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1.
Medicina (B.Aires) ; 81(2): 208-213, June 2021. graf
Article in Spanish | LILACS | ID: biblio-1287272

ABSTRACT

Resumen El manejo de las reacciones adversas inducidas por los inhibidores del punto de control inmunitario (IPCI) en cáncer, demanda un trabajo multidisciplinario. Revisamos las causas y el curso clínico de las consultas e internaciones debidas a reacciones adversas de los IPCI entre septiembre de 2015 y julio de 2019 en el Instituto Alexander Fleming. Se registraron los datos demográficos, diagnóstico oncológico, reacción adversa y su grado, requerimiento de internación, tratamiento, mortalidad y evaluación de la reexposición. Se registraron 124 reacciones adversas por IPCI en 89 pacientes. Sesenta y ocho recibían monoterapia y 21 terapia combinada. Las manifestaciones cutáneas fueron las más frecuentes, seguidas de las generales, endocrinas (con mayor frecuencia hipotiroidismo), colitis, neumonitis, neurológicas y hepatitis. Fueron graves (grado ≥ 3), 26 toxicidades en 25 pacientes. Se internaron 15, y 6 de ellos requirieron terapia intensiva. Un caso fue fatal. Recibieron glucocorticoides 34 (12 de ellos por vía intravenosa). Un paciente recibió micofenolato y uno inmuno globulina endovenosa. En 20 se discontinuó el tratamiento. Ocho se reexpusieron y uno de ellos debió suspender definitivamente. Se presenta en esta serie de casos nuestra experiencia con el diagnóstico y tratamiento de las reacciones adversas de una familia de drogas cuya utilización ha crecido en los últimos años.


Abstract The management of patients with immune-related adverse events (irAEs) frequently demands a multidisciplinary approach. We reviewed the causes and clinical course of medical visits and admissions at the Instituto Alexander Fleming due to irAEs between September 2015 and July 2019. Demographic data, diagnosis, toxicity and its severity, requirement of admission, treatment, mortality, and evaluation of the re-administration of immunotherapy were collected. We found 124 irAEs in 89 patients. Sixty-eight of them received monotherapy (76.4%) and 21 (23.6%) combination of drugs. Cutaneous manifestations were the most frequent cause of irAEs, followed by general manifestations, endocrine dysfunctions (hypothyroidism the most frequent), colitis, pneumonitis, neurologic dis orders, and hepatitis. In 26 adverse events (in 25 patients), severity grade was ≥ 3. Fifteen were admitted and 6 required ICU admission. One patient died. Thirty-four received glucocorticoids, 12 of them by intravenous route. One patient received mycophenolate and one IVIG. In 20, the treatment was discontinued; 8 were re-exposed, with definitive discontinuation in one patient. In this case series we report our experience in the diagnosis and management of adverse reactions related to a family of drugs whose use has grown in recent years.


Subject(s)
Humans , Drug-Related Side Effects and Adverse Reactions , Neoplasms/drug therapy , Nervous System Diseases , Immune Checkpoint Inhibitors , Immunologic Factors/therapeutic use , Immunotherapy
2.
Article in English | WPRIM | ID: wpr-921072

ABSTRACT

INTRODUCTION@#The use of drugs that modulate the immune system during paediatric severe sepsis and septic shock may alter the course of disease and is poorly studied. This study aims to characterise these children who received immunomodulators and describe their clinical outcomes.@*METHODS@#This is a retrospective chart review of patients with severe sepsis and septic shock admitted into the paediatric intensive care unit (PICU). Clinical, haematological and outcome characteristics of patients with or without exposure to immune-modulating drugs were compared. Primary outcome was PICU mortality; secondary outcomes were 28-day ventilator-free days (VFD) and intensive care unit-free days (IFD). Univariate and multivariable analyses were performed for these outcomes.@*RESULTS@#A total of 109 patients with paediatric severe sepsis or septic shock were identified. Of this number, 47 (43.1%), 16 (14.7%) and 3 (2.8%) patients received systemic corticosteroids, intravenous immunoglobulins and granulocyte colony stimulating factor, respectively. Patients who received immune-modulating drugs were more likely to require invasive ventilation (38/54 [70.4%] versus 26/55 [47.3%], @*CONCLUSION@#Immune-modulating drugs were frequently used in paediatric severe sepsis and septic shock. Patients who received these drugs seemed to require more PICU support. Further studies are required to examine this association thoroughly.


Subject(s)
Child , Humans , Immunologic Factors/therapeutic use , Intensive Care Units, Pediatric , Retrospective Studies , Sepsis/drug therapy , Shock, Septic/drug therapy
4.
Washington; PAHO; Oct. 09, 2020. 103 p.
Non-conventional in English | PIE, LILACS, PIE | ID: biblio-1127989

ABSTRACT

As of 31 October 2020 This is the tenth edition of this summary of rapid systematic reviews, which includes the results of a rapid systematic review of currently available literature. More than 200 therapeutic options or their combinations are being investigated in more than 1,700 clinical trials. In this review, 46 therapeutic options are examined. The Pan American Health Organization (PAHO) is continually monitoring ongoing research on any possible therapeutic options. As evidence emerges, then PAHO will immediately assess and update its position, and particularly as it applies to any special sub-group populations such as children, expectant mothers, those with immune conditions, etc.


Subject(s)
Humans , Pneumonia, Viral/drug therapy , Coronavirus Infections/drug therapy , Pandemics/prevention & control , Betacoronavirus/drug effects , Antiviral Agents/therapeutic use , Clinical Trials as Topic , Immunologic Factors/therapeutic use
5.
Washington; PAHO; Oct. 30, 2020. 121 p.
Non-conventional in English | PIE, LILACS, PIE | ID: biblio-1127985

ABSTRACT

As of 31 October 2020 This is the tenth edition of this summary of rapid systematic reviews, which includes the results of a rapid systematic review of currently available literature. More than 200 therapeutic options or their combinations are being investigated in more than 1,700 clinical trials. In this review, 46 therapeutic options are examined. The Pan American Health Organization (PAHO) is continually monitoring ongoing research on any possible therapeutic options. As evidence emerges, then PAHO will immediately assess and update its position, and particularly as it applies to any special sub-group populations such as children, expectant mothers, those with immune conditions, etc.


