Análisis de impacto presupuestal de la temozolomida para el tratamiento de pacientes adultos con diagnóstico de novo de glioma maligno en Colombia / Budgetary impact analysis of temozolomide for the treatment of adult patients with de novo diagnosis of malignant glioma in Colombia

Tecnologías evaluadas: Nueva: temozolomida. Población: Pacientes mayores de 16 años con diagnóstico reciente de glioblástoma multiforme en Colombia. Perspectiva: La perspectiva del presente AIP corresponde al tercero pagador, que en este caso es el Sistema General de Seguridad Social en Salud (SGSSS) en Colombia. Horizonte temporal: El horizonte temporal de este AIP en el caso base corresponde a un año. Adicionalmente se reportan las estimaciones del impacto presupuestal para los años 2 y 3, bajo el supuesto de la inclusión en el POS en el año 1. Costos incluidos: Costos de las tecnologías analizadas. Fuente de costos: Los precios de cada tecnología considerada fueron consultados en el manual tarifario ISS 2001 y ajustados con un +25%, +30% y +48%. Escenarios: Para este AIP no fueron diseñados escenarios de adopción debido a que la tecnología evaluada ya se utiliza en la práctica clínica colombiana, para toda la población objetivo del análisis. Resultados: El caso base involucraría una inversión total de $29.494.699.472\r\npara el año 1, $4.225.358.276,32 para el año 2 y $ 4.974.085.010,60 para el año 3. En el caso base se asuma la inclusión de la temozolomida en el POS.(AU)

Excimer laser phototherapeutic keratectomy in conjunction with mitomycin C in corneal macular and granular dystrophies / Ceratectomia fototerapêutica com excimer laser em conjunto com mitomicina C em distrofias granular e macular da córnea

ABSTRACT Purpose: To evaluate the visual outcomes, recurrence patterns, safety, and efficacy of excimer laser phototherapeutic keratectomy (PTK) in conjunction with mitomycin C (MMC) for corneal macular and granular diystrophies. Methods: The patients were divided into two groups. Group 1 included patients with macular corneal dystrophy (MCD) that caused superficial corneal plaque opacities, and Group 2 included patients with granular corneal dystrophy (GCD). Patients in both groups were pre-, peri-, and postoperatively evaluated. The groups were compared in terms of uncorrected visual acuity (VA), best spectacle-corrected VA, presence of mild or significant recurrence, and time of recurrence. Results: Eighteen eyes (nine with MCD and nine with GCD) of 18 patients (10 men and eight women) were included. PTK was performed for each eye that was included in this study. The mean ablation amount was 117.8 ± 24.4 µm and 83.5 ± 45.7 µm in MCD and GCD, respectively, (p=0.18). The postoperative improvement of the mean VA was similar between the two groups before recurrences (p>0.43) and after recurrences (p>0.71). There were no statistically significant differences in the recurrence rate and the recurrence-free period for any recurrence type. Conclusion: PTK was an effective, safe, and minimally invasive procedure for patients with MCD and GCD. PTK in conjunction with MMC was similarly effective for both groups in terms of recurrence and visual outcomes.

