Mechanical properties and immunotherapeutic effects of dissolving microneedles with different drug loadings based on hyaluronic acid

Abstract Improving vaccine immunity and reducing antigen usage are major challenges in the clinical application of vaccines. Microneedles have been proven to be painless, minimally invasive, highly efficient, and have good patient compliance. Compared with traditional transdermal drug delivery, it can effectively deliver a large-molecular-weight drug into the skin, resulting in a corresponding immune response. However, few studies have examined the relationship between microneedle loading dose and immune effects. In this study, the hyaluronic acid (HA) conical and pyramidal dissolving microneedles were prepared by the two-step vacuum drying method, respectively. The model drug ovalbumin (OVA) was added to HA to prepare dissolving microneedles with different loading amounts. The mass ratios of HA to OVA were 5:1, 5:3, and 5:5. The mechanical properties of the dissolving microneedles were characterized using nanoindentation and in vitro puncture studies. The immune effects of the matrix and drug content were studied in Sprague-Dawley (SD) rats. Finally, the diffusion behavior of OVA and the binding mode of HA and OVA in the microneedles were simulated using Materials Studio and Autodocking software. The experimental results showed that the conical microneedles exhibited better mechanical properties. When the mass ratio of HA to OVA was 5:3, the immune effect can be improved by 37.01% compared to subcutaneous injection, and achieved a better immune effect with relatively fewer drugs. This conclusion is consistent with molecular simulations. This study provides theoretical and experimental support for the drug loading and efficacy of microneedles with different drug loadings

Gammaglobulina subcutánea: Revisión sistemática / Subcutaneous gamma globulin: A systematic review

Las inmunodeficiencias primarias constituyen enfermedades determinadas genéticamente, caracterizadas por la alteración cuantitativa y/o funcional de distintos mecanismos implicados en la respuesta inmunitaria. Algunas de ellas se caracterizan por una alteración en la producción de anticuerpos, por lo que algunos pacientes se benefician con la administración supletoria de gammaglobulina, la cual se administra mayormente por vía endovenosa, siendo la vía subcutánea una alternativa terapéutica. La siguiente revisión sistemática tiene por objetivo determinar si la gammaglobulina subcutánea tiene alguna ventaja frente al clásico uso de gammaglobulina endovenosa, en pacientes pediátricos con inmunodeficiencias primarias, revisando la bibliografía disponible hasta la actualidad (AU)

Primary immunodeficiencies are genetically determined diseases characterized by the quantitative and/or functional alteration of different mechanisms involved in the immune response. Some of these diseases are characterized by an alteration in the antibody production and therefore some patients benefit from the supplementary administration of gamma globulin, which is mostly administered intravenously, with the subcutaneous route being a therapeutic alternative. The following systematic literature review aims to determine whether subcutaneous gamma globulin has any advantage over the classic use of intravenous gamma globulin in pediatric patients with primary immunodeficiencies (AU)

Tratamento farmacológico da estrongiloidíase em pacientes transplantados / Pharmacological treatment of strongilloidiasis in transplanted patients

O objetivo deste artigo foi comparar o uso da ivermectina e do albendazol em pacientes transplantados e relatar os respectivos sucessos terapêuticos nessa população. Foram analisados artigos que abordassem relatos de casos publicados nos últimos 4 anos no PubMed® relacionando os descritores "transplante de órgãos", "estrongiloidíase" e "tratamento". Foram encontrados e analisados dez relatos de caso que abordaram a estrongiloidíase em situa- ção pós-transplante contemplando 13 indivíduos. Desses, cinco (38,5%) utilizaram ambos os medicamentos, dos quais quatro (80%) se curaram, tendo recebido albendazol e ivermectina por via subcutânea (50%) ou albendazol e ivermectina por vias oral/ subcutânea (50%). O paciente que morreu recebeu albendazol e ivermectina por via subcutânea. Sete (53,8%) indivíduos utiliza- ram apenas ivermectina, dos quais três (42,8%) se curaram tendo recebido o medicamento oral (dois pacientes) ou subcutâneo (um paciente); dois (28,6%) morreram recebendo o medicamento via oral, dois (28,6%) usaram profilaticamente via oral e apenas um não manifestou sintomas. Apenas um (7,7%) indivíduo utilizou somente albendazol via oral tendo sobrevivido à infecção. A uti- lização combinada dos medicamentos ivermectina e albendazol parece ter efeito positivo no tratamento da estrongiloidíase. A administração da ivermectina por via subcutânea apresentou resultados promissores, contudo estudos controlados de siner- gia medicamentosa e vias de administração devem ser realizados para efetiva avaliação.

The objective of this article was to compare the use of ivermec- tin and albendazole in transplanted patients and to report the respective therapeutic successes in this population.Articles ad- dressing case reports published in the last 4 years in the PubMed relating the descriptors "organ transplantation", "strongyloidia- sis", and "treatment" were analyzed. Ten case reports addres- sing strongyloidiasis in a post-transplant situation, covering 13 individuals, were found and analyzed. Of these, five (38.5%) used both drugs of which 4 (80%) were cured having received subcu- taneous albendazole and ivermectin (50%) or oral/subcutaneous albendazole and ivermectin (50%). The patient who died received subcutaneous albenzadole and ivermectin. Seven (53.8%) indi- viduals used only ivermectin, of which three (42.8%) were cured having received the oral (2/3) or subcutaneous (1/3) medication, two (28.6%) died receiving the oral medication, and two (28.6%) used oral medication prophylactically, and only one did not show symptoms. Only one (7.7%) individual used only oral albenzadole and survived the infection. The combined use of the drugs iver- mectin and albendazole seems to have a positive effect on the treatment of strongyloidiasis. The administration of subcuta- neous Ivermectin has shown promising results; however, con- trolled studies of drug synergy and administration routes shall be performed for effective evaluation.