Subject(s)
Humans , Pneumonia, Viral/drug therapy , Coronavirus Infections/drug therapy , Pandemics/prevention & control , Betacoronavirus/drug effects , Antiviral Agents/therapeutic use , Clinical Trials as Topic , Immunologic Factors/therapeutic use
6.
Washington; PAHO; Sept. 22, 2020. 81 p.
Non-conventional in English | PIE, LILACS, PIE | ID: biblio-1127987

ABSTRACT

As of 31 October 2020 This is the tenth edition of this summary of rapid systematic reviews, which includes the results of a rapid systematic review of currently available literature. More than 200 therapeutic options or their combinations are being investigated in more than 1,700 clinical trials. In this review, 46 therapeutic options are examined. The Pan American Health Organization (PAHO) is continually monitoring ongoing research on any possible therapeutic options. As evidence emerges, then PAHO will immediately assess and update its position, and particularly as it applies to any special sub-group populations such as children, expectant mothers, those with immune conditions, etc.


Subject(s)
Humans , Pneumonia, Viral/drug therapy , Coronavirus Infections/drug therapy , Pandemics/prevention & control , Betacoronavirus/drug effects , Antiviral Agents/therapeutic use , Clinical Trials as Topic , Immunologic Factors/therapeutic use
7.
Arq. bras. oftalmol ; 83(5): 402-409, Sept.-Oct. 2020. tab, graf
Article in English | LILACS | ID: biblio-1131633

ABSTRACT

ABSTRACT Purpose: To compare the benefits and side effects of pars plana vitrectomy with those of systemic immune modulator therapy for patients with complicated intermediate uveitis. Methods: This prospective clinical trial enrolled patients with recurrent intermediate uveitis who exhibited minimal improvement of visual acuity, despite injections of periocular steroids. Twenty patients were randomized to the pars plana vitrectomy group or oral steroid and cyclosporine-A group (10 eyes of 10 patients per group). Follow-up was performed for 24 months to study changes in visual acuity, binocular indirect ophthalmoscopy score, fluorescein angiography, and optical coherence tomography findings. Results: Visual acuity (logarithm of the minimal angle of resolution) significantly improved from 0.71 to 0.42 (p=0.001) in the surgical group, whereas it improved from 0.68 to 0.43 (p=0.001) in the immune modulator therapy group. Seven patients (70%) in the surgical group gained ≥2 lines, and six patients (60%) in the immune modulator therapy group gained ≥2 lines (p=0.970). Fluorescein angiography and optical coherence tomography studies showed that six of seven pars plana vitrectomy patients who had cystoid macular edema experienced improvement, whereas two patients with diffuse macular edema did not experience improvement. In the immune modulator therapy group, three of six patients with cystoid macular edema did not experience improvement, whereas two patients with diffuse macular edema experienced improvement. Conclusions: Pars plana vitrectomy and immune modulator therapy resulted in significant improvement in visual function in patients with persistent inflammation secondary to chronic intermediate uveitis. Despite this success, there remains a need for the determination of optimal indications for the use of each modality. Immune modulator therapy was successful for the treatment of diffuse macular edema associated with chronic intermediate uveitis, whereas pars plana vitrectomy was not.


RESUMO Objetivo: Comparar os benefícios e efeitos co laterais da vitrectomia via pars plana com os da terapia imunomo duladora sistêmica em pacientes com uveíte intermediária complicada. Métodos: Estudo clínico prospectivo incluiu pacientes com uveíte intermediária recorrente que apresentaram melhora minima da acuidade visual, apesar das injeções perioculares de esteroides. Vinte pacientes foram randomizados para o grupo de vitrectomia via pars plana ou esteróide oral e ciclosporina A (10 olhos de 10 pacientes por grupo). O acompanhamento foi de 24 meses para estudar al te rações na acuidade visual, o escore da oftalmoscopia binocular indireta, a angiofluoresceinografia e achados na to mográfica de coerência óptica. Resultados: A acuidade visual (logaritmo do ângulo mínimo de resolução) melhorou significativamente de 0,71 para 0,42 (p=0,001) no grupo cirúrgico, enquanto melhorou de 0,68 para 0,43 (p=0,001) no grupo da terapia imunomoduladora. Sete pacientes (70%) no grupo cirúrgico ganharam ≥2 linhas e seis pacientes (60%) no grupo da terapia imunomoduladora ganharam ≥2 linhas (p=0,970). Os estudos de angiofluoresceinografia e tomografia de coerência óptica mostraram que seis dos sete pacientes da vitrectomia via pars plana que apresentaram edema macular cistóide melhoraram, enquanto dois pacientes com edema macular difuso não apresentaram melhora. No grupo da terapia imunomoduladora, três dos seis pacientes com edema macular cistoide não apresentaram melhora, enquanto dois pacientes com edema macular difuso melhoraram. Conclusões: A vitrectomia via pars plana e a terapia imunomoduladora resultaram em melhora significative da função visual dos pacientes com inflamação persistente secundária a uveíte intermediária crônica. Apesar desse sucesso, continua sendo necessário determinar as melhores indicações para o uso de cada modalidade. A terapia imunomoduladora foi bem sucedida no tratamento do edema macular difuso associado à uveíte intermediária crônica, enquanto a vitrectomia via pars plana não foi.


