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BACKGROUND: This study examines the association of standard-of-care systemic lupus erythematosus (SLE) medications with key outcomes such as low disease activity attainment, flares, damage accrual, and steroid-sparing, for which there is current paucity of data. METHODS: The Asia Pacific Lupus Collaboration (APLC) prospectively collects data across numerous sites regarding demographic and disease characteristics, medication use, and lupus outcomes. Using propensity score methods and panel logistic regression models, we determined the association between lupus medications and outcomes. RESULTS: Among 1707 patients followed over 12,689 visits for a median of 2.19 years, 1332 (78.03%) patients achieved the Lupus Low Disease Activity State (LLDAS), 976 (57.18%) experienced flares, and on most visits patients were taking an anti-malarial (69.86%) or immunosuppressive drug (76.37%). Prednisolone, hydroxychloroquine and azathioprine were utilised with similar frequency across all organ domains; methotrexate for musculoskeletal activity. There were differences in medication utilisation between countries, with hydroxychloroquine less frequently, and calcineurin inhibitors more frequently, used in Japan. More patients taking leflunomide, methotrexate, chloroquine/hydroxychloroquine, azathioprine, and mycophenolate mofetil/mycophenolic acid were taking ≤ 7.5 mg/day of prednisolone (compared to > 7.5 mg/day) suggesting a steroid-sparing effect. Patients taking tacrolimus were more likely (Odds Ratio [95% Confidence Interval] 13.58 [2.23-82.78], p = 0.005) to attain LLDAS. Patients taking azathioprine (OR 0.67 [0.53-0.86], p = 0.001) and methotrexate (OR 0.68 [0.47-0.98], p = 0.038) were less likely to attain LLDAS. Patients taking mycophenolate mofetil were less likely to experience a flare (OR 0.79 [0.64-0.97], p = 0.025). None of the drugs was associated with a reduction in damage accrual. CONCLUSIONS: This study suggests a steroid-sparing benefit for most commonly used standard of care immunosuppressants used in SLE treatment, some of which were associated with an increased likelihood of attaining LLDAS, or reduced incidence of flares. It also highlights the unmet need for effective treatments in lupus.
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Antimaláricos , Azatioprina , Glucocorticoides , Hidroxicloroquina , Imunossupressores , Lúpus Eritematoso Sistêmico , Metotrexato , Prednisolona , Padrão de Cuidado , Humanos , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Feminino , Imunossupressores/uso terapêutico , Hidroxicloroquina/uso terapêutico , Masculino , Glucocorticoides/uso terapêutico , Adulto , Azatioprina/uso terapêutico , Prednisolona/uso terapêutico , Metotrexato/uso terapêutico , Antimaláricos/uso terapêutico , Estudos de Coortes , Pessoa de Meia-Idade , Ácido Micofenólico/uso terapêutico , Leflunomida/uso terapêutico , Inibidores de Calcineurina/uso terapêutico , Modelos Logísticos , Pontuação de Propensão , Índice de Gravidade de Doença , Tacrolimo/uso terapêutico , Exacerbação dos Sintomas , Resultado do Tratamento , Antirreumáticos/uso terapêuticoRESUMO
Introducción: La respuesta al tratamiento inmunosupresor en la hepatitis autoinmune influye en el curso clínico de la enfermedad y se asocia a mayor sobrevida. Objetivo: Describir la respuesta al tratamiento inmunosupresor en pacientes con hepatitis autoinmune. Método: Se realizó un estudio descriptivo, longitudinal, ambispectivo, en 32 enfermos con hepatitis autoinmune, los cuales recibieron tratamiento inmunosupresor con evaluación de la respuesta a los 6 meses. Las variables incluidas fueron: tipo de hepatitis autoinmune, forma de presentación, forma de debut y respuesta al tratamiento. Se utilizaron medidas descriptivas de resumen: media y desviación estándar para variables cuantitativas y porcentaje para las variables cualitativas. Para estimar la función de supervivencia se utilizó la curva de Kaplan-Meier y Log-rank para la comparación de medias. Resultados: El 71,9 % de los enfermos estaban con cirrosis en el momento del diagnóstico. Los 13 pacientes con remisión bioquímica permanecieron sin progresión en la evaluación actual. La supervivencia en los pacientes respondedores fue del 100 % y en los no respondedores de 47,5 % a los 10 años de seguimiento. Conclusiones: La respuesta al tratamiento inmunosupresor tiene un impacto positivo en la no progresión de la hepatitis autoinmune y se asoció a mayor supervivencia.
Introduction: The response to immunosuppressive treatment in autoimmune hepatitis influences the clinical course of the disease and is associated with a longer survival. Objective: Describe the response to immunosuppressive treatment in patients with autoimmune hepatitis. Method: A descriptive, longitudinal, ambispective study was carried out in 32 patients with autoimmune hepatitis, who received immunosuppressive treatment with response evaluation at 6 months. The variables included were: type of autoimmune hepatitis, form of presentation, form of onset, and response to treatment. Descriptive summary measures were used: mean and standard deviation for quantitative variables and percentage for qualitative variables. To estimate the survival function, the Kaplan-Meier curve and Log-rank were used to compare means. Results: 71.9 % of the patients were already cirrhotic at the time of diagnosis. The 13 patients with biochemical remission, remained without progression in the current evaluation. Survival in responding patients was 100 %, while in non-responders it was 47.5% at 10-year follow-up. Conclusions: The response to immunosuppressive treatment has a positive impact on the non-progression of autoimmune hepatitis and was associated with greater survival.
