Citations

Abstract IntroductionPatient satisfaction is defined as the perception that one’s general health care needs are being met. Prior research suggests that positive patient satisfaction with health care facilitates the physician-patient relationship and enhances the quality of life. Unfortunately, little is known about what factors play a role in influencing patient satisfaction. Objective The primary purpose of this study was to assess patient satisfaction (as measured by the PSQ-18 Patient Satisfaction Questionnaire) of patients seen by general psychiatry residents and to examine what factors might impact patient satisfaction. A secondary purpose was to explore the effects of (three one hour sessions) mentalization skills training on the physician-patient relationship and patient satisfaction. We hypothesized that depressive and anxiety symptoms would negatively impact patient satisfaction. We hypothesized that patients’ satisfaction scores would improve if care was provided by residents who completed mentalization training.MethodsThis was a prospective case-control study, enrolling adult patients (n = 157) referred for psychiatric assessment in a psychiatric resident outpatient clinic. The Short Form PSQ-18 for patients was the primary outcome variable and was compared to Patient Health Questionaire (PHQ-9) and anxiety Generalized Anxiety Disorder 7-Item scale (GAD-7) questionnaires. Outcome data from the PSQ-18 was compared among residents who either had or had not completed mentalization training. The data were analyzed with univariate analyses and to test multiple linear regression. ResultsOverall the patients were satisfied with clinician communication and interpersonal manner (PSQ-18 average scores of 4.21 +/- 0.66 and 4.15+/-0.69 respectively). The patients score on PHQ-9 was inversely related to their scores on time spent (TS) [p = 0.01] and accessibility/convenience (AC) [0.0009] subscale of patient satisfaction. GAD-7 score was inversely related to patients scores on AC subscale (p = 0.01). In regards to mentalization training, there was no difference in IRI (Interpersonal Reactivity Index) scores between the groups aside from Perspective taking (PT) subscale ( p = 0.029). Conclusions Our study reveals that depression and anxiety can negatively impact PSQ-18 patient scoring in psychiatric outpatients seen for the first time in a resident clinic. However, this study failed to show that a brief mentalization- based training could improve patient satisfaction scores that were already quite high at baseline.

This cross-sectional study analyzed a database of Congressional candidate campaign websites to assess the frequency and specificity of pediatric health policy discussions in political campaigns.

Abstract Introduction Sleep disturbances, including rapid eye movement (REM) behavior disorder (RBD), are known manifestations of voltage-gated-potassium-channel-complex VGKC-IgG seropositivity (VGKC+). Discovery of leucine-rich, glioma inactivated protein 1 (LGI1) and contactin-associated protein 2 (CASPR2) have refined our understanding of VGKC+. VGKC+ without LGI1/CASPR2-IgG (“double-negative”) has lost its clinical significance. Previous detailed sleep analysis of these subtypes has been limited. Methods We performed a retrospective study to characterize clinical and polysomnographic features of LGI1/CASPR2 seropositive (LGI1+/CASPR2+) and VGKC double-negative patients, including quantitative REM sleep without atonia (RSWA). Quantified RSWA was compared to matched controls and normative RSWA percentiles. Results Eleven LGI1+/CASPR2+ (LGI1+, 9) and twelve VGKC double-negative patients were analyzed. Insomnia was seen in 55% of LGI1+/CASPR2+ and 8% of VGKC double-negative patients (p=0.05). The LGI1+/CASPR2+ group had reduced slow wave sleep compared to the VGKC double-negative group. Five LGI1+ patients had clinical dream enactment behavior (DEB). Eight LGI1+ patients met quantitative diagnostic levels of RSWA. Higher RSWA levels were seen in the LGI1+/CASPR2+ group. Ten LGI1+/CASPR2+ patients received immunotherapy; all ten neurologically benefited with sleep benefits in 6/10. Conclusion Sleep disorders such as insomnia and RBD are part of the LGI1/CASPR2 autoimmune phenotype. Objective sleep manifestations can be seen on polysomnogram in the form of reduced N3 and elevated RSWA as compared to controls. Quantitative RSWA analysis identified RBD in more LGI1+ patients than clinical report or qualitative RSWA. In this study, RBD was only seen with LGI1+, not CASPR2+. The intermediate RSWA levels of the VGKC double-negative patients may suggest a spectrum of abnormal motor activity in these related antibodies. Additional studies are needed to further explore the biomarker potential of quantitative RSWA in autoimmune neurological conditions. Support This project was supported by the National Center forResearch Resources, National Institutes of Health, through Grant Number 1 UL1 RR024150- 01.