Subject(s)
Humans , Vitrectomy , Uveitis, Intermediate , Macular Edema , Immunologic Factors , Visual Acuity , Uveitis, Intermediate/therapy , Prospective Studies , Retrospective Studies , Immunologic Factors/therapeutic use
8.
Washington; PAHO; Aug. 11, 2020. 91 p.
Monography in English | PIE, LILACS, PIE | ID: biblio-1094870

ABSTRACT

More than 200 therapeutic options or their combinations are being investigated in more than 1,700 clinical trials. In this review we examined 30 therapeutic options. Findings from the RECOVERY Trial showed that low doses of dexamethasone (6 mg of oral or intravenous preparation once daily for 10 days) significantly reduced mortality by one-third in ventilated patients and by one fifth in patients receiving oxygen only. The anticipated RECOVERY. Trial findings and WHO's SOLIDARITY Trial findings both show no benefit via use of hydroxychloroquine and lopinavir/ritonavir in terms of reducing 28-day mortality or reduced time to clinical improvement or reduced adverse events. Currently, there is no evidence of benefit in critical outcomes (i.e. reduction in mortality) from any therapeutic option (though remdesivir is revealing promise as one option based on 2 randomized controlled trials) and that conclusively allows for safe and effective use to mitigate or eliminate the causative agent of COVID-19. Currently, as to ivermectin, we found 1 in vitro study and 4 observational studies that were largely confounded (nonrandomized), and lacked the methodological rigor to allow much confidence in the results. They were pre-print and non-peer reviewed and were judged to be of high risk of bias and very low quality of evidence. The researchers concluded in large part that the findings could be considered hypothesis testing and urged the conduct of large sample sized RCTs to assess any clinical benefit. Currently, as to favipiravir, we found 1 RCT and 2 observational studies. The results were inconclusive for benefits of favipiravir, and sample sizes were small and results came via largely preprints and non-peer reviewed publications. The 2 nonrandomized observational designs revealed sub-optimal methods with no optimal adjustments, masking, or stratification. A recent release by Glenmark announced promising results from a Phase 3 Clinical Trial of favipiravir in patients with mild to moderate COVID-19. A Phase 3 RCT demonstrates statistically significant faster time to clinical improvement with favipiravir treatment compared to control (n=150 patients).


Subject(s)
Humans , Pneumonia, Viral/drug therapy , Coronavirus Infections/drug therapy , Pandemics/prevention & control , Betacoronavirus/drug effects , Antiviral Agents/therapeutic use , Clinical Trials as Topic , Immunologic Factors/therapeutic use
9.
Arq. neuropsiquiatr ; 78(7): 430-439, July 2020. tab
Article in English | LILACS | ID: biblio-1131732

ABSTRACT

ABSTRACT Background: The novel coronavirus disease 2019 (COVID-19) pandemic poses a potential threat to patients with autoimmune disorders, including multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD). Such patients are usually treated with immunomodulatory or immunosuppressive agents, which may tamper with the organism's normal response to infections. Currently, no consensus has been reached on how to manage MS and NMOSD patients during the pandemic. Objective: To discuss strategies to manage those patients. Methods: We focus on how to 1) reduce COVID-19 infection risk, such as social distancing, telemedicine, and wider interval between laboratory testing/imaging; 2) manage relapses, such as avoiding treatment of mild relapse and using oral steroids; 3) manage disease-modifying therapies, such as preference for drugs associated with lower infection risk (interferons, glatiramer, teriflunomide, and natalizumab) and extended-interval dosing of natalizumab, when safe; 4) individualize the chosen MS induction-therapy (anti-CD20 monoclonal antibodies, alemtuzumab, and cladribine); 5) manage NMOSD preventive therapies, including initial therapy selection and current treatment maintenance; 6) manage MS/NMOSD patients infected with COVID-19. Conclusions: In the future, real-world case series of MS/NMOSD patients infected with COVID-19 will help us define the best management strategies. For the time being, we rely on expert experience and guidance.


RESUMO Introdução: A mais recente pandemia causada pelo coronavírus SARS-CoV-2 (COVID-19, do inglês coronavirus disease 2019) representa uma ameaça potencial para pacientes com doenças autoimunes, incluindo esclerose múltipla (EM) e transtorno do espectro de neuromielite óptica (NMOSD, do inglês neuromyelitis optica spectrum disorders). Esses pacientes são geralmente tratados com medicamentos imunomoduladores ou imunossupressores que podem alterar a resposta normal do organismo a infecções. Até o momento, não há consenso sobre como o manejo dos pacientes com EM e NMOSD deve ser realizado durante a pandemia. Objetivo: Discutir estratégias para manejar esses pacientes. Métodos: Focamos em como 1) reduzir o risco de infecção por COVID-19, como distanciamento social, telemedicina e exames laboratoriais e de imagem em intervalos mais amplos; 2) manejo de surtos, incluindo evitar tratamento de surto leve e uso de corticoide oral; 3) gerenciar terapias modificadoras de doença, como a preferência por medicamentos associados a menor risco de infecção (interferons, glatirâmer, teriflunomida e natalizumabe) e infusão em intervalo estendido de natalizumabe, quando seguro; 4) individualizar a escolha da terapia de indução para EM (anticorpos monoclonais anti-CD20, alentuzumabe e cladribina); 5) manejar terapias preventivas de NMOSD, incluindo seleção inicial de terapia e manutenção do tratamento atual; 6) manejar pacientes com EM/NMOSD que foram infectados por COVID-19. Conclusão: No futuro, séries de casos de pacientes com MS/NMOSD infectados com COVID-19 nos ajudará a definir as melhores estratégias de manejo. Por enquanto, contamos com a experiência e orientação especializadas.