Efficacy and safety of dupilumab in two adolescents with severe atopic dermatitis / Eficácia e segurança do uso de dupilumabe em dois adolescentes com dermatite atópica grave

ABSTRACT We report the cases of two adolescent siblings with severe atopic dermatitis, who, despite weighing approximately 40kg, presented a good response to dupilumab with the off-label dose for individuals aged 12 years and weighing 60kg. Both had already used cyclosporine, azathioprine, methotrexate and oral corticosteroids for long periods, plus topical treatments with no adequate disease control. Skin lesions were constant and widespread, with frequent skin infections and very poor quality of life, with numerous physical and psychosocial consequences, such as dropping out of school activities due to severe itching, appearance and bullying. They also showed delayed growth and development. In 2018, dupilumab, an immunobiological agent, was approved for treatment of moderate to severe atopic dermatitis in adults and, in 2019, extended to the 12-17-year age group. Although it had already been approved by the Brazilian Health Surveillance Agency, the 200mg presentation (indicated for the weight of patients) was not available, with no expected arrival date. Therefore, weighing the risks and benefits of the situation of both, we chose to treat them with an adult dose (loading dose of 600mg subcutaneously, and 300mg subcutaneously every 2 weeks) despite the low weight. So far, they have received eight injections, showing significant improvement of disease and quality of life. There were no major adverse effects, only worsening of allergic conjunctivitis in one of them. The patients and their family are very satisfied, and we believe that the therapy has been successful.

RESUMO Relatamos os casos de dois irmãos adolescentes com dermatite atópica grave e que, apesar de pesarem cerca de 40kg, apresentaram boa resposta ao dupilumabe com a dose off-label para indivíduos com 12 anos e peso de 60kg. Ambos já tinham usado ciclosporina, azatioprina, metotrexato e corticoide oral por longos períodos, acrescidos de tratamentos tópicos sem controle adequado da doença. As lesões cutâneas eram constantes e disseminadas, e os irmãos apresentavam infeções de pele frequentes e qualidade de vida muito ruim, com inúmeras consequências físicas e psicossociais, como o abandono da atividade escolar pelo prurido intenso, pela aparência e pelo bullying sofrido. Apresentavam também retardo de crescimento e de desenvolvimento. Em 2018, o dupilumabe, um agente imunobiológico, foi aprovado para o tratamento de dermatite atópica moderada a severa para adultos e, em 2019, ampliado para faixa etária de 12 a 17 anos. Embora já tivesse a aprovação da Agência Nacional de Vigilância Sanitária no Brasil, a apresentação de 200mg (indicada para o peso dos pacientes) não estava disponível, sem previsão de chegada. Assim, pesando os riscos e benefícios da situação de ambos, optamos por tratá-los com dose de adulto (ataque de 600mg por via subcutânea e 300mg por via subcutânea a cada 2 semanas) apesar do baixo peso. Até o momento, eles realizaram oito aplicações, apresentando importante melhora da doença e da qualidade de vida. Não houve efeitos adversos importantes - apenas a piora da conjuntivite alérgica em um deles. Os pacientes e sua família estão muito satisfeitos, e nós avaliamos que a terapia está sendo bem-sucedida.

Inmunoterapia con ácaros Valergen por vía sublingual y subcutánea en pacientes alérgicos. Cabaiguán 2010-2019 / Sublingual and subcutaneous Valergen mite immunotherapy in allergic patients in Cabaiguán 2010-2019

RESUMEN Fundamento: La inmunoterapia consiste en la administración de dosis crecientes del alérgeno para controlar la sensibilidad hacia este. Objetivo: Describir el comportamiento de la inmunoterapia por vía subcutánea o sublingual a ácaros. Metodología: Estudio retrospectivo realizado en Cabaiguán, periodo de 2010 a 2019, el universo de 267 pacientes con pruebas positivas a ácaros y la muestra de 53 pacientes. Los datos se obtuvieron del registro de datos. Resultados: Usó la vía sublingual el 60.4 %, predominó el grupo de edad entre 5-18 años (41.5 %), la vía subcutánea se utilizó en un 39.6 %, fue más frecuente en el sexo masculino (58.5 %). La vía subcutánea se indicó mayoritariamente en la rinitis alérgica (20.7 %) y la sublingual en el asma (32.1 %); para ambas, fue el Dermatofagoide pteronyssinus el ácaro de mayor sensibilidad y utilización (43.4 %), el tiempo de administración dominante fue de 3 años (67.9 %). El control de los síntomas se alcanzó con la vía sublingual (37.7 %). En la vía sublingual no se presentaron eventos adversos en el 43.3 %, con la vía subcutánea 11.3 % de los eventos adversos fueron locales y 7.6 % sistémicos leves. Conclusiones: La vía sublingual fue la más utilizada, la de mayor control de los síntomas y menos eventos adversos en el estudio.