RESUMO Objetivo: Avaliar os resultados visuais, padrões de recorrência, segurança e eficácia da ceratectomia fototerapêutica (PTK) por excimer laser em conjunto com mitomicina C (MMC) em distrofias macular e granular da córnea. Métodos: Os pacientes foram divididos em dois grupos. Grupo 1 incluiu pacientes com distrofia macular de córnea (MCD) que causaram opacidades superficiais corneanas em placa e o grupo 2 incluiu pacientes com distrofia corneana granular (GCD). Todos os pacientes em ambos os grupos foram avaliados no pré, per e pós-operatório. Os grupos foram comparados em termos de acuidade visual (VA) não corrigida, VA melhor corrigida por óculos, presença de recorrência leve ou significativa e o tempo de recorrência. Resultados: Dezoito olhos de 18 pacientes (10 homens e 8 mulheres) foram incluídos no estudo, 9 olhos com MCD e 9 olhos com GCD. Um procedimento de PTK foi realizado em cada olho incluídos neste estudo. A quantidade média de ablação foi 117,8 ± 24,4, 83,5 ± 45,7 µm de MCD e GCD, respectivamente, (p=0,18). A melhora pós-operatória da acuidade visual média foi semelhante entre os dois grupos antes de as recidivas (p>0,43) e após as recidivas (p>0,71). Não houve diferença estatisticamente significativa na taxa de recorrência ou do período livre de recorrência para qualquer tipo de recorrência. Conclusão: PTK foi um procedimento eficaz, seguro e minimamente invasivo para pacientes MCD e GCD. PTK em conjunto com MMC é igualmente eficaz para ambos os grupos em termos de recorrência e resultados visuais.

Comparative histological study on wound healing on rat's skin treated with Mitomycin C or Clobetasol propionate

PURPOSE:To compare histologically the action of Mitomycin C and that of Clobetasol propionate for surgical wound healing in rats.METHODS:A circular skin fragment was surgically removed from 57 Wistar rats. Twenty-two animals were treated with Mitomycin C with topical medication in a single dose, 22 with Clobetasol propionate with a cream medication once a day for 15 days and 13 did not receive any medication. The animals were euthanized 30 and 60 days, and the scars subjected to histological examination.RESULTS: The histological analysis on the samples did not show statistically significant differences regarding the quantities of fibroblasts, fibrocytes and vascular proliferation in the three groups, in the evaluations after 30 and 60 days. In the treated groups with Mitomycin C and Clobetasol there was a decrease in collagen concentration over the 30-day period and an increase in collagen concentration over the 60-day period, in comparison with the control group.CONCLUSIONS: The actions of Mitomycin C and Clobetasol were equivalent and not interfere in fibroplasias and in angiogenesis. Both drugs initially cause a decrease in collagen over a 30-day period and an increase over a 60-day period, demonstrating a delay in the wound healing.

A resistência das células T98G e U87MG à temozolamida está correlacionada com a expressão de genes de reparo de DNA / The resistance of T98G and U87MG cell lines to temozolomide is correlated with the expression of DNA repair genes

Os gliomas são tumores cerebrais definidos patologicamente pela presença de células com características histológicas e imuno-histoquímicas que evidenciam diferenciação glial. Dentre eles, os astrocitomas são os mais frequentes em adultos. Estes tumores normalmente apresentam infiltração difusa no tecido adjacente, são resistentes aos tratamentos e têm uma tendência natural para a progressão maligna. O tratamento padrão atual consiste na realização de ressecção cirúrgica do tecido tumoral seguida de radio e quimioterapia concomitantes, porém o prognóstico permanece extremamente pobre. O quimioterápico padrão-ouro no tratamento de GBM é o agente alquilante de DNA temozolamida (TMZ). Entretanto, os danos induzidos pela TMZ podem ser revertidos pela ação da maquinaria de reparo de DNA, impedindo a morte celular e levando à resistência do GBM ao tratamento. No presente estudo correlacionamos a expressão dos genes ATM, BRCA2, BRIP1, EXO1, NEIL3, RAD54L e XRCC2, envolvidos em reparo de DNA e sabidamente superexpressos em GBM, com a resistência das linhagens celulares T98G e U87MG ao tratamento com TMZ. Mostramos que a linhagem T98G é a mais resistente ao tratamento com TMZ, e apresenta superexpressão de BRCA2, BRIP1, EXO1, NEIL3, RAD54L e XRCC2 e sub-expressão de ATM. Vimos também que a linhagem U87MG, mais sensível ao tratamento com TMZ, apresenta expressão reduzida dos genes ATM, BRCA2 e EXO1. Portanto, estes dados sugerem uma correlação positiva entre a expressão de genes de reparo de DNA e a resistência das células de GBM à TMZ.(AU)

