'observer les modalités d'utilisation pour permettre d'ajuster les objectifs et les cibles thérapeutiques en prenant comme référence les recommandations. Matériels et Méthodes : Il s'agit d'une étude prospective descriptive sur trois mois, en 2018, de la prescription de l'oxygène au service des urgences et de soins intensifs dans un hôpital de référence de Mahajanga. Quatre obus et quatre extracteurs étaient les sources d'oxygène pour 18 lits d'accueil, de déchoquage et de soins intensifs. Ni un générateur d'oxygène ni des matériels de ventilation spécifique n'étaient disponibles. L'étude statistique a été réalisée avec le logiciel SPSS® v.20, le test Khi2 utilisé pour la comparaison des valeurs avec un seuil de signification p˂0,05. Résultats : Sur 599 admissions, 244 patients (40,7%) bénéficiant d'un apport en oxygène ont été inclus dans l'étude. L'âge moyen était de 47,6 ans avec prédominance masculine (sex-ratio de 1,4). Une saturation d'au plus 90% a été retrouvée dans 25% des cas. Les 40% des patients ont été référés pour une « oxygénothérapie ¼. Les pathologies en cause étaient neurologiques dans 34,4% des cas, touchant la tranche d'âge de 40 à 60 ans (p=0,006), respiratoires pour 21,7% et cardio-vasculaires dans 13,9%. Les lunettes à oxygène étaient utilisées à 71,7%, l'obus à oxygène à 69,3% dans les premières 24 heures (p=0,001). La mortalité était de 22,5% avec 60,6% des patients décédés qui avaient une saturation en oxygène de 90% au maximum (p=0,05). Conclusion : Un algorithme standard avec une saturation pulsée en oxygène ciblée et des techniques plus appropriées auraient permis d'économiser l'oxygène hospitalier et de réduire la mortalité.

Background: Oxygen is a drug. An inappropriate prescription can lead to insufficient or excessive intake, which is a source of hospital expenditure in low-income countries. The aim of the study was to assess the prescription of oxygen therapy in an emergency and intensive care unit and to observe the modalities of its use to allow adjustment of the therapeutic objectives and targets according to the current recommendations. Materials and Methods: We conducted a prospective descriptive study over three months, in 2018, of the prescription of oxygen in the Emergency and Intensive Care Department, of a referral hospital in Mahajanga. Four oxygen cylinder and 4 concentrators were available as oxygen sources for 18 beds intended for patient reception, destock and intensive care. The hospital did not have an oxygen generator or specific ventilation equipment. The statistical study was carried out with SPSS® v.20 software, the Khi2 test used for the comparison of values with a significance level p˂0.05. Results: Of 599 admissions, 244 patients (40.7%) receiving oxygen were included in the study. The average age was 47.6 years with a male predominance (sex ratio : 1.4). Oxygen saturation ≤90% was found in 25% of cases. The 40% of patients were referred for "oxygen therapy". The main disease were neurological in 34.4%, affecting the age group of 40 to 60 years (p=0.006); respiratory for 21.7% and cardiovascular in 13.9%. Nasal cannulas were used in 71.7%, the oxygen cylinder in 69.3% in the first 24 hours (p=0.001). Mortality was 22.5% of which 60.6% had oxygen saturation ≤90% (p=0.05). Conclusion: Using a standard algorithm with targeted SpO2 and more appropriate techniques would have saved hospital oxygen and reduced mortality.

Captopril oral solution for pediatric use: formulation, stability study and palatability assessment in vivo

Abstract he aim of this work was to develop an oral solution of captopril at 5 mg/mL preservative-free. Two formulations were prepared, one containing sweetener (formulation 1) and the other without this excipient (formulation 2). The results found of validation parameters from analytical method performed by HPLC for captopril were, linearity 0.9998, the limit of detection 15.71 µg/mL, the limit of quantification 47.60 µg/mL, repeatability 1.05%, intermediate precision 2.42%, accuracy intraday 101,53%, accuracy inter-day 99.85%. Moreover, the results found for captopril disulfide were, linearity 0.9999, limit of detection 0.65 µg/mL, limit of quantification 1.96 µg/mL, repeatability 2.28%, intermediate precision 1.51%, accuracy intraday 101.36%, accuracy inter-day 100.29%. The appearance of formulations was clear and colorless, pH measures were 3.12 and 3.04, dosage of captopril and captopril disulfide were 99.45% and 99.82%, 0.24% and 0.12% for formulation 1 and formulation 2, respectively. The stability study demonstrated that the concentration of captopril and captopril disulfide in the formulations was > 90% and below 3%, respectively. The in vivo palatability study in animals and humans showed that Formulation 1 containing the sweetener had better acceptance. Thus, the sweetener was able to improve the unpleasant taste of the formulation

Estudio comparativo de una asociación de diclofenac, betametasona y vitamina b12 (blokium b12®) con diclofenac (sin asociar) en el tratamiento de patología dolorosa de columna con compromiso neural / COMPARATIVE STUDY OF AN ASSOCIATION OF DICLOFENAC, BETAMETASONE AND VITAMIN B12 (BLOKIUM B12®) WITH DICLOFENAC (WITHOUT ASSOCIATION) IN THE TREATMENT OF PAINFUL SPINE PATHOLOGY WITH NEURAL COMMITMENT