ABSTRACT Background: Immunotherapy consists of the administration of the allergen increasing doses to control sensitivity towards it. Objective: To describe the behavior of subcutaneous or sublingual immunotherapy to mites. Methodology: Retrospective study carried out in Cabaiguán, from 2010 to 2019, the universe of 267 patients with positive tests to mites and the sample 53 patients. Data were obtained from the data record. Results: 60.4 % used sublingual, the age group between 5-18 years prevailed (41.5 %), the subcutaneous was used in 39.6 %, and it was more frequent in males (58.5 %). The subcutaneous was indicated mainly in allergic rhinitis (20.7 %) and sublingual in asthma (32.1 %); for both, Dermatofagoide pteronyssinus was the highest sensitivity and use mite (43.4 %) the dominant administration time was 3 years (67.9 %). Symptom control was achieved by sublingual (37.7 %). In sublingual, there were no adverse events in 43.3 %, with the subcutaneous, 11.3 % of the adverse events were local and 7.6 % were mild systemic. Conclusions: Sublingual was the most used, the one with the highest control of symptoms and the fewest adverse events in the study.

Fatores associados com a escolha da terapia nos pacientes com doença inflamatória intestinal no Brasil / Factors associated with patient´s preference in choosing their therapy for inflammatory bowel disease in brazil

BACKGROUND: Biological therapy and new drugs have revolutionized the treatment of inflammatory bowel disease. Ideally, the choice of medication should be a shared decision with the patient, aiming at greater satisfaction, compliance, and consequently, favorable clinical outcome. OBJECTIVE: This study aims to evaluate patient's preferences in the choice of their therapy and the factors that influence this choice. METHODS: This cross-sectional study enrolled 101 outpatients with Crohn's disease or ulcerative colitis. The inclusion criteria were age ≥18 years and no previous exposure to biological therapy. Patients' preferences were assessed through questions that addressed the preferred mode of administration (oral, subcutaneous, or intravenous) and the factors that determined the choice of medication (efficacy, medical indication, fear of medication, convenience, mode of application, and personal doctors' indication). RESULTS: The mean age was 43.6±13.5 years, 75.3% were female, and 81.2% were cases of ulcerative colitis. Regarding the mode of administration, the majority of patients preferred oral (87.1%), followed by intravenous (6.93%) and subcutaneous (5.94%) medications. The reasons were "I prefer to take it at home" (42.57%), "I have more freedom" (36.63%), "I don't like self-application" (29.70%), and "I believe it works better" (19.80%). Younger patients and patients in clinical disease activity preferred intravenous mode compared to the oral route (P<0.05). Doctor's opinion (98%) was an important factor associated with the medication choice. CONCLUSION: Oral route was the preferred mode of administration and most patients took their physician's opinion into account in their choice of medication.

RESUMO CONTEXTO: A terapia biológica e os novos medicamentos revolucionaram o tratamento da doença inflamatória intestinal. A escolha do medicamento deve ser compartilhada com o paciente, visando maior satisfação, adesão e, consequentemente, desfecho clínico favorável. OBJETIVO: Este estudo teve como objetivo avaliar as preferências do paciente na escolha de sua terapia e os fatores que influenciaram essa escolha. MÉTODOS: Este estudo transversal incluiu 101 pacientes ambulatoriais com doença de Crohn ou retocolite ulcerativa. Os critérios de inclusão foram idade ≥18 anos e nenhuma exposição prévia à terapia biológica. A preferência dos pacientes foi avaliada por meio de perguntas que abordaram o modo de administração preferido (oral, subcutâneo ou intravenoso) e os fatores que determinaram a escolha do medicamento (eficácia, indicação médica, medo da injeção, conveniência, modo de aplicação e opinião pessoal do médico). RESULTADOS: A idade média foi de 43,6±13,5 anos, 75,3% eram mulheres e 81,2% eram portadores de retocolite ulcerativa. Em relação ao modo de administração, a maioria dos pacientes preferiu os medicamentos orais (87,1%), seguidos dos endovenosos (6,93%) e subcutâneos (5,94%). Os motivos foram "prefiro aplicar em casa" (42,57%), "tenho mais liberdade com essa medicação" (36,63%), "não gosto de autoaplicação" (29,70%) e "acredito que funcione melhor" (19,80%). Pacientes jovens e pacientes em atividade clínica preferiram a via intravenosa em comparação com a via oral (P<0,05). A opinião do médico (98%) foi um fator importante associado à escolha do medicamento. CONCLUSÃO: A via oral foi preferida e a maioria dos pacientes levou em consideração a opinião do seu médico na escolha do medicamento.

Cutaneous infection by Mycobacterium lentiflavum after subcutaneous injection of lipolytic formula

Abstract The incidence of nontuberculous mycobacterial infections is increasing worldwide; by 2017, more than 190 species and subspecies have been documented. Although classically associated with immunosuppression, the recognition of these etiological agents in diseases affecting immunocompetent individuals and in healthcare-associated infections, such as after surgical and cosmetic procedures, makes the study of the epidemiology and pathogenesis of these microorganisms relevant in medical practice. Mycobacterium lentiflavum is slow-growing and rarely affects the skin. A case of cutaneous mycobacteriosis caused by M. lentiflavum is reported in an immunocompetent patient after subcutaneous injection of a lipolytic compound, treated with clarithromycin and levofloxacin.

