Securing direct stakeholder feedback to inform clinical research in serious mental illness: Results of a patient and family perspectives survey.

Mental illness research routinely includes unfamiliar or potentially frightening procedures like lumbar puncture (LP), contributing to low enrollment and retention. Previous studies related to LP acceptance have focused on older individuals, and little information on participant preferences for educational materials is available. We developed an online survey assessing existing knowledge, comfort and concerns, and preferences for educational materials in the context of our clinical study on schizophrenia spectrum conditions (SSCs). We found that participants were generally knowledgeable and interested in engaging with clinical SSC research. Frequency of engagement with research publications differed significantly by participant groups and age. Comfort levels were consistently highest for study procedures other than LP, though surprisingly the average number of informational needs per procedure was not significantly different for LP compared to other procedures. Preferences for format and source of educational materials varied across participant groups and age. Our results suggest that younger individuals with an SSC diagnosis are likely to have limited exposure to information, and proactively providing accessible and accurate educational materials may improve positive perceptions of LP. Providing content in a range of formats and sources will ensure that participants and their support networks have access to their preferred resources.

Lived Experience-Led Research Agenda to Address Early Death in People With a Diagnosis of a Serious Mental Illness: A Consensus Statement.

Importance: People with serious mental illness (SMI), defined as a diagnosis of schizophrenia spectrum disorder, bipolar disorder, or disabling major depressive disorder) die approximately 10 to 25 years earlier than the general population. Objective: To develop the first-ever lived experience-led research agenda to address early mortality in people with SMI. Evidence Review: A virtual 2-day roundtable comprising 40 individuals convened on May 24 and May 26, 2022, and used a virtual Delphi method to arrive at expert group consensus. Participants responded to 6 rounds of virtual Delphi discussion via email that prioritized research topics and agreement on recommendations. The roundtable was composed of individuals with lived experience of mental health and/or substance misuse, peer support specialists, recovery coaches, parents and caregivers of people with SMI, researchers and clinician-scientists with and without lived experience, policy makers, and patient-led organizations. Twenty-two of 28 (78.6%) of the authors who provided data represented people with lived experiences. Roundtable members were selected by reviewing the peer-reviewed and gray literature on early mortality and SMI, direct email, and snowball sampling. Findings: The following recommendations are presented in order of priority as identified by the roundtable participants: (1) improve the empirical understanding of the direct and indirect social and biological contributions of trauma on morbidity and early mortality; (2) advance the role of family, extended families, and informal supporters; (3) recognize the importance of co-occurring disorders and early mortality; (4) redefine clinical education to reduce stigma and support clinicians through technological advancements to improve diagnostic accuracy; (5) examine outcomes meaningful to people with an SMI diagnosis, such as loneliness and sense of belonging, and stigma and their complex relationship with early mortality; (6) advance the science of pharmaceuticals, drug discovery, and choice in medication use; (7) use precision medicine to inform treatment; and (8) redefine the terms system literacy and health literacy. Conclusions and Relevance: The recommendations of this roundtable are a starting point for changing practice and highlighting lived experience-led research priorities as an option to move the field forward.

Needs and Experiences of Users of Digital Navigation Tools for Mental Health Treatment and Supportive Services: Survey Study.

BACKGROUND: Despite a recent proliferation in web-based and digital resources that are designed to assist users in finding appropriate mental health treatment and supportive services, it can be overwhelming, confusing, and difficult for an individual or family member to access and use an appropriate navigation tool. As digital resources are increasingly sought after, there is an urgent need for a clearer understanding of digital navigation tools in order to help link individuals with the tool that is best suited to their needs. OBJECTIVE: The objective of this study was to determine the needs of individuals seeking mental health treatment and supportive services and to quantify their experiences and satisfaction with available digital navigation tools. METHODS: A survey was offered via an email newsletter and social media posting throughout the extended membership of the National Alliance on Mental Illness, which includes both individuals with a mental health condition and their family members and support networks. A 13-item anonymous survey, which consisted of multiple-choice and open response options, was developed to measure participants' past use of and experiences with web-based, mobile, and phone-based navigation tools. The survey was available from April 9 through May 21, 2020. RESULTS: A total of 478 respondents completed the survey; the majority of respondents were female (397/478, 83.1%) and aged ≥35 years (411/478, 86%). Younger respondents were more likely to report seeking mental health services for themselves, while older respondents were more likely to be searching for such services on behalf of a family member. The majority of respondents seeking such services on behalf of a family member (113/194, 58.2%) required a combination of mental health treatment and supportive services. Furthermore, two-thirds of respondents (322/478, 67.4%) used a navigation tool to find treatment or services. The majority of respondents who provided feedback about their experiences with navigation tools (224/280, 80%) reported difficulties, with data availability and accuracy being the most commonly reported issues. CONCLUSIONS: The survey results suggest that issues with data availability and accuracy in available navigation tools remain a major barrier for locating timely and appropriate mental health treatment and supportive services within the population of individuals seeking such services. Particularly for individuals seeking care on behalf of a family member, improving the accuracy of and users' experiences with navigation tools could have a major impact on effectively connecting people to treatment and support services.

