Longitudinal association of homonegative school climate with body dysmorphic disorder among cisgender sexual minority adolescents: Testing mediation through proximal minority stressors.

In a US national cohort study of cisgender sexual minority adolescents (SMAs), we prospectively (1) assessed whether within-person changes in homonegative school climate (i.e., school contextual factors that lead SMAs to feel unsafe or threatened) were associated with risk of probable body dysmorphic disorder (BDD) and (2) tested whether internalized homonegativity and negative expectancies mediated this association. Data came from consecutive time points (18-month, 24-month, 30-month) of the Adolescent Stress Experiences over Time Study (ASETS; N = 758). The Body Dysmorphic Disorder Questionnaire measured probable BDD. Sexual Minority Adolescent Stress Inventory subscales measured past 30-day minority stress experiences. Multilevel models were specified with person mean-centered predictor variables to capture within-person effects. Across one year of follow-up, 26.86% screened positive for probable BDD at least once. Model results indicated significant total (risk ratio [RR]=1.43, 95% credible interval [CI]=1.35-1.52) and direct effects (RR=1.18, 95% CI=1.05-1.34) of homonegative school climate. Internalized homonegativity was independently associated with probable BDD (RR=1.28, 95% CI=1.12-1.46) and mediated 49.7% (95% CI=12.4-82.0) of the total effect. There was limited evidence of mediation via negative expectancies. Implementing SMA-protective school policies and targeting internalized homonegativity in clinical practice may reduce the prevalence and incidence of probable BDD among cisgender SMAs.

A phase 1 trial of intravenous liposomal irinotecan in patients with recurrent high-grade glioma.

PURPOSE: Preclinical activity of irinotecan has been seen in glioma models, but only modest efficacy has been noted in clinical studies, perhaps related to drug distribution and/or pharmacokinetic limitations. In preclinical testing, irinotecan liposome injection (nal-IRI) results in prolongation of drug exposure and higher tissue levels of drug due to slower metabolism and the effect of enhanced permeability and retention. The objective of the current study was to assess the safety and pharmacokinetics (PK) of nal-IRI and to determine the maximum tolerated dose (MTD) in patients with recurrent high-grade glioma stratified based on UGT1A1 genotyping. METHODS: This phase I study stratified patients with recurrent high-grade glioma into 2 groups by UGT1A1 status: homozygous WT ("WT") vs heterozygous WT/*28 ("HT"). Patients who were homozygous *28 were ineligible. The design was a standard 3 + 3 phase I design. WT patients were started at 120 mg/m2 intravenously every 3 weeks with dose increases in 60 mg/m2 increments. HT patients were started at 60 mg/m2, with dose increases in 30 mg/m2 increments. The assessment period for dose-limiting toxicity was 1 cycle (21 days). RESULTS: In the WT cohort (n = 16), the MTD was 120 mg/m2. In the HT cohort (n = 18), the MTD was 150 mg/m2. Dose-limiting toxicity in both cohorts included diarrhea, some with associated dehydration and/or fatigue. PK results were comparable to those seen in other PK studies of nal-IRI; UGT1A1*28 genotype (WT vs. HT) did not affect PK parameters. CONCLUSIONS: Nal-IRI had no unexpected toxicities when given intravenously. Of note, UGT1A1 genotype did not correlate with toxicity or affect PK profile.

Phase I cancer clinical trials.

An efficient phase I trial is a crucial step in developing a new drug in a safe and timely manner. The main objective of a phase I trial is to determine the maximum tolerated dose in order to recommend the dose for a phase II trial. There are many designs that are implemented in phase I trials. Rule-based designs such as the traditional 3 + 3 method and rolling six design are easy to implement and assess for safety using a conservative approach. Model-based designs such as the continual reassessment method and the time-to-event continual reassessment method use mathematical models to increase the precision of dose estimation. The advantages and shortcomings of these designs, along with other designs, are reviewed.

Indications and Efficacy of Gamma Knife Stereotactic Radiosurgery for Recurrent Glioblastoma: 2 Decades of Institutional Experience.

BACKGROUND: The role of stereotactic radiosurgery (SRS) for recurrent glioblastoma and the radionecrosis risk in this setting remain unclear. OBJECTIVE: To perform a large retrospective study to help inform proper indications, efficacy, and anticipated complications of SRS for recurrent glioblastoma. METHODS: We retrospectively analyzed patients who underwent Gamma Knife SRS between 1991 and 2013. We used the partitioning deletion/substitution/addition algorithm to identify potential predictor covariate cut points and Kaplan-Meier and proportional hazards modeling to identify factors associated with post-SRS and postdiagnosis survival. RESULTS: One hundred seventy-four glioblastoma patients (median age, 54.1 years) underwent SRS a median of 8.7 months after initial diagnosis. Seventy-five percent had 1 treatment target (range, 1-6), and median target volume and prescriptions were 7.0 cm 3 (range, 0.3-39.0 cm 3 ) and 16.0 Gy (range, 10-22 Gy), respectively. Median overall survival was 10.6 months after SRS and 19.1 months after diagnosis. Kaplan-Meier and multivariable modeling revealed that younger age at SRS, higher prescription dose, and longer interval between original surgery and SRS are significantly associated with improved post-SRS survival. Forty-six patients (26%) underwent salvage craniotomy after SRS, with 63% showing radionecrosis or mixed tumor/necrosis vs 35% showing purely recurrent tumor. The necrosis/mixed group had lower mean isodose prescription compared with the tumor group (16.2 vs 17.8 Gy; P = .003) and larger mean treatment volume (10.0 vs 5.4 cm 3 ; P = .009). CONCLUSION: Gamma Knife may benefit a subset of focally recurrent patients, particularly those who are younger with smaller recurrences. Higher prescriptions are associated with improved post-SRS survival and do not seem to have greater risk of symptomatic treatment effect.

Rehabilitación integral después del infarto miocárdiaco agudo / Integral rehabilitation after acute myocardial infarction

Se estudia el efecto alcanzado por los métodos de rehabilitación dirigidos a 50 pacientes menores de 65 años que habían sufrido un IMA (infarto miocardio agudo). El grupo II que cumplimentó las 3 fases del tratamiento rehabilitatorio, experimentó una mejoría estadísticamente significativa en casi todos los parámetros ergonométricos estudiados en relación con el grupo I que realizó las 2 primeras fases del programa. Al resaltar la carga tolerada, que aumentó de 67,5 hasta 98,9 watt (P<0,01); así como la capacidad física de trabajo que de un 51,7 al inicio se eleva hasta el 76,3 (P<0,01) 6 meses después. La eficacia de la rehabilitación se manifestó, además, en las mejorías obtenidas en el doble producto, la frecuencia cardíaca de entrenamiento, los reingresos hospitalarios y en la reincorporación al trabajo; donde se reintegró el 84,0 de los pacientes . Estas correlaciones fueron significativas en relación con el grupo I (P<0,05). Se concluye que la rehabilitación cardiovascular precoz y dirigida es beneficiosa en el orden médico, social y económico