Psychiatry Consultation in Primary Care: Examining Treatment Access for Adolescent Depression.

PURPOSE: Youth in the United States are experiencing mental health concerns at an unprecedented level. Child Psychiatry Access Programs offer an innovative approach to close the gap between the need for care and insufficient mental health workforce. This study examined whether primary care provider consultation with a Child Psychiatry Access Program, Michigan Clinical Consultation & Care (MC3), was associated with greater access to treatment for adolescents with moderate to severe depression symptoms. METHODS: A retrospective chart review was conducted of primary care visits between 2017 and 2021 for adolescent patients with first-time positive scores on the Patient Health Questionnaire-9. Descriptive statistics and logistic regression were used to examine if patients whose primary care provider used MC3 psychiatric consultations had improved access to depression treatment compared to those who did not. RESULTS: Four hundred seventy nine patients reported Patient Health Questionnaire-9 scores indicating moderate to severe depression symptoms. Compared to non-MC3 consult patients (n = 409), MC3 consult patients (n = 70) had higher odds of being prescribed antidepressant medications (odds ratio [OR], 2.16; 95% confidence interval [CI] [1.11-4.22], p = .05), 4 times higher odds of having a primary care follow-up visit to monitor depression symptoms (OR, 4.56, 95% CI [2.56-8.14], p < .001), and higher odds of accessing mental health therapy (OR, 2.14; 95% CI [1.13-4.05], p = .05). DISCUSSION: Use of MC3 consultations was associated with increased utilization of evidence-based depression treatments including medication, therapy, and follow-up care. Greater adoption of models such as MC3 may increase the capacity for addressing mental health needs in children.

Disparity landscapes of viral-induced structural variations in HCC: Mechanistic characterization and functional implications.

BACKGROUND AND AIMS: HCC is the most common type of primary liver cancer and is a common malignancy worldwide. About half of all new liver cancers worldwide each year occur in China, including Hong Kong, due to a high prevalence of HBV infection. HBV DNA integrates into the human genome, disrupting the endogenous tumor suppressors/regulatory genes or enhancing the activity of proto-oncogenes. It would be useful to examine the different NGS-based databases to provide a more unbiased and comprehensive survey of HBV integration. APPROACH AND RESULTS: We aimed to take advantage of publicly available data sets of different regional cohorts to determine the disparity landscapes of integration events among sample cohorts, tissue types, chromosomal positions, individual host, and viral genes, as well as genic locations. By comparing HCC tumors with non tumorous livers, the landscape of HBV integration was delineated in gene-independent and gene-dependent manners. Moreover, we performed mechanistic investigations on how HBV-TERT integration led to TERT activation and derived a score to predict patients' prognostication according to their clonal disparity landscape of HBV integration. CONCLUSIONS: Our study uncovered the different levels of clonal enrichment of HBV integration and identified mechanistic insights and prognostic biomarkers. This strengthens our understanding of HBV-associated hepatocarcinogenesis.

Airways abnormalities in a prospective cohort of patients with rheumatoid arthritis.

BACKGROUND: Rheumatoid arthritis (RA) affects roughly 1% of the population and commonly involves the lungs. Of lung involvement in RA, interstitial lung disease (ILD) is well-known; however, airways disease in RA is relatively understudied. RESEARCH QUESTIONS: What are the baseline airways abnormalities in a prospective cohort of patients with RA based on pulmonary function tests (PFT), high-resolution CT scans (HRCT) and computational imaging analysis and are there associations between these abnormalities and respiratory symptoms? STUDY DESIGN AND METHODS: In this single-center study, 188 patients with RA without a clinical diagnosis of ILD underwent HRCT and PFT. Radiologists assessed HRCTs for airway abnormalities. Computational imaging via VIDA Vision software and in-house quantitative CT (qCT) analysis was applied to 147 HRCTs to quantify airway abnormalities. RESULTS: Airways obstruction (FEV1/FVC ratio < 0.7) was present in 20.7% of patients, and associated with older age, male sex and higher smoking rate. Radiologists identified airway abnormalities in 61% of patients-55% had bronchial wall thickening, 12% bronchiectasis, and 5% mosaic attenuation; these airways findings were associated with older age, male sex, lower FEV1, FVC, FEV1/FVC ratios, and higher rates of rheumatoid factor positivity. Prespecified qCT metrics (wall thickening % and emphysema %) correlated with PFT obstruction and more severe respiratory symptoms including shortness of breath and cough. INTERPRETATION: There were high rates of airways abnormalities in this prospective RA cohort based on three methods of detection. There were significant associations between qCT measures and respiratory symptoms. Airways disease may be an under-recognized extra-articular manifestation of RA and qCT may be a sensitive method to detect the clinical impact on respiratory symptoms.