El dolor lumbar bajo y el dolor cervical con o sin irradiación son causas muy comunes de consulta a los médicos generalistas en los países desarrollados. La discopatía aguda y el dolor por estenosis del canal espinal son los diagnósticos más frecuentes. La postura tradicional ha sido la de administrar antiinflamatorios no esteroideos (AINES) para estas lumbalgias o cervicalgias agudas. Cuando existe irradiación neural por compresión radicular es usual asociar al AINE un corticoide a baja dosis, así como un antineurítico, para lograr un mejor resultado. Con el objeto de documentar la utilidad de esta práctica habitual, efectuamos en 142 pacientes ambulatorios un estudio multicéntrico randomizado que compara la efectividad y la tolerancia de una asociación a dosis fija de diclofenac, betametasona y cianocobalamina administrada por vía oral versus la administración de diclofenac como monofármaco en el tratamiento de la patología dolorosa de la columna lumbar y cervical asociada a compresión neural. La asociación demostró ser más eficaz en controlar el dolor y mejorar la funcionalidad de los pacientes que la administración de diclofenac en forma aislada y se asoció a escasos efectos colaterales, principalmente digestivos

Low back pain and neck pain with or without radiation are very common causes of consultation with general practitioners in developed countries. Acute discopathy and pain due to spinal canal stenosis are the most frequent diagnoses. The traditional approach has been to administer non-steroidal antiinflammatory drugs (NSAIDs) for these acute low back or cervical pain. When there is neural radiation due to root compression, it is usual to associate a low-dose corticosteroid with the NSAID, as well as an antineuritic, to achieve a better result. In order to document the usefulness of this routine practice, we conducted a randomized multicenter study in 142 outpatients that compared the effectiveness and tolerance of a fixed-dose combination of diclofenac, betamethasone, and cyanocobalamin administered orally versus the administration of diclofenac as Monopharmaceutical in the treatment of painful pathology of the lumbar and cervical spine associated with neural compression. The association proved to be more effective in controlling pain and improving the functionality of patients than the administration of diclofenac in isolation and was associated with few side effects, mainly digestive

Past, present, and future of COVID-19: a review

SARS-CoV-2 has recently emerged, becoming a global threat, affecting directly all human beings owing to its morbidity and mortality and indirectly, due to the enormous economic and psychological impact produced by social isolation, the most effective measure so far, but unsustainable for a long period. The scientific effort to understand and control SARS-CoV-2 transmission and clinical impact has been huge, and important achievements are highlighted in this review. Diagnosis is central and is the first step in recognizing and fighting any infectious agent. Instrumental to that is the quality of the data, relying on serological and molecular surveys in addition to trustworthy clinical records. However, the fast spread of a virus adapted for human-to-human respiratory transmission raised a demand for millions of molecular tests that are simply not available. Several candidate drugs are under evaluation in clinical trials. Those with an already recognized safety profile are more auspicious, since, if proven effective, can cut several steps of production and phase 2 and 3 trials. More than one hundred vaccine prototypes are in different stages of development, however, safety and efficacy evaluations cannot be obviated, implicating, most optimistically, in at least months for us to have an effective immunization, the definite measure to allow a safe return to the pre-pandemic lifestyle. Science has never been more necessary and present in daily life. Relying on the best of human wit is the only way out to this pandemic, saving as many lives as possible.

Evaluación de la Calidad vs precio de comprimidos de Metformina de 850mg de producción nacional e importados, comercializados en Paraguay utilizados para el control de diabetes / Quality vs. price evaluation of national and imported 850 mg metformin tablets marketed for the control of diabetes in Paraguay

La metformina es un fármaco de primera elección, solo o combinado, en el tratamiento inicial de pacientes con diabetes tipo 2, cuya prevalencia a nivel nacional es de 8,0% en hombres y 8,3% en mujeres, con un gasto anual de 283 USD/persona. El estudio fue realizado con el objetivo de evaluar la calidad fisicoquímica y precio de comprimidos de 850 mg de metformina comercializados en nuestro país. Se analizaron medicamentos de producción nacional e importada, conteniendo 850 mg de metformina HCl, tomando como referencia la Farmacopea de los Estados Unidos (USP 38). Para evaluar la calidad de los productos se realizaron ensayos físicos químicos, además de los perfiles de disolución según el medio propuesto por la USP 38. Los resultados obtenidos se encontraron dentro de las especificaciones de valoración, entre 96% y 101% de metformina y los perfiles de disolución entre 70% y 90% de la cantidad declarada en 20 minutos, con una eficiencia de disolución (EF) entre 58% y 93%, mostrando que no existe diferencia estadísticamente significativa (p=0,41). La variación de precios encontrados fue entre 3,6 USD y 8,4 USD. Los productos analizados pueden ser intercambiables en cuanto a la calidad y los perfiles de disolución in vitro, siendo una herramienta para demostrar intercambiabilidad de productos farmacéuticos, buscando el precio más accesible en el mercado nacional y facilitando el tratamiento adecuado sobre todo para la población de escasos recursos manteniendo la calidad y eficacia del mismo(AU)

Experiencia peruana en el tratamiento de hepatitis crónica C con las nuevas drogas antivirales de acción directa / Peruvian experience in the treatment of chronic hepatites C with the new direct acting antiviral drugs

