Identifying competencies for an advanced practice physiotherapy role within an interprofessional chronic pain clinic.

BACKGROUND: Advanced practice physiotherapy (APP) models of care have shown success in access, safety, satisfaction, and care quality for musculoskeletal pain conditions in various settings. Yet, there is a gap in defining competencies for physiotherapists to be the initial point of contact for people with chronic pain. This study aims to identify and agree upon the competencies necessary for a physiotherapist to fulfill the role of an APP in an interprofessional chronic pain clinic. METHODS: Three focus groups were conducted using a Nominal Group Technique and a modified Delphi process. Consensus on the competency, defined as agreement by ≥ 75% of participants, was sought. RESULTS: Twenty-three experts (17 healthcare providers and six individuals with chronic pain) participated in the focus group discussions. Twenty completed the follow-up Delphi surveys. Ten essential competencies for an APP role in interprofessional chronic pain clinics were identified and achieved consensus: 1) use an evidence-based approach to practice; 2) communicate effectively with the patient; 3) perform a comprehensive assessment; 4) determine pain-related diagnoses; 5) develop therapeutic relationships; 6) provide appropriate care; 7) support patients through transitions in care; 8) collaborate with members of the interprofessional team; 9) advocate for the needs of the patients; and 10) use a reflective approach to practice. CONCLUSION: This study identified ten competencies essential for physiotherapists to fulfill an APP role within interprofessional chronic pain clinics. These competencies serve as a foundation for informing a training program and future research evaluating the effectiveness of the APP model in this setting.

Genotype-by-environment interactions govern fitness changes associated with adaptive mutations in two-component response systems.

Introduction: Two-component response systems (TCRS) are the main mechanism by which prokaryotes acclimate to changing environments. These systems are composed of a membrane bound histidine kinase (HK) that senses external signals and a response regulator (RR) that activates transcription of response genes. Despite their known role in acclimation, little is known about the role TCRS play in environmental adaptation. Several experimental evolution studies have shown the acquisition of mutations in TCRS during adaptation, therefore here we set out to characterize the adaptive mechanism resulting from these mutations and evaluate whether single nucleotide changes in one gene could induce variable genotype-by-environment (GxE) interactions. Methods: To do this, we assessed fitness changes and differential gene expression for four adaptive mutations in cusS, the gene that encodes the HK CusS, acquired by Escherichia coli during silver adaptation. Results: Fitness assays showed that as the environment changed, each mutant displayed a unique fitness profile with greatest fitness in the original selection environment. RNAseq then indicated that, in ± silver nitrate, each mutant induces a primary response that upregulates cusS, its RR cusR, and constitutively expresses the target response genes cusCFBA. This then induces a secondary response via differential expression of genes regulated by the CusR through TCRS crosstalk. Finally, each mutant undergoes fitness tuning through unique tertiary responses that result in gene expression patterns specific for the genotype, the environment and optimized for the original selection conditions. Discussion: This three-step response shows that different mutations in a single gene leads to individualized phenotypes governed by unique GxE interactions that not only contribute to transcriptional divergence but also to phenotypic plasticity.

"It's a stressful, trying time for the caretaker": an interpretive description qualitative study of postoperative transitions in care for older adults with frailty from the perspectives of informal caregivers.

BACKGROUND: Older adults with frailty have surgery at a high rate. Informal caregivers often support the postoperative transition in care. Despite the growing need for family and caregiver support for this population, little is known about the experience of providing informal care to older adults with frailty during the postoperative transition in care. The purpose of this study was to explore what is important during a postoperative transition in care for older adults with frailty from the perspective of informal caregivers. METHODS: This was a qualitative study using an interpretive description methodology. Seven informal caregivers to older adults [aged ≥ 65 years with frailty (Clinical Frailty Scale score ≥ 4) who had an inpatient elective surgery] participated in a telephone-based, semi-structured interview. Audio files were transcribed and analyzed using reflexive thematic analysis. RESULTS: Four themes were constructed: (1) being informed about what to expect after surgery; (2) accessible communication with care providers; (3) homecare resources are needed for the patient; and (4) a support network for the caregivers. Theme 4 included two sub-themes: (a) respite and emotional support and (b) occupational support. CONCLUSIONS: Transitions in care present challenges for informal caregivers of older adults with frailty, who play an important role in successful transitions. Future postoperative transitional care programs should consider making targeted information, accessible communication, and support networks available for caregivers as part of facilitating successful transitions in care.

