Indigenous Elder advisors in Pelican Narrows, a Cree community in Northern Saskatchewan, have indicated that Western pain scales may not be responsive tools for pain assessments within their community. This study employed a mixed methods research design that involved two phases. Phase one was the development of a pain scale in collaboration with an Elder and a Knowledge Keeper. Phase two was a pilot of the CDPS utilised during virtual physiotherapy sessions for chronic back pain. Twenty-seven participants completed the pre-physiotherapy treatment questionnaires, and 10 participants engaged in semi-structured interviews (9 community members; 1 healthcare provider). A weighted kappa analysis yielded k = 0.696, indicating a good agreement between the CDPS and Faces Pain Scale-Revised in terms of documenting participants' pain. Qualitative data from interviews with community members revealed three major themes: 1) Learnings Regarding Pain Scales, 2) Patient Centered Care; and 3) Strength-Based Solutions for Improving Pain Communication. Two themes were uncovered through conversations with the HCP: 1) Perspectives on CDPS and 2) Healthcare Provider Experiences Communicating about Pain. Moreover, a patient-centredcentred approach is important to ensure comprehensive pain assessments.

It is unknown if genetics underpin the most extreme manifestations of the athlete's heart. We aim to elucidate if rare single nucleotide variants (SNVs) in cardiomyopathy genes are correlated with features of extreme cardiac athletic remodelling. Young (<30years) endurance athletes (n=247; median age 18 years (IQR: 17-20); 77.7% males) and older (>30years) athletes (n=241; median 53years (IQR: 43–65); 78.4% male) received resting and ambulatory electrocardiography and cardiac MRI. DNA samples were evaluated for rare (minor allele frequency <0.1%) SNVs in 24 genes associated with dilated or arrhythmogenic cardiomyopathies. Athletes harbouring variants classified pathogenic, likely pathogenic and variants of uncertain significance with high deleterious scores from in-silico prediction were considered genotype+ and 1:2 matched to athletes without variants (genotype-). Prevalence of extreme remodelling features were compared using Chi square analysis, while continuous variables were compared using Mann-Whitney U tests. Of 488 athletes, 71 (14.5%) harboured ≥1 SNV, 35 of which (7.2% of total; 17 young athletes) were deemed Genotype+. Prevalence of extreme right ventricular (RV) and left ventricular (LV) volume enlargement and extreme LV mass elevation were similar between Genotype+ and Genotype- young and older athletes. An RV:LV volume ratio >1.2 and a high or low LV volume:mass ratio was equally prevalent among genotypes in both age groups. There were no differences in the burden of arrhythmia, ectopy, marked bradycardia, conduction blocks and pauses between genotype groups. The lack of association between SNVs and phenotype suggests cardiac remodelling in athletes is not determined by rare variants in common cardiomyopathy-associated genes.

Background: Rural injured workers requiring multidisciplinary assessments for musculoskeletal disorders face health access disparities, which include travel to urban centers. Virtual care can enhance access to multidisciplinary team care for musculoskeletal conditions in rural areas. Materials and Methods: A retrospective chart audit of 136 multidisciplinary assessment reports of injured workers was conducted. Comprehensive management recommendations from the health care assessment team were extracted for analysis. The health care team used virtual technologies to join with patients and at least one local rural health practitioner in one of three locations. Remote presence robotics (RPR; Xpress Technology™) or laptop-based telehealth was used to complete the assessments. Results: RPR were used in 46% of assessments over two sites, with 54% using laptop-based telehealth at a third site. Frequencies of team members' assessment using technologies were as follows: physical therapist (100%), psychologist (78%), plastic surgeon (8%), and physician (43%). Spine (42%) and shoulder (32%) disorders were the most common problems. Most workers (79%) were 3 or more months postinjury. The most common management recommendation was the need for daily comprehensive rehabilitation care (76%). Travel time was saved by 89% of participants. Conclusions: Virtual care was used to unite multidisciplinary assessment teams for the evaluation of injured rural workers with complex musculoskeletal injuries. Future research recommendations include comparing between virtual and fully in-person multidisciplinary assessment and recommendation findings, and evaluation of patient and practitioner experiences with comprehensive virtual team assessments.

