Abstract (Objective) Plasmodium vivax predominantly infects many people in numerous tropical areas, including Southeast Asia, the Western Pacific, the Americas, and the Eastern Mediterranean. The uniqueness of forming dormant stages can lead to relapse in vivax malaria upon further infection. This study used molecular docking and dynamic simulation to predict potential bioactive compounds from the Zingiberaceae plant family as inhibitors by targeting Plasmodium vivax Duffy Binding Protein (PvDBP). PvDBP-DARC molecular interaction is required to mediate the merozoite invasion process into red blood cells. Inhibiting this process can possibly control parasite growth and development. (Methodology) Molecular docking screening was conducted by using 138 natural compounds from the Zingiberaceae plant family targeting Plasmodium vivax Duffy binding protein (PvDBP). The top two compounds with the lowest binding energy were selected to be analyzed by pharmacokinetics prediction and molecular dynamic (MD) simulation. (Results) Molecular docking screening resulted in the top two compounds with the lowest binding energy value, including 5,7-dihydroxyflavanone (-9.3 kcal/mol) and pinostrobin (-9.2 kcal/mol). These compounds are predicted to have stronger interaction than chloroquine as a control. Furthermore, the potential compounds also interact with DARC binding site residues and maintain them during the molecular dynamic simulation process. Otherwise, chloroquine as a control cannot retain 75% binding residues towards PvDBP. A molecular dynamic study revealed that all three complexes have relatively similar stability. (Conclusions) We predicted that the two bioactive compounds (5,7-dihydroxyflavanone and pinostrobin) have the potential as merozoite invasion inhibitors.

Resumen (Objetivo) Plasmodium vivax infecta ampliamente a muchas personas en algunas regiones. La singularidad de formar una etapa latente hace que la malaria vivax pueda ser inducida por una recaída por una infección adicional. En el presente estudio, utilizamos un enfoque de simulación dinámica y acoplamiento molecular ara predecir la posibilidad de que compuestos bioactivos de la familia de plantas Zingiberaceae sean candidatos a fármaco contra la malaria dirigiéndose a la proteína de unión a Duffy de Plasmodium vivax (PvDBP). Se requiere la interacción molecular PvDBP-DARC para mediar el proceso de invasión de merozoitos en los glóbulos rojos. La inhibición de este proceso posiblemente pueda controlar el crecimiento y desarrollo del parásito. (Metodología) El análisis de acoplamiento molecular dio como resultado los dos compuestos principales con el valor de energía de unión más bajo, incluida la 5,7-dihidroxiflavanona (-9,3 kcal/mol) y la pinostrobina (-9,2 kcal/mol). (Resultados) Estos compuestos previstos tienen una interacción más fuerte que la cloroquina como control. Además, los compue potenciales también interactúan con los residuos del sitio de unión de DARC y lo mantienen durante el proceso de simulación de dinámica molecular. De lo contrario, la cloroquina como control no puede retener el 75% de los residuos de unión hacia PvDBP. El estudio de dinámica molecular reveló que los tres complejos tienen una estabilidad relativamente similar. (Conclusiones) Predijimos que los dos compuestos bioactivos tienen potencial como inhibidores de la invasión de merozoitos.

Resumo (Objetivo) O Plasmodium vivax infecta amplamente muitas pessoas em algumas regiões. A singularidade de formar um estágio latente significa que a malária vivax pode ser induzida por recaída devido à infecção adicional. No presente estudo, utilizamos uma abordagem de simulação dinâmica e de acoplamento molecular para prever a possibilidade de compostos bioativos da família de plantas Zingiberaceae como candidatos a medicamentos antimaláricos, visand o aproteína de ligação Duffy do Plasmodium vivax (PvDBP). A interação molecular PvDBP-DARC é necessária para mediar o processo de invasão de merozoítos nos glóbulos vermelhos. A inibição deste processo pode possivelmente controlar o crescimento e desenvolvimento do parasita. (Metodologia) A análise de acoplamento molecular resultou nos dois principais compostos com o menor valor de energia de ligação, incluindo ,7-dihidroxiflavanona (-9,3 kcal/mol) e pinostrobina (-9,2 kcal/mol). (Resultados) Esses compostos previstos têm uma interação mais forte do que a cloroquina como controle. Além disso, os compostos potenciais também interagem e mantêm resíduos do sítio de ligação do DARC durante o processo de simulação de dinâmica molecular. Caso contrário, a cloroquina como controle não pode reter 75% dos resíduos de ligação ao três complexos apresentam estabilidade relativa compostos bioativos têm potencial como inibidor Palavras chave: Medicamentos antimalária; ePvmeesdmsilDBP. ntesa invício;O estudo de dinâmica molecular revelou que os emelhante. (Conclusões) Previmos que os dois asão de merozoítos. Plasmodium vivax; PvDBP; Zingiberáceas.

Resumen Introducción : Los ensayos clínicos que involucran medicamentos, tienen como objetivo determinar su eficacia y seguridad. En Argentina, estos estudios se presentan ante la agencia reguladora Administración Nacional Medicamentos, Alimentos y Tecnología Médica (ANMAT), para registrarlos; o bien ante el Ministerio de Salud de la Nación (MSAL). El objetivo de este trabajo fue conocer cuáles son los medicamentos de interés y quiénes son los que llevan adelante este tipo investiga ción clínica en Argentina. Materiales y métodos : Se exploraron las bases de datos MSAL/ANMAT. Las variables fueron fechas de solicitud del trámite, institución solicitante, fase del es tudio, modalidad de enrolamiento, producto investigado, grupo terapéutico, comparador, enfermedad involucrada y lugar de realización de laboratorio. Resultados : Se detectaron en el periodo 201 protoco los, todos ellos con fines registrales. Veinte compañías farmacéuticas realizaron el 60% de los estudios (17 de capitales extranjeros). El 70% fueron fase III (90% multicéntricos). Tres de cada 4 ensayos correspondie ron al grupo de oncológicos/ inmunosupresores. En el 65% el comparador fue placebo. El 71% de los estudios se realizaron en instituciones de la Ciudad Autónoma de Buenos Aires. El 98 % de controles de laboratorio se realizaron en el exterior. Discusión : Las compañías farmacéuticas extranjeras son quienes realizan con fines registrales el mayor núme ro de ensayos clínicos sobre medicamentos en Argentina. El predominio del uso de placebo como comparador re sulta inapropiado, ya que el verdadero valor del estudio es cuando un fármaco innovador demuestra superioridad contra otro ya existente de reconocida eficacia. Las en fermedades oncológicas/inmunológicas fueron aquellas que despertaron mayor interés entre los investigadores y patrocinantes por prevalencia y rentabilidad.

