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Very-Long-Chain Acyl-CoA Dehydrogenase Deficiency (VLCADD) is a fatty acid oxidation disorder characterized by the decreased ability of the enzyme very-long-chain acyl-CoA dehydrogenase to break down fatty acids with 14 to 20-long carbon chains. The resulting clinical manifestations are variable in severity and include hypoketotic hypoglycemia, rhabdomyolysis, and cardiomyopathy. Treatment can consist of limiting the dietary intake of long-chain fatty acids, the prevention of fasting, and the supplementation of medium-chain fats. This study, conducted in the context of a 5-year long-term follow-up on VLCADD, evaluates how the diagnosis of this fatty acid disorder impacts the family, specifically as it relates to the medical diet and barriers to care. Caregivers (n = 10) of individuals with VLCADD responded to a survey about how VLCADD potentially impacts their family. The review included the clinical outcomes of the patients (n = 11), covering instances of rhabdomyolysis, cardiomyopathy, and hospitalizations related to VLCADD. Families affected by VLCADD experience barriers to care, including difficulties with finances, ability to work, and access to nutrition.

BACKGROUND: Cardiovascular and critical care professional societies recommend incorporating family engagement practices into routine clinical care. However, little is known about current family engagement practices in contemporary cardiac intensive care units (CICUs). METHODS: We implemented a validated 12-item family engagement practice survey among site investigators participating in the Critical Care Cardiology Trials Network, a collaborative network of CICUs in North America. The survey includes 9 items assessing specific engagement practices, 1 item about other family-centered care practices, and 2 open-ended questions on strategies and barriers concerning family engagement practice. We developed an engagement practice score by assigning 1 point for each family engagement practice partially or fully adopted at each site (max score 9). We assessed for relationships between the engagement practice score and CICU demographics. RESULTS: All sites (N=39; 100%) completed the survey. The most common family engagement practices were open visitation (95%), information and support to families (85%), structured care conferences (n=82%), and family participation in rounds (77%). The median engagement practice score was 5 (interquartile range, 4). There were no differences in engagement practice scores by geographic region or CICU type. The most commonly used strategies to promote family engagement were family presence during rounds (41%), communication (28%), and family meetings (28%). The most common barriers to family engagement were COVID-related visitation policies (38%) and resource limitations (13%). CONCLUSIONS: Family engagement practices are routinely performed in many CICUs; however, considerable variability exists. There is a need for strategies to address the variability of family engagement practices in CICUs.

INTRODUCTION: Given variability in parental leave policies in gastroenterology (GI) with little data on outcomes, the American College of Gastroenterology conducted a survey to assess policies and outcomes. METHODS: A survey was distributed to American College of Gastroenterology members with questions on demographics, fertility, pregnancy outcomes, and parental leave policies. RESULTS: There were 796 responses, with 52.5% female individuals. Many (57%) delayed parenting. High rates of infertility (21%) and pregnancy complications (68%) were observed. Satisfaction with parental leave policies in GI was low (35%). DISCUSSION: Our survey highlights the need for policies that support the well-being of our GI colleagues and families.

Abstract Purpose: Germline pathogenic variants in CHEK2 confer moderately elevated breast cancer risk (odds ratio, OR ∼ 2.5), qualifying carriers for enhanced breast cancer screening. Besides pathogenic variants, dozens of missense CHEK2 variants of uncertain significance (VUS) have been identified, hampering the clinical utility of germline genetic testing (GGT). Experimental Design: We collected 460 CHEK2 missense VUS identified by the ENIGMA consortium in 15 countries. Their functional characterization was performed using CHEK2-complementation assays quantifying KAP1 phosphorylation and CHK2 autophosphorylation in human RPE1–CHEK2-knockout cells. Concordant results in both functional assays were used to categorize CHEK2 VUS from 12 ENIGMA case–control datasets, including 73,048 female patients with breast cancer and 88,658 ethnicity-matched controls. Results: A total of 430/460 VUS were successfully analyzed, of which 340 (79.1%) were concordant in both functional assays and categorized as functionally impaired (N = 102), functionally intermediate (N = 12), or functionally wild-type (WT)–like (N = 226). We then examined their association with breast cancer risk in the case–control analysis. The OR and 95% CI (confidence intervals) for carriers of functionally impaired, intermediate, and WT-like variants were 2.83 (95% CI, 2.35–3.41), 1.57 (95% CI, 1.41–1.75), and 1.19 (95% CI, 1.08–1.31), respectively. The meta-analysis of population-specific datasets showed similar results. Conclusions: We determined the functional consequences for the majority of CHEK2 missense VUS found in patients with breast cancer (3,660/4,436; 82.5%). Carriers of functionally impaired missense variants accounted for 0.5% of patients with breast cancer and were associated with a moderate risk similar to that of truncating CHEK2 variants. In contrast, 2.2% of all patients with breast cancer carried functionally wild-type/intermediate missense variants with no clinically relevant breast cancer risk in heterozygous carriers.