The impact of emergency medicine residents on clinical productivity.

CONTEXT: Faculty productivity is of interest for hospital and university administrators as pressure is placed on them by government and private payors. Further, the effect of trainees on clinical productivity is of personal interest to physicians because their performance evaluations and earning potential are often tied to their productivity. Several groups have utilized creative methodology to study the effect of learners on emergency department (ED) productivity, but they were faced with multiple confounding variables for which it was difficult to adjust. In this study, we utilize relative value unit (RVU)/h to study the effect of resident physicians and medical students on the productivity of academic emergency physicians (EPs) during the implementation of a new residency program. Each physician's productivity on shifts with distinct types of learners present is compared to their shifts worked without any learners during the same time frame. Each attending physician serves as their own control while the confounding variables introduced by comparing over multiple years are minimized. OBJECTIVES: The objective of this study is to measure the influence of emergency medicine (EM) residents on the clinical productivity of attending EPs. METHODS: We conducted an observational study of a single ED during implementation of a new residency program. The productivity of each EP was measured by RVU/h billed. Trainees' schedules and end-of-shift evaluations were utilized to determine what learners (if any) were working with the EP on each shift. RVU/h calculations were performed for each EP (overall, when working without learners, and when working with each of the four learner categories). The primary outcome (determined a priori) was the difference in RVU/h for the attending EPs when they worked without learners compared to when they worked a majority of their shift with at least one learner. The secondary outcome (also determined a priori) was determining the influence of the learners of each type on EP RVU/h for the subgrouped shifts in which a learner was present for the majority of the shift. RESULTS: There was no significant difference in mean EP RVU/h when attendings worked with a medical student or non-EM R1 in comparison to working without learners in the 1761 ED encounters analyzed (12.95 RVU/h vs. 12.52 RVU/h; p=0.125). Although there was variability among individual physicians, EP RVU/h increased significantly for the overall group when one or more EM R1s were present (15.19 RVU/h with one EM R1 present, 15.25 RVU/h with two, 24.75 RVU/h with three; p<0.001). Similarly, mean EP productivity increased significantly with the addition of an EM R2 (17.96 RVU/h vs. 16.84 RVU/h; p=0.001). CONCLUSIONS: The presence of EM residents was positively associated with the clinical productivity of EM faculty as measured by RVU/h. There was also a positive association between productivity and the number of EM residents present as well as their training level. Non-EM residents and medical students had no effect on EP productivity.

Physical Resilience as a Predictor of Lifespan and Late-Life Health in Genetically Heterogeneous Mice.

Dynamic measures of resilience-the ability to resist and recover from a challenge-may be informative of the rate of aging before overt manifestations such as chronic disease, disability, and frailty. From this perspective mid-life resilience may predict longevity and late-life health. To test this hypothesis, we developed simple, reproducible, clinically relevant challenges, and outcome measures of physical resilience that revealed differences between and within age groups of genetically heterogeneous mice, and then examined associations between mid-life resilience and both lifespan and late-life measures of physiological function. We demonstrate that time to recovery from isoflurane anesthesia and weight change following a regimen of chemotherapy significantly differed among young, middle-aged, and older mice, and were more variable in older mice. Females that recovered faster than the median time from anesthesia (more resilient) at 12 months of age lived 8% longer than their counterparts, while more resilient males in mid-life exhibited better cardiac (fractional shortening and left ventricular volumes) and metabolic (glucose tolerance) function at 24 months of age. Moreover, female mice with less than the median weight loss at Day 3 of the cisplatin challenge lived 8% longer than those that lost more weight. In contrast, females who had more weight loss between Days 15 and 20 were relatively protected against early death. These data suggest that measures of physical resilience in mid-life may provide information about individual differences in aging, lifespan, and key parameters of late-life health.

