Using the Translating Research into Practice framework to develop a diabetes prevention intervention in primary care: a mixed-methods study.

BACKGROUND: Pre-diabetes affects one-third of US adults and increases the risk of type 2 diabetes. Effective evidence-based interventions, such as the Diabetes Prevention Program, are available, but a gap remains in effectively translating and increasing uptake of these interventions into routine care. METHODS: We applied the Translating Research into Practice (TRiP) framework to guide three phases of intervention design and development for diabetes prevention: (1) summarise the evidence, (2) identify local barriers to implementation and (3) measure performance. In phase 1, we conducted a retrospective cohort analysis of linked electronic health record claims data to evaluate current practices in the management of pre-diabetes. In phase 2, we conducted in-depth interviews of 16 primary care physicians, 7 payor leaders and 31 patients to elicit common barriers and facilitators for diabetes prevention. In phase 3, using findings from phases 1 and 2, we developed the core elements of the intervention and performance measures to evaluate intervention uptake. RESULTS: In phase 1 (retrospective cohort analysis), we found few patients with pre-diabetes received diabetes prevention interventions. In phase 2 (stakeholder engagement), we identified common barriers to include a lack of knowledge about pre-diabetes among patients and about the Diabetes Prevention Program among clinicians. In phase 3 (intervention development), we developed the START Diabetes Prevention Clinical Pathway as a systematic change package to address barriers and facilitators identified in phases 1 and 2, performance measures and a toolkit of resources to support the intervention components. CONCLUSIONS: The TRiP framework supported the identification of evidence-based care practices for pre-diabetes and the development of a well-fitted, actionable intervention and implementation plan designed to increase treatment uptake for pre-diabetes in primary care settings. Our change package can be adapted and used by other health systems or clinics to target prevention of diabetes or other related chronic conditions.

Association of Occupational Dysfunction and Hospital Admissions With Different Polygenic Profiles in Bipolar Disorder.

OBJECTIVE: Many but not all persons with bipolar disorder require hospital care because of severe mood episodes. Likewise, some but not all patients experience long-term occupational dysfunction that extends beyond acute mood episodes. It is not known whether these dissimilar outcomes of bipolar disorder are driven by different polygenic profiles. Here, polygenic scores (PGSs) for major psychiatric disorders and educational attainment were assessed for associations with occupational functioning and psychiatric hospital admissions in bipolar disorder. METHODS: A total of 4,782 patients with bipolar disorder and 2,963 control subjects were genotyped and linked to Swedish national registers. Longitudinal measures from at least 10 years of registry data were used to derive percentage of years without employment, percentage of years with long-term sick leave, and mean number of psychiatric hospital admissions per year. Ordinal regression was used to test associations between outcomes and PGSs for bipolar disorder, schizophrenia, major depressive disorder, attention deficit hyperactivity disorder (ADHD), and educational attainment. Replication analyses of hospital admissions were conducted with data from the Bipolar Disorder Research Network cohort (N=4,219). RESULTS: Long-term sick leave and unemployment in bipolar disorder were significantly associated with PGSs for schizophrenia, ADHD, major depressive disorder, and educational attainment, but not with the PGS for bipolar disorder. By contrast, the number of hospital admissions per year was associated with higher PGSs for bipolar disorder and schizophrenia, but not with the other PGSs. CONCLUSIONS: Bipolar disorder severity (indexed by hospital admissions) was associated with a different polygenic profile than long-term occupational dysfunction. These findings have clinical implications, suggesting that mitigating occupational dysfunction requires interventions other than those deployed to prevent mood episodes.

Using our understanding of interactions between helminth metabolism and host immunity to target worm survival.

Helminths can adapt to environmental conditions in the host, utilising anaerobic processes like fermentation and malate dismutation to produce energy from carbohydrate. Although targeting carbohydrate metabolism is an established therapeutic strategy to combat helminth infection, questions remain over the metabolic pathways they employ as adults to survive and evade host immunity. Helminths also use amino acid, polyunsaturated fatty acid (PUFA), and cholesterol metabolism, a possible strategy favouring the production of immunomodulatory compounds that may influence survival in the host. Here, we discuss the significance of these differing metabolic pathways and whether targeting of helminth metabolic pathways may allow for the development of novel anthelmintics.

Protein-truncating variants in BSN are associated with severe adult-onset obesity, type 2 diabetes and fatty liver disease.

