Assessment of the Impact of RNase in Patients With Severe Fatigue Related to Post-Acute Sequelae of SARS-CoV-2 Infection (PASC): A Randomized Phase 2 Trial of RSLV-132.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA and RNA debris persist in viral reservoirs for weeks to months following infection, potentially triggering interferon production and chronic inflammation. RSLV-132 is a biologic drug composed of catalytically active human RNase1 fused to human IgG1 Fc and is designed to remain in circulation and digest extracellular RNA. We hypothesized that removal of SARS-CoV-2 viral RNA from latent reservoirs may improve inflammation, neuroinflammation, and fatigue associated with post-acute sequelae of SARS-CoV-2 infection (PASC). METHODS: This was a phase 2, double-blind, placebo-controlled randomized clinical trial in participants with a 24-week history of PASC and severe fatigue. The primary endpoint of the trial assessed the impact of 6 intravenous doses of RSLV-132 on the mean change from baseline at day 71 in the Patient-Reported Outcomes Measurement Information System Fatigue Short Form 7a (PROMIS Fatigue SF 7a). RESULTS: A statistically significant difference on day 71 was not observed with respect to the primary or secondary endpoints. This was likely due to a placebo response that increased during the trial. Statistically significant improvement in fatigue as measured by the PROMIS Fatigue SF 7a, Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue), and Physicians Global Assessment (PGA) instruments were observed earlier in the trial, with women demonstrating greater responses to RSLV-132 than men. CONCLUSION: While fatigue was not statistically significantly improved at Day 71, earlier timepoints revealed statistically significant improvement in fatigue and physician global assessment. The data suggest eliminating latent viral RNA by increasing serum RNase activity may improve fatigue in PASC patients. Women may respond better to this approach than men. Future studies will aim to confirm these findings.

Obesity in Adults: A 2022 Adapted Clinical Practice Guideline for Ireland.

BACKGROUND: 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. SUMMARY: 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. KEY MESSAGES: 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.

The impact of the COVID-19 pandemic on medical student education: Implementation and outcome of a virtual general surgery curriculum.

BACKGROUND: Due to the COVID-19 pandemic, medical schools were forced to adapt clinical curricula. The University of Washington School of Medicine created a hybrid in person and virtual general surgery clerkship. METHODS: The third year general surgery clerkship was modified to a 4-week in person and 2-week virtual clerkship to accommodate the same number of learners in less time. All students completed a survey to assess the impact of the virtual clerkship. RESULTS: The students preferred faculty lectures over national modules in the virtual clerkship. 58.6% indicated they would prefer the virtual component before the in-person experience. There was no change from previous years in final grades or clerkship exam scores after this hybrid curriculum. CONCLUSIONS: If the need for a virtual general surgery curriculum arises again in the future, learners value this experience at the beginning of the clerkship and prefer faculty lectures over national modules.

Long-Acting Reversible Contraception: An Essential Guide for Pediatric Primary Care Providers.

Long-acting reversible contraception (LARC) methods are 20% more effective than traditional contraceptives and are recommended by the American Academy of Pediatrics and American College of Obstetrics and Gynecology as first-line contraception for adolescent girls. Large studies show that LARC use reduces unintended pregnancies, increases user satisfaction, and prolongs duration of use. This article prepares the primary care provider (PCP) with knowledge on safety, efficacy, eligibility, confidentiality, anticipatory guidance, how to find a LARC provider, and guidance on common side effects so the PCP can confidently counsel adolescent patients on LARC methods.

The WWAMI Targeted Rural Underserved Track (TRUST) Program: An Innovative Response to Rural Physician Workforce Shortages.

PROBLEM: Too few physicians practice in rural areas. To address the physician workforce needs of the Washington, Wyoming, Alaska, Montana, and Idaho (WWAMI) region, the University of Washington School of Medicine developed the Targeted Rural Underserved Track (TRUST) program in August 2008. TRUST is a four-year curriculum centered on a clinical longitudinal continuity experience with students repeatedly returning to a single site located in a rural community or small city. APPROACH: The overarching theme of TRUST is one of linkages. Students are strategically linked to a rural community, known as their TRUST continuity community (TCC). The program begins with a targeted admission process and combines new and established programs and curricular elements to form a cohesive educational experience. This experience includes repeated preclinical visits, clerkships, and electives at a student's TCC, and rural health courses, the Underserved Pathway, and the Rural Underserved Opportunities Program (which includes a community-oriented primary care scholarly project). OUTCOMES: TRUST was piloted in Montana in 2008. With the matriculating class of 2015, every state in the WWAMI region will have TRUST students. From 2009 (the year targeted admissions began) to 2015, 123 students have been accepted into TRUST. Thirty-three students have graduated. Thirty (90.9%) of these graduates have entered residencies in needed regional specialties. NEXT STEPS: Next steps include implementing a robust evaluation program, obtaining secure institutional programmatic funding, and further developing linkages with regional rural residency programs. TRUST may be a step forward in addressing regional needs and a reproducible model for other medical schools.