Ivermectina subcutánea en el tratamiento de un síndrome de hiperinfección por Strongyloides stercoralis / Subcutaneous ivermectin for the treatment of the hyperinfection syndrome by Strongyloides stercoralis

La estrongiloidiasis es una enfermedad causada por el nematodo Strongyloides stercoralis, endémico en las regiones rurales de los países tropicales y subtropicales. Los pacientes inmunosuprimidos tienen un mayor riesgo de infección con este parásito y pueden terminar desarrollando un síndrome de hiperinfección que conlleva un alto riesgo de muerte. En el tratamiento se utiliza la ivermectina, pero, ni en Colombia ni en el mundo, existe una presentación parenteral del medicamento para uso en humanos, lo cual es un problema en aquellos pacientes que puedan tener comprometida la absorción intestinal, como es el caso de aquellos con obstrucciones intestinales. Se reporta el caso de un síndrome de hiperinfección por S. stercoralis en Colombia tratado con ivermectina subcutánea; la idea al presentarlo es incentivar los estudios de farmacocinética y farmacodinamia que analicen esta vía de administración como alternativa para el tratamiento de pacientes con riesgo de fracaso terapéutico con la vía oral.

Strongyloidiasis is a disease caused by the nematode Strongyloides stercoralis that is endemic in rural regions in tropical and subtropical countries. Immunosuppressed patients have an increased risk of infection by this parasite and are at risk of developing a hyperinfection syndrome which involves a higher risk of death. The syndrome is treated with ivermectin, however, there is no parenteral presentation of this medication for human use in Colombia or the world, which is an important problem in patients who have compromised enteral absorption, for instance, those with intestinal obstructions. We present a case of hyperinfection syndrome by Strongyloides stercoralis in Colombia, which was treated with subcutaneous ivermectin. Our purpose is to encourage pharmacokinetic and pharmacodynamic studies to establish this route of administration in the future as an alternative for those patients who have a high risk of therapeutic failure with the oral route.

Safety and tolerability of a single dose T0001 in Chinese healthy adult volunteers: a first-in-human ascending dose study

T0001 is the first mutant of etanercept with a higher affinity to tumor necrosis factor α (TNF-α) than etanercept. In order to investigate the safety and tolerability of T0001, a study was carried out in healthy Chinese subjects. A first-in-human, dose escalation study was conducted in healthy Chinese subjects. Fifty-six subjects were divided into six dose cohorts (10 mg, 20 mg, 35 mg, 50 mg, 65 mg and 75 mg) to receive a single subcutaneous injection of T0001. Safety and tolerability assessment were based on the records of vital signs, physical examinations, clinical laboratory tests, 12-lead electrocardiograms and adverse events (AEs). All subjects were in good compliance and none withdraw due to AEs. No serious AEs occurred. A total of twenty-three AEs in sixteen subjects were recorded, and eighteen of these AEs were believed to be related to T0001. The most frequently reported AEs were injection site reactions and white blood cell count increase. All these AEs were of mild to moderate intensity and most of them recovered spontaneously within 14 days. In this study, no dose-limiting toxicity was observed, and the maximum tolerated dose was identified as 75 mg. T0001 was considered safe and generally well tolerated at doses up to 75 mg in healthy Chinese volunteers

Práticas de medicações injetáveis: conduta referida de profissionais de enfermagem / Prácticas de medicaciones inyectables: conducta referida de los profesionales de enfermería / Injectable medications: self-reported practices of nursing professionals

RESUMO Objetivo: Identificar a conduta referida de profissionais da enfermagem, do estado de São Paulo, sobre Práticas de Medicações Injetáveis. Método: Estudo tipo survey que identificou a frequência referida sobre Práticas de Medicações Injetáveis mediante resposta de questionário eletrônico, validado, entre setembro e dezembro de 2017. Resultados: Considerando as 1.295 respostas computadas, foram identificadas inconformidades como compartilhamento de frascos multidoses para dois ou mais pacientes (10,8%), reutilização de insumos de uso único, como seringas para salinização de pacientes diferentes (1,2%) e reencape de agulhas após uso (4,9%). Foram referidas maior adesão ao uso de luvas para administração de injeções endovenosas (80,5%) e falta de treinamento para manipulação de dispositivos de segurança (13%). Dados correlacionais apontaram que, quanto maior a idade, melhor era a conduta referida na prática de injetáveis. Conclusão: Embora a maioria das condutas configure-se dentro das Boas Práticas de Medicações Injetáveis, há relatos de práticas de risco, como compartilhamento de insumos de uso único. O treinamento para uso de dispositivos de segurança ainda não é uma realidade para todos os profissionais, visto que muitos o referiram como raro.

RESUMEN Objetivo: Identificar la conducta de profesionales de enfermería del estado de São Paulo sobre Prácticas de Medicaciones Inyectables. Método: Se trata de un estudio tipo survey, el cual identificó la frecuencia de Prácticas de Medicaciones Inyectables mediante respuesta de un cuestionario electrónico, validado entre septiembre y diciembre de 2017. Resultados: Teniendo en cuenta las 1.295 respuestas computadas, se identificaron inconformidades como el uso de frascos de dosis múltiples para dos o más pacientes (10,8%), la reutilización de insumos de un solo uso, como jeringas para la salinización de diferentes pacientes (1,2%) y el reencapuchado de agujas después de su uso (4,9%). Sobresalió la adhesión al uso de guantes para las inyecciones intravenosas (80,5%) y la falta de capacitación sobre la manipulación de dispositivos de seguridad (13%). Los datos correlativos señalaron que, a mayor edad, mejor la conducta referida en la práctica de los inyectables. Conclusión: Aunque la mayoría de las conductas se configuran dentro de las Buenas Prácticas de Medicaciones Inyectables, se informa sobre la existencia de prácticas de riesgo, como el compartir insumos de un solo uso. La capacitación en el uso de dispositivos de seguridad aún no es una realidad para todos los profesionales y muchos han declarado que raramente se los entrena en esa área.

