Under-perception of airflow limitation, self-efficacy, and beliefs in older adults with asthma.

OBJECTIVE: Under-perception of airflow limitation is more common in older adults with asthma and may lead to under-reporting of asthma symptoms. Asthma management self-efficacy is linked with better asthma control and quality of life (QoL). We sought to examine asthma and medication beliefs as a mediator in the relationship between both under-perception and self-efficacy with asthma outcomes. METHODS: This cross-sectional study recruited participants with asthma ≥60 years from hospital-affiliated practices in East Harlem and the Bronx, New York. Perception of airflow limitation was measured for 6 weeks by having participants enter peak expiratory flow (PEF) estimates into an electronic peak flow meter followed by PEF blows. We used validated instruments to assess asthma and medication beliefs, asthma management self-efficacy, asthma control, and QoL. Asthma self-management behaviors (SMB) were quantified by electronic and self-report measures of inhaled corticosteroid (ICS) adherence and observation of inhaler technique. RESULTS: The sample comprised 331 participants (51% Hispanic, 27% Black, 84% female). Beliefs mediated the relationship between greater under-perception and better self-reported asthma control (ß = -0.08, p = .02) and better asthma QoL (ß =0.12, p = .02). Higher self-efficacy was also associated with better reported asthma control (ß = -0.10, p = .006) and better asthma QoL (ß =0.13, p = .01) in this indirect effect through beliefs. Accurate perception of airflow limitation was associated with higher adherence to SMB (ß = 0.29, p = .003). CONCLUSIONS: Less threatening asthma beliefs may be maladaptive in under-perception of airflow limitation by contributing to under-reporting of asthma symptoms, but adaptive in the context of higher self-efficacy and better asthma control.

Feasibility and clinical utility of using the tone matching test for assessment of early auditory processing in schizophrenia.

Early auditory processing (EAP) deficits are prevalent in schizophrenia and linked to disturbances in higher order cognition and daily functioning. Treatments that target EAP have the potential to drive downstream cognitive and functional improvements, but clinically feasible means to detect EAP impairment are lacking. This report describes the clinical feasibility and utility of using the Tone Matching (TM) Test to assess EAP in adults with schizophrenia. Clinicians were trained to administer the TM Test as part of a baseline cognitive battery to inform choice of cognitive remediation (CR) exercises. Only if the TM Test indicated EAP impairment, were the recommended CR exercises to include EAP training. Results indicated clinicians included the TM Test in all baseline assessments and identified 51.72% as EAP impaired. There were significant positive relationships between TM Test performance and cognitive summary scores, confirming instrumental validity. All clinicians found the TM Test useful for CR treatment planning. CR participants with impaired EAP spent significantly more training time on EAP exercises compared to CR participants with intact EAP (20.11% vs 3.32%). This study found that it is feasible to use the TM Test in community clinics and the test was perceived as clinically useful for personalizing treatment.

The Relationship Between Depressive Symptoms, eHealth Literacy, and Asthma Outcomes in the Context of a Mobile Health Intervention.

OBJECTIVE: The ASTHMAXcel PRO mobile app provides asthma education and collects asthma outcome data. The objective of this study was to evaluate the associations between health/electronic health literacy (eHealth literacy) and depressive symptoms with app usage and clinical outcomes. METHODS: Adults with persistent asthma were recruited to use the app. Participants completed the Patient Health Questionnaire-9 to assess for depressive symptoms, Asthma Control Test, Mini Asthma Quality of Life (QOL) Questionnaire, and the Newest Vital Sign tool to measure health literacy. Data on a subset of participants were available on eHealth literacy ( n = 24) and average number of app logins across 2 months ( n = 40). RESULTS: The total study sample included 96 participants (46% non-Hispanic Black, 44.4% Hispanic). The average participant age was 44.0 (standard deviation = 14.9) years, with 74% identifying as female. Increased depressive symptoms were associated with worse asthma control ( ß = -0.46, p < .001) and asthma QOL ( ß = -0.38, p < .001), but not eHealth literacy. Higher eHealth literacy was associated with worse asthma QOL ( ß = -0.48, p = .02) and more app logins ( ß = 0.59, p = .04). Newest Vital Sign scores were not associated with any of the other measures. CONCLUSIONS: Depressive symptoms were associated with worse asthma outcomes. eHealth literacy was associated with increased patient engagement with the app and worse asthma QOL, which may reflect patients with worse QOL seeking out health information on the Internet (although directionality could not be assessed). Digital health literacy may be key to increasing patient engagement with mobile health interventions.Trial Registration: National Clinical Trial No. 03847142, https://clinicaltrials.gov/ct2/show/NCT03847142 .