Subject(s)
Humans , Pneumonia, Viral/prevention & control , Neuromyelitis Optica/drug therapy , Coronavirus Infections/prevention & control , Coronavirus , Immunosuppressive Agents/therapeutic use , Multiple Sclerosis/drug therapy , Pneumonia, Viral/epidemiology , China/epidemiology , Risk , Neuromyelitis Optica/diagnosis , Telemedicine , Infectious Disease Transmission, Professional-to-Patient/prevention & control , Infectious Disease Transmission, Patient-to-Professional/prevention & control , Coronavirus Infections , Coronavirus Infections/epidemiology , Disease Susceptibility , Pandemics , Betacoronavirus , Immunologic Factors/therapeutic use , Multiple Sclerosis/diagnosis
10.
Rev. méd. Chile ; 148(7): 1031-1033, jul. 2020.
Article in Spanish | LILACS | ID: biblio-1139406

ABSTRACT

Myasthenia gravis (MG) is a heterogeneous disease, and there is no unique therapeutic approach for all patients. In 2013 the Myasthenia Gravis American Foundation (MGFA) panel of experts defined refractory MG as the lack of change or deterioration after the use of corticosteroids and two immunosuppressive agents, in adequate doses and time. We report a 51-years-old female with MG of bulbar predominance, who presented four myasthenic crises in 17 months despite the use of corticosteroids, azathioprine and mycophenolate. The high costs associated with her hospitalizations, as well as severe caloric - protein malnutrition, the need for tracheostomy and gastrostomy support, led us to use rituximab. The patient evolved with an excellent response, free of crises after 30 months. She gained 12 kg of weight, without tracheostomy and gastrostomy, only using pyridostigmine support 4 times a day.


Subject(s)
Humans , Female , Middle Aged , Rituximab/therapeutic use , Myasthenia Gravis/drug therapy , Immunologic Factors/therapeutic use , Myasthenia Gravis/diagnosis
11.
Brasil; Brasil. Ministério da Saúde; abr. 2020.
Non-conventional in Portuguese | ColecionaSUS, LILACS, ColecionaSUS, BRISA | ID: biblio-1096179

ABSTRACT

OBJETIVO Análise da Proposta de tratamento farmacológico imunomodulador para casos internados com SARS-CoV-2 - versão 30/03/2020 (Versão número 2) do Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo. DA ANÁLISE O protocolo em questão propõe estadiamentos da doença SARS-CoV-2, bem como possíveis tratamentos. Os autores da proposta do HC de Ribeirão Preto utilizaram as seguintes referências: Mehta et al. (2020); Siddiqu et al. (2020) e Fardet et al. (2014). Para elaboração desta Nota Técnica, foi realizada uma análise das referências citadas na proposta do HC e outras complementares. O espectro clínico da infecção por coronavírus é amplo e se apresenta desde um resfriado a acometimento pulmonar grave. A manifestação da COVID-19 é principalmente respiratória, podendo ocasionar insuficiência respiratória e morte. Os sintomas mais relatados incluem febre, tosse seca, mialgia ou fadiga, pneumonia e dispneia. Sintomas menos comuns incluem cefaleia, diarreia, hemoptise, coriza e tosse com secreção. O diagnóstico depende da investigação clínico-epidemiológica e dos exames físico e laboratorial. Os casos suspeitos devem ser notificados imediatamente, pelo meio de comunicação mais rápida disponível (em até 24 horas), devido à potencial emergência de saúde pública de importância nacional. Por ser um vírus novo, ainda não há vacina ou tratamento antiviral específico para tratar a COVID-19. O tratamento atual é sintomático, visando ao alívio dos sintomas. Em casos mais graves, há a necessidade de cuidados de suporte para as complicações ou internação em unidade de terapia intensiva (UTI) para manutenção das funções de órgãos vitais. No entanto, existem estudos internacionais publicados e em andamento sobre o uso de medicamentos no atendimento a pacientes com COVID-19, que usam diferentes terapias medicamentosas, mas oferecem um nível limitado de evidência. Entre os medicamentos estudados, estão a cloroquina, hidroxicloroquina, azitromicina, remdesivir, entre outros. Para a elaboração de um protocolo clínico ou diretrizes terapêuticas, as recomendações devem ser baseadas em evidência científica e considerar critérios de eficácia, segurança, efetividade e custo-efetividade das tecnologias recomendadas, com base na literatura disponível e considerando o contexto epidemiológico e situacional relacionado a condição clínica. CONCLUSÕES: As referências utilizadas para elaboração da proposta explicam acerca da tempestade inflamatória que ocorre na COVID-19 e sua semelhança à sHLH, contudo, a proposta pouco fala sobre o rastreamento e a conduta de tratamento da hiperinflamação. A hidroxicloroquina e a cloroquina são tratamento promissores, sendo encontrados 25 estudos em andamento no ClinicalTrials.gov, mas é necessária precaução, sobretudo se forem considerados o baixo nível de evidências atualmente disponível e os possíveis eventos adversos do uso dos medicamentos. Ressalta-se que a bula da cloroquina não indica o uso concomitante da heparina devido a possíveis eventos adversos, como trombocitopenia. Também foram encontrados estudos envolvendo o tocilizumabe e a imunoglobulina, mas sem resultados conclusivos. A presente nota será atualizada quando surgirem novas informações a respeito das tecnologias citadas.


Subject(s)
Humans , Immunoglobulin G/therapeutic use , Dexamethasone/therapeutic use , Chloroquine/therapeutic use , Coronavirus Infections/drug therapy , Hydroxychloroquine/therapeutic use , Immunologic Factors/therapeutic use , Technology Assessment, Biomedical , Cost Efficiency Analysis
12.
Ciênc. Saúde Colet ; 25(3): 869-878, mar. 2020. tab, graf
Article in Portuguese | LILACS | ID: biblio-1089474

