Using a Community-Informed Translational Model to Prioritize Translational Benefits in Youth Concussion Return-to-Learn Programs.

BACKGROUND: The Translational Science Benefit Model (TSBM) was developed to broadly capture systematic measures of health and societal benefits from scientific research, beyond traditional outcome measures. We aimed to develop a systematic process for the application of the TSBM and to then provide an example of a novel application of the TSBM to an ongoing Return-to-Learn (RTL) after youth concussion project involving partnerships with community stakeholders. METHODS: We invited investigators, project advisory board, and participants of the RTL project to participate in a modified Delphi process. We first generated a list of potential translational benefits using the indicators of the TSBM as guideposts. We then prioritized the benefits on an adapted Eisenhower matrix. RESULTS: We invited 35 concussion care or research experts to participate, yielding 20 ranked translational benefits. Six of these recommendations were ranked high priority, six were regarded as investments, and eight were ranked as either low yield or low priority. DISCUSSION: This study found that activities such as education and training of stakeholders, development of policy and consensus statements, and innovation in dissemination, were perceived as higher priority than other activities. Our approach using a modified Delphi process and incorporating the TSBM can be replicated to generate and prioritize potential benefits to society from research studies.

Placebo analgesia and nocebo hyperalgesia in patients with Alzheimer disease and healthy participants.

ABSTRACT: The role of placebo analgesia and nocebo hyperalgesia in patients with Alzheimer disease (AD) is largely unknown, with only few studies in the area. Therefore, this study aims to investigate to which extent placebo analgesia and nocebo hyperalgesia effects are present in patients experiencing mild-to-moderate AD. Twenty-one patients with AD (test population) and 26 healthy participants (HP; design validation) were exposed to thermal pain stimulation on 3 test days: Lidocaine condition (open/hidden lidocaine administration), capsaicin condition (open/hidden capsaicin administration), and natural history (no treatment), in a randomized, within-subject design. Open lidocaine and open capsaicin were accompanied by verbal suggestions for pain relief and pain increase, respectively. Expected pain and actual pain intensity were measured on a numerical rating scale (0-10). Placebo and nocebo effects were calculated as pain differences in open-hidden lidocaine and capsaicin, respectively, controlled for no treatment. Healthy participants obtained a placebo effect ( P = 0.01) and a trend for a nocebo effect ( P = 0.07). Patients with AD did not obtain a placebo effect ( P = 0.44) nor a significant nocebo effect ( P = 0.86). Healthy participants expected lower and higher pain with open vs hidden lidocaine and capsaicin, respectively ( P < 0.001). The same expectation effects were seen in patients with AD (open vs hidden lidocaine, P = 0.008; open vs hidden capsaicin, P < 0.001). With a well-controlled experimental setting, this study suggests that patients with AD may not experience placebo analgesia effects. Nocebo hyperalgesia effects in patients with AD needs further research. These findings may have implications for the conduction of clinical trials and the treatment of patients with AD in clinical practice.

The Translational Science Benefits Model, a new training tool for demonstrating implementation science impact: A pilot study.

Introduction: Demonstrating the impact of implementation science presents a new frontier for the field, and operationalizing downstream impact is challenging. The Translational Science Benefits Model (TSBM) offers a new approach for assessing and demonstrating research impact. Here we describe integration of the TSBM into a mentored training network. Methods: Washington University's Clinical and Translational Science Awards TSBM team collaborated with a National Institute of Mental Health-supported training program, the Implementation Research Institute (IRI), a 2-year training institute in mental health implementation science. This partnership included three phases: (1) introductory workshop on research impact, (2) workshop on demonstrating impact, and (3) sessions to guide dissemination, including interactive tools and consultation with the TSBM research team. Fifteen IRI alumni were invited to participate in the pilot; six responded agreeing to participate in the training, develop TSBM case studies, and provide feedback about their experiences. Participants applied the tools and gave feedback on design, usability, and content. We present their case studies and describe how the IRI used the results to incorporate TSBM into future trainings. Results: The case studies identified 40 benefits spanning all four TSBM domains, including 21 community, 11 policy, five economic, and three clinical benefits. Participants reported that TSBM training helped them develop a framework for talking about impact. Selecting benefits was challenging for early-stage projects, suggesting the importance of early training. Conclusions: The case studies showcased the institute's impact and the fellows' work and informed refinement of tools and methods for incorporating TSBM into future IRI training.