Objetivos: La terapia ideal para la hepatitis crónica C consiste en el uso de drogas antivirales de acción directa (DAA). En el Perú la experiencia en vida real con DAA no se conoce, por lo que el objetivo del presente estudio es reportar la alta eficacia terapéutica con estos esquemas. Material y métodos: Mediante correo electrónico se invitó a participar a través de una encuesta a médicos hepatólogos a nivel nacional. Se incluyeron los datos de 4 médicos. Los resultados fueron analizados con estadística descriptiva. Resultados: Se incluyeron 63 pacientes, la edad promedio fue 59 años, varones fueron 49,21%, cirrosis estuvo presente en el 49,21% (31/63), 34,92% había sido no respondedor a terapia con PEGIFN/RBV. El Genotipo 1 estuvo presente en 93,65% de casos, siendo el 1a el predominante (58,73%). Solo hubo dos casos de genotipo 2 y uno de genotipo 3. Se utilizaron 10 esquemas de combinación con DAA, siendo los más eficaces, Sofosbuvir/Ledipasvir, Sofosbuvir/Ledipasvir/ Ribavirina y Sofosbuvir/Simeprevir, en todos ellos se logró Respuesta Viral Sostenida (RVS) de 100%. Con los otros 7 esquemas la RVS fue menor a 90% o solo se había incluido uno o dos pacientes. La tolerancia a la terapia fue adecuada y todos los pacientes culminaron la terapia. Conclusiones: En vida real los esquemas de terapia antiviral para hepatitis C con DAA tienen alta eficacia y seguridad. Las mejores respuestas se obtuvieron con Sofosbuvir/Ledipasvir, Sofosbuvir/Ledipasvir/Ribavirina y Sofosbuvir/Simeprevir. Esta data puede ser útil para considerar estrategias de tratamiento con el enfoque de salud pública.

Objective: The ideal therapy for chronic hepatitis C is the use of direct acting antivirals (DAA). In Peru there is no data in this aspect, in that sense it is necessary to report real life experience with these drugs. Material and methods: A digital survey was sent through e-mail to hepatologists, and the data of four is considered in this study. Statistical analysis was descriptive. Results: We included 63 patients, mean age was 59 years, 49.21% were male, cirrhosis was present in 49.21%, and 34.92% was non-responder to PEGIFN and Ribavirin. Genotype 1 was present in 93.65%, and subtype 1a was 58.73%, there were only 2 cases with Gt 2 and one with Gt 3. There were 10 different DAA combinations used, and the most effective were Sofosbuvir/ Ledipasvir, Sofosbuvir/Ledipasvir/Ribavirina and Sofosbuvir/Simeprevir, in all these cases the Sustained Viral Response (SVR) was 100%. The other combinations had SVR < 90% or only 1-2 patients included. All patients tolerated treatments and no serious adverse events occurred. Conclusions: In real life antiviral treatment for hepatitis C with AAD is effective and well tolerated. The best SVR was obtained with Sofosbuvir/Ledipasvir, Sofosbuvir/Ledipasvir/Ribavirina and Sofosbuvir/Simeprevir. This report may be useful to consider treatment strategies with focus in public health.

Added therapeutic value of new drugs approved in Brazil from 2004 to 2016 / Valor terapêutico acrescentado de novos medicamentos aprovados no Brasil de 2004 a 2016 / Valor terapéutico añadido de los nuevos medicamentos aprobados en Brasil desde 2004 a 2016

Abstract: This study aimed to assess the level of therapeutic innovation of new drugs approved in Brazil over 13 years and whether they met public health needs. Comparative descriptive analysis of therapeutic value assessments performed by the Brazilian Chamber of Drug Market Regulation (CMED) and the French drug bulletin Prescrire for new drugs licensed in Brazil, from January 1st 2004 to December 31st 2016. The extent to which new drugs met public health needs was examined by: checking inclusions into government-funded drug lists and/or clinical guidelines; comparing Anatomical Therapeutic Chemical Classification (ATC) codes and drug indications with the list of conditions contributing the most to the national disease burden; and assessing new medicines aimed to treat neglected diseases. 253 new drugs were approved. Antineoplastics, immunossupressants, antidiabetics and antivirals were the most frequent. Thirty-three (14%) out of 236 drugs assessed by the Brazilian chamber and sixteen (8.2%) out of 195 assessed by the French bulletin Prescrire were considered innovative. Thirty-six drugs (14.2%) were selected for coverage by the Brazilian Unified National Health System (SUS), seven of which were therapeutically innovative, and none were aimed to treat neglected disease. About 1/3 of the drugs approved aimed to treat conditions among the top contributors to Brazil's disease burden. Few therapeutically innovative drugs entered the Brazilian market, from which only a small proportion was approved to be covered by the SUS. Our findings suggest a divergence between public health needs, research & development (R&D) and drug licensing procedures.

