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Providers currently rely on universal screening to identify health-related social needs (HRSNs). Predicting HRSNs using EHR and community-level data could be more efficient and less resource intensive. Using machine learning models, we evaluated the predictive performance of HRSN status from EHR and community-level social determinants of health (SDOH) data for Medicare and Medicaid beneficiaries participating in the Accountable Health Communities Model. We hypothesized that Medicaid insurance coverage would predict HRSN status. All models significantly outperformed the baseline Medicaid hypothesis. AUCs ranged from 0.59 to 0.68. The top performance (AUC = 0.68 CI 0.66–0.70) was achieved by the “any HRSNs” outcome, which is the most useful for screening prioritization. Community-level SDOH features had lower predictive performance than EHR features. Machine learning models can be used to prioritize patients for screening. However, screening only patients identified by our current model(s) would miss many patients. Future studies are warranted to optimize prediction of HRSNs.

Background Despite the critical need for comprehensive and effective chronic pain care, delivery of such care remains challenging. Group medical visits (GMVs) offer an innovative and efficient model for providing comprehensive care for patients with chronic pain. The purpose of this systematic review was to identify barriers and facilitators (determinants) to implementing GMVs for adult patients with chronic pain. Methods The review included peer-reviewed studies reporting findings on implementation of GMVs for chronic pain, inclusive of all study designs. Pubmed, EMBASE, Web of Science, and Cochrane Library were searched. Studies of individual appointments or group therapy were excluded. The Mixed Methods Appraisal Tool was used to determine risk of bias. Data related to implementation determinants were extracted independently by two reviewers. Data synthesis was guided by the updated Consolidated Framework for Implementation Research. Results Thirty-three articles reporting on 25 studies met criteria for inclusion and included qualitative observational ( n  = 8), randomized controlled trial ( n  = 6), quantitative non-randomized ( n  = 9), quantitative descriptive ( n  = 3), and mixed methods designs ( n  = 7). The studies included in this review included a total of 2364 participants. Quality ratings were mixed, with qualitative articles receiving the highest quality ratings. Common multi-level determinants included the relative advantage of GMVs for chronic pain over other available models, the capability and motivation of clinicians, the cost of GMVs to patients and the health system, the need and opportunity of patients, the availability of resources and relational connections supporting recruitment and referral to GMVs within the clinic setting, and financing and policies within the outer setting. Conclusions Multi-level factors determine the implementation of GMVs for chronic pain. Future research is needed to investigate these determinants more thoroughly and to develop and test implementation strategies addressing these determinants to promote the scale-up of GMVs for patients with chronic pain. Trial registration This systematic review was registered with PROSPERO 2021 CRD42021231310 .

Adeno-associated virus (AAV)-based vectors are widely used for gene therapy, but the effect of pre-existing antibodies resulting from exposure to wild-type AAV is unclear. In addition, other poorly defined plasma factors could inhibit AAV vector transduction where antibodies are not detected. To better define the relationship between various forms of pre-existing AAV immunity and gene transfer, we studied valoctocogene roxaparvovec (BMN 270) in cynomolgus monkeys with varying pre-dose levels of neutralizing anti-AAV antibodies and non-antibody transduction inhibitors. BMN 270 is an AAV5-based vector for treating hemophilia A that encodes human B domain-deleted factor VIII (FVIII-SQ). After infusion of BMN 270 (6.0 × 1013 vg/kg) into animals with pre-existing anti-AAV5 antibodies, there was a mean decrease in maximal FVIII-SQ plasma concentration (Cmax) and AUC of 74.8% and 66.9%, respectively, compared with non-immune control animals, and vector genomes in the liver were reduced. In contrast, animals with only non-antibody transduction inhibitors showed FVIII-SQ plasma concentrations and liver vector copies comparable with those of controls. These results demonstrate that animals without AAV5 antibodies are likely responders to AAV5 gene therapy, regardless of other inhibiting plasma factors. The biological threshold for tolerable AAV5 antibody levels varied between individual animals and should be evaluated further in clinical studies.

Teach Back is a commonly used communication method to improve patient understanding and retention of health information. The method has been shown to be effective in improving patient and healthcare system outcomes, including patient health literacy and hospital readmissions. Community health workers (CHWs) are frontline healthcare workers who can help address patient health and social needs associated with hospital readmissions. However, a gap exists in Teach Back curricula and training methods reflecting the scope of work for CHWs. The objective of this training was to provide CHWs with didactic information and skill building practice curriculum focused on the integration of Teach Back into clinical patient interactions, care coordination, and follow-up support. A multidisciplinary team of academic and clinical partners at a large academic health university developed, implemented, and evaluated a 3-week pilot Teach Back training with CHWs through a quality improvement approach. The CHWs reported overall satisfaction with the training and instructors. The academic clinical partnership allowed the training to be tailored to the daily clinical workflow as reflected in the CHWs agreement that the training was relevant and practical. With the repeated exposure to Teach Back each week, the CHWs also reported an increase in confidence and conviction in using Teach Back. Additional implementation and evaluation of the training curriculum for CHWs is needed to gain further insights into Teach Back and training best practices and translation into practice.

