Germline Testing Identifies Pathogenic/Likely Pathogenic Variants in Patients with Pancreatic Neuroendocrine Tumors.

Ten percent of pancreatic neuroendocrine tumors (pNET) are related to inherited syndromes (MEN1, MEN4, VHL, NF1, and TSC). Growing evidence suggests that clinically sporadic pNETs can also harbor germline pathogenic variants. In this study, we report the prevalence of pathologic/likely pathologic (P/LP) germline variants in a high-risk cohort and an unselected cohort. We collected clinical data of patients with pNETs seen at MD Anderson Cancer Center and Johns Hopkins Hospital. The high-risk cohort included (n = 132) patients seen at MD Anderson Cancer Center who underwent germline testing for high-risk criteria (early onset, personal or family history of cancer, and syndromic features) between 2013 and 2019. The unselected cohort included (n = 106) patients seen at Johns Hopkins Hospital who underwent germline testing following their diagnosis of pNETs between 2020 and 2022. In the high-risk cohort (n = 132), 33% (n = 44) had P/LP variants. The majority of the patients had P/LP variants in MEN1 56% (n = 25), followed by DNA repair pathways 18% (n = 8), and 7% (n = 3) in MSH2 (Lynch syndrome). Patients with P/LP were younger (45 vs. 50 years; P = 0.002). In the unselected cohort (n = 106), 21% (n = 22) had P/LP. The majority were noted in DNA repair pathways 40% (n = 9) and MEN1 36% (n = 8). Multifocal tumors correlated with the presence of P/LP (P = 0.0035). MEN1 germline P/LP variants correlated with younger age (40 vs. 56 years; P = 0.0012), presence of multifocal tumors (P < 0.0001), and World Health Organization grade 1 histology (P = 0.0078). P/LP variants are prevalent in patients with clinically sporadic pNET irrespective of high-risk features. The findings support upfront universal germline testing in all patients with pNET. Prevention Relevance: Here, we present germline data from the largest reported cohort of patients with pNET (n = 238), comprising both a high-risk cohort and an unselected cohort. In both cohorts, we identify a high number of P/LPs, including those in the DNA repair pathway. Our findings support universal germline testing in patients with pNET.

The Decline of Basic Ophthalmology in General Medical Education: A Scoping Review and Recommended Potential Solutions.

OBJECTIVE: This literature review aims to explore research and conceptual pieces on the state of ophthalmology education and suggest potential ways to address current challenges. METHODS: A search was conducted in PubMed, ERIC, Web of Science, and Google Scholar with combinations of the following search terms: "ophthalmology education," "undergraduate medical education," "medical student," "United States," and "Canada." Eliminating irrelevant articles yielded 47 articles. Three were excluded because of region and focus, leaving 44. After examining the citations, we generated an additional 22 texts for review, totaling 66 articles. RESULTS: Four primary themes were identified: (1) challenges to ophthalmological education in the U.S. and Canada, (2) potential remedies for optimizing ophthalmology curriculum, (3) technology in ophthalmology education, and (4) innovative ophthalmology teaching approaches. Major challenges included the lack of a standardized curriculum and inadequate clinical exposure and skills training. A number of remedies were proposed, such as standardizing curriculum and furthering faculty involvement, utilizing technology as time-effective learning aids, and employing innovative teaching approaches such as service learning. CONCLUSION: In light of challenges in ophthalmology education, curriculum designers should consider Cognitive Load Theory (CLT) to assist students to remember meaningful exposures to ophthalmology knowledge and techniques. Based on CLT, we suggest two potential approaches to incorporating ophthalmology curriculum. The first is to embrace interdisciplinary collaborations and place ophthalmology knowledge in varied contexts to facilitate schema construction. The second is to incorporate ophthalmology diagnostics requirements into OSCEs and utilize simulation models for students to gradually increase the fidelity of tasks and devote cognitive resources fully to learning.

Bacterial and fungal characterization of pancreatic adenocarcinoma from Endoscopic Ultrasound-guided biopsies.