Resumo: O objetivo foi avaliar o nível de inovação terapêutica de novos medicamentos aprovados no Brasil ao longo de 13 anos e se eles atendem a necessidades de saúde pública. Foi feita uma análise comparativa descritiva da avaliação de valor terapêutico realizada pela Câmara de Regulação do Mercado de Medicamentos (CMED) e pelo boletim de medicamentos francês Prescrire para novos medicamentos licenciados no Brasil entre 1º de janeiro de 2004 e 31 de dezembro de 2016. Examinamos em que medida os novos medicamentos atendem a necessidade de saúde pública por meio de: checagem da inclusão em listas de medicamentos financiados pelo governo e/ou diretrizes clínicas; comparação de códigos da Classificação Anatômica Terapêutica Química (ATC, em inglês) e indicações de medicamentos com a lista de condições que mais contribuem para a carga de doença nacional; e avaliação de se os novos medicamentos tinham por objetivo tratar doenças negligenciadas. Foram aprovados 253 novos medicamentos. Antineoplásicos, imunossupressores, antidiabéticos e antivirais foram os mais frequentes. Trinta e três (14%) dos 236 medicamentos avaliados pela Câmara brasileira e 16 (8,2%) dos 195 avaliados pelo boletim francês Prescrire foram considerados inovadores. Trinta e seis medicamentos (14,2%) foram selecionados para cobertura no Sistema Único de Saúde (SUS), sete dos quais eram inovadores do ponto de vista terapêutico e nenhum dos quais tinha por objetivo tratar uma doença negligenciada. Em torno de 1/3 dos medicamentos aprovados tinha por objetivo o tratamento de doenças que figuram entre as principais contribuidoras da carga de doença no Brasil. Poucos medicamentos inovadores do ponto de vista terapêutico entraram no mercado brasileiro, dos quais apenas uma pequena proporção foi aprovada para ser coberta pelo SUS. Nossos resultados sugerem uma divergência entre necessidades de saúde pública, pesquisa e desenvolvimento (P&D) e procedimentos de licenciamento de medicamentos.

Resumen: El objetivo fue evaluar el nivel de innovación terapéutica de los nuevos medicamentos aprobados en Brasil durante 13 años y si cumplen con las necesidades sanitarias. Llevamos a cabo un análisis comparativo descriptivo acerca del valor terapéutico presente en las evaluaciones realizadas por la Cámara de Regulación del Mercado de Medicamentos (CMED) y la revista francesa Prescrire sobre los nuevos medicamentos autorizados en Brasil, desde el 1º de enero 2004 hasta el 31de diciembre de 2016. Su alcance, es decir, hasta qué punto los nuevos medicamentos cumplían con las necesidades de salud pública se comprobaron revisando las inclusiones en listas de medicamentos subvencionados por el gobierno y/o directrices clínicas; comparando los códigos de la Classificación Anatómicos Terapéuticos Químicos (ATC por sus siglas en inglés) y las indicaciones de los medicamentos respecto a la lista de enfermedades que contribuían a la mayor carga de morbilidad nacional; y asesorando si los nuevos medicamentos tenían como objetivo tratar enfermedades desatendidas. Se aprobaron 253 nuevos medicamentos. Los antineoplásicos, inmunosupresores, antidiabéticos y antivirales fueron los más frecuentes. Treinta y tres (14%), aparte de los 236 medicamentos evaluados por la Cámara Brasileña, y 16 (8,2%), aparte de los 195 evaluados por la revista francesa Prescrire, se consideraron innovadores. Treinta y seis medicamentos (14,2%) se seleccionaron para que tuvieran cobertura por el Sistema Único de Salud (SUS), siete de ellos eran terapéuticamente innovadores, y ninguno tenía como meta tratar enfermedades desatendidas. Alrededor de 1/3 de las medicinas aprobadas tenían como meta tratar problemas de salud entre las enfermedades con mayor carga de morbilidad en Brasil. Pocos medicamentos terapéuticamente innovadores accedieron al mercado brasileño y de éstos sólo una pequeña parte fueron aprobados para que fueran cubiertos por el SUS. Nuestros resultados sugieren una divergencia entre las necesidades públicas de salud, investigación & desarrollo (I&D) y los procedimientos para la autorización de medicamentos.

Assessing the overall medication use by elderly people in a Brazilian hospital using the start/stopp criteria version 2

To estimate the frequency of the use of medicines listed in the Screening Tool to Alert Doctors to the Right Treatment (START) and Screening Tool of Older Person's Prescriptions (STOPP) criteria version 2 among the elderly. A cross-sectional study was conducted on elderly who were attended in medical clinic and cardiology sectors in a hospital in southern Brazil attended at a hospital from February through September 2016. A data-collection tool was used to obtain information on variables, such as demographic and clinical data, and medications used before and during the hospitalization period. The adequacy of the medicines taken was examined with regard to omission (START) or inappropriate use (STOPP). This study was approved by the Research Ethics Committee of the University of Southern Santa Catarina. A total of 307 subjects were included in the final sample. The mean age was 75.2 years (SD = 8; range 65-102). Of the total, 93.5% had had at least one potential prescribing omission (PPO) listed in the START criteria, whereas 95.4% used at least one medicine of the STOPP criteria. PPO was significantly associated with lower mean age (74.9 years, SD = 7.9 versus 79.0 years, SD = 8.8) among the elderly who did not have PPOs detected by the START criteria (p-value=0.03). Furthermore, PPO was associated with longer hospital stay (18 versus 9 days; p-value=0.03). This study revealed inadequate prescription affecting 99.3% of the participating patients. To the best of our knowledge, this was the first to use the START and STOPP criteria, version 2, in Brazil.

Valor terapéutico y precio de los nuevos fármacos comercializados en Argentina: ¿valen lo que cuestan? / Therapeutic value and price of the new pharmaceuticals commercialized in Argentina: Are they worth what they cost?