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This study aimed to evaluate humoral responses after vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) of patients with inflammatory bowel disease (IBD). Patients with IBD enrolled in a tertiary outpatient unit were followed up between September 2021 and September 2022 via serial blood collection. Immunoglobulin G antibody titers against SARS-CoV-2 were measured before administration and 1 and 6 months after the administration of two doses of different vaccination regimens. The results were compared with those of a healthy control group obtained during the same period. The mean pre-vaccination antibody titers were 452.0 and 93.3 AU/mL in the IBD (n = 42) and control (n = 89) groups, respectively. After two doses of the vaccine, the titers significantly increased in both groups (IBD, 8568.0 AU/mL; control, 7471.0 AU/mL; p < 0.001). One month after the second dose, no significant differences were observed between the two groups (p = 0.955). Significant differences between vaccination schemes in the IBD group were observed, with higher titers in those who received Pfizer, younger patients (p < 0.005), and those with a previous coronavirus disease 2019 (COVID-19) infection (p < 0.012). The use of immunosuppressants and immunobiologicals did not affect the overall humoral response to COVID-19 vaccine in patients with IBD, but specific vaccine regimens, age, and previous coronavirus infection significantly did. This study reinforces the positive impact of booster doses and the safety of SARS-CoV-2 vaccination.
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El síndrome de Vogt-Koyanagi-Harada es una enfermedad autoinmune multisistémica crónica, caracterizada por panuveítis difusa granulomatosa bilateral con desprendimiento exudativo de retina y papilitis. Compromete el sistema nervioso central (meninges, disacusia neurosensorial) así como piel y mucosas. A pesar de ser una enfermedad compleja y poco frecuente, se hace necesario comprender la importancia del diagnóstico rápido y el tratamiento oportuno con seguimiento especializado. Es por ello que se decidió realizar una revisión de la literatura con el objetivo de actualizar los conocimientos existentes sobre este tema. La búsqueda se realizó en diferentes publicaciones y textos básicos de la especialidad. Las fuentes consultadas fueron las bases de datos PubMed y Google Scholar. El diagnóstico de la enfermedad es esencialmente clínico y son los oftalmólogos quienes más lo sospechan por ser los síntomas oculares los más frecuentes y dramáticos. El pronóstico visual de los pacientes es generalmente bueno si el diagnóstico es precoz y se indica un tratamiento adecuado. Los corticosteroides sistémicos a altas dosis asociados a inmunosupresores y agentes biológicos tienen gran impacto en la evolución de la enfermedad, sobre todo estos últimos a nivel mundial, previniendo complicaciones y permitiendo resultados visuales satisfactorios para una mejor calidad de vida del paciente(AU)
Vogt-Koyanagi-Harada syndrome is a chronic multisystem autoimmune disease characterized by bilateral diffuse granulomatous panuveitis with exudative retinal detachment and papillitis. It involves the central nervous system (meninges, sensorineural dysacusis) as well as skin and mucous membranes. In spite of being a complex and infrequent disease, it is necessary to understand the importance of rapid diagnosis and timely treatment with specialized follow-up. For this reason, it was decided to carry out a review of the literature with the aim of updating the existing knowledge on this subject. The search was carried out in different publications and basic texts of the specialty. The sources consulted were the PubMed and Google Scholar databases. The diagnosis of the disease is essentially clinical and it is the ophthalmologists who suspect it the most because the ocular symptoms are the most frequent and dramatic. The visual prognosis of patients is generally good if the diagnosis is early and adequate treatment is indicated. Systemic corticosteroids at high doses associated with immunosuppressants and biological agents have a great impact on the evolution of the disease, especially the latter worldwide, preventing complications and allowing satisfactory visual results for a better quality of life of the patient(AU)
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Humanos , Doenças Autoimunes/etiologia , Descolamento Retiniano/diagnóstico por imagem , Pan-Uveíte/diagnóstico , Corticosteroides/uso terapêutico , Literatura de Revisão como AssuntoRESUMO
Psoriasis is a recurring, immune-mediated dermatological disorder. Many therapeutic agents are available for the treatment of psoriasis, including immunosuppressants and biologic treatments with immunosuppressant action. The employment of nanotechnology allows drug tailoring to achieve dermal targeting, improve efficacy and minimize undesirable effects. Here we discuss the use of the topical route in combination with nano-based drug delivery systems containing immunosuppressants for the management of psoriasis. This review is based on articles selected from 2011 to 2022, using the keywords "Psoriasis" AND "Immunosuppressants" AND "Nano*" in the main databases. Fifty-seven articles were retrieved, although only forty-two matched the inclusion criteria. Nanocarriers such as liposomes, ethosomes, niosomes, solid lipid nanoparticle, nanostructured lipid carriers and microspheres containing immunosuppressive drugs (methotrexate, cyclosporine, tacrolimus, and etanercept) were identified. The main findings of these studies are related to the improved in vitro/ex vivo permeation/penetration and therapeutic efficacy of nanoparticles in vitro and in vivo, compared to the drug in solution. Based on the studies discussed in this review, encapsulation in several types of nanocarriers decreases toxicity, dose, and dose frequency. Furthermore, it enables specific targeting of the active drug, pointing to the possibility of improving topical therapy for psoriasis. In conclusion, nanoformulations represent a novel and promising tool for psoriasis treatment.
