Custeio Baseado em Atividade e Tempo (TDABC) do modelo CEDMAC de terapia assistida para dispensação de medicamentos imunobiológicos para doenças reumatológicas no SUS / Time-Driven Activity Based Costing (TDABC) of the CEDMAC model of assisted therapy for dispensing immunobiological rheumatologic medications at SUS

Objetivos: Mensurar o custo dos procedimentos de infusão de imunobiológicos no modelo CEDMAC (Centro de Dispensação de Medicações de Alto Custo) e estimar o custo minimização integral gerada pela existência desse modelo. Métodos: A metodologia de Custeio Baseado em Atividade e Tempo (TDABC) foi usada para calcular os custos dos procedimentos. Tempos de atividades, capacidades máximas de atendimento e fluxos dos processos internos foram obtidos em entrevistas e validados por meio de acompanhamento de pacientes. Os procedimentos foram categorizados em três tipos: a) aplicação subcutânea, b) infusão endovenosa rápida e c) infusão endovenosa longa. O custo-minimização foi estimado a partir de análise de 2017 para pacientes com artrite reumatoide (AR). Resultados: Ao longo de 2019, foram realizados 12.074 atendimentos no CEDMAC. Desses atendimentos, 60% foram de aplicação subcutânea (custo de R$ 117,90), 30%, de infusão endovenosa rápida (custo de R$ 169,90) e 10%, de endovenosa longa (custo de R$ 217,50). Usando a análise realizada em 2017, foi possível calcular o custo-minimização integral do modelo (uma economia líquida estimada de R$ 1.258.024,26 ao ano) e também extrapolar esses valores para todo o SUS caso o modelo fosse difundido no país (uma economia líquida estimada de R$ 189.401.652,88). Conclusão: Utilizando o método de TDABC, foi possível realizar de maneira rápida e eficiente o custeio dos principais procedimentos realizados no modelo CEDMAC. Essa análise embasará a solicitação da incorporação desses procedimentos na tabela unificada do SUS. Caso os procedimentos sejam incorporados e o modelo CEDMAC, difundido pelo Brasil, estima-se que a economia gerada seja da ordem de 189 milhões de reais ao ano.

Objectives: To measure the costs of immunobiological infusion procedures in the CEDMAC model (Centro de Dispensação de Medicações de Alto Custo) and to estimate the full cost-minimization generated by the existence of this model. Methods: Time-Driven Activity Based Costing (TDABC) methodology was used to calculate the procedures costs. Activity times, service capacities and internal flows were obtained from employee interviews and validated by follow-up with patients. Procedures were categorized into three types: a) subcutaneous, b) intravenous fast infusion, and c) intravenous slow infusion. The full cost-minimization was estimated based on a 2017 analysis of the cost-minimization for rheumatoid arthritis (RA) patients. Results: In 2019, 12,074 patients were attended at CEDMAC. Of these, 60% of infusions were subcutaneous (costing R$ 117.90 each), 30% were fast intravenous infusion (costing R$ 169.90), and 10% were slow intravenous infusion (costing R$ 217.50). Using a 2017 RA analysis, it was possible to calculate the full cost-minimization of the model, with an estimated net savings of R$ 1,258,024.26 per year. The estimated net savings if the model were disseminated throughout the country for the entire SUS would be R$ 189,401,652.88. Conclusion: Using the TDABC method it was possible to quickly and efficiently estimate the cost allocation of the main procedures performed in the CEDMAC model. This analysis will support the request for incorporating these procedures into SUS. If the procedures were incorporated, and the CEDMAC model was disseminated throughout Brazil, the savings generated by this initiative could be up to 189 million reais per year.

Assisted therapy model for dispensing immunobiological drugs for rheumatoid arthritis by the Brazilian Unified Health System: rational use of resources reduces expenses

Objective: The incorporation of immunobiological agents for rheumatoid arthritis (RA) treatment at the Brazilian Unified Health System (SUS) represented a significant advance but had an important impact on the budget. As the current model of direct patient delivery had deficiencies, the CEDMAC model of assisted therapy was implemented to focus on rational use to minimize expenses and increase access. However, there is no data to compare the two models. Thus, this study aimed to compare the number of bottles effectively dispensed by the CEDMAC model to direct dispensing and assess its financial impact. Methods: Care of RA patients at CEDMAC in 2015, whose immunobiological drugs were provided by the Ministry of Health, were included. Drug and dose received, prescribed dose, the number of bottles, cancellations due to contraindication, and absences were recorded. As a comparison, the number of bottles that would be delivered by direct dispensing was estimated. The difference between the total number of bottles dispensed by the two systems and the financial impact of the purchase price in 2015 was calculated. Results: In 2015, CEDMAC provided 3,784 consultations for RA patients. The total number of bottles of immunobiological agents prescribed was 10,000 bottles, and 1,946 (19.5%) were not used for bottle optimization, contraindications, or absenteeism. Unused bottles reduced expenses by R$ 806,132.62. The expansion of the model to the entire SUS would reduce costs by R$ 121,110,388.27. Conclusion: The CEDMAC assisted therapy model considerably reduces the volume of dispensed bottles and can significantly reduce expenses in the supply of immunobiological agents for RA at SUS.

