Substance use identification and follow-up rates among commercial and Medicare health insurance members in primary care and other settings.

BACKGROUND: The objective of this study was to investigate factors associated with substance use disorder identification and follow-up rates among samples of members of a private health insurance plan. METHODS: In an observational study, samples of claims data for 2017 for Commercial and Medicare members from a private health insurer were accessed and analyzed using descriptive statistics, decision tree analysis, and linear regression models. RESULTS: Commercial and Medicare members differed in age. Medicare members had higher rates of inclusion in a measure of substance use disorder than Commercial members, lower rates of initial short term follow-up, more opioid prescriptions from primary care provides, fewer prescriptions for opioid treatment, and higher rates of selected comorbid conditions. Mental health diagnoses and substance use disorder co-occurred frequently and to a greater extent in the Medicare sample. Among commercial members, there were primarily alcohol problems that increased with age, while opioid problems at about 10% peaked in the mid-twenties. More males were included among all substance types. The overall rate for an initial short term follow-up visit indicating initiation of treatment was 30%. There were large differences in the follow-up rates across settings with a very low rate (4.6% for alcohol and 6.9% for opioid) in primary care settings. CONCLUSIONS: These results suggest that increased attention in primary care to young adult males and to older adults, may help to reduce substance use disorder rates, especially alcohol use disorders.

Development and Implementation of a Bedside Peripherally Inserted Central Catheter Service in a PICU.

OBJECTIVES: To create a bedside peripherally inserted central catheter service to increase placement of bedside peripherally inserted central catheter in PICU patients. DESIGN: Two-phase observational, pre-post design. SETTING: Single-center quaternary noncardiac PICU. PATIENTS: All patients admitted to the PICU. INTERVENTIONS: From June 1, 2015, to May 31, 2017, a bedside peripherally inserted central catheter service team was created (phase I) and expanded (phase II) as part of a quality improvement initiative. A multidisciplinary team developed a PICU peripherally inserted central catheter evaluation tool to identify amenable patients and to suggest location and provider for procedure performance. Outcome, process, and balancing metrics were evaluated. MEASUREMENTS AND MAIN RESULTS: Bedside peripherally inserted central catheter service placed 130 of 493 peripherally inserted central catheter (26%) resulting in 2,447 hospital central catheter days. A shift in bedside peripherally inserted central catheter centerline proportion occurred during both phases. Median time from order to catheter placement was reduced for peripherally inserted central catheters placed by bedside peripherally inserted central catheter service compared with placement in interventional radiology (6 hr [interquartile range, 2-23 hr] vs 34 hr [interquartile range, 19-61 hr]; p < 0.001). Successful access was achieved by bedside peripherally inserted central catheter service providers in 96% of patients with central tip position in 97%. Bedside peripherally inserted central catheter service central line-associated bloodstream infection and venous thromboembolism rates were similar to rates for peripherally inserted central catheters placed in interventional radiology (all central line-associated bloodstream infection, 1.23 vs 2.18; p = 0.37 and venous thromboembolism, 1.63 vs 1.57; p = 0.91). Peripherally inserted central catheters in PICU patients had reduced in-hospital venous thromboembolism rate compared with PICU temporary catheter in PICU rate (1.59 vs 5.36; p < 0.001). CONCLUSIONS: Bedside peripherally inserted central catheter service implementation increased bedside peripherally inserted central catheter placement and employed a patient-centered and timely process. Balancing metrics including central line-associated bloodstream infection and venous thromboembolism rates were not significantly different between peripherally inserted central catheters placed by bedside peripherally inserted central catheter service and those placed in interventional radiology.

Dissociated nonsteroidal glucocorticoid receptor modulators; discovery of the agonist trigger in a tetrahydronaphthalene-benzoxazine series.

The tetrahydronaphthalene-benzoxazine glucocorticoid receptor (GR) partial agonist 4b was optimized to produce potent full agonists of GR. Aromatic ring substitution of the tetrahydronaphthalene leads to weak GR antagonists. Discovery of an "agonist trigger" substituent on the saturated ring of the tetrahydronaphthalene leads to increased potency and efficacious GR agonism. These compounds are efficacy selective in an NFkB GR agonist assay (representing transrepression effects) over an MMTV GR agonist assay (representing transactivation effects). 52 and 60 have NFkB pIC(50) = 8.92 (105%) and 8.69 (92%) and MMTV pEC(50) = 8.20 (47%) and 7.75 (39%), respectively. The impact of the trigger substituent on agonism is modeled within GR and discussed. 36, 52, and 60 have anti-inflammatory activity in a mouse model of inflammation after topical dosing with 52 and 60, having an effect similar to that of dexamethasone. The original lead was discovered by a manual agreement docking method, and automation of this method is also described.

N-4-Pyrimidinyl-1H-indazol-4-amine inhibitors of Lck: indazoles as phenol isosteres with improved pharmacokinetics.

2,4-Dianilino pyrimidines are well-known inhibitors of tyrosine kinases including lymphocyte specific kinase (Lck). Structure-activity relationships at the 4-position are discussed and rationalised. Examples bearing a 2-methyl-5-hydroxyaniline substituent at the 4-position were especially potent but showed poor oral pharmacokinetics. Replacement of this substituent by 4-amino(5-methyl-1H-indazole) yielded compounds with comparable enzyme potency and improved pharmacokinetic properties.