Low-income fathers are emotionally resilient: A qualitative exploration of paternal emotions across early parenting.

Emotions play an important role in fostering positive parenting and healthy child development. This qualitative study explored the affective experiences of racially diverse US fathers with low income across the prenatal, postnatal, and early childhood periods. Semi-structured interviews were conducted with 24 fathers. Interview questions asked about fathers' early parenting experiences that elicit parenting emotions of different valence. Results from thematic analysis demonstrated activation of multiple emotions depending on different proximal and distal experiences. Specific to proximal experiences, fathers reported feeling both excited and anxious about pregnancy and joyful and disappointed at childbirth. Related to distal experiences, fathers reported feeling encouraged by their social support networks that further aid their parenting, but feeling marginalized given systematic barriers (e.g., societal bias, high incarceration rates of Black fathers). Most importantly, fathers' parenting emotions, especially negative ones, led to them resolving to stay involved in their children's lives, gaining a sense of responsibility, and changing behaviors to do right by their children. Fathers resorted to various coping strategies to regulate their negative emotions. Overall, fathers with low income are emotionally resilient. Infant and early childhood health professionals should support fathers' mental health to promote father-child engagement and thus, ultimately, young children's mental health and wellbeing.

Las emociones juegan un papel importante en fomentar una crianza positiva y un saludable desarrollo del niño. Este estudio cualitativo exploró las experiencias afectivas de papás de Estados Unidos de bajos recursos económicos que son racialmente diversos a lo largo de los períodos prenatal, postnatal y la temprana niñez. Se llevaron a cabo entrevistas semiestructuradas con 24 papás. Las preguntas de la entrevista trataban acerca de las tempranas experiencias de crianza de los papás que provocaban emociones de crianza de valencia diferente. Los resultados de análisis temáticos demostraron la activación de múltiples emociones dependiendo de diferentes emociones proximales y distales. Específico a las experiencias proximales, los papás reportaron sentirse tanto emocionados como ansiosos acerca del embarazo y alegres y decepcionados al momento del nacimiento. Con relación a las experiencias distales, los papás reportaron sentirse animados por parte de sus redes de apoyo social que ayudaron en su acercamiento a la crianza y sentirse marginalizados dadas las barreras sistemáticas. De manera más importante, las emociones de crianza de los papás especialmente las negativas, les llevaron a decidir mantenerse involucrados en las vidas de sus niños, adquiriendo un sentido de responsabilidad y cambiando conductas para hacer lo correcto con sus niños. Los papás recurrieron a varias estrategias para regular sus emociones negativas. En general, los papás de bajas entradas económicas son emocionalmente fuertes. Los profesionales de la salud infantil y en la temprana niñez deben apoyar la salud mental de los papás para promover la compenetración papá­niño y a la larga, la salud mental y el bienestar de los niños pequeños.

Single-cell analysis of breast cancer metastasis reveals epithelial-mesenchymal plasticity signatures associated with poor outcomes.

Metastasis is the leading cause of cancer-related deaths. It is unclear how intratumor heterogeneity (ITH) contributes to metastasis and how metastatic cells adapt to distant tissue environments. The study of these adaptations is challenged by the limited access to patient material and a lack of experimental models that appropriately recapitulate ITH. To investigate metastatic cell adaptations and the contribution of ITH to metastasis, we analyzed single-cell transcriptomes of matched primary tumors and metastases from patient-derived xenograft models of breast cancer. We found profound transcriptional differences between the primary tumor and metastatic cells. Primary tumors upregulated several metabolic genes, whereas motility pathway genes were upregulated in micrometastases, and stress response signaling was upregulated during progression. Additionally, we identified primary tumor gene signatures that were associated with increased metastatic potential and correlated with patient outcomes. Immune-regulatory control pathways were enriched in poorly metastatic primary tumors, whereas genes involved in epithelial-mesenchymal transition were upregulated in highly metastatic tumors. We found that ITH was dominated by epithelial-mesenchymal plasticity (EMP), which presented as a dynamic continuum with intermediate EMP cell states characterized by specific genes such as CRYAB and S100A2. Elevated expression of an intermediate EMP signature correlated with worse patient outcomes. Our findings identified inhibition of the intermediate EMP cell state as a potential therapeutic target to block metastasis.

Associations between 6-minute walk distance and physiologic measures and clinical outcomes in myositis-associated interstitial lung disease.

