A Review of Existing and New Treatments for the Management of Hand Eczema.

Hand eczema is a chronic condition that affects an estimated 14.5% of the general population. It has severe quality of life ramifications in those that struggle with it, including days missed from work or school, productivity loss and impaired work functioning. For years, the standard of care included topical moisturizing creams, topical steroids and more recently systemic agents. As new therapeutic targets emerge and recent advances are being developed, it is now more possible than ever that hand eczema can be managed via the underlying mechanisms. A review of the literature was conducted to identify current treatment options for hand eczema and chronic hand eczema. The terms 'hand eczema', 'hand dermatitis' were used to search PubMed, CENTRAL and Embase. To identify new therapies still undergoing investigation, we used the terms 'hand eczema', 'hand dermatitis', 'atopic dermatitis', and 'vesicular eczema of hands and/or feet' to search Clinicaltrials.gov for all studies until December 2022. There were 56 ongoing clinical trials identified for pharmacological treatments for hand eczema on Clinicaltrials.gov from 2000 - 2022, with 16 that are new or ongoing. These included studies for dupilumab, ruxolitinib, delgocitinib (LEO124249), gusacitinib (ASN002), AFX 5931, and roflumilast (ARQ-252). Two major classes of drugs emerging for the treatment of hand eczema include IL-4/IL-13 inhibitors and JAK inhibitors. With the increase in efficacy seen with these new drugs, we are also noting improved adverse effect profiles, making them attractive options to add to a clinician's management toolbox for patients with hand eczema.

The association between immigration status and the development of type 2 diabetes in women with a prior diagnosis of gestational diabetes: A population-based study.

AIMS: The aim of this study was to examine the influence of immigration status and region of origin on the risk of type 2 diabetes in women with prior gestational diabetes (GDM). METHODS: This retrospective population-based cohort study included women with gestational diabetes (GDM) aged 16 to 50 years in Ontario, Canada, who gave birth between 2006 and 2014. We compared the incidence of type 2 diabetes after delivery between long-term residents and immigrants-overall, by time since immigration and by region of-using Cox regression adjusted for age, year, neighbourhood income, rurality, infant birth weight and presence of hypertensive disorders of pregnancy (HDP). RESULTS: Among 38,515 women with prior GDM (42% immigrants), immigrants had a significantly higher risk of type 2 diabetes compared with long-term residents (adjusted hazard ratio [HR] 1.19, 95% confidence interval [CI] 1.13-1.26), with no meaningful difference based on time since immigration. The highest adjusted relative risks of type 2 diabetes compared with long-term residents were found for immigrants from Sub-Saharan Africa (HR 1.63, 95% CI 1.40-1.90), Latin America/Caribbean (HR 1.44, 95% CI 1.28-1.62) and South Asia (HR 1.34, 95% CI 1.25-1.44). CONCLUSIONS: Immigration is associated with a significantly higher risk of type 2 diabetes after GDM, particularly for women from certain low- and middle-income countries. Diabetes prevention strategies will need to consider the unique needs of immigrants from these regions.

Exploring the Quality of Narrative Feedback Provided to Residents During Ambulatory Patient Care in Medicine and Surgery.