Background: Effective provider communication skills are important for patient decision-making and understanding, particularly for those with low health literacy. A gap exists in training methods and curriculum for community health workers (CHWs). Brief description of activity: Through a clinical and academic partnership, pilot training curriculum focused on patient communication skills was developed to align with CHW scope of work. Implementation: The curriculum was implemented in three 2-hour training sessions over WebEx with seven state-certified CHWs. The goal was for CHWs to understand the key elements and application of active listening, Teach Back, and action planning in a clinical setting. The sessions included didactic and skills practice modules for each skill. Results: A survey was distributed to CHWs to evaluate knowledge, skills, and attitudes and reactions to training methods, instructors, and relevance using the Kirkpatrick's evaluation model (Reaction and Learning). Although CHWs agreed that they had actively participated in the training and that the instructors were well-prepared, there was less agreement that the course was relevant. CHWs reported an increase in understanding of active listening and action planning, capability of using Teach Back and providing social support, and ability to teach, whereas a decrease was reported in the capability to use action planning. When probed about training relevance, CHWs felt action listening and Teach Back were relevant, but that action planning was not relevant to their responsibilities. This gap in responsibilities was also acknowledged by the clinical leadership. Lessons learned: The training allowed the CHWs to build on subsequent skills from previous sessions and to discuss struggles. A need for tools for integrating the skills in the clinical workflow were requested by CHWs and clinical leadership. These tools offer the opportunity to tailor future trainings on communication skills or patient scenarios. Future trainings should include CHWs to provide insight into scope of work. [HLRP: Health Literacy Research and Practice. 2022;6(2):e142–e150.] Plain Language Summary: It is important for community health workers to communicate with patients so that patients can understand information and make their own decisions. There is not enough known about the best way to train CHWs in patient communication. This training was created to help CHWs use three patient communication skills in their clinic.

Functional connection among the information-processing (grey-matter) centres within the CNS are necessary for the coordinated processing of perception, affect, thought and behaviour. Myelinated neuronal bundles provide the links among such processing centres. Magnetic resonance diffusion tensor imaging (DTI) can assess the physical integrity of myelin. Using DTI, the authors assessed diffusivity (Dm) within whole brain in 14 controls and within 13 acutely psychotic, drug-free schizophrenics both before and after 28 d of antipsychotic drug treatment. Drug-responder schizophrenicss (D-RS) (n=8) were differentiated from poor responders (PR) (n=5) according to previously defined criteria. Differences of Dm at both baseline and following treatment were assessed using Dm distributional analyses and Statistical Parametric Software (SPM2). Impaired physical integrity of myelin, demonstrated by an increase (overall p<0.05) of Dm, was found in the D-RS patients, with multiple regions demonstrating p<0.0005 patient–control differences. The pathological increase in Dm was reduced (p<0.03) following treatment-associated reduction of psychotic symptoms by 84%. Dm of PR patients did not differ from controls at baseline or following subacute treatment. While the pathophysiology(ies) underlying psychosis in poorly responsive (PR) schizophrenics does not appear to be related to a disordered myelin, the findings are consistent with a partially reversible disorder of myelin integrity, and may underlie a dys-synchrony of information processing in a major subgroup of drug-responsive patients with schizophrenia. An antipsychotic drug-induced cascade may partially restore myelin integrity and functional connectivity concomitant with antipsychotic effects in such D-RS patients.

Introduction: The Accountable Health Communities (AHC) Model was designed to address the health-related social needs of Centers for Medicare & Medicaid Services beneficiaries. Bridge organizations across the AHC Model have identified lack of technical assistance and peer planning as potential barriers to Model success, particularly around patient navigation. The technical assistance and peer planning literature lacks an organizing, conceptual framework, but implementation science frameworks could serve as useful guides. The Strengthening Peer AHC Navigation (SPAN) research protocol seeks to fill this gap and will apply three implementation science frameworks, Consolidated Framework for Implementation Research, Intervention Mapping, and the Expert Recommendations for Implementing Change compilation, to develop a multi-level quality improvement intervention and evaluate the impact of peer planning on Model outcomes. The aims of the SPAN study are to implement and evaluate a novel multi-level quality improvement intervention to improve AHC implementation and navigation milestones through structured peer planning and to provide successful technical assistance for the AHC Model. Methods and Analysis: The quality improvement intervention is outlined in four Tasks: (1) Assessment – to conduct an assessment of each bridge organization's current implementation, needs, and readiness in AHC Model navigation activities; (2) Planning – to engage in a peer planning approach to build capacity for AHC Model navigation activities; (3) Implementation with technical assistance – Co-creation of a quality improvement protocol for AHC Model navigation activities; and (4) Evaluation – measure the impact of the peer planning and technical assistance approach. Alongside the development and implementation of the quality improvement intervention, this protocol describes a mixed method, convergent parallel study design which will be used to evaluate whether the quality improvement intervention will lead to better outcomes. Tasks will be replicated with five bridge organizations participating in the AHC Model. Discussion: This research protocol provides a framework that can be used to conduct structured peer planning with technical assistance for social needs programs. This study will provide data on both implementation and outcomes which eventually may impact healthcare cost and utilization.