Genetic causes of familial dilated cardiomyopathy (DCM) show marked variability in penetrance and severity. The impact of gene-environment interactions (co-morbidities and lifestyle) on phenotype is not well understood. A retrospective longitudinal study was conducted. Individuals with DCM variant (G+) and their genotyped family members were invited to take part. All participants underwent a detailed clinical interview and file review. Disease trajectory and clinical events were correlated with known heart failure (HF) environmental factors. 39 families met inclusion criteria and 105 individuals from 31 families consented. Mean age was 48 years and median follow-up was 7 years. Left ventricular (LV) reverse remodelling with HF therapy occurred in 19 (54%) affected G+ patients and was associated with treatment of a reversible environmental risk factor in 14 (73%). LV ejection fraction (LVEF) deterioration occurred in 22 G+ patients, and11 (50%) had a new reversible environmental factor. The presence of environmental factors was associated with DCM in G+ individuals (OR 5.5, p=0.004). However, factors that primarily impact systolic function (alcohol, arrhythmias) were associated with younger age at DCM onset (HR 2.0, p=0.014), while metabolic factors (diabetes, obesity) were associated with adverse events (OR 9.3, p=0.001). Environmental factors were significantly associated with DCM penetrance, adverse events and LVEF trajectory. These data highlight the key role of risk factor reduction in clinical management of genetically-mediated DCM.Tabled 1DCM (EF <50%)Adverse eventsORpORpEnvironmental Factor5.530.0043.830.025Systolic Factor5.210.0062.460.120Metabolic Factor4.390.0059.30.001 Open table in a new tab

This study examines cross-sectional clusters and longitudinal predictions using an expanded SAVA syndemic conceptual framework-SAVA MH + H (substance use, intimate partner violence, mental health, and homelessness leading to HIV/STI/HCV risks)-among women recently released from incarceration (WRRI) (n = 206) participating in the WORTH Transitions (WT) intervention. WT combines two evidence-based interventions: the Women on the Road to Health HIV intervention, and Transitions Clinic. Cluster analytic and logistic regression methods were utilized. For the cluster analyses, baseline SAVA MH + H variables were categorized into presence/absence. For logistic regression, baseline SAVA MH + H variables were examined on a composite HIV/STI/HCV outcome collected at 6-month follow-up, controlling for lifetime trauma and sociodemographic characteristics. Three SAVA MH + H clusters were identified, the first of which had women with the highest overall levels of SAVA MH + H variables, 47% of whom were unhoused. Hard drug use (HDU) was the only significant predictor of HIV/STI/HCV risks in the regression analyses. HDUs had 4.32-fold higher odds of HIV/STI/HCV outcomes than non-HDUs (p = 0.002). Interventions such as WORTH Transitions must differently target identified SAVA MH + H syndemic risk clusters and HDU to prevent HIV/HCV/STI outcomes among WRRI.