RESUMEN En Argentina, los nuevos medicamentos pueden ser autorizados presentando el certificado de aprobación en al menos uno de los 15 países considerados de alta vigilancia sanitaria, sin necesidad de realizar una evaluación propia de eficacia, seguridad o valor terapéutico agregado por el nuevo producto. En este artículo, evaluamos los nuevos medicamentos comercializados en Argentina en el año 2016, utilizando diferentes enfoques: su aprobación por otras agencias reguladoras, demostración de eficacia en ensayos clínicos aleatorizados, tipo de desenlaces estudiados, calificación del valor terapéutico agregado por medio de dos escalas reconocidas y el precio de venta al público. Se concluye que, como reflejo de lo que ocurre en los países desarrollados, los nuevos medicamentos ingresan con precios exorbitantes, pero la mayoría no representa un avance terapéutico significativo. El resultado es un aumento de riesgos para los pacientes y una sobrecarga para los sistemas de financiación públicos y privados.

ABSTRACT In Argentina, new drugs can be authorized by presenting the drug's certificate of approval in at least one of 15 countries considered to have rigorous health surveillance, without needing to carry out a local evaluation of the efficacy, safety or added therapeutic value of the new product. In this article, we evaluate the new drugs commercialized in Argentina in 2016 using different approaches: their approval by other regulatory agencies, the demonstration of their efficacy in randomized clinical trials, types of outcomes studied, rating of their added therapeutic value using two widely recognized scales, and their sale price to the public. It is concluded that, as a reflection of what occurs in developed countries, new drugs enter the market at exorbitant prices, but the majority do not represent a significant therapeutic advancements. The result is increased risks to patients and an overburdening of the public and private funding systems.

Neurogenesis and gliogenesis modulation in cerebral ischemia by CDK5 RNAi-based therapy / Modulación de la neurogénesis y la gliogénesis en la isquemia cerebral mediante una terapia basada en la interferencia de CDK5

Abstract Introduction: Cerebral ischemia is the third cause of death risk in Colombia and the first cause of physical disability worldwide. Different studies on the silencing of the cyclin-dependent kinase 5 (CDK5) have shown that reducing its activity is beneficial in ischemic contexts. However, its effect on neural cell production after cerebral ischemia has not been well studied yet. Objective: To evaluate CDK5 silencing on the production of neurons and astrocytes after a focal cerebral ischemia in rats. Materials and methods: We used 40 eight-week-old male Wistar rats. Both sham and ischemia groups were transduced at CA1 hippocampal region with an adeno-associated viral vector using a noninterfering (shSCRmiR) and an interfering sequence for CDK5 (shCDK5miR). We injected 50 mg/kg of bromodeoxyuridine intraperitoneally from hour 24 to day 7 post-ischemia. We assessed the neurological abilities during the next 15 days and we measured the immunoreactivity of bromodeoxyuridine (BrdU), doublecortin (DCX), NeuN, and glial fibrillary acid protein (GFAP) from day 15 to day 30 post-ischemia. Results: Our findings showed that CDK5miR-treated ischemic animals improved their neurological score and presented increased BrdU+ cells 15 days after ischemia, which correlated with higher DCX and lower GFAP fluorescence intensities, and, although mature neurons populations did not change, GFAP immunoreactivity was still significantly reduced at 30 days post-ischemia in comparison with untreated ischemic groups. Conclusion: CDK5miR therapy generated the neurological recovery of ischemic rats associated with the induction of immature neurons proliferation and the reduction of GFAP reactivity at short and longterm post-ischemia.

Resumen Introducción. La isquemia cerebral es la tercera causa de riesgo de muerte en Colombia y la primera causa de discapacidad física en el mundo. En diversos estudios en los que se silenció la cinasa 5 dependiente de la ciclina (CDK5) se ha demostrado que la reducción de su actividad es beneficiosa frente a la isquemia. Sin embargo, su efecto sobre la neurogénesis después de la isquemia no se ha dilucidado suficientemente. Objetivo. Evaluar el silenciamiento de la CDK5 en la neurogénesis y la gliogénesis después de la isquemia cerebral focal en ratas. Materiales y métodos. Se usaron 40 machos de rata Wistar de ocho semanas de edad. Los grupos de control y los isquémicos sometidos a transducción en la región del hipocampo CA1, se inyectaron intraperitonealmente por estereotaxia con 50 mg/kg de bromodesoxiuridina (BrdU) a partir de las 24 horas y hasta el día 7 después de la isquemia, con un vector viral asociado a adenovirus usando una secuencia no interferente (SCRmiR) y una interferente (CDK5miR). Se evaluó la capacidad neurológica durante los quince días siguientes y se detectó la capacidad de inmunorreacción para la BrdU, la proteína doblecortina (DCX), los núcleos neuronales (NeuN), y la proteína fibrilar acídica de la glía (Glial Fibrillary Acidic Protein, GFAP) a los 15 y 30 días de la isquemia. Resultados. Los animales isquémicos tratados con CDK5miR mejoraron su puntuación neurológica y presentaron un incremento de la BrdU+ a los 15 días de la isquemia, lo cual se correlacionó con una mayor intensidad de la DCX+ y una menor de la GFAP+. No hubo modificación de los NeuN+, pero sí una reducción significativa de la GFAP+ a los 30 días de la isquemia en los animales tratados comparados con los animales isquémicos no tratados. Conclusión. La terapia con CDK5miR generó la recuperación neurológica de ratas isquémicas asociada con la inducción de la neurogénesis y el control de la capacidad de reacción de la proteína GFAP a corto y largo plazo después de la isquemia.