Development of the First Episode Digital Monitoring mHealth Intervention for People With Early Psychosis: Qualitative Interview Study With Clinicians.

BACKGROUND: Mobile health (mHealth) technologies have been used extensively in psychosis research. In contrast, their integration into real-world clinical care has been limited despite the broad availability of smartphone-based apps targeting mental health care. Most apps developed for treatment of individuals with psychosis have focused primarily on encouraging self-management skills of patients via practicing cognitive behavioral techniques learned during face-to-face clinical sessions (eg, challenging dysfunctional thoughts and relaxation exercises), reminders to engage in health-promoting activities (eg, exercising, sleeping, and socializing), or symptom monitoring. In contrast, few apps have sought to enhance the clinical encounter itself to improve shared decision-making (SDM) and therapeutic relationships with clinicians, which have been linked to positive clinical outcomes. OBJECTIVE: This qualitative study sought clinicians' input to develop First Episode Digital Monitoring (FREEDoM), an app-based mHealth intervention. FREEDoM was designed to improve the quality, quantity, and timeliness of clinical and functional data available to clinicians treating patients experiencing first-episode psychosis (FEP) to enhance their therapeutic relationship and increase SDM. METHODS: Following the app's initial development, semistructured qualitative interviews were conducted with 11 FEP treatment providers at 3 coordinated specialty care clinics to elicit input on the app's design, the data report for clinicians, and planned usage procedures. We then generated a summary template and conducted matrix analysis to systematically categorize suggested adaptations to the evidence-based intervention using dimensions of the Framework for Reporting Adaptations and Modifications-Enhanced (FRAME) and documented the rationale for adopting or rejecting suggestions. RESULTS: The clinicians provided 31 suggestions (18 adopted and 13 rejected). Suggestions to add or refine the content were most common (eg, adding questions in the app). Adaptations to context were most often related to plans for implementing the intervention, how the reported data were displayed to clinicians, and with whom the reports were shared. Reasons for suggestions primarily included factors related to health narratives and priorities of the patients (eg, focus on the functional impact of symptoms vs their severity), providers' clinical judgment (eg, need for clinically relevant information), and organizations' mission and culture. Reasons for rejecting suggestions included requests for data and procedures beyond the intervention's scope, concerns regarding dilution of the intervention's core components, and concerns about increasing patient burden while using the app. CONCLUSIONS: FREEDoM focuses on a novel target for the deployment of mHealth technologies in the treatment of FEP patients-the enhancement of SDM and improvement of therapeutic relationships. This study illustrates the use of the FRAME, along with methods and tools for rapid qualitative analysis, to systematically track adaptations to the app as part of its development process. Such adaptations may contribute to enhanced acceptance of the intervention by clinicians and a higher likelihood of integration into clinical care. TRIAL REGISTRATION: ClinicalTrials.gov NCT04248517; https://tinyurl.com/tjuyxvv6.

Feasibility and acceptability of remotely accessed cognitive remediation for schizophrenia in public health settings.

Cognitive remediation (CR) is an evidence-based therapy used to improve cognition in people with schizophrenia. However, it often requires multiple in-person clinic sessions per week, which can limit scalability. This mixed methods study considered the feasibility and acceptability of a hybrid approach, which allowed for half the sessions to be conducted remotely as homework, without the clinician present. Individuals with schizophrenia were randomized to either all in-clinic or hybrid conditions and completed questionnaires and individual interviews about their experience. CR clinicians provided feedback in complement. Because of limited access to technology, most Hybrid CR participants had to come to clinic to access computers and often sought clinician support to do their homework. Participants in the two conditions were equally satisfied per the Client Satisfaction Questionnaire, and the majority reported perceived benefit and enjoyment. Both CR participants and clinicians identified access to technology as a barrier to program feasibility, while availability of clinician support positively impacted acceptability. Suggestions to improve CR highlighted adopting a flexible approach to providing CR that accounts for participant access to technology, potential benefit from peer interaction, and need for clinician support.