Introduction: The tumor microbiome (TM) has been linked to pancreatic cancer prognosis. Specific microbes can confer tumor resistance to therapies. Early knowledge of the TM at time of diagnosis would be clinically relevant for precision therapy based on microbial composition. However, it is difficult to define the TM prior to surgical resection. Methods: In this pilot feasibility study, patients underwent Endoscopic Ultrasound-Fine Needle Aspiration (EUS-FNA) biopsy of pancreatic adenocarcinoma. These samples were analyzed using 16S rRNA and internal transcribed spacer (ITS) sequencing for characterization of the tumor bacteria and fungi. Result: After in silico decontamination and comparison to non-matched tumor, we were able to characterize the TM in biopsies, which was comparable to the TM from surgical specimens. Discussion: EUS-FNA biopsy may represent a feasible modality to characterize the pancreatic TM prior to surgical resection with proper decontamination strategies and improvements in matched controls.

Management of Individuals With Diabetes at High Risk for Hypoglycemia: An Endocrine Society Clinical Practice Guideline.

CONTEXT: Hypoglycemia in people with diabetes is common, especially in those taking medications such as insulin and sulfonylureas (SU) that place them at higher risk. Hypoglycemia is associated with distress in those with diabetes and their families, medication nonadherence, and disruption of life and work, and it leads to costly emergency department visits and hospitalizations, morbidity, and mortality. OBJECTIVE: To review and update the diabetes-specific parts of the 2009 Evaluation and Management of Adult Hypoglycemic Disorders: Endocrine Society Clinical Practice Guideline and to address developing issues surrounding hypoglycemia in both adults and children living with diabetes. The overriding objectives are to reduce and prevent hypoglycemia. METHODS: A multidisciplinary panel of clinician experts, together with a patient representative, and methodologists with expertise in evidence synthesis and guideline development, identified and prioritized 10 clinical questions related to hypoglycemia in people living with diabetes. Systematic reviews were conducted to address all the questions. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was used to assess the certainty of evidence and make recommendations. RESULTS: The panel agreed on 10 questions specific to hypoglycemia risk and prevention in people with diabetes for which 10 recommendations were made. The guideline includes conditional recommendations for use of real-time continuous glucose monitoring (CGM) and algorithm-driven insulin pumps in people with type 1 diabetes (T1D), use of CGM for outpatients with type 2 diabetes at high risk for hypoglycemia, use of long-acting and rapid-acting insulin analogs, and initiation of and continuation of CGM for select inpatient populations at high risk for hypoglycemia. Strong recommendations were made for structured diabetes education programs for those at high risk for hypoglycemia, use of glucagon preparations that do not require reconstitution vs those that do for managing severe outpatient hypoglycemia for adults and children, use of real-time CGM for individuals with T1D receiving multiple daily injections, and the use of inpatient glycemic management programs leveraging electronic health record data to reduce the risk of hypoglycemia. CONCLUSION: The recommendations are based on the consideration of critical outcomes as well as implementation factors such as feasibility and values and preferences of people with diabetes. These recommendations can be used to inform clinical practice and health care system improvement for this important complication for people living with diabetes.

SGLT-2 inhibitors or GLP-1 receptor agonists for adults with type 2 diabetes: a clinical practice guideline.