ABSTRACT Objective: To identify the self-reported injectable medications of nursing professionals in the state of São Paulo. Method: Survey study that assessed the self-reported frequency of injection medications through a validated electronic questionnaire, applied from September to December 2017. Results: The 1,295 computed responses showed non-compliances such as sharing multidose vials for two or more patients (10.8%), reusing single-use supplies, such as use of saline flush syringes for different patients (1.2%) and needle recapping after use (4.9%). Greater adherence to glove use for administration of intravenous injections (80.5%) and lack of training for handling safety devices (13%) were reported. Correlational data showed that, the older the age, the better the self-reported injecting practices. Conclusion: Although most practices are within Safe Injecting practices, there are reports of risky practices, such as sharing single-use supplies. Training for the use of safety devices is not yet a reality for all professionals, since many reported it as rare.

Efeito do uso de minerais traços (cobre, zinco, selênio e manganês) e vitaminas (A e E) injetáveis sobre o estresse oxidativo e função de neutrófilos de fêmeas da raça Holandesa no período de transição / Effect of use of injected trace minerals (copper, zinc, selenium, and manganese) and vitamins (A and E) on oxidative stress and neutrophil function in females of Hostein cows during transitionl

O objetivo deste estudo foi avaliar o efeito metafilático de minerais traços e vitaminas A e E injetáveis, em parâmetros do estresse oxidativo e na função de neutrófilos em fêmeas da raça Holandesa no período de transição. Sessenta animais foram divididos em dois grupos: animais que receberam minerais traços e vitaminas A e E injetáveis (GMTV) (n= 30) e grupo controle (GC) (n= 30). Não houve diferença significativa entre os grupos nos parâmetros avaliados, porém observou-se diferença significativa entre tratamento e dia para os valores da SOD, com maior atividade dessa enzima em fêmeas GMTV, nas semanas próximas ao parto. Observou-se diferença de dia e para interação tratamento e dia para o TBARS, em que fêmeas GMTV mostraram menores valores de TBARS em todos os momentos, exceto sete dias após o parto. Houve efeito significativo de dia para leucócitos, interação tratamento e dia para neutrófilos e interação tratamento e dia para fagocitose de neutrófilos, em que as fêmeas GMTV apresentaram valores menores de leucócitos e neutrófilos próximo ao parto, além de maior fagocitose de neutrófilos. Pode-se observar que houve melhora no sistema oxidativo e imune de fêmeas GMTV, resposta que provavelmente está relacionada com a administração dos minerais traços e vitaminas A e E.(AU)

This study evaluates the metaphylactic of the subcutaneous administration of a trace minerals and vitamins A and E, on the oxidative stress and neutrophil function in Holsteins cows under the transition period. Sixty females were divided in two groups: group with trace minerals and vitamins (GMTV) (n= 30) and group control (GC) (n= 30). There was no significant difference between those groups; however, we find significant difference between treatment and day for Superoxide dismutase (SOD) values with higher activity of this enzyme in females GMTV on the weeks next to the parturition. Still, there was difference on day and, for interactions between treatment and day for TBARS, were females GMTV showed lower values of TBARS in all moments, except on day seven after the parturition. For leucocytes, there is a significant effect by day, interaction on treatment and day on neutrophils, and interaction treatment and day for neutrophil phagocytosis, were females GMTV showed lower values of leucocytes and neutrophils next to the parturition, and an increase of neutrophils phagocytosis. In summary, cows from the GMTV group had an improvement on the immune and oxidative systems, probably correlated with the administration of this supplement.(AU)

Elaboração e validação de checklist para administração de medicamentos para pacientes em protocolos de pesquisa / Elaboración y validación de checklist para la administración de medicamentos para pacientes en protocolos de investigación / Elaboration and validation of a drug administration checklist for patients in research protocols

Resumo OBJETIVO Descrever a elaboração e validação de um checklist como estratégia de administração segura de medicamentos. MÉTODO Estudo de validação por consenso de especialistas conduzido de janeiro a junho de 2018 em um Centro de Pesquisa Clínica de um hospital universitário. O checklist foi validado por três enfermeiros assistenciais, dois técnicos de enfermagem, um farmacêutico, dois enfermeiros professores e um médico professor, todos com ampla experiência na administração de medicamentos e em pesquisa clínica. Para a lista final foi considerado consenso de 100% entre os especialistas. RESULTADOS Elaborou-se um guia composto por seis itens a serem checados pela equipe assistencial antes, durante e após a administração de medicamentos de Pesquisa Clínica. CONCLUSÃO A validação do checklist forneceu elementos norteadores para a prevenção de comportamentos que podem levar ao risco de eventos adversos e também permitiu que as equipes assistenciais buscassem estratégias seguras de cuidado na administração de medicamentos.