Opportunistic infections in pediatrics: when to suspect and how to approach / Infecções oportunistas em pediatria: quando suspeitar e como abordar

Abstract Objectives To describe the characteristics of opportunistic infections in pediatrics regarding their clinical aspects, as well as the diagnostic strategy and treatment. Source of data Non-systematic review of literature studies in the PubMed database. Synthesis of data Opportunistic infections caused by non-tuberculous mycobacteria, fungi, Herpesvirae, and infections affecting individuals using immunobiological agents are analyzed. Because these are severe diseases with a rapid evolution, diagnostic suspicion should be early, associated with the patient's clinical assessment and history pointing to opportunistic infections. Whenever possible, samples of secretions, blood, and other fluids and tissues should be collected, with early therapy implementation. Conclusions Despite the improved diagnosis of opportunistic infections in recent years, they remain a challenge for pediatricians who are not used to these infections. They should raise the suspicion and start treating the case, but should also resort to specialists in the management of these infections to provide a better outcome for these patients, who still have high mortality.

Resumo Objetivos Descrever as características das infecções oportunistas em pediatria em seus aspectos clínicos, bem como a estratégia diagnóstica e o tratamento. Fonte dos dados Revisão de trabalhos de literatura de forma não sistemática na base de dados Pubmed. Síntese dos dados São apresentadas as infecções oportunistas causadas por micobactérias não tuberculosas, fungos, herpervírus e as infecções que acometem indivíduos em uso de imunobiológicos. Por se tratar de doenças graves e de evolução rápida, a suspeita diagnóstica deve ser precoce, associada à clínica do paciente e aos dados de história que apontam para infecções oportunistas. Sempre que possível, amostras de secreções, sangue e outros fluidos e de tecidos devem ser coletadas, com instituição precoce de terapia. Conclusões Apesar da melhoria do diagnóstico de infecções oportunistas nos últimos anos, elas ainda são um desafio para o pediatra pouco habituado a essas infecções. Ele deve fazer a suspeita e iniciar a condução do caso, mas recorrer a especialistas com prática no manejo dessas infecções de modo a propiciar um melhor desfecho para esses pacientes que ainda apresentam alta mortalidade.

Guia prático de atualização: medicamentos biológicos no tratamento da asma, doenças alérgicas e imunodeficiências / Practical update guide: biological drugs in the treatment of asthma, allergic diseases and immunodeficiencies

O presente guia apresenta revisão extensa sobre imunobiológicos utilizados, liberados e ainda sob estudo, para o tratamento da asma, doenças alérgicas e imunodeficiências. Além das características físico-químicas de alguns desses fármacos, são revisadas as indicações e os resultados de estudos clínicos realizados para avaliar eficácia e segurança. Separados por doença específica, são apresentados os principais agentes disponíveis e aprovados para utilização segundo as normas regulatórias nacionais.

This guide presents an extensive review of immunobiological drugs used, approved and/or under investigation for the treatment of asthma, allergic diseases and immunodeficiencies. In addition to the physicochemical characteristics of some of these drugs, their indications and results of clinical studies evaluating efficacy and safety are reviewed. The main agents available and approved for use in each specific disease according to national regulatory standards are presented.

Recent advances of microneedles for biomedical applications: drug delivery and beyond

The microneedle (MN), a highly efficient and versatile device, has attracted extensive scientific and industrial interests in the past decades due to prominent properties including painless penetration, low cost, excellent therapeutic efficacy, and relative safety. The robust microneedle enabling transdermal delivery has a paramount potential to create advanced functional devices with superior nature for biomedical applications. In this review, a great effort has been made to summarize the advance of microneedles including their materials and latest fabrication method, such as three-dimensional printing (3DP). Importantly, a variety of representative biomedical applications of microneedles such as disease treatment, immunobiological administration, disease diagnosis and cosmetic field, are highlighted in detail. At last, conclusions and future perspectives for development of advanced microneedles in biomedical fields have been discussed systematically. Taken together, as an emerging tool, microneedles have showed profound promise for biomedical applications.