Gliomas are brain tumors pathologically defined by the presence of cells with histological and immunohistochemical characteristics of glial differentiation. Among them, astrocytomas are the most common in adults. These tumors usually show diffuse infiltration into adjacent tissue, are resistant to treatment and have a natural tendency to malignant progression. The current standard treatment consists in surgical removal of the tumor followed by radiotherapy and concurrent chemotherapy. However, the prognosis remains extremely poor. The first line chemotherapy for GBM treatment is the DNA alkylating agent temozolamide (TMZ). Nevertheless, TMZ-induced damage can be reversed by the action of DNA repair machinery that prevents cell death and leads to relapse. In this study we correlated the expression of the DNA damage-signaling gene, ATM kinase, and the DNA repair genes BRCA2, BRIP1, EXO1, NEIL3, RAD54L and XRCC2, with the resistance of T98G and U87MG cell lines to TMZ. T98G cells were more resistant to TMZ treatment and showed overexpression of all DNA repair genes, while ATM kinase was down regulated. We also observed that U87MG cells, more sensitive to TMZ, have reduced expression of ATM, BRCA2 and EXO1. Therefore, these data suggest a positive correlation between the expression of DNA repair genes and the resistance of GBM cells to TMZ.(AU)

Efectividad y seguridad de temozolamida, en monoterapia o como terapia combinada con radioterapia, comparada con radioterapia o bevacizumab para gliomas malignos / Effectiveness and safety of temozolomide, as monotherapy or as combination therapy with radiotherapy, compared to radiotherapy or bevacizumab for malignant gliomas

Introducción: en países desarrollados la incidencia de tumores malignos del SNC es de 7,27 casos por cada 100.000 habitantes. Los gliomas representan el 28 % de todas las neoplasias del SNC y el 80% de los tumores malignos. Estos últimos son más frecuentes en hombres (55%) que en mujeres (45%), y su subtipo histológico más común es el glioblastoma (3.19 casos por cada 100.000 habitantes). El estándar actual de tratamiento para las neoplasias cerebrales consiste, para los casos en los que es posible, de una resección del tumor, seguido por un tratamiento concurrente de radioterapia y temozolamida. La administración de radioterapia, en ciclos diarios de 2 Gy hasta completar un 60 Gy, ligada a dosis diarias de temozolamida, y seguida por ciclos mensuales de esta última al término de la Radioterapia, se denomina Protocolo Stupp. Objetivo: examinar los beneficios y riesgos del uso de la temozolamida en pacientes con gliomas malignos, como uno de los criterios para informar la toma de decisiones relacionada con la posible inclusión de tecnologías en el Plan Obligatorio de Salud, en el marco de su actualización integral para el año 2015. Metodología: a partir de la pregunta PICO se establecieron los criterios de elegibilidad para la realización de la búsqueda de la evidencia científica (a ensayos clínicos, revisiones sistemáticas de estudios observacionales y estudios de cohortes analíticas), se realizó la tamización y selección de la evidencia evaluando su calidad y posteriormente se realizó la extracción de datos y la síntesis de la evidencia. Resultados: tres experimentos clínicos, abarcando un total de 745 pacientes, que evaluaron la temozolamida en combinación con radioterapia y en comparación con Radioterapia sola, para el tratamiento del glioblastoma multiforme. La temozolamida aumento Supervivencia Global [hazard ratio (HR) 0,60; intervalo de confianza del 95% (IC) 0,46 a 0,79; valor de p 0,0003] y el aumento de la Supervivencia Libre de Progresión (HR 0,63, IC del 95%: 0,43 a 0,92; valor P 0,02), en comparación con la radioterapia sola. Conclusiones: cuando la temozolamida se administra tanto en fases concomitante y adyuvante, es una terapia primaria eficaz para los glioblastomas malignos en comparación con la Radioterapia sola. Estos efectos se expresan tanto en la Supervivencia Global como en la Supervivencia Libre de Progresión. (AU)

Meta-Analysis of First-Line Triple Therapy for Helicobacter pylori Eradication in Korea: Is It Time to Change?