Inmunología y consumo de medicamentos: reacciones adversas de baja frecuencia tipo B / Immunology and drugs´ consumption: type B low-frequency adverse reactions

Introducción: para el Sistema Cubano de Farmacovigilancia, es importante la detección de efectos adversos ocasionales, raros o muy raros e incluso no descritos, este es el punto de partida para generar hipótesis de relaciones causales entre la administración de un fármaco y la aparición de un determinado efecto adverso. Objetivo: describir las reacciones adversas tipo B en Cuba notificadas al sistema de farmacovigilancia y las bases inmunológicas para su interpretación. Materiales y métodos: se realizó una investigación documental y análisis de contenido de las publicaciones identificadas en la literatura nacional e internacional que tratan el tema. Resultados: se presentan los elementos teóricos metodológicos para el abordaje de la seguridad del consumo de medicamentos, farmacovigilancia y reacciones adversas a medicamentos, así como su interpretación inmunológica y perfil de baja frecuencia tipo B. Conclusiones: el perfil de reacciones adversas tipo B en Cuba es alto por lo que el estudio de estas teniendo en cuanta su interpretación inmunológica resulta información valiosa para la caracterización de la seguridad de los medicamentos y para la toma de decisiones en salud (AU).

Introduction: for the Cuban System of Pharmacovigilance, the detection occasionally adverse, rare or very rare, and even non-described is important. This is the starting point to generate hypotheses of casual relations between drug administration and the emergency of a determinate adverse effect. Objective: to describe the type B adverse reactions in Cuba that have been notified to the pharmacovigilance system and the immunologic bases for their interpretation. Material and methods: it was carried out a documental research and a content analysis of the identified national and international publications dealing with the theme. Results: the theoretical and methodological elements for dealing with drug consumption security, pharmacovigilance and drug adverse reactions are given, and also their immunologic interpretation and type B low-frequency profile. Conclusions: the type B adverse reaction´s profile in Cuba is high; therefore their study, taking into account their immunologic interpretation is a valuable information for characterizing drugs security and for taking decisions in public health care (AU).

Diez años de la regulación de los productos de uso y consumo humano en el Instituto Nacional de Higiene "Rafael Rangel" (2008-2018) / Ten years of the sanitary regulation of the products of use and human consumption in the National Institute of Hygiene "Rafael Rangel" (2008-2018)

La Gerencia Sectorial de Registro y Control se crea en el año 1993 con el objetivo de proteger la salud y la vida de la población Venezolana, estando conformada por la División de Control de Medicamentos y Cosméticos, la División de Control de Alimentos y la División de Control Nacional de Productos Biológicos. Esta Gerencia viene a llenar un vacío legal existente en materia de salud y entre sus funciones se encuentran: •Otorgar el Registro Sanitario, Renovación y Cambios Post- Registro a los Medicamentos (Especialidades Farmacéuticas y Productos Biológicos) comercializados en el país, previa evaluación de su calidad, seguridad y eficacia. •Realizar el Control Sanitario de los medicamentos. •Evaluar con fines de registro y control sanitario los alimentos, productos naturales, cosméticos, productos médicos y otros productos de uso y consumo humano. •Evaluar los Protocolos de Investigación Clínica de Medicamentos. •Efectuar la Farmacovigilancia de los medicamentos distribuidos a nivel nacional. •Evaluar el desempeño en Serología de los Bancos de Sangre del país. •Coordinar la Red Venezolana de Laboratorios de Análisis de Alimentos. •Participar en las Redes Internacionales de Armonización y Cooperación en el área de competencia.

The Sectorial Management of Registration and Control was created in 1993 with the objective of protecting the health and life of the Venezuelan population, being formed by the Division of Control of Medicines and Cosmetics, the Division of Food Control and the Division of National Control of Biological Products. This Management comes to fill an existent legal void in matter of health and between its functions they are: •Grant the Sanitary Registration, Renewal and Post-Registration Changes to Drugs (Pharmaceutical Specialties and Biological Products) marketed in the country, after evaluating their quality, safety and efficacy. •Carry out the Sanitary Control of medicines. •Evaluate for sanitary registration and control purposes food, natural products, cosmetics, medical products and other products for human use and consumption. •Evaluate the Clinical Drug Resechar Protocols. •Carry out pharmacovigilance of medicines distributed nationwide. •Evaluate the performance in Serology of the Blood Banks of the country. •Coordinate the Venezuelan Network of Food Analysis Laboratories. •Participate in the International Networks of Harmonization and Cooperation in the eaar of competence

Sedación en la oficina del odontólogo: ¿Midazolam o Clonazepam? / Midazolam or Clonazepam for sedation at the dentistry office?

