Improving Referral Patterns for Bronchoscopic Lung Volume Reduction: A Quality Improvement Initiative.

Bronchoscopic lung volume reduction (BLVR) is a minimally invasive treatment option for patients with severe emphysema and hyperinflation refractory to optimal medical care. This therapy is effective in improving functional status and quality of life, underscoring the importance of identifying potential procedure candidates. To our knowledge, scalable strategies to improve the referral of advanced lung disease patients are lacking. This quality improvement project aimed to increase identification and referral for BLVR in a large Veterans Affairs academic medical center. We show implementing case identification within a pulmonary function testing report, in conjunction with provider education, increased referral rates for BLVR. Because of the ubiquity of lung function testing, other advanced lung disease programs may consider adopting this strategy to improve patients' access to timely clinical evaluation and therapy.

Donepezil-associated survival benefits among Alzheimer's disease patients are retained but not enhanced during COVID-19 infections.

Background and Aim: Donepezil is a front-line treatment for Alzheimer's disease. Donepezil treatment is associated with decreased risk of all-cause mortality. Specific protection is observed in pneumonia and cardiovascular disease. We hypothesized that donepezil treatment would improve mortality among Alzheimer's patients following infection with COVID-19. The objective of this study is to assess the influence of ongoing donepezil treatment on survival in Alzheimer's disease patients after polymerase chain reaction (PCR)-confirmed COVID-19 infection. Methods: This is a retrospective cohort study. We conducted a national survey of Veterans with Alzheimer's disease to assess the influence of ongoing donepezil treatment on survival in Alzheimer's disease patients after PCR-confirmed COVID-19 infection. We assessed all-cause 30-day mortality stratified by COVID-19 infection and donepezil use, estimating odds ratios using multivariate logistic regression. Results: Among people with Alzheimer's disease and COVID-19, all-cause 30-day mortality was 29% (47/163) for people taking donepezil compared with 38% (159/419) for those who were not. Among people with Alzheimer's disease without COVID-19, all-cause 30-day mortality was 5% (189/4189) for people taking donepezil compared with 7% (712/10,241) for those who were not. Adjusting for covariates, the decrease in mortality associated with donepezil did not differ between people with and without COVID-19 (interaction p = 0.710). Conclusion: The known survival benefits of donepezil were retained but not found to be specific to COVID-19 among people with Alzheimer's disease.

What are key characteristics of adults with advanced heart failure discharged from ICU?

BACKGROUND: As the number of people with heart failure and treatment complexity increases, many hospitals are implementing Advanced Heart Failure Intensive Care Units (AHFICU). However, little evidence concerning the clinical characteristics of people admitted to AHFICUs exists. Understanding the clinical characteristics of people admitted to the AHFICU will assist nurses with implementing tailored interventions to ensure high-quality care delivery. AIM: The purpose of this study was to describe the clinical characteristics of people who are admitted to and discharged from an AHFICU. STUDY DESIGN: Baseline data from a longitudinal descriptive study were collected on adults (N = 43) admitted to an AHFICU. Heart failure severity, self-management ability, cognition, sleep quality, and other clinical characteristics were assessed. RESULTS: Most study participants were New York Heart Association functional class IV (n = 24) or class III (n = 14), indicating poor functional capacity. Over half had mild cognitive impairment and poor sleep quality was prevalent (92.7%). Participants had adequate levels of heart failure knowledge, but low levels of heart failure self-management decision-making and ability. CONCLUSIONS: Interventions to address the unique clinical characteristics of AHFICU patients include sleep hygiene, integration of cognitive, sleep, and self-management assessments into the electronic medical record. Addressing the unique clinical needs of people with heart failure will lead to patient-centered, evidence-based, and safe care. RELEVANCE TO CLINICAL PRACTICE: Understanding characteristics of this population addresses this evidence gap and targeted clinical interventions to address unique discharge needs of this population are proposed. Sleep quality education should be done throughout hospitalization on sleep strategies and self-management coaching to facilitate adoption of new sleep routines. Healthcare providers should ensure each patient has care support upon discharge and take cognitive status into consideration during teaching. Addressing self-management readiness should include providing scenarios as part of discharge preparation. Providers must include addressing comorbidities and how they may affect heart failure self-management, such as teaching about sleep apnea device use and encouraging compliance.

Sleep Quality in the Advanced Heart Failure ICU.

In this study, we evaluated sleep quality changes in persons with advanced heart failure (HF) who were admitted to the intensive care unit. Sleep quality was assessed at admission, during hospitalization, and post-discharge. Statistical tests compared within subject mean sleep quality over time (n = 22). Poor quality sleep was reported by 96% of participants at admission, 96% during hospitalization, and 86% post-discharge. Significant differences were found between timepoints in global sleep quality, subject sleep quality, sleep duration, and habitual sleep efficiency. A greater proportion of these participants had poor global sleep quality during hospitalization than previously reported. Participants reported better sleep post-discharge than admission and during hospitalization. Interventions enhancing hospital sleep, along with home sleep self-management education, would improve HF outcomes. Implementation science methods are warranted to integrate efficacious interventions in this population.