ABSTRACT

Resumo O presente estudo tem como objetivo caracterizar o perfil epidemiológico de vítimas de acidentes escorpiônicos e ofídicos e avaliar a adequação das prescrições de soros antivenenos. Estudo transversal cujas fontes de dados foram as fichas de notificação de acidentes por animais peçonhentos do Sistema de Informação de Agravos de Notificação no município de Vitória da Conquista (BA), Brasil. Foram incluídas as informações de acidentes escorpiônicos ou ofídicos no período entre julho de 2016 e junho de 2017 atendidos no município. Os dados obtidos e as variáveis de interesse foram analisadas de acordo com as perguntas deste estudo. No período observado foram atendidas 293 vítimas de acidentes por animais peçonhentos. Destas, 149 (50,9%) foram homens e 114 (38,9%) possuíam entre 20 a 59 anos. Foram 235 (80,9%) casos de escorpionismo e 58 (19,1%) de ofidismo. Destes, 203 (69,3%) foram classificados como leves e em 200 (68,5%) casos foi prescrita soroterapia para estes pacientes. Quanto à adequação das prescrições, 172 (59,7%) foram julgadas inadequadas e destas, o uso de número de ampolas acima do indicado foi a mais frequente. A prescrição inapropriada de soros antivenenos ocorreu em aproximadamente em 60% dos casos avaliados. Apesar disso, a maioria dos acidentes foi classificada como leve, em homens jovens.


Abstract This study aims to characterize the epidemiological profile of victims of scorpion and snakebite envenomations and to evaluate the adequacy of antivenom sera prescriptions. This is a cross-sectional study whose data sources were the envenomation notification information sheets of the Notifiable Diseases Information System in the city of Vitória da Conquista (BA), Brazil. We included information on scorpion or snakebite envenomations attended in the municipality in the period between July 2016 and June 2017. The data obtained and the variables of interest were analyzed according to the questions of this study. In the observed period, 293 victims of envenomations were treated. Of these, 149 (50.9%) were men, and 114 (38.9%) were 20-59 years old. In total, 235 (80.9%) cases of scorpionism and 58 (19.1%) of ophidism were reported. Of these, 203 (69.3%) were classified as mild, and in 200 (68.5%) cases, serum therapy was prescribed for the patients. Regarding the adequacy of the prescriptions, 172 (59.7%) were considered inadequate, and of these, the use of some vials above than indicated was the most frequent. The inappropriate prescription of antivenom sera occurred in approximately 60% of the evaluated cases. Despite this, most accidents were classified as mild - in young men.


Subject(s)
Humans , Male , Female , Infant , Child, Preschool , Child , Adolescent , Adult , Young Adult , Snake Bites/drug therapy , Scorpion Stings/drug therapy , Immunologic Factors/therapeutic use , Brazil , Antivenins/therapeutic use , Urban Health , Cross-Sectional Studies , Drug Utilization/statistics & numerical data , Emergency Medical Services , Emergency Treatment , Hospitals, Public , Middle Aged
13.
Rev. habanera cienc. méd ; 19(1): 10-29, ene.-feb. 2020. tab, graf
Article in Spanish | LILACS, CUMED | ID: biblio-1099142

ABSTRACT

Introducción: La Enfermedad del Injerto Contra el Hospedador es la complicación más frecuente de los Trasplantes de Células Madre Hematopoyéticas y de todos los trasplantes que contengan células inmunocompetentes alogénicas, el 100 por ciento la padecen y cerca del 30 por ciento mueren por su causa; una proporción alta de casos son esteroide-refractarios, asimismo otras medidas inmunosupresoras modernas fracasan. En los campos de la Inmunoterapia y la Vaccinología también existe una escasez preocupante de inmunomoduladores de origen biológico potentes, efectivos, seguros y de amplio espectro. Existe un modelo híbrido murino de gran utilidad metodológica para estudios experimentales. Objetivo: Evaluar dos formulaciones novedosas de origen biotecnológico, una de ellas inmunopotenciadora y otra inmunosupresora, desarrolladas como cocleatos. Material y Métodos: Mediante Microscopia Electrónica y RT-PCR se caracterizaron las formulaciones como nanopartículas y su capacidad de regular la expresión del ARNm de linfoquinas definitorias de sus perfiles, respectivamente. Empleando el modelo de Enfermedad del Injerto Contra el Hospedador en ratón híbrido F1 (CBAxC57BL), se evaluó su carácter inmunomodulador in vivo . Resultados: Partiendo de los proteoliposomas de Neisseria meningitidis, se obtuvieron dos formulaciones en forma de cocleatos, ambas con diámetros de partícula inferior a 100nm. La Formulación 1mostró un perfil proinflamatorio con potente capacidad de aumentar el IFNγ y el TNFα y potenció el Índice de Bazo hasta 2,05 en el modelo EICH con p=0,0002. La Formulación 2 mostró un perfil supresor-regulatorio con potente capacidad de aumentar la IL-10 y el TGFβ y además de suprimir la producción de TNFα. En el modelo usado, esta formulación, suprimió el Índice de Bazo de manera dosis dependiente y con alta significación estadística. Se corroboró el conocido perfil de seguridad y ausencia de reactogenicidad de ambas formulaciones. Conclusiones: Ambas formulaciones tienen potencial aplicación en los campos de la terapia de Enfermedad del Injerto Contra el Hospedador en otras patologías y en Vaccinología. Los resultados obtenidos en el presente trabajo fundamentan la conveniencia de continuar el desarrollo farmacéutico y completar la preclínica de ambas formulaciones(AU)