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Nanopartículas , Psoríase , Humanos , Imunossupressores , Portadores de Fármacos , Psoríase/tratamento farmacológico , Metotrexato , NanotecnologiaRESUMO
OBJECTIVE: We studied infection rates and risk factors for infection in current patients with idiopathic nephrotic syndrome (INS). STUDY DESIGN: This retrospective cohort study included the clinical data for children with diagnosed INS in our center between January 2010 and December 2020. The infection rates and risk factors were analyzed. RESULTS: We enrolled 187 patients, including 85 cases with steroid-dependent/frequently relapsing nephrotic syndrome and 45 with steroid-resistant nephrotic syndrome. Infection was observed a total of 84 times in 55 patients (95.5 per 1000 person-years). Pneumonia was the most common infection (21 cases, 23.9 per 1000 person-years), followed by febrile neutropenia (12 cases, 13.7 per 1000 person-years), whereas peritonitis and bacteremia were observed in only 3 and 2 cases, respectively. The multivariate analyses by logistic regression showed that rituximab treatment was significantly associated with infections in pediatric INS (P = .001). The infection rate during the B-cell-depleted state with immunosuppressants (318 per 1000 person-years) was greater than that with normal B-cell count with immunosuppressants (109 per 1000 person-years) or without immunosuppressants (76 per 1000 person-years). CONCLUSION: Common infections, such as peritonitis and bacteremia, decreased, whereas infections associated with medication (eg, rituximab) increased. The rate of infection increases during B-cell depletion after treatments with rituximab and other immunosuppressants.
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Síndrome Nefrótica , Criança , Humanos , Rituximab/uso terapêutico , Síndrome Nefrótica/complicações , Síndrome Nefrótica/tratamento farmacológico , Síndrome Nefrótica/epidemiologia , Japão/epidemiologia , Estudos Retrospectivos , Imunossupressores/uso terapêutico , RecidivaRESUMO
O desenvolvimento da síndrome metabólica após o transplante renal (TxR) é evidenciado na literatura e se caracteriza por alterações que conferem a redução da função do enxerto. Objetivo: O objetivo deste trabalho é descrever a prevalência da síndrome metabólica e identificar variáveis que se associam à síndrome metabólica em receptores de TxR tardio. Metodologia: Trata-se de um estudo transversal analítico realizado com pacientes receptores de TxR. Foram incluídos participantes com idade superior ou igual a 18 anos, receptores de TxR tardio em acompanhamento superior a 6 meses. A análise descritiva dos dados foi expressa por médias, desvio padrão, medianas e percentuais. A normalidade dos dados foi verificada pelo teste de Shapiro-Wilk ao nível de 5% de significância. Aplicou-se o teste de comparação de médias para duas amostras independentes, teste t de Student. Foi utilizado o teste de correlação de Pearson para avaliar as possíveis relações existentes entre a variável tempo pós TxR com as outras variáveis de interesse. Resultados: Ao avaliar 43 pacientes com idade média de 50,9 ± 9,8 anos, notou-se que a síndrome metabólica esteve presente em 53,85% dos voluntários e que se associou ao peso prévio (p= 0,018), concentrações séricas de triglicerídeos (p= 0,001), menores médias de HDL (p= 0,053) e, também, foi verificada uma associação marginal com a circunferência da cintura (p= 0,051). A SM foi prevalente no período pós TxR. Ainda, as maiores médias de peso prévio ao TxR, de circunferência da cintura, de triglicerídeos e as menores médias de HDL se associaram à SM
The onset of metabolic syndrome (MS) after kidney transplantation (KTx) is evidenced in the literature and this is characterized by alterations that confer a reduction in the function of the transplantation. Objective: The aim of this research is to describe the prevalence of the metabolic syndrome and to identify the variables that are associated with the metabolic syndrome in recipients of belated KTx. Methods: This is an analytical cross-sectional study carried out with patients receiving KTx. Participants aged 18 years or older, recipients of late KTx with follow-up longer than 6 months, were included. The descriptive analysis of the data was expressed as means, standard deviation, medians and percentages. Data normality was verified using the Shapiro-Wilk test at a 5% significance level. The mean comparison test was applied for two independent samples, Student's t test. Pearson's correlation test was used to assess possible association between the variable time after KTx and the other variables of interest. Results: Forty-three patients with a mean age of 50.9 ± 9.8 years were evaluated and metabolic syndrome was present in 53.85% of the volunteers. There was an association with previous weight (p= 0.018), serum triglyceride concentrations (p= 0.001) and lower HDL means (p= 0.053) and and a marginal association with waist circumference (p=0,0051). MS was prevalent in the post-KTx period. Furthermore, the highest means of weight prior to KTx, waist circumference, TG and the lowest means of HDL were associated with MS
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Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Adulto Jovem , Transplante de Rim/efeitos adversos , Síndrome Metabólica/epidemiologia , Diabetes Mellitus , Transplantados , Imunossupressores/efeitos adversos , Imunossupressores/uso terapêuticoRESUMO
