Clinical Effectiveness of an Outpatient Multidisciplinary Chronic Pain Management Telementoring Service.

OBJECTIVE: The objective of this study was to assess the effectiveness of a Pain E-Consult Program (PEP), a multidisciplinary telementoring service based on the Extension for Community Healthcare Outcomes (ECHO) model to reduce opioid use in the outpatient setting. MATERIALS AND METHODS: This was a retrospective matched cohort study conducted in an integrated health care delivery system. Adult patients without cancer and with a 90-day morphine milligram equivalent (MME) ≥30 mg/d between April 1, 2016, and June 30, 2017, were included. Patients whose primary care clinician received the PEP (observation) were compared with usual care (control) patients. Observation patients were matched up to 1:5 to control patients. Outcomes included change in MME and initiation of nonopioid alternative medications. Multivariable regression analyses were performed. RESULTS: A total of 665 patients were matched: 125 and 540 in the observation and control groups, respectively. Patients were primarily female, white, and Medicare beneficiaries. The observation group had a statistically significantly greater decrease in median MME/day during the 6-month (-7.4 vs. 1.5 mg, P=0.002) and 12-month (-15.1 vs. -2.8 mg, P<0.001) follow-up and rates of ≥20% decrease (6 mo: 41.6% vs. 24.6%, P=0.003; 12 mo: 48.0% vs. 32.6%, P=0.017). There were no differences in the rates of initiation of nonopioid alternative medications. CONCLUSIONS: A PEP was associated with greater reductions in MME/day compared with usual care despite similar rates of nonopioid alternative medication initiation. A prospective randomized study of this program should be undertaken to confirm these findings.

Mutant Brca2/p53 mice exhibit altered radiation responses in the developing mammary gland.

Appropriate balance between proliferation and apoptosis is critical for mammary gland development and is often altered during tumorigenesis. Carcinogens like radiation induce DNA damage and activate protective responses such as cell cycle arrest and apoptosis. We used mice carrying Brca2(-/-) and/or p53(-/-) mutations to evaluate the individual and combined effects of these genes on cell proliferation and apoptosis in the developing mammary gland. Mice were exposed to 5Gy of radiation or chamber exposure (controls) followed by injection with BrdU. Mammary glands were collected 6 h post-radiation exposure and evaluated for proliferation (BrdU) and apoptosis (TUNEL) in terminal end buds (TEB) and ducts. Under control conditions, the Brca2 mutation reduced proliferation and apoptosis in TEB but not ducts, whereas the p53 mutation reduced apoptosis in TEB and ducts but did not influence proliferation. Despite these alterations in proliferation and/or apoptosis, neither mutation, either individually or combined, significantly altered the overall balance between the two as measured by the proliferation to apoptosis ratio (growth index). Following irradiation, the Brca2 mutation had no significant effect on proliferation or apoptosis, whereas the p53 mutation resulted in reduced apoptosis in TEB and ducts but did not significantly influence proliferation. Neither mutation by itself altered the growth index in the TEB after irradiation although combined Brca2/p53 mutation caused significantly increased proliferation, reduced apoptosis, and an elevated growth index in TEB and ducts. These results reveal both independent and collaborative growth regulatory roles for Brca2 and p53 under normal and adverse environmental conditions. Additionally, we demonstrate the importance of gene-environment interactions by showing that Brca2- and p53-deficient mice can compensate for their genetic deficiencies under control conditions but not after exposure to radiation. We also demonstrate distinct spatial differences in the cellular functions of Brca2 and p53 and show that combined mutation of both genes is more detrimental than loss of either gene alone.