Understanding preferences for receiving health communications and information about clinical trials: a cross-sectional study among US adults.

OBJECTIVE: Effective health communication is critical for understanding and acting on health information. This cross-sectional study explored participants' understanding of their health condition, their preferences for receiving health communications, and their interest in receiving clinical trial results across several therapeutic areas. METHODS: The study recruited participants via social media, email newsletters, and advocacy organizations. An online screener captured demographic information (health conditions, age, race/ethnicity, gender, and education). Eligible participants were emailed an online survey assessing preferred sources and formats for receiving health information, interest in learning about topics related to the results of clinical trials, and health literacy levels. RESULTS: In total, 449 participants (median age, 35 years [range, 18-76]; White, 53%; higher education, 65%; mean (range) health literacy score, 1.9 [0.4-3.0]) from 45 US states completed the survey representing 12 disease indications (bipolar, blood and solid tumor cancers, irritable bowel syndrome, inflammatory bowel disease, major depressive disorder, migraine, Parkinson's, psoriasis/atopic dermatitis, retinal vein occlusion/macular degeneration, rheumatoid arthritis, and spasticity). Healthcare providers were the preferred source of health information (59%), followed by Internet searches (11%). Least preferred sources were social media (5%), friends/family (3%), and email newsletters (2%). Participants preferred multiple formats and ranked reading materials online as most preferred (33%), along with videos (28%) and infographics (27%). Printed materials (14%) and audio podcasts (9%) were the least preferred formats. A majority of the participants reported that the health information they found was hard to understand (57%) and confusing (62%). Most participants (85%) were somewhat/very interested in learning about clinical trial results, with the highest interest in short summaries of safety (78%) and efficacy (74%) results. CONCLUSION: Effective health communication may be achieved via multiple formats shared directly by healthcare providers.

Researchers wanted to learn how people preferred to receive health-related communications, including information about the results of clinical trials. They surveyed 449 people from 45 US states with 12 different health conditions. The survey questions asked people about their preferred sources and ways of getting health information. It also asked about their interest in learning about clinical trials related to their health condition. The results showed that most people preferred to get health information from their healthcare providers (59%). The Internet was the second most popular choice (11%) for getting health information. People did not like getting health information from social media, friends or family, or email newsletters as much. When it came to how health information was shared, people liked reading materials online (33%), watching videos (28%), and looking at infographics (27%). They did not like printed materials and audio podcasts as much. Most people (85%) were interested in learning about the results of clinical trials in short summaries. They wanted to know about the safety (78%) and how well the treatments worked (74%) in the short summaries. In conclusion, people liked getting health information from healthcare providers like doctors, nurses, and others in different formats. Sharing information in different formats through healthcare providers may improve communication for patients with different health conditions.

Deficient Natural Killer Dendritic Cell Responses Underlay the Induction of Theiler's Virus-Induced Autoimmunity.

UNLABELLED: The initiating events in autoimmune disease remain to be completely understood, but it is thought that genetic predisposition synergizes with "environmental" factors, including viral infection, leading to disease. One elegant animal model used to study the pathogenesis of multiple sclerosis that perfectly blends genetics and environmental components in the context of virus-induced autoimmunity is Theiler's murine encephalitis virus-induced demyelinating disease (TMEV-IDD). TMEV-infected disease-susceptible SJL/J mice develop a persistent central nervous system (CNS) infection and later develop autoimmune demyelination, while disease-resistant C57BL/6 (B6) mice rapidly clear the infection and develop no autoimmune pathology. Mice of the (B6 × SJL/J)F1 cross between these two mouse strains are classified as intermediately susceptible. We employed this model to investigate if rapid virus clearance in B6 versus SJL/J mice was perhaps related to differences in the innate immune response in the CNS of the two strains in the first few days following intracerebral virus inoculation. Here we show that SJL/J mice lack, in addition to NK cells, a novel innate immune subset known as natural killer dendritic cells (NKDCs), which express phenotypic markers (CD11c(int) NK1.1(+)) and functional activity of both NK cells and DCs. These NKDCs are activated in the periphery and migrate into the infected CNS in a very late antigen 4 (VLA-4)-dependent fashion. Most significantly, NKDCs are critical for CNS clearance of TMEV, as transfer of NKDCs purified from B6 mice into TMEV-IDD-susceptible (B6 × SJL/J)F1 mice promotes viral clearance. Together the findings of this work show for the first time a link between NKDCs, viral infection, and CNS autoimmunity. IMPORTANCE: Viral infection is an important cofactor, along with genetic susceptibility, in the initiation of a variety of organ-specific autoimmune diseases. Thus, in-depth understanding of how virus infections trigger autoimmunity may lead to novel ways to prevent or treat these diseases. Theiler's murine encephalitis virus-induced demyelinating disease (TMEV-IDD) serves as an important model for the human T cell-mediated autoimmune demyelinating disease multiple sclerosis. Induction of TMEV-IDD is genetically controlled as SJL/J mice develop persistent central nervous system (CNS) infection leading to chronic autoimmune demyelination, while C57BL/6 mice rapidly clear virus and are disease resistant. We determined that, as opposed to resistant B6 mice, disease-susceptible SJL/J mice lacked a unique innate immune population, the natural killer dendritic cell (NKDC), which was shown to play a critical role in early CNS virus clearance via its ability to both present virus antigen to T cells and to lyse target cells.

Virus infection, antiviral immunity, and autoimmunity.

