Development and Implementation of an Online Pain Management Continuing Education Program.

BACKGROUND: Multiple studies indicate a lack of pain management training across a range of healthcare specialties. The online Joint Pain Education Program (OJPEP) was created to provide content covering various topics that range from general pain science to integrative care to pain management. The present study evaluates the feasibility of an interdisciplinary, self-guided, online pain management continuing education program, the OJPEP. PARTICIPANTS/SUBJECTS: A total of 228 learners participted in this study. Of the 228 learners, 58 learners identified as registered nurses and 12 learners identified as nurse practitioners. DESIGN: Prospective single-arm education feasibility study. METHODS: Potential learners were provided invitations to participate via emails from clinic leadership and postings to hospital intranet websites. Learners registered online and could select up to eight modules, based on the materials developed from a Department of Defense/Veterans Administration project. Learners evaluated their satisfaction with module quality and applicability. RESULTS: A variety of providers, predominately non-prescribers, across many health care specialties, registered for modules. Across all modules except one, less than half of participants who registered completed the selected module. Time stamps indicated many learners skipped module content. Of those who completed the continuing education evaluation to obtain certificates, the majority indicated the content was of high-quality, appropriate, and evidence-based. One-third to approximately one-half of learners indicated that they would apply content in their clinical practice. Completion of the intended 3-month follow-up survey was poor. CONCLUSIONS: Though modules were acceptable per learner responses, future work is needed to: develop modules that are more engaging (e.g., interactive) and applicable to learners; and improve implementation methods to include dissemination and evaluation metrics.

Progesterone induces apoptosis by activation of caspase-8 and calcitriol via activation of caspase-9 pathways in ovarian and endometrial cancer cells in vitro.

Previously we have shown inhibition of endometrial cancer cell growth with progesterone and calcitriol. However, the mechanisms by which the two agents attenuate proliferation have not been well characterized yet. Herein, we investigated how progesterone and calcitriol induce apoptosis in cancer cells. DNA fragmentation was upregulated by progesterone and calcitriol in ovarian and endometrial cancer cells. Time-dependent treatment of ovarian cancer cells, ES-2, and TOV-21G with progesterone enhanced caspase -8 activity after 12 h, whereas OV-90, TOV-112D, HEC-1A, and HEC-59 cells showed increased activity after 24 h. Caspase 9 activity was increased in all cell lines after 24 h treatment with calcitriol. Pretreatment of cancer cells with a caspase-8 inhibitor (z-IETD-fmk) or caspase-9 inhibitor (Z-LEHD-fmk) significantly attenuated progesterone and calcitriol induced caspase-8 and caspase-9 expression, respectively. The expression of FasL, Fas, FAD, and pro-caspase-8, which constitute the death-inducing signaling complex (DISC), was upregulated in progesterone treated cancer cells. Knockdown of FAS or FADD with specific siRNAs significantly blocked progesterone-induced caspase-8. Cleavage of the BID was not affected by caspase-8 activation suggesting the absence of cross-talk between caspase-8 and caspase-9 pathways. Calcitriol treatment decreased mitochondrial membrane potential and increased the release of cancer cytochrome C. These findings indicate that progesterone induces apoptosis through activation of caspase-8 and calcitriol through caspase-9 activation in cancer cells. A combination of progesterone-calcitriol activates both extrinsic and intrinsic apoptotic pathways in cancer cells.

Progesterone-Calcitriol Combination Enhanced Cytotoxicity of Cisplatin in Ovarian and Endometrial Cancer Cells In Vitro.

: Initially, patients that respond to cisplatin (DDP) treatment later relapse and develop chemoresistance. Agents that enhance DDP effectiveness will have a significant impact on cancer treatment. We have shown pronounced inhibitory effects of the progesterone-calcitriol combination on endometrial and ovarian cancer cell growth. Here, we examined whether and how progesterone-calcitriol combination potentiates DDP anti-tumor effects in cancer cells. Ovarian and endometrial cancer cells treated with various concentrations of DDP showed a concentration-dependent decrease in cell proliferation. Concurrent treatment of cells with DDP and progesterone-calcitriol ombination potentiated anticancer effects of DDP compared to DDP-calcitriol, or DDP-progesterone treated groups. The anticancer effects were mediated by increased caspase-3, BAX, and decreased BCL2 and PARP-1 expression in DDP and progesterone-calcitriol combination-treated cells. Stimulation of the PI3K/AKT and MAPK/ERK pathways seen in cancer cells was reduced in DDP-progesterone-calcitriol treated cells. Pretreatment of cells with specific inhibitors further diminished AKT and ERK expression. Furthermore, progesterone-calcitriol potentiated the anti-growth effects of DDP on cancer cells by attenuating the expression of SMAD2/3, multidrug resistance protein- 1 (MDR-1), and ABC transporters (ABCG1, and ABCG2), thereby impeding the efflux of chemo drugs from cancer cells. These results suggest a potential clinical benefit of progesterone-calcitriol combination therapy when used in combination with DDP.