Obesity is a major risk factor for many common diseases and has a substantial heritable component. To identify new genetic determinants, we performed exome-sequence analyses for adult body mass index (BMI) in up to 587,027 individuals. We identified rare loss-of-function variants in two genes (BSN and APBA1) with effects substantially larger than those of well-established obesity genes such as MC4R. In contrast to most other obesity-related genes, rare variants in BSN and APBA1 were not associated with normal variation in childhood adiposity. Furthermore, BSN protein-truncating variants (PTVs) magnified the influence of common genetic variants associated with BMI, with a common variant polygenic score exhibiting an effect twice as large in BSN PTV carriers than in noncarriers. Finally, we explored the plasma proteomic signatures of BSN PTV carriers as well as the functional consequences of BSN deletion in human induced pluripotent stem cell-derived hypothalamic neurons. Collectively, our findings implicate degenerative processes in synaptic function in the etiology of adult-onset obesity.

A qualitative feasibility study of a prototype patient-centered video intervention to increase uptake of cancer genetic testing among Black Americans.

BACKGROUND: Health advances due to developments in genomic medicine are unequally experienced in the USA; racial differences in the uptake of genetic testing are one factor in this disparity. In collaboration with Black patients and diverse health care providers, we are developing a patient-centered video intervention to increase cancer genetic testing among eligible Black Americans. The objective of the pilot work is to explore the acceptability of and support for the intervention and key content components. METHODS: In order to create a patient-centered video intervention prototype, we conducted a targeted, secondary analysis of 47 coded transcripts from video-taped qualitative interviews with people with a known genetic or inherited cancer risk. The review focused on decision-making, testing experiences, and perceived value of genetic testing. We subsequently generated a 15-min video montage of content from 9 diverse (age, gender, race) participants. We used the prototype video as prompt material for semi-structured interviews with 10 Black patients who had undergone genetic testing in the last 2 years and 10 racially diverse providers (genetic counselors, a nurse, and medical oncologists) who provide management recommendations for high-risk patients. Interviews sought to understand the acceptability of a video intervention to enhance informed decision-making by Black patients and key elements for intervention efficacy. RESULTS: Study participants were generally positive about the prototype video and provided guidance for intervention development. Interviewed patients prioritized perceived authenticity and relatability of video participants. The presentation of patients' perspectives on testing, their experiences of testing, and the benefits of having test results were all seen as useful. The benefits of testing for self and family were identified as important considerations. Privacy concerns and science skepticism were identified as germane issues, with guidance to present barriers to testing alongside possible solutions. The inclusion of clinicians was seen as potentially useful but with caution that clinicians are not universally trusted. CONCLUSIONS: Study findings provided critical input for the creation of a professionally produced, tailored intervention video for a randomized clinical trial with Black Americans to evaluate the influence on uptake of genetic testing. The interviews suggest the acceptability and potential utility of an authentic, realistic, and tailored, patient-centered video intervention to increase consideration and uptake of genetic testing.

Health and Wellness Coaching and Sustained Gains: A Rapid Systematic Review.

The Transtheoretical Model of Change identifies key stages in behavior change, including a maintenance stage occurring when a behavior has been upheld for at least 6 months. Health and wellness coaching has demonstrated support for health behavior change, but maintenance of gains has received little attention. Our rapid systematic literature review characterizes both the research exploring sustained gains with health and wellness coaching and what is known about sustained gains after the completion of a health and wellness coaching engagement. Guided by The Cochrane Rapid Reviews Methods Group "Interim Guidance," we drew 231 studies from the 2018 and 2020 Sforzo et al "Compendium of the health and wellness coaching literature," and "Addendum…" appendices. Initial screening and coding for inclusion and exclusion criteria yielded 28 studies for data extraction. We examined studies across outcome categories (physiological, behavioral, psychological, and health risk assessment) to determine whether outcome measures were: not sustained; partially sustained; fully sustained; or improved from immediate post-intervention to a later follow-up period. Twenty-five of the 28 studies reviewed demonstrated partially, or fully, sustained or improved outcomes in one or more variables studied, with sustained gains demonstrated across outcome categories, strengthening confidence in HWC as a facilitator of lasting change.

Benefit-risk assessment for the Novavax COVID-19 vaccine (NVX-CoV2373).

A benefit-risk assessment of NVX-CoV2373, a vaccine to prevent COVID-19, was conducted to determine if the benefits of vaccination outweigh the risks of myocarditis/pericarditis. This analysis used data on myocarditis/pericarditis cases observed in the NVX-CoV2373 clinical studies, real-world data of mRNA COVID vaccine effectiveness against predominant SARS-CoV-2 strains in early 2023, and recent COVID-19 burden of disease data from the United States. The benefits of NVX-CoV2373 vaccination were estimated as the number of COVID-19 cases, hospitalizations, and deaths prevented. The risks of myocarditis/pericarditis cases and related hospitalizations and deaths occurring within 7 days of vaccination were also estimated. In our analysis, vaccination with NVX-CoV2373, per 100,000 vaccinated, resulted in an estimated 1805 COVID-19 cases prevented compared with an estimated 5.3 excess myocarditis/pericarditis cases. The number of COVID-19 hospitalizations and deaths prevented were also greater than vaccine-associated myocarditis/pericarditis hospitalizations and deaths. Our analysis indicates a positive benefit-risk balance for NVX-CoV2373.