Abstract Introduction : Clinical trials that involve medicines are performed in order to determine their effectiveness and safety. In Argentina, these studies are presented either to National Administration of Drugs, Food and Medical Technology (ANMAT) to obtain drug registra tion, or to the National Ministry of Health (MSAL) (to obtain the official recognition). This work was carried out to increase the knowledge about the clinical trials performed in Argentina. Materials and methods : The MSAL/ANMAT databas es were explored. The variables were: dates of request, institution, phase of the study, enrollment modality, product investigated, therapeutic group, comparator, pathology involved, and location of laboratory perfor mance. Results : A total of 201 protocols were detected in the period of study, all of them performed with registration purposes. Twenty pharmaceutical companies carried out 60% of the studies (17 with foreign capital). Seventy percent were phase III (90% multicenter protocols). Three out of 4 trials corresponded to the oncology/ immunosuppressant therapeutical group. In 65% the comparator used was placebo. A 71% of the studies were carried out in health institutions of Buenos Aires City. Ninety-eight per cent of laboratory controls were carried out abroad. Discussion : Foreign pharmaceutical companies are the only ones that carry out clinical trials on medicines in Argentina, all of them for registration purposes. The use of placebo as a comparator is inappropriate, since each drug is expected to be validated against another of recognized efficacy already available in the market. Oncological/immunological pathologies are the ones that arouse greater interest among local researchers due to their prevalence and their greater profitability in the pharmaceutical market.

Abstract Introduction: Acute cholecystitis is one of the most common complications of cholelithiasis. In Colombia, there are no studies on its prevalence or the sociodemographic characteristics of the affected population. Objectives: To establish the prevalence of acute cholecystitis in Colombia and describe the associated sociodemographic characteristics. Materials and Methods: A descriptive cross-sectional study was conducted using data from the individual service provision records (RIPS) from 2018 to 2022. Results: A total of 343,254 cases of acute cholecystitis were identified in Colombia, with a prevalence of 681 cases per 100,000 inhabitants and a female-to-male ratio of 2.3:1. The highest number of reported cases was in the 34 to 39-year age group. The departments with the most cases are located in the southeast of the country, including Nariño, Valle del Cauca, Caquetá, and Tolima. Conclusion: This study presents epidemiological and sociodemographic information on acute cholecystitis in Colombia. There are few epidemiological studies on this disease in Latin America, however, the prevalence found is similar to that reported in countries like the United States.

Resumen Introducción: La calidad de la colonoscopia es un factor determinante en los desenlaces clínicos y depende en gran medida de la limpieza intestinal lograda con una adecuada preparación. El tipo de agente, la adherencia y tolerabilidad son factores que pueden influenciar la calidad de la limpieza y, por ende, los resultados del procedimiento. Con este estudio se busca evaluar cuáles son los motivos que determinan la escogencia del agente para la preparación y su impacto en la calidad de la colonoscopia. Metodología: Estudio observacional de corte transversal con una muestra de 530 pacientes. Agentes evaluados: polietilenglicol (PEG), picosulfato de sodio y sulfato de sodio-potasio-magnesio (sulfato de Na-K-Mg), con sus esquemas de dosis continua y dividida, según el caso. Los motivos para la selección y la tolerabilidad se evaluaron por medio de una encuesta. La limpieza intestinal fue determinada por el endoscopista mediante la escala de Boston. Resultados: La edad promedio fue de 52,7 años (± 13,4), 60% fueron mujeres. El agente más elegido fue PEG (81,9 %) en el esquema de dosis completa (74,5%). El principal factor determinante fue la disponibilidad del fármaco, con un 42,6%. Se presentaron síntomas indeseables en el 62,6% de los pacientes; sin embargo, el 99,4% lograron una preparación adecuada (Boston ≥6). Conclusión: El principal factor relacionado con la selección del agente para la preparación intestinal es la disponibilidad. La tolerabilidad objetiva no condiciona diferencias relevantes en la calidad de la limpieza ni el éxito del procedimiento.

ABSTRACT Introduction: Tramadol/paracetamol combination is one of the most prescribed pain medications in Portugal. At the Regional Health Administration of Lisbon and Tagus Valley, 1 119 229 packages of tramadol/paracetamol were prescribed for 12 months, corresponding to the second most prescribed analgesic. We ask whether this drug is prescribed for acute and irruptive pain or if it is prescribed as a long-term treatment for chronic pain. Methods: This cross-sectional study describes the prescription of tramadol/paracetamol in a Portuguese primary care unit. The population studied corresponds to the 344 patients who received a tramadol/paracetamol prescription between July 2020 and June 2021. Results: In this period, a total of 687 prescriptions were made, corresponding to 2500 packages of tramadol/paracetamol, of which 1874 were bought. There was no statistically significant difference between the number of packages bought over the 4 trimesters (p = 0.275) and 35.3% of the patients bought this medication in more than one trimester. We found that 16.5% bought tramadol/paracetamol in an amount that allows a use of more than 90 days. Conclusion: This demonstrates that the tramadol/paracetamol combination plays a central role in the treatment of pain and that a significant percentage of patients use this medication chronically, questioning the adequacy of this therapy in these patients. However, larger studies that assess pain control are needed to support the results presented in this work.

