Structured Management of Chronic Nonmalignant Pain with Opioids in a Rural Primary Care Office.

INTRODUCTION: The use of opioid medication for nonmalignant chronic pain (NMCP) increased dramatically during the last 20 years. There have been regulatory changes implemented to reduce the risk of harm to both patients and society. Much of the burden of monitoring these patients is falling on primary care physicians (PCPs), who do not have the time or resources to handle what is entailed in a best-practice approach to NMCP. METHODS: A retrospective study was conducted with all patients on opioid medication for NMCP who were enrolled onto an individual PCP's practice. All were required to engage with a new care system. Patients had the option to remain on opioids, to wean opioids, or to transfer care. Patients who remained in the practice on opioids were required to have an office visit on a day dedicated solely to NMCP every 3 months. Each visit involved verifying the controlled substance contract, a urine drug screen, board of pharmacy monitoring, pain-targeted history and physical, calculation of the average morphine equivalents used, and evaluations of pain, functional status, and mood. Characteristics more likely to lead to weaning from opioids were monitored, as was the program effect on the patients remaining on opioids. RESULTS: With this practice model, 32 patients treated with opioids for NMCP were enrolled. Of these, 38% (n = 12) elected to wean opioids, 53% (n = 17) continued opioid medication, and 9% (n = 3) transferred care. Mean morphine equivalent mg/day was the prime determinant for ability to wean (17.01 mg/day) compared with maintaining (30.61 mg/day) (P = .0397; CI, 0.68 to 26.51). Patients maintaining opioid treatment showed no statistically significant change in any measured data point from beginning until end of the evaluation period. CONCLUSION: Given the choice of following a specific structured care system of opioid medication management or leaving the practice, most patients agreed to the structured system. This approach provided a high degree of compliance with controlled substance regulations and is associated with a reduced number of opioid prescriptions. Patients who were on lower doses of opioid medication are more likely to wean their use with this model.

Inhibition profile of Leishmania mexicana arginase reveals differences with human arginase I.

Arginase (ARG), the enzyme that catalyzes the conversion of arginine to ornithine and urea, is the first and committed step in polyamine biosynthesis in Leishmania. The creation of a conditionally lethal Δarg null mutant in Leishmania mexicana has established that ARG is an essential enzyme for the promastigote form of the parasite and that the enzyme provides an important defense mechanism for parasite survival in the eukaryotic host. Furthermore, human ARGI (HsARGI) has also been implicated as a key factor in parasite proliferation. Thus, inhibitors of ARG offer a rational paradigm for drug design. To initiate a search for inhibitors of the L. mexicana ARG (LmARG), recombinant LmARG and HsARGI enzymes were purified from Escherichia coli. Both LmARG and HsARGI were specific for l-arginine and exhibited no activity with either d-arginine or agmatine as possible substrates. LmARG exhibited a K(m) of 25±4mM for l-arginine, a pH optimum ∼9.0, and was dependent upon the presence of a divalent cation, preferentially manganese. A K(m) of 13.5 ± 2mM for l-arginine was calculated for the HsARGI. A collection of 37 compounds was evaluated against both enzymes. Twelve of these compounds were identified as being either strong inhibitors of both LmARG and HsARGI or differential inhibitors between the two enzymes. Of the 12 compounds, six were selected for further analysis and the type and extent of inhibition determined.