Resumen OBJETIVO Describir la elaboración y validación de un checklist como estrategia de administración segura de medicamentos. MÉTODO Estudio de validación por consenso de especialistas conducido de enero a junio/2018 en Centro de Investigación Clínica de un hospital universitario. El checklist fue validado por tres enfermeros asistenciales, dos técnicos de enfermería, un farmacéutico, dos enfermeros profesores y un médico profesor todos con amplia experiencia en administración y supervisión de medicamentos y investigación clínica. Para la lista final se consideró consenso del 100% entre los expertos. RESULTADOS Elaboró ​​un guía compuesto por seis ítems a ser chequeados por el equipo asistencial antes, durante y después de la administración de medicamentos de Investigación Clínica. CONCLUSIÓN La validación del checklist proporcionó elementos orientadores para la prevención de comportamientos que pueden llevar al riesgo de eventos adversos y también permitió a los equipos asistenciales buscar estrategias seguras de cuidado en la administración de medicamentos.

Abstract OBJECTIVE To describe the elaboration and validation of a checklist as a strategy for safe drug administration. METHOD It is a Validation study by consensus of experts conducted from January to June 2018, in a Clinical Research Center of a university hospital. The checklist was validated by three nurses, two nursing technicians, a pharmacist, two nurse teachers and one medical teacher, all with extensive experience in drug administration and in clinical research. For the final version of the checklist, a consensus of 100% was considered. RESULTS A guide was prepared consisting of six items to be checked by the care team before, during and after administration of Clinical Research drugs. CONCLUSION The validation of the checklist provided guiding elements for the prevention of behaviors that could lead to the risk of adverse events and also allowed the care teams to seek safe strategies of care in drug administration.

Dupilumab in the treatment of severe atopic dermatitis refractory to systemic immunosuppression: case report / Dupilumabe no tratamento da dermatite atópica grave refratária à imunossupressão sistêmica: relato de caso

ABSTRACT Case report of a patient with severe atopic dermatitis who showed a good response to dupilumab. She had already used two immunosuppressive agents, cyclosporine A and mycophenolate mofetil, for the treatment of atopic dermatitis with no proper control of the disease. She had also been taking all measures to control severe cases of the disease: bath and environmental controls, topical potent corticosteroids and emollients. She presented constant pruritus and skin lesions, frequent skin infections e poor quality of life. She also developed depression due to her disease. Recently, dupilumab, a new biological agent, was approved for the treatment of moderate/severe atopic dermatitis in many countries, including Brazil. Dupilumab is a monoclonal antibody with a common alpha chain of interleukin (IL) 4 and IL-13 receptors, two cytokines involved in the Th2 profile immune response that promote atopic inflammation. In a pioneer way in Brazil, the patient initiated the treatment with an attack dose of 600mg subcutaneous of dupilumab and 300mg subcutaneous every other week. Up to now, she has taken four applications, presenting a great improvement of the disease and her quality of life. There were no adverse effects, nor in the injection site nor of other kind. Patient and her family are very satisfied, and the medical team evaluates that the treatment is being well succeed. The case report described here subsidizes the use of dupilumab in the treatment of severe atopic dermatitis refractory to use of immunosuppressive agents.

RESUMO Relatamos o caso de uma paciente com dermatite atópica grave, que mostrou boa resposta ao dupilumabe. Ela já tinha usado dois agentes imunossupressores, a ciclosporina A e o micofenolato de mofetila, para o tratamento da dermatite atópica, sem obter o controle adequado da doença. Ela também vinha fazendo uso de todas as medidas de controle para casos graves da doença: cuidados com o banho, controle ambiental, corticosteroides potentes tópicos e emolientes. Apresentava prurido e lesões cutâneas constantes, infeções de pele frequentes e qualidade de vida ruim. Passou a apresentar depressão devido à sua doença. Recentemente, o dupilumabe, um agente biológico novo, foi aprovado para o tratamento de dermatite atópica moderada a severa em muitos países, incluindo o Brasil. Dupilumabe é um anticorpo monoclonal cujo alvo é a cadeia alfa comum aos receptores da interleucina (IL) 4 e IL-13, duas citocinas envolvidas no perfil de resposta imune Th2, que promove inflamação atópica. De modo pioneiro no Brasil, a paciente iniciou o tratamento, com dose de ataque de 600mg por via subcutânea de dupilumabe e 300mg também por via subcutânea a cada 2 semanas. Até o momento deste relato, ela realizou quatro aplicações, apresentando grande melhora da doença e da qualidade de vida. Não houve efeitos adversos, nem no local da injeção e nem de outro tipo. A paciente e sua família estão muito satisfeitas, e os médicos que a tratam avaliam que a terapia está sendo bem-sucedida. Este relato de caso subsidia o uso de dupilumabe no tratamento da dermatite atópica grave refratária ao uso de imunossupressores.

Inyección subcutánea de mercurio elemental. Importancia de la remoción precoz / Subcutaneous injection of metallic mercury. The importance of early removal

La inyección subcutánea o intramuscular de mercurio elemental, sea accidental o intencional, es una forma poco frecuente de intoxicación. Presentamos el caso de un hombre de 22 años de edad, con antecedentes de rasgos psicóticos y lesiones autolíticas, que se inyectó mercurio elemental en el tejido celular subcutáneo del cuello, tórax y abdomen, tres meses antes de su internación. Las áreas afectadas fueron localizadas mediante el examen físico, radiografías y tomografías. Se realizó el dosaje de mercurio en sangre y orina. Se resecó quirúrgicamente el mercurio de las zonas comprometidas. La detección y remoción precoz del mercurio, mediante cirugía y eventual quelación, es necesaria para prevenir complicaciones a corto y largo plazo.

