Pharmacotherapy assessment and adverse drug reactions in older patients admitted to intensive care.

INTRODUCTION: Older patients are more susceptible to medication use, and physiological changes resulting from aging and organic dysfunctions presented by critically ill patients may alter the pharmacokinetic or pharmacodynamic behavior. Thus, critically ill older people present greater vulnerability to the occurrence of pharmacotherapeutic problems. OBJECTIVE: To evaluate pharmacotherapy and the development of potential adverse drug reactions (ADRs) in older patients admitted to an intensive care unit (ICU). METHOD: A cohort study was conducted in an ICU for adults of a Brazilian University Hospital during a 12-month period. The patients' pharmacotherapy was evaluated daily, considering the occurrence of ADRs and drug-drug interactions (DDIs), the use of potentially inappropriate medications (PIMs) for older people, and the pharmacotherapy anticholinergic burden (ACB). A trigger tool was used for active search of ADRs, with subsequent causality evaluation. PIM use was evaluated by means of the Beers criteria and the STOPP/START criteria. The ABC scale was employed to estimate ACB. The Micromedex® and Drugs.com® medication databases were employed to evaluate the DDIs. RESULTS: The sample of this study consisted of 41 patients, with a mean age of 66.8 years old (±5.2). The 22 triggers used assisted in identifying 15 potential ADRs, and 26.8% of the patients developed them. The mean estimated ACB score was 3.0 (±1.8), and the patients used 3.1 (±1.4) and 3.3 (±1.6) PIMs according to the Beers and the STOPP criteria, respectively. A total of 672 DDIs were identified, with a mean of 16.8 (±9.5) DDIs/patient during ICU hospitalization. Our findings show an association between occurrence of ADRs in the ICU and polypharmacy (p=.03) and DDIs (p=.007), corroborating efforts for rational medication use as a preventive strategy. CONCLUSIONS: Using tools to evaluate the pharmacotherapy for older people in intensive care can assist in the recognition and prevention of pharmacotherapeutic problems, with emphasis on the identification of ADRs through the observation of triggers and subsequent causality analysis.

Prediction of adverse drug reactions in geriatric patients admitted to intensive care units. / [Artículo traducido] Predicción de reacciones adversas a medicamentos en pacientes geriátricos ingresados en unidades de cuidados intensivos.

INTRODUCTION: Intensive Care Units (ICUs) pose challenges in managing critically-ill patients with polypharmacy, potentially leading to Adverse Drug Reactions (ADRs), particularly in the elderly. OBJECTIVE: To evaluate whether the severity and clinical prognosis scores used in ICUs correlate with the prediction of ADRs in aged patients admitted to an ICU. METHODS: A cohort study was conducted in a Brazilian University Hospital ICU. APACHE II and SAPS 3 assessed clinical prognosis, while GerontoNet ADR Risk Score and BADRI evaluated ADR risk at ICU admission. Severity of the patients' clinical conditions was evaluated daily based on the SOFA score. Adverse Drug Reaction (ADR) screening was performed daily through the identification of ADR triggers. RESULTS: 1295 triggers were identified (median 30 per patient, IQR = 28), with 15 suspected ADRs. No correlation was observed between patient severity and ADRs at admission (p=0.26), during hospitalization (p=0.91), or at follow-up (p=0.77). There was also no association between death and ADRs (p=0.28) or worse prognosis and ADRs (p>0.05). Higher BADRI scores correlated with more ADRs (p=0.001). CONCLUSIONS: The data suggest that employing the severity and clinical prognosis scores used in Intensive Care Units is not sufficient to direct active pharmacovigilance efforts, which are therefore indicated for critically ill patients.

Management of hereditary hemorrhagic telangiectasia-like symptoms induced by trastuzumab emtansine in a breast cancer patient: case report.

Trastuzumab emtansine (T-DM1) is a targeted therapy combining trastuzumab and emtansine for human epidermal growth factor receptor 2(HER2)-positive breast cancer, with common side effects including fatigue, nausea, pain, headache, low platelet count, and elevated liver enzymes. Hereditary Hemorrhagic Telangiectasia (HHT) is an autosomal dominant vascular dysplasia characterized by vascular malformations and telangiectasias in various organs. We present a case of a female patient with advanced breast cancer who developed HHT-like symptoms while on T-DM1 treatment. A 59-year-old woman treated with radiotherapy and T-DM1 every 21 days developed recurring nosebleeds and mucocutaneous and liver telangiectasias indistinguishable from HHT three months after receiving the first dose of T-DM1. Other organ vascular malformations were ruled out through screening protocols. The patient had no previous HHT symptoms or family history. Nasal care measures like lubrication and antifibrinolytics (tranexamic acid) were provided. In addition, propranolol was also prescribed due to its antiangiogenic and antitumoral properties, leading to significantly decreased epistaxis and telangiectasias. Microtubule disruptions caused by T-DM1, along with other angiogenic mechanisms may contribute to the development of telangiectasias resembling HHT. The use of propranolol, an initial approach for HHT, proved to be effective in this case. It is crucial for oncologists and HHT specialists to be aware of this rare adverse event associated with T-DM1 and to implement appropriate management strategies.