Introduction: Graft-versus-host disease is the most frequent complication of Hematopoietic Stem Cell Transplants and all transplants containing allogeneic immunocompetent cells; 100 percent of patients suffer from this complication and about 30 percent die for this particular cause. A high proportion of cases are steroid-refractory; likewise, other modern immunosuppressive measures fail. In the fields of Immunotherapy and Vaccinology, there is also a worrying shortage of powerful, effective, safe and broad spectrum immunomodulators of biological origin. There is a hybrid murine model of great methodological utility for experimental studies. Objective: To evaluate two novel formulations of biotechnological origin: an immunopotentiator formulation and an immunosuppressive one, which were developed as cochleates. Material and Methods: The formulations assayed by Electron Microscopy and RT-PCR were characterized as nanoparticles and for their capacity to regulate lymphokine mRNA expression profile, respectively. The immunomodulatory character was evaluated in vivo using Graft-versus-host disease in (CBAxC57BL) F1 hybrid mice. Results: Starting from the proteoliposomes derived from Neisseria meningitides, two cochleate formulations were obtained, both with particle diameters below 100 nm. Formulation 1 showed a proinflammatory profile with potent capacity to increase IFNγ and TNFα, and potentiated the Spleen Index up to 2.05 in the GVDH model with p = 0.0002. Formulation 2 showed a suppressor/regulatory profile with potent capacity to increase IL-10 and TGFβ and suppress the production of TNFα. In the model used, this formulation suppressed the Spleen Index in a dose-dependent manner with high statistical significance. The known safety profile and absence of reactogenicity of both formulations was corroborated. Conclusions: Both formulations have potential application in the fields of GVHD therapy and other pathologies as well as in Vaccinology. The results obtained in the present work suggest the usefulness to continue with the pharmaceutical development and complete the preclinical studies of both formulations(AU)


Subject(s)
Humans , Male , Female , Hematopoietic Stem Cell Transplantation/adverse effects , Graft vs Host Disease/complications , Host vs Graft Reaction/genetics , Immunologic Factors/therapeutic use , Immunosuppressive Agents/immunology
14.
Chinese Medical Journal ; (24): 2595-2598, 2020.
Article in English | WPRIM | ID: wpr-877820

ABSTRACT

With the increasing use of immune checkpoint inhibitors (ICI) including anti-cytotoxic T lymphocyte associated antigen-4 (CTLA-4) and anti-programmed cell death-1 (PD-1) in cancers, ICI-induced type 1 diabetes has been reported throughout the world. In this review, we aim to summarize the characteristics of this disease and discuss the mechanism of it. As an immune-related adverse event, type 1 diabetes developed after the administration of anti-PD-1 or anti-PD-ligand 1 (PD-L1) in the combination with or without anti-CTLA-4. It usually presented with acute onset, and 62.1% of the reported cases had diabetic ketoacidosis. Only a third of them had positive autoantibodies associated with type 1 diabetes. Susceptible HLA genotypes might be associated. T-cell-stimulation by blocking of the interaction of PD-1 and PD-L1 in pancreatic β cells was the main mechanism involved in the pathology. Insulin was the only effective treatment of ICI-induced type 1 diabetes. In conclusions, ICI-induced type 1 diabetes is a potentially life-threating adverse event after the immunotherapy of cancers. Screening and early recognition is important. Further investigation of the mechanism may help to better understand the pathology of type 1 diabetes.


Subject(s)
CTLA-4 Antigen , Diabetes Mellitus, Type 1/chemically induced , Humans , Immune Checkpoint Inhibitors , Immunologic Factors/therapeutic use , Immunotherapy/adverse effects , Neoplasms/drug therapy
15.
Arq. neuropsiquiatr ; 77(3): 166-173, Mar. 2019. tab, graf
Article in English | LILACS | ID: biblio-1001345

ABSTRACT

ABSTRACT It is currently unknown how genetic factors may influence the clinical course of multiple sclerosis (MS). Objective: We examined the impact of CIITA polymorphisms −168A/G (rs3087456) and +1614G/C (rs4774) on the risk of disability progression, severity and on responses to first-line immunomodulator treatments. Methods: Genomic DNA was extracted from blood samples. We used ABI3730xl and GeneMapper v.4.0 software to identify genotype variations. All patients were followed up and clinically reassessed at three-month intervals. Disability progression was measured by the Expanded Disability Status Scale and disease severity by the Multiple Sclerosis Spasticity Scale (MSSS). Results: We included 37 men and 80 women. We found no evidence regarding the influence of the single nucleotide polymorphisms studied in the Expanded Disability Status Scale or therapeutic response of the evaluated drugs. We performed a logistic regression analysis with the MSSS and found that a less severe MS course was associated with wild type CIITA −168AA and CIITA +1614GG, as the chance of the patient progressing to MSSS2 and MSSS3 decreased in 61% and 75% with CIITA −168AA and 66% and 75% with CIITA +1614GG, respectively (p < 0.0001). Although less significant, the CIITA +1614 GC also pointed to a less severe MS course and the chance of the patient progressing to MSSS3 decreased 79% (p = 0.015). We also observed that the CIITA −168GG genotype was more frequent in MSSS2 and MSSS3 and had 40% lower odds ratio to becoming more severe MS. Conclusion: These data suggest that CIITA −168AA, CIITA +1614GG and CIITA +1614 GC polymorphisms may be associated with a better MS clinical course. This knowledge may be useful for a better understanding of MS and its therapeutic management.


RESUMO Atualmente não se sabe como os fatores genéticos podem influenciar o curso clínico da esclerose múltipla (EM). Objetivo: Examinamos o impacto dos polimorfismos CIITA −168A/G (rs3087456) e CIITA +1614G/C (rs4774) no risco de progressão da incapacidade, gravidade e resposta aos tratamentos imunomoduladores de primeira linha. Métodos: O DNA genômico foi extraído de amostras de sangue. Utilizamos o software ABI3730xl e GeneMapper v.4.0 (Applied Biosystems) para identificar variações genotípicas. Todos os pacientes foram acompanhados e reavaliados clinicamente em intervalos de três meses. A progressão da incapacidade foi medida pela EDSS e a gravidade da doença pelo MSSS. Resultados: Incluímos 37 homens e 80 mulheres. Não encontramos evidências sobre a influência dos SNPs estudados no EDSS e na resposta terapêutica aos fármacos avaliados. Realizamos uma análise de regressão logística com o MSSS e observamos uma evolução menos grave da EM associada aos tipos selvagens CIITA −168AA e CIITA +1614GG, pois a chance do paciente atingir MSSS2 e MSSS3 diminuiu em 61%/75%, e 66/75% respectivamente (p < 0,0001). Embora menos significativo, o CIITA +1614GC também foi relacionado com evolução menos grave da EM e a chance do paciente atingir o MSSS3 diminuiu 79% (p = 0,015). Nós também observamos que o genótipo CIITA −168GG foi mais frequente no MSSS2 e MSSS3 e teve uma razão de chance 40% menor para atingir forma mais grave da EM. Conclusão: Estes dados sugerem que os polimorfismos CIITA −168AA, CIITA +1614GG e CIITA +1614GC podem estar associados a um melhor curso clínico da EM. Este conhecimento pode ser útil para uma melhor compreensão da EM e o seu manejo terapêutico.