A genome-scale RNAi screen was performed in a mammalian cell-based assay to identify modifiers of mutant huntingtin toxicity. Ontology analysis of suppressor data identified processes previously implicated in Huntington's disease, including proteolysis, glutamate excitotoxicity, and mitochondrial dysfunction. In addition to established mechanisms, the screen identified multiple components of the RRAS signaling pathway as loss-of-function suppressors of mutant huntingtin toxicity in human and mouse cell models. Loss-of-function in orthologous RRAS pathway members also suppressed motor dysfunction in a Drosophila model of Huntington's disease. Abnormal activation of RRAS and a down-stream effector, RAF1, was observed in cellular models and a mouse model of Huntington's disease. We also observe co-localization of RRAS and mutant huntingtin in cells and in mouse striatum, suggesting that activation of R-Ras may occur through protein interaction. These data indicate that mutant huntingtin exerts a pathogenic effect on this pathway that can be corrected at multiple intervention points including RRAS, FNTA/B, PIN1, and PLK1. Consistent with these results, chemical inhibition of farnesyltransferase can also suppress mutant huntingtin toxicity. These data suggest that pharmacological inhibition of RRAS signaling may confer therapeutic benefit in Huntington's disease.

Evidence of immune activation has occasionally, but not consistently, been reported in schizophrenia. Investigations of cytokine abnormalities in serum, and occasionally in CSF, have yielded inconsistent results, which have been difficult to resolve. In such studies, schizophrenia has been assumed to consist of a single process rather than a group of disorders. This study assesses differences in the pro-inflammatory cytokine, interleukin-6 (IL-6) in the cerebrospinal fluid (CSF) in two previously delineated subtypes of schizophrenics (‘delayed-responders’ (DR) ( n =23) and ‘poor-responders’ (PR) ( n =8)) during periods of neuroleptic-free psychotic exacerbation, and in a comparison group of normal controls ( n =14). The two response subtypes were separated by subsequent treatment response (greater/less than 60% reduction of SAPS scores from baseline during 6 months of systematic treatment). The IL-6 assay, a sandwich enzyme-linked immunosorbent assay, was sensitive and reliable to detect IL-6 levels in the CSF of all subjects. CSF IL-6 was found to be significantly higher in the DR than the PR ( P =0.017) and the controls ( P =0.013). In addition to supporting the concept of heterogeneity in schizophrenia, this study also provides evidence that a central immune process may be occurring centrally in one subtype of schizophrenia.

BackgroundIntegration of health-related social needs (HRSNs) data into clinical care is recognized as a driver for improving healthcare. However, few published studies on HRSNs and their impact are available. CMS sought to fill this gap through the Accountable Health Communities (AHC) Model, a national RCT of HRSN screening, referral, and navigation. Data from the AHC Model could significantly advance the field of HRSN screening and intervention in the USA.ObjectiveTo present data from the Greater Houston AHC (GH-AHC) Model site on HRSN frequency and the association between HRSNs, sociodemographic factors, and self-reported ED utilization using a cross-sectional design. Analyses included descriptive statistics and multinomial logistic regression.Participants (or Patients or Subjects)All community-dwelling Medicare, Medicaid, or dually covered beneficiaries at participating GH-AHC clinical delivery sites were eligible.Main MeasuresSelf-reported ED utilization in the previous 12 months served as the outcome; demographic characteristics including race, ethnicity, age, sex, income, education level, number of people living in the household, and insurance type were treated as covariates. HRSNs included food insecurity, housing instability, transportation, difficulty paying utility bills, and interpersonal safety. Clinical delivery site type was used as the clustering variable.Key ResultsFood insecurity was the most common HRSN identified (38.7%) followed by housing instability (29.0%), transportation (28.0%), and difficulty paying utility bills (26.7%). Interpersonal safety was excluded due to low prevalence. More than half of the beneficiaries (56.9%) reported at least one of the four HRSNs. After controlling for covariates, having multiple co-occurring HRSNs was strongly associated with increased risk of two or more ED visits (OR 1.8–9.47 for two to four needs, respectively; p < 0.001). Beneficiaries with four needs were at almost 10 times higher risk of frequent ED utilization (p < 0.001).ConclusionsTo our knowledge, this is only the second published study to report screening data from the AHC Model. Future research focused on the impact of multiple co-occurring needs on health outcomes is warranted.