Use of sodium dichloroacetate for cancer treatment: a scoping review / Uso de dicloroacetato de sodio para el tratamiento del cáncer en pacientes adultos: una revisión

Abstract In recent years, drug repurposing (DR) has gained significant attention as a promising strategy for iden tifying new therapeutic uses of existing drugs. One po tential candidate for DR in cancer treatment is sodium dichloroacetate (DCA), which has been shown to alter tumor metabolism and decrease apoptosis resistance in cancer cells. In this paper, we present a scoping review of the use of DCA for cancer treatment in adult patients, aiming to identify key research gaps in this area. This scoping review aims to explore the existing scientific literature to provide an overview of the use of DCA (any dose, frequency, or route of administration) in adults with cancer. A comprehensive literature search of the medical databases MEDLINE/PubMed, LILACS, EPISTEMONI KOS, the Cochrane Library, and ClinicalTrials was performed. We included publications reporting on adult patients diagnosed with any type of cancer treated with sodium dichloroacetate in combination or not with other drugs. All types of study design were included. A total of 12 articles were included, most of them were case reports. We found a high degree of heteroge neity between them. The most frequent adverse events in the evaluated studies were asthenia, reversible toxic ity, and an increase in liver enzymes. Effectiveness was difficult to evaluate. We conclude that there is insufficient evidence to affirm that treatment with DCA in cancer patients is effective or is safe.

Resumen El reposicionamiento de fármacos (RF) es un enfo que terapéutico reciente que se presenta como una estrategia prometedora para identificar nuevos usos terapéuticos de fármacos existentes. Un candidato potencial para RF en el tratamiento del cáncer es el dicloroacetato de sodio (DCA), el cual ha mostrado la capacidad de alterar el metabolismo tumoral y dismi nuir la resistencia a la apoptosis de células tumorales. La presente es una revisión (scoping review) del uso del DCA para el tratamiento del cáncer en pacientes adultos, que tiene como objetivo identificar brechas de investigación claves en esta área. Esta revisión pretende explorar la literatura científica existente, para propor cionar una visión general del uso del DCA (cualquier dosis, frecuencia o vía de administración) en individuos adultos con cáncer. Se llevó a cabo una búsqueda exhaustiva de la lite ratura en las bases médicas de datos MEDLINE/PubMed, LILACS, EPISTEMONIKOS, the Cochrane Library y Clini calTrials. Se incluyeron publicaciones que informaban sobre pacientes adultos diagnosticados con cualquier tipo de cáncer, tratados con DCA, en combinación o no con otros fármacos. Dichos estudios presentaban distintos tipos de diseño. Se incluyó un total de 12 artículos, la mayoría de los cuales fueron reportes de casos. Se encontró un alto grado de heterogeneidad entre los mismos. Los even tos adversos más frecuentes fueron astenia, toxicidad reversible y aumento de las enzimas hepáticas, siendo la efectividad terapéutica difícil de evaluar. Concluimos que existe evidencia insuficiente para afirmar que el tratamiento con DCA en pacientes con cáncer es efectivo y/o seguro.

[Off-label use of intravenous immunoglobulin g in a highly complex pediatric hospital in Argentina. A prospective observational study] / Uso "off label" de inmunoglobulina g endovenosa en un hospital pediátrico de alta complejidad de Argentina.

Introduction: The World Health Organization recommends prioritizing safe and effective drugs proven by clinical or epidemiological studies. However, in population groups with little research, a drug can be used for an indication or pharmaceutical form different from that approved by the regulatory agency (off-label), extrapolating data from studies in adults and exposing pediatric patients. to develop an Adverse Drug Reaction (ADR) due to safety considerations that have not been systematically studied. Intravenous immunoglobulin (IVIg), a high-cost drug, is used with scant evidence in some low-prevalence pathologies. This paper describes and analyzes the off-label use of IVIg at the J. P. Garrahan Pediatric Hospital. Methods: Observational, descriptive, prospective study on off-label indications of IVIg. The sampling technique was non-probabilistic and for convenience during 7 months. Results: 305 IVIg infusions were studied, corresponding to 111 patients. The indication classification showed that 22% (n=67) of the infusions were off-label. In neurology there was a higher percentage of off-label indications (46%) and within them 45% corresponded to the use in neurological disorders. 81% of the doses indicated off-label were in the range 0.8-1g/kg. The off-label infusions presented 61.5% (n=8) of the ADRs. Those from the Neurology service represented 87.5%; 75% being from the "Neurological disorders" group. Conclusion: In some cases, IVIg was indicated in an off-label manner, finding a statistically significant relationship with the appearance of ADR. This finding motivates the proposition of new hypotheses to carry out more studies.