CLINICAL QUESTION: What are the benefits and harms of sodium-glucose cotransporter 2 (SGLT-2) inhibitors and glucagon-like peptide 1 (GLP-1) receptor agonists when added to usual care (lifestyle interventions and/or other diabetes drugs) in adults with type 2 diabetes at different risk for cardiovascular and kidney outcomes? CURRENT PRACTICE: Clinical decisions about treatment of type 2 diabetes have been led by glycaemic control for decades. SGLT-2 inhibitors and GLP-1 receptor agonists are traditionally used in people with elevated glucose level after metformin treatment. This has changed through trials demonstrating atherosclerotic cardiovascular disease (CVD) and chronic kidney disease (CKD) benefits independent of medications' glucose-lowering potential. RECOMMENDATIONS: The guideline panel issued risk-stratified recommendations concerning the use of SGLT-2 inhibitors or GLP-1 receptor agonists in adults with type 2 diabetes• Three or fewer cardiovascular risk factors without established CVD or CKD: Weak recommendation against starting SGLT-2 inhibitors or GLP-1 receptor agonists.• More than three cardiovascular risk factors without established CVD or CKD: Weak recommendation for starting SGLT-2 inhibitors and weak against starting GLP-1 receptor agonists.• Established CVD or CKD: Weak recommendation for starting SGLT-2 inhibitors and GLP-1 receptor agonists.• Established CVD and CKD: Strong recommendation for starting SGLT-2 inhibitors and weak recommendation for starting GLP-1 receptor agonists.• For those committed to further reducing their risk for CVD and CKD outcomes: Weak recommendation for starting SGLT-2 inhibitors rather than GLP-1 receptor agonists. HOW THIS GUIDELINE WAS CREATED: An international panel including patients, clinicians, and methodologists created these recommendations following standards for trustworthy guidelines and using the GRADE approach. The panel applied an individual patient perspective. THE EVIDENCE: A linked systematic review and network meta-analysis (764 randomised trials included 421 346 participants) of benefits and harms found that SGLT-2 inhibitors and GLP-1 receptor agonists generally reduce overall death, and incidence of myocardial infarctions, and end-stage kidney disease or kidney failure (moderate to high certainty evidence). These medications exert different effects on stroke, hospitalisations for heart failure, and key adverse events in different subgroups. Absolute effects of benefit varied widely based on patients' individual risk (for example, from five fewer deaths in the lowest risk to 48 fewer deaths in the highest risk, for 1000 patients treated over five years). A prognosis review identified 14 eligible risk prediction models, one of which (RECODe) informed most baseline risk estimates in evidence summaries to underpin the risk-stratified recommendations. Concerning patients' values and preferences, the recommendations were supported by evidence from a systematic review of published literature, a patient focus group study, a practical issues summary, and a guideline panel survey. UNDERSTANDING THE RECOMMENDATION: We stratified the recommendations by the levels of risk for CVD and CKD and systematically considered the balance of benefits, harms, other considerations, and practical issues for each risk group. The strong recommendation for SGLT-2 inhibitors in patients with CVD and CKD reflects what the panel considered to be a clear benefit. For all other adults with type 2 diabetes, the weak recommendations reflect what the panel considered to be a finer balance between benefits, harms, and burdens of treatment options. Clinicians using the guideline can identify their patient's individual risk for cardiovascular and kidney outcomes using credible risk calculators such as RECODe. Interactive evidence summaries and decision aids may support well informed treatment choices, including shared decision making.

A Predictive Model for Primary Care Providers to Identify Children at Greatest Risk for Early Childhood Caries.

Purpose: The purpose of this study was to create an early childhood caries (ECC) risk-screening tool that fits into the primary care provider (PCP) well-child workflow. Methods: Integrated health records were employed to develop a predictive model for infants/toddlers at ECC risk; 2,009 patients with 12-, 15-, or 18-month well-child visits and at least one dental visit were used to develop a predictive model for ECC risk at the first dental visit. Independent model validation used 880 18- to 48-month-olds at their first dental appointment after at least one well-child visit. Results: Age at the first dental visit strongly predicted caries risk (odds ratio for one-year increase in age equals 2.11; 95 percent confidence interval equals 1.80 to 2.47). Three factors predicted high-caries risk: breast feeding status, preferred language not English, and no-show rates for pediatric clinic visits greater than 20 percent. All three non-age risk factors in well-child exams prior to 18 months predicted 42 percent probability of having caries if present for the first dental visit at 18 months. If that child was not seen until four years of age for the first dental visit, the probability of high caries risk increased to 83 percent. Model performance for independent validation was very close to expected performance. Conclusions: Existing clinical documentation plus a validated predictive model enables an effective caries risk assessment within well-child visits.

