Functional and biochemical parameters of peptide antigen presentation

To understand the mechanism by which peptide antigens are processed and presented to T cells, we examined the T-cell response to the 13-amino-acid peptide [alpha]-melanocyte-stimulating hormone ([alpha]-MSH). To determine the fine specificity of T-cell recognition, T cells specific for [alpha]-MSH, and genetically restricted by I-Ab/d, were challenged with different [alpha]-MSH analogs and homologs. It was found that intact [alpha]-MSH, including the blocked amino and carboxy termini of the native molecule, was required for T-cell responsiveness. Antigen-presenting cells (APC) could be briefly pulsed with [alpha]-MSH and then present the [alpha]-MSH antigenic determinant to T cells, indicating that the relevant antigen was retained by the APC. APC stimulatory capacity was dramatically reduced by aldehyde treatment of the APC, or by pulsing the APC with [alpha]-MSH at low temperature. Efficient [alpha]-MSH pulsing was also impaired by treatment of the APC with the carboxylic ionophore, monensin, but not by the lysosomotropic agents chloroquine and methylamine. In addition, isolated APC plasma membranes added to the T cells in the presence of soluble [alpha]-MSH were not stimulatory. However, plasma membranes isolated from APC that had been previously pulsed with [alpha]-MSH retained stimulatory activity for T-cell responses. The only detectable [alpha]-MSH contained in these pulsed APC membranes was in an acid-stable complex of higher molecular weight than native peptide. The amount of [alpha]-MSH detected in the cellular membrane fraction isolated by density gradient sedimentation was also reduced by treatments that reduced the APC stimulatory capacity, such as pulsing at low temperature or in the presence of monensin. Taken together, these results suggest that processing of [alpha]-MSH is unlike that heretofore described for other peptide antigens and seems to involve APC handling to form the stimulatory moiety presented on the APC surface.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/27319/1/0000341.pd

Policy and practices in primary care that supported the provision and receipt of care for older persons during the COVID-19 pandemic: a qualitative case study in three Canadian provinces

Abstract Background The effects of the COVID-19 pandemic on older adults were felt throughout the health care system, from intensive care units through to long-term care homes. Although much attention has been paid to hospitals and long-term care homes throughout the pandemic, less attention has been paid to the impact on primary care clinics, which had to rapidly change their approach to deliver timely and effective care to older adult patients. This study examines how primary care clinics, in three Canadian provinces, cared for their older adult patients during the pandemic, while also navigating the rapidly changing health policy landscape. Methods A qualitative case study approach was used to gather information from nine primary care clinics, across three Canadian provinces. Interviews were conducted with primary care providers (n = 17) and older adult patients (n = 47) from October 2020 to September 2021. Analyses of the interviews were completed in the language of data collection (English or French), and then summarized in English using a coding framework. All responses that related to COVID-19 policies at any level were also examined. Results Two main themes emerged from the data: (1) navigating the noise: understanding and responding to public health orders and policies affecting health and health care, and (2) receiving and delivering care to older persons during the pandemic: policy-driven challenges & responses. Providers discussed their experiences wading through the health policy directives, while trying to provide good quality care. Older adults found the public health information overwhelming, but appreciated the approaches adapted by primary care clinics to continue providing care, even if it looked different. Conclusions COVID-19 policy and guideline complexities obliged primary care providers to take an important role in understanding, implementing and adapting to them, and in explaining them, especially to older adults and their care partners

Obesity in adults: a 2022 adapted clinical practice guideline for Ireland

This Clinical Practice Guideline (CPG) for the management of obesity in adults in Ireland, adapted from the Canadian CPG, defines obesity as a complex chronic disease characterised by excess or dysfunctional adiposity that impairs health. The guideline reflects substantial advances in the understanding of the determinants, pathophysiology, assessment, and treatment of obesity. It shifts the focus of obesity management toward improving patient-centred health outcomes, functional outcomes, and social and economic participation, rather than weight loss alone. It gives recommendations for care that are underpinned by evidence-based principles of chronic disease management; validate patients' lived experiences; move beyond simplistic approaches of "eat less, move more" and address the root drivers of obesity. People living with obesity face substantial bias and stigma, which contribute to increased morbidity and mortality independent of body weight. Education is needed for all healthcare professionals in Ireland to address the gap in skills, increase knowledge of evidence-based practice, and eliminate bias and stigma in healthcare settings. We call for people living with obesity in Ireland to have access to evidence-informed care, including medical, medical nutrition therapy, physical activity and physical rehabilitation interventions, psychological interventions, pharmacotherapy, and bariatric surgery. This can be best achieved by resourcing and fully implementing the Model of Care for the Management of Adult Overweight and Obesity. To address health inequalities, we also call for the inclusion of obesity in the Structured Chronic Disease Management Programme and for pharmacotherapy reimbursement, to ensure equal access to treatment based on health-need rather than ability to pay