RESUMO Introdução: A combinação tramadol/paracetamol é um dos medicamentos mais prescritos para a dor em Portugal. Na Administração Regional de Saúde de Lisboa e Vale do Tejo, ao longo de 12 meses, foram prescritas 1 119 229 embalagens de tramadol/paracetamol, constituindo o segundo analgésico mais prescrito. Estes números fazem questionar se este fármaco é prescrito para dor aguda e dor crónica agudizada ou se é prescrito como tratamento prolongado para dor crónica. Métodos: Este é um estudo transversal que descreve a prescrição tramadol/paracetamol numa Unidade de Saúde Familiar portuguesa. A população em estudo corresponde aos 344 utentes a que foi prescrito tramadol/paracetamol no período compreendido entre Julho de 2020 e Junho de 2021. Resultados: Neste período foram emitidas 687 receitas que corresponderam a 2500 embalagens de tramadol/paracetamol, das quais 1874 foram dispensadas. Não houve diferença estatisticamente significativa entre o número de embalagens dispensadas ao longo dos 4 trimestres (p=0,275) e 35,3% dos utentes dispensaram receitas em mais do que um trimestre. Verificou-se que 16,5% dos utentes comprou esta combinação em quantidade que permite uma utilização superior a 90 dias. Conclusão: Assim se demonstra que a combinação tramadol/paracetamol desempenha um papel central no tratamento da dor e que uma percentagem significativa dos utentes utiliza este medicamento de forma crónica, questionando-se a adequação da terapêutica nestes doentes. Contudo, são necessários estudos mais alargados e que avaliem o controlo da dor para suportar os resultados apresentados neste trabalho.

RESUMEN: En este estudio, nuestro objetivo fue examinar el efecto de la coadministración del nuevo fármaco vasodilatador Riociguat junto con resveratrol para recuperar la neurodegeneración en lesiones por ataques cerebrovasculares experimentales. Para ello, se dividieron 35 ratas hembras adultas en cinco grupos (Control, MCAO, MCAO + R, MCAO + BAY, MCAO + C) de siete animales en cada uno. Los animales del grupo control no fueron sometidos a ninguna aplicación durante el experimento y se sacrificaron al final del estudio. Las ratas de los grupos expuestas a la oclusión de la arteria cerebral media (MCAO) indujeron un ataque cerebrovascular isquémico. El grupo MCAO + R recibió 30 mg/kg de resveratrol y el grupo MCAO + BAY recibió 10 mg/kg de Riociguat. El grupo MCAO + C recibió ambos fármacos simultáneamente. Los fármacos se administraron antes de la reperfusión y las dosis adicionales se administraron a las 24 y 48 horas de la reperfusión. Todos los animales en este estudio fueron sacrificados a las 72 horas del experimento. Se recibieron cerebros totales para su análisis. Los resultados indicaron que la MCAO provocaba lesiones graves en la estructura cerebral. Los niveles tisulares de Bax, IL-6 e IL- 1ß estaban regulados positivamente, pero se suprimió la inmunoexpresión antiapoptótica de Bcl-2 (p <0,05). En los animales tratados con resveratrol y Riociguat, las neurodegeneraciones y las expresiones de proteínas asociadas a la apoptosis y la inflamación mejoraron en comparación con el grupo MCAO, sin embargo el mayor éxito se obtuvo en el tratamiento combinado de animales expuestos en el grupo MCAO + C. Este estudio indicó que el nuevo estimulador de guanilato ciclasa soluble Riociguat no solo es un fármaco neuroprotector potente en el ataque cerebrovascular inducido por MCAO, sino que también la administración sinérgica de Riociguat junto con resveratrol tiene el potencial para aumentar el efecto neuroprotector del resveratrol en ratas experimentales expuestas a un ataque cerebrovascular.

SUMMARY: In this study we aimed to examine the effect of novel vasodilatory drug Riociguat co-administration along resveratrol to recover neurodegeneration in experimental stroke injury. For that purpose, thirty-five adult female rats were divided into five groups (Control, MCAO, MCAO + R, MCAO + BAY, MCAO + C) of seven animals in each. Animals in Control group did not expose to any application during the experiment and sacrificed at the end of the study. Rats in the rest groups exposed to middle cerebral artery occlusion (MCAO) induced ischemic stroke. MCAO + R group received 30 mg/kg resveratrol, and MCAO + BAY group received 10 mg/kg Riociguat. The MCAO + C group received both drugs simultaneously. The drugs were administered just before the reperfusion, and the additional doses were administered 24h, and 48h hours of reperfusion. All animals in this study were sacrificed at the 72nd hour of experiment. Total brains were received for analysis. Results of this experiment indicated that MCAO led to severe injury in cerebral structure. Bax, IL-6 and IL-1ß tissue levels were up-regulated, but anti-apoptotic Bcl-2 immunoexpression was suppressed (p<0.05). In resveratrol and Riociguat treated animals, the neurodegenerations and apoptosis and inflammation associated protein expressions were improved compared to MCAO group, but the most success was obtained in combined treatment exposed animals in MCAO + C group. This study indicated that the novel soluble guanylate stimulator Riociguat is not only a potent neuroprotective drug in MCAO induced stroke, but also synergistic administration of Riociguat along with resveratrol have potential to increase the neuroprotective effect of resveratrol in experimental cerebral stroke exposed rats.

