Changes in voluntary admission and restraint use after a comprehensive tobacco-free policy in inpatient psychiatric health facilities.

Background: Cardiovascular and respiratory diseases, predominantly due to tobacco use, are the leading causes of death among individuals with serious and persistent mental illness. However, many psychiatric health facilities do not routinely treat tobacco use disorder. The purpose of the current study was to examine the impact of implementing a tobacco-free policy in inpatient psychiatric health facilities in a large, urban setting on behavioral problems, treatment access, and tobacco treatment. Methods: Data on seclusion and restraint incidents, voluntary commitment at admission for each hospitalization episode, and nicotine replacement therapy (NRT) prescriptions were collected through secondary analysis of Medicaid administrative records from baseline in January 2015 (n = 8983) to follow-up in December 2016 (n = 9685) at 14 inpatient psychiatric health facilities. Results: There were no significant changes from baseline to follow-up in odds of seclusion and restraint incidents or voluntary admission status. There was a significant increase in the odds of NRT prescriptions at both 30 and 180 days post discharge (odds ratio [OR] range = 1.58-2.09, P < .01). Conclusions: In a large, urban setting among Medicaid enrollees, implementation of a tobacco-free policy in inpatient psychiatric health facilities had no negative impact on behavioral problems or treatment access and improved access to NRT, although overall NRT use remained low. This study challenges perceptions among some providers that addressing tobacco use disorder will negatively impact treatment outcomes in individuals with serious mental illness. These findings support tobacco-free policies in psychiatric health facilities and the role of psychiatric health providers in treating tobacco use in this population, which is at high risk for tobacco-related mortality.

Safety of dose-reduced pemetrexed in patients with renal insufficiency.

PURPOSE: Pemetrexed has been shown to be effective in the treatment of advanced and metastatic nonsquamous nonsmall cell lung cancer. In this population, renal insufficiency is common; however, pemetrexed is not recommended in patients with a creatinine clearance (CrCl) < 45 ml/min due to increased myelosuppression reported in phase I trials. The primary objective of this study is to determine the safety of dose-reduced pemetrexed in patients with a CrCl < 45 ml/min. METHODS: This is a retrospective case series describing the incidence of grade 3 or higher toxicity in patients with CrCl < 45 ml/min treated with dose-reduced pemetrexed at The James Cancer Hospital and Solove Research Institute at The Ohio State University. RESULTS: A total of eighteen patients were included. Seven (39%) patients experienced a grade ≥ 3 toxicity. Only 18% of administrations led to a grade ≥ 3 toxicity. Four (22%) patients had grade ≥ 3 hematologic toxicity; three of which were receiving concomitant platinum agents. The fourth patient had a CrCl < 30 ml/min. No patients receiving single-agent pemetrexed with a CrCl > 30 ml/min experienced grade ≥ 3 hematologic toxicity. CONCLUSIONS: Dose-adjusted pemetrexed may be cautiously administered to patients with a CrCl between 30 and 45 ml/min. Extra caution is warranted in patients receiving concomitant chemotherapy with a platinum agent as well as those with a CrCl < 30 ml/min. Pemetrexed in combination with a platinum agent should not be routinely recommended for patients with a CrCl < 30 ml/min.

Correlation of genomic alterations assessed by next-generation sequencing (NGS) of tumor tissue DNA and circulating tumor DNA (ctDNA) in metastatic renal cell carcinoma (mRCC): potential clinical implications.

INTRODUCTION: Tumor tissue and circulating tumor DNA (ctDNA) next-generation sequencing (NGS) testing are frequently performed to detect genomic alterations (GAs) to help guide treatment in metastatic renal cell carcinoma (mRCC), especially after progression on standard systemic therapy. Our objective was to assess if GAs detected by ctDNA NGS are different from those detected by tumor tissue NGS, specifically in patients with mRCC, and if these platforms are interchangeable or complimentary. RESULTS: When controlling for genes tested by both platforms, the median mutation rate for ctDNA was similar to tissue (median 3.0 vs. 1.0, p = 0.14). However, the concordance rate between the two platforms was only 8.6%. When comparing GAs by molecular pathway, GAs in tumor tissue were more common for the DNA repair and epigenetic pathways. MATERIALS AND METHODS: Results of NGS testing from tumor tissue and ctDNA from 19 sequential mRCC patients were compared. GAs in each were statistically evaluated using the Wilcoxon signed-rank test. The Fischer's exact test was used to compare the incidence of mutations in selected molecular pathways. CONCLUSIONS: When controlling for genes tested by both platforms, similar number of GAs were detected by both tissue and ctDNA based NGS. However, there was discordance in the type of GAs detected suggesting that ctDNA NGS may be more reflective of dynamic tumor genomic heterogeneity. Hence, these two platforms may be considered complementary to each other, rather than interchangeable, for assessment of tumor GAs to guide selection of targeted clinical trial therapies.

Effect of fondaparinux prophylaxis on anti-factor Xa concentrations in patients with morbid obesity.

PURPOSE: Anti-factor Xa values in morbidly obese patients receiving standard doses of fondaparinux sodium for the prevention of venous thromboembolism (VTE) were analyzed in a retrospective chart evaluation. SUMMARY: The administration of low-molecular-weight heparins to obese patients (body mass index [BMI] of ≥30 kg/m(2)) at the dose recommended for VTE prophylaxis has been reported to result in increased thromboembolic events and decreased anti-factor Xa levels, and some evidence indicates that weight-based dosing adjustments may be appropriate. To study this phenomenon among morbidly obese patients (BMI of ≥40 kg/m(2)), a review of the charts of 45 adult patients for whom steady-state anti-factor Xa laboratory values were obtained after at least four fondaparinux injections was conducted; in all instances, fondaparinux sodium was given at the standard dose (2.5 mg once daily). Of the total of 47 anti-factor Xa values analyzed, 22 (47%) were below the study institution's target peak range (0.3-0.5 mg/L), 20 values (43%) were within the range, and 5 (11%) were above the range. No documented thromboembolic events occurred during hospitalization in the cases evaluated. A stepwise linear regression analysis of selected demographic and clinical variables indicated that better renal function, male sex, increased BMI, and fewer fondaparinux doses were associated with a greater likelihood of diminished anti-factor Xa activity in the cases evaluated. CONCLUSION: Anti-factor Xa concentrations in morbidly obese patients receiving fondaparinux sodium 2.5 mg subcutaneously daily for VTE prophylaxis were within or above the target range in 53% of the instances evaluated.