The effects of concurrent oral paliperidone or risperidone use with paliperidone long-acting injection.

INTRODUCTION: Dosing recommendations for paliperidone long-acting injectable antipsychotic (LAIA) do not include oral antipsychotic (OAP) overlap; however, OAPs are often given concurrently despite limited evidence describing both the risks and benefits of this practice. METHODS: A retrospective chart review was conducted in patients initiated on paliperidone palmitate (PP) during a psychiatric hospitalization to compare patients who received OAP overlap versus those who did not. The primary outcome is the proportion of patients who receive prescription claims for benztropine, a medication commonly prescribed for extrapyramidal symptoms, at the time of LAIA discontinuation and 6 months postdischarge. Secondary outcomes include prescription claims for beta blockers and diphenhydramine, number of psychiatric emergency visits and hospitalizations, length of stay of the index hospitalization, frequency of LAIA discontinuation and the time to LAIA discontinuation. RESULTS: There is a significant difference in the proportion of benztropine prescription claims in the OAP overlap group versus the no-overlap group at the time of LAIA discontinuation (30% vs 0%, P = .046) but not at 6 months postdischarge. There are also significant differences in the number of psychiatric emergency visits (0.7 vs 0.1, P = .02) and psychiatric hospitalizations (0.6 vs 0.1, P = .029) at the time of LAIA discontinuation. No other differences are observed in defined secondary outcomes. DISCUSSION: Patients who receive OAP overlap while receiving PP receive more benztropine and have more psychiatric emergency visits and hospitalizations than those treated without OAP. Larger studies with better control for confounding variables are needed to confirm these results.

The effects of cytochrome P450 2D6 inhibitors on a high-dose tramadol taper for medically supervised opioid withdrawal: a retrospective chart review.

Background: Tramadol is used off-label for medically supervised opioid withdrawal. Tramadol is metabolized by CYP2D6 to an active metabolite with significantly more pharmacologic activity compared to the parent compound.Objectives: The objective of this study is to evaluate the effects of CYP2D6 inhibitors on patient response to a tramadol taper for medically supervised opioid withdrawal.Methods: A retrospective chart review of patients who received a tramadol taper for medically supervised opioid withdrawal was conducted comparing patients who received concomitant moderate-to-strong CYP2D6 inhibitors to patients without concomitant therapy. The primary outcome was the change in Clinical Institute Narcotic Assessment (CINA) scores from baseline to discharge. Secondary outcomes included area under the curve of CINA scores over time, additional CINA outcomes, length of stay, and readmissions.Results: Of 100 charts reviewed, 30 patients received a concomitant moderate-to-strong CYP2D6 inhibitor. There were no statistically significant differences between the baseline demographics of the two groups. Change from baseline CINA to discharge did not differ significantly between the Non-2D6 group and the 2D6 group (-4.0 ± 3.83 and -4.5 ± 4.48 respectively; p = 0.606). The average CINA score for nausea and vomiting was significantly higher in the Non-2D6 group compared to the 2D6 group (0.34 ± 0.35 and 0.18 ± 0.33 respectively; p = 0.019). Otherwise there were no significant differences found in any secondary outcomes.Conclusions: Based on these results, moderate-to-strong CYP2D6 inhibitors do not appear to have a significant impact on the withdrawal course for patients treated with a high-dose tramadol taper.

The development and psychometric properties of the bipolar disorders knowledge scale.