Las enfermedades reumáticas son un grupo de afecciones, la mayoría de ellas con afectación inmunológica y compromiso sistémico, que generan distintos grados de discapacidad funcional y disminución de la percepción de calidad de vida de los pacientes que las padecen. Constituyen una de las primeras causas de discapacidad, de invalidez temporal y definitiva, de afectación laboral y se sitúan dentro de los 10 primeros motivos de consultas en el primer nivel de atención de salud. Los pacientes con este tipo de enfermedad han sido considerados como pacientes inmunodeprimidos lo cual no se corresponde directamente con los mecanismos de producción de la gran mayoría de las enfermedades reumáticas. En el presente reporte se abordan los mitos y realidades que engloban a las enfermedades reumáticas y la supuesta inmunosupresión que generan, desde la perspectiva etiopatogénica. El esclarecimiento de estos elementos es indispensable para poder enfrentar adecuadamente, desde el punto de vista terapéutico y de autocuidado a los pacientes con enfermedades reumáticas. Se concluye, que con base en los elementos etiopatogénicos de las enfermedades reumáticas y el análisis de la expresión de la respuesta inmunológica normal y en pacientes reumáticos, estos no pueden ser considerados como personas inmunodeprimidas. La prescripción de inmunosupresores se realiza con la finalidad de restaurar la respuesta inmunológica normal.
Rheumatic diseases are a group of conditions, most of them with immunological affectation and systemic compromise, which generate different degrees of functional disability and decrease in the perception of quality of life of the patients who suffer from them. They constitute one of the main causes of disability, of temporary and definitive invalidity, of labor affectation and are among the first 10 reasons for consultations in the first level of health care. Patients with this type of disease have been considered immunocompromised, which does not correspond directly to the mechanisms of production of the vast majority of rheumatic diseases. This report addresses the myths and realities that encompass rheumatic diseases and the supposed immunosuppression they generate, from the etiopathogenic perspective of this group of diseases. The clarification of these elements is essential to be able to deal adequately, from the therapeutic and self-care point of view, with patients with rheumatic diseases. It is concluded that, based on the etiopathogenic elements of rheumatic diseases and the analysis of the expression of the normal immune response and in rheumatic patients, these cannot be considered as immunosuppressed people. The prescription of immunosuppressants is made in order to restore the normal immune response.
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Introduction: Advances in liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) have enabled the quantification of immunosuppressants using microsampling techniques. In this context, dried matrix on paper discs (DMPD) could be a useful alternative to conventional venipuncture. Although analytical validation is necessary to establish the suitability of method performance, it is not sufficient to proceed with its implementation into routine clinical practice. Also necessary is that equivalence between sampling methods be demonstrated in a clinical validation study. Objetives: To clinically validate a LC-MS/MS method for the quantification of tacrolimus, sirolimus, everolimus and cyclosporin A using DMPD. Methods: According to the recommendations of international guidelines, at least 40 whole blood (WB) and DMPD paired samples for each analyte were collected by skilled technicians and analyzed using LC-MS/MS. Results were evaluated in terms of statistical agreement and bias values at medical decision points. Results: For all analytes, Passing-Bablok regression analysis revealed that confidence intervals (CIs) for slopes and intercepts included 1 and 0, respectively. It also showed that biases at medical decision points were not clinically relevant. No statistically significant differences between DMPD and WB were found using difference plots and agreement analysis. In this regard, CIs for bias estimators included 0, and more than 95% of the results fell within the limits of agreement. Conclusion: The feasibility of the clinical application of simultaneous quantification of tacrolimus, sirolimus, everolimus and cyclosporin A in DMPD was demonstrated. Results showed that this microsampling technique is interchangeable with conventional WB sampling when specimens are collected by trained personnel.
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Most patients with atopic dermatitis (AD) have a good response to topical treatment. However, some need systemic therapy in order to satisfactorily control the disease. Azathioprine is an accessible drug for patients in many countries, including underdeveloped countries, and therefore it is used by many dermatologists in moderate and severe AD. It is important to have a deep knowledge and understanding about this drug since it is an alternative therapy as a steroid-sparing agent and an affordable one. However, when it comes to systemic therapy for AD, it is not always clear its indications and it is necessary to have a closer follow-up of the patient. In this paper, we describe thoroughly its indications in AD, the mechanism of action of the drug, as well as the interactions, adverse effects, adequate monitoring, and precautions in special population that must be considered when prescribing azathioprine. This review will help dermatologists prescribe it safely to all patients who require it.