Expanding clinical medical training opportunities at the University of Nairobi: adapting a regional medical education model from the WWAMI program at the University of Washington.

A major medical education need in Sub-Saharan Africa includes expanding clinical training opportunities to develop health professionals. Medical education expansion is a complicated process that requires significant investment of financial and human resources, but it can also provide opportunities for innovative approaches and partnerships. In 2010, the U.S. President's Emergency Plan for AIDS Relief launched the Medical Education Partnership Initiative to invest in medical education and health system strengthening in Africa. Building on a 30-year collaborative clinical and research training partnership, the University of Nairobi in Kenya developed a pilot regional medical education program modeled on the WWAMI (Washington, Wyoming, Alaska, Montana, and Idaho) medical education program at the University of Washington in the United States. The University of Nairobi adapted key elements of the WWAMI model to expand clinical training opportunities without requiring major capital construction of new buildings or campuses. The pilot program provides short-term clinical training opportunities for undergraduate students and recruits and trains clinical faculty at 14 decentralized training sites. The adaptation of a model from the Northwestern United States to address medical education needs in Kenya is a successful transfer of knowledge and practices that can be scaled up and replicated across Sub-Saharan Africa.

Challenges and opportunities in building a sustainable rural primary care workforce in alignment with the Affordable Care Act: the WWAMI program as a case study.

The authors examine the potential impact of the Patient Protection and Affordable Care Act (ACA) on a large medical education program in the Northwest United States that builds the primary care workforce for its largely rural region. The 42-year-old Washington, Wyoming, Alaska, Montana, and Idaho (WWAMI) program, hosted by the University of Washington School of Medicine, is one of the nation's most successful models for rural health training. The program has expanded training and retention of primary care health professionals for the region through medical school education, graduate medical education, a physician assistant training program, and support for practicing health professionals.The ACA and resulting accountable care organizations (ACOs) present potential challenges for rural settings and health training programs like WWAMI that focus on building the health workforce for rural and underserved populations. As more Americans acquire health coverage, more health professionals will be needed, especially in primary care. Rural locations may face increased competition for these professionals. Medical schools are expanding their positions to meet the need, but limits on graduate medical education expansion may result in a bottleneck, with insufficient residency positions for graduating students. The development of ACOs may further challenge building a rural workforce by limiting training opportunities for health professionals because of competing demands and concerns about cost, efficiency, and safety associated with training. Medical education programs like WWAMI will need to increase efforts to train primary care physicians and increase their advocacy for student programs and additional graduate medical education for rural constituents.

Family context as it relates to weight-related behaviors in preadolescent African American girls.

OBJECTIVE: To examine family context in relation to body image, weight concerns, and weight control behaviors in preadolescent African American girls. METHODS: Cross-sectional baseline data were analyzed from 303 African American girls 8 to 10 years old and a caregiver in the Girls health Enrichment Multi-site Studies Phase 2(GEMS), an obesity prevention intervention trial. RESULTS: Fruit, juice, and vegetable accessibility and family support for healthy eating and physical activity were significantly related to girls' body image and weight control behaviors. CONCLUSIONS: A comprehensive understanding of family factors may improve future programs aimed at preadolescent girls.

Treatment of eating disorders in primary care: a systematic review.

This review evaluated psychological treatments for Anorexia Nervosa, Bulimia Nervosa, and Binge Eating Disorder conducted in primary care. Five studies met inclusion criteria. Guided self-help cognitive-behavioral therapy via a self-help book may be a beneficial, first-line treatment for reducing binging and purging symptoms. Outcomes combining self-help with antidepressants remain unclear, although antidepressants alone may provide reduction of symptoms. High attrition and non-compliance rates among studies reviewed indicate the importance of a strong therapeutic alliance between provider and patient. Further research in primary care is needed to develop a standard of care for patients with eating disorders.

The prevalence of emotional and behavior problems in pediatric primary care serving rural children.