OBJECTIVES: The transition to competency-based medical education (CBME) has increased the volume of residents' assessment data; however, the quality of the narrative feedback is yet to be used as feedback-on-feedback for faculty. Our objectives were (1) to explore and compare the quality and content of narrative feedback provided to residents in medicine and surgery during ambulatory patient care and (2) to use the Deliberately Developmental Organization framework to identify strengths, weaknesses, and opportunities to improve quality of feedback within CBME. METHODS: We conducted a mixed convergent methods study with residents from the Departments of Surgery (DoS; n = 7) and Medicine (DoM; n = 9) at Queen's University. We used thematic analysis and the Quality of Assessment for Learning (QuAL) tool to analyze the content and quality of narrative feedback documented in entrustable professional activities (EPAs) assessments for ambulatory care. We also examined the association between the basis of assessment, time to provide feedback, and the quality of narrative feedback. RESULTS: Forty-one EPA assessments were included in the analysis. Three major themes arose from thematic analysis: Communication, Diagnostics/Management, and Next Steps. Quality of the narrative feedback varied; 46% had sufficient evidence about residents' performance; 39% provided a suggestion for improvement; and 11% provided a connection between the suggestion and the evidence. There were significant differences between DoM and DoS in quality of feedback scores for evidence (2.1 [1.3] vs. 1.3 [1.1]; p < 0.01) and connection (0.4 [0.5] vs. 0.1 [0.3]; p = 0.04) domains of the QuAL tool. Feedback quality was not associated with the basis of assessment or time taken to provide feedback. CONCLUSION: The quality of the narrative feedback provided to residents during ambulatory patient care was variable with the greatest gap in providing connections between suggestions and evidence about residents' performance. There is a need for ongoing faculty development to improve the quality of narrative feedback provided to residents.

Transitioning to virtual ambulatory care during the COVID-19 pandemic: a qualitative study of faculty and resident physician perspectives.

BACKGROUND: The COVID-19 pandemic resulted in a rapid shift from in-person to virtual care delivery for many medical specialties across Canada. The purpose of this study was to explore the lived experiences of resident physicians and faculty related to teaching, learning and assessment during ambulatory virtual care encounters within the competency-based medical education model. METHODS: In this qualitative phenomenological study, we recruited resident physicians (postgraduate year [PGY] 1-5 trainees) and faculty from the Departments of Surgery and Medicine at Queen's University, Ontario, via purposive sampling. Participants were not required to have exposure to virtual care. Interviews were conducted from September 2020 to March 2021 by 1 researcher, and 2 researchers conducted focus groups via Zoom to explore participants' experiences with the transition to virtual care. These were audio-recorded and transcribed verbatim; qualitative data were analyzed thematically. RESULTS: There were 18 male and 19 female participants; 20 were resident physicians and 17 were faculty; 19 were from the Department of Surgery and 18 from the Department of Medicine. All faculty participants had participated in virtual care during ambulatory care; 2 PGY-1 residents in surgery had not actively participated in virtual care, although they had participated in clinics where faculty were using virtual care. The mean age of faculty participants was 38 (standard deviation [SD] 8.6) years, and the mean age of resident physicians was 29 (SD 5.4) years. Overall, 28 interviews and 4 focus groups (range 2-3 participants per group) were conducted, and 4 themes emerged: teaching and learning, assessment, logistical considerations, and suggestions. Barriers to teaching included the lack of direct observations and teaching time, and barriers to assessment included an absence of specific Entrustable Professional Activities (EPAs) and feedback focused on virtual care-related competencies. Logistical challenges included lack of technological infrastructure, insufficient private office space and administrative burdens. Both resident physicians and faculty did not foresee virtual care limiting resident physicians' ability to progress within competency-based medical education. Benefits of virtual care included increased accessibility to patients for follow-up visits, for disclosing patients' results and for out-of-town visits. Suggestions included faculty development, improved access to technology and space, educational guidelines for conducting virtual care encounters, and development of virtual care-specific competencies and EPAs. INTERPRETATION: In the postgraduate program we studied, virtual care imposed substantial barriers on teaching, learning and assessment during the first year of the COVID-19 pandemic. Adapting to new circumstances such as virtual care with suggestions from resident physicians and faculty may help to ensure the continuity of postgraduate medical education throughout the COVID-19 pandemic.

It is no skin off my nose: The relationship between the skin and allergic rhinitis.