Accidental or intentional subcutaneous or intramuscular injection of metallic mercury is an uncommon form of intoxication. We present the case of a 22 year-old man, who had psychotic disorders and autoaggressive behavior, with a preceding history of self-injection of mercury into the soft tissues of the neck, thorax and abdomen. Clinical examination, radiographs, and computed tomography showed the affected area. Mercury was measured in blood and urine. The mercury was surgically resected from the affected areas. Early detection and removal of mercury from the body by physical removal or chelation is required to prevent short- and long-term toxicity.

Preoperative subcutaneous sildenafil injection increases random flap survival in rats

Abstract Purpose: To investigate the effect of subcutaneous sildenafil on random flap survival. Methods: Fourteen Wistar rats, which were divided in to two groups, were used for this experimental study. Rats in the sildenafil group received subcutaneous sildenafil injections daily for seven days before flap elevation. At the end of the treatment period, 9x3 cm dorsal skin flaps were elevated and reinserted back into their place in all of the animals. Necrotic and whole flaps areas were recorded on graph papers. Seven days after the flap elevation samples for histological examination were taken and angiographies were performed to visualize the flap vascularization. Results: The calculated average percentage of necrotic flap areas were 18.29% and 42.26% in the sildenafil and control group respectively.(p=0.0233). In selected angiography images, vessels were found to be more prominent in the sildenafil group. The average number of capillary formations under light microscopy was higher in the sildenafil group (p= 0.0286). Conclusion: The subdermal high dose sildenafil has a positive effect on flap survival.

The effects of subcutaneous injection of nicotine on osseointegration of machined and anodized implants in rabbits

Abstract Purpose: To evaluate the influence of subcutaneous injection nicotine in osseointegration process on different implant surfaces. Methods: Twenty-two male rabbits were distributed into two groups according to the subcutaneous injections: (1) nicotine 3 mg/day/kg and (2) 0.9 % NaCI 3 mL/day/kg, three times a day; subgroups were then designated-machined and anodized implants were placed in the right and left tibia bones, respectively. The animals were submitted euthanasia after periods of eight weeks to determine nicotine and cotinine levels, alkaline phosphatase and biomechanical analysis. Results: The plasmatic levels of nicotine and cotinine were 0.5 ± 0.28 ng/mL and 9.5 ± 6.51 ng/mL, respectively. The alkaline phosphatase analyses in blood levels in control group were observed 40.8 ± 11.88 UI/L and 40.75 ± 12.46 UI/L, for the surfaces machined and anodized, respectively. In the test group was observed levels 37.9 ± 4.84 UI/L, for both implant surfaces. No significant differences were observed between control and test groups and between the implant surfaces regarding alkaline phosphatase blood levels. For biomechanics, no significant differences were observed in control group between the machined (25±8.46 Ncm) or anodized (31.2 ± 6.76 Ncm) implants. However, the treatment with nicotine induced higher torque than control in both machined (38.3 ± 13.52 Ncm) and anodized (35.5 ± 14.17 Ncm) implants, with p = 0.0024 and p = 0.0121, respectively. Conclusion: Subcutaneous injection of nicotine following implant insertion didn't have effect on osseointegration, independently from the implant surface.

Injerto dermo-epidérmico como tratamiento del siliconoma de extremidad inferior / Dermoepidermal graft as treatment of lower extremity siliconoma

Resumen Introducción A pesar de la evidencia sobre los malos resultados y riesgos del uso de inyecciones subcutáneas de silicona para mejorar el contorno corporal, esta técnica sigue siendo utilizada por personas no calificadas. Caso clínico Paciente de 56 años quien consultó por cuadro de celulitis en pierna izquierda. Se obtuvo el antecedente de intervención con silicona en cara, dorso de las manos, glúteos y piernas el año 2000. El cuadro progresó con múltiples abscesos en la totalidad de la pierna y sepsis. Se realizaron aseos quirúrgicos exponiendo planos fascial y muscular, se utilizó terapia local con sistemas de presión negativa y posterior injerto dermo-epidérmico (IDE). El manejo multidisciplinario se realizó en unidades críticas. Los resultados del manejo fueron satisfactorios, salvando la extremidad con cobertura total, logrando el alta luego de 4 meses. Conclusión A pesar de conocerse los peligros de la inyección de silicona, este sigue siendo un procedimiento frecuente. En nuestra paciente se manifestó como fascitis de la pierna, requiriendo tratamiento quirúrgico agresivo. Conocer esta entidad, su diagnóstico y tratamiento es fundamental para tratar pacientes con complicaciones graves.

Introduction Despite the evidence of poor performance and risks of using silicone subcutaneous injections to improve body contour, this technique is still used by untrained people, generating an iatrogenic entity with serious complications. Case report 56 year old female presented left lower extremity cellulitis. A history of previous intervention with silicone injections in face, back of hands, buttocks and legs in year 2000 was obtained. An inflammatory process progressed locally and systemically with multiple abscesses, subcutaneous thickness in the entire leg and sepsis, requiring multiple surgical procedures, reaching fascial and muscle planes exposition of the left leg. The patient underwent local therapy with negative pressure systems and subsequent dermoepidermal graft. Multidisciplinary management was performed on a critical unit. The results were satisfactory, preserving the limb with full coverage. She was discharged after four months of inpatient management. Conclusion Despite knowing the risks of silicone injection (industrial or medical) it remains a common procedure. In our patient she presented as leg fasciitis, requiring aggressive surgical treatment. Knowing this entity, its diagnosis and treatment is essential to treat patients with serious complications.