Abstract Introduction Post-traumatic stress disorder (PTSD) is characterized by persistent mental and emotional stress following one or more significant physical or psychological traumatic incidents earlier in life. Vivid recall of the events, including traumatic nightmares, and prominent sleep disturbance are usual in PTSD. Previous studies have suggested that PTSD may share some clinical features with idiopathic REM sleep behavior disorder (iRBD) including altered REM sleep without atonia (RSWA) levels. Our group has previously found evidence for altered RSWA control in patients with psychiatric disease, including a pilot sample of PTSD patients with iRBD. We aimed to comparatively analyze RSWA levels between patients with PTSD, PTSD and RBD (PTSD+RBD), iRBD, and controls. Methods We selected 18 PTSD, 18 PTSD+RBD, 15 iRBD, and 51 healthy control patients matched for age and sex from the Mayo Clinic Center for Sleep Medicine’s polysomnography database for RSWA quantification. RSWA amounts in the submentalis (SM) and anterior tibialis (AT) were quantitatively analyzed as a percentage of REM sleep duration, in accordance with previously published methods. Non-parametric analyses were performed to compare RSWA, patient demographics, and PSG data across groups. Significance was set at p < 0.016. Results Patients with PTSD had significantly higher RSWA than controls in all RSWA density measures (p < 0.016 for all). All measures of RSWA, excluding average SM duration, were significantly greater in PTSD+RBD patients compared with controls (p < 0.016 for all). Within the PTSD group, patients on antidepressants did not have significantly higher RSWA in any of the measures. PTSD+RBD patients had significantly higher SM Phasic, AT Any, SM+AT Any, and Tonic RSWA measures than PTSD patients (p < 0.016 for all). Conclusion PTSD patients have significantly higher RSWA than controls, with PTSD+RBD patients having higher RSWA levels than PTSD patients. These data provide the first evidence for abnormal RSWA control in patients with chronic PTSD. This provides evidence of a unique biology in PTSD that could imply a future risk for neurodegenerative disease in PTSD similar to RBD patients. Further prospective studying will need to be performed on patients with PTSD to understand the unique biology. Support

e24114 Background: Pharmacogenomics (PGx) testing is used increasingly in cancer supportive care for drug and dose selection, and side effects prediction with antidepressants, antiemetics, and pain medications. Genetic variants in genes that encode for drug metabolizing enzymes (CYPs), transporters (SLC6A4) and drug receptors (HTR2A, OPRM1, etc) are well known for these medications. They contribute to inter-individual differences in medication safety and efficacy. We report on their frequency and effect on supportive care drugs in patients with solid tumors. Methods: Between 06/06/19 and 12/18/19, solid tumor cancer patients at Mayo Clinic Arizona were enrolled in a PGx prospective study. They were genotyped using a multi-gene panel, OneOme RightMed. The panel assessed 27 genes, including CYP2C9, CYP2C19, CYP2D6, CYP3A4, COMT, OPRM1, GRIK4, HTR2A, SLC6A4, associated with pain medications, antidepressants, and antiemetics. PGx pharmacist provided medication recommendations and dose adjustments based on PGx test results and concurrent medications. Results: 200 patients were swabbed and 196 patients were genotyped. The results were available within 5 days. All patients were also assessed for pheno-conversion (drug-drug-gene interactions) by a pharmacist. Recommendations were made based on predicted phenotype. Various solid tumor types were represented, including prostate (19.9%), colorectal (17.9%), melanoma (14.8%), and others (47.4%). Median age was 65 with 59.2% patients being male and 40.85% female. All had at least one actionable polymorphism related to these medications. The most significant findings were related to CYP2C19 and CYP2D6 genes. Of 196 patients, a total of 132 (67.3%) had other than normal CYP2D6 metabolizer phenotype and 112 (57.1%) had other than normal CYP2C19 metabolizer phenotype. Based on these genotypes, alternatives to pain medications were recommended for 37 patients, to ondansetron in 9 patients, and to anti-depressants in 51 patients. Conclusions: Genetic variants were commonly found that affect supportive care medications used in oncology practice and contribute to inter-individual differences associated with increased risk of adverse drug effects and reduced efficacy. PGx guided recommendation may help physicians in individualizing medication treatment outcomes for patients with different cancer types and with polypharmacy. PGx trained pharmacist can serve as a valuable asset in optimizing personalized medication management.