Introducción: Con frecuencia anestesiólogos son requeridos para trabajar fuera de pabellón quirúrgico intrahospitalario. Un campo interesante es la sedación en la consulta odontológica. Esto plantea un desafío dada la lejanía de un hospital, que le impide contar con ayuda inmediata en caso de una situación de emergencia y a la angustia que genera al paciente el procedimiento, por lo que debe lograrse un perfecto balance entre seguridad y ansiolisis. Material y Método: Se estudiaron pacientes sometidos a instalación de implantes dentales. Se comparó el uso de midazolam (M) y clonazepam (C) evaluando la satisfacción del implantólogo y del paciente. Resultados: Se estudiaron 67 pacientes y al evaluar su satisfacción, ésta se catalogó como buena y muy buena con ambos fármacos. Sin embargo en la evaluación del odontólogo se encontraron diferencias, ya que en el grupo M, tres casos fueron evaluados como regulares y ningún caso en el grupo C (p < 0.05). La causa de esta mala evaluación, fue explicada por el operador debido a que estos enfermos no fueron capaces de abrir la boca de manera satisfactoria. No se registraron episodios de desaturación, hipotensión, ni crisis hipertensiva. Discusión: Se demostró que la sedación con benzodiacepinas fue útil y segura. Sin embargo, la utilización de midazolam llevaría a un estado de hipnosis más profundo que impediría al paciente abrir bien su boca, hecho que dificultó el procedimiento dental. En conclusión el clonazepam podría tener la ventaja de lograr altos niveles de satisfacción tanto del profesional como del paciente.

Background: Increasingly, anesthesiologists are often required to perform procedures outside the operating room. An interesting field is sedation in the dental office. This poses a major challenge given the remoteness of a hospital and the anxiety generated in the patient. Therefore a perfect balance must be achieved between anxiolysis and safety for each case. Materials and Methods: We prospectively studied patients undergoing dental implants. We compared the use of two benzodiazepines, midazolam (M) and clonazepam (C) and evaluated the satisfaction of both the dental surgeon and the patient. Results: We studied 67 patients. When assessing patient satisfaction the patients were classified as good and very good with both drugs. However dentists in the evaluation some differences were found between the two groups, in the M group, three cases were evaluated as fair and no cases in group C (p <0.05). The cause of this poor assessment was explained by the operator, as a result of these three patients not being able to open their mouths during the procedure. There were no episodes of desaturation, hypotension or hypertensive crisis in any of the patients. Discussion: We demonstrated that sedation with benzodiazepines in the dentist's office as a useful and safe alternative with either midazolam or clonazepam. However, the use of midazolam leads to a deeper state of hypnosis that would prevent the patient to open the mouth suffuciently, making it difficult a dental procedure. In conclusion clonazepam could have the advantage of achieving high levels of satisfaction from both the dentist and the patient.

Evaluation of risk factors that contribute to falls among the elderly / Avaliação dos fatores de risco que contribuem para queda em idosos

Abstract Objective: to determine the incidence of falls among the elderly population of the city of Barbacena in the state of Minas Gerais, together with causal factors, circumstances and major consequences. Methods: a cross-sectional study was performed through questionnaires applied to 206 patients over the age of 60, from November 2014 to February 2015 in the city of Barbacena, in the state of Minas Gerais. Risk factors related to falls were analyzed, as well as the incidence of falls and the consequences for the lives of elderly persons. The existence of a relationship between the reporting of falls and possible risk factors was determined by the Chi-squared and Fischer's exact tests as indicated. Results: an incidence of falls of 36.41% was observed among the elderly, 45.95% of which occurred outside the home. A total of 85.71% of respondents had previously suffered strokes and 39.78% were taking medication. Among elderly persons who have fallen and suffered fractures (18.67%), 50% had suffered strokes, 50% were suffering from chronic kidney disease, and 61.54% could not perform their activities of daily living after the fall. Conclusion: it was concluded that the incidence of falls among the elderly was 36.41%, while the most correlated factors were drug use, stroke victims and people with chronic kidney disease. Among those who suffered fractures, 61.54% failed to perform activities of daily living. Preventing falls is a public health concern, and simple changes can reduce its prevalence. AU

Resumo Objetivo: descrever incidência de quedas em idosos no município de Barbacena, MG, com seus fatores causais, circunstâncias e consequências. Método: estudo de corte transversal, realizado mediante aplicação de questionários em 206 pacientes acima de 60 anos de idade, de novembro 2014 a fevereiro de 2015. Foram analisados fatores de risco, incidência e consequência das quedas na vida dos idosos. Foram construídas distribuições de frequência e calculadas as médias, desvios-padrão e percentagens. A existência de relação entre o relato de quedas e seus possíveis fatores de risco foi determinada por Teste qui-quadrado e exato de Fischer conforme a indicação. Resultados: observou-se a incidência de 36,41% de queda em idoso, sendo que 45,95% ocorreram fora de casa, 85,71% dos pesquisados já haviam sofrido acidente vascular encefálico (AVE) e 39,78% faziam uso de medicamento. Dos idosos que caíram e sofreram fratura (18,67%), 50% já tinham sofrido episódio de AVE e 50% eram portadores de doença renal crônica, sendo que 61,54% deixaram de realizar suas atividades diárias após a queda. Conclusão: a incidência de queda em idosos foi de 36,41%. Os fatores mais correlacionados foram uso de medicamentos, vítimas de AVE, portadores de doença renal crônica e, dos que sofreram fratura, 61,54% deixaram de realizar atividades diárias. Desta forma, a prevenção das quedas é uma preocupação de saúde pública e mudanças relativamente simples podem reduzi-las. AU

Surface Degradation of Resin-based Materials by Pediatric Syrup Containing Amoxicillin under Erosive Challenge