Behavioral cross-sensitization between testosterone and fenproporex in adolescent and adult rats

The abuse of psychoactive drugs is considered a global health problem. During the last years, a relevant number of studies have investigated the relationship between anabolic-androgenic steroids (AAS) and other psychoactive drugs. AAS, such as testosterone, can cause a dependence syndrome that shares many features with the classical dependence to psychoactive substances. Pre-clinical evidence shows that there are interactions between testosterone and psychoactive drugs, such as cocaine. However, few studies have been performed to investigate the effect of repeated testosterone treatment on behavioral effects of amphetamine derivatives, such as fenproporex. The purpose of the present study was to investigate the effects of repeated testosterone administration on fenproporex-induced locomotor activity in adolescent and adult rats. Adolescent male Wistar rats were injected with testosterone (10 mg/kg sc for 10 days). After 3 days, animals received an acute injection of fenproporex (3.0 mg/kg ip) and the locomotor activity was recorded during 40 min. Thirty days later, the same animals received the same treatment with testosterone followed by a fenproporex challenge injection as described above. Our results demonstrated that repeated testosterone induced behavioral sensitization to fenproporex in adolescent but not in adult rats. These findings suggest that repeated AAS treatment might increase the dependence vulnerability to amphetamine and its derivatives in adolescent rats.

Avaliação ultraestrutural de agulhas e seu papel no conforto durante a administração subcutânea de medicamentos / Evaluación ultraestructural de agujas y su papel en el confort durante la administración subcutánea de fármacos / Ultra-structural evaluation of needles and their role for comfort during subcutaneous drug administration

RESUMO Objetivo Avaliar a morfologia de biséis de agulhas hipodérmicas após a aspiração de drogas e a percepção de conforto ocasionado pela troca ou não de agulhas entre preparo e administração de medicamentos pela via subcutânea. Método Pesquisa experimental realizada em dois momentos. Inicialmente, agulhas hipodérmicas foram analisadas por microscopia eletrônica de varredura e, em seguida, um ensaio piloto foi conduzido com os participantes, que indicaram o nível de conforto percebido no momento da penetração dos biséis das agulhas durante a administração pela via subcutânea. Resultados Participaram do estudo 41 pacientes adultos internados. Apesar de as agulhas terem apresentado de discreta a importante alteração morfológica, quando avaliadas por ultramicroscopia, os participantes deste estudo não foram capazes de relatar alterações sensoriais significativas durante a penetração destas nas duas técnicas adotadas. Conclusões A padronização de seringas com agulhas fixas ou o uso de uma única agulha tanto para o preparo quanto para a administração de medicamentos pela via subcutânea devem ser considerados como estratégias para redução da produção de resíduos perfurocortantes, diminuição do custo por procedimento e limitação do risco de contaminação de dispositivos considerados críticos.

RESUMEN Objetivo Evaluar la morfología de biseles de agujas hipodérmicas luego de la aspiración de drogas y la percepción de confort ocasionado por el cambio de agujas entre la preparación y la administración de fármacos por la vía subcutánea. Método Investigación experimental llevada a cabo en dos momentos. Inicialmente, agujas hipodérmicas fueron analizadas por microscopia electrónica de barrido y, a continuación, un ensayo piloto fue conducido con los participantes, quienes señalaron el nivel de confort percibido en el momento de la penetración de los biseles de las agujas durante la administración por la vía subcutánea. Resultados Participaron en el estudio 41 pacientes adultos ingresados. A pesar de que las agujas hayan presentado de discreta a importante modificación morfológica, cuando evaluados por ultramicroscopia, los participantes de este estudio no fueron capaces de relatar modificaciones sensoriales significativas durante la penetración de esas en ambas técnicas adoptadas. Conclusión La estandarización de jeringas con agujas fijas o el empleo de una sola aguja tanto para la preparación como la administración de fármacos por la vía subcutánea se deben considerar como estrategias para reducción de la producción de residuos punzocortantes, reducción del costo por procedimiento y limitación del riesgo de contaminación de dispositivos considerados críticos.

ABSTRACT Objective To evaluate the morphology of hypodermic needle bevels after drug aspiration, and the perception of comfort caused by the change or not of needles between preparation and subcutaneous drug administration. Method Experimental research carried out in two moments. Initially, hypodermic needles were analyzed by scanning electron microscopy, and then a pilot trial was conducted with the participants, which indicated the level of comfort perceived at the time of needle bevel penetration during subcutaneous administration. Results Forty-one adult inpatients participated in the study. Although the needles presented a slight to significant morphological alteration when evaluated by ultramicroscopy, the participants in this study were not able to report significant sensory changes during their penetration in the two techniques used. Conclusions The standardization of fixed needle syringes, or the use of a single needle for both the preparation and the subcutaneous drug administration should be considered as strategies to reduce the production of sharp-perforating residues, to decrease the cost per procedure, and to limit the risk of contamination of critical devices.