Trifluridina/cloridrato de tipiracila no tratamento de pacientes com carcinoma colorretal metastático politratados: uma análise de custo-efetividade na perspectiva de pagadores privados no Brasil / Trifluridine/tipiracil hydrochloride in the treatment of polytreated metastatic colorectal carcinoma: a cost-effectiveness analysis in the private payer perspective in Brazil

Objetivo: Avaliar a custo-efetividade da trifluridina/cloridrato de tipiracila (FTD/TPI) em comparação ao melhor cuidado de suporte (sigla em inglês BSC, best supportive care) e ao regorafenibe para o tratamento em pacientes com câncer colorretal metastático (CCRm) politratados (terceira linha ou linhas posteriores) sob a perspectiva de pagadores privados no Brasil. Métodos: Foi construído um modelo de sobrevida particionado considerando três estados de saúde. A efetividade foi medida em anos-vida ganhos e Quality-Adjusted Life Years (QALY). Os custos foram obtidos a partir da perspectiva do sistema de saúde privado brasileiro considerando um horizonte temporal de cinco anos. Também foram realizadas análises de sensibilidade univariada e probabilística para avaliar a robustez do modelo. Resultados: A utilização de FTD/TPI pode gerar melhores desfechos clínicos versus BSC e economia de recursos versus regorafenibe. FTD/TPI proporcionou mais 0,098 anos de vida por paciente e uma qualidade de vida incremental de 0,072, comparada ao BSC. Já em relação ao regorafenibe, a FTD/TPI apresentou redução de R$ 2.088,49 nos custos por paciente e benefícios clínicos com incremento marginal. Conclusão: FTD/TPI representa uma opção de tratamento de CCRm custo-efetiva, comparada ao regorafenibe, na perspectiva de pagadores privados no Brasil

Objective: To determine the cost-effectiveness analysis of trifluridine/tipiracil chloridrate (FTD/TPI) compared to best supportative care (BSC) and regorafenib for the treatment of polytreated metastatic colorectal carcinoma (mCRC) (3rd line or later lines) in the private payer perspective in Brazil. Methods: A partitioned survival model was developed based on three health states. Effectiveness was measured in life-years gained and Quality-Adjusted Life Years (QALYs). Costs were obtained from the perspective of the supplementary healthcare system in Brazil considering a time horizon of five years. Univariate and probabilistic sensitivity analyses were performed to evaluate the robustness of the model. Results: The use of FTD/TPI may generate better clinical outcomes versus BSC and resource savings versus regorafenib. FTD/TPI provided more 0,098 years of life per patient and an incremental quality of life of 0,072 compared to BSC. Regarding regorafenib, FTD/TPI provided a cost reduction of R$ 2.088,49 per patient and similar clinical benefits. Conclusion: FTD/TPI represents a cost-effective treatment option for mCRC compared to regorafenib from the perspective of the supplementary healthcare system in Brazil

Herpes simplex virus: isolation, cytopathological characterization and antiviral sensitivity

BACKGROUND: Herpes simplex virus (HSV) infection is an endemic disease and it is estimated that 6095% of the adult population are infected with symptoms that are usually self-limiting, though they can be serious, extensive and prolonged in immunocompromised individuals, highlighted by the emergence of drug-resistant strains. The study of the wild-type HSV strains based on the cytopathogenic features and its antiviral sensitivity are important in the establishment of an antivirogram for controlling the infection. OBJECTIVE: This study sought to isolate and examine the cytopathological characteristics of circulating strains of the Herpes simplex virus, from clinical specimens and their sensitivity to commercially available antiherpesvirus drugs, acyclovir, phosphonophormic acid and trifluridine. METHODS: Herpes simplex virus isolation, cytopathological features and antiviral sensitivity assays were performed in cell culture by tissue culture infectious dose or plaque forming unit assay. RESULTS: From twenty-two clinical specimens, we isolated and adapted nine strains. Overall, the cytopathic effect was detected 24 h post-infection (p.i.) and the presence of syncytia was remarkable 48 h p.i., observed after cell staining. Out of eight isolates, four developed plaques of varying sizes. All the isolates were sensitive to acyclovir, phosphonophormic and trifluridine, with the percentage of virus inhibition (%VI) ranging from 49.7-100%. CONCLUSIONS: The methodology for HSV isolation and characterization is a straightforward approach, but the drug sensitivity test, regarded as being of great practical importance, needs to be better understood. .

Herpes simplex uveitis

BACKGROUND: Uveitis in herpes simplex virus (HSV) ocular disease is usually associated with corneal stromal disease. It has generally been believed that herpetic uveitis in the absence of corneal disease is very rare. When seen it is usually attributed to varicella zoster virus (VZV) infections. The diagnosis of uveitis caused by herpes simplex is often not diagnosed resulting in inadequate treatment and a poor visual result. METHODS: Seven patients from a large uveitis practice who presented with a clinical picture of: anterior uveitis and sectoral iris atrophy without keratitis, a syndrome highly suggestive of herpetic infection, are reported. Polymerase chain reaction (PCR) was done in the aqueous of four of them and was positive for HSV. One patient had bilateral disease. Most of the patients also had severe secondary glaucoma. RESULTS: Of the seven patients presented five had no history of any previous corneal disease. Two had a history of previous dendritic keratitis which was not active at the time of uveitis development. One patient with bilateral disease was immunosuppressed at the time when the uveitis developed. Six of the seven patients had elevated intraocular pressures at the time of uveitis and five required glaucoma surgery. Intractable glaucoma developed in two patients leading to rapid and severe visual loss despite aggressive management. CONCLUSION: Findings suggest that uveitis without corneal involvement may be a more frequent manifestation of ocular herpes simplex disease than previously thought. Absence of corneal involvement delays a correct diagnosis and may worsen visual outcome. Primary herpetic uveitis (when there is no history of previous corneal disease) seems to be more severe than the uveitis in patients with previous corneal recurrences. The associated glaucoma may be a devastating complication