Subject(s)
Humans , Male , Female , Adolescent , Adult , Middle Aged , Aged , Young Adult , Nuclear Proteins/genetics , Trans-Activators/genetics , Disease Progression , Polymorphism, Single Nucleotide/genetics , Multiple Sclerosis/genetics , Time Factors , Severity of Illness Index , Logistic Models , Retrospective Studies , Interferon-beta/therapeutic use , Disability Evaluation , Kaplan-Meier Estimate , Genetic Association Studies , Glatiramer Acetate/therapeutic use , Gene Frequency , Genotype , Immunologic Factors/therapeutic use , Multiple Sclerosis/mortality , Multiple Sclerosis/drug therapy
16.
J. bras. pneumol ; 45(6): e20180225, 2019. tab, graf
Article in English | LILACS | ID: biblio-1040292

ABSTRACT

ABSTRACT Objective: To describe the incidence of active tuberculosis and the occurrence of adverse events after isoniazid treatment in patients with latent tuberculosis infection (LTBI) who also had chronic inflammatory diseases and were treated with immunobiologic agents in an endemic area in Brazil. Methods: The diagnosis of LTBI was based on anamnesis, clinical examination, chest X-ray, and a tuberculin skin test (TST). Patients received prophylactic treatment (isoniazid for six months) in accordance with the Brazilian guidelines. Results: A total of 101 patients were evaluated between July of 2011 and July of 2015. Of those, 55 (54.46%) were women (mean age, 53.16 ± 1.76 years) and 46 (45.54%) were men (mean age, 45.39 ± 2.13 years). A total of 79 patients (78.22%) were being treated with immunobiologic agents and 22 (21.78%) were being treated with immunomodulatory or immunosuppressive agents. In the screening for LTBI, 53 patients (52.48%) had a TST induration ≥ 10 mm. Chest X-ray findings consistent with LTBI were observed in 36 patients (35.64%). Isoniazid preventive therapy was effective in 96 (95.05%) of the 101 patients evaluated. It is of note that 84 (83.17%) of the patients experienced no adverse effects from the use of isoniazid and that 83 (98.81%) of those patients completed the prophylactic treatment (p = 0.002). Active tuberculosis was diagnosed in 5 (6.33%) of the 79 patients treated with immunobiologic agents and in 1 (4.55%) of the 22 patients treated with other immunomodulators/immunosuppressants. Conclusions: A six-month course of isoniazid proved to be safe and effective in the treatment of LTBI, which is essential to reducing the risk of developing active tuberculosis.


RESUMO Objetivo: Descrever a incidência de tuberculose ativa e a ocorrência de eventos adversos do tratamento com isoniazida em pacientes diagnosticados com tuberculose latente (TBL), portadores de doenças inflamatórias crônicas e tratados com agentes imunobiológicos em uma área endêmica no Brasil. Métodos: O diagnóstico de TBL foi feito com base em anamnese, exame clínico, radiografia de tórax e teste tuberculínico (TT). O tratamento profilático foi realizado segundo diretrizes brasileiras com isoniazida por seis meses. Resultados: Foram estudados 101 pacientes entre julho de 2011 e julho de 2015. Desses, 55 (54,46%) eram mulheres (média de idade = 53,16 ± 1,76 anos) e 46 (45,54%) eram homens (média de idade = 45,39 ± 2,13 anos), sendo que 79 (78,22%) foram tratados com agentes imunobiológicos e 22 (21,78%) com outros agentes imunomoduladores ou imunossupressores. Na triagem para TBL, 53 pacientes (52,48%) apresentaram TT ≥ 10 mm. A radiografia de tórax alterada por imagens compatíveis com TBL foi observada em 36 pacientes (35,64%). O tratamento profilático com isoniazida mostrou uma eficácia de 95,05% (96/101). É relevante mencionar que 84 (83,17%) dos pacientes não apresentaram nenhum efeito adverso à isoniazida e, desses, 83 (98,81%) completaram o tratamento profilático (p = 0,002). Tuberculose ativa foi diagnosticada em 5 (6,33%) dos 79 pacientes tratados com agentes imunobiológicos e em 1 (4,55%) dos 22 pacientes tratados com outros imunomoduladores/imunossupressores. Conclusões: O uso de isoniazida por seis meses mostrou-se seguro e eficaz no tratamento da TBL nesses pacientes, o que é essencial para reduzir o risco de desenvolvimento de tuberculose ativa.