To develop and evaluate the immunologic ramifications of a novel immunotherapy-eluting microsphere following transarterial embolization of orthotopic hepatocellular carcinoma (HCC) tumors in a rat model. A novel absorbable microsphere (immunobead) was developed to elute the Toll-like receptor 7 agonist imiquimod. An HCC model was generated by orthotopic implantation of RH7777 hepatoma cells in Buffalo rats. Animals were then randomized to undergo transarterial embolization with immunobead versus saline sham (n = 12 per arm). Three days following intervention, immune profiling was performed using flow cytometry, immunohistochemistry (IHC), Nanostring transcriptomics, and single cell RNA sequencing (scRNAseq). Additionally, the deposition of imiquimod as well as metabolic alterations were visualized using mass spectrometry imaging (MSI). MSI revealed > 3:1 tumor-to-background deposition of imiquimod within the target tumor. Metabolic analysis revealed decreases in metabolites (glutathione, histamine, and adenosine) within the tumor associated with immunosuppressive microenvironments following immunobead embolization relative to sham. IHC revealed an increase in CD4+ and CD8+ T cells within the tumor following immunobead embolization. These findings were corroborated on flow cytometry which revealed an increase in CD45+CD3+CD8a+ T cells (39% immunobead vs 19% sham, P < 0.05) as well as a decrease in M2 macrophages (CD163+, 9% vs 23%, P < 0.05). scRNAseq revealed an important increase in Batf3+ conventional dendritic cell type 1 (cDC1, P < 0.005) and Irf4+ conventional dendritic cell type 2 (cDC2, P < 0.01) following immunobead embolization relative to sham, key drivers of antigen presentation and adaptive immunity. There was also an increase in the overall cell percentages for CD8+ effector memory T cells and CD8+ activated T cells and a decrease in regulatory T cells following immunobead embolization. Transcriptional profiling of the tumor following immunobead embolization revealed numerous differentially expressed gene pathways indicative of a shift away from immunosuppression, including downregulation of the Wnt/beta-catenin pathway, checkpoint inhibitors including Marco and Ctla4, and immunosuppressive cytokines such as IL6. Transarterial embolization with immunobead effectively diminished the immunosuppressive liver tumor microenvironment and enhance immunostimulatory signals. Embolization with immunobead is a promising approach to augment antitumoral immune mechanisms in HCC.

NSW HEARTS aims to recruit a large, well-characterised and inclusive cohort of patients with inherited cardiomyopathies living in New South Wales (NSW), Australia, for cross-sectional and longitudinal analysis. Specifically, we seek to: (1) Understand the underlying genetic basis of disease; (2) Characterise disease expression, natural history and clinical course of inherited cardiomyopathies; (3) Investigate the clinical utility of polygenic risk scores and understand how these can inform family screening recommendations; and (4) Describe patterns of care and burden of disease for patients with inherited cardiomyopathies using NSW Health linked datasets. We will recruit patients with a clinical diagnosis of hypertrophic (HCM), dilated (DCM), arrhythmogenic (ACM), restrictive (RCM), left ventricular non-compaction (LVNC) cardiomyopathies, as well as those with clinically unclassified heritable cardiomyopathies. Patients will be >18 years of age and reside in NSW. Recruitment will occur from clinical sites (e.g., Royal Prince Alfred Hospital, St Vincent’s Hospital and Westmead Hospital in Sydney), from existing studies such as the Australian Genetic Heart Disease Registry, and via self-referral. We will support the recruitment of individuals from diverse ancestry groups. We will collect detailed clinical, environmental and health status information at baseline and in follow-up. A blood sample will be collected for whole-genome sequencing and stored at the NSW Health Statewide Biobank. A sub-group will undergo cardiac magnetic resonance imaging at two sites in Sydney. Participants will be engaged to participate now and into the future. NSW HEARTS will be an important resource for studying inherited cardiomyopathies. By better defining these diseases, we will be able to provide tailored advice regarding personalised therapeutic options, risk stratification, overall prognosis, and optimised family screening.

