Telomerase Reverse Transcriptase Promoter Mutations in A Cohort Of Adult Gliomas - Clinicopathological Correlates.

Background: Introduction: Gliomas were previously classified histologically, although now the latest WHO classification incorporates several molecular markers to classify these. Detection of TERT promoter mutations is assuming increased importance due to its relevance to prognostication. Objective: : The aim of this study was to determine the frequency of TERT promoter mutations, association of TERT promoter mutations with other molecular alterations and to assess the role of TERT promoter mutations in overall survival and progression-free survival in relation to histological and molecular glioma subtypes. Materials and Methods: This study analyzed a cohort of 107 adult patients with diffuse gliomas, WHO grades II and III and glioblastoma, by immunohistochemistry for IDH and ATRX mutations, FISH for 1p/19q co-deletions and PCR sequencing for TERT promoter mutation. Further, five glioma molecular sub-groups were derived using three molecular alteration and included the sub-groups with: i) IDH mutations only, ii) IDH and TERT mutations only, iii) IDH and 1p/19q co-deletion only, iv) Triple negative, and v) Triple positive. Results: IDH mutations and 1p/19q co-deletions were individually and significantly associated with an improved progression free (P = 0.001 and P = 0.002, respectively) and overall survival (P = 0.000 and P = 0.005, respectively) in the present cohort of gliomas. TERT promoter mutations occurred frequently in anaplastic oligodendrogliomas (94%), oligodendrogliomas (87.5%) and glioblastomas (54%). Sub-division into molecular sub-groups showed that the triple-positive tumors carried the best prognosis, followed by IDH only, triple negative and finally the TERT mutation only tumors (P < 0.000). Conclusion: : This indicates that sub-classification using these molecular markers separates tumors into prognostically relevant categories.

Patient attrition from the HIV antiretroviral therapy program at two hospitals in Haiti / Abandono del programa de tratamiento antirretrovírico de la infección por el VIH en pacientes de dos hospitales de Haití

OBJECTIVE: To identify factors associated with antiretroviral therapy (ART) attrition among patients initiating therapy in 2005-2011 at two large, public-sector department-level hospitals, and to inform interventions to improve ART retention. METHODS: This retrospective cohort study used data from the iSanté electronic medical record (EMR) system. The study characterized ART attrition levels and explored the patient demographic, clinical, temporal, and service utilization factors associated with ART attrition, using time-to-event analysis methods. RESULTS: Among the 2 023 patients in the study, ART attrition on average was 17.0 per 100 person-years (95% confidence interval (CI): 15.8-18.3). In adjusted analyses, risk of ART attrition was up to 89% higher for patients living in distant communes compared to patients living in the same commune as the hospital (hazard ratio: 1.89, 95%CI: 1.54-2.33; P < 0.001). Hospital site, earlier year of ART start, spending less time enrolled in HIV care prior to ART initiation, receiving a non-standard ART regimen, lacking counseling prior to ART initiation, and having a higher body mass index were also associated with attrition risk. CONCLUSIONS: The findings suggest quality improvement interventions at the two hospitals, including: enhanced retention support and transportation subsidies for patients accessing care from remote areas; counseling for all patients prior to ART initiation; timely outreach to patients who miss ART pick-ups; "bridging services" for patients transferring care to alternative facilities; routine screening for anticipated interruptions in future ART pick-ups; and medical case review for patients placed on non-standard ART regimens. The findings are also relevant for policymaking on decentralization of ART services in Haiti.

OBJETIVO: Determinar los factores asociados con el abandono del tratamiento antirretrovírico en los pacientes que iniciaron el tratamiento en el período del 2005 al 2011 en dos grandes hospitales públicos de nivel departamental, y fundamentar las intervenciones necesarias para mejorar la retención de los pacientes en el tratamiento. MÉTODOS: Este estudio retrospectivo de cohortes empleó los datos del sistema de registro médico electrónico iSanté. Se describieron los niveles de abandono del tratamiento y se exploraron los factores demográficos, clínicos, temporales y de utilización de los servicios que se asociaban con su abandono, usando métodos de análisis del tiempo trascurrido hasta un evento. RESULTADOS: El abandono del tratamiento entre los 2 023 pacientes incluidos en el estudio fue en promedio de 17,0 por 100 personas-años (intervalo de confianza (IC) de 95%: 15,8-18,3). En los análisis ajustados, el riesgo de abandono del tratamiento fue de hasta 89% mayor en los pacientes que vivían en comunas distantes, en comparación con los pacientes que vivían en la misma comuna en que se ubicaba el hospital (razón de riesgo: 1,89; IC de 95%: 1,54-2,33; P < 0,001). La ubicación del hospital, el inicio del tratamiento en un año calendario anterior, un menor tiempo de inclusión en el programa de atención a la infección por el VIH antes de iniciar el tratamiento, la administración de un régimen terapéutico no estándar, la falta de orientación antes de iniciar el tratamiento y un mayor índice de masa corporal también se asociaron con un riesgo más elevado de abandono. CONCLUSIONES: Los resultados sugieren algunas intervenciones de mejora de la calidad en ambos hospitales, entre ellas: un mayor apoyo a la retención y subsidios de transporte para los pacientes que acuden desde zonas remotas para ser atendidos; la orientación a todos los pacientes antes del inicio del tratamiento antirretrovírico; el contacto oportuno de los servicios con los pacientes que omiten alguna recogida de medicación; "servicios de conexión" para transferir la atención de los pacientes a otros establecimientos alternativos; el tamizaje sistemático de las interrupciones previstas en las próximas recogidas de medicación; y la revisión médica de los casos de pacientes que siguen un tratamiento no estándar. Estos hallazgos son también pertinentes en materia de formulación de políticas de descentralización de los servicios de tratamiento antirretrovírico en Haití.

Patient attrition from the HIV antiretroviral therapy program at two hospitals in Haiti.

OBJECTIVE: To identify factors associated with antiretroviral therapy (ART) attrition among patients initiating therapy in 2005-2011 at two large, public-sector department-level hospitals, and to inform interventions to improve ART retention. METHODS: This retrospective cohort study used data from the iSanté electronic medical record (EMR) system. The study characterized ART attrition levels and explored the patient demographic, clinical, temporal, and service utilization factors associated with ART attrition, using time-to-event analysis methods. RESULTS: Among the 2 023 patients in the study, ART attrition on average was 17.0 per 100 person-years (95% confidence interval (CI): 15.8-18.3). In adjusted analyses, risk of ART attrition was up to 89% higher for patients living in distant communes compared to patients living in the same commune as the hospital (hazard ratio: 1.89, 95%CI: 1.54-2.33; P < 0.001). Hospital site, earlier year of ART start, spending less time enrolled in HIV care prior to ART initiation, receiving a non-standard ART regimen, lacking counseling prior to ART initiation, and having a higher body mass index were also associated with attrition risk. CONCLUSIONS: The findings suggest quality improvement interventions at the two hospitals, including: enhanced retention support and transportation subsidies for patients accessing care from remote areas; counseling for all patients prior to ART initiation; timely outreach to patients who miss ART pick-ups; "bridging services" for patients transferring care to alternative facilities; routine screening for anticipated interruptions in future ART pick-ups; and medical case review for patients placed on non-standard ART regimens. The findings are also relevant for policymaking on decentralization of ART services in Haiti.