TPS5100 Background: First-line treatment of mRCC has rapidly changed to include IPI-NIVO or CABO, with clinical benefit of each based on the Checkmate 214 and CABOSUN (A031203) trials. Combination immunotherapy with VEGF therapies has shown benefit over sunitinib in the JAVELIN 101 and KEYNOTE 426 trials. It is yet unclear which patients (pts) benefit most from combination immunotherapy-VEGF inhibitors, and the optimal sequence of drugs. Methods: In an adaptive, randomized, multicenter phase 3 trial (Alliance A031704, PDIGREE), pts start treatment with induction IPI 1 mg/kg and NIVO 3 mg/kg intravenously (IV) once every 3 weeks. Key inclusion criteria include clear cell mRCC, International Metastatic RCC Database Consortium (IMDC) intermediate or poor risk, Karnofsky performance status > 70, and no prior treatments for mRCC. Based on 3-month radiographic assessment (after completing IPI-NIVO combination), pts with complete responses (CR) undergo maintenance NIVO 480 mg IV every 4 weeks; pts with progression of disease (PD) switch to CABO 60 mg oral daily; pts with non-CR/non-PD are randomized to NIVO 480 mg IV every 4 weeks versus NIVO 480 mg IV every 4 weeks with CABO 40 mg oral daily. Randomization is stratified by IMDC risk criteria and presence of bone metastases. The primary endpoint of the study is overall survival (OS). We hypothesize that 3-year OS will improve to 70% for NIVO-CABO compared to 60% for NIVO alone; to achieve 85% power with a two-sided alpha of 0.05 and exponential distribution, 696 patients will be randomized. Accounting for 30% patients with either CR or PD, and 5% dropout from toxicity, up to 1046 pts will be enrolled. Key secondary endpoints include progression-free survival, 12-month CR rate, overall response rate based on RECIST 1.1 and irRECIST criteria, and toxicity profiles. Quality of life will be assessed based on the FKSI-19, PROMIS-fatigue, and EQ5D-5L questionnaires. Biomarkers associated with CR, tissue-based and plasma-based biomarkers will be assessed. Updated enrollment through May 2020 will be presented. Clinical trial information: NCT03793166 .