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Dermatite Atópica , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Azatioprina/efeitos adversos , Dermatite Atópica/terapia , Humanos , Imunossupressores/efeitos adversosRESUMO
RESUMO Objetivo: construir e validar por concordância uma cartilha educativa sobre o uso dos imunossupressores no pós-transplante renal. Método: estudo metodológico, realizado em um ambulatório de acompanhamento de pacientes pós transplantados, no período de dezembro de 2019 a agosto de 2020. Desenvolvido em duas fases: construção da cartilha e validação por concordância do material por juízes especialistas. Foi considerado o nível de concordância de, no mínimo, 80% para se garantir a validação do material. Resultados: dos 30 itens avaliados da cartilha, na primeira fase, 15 foram modificados. Após as modificações do material, na segunda fase, somente um item apresentou valor de concordância inferior a 80%. Conclusão: a cartilha foi validada do ponto de vista de conteúdo e aparência, possibilitando auxílio aos profissionais de saúde no processo de educação em saúde, sendo um alicerce na assistência prestada aos pacientes transplantados renais.
ABSTRACT Objective: Construct and validate by agreement an educational booklet on the use of immunosuppressive drugs after kidney transplantation. Method: Methodological study carried out in an outpatient follow-up clinic for post-transplant patients, from December 2019 to August 2020. It was developed in two phases: construction of the booklet and validation by agreement of the material by expert judges. A minimum level of agreement of 80% was necessary for the validation of the material. Results: Of the 30 items evaluated in the booklet, in the first phase, 15 were modified. After the modifications in the material performed in the second phase, only one item had an agreement value lower than 80%. Conclusion: The booklet was validated in content and appearance. Thus, the material could be used to assist health professionals in the health education process and support the care provided to kidney transplant patients.
RESUMEN Objetivo: construir y validar por concordancia un folleto educativo sobre el uso de los inmunosupresores en el postrasplante renal. Método: estudio metodológico, realizado en un ambulatorio de seguimiento de pacientes post-trasplantados, en el periodo diciembre de 2019 a agosto de 2020. Desarrollado en dos fases: construcción del folleto y validación por concordancia del material por jueces especialistas. Se consideró un nivel de concordancia de al menos un 80% para garantizarse la validación del material. Resultados: de los 30 ítems evaluados del folleto en la primera fase, 15 fueron modificados. Después de las modificaciones del material, en la segunda fase, sólo un ítem presentó valor de concordancia inferior a 80%. Conclusión: el folleto fue validado desde el punto de vista del contenido y apariencia, posibilitando auxilio a los profesionales de la salud en el proceso de educación en salud, siendo una piedra angular en la asistencia prestada a los pacientes trasplantados renales.
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Comportamento Sexual , Infecções por HIV , Saúde ReprodutivaRESUMO
The development of nanoparticles (NPs) with potential therapeutic uses represents an area of vast interest in the scientific community during the last years. Recently, the pandemic caused by COVID-19 motivated a race for vaccines creation to overcome the crisis generated. This is a good demonstration that nanotechnology will most likely be the basis of future immunotherapy. Moreover, the number of publications based on nanosystems has significantly increased in recent years and it is expected that most of these developments can go on to experimentation in clinical stages soon. The therapeutic use of NPs to combat different diseases such as cancer, allergies or autoimmune diseases will depend on their characteristics, their targets, and the transported molecules. This review presents an in-depth analysis of recent advances that have been developed in order to obtain novel nanoparticulate based tools for the treatment of allergies, autoimmune diseases and for their use in vaccines. Moreover, it is highlighted that by providing targeted delivery an increase in the potential of vaccines to induce an immune response is expected in the future. Definitively, the here gathered analysis is a good demonstration that nanotechnology will be the basis of future immunotherapy.
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RESUMEN Introducción: Las enfermedades reumáticas son un grupo de alrededor de 250 afecciones que afectan fundamentalmente el sistema osteomioarticular, aunque la mayoría tiene un carácter sistémico. En el caso del sistema digestivo el compromiso puede estar causado por el propio proceso inflamatorio de la enfermedad o secundario a la afectación que causa los distintos grupos farmacológicos usados contra las enfermedades reumáticas. Objetivo: Caracterizar el compromiso digestivo de una cohorte de paciente con enfermedades reumáticas durante un periodo de estudio de 5 años. Métodos: Investigación básica, no experimental, descriptiva y longitudinal que incluyó como población de estudio una cohorte de 109 pacientes con diagnóstico de enfermedades reumáticas según criterios del Colegio Americano de Reumatología. Se identificaron las características generales de los pacientes, de las enfermedades reumáticas incluidas en la investigación y las principales manifestaciones digestivas identificadas. Resultado: Promedio de edad de 57,83 años, predominio de pacientes femeninas (71,56 %), procedencia urbana (55,05 %) y con diagnóstico de artritis reumatoide (50,46 %). El 90,82 % de los pacientes refirió haber utilizado glucocorticoides. El 94,49 % de los pacientes presentó algún tipo de manifestación extraarticular digestiva. La gastritis (36,89 %), úlcera péptica (25,24 %), reflujo gastroesofágico (18,45 %) y sequedad bucal (15,53 %) fueron las de mayor frecuencia de presentación. Conclusiones: Las manifestaciones digestivas constituyen una expresión extraarticular frecuente en el curso de las enfermedades reumáticas. Su origen pude estar supeditado a la patogenia de la enfermedad o a los eventos adversos de los grupos farmacológicos utilizados en los esquemas terapéuticos de las enfermedades reumáticas. Los glucocorticoides fueron el grupo farmacológico más usado. Algunas manifestaciones digestivas puede llegar a poner en peligro la vida de los pacientes.