Soccer and Benign Paroxysmal Positional Vertigo.

Introduction. Benign paroxysmal positional vertigo (BPPV) is the most common cause of vertigo among adults. The etiology of BPPV is unknown in approximately 50 percent of cases. This condition is also termed primary BPPV, if the etiology is unknown, and secondary BPPV if patients have identified predisposing factors. A few studies suggest that there is a correlation between the development of BPPV and specific sports. Case Report. A 19-year-old male presented with recurrent episodes of vertigo during soccer play. Eight months prior to referral, the patient was involved in a car accident with a mild head trauma. The patient was later diagnosed with BPPV several times. Discussion. Soccer might be a plausible BPPV trigger, especially if there is a prehistory of head trauma. This is most likely due to the demands of the game such as the change of directions, repetitive head impacts (headers or head collisions), accelerations/decelerations, jumps, foot landings, and rapid head movements.

Tailoring dissemination of evidence to preferences of tobacco control partners: results from an academic-community partnership.

BACKGROUND: Tobacco control program leaders and their partners, who often present evidence to policymakers, can increase the use of evidence in program and policy development. However, up-to-date evidence from the scientific community about what works is slow to reach leaders. We describe efforts to understand and utilize tobacco control leaders' preferences for receiving evidence and report on resulting dissemination strategies, translational products, and outcomes. METHODS: This work is part of the Advancing Science and Practice in the Retail Environment (ASPiRE) Center, an interdisciplinary research center focused on understanding and evaluating tobacco retail policy. Participants were members of the ASPiRE Community Advisory Board (CAB), comprised of tobacco control leaders from 30 metropolitan areas representing all regions of the US plus nine representatives from leading national tobacco control organizations (N = 39). During meetings in February 2019 and October 2020, all CAB members were invited to participate in live polls consisting of six survey questions each. Questions addressed preferences for receiving scientific evidence and their anticipated use of ASPiRE translational products. Responses were analyzed descriptively and informed translational product development and communications with ASPiRE contact list members (N = 125). ASPiRE email and website interactions were tracked from March 2019 to May 2021 as a complementary indication of content use. RESULTS: Response rates for 2019 and 2020 CAB meetings were 66% (n = 26) and 59% (n = 23), respectively. CAB members indicated preferences for email communication (33%) and webinars (31%), communications once per month (46%), and short-format documents (28%). In response, the team developed translational short-format products including case studies, fact sheets, and research briefs. On average, 52% (SD = 14%) of recipients opened the newsletter and 17% (SD = 9%) clicked a link within the newsletter. Overall, 95% of responding CAB members found the products useful and all responding CAB members reported using them to communicate evidence to policymakers, staff, and coalition members. CONCLUSIONS: Our successful dissemination approach to making evidence more accessible and useable for tobacco control leaders could be adapted by researchers working with community partners to assess and respond to stakeholders' preferences for receiving evidence in other areas of health policy.

Postoperative Pain Mediates the Association Between Peripheral Nerve Blocks and Postoperative Sleep Following Lower Extremity Arthroplasty.