As a group of disorders, autoimmunity ranks as the third most prevalent cause of morbidity and mortality in the Western World. However, the etiology of most autoimmune diseases remains unknown. Although genetic linkage studies support a critical underlying role for genetics, the geographic distribution of these disorders as well as the low concordance rates in monozygotic twins suggest that a combination of other factors including environmental ones are involved. Virus infection is a primary factor that has been implicated in the initiation of autoimmune disease. Infection triggers a robust and usually well-coordinated immune response that is critical for viral clearance. However, in some instances, immune regulatory mechanisms may falter, culminating in the breakdown of self-tolerance, resulting in immune-mediated attack directed against both viral and self-antigens. Traditionally, cross-reactive T-cell recognition, known as molecular mimicry, as well as bystander T-cell activation, culminating in epitope spreading, have been the predominant mechanisms elucidated through which infection may culminate in an T-cell-mediated autoimmune response. However, other hypotheses including virus-induced decoy of the immune system also warrant discussion in regard to their potential for triggering autoimmunity. In this review, we discuss the mechanisms by which virus infection and antiviral immunity contribute to the development of autoimmunity.

Molecular mimicry as an inducing trigger for CNS autoimmune demyelinating disease.

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) that affects about 0.1% of the worldwide population. This deleterious disease is marked by infiltration of myelin-specific T cells that attack the protective myelin sheath that surrounds CNS nerve axons. Upon demyelination, saltatory nerve conduction is disrupted, and patients experience neurologic deficiencies. The exact cause for MS remains unknown, although most evidence supports the hypothesis that both genetic and environmental factors contribute to disease development. Epidemiologic evidence supports a role for environmental pathogens, such as viruses, as potentially key contributors to MS induction. Pathogens can induce autoimmunity via several well-studied mechanisms with the most postulated being molecular mimicry. Molecular mimicry occurs when T cells specific for peptide epitopes derived from pathogens cross-react with self-epitopes, leading to autoimmune tissue destruction. In this review, we discuss an in vivo virus-induced mouse model of MS developed in our laboratory, which has contributed greatly to our understanding of the mechanisms underlying molecular mimicry-induced CNS autoimmunity.

Current landscape for T-cell targeting in autoimmunity and transplantation.

In recent years, substantial advances in T-cell immunosuppressive strategies and their translation to routine clinical practice have revolutionized management and outcomes in autoimmune disease and solid organ transplantation. More than 80 diseases have been considered to have an autoimmune etiology, such that autoimmune-associated morbidity and mortality rank as third highest in developed countries, after cardiovascular diseases and cancer. Solid organ transplantation has become the therapy of choice for many end-stage organ diseases. Short-term outcomes such as patient and allograft survival at 1 year, acute rejection rates, as well as time course of disease progression and symptom control have steadily improved. However, despite the use of newer immunosuppressive drug combinations, improvements in long-term allograft survival and complete resolution of autoimmunity remain elusive. In addition, the chronic use of nonspecifically targeted immunosuppressive drugs is associated with significant adverse effects and increased morbidity and mortality. In this article, we discuss the current clinical tools for immune suppression and attempts to induce long-term T-cell tolerance induction as well as much-needed future approaches to produce more short-acting, antigen-specific agents, which may optimize outcomes in the clinic.

The role of antigen presenting cells in multiple sclerosis.

Multiple sclerosis (MS) is a debilitating T cell mediated autoimmune disease of the central nervous system (CNS). Animal models of MS, such as experimental autoimmune encephalomyelitis (EAE) and Theiler's murine encephalomyelitis virus-induced demyelinating disease (TMEV-IDD) have given light to cellular mechanisms involved in the initiation and progression of this organ-specific autoimmune disease. Within the CNS, antigen presenting cells (APC) such as microglia and astrocytes participate as first line defenders against infections or inflammation. However, during chronic inflammation they can participate in perpetuating the self-destructive environment by secretion of inflammatory factors and/or presentation of myelin epitopes to autoreactive T cells. Dendritic cells (DC) are also participants in the presentation of antigen to T cells, even within the CNS. While the APCs alone are not solely responsible for mediating the destruction to the myelin sheath, they are critical players in perpetuating the inflammatory milieu. This review will highlight relevant studies which have provided insight to the roles played by microglia, DCs and astrocytes in the context of CNS autoimmunity.

Have we overestimated the benefit of human(ized) antibodies?

The infusion of animal-derived antibodies has been known for some time to trigger the generation of antibodies directed at the foreign protein as well as adverse events including cytokine release syndrome. These immunological phenomena drove the development of humanized and fully human monoclonal antibodies. The ability to generate human(ized) antibodies has been both a blessing and a curse. While incremental gains in the clinical efficacy and safety for some agents have been realized, a positive effect has not been observed for all human(ized) antibodies. Many human(ized) antibodies trigger the development of anti-drug antibody responses and infusion reactions. The current belief that antibodies need to be human(ized) to have enhanced therapeutic utility may slow the development of novel animal-derived monoclonal antibody therapeutics for use in clinical indications. In the case of murine antibodies, greater than 20% induce tolerable/negligible immunogenicity, suggesting that in these cases humanization may not offer significant gains in therapeutic utility. Furthermore, humanization of some murine antibodies may reduce their clinical effectiveness. The available data suggest that the utility of human(ized) antibodies needs to be evaluated on a case-by-case basis, taking a cost-benefit approach, taking both biochemical characteristics and the targeted therapeutic indication into account.