Intranasal Oxytocin Modulates Decision-Making Depending on Outcome Predictability-A Randomized Within-Subject Controlled Trial in Healthy Males.

Oxytocin (OT) has been extensively studied with regard to its socio-cognitive and -behavioral effects. Its potential as a therapeutic agent is being discussed for a range of neuropsychiatric conditions. However, there is limited evidence of its effects on non-social cognition in general and decision-making in particular, despite the importance of these functions in neuropsychiatry. Using a crossover/within-subject, blinded, randomized design, we investigated for the first time if intranasal OT (24 IU) affects decision-making differently depending on outcome predictability/ambiguity in healthy males. The Iowa Gambling Task (IGT) and the Cambridge Risk Task (CRT) were used to assess decision-making under low outcome predictability/high ambiguity and under high outcome probability/low ambiguity, respectively. After administration of OT, subjects performed worse and exhibited riskier performance in the IGT (low outcome predictability/high ambiguity), whereas they made borderline-significant less risky decisions in the CRT (high outcome probability/low ambiguity) as compared to the control condition. Decision-making in healthy males may therefore be influenced by OT and adjusted as a function of contextual information, with implications for clinical trials investigating OT in neuropsychiatric conditions.

Divergent effects of oxytocin on "mind-reading" in healthy males.

The neuropeptide oxytocin (OT) has been associated with a broad range of human behaviors, particularly in the domain of social cognition, and is being discussed to play a role in a range of psychiatric disorders. Studies using the Reading The Mind In The Eyes Test (RMET) to investigate the role of OT in mental state recognition reported inconsistent outcomes. The present study applied a randomized, double-blind, cross-over design, and included measures of serum OT. Twenty healthy males received intranasal placebo or OT (24 IU) before performing the RMET. Frequentist and Bayesian analyses showed that contrary to previous studies (Domes et al., 2007; Radke & de Bruijn, 2015), individuals performed worse in the OT condition compared to the placebo condition (p = 0.023, Cohen's d = 0.55, 95% confidence interval [CI] [0.08, 1.02], BF10 = 6.93). OT effects did not depend on item characteristics (difficulty, valence, intensity, sex) of the RMET. Furthermore, OT serum levels did not change after intranasal OT administration. Given that similar study designs lead to heterogeneous outcomes, our results highlight the complexity of OT effects and support evidence that OT might even interfere with social cognitive abilities. However, the Bayesian analysis approach shows that there is only moderate evidence that OT influences mind-reading, highlighting the need for larger-scale studies considering the discussed aspects that might have led to divergent study results.

Multiple Biomarker Testing Tissue Consumption and Completion Rates With Single-gene Tests and Investigational Use of Oncomine Dx Target Test for Advanced Non-Small-cell Lung Cancer: A Single-center Analysis.

INTRODUCTION: First-line targeted therapies have been developed for advanced non-small-cell lung cancer (NSCLC). However, small biopsy samples pose a challenge to testing all relevant biomarkers. The present study characterized clinician-ordered single-gene lung cancer testing and evaluated tissue stewardship and the ability to successfully determine mutation status with single-gene testing or investigational use of the Oncomine Dx Target Test. MATERIALS AND METHODS: Clinician-submitted orders for 3659 single-gene tests (EGFR, ALK, ROS1, BRAF, KRAS, ERBB2, MET, RET, FGFR1) across 1402 samples at a large US-based commercial reference laboratory and 169 investigational Oncomine Dx Target Tests were retrospectively evaluated. The testing success rates and tissue consumption were evaluated by sample type, test type, and number of single-gene tests per sample. RESULTS: The large majority of lung tissue samples submitted for clinical testing were small (70.5% core needle biopsies; 10.0% fine needle aspirations). With single-gene testing, mutation status was successfully reported for ≥ 1 biomarker for 88.4% of the clinical samples. The success rates decreased and tissue consumption increased with testing of additional biomarkers. Investigational Oncomine Dx Target Tests were permitted 1 tissue slide each and demonstrated success rates similar to single-gene testing for ≥ 5 biomarkers on core needle biopsies, ≥ 4 biomarkers on fine needle aspirations, and ≥ 2 biomarkers on surgical resection specimens. CONCLUSION: Tissue stewardship is important to enable successful completion of genetic testing and informed NSCLC treatment decisions. Preliminary assessment of the investigational Oncomine Dx Target Test suggests it could facilitate access to multiple biomarker testing using small tissue samples to support therapy decisions for patients with advanced NSCLC.

Budget Impact of Next-Generation Sequencing for Molecular Assessment of Advanced Non-Small Cell Lung Cancer.