Objective: To investigate the effect of a pediatric syrup containing Amoxicillin on resin-based on the surfaces of resin-based materials under pH cycling. Material and Methods: Cylindrical samples (n=60) of a compomer (Freedom) and a microhybrid composite (TPH Spectrum) were prepared following the manufacturer's instructions. The specimens were divided into two groups and treated for 30min, twice a day, for 14 days with a pediatric syrup containing Amoxicillin, Amoxil™ 500mg/5ml (experimental group) or Distilled water (control group). During the 14 days, the samples were submitted to pH cycling (3h in demineralizing, 20h in remineralizing saliva, and 1h for treatment). The surface roughness was evaluated at baseline, on the 7th and 14th days of erosive challenge using a profilometer and illustrated by SEM. The data were statistically analyzed by one-way ANOVA, Tukey HSD and paired T- tests (p < 0.05). At baseline, the mean Ra TPH = mean Ra F (p > 0.05). Results: After 7 days, it was observed no erosion (p = 0.674) for THP Spectrum (0.19 Ra) and an increasing of Ra (p = 0.02) for Freedom (19.95 Ra). After 14 days, it was observed an increasing of Ra for both THP Spectrum (0.56 Ra) and for Freedom (3.44 Ra), demonstrating that the degradation was treatment and time-dependent (p < 0.001). The pediatric syrup containing Amoxicillin increased the surface roughness of the TPH Spectrum surface one and a half times (p = 0.003) and the surface roughness of Freedom was increased by more than two times (p < 0.001). SEM images showed different aspects of the surfaces of the two materials with a loss of integrity to both. Conclusion: The pediatric syrup containing Amoxicillin under pH cycling increased the roughness of the both tested resin-based restorative materials.

O julgamento do caso da fosfoetanolamina e a jurisprudência do Supremo Tribunal Federal / The judgment on the phosphoethanolamine case and the jurisprudence of the Brazilian Federal Supreme Court

Recentemente noticiou-se a difusão do uso da substância fosfoetanolamina sintética, conhecida como a pílula do câncer, entre portadores de neoplasia maligna. Ocorre que a substância, além de não contar com registro na Agência Nacional de Vigilância Sanitária, sequer havia concluído os estudos clínicos necessários à garantia de sua eficácia e segurança. Não obstante, o governo federal editou a Lei n. 13.269/2016, que autorizava o fornecimento pelo Sistema Único de Saúde sob determinadas condições, e diversas liminares foram concedidas obrigando o Estado a fornecê-la. A questão foi apreciada pelo Supremo Tribunal Federal em dois rumorosos julgamentos, em que a Corte suspendeu todas as liminares concedidas e suspendeu a eficácia da referida lei por indícios de inconstitucionalidade. Neste artigo analisamos os fundamentos das citadas decisões no contexto de posicionamentos anteriores da Corte e das orientações estabelecidas no julgamento do Agravo Regimental na Suspensão de Tutela Antecipada 175

Widespread use of the synthetic substance phosphoethanolamine, known as the cancer pill, was recently reported among patients with malignant neoplasm. However, the substance was not registered in the Brazilian National Health Surveillance Agency and the clinical studies necessary to guarantee its effectiveness and safety had not even been completed. Nevertheless, the federal government enacted Law number 13.269/2016, authorizing provision by the Brazilian National Public Health System under certain conditions, and various injunctions were granted that forced the state to provide it. The question was considered by the Supreme Court in two important judgments in which the Court suspended all injunctions granted and suspended the effectiveness of the law based on evidence of unconstitutionality. In this article, we analyze the legal grounds of the decisions in the context of previous positions of the Court and the guidelines established in judgment of STA 175-AgR/CE

Protocolos de Seguridad del Paciente / Protocols of security of the Patient

Los documentos que definen estándares de atención no constituyen un objetivo en sí mismo, sino que en realidad son herramientas necesarias tanto en la disminución de la variabilidad innecesaria en los procesos, así como de la evaluación y mejoras de la calidad asistencial. Uno de estos documentos es el protocolo que en términos generales, es definido como un acuerdo entre profesionales expertos en un determinado tema y en el cuál se han clarificado las actividades a realizar ante una determinada tarea. Desde ésta forma de ver las cosas, serían susceptibles de protocolizarse aquellas actividades físicas, verbales y mentales que son planificadas y realizadas por los profesionales, incluyéndose tanto actividades autónomas como delegadas. Este documento aglutina cuatro Protocolos que han demostrado tener un alto impacto en mejorar la seguridad de los pacientes durante la atención en salud, buscando se constituyan en herramienta para mejorar la calidad de la atención en salud, un compromiso de todos.

Antidepresivos: controversia sobre su eficaciaen el trastorno depresivo mayor / Antidepressants: controversy over its efficacy in major depressive disorder

En los últimos años se ha observado un aumento sistemático del consumo de antidepresivos. Sin embargo, la eficacia en el tratamiento del trastorno depresivo mayor es objeto de debate. El objetivo del presente trabajo es analizar algunos factores que hacen a la construcción de la evidencia. Se presentan algunos estudios que han tenido impacto y controversia en este tema.

In recent years there has been a systematic increase in the use of antidepressants. However, efficacy in the treatment of major depressive disorder is the subject of debate. The objective of this paper is to analyze some factors that make the construction of evidence. Some studies that have had impact and controversy on this topic are presented.