Multi-centre cluster randomised trial comparing a community group exercise programme with home based exercise with usual care for people aged 65 and over in primary care: protocol of the ProAct 65+trial

Background: Regular physical activity reduces the risk of mortality from all causes, with a powerful beneficial effect on risk of falls and hip fractures. However, physical activity levels are low in the older population and previous studies have demonstrated only modest, short-term improvements in activity levels with intervention.Design/Methods: Pragmatic 3 arm parallel design cluster controlled trial of class-based exercise (FAME), home-based exercise (OEP) and usual care amongst older people (aged 65 years and over) in primary care. The primary outcome is the achievement of recommended physical activity targets 12 months after cessation of intervention. Secondary outcomes include functional assessments, predictors of exercise adherence, the incidence of falls, fear of falling, quality of life and continuation of physical activity after intervention, over a two-year follow up. An economic evaluation including participant and NHS costs will be embedded in the clinical trial.Discussion: The ProAct65 trial will explore and evaluate the potential for increasing physical activity among older people recruited through general practice. The trial will be conducted in a relatively unselected population, and will address problems of selective recruitment, potentially low retention rates, variable quality of interventions and falls risk.Trial Registration: Trial Registration: ISRCTN4345377

Use of an electronic wellness instrument in the integrated health and social care of older adults: a group concept mapping study

Abstract Background Health system fragmentation directly contributes to poor health and social outcomes for older adults with multiple chronic conditions and their care partners. Older adults often require support from primary care, multiple specialists, home care, community support services, and other health-care sectors and communication between these providers is unstructured and not standardized. Integrated and interprofessional team-based models of care are a recommended strategy to improve health service delivery to older adults with complex needs. Standardized assessment instruments deployed on digital platforms are considered a necessary component of integrated care. The aim of this study was to develop strategies to leverage an electronic wellness instrument, interRAI Check Up Self Report, to support integrated health and social care for older adults and their care partners in a community in Southern Ontario, Canada. Methods Group concept mapping, a participatory mixed-methods approach, was conducted. Participants included older adults, care partners, and representatives from: home care, community support services, specialized geriatric services, primary care, and health informatics. In a series of virtual meetings, participants generated ideas to implement the interRAI Check Up and rated the relative importance of these ideas. Hierarchical cluster analysis was used to map the ideas into clusters of similar statements. Participants reviewed the map to co-create an action plan. Results Forty-one participants contributed to a cluster map of ten action areas (e.g., engagement of older adults and care partners, instrument’s ease of use, accessibility of the assessment process, person-centred process, training and education for providers, provider coordination, health information integration, health system decision support and quality improvement, and privacy and confidentiality). The health system decision support cluster was rated as the lowest relative importance and the health information integration was cluster rated as the highest relative importance. Conclusions Many person-, provider-, and system-level factors need to be considered when implementing and using an electronic wellness instrument across health- and social-care providers. These factors are highly relevant to the integration of other standardized instruments into interprofessional team care to ensure a compassionate care approach as technology is introduced

Oncologic Outcomes of Surgically Treated Cervical Cancer with No Residual Disease on Hysterectomy Specimen: A 4C (Canadian Cervical Cancer Collaborative) Working Group Study