Evaluation of the immunobiological effects of a regenerative far-infrared heating system in pigs

Thermal conditions are an important environmental factor in maintaining healthy pigs because they affect feed intake, growth efficiency, reproduction and immune responses in pigs. RAVI, a regenerative far-infrared heating system, can effect pig production by emitting an optimal far-infrared wavelength. Far-infrared radiation has been reported to increase microvascular dilation and vascular flow volume. The purpose of this study was to evaluate the immunobiological differences between pigs raised with the RAVI system and the gasoline heater system. Twenty-six-week-old weaned pigs were raised in two rooms that were equipped with a RAVI system or a gasoline heater for 8 weeks. A porcine atrophic rhinitis vaccine was administered after two weeks and transcriptome analysis in whole blood were analyzed at 2-week intervals. Signaling pathway analyses of the RAVI group at 8 weeks showed the activation of pathways related to nitric oxide (NO) production. This suggests that the application of RAVI might induce the production of NO and iNOS, which are important for increasing the immune activity. Similar to the result of microarray, phenotypic changes were also observed at a later period of the experiment. The increase in body weight in the RAVI group was significantly higher than the gasoline heater group at 8 weeks. The antibody titer against the vaccine in the RAVI group was also higher than that the gasoline heater group at 4 weeks and 8 weeks. This evaluation of the use of a far-infrared heating system with pigs will be helpful for applications in the pig farm industry and pig welfare.

Guia prático de atualização em dermatite atópica - Parte II: abordagem terapêutica. Posicionamento conjunto da Associação Brasileira de Alergia e Imunologia e da Sociedade Brasileira de Pediatria / Updated practical guide on atopic dermatitis - Part II: treatment approach. Joint position paper of the Brazilian Association of Allergy and Immunology and the Brazilian Society of Pediatrics

Nas últimas décadas o conhecimento sobre a etiopatogenia da dermatite atópica (DA) avançou muito. Além da identificação dos principais agentes desencadeantes e/ou agravantes envolvidos na expressão clínica da DA, verificou-se ser a integridade da barreira cutânea um dos pontos fundamentais para a manutenção da homeostase da pele. Assim, no tratamento do paciente com DA, além da evitação dos agentes desencadeantes e/ou irritantes, o uso de hidratantes é parte fundamental, e acredita-se que tenha ação preventiva de surtos agudos. Além disso, a aquisição de agentes anti-inflamatórios de uso tópico tem permitido o controle de pacientes com formas leves a moderadas da DA. Embora tenham uso mais restrito, os agentes imunossupressores sistêmicos também têm sido empregados no tratamento de pacientes com DA grave ou refratária aos procedimentos habituais. Comenta-se também a imunoterapia alérgeno-específica como tratamento adjuvante da DA para alguns pacientes, sobretudo alérgicos aos ácaros e com manifestações respiratórias associadas. A aquisição de novos agentes, os imunobiológicos, também são apresentados à luz das evidências científicas e clínicas atuais. O presente guia prático de atualização em dermatite atópica ­ abordagem terapêutica teve por objetivo rever os esquemas de tratamento disponíveis e empregados no acompanhamento de pacientes com DA, além de apresentar terapêuticas futuras, como os agentes imunobiológicos que em breve estarão à disposição para o tratamento de formas mais graves e/ou refratárias da DA.

Over the last few decades, knowledge of the etiopathogenesis of atopic dermatitis (AD) advanced greatly. The main triggering and/or aggravating factors involved in the clinical expression of AD have been identified, and cutaneous barrier integrity has been found to be key for the maintenance of skin homeostasis. Thus, when treating patients with AD, in addition to avoiding triggering and/ or irritating agents, recommending the use of skin moisturizers is paramount ­ and believed to have a preventive action against acute outbreaks. Moreover, topical anti-inflammatory agents have allowed AD control in patients with mild to moderate forms of the disease. Although more restricted, systemic immunosuppressive agents have also been used in the treatment of patients with severe or refractory AD. Specific allergen immunotherapy is presented as a possible adjunctive treatment for AD in some patients, especially those allergic to mites and presenting associated respiratory manifestations. Finally, the use of new immunobiological agents is discussed in the light of the scientific and clinical evidence currently available. The objectives of this updated practical guide on atopic dermatitis ­ treatment approach were to review the treatment regimens available and used in the follow-up of patients with AD and to present new therapies (e.g., immunobiological agents) that will soon be available for the treatment of more severe and/ or refractory forms of AD.