Geriatric assessment-guided interventions for older adults with multiple myeloma: A feasibility and acceptability study.

INTRODUCTION: Geriatric assessment (GA)-guided supportive care programs have been successful in improving treatment outcomes for older adults with solid-organ cancers. This study aimed to evaluate the feasibility of a GA-guided supportive care program among older adults treated for multiple myeloma (MM). MATERIALS AND METHODS: The study utilized an existing registry of adults with plasma cell disorders at the University of North Carolina. Patients with MM, aged 60 or older, and having a GA-identified deficit in one or more problem area were offered referrals to supportive care resources during routine visits. Problem areas included physical function deficits, polypharmacy, and anxiety or depression. Patients with physical function deficits were offered referral to physical therapy (PT), those with polypharmacy to an Oncology Clinical Pharmacist Practitioner (CPP), and those with mental health symptoms to the Comprehensive Cancer Support Program (CCSP). RESULTS: Of the 58 individuals identified as having at least one deficit on the GA, PT was the most commonly identified relevant resource (79%), followed by CPP visits (57%). Among individuals that were offered referral(s) to at least one new supportive care resource, the acceptance rate was 50%. Referral acceptance rates were highest among those recommended for a CPP visit (55% of those approached) and lowest for CCSP (0%). DISCUSSION: The study examined the feasibility and acceptability of a referral program for supportive care resources among older adults with MM who have deficits on GA. The most commonly identified deficit was physical functioning, followed by polypharmacy and mental health. The study found that physical interventions and referrals to CPPs were the most accepted interventions. However, the low proportion of patients who accepted physical therapy referrals indicates the need for tailored and more personalized approaches. Further research is needed to explore the feasibility and impact of supportive care referral programs for older adults with MM.

"Like fighting a fire with a water pistol": A qualitative study of the work experiences of critical care nurses during the COVID-19 pandemic.

AIM: To understand the experience of critical care nurses during the COVID-19 pandemic, through the application of the Job-Demand-Resource model of occupational stress. DESIGN: Qualitative interview study. METHODS: Twenty-eight critical care nurses (CCN) working in ICU in the UK NHS during the COVID-19 pandemic took part in semi-structured interviews between May 2021 and May 2022. Interviews were guided by the constructs of the Job-Demand Resource model. Data were analysed using framework analysis. RESULTS: The most difficult job demands were the pace and amount, complexity, physical and emotional effort of their work. Prolonged high demands led to CCN experiencing emotional and physical exhaustion, burnout, post-traumatic stress symptoms and impaired sleep. Support from colleagues and supervisors was a core job resource. Sustained demands and impaired physical and psychological well-being had negative organizational consequences with CCN expressing increased intention to leave their role. CONCLUSIONS: The combination of high demands and reduced resources had negative impacts on the psychological well-being of nurses which is translating into increased consideration of leaving their profession. IMPLICATIONS FOR THE PROFESSION AND/OR PATIENT CARE: The full impacts of the pandemic on the mental health of CCN are unlikely to resolve without appropriate interventions. IMPACT: Managers of healthcare systems should use these findings to inform: (i) the structure and organization of critical care workplaces so that they support staff to be well, and (ii) supportive interventions for staff who are carrying significant psychological distress as a result of working during and after the pandemic. These changes are required to improve staff recruitment and retention. REPORTING METHOD: We used the COREQ guidelines for reporting qualitative studies. PATIENT AND PUBLIC CONTRIBUTION: Six CCN provided input to survey content and interview schedule. Two authors and members of the study team (T.S. and S.C.) worked in critical care during the pandemic.

"I can't imagine having to do it on your own": a qualitative study on postoperative transitions in care from the perspectives of older adults with frailty.