Abstract Background: Antimicrobial resistance (AMR) is one of the greatest threats to global public health. Contributing to this process, among other factors, is the indiscriminate use of antimicrobials in community-acquired respiratory infections. Each country has implemented strategies to confront this growing phenomenon. The objective of this review was to determine Chilean initiatives to deal with Antimicrobial Resistance (AMR), antibiotic use and prescribing, and availability of susceptibility data, for the critical community-acquired respiratory tract infection (CA-RTI) pathogens Streptococcus pneumoniae and Haemophi/us influenzae and to spot areas where more information is needed and suggest a call to action to enhance patient clinical outcomes, through a narrative review of the literature. In Chile, antibiotics sales only occur under medical prescription; however, in later years, a new consumption associated with physician drug prescription has emerged in the community, especially for penicillin derivatives, quinolones, and macrolides. Data have shown a susceptibility reduction to amoxicillin and clavulanate combination and other antibiotics against S. pneumoniae. As a consequence, the local government proposed the National Plan on Antimicrobial Resistance 2017-2020. The new version from 2021 to 2025 led to a decreasing trend in Chile's 5. pneumoniae and H. influenzae isolates. Such results highlight the importance of the development of local guidelines.

Resumen Introducción: La resistencia a antimicrobianos (RAM), es una de las mayores amenazas para la salud pública mundial. Contribuyen a este proceso, entre otros factores, el indiscriminado uso de antimicrobianos en las infecciones respiratorias adquiridas en la comunidad. Cada país ha puesto en práctica estrategias para enfrentar este creciente fenómeno. El objetivo de esta revisión fue determinar las iniciativas chilenas para abordar la RAM, el uso y la prescripción de antimicrobianos y la disponibilidad de datos de susceptibilidad para los patógenos Streptococcuspneumoniae y Haemophilus influenzae, patógenos críticos de la infección del tracto respiratorio adquirida en la comunidad (ITRAC) y detectar las áreas donde se necesita más información y sugerir un llamado a la acción para mejorar los resultados clínicos de los pacientes, a través de una revisión narrativa de la literatura. En Chile, la venta de antimicrobianos solo se realiza bajo prescripción médica; sin embargo, en los últimos años ha surgido un nuevo consumo asociado a la prescripción de medicamentos en el ámbito comunitario por parte de los médicos, especialmente para derivados de penicilina, quinolonas y macrólidos. Los datos han demostrado una reducción de la susceptibilidad in vitro a la combinación de amoxicilina y ácido clavulánico y otros antimicrobianos frente a 5. pneumoniae. En consecuencia, el gobierno local propuso el plan nacional de resistencia antimicrobiana 2017-2020. La nueva versión de 2021 a 2025 podría explicar la tendencia decreciente de aislados de 5. pneumoniae y H. influenzae en Chile. Tales resultados destacan la importancia del desarrollo de guías locales.

Resumen El diagnóstico electrocardiográfico de infarto agudo de miocardio (IAM) en el paciente con marcapasos siempre ha sido un problema en la práctica clínica, provocando retrasos en el manejo y peores desenlaces clínicos. Aunque el bloqueo completo de rama izquierda (BCRI) y la estimulación del ventrículo derecho pueden producir anomalías en el electrocardiograma (ECG), cambios morfológicos específicos a menudo permiten el diagnóstico de IAM o un infarto antiguo. Reporte de caso: Paciente de 76 años con antecedente de implante de marcapasos definitivo por bloqueo auriculoventricular de 3° grado, que ingresó por dolor precordial. A su ingreso hemodinámicamente estable, pero con ECG que muestra ritmo de marcapasos con BCRI cumpliendo Sgarbossa 2 puntos (elevación discordante del segmento ST > 5 mm en derivaciones V1 a V3) y relación ST/S < -0.25 en derivaciones V3-V4. Laboratorios con elevación de troponinas, integrándose diagnóstico de IAM y pasando a angiografía coronaria urgente. Se documentó lesión en arteria coronaria descendente anterior y se implantó stent liberador de fármaco angiográficamente exitoso. Se egresó estable, asintomático y con manejo farmacológico para prevención secundaria. Conclusión: La identificación por ECG de un IAM en pacientes portadores de marcapasos es fundamental para iniciar terapia de reperfusión. Las recomendaciones de las guías cambian constantemente, pero un algoritmo que utiliza la inestabilidad hemodinámica y los criterios de Sgarbossa modificados (CSM) para decidir el manejo de estos pacientes pudiera ser una herramienta con una alta sensibilidad y permitirá a los médicos tener la mejor toma de decisiones sin esperar resultados de laboratorio. Los CSM, que son más sensibles que los criterios originales, continúan siendo útiles en el diagnóstico de IAM. Los médicos deben elegir cuidadosamente el límite de CSM apropiado (relación ST/T -0.20 y -0.25) de acuerdo con cada caso.

Abstract The electrocardiographic diagnosis of acute myocardial infarction (AMI) in patients with pacemakers has always been a problem in clinical practice, causing delays in management and worse clinical outcomes. Although complete left bundle branch block (LBBB) and right ventricular pacing can produce electrocardiogram (ECG) abnormalities, specific morphological changes often allow the diagnosis of AMI or an old infarction. Case report: A 76-year-old patient with history of permanent pacemaker implantation due to a 3rd-degree atrioventricular block was admitted for chest pain. Upon admission, he was hemodynamically stable but with ECG showing pacemaker rhythm with LBBB fulfilling 2 points of Sgarbossa criteria (discordant elevation of the ST segment > 5 mm in leads V1 to V3) and ST/S ratio < -0.25 in leads V3-V4. Laboratories showed elevated troponins, integrating diagnosis of AMI, and moving on to urgent coronary angiography. A lesion on the anterior descending coronary artery was documented, and a drug-eluting stent was successfully implanted. The patient was discharged stable, asymptomatic, and with pharmacological management for secondary prevention. Conclusion: ECG identification of an AMI in patients with pacemakers is essential to initiate reperfusion therapy. Guideline recommendations are constantly changing, but an algorithm that uses hemodynamic instability and the modified Sgarbossa criteria (MSC) to decide these patients’ management could be a high-sensitivity tool and allow physicians to make the best decisions without waiting for laboratory results. MSC, which are more sensitive than the original criteria, continue to be helpful in the diagnosis of AMI. Clinicians should carefully choose the appropriate MSC cut-off (ST/T Ratio -0.20 and -0.25) on a case-by-case basis.

