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Abstract The US Food and Drug Agency (FDA) requires clinical trials targeting cognitive impairment associated with schizophrenia (CIAS) to demonstrate the functional relevance of cognitive improvements by employing a functional co-primary measure. Although quantitative evidence supports the suitability of the Virtual Reality Functional Capacity Assessment Tool (VRFCAT) for this purpose, FDA guidelines for qualification of clinical outcome assessments require evidence of content validity, defined as qualitative evidence that key stakeholders view the measure as relevant and important. To collect this important qualitative data, semi-structured interviews were conducted with outpatients with schizophrenia (n = 24), caregivers (n = 12), and professional peer support specialists (n = 12) to elicit their views about the definition and importance of functional independence, the importance of the functional domains assessed by the VRFCAT (meal planning, using transportation, handling money, shopping), and the relevance of the VRFCAT tasks to these domains. Qualitative thematic analyses revealed consistent themes across groups in defining functional independence, including performing instrumental self-care, financial, and social tasks; making decisions autonomously; and not depending on others to carry out daily activities. There were, however, notable differences in their views regarding the importance of and barriers to functional independence. All groups viewed the VRFCAT as assessing skill domains that are central to independent functioning and, with some minor differences, the VRFCAT tasks were viewed as relevant and meaningful examples of the domains. These qualitative results provide converging evidence that key stakeholders view the VRFCAT as a content-valid measure.

Background: The US Department of Veterans Affairs, Department of Defense (VA/DoD) clinical guidelines recommend extended-release naltrexone (XR-NTX) as a treatment option for moderate-to-severe alcohol use disorder (AUD); however, contemporary real-world outcomes related to this guideline are lacking. This retrospective, observational, descriptive study examined treatment patterns and healthcare resource use (HCRU) among veterans with an AUD diagnosis who initiated XR-NTX. Methods: Veterans with incident AUD who initiated XR-NTX between 8/2014 and 11/2018 were identified. Treatment patterns and HCRU were assessed during the 1-year baseline period before and following XR-NTX initiation (the index date). Results: Of the 3665 VA patients (mean [SD] age: 46 [12.5] years; male: 89.7%; White: 76.9%) included in the study, time from AUD diagnosis to XR-NTX initiation was highly variable (mean [range]: 13.6 [0-50.5 months]). Patients received a mean [SD] of 6.8 [6.1] XR-NTX administrations; 44.4% received ⩾6. Mean [SD] time to XR-NTX discontinuation was 93.4 [75.7] days, and 31.3% of discontinuing patients resumed XR-NTX therapy. Of those who received other subsequent medications for AUD, 38.6% (acamprosate) to 47.8% (disulfiram) re-initiated XR-NTX. The proportion of patients with ⩾1 inpatient admissions decreased during follow-up compared with baseline (all-cause: 61.5% to 37.8%; AUD-related: 58.0%-35.4%); with a smaller decrease observed in emergency department (ED) visits. In contrast, more patients had ⩾1 outpatient visits during follow-up (all-cause: 97.5%-99.7%; AUD-related: 84.4%-92.7%). Compared with baseline, mean number of inpatient admissions and ED visits decreased during follow-up, while the number of outpatient visits increased for both all-cause and AUD-related care. Conclusions: Among VA patients with AUD who initiated XR-NTX, we observed reductions in all-cause and AUD-related acute care, and increases in outpatient care. This finding demonstrates a possible transition from acute, inpatient treatment to long-term, outpatient care that may reflect a reduction in disease severity. Additional research is warranted.

Aim: Patients receiving checkpoint inhibitors (CPI) are frequently on other medications for co-morbidities. We explored the impact of concomitant medication use on outcomes. Materials & methods: 210 metastatic cancer patients on CPI were identified and association between concomitant medication use and immune-related adverse events with clinical outcomes was determined. Results: Aspirin, metformin, β-blockers and statins were not shown to have any statistically significant difference on clinical benefit. 26.3% patients with clinical benefit developed rash versus 11.8% without clinical benefit (p < 0.05) on multivariate analysis. Conclusion: Use of common prescription and nonprescription medications in patients with multiple co-morbidities appears safe and does not have an adverse effect on CPI efficacy. The presence of rash predicted for a better response.

AbstractTo examine long-term effects of early intervention services (EIS) for first-episode psychosis, we compared Heinrichs-Carpenter Quality of Life (QLS) and Positive and Negative Syndrome Scale (PANSS) scores and inpatient hospitalization days over 5 years with data from the site-randomized RAISE-ETP trial that compared the EIS NAVIGATE (17 sites; 223 participants) and community care (CC) (17 sites; 181 participants). Inclusion criteria were: age 15–40 years; DSM-IV diagnoses of schizophrenia, schizoaffective disorder, schizophreniform disorder, brief psychotic disorder, or psychotic disorder not otherwise specified; first psychotic episode; antipsychotic medication taken for ≤6 months. NAVIGATE-randomized participants could receive NAVIGATE from their study entry date until NAVIGATE ended when the last-enrolled NAVIGATE participant completed 2 years of treatment. Assessments occurred every 6 months. 61% of participants had assessments conducted ≥2 years; 31% at 5 years. Median follow-up length was CC 30 months and NAVIGATE 38 months. Primary analyses assumed data were not-missing-at-random (NMAR); sensitivity analyses assumed data were missing-at-random (MAR). MAR analyses found no significant treatment-by-time interactions for QLS or PANSS. NMAR analyses revealed that NAVIGATE was associated with a 13.14 (95%CI:6.92,19.37) unit QLS and 7.73 (95%CI:2.98,12.47) unit PANSS better improvement and 2.53 (95%CI:0.59,4.47) fewer inpatient days than CC (all comparisons significant). QLS and PANSS effect sizes were 0.856 and 0.70. NAVIGATE opportunity length (mean 33.8 (SD = 5.1) months) was not associated (P = .72) with QLS outcome; duration of untreated psychosis did not moderate (P = .32) differential QLS outcome. While conclusions are limited by the low rate of five-year follow-up, the data support long-term benefit of NAVIGATE compared to community care.