Introducción: La Organización Mundial de la Salud recomienda priorizar fármacos seguros y eficaces comprobados mediante estudios clínicos o epidemiológicos. Sin embargo, en grupos poblacionales con escasa investigación, un fármaco puede utilizarse para una indicación o, forma farmacéutica diferente a la aprobada por la agencia reguladora ("off label"), extrapolando datos provenientes de estudios en adultos y, exponiendo a los pacientes pediátricos a desarrollar una Reacción Adversa Medicamentosa (RAM) por consideraciones de seguridad no estudiadas sistemáticamente. Inmunoglobulina G endovenosa (IgG EV), medicamento de alto costo, es utilizado con escasa evidencia en algunas patologías poco prevalentes. Este trabajo describe y analiza el uso "off label" de IgG EV en el Hospital de Pediatría J. P. Garrahan. Métodos: Estudio observacional, descriptivo, prospectivo sobre indicaciones "off label" de IgG EV. La técnica de muestreo fue no probabilística y por conveniencia durante 7 meses. Resultados: Se estudiaron 305 infusiones de IgG EV que correspondieron a 111 pacientes. La clasificación de la indicación mostró que 22% (n=67) de las infusiones fueron "off label". En neurología hubo mayor porcentaje de indicaciones "off label" (46%) y dentro de ellas el 45% correspondió al uso en desórdenes neurológicos. El 81% de dosis indicadas "off label" estuvieron en rango 0,8-1g/kg. Las infusiones indicadas "off label" presentaron el 61.5% (n=8) de las RAM. Las del servicio de Neurología, representaron el 87,5 %, siendo 75% del grupo "Desórdenes neurológicos". Conclusión: En algunos casos IgG EV fue indicada en forma "off label", encontrándose una relación estadísticamente significativa con la aparición de RAM. Este hallazgo motiva al planteo de nuevas hipótesis para realizar más estudios.

Antivirales de acción directa contra la hepatitis C: revisión narrativa / Direct acting antivirals against hepatitis C: Literature review

Desde los años ochenta se ha explorado el tratamiento para el virus de la hepatitis C, aunque en ese entonces los medicamentos disponibles eran poco toleradas y poco eficaces. En el 2011, la introducción de antivirales de acción directa transformó significativamente el curso de la enfermedad, logrando tasas de curación superiores al 90 % en los pacientes. Este avance ha permitido prevenir complicaciones futuras con efectos adversos mínimos. La presente revisión aborda la línea de tiempo del descubrimiento de los antivirales, su mecanismo de acción, sus indicaciones y potencial impacto en la salud pública.

Since the 1980s, the treatment of hepatitis C has been explored, although at that time, the available medications were poorly tolerated and ineffective. In 2011, the introduction of direct-acting antivirals significantly transformed the course of the disease, achieving cure rates of over 90% in patients. This advance has made it possible to prevent future complications with minimal adverse effects. This review addresses the timeline of the discovery of antivirals, their mechanism of action, and their impact on medicine.

Prediction of adverse drug reactions in geriatric patients admitted to intensive care units.

INTRODUCTION: Intensive care units (ICUs) pose challenges in managing critically ill patients with polypharmacy, potentially leading to adverse drug reactions (ADRs), particularly in the elderly. OBJECTIVE: To evaluate whether the severity and clinical prognosis scores used in ICUs correlate with the prediction of ADRs in aged patients admitted to an ICU. METHODS: A cohort study was conducted in a Brazilian University Hospital ICU. APACHE II and SAPS 3 assessed clinical prognosis, while GerontoNet ADR Risk Score and BADRI evaluated ADR risk at ICU admission. Severity of the patients' clinical conditions was evaluated daily based on the SOFA score. ADR screening was performed daily through the identification of ADR triggers. RESULTS: 1295 triggers were identified (median 30 per patient, IQR=28), with 15 suspected ADRs. No correlation was observed between patient severity and ADRs at admission (p=0.26), during hospitalization (p=0.91), or at follow-up (p=0.77). There was also no association between death and ADRs (p=0.28) or worse prognosis and ADRs (p>0.05). Higher BADRI scores correlated with more ADRs (p=0.001). CONCLUSIONS: These data suggest that employing the severity and clinical prognosis scores used in ICUs is not sufficient to direct active pharmacovigilance efforts, which are therefore indicated for critically ill patients.