PURPOSE: Bipolar Disorder (BD) presents in 1-4% of the world's population, carrying significant financial and functional consequences. Beyond the direct disease burden, patients with BD experience a high degree of both internal and external stigma. Additionally, medication adherence tends to be poor in patients with BD. Knowledge appears to play a role in mitigating both stigma and non-adherence, but these relationships have not been fully elucidated. The Bipolar Disorder Knowledge Scale (BDKS) was designed to explore the role of knowledge and better define such relationships. This research provides the evidence for the reliability and validity of the scale. METHODS: Forty-seven items were developed to assess knowledge of BD. The 47-item survey was sent out to two groups: first a group of 43 pharmacists with BCPP credentials from the College of Psychiatric and Neurologic Pharmacists (CPNP) who were recruited from the CPNP directory, and second a group of 250 members of the general public who were recruited using Qualtrics Online Sample service. Participants were surveyed on their education status, health literacy, BD diagnostic status, and exposure to patients with BD. Participants then completed the 47-item scale. After 48 h 100 members from the original general public group were sent the same survey to assess test-retest reliability. For each item a difficulty index to evaluate how well participants performed on the item and a discrimination index to determine how well each item performed in high-scorers versus low scorers were calculated. Additionally, Cronbach's alpha was calculated to determine internal consistency validity and a Pearson correlation was run to determine test-retest reliability. Items were removed based on the results from the difficulty index, discrimination index, and Cronbach's alpha. Finally the pharmacist final scores were compared to the general public using an unpaired t-test to assess whether content experts were more likely to perform better on the scale. Following item removal, the scale was finalized at 25-items. RESULTS: The mean score for the scale was 34.48 (71.83%; SD: 5.50) and the Cronbach's alpha was 0.773 before item analysis. Following item analysis, 22 items were dropped leaving 25 items on the final version of the scale. The remaining items retained a difficulty index below 90% and a discrimination index above 20%. The mean of the 25-item scale was 18.40 (73.6%; SD: 4.13) for the general public and 23.20 (92.8%; SD: 1.36) for the pharmacists group (p < 0.001). The Cronbach's alpha for the finalized scale was 0.760, indicating a high-degree of internal consistency. While this is lower than the original alpha, this may be explained by the reduced number of scale items. A 25-item scale is much more practical and the items on the scale retain stronger item analysis statistics. Finally, the Pearson Correlation for the group who underwent the test-retest procedure was 0.841 (p < 0.001) indicating strong test-retest reliability. CONCLUSION: The BDKS is a 25-item true-false scale that takes approximately 5-10 min to complete. The scale assesses knowledge of BD with items targeting diagnosis, etiology, disease course, symptoms, treatment, and life impact. The scale has shown strong internal consistency and test-retest reliability in a general population and will be useful for evaluating knowledge of BD as it relates to stigma, non-adherence, and other variables.

Luteolin Decreases Epidermal Growth Factor Receptor-Mediated Cell Proliferation and Induces Apoptosis in Glioblastoma Cell Lines.

Glioblastomas are a subtype of gliomas, which are the most aggressive and deadly form of brain tumours. The epidermal growth factor receptor (EGFR) is over-expressed and amplified in glioblastomas. Luteolin is a common bioflavonoid found in a variety of fruits and vegetables. The aim of this study was to explore the molecular and biological effects of luteolin on EGF-induced cell proliferation and the potential of luteolin to induce apoptosis in glioblastoma cells. In vitro cell viability assays demonstrated that luteolin decreased cell proliferation in the presence or absence of EGF. Immunoblots revealed that luteolin decreased the protein expression levels of phosphorylated Akt, mTOR, p70S6K and MAPK in the presence of EGF. Furthermore, our results revealed the ability of luteolin to induce caspase and PARP cleavages in glioblastoma cells in addition to promoting cell cycle arrest. Our results demonstrated that luteolin has an inhibitory effect on downstream signalling molecules activated by EGFR, particularly the Akt and MAPK signalling pathways, and provided a rationale for further clinical investigation into the use of luteolin as a therapeutic molecule in the management of glioblastoma.

The antiproliferative and apoptotic effects of apigenin on glioblastoma cells.

OBJECTIVES: Glioblastoma (GBM) is highly proliferative, infiltrative, malignant and the most deadly form of brain tumour. The epidermal growth factor receptor (EGFR) is overexpressed, amplified and mutated in GBM and has been shown to play key and important roles in the proliferation, growth and survival of this tumour. The goal of our study was to investigate the antiproliferative, apoptotic and molecular effects of apigenin in GBM. METHODS: Proliferation and viability tests were carried out using the trypan blue exclusion, MTT and lactate dehydrogenase (LDH) assays. Flow cytometry was used to examine the effects of apigenin on the cell cycle check-points. In addition, we determined the effects of apigenin on EGFR-mediated signalling pathways by Western blot analyses. KEY FINDINGS: Our results showed that apigenin reduced cell viability and proliferation in a dose- and time-dependent manner while increasing cytotoxicity in GBM cells. Treatment with apigenin-induced is poly ADP-ribose polymerase (PARP) cleavage and caused cell cycle arrest at the G2M checkpoint. Furthermore, our data revealed that apigenin inhibited EGFR-mediated phosphorylation of mitogen-activated protein kinase (MAPK), AKT and mammalian target of rapamycin (mTOR) signalling pathways and attenuated the expression of Bcl-xL. CONCLUSION: Our results demonstrated that apigenin has potent inhibitory effects on pathways involved in GBM proliferation and survival and could potentially be used as a therapeutic agent for GBM.