BACKGROUND: Adults aged 65 and older have surgery more often than younger people and often live with frailty. The postoperative transition in care from hospital to home after surgey is a challenging time for older adults with frailty as they often experience negative outcomes. Improving postoperative transitions in care for older adults with frailty is a priority. However, little knowledge from the perspective of older adults with frailty is available to support meaningful improvements in postoperative transitions in care. OBJECTIVE: To explore what is important to older adults with frailty during a postoperative transition in care. METHODS: This qualitative study used an interpretive description methodology. Twelve adults aged ≥ 65 years with frailty (Clinical Frailty Scale score ≥ 4) who had an inpatient elective surgery and could speak in English participated in a telephone-based, semi-structured interview. Audio files were transcribed and analyzed using thematic analysis. RESULTS: Five themes were constructed: 1) valuing going home after surgery; 2) feeling empowered through knowledge and resources; 3) focusing on medical and functional recovery; 4) informal caregivers and family members play multiple integral roles; and 5) feeling supported by healthcare providers through continuity of care. Each theme had 3 sub-themes. CONCLUSION: Future programs should focus on supporting patients to return home by empowering patients with resources and clear communication, ensuring continuity of care, creating access to homecare and virtual support, focusing on functional and medical recovery, and recognizing the invaluable role of informal caregivers.

Antigen-specific T cell responses in SARS-CoV-2 mRNA-vaccinated children.

SARS-CoV-2 mRNA vaccines elicit humoral responses in children that are comparable to those in adults. However, early-life T cell responses are distinct from adult ones, and questions remain about the nature and kinetics of mRNA vaccine-induced T cell responses in children. We report that Pfizer BNT162b2 mRNA vaccination elicits a significant antigen-specific CD4+ T cell response in the ≥12-year-old cohort. This response is weaker in magnitude in the 5- to 11-year-old cohort and is not improved by a higher vaccine dose (Moderna mRNA1273, 100 µg), suggesting distinct developmental programming that may underscore early-life T cell immunity. Increased effector phenotypes of antigen-specific T cells in younger children correspond with elevated anti-receptor binding domain antibody levels, albeit at the cost of memory generation. These studies highlight aspects of age-specific adaptive immune responses and the need for careful consideration of priming conditions including vaccine dose and adjuvant in the pediatric population.

Primary mediastinal seminoma presenting with paraneoplastic anti-Hu encephalitis: a case report and literature review.

Primary mediastinal seminomas are exceedingly rare tumors, often localized to the anterior mediastinum. They may present with numerous complications, including superior vena cava syndrome, chylothorax, and pericardial effusions. Less commonly, they may present with paraneoplastic encephalitis. In this report we describe a case of a 19-year-old male with no significant past medical history who presented with bilateral hearing loss, progressive neuropathy, and ataxia. Subsequently the patient was found to have mediastinal mass with a high-titer anti-Hu antibody. To our knowledge, only one other case of mediastinal seminoma presenting with anti-Hu antibodies has been described in the literature. In this report, we describe a rare case of mediastinal seminoma, describe treatment options, and discuss additional known cases presenting with paraneoplastic encephalitis.

Direct cost variance analysis of peroral endoscopic myotomy vs heller myotomy for management of achalasia: A tertiary referral center experience.

BACKGROUND: Laparoscopic Heller myotomy (LHM) has been the traditional surgical treatment for achalasia. Recently, peroral endoscopic myotomy (POEM) has demonstrated similar clinical outcomes with shorter procedure times. Studies comparing the direct cost-effectiveness of POEM vs LHM are limited. AIM: To compare costs of POEM vs LHM. METHODS: This retrospective chart review aimed to compare the outcomes and cost of clinical care between patients who underwent POEM and LHM procedures for achalasia. The study was conducted at a tertiary academic center from January 2019 to December 2020. Clinical outcomes, including post-operative Eckardt scores and adverse events, were assessed and compared between the two groups. Direct cost variance analysis was utilized to evaluate the cost of clinical care incurred by patients undergoing POEM in the year preceding the procedure, during the index admission, and one year post-procedure, in comparison to patients undergoing LHM. RESULTS: Of 30 patients were included (15 POEM and 15 LHM) in the study. Patients in the POEM group had a mean Eckardt score of 0.5 ± 0.5 post-procedure, which was no different from patients in the LHM group (0.7 ± 0.6, P = 0.17) indicating comparative efficacy. However, the total costs of the admission for the procedure in the LHM group were on average $1827 more expensive than in the POEM group (P < 0.01). Total healthcare costs one year prior to index procedure were $7777 higher in the LHM group, but not statistically different (P = 0.34). The patients in the LHM group one year after the index procedure had accrued $19730.24 larger total cost, although this was not statistically different from POEM group (P = 0.68). CONCLUSION: Despite similar clinical outcomes, the cost of the index procedure admission for POEM was significantly lower than for LHM. The difference was primarily related to shorter time increments utilized in the operating room during the index procedure, and shorter length of hospital stay following POEM.