Proton pump inhibitor (PPI)-based triple therapy consisting of PPI, amoxicillin, and clarithromycin, is the recommended first-line treatment for Helicobacter pylori infection. However, the eradication rate of triple therapy has declined over the past few decades. We analyzed the eradication rate and adverse events of triple therapy to evaluate current practices in Korea. A comprehensive literature search was performed up to August 2013 of 104 relevant studies comprising 42,124 patients. The overall eradication rate was 74.6% (95% confidence interval [CI], 72.1%-77.2%) by intention-to-treat analysis and 82.0% (95% CI, 80.8%-83.2%) by per-protocol analysis. The eradication rate decreased significantly from 1998 to 2013 (P < 0.001 for both intention-to-treat and per-protocol analyses). Adverse events were reported in 41 studies with 8,018 subjects with an overall incidence rate of 20.4% (95% CI, 19.6%-21.3%). The available data suggest that the effectiveness of standard triple therapy for H. pylori eradication has decreased to an unacceptable level. A novel therapeutic strategy is warranted to improve the effectiveness of first-line treatment for H. pylori infection in Korea.

Importance of CYP2C19 genetic polymorphism in the eradication of Helicobacter pylori in north Indians.

Background & objectives: Genetic polymorphism of CYP2C19 is known to occur with a frequency of 12 per cent in north Indian population. But no study correlated CYP2C19 genetic polymorphism with eradication of Helicobacter pylori in north Indian gastritis patients positive for H. pylori and hence this study. Methods: Ninety one consecutive patients positive for H. pylori fulfilling the study criteria were phenotyped and genotyped for CYP2C19. They were given 20 mg omeprazole (OPZ), 750 mg amoxicillin (AMC) and 500 mg tinidazole (TNZ) (bid) for 7 days followed by 20 mg OPZ (qd) for 21 days. Non eradicated extensive metabolizers (EMs) were retreated with 40 mg OPZ (bid) and 500 mg AMC (qid) for 14 days. Results: EMs and poor metabolizers (PMs) excreted 4.26 ± 0.34 (95% CI 3.59-4.92) and 0.73 ± 0.05 (95% CI 0.63-0.82) μmol 5-OH-OPZ in 8 h, respectively. After initial therapy, EMs demonstrated 37 per cent (95% CI: 24.5-49.5) and PMs 92 per cent (95% CI: 77-107) eradication of H. pylori. Non eradicated EMs after retreatment demonstrated 90 per cent (95% CI: 79-101) eradication. Interpretation & conclusions: This study demonstrated a direct correlation between CYP2C19 genetic polymorphism and H. pylori eradication in north Indian patients with gastritis. Knowing the CYP2C19 phenotype of a patient may help in prescribing optimum dose of proton pump inhibitor to achieve better therapeutic outcome.

The surgical outcome of primary trabeculectomy with mitomycin C and A fornix-based conjunctival flap technique in Thailand.