2019 Endocrine Society Measures Set for Older Adults With Type 2 Diabetes Who Are at Risk for Hypoglycemia.

CONTEXT: Hypoglycemia in the outpatient setting has a significant financial impact on the health care system and negative impact on a person's quality of life. Primary care physicians must address a multitude of issues in a visit with a person with type 2 diabetes mellitus (T2DM), often leaving little time to ask about hypoglycemia. OBJECTIVE: To develop quality measures that focus on outpatient hypoglycemia episodes for patients 65 and older with T2DM, which facilitate a clinician's ability to identify opportunities to improve the quality of care and reduce hypoglycemic episodes. PARTICIPANTS AND PROCESS: A technical expert panel established by the Endocrine Society in March 2019, which includes endocrinologists, primary care physicians, a diabetes care and education specialist/pharmacist, and a patient, developed 3 outpatient hypoglycemia quality measures. The measure set is intended to improve quality of care for patients with T2DM who are at greatest risk for hypoglycemia. The measures were available for public comment in July 2019. A fourth measure on shared decision-making was removed from the final measure set based on public feedback. CONCLUSION: A lack of outpatient hypoglycemia measures focusing on older adults with T2DM is a barrier to improving care of people with diabetes and reducing hypoglycemic episodes. This paper provides measure specifications for 3 measures that may be used to focus quality improvement efforts on patients at greatest risk for hypoglycemia.

What Low-income Smokers Have Learned from Public Health Pedagogy: A Narrative Inquiry.

Objectives: Health advocates have been working to educate the public about the harms of smoking for more than 50 years. However, smoking rates have reduced more slowly among people with low incomes. The purpose of this study was to evaluate what low-income smokers have learned from a lifetime of exposure to public health education and how this knowledge may have translated into smoking-related behaviors. Methods: We used narrative inquiry and elicitation interview techniques. Interviews were recorded, transcribed verbatim, coded, and organized into themes using the constant comparative method. Results: All participants were aware of smoking-related harms to health but negative experiences with quitting, cessation medications, and healthcare professionals contributed to avoiding or rejecting educational messages. Participants' perceptions of hypocritical societal tobacco control policies also led some to believe that the harms of tobacco use were exaggerated, or were being used to control or manipulate them. This contributed to a distrust of the government, public health advocates, and healthcare providers. Conclusions: Low-income smokers were aware of the harms of smoking and that quitting would improve their health. Public health advocates should consider developing messages that attempt to foster trust in healthcare professionals and are consistent with low-income adult smokers' quitting experiences.

Men's Help-Seeking Attitudes in Rural Communities Affected by a Natural Disaster.

The article describes a mixed methods study of help-seeking in men living in the Chilean Central Valley, following exposure to a major earthquake event in 2010. The results identify that, within the sample, positive attitudes toward help-seeking correlated with younger age, higher education levels, above-average incomes, and stable personal relationships. It appears that education plays a significant role in shaping such positive attitudes, particularly by influencing views of gender roles and help-seeking. Conversely, older men's reticence toward seeking help appeared linked to negative perceptions of available services and the influence of traditional notions of masculinity. The study concludes that adapting interventions and service offers to men's needs in rural contexts must include an ecosystemic analysis of their reality and incorporate an understanding of masculinity socialization processes.

Improving Patient Experience and Treatment Adherence in the Adult, Outpatient Hemodialysis Population.

BACKGROUND: The commonly employed medication reconciliation process leaves room for mismanagement of medications in the complex end-stage renal disease patient population. PURPOSE: The purpose of this quality improvement project was to implement and evaluate a multidisciplinary education and feedback intervention designed to improve self-management for adults with end-stage renal disease. METHODS: A pre-post, same subject repeated measures design was used to evaluate the intervention. Laboratory values, vital signs, interdialytic weight gains, dialysis attendance, and questionnaires were used to assess regimen adherence. RESULTS: We observed improvements in patient outcomes including laboratory values, vital signs, and interdialytic weight gains. Significant improvements in process outcomes were also seen, including accuracy of medication lists, dialysis attendance, and use of remote pharmacy services. CONCLUSIONS: A comprehensive medication review, with concurrent pharmacist access, represents a time-effective approach to improved self-management and end-stage renal disease outcomes.

Bioinformatics core competencies for undergraduate life sciences education.