Myocardial Recovery in Recent Onset Dilated Cardiomyopathy: Role of CDCP1 and Cardiac Fibrosis.

BACKGROUND: Dilated cardiomyopathy (DCM) is a major cause of heart failure and carries a high mortality rate. Myocardial recovery in DCM-related heart failure patients is highly variable, with some patients having little or no response to standard drug therapy. A genome-wide association study may agnostically identify biomarkers and provide novel insight into the biology of myocardial recovery in DCM. METHODS: A genome-wide association study for change in left ventricular ejection fraction was performed in 686 White subjects with recent-onset DCM who received standard pharmacotherapy. Genome-wide association study signals were subsequently functionally validated and studied in relevant cellular models to understand molecular mechanisms that may have contributed to the change in left ventricular ejection fraction. RESULTS: The genome-wide association study identified a highly suggestive locus that mapped to the 5'-flanking region of the CDCP1 (CUB [complement C1r/C1s, Uegf, and Bmp1] domain containing protein 1) gene (rs6773435; P=7.12×10-7). The variant allele was associated with improved cardiac function and decreased CDCP1 transcription. CDCP1 expression was significantly upregulated in human cardiac fibroblasts (HCFs) in response to the PDGF (platelet-derived growth factor) signaling, and knockdown of CDCP1 significantly repressed HCF proliferation and decreased AKT (protein kinase B) phosphorylation. Transcriptomic profiling after CDCP1 knockdown in HCFs supported the conclusion that CDCP1 regulates HCF proliferation and mitosis. In addition, CDCP1 knockdown in HCFs resulted in significantly decreased expression of soluble ST2 (suppression of tumorigenicity-2), a prognostic biomarker for heart failure and inductor of cardiac fibrosis. CONCLUSIONS: CDCP1 may play an important role in myocardial recovery in recent-onset DCM and mediates its effect primarily by attenuating cardiac fibrosis.

Delivering Team-Based Primary Care for the Management of Chronic Low Back Pain: An Interpretive Description Qualitative Study of Healthcare Provider Perspectives.

Background: Chronic low back pain (LBP) is a prevalent and disabling health issue. Team-based models of primary care are ideally positioned to provide comprehensive care for patients with chronic LBP. A better understanding of primary care team perspectives can inform future efforts to improve how team-based care is provided for patients with chronic LBP in this practice setting. Aims: The aim of this study was to understand health care providers' experiences, perceived barriers and facilitators, and recommendations when providing team-based primary care for the management of chronic LBP. Methods: We conducted an interpretive description qualitative study based on focus group discussions with health care providers from team-based primary care settings in Ontario, Canada. Data were analyzed using thematic analysis. Results: We conducted five focus groups with five different primary care teams, including a total of 31 health care providers. We constructed four themes (each with subthemes) related to experiences, perceived barriers and facilitators, and recommendations to providing team-based primary care for the management of chronic LBP, including (1) care pathways and models of service delivery, (2) team processes and organization, (3) team culture and environment, and (4) patient needs and readiness. Conclusions: Primary care teams are implementing diverse care pathways and models of service delivery for the management of patients with chronic LBP, which can be influenced by patient, team, and organizational factors. Results have potential implications for future research and practice innovations to improve how team-based primary care is delivered for patients with chronic LBP.