RESUMEN Introducción: se estima que, en 2050, la población mundial mayor de 65 años se habrá duplicado en relación a la de 2020, pasando del ocho al 16 por ciento. Algunos estudios apuntan a que el 0,3 por ciento del gasto global en salud podría evitarse mediante el adecuado manejo de la polifarmacia. Una asistencia de calidad requiere actividades preventivas de revisión y evaluación sistemática de los tratamientos de larga evolución. Objetivo: describir el comportamiento del de la farmacoterapia en adultos mayores y cómo modificar la farmacodependencia en ellos. Métodos: se realizó una revisión bibliográfica acerca de la temática de estudio relacionándose 45 artículos obtenidos de las bases de datos de Google Scholar, Google Académico y Scielo. Desarrollo: los tratamientos inútiles o perjudiciales por emplear fármacos de escaso o nulo valor terapéutico, baja seguridad o una prescripción deficiente de probada eficacia y seguridad, obedecen a disímiles causas y refleja los riesgos a que están sometidas las poblaciones por la conducta médica. Una prescripción adecuada debe equilibrar las expectativas de vida del paciente, los objetivos terapéuticos y el tiempo que necesita el fármaco para alcanzar estos objetivos, una vez lo haya hecho se debe desaconsejar su uso. Conclusiones: los profesionales encargados de la prescripción al anciano deben dar cumplimiento a los postulados frente a la polifarmacia, prescripción inapropiada, retomar los pasos de la terapéutica razonada a partir del método científico, la medicina basada en evidencias y las bases farmacológicas que rigen el uso racional de los medicamentos.

ABSTRACT Introduction: it is estimated that by 2050, the world's population over 65 years of age will have doubled from 8 to 16 per cent in 2020. Some studies suggest that 0.3 per cent of global health expenditure could be avoided through the appropriate management of polypharmacy. Quality care requires preventive activities to systematically review and evaluate long-standing treatments. Objective: to describe the behaviour of pharmacotherapy in older adults and how to modify drug dependence in them. Methods: a literature review was carried out on the subject of the study, relating 45 articles obtained from the Google Scholar, Google Scholar and Scielo databases. Development: useless or harmful treatments due to the use of drugs of little or no therapeutic value, low safety or poor prescribing of proven efficacy and safety, are due to a variety of causes and reflect the risks to which populations are subjected by medical conduct. Appropriate prescribing should balance the patient's life expectancy, therapeutic goals and the time needed for the drug to achieve these goals, and once it has done so, its use should be discouraged. Conclusions: professionals in charge of prescribing to the elderly should comply with the postulates against polypharmacy, inappropriate prescribing, and take up the steps of reasoned therapy based on the scientific method, evidence-based medicine and the pharmacological bases that govern the rational use of drugs.

Abstract Introduction: Patients with type 2 diabetes mellitus (DBT2) present microvascular damage mediated by inflammatory processes, which can be assessed by mean platelet volume (MPV). Objective: To determine whether treatment of patients with DM2 improves the pro-inflammatory state, assessed by MPV. Material and methods: Retrospective, observational, and descriptive study of 139 clinical histories of patients diagnosed with DBT2 who met the selection criteria, and whose laboratory results and medical notes were analyzed, using a statistical analysis with frequencies and percentages for nominal qualitative variables, with measures of central tendency and dispersion in quantitative variables, using the Chi-square test, Kruskal-Wallis test, and Mann-Whitney U test. The Belmont principles, the ethical principles of the Declaration of Helsinki, the General Health Law in Mexico, and the guidelines of the Council for International Organizations of Medical Sciences (CIOMS) were respected. This protocol was submitted to the Health Research Committee 301, and the Research Ethics Committee 3018, with folio R-2021-301-023. Results: The average age of the participants was 55.16 ± 14.208 years, 60% were female; the association between the use of each drug and the MPV was not significant (p = 0.568; 95% confidence interval [95% CI]: 0.486 to 0.651). When comparing the group of healthy individuals with each drug studied, significance was found with dapagliflozin (p = 0.001; 95% CI: 0.000 to 0.021). Conclusion: Dapagliflozin in the treatment of patients with DBT2 significantly improves MPV by reducing microvascular damage mediated by inflammatory processes.

Resumen Introducción: El paciente con diabetes mellitus tipo 2 (DBT2) presenta daños microvasculares mediados por procesos inflamatorios, los cuales pueden ser valorados por el volumen plaquetario medio (VPM). Objetivo: Conocer si el tratamiento del paciente con DBT2 mejora el estado proinflamatorio, valorado por medio del VPM. Material y métodos: Estudio retrospectivo, observacional y descriptivo en 139 historias clínicas de pacientes con diagnóstico de DBT2 que cumplieron los criterios de selección, y de las que se analizaron los resultados de laboratorio y las notas médicas, mediante un análisis estadístico con frecuencias, porcentajes para variables cualitativas nominales, con medidas de tendencia central y dispersión en variables cuantitativas, mediante pruebas de chi al cuadrado, de Kruskal-Wallis y de la U de Mann-Whitney. Se respetaron los principios de Belmont, los principios éticos de la Declaración de Helsinki, la Ley General de Salud en México y pautas del Council for International Organizations of Medical Sciences (CIOMS); este protocolo se sometió al Comité de Investigación en Salud 301 y al comité de ética en investigación 3018, con folio R-2021-301-023. Resultados: El promedio de edad de los participantes fue de 55.16 ± 14.208 años, el 60% eran de sexo femenino; la asociación entre el uso de cada fármaco y el VPM fue no significativa (p = 0.568; IC 95%: 0.486 a 0.651). Al comparar el grupo de individuos sanos con cada fármaco estudiado se encuentra significación con la dapagliflozina (p = 0.001; IC 95%: 0.000 a 0.021). Conclusión: La dapagliflozina en el tratamiento del paciente con DBT2 mejora el VPM de forma significativa mediante la disminución de los daños microvasculares mediados por procesos inflamatorios.