OBJECTIVE: Evidence supports the relationship between the skin barrier and allergic conditions. This narrative review evaluates what role the cutaneous barrier may play in the pathogenesis, disease course, and management of allergic rhinitis (AR). DATA SOURCES: A literature review of the MEDLINE (PubMed), Embase, Cochrane, and SCOPUS Sciverse databases was conducted to identify available evidence. Reference lists of pertinent papers were searched using a snowball technique. STUDY SELECTIONS: Papers published in English from all years until December 2020 were included. Papers that did not address the relationship between AR and the skin and hypothesis papers were excluded. RESULTS: The cutaneous barrier shares histologic characteristics with the sinonasal epithelial barrier, which may explain commonalities between AR and atopic dermatitis. A disruption in the epithelial barrier could be a common pathway in the development of multiple allergic conditions. The skin is a common target for the treatment of AR. Available data that look at the relationship between the skin and AR often include other topics such as other atopic disorders and the role of the epithelial barrier. Increased understanding of how the cutaneous barrier affects AR may lead to new innovations in its management. CONCLUSION: The connection between the cutaneous barrier and AR holds possibilities for further investigation, and these may lead to a better understanding and future innovations for all atopic diseases.

Lipid nanoparticle delivery of glucagon receptor siRNA improves glucose homeostasis in mouse models of diabetes.

OBJECTIVE: Hyperglucagonemia is present in many forms of diabetes and contributes to hyperglycemia, and glucagon suppression can ameliorate diabetes in mice. Leptin, a glucagon suppressor, can also reverse diabetes in rodents. Lipid nanoparticle (LNP) delivery of small interfering RNA (siRNA) effectively targets the liver and is in clinical trials for the treatment of various diseases. We compared the effectiveness of glucagon receptor (Gcgr)-siRNA delivered via LNPs to leptin in two mouse models of diabetes. METHODS: Gcgr siRNA encapsulated into LNPs or leptin was administered to mice with diabetes due to injection of the ß-cell toxin streptozotocin (STZ) alone or combined with high fat diet (HFD/STZ). RESULTS: In STZ-diabetic mice, a single injection of Gcgr siRNA lowered blood glucose levels for 3 weeks, improved glucose tolerance, and normalized plasma ketones levels, while leptin therapy normalized blood glucose levels, oral glucose tolerance, and plasma ketones, and suppressed lipid metabolism. In contrast, in HFD/STZ-diabetic mice, Gcgr siRNA lowered blood glucose levels for 2 months, improved oral glucose tolerance, and reduced HbA1c, while leptin had no beneficial effects. CONCLUSIONS: While leptin may be more effective than Gcgr siRNA at normalizing both glucose and lipid metabolism in STZ diabetes, Gcgr siRNA is more effective at reducing blood glucose levels in HFD/STZ diabetes.

Glucagon receptor gene deletion in insulin knockout mice modestly reduces blood glucose and ketones but does not promote survival.

OBJECTIVE: It has been thought that the depletion of insulin is responsible for the catabolic consequences of diabetes; however, evidence suggests that glucagon also plays a role in diabetes pathogenesis. Glucagon suppression by glucagon receptor (Gcgr) gene deletion, glucagon immunoneutralization, or Gcgr antagonist can reverse or prevent type 1 diabetes in rodents suggesting that dysregulated glucagon is also required for development of diabetic symptoms. However, the models used in these studies were rendered diabetic by chemical- or immune-mediated ß-cell destruction, in which insulin depletion is incomplete. Therefore, it is unclear whether glucagon suppression could overcome the consequence of the complete lack of insulin. METHODS: To directly test this we characterized mice that lack the Gcgr and both insulin genes (GcgrKO/InsKO). RESULTS: In both P1 pups and mice that were kept alive to young adulthood using insulin therapy, blood glucose and plasma ketones were modestly normalized; however, mice survived for only up to 6 days, similar to GcgrHet/InsKO controls. In addition, Gcgr gene deletion was unable to normalize plasma leptin levels, triglycerides, fatty acids, or hepatic cholesterol accumulation compared to GcgrHet/InsKO controls. CONCLUSION: Therefore, the metabolic manifestations associated with a complete lack of insulin cannot be overcome by glucagon receptor gene inactivation.