OBJECTIVES: Despite substantial research showing the bidrectional relationship between sleep and pain, there remains a dearth of research examining the role of perioperative pain management interventions in mitigating postoperative sleep disturbances. This secondary analysis of a prospective observational multisite study examined the association between peripheral nerve block (PNB) use during total knee or total hip arthroplasty (TKA/THA) procedures and postoperative pain and sleep outcomes. MATERIALS AND METHODS: Adult patients undergoing TKA or THA procedures were recruited from 2 tertiary care facilities. Average pain and sleep disturbance scores were collected preoperatively and at 1- and 2-week postoperatively. Participants were not randomized to receive PNB. Postoperative outcomes were compared based on receipt of PNB during surgery. Structural equation modeling path analysis was utilized to model multiple co-occurring relationships, including mediation pathways between perioperative pain management approaches, pain, and postoperative sleep outcomes. RESULTS: Of the 197 participants, 53% received PNB. Mediation analyses indicated that PNB was indirectly associated with 1-week sleep disturbance via its effects on 1-week pain intensity (ß=-0.02, 95% confidence interval [CI] -0.04, -0.001, P=0.04). In addition, PNB was indirectly associated with 2-week sleep disturbance, via its effects on 1-week pain intensity and 1-week sleep disturbance (ß=-0.04, 95% CI -0.07, -0.02, P=0.04). Lastly, PNB was indirectly associated with 2-week pain intensity via its effects on 1-week pain intensity (ß=-0.10, 95% CI -0.19, -0.02, P=0.02). CONCLUSIONS: Receipt of PNB during TKA or THA was found to be associated with improved 1-week postoperative pain intensity, which in turn was found to be associated with lower sleep disturbances at both 1- and 2-week postoperative time points. Multimodal opioid sparing pain management interventions, capable of improving postoperative sleep, are vital to improving recovery and rehabilitation following arthroplasty.

Comprehensive RNA analysis of CSF reveals a role for CEACAM6 in lung cancer leptomeningeal metastases.

Non-small cell lung cancer (NSCLC) metastatic to the brain leptomeninges is rapidly fatal, cannot be biopsied, and cancer cells in the cerebrospinal fluid (CSF) are few; therefore, available tissue samples to develop effective treatments are severely limited. This study aimed to converge single-cell RNA-seq and cell-free RNA (cfRNA) analyses to both diagnose NSCLC leptomeningeal metastases (LM), and to use gene expression profiles to understand progression mechanisms of NSCLC in the brain leptomeninges. NSCLC patients with suspected LM underwent withdrawal of CSF via lumbar puncture. Four cytology-positive CSF samples underwent single-cell capture (n = 197 cells) by microfluidic chip. Using robust principal component analyses, NSCLC LM cell gene expression was compared to immune cells. Massively parallel qPCR (9216 simultaneous reactions) on human CSF cfRNA samples compared the relative gene expression of patients with NSCLC LM (n = 14) to non-tumor controls (n = 7). The NSCLC-associated gene, CEACAM6, underwent in vitro validation in NSCLC cell lines for involvement in pathologic behaviors characteristic of LM. NSCLC LM gene expression revealed by single-cell RNA-seq was also reflected in CSF cfRNA of cytology-positive patients. Tumor-associated cfRNA (e.g., CEACAM6, MUC1) was present in NSCLC LM patients' CSF, but not in controls (CEACAM6 detection sensitivity 88.24% and specificity 100%). Cell migration in NSCLC cell lines was directly proportional to CEACAM6 expression, suggesting a role in disease progression. NSCLC-associated cfRNA is detectable in the CSF of patients with LM, and corresponds to the gene expression profile of NSCLC LM cells. CEACAM6 contributes significantly to NSCLC migration, a hallmark of LM pathophysiology.

A Novel Brain-Permeant Chemotherapeutic Agent for the Treatment of Brain Metastasis in Triple-Negative Breast Cancer.