OBJECTIVES: To examine the prevalence of parent-reported emotional and behavior problems in pediatric primary care clinics serving rural Appalachia using methods commensurate with studies of broader samples. METHODS: Parents presenting to pediatric primary care clinics completed a rating scale (Pediatric Symptom Checklist) of psychosocial problems for their child. RESULTS: Approximately 21% of all rating scales were in the clinically significant range. Across all parents, 63% identified the child's physician as their most common source of help. In contrast, mental health professionals had been sought out by only 24% of the sample. CONCLUSIONS: These data replicate previous findings showing high rates of parent-rated psychosocial problems in pediatric primary care. Given the prevalence of these problems in primary care and parents' frequent help seeking in this setting, more research is needed on innovative approaches to integrated care in rural settings.

Audiovisual speech in older and younger adults: integrating a distorted visual signal with speech in noise.

Age-related changes to sensation and cognition may contribute to the differences found between younger and older adults using audiovisual speech. To evaluate this issue, younger and older adults repeated the final word of audio or audiovisual sentences in background noise. Although younger adults performed better than older adults, both age groups demonstrated the same level of visual enhancement in normal audiovisual conditions. However, when the visual speech was blurred, older adults had almost no audiovisual enhancement, whereas younger adults' enhancement was unaffected. These findings are discussed in terms of their implications for audiovisual integration over the course of the life span.

The failed repressor: EEG asymmetry as a moderator of the relation between defensiveness and depressive symptoms.

This study assessed the joint effects of defensiveness and frontal asymmetry in predicting symptoms of depression and anxiety. Depression symptoms were measured with the Beck Depression Inventory (BDI) and anxiety symptoms with the Taylor Manifest Anxiety Scale (TMAS). Defensiveness was assessed with both the Marlowe Crowne Social Desirability Scale (MCSD) and the Eysenck Personality Questionnaire L scale (EPQL). Participants completed two EEG recording sessions 3 weeks apart. Six baselines, three eyes open and three eyes closed, were recorded in each session. Alpha power (8-13 Hz) was computed and log transformed. R-L asymmetry was computed at eight pairs of homologous sites for aggregated data. Defensiveness (EPQL and MCSD scores) and depression symptoms (BDI) were assessed at the beginning of the first session. L and MCSD correlated positively with anterior R-L asymmetries. For both scales, the highest correlations were observed at F8-F7. L interacted with F8-F7 asymmetry to predict depressive symptoms. Among left frontally active individuals, there was trend toward a negative correlation between L and BDI. Among the right frontally active individuals, the correlation between L and the BDI was positive. MCSD did not moderate the relation between F8-F7 asymmetry and BDI. The results are consistent with the hypothesis that defensiveness protects against symptoms of depression in the context of left frontal activity, and serves as a diathesis for depression in the context of right frontal activity. High-defensive individuals who are right frontally active may represent "failed repressors," i.e. individuals for whom defensiveness does not protect against depression, and may even exacerbate it.

Clonidine facilitates controlled hypotension in adolescent children.

UNLABELLED: In this randomized, double-blinded, placebo-controlled trial, we investigated whether clonidine lessened the requirements for isoflurane, fentanyl, and labetalol to provide controlled hypotension in children who underwent oromaxillofacial surgery. We also studied preoperative sedative effects, the hemodynamic response to nasotracheal intubation, and recovery characteristics. Thirty-nine healthy children, aged 10-16 yr, received clonidine 5 micro g/kg or placebo on the night before surgery and 90 min before surgery. By self-assessment, children in both groups showed similar anxiety, whereas observers rated clonidine patients as more sedated (P < 0.01). Heart rate during induction remained significantly decreased in clonidine patients compared with placebo patients (P < 0.001), as did arterial blood pressure before induction (P < 0.01) and peak pressure after intubation (P < 0.001). Children who took clonidine required significantly less isoflurane to maintain a mean arterial blood pressure of 60 +/- 4 mm Hg (mean isoflurane concentration, clonidine 0.99% versus placebo 1.33; P = 0.0004) and required less fentanyl than placebo patients (P = 0.002). Fewer treatment patients received labetalol (clonidine, n = 3 versus placebo, n = 13; P = 0.004). There was a trend toward faster recovery in the clonidine group, with a shortened recovery room stay (P = 0.03). We conclude that clonidine is a useful adjunct for controlled hypotension in children. IMPLICATIONS: This study shows that adolescents having major jaw surgery are helped by the blood pressure-decreasing drug clonidine. This drug allows smaller doses of anesthetics, pain relievers, and blood pressure-decreasing drugs to be used; reduces changes in heart rate and blood pressure; and provides faster recovery from the anesthetic.