Identifying sociodemographic profiles of veterans at risk for high-dose opioid prescribing using classification and regression trees.

OBJECTIVE: To identify sociodemographic profiles of patients prescribed high-dose opioids. DESIGN: Cross-sectional cohort study. SETTING/PATIENTS: Veterans dually-enrolled in Veterans Health Administration and Medicare Part D, with ≥1 opioid pre-scription in 2012. MAIN OUTCOME MEASURES: We identified five patient-level demographic characteristics and 12 community variables re-flective of region, socioeconomic deprivation, safety, and internet connectivity. Our outcome was the proportion of vet-erans receiving >120 morphine milligram equivalents (MME) for ≥90 consecutive days, a Pharmacy Quality Alliance measure of chronic high-dose opioid prescribing. We used classification and regression tree (CART) methods to identify risk of chronic high-dose opioid prescribing for sociodemographic subgroups. RESULTS: Overall, 17,271 (3.3 percent) of 525,716 dually enrolled veterans were prescribed chronic high-dose opioids. CART analyses identified 35 subgroups using four sociodemographic and five community-level measures, with high-dose opioid prescribing ranging from 0.28 percent to 12.1 percent. The subgroup (n = 16,302) with highest frequency of the outcome included veterans who were with disability, age 18-64 years, white or other race, and lived in the Western Census region. The subgroup (n = 14,835) with the lowest frequency of the outcome included veterans who were with-out disability, did not receive Medicare Part D Low Income Subsidy, were >85 years old, and lived in communities within the second and sixth to tenth deciles of community public assistance. CONCLUSIONS: Using CART analyses with sociodemographic and community-level variables only, we identified sub-groups of veterans with a 43-fold difference in chronic high-dose opioid prescriptions. Interactions among disability, age, race/ethnicity, and region should be considered when identifying high-risk subgroups in large populations.

Assessing spontaneous passage of prophylactic pancreatic duct stents by X-ray: is a radiology report adequate?

BACKGROUND: Pancreatic duct stents are frequently placed for prophylaxis of post-endoscopic retrograde cholangiopancreatography pancreatitis. Because of concern for possible secondary ductal changes from a retained stent, these stents need to be monitored and removed if retained. Usually an abdominal X-ray is performed to assess retained stent, and if present, an esophagogastroduodenoscopy is performed to remove the stent. Limited data is published on false-negative radiology reports for spontaneous passage of stents. METHODS: Using an Institutional Review Board-approved stent log, a retrospective chart review of all pancreatic duct stents placed at our institution from 2008 to 2014 was performed. RESULTS: A total of 856 pancreatic duct stents were placed during the study period. Of these, 435 (50.8%) were prophylactic stents and 421 (49.2%) were therapeutic. Complete follow-up data were available in 426 (97.9%) patients with prophylactic stents. Six patients (1.4%) were lost to follow up and three (0.7%) expired prior to removal. In all, 283 (66%) had follow-up imaging, with 167 (39.2%) having the official radiology read with no retained pancreatic duct stent in place. Eight of these cases were "false-negative" radiology interpretation (4.8% of cases read as "no stent," NNH = 20). The stent was found either by review of image by an endoscopist or incidental stent discovery during a follow-up procedure. CONCLUSION: Radiologist interpretation of abdominal X-rays to assess spontaneous passage of prophylactic pancreatic ducts stents resulted in a false-negative interpretation in approximately 5% of cases. Independent review of the images by the endoscopist may be beneficial given unfamiliarity of these stents by radiologists.

Therapeutic approach guided by genetic alteration: use of MTOR inhibitor in renal medullary carcinoma with loss of PTEN expression.

Renal Medullary Cancer (RMC) is a rare and aggressive type of renal cell cancer that presents predominantly in patients with sickle cell hemoglobinopathies, and is typically metastatic at the time of presentation. Although platinum based chemotherapeutic regimens have recently emerged as the best option for producing a clinically significant response as reported in various case series, the response is far from satisfactory, as most RMC patients still succumb to their disease within a year of diagnosis. There is currently no standard of care for treatment of this disease. We report, to our knowledge, the first case of RMC where in molecular characterization of the tumor was used to guide therapy. In our patient, molecular analysis identified a decreased expression of Ribonucleotide Reductase M1(RRM1) and phosphatase and tensin homolog (PTEN). Based on these results of PTEN deficiency, we started our patient on everolimus (an MTOR inhibitor) maintenance after treating him with an induction chemotherapy regimen of Paclitaxel-Cisplatin-Gemcitabine (PCG). His tumor responded to induction therapy and he went into complete remission and remained in remission for 7 months. He is now alive about 14 months from his diagnosis and is asymptomatic with minimal disease. The rarity of RMC makes it very difficult to do any meaningful clinical trials in this group of patients. The overall prognosis for RMC remains very poor and knowledge about driver mutations may help in guiding therapy to improve survival in this select group of patients, where there is dearth of available therapies.

Expanding the utility of 4-cyano-L-phenylalanine as a vibrational reporter of protein environments.

The ability to genetically incorporate amino acids modified with spectroscopic reporters site-specifically into proteins with high efficiency and fidelity has greatly enhanced the ability to probe local protein structure and dynamics. Here, we have synthesized the unnatural amino acid (UAA), 4-cyano-L-phenylalanine (pCNPhe), containing the nitrile vibrational reporter and three isotopomers ((15)N, (13)C, (13)C(15)N) of this UAA to enhance the ability of pCNPhe to study local protein environments. Each pCNPhe isotopic variant was genetically incorporated in an efficient, site-specific manner into superfolder green fluorescent protein (sfGFP) in response to an amber codon with high fidelity utilizing an engineered, orthogonal aminoacyl-tRNA synthetase. The isotopomers of 4-cyano-L-phenylalanine permitted the nitrile symmetric stretch vibration of these UAAs to be unambiguously assigned utilizing the magnitude and direction of the isotopic shift of this vibration. The sensitivity of the nitrile symmetric stretching frequency of each isotopic variant to the local environment was measured by individually incorporating the probes into two distinct local environments of sfGFP. The UAAs were also utilized in concert to probe multiple local environments in sfGFP simultaneously to increase the utility of 4-cyano-L-phenylalanine.

Modulating Accidental Fermi Resonance: What a Difference a Neutron Makes.

Vibrational reporters have shown significant promise as sensitive probes of local environments in proteins and nucleic acids. The utility of two potential vibrational probes, the cyanate and azide groups in phenyl cyanate and 3-azidopyridine, respectively, has been hindered by accidental Fermi resonance. Anharmonic coupling, between the fundamental -OCN or -N(3) asymmetric stretch vibration with a near resonant combination band, results in an extremely broad and complex absorption profile for each of these probes. A total of eight phenyl cyanate and six 3-azidopyridine isotopomers were synthesized and studied. Isotopic editing effectively modulated the accidental Fermi resonance - the absorption profiles of several isotopomers were greatly simplified while others remained complex. The origins of the observed profiles are discussed. Addition of a single neutron to the middle atom of the oscillator converted the absorption profile to essentially a single band resulting from either the cyanate or azide asymmetric stretch vibration.