Use of sodium dichloroacetate for cancer treatment: a scoping review.

In recent years, drug repurposing (DR) has gained significant attention as a promising strategy for identifying new therapeutic uses of existing drugs. One potential candidate for DR in cancer treatment is sodium dichloroacetate (DCA), which has been shown to alter tumor metabolism and decrease apoptosis resistance in cancer cells. In this paper, we present a scoping review of the use of DCA for cancer treatment in adult patients, aiming to identify key research gaps in this area. This scoping review aims to explore the existing scientific literature to provide an overview of the use of DCA (any dose, frequency, or route of administration) in adults with cancer. A comprehensive literature search of the medical databases MEDLINE/PubMed, LILACS, EPISTEMONIKOS, the Cochrane Library, and ClinicalTrials was performed. We included publications reporting on adult patients diagnosed with any type of cancer treated with sodium dichloroacetate in combination or not with other drugs. All types of study design were included. A total of 12 articles were included, most of them were case reports. We found a high degree of heterogeneity between them. The most frequent adverse events in the evaluated studies were asthenia, reversible toxicity, and an increase in liver enzymes. Effectiveness was difficult to evaluate. We conclude that there is insufficient evidence to affirm that treatment with DCA in cancer patients is effective or is safe.

El reposicionamiento de fármacos (RF) es un enfoque terapéutico reciente que se presenta como una estrategia prometedora para identificar nuevos usos terapéuticos de fármacos existentes. Un candidato potencial para RF en el tratamiento del cáncer es el dicloroacetato de sodio (DCA), el cual ha mostrado la capacidad de alterar el metabolismo tumoral y disminuir la resistencia a la apoptosis de células tumorales. La presente es una revisión (scoping review) del uso del DCA para el tratamiento del cáncer en pacientes adultos, que tiene como objetivo identificar brechas de investigación claves en esta área. Esta revisión pretende explorar la literatura científica existente, para proporcionar una visión general del uso del DCA (cualquier dosis, frecuencia o vía de administración) en individuos adultos con cáncer. Se llevó a cabo una búsqueda exhaustiva de la literatura en las bases médicas de datos MEDLINE/PubMed, LILACS, EPISTEMONIKOS, the Cochrane Library y ClinicalTrials. Se incluyeron publicaciones que informaban sobre pacientes adultos diagnosticados con cualquier tipo de cáncer, tratados con DCA, en combinación o no con otros fármacos. Dichos estudios presentaban distintos tipos de diseño. Se incluyó un total de 12 artículos, la mayoría de los cuales fueron reportes de casos. Se encontró un alto grado de heterogeneidad entre los mismos. Los eventos adversos más frecuentes fueron astenia, toxicidad reversible y aumento de las enzimas hepáticas, siendo la efectividad terapéutica difícil de evaluar. Concluimos que existe evidencia insuficiente para afirmar que el tratamiento con DCA en pacientes con cáncer es efectivo y/o seguro.

hsa­miR­455­3P as a predictive biomarker of anemia in patients with non­small cell lung cancer treated with carboplatin plus paclitaxel.

Lung cancer is the leading cause of cancer-related morbidity and mortality worldwide. The initial treatment of lung cancer depends on the definition of the tumor type and its staging. The most common treatment is chemotherapy, and the first-line treatment is a combination of carboplatin and paclitaxel. Although this treatment has good efficacy, there is a high prevalence of adverse events, particularly hematological reactions. Studies on new biomarkers related to these adverse events, such as circulating microRNAs (miRNAs/miRs), are important for optimizing the quality of life of patients. miRNAs have high stability in several biological fluids and they have specific expressions in different tissues or pathologies. Thus, the present study aimed to assess the relationship between circulating miRNAs and adverse hematologic reactions caused by treatment with carboplatin + paclitaxel in patients with lung cancer. Blood was collected from patients before and 15 days after chemotherapy for hematological adverse reaction analysis, microarray and quantitative (q)PCR validation. Adverse reactions were classified according to the Common Terminology Criteria for Adverse Events v4.0. Microarray analysis was performed using plasma from six patients without anemia and six patients with anemia, and nine miRNAs were differentially expressed. miR-1273g-3p, miR-3613-5p and miR-455-3p, identified using microarray, were assessed using qPCR in 20 patients without anemia and 26 patients with anemia. Bioinformatic analyses of miR-455-3p were performed using miRWalk, the Database for Annotation, Visualization and Integrated Discovery and GeneMania software. Microarray analysis of patients with and without anemia revealed nine significant differentially-expressed plasma miRNAs among these patients. Of these, miR-1273g-3p, miR-3613-5p and miR-455-3p were chosen for further assessment. Only miR-455-3p demonstrated a significant reduction in expression (P=0.04) between the groups before chemotherapy with carboplatin + paclitaxel. Bioinformatics analysis of miR-455-3p revealed a relationship between this miRNA and the hematopoietic pathway, particularly with respect to the RUNX family transcription factor 1 (RUNX1) and TAL bHLH transcription factor 1, erythroid differentiation factor (TAL1) genes. The most prevalent adverse reactions in patients with lung cancer treated with carboplatin + paclitaxel were hematological, particularly anemia. This adverse reaction, caused by dysfunction of the hematopoietic system, may be explained by a possible association between the important genes in this system, RUNX1 and TAL1, and hsa-miR-455-3p.