Subject(s)
Humans , Male , Female , Adult , Middle Aged , Aged , Young Adult , Latent Tuberculosis/diagnosis , Latent Tuberculosis/drug therapy , Immunologic Factors/therapeutic use , Immunosuppressive Agents/therapeutic use , Isoniazid/therapeutic use , Antitubercular Agents/therapeutic use , Time Factors , Brazil/epidemiology , Tuberculin Test/methods , Radiography, Thoracic , Multivariate Analysis , Prospective Studies , Risk Factors , Treatment Outcome , Antibiotic Prophylaxis/methods , Endemic Diseases , Latent Tuberculosis/epidemiology
17.
Rev. méd. Maule ; 33(2): 20-24, sept. 2018. tab
Article in Spanish | LILACS | ID: biblio-1292505

ABSTRACT

The term autoimmune cytopenias is referred to a heterogeneous group of diseases characterized by a reduced peripheral blood cell counts in one or more cellular series, because an immunological disorder. The first line therapy is steroids, followed by splenectomy or immunesupressant therapy in non-responders. Rituximab is an anti CD20 monoclonal antibody used as a third line in refractory patients or as an alternative to splenectomy. We present a retrospective study of nine patients with autoimmune cytopenias treated in a public hospital setting with rituximab. Five patients with the diagnosis of inmune thrombocytopenic purpura received it, all of them achieved hematological response (4 complete and one partial). The median time to the best response was 6 weeks, staying in this category after 6 months of follow up. Four patients with autoimmune hemolytic anemia received rituximab, three of them achieving partial response and one was lost from follow up. No severe adverse effects related to rituximab were registered.


Subject(s)
Humans , Male , Female , Adult , Middle Aged , Aged , Autoimmune Diseases/drug therapy , Thrombocytopenia/drug therapy , Antibodies, Monoclonal, Murine-Derived/therapeutic use , Immunologic Factors/therapeutic use , Anemia, Hemolytic, Autoimmune/drug therapy , Neutropenia/drug therapy , Retrospective Studies , Purpura, Thrombocytopenic, Idiopathic/immunology , Rituximab/administration & dosage
18.
Arq. neuropsiquiatr ; 76(8): 539-554, Aug. 2018. tab, graf
Article in English | LILACS | ID: biblio-950578

ABSTRACT

ABSTRACT The expanding therapeutic arsenal in multiple sclerosis (MS) has allowed for more effective and personalized treatment, but the choice and management of disease-modifying therapies (DMTs) is becoming increasingly complex. In this context, experts from the Brazilian Committee on Treatment and Research in Multiple Sclerosis and the Neuroimmunology Scientific Department of the Brazilian Academy of Neurology have convened to establish this Brazilian Consensus for the Treatment of MS, based on their understanding that neurologists should be able to prescribe MS DMTs according to what is better for each patient, based on up-to-date evidence and practice. We herein propose practical recommendations for the treatment of MS, with the main focus on the choice and management of DMTs, as well as present a review of the scientific rationale supporting therapeutic strategies in MS.


RESUMO O crescent arsenal terapêutico na esclerose múltipla (EM) tem permitido tratamentos mais efetivos e personalizados, mas a escolha e o manejo das terapias modificadoras da doença (TMDs) tem se tornado cada vez mais complexos. Neste contexto, especialistas do Comitê Brasileiro de Tratamento e Pesquisa em Esclerose Múltipla e do Departamento Científico de Neuroimunologia da Academia Brasileira de Neurologia reuniram-se para estabelecer este Consenso Brasileiro para o Tratamento da EM, baseados no entendimento de que neurologistas devem ter a possibilidade de prescrever TMDs para EM de acordo com o que é melhor para cada paciente, com base em evidências e práticas atualizadas. Por meio deste documento, propomos recomendações práticas para o tratamento da EM, com foco principal na escolha e no manejo das TMDs, e revisamos os argumentos que embasam as estratégias de tratamento na EM.


Subject(s)
Humans , Vitamin D/therapeutic use , Immunologic Factors/therapeutic use , Immunosuppressive Agents/therapeutic use , Multiple Sclerosis/drug therapy , Recurrence , Brazil , Academies and Institutes , Neurology
20.
Arq. neuropsiquiatr ; 76(1): 6-12, Jan. 2018. tab, graf
Article in English | LILACS | ID: biblio-888336

ABSTRACT

ABSTRACT The perception of multiple sclerosis (MS) severity and risk associated with therapies might influence shared decision making in different countries. We investigated the perception of MS severity and factors associated with risk acceptance in Brazil in 96 patients with relapsing-remitting MS using a standardized questionnaire and compared this with two European cohorts. Multiple sclerosis was perceived as a very severe disease and the risk of developing progressive multifocal leukoencephalopathy due to natalizumab was seen as moderate to high. Seventy-six percent considered a risk of 1:1,000, or higher, an impediment for natalizumab use. Older age was the only variable associated with higher risk acceptance and our patients showed a more conservative profile than German and Spanish patients. Our patients perceived MS severity and progressive multifocal leukoencephalopathy risk similarly to elsewhere, but their willingness to take risks was more conservative. This should be considered when discussing therapeutic options and it might have an impact on guideline adaptations.


RESUMO A percepção de gravidade da esclerose múltipla (EM) e riscos associado a terapias podem influenciar a escolha de tratamento em diferentes países. Investigamos a percepção da gravidade da EM e fatores associados à aceitação de risco em 96 pacientes com EM remitente-recorrentecom um questionário e comparamos com duas coortes europeias. A EM foi percebida como muito grave e o risco de desenvolver leucoencefalopatia multifocal progressiva devido ao natalizumabe, como moderado a alto, sendo que76% consideraram um risco de 1: 1.000 ou maior como impeditivo deseu uso. Idade mais avançada foi a única variável associada àaceitação de risco mais elevado e nossos pacientes revelaram um perfil mais conservador do que os pacientes alemães e espanhóis. Esses dados devem ser considerados ao discutir opções terapêuticas e pode ter impacto nas adaptações de diretrizes locais.


Subject(s)
Humans , Adult , Perception , Risk-Taking , Multiple Sclerosis, Relapsing-Remitting/drug therapy , Natalizumab/therapeutic use , Immunologic Factors/therapeutic use , Personality , Severity of Illness Index , Brazil , Health Knowledge, Attitudes, Practice , Surveys and Questionnaires , Age Factors , Leukoencephalopathy, Progressive Multifocal/chemically induced , Risk Assessment , Multiple Sclerosis, Relapsing-Remitting/psychology , Educational Status , Natalizumab/adverse effects , Immunologic Factors/adverse effects
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