Fine-mapping genomic loci refines bipolar disorder risk genes.

Bipolar disorder (BD) is a heritable mental illness with complex etiology. While the largest published genome-wide association study identified 64 BD risk loci, the causal SNPs and genes within these loci remain unknown. We applied a suite of statistical and functional fine-mapping methods to these loci, and prioritized 22 likely causal SNPs for BD. We mapped these SNPs to genes, and investigated their likely functional consequences by integrating variant annotations, brain cell-type epigenomic annotations, brain quantitative trait loci, and results from rare variant exome sequencing in BD. Convergent lines of evidence supported the roles of SCN2A, TRANK1, DCLK3, INSYN2B, SYNE1, THSD7A, CACNA1B, TUBBP5, PLCB3, PRDX5, KCNK4, AP001453.3, TRPT1, FKBP2, DNAJC4, RASGRP1, FURIN, FES, YWHAE, DPH1, GSDMB, MED24, THRA, EEF1A2, and KCNQ2 in BD. These represent promising candidates for functional experiments to understand biological mechanisms and therapeutic potential. Additionally, we demonstrated that fine-mapping effect sizes can improve performance and transferability of BD polygenic risk scores across ancestrally diverse populations, and present a high-throughput fine-mapping pipeline (https://github.com/mkoromina/SAFFARI).

Identifying genetic differences between bipolar disorder and major depression through multiple GWAS.

Background: Accurate diagnosis of bipolar disorder (BD) is difficult in clinical practice, with an average delay between symptom onset and diagnosis of about 7 years. A key reason is that the first manic episode is often preceded by a depressive one, making it difficult to distinguish BD from unipolar major depressive disorder (MDD). Aims: Here, we use genome-wide association analyses (GWAS) to identify differential genetic factors and to develop predictors based on polygenic risk scores that may aid early differential diagnosis. Methods: Based on individual genotypes from case-control cohorts of BD and MDD shared through the Psychiatric Genomics Consortium, we compile case-case-control cohorts, applying a careful merging and quality control procedure. In a resulting cohort of 51,149 individuals (15,532 BD cases, 12,920 MDD cases and 22,697 controls), we perform a variety of GWAS and polygenic risk scores (PRS) analyses. Results: While our GWAS is not well-powered to identify genome-wide significant loci, we find significant SNP-heritability and demonstrate the ability of the resulting PRS to distinguish BD from MDD, including BD cases with depressive onset. We replicate our PRS findings, but not signals of individual loci in an independent Danish cohort (iPSYCH 2015 case-cohort study, N=25,966). We observe strong genetic correlation between our case-case GWAS and that of case-control BD. Conclusions: We find that MDD and BD, including BD with a depressive onset, are genetically distinct. Further, our findings support the hypothesis that Controls - MDD - BD primarily lie on a continuum of genetic risk. Future studies with larger and richer samples will likely yield a better understanding of these findings and enable the development of better genetic predictors distinguishing BD and, importantly, BD with depressive onset from MDD.

Key subphenotypes of bipolar disorder are differentially associated with polygenic liabilities for bipolar disorder, schizophrenia, and major depressive disorder.

Bipolar disorder (BD) features heterogenous clinical presentation and course of illness. It remains unclear how subphenotypes associate with genetic loadings of BD and related psychiatric disorders. We investigated associations between the subphenotypes and polygenic risk scores (PRS) for BD, schizophrenia, and major depressive disorder (MDD) in two BD cohorts from Sweden (N = 5180) and the UK (N = 2577). Participants were assessed through interviews and medical records for inter-episode remission, psychotic features during mood episodes, global assessment of functioning (GAF, function and symptom burden dimensions), and comorbid anxiety disorders. Meta-analyses based on both cohorts showed that inter-episode remission and GAF-function were positively correlated with BD-PRS but negatively correlated with schizophrenia-PRS (SCZ-PRS) and MDD-PRS. Moreover, BD-PRS was negatively, and MDD-PRS positively, associated with the risk of comorbid anxiety disorders. Finally, SCZ-PRS was positively associated with psychotic symptoms during mood episodes. Assuming a higher PRS of certain psychiatric disorders in cases with a positive family history, we further tested the associations between subphenotypes in index BD people and occurrence of BD, schizophrenia, or MDD in their relatives using Swedish national registries. BD patients with a relative diagnosed with BD had: (1) higher GAF and lower risk of comorbid anxiety than those with a relative diagnosed with schizophrenia or MDD, (2) lower risk of psychotic symptoms than those with a relative diagnosed with schizophrenia. Our findings shed light on the genetic underpinnings of the heterogeneity in clinical manifestations and course of illness in BD, which ultimately provide insights for developing personalized approaches to the diagnosis and treatment.