Minimally invasive surgery for the treatment of macroscopic cervical cancer leads to worse oncologic outcomes than with open surgery. Preoperative conization may mitigate the risk of surgical approach. Our objective was to describe the oncologic outcomes in cases of cervical cancer initially treated with conization, and subsequently found to have no residual cervical cancer after hysterectomy performed via open and minimally invasive approaches. This was a retrospective cohort study of surgically treated cervical cancer at 11 Canadian institutions from 2007 to 2017. Cases initially treated with cervical conization and subsequent hysterectomy, with no residual disease on hysterectomy specimen were included. They were subdivided according to minimally invasive (laparoscopic/robotic (MIS) or laparoscopically assisted vaginal/vaginal hysterectomy (LVH)), or abdominal (AH). Recurrence free survival (RFS) and overall survival (OS) were estimated using Kaplan–Meier analysis. Chi-square and log-rank tests were used to compare between cohorts. Within the total cohort, 238/1696 (14%) had no residual disease on hysterectomy specimen (122 MIS, 103 AH, and 13 VLH). The majority of cases in the cohort were FIGO 2018 stage IB1 (43.7%) and underwent a radical hysterectomy (81.9%). There was no statistical difference between stage, histology, and radical vs simple hysterectomy between the abdominal and minimally invasive groups. There were no significant differences in RFS (5-year: MIS/LVH 97.7%, AH 95.8%, p = 0.23) or OS (5-year: MIS/VLH 98.9%, AH 97.4%, p = 0.10), although event-rates were low. There were only two recurrences. In this large study including only patients with no residual cervical cancer on hysterectomy specimen, no significant differences in survival were seen by surgical approach. This may be due to the small number of events or due to no actual difference between the groups. Further studies are warranted

Where and With Whom Does a Brief Social-Belonging Intervention Promote Progress in College?

A promising way to mitigate inequality is by addressing students’ worries about belonging. But where and with whom is this social-belonging intervention effective? Here we report a team-science randomized controlled experiment with 26,911 students at 22 diverse institutions. Results showed that the social-belonging intervention, administered online before college (in under 30 minutes), increased the rate at which students completed the first year as full-time students, especially among students in groups that had historically progressed at lower rates. The college context also mattered: The intervention was effective only when students’ groups were afforded opportunities to belong. This study develops methods for understanding how student identities and contexts interact with interventions. It also shows that a low-cost, scalable intervention generalizes its effects to 749 4-year institutions in the United States

Pain, Analgesic Use, and Patient Satisfaction With Spinal Versus General Anesthesia for Hip Fracture Surgery : A Randomized Clinical Trial.

BACKGROUND: The REGAIN (Regional versus General Anesthesia for Promoting Independence after Hip Fracture) trial found similar ambulation and survival at 60 days with spinal versus general anesthesia for hip fracture surgery. Trial outcomes evaluating pain, prescription analgesic use, and patient satisfaction have not yet been reported. OBJECTIVE: To compare pain, analgesic use, and satisfaction after hip fracture surgery with spinal versus general anesthesia. DESIGN: Preplanned secondary analysis of a pragmatic randomized trial. (ClinicalTrials.gov: NCT02507505). SETTING: 46 U.S. and Canadian hospitals. PARTICIPANTS: Patients aged 50 years or older undergoing hip fracture surgery. INTERVENTION: Spinal or general anesthesia. MEASUREMENTS: Pain on postoperative days 1 through 3; 60-, 180-, and 365-day pain and prescription analgesic use; and satisfaction with care. RESULTS: A total of 1600 patients were enrolled. The average age was 78 years, and 77% were women. A total of 73.5% (1050 of 1428) of patients reported severe pain during the first 24 hours after surgery. Worst pain over the first 24 hours after surgery was greater with spinal anesthesia (rated from 0 [no pain] to 10 [worst pain imaginable]; mean difference, 0.40 [95% CI, 0.12 to 0.68]). Pain did not differ across groups at other time points. Prescription analgesic use at 60 days occurred in 25% (141 of 563) and 18.8% (108 of 574) of patients assigned to spinal and general anesthesia, respectively (relative risk, 1.33 [CI, 1.06 to 1.65]). Satisfaction was similar across groups. LIMITATION: Missing outcome data and multiple outcomes assessed. CONCLUSION: Severe pain is common after hip fracture. Spinal anesthesia was associated with more pain in the first 24 hours after surgery and more prescription analgesic use at 60 days compared with general anesthesia. PRIMARY FUNDING SOURCE: Patient-Centered Outcomes Research Institut