BACKGROUND: Genetic testing for nonsquamous advanced non-small cell lung cancer (aNSCLC) is recommended to guide first-line therapy. Activating mutations can be identified via single-gene testing or next-generation sequencing (NGS). OBJECTIVES: To evaluate the budget impact of NGS instead of single-gene testing for tissue-based molecular assessment of aNSCLC from the US health care payer perspective. METHODS: An annual cohort of newly diagnosed patients with nonsquamous aNSCLC in a hypothetical 1-million-member health care plan was evaluated using a Markov model over 5 years. Epidemiology and testing rates (EGFR, ALK, ROS1, BRAF, MET, HER2, and RET) were from the literature. Treatments were determined by available genetic information. Safety, progression, and survival with targeted therapy or chemotherapy were from randomized clinical trials. Single-gene testing and first-line and maintenance treatment costs were from RED BOOK and Medicare fee schedules; NGS testing, adverse event, and progression costs to payers were from the literature. RESULTS: Three hundred sixteen testing-eligible patients with aNSCLC were expected annually, of whom 179 undergo genetic testing. Of 57 patients expected to have activating mutations, single-gene testing identified 35, whereas NGS identified 54. NGS, instead of single-gene testing, decreased expected testing procedure-related costs to the health plan payer by $24,651. First-line and maintenance treatment costs increased by $842,205, offset by a $385,000 decrease in second-line treatment and palliative care costs. Over 5 years, total budget impact was $432,554 ($0.0072 per member per month). CONCLUSIONS: NGS is expected to identify more patients with activating mutations, thereby better enabling selection for targeted therapy and clinical trial enrollment. The budget impact to US payers is expected to be minimally cost-additive.

Assessment of the relationship between diabetes treatment intensification and quality measure performance using electronic medical records.

AIMS: Assess the relationship between timely treatment intensification and hemoglobin A1C (HbA1C) control quality-of-care performance measures, i.e., HbA1C levels, among patients with uncontrolled type 2 diabetes. MATERIALS AND METHODS: Electronic medical records and diabetes registry data from a large, accountable care organization (ACO) were used to isolate a sample of adult patients with type 2 diabetes who received at least one oral antidiabetes agent and had at least one HbA1C level measurement ≥8.0% (64 mmol/mol; i.e., uncontrolled diabetes) between 7/1/2011 and 6/30/2015. Treatment intensification status was evaluated for each patient during a 120-day treatment intensification window following the index HbA1c measure. Two-level hierarchical generalized linear models, with patients aggregated at the physician level, were used to assess the association between treatment intensification and achieving HbA1C quality performance measures. RESULTS: 547 patients met study selection criteria and 480 patients had at least one HbA1C test after the treatment intensification window and were used for the statistical analyses. About 40% of patients who had uncontrolled diabetes received treatment intensification during the 120-day window. Greater index HbA1C, greater patient body mass index, and fewer unique pre-index oral antidiabetes agents were significantly associated with greater likelihood of receiving timely treatment intensification. The odds of receiving treatment intensification were about 1.8 times higher (P = 0.0027) among patients with poor index HbA1C control (HbA1c level >9.0% [75 mmol/mol]) compared to other patients (index HbA1c 8.0% - 9.0%). Hispanic patients (compared to White patients) were significantly more likely to exhibit poor control after treatment intensification (odds ratio [OR] 2.91, P = 0.0304), underscoring the difficulty of controlling diabetes in this vulnerable group. In contrast, being male and being treated primarily by an internist (compared to primary treatment by a family medicine specialist) were both significantly associated with achieving superior control (HbA1c level <8.0%) after treatment intensification (OR 0.53 [P = 0.0165]; OR 0.41 [P = 0.0275], respectively). CONCLUSIONS: Timely treatment intensification was significantly associated with greater likelihood of patients achieving superior HbA1C control (<8.0%) and better HbA1C control quality performance for the practice. Even in an ACO with resources dedicated to diabetes control, it is incumbent upon clinicians to readily identify and open dialogues with patients who may benefit from closely supervised, individualized attention.

Challenges of proper placebo control for non-invasive brain stimulation in clinical and experimental applications.

A range of techniques are now available for modulating the activity of the brain in healthy people and people with neurological conditions. These techniques, including transcranial magnetic stimulation (TMS) and transcranial current stimulation (tCS, which includes direct and alternating current), create magnetic or electrical fields that cross the intact skull and affect neural processing in brain areas near to the scalp location where the stimulation is delivered. TMS and tCS have proved to be valuable tools in behavioural neuroscience laboratories, where causal involvement of specific brain areas in specific tasks can be shown. In clinical neuroscience, the techniques offer the promise of correcting abnormal activity, such as when a stroke leaves a brain area underactive. As the use of brain stimulation becomes more commonplace in laboratories and clinics, we discuss the safety and ethical issues inherent in using the techniques with human participants, and we suggest how to balance scientific integrity with the safety of the participant.