Manejo dos eventos adversos do dupilumabe na dermatite atópica e no prurigo nodular / Management of the adverse effects of dupilumab in atopic dermatitis and prurigo nodularis

A dermatite atópica (DA) e o prurigo nodular (PN) são doenças inflamatórias da pele que cursam com lesões variadas, como eczemas, pápulas e nódulos, acompanhados de intenso prurido e, nos casos graves, de importante prejuízo da qualidade de vida para os pacientes e seus familiares. O dupilumabe está aprovado no Brasil para o manejo das duas condições: DA moderada/grave e PN que não responde aos tratamentos tópicos. A eficácia e segurança do dupilumabe foram amplamente estabelecidas para ambas as condições em ensaios clínicos e estudos de vida real. Este artigo tem como objetivo revisar os principais eventos adversos (EAD) associados ao uso do dupilumabe em DA e PN, e auxiliar no seu manejo. Desde o início do uso da medicação, há alguns anos, os principais EAD reportados foram: a reação no local da injeção, a doença da superfície ocular (conjuntivite não infecciosa, blefarite, olhos secos), a eosinofilia e o eritema de face/pescoço. Outras manifestações também foram observadas em pacientes com DA em uso de dupilumabe, mas sem associação comprovada: psoríase, artralgia e alopecia areata. Apesar de muito infrequentemente levarem à suspensão do dupilumabe, é fundamental que os médicos prescritores deste medicamento para estas condições, dermatologistas e imunoalergistas, saibam detectar e manejar seus possíveis eventos adversos.

Atopic dermatitis (AD) and prurigo nodularis (PN) are inflammatory skin diseases characterized by various lesions such as eczema, papules, and nodules, with marked pruritus and, in severe cases, significant impairment of quality of life for patients and their families. Dupilumab is approved in Brazil for the management of both moderate/severe AD and PN that does not respond to topical treatments. The efficacy and safety of dupilumab have been extensively established for both conditions in clinical trials and real-world studies.This article aims to review the main adverse events (AEs) associated with the use of dupilumab in AD and PN and assist in their management. Since the introduction of dupilumab a few years ago, the main reported AEs have been injection site reactions, ocular surface disease (non-infectious conjunctivitis, blepharitis, dry eyes), eosinophilia, and facial/neck erythema. Other manifestations have also been observed in patients with AD on dupilumab, but without proven association: psoriasis, arthralgia, and alopecia areata. Although AEs very infrequently lead to discontinuation of dupilumab, it is crucial that physicians prescribing it for these conditions, dermatologists, and immunologists know how to detect and manage its possible adverse effects.

Clinical efficacy and safety of flumatinib versus dasatinib combined with multi-drug chemotherapy in adults with Philadelphia-positive acute lymphoblastic leukemia.