Abstract Acute gastroenteritis (AGE) remains one of the most frequent diseases in pediatric age with oral rehydration being the cornerstone of its treatment. Racecadotril is an antidiarrheal drug used for the treatment of acute diarrhea in children, as it reduces the secretion of water and electrolytes by the digestive tract. Although it could be considered in the treatment of AGE, it is not clear whether racecadotril is really effective. The objective of this study is to assess whether there is evidence to support its use in the treatment of AGE in pediatrics, through a literature review. A search of articles published in the last 10 years, in Portuguese or English, was carried out in the MEDLINE databases; NICE; Cochrane Library; BMJ; CPG Infobase - Clinical Practice Guidelines; Bandolier. The keywords used were “Racecadotril”, “Child”, “Child, Preschool”, “Diarrhea” and “Gastroenteritis”. The selection of articles was made in duplicate by the authors who, when in doubt, jointly discussed its inclusion/exclusion. The Strength of Recommendation Taxonomy scale was used to assign levels of evidence and strengths of recommendation. A total of 443 articles were obtained, and in the end, eight articles were included: three meta-analyses, two reviews, two guidelines and one expert opinion. The studies included in this review demonstrated a reduction in the number and volume of stools, in duration of diarrhea, and in healing time. It is concluded that racecadotril seems to be effective in the treatment of acute diarrhea and can be considered in conjunction with the oral rehydration solution (SORT B).

Resumo A gastroenterite aguda (GEA) continua a ser uma das patologias mais frequentes em idade pediátrica, sendo que a rehidratação oral permanece a pedra angular do seu tratamento. O racecadotril é um fármaco antidiarreico utilizado no tratamento da diarreia aguda em crianças, dado que reduz a secreção de água e eletrólitos pelo aparelho digestivo. Apesar de poder ser considerado no tratamento da GEA, não é claro se é realmente eficaz. O objetivo deste trabalho é, através de uma revisão bibliográfica, avaliar se existe evidência que suporte o seu uso no tratamento da diarreia aguda em idade pediátrica. Foi realizada uma pesquisa de artigos publicados nos últimos 10 anos, na língua portuguesa ou inglesa, nas bases de dados MEDLINE; NICE; Cochrane Library; BMJ; CPG Infobase - Clinical Practice Guidelines; Bandolier. As palavras-chave utilizadas foram “Racecadotril”, “Child”, “Child, Preschool”, “Diarrhea” e “Gastroenteritis”. A seleção dos artigos foi feita em duplicado pelas autoras que, perante dúvidas, discutiram conjuntamente a sua inclusão/exclusão. Para a atribuição dos níveis de evidência e forças de recomendação, foi usada a escala Strenght of Recommendation Taxonomy. Obtiveram-se um total de 443 artigos, tendo, no final, sido incluídos oito artigos: três meta-análises, duas revisões, duas guidelines e uma opinião de peritos. Os estudos incluídos nesta revisão demonstraram uma redução no número e volume de dejeções, na duração da diarreia e no tempo de cura. Conclui-se que o racecadotril parece ser eficaz no tratamento da diarreia aguda e pode ser considerado em conjunto com a solução de rehidratação oral (SORT B).

ABSTRACT Introduction: Nystatin is an antifungal drug widely used to treat oral candidiasis, a common infection in the mouth caused by the fungus Cándida. In the development of pharmaceutical products, it is essential to use a specific analytical method that allows the precise quantification of the active ingredient present in the formulation. Objective: To validate an analytical method using high performance liquid chromatography for the quantification of nystatin in ointment. Methods: This is an applied research with a quantitative approach. The technique used for the validation of the analytical method is high-performance liquid chromatography. Analysis of the following parameters is included: specificity, accuracy and precision. Statistical tools were used to analyze the results, highlighting data analysis, coefficient of variation and statistical comparison. Results: The validation parameters evaluated confirmed their specificity, for which no interferences were found in the analysis. The accuracy of 98.83% with C.V. of 0.48%. The intermediate precision with coefficient of variation (C.V.) (%) ≤ 2 %. It is determined that the proposed method is suitable for the quantification of Nystatin ointment. Conclusions: The validated method for the active pharmaceutical ingredient nystatin can be applied in quality control due to its specificity, precision and linearity within the concentration range studied. By using this new method, accurate results are obtained that do not differ statistically from those obtained by the established US Pharmacopeia method.

RESUMEN Introducción: La nistatina es un fármaco antifúngico ampliamente utilizado para tratar la candidiasis oral, una infección común en la boca, causada por el hongo Candida albicans. En el desarrollo de productos farmacéuticos es fundamental utilizar un método analítico específico que permita la cuantificación precisa del principio activo presente en la formulación. Objetivo: Validar un método analítico utilizando cromatografía líquida de alta resolución para la cuantificación de nistatina en ungüento. Métodos: Es una investigación aplicada con enfoque cuantitativo. La técnica utilizada para la validación del método analítico es la cromatografía líquida de alta resolución. Se incluye análisis de los parámetros: especificidad, exactitud y precisión. Para analizar los resultados, se emplearon herramientas estadísticas, como el coeficiente de variación y la comparación estadística. Resultados: Los parámetros de validación evaluados confirmaron su especificidad, para ello no se encontraron interferencias en el análisis. La exactitud del 98,83 % con coeficiente de variación (C.V.) de 0,48 %. La precisión intermedia con C.V. (%) ≤ 2 %. Se determinó que el método propuesto es apto para la cuantificación de nistatina ungüento. Conclusiones: El método validado para el ingrediente farmacéutico activo nistatina se puede aplicar en el control de calidad debido a su especificidad, precisión y linealidad dentro del rango de concentración estudiado. Al utilizar este nuevo método, se obtienen resultados precisos que no difieren estadísticamente de los obtenidos por el método establecido en la Farmacopea de los EE. UU.