Contexte: La lombalgie chronique est un probléme de santé répandu et invalidant. Les modéles de soins primaires en équipe sont particuliérement bien placés pour dispenser des soins complets aux patients souffrant de lombalgie chronique. Une meilleure compréhension des perspectives de l'équipe de soins primaires peut éclairer les efforts futurs visant à améliorer la façon dont les soins en équipe sont dispensés aux patients atteints de lombalgie chronique dans ce cadre de pratique.Objectifs: L'objectif de cette étude était de comprendre les expériences des prestataires de soins de santé, les obstacles et les facilitateurs perçus, ainsi que les recommandations pour la prestation de soins primaires en équipe dans le cadre de la prise en charge de la lombalgie chronique.Méthodes: Nous avons mené une étude qualitative de description interprétative basée sur des discussions de groupe avec des prestataires de soins de santé issus de milieux de soins primaires en équipe en Ontario, au Canada. Les données ont été analysées à l'aide d'une analyse thématique.Résultats: Nous avons organisé cinq groupes de discussion avec cinq équipes de soins primaires différentes, auxquels ont participé 31 prestataires de soins de santé. Nous avons construit quatre thémes (chacun avec des sous-thémes) liés aux expériences, aux obstacles et aux facilitateurs perçus, ainsi qu'aux recommandations relatives à la prestation de services primaires en équipe pour la prise en charge de la lombalgie chronique, y compris (1) les parcours de soins et les modéles de prestation de services, (2) les processus et l'organisation de l'équipe, (3) la culture et l'environnement de l'équipe, et (4) les besoins des patients et leur état de préparation.Conclusions: Les équipes de soins primaires mettent en œuvre divers parcours de soins et modéles de prestation de services pour la prise en charge des patients atteints de lombalgie chronique, qui peuvent être influencés par des facteurs liés au patient, à l'équipe et à l'organisation. Les résultats ont des implications potentielles pour la recherche future et les innovations dans la pratique afin d'améliorer la façon dont les soins primaires en équipe sont dispensés aux patients atteints de lombalgie chronique.

Assessing the feasibility of a clinical trial to evaluate an advanced practice physiotherapy model of care in chronic pain management: a feasibility study.

BACKGROUND: Chronic pain management is challenging for health systems worldwide. Clinical practice guidelines recommend interprofessional chronic pain management, but chronic pain clinics often have lengthy wait-lists. Advanced practice physiotherapists (APP) in orthopedic clinics and emergency departments have provided effective care and reduced wait times. The purpose of this study is to determine the feasibility of a clinical trial to evaluate the effects of integrating an APP into a chronic pain clinic setting. The primary objectives are as follows: (1) determine the feasibility of implementing trial methods by evaluating participant recruitment rates, retention, and assessment completion; (2) determine the feasibility of implementing the APP model of care by monitoring care provided and treatment fidelity; and (3) assess contextual factors that may influence implementation of the APP model of care by exploring the perspectives of patient participants and healthcare providers related to the model of care. METHODS: This will be a single-arm feasibility study with embedded qualitative interviews to assess contextual factors influencing implementation by exploring participant and provider perspectives. Approximately 40 adults with chronic musculoskeletal pain referred for care at an interprofessional chronic pain clinic will be invited to participate in the feasibility study. Approximately 10-12 patient participants and 5-10 health professionals from the interprofessional team will be interviewed using an interpretive description approach. The APP model of care will involve participants seeing a physiotherapist as the first point of contact within the interprofessional team. The APP will complete an initial assessment and make care recommendations. Outcome measures planned for the full trial will be reported descriptively, including pain severity, pain interference, health-related quality of life, psychosocial risk factors for chronic pain, treatment satisfaction, perceived change, healthcare utilization, and healthcare costs over one year. DISCUSSION: This study will inform plans to implement a full-scale study to evaluate the impact of an APP model of care in an interprofessional chronic pain management program. The results of the full study are intended to inform stakeholders considering this model to improve patient-centered and health system outcomes in interprofessional pain management program settings. TRIAL REGISTRATION: ClinicalTrials.gov, NCT05336903 (Registered April 5, 2022).

Characteristics of interprofessional rehabilitation programs for patients with chronic low back pain evaluated in the literature: a scoping review protocol.