INTRODUCTION: Flumatinib, a highly selective ABL kinase inhibitor, exhibits stronger inhibition of intracellular BCR-ABL tyrosine kinase activity, compared to Imatinib. However, there is limited research comparing the real-world efficacy and safety of flumatinib and dasatinib in patients with Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL). OBJECTIVE: Investigating the differences in therapeutic efficacy and safety between flumatinib and dasatinib in combination with multi-drug chemotherapy for the treatment of newly diagnosed Ph+ ALL. METHOD: In this study, we assessed 43 patients with newly diagnosed Ph+ ALL (20 in the flumatinib group, 23 in the dasatinib group). RESULTS: There were no significant differences in gender, age, fusion gene type, initial blood routine, bone marrow blast cell ratio or chromosome karyotype between the two groups. Within 1 month, there were no significant differences in the complete response (CR), major molecular response (MMR) or minimal residual disease (MRD) negativity rate between the flumatinib and dasatinib groups. Similarly, within 3 months, there were no significant differences in CR or MMR rates between the two groups. However, the rates of complete molecular response (CMR) and MRD negativity within 3 months were significantly higher in the flumatinib group, compared to the dasatinib group (P < 0.05). Additionally, the flumatinib group exhibited fewer adverse reactions compared to the dasatinib group. CONCLUSION: These findings suggest that flumatinib is a safe and effective tyrosine kinase inhibitor (TKI) for achieving CMR and MRD negativity in patients with Ph+ ALL, as supported by this small series of patients.

Safety and possible anti-inflammatory effect of paclitaxel associated with LDL-like nanoparticles (LDE) in patients with chronic coronary artery disease: a double-blind, placebo-controlled pilot study.

Introduction: Studies in cholesterol-fed rabbits showed that anti-proliferative chemotherapeutic agents such as paclitaxel associated with solid lipid nanoparticles (LDE) have marked anti-atherosclerotic effects. In addition, association with LDE nearly abolishes paclitaxel toxicity. We investigated whether treatment with LDE-paclitaxel changes plaque progression by coronary CT angiography and is safe in patients with chronic coronary artery disease. Methods: We conducted a prospective, randomized, double-blind, placebo-controlled pilot study in patients with multi-vessel chronic coronary artery disease. Patients were randomized to receive IV infusions of LDE-paclitaxel (paclitaxel dose: 175 mg/m2 body surface) or LDE alone (placebo group), administered every 3 weeks for 18 weeks. All participants received guideline-directed medical therapy. Clinical and laboratory safety evaluations were made at baseline and every 3 weeks until the end of the study. Analysis of inflammatory biomarkers and coronary CTA was also performed at baseline and 4 weeks after treatment. Results: Forty patients aged 65.6 ± 8 years, 20 in LDE-paclitaxel and 20 in placebo group were enrolled. Among those, 58% had diabetes, 50% had myocardial infarction, and 91% were in use of statin and aspirin. Baseline demographics, risk factors, and laboratory results were not different between groups. In all patients, no clinical or laboratory toxicities were observed. From the baseline to the end of follow-up, there was a non-significant trend toward a decrease in IL-6 levels and hsCRP in the LDE-paclitaxel group (-16% and -28%, respectively), not observed in placebo. Regarding plaque progression analysis, variation in plaque parameter values was wide, and no difference between groups was observed. Conclusion: In patients with multivessel chronic coronary artery disease and optimized medical therapy, LDE-paclitaxel was safe and showed clues of potential benefits in reducing inflammatory biomarkers. Clinical Trial Registration: https://clinicaltrials.gov/study/NCT04148833, identifier (NCT04148833).

Adverse reactions induced by MDT/WHO (Rifampicin+Clofazimine+Dapsone) and ROM (Rifampicin+Ofloxacin+Minocycline) regimens used in the treatment of leprosy: a cohort study in a National Reference Center in Brazil.

Background: Recommended standard treatment for leprosy is multidrugtherapy (MDT/WHO), consisting Rifampicin+Dapsone+Clofazimine. Other medications are recommended in cases of resistance, adverse reactions and intolerances, including ROM regimen, Rifampicin+Ofloxacin+Minocycline. Therefore, pharmacovigilance is an important tool in understanding these adverse drug reactions (ADRs), supporting pharmacotherapy management and medication safety. This study seeks to evaluate ADRs comparing two therapeutic regimens, MDT and ROM, used in treatment of patients with leprosy, analyzing prognostic factors regarding risk and safety. Methods:A retrospective cohort study was performed by assessing medical records of 433 patients diagnosed with leprosy from 2010 to 2021 at a National Reference Center in Brazil. They were subject to 24 months or more of treatment with MDT or ROM regimens. ADR assessments were analyzed by two experienced researchers, who included clinical and laboratory variables, correlating them with temporality, severity and the causality criteria of Naranjo and WHO. Results: The findings observed an average of 1.3 reactions/patient. Out of individuals experiencing reactions, 67.0% (69/103) were utilizing MDT/MB, while 33.0% (34/103) were using ROM. The median time for ADR of 79 days for MDT and 179 days for ROM. In first reaction, Dapsone was the most frequently involved medication; the most affected system was hematopoietic. As compared to Clofazimine, results indicated that use of Dapsone was associated with 7% increased risk of ADR occurrence (HR: 1.07; p = 0.866). Additionally, Rifampicin was linked to 31% increased risk of ADRs (HR: 1.31; p = 0.602); and Ofloxacin showed 35% elevated risk (HR: 1.35; p = 0.653). Conversely, results for Minocycline indicated 44% reduction in the risk of ADRs (HR: 0.56; p = 0.527), although statistical significance was not reached. The use of MDT conferred 2.51 times higher risk of developing ADRs in comparison to ROM. Conclusion: The comparison between MDT and ROM revealed that MDT caused more ADRs, and these reactions were more severe, indicating less safety for patients. Dapsone was the most common medication causing ADRs, followed by Rifampicin. The combination with Clofazimine was associated with an additional risk of ADRs, warranting further studies to confirm this hypothesis. Given the high magnitude of ADRs, healthcare teams need to monitor patients undergoing leprosy treatment with focus on pharmacovigilance.