Development of metastases to central nervous system (CNS) is an increasing clinical issue following the diagnosis of advanced breast cancer. The propensity to metastasize to CNS varies by breast cancer subtype. Of the four breast cancer subtypes, triple-negative breast cancers (TNBC) have the highest rates of both parenchymal brain metastasis and leptomeningeal metastasis (LM). LM is rapidly fatal due to poor detection and limited therapeutic options. Therapy of TNBC brain metastasis and LM is challenged by multifocal brain metastasis and diffuse spread of LM, and must balance brain penetration, tumor cytotoxicity, and the avoidance of neurotoxicity. Thus, there is an urgent need for novel therapeutic options in TNBCs CNS metastasis. QBS10072S is a novel chemotherapeutic that leverages TNBC-specific defects in DNA repair and LAT1 (L-amino acid transporter type 1)-dependent transport into the brain. In our study, activity of QBS10072S was investigated in vitro with various cell lines including the human TNBC cell line MDA-MB-231 and its brain-tropic derivative MDA-MB-231-BR3. QBS10072S was preferentially toxic to TNBC cells. The efficacy of QBS10072S against brain metastasis and LM was tested using a model of brain metastasis based on the internal carotid injection of luciferase-expressing tumor cells into NuNu mice. The compound was well tolerated, delayed tumor growth and reduced leptomeningeal dissemination, resulting in significant extension of survival. Given that current treatments for LM are palliative with only few studies reporting a survival benefit, QBS10072S is planned to be investigated in clinical trials as a therapeutic for TNBC LM. SIGNIFICANCE: TNBC brain metastasis often involves dissemination into leptomeninges. Treatment options for TNBC leptomeningeal metastasis are limited and are mostly palliative. Our study demonstrates significant efficacy of the brain-penetrating agent QBS10072S against TNBC brain metastasis and leptomeningeal spread.

Ultrasound 3D reconstruction of malignant masses in robotic-assisted partial nephrectomy using the PAF rail system: a comparison study.

PURPOSE: In robotic-assisted partial nephrectomy (RAPN), the use of intraoperative ultrasound (IOUS) helps to localise and outline the tumours as well as the blood vessels within the kidney. The aim of this work is to evaluate the use of the pneumatically attachable flexible (PAF) rail system for US 3D reconstruction of malignant masses in RAPN. The PAF rail system is a novel device developed and previously presented by the authors to enable track-guided US scanning. METHODS: We present a comparison study between US 3D reconstruction of masses based on: the da Vinci Surgical System kinematics, single- and stereo-camera tracking of visual markers embedded on the probe. An US-realistic kidney phantom embedding a mass is used for testing. A new design for the US probe attachment to enhance the performance of the kinematic approach is presented. A feature extraction algorithm is proposed to detect the margins of the targeted mass in US images. RESULTS: To evaluate the performance of the investigated approaches the resulting 3D reconstructions have been compared to a CT scan of the phantom. The data collected indicates that single camera reconstruction outperformed the other approaches, reconstructing with a sub-millimetre accuracy the targeted mass. CONCLUSIONS: This work demonstrates that the PAF rail system provides a reliable platform to enable accurate US 3D reconstruction of masses in RAPN procedures. The proposed system has also the potential to be employed in other surgical procedures such as hepatectomy or laparoscopic liver resection.

"Hearing from all sides" How legislative testimony influences state level policy-makers in the United States.

BACKGROUND: This paper investigates whether state legislators find testimony influential, to what extent testimony influences policy-makers' decisions, and defines the features of testimony important in affecting policy-makers' decisions. METHODS: We used a mixed method approach to analyze responses from 862 state-level legislators in the United States (U.S.). Data were collected via a phone survey from January-October, 2012. Qualitative data were analyzed using a general inductive approach and codes were designed to capture the most prevalent themes. Descriptive statistics and cross tabulations were also completed on thematic and demographic data to identify additional themes. RESULTS: Most legislators, regardless of political party and other common demographics, find testimony influential, albeit with various definitions of influence. While legislators reported that testimony influenced their awareness or encouraged them to take action like conducting additional research, only 6% reported that testimony changes their vote. Among those legislators who found testimony influential, characteristics of the presenter (e.g., credibility, knowledge of the subject) were the most important aspects of testimony. Legislators also noted several characteristics of testimony content as important, including use of credible, unbiased information and data. CONCLUSION: Findings from this study can be used by health advocates, researchers, and individuals to fine tune the delivery of materials and messages to influence policy-makers during legislative testimony. Increasing the likelihood that information from scholars will be used by policy-makers may lead to the adoption of more health policies that are informed by scientific and practice-based evidence.