Reações infusionais imediatas a agentes imunobiológicos endovenosos no tratamento de doenças autoimunes: experiência de 2.126 procedimentos em um centro de infusão não oncológico / Immediate infusional reactions to intravenous immunobiological agents for the treatment of autoimmune diseases: experience of 2126 procedures in a non-oncologic infusion centre

Introdução: Com o crescimento do uso de drogas imunobiológicas (IBD) ampliamos o conhecimento sobre sua eficácia e segurança. Objetivo: Analisar as reações infusionais imediatas (RII) às IBD endovenosas - infliximabe (IFX), rituximabe (RTX), abatacepte (ABT) e tocilizumabe (TCZ) - no tratamento de doenças autoimunes. Método: Avaliamos 2.126 infusões feitas no CID (Centro de Infusão) em 268 pacientes. A droga usada, a indicação clínica, o tempo de infusão e o uso de pré-medicação foram determinados pelo médico prescritor. Foram consideradas RII todas as intercorrências apresentadas durante a infusão e/ou período observacional de 30 minutos. A conduta adotada nas RII seguiu os protocolos do CID. Resultados: Em relação ao tipo de IBD, as infusões foram distribuídas em: IFX (1.584; 74,5%), TCZ (226; 10,63%), RTX (185; 8,7%) e ABT (131; 6,16%). As RII foram descritas em 87 procedimentos (4,09%): 77 no grupo IFX e 10 no grupo RTX. Não foram descritas RII nos grupos de ABT e TCZ. A maioria foi considerada leve (n = 5; 41,17%) ou moderada (n = 50; 58,81%) e não houve reações graves. Das infusões interrompidas, 79 (92,9%) foram reiniciadas e concluídas com êxito. Apenas seis (0,28%) não foram concluídas por causa das RII. Conclusão: Apesar da diferença entre o número de procedimentos por droga, trata-se de uma análise de "vida real", na qual a incidência de RII foi semelhante à descrita na literatura. A baixa incidência de RII corrobora os dados de segurança tanto de forma quantitativa como qualitativa e ressalta a importância do acompanhamento médico especializado durante a infusão. .

Introduction: With the increasing use of immunobiological drugs (IBD), the knowledge about their effectiveness and safety has increased. Objective: To analyze the immediate infusional reactions (IIR) to intravenous IBD: infliximab (IFX), rituximab (RTX), abatacept (ABT) and tocilizumab (TCZ) on the treatment of autoimmune diseases. Method: 2126 infusions performed in the Infusion Centre - CID in 268 patients were analyzed. The used drug, its clinical indication, infusion time, and use of premedication were determined by the prescribing physician. All intercurrences presented during infusion and/or during a thirty minutes observation period were considered as IIR. The approach adopted in IIR followed the protocols of the Infusion Centre - CID. Results: Regarding the type of IBD, the infused drugs given were: IFX (1584, 74.5%), TCZ (226, 10.63%), RTX (185, 8.7%) and ABT (131, 6,16%). IIR were described in 87 procedures (9.4%): 77 - IFX group and 10 - RTX group. IIR were not described in ABT and TCZ groups. Most were considered as mild (n = 5; 41.17%) or moderate (n = 50, 58.81%) reactions; there were no serious reactions. Regarding to discontinue infusions, 79 (92.9%) were resumed and completed successfully. Only six (0.28% of infusions) were not completed because of IIR. Conclusion: Despite the differences between the number of procedures per drug, ours is a "real life" analysis, where the incidence of IIR was similar to that described in the literature. The low incidence of IIR corroborates the safety data, both quantitatively and qualitatively, and underscores the importance of specialized medical support during infusion. .

Physicochemical properties of a polysaccharide RAP-B-l from Rubus amabilis and its immunomodulating effects / 国际药学研究杂志

Objective To investigate the physicochemical properties and immunobiological activity of a polysaccharide (RAP-B-l) from stems of Rubus amabilis.

Physicochemical properties of a polysaccharide RAP-B-1 from Rubus amabilis and its immunomodulating effects / 国际药学研究杂志

Objective To investigate the physicochemica l properties and immunobiological activity of a polysaccharide (RAP-B-1) from stems of Rubus amabilis. Methods The crude polysaccharide (RAP) was obtained successively by boiling, ethanol precipitating and dialyzing. RAP was isolated with DEAE-cellulose and Sephadex G-100 to obtain a polysaccharide RAP-B-1. The physicochemical properties of RAP-B-1 were studied by hydrolysis, periodate oxidation, Smith degradation and methylation, CE, IR, NMR and GC-MS. The immunobiological activities were estimated by the proliferative activity of spleen lymphocytes and phagocytic activity of peritoneal macrophages in mice. Results The molecular weight of RAP-B-1 was 4.80×104 with specific optical rotation value [α] 20D+68.3 (c=1,H2O), and was composed of eight monosaccharides. The molar ratios were as Xyl: Ara: Glc: Rha:Gal: Man: GlcA: GalA = 1.0:6.9:0.8:1.1:6.9:0.3:0.5:3.3. RAP-B-1 was an arabinogalactan. The linkages of arabinose were →1) Ara (2,3→,→1) Ara(5→and→1) Ara, and the linkages of galactose were→1) Gal(4→,→1) Gal(6→and→1) Gal. RAP-B-1 could improve the proliferative activity of spleen T cells(P<0.05) and booste phagocytic activity of peritoneal macrophages at 50μg/ml concentration(P<0.01). Conclusion RAP-B-1 is an arabinogalactan and has immunobiological activity.