ABSTRACT Introduction: Different parameters of suicide attempts treated since the implementation of the Attention to Suicide Risk Program (ARSUIC) in 2012 at the Hospital Ramón y Cajal in Madrid Region are described in this paper. Method: The sample was composed of 107 patients and the information was collected through a questionnaire created ad hoc with the following variables: type of suicidal ideation; drug use immediately prior to the attempt; method (in case of drug overdosing: drug/s used); location; accessibility to rescue; planning; intentionality; criticism; and brakes. Results: Descriptive statistics were obtained and a comparison by gender was made through the x2 and contingency coefficients tests. The data from the retrospective longitudinal study showed that the most common profile was of patients with unstructured ideas of death and no previous drug use who took an unplanned drug overdose in the family home, with the intention of self-harm or avoidance of discomfort, especially with benzodiazepines. Patients tend to ask for help afterwards and criticise the attempt, but potential restraints are often not recorded in the clinical report. Regarding the dissimilarities based on gender, statistically significant differences were found in prior alcohol consumption, in favour of men and in the overdose method, specifically with benzodiazepines, in favour of women. Conclusions: Knowing the types of attempts at self-harm is essential for improving prevention, understanding and patient management.

RESUMEN Introducción: En el presente trabajo se describen distintos parámetros de las tentativas de suicidio atendidas desde la implementación del programa de Atención al Riesgo Suicida (ARSUIC) en 2012 en el Hospital Ramón y Cajal de la Comunidad de Madrid, España. Métodos: La muestra estuvo compuesta por 107 pacientes y la información se recogió a través de un cuestionario creado ad hoc con las siguientes variables: tipo de ideación suicida, consumo de tóxicos inmediatamente antes, método (en caso de sobreingesta medicamentosa: fármaco/s utilizado/s), ubicación, accesibilidad al rescate, planificación, intencionalidad, crítica y frenadores. Resultados: Se obtuvieron estadísticos descriptivos y se realizó una comparación por sexo a través de las pruebas de x2 y coeficientes de contingencia. Los datos del estudio longitudinal retrospectivo mostraron como perfil más frecuente el de pacientes con ideas de muerte no estructuradas, sin consumo previo de tóxicos, que se realizan en el domicilio familiar de manera no planificada y con intención autolítica o evitativa del malestar de una sobreingesta medicamentosa, especialmente con benzodiacepinas. Los pacientes tienden a solicitar auxilio posterior y realizar crítica del intento, y los potenciales frenadores con frecuencia no se recogen en el informe clínico. Respecto a las disimilitudes en función del sexo, se encontraron diferencias estadísticamente significativas en el consumo previo de alcohol, a favor de los hombres, y en el método sobreingesta, concretamente con benzodiacepinas, a favor de las mujeres. Conclusiones: Profundizar en las tipologías de los intentos autolíticos resulta fundamental para mejorar la prevención, la comprensión y el abordaje sanitario.

SUMMARY: As the economy develops and living standards improve, overweight and obesity are increasingly prevalent. Currently, weight-loss medications are primarily administered orally or intravenously, which can result in poor targeting, low bioavailability, frequent administration, and high toxicity and side effects. The study aimed to address these challenges by preparing polylactic acid- polyethylene glycol staple fibers that carry the browning drug pioglitazone hydrochloride using electrostatic spinning and freeze-cutting techniques. Animal experiments were conducted to test the effectiveness of these fibers. Additionally, the study investigated the expression of uncoupling protein genes in rats exposed to different water temperatures by measuring changes in serum urea nitrogen and mRNA expression levels of skeletal muscle uncoupling protein genes. The physiological and genetic effects of low-temperature swimming exercise on changes in energy metabolism in rats were also analyzed at both the individual and molecular levels. The results revealed that serum urea nitrogen remained more stable in hypothermic swimming rats compared to rats in the swimming group. Furthermore, the study observed an induced up-regulation of uncoupling proteins in the skeletal muscle of Wistar rats in response to external temperature stimulation, and the expression of mRNA for skeletal muscle uncoupling proteins significantly increased as the temperature decreased. And the prepared short nanofibers also had a significant promotive effect on uncoupling protein gene, COX7A1, while suppressing the expression of lipogenic gene.

RESUMEN: A medida que la economía se desarrolla y los niveles de vida mejoran, el sobrepeso y la obesidad son cada vez más frecuentes. Actualmente, los medicamentos para bajar de peso se administran principalmente por vía oral o intravenosa, lo que puede resultar en una mala focalización, baja biodisponibilidad, administración frecuente y alta toxicidad y efectos secundarios. El estudio tuvo como objetivo abordar estos desafíos mediante la preparación de fibras cortadas de ácido poliláctico y polietilenglicol que transportan el fármaco pardo clorhidrato de pioglitazona mediante técnicas de hilado electrostático y liofilización. Se realizaron experimentos con animales para probar la eficacia de estas fibras. Además, el estudio investigó la expresión de genes de proteínas desacopladoras en ratas expuestas a diferentes temperaturas del agua midiendo los cambios en el nitrógeno ureico sérico y los niveles de expresión de ARNm de genes de proteínas desacopladoras del músculo esquelético. También se analizaron los efectos fisiológicos y genéticos del ejercicio de natación a baja temperatura sobre los cambios en el metabolismo energético en ratas, tanto a nivel individual como molecular. Los resultados revelaron que el nitrógeno ureico sérico permaneció más estable en ratas nadadoras hipotérmicas en comparación con las ratas del grupo de natación. Además, el estudio observó una regulación positiva inducida de las proteínas desacopladoras en el músculo esquelético de ratas Wistar en respuesta a la estimulación de la temperatura externa, y la expresión de ARNm para las proteínas desacopladoras del músculo esquelético aumentó significativamente a medida que disminuía la temperatura. Además, las nanofibras cortas preparadas también tuvieron un efecto promotor significativo sobre el gen de la proteína de desacoplamiento, COX7A1, al tiempo que suprimieron la expresión del gen lipogénico.