Experimental ulcerative herpetic keratitis: Humoral immune response and its role in corneal protection

Twenty five rabbits were inoculated with HSV type [1] to estimate the humoral immune response and corneal protection. The serum neutralizing antibody could be detected 15 days after inoculation. Ig[G], Ig[A] and Ig[M] specific to the virus were detected by immunofluorescence. Only corneae of 2 out of 14 immunized rabbits developed corneal ulcers, when challenged with the virus, as compared to 5 non-immunized that developed ulcer. The 2 immunized rabbits that developed corneal ulcers showed complete healing in 3 days to treatment with trifluorotrhymidine as compared to 6 days for the non-immunized control group [5 rabbits]

Infecciones por virus herpes: drogas antiherpéticas: I / Herpesvirus infections: antiherpetic drugs: I

Aunque los antivirales sintéticos inhiben in vitro casi todos los virus del grupo herpes la terapia está virtualmente restringida a las infecciones por el virus herpes simplex y varicela zoster. Ninguna de estas drogas es realmente eficaz contra citomegalovirus; algunas tendrían cierta acción contra el virus Epstein-Barr. Las drogas antiherpéticas sólo actúan sobre el virus que replica, sin alcanzar al virus en estado de latencia. Deben ser usadas con precaución ya que aún no se han valorado sus efectos colaterales cuando se suministran por largos períodos. Las drogas antiherpéticas autorizadas por la FDA son: 1) la iododeoxiuridina en solución (0,1 por ciento) o unguento (0,5 por ciento) para uso oftálmico; 2) la trifluorotimidina en solución oftálmica (0,1 por ciento); 3) la adenina arabinosido en frasco ampolla de 1 gramo para uso intravenoso y 4) el aciclovir como unguento oftálmico (0,3 por ciento), crema dérmica (5 por ciento en base de propilenglicol al 40 por ciento), tabletas (400 y 200 mg) o jarabe para uso oral, frascos ampolla de 250 mg para uso intravenoso. El unguento dérmico es poco efectivo

Influência de iododesoxiuridina, iododesoxicitidina e trifluorotimidina sobre a regeneração do epitélio corneano em coelhos, estudo clínico e histopatológico / Effect of iodo-5-deoxy-2-uridine (IDU); iodo-5-deoxy-2-citidine (IDC) and trifluoromethydine (TFT) on corneal reepithelization. Clinical and histological study

O autor estudou, clínica e histologicamente, o efeito de três medicamentos antivirais (iodo-5-desoxi-2'uridina - IDU 0,1 por cento; iodo-5-desoxi-2'citidina - IDC 1 por cento e trifluorotimidina - TFT 1 por cento) sobre a reepitelização corneana em 56 coelhos albinos. A despitelização foi feita pelo método de Moses, que sabidamente não lesa a membrana basal. O estudo da velocidade de regeneração foi realizado com um analisador de imagens computadorizado, conferindo maior precisão ao método empregado. A histopatologia foi executada sob microscopia óptica. Conclui que, estatisticamente, não houve diferença significativa entre as substâncias, ou seja, as drogas não alteraram a velocidade de reepitelização. Histologicamente houve diferença entre os fármacos estudados obedecendo à seguinte ordem de toxicidade: controle, IDC, TFT e IDU.

randomised double-controlled clinical study of trifluridine and adenine arabinoside in herpetic keratitis

This study included 213 patients with different herpetic lesions. They were randomly divided into two treatment-groups. Group 1 included 144 patients [88 men and 56 women] received 3% Ara-A [Vidarabine] ointment 5 times daily. Thereapy was continued for a period of 7-15 days. The results of therapy in different herpetic lesions by the two drugs were compared and discussed

Antivirales / Antiviral agents

Se pretende con este resumen dar un panorama del estado actual del tema antivirales. Sobre el mismo-a criterio del autor-hay cierta confusión sobre la existencia o no de productos químicos capaces de actuar in vivo sobre los virus. Probablemente, para los que desconozcan el tema, puede resultar una sorpresa el hecho de que desde hace años, existen y se los usan, si bien en algunos casos su efectividad puede ser controvertida por no existir todavía suficientes pruebas clínicas que se determinen su eficacia o no. Para los que conozcan el tema, esta actualización podría contribuir a ubicarse y tomar una postura frente al uso de los antivirales. Por último, el autor se ha limitado a comentar trabajos que en general demuestran que actualmente hay antivirales con un grado aceptable de eficacia. El uso o no de ellos, será decisión del médico

Ceratite herpética / Herpetic keratitis

O autor relata o esquema de tratamento para Ceratite Herpética em sua forma epitelial com os meios e drogas encontradas comercialmente. Cita algumas teorias que procuram explicar a permanência do vírus em forma latente no hospedeiro