Although bioinformatics is becoming increasingly central to research in the life sciences, bioinformatics skills and knowledge are not well integrated into undergraduate biology education. This curricular gap prevents biology students from harnessing the full potential of their education, limiting their career opportunities and slowing research innovation. To advance the integration of bioinformatics into life sciences education, a framework of core bioinformatics competencies is needed. To that end, we here report the results of a survey of biology faculty in the United States about teaching bioinformatics to undergraduate life scientists. Responses were received from 1,260 faculty representing institutions in all fifty states with a combined capacity to educate hundreds of thousands of students every year. Results indicate strong, widespread agreement that bioinformatics knowledge and skills are critical for undergraduate life scientists as well as considerable agreement about which skills are necessary. Perceptions of the importance of some skills varied with the respondent's degree of training, time since degree earned, and/or the Carnegie Classification of the respondent's institution. To assess which skills are currently being taught, we analyzed syllabi of courses with bioinformatics content submitted by survey respondents. Finally, we used the survey results, the analysis of the syllabi, and our collective research and teaching expertise to develop a set of bioinformatics core competencies for undergraduate biology students. These core competencies are intended to serve as a guide for institutions as they work to integrate bioinformatics into their life sciences curricula.

Strengthening the American Academy of Pediatric Dentistry's Public Policy Advocate Network: Identifying Advocacy Efforts and Recommendations.

PURPOSE: The purposes of this study were to collect information on involvement, training, and barriers to participation in advocacy efforts for Public Policy Advocates (PPAs) of the American Academy of Pediatric Dentistry (AAPD) and make recommendations to the AAPD. METHODS: Preliminary data were collected from the PPAs during structured AAPD program meetings, conference calls, and individual interviews. Based on these data, a survey was created, piloted, and sent electronically to all PPAs. Data were analyzed and collated by frequencies. RESULTS: Responses from 38 PPAs (100 percent) revealed they were involved with state legislatures and state chapters of the AAPD and American Dental Association. Eighty-two percent of the PPAs requested additional public policy training and clearer communication channels within the network. PPAs are funding their own advocacy efforts, and the time and resources spent away from patient care is a financial barrier. CONCLUSIONS: The Public Policy Advocate network holds a broad policy skill set and voluntarily commits time and resource to advocate for the support of the pediatric dental patient at state and federal government levels. The American Academy of Pediatric Dentistry can strengthen the PPA's self-directed leadership role at state and federal levels through formalized training, restructuring of the network, and increased resources.

Pediatric Dentists' Attitudes, Perceptions, and Experience with the Affordable Care Act.

PURPOSE: Pediatric oral health benefits were designated as one of 10 Essential Health Benefits (EHB) in the Affordable Care Act. Although it provided coverage for many children, several issues prevent its success. The purpose of this study was to document experience with, attitudes toward, and perceptions of the Affordable Care Act (ACA) among pediatric dentists. METHODS: The study was conducted using a survey consisting of nine multiple choice questions and one open-ended item and was distributed electronically in November 2015 to active and life members of the American Academy of Pediatric Dentistry. RESULTS: Respondents reported patients deferring treatment due to high out-of-pocket costs. Providers perceive that patients do not have enough information to understand their benefits. Providers reported not having enough information to understand how these benefits affect their practices. CONCLUSIONS: Pediatric dentists report deferral of both preventive and restorative care due to high out-of-pocket costs. Pediatric dentists do not feel they have adequate information regarding the Affordable Care Act and its effect on their practices. The majority of pediatric dentists believe that parents have difficulty understanding their children's benefits.

Longitudinal Study of Insomnia Symptoms Among Women During Perimenopause.