The Emerging Scholars' Network Within MNRS: From Acorns to Oaks.

As the nursing faculty shortage persists, there is an urgent need to develop emerging nurse scholars into research leaders capable of advocating for the profession and expanding on the mission to improve health. To address this need, the Midwest Nursing Research Society (MNRS) commissioned a student task force that led to the development of the Emerging Scholars Network (ESN). The purpose of this article is to describe how the ESN was developed, integrated, and promoted within the MNRS to advance the overall mission and sustainability of the society. The establishment and success of the ESN is described using the Five Developmental Stages of Organization Evolution. These stages include the following: (a) Developing a Concept; (b) Launching a Start-Up; (c) Establishing Credibility; (d) Creating Sustainability; and (e) Road to Maturing and Legacy. Recommendations for continued development of the ESN are provided.

Autism-specific maternal autoantibodies produce behavioral abnormalities in an endogenous antigen-driven mouse model of autism.

Immune dysregulation has been noted consistently in individuals with autism spectrum disorder (ASD) and their families, including the presence of autoantibodies reactive to fetal brain proteins in nearly a quarter of mothers of children with ASD versus <1% in mothers of typically developing children. Our lab recently identified the peptide epitope sequences on seven antigenic proteins targeted by these maternal autoantibodies. Through immunization with these peptide epitopes, we have successfully created an endogenous, antigen-driven mouse model that ensures a constant exposure to the salient autoantibodies throughout gestation in C57BL/6J mice. This exposure more naturally mimics what is observed in mothers of children with ASD. Male and female offspring were tested using a comprehensive sequence of behavioral assays, as well as measures of health and development highly relevant to ASD. We found that MAR-ASD male and female offspring had significant alterations in development and social interactions during dyadic play. Although 3-chambered social approach was not significantly different, fewer social interactions with an estrous female were noted in the adult male MAR-ASD animals, as well as reduced vocalizations emitted in response to social cues with robust repetitive self-grooming behaviors relative to saline treated controls. The generation of MAR-ASD-specific epitope autoantibodies in female mice prior to breeding created a model that demonstrates for the first time that ASD-specific antigen-induced maternal autoantibodies produced alterations in a constellation of ASD-relevant behaviors.

Peptides of neuron specific enolase as potential ASD biomarkers: From discovery to epitope mapping.

Autism spectrum disorder (ASD) is an important health issue and affects 1 in 59 children in the US. Prior studies determined that maternal autoantibody related (MAR) autism is thought to be associated with ~23% of ASD cases. We previously identified seven MAR-specific autoantigens including CRMP1, CRMP2, GDA, LDHA, LDHB, STIP1, and YBX1. We subsequently described the epitope peptide sequences recognized by maternal autoantibodies for each of the seven ASD-specific autoantigens. The aim of the current study was to expand upon our previous work and identify additional antigens recognized by the ASD-specific maternal autoantibodies, as well as to map the unique ASD-specific epitopes using microarray technology. Fetal Rhesus macaque brain tissues were separated by molecular weight and a fraction containing bands between 37 and 45 kDa was analyzed using 2-D gel electrophoresis, followed by peptide mass mapping using MALDI-TOF MS and TOF/TOF tandem MS/MS. Using this methodology, Neuron specific enolase (NSE) was identified as a target autoantigen and selected for epitope mapping. The full NSE sequence was translated into 15-mer peptides with an overlap of 14 amino acids onto microarray slides and probed with maternal plasma from mothers with an ASD child and from mothers with a Typically Developing child (TD) (ASD = 27 and TD = 21). The resulting data were analyzed by T-test. We found 16 ASD-specific NSE-peptide sequences for which four sequences were statistically significant (p < 0.05) using both the t-test and SAM t-test: DVAASEFYRDGKYDL (p = 0.047; SAM score 1.49), IEDPFDQDDWAAWSK (p = 0.049; SAM score 1.49), ERLAKYNQLMRIEEE (p = 0.045; SAM score 1.57), and RLAKYNQLMRIEEEL (p = 0.017; SAM score 1.82). We further identified 5 sequences that were recognized by both ASD and TD antibodies suggesting a large immunodominant epitope (DYPVVSIEDPFDQDDWAAW). While maternal autoantibodies against the NSE protein are present both in mothers with ASD and mothers of TD children, there are several ASD-specific epitopes that can potentially be used as MAR ASD biomarkers. Further, studies including analysis of NSE as a target protein in combination with the previously identified MAR ASD autoantigens are currently underway.

Towards a nanoparticle-based prophylactic for maternal autoantibody-related autism.

Recently, the causative agents of Maternal Autoantibody-Related (MAR) autism, pathological autoantibodies and their epitopic targets (e.g. lactate dehydrogenase B [LDH B] peptide), have been identified. Herein, we report on the development of Systems for Nanoparticle-based Autoantibody Reception and Entrapment (SNAREs), which we hypothesized could scavenge disease-propagating MAR autoantibodies from the maternal blood. To demonstrate this functionality, we synthesized 15 nm dextran iron oxide nanoparticles surface-modified with citric acid, methoxy PEG(10 kDa) amine, and LDH B peptide (33.8 µg peptide/cm2). In vitro, we demonstrated significantly lower macrophage uptake for SNAREs compared to control NPs. The hallmark result of this study was the efficacy of the SNAREs to remove 90% of LDH B autoantibody from patient-derived serum. Further, in vitro cytotoxicity testing and a maximal tolerated dose study in mice demonstrated the safety of the SNARE formulation. This work establishes the feasibility of SNAREs as the first-ever prophylactic against MAR autism.