OBJECTIVE: To determine the surgical outcome of primary trabeculectomy with mitomycin C (MMC) and fornix-based conjunctival flap technique in Thai patients. MATERIAL AND METHOD: This retrospective review was conducted from the clinical records of all Thai glaucoma patients who underwent a primary trabeculectomy with MMC using a fornix-based conjunctival flap technique by or under supervision of one ophthalmologist (NK) between February 2004 and July 2006 at Siriraj Hospital, School of Medicine, Mahidol University, Bangkok, Thailand. RESULTS: There were 69 eyes from 60 patients. Postoperatively, mean intraocular pressure (IOP) was significantly decreased from 26.1 +/- 11.7 mmHg to 11.7 +/- 4.4 mmHg (p < 0.001) and mean number of anti-glaucoma medication was significantly reduced from 3.9 +/- 0.7 to 0.3 +/- 0.9 (p < 0.001) at last visit. Sixty-seven eyes (96.8%) were considered as success. Eight eyes (11.6%) in this group needed topical anti-glaucoma medications. Two eyes (2.9%) were considered as failure. Mean follow-up period was 7.7 +/- 4.0 months. Complications included bleb leaking in 16 eyes, choroidal detachment in four eyes, and blebitis in two eyes. Seven eyes with leaking bleb resolved spontaneously. CONCLUSION: Primary trabeculectomy with MMC using afornix-based conjunctival flap technique is effective as a treatment for Thai glaucoma patients. There is a high rate of success (96.8%) with the low rate of complication.

Impacto da adição da temozolamida à radioterapia no tratamento de crianças portadoras de tumor de tronco cerebral / Impact of the addition of temozolomide to radiotherapy in the treatment of children with brain stem tumors

OBJETIVO: Analisar o impacto da adição da temozolamida à radioterapia em tumores de tronco cerebral em crianças. MATERIAL E MÉTODO: Entre 2000 e 2005 foram analisadas, retrospectivamente, 64 crianças com tumor do tronco cerebral. Dessas crianças, 32 receberam temozolamida(grupo 1) e 32 não a receberam (grupo 2). RESULTADOS: A idade mediana no grupo 1 foi de 8,2 anos e no grupo 2 foi de 7,5 anos. A localização tumoral era predominantemente difusa (53%) emambos os grupos. Todos os pacientes receberam radioterapia com doses superiores a 50 Gy. No grupo1 foram ministrados nove ciclos, em média, de quimioterapia (3û14 ciclos). O tempo de progressão de doença foi de 7,9 meses no grupo 2 versus 13,8 meses no grupo 1. A sobrevida global foi de 8,8 meses (0,3û30,9 meses) no grupo 1 e de 14,6 meses (4,3û33 meses) no grupo 2. CONCLUSÃO: A utilização da temozolamida após a radioterapia proporcionou aumento da sobrevida, deseis meses em média, nos pacientes pediátricos com tumor do tronco cerebral.

OBJECTIVE: To analyze the impact of adding temozolomide to radiotherapyin pediatric brain stem tumors. MATERIAL AND METHOD: Between 2000 and 2005, 64 children with brain stem tumor were analyzed: 32 received temozolomide (group 1) and 32 did not(group 2). RESULTS: The median age of patients in group 1 was 8.2 year-old and in group 2 was 7.5 year-old. The predominant tumoral localization was diffuse (53%) in both groups. All of the patients were submitted to radiotherapy. In group 1, the median number of temozolomide cycles was 9 (3û14 cycles). Time of disease progression was 7.9 months in group 2 versus 13.8 months in group 1. Overall survival was 8.8 months (0.3û30.9 months) in group 1 and 14.6 months (4.3û33 months) in group 2. CONCLUSION: In our institution,adding temozolomide to radiotherapy increased the overall survival in approximately six months in brain stem pediatric tumors.

A comparative study of injection placentrex and conventional therapy in treatment of pelvic inflammatory disease.

To compare the effect of placentrex injection given along with conventional therapy, with conventional treatment alone on the symptoms and signs of pelvic inflammatory disease (PID) ie, abdominal pain, dysmenorrhoea and adnexal tenderness, 50 out of 100 women with PID were randomly assigned to receive intramuscular placentrex injection along with two-week conventional therapy and 50 received conventional treatment only. Abdominal pain, dysmenorrhoea and adnexal tenderness were evaluated at the end of 2 months. There was marked reduction in the sign of adnexal tenderness in the placentrex group as compared to conventional treatment group (p < 0.001). Subjective symptoms of lower abdominal pain and dysmenorrhoea were also relieved better in placentrex group (p < 0.01 and 0.05 respectively). This study showed significant and persistent improvement of signs and symptoms of PID in women who received injection placentrex.