Abstract A problem with the supply of the medicine Ozempic® (semaglutide) was recently reported, which affects several countries, including Portugal. This drug, a glucagon-like peptide 1 analogue, is approved for the treatment of patients with type 2 diabetes mellitus not satisfactorily controlled, being partially reimbursed only for patients who also have a body mass index equal to, or greater than, 35 kg/m2. The drug stock-out seems to have been due to its off-label prescription, carried out with the aim of weight loss in overweight or obese people, but not in diabetic patients. The off-label use of semaglutide in Portugal raises ethical and economic problems. Despite the efforts that have been made to reduce the prevalence of overweight and obese people in our country, namely through the creation of health programs, we consider that there is still significant room for improvement in the field of preventive medicine.

Resumo Foi recentemente comunicado um problema no abastecimento do medicamento Ozempic® (semaglutido), situação que afetou vários países, incluindo Portugal. Este medicamento, um análogo do péptido-1 semelhante ao glucagon, está indicado no nosso país para o tratamento de diabetes mellitus tipo 2 insuficientemente controlada, sendo comparticipado apenas para estes doentes, desde que apresentem também um valor de índice de massa corporal igual ou superior a 35 kg/m2. A ruptura de stock do fármaco parece ter sido devida à sua prescrição off-label, realizada com o objetivo da perda de peso em pessoas com excesso de peso ou obesos, mas não diabéticos. A utilização off-label do semaglutido em Portugal levanta vários problemas, nomeadamente éticos e económicos. Apesar dos esforços que têm sido feitos para a diminuição da prevalência de pessoas com excesso de peso e obesidade no nosso país, nomeadamente através da criação de programas de saúde, considera-se que ainda existe margem significativa para uma melhoria no âmbito da medicina preventiva.

Abstract Introduction: Erythema nodosum is a rare disease whose pathophysiology is based on a type 4 delayed hypersensitivity response and its most common form of presentation is in the form of bilateral and symmetrical nodules and cutaneous plaques, predominantly affecting the pre-tibial region. Although the idiopathic etiology is still quite frequent, close to half of the cases are of secondary etiology, with oral contraceptives being amongst the most associated drugs with this entity, and this causal relationship being described for a greater number of estroprogestative associations. A rare case of erythema nodosum secondary to the association of ethinyl estradiol 0.03 mg + levonorgestrel 0.15 mg is described. Case description: We report a case of a 20-year-old woman who developed painful unilateral nodules in the pre-tibial region, related to the initiation of the combination of ethinyl estradiol 0.03 mg, and levonorgestrel 0.15 mg. The user describes the injuries as being longstanding, although she has never sought medical care in the past. After further investigation of the clinical history and suspicion of the causal relationship between the combined oral contraceptive and the appearance of lesions compatible with erythema nodosum, it was decided to suspend the same and start prednisolone 20 mg/day, with the user having a very favorable evolution. After discussing the existing therapeutic options, the user chose to switch to Implanon®. Conclusion: The literature is increasingly reporting the causal relationship between oral contraceptives, not only the combined type but also the isolated type, and the appearance of erythema nodosum. This is a rare and complex relationship. When a patient starts with painful nodules, a case of erythema nodosum must be considered, being aware of potential triggers - as combined oral contraceptives. In these cases, options must be explained to the user; therapeutic suspension is not the only way.

Resumo Introdução: O eritema nodoso é uma doença rara cuja fisiopatologia assenta numa resposta de hipersensibilidade tardia do tipo 4 e o seu modo de apresentação mais comum é sob a forma de nódulos e placas cutâneas bilaterais e simétricas, afetando predominantemente a região pré-tibial. Apesar da etiologia idiopática ainda ser bastante frequente, perto de metade dos casos são de etiologia secundária, estando os anticoncecionais orais entre os fármacos mais associados a esta entidade e sendo descrita esta relação causal para um número crescente de associações estroprogestativas. Descreve-se um caso raro de eritema nodoso secundário à associação de etinilestradiol 0,03 mg + levonorgestrel 0,15 mg. Descrição do caso: Relata-se o caso de uma mulher de 20 anos, que desenvolveu nódulos dolorosos na região pré-tibial do membro inferior direito, relacionando com o início da toma da associação de etinilestradiol 0,03 mg e levonorgestrel 0,15 mg. A utente descreve as lesões como sendo já crónicas, embora nunca tenha procurado cuidados médicos no passado. Após investigação mais aprofundada da história clínica e suspeição da relação causal entre o fármaco e o aparecimento das lesões compatíveis com um eritema nodoso optou-se por suspender o mesmo e iniciar prednisolona 20 mg/dia, tendo a utente evoluído no sentido da resolução clínica. Após discussão das opções terapêuticas existentes, a utente optou pela colocação de Implanon®. Conclusão: Na literatura é cada vez mais relatada a relação causal entre a toma de contracetivos orais, não só do tipo combinado como também do tipo isolado, e o aparecimento de eritema nodoso. Esta relação é rara e complexa. Perante um quadro de nódulos dolorosos dever-se-á considerar a hipótese de se tratar de um caso de eritema nodoso, estando atentos a potenciais triggers - caso dos contracetivos orais combinados. Nestes casos dever-se-á explicar à utente quais as suas opções, não sendo a suspensão terapêutica o único caminho a seguir.