Stigma and functional neurological disorder: a research agenda targeting the clinical encounter.

Stigma against patients with functional neurological disorder (FND) presents obstacles to diagnosis, treatment, and research. The lack of biomarkers and the potential for symptoms to be misunderstood, invalidated, or dismissed can leave patients, families, and healthcare professionals at a loss. Stigma exacerbates suffering and unmet needs of patients and families, and can result in poor clinical management and prolonged, repetitive use of healthcare resources. Our current understanding of stigma in FND comes from surveys documenting frustration experienced by providers and distressing healthcare interactions experienced by patients. However, little is known about the origins of FND stigma, its prevalence across different healthcare contexts, its impact on patient health outcomes, and optimal methods for reduction. In this paper, we set forth a research agenda directed at better understanding the prevalence and context of stigma, clarifying its impact on patients and providers, and promoting best practices for stigma reduction.

Regulatory perspective on minimal residual disease flow cytometry testing in multiple myeloma.

The FDA has co-sponsored three workshops to address minimal residual disease (MRD) detection in acute lymphocytic leukemia (ALL), chronic lymphocytic leukemia (CLL), and acute myeloid leukemia (AML) as well as an FDA-NCI roundtable symposium on MRD detection and its use as a response biomarker in Multiple Myeloma (MM). As clinical outcomes in MM continue to improve with the introduction of new therapeutics, consideration of biomarkers and their development as validated surrogate endpoints that can be used in the place of traditional clinical trial endpoints of progression-free survival (PFS) will be fundamental to expeditious drug development. This article will describe the FDA drug approval process, the regulatory framework through which a biomarker can be used as a surrogate endpoint for drug approval, and how MRD detection in MM fits within this context. In parallel, this article will also describe the FDA current device clearance process with emphasis on the analytical development as it might apply to an in vitro diagnostic assay for the detection of MRD in MM. It is anticipated that this Special Issue may possibly represent how MRD might serve as a drug development tool in hematological malignancies.

Norepinephrine regulates hepatic innate immune system in leptin-deficient mice with nonalcoholic steatohepatitis.

It is not known why natural killer T (NKT) cells, which modulate liver injury by regulating local cytokine production, are reduced in leptin-deficient ob/ob mice. NKT cells express adrenoceptors. Thus, we hypothesize that the low norepinephrine (NE) activity of ob/ob mice promotes depletion of liver NKT cells, thereby sensitizing ob/ob livers to lipopolysaccharide (LPS) toxicity. To evaluate this hypothesis, hepatic NKT cells were quantified in wild-type mice before and after treatment with NE inhibitors, and in dopamine beta-hydroxylase knockout mice (which cannot synthesize NE) and ob/ob mice before and after 4 weeks of NE supplementation. Decreasing NE activity consistently reduces liver NKT cells, while increasing NE has the opposite effect. Analysis of hepatic and thymic NKT cells in mice of different ages demonstrate an age-related accumulation of hepatic NKT cells in normal mice, while liver NKT cells become depleted after birth in ob/ob mice, which have increased apoptosis of hepatic NKT cells. NE treatment inhibits apoptosis and restores hepatic NKT cells. In ob/ob mice with reduced hepatic NKT cells, hepatic T and NKT cells produce excessive T helper (Th)-1 proinflammatory cytokines and the liver is sensitized to LPS toxicity. NE treatment decreases Th-1 cytokines, increases production of Th-2 cytokines, and reduces hepatotoxicity. Studies of CD1d-deficient mice, which lack the receptor required for NKT cell development, demonstrate that they are also unusually sensitive to LPS hepatotoxicity. In conclusion, low NE activity increases hepatic NKT cell apoptosis and depletes liver NKT cells, promoting proinflammatory polarization of hepatic cytokine production that sensitizes the liver to LPS toxicity.