OBJECTIVE: To describe the prevalence of insomnia symptoms among women during perimenopause and to examine differences in self-reported insomnia symptoms at different stages of perimenopause over 10 years. DESIGN: Secondary analysis of self-reported sleep symptoms and clinical variables using 10 years of publicly available data from the Study of Women Across the Nation (SWAN). SETTING: The data set of women's insomnia symptoms was obtained from publicly available data from the SWAN. The parent study settings included Detroit, Michigan; Northern New Jersey; Los Angeles, California; Boston, Massachusetts; Chicago, Illinois; and Pittsburgh, Pennsylvania. PARTICIPANTS: Multiethnic midlife women with a mean age of 46 years (N = 3,302) categorized as pre- and perimenopausal at baseline. METHODS: Dependent variables included self-reported insomnia symptoms: difficulty falling asleep (sleep latency), wake after sleep onset, early morning awakenings, and sleep quality. Descriptive analysis was completed for each 1-year study interval. Repeated measures logistic regression was used to identify whether insomnia symptoms changed over time by stage of perimenopause. RESULTS: Insomnia symptoms were present in 31% to 42% of perimenopausal women at any 1-year study interval. Insomnia symptoms were more prevalent in the late stage of perimenopause than the early stage (p < .001). The odds of having any insomnia symptoms were 1.3 times greater for women in the late stage of perimenopause than in the early stage (95% confidence interval [1.2, 1.5], p < .001). CONCLUSION: Insomnia symptoms are prevalent in women transitioning to menopause, and stage of perimenopause may heighten the risk to develop symptoms of insomnia disorder, which is associated with negative cardiometabolic outcomes.

Do Biology Majors Really Differ from Non-STEM Majors?

Recent calls to action urge sweeping reform in science education, advocating for improved learning for all students-including those majoring in fields beyond the sciences. However, little work has been done to characterize the differences-if any exist-between students planning a career in science and those studying other disciplines. We describe an attempt to clarify, in broad terms, how non-STEM (science, technology, engineering, and mathematics) majors differ from life sciences majors, and how they are similar. Using survey responses and institutional data, we find that non-STEM majors are not unilaterally science averse; non-STEM majors are more likely than biology majors to hold misconceptions about the nature of science, yet they are not completely ignorant of how science works; non-STEM majors are less likely than biology majors to see science as personally relevant; and non-STEM majors populations are likely to be more diverse-with respect to incoming knowledge, perceptions, backgrounds, and skills-than a biology majors population. We encourage science educators to consider these characteristics when designing curricula for future scientists or simply for a well-informed citizenry.

Assessing attitudes and actions of pediatric dentists toward childhood obesity and sugar-sweetened beverages.

OBJECTIVES: Childhood obesity is a major US health concern, and oral health professionals have opportunities to participate in an interprofessional effort to intervene owing to their access to young patients and their abilities in addressing obesity-related dietary habits like consumption of sugar-sweetened beverages (SSBs). This study determined attitudes, behaviors, future intentions, and perceived barriers of pediatric dentists regarding efforts to prevent childhood obesity and reduce children's consumption of SSBs. METHODS: The American Academy of Pediatric Dentistry conducted an online electronic survey with a convenience sample of approximately 7,450 pediatric dentists and pediatric dental residents during spring 2016. RESULTS: Over 17 percent of pediatric dentists offer childhood obesity interventions. Of those not providing interventions, 67 percent were interested in offering obesity-prevention services. Nearly 94 percent of pediatric dentists offer information or other interventions on consumption of SSBs. Statistically significant barriers to providing healthy weight interventions were fear of offending parents, appearing judgmental, or creating parent dissatisfaction and a lack of parental acceptance of guidance about weight management from a dentist. Significant barriers to SSB interventions were sufficient time and health professional education. CONCLUSIONS: More pediatric dentists stated they offer childhood obesity interventions than in previous surveys reporting 6 percent, but respondents suggested that a child's weight is seen as a medical rather than dental issue. Most pediatric dentists provide interventions related to consumption of SSBs, perceiving the issue as integral to their care of children.

It's not about you: a simple proposition for improving biology education.

THE Genetics Society of America's Elizabeth W. Jones Award for Excellence in Education recognizes significant and sustained impact on genetics education. Consistent with her philosophy of linking research and education, the 2014 Awardee Robin Wright includes undergraduate students in all of her research. She seeks to teach how to think like and to actually be a biologist, working in teams and looking at real-world problems. She emphasizes a learner-centered model of classroom work that promotes and enhances lifelong skills, and has transformed biology education at the University of Minnesota through several efforts including developing the interactive, stimulating Foundations of Biology course sequence, encouraging active learning and open-ended research; supporting the construction of Active Learning Classrooms; and establishing Student Learning Outcomes, standards that measure biology education. She serves as founding editor-in-chief of CourseSource, focusing national effort to collect learner-centered, outcomes-based teaching resources in undergraduate biology.