Genome sequencing and de novo assembly of Trichoderma longibrachiatum isolate collected from Florida agricultural soils.

We report a draft genome assembly of Trichoderma longibrachiatum isolate GEV 3550, obtained from Florida, United States of America.

Adenomyoepithelioma of the Breast: Radiologic-Pathologic Correlation and Management.

Adenomyoepithelioma (AME) is a rare, usually benign breast neoplasm with low potential for malignant transformation. Imaging features are nonspecific and overlap with other benign and malignant breast lesions. On mammography, AME most often presents as a mass, usually oval in shape, with variable reported margins. Less commonly, AME can present mammographically as an asymmetry or can be mammographically occult. Associated calcifications are uncommon. On US, AME is usually seen as a hypoechoic oval mass, but it can also manifest as a complex cystic and solid mass. On US, the majority of AME have noncircumscribed margins (indistinct, angular, or microlobulated). Internal vascularity is usually present, and posterior enhancement can be seen. Although there is limited literature on MRI features, the most frequent finding is an irregular mass with washout kinetics; T2 hyperintensity can be observed. These nonspecific and often suspicious imaging features usually merit biopsy. On histologic analysis, AME is characterized by a biphasic proliferation of myoepithelial and epithelial cells. Pathologic diagnosis can be difficult due to the variety of histologic features of AME and heterogeneity in these tumors, especially when sampling is limited, such as in core needle biopsies. Wide local surgical excision of AME is recommended due to potential for recurrence and malignant transformation.

Exploring dermatologists' perspectives on vaccines in dermatology: a qualitative study.

Vaccination rates among adults in the United States, including dermatology patients, remain suboptimal. Previous research has concluded that outpatient specialty offices often have administrative and patient-related barriers to administering vaccines in their clinics, however, this has never been examined specifically in dermatology. This study aims to examine dermatologists' perspectives on vaccine education in dermatology clinics, identify facilitators and barriers to vaccine administration in dermatology clinics, and explore strategies to improve vaccination rates in dermatology patients. Virtual, semi-structured interviews were conducted with board-certified dermatologists to explore their perspectives on vaccines in dermatology clinic. The Consolidated Framework for Implementation Research was used to analyze the data. Participating dermatologists were 60% female (n = 9) and 40% male (n = 6) and had a median of 7 years of clinic experience (min-max: 3-39 years). Vaccine education emerged as one of the prominent themes during the interview with dermatologists, who emphasized the importance of comprehensive vaccine education for both healthcare providers and patients. Barriers identified encompassed patient hesitancy, lack of provider knowledge, resource limitations, and logistical challenges. Dermatologists proposed solutions such as standardized protocols, improved patient communication, enhanced coordination with other healthcare providers, and increased clinic resources. These results emphasize that dermatologists can play a crucial role in advocating for and addressing preventative care through vaccine implementation and provide a high-level framework to think about implementation. Additionally, this study highlights the need for comprehensive vaccine education, systematic implementation strategies, and organizational support within dermatology clinics to improve vaccine administration for patients.

Evaluation of an infection control protocol to limit COVID-19 at residential summer camps in 2021.

AIM: To assess the effectiveness of an infection control protocol developed to mitigate the spread of COVID-19 at two multi-week residential summer camps in 2021. SUBJECT AND METHODS: Data were collected from 595 camp attendees and staff members at two wilderness camps in Northern Minnesota. Testing was undertaken in all unvaccinated campers before arrival at camp, on day 4 of camp, and in the event of respiratory symptoms. Campers were limited to cohorts during the first 4 days of camp and wore masks indoors. The number of positive COVID-19 cases measured the efficacy of the protocol. RESULTS: The testing and cohorting protocol successfully prevented the spread of COVID-19 among campers and staff. During the first summer session, there were zero positive cases of COVID-19 among 257 campers and 127 staff. During the second summer session, compliance with the protocol limited the spread of COVID-19 to just three individuals of 266 campers and 129 staff. Maintaining cohorts at arrival limited spread from a single positive case to only two tent companions. CONCLUSION: The testing and cohorting protocol limited the spread of COVID-19 among residential summer wilderness campers and staff. Post-arrival testing ensured newly acquired virus was limited in spread before COVID-19 precautions were relaxed on camp day 5. A strict evidence-based cohorting protocol limited in-camp spread and allowed for a successful summer camp season. The usefulness of this protocol with an evolving pandemic, increasing vaccination rates, and virus variants could have implications for future practice.