4086 Background: The randomized phase III CALGB/SWOG 80405 trial found no difference in overall survival (OS) in first-line mCRC pts treated with either bevacizumab (Bev) or cetuximab (Cet) combined with the same chemotherapy. We investigated the potential prognostic and predictive value of HER2 amplification and HER2 gene expression using NGS and Nanostring data. Methods: Primary tumor DNA from 559 patients (pts) was profiled for HER2 amplification by NGS (Foundation One). Tumor tissue from 925 pts was tested for Nanostring gene expression using an 800 gene panel. OS and progression free survival (PFS) were the endpoints as time-to-event variables. Cox proportional hazard models with gene expression fitted with linear spline (one internal knot at median) were used, adjusting for pts baseline characteristics, treatment assignment, and molecular features (microsatellite instability, BRAF, all RAS). Results: Of 505 tumors with both NGS and Nanostring data, 16 harbored HER2 amplification (copy number variation > 6), limited to microsatellite stable tumors and significantly associated with HER2 expression ( P < 0.001) and wild-type RAS ( P = 0.036). HER2 amplification was neither prognostic nor predictive for OS or PFS. Conversely, HER2 expression higher than median was associated with longer PFS ( P = 0.018) but not OS ( P = 0.13). Among pts with HER2 not amplified, higher HER2 expression was associated with better OS (hazard ratio [HR], 0.83; 95%CI, 0.72-0.97; P = 0.016) and PFS (HR, 0.85; 95%CI, 0.74-0.98; P = 0.027) when the expression was less than median. Additionally, in pts with no HER2 amplification and HER2 expression lower than median, treatment with Cet was associated with worse PFS compared to Bev (HR, 1.46; 95%CI, 1.12-1.90; P = 0.005). This effect was not observed with expression higher than median regardless of HER2 amplification status. Conclusions: To our knowledge, this is the largest analysis of HER2 amplification and gene expression in mCRC pts treated with standard therapy. Our results provide novel insight on the predictive and prognostic value of HER2 gene expression in pts treated with Cet- and Bev-based regimens. Upon validation, these findings could inform pts selection and the design of more effective treatment options for pts with low HER2 expression. Clinical trial information: NCT00265850.

4003 Background: Aspirin and cyclooxygenase-2 (COX-2) inhibitors have been associated with a reduced risk of colorectal polyps and cancer in observational and randomized studies. CALGB/SWOG 80702 tested the effect of celecoxib, a COX-2 inhibitor, on reducing the risk of recurrence in stage III CC. Methods: CALGB/SWOG 80702 is a 2x2 randomized controlled phase III trial of 3 v 6 months of adjuvant FOLFOX (data previously reported as part of the IDEA collaboration) with concurrent celecoxib (400 mg daily) v placebo x 3 yrs for patients (pts) with resected stage III CC. The primary endpoint of the trial is disease-free survival (DFS), defined as time from randomization to recurrence or death from any cause. The trial was designed to provide 91% power to detect a hazard ratio (HR) of 0.79 in favor of celecoxib with 2-sided alpha = 0.05 (775 events required); due to slowing accumulation of events 4 years after complete accrual, power was lowered to 85% with same HR and alpha assumptions (696 events required). The DSMB released data on February 24, 2020 at median f/u of 5.6 yrs with 689 DFS events. Results: Between June 2010 and November 2015, 2,526 pts were consented and randomized to the trial. Treatment arms were well balanced by patient and tumor prognostic features, as well as low-dose aspirin use. Baseline characteristics included 45% female, 18% non-White, 8% Hispanic, 15% T4, 26% N2. 3-yr DFS for celecoxib was 76.3% v 73.3% for placebo (HR 0.89 [95% CI 0.77-1.04]; P = 0.14). 5-yr overall survival (OS) was 83.9% for celecoxib v 81.7% for placebo (HR 0.87 [95% CI 0.72-1.05]; P = 0.14). When considering the 4 treatment arms separately, 3-yr DFS was 77.0% for 12 months FOLFOX + celecoxib, 74.9% for 12 months FOLFOX + placebo, 75.5% for 6 months FOLFOX + celecoxib, and 71.9% for 6 months FOLFOX + placebo (log rank P = 0.22; P interaction = 0.64). There were no significant differences in grade 3-4 toxicity with celecoxib v placebo. Compliance with protocol celecoxib treatment, defined as 3 yrs of therapy completion or recurrence/death while on treatment, was 58.1% pts on celecoxib and 60.2% pts on placebo. Conclusions: The addition of celecoxib to standard chemotherapy did not significantly improve DFS or OS. Clinical trial information: NCT01150045 .