PGN-EDO51 is PepGen's clinical candidate to treat individuals with Duchenne muscular dystrophy (DMD) amenable to exon 51 skipping. It is the first of a series of therapies based on our Enhanced Delivery Oligonucleotide (EDO) platform and will be followed by programs to address myotonic dystrophy type one, other subgroups of DMD and other neuromuscular and neurological disorders. Therapeutic oligonucleotides are precision medicines that modulate the genetic machinery and have shown great promise in treating genetic disorders. First generation oligonucleotides resulted in suboptimal delivery to muscle and therefore afford limited dystrophin production and limited therapeutic benefit in people with DMD. PepGen's EDO technology efficiently and effectively delivers oligonucleotides to skeletal, smooth and cardiac muscle, offering great promise for neuromuscular diseases. Studies in the mdx mouse model of DMD demonstrated robust dystrophin production in key tissues following a single administration, inducing 91% of normal levels in quadriceps seven days after dosing. Single dose studies in non-human primates (NHPs) established that PGN-EDO51 leads to robust exon skipping in muscle and drives broad biodistribution, with significant levels detected in skeletal, smooth and cardiac muscles and in CNS tissues. Repeat dose studies in NHPs demonstrated that exon skipping levels accumulate. Following three doses of 30 mg/kg, exon skipping levels of 78% in biceps, 76% in diaphragm and 24% in left ventricle were obtained. PGN-EDO51 was well tolerated at target doses, and clinical trials enabling toxicology studies have been completed. The high levels of activity and the tolerability of our approach demonstrated by the totality of studies supported our Clinical Trial Application to Health Canada and the initiation of our Phase 1 clinical trial in early 2022. Results from this Phase 1 safety study in healthy volunteers and plans for our Phase 2 studies will be discussed. PGN-EDO51 is PepGen's clinical candidate to treat individuals with Duchenne muscular dystrophy (DMD) amenable to exon 51 skipping. It is the first of a series of therapies based on our Enhanced Delivery Oligonucleotide (EDO) platform and will be followed by programs to address myotonic dystrophy type one, other subgroups of DMD and other neuromuscular and neurological disorders. Therapeutic oligonucleotides are precision medicines that modulate the genetic machinery and have shown great promise in treating genetic disorders. First generation oligonucleotides resulted in suboptimal delivery to muscle and therefore afford limited dystrophin production and limited therapeutic benefit in people with DMD. PepGen's EDO technology efficiently and effectively delivers oligonucleotides to skeletal, smooth and cardiac muscle, offering great promise for neuromuscular diseases. Studies in the mdx mouse model of DMD demonstrated robust dystrophin production in key tissues following a single administration, inducing 91% of normal levels in quadriceps seven days after dosing. Single dose studies in non-human primates (NHPs) established that PGN-EDO51 leads to robust exon skipping in muscle and drives broad biodistribution, with significant levels detected in skeletal, smooth and cardiac muscles and in CNS tissues. Repeat dose studies in NHPs demonstrated that exon skipping levels accumulate. Following three doses of 30 mg/kg, exon skipping levels of 78% in biceps, 76% in diaphragm and 24% in left ventricle were obtained. PGN-EDO51 was well tolerated at target doses, and clinical trials enabling toxicology studies have been completed. The high levels of activity and the tolerability of our approach demonstrated by the totality of studies supported our Clinical Trial Application to Health Canada and the initiation of our Phase 1 clinical trial in early 2022. Results from this Phase 1 safety study in healthy volunteers and plans for our Phase 2 studies will be discussed.

BackgroundU.S. women recently released from incarceration experience significantly higher rates of trauma and exacerbation of mental health conditions, and the period following release has been identified as a window of heightened risk for mental health distress and human immunodeficiency virus (HIV), sexually transmitted infections (STI) and hepatitis C (HCV) transmissions. Despite these vulnerabilities, and an urgent need for supports, optimal engagement strategies remain unclear. WORTH Transitions is a program made up of two evidence-based interventions focused on improving the health of women returning to the community from incarceration with substance use disorders. Combining the two was designed to reduce HIV/STIs/HCV risks and increase overall health treatment engagement using a community health worker led intervention. MethodsWe examined associations between trauma, mental health symptomology, and HIV/STI/HCV outcomes among women who engaged in the WORTH Transitions intervention (N = 206) Specifically, bivariate and longitudinal multivariate models were created to examine associations between trauma and mental health distress (defined as depressive and PTSD symptoms), on (1) types of engagement in HIV/STIs/HCV prevention and behavioral health services; and (2) HIV/STIs/HCV risk outcomes. The women who engaged in the intervention were 18 years and older and some were White, Black and other racial or ethnic minority. ResultsPTSD symptomology and being a Black or indigenous woman of color was significantly (p = 0.014) associated with individual or group session engagement. Neither trauma nor PTSD symptoms were associated with higher HIV/STIs/HCV risks. Instead, relative to those who did not engage in HIV/STI/HCV risky behaviors, PTSD symptomology (p = 0.040) was associated with more than 3-fold increase in the probability of being lost to follow up (relative risk ratio = 3.722). ConclusionGiven the impact of PTSD-related symptoms on driving both engagement in HIV/STIs/HCV prevention services and intervention attrition among women leaving incarceration, physical and behavioral health interventions must be both overtly trauma- and mental health-informed. As was the case with WORTH Transitions, physical and behavioral health services for this population must include intentional and active support of the forms of treatment participants endorse to ensure maximal engagement.