Background and Objectives: Preceptors in family medicine residencies need feedback to improve. When we found no validated, behavior-based tool to assess the outpatient precepting of family medicine residents, we sought to fill this gap by developing and initially validating the Mayo Outpatient Precepting Evaluation Tool (MOPET). Methods: To develop the MOPET, we applied the Stanford Faculty Development Program (SFDP) theoretical framework for education, more recent work on peer review of medical teaching, and expert review of items. The residency behavioral scientist and a volunteer physician independently completed the MOPET while co-observing a precepting physician during continuity clinic sessions (N=20). We assessed the tool’s validity via interrater reliability and cross-validation with the SFDP-26. Results: The tool demonstrated high interrater reliability for the following effective teaching behaviors: (a) allowing the resident to present without interrupting, (b) encouraging the formulation of a goal, (c) checking in on the resident’s goal, (d) using multimodal teaching aids, (e) asking to discuss the differential diagnosis, (f) asking to discuss alternative management, (g) encouraging the resident to pursue literature and/or other resources, and (h) reinforcing self-directed learning. The MOPET measures strongly correlated with most items from the SFDP-26, indicating good cross-validity. Conclusions: The MOPET is a theoretically sound, behavior-based, reliable, and initially validated tool for peer review of outpatient family medicine resident teaching. This tool can support faculty development in outpatient clinical learning environments.

AbstractBackgroundParadoxical lucidity is characterized by spontaneous mental clarity with verbal or non‐verbal communication or behavior among people with AD who had previously been thought to lack the cognitive capacity to do so. With a paucity of data available, family caregivers (FCGs) provide critical perspectives on characteristics of these episodes of lucidity (EL).MethodTwenty‐four FCGs who witnessed at least one EL were interviewed about the experience. Qualitative data were transcribed, double coded, and analyzed to help characterize ELs.ResultFCGs described ELs as indelible moments, possibly triggered by music, food, holidays, or impending death. The spontaneity of the EL, its duration, the connectedness with FCGs, and coherence of communication varied. Instead of seeing them as cognitive fluctuations, FCGs often assigned metaphysical meaning to ELs.ConclusionFCG descriptions of ELs had few common patterns, suggestions they are heterogenous. Their impact on FCGs, however, was enduring.

Introduction. We assessed the effects of a polygenic risk score (PRS), monogenic variants (Mono + ), and family history (FamHx) on the risk of coronary heart disease (CHD) and whether incorporating a PRS into the Pooled Cohort Equations (PCE) improves risk prediction. Method. In 199,997 UK Biobank participants, we calculated a PRS CHD (metaGRS, based on ~1.6 million single nucleotide variants), identified individuals with monogenic etiology (presence of a pathogenic variant in LDLR , APOB , or PCSK9 ), and ascertained family history of CHD (CHD in a first-degree relative). Odds of CHD (myocardial infarction/ coronary revascularization/ cardiovascular death) associated with PRS CHD , Mono + , and FamHx at age 55 were computed using logistic regression analyses adjusted for age, sex, and first 4 principal components of ancestry. We combined PRS CHD and PCE into an integrated score (IS) and assessed net reclassification using an actionable risk threshold of 7.5%. Results. The odds ratio (OR) for CHD in the top 5 th percentile of PRS CHD (PRS P95 ), Mono + , and FamHx were 3.37 (2.98 - 3.81), 2.68 (1.67 - 4.07), and 1.61 (1.47 - 1.76), respectively (all p<0.001). These effects were independent and similar in different subgroups. ( Figure 1-A ) Compared to PRS Q2-4 Mono - (3 middle quintiles of PRS CHD and no monogenic variants), the OR for CHD ranged from 1.73 (0.28 - 5.48, p = 0.446) in PRS Q1 Mono + to 5.10 (2.14 - 10.24, p <0.001) in PRS Q5 Mono + . A similar pattern was seen for other combinations, indicating additive effects ( Figure 1-B ). Incorporating PRS CHD into PCE resulted in a net reclassification improvement of 4.56%. Compared to those with high PCE and low IS, the hazard ratio for CHD in those with low PCE and high IS was 1.48 (1.34 - 1.64, p <0.001). Conclusion. The CHD risk associated with PRS CHD , monogenic variants, and family history is independent and additive. Combining PRS CHD and PCE improved risk prediction, that could improve further by adding monogenic variants and family history.

Abstract Introduction We sought to determine what type of treatment reengagement after smoking relapse would increase long-term cessation. Aims and Methods Participants were military personnel, retirees, and family members (TRICARE beneficiaries) recruited across the United States from August 2015 through June 2020. At baseline, consented participants (n = 614) received a validated, four-session, telephonic tobacco-cessation intervention with free nicotine replacement therapy. At the 3-month follow-up, 264 participants who failed to quit or relapsed were offered the opportunity to reengage in cessation. Of these, 134 were randomized into three reengagement conditions: (1) repeat initial intervention (“recycle”), (2) Smoking reduction with eventual cessation goal (“rate reduction”), or (3) Choose #1 or #2 (“choice”). Prolonged abstinence and 7-day point prevalence abstinence were measured at 12 months. Results Despite being in a clinical trial advertised as having the opportunity for reengagement, only 51% (134 of the 264) of participants who still smoked at 3-month follow-up were willing to reengage. Overall, participants randomized to recycle had higher prolonged cessation rates at 12 months than rate reduction conditions (OR = 16.43, 95% CI: 2.52 to 107.09, Bonferroni adjusted p = .011). When participants who randomly received recycle or rate reduction were pooled, respectively, with participants who chose recycle or rate reduction in the Choice group, recycle had higher prolonged cessation rates at 12 months than rate reduction (OR = 6.50, 95% CI: 1.49 to 28.42, p = .013). Conclusions Our findings suggest service members and their family members who fail to quit smoking but are willing to reengage in a cessation program are more likely to benefit from repeating the same treatment. Implications Finding methods that are both successful and acceptable to reengage people who smoke who want to quit can have a significant impact on improving the health of the public by reducing the portion of the population who smoke. This study suggests that repeating established cessation programs will result in more people ready to quit successfully achieving their goal.