TPS3154 Background: Immune-related Adverse Events (irAEs) are rare but serious sequelae of treatment with immuno-oncology (IO) therapeutics. These therapeutics, including monoclonal antibodies targeting programmed cell death protein 1 (PD-1), programmed death-ligand 1 (PD-L1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), have had transformative effects on outcomes for patients (pts) with advanced cancers. Although most pts tolerate the therapies well, a few experience irAEs ranging in severity up to life-threatening. These irAEs involve diverse organs including the heart, kidney, liver and lung, and gastrointestinal, musculoskeletal, central and peripheral nervous systems. Because of the relatively low incidence and wide variety of irAEs due to various immunotherapies for multiple tumor types, establishment of an efficient centralized repository for acquisition and organized distribution of well-annotated biospecimens is vital for translational studies that improve understanding of the molecular pathogenesis and treatment of these significant toxicities. Methods: This multi-institutional study is open at sites across the National Clinical Trial Network to pts who received ≥ 1 IO therapeutics (e.g., CTLA-4, PD-1 or PD-L1 inhibitor) and experienced 1) ≥ 1 serious (grade 3–5) adverse events that are likely immune-related, 2) rare infection or 3) tumor hyperprogression. IrAEs of interest include myocarditis, colitis, hepatitis, nephritis, myositis, pneumonitis, meningitis/encephalitis, dermatitis, endocrinopathies and neuropathy. Pts may be on an NCTN or non-NCTN IO trial or be receiving standard-of-care therapy. Registration must occur ≤ 72 hours after confirmation of the irAE event. Clinical data are collected at registration, 1 month after registration and for up to 1 year. Biospecimens (tumor blocks, biopsies of inflammatory tissues used to establish irAE diagnosis, and serial blood samples for isolation of plasma, serum and peripheral blood mononuclear cells) are collected at 1-2 timepoints. Stool samples are collected from pts experiencing colitis. Imaging data are collected for pts with hyperprogression or pneumonitis. Goal accrual is 240 pts. Biospecimens and data will be made available to investigators following future submission and approval of proposals. Support: U10CA180821, U10CA180882, U24CA196171; U10CA180820 (ECOG-ACRIN); U10CA180888 (SWOG); U10CA180868 (NRG); https://acknowledgments.alliancefound.org; Clinical trial information: NCT04242095 .

Abstract Direct oral anticoagulants (DOACs) are an emerging treatment option for patients with cancer and acute venous thromboembolism (VTE), but studies have reported inconsistent results. This systematic review and meta-analysis compared the efficacy and safety of DOACs and low-molecular-weight heparins (LMWHs) in these patients. MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, and conference proceedings were searched to identify relevant randomized controlled trials. Additional data were obtained from the original authors to homogenize definitions for all study outcomes. The primary efficacy and safety outcomes were recurrent VTE and major bleeding, respectively. Other outcomes included the composite of recurrent VTE and major bleeding, clinically relevant nonmajor bleeding (CRNMB), and all-cause mortality. Summary relative risks (RRs) were calculated in a random effects meta-analysis. In the primary analysis comprising 2607 patients, the risk of recurrent VTE was nonsignificantly lower with DOACs than with LMWHs (RR, 0.68; 95% CI, 0.39-1.17). Conversely, the risks of major bleeding (RR, 1.36; 95% CI, 0.55-3.35) and CRNMB (RR, 1.63; 95% CI, 0.73-3.64) were nonsignificantly higher. The risk of the composite of recurrent VTE or major bleeding was nonsignificantly lower with DOACs than with LMWHs (RR, 0.86; 95% CI, 0.60-1.23). Mortality was comparable in both groups (RR, 0.96; 95% CI, 0.68-1.36). Findings were consistent during the on-treatment period and in those with incidental VTE. In conclusion, DOACs are an effective treatment option for patients with cancer and acute VTE, although caution is needed in patients at high risk of bleeding.