Background: Notifying a patient’s loved one about their death is a particularly challenging skill that requires specific training. Objective: We aimed to evaluate fourth year medical student (MS4) perspectives on a formative standardized patient (SP) encounter focused on death notification over the telephone. Design/Methods: As part of an MS4 capstone advanced communication skills workshop, an SP case was created for students to practice notification of death over the …

The so-called Diet Coke and Mentos experiment is initiated by dropping Mentos candies into a bottle of Diet Coke or other carbonated beverage. This causes the beverage to rapidly degas, causing foam to stream out of the bottle. Simple application of the gas laws leads to the straightforward prediction that ejection of greater foam volume is expected at lower atmospheric pressure. This hypothesis is bolstered when principles of bubble physics are taken into account. This hypothesis was tested and confirmed by monitoring the foam produced during the Diet Coke and Mentos experiment at various altitudes above sea level. Upon further application of the aforementioned principles, a relationship between degassing kinetics, beverage CO2 concentration, and the size of pores on the candy surface that serve as nucleation sites can be derived. Using this relationship and experimental measurements of degassing kinetics, students estimated that the nucleation sites on Mentos candies are on the order of 2-7 mu m in dimension. Students in Physical Chemistry, General Chemistry, and nonmajors' courses have found these experiments to be of great interest.

Strong evidence for improving clinical outcomes exists for the Diabetes Prevention Program (DPP) and diabetes self-management education (DSME) yet traditional methods of education and outreach have been minimally effective at engaging high-risk Hispanics. Scripps Whittier Diabetes Institute, San Diego, CA, has delivered culturally appropriate DSME and DPP programs for over 25 years and was seeking an effective method to further engage diverse communities. Facebook is the number one platform for U.S. Hispanics’ communication. Nearly half (48%) of U.S. Hispanics’ Facebook friends are family members, compared to 36% for the total population. Hispanics are the most mobile and socially active group in the U.S. and converse in the language of their preference. On-line messaging developed in Spanish and English utilized patient stories to increase understanding of diabetes risk and encourage an online risk assessment. The audience included adults ages 40+ in Chula Vista; along the Mexican American border. The campaign landing page included calls to action, helpful information regarding diabetes risk factors and links to inspiring patient stories. Nurturing emails were sent to all leads with lifestyle tips and call to action to register for a diabetes program. Bi-lingual telephone outreach was conducted within one week of the risk assessment completion to make a personal connection and answer questions. In the first 75 days of the campaign, 92 assessments were initiated: 66 completed: 26 abandoned. Of the leads sent: 75% were from the Spanish language campaign; 0.67% click-through-rate from Facebook to the landing page; of the 1800 clicks, 75% came from the Spanish language ads; 60-75% of the clicks are from a female audience for both English and Spanish; and nearly 50/50 split between at risk and not at risk for T2DM.This social media campaign pilot was effective in increasing awareness of diabetes risks, DPP and DSME in Hispanic communities, especially in the Spanish speaking, female population. Disclosure A. Philis-Tsimikas: Advisory Panel; Self; Lilly Diabetes, Medtronic, Novo Nordisk A/S, Sanofi. Employee; Spouse/Partner; Ionis Pharmaceuticals, Inc. Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Dexcom, Inc., Lilly Diabetes, Medtronic, Novo Nordisk A/S, Sanofi. M. Ruiz: None. A.L. Fortmann: None. E. Aguilar: None. R. Johnson: None. A. Kienast: None. C. Walker: None. Funding Woltman Family Foundation