Percepção dos profissionais de enfermagem sobre manejo de reação infusional a antineoplásicos: estudo qualitativo / Perception of nursing professionals on the management of infusion reactions to antineoplastics: qualitative study

Identificar a percepção dos profissionais de enfermagem sobre o manejo de reação infusional imediata a antineoplásicos. Método: Trata-se de um estudo descritivo de caráter exploratório com abordagem qualitativa realizado em um hospital no Rio Grande do Sul. Resultados: Todos os participantes afirmaram saber identificar uma reação infusional. Após a identificação da reação, nota-se que a maioria obedeceu a uma ordem de condutas a serem realizadas. Quanto aos cuidados para prevenção das reações infusionais, a maioria dos participantes mencionou a administração de medicamentos pré-quimioterápicos, como antialérgicos e antieméticos. Conclusão: Os achados demonstram que a maioria dos profissionais sabe reconhecer e manejar, porém há a necessidade de treinamentos e padronização das ações.(AU)

To identify the perception of nursing professionals about the management of immediate infusion reactions to antineoplastic drugs. Method: This is a descriptive, exploratory study with a qualitative approach carried out in a hospital in Rio Grande do Sul. Results: All the participants said they knew how to identify an infusion reaction. After identifying the reaction, it was noted that the majority followed an order of conduct to be carried out. As for precautions to prevent infusion reactions, most of the participants mentioned the administration of pre-chemotherapy drugs, such as anti-allergic and anti-emetic drugs. Conclusion: The findings show that most professionals know how to recognize and manage them, but there is a need for training and standardization of actions.(AU)

Identificar la percepción de los profesionales de enfermería sobre el manejo de las reacciones infusionales inmediatas a medicamentos antineoplásicos. Método: Se trata de un estudio descriptivo, exploratorio, con abordaje cualitativo, realizado en un hospital de Rio Grande do Sul. Resultados: Todos los participantes afirmaron saber identificar una reacción a la infusión. Después de identificar la reacción, la mayoría siguió un orden de conducta. En cuanto a las precauciones para prevenir las reacciones a la infusión, la mayoría de los participantes mencionó la administración de fármacos prequimioterápicos, como antialérgicos y antieméticos. Conclusión: Los hallazgos muestran que la mayoría de los profesionales saben reconocerlas y manejarlas, pero es necesaria la formación y la estandarización de actuaciones.(AU)

Side effects of chronic systemic glucocorticoid therapy: what dermatologists should know.

In dermatologists' clinical practice, the use of systemic glucocorticoids is recurrent for the management of different comorbidities that require chronic immunosuppression. The prescription of this medication requires caution and basic clinical knowledge due to the several adverse effects inherent to the treatment. However, different doubts may arise or inappropriate conduct may be adopted due to the lack of objective and specific guidelines for the screening, prophylaxis and management of complications from chronic corticosteroid therapy. Considering this problem, the authors carried out a narrative review of the literature to gather up-to-date data on adverse effects secondary to the chronic use of systemic glucocorticoids. The broad approach to this topic made it possible to review the pathophysiology and risk factors for these complications, as well as to develop updated orientation that can be used as a learning tool and quick reference for dermatologists during their clinical practice with glucocorticoids.

Side effects of chronic systemic glucocorticoid therapy: what dermatologists should know

Abstract In dermatologists' clinical practice, the use of systemic glucocorticoids is recurrent for the management of different comorbidities that require chronic immunosuppression. The prescription of this medication requires caution and basic clinical knowledge due to the several adverse effects inherent to the treatment. However, different doubts may arise or inappropriate conduct may be adopted due to the lack of objective and specific guidelines for the screening, prophylaxis and management of complications from chronic corticosteroid therapy. Considering this problem, the authors carried out a narrative review of the literature to gather up-to-date data on adverse effects secondary to the chronic use of systemic glucocorticoids. The broad approach to this topic made it possible to review the pathophysiology and risk factors for these complications, as well as to develop updated orientation that can be used as a learning tool and quick reference for dermatologists during their clinical practice with glucocorticoids.