Immunobiological characteristic of grass pollen allergens / Монголын Анагаах Ухаан

Grass pollens are one of the most important airborne allergen sources worldwide. The Poaceaefamily comprises about 9000 species, 20 species from five subfamilies are considered to be the mostfrequent causes of grass pollen allergy, and the allergenic relationships among them closely follow theirphylogenetic relationships. The allergic immune response to pollen of several grass species has beenstudied extensively over more than three decades. Eleven groups of allergens have been identified anddescribed, in most cases from more than one species. The most complete set of allergens has so farbeen isolated and cloned from Phleum pratense (timothy grass) pollen. Based on the prevalence of IgEantibody recognition among grass pollen-sensitized individuals, several allergens qualify as major, butmembers of two groups, groups 1 and 5, have been shown to dominate the immune response to grasspollen extract. Isoform variation has been detected in members of several of the allergen groups, whichin some cases can be linked to observed genetic differences. N-linked glycosylation occurs in membersof at least three groups. Carbohydrate- reactive IgE antibodies have been attributed to grass pollensensitization and found to cross-react with glycan structures from other allergen sources, particularlyvegetable foods. Another cause of extensive cross-reactivity are the group 12 allergens (profilins), whichbelong to a family of proteins highly conserved throughout the plant kingdom and present in all tissues.Members of eight allergen groups have been cloned and expressed as recombinant proteins capableof specific IgE binding. This development now allows diagnostic dissection of the immune response tograss pollen with potential benefits for specific immunotherapy.

Vacinação contra febre amarela em pacientes com diagnósticos de doenças reumáticas, em uso de imunossupressores / Vaccination against yellow fever among patients on immunosuppressors with diagnoses of rheumatic diseases

A febre amarela é endêmica em alguns países. A vacina, único modo eficaz de proteção, é contra-indicada em pacientes imunocomprometidos. Nosso objetivo é relatar uma série de casos de pacientes reumatológicos, usuários de imunossupressores, vacinados contra a doença. Foi feito um estudo retrospectivo, por meio de questionário aplicado em pacientes reumatológicos medicados com imunossupressores, vacinados 60 dias antes da investigação. Foram avaliados 70 pacientes, com idade média de 46 anos, 90 por cento mulheres, portadores de artrite reumatóide (54), lupus eritematoso sistêmico (11), espondiloartropatias (5) e esclerose sistêmica (2). Os esquemas terapêuticos incluíam metotrexato (42), corticoesteróides (22), sulfassalazina (26), leflunomida (18), ciclofosfamida (3) e imunobiológicos (9). Dezesseis (22,5 por cento) pacientes relataram efeitos adversos menores. Dentre os 8 pacientes, em uso de imunobiológicos, apenas um apresentou efeito adverso, leve. Entre pacientes em uso de imunussopressores, reações adversas não foram mais freqüentes do que em imunocompetentes. Este é o primeiro estudo sobre o tema.

Yellow fever is endemic in some countries. The anti-yellow fever vaccine is the only effective means of protection but is contraindicated for immunocompromised patients. The aim of this paper was to report on a case series of rheumatological patients who were using immunosuppressors and were vaccinated against this disease. This was a retrospective study by means of a questionnaire applied to these patients, who were vaccinated 60 days before the investigation. Seventy patients of mean age 46 years were evaluated. Most of them were female (90 percent). There were cases of rheumatoid arthritis (54), systemic lupus erythematosus (11), spondyloarthropathy (5) and systemic sclerosis (2). The therapeutic schemes included methotrexate (42), corticosteroids (22), sulfasalazine (26), leflunomide (18), cyclophosphamide (3) and immunobiological agents (9). Sixteen patients (22.5 percent) reported some minor adverse effect. Among the eight patients using immunobiological agents, only one presented a mild adverse effect. Among these patients using immunosuppressors, adverse reactions were no more frequent than among immunocompetent individuals. This is the first study on this topic.