Abstract Despite its unique efficacy, clozapine remains underutilized in the United States. Perceptions about clozapine and barriers to its use have been examined among prescribers, but insufficiently studied among consumers. We surveyed 211 antipsychotic consumers (86 on clozapine and 125 on other antipsychotics) on their medication-related perspectives in a public hospital system in Atlanta, Georgia, USA. In contrast to their previous regimen, 72% of clozapine consumers reported they were more satisfied with clozapine. When compared with consumers taking other antipsychotics, clozapine consumers reported more side effects but did not differ on other measures of satisfaction or efficacy. We found Caucasians to be overrepresented among clozapine, as compared to other antipsychotic consumers. Side effects most strongly associated with poor safety ratings were sedation, limb jerking, and dizziness when standing. However, clozapine was only rated less safe by consumers who experienced more than one of these side effects. We used an unsupervised clustering approach to identify three major groups of clozapine consumers. Cluster A (19%) had the lowest safety ratings, aversion to blood work, and a high rate of side effects that associate with lower safety ratings. Cluster B (25%) experienced more hospitalizations and reported satisfaction with clozapine that correlated with efficacy ratings, irrespective of safety ratings. Cluster C (56%) experienced fewer hospitalizations, fewer previous drug trials, greater educational attainment, lower rates of smoking, and rated clozapine more highly. This work identifies common side effects that influence the subjective safety of clozapine and suggests that attitudes toward clozapine depend on context-specific factors.

AbstractAimsRates of obesity have reached epidemic proportions, especially among people with psychiatric disorders. While the effects of obesity on the brain are of major interest in medicine, they remain markedly under‐researched in psychiatry.MethodsWe obtained body mass index (BMI) and magnetic resonance imaging‐derived regional cortical thickness, surface area from 836 bipolar disorders (BD) and 1600 control individuals from 14 sites within the ENIGMA‐BD Working Group. We identified regionally specific profiles of cortical thickness using K‐means clustering and studied clinical characteristics associated with individual cortical profiles.ResultsWe detected two clusters based on similarities among participants in cortical thickness. The lower thickness cluster (46.8% of the sample) showed thinner cortex, especially in the frontal and temporal lobes and was associated with diagnosis of BD, higher BMI, and older age. BD individuals in the low thickness cluster were more likely to have the diagnosis of bipolar disorder I and less likely to be treated with lithium. In contrast, clustering based on similarities in the cortical surface area was unrelated to BD or BMI and only tracked age and sex.ConclusionsWe provide evidence that both BD and obesity are associated with similar alterations in cortical thickness, but not surface area. The fact that obesity increased the chance of having low cortical thickness could explain differences in cortical measures among people with BD. The thinner cortex in individuals with higher BMI, which was additive and similar to the BD‐associated alterations, may suggest that treating obesity could lower the extent of cortical thinning in BD.

γ-aminobutyric acid (GABA) is a major inhibitory neurotransmitter implicated in neuropsychiatric disorders. The best method for quantifying GABA is proton magnetic resonance spectroscopy (1H MRS). Considering that accurate measurements of GABA are affected by slight methodological alterations, demonstrating GABA reproducibility in healthy volunteers is essential before implementing the changes in vivo. Thus, our study aimed to evaluate the back-to-back (B2B) and day-to-day (D2D) reproducibility of GABA+ macromolecules (GABA+) using a 3 Tesla MRI scanner, the new 32-channel head coil (CHC), and Mescher–Garwood Point Resolved Spectroscopy (MEGA-PRESS) technique with the scan time (approximately 10 min), adequate for psychiatric patients. The dorsomedial pre-frontal cortex/anterior cingulate cortex (dmPFC/ACC) was scanned in 29 and the dorsolateral pre-frontal cortex (dlPFC) in 28 healthy volunteers on two separate days. Gannet 3.1 was used to quantify GABA+. The reproducibility was evaluated by Pearson’s r correlation, the interclass-correlation coefficient (ICC), and the coefficient of variation (CV%) (r/ICC/CV%). For Day 1, B2B reproducibility was 0.59/0.60/5.02% in the dmPFC/ACC and 0.74/0.73/5.15% for dlPFC. For Day 2, it was 0.60/0.59/6.26% for the dmPFC/ACC and 0.54/0.54/6.89 for dlPFC. D2D reproducibility of averaged GABA+ was 0.62/0.61/4.95% for the dmPFC/ACC and 0.58/0.58/5.85% for dlPFC. Our study found excellent GABA+ repeatability and reliability in the dmPFC/ACC and dlPFC.