Identification of the antigenic epitopes of maternal autoantibodies in autism spectrum disorders.

Several groups have described the presence of fetal brain-reactive maternal autoantibodies in the plasma of some mothers whose children have autism spectrum disorder (ASD). We previously identified seven autoantigens targeted by these maternal autoantibodies, each of which is expressed at significant levels in the developing brain and has demonstrated roles in typical neurodevelopment. To further understand the binding repertoire of the maternal autoantibodies, as well as the presence of any meaningful differences with respect to the recognition and binding of these ASD-specific autoantibodies to each of these neuronal autoantigens, we utilized overlapping peptide microarrays incubated with maternal plasma samples obtained from the Childhood Autism Risk from Genetics and Environment (CHARGE) Study. In an effort to identify the most commonly recognized (immunodominant) epitope sequences targeted by maternal autoantibodies for each of the seven ASD-specific autoantigens, arrays were screened with plasma from mothers with children across diagnostic groups (ASD and typically developing (TD)) that were positive for at least one antigen by western blot (N = 67) or negative control mothers unreactive to any of the autoantigens (N = 18). Of the 63 peptides identified with the discovery microarrays, at least one immunodominant peptide was successfully identified for each of the seven antigenic proteins using subsequent selective screening microarrays. Furthermore, while limited by our relatively small sample size, there were peptides that were distinctly recognized by autoantibodies relative to diagnosis For example, reactivity was observed exclusively in mothers of children of ASD towards several peptides, including the LDH-B peptides DCIIIVVSNPVDILT (9.1% ASD vs. 0% TD; odds ratio (95% CI) = 6.644 (0.355-124.384)) and PVAEEEATVPNNKIT (5.5% ASD vs. 0% TD; odds ratio (95% CI) = 4.067 (0.203-81.403)).These results suggest that there are differences in the binding repertoire between the antigen positive ASD and TD maternal samples. Further, the autoantibodies in plasma from mothers of children with ASD bound to a more diverse set of peptides, and there were specific peptide binding combinations observed only in this group. Future studies are underway to determine the critical amino acids necessary for autoantibody binding, which will be essential in developing a potential therapeutic strategy for maternal autoantibody related (MAR) ASD.

Octogenarians' post-acute care use after cardiac valve surgery and recovery: clinical implications.

Octogenarians receiving cardiac valve surgery is increasing and recovery is challenging. Post-acute care (PAC) services assist with recovery, yet services provided in facilities do not provide adequate cardiac-focused care or long-term self-management support. The purpose of the paper was to report post-acute care discharge rates in octogenarians and propose clinical implications to improve PAC services. Using a 2003 Medicare Part A database, we studied post-acute care service use in octogenarians after cardiac valve surgery. We propose expansion of the Geriatric Cardiac Care model to include broader clinical therapy dynamics. The sample (n = 10,062) included patients over 80 years discharged from acute care following valve surgery. Post-acute care services were used by 68% of octagarians following cardiac valve surgery (1% intermediate rehabilitation, 35% skilled nursing facility, 32% home health). The large percentage of octagarians using PAC point to the importance of integrating geriatric cardiac care into post-acute services to optimize recovery outcomes.

Autoimmunity, Autoantibodies, and Autism Spectrum Disorder.

Auism spectrum disorder (ASD) now affects one in 68 births in the United States and is the fastest growing neurodevelopmental disability worldwide. Alarmingly, for the majority of cases, the causes of ASD are largely unknown, but it is becoming increasingly accepted that ASD is no longer defined simply as a behavioral disorder, but rather as a highly complex and heterogeneous biological disorder. Although research has focused on the identification of genetic abnormalities, emerging studies increasingly suggest that immune dysfunction is a viable risk factor contributing to the neurodevelopmental deficits observed in ASD. This review summarizes the investigations implicating autoimmunity and autoantibodies in ASD.

Maternal Anti-Fetal Brain IgG Autoantibodies and Autism Spectrum Disorder: Current Knowledge and its Implications for Potential Therapeutics.

Several studies have found a correlation between the presence of circulating maternal autoantibodies and neuronal dysfunction in the neonate. Specifically, maternal anti-brain autoantibodies, which may access the fetal compartment during gestation, have been identified as one risk factor for developing autism spectrum disorder (ASD). Studies by our laboratory elucidated seven neurodevelopmental proteins recognized by maternal autoantibodies whose presence is associated with a diagnosis of maternal autoantibody-related (MAR) autism in the child. While the specific process of anti-brain autoantibody generation is unclear and the detailed pathogenic mechanisms are currently unknown, identification of the maternal autoantibody targets increases the therapeutic possibilities. The potential therapies discussed in this review provide a framework for possible future medical interventions.