BACKGROUND: Interprofessional rehabilitation programs have demonstrated effectiveness at improving health-related quality of life, function, work abilities, and reducing pain, for patients with chronic low back pain (CLBP). However, the characteristics of interprofessional rehabilitation programs vary widely across studies. Therefore, clarifying and describing key characteristics of interprofessional rehabilitation programs for patients with CLBP will be valuable for future intervention design and implementation. This scoping review aims to identify and describe the key characteristics of interprofessional rehabilitation programs for patients with CLBP. METHODS: Our scoping review will follow the framework developed by Arksey and O'Malley, further enhanced by Levac et al. and the Joanna Briggs Institute (JBI). Electronic databases, including MEDLINE, EMBASE, CINAHL, PsycINFO, SCOPUS, PubMed, Web of Science, and Cochrane Library, will be searched to identify relevant published studies. Our scoping review will consider all primary source peer-reviewed published articles that evaluated interprofessional rehabilitation programs for adults with CLBP from all countries and any therapeutic settings. The Covidence software will be used to remove duplicates, article screening, record the step-by-step selection process, and data extraction. The analysis will involve a descriptive numerical summary and narrative analysis. Data will be presented in graphical and tabular format based on the nature of the data. DISCUSSION: This scoping review is expected to provide a source of evidence for developing and implementing interprofessional rehabilitation programs in new settings or contexts. As such, this review will guide future research and provide key information to health professionals, researchers and policymakers interested in designing and implementing evidence and theory-informed interprofessional rehabilitation programs for patients with CLBP. TRIAL REGISTRATION: https://osf.io/rquxv .

Implementing Smartphone Tutorials for Patients With Severe Glaucoma.

Purpose The purpose of the study is to determine if instructional videos detailing the use of smartphone accessibility features may be used to improve quality of life and comfort with phone usage among patients with severe glaucoma. Design The design of the present study is an interventional case series. Methods The patients with vision loss due to severe glaucoma were recruited from one institution. Two surveys were completed to provide baseline data: one detailed their current use of smartphone accessibility features, and the other provided survey was the EuroQol 5 Dimension 5 Level (EQ-5D-5L) (EuroQol Group, Rotterdam, Netherlands), which is used to assess the quality of life. Then, the patients were shown a brief video with instructions on configuring the use of voice-over, magnification, and zoom functions, along with other features. To conclude, the patients completed the same surveys either at follow-up visits or by phone calls. Results Fifteen patients were recruited to participate in the study. At baseline, the participants used a median of one accessibility feature, with the most common feature being "text sizing/bolding." At follow-up, the participants averaged the gain of use of one accessibility feature and reported a decrease in text messaging visual limitation, although these findings did not reach statistical significance. Overall, the quality of life, as measured by the EQ-5D-5L, demonstrated a non-statistically significant increase of six points. Conclusions Despite the lack of statistical significance, our results indicate that providing instructional videos may benefit the patients' ability to navigate on their smartphones. Incorporating links or Quick Response (QR) codes to these instructional videos provides an opportunity to improve the quality of life at no additional risk to the patient. Further studies are needed with an increased population to investigate for any significance of our findings.

Senescent Cells: A Therapeutic Target in Cardiovascular Diseases.

Senescent cell accumulation has been observed in age-associated diseases including cardiovascular diseases. Senescent cells lack proliferative capacity and secrete senescence-associated secretory phenotype (SASP) factors that may cause or worsen many cardiovascular diseases. Therapies targeting senescent cells, especially senolytic drugs that selectively induce senescent cell removal, have been shown to delay, prevent, alleviate, or treat multiple age-associated diseases in preclinical models. Some senolytic clinical trials have already been completed or are underway for a number of diseases and geriatric syndromes. Understanding how cellular senescence affects the various cell types in the cardiovascular system, such as endothelial cells, vascular smooth muscle cells, fibroblasts, immune cells, progenitor cells, and cardiomyocytes, is important to facilitate translation of senotherapeutics into clinical interventions. This review highlights: (1) the characteristics of senescent cells and their involvement in cardiovascular diseases, focusing on the aforementioned cardiovascular cell types, (2) evidence about senolytic drugs and other senotherapeutics, and (3) the future path and clinical potential of senotherapeutics for cardiovascular diseases.