ABSTRACT Introduction: Rheumatic diseases are a group of around 250 conditions that mainly affect the osteomyoarticular system, but most of them have a systemic nature, which is why they affect different organs and organ systems. In the case of the digestive system, the compromise may be caused by the inflammatory process of the disease itself or secondary to the affectation generated by the different pharmacological groups that are used to control rheumatic diseases. Objective: To characterize the digestive compromise of a cohort of patients with rheumatic diseases during a study period of 5 years. Methods: Basic, non-experimental, descriptive, correlational and longitudinal research that included as a study population a cohort of 109 patients diagnosed with rheumatic diseases according to the criteria of the American College of Rheumatology. The general characteristics of the patients, the rheumatic diseases included in the research, the main digestive manifestations identified were identified. Result: Average age of 57.83 years, predominance of female patients (71.56%), urban origin (55.05%) and with a diagnosis of rheumatoid arthritis (50.46%). 90.82% of the patients reported having used glucocorticoids. 94.49% of the patients presented some type of extra-articular digestive manifestation. Gastritis (36.89%), peptic ulcer (25.24%), gastroesophageal reflux (18.45%) and dry mouth (15.53%) were the ones with the highest frequency of presentation. Conclusions: Digestive manifestations are a frequent extra-articular expression in the course of rheumatic diseases. Its origin may be subject to the etiopathogenic mechanisms of the disease or to the adverse events of the pharmacological groups used in the therapeutic regimens for rheumatic diseases. Glucocorticoids were the most frequently used pharmacological group in the therapeutic regimens for rheumatic diseases. The presence of some digestive manifestations endanger the lives of patients.
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HumanosRESUMO
Tremor is the most common movement disorder and there are numerous causes of tremor. In many individuals, tremor can be due to drugs. The most common drugs associated with tremor include amiodarone, selective serotonin (and norepinephrine) reuptake inhibitors (SSRIs/SNRIs), amitriptyline, lithium, valproate, ß-adrenoceptor agonists, dopamine receptor antagonists, VMAT2 inhibitors, or drugs of abuse: ethanol, cocaine, etc. Drug-induced tremor usually resembles essential or parkinsonian tremor, depending on the offending drug; however, features such as unilateral, task-specific, position-dependent tremor or sudden onset, distractibility, entrainment and arrest with contralateral movements suggest etiologies such as dystonic or functional (psychogenic) tremor. Risk factors for drug-induced tremor include polypharmacy, male gender, older age, high doses and immediate-release preparations or reaching toxic levels of the offending drugs. Drug-induced tremor usually resolves once the offending medication is discontinued, however, persistent tremor may be observed in some cases (tardive tremor). In this manuscript, we discuss the most common causes of drug-induced tremor. This article is part of the Special Issue "Tremor" edited by Daniel D. Truong, Mark Hallett, and Aasef Shaikh.
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Inibidores da Recaptação de Serotonina e Norepinefrina , Tremor , Amitriptilina , Humanos , Masculino , Serotonina , Inibidores Seletivos de Recaptação de Serotonina/uso terapêutico , Tremor/induzido quimicamente , Tremor/diagnósticoRESUMO
Microorganisms are remarkable producers of a wide diversity of natural products that significantly improve human health and well-being. Currently, these natural products comprise half of all the pharmaceuticals on the market. After the discovery of penicillin by Alexander Fleming 85 years ago, the search for and study of antibiotics began to gain relevance as drugs. Since then, antibiotics have played a valuable role in treating infectious diseases and have saved many human lives. New molecules with anticancer, hypocholesterolemic, and immunosuppressive activity have now been introduced to treat other relevant diseases. Smaller biotechnology companies and academic laboratories generate novel antibiotics and other secondary metabolites that big pharmaceutical companies no longer develop. The purpose of this review is to illustrate some of the recent developments and to show the potential that some modern technologies like metagenomics and genome mining offer for the discovery and development of new molecules, with different functions like therapeutic alternatives needed to overcome current severe problems, such as the SARS-CoV-2 pandemic, antibiotic resistance, and other emerging diseases. KEY POINTS: ⢠Novel alternatives for the treatment of infections caused by bacteria, fungi, and viruses. ⢠Second wave of efforts of microbial origin against SARS-CoV-2 and related variants. ⢠Microbial drugs used in clinical practice as hypocholesterolemic agents, immunosuppressants, and anticancer therapy.