Discovery of a Glucocorticoid Receptor (GR) Activity Signature Using Selective GR Antagonism in ER-Negative Breast Cancer.

Purpose: Although high glucocorticoid receptor (GR) expression in early-stage estrogen receptor (ER)-negative breast cancer is associated with shortened relapse-free survival (RFS), how associated GR transcriptional activity contributes to aggressive breast cancer behavior is not well understood. Using potent GR antagonists and primary tumor gene expression data, we sought to identify a tumor-relevant gene signature based on GR activity that would be more predictive than GR expression alone.Experimental Design: Global gene expression and GR ChIP-sequencing were performed to identify GR-regulated genes inhibited by two chemically distinct GR antagonists, mifepristone and CORT108297. Differentially expressed genes from MDA-MB-231 cells were cross-evaluated with significantly expressed genes in GR-high versus GR-low ER-negative primary breast cancers. The resulting subset of GR-targeted genes was analyzed in two independent ER-negative breast cancer cohorts to derive and then validate the GR activity signature (GRsig).Results: Gene expression pathway analysis of glucocorticoid-regulated genes (inhibited by GR antagonism) revealed cell survival and invasion functions. GR ChIP-seq analysis demonstrated that GR antagonists decreased GR chromatin association for a subset of genes. A GRsig that comprised n = 74 GR activation-associated genes (also reversed by GR antagonists) was derived from an adjuvant chemotherapy-treated Discovery cohort and found to predict probability of relapse in a separate Validation cohort (HR = 1.9; P = 0.012).Conclusions: The GRsig discovered herein identifies high-risk ER-negative/GR-positive breast cancers most likely to relapse despite administration of adjuvant chemotherapy. Because GR antagonism can reverse expression of these genes, we propose that addition of a GR antagonist to chemotherapy may improve outcome for these high-risk patients. Clin Cancer Res; 24(14); 3433-46. ©2018 AACR.

GR and ER Coactivation Alters the Expression of Differentiation Genes and Associates with Improved ER+ Breast Cancer Outcome.

UNLABELLED: In estrogen receptor (ER)-negative breast cancer, high tumor glucocorticoid receptor (GR) expression has been associated with a relatively poor outcome. In contrast, using a meta-analysis of several genomic datasets, here we find that tumor GR mRNA expression is associated with improved ER(+) relapse-free survival (RFS; independently of progesterone receptor expression). To understand the mechanism by which GR expression is associated with a better ER(+) breast cancer outcome, the global effect of GR-mediated transcriptional activation in ER(+) breast cancer cells was studied. Analysis of GR chromatin immunoprecipitation followed by high-throughput sequencing in ER(+)/GR(+) MCF-7 cells revealed that upon coactivation of GR and ER, GR chromatin association became enriched at proximal promoter regions. Furthermore, following ER activation, increased GR chromatin association was observed at ER, FOXO, and AP1 response elements. In addition, ER associated with GR response elements, suggesting that ER and GR interact in a complex. Coactivation of GR and ER resulted in increased expression (relative to ER activation alone) of transcripts that encode proteins promoting cellular differentiation (e.g., KDM4B, VDR) and inhibiting the Wnt signaling pathway (IGFBP4). Finally, expression of these individual prodifferentiation genes was associated with significantly improved RFS in ER(+) breast cancer patients. Together, these data suggest that the coexpression and subsequent activity of tumor cell GR and ER contribute to the less aggressive natural history of early-stage breast cancer by coordinating the altered expression of genes favoring differentiation. IMPLICATIONS: The interaction between ER and GR activity highlights the importance of context-dependent nuclear receptor function in cancer. Mol Cancer Res; 14(8); 707-19. ©2016 AACR.