Intraoperative application of topical mitomycin C 0.05 for pterygium surgery

BACKGROUND: Pterygium recurrence is a common problem encountered by ophthalmic surgeons. Several methods have been suggested to avoid these recurrences. We studied the recurrence rate of pterygium after administration of a single intraoperative dosage of topical mitomycin C 0.05. METHODS: A retrospective analysis of fifty eyes in forty-nine patients who underwent pterygium excision by the same surgeon using intraoperative topical mitomycin C during the years 2002--2003. Mitomycin concentration was 0.05 applied to pterygium and adjacent areas after undermining and separation from sclera but prior to excision for three minutes. Postoperative follow up time was 12 months. RESULTS: The pterygium recurred in 4 (8) eyes. Another four eyes (8) had a cosmetically acceptable recurrence of < 2.0 mm. The only complication was a corneal dellen in one eye. CONCLUSION: Intraoperative administration of mitomycin C at 0.05 is safe and effective in preventing pterygium recurrences

Granulomatose de Wegener: aspectos clínicos e terapêuticos / Wegener's granulomatosis: clinical aspects and therapeutics

A granulomatose de Wegener constitui-se em uma vasculite granulomatosa necrosante que acomete vários sistemas orgânicos, notadamente o trato respiratório e os rins. Possui etiologia desconhecida, provavelmente relacionada à hipersensibilidade a antígenos inalados causadores de infecçäo. Estes agentes parecem estimular a produçäo de auto-anticorpos contra antígenos no citoplasma de neutrófilos. Clinicamente, surge em torno da quarta e quinta décadas, através de um quadro de sinusite associado a sintomas constitucionais como febre, fadiga e mal-estar geral. Este quadro inespecífico dificulta o diagnóstico precoce, possibilitando o desenvolvimento de doença disseminada. A clínica do órgäo acometido, associada à presença do anticorpo antineutrofílico citoplasmático (c-ANCA) e os achados anatomopatológicos confirmam o diagnóstico de doença ativa. O tratamento é feito através da associaçäo de corticóides e ciclofosfamida, o que possibilita o controle da doença a curto e médio prazo. As recidivas säo ainda freqüentes, podendo ocorrer em até 20 anos após o início do tratamento.

Phase 1 and 2 trials of diaziquone (AZQ) in patients with brain tumors: a clinical review

La diaziquona es una aziridinilobenzoquinona con acción alquilante y lipofilicidad que permite que la droga cruce la barrera hematoencefálica. Este comupuesto muestra un espectro amplio de actividades en rumores murinos, incluyendo actividad curativa contra varios tumores endoencefálicos implantados (ependimoblastoma). Este artículo revisa la información clínica disponible sobre diaziquona en pacientes con tumores cerebrales. En diez estudios Fase1, se observaron indicadores de actividad SNC en tumores metástaticos y primarios en varios pacientes. En cuatro estudios preliminares Fase 2, se administró la droga cada cuatro semanas a pacientes con tumores cerebrales. El regimen de tratamiento y las respuestas fueron las siguientes: 22.5 a 27.5 mg/m2 cada 4 semanas produjo 5 respuestas parciales (PR) en 29 casos evaluables (EC); de 6 a 8 mg/m2qd x 5,4 PR/16 EC; 20 mg/m2 (días 1, 8), 4 PR/15 EC; 17.5 mg/m2 (días 1,8), 1 PR/20 EC. Se observaron remisiones prolongadas y estabilización de la enfermedad en algunos de estos pacientes, la mayoría de los cuales habían sido previamente tratados con radioterapia y quimioterapia. La toxicidad más signficativa fue la hipoplasia de la médula ósea. Al parecer, la actividad máxima de diaziquona es contra los tumores cerebrales primarios y en futuras evaluaciones este compuesto debe ser la primera droga en la quimioterapia