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Produtos Biológicos , Tratamento Farmacológico da COVID-19 , Antibacterianos/metabolismo , Bactérias/metabolismo , Produtos Biológicos/uso terapêutico , Humanos , SARS-CoV-2RESUMO
RESUMO Objetivo: construir e validar por concordância uma cartilha educativa sobre o uso dos imunossupressores no pós-transplante renal. Método: estudo metodológico, realizado em um ambulatório de acompanhamento de pacientes pós transplantados, no período de dezembro de 2019 a agosto de 2020. Desenvolvido em duas fases: construção da cartilha e validação por concordância do material por juízes especialistas. Foi considerado o nível de concordância de, no mínimo, 80% para se garantir a validação do material. Resultados: dos 30 itens avaliados da cartilha, na primeira fase, 15 foram modificados. Após as modificações do material, na segunda fase, somente um item apresentou valor de concordância inferior a 80%. Conclusão: a cartilha foi validada do ponto de vista de conteúdo e aparência, possibilitando auxílio aos profissionais de saúde no processo de educação em saúde, sendo um alicerce na assistência prestada aos pacientes transplantados renais.
ABSTRACT Objective: Construct and validate by agreement an educational booklet on the use of immunosuppressive drugs after kidney transplantation. Method: Methodological study carried out in an outpatient follow-up clinic for post-transplant patients, from December 2019 to August 2020. It was developed in two phases: construction of the booklet and validation by agreement of the material by expert judges. A minimum level of agreement of 80% was necessary for the validation of the material. Results: Of the 30 items evaluated in the booklet, in the first phase, 15 were modified. After the modifications in the material performed in the second phase, only one item had an agreement value lower than 80%. Conclusion: The booklet was validated in content and appearance. Thus, the material could be used to assist health professionals in the health education process and support the care provided to kidney transplant patients.
RESUMEN Objetivo: construir y validar por concordancia un folleto educativo sobre el uso de los inmunosupresores en el postrasplante renal. Método: estudio metodológico, realizado en un ambulatorio de seguimiento de pacientes post-trasplantados, en el periodo diciembre de 2019 a agosto de 2020. Desarrollado en dos fases: construcción del folleto y validación por concordancia del material por jueces especialistas. Se consideró un nivel de concordancia de al menos un 80% para garantizarse la validación del material. Resultados: de los 30 ítems evaluados del folleto en la primera fase, 15 fueron modificados. Después de las modificaciones del material, en la segunda fase, sólo un ítem presentó valor de concordancia inferior a 80%. Conclusión: el folleto fue validado desde el punto de vista del contenido y apariencia, posibilitando auxilio a los profesionales de la salud en el proceso de educación en salud, siendo una piedra angular en la asistencia prestada a los pacientes trasplantados renales.
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AIM: This study assessed the efficacy and safety of upadacitinib (UPA), in combination with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), in Chinese, Brazilian, and South Korean patients with active rheumatoid arthritis (RA) and an inadequate response (IR) to csDMARDs. METHODS: Patients on stable csDMARDs were randomized (1:1) to once-daily UPA 15 mg or matching placebo (PBO) for a 12-week, double-blind period. The primary endpoint was the proportion of patients achieving ≥20% improvement in American College of Rheumatology criteria (ACR20) at week 12. RESULTS: In total, 338 patients were randomized and treated, of whom 310 (91.7%) completed the double-blind phase. The study met the primary endpoint of ACR20 at week 12 for UPA 15 mg vs PBO (71.6% vs 31.4%, P < .001), with a treatment difference observed as early as week 1. All ranked and other key secondary endpoints, including more stringent responses such as ACR50, ACR70 (≥50%/70% improvement in ACR criteria), and Disease Activity Score in 28 joints using C-reactive protein <2.6, were met for UPA 15 mg vs PBO. The incidence of serious infections (2.4% vs 0.6%) and herpes zoster (HZ: 1.8% vs 0.6%) was higher with UPA 15 mg vs PBO. There was one case of venous thromboembolism reported in the UPA group. CONCLUSION: UPA 15 mg in combination with csDMARDs demonstrated clinical and functional improvement and an acceptable safety profile over 12 weeks among patients from China, Brazil, and South Korea who had moderately to severely active RA and an IR to csDMARDs.
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Artrite Reumatoide/tratamento farmacológico , Compostos Heterocíclicos com 3 Anéis/administração & dosagem , Inibidores de Janus Quinases/administração & dosagem , Adulto , Antirreumáticos/uso terapêutico , Brasil , China , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Compostos Heterocíclicos com 3 Anéis/efeitos adversos , Humanos , Inibidores de Janus Quinases/efeitos adversos , Masculino , Pessoa de Meia-Idade , República da Coreia , Resultado do TratamentoRESUMO
INTRODUCTION: Due to its high specificity and sensitivity, liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) is the gold standard method for immunosuppressant quantification in therapeutic drug monitoring. In this context, dried blood spots (DBS) have become a promising strategy as a sample collection procedure. Although the advantages of DBS over venipuncture are well known, this approach has limitations that strongly influence the acceptance of analytical results. Among them, the most important is hematocrit (Ht). The easiest way of overcoming this problem is by analyzing complete spots. In this strategy, called dried matrix on paper discs (DMPD), blood is volumetrically applied on pre-punched discs. OBJECTIVES: To validate an LC-MS/MS method for the quantification of tacrolimus, sirolimus, everolimus and cyclosporin A using DMPD. METHODS: The procedure was validated according to international guidelines using a commercial kit. The following performance parameters were evaluated: selectivity, carryover, linearity, accuracy, precision, lower limit of quantitation, relative recovery, commutability and stability. In addition, a method comparison study was performed to evaluate the clinical influence of Ht on the results. RESULTS: All performance parameters were within acceptance criteria and, hence, it was determined that the validated method is fit for the intended purpose. Likewise, calculated bias values on medical decision levels showed that there was no clinical influence of Ht on the results. CONCLUSION: Unlike other similar methodologies that have been published, here, a simple method has been fully validated. This is the first LC-MS/MS methodology adapting a commercial kit to use DMPD as a sampling strategy.