The Role of Mobile Genetic Elements in Virulence Factor Carriage from Symptomatic and Asymptomatic Cases of Escherichia coli Bacteriuria.

Uropathogenic Escherichia coli (UPEC) is extremely diverse genotypically and phenotypically. Individual strains can variably carry diverse virulence factors, making it challenging to define a molecular signature for this pathotype. For many bacterial pathogens, mobile genetic elements (MGEs) constitute a major mechanism of virulence factor acquisition. For urinary E. coli, the total distribution of MGEs and their role in the acquisition of virulence factors is not well defined, including in the context of symptomatic infection versus asymptomatic bacteriuria (ASB). In this work, we characterized 151 isolates of E. coli, derived from patients with either urinary tract infection (UTI) or ASB. For both sets of E. coli, we catalogued the presence of plasmids, prophage, and transposons. We analyzed MGE sequences for the presence of virulence factors and antimicrobial resistance genes. These MGEs were associated with only ~4% of total virulence associated genes, while plasmids contributed to ~15% of antimicrobial resistance genes under consideration. Our analyses suggests that, across strains of E. coli, MGEs are not a prominent driver of urinary tract pathogenesis and symptomatic infection. IMPORTANCE Escherichia coli is the most common etiological agent of urinary tract infections (UTIs), with UTI-associated strains designated "uropathogenic" E. coli or UPEC. Across urinary strains of E. coli, the global landscape of MGEs and its relationship to virulence factor carriage and clinical symptomatology require greater clarity. Here, we demonstrate that many of the putative virulence factors of UPEC are not associated with acquisition due to MGEs. The current work enhances our understanding of the strain-to-strain variability and pathogenic potential of urine-associated E. coli and points toward more subtle genomic differences distinguishing ASB from UTI isolates.

DR3 Regulates Intestinal Epithelial Homeostasis and Regeneration After Intestinal Barrier Injury.

BACKGROUND & AIMS: Tumor necrosis factor (TNF) superfamily member tumor necrosis factor-like protein 1A (TL1A) has been associated with the susceptibility and severity of inflammatory bowel diseases. However, the function of the tumor necrosis factor-like protein 1A and its receptor death receptor 3 (DR3) in the development of intestinal inflammation is incompletely understood. We investigated the role of DR3 expressed by intestinal epithelial cells (IECs) during intestinal homeostasis, tissue injury, and regeneration. METHODS: Clinical phenotype and histologic inflammation were assessed in C57BL/6 (wild-type), Tl1a-/- and Dr3-/- mice in dextran sulfate sodium (DSS)-induced colitis. We generated mice with an IEC-specific deletion of DR3 (Dr3ΔIEC) and assessed intestinal inflammation and epithelial barrier repair. In vivo intestinal permeability was assessed by fluorescein isothiocyanate dextran uptake. Proliferation of IECs was analyzed by bromodeoxyuridine incorporation. Expression of DR3 messenger RNA was assessed by fluorescent in situ hybridization. Small intestinal organoids were used to determine ex vivo regenerative potential. RESULTS: Dr3-/- mice developed more severe colonic inflammation than wild-type mice in DSS-induced colitis with significantly impaired IEC regeneration. Homeostatic proliferation of IECs was increased in Dr3-/- mice, but blunted during regeneration. Cellular localization and expression of the tight junction proteins Claudin-1 and zonula occludens-1 were altered, leading to increased homeostatic intestinal permeability. Dr3ΔIEC mice recapitulated the phenotype observed in Dr3-/- mice with increased intestinal permeability and IEC proliferation under homeostatic conditions and impaired tissue repair and increased bacterial translocation during DSS-induced colitis. Impaired regenerative potential and altered zonula occludens-1 localization also were observed in Dr3ΔIEC enteroids. CONCLUSIONS: Our findings establish a novel function of DR3 in IEC homeostasis and postinjury regeneration independent of its established role in innate lymphoid cells and T-helper cells.