Bilateral acute depigmentation of the iris (BADI) and bilateral acute iris transillumination (BAIT): A case series from a center in Brazil

ABSTRACT Bilateral acute depigmentation of the iris and bilateral acute iris transillumination (BAIT) are similar clinical entities. The former causes acute-onset depigmentation of the iris stroma without transillumination, whereas the latter causes depigmentation of the iris pigment epithelium with transillumination. The etiopathogenesis of these conditions is not yet fully understood, but the proposed causes include the use of systemic antibiotics (especially moxifloxacin) and viral triggers. We present a case series of five female patients with a mean age of 41 (32-45) years, all of whom suffered acute onset of bilateral pain and redness of the eyes after moxifloxacin use (oral or topical). It is important for ophthalmologists to be aware of the two forms of iris depigmentation since this case series suggests that SARS-CoV-2 or its empirical treatment with moxifloxacin may trigger iris depigmentation. If this is the case, clinicians will likely see increased incidences of bilateral acute depigmentation of the iris and bilateral acute iris transillumination during and after the COVID-19 pandemic.

Mortality and years of life lost related to adverse drug events in Brazil

ABSTRACT OBJECTIVE To assess regional and national mortality and years of life lost (YLL) related to adverse drug events in Brazil. METHODS This is an ecological study in which death records from 2009 to 2018 from the Mortality Information System were analyzed. Codes from the International Classification of Diseases 10th revision (ICD-10) that indicated drugs as the cause of death were identified. The number of deaths and the YLL due to adverse drug events were obtained. Crude, age- and gender-specific, and age-adjusted mortality rates and YLL rates per 100,000 inhabitants were formed by year, age group, gender, and Brazilian Federative Unit. Rate ratios were calculated by comparing rates from 2009 to 2018. A joinpoint regression model was applied for temporal analysis. RESULTS For the selected ICD-10 codes, a total of 95,231 deaths and 2,843,413 YLL were recorded. Mortality rates from adverse drug events increased by a mean of 2.5% per year, and YLL rates increased by 3.7%. Increases in rates were observed in almost all age groups for both genders. Variations in rates were found between Federative Units, with the highest age-adjusted mortality and YLL rates occurring in the Distrito Federal. CONCLUSIONS The numbers and rates of deaths and YLL increased during the study period, and variations in rates of deaths and YLL were observed between Brazilian Federative Units. Information on multiple causes of death from death certificates can be useful for quantifying adverse drug events and analyzing them geographically, by age and by gender.

Intervenções educativas para prevenção e conduta dos eventos adversos pós-vacinação: uma revisão sistemática / Educational interventions for the prevention and management of adverse events following immunisation: a systematic review

Resumo O estudo tem como objetivo investigar as intervenções educativas para a prevenção e conduta dos eventos adversos pós-vacinação. Trata-se de uma revisão sistemática realizada por meio da análise de estudos observacionais sem restrição de idioma e ano com registro no PROSPERO pelo identificador CRD42022313144 e busca nas bases de dados MEDLINE, LILACS, Embase, CINAHL e Scopus. Dois pesquisadores selecionaram os estudos, extraíram os dados e avaliaram o risco de viés, as discordâncias foram resolvidas por um terceiro pesquisador. Atenderam os critérios de inclusão da revisão sistemática um total de seis artigos e os estudos apresentaram melhoras significativas pós-intervenção na conduta dos profissionais em relação à imunização. Conclui-se que o fornecimento de estratégias educativas de educação permanente no âmbito vacinal da atenção primária é eficaz para reduzir e/ou erradicar os erros de imunização e eventos adversos pós-vacinação.

Abstract This study investigated educational interventions for the prevention and management of adverse events following immunisation. This a systematic review was conducted by examining observational studies, with no restriction as to language or year, registered in PROSPERO with the identifier CRD42022313144 and by searching the MEDLINE, LILACS, Embase, CINAHL and Scopus databases. Two researchers selected the studies, extracted the data and assessed the risk of study bias; disagreements were resolved by a third researcher. A total of six articles met the inclusion criteria of the systematic review and the studies reported significant post-intervention improvements in staff conduct in relation to immunisation. It was concluded that educational strategies that lead to continued professional development in relation to vaccination in primary care were effective in reducing and/or eradicating immunisation errors and adverse events following immunisation.