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Se describe el caso clínico de una paciente con diagnóstico histológico de mastitis granulomatosa idiopática, enfermedad poco frecuente en la que se utilizan inmunosupresores como tratamiento descripto y puede confundirse con otras entidades atendidas en la especialidad. Se describe el caso y se realiza una revisión de la literatura.
The clinical case of a patient with a histological diagnosis of idiopathic granulomatous mastitis is described, a rare disease in which immunosuppressants are used as the described treatment and can be confused with other entities treated in the specialty. The case is described and a literature review is carried out.
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Humanos , Feminino , Adulto , Metotrexato/uso terapêutico , Mastite Granulomatosa/diagnóstico , Mastite Granulomatosa/tratamento farmacológico , Imunossupressores/uso terapêutico , Mastite Granulomatosa/imunologiaRESUMO
Idiopathic retroperitoneal fibrosis is a rare fibro-inflammatory disease of varied etiology which usually originates around aorta and spreads caudally along Iliac vessels into adjacent retroperitoneum causing ureteral obstruction as the most frequent complication.A 53-year-old male patient presented with complaint of mild pain in both the legs off and on. On investigating further, we found that he had been struggling with intermittent relapses every 3-4 years for last 20 years since he was first diagnosed with Idiopathic Retroperitoneal Fibrosis. He was 33-year-old when he first developed the symptoms of anuria for 48 hours and was diagnosed with Idiopathic retroperitoneal fibrosis. This was followed by atrophy of left kidney and hypertension 6 years later, then hypothyroidism after another 3years and finally involvement of Inferior Vena Cava and acute Deep Vein Thrombosis of lower limbs after another 3-4 years. His deep vein thrombosis was well managed in time. He was put on glucocorticoids everytime he had a relapse and a complication.We did a review of literature to understand recent advances about its pathogenesis, diagnosis, investigations and management. We searched in PubMed using terms like retroperitoneal fibrosis alone and in combination with related terms such as Inferior Vena Cava thrombosis, Deep Vein Thrombosis, Tamoxifen, Methotrexate. This case is unique as it is very rare to find acute Deep Vein Thrombosis in Idiopathic retroperitoneal fibrosis without development of any collaterals when Inferior Vena Cava lumen is compromised to almost complete obstruction.After a follow up of 20 years patient is doing well in terms of physical activity and psychological wellbeing with anti-hypertensives, thyroxine and anti-coagulants. Is the disease-free interval actually free of the disease or it just subsided with immunosuppressants to become active after some time?
La fibrosis retroperitoneal idiopática es una enfermedad fibroinflamatoria rara, de etiología variada que generalmente se origina alrededor de la aorta y se propaga caudalmente a lo largo de los vasos ilíacos en retroperitoneo adyacente causando obstrucción ureteral como la complicación más frecuente.Reportamos el caso de un paciente varón de 53 años que se presentó con un dolor leve en ambas piernas. Al investigar más a fondo, descubrimos que había estado luchando con recaídas intermitentes cada 3-4 años durante los últimos 20 años desde que se le diagnosticó por primera vez fibrosis retroperitoneal idiopática. Tenía 33 años cuando desarrolló por primera vez los síntomas de anuria durante 48 horas y se le diagnosticó fibrosis retroperitoneal idiopática. Esto fue seguido por atrofia del riñón izquierdo e hipertensión 6 años después, luego hipotiroidismo después de otros 3 años y finalmente afectación de la vena cava inferior y trombosis venosa profunda aguda de las extremidades inferiores después de otros 3-4 años. Su trombosis venosa profunda se controló bien a tiempo. Le recetaron glucocorticoides cada vez que tenía una recaída y una complicación.Hicimos una revisión de la literatura para comprender los avances recientes sobre su patogenia, diagnóstico, investigaciones y manejo. Se realizaron búsquedas en PubMed utilizando términos como fibrosis retroperitoneal sola y en combinación con términos relacionados como trombosis de la vena cava inferior, trombosis venosa profunda, tamoxifeno, metotrexato. Este caso es único, ya que es muy raro encontrar trombosis venosa profunda aguda en fibrosis retroperitoneal idiopática sin desarrollo de colaterales cuando la luz de la vena cava inferior está comprometida hasta una obstrucción casi completa.Después de un seguimiento de 20 años, el paciente se encuentra bien en términos de actividad física y bienestar psicológico con antihipertensivos, tiroxina y anticoagulantes. ¿El intervalo libre de enfermedad está realmente libre de la enfermedad o simplemente disminuyó con inmunosupresores para activarse después de algún tiempo?