Dexamethasone Suppression Testing in a Contemporary Cohort with Adrenal Incidentalomas in Two U.S. Integrated Healthcare Systems.

Autonomous cortisol secretion (ACS) from an adrenal adenoma can increase the risk for comorbidities and mortality. The dexamethasone suppression test (DST) is the standard method to diagnose ACS. A multi-site, retrospective cohort of adults with diagnosed adrenal tumors was used to understand patient characteristics associated with DST completion and ACS. Time to DST completion was defined using the lab value and result date; follow-up time was from the adrenal adenoma diagnosis to the time of completion or censoring. ACS was defined by a DST > 1.8 µg/dL (50 nmol/L). The Cox proportional hazards regression model assessed associations between DST completion and patient characteristics. In patients completing a DST, a logistic regression model evaluated relationships between elevated ACS and covariates. We included 24,259 adults, with a mean age of 63.1 years, 48.1% obese, and 28.7% with a Charlson comorbidity index ≥ 4. Approximately 7% (n = 1768) completed a DST with a completion rate of 2.36 (95% CI 2.35, 2.37) per 100 person-years. Fully adjusted models reported that male sex and an increased Charlson comorbidity index were associated with a lower likelihood of DST completion. Current or former smoking status and an increased Charlson comorbidity index had higher odds of a DST > 1.8 µg/dL. In conclusion, clinical policies are needed to improve DST completion and the management of adrenal adenomas.

Time to put it out - nurse-facilitated tobacco treatment in a comprehensive cancer center.

Few cancer patients receive guideline-concordant care for treatment of tobacco dependence. The purpose of this pilot trial was to obtain preliminary estimates of effectiveness of an evidence-based practice intervention on the delivery of tobacco treatment and cessation outcomes in cancer patients. We conducted a pragmatic implementation trial with a before-after design in 119 current or recently quit adult smokers with cancer who met with a clinician at a single National Cancer Institute designated comprehensive cancer center (CCC) (n = 61 pre-implementation, n = 58 post-implementation). We used a multi-component strategy based on the Chronic Care Model to implement National Comprehensive Cancer Network (NCCN) guidelines for smoking cessation. Smoking cessation counseling during the index visit was assessed by exit interview and patients were interviewed by phone to assess cessation outcomes at 3-month follow-up. Performance of cessation counseling and 7-day point prevalence abstinence (PPA) were compared across the pre- and post-implementation periods using log-logistic regression, accounting for clustering by nursing staff. More patients had received assistance in quitting at the index visit during the post-implementation period compared to the pre-implementation period (30 vs. 10%, p < .01). At 3-month follow-up, 38 and 14% of participants had discussed smoking cessation medication with a CCC healthcare professional and 57 and 27% of participants had used pharmacotherapy, respectively (p < .01 for both comparisons). Seven-day PPA at 3-month follow-up was similar in both periods, however (14 vs. 12%, respectively). A multi-component tobacco treatment intervention increased the proportion of smokers who received assistance in quitting smoking during usual cancer care but did not improve cessation outcomes.

Few patients with cancer receive help in quitting smoking. We conducted a pilot before-after trial to determine the effectiveness of an evidence-based practice intervention, including brief cessation counseling during the clinic visit and referral to an onsite tobacco treatment specialist, on the delivery of stop smoking services and cessation outcomes at a NCI-designated Comprehensive Cancer Center. During the post-implementation period, cancer patients who smoke were more likely to have received assistance in quitting in clinic and during 3-month follow-up. This change in process of care did not translate into improved short-term abstinence from tobacco, however. Greater and more sustained participation in tobacco treatment will be needed to improve cessation outcomes in this population.

Increases in Neisseria gonorrhoeae With Reduced Susceptibility to Azithromycin Among Men Who Have Sex With Men in Seattle, King County, Washington, 2012-2016.

Background: Antimicrobial-resistant Neisseria gonorrhoeae is a major public health threat. The Centers for Disease Control and Prevention (CDC) recommends ceftriaxone 250 mg plus azithromycin (AZM) 1 g for gonorrhea treatment. Resistance to AZM could affect gonorrhea control efforts. Methods: Using gonococcal isolates collected at the Public Health-Seattle & King County (PHSKC) Sexually Transmitted Disease (STD) Clinic from 2012 to 2016, focusing on 2014-2016, we compared cases with the CDC AZM alert value minimum inhibitory concentration (MIC) (≥2 µg/mL) to those with AZM MIC ≤1 µg/mL, antimicrobial susceptibility profiles and clinical outcomes. Results: In 2012 and 2013, none of the 263 patients from whom we isolated N. gonorrhoeae from the urethra were infected with organisms with an AZM MIC ≥2 µg/mL. Between 2014 and 2016, 4.4% of 926 gonorrhea cases demonstrated reduced susceptibility to AZM; 93% of these cases occurred among men who have sex with men (MSM). Among MSM, 5.0% of 2014-2016 cases demonstrated reduced susceptibility to AZM. No AZM alert value isolates had concomitant cephalosporin resistance. There were 2 potential treatment failures: 1 pharyngeal infection treated with AZM 2 g alone, and 1 pharyngeal infection that persisted after study drug. Conclusions: Among MSM with gonorrhea in Seattle, 5% have gonorrhea with reduced susceptibility to AZM. The World Health Organization recommends changing treatment guidelines when >5% of isolates are resistant to a recommended drug. The emergence of resistant AZM gonorrhea should prompt reconsideration of current treatment recommendations, and highlights the need for new therapies for gonorrhea.

Defining drug disposition determinants: a pharmacogenetic-pharmacokinetic strategy.

In preclinical and early clinical drug development, information about the factors influencing drug disposition is used to predict drug interaction potential, estimate and understand population pharmacokinetic variability, and select doses for clinical trials. However, both in vitro drug metabolism studies and pharmacogenetic association studies on human pharmacokinetic parameters have focused on a limited subset of the proteins involved in drug disposition. Furthermore, there has been a one-way information flow, solely using results of in vitro studies to select candidate genes for pharmacogenetic studies. Here, we propose a two-way pharmacogenetic-pharmacokinetic strategy that exploits the dramatic recent expansion in knowledge of functional genetic variation in proteins that influence drug disposition, and discuss how it could improve drug development.