The Effect of Reducing Intravenous Push Opioid Use on Hospital Medicine Patients' Pain Experience During Hospitalization.

OBJECTIVE: To determine the efficacy of a program to limit the use of the intravenous (IV) push route for opioids on the experience of pain by inpatients and on associated safety events. DESIGN: Retrospective cohort study. SETTING: Two inpatient general medicine floor units at an urban tertiary care academic medical center. SUBJECTS: 4,752 inpatient opioid recipients. METHODS: Patients in one unit were exposed to a multidisciplinary intervention to limit the prescription of opioids via the IV push route, with the other unit used as a control unit. The primary study outcome was the mean numeric pain score per patient during the hospital stay. Secondary measures included the hospital length of stay and postdischarge patient satisfaction. Fidelity measures included the percentage of the patient population exposed to each opioid administration route and the amount of opioid administered per route. Safety measures included patient disposition, transfer to intensive care, and incidence of naloxone administration. RESULTS: The intervention was successful in decreasing both the percentage of patients exposed to IV push opioids and the amount of opioid administered via the IV push route, but no associated changes in other study outcomes were identified. CONCLUSIONS: For the treatment of acute pain in medical inpatients, no evidence of benefit or harm was identified in relation to an increase or decrease in the use of the IV push opioid route.

Local Disease Control in Ocular Adnexal Lymphoproliferative Disorders: Comparative Outcomes of MALT Versus Non-MALT Histologies.

INTRODUCTION: Ocular adnexal lymphoproliferative disorders (OALDs) are almost exclusively of B-cell origin, with the majority being extra-nodal marginal zone lymphomas of mucosa-associated lymphoid tissue (MALT). The comparative efficacy of involved field radiation therapy (IFRT) in MALT vs. non-MALT OALDs is not known. MATERIALS AND METHODS: We present a single-center, large cohort, retrospective study of the efficacy of IFRT in OALDs. Failure-free survival (FFS), complete remission, and local, regional, and distant failure were determined for 112 patients with MALT OALDs (n = 71) and non-MALT OALDs (n = 41) cohorts. RESULTS: Fifty-six patients with MALT OALD and 26 patients with non-MALT OALD received IFRT only (without any planned concurrent or sequential systemic chemothereapy or chemo-immunotherapies). Among the OALD cohorts treated with only IFRT, complete remission was achieved in 49 (87.5%) patients in the MALT cohort and 23 (88.4%) in the non-MALT cohort (P = .99). Clinically, resolution of symptoms occurred in 83.3% and 93.3% of the patients in the MALT and non-MALT cohorts, respectively. Local failure occurred in 4 (7.1%) patients in the MALT cohort, compared with 4 (15.3%) patients in the non-MALT cohort (P = .24). Regional failure (or extra-orbital failure) occurred in 5 (8.9%) patients in the MALT cohort and in 3 (11.5%) patients in the non-MALT cohort (P = .71). Distant failure was reported in 1 (1.7%) and 2 patients (7.6%) in the MALT and non-MALT cohorts, respectively (P = .18). The median follow-up of survivors was 5.1 years (range, 0.1-22.5 years) in the MALT cohort and 3.9 years (range, 0.1-22.9 years) in the non-MALT cohort. The 5-year and 10-year FFS was 95% (95% confidence interval [CI], 88%-100%) and 83% (95% CI, 70%-98%) for the ocular MALT and 67% (95% CI, 48%-94%) and 56% (95% CI, 34%-91%) for the non-MALT cohorts, respectively (log rank for P = .025). On multivariate analyses, age (hazard ratio [HR], 1.06; 95% CI, 1.10-1.12; P = .03), presence of non-MALT histology (HR, 13.9; 95% CI, 2.05-94.4; P = .007), and radiation dose < 30.6 Gy (HR, 5.27; 95% CI, 1.14-24.3; P = .03) were associated with worse FFS. The 5-year and 10-year overall survival was 92% (95%, CI 83%-100%) and 80% (95% CI, 66%-96%) for the MALT and 78% (95% CI, 61%-100%) and 62% (95% CI, 38%-100%) for the non-MALT cohorts, respectively (P = .80). CONCLUSION: Our results reveal that IFRT provided excellent disease control with superior FFS in the MALT cohort when compared with the non-MALT group.

Combination of an allosteric Akt Inhibitor MK-2206 with etoposide or rapamycin enhances the antitumor growth effect in neuroblastoma.

PURPOSE: Activation of Akt is a marker of decreased event-free or overall survival in neuroblastoma patients. MK-2206, a novel allosteric Akt inhibitor, is now tested in clinical trials in adult cancers. In this study, effect of MK-2206 on tumor growth and murine survival, alone or in combination, with etoposide or rapamycin was evaluated. EXPERIMENTAL DESIGN: The anticell proliferation effect of MK-2206 was tested in eight neuroblastoma cell lines by MTS assay. Caspase-3/7 activity, cell-cycle analysis, and reactive oxygen species (ROS) production were determined. Effect of MK-2206 combined with etoposide or rapamycin was evaluated in vitro and in vivo. Akt phosphorylation was measured by Western blotting in neuroblastoma cells and tumors. RESULTS: In vitro, MK-2206 treatment inhibited neuroblastoma cell proliferation, which was accompanied by a cell line selective G(1) arrest of cell cycle or production of ROS. A synergistic effect between MK-2206 and etoposide was detected in four tested neuroblastoma cell lines via caspase-dependent apoptosis, whereas increased inhibition of cell growth induced by combination of MK-2206 and rapamycin was mediated by ROS production. In vivo, MK-2206 alone decreased tumor growth and increased murine survival at dose that inhibited Akt phosphorylation in tumors. MK-2206, in combination with etoposide or rapamycin, caused a significant decrease in tumor growth and increase of murine survival compared with MK-2206 alone. CONCLUSION: Akt inhibition by MK-2206 increased the efficacy of etoposide or rapamycin. Our study supports future clinical evaluation of MK-2206 in combination with conventional cytotoxic therapy or with rapamycin in high-risk neuroblastoma patients.