OBJECTIVE: The 6-min walk test (6MWT) is a simple test widely used to assess sub-maximal exercise capacity in chronic respiratory diseases. We explored the relationship of 6-min walk distance (6MWD) with measurements of physiological, clinical, radiographic measures in patients with myositis-associated interstitial lung disease (MA-ILD). METHOD: We analyzed data from the Abatacept in Myositis Associated Interstitial lung disease (Attack My-ILD) study, a 48-week multicentre randomized trial of patients with anti-synthetase antibodies and active MA-ILD. 6MWD, forced vital capacity (FVC), diffusing capacity (DLCO), high resolution CT, and various physician/patient reported outcome measures were obtained during the trial. Spearman's correlations and repeated-measures analysis with linear mixed-effects models were used to estimate the associations between 6MWD and various physiologic, clinical and radiographic parameters both cross-sectionally and longitudinally. RESULTS: Twenty participants with a median age of 57, 55% male and 85% white were analyzed. Baseline 6MWD did not associate with baseline PFTs. Repeated-measures analysis showed 6MWD over time associated with FVC over time, but not with DLCO. 6MWD over time also correlated with UCSD dyspnea score, Borg scores, as well as global disease activity and muscle strength over time. Emotional role functioning, vitality, general health and physical functioning scores by short form 36 also correlated with 6MWD over time. CONCLUSIONS: : Exploratory work in a small cohort of MA-ILD demonstrated 6MWD over time associated with parallel changes in FVC and patient reported outcomes of dyspnea, but not with DLCO. Larger studies are needed to validate the reliability, responsiveness and utility of the 6MWT in MA-ILD. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT03215927.

Resolution of Optimal Mitochondrial and Nuclear DNA Enrichment in Target-Panel Sequencing and Physiological Mitochondrial DNA Copy Number Estimation in Liver Cancer and Non-Liver Cancer Subjects.

Mitochondria generate energy to support cells. They are important organelles that engage in key biological pathways. The dysfunction of mitochondria can be linked to hepatocarcinogenesis, which has been actively explored in recent years. To investigate the mitochondrial dysfunction caused by genetic variations, target-panel sequencing is a flexible and promising strategy. However, the copy number of mitochondria generally exceeds nuclear DNA, which raises a concern that uneven target enrichment of mitochondrial DNA (mtDNA) and nuclear DNA (ncDNA) in target-panel sequencing would lead to an undesirably biased representation of them. To resolve this issue, we evaluated the optimal pooling of mtDNA probes and ncDNA probes by a series of dilutions of mtDNA probes in both genomic DNA (gDNA) and cell-free DNA (cfDNA) samples. The evaluation was based on read count, average sequencing depth and coverage of targeted regions. We determined that an mtDNA:ncDNA probe ratio of around 1:10 would offer a good balance of sequencing performance and cost effectiveness. Moreover, we estimated the median physiological mtDNA:ncDNA copy ratio as 38.1 and 2.9 in cfDNA and gDNA samples of non-liver cancer subjects, respectively, whereas they were 20.0 and 2.1 in the liver cancer patients. Taken together, this study revealed the appropriate pooling strategy of mtDNA probes and ncDNA probes in target-panel sequencing and suggested the normal range of physiological variation of the mtDNA:ncDNA copy ratio in non-liver cancer individuals. This can serve as a useful reference for future target-panel sequencing investigations of the mitochondrial genome in liver cancer.

Digital Innovation to Grow Quality Care Through an Interprofessional Care Team (DIG IT) Among Underserved Patients With Hypertension.

PURPOSE: The impact of digital health on medically underserved patients is unclear. This study aimed to determine the early impact of a digital innovation to grow quality care through an interprofessional care team (DIG IT) on the blood pressure (BP) and 10-year atherosclerotic cardiovascular disease (ASCVD) risk score of medically underserved patients. METHODS: This was a 3-month, prospective intervention study that included patients aged 40 years or more with BP of 140/90 mmHg or higher who received care from DIG IT from August through December 2021. Sociodemographic and clinical outcomes of DIG IT were compared with historical controls (controls) whose data were randomly extracted by the University of California Data Warehouse and matched 1:1 based on age, ethnicity, and baseline BP of the DIG IT arm. Multiple linear regression was performed to adjust for potential confounding factors. RESULTS: A total of 140 patients (70 DIG IT, 70 controls) were included. Both arms were similar with an average age (SD) of 62.8 (9.7) years. The population was dominated by Latinx (79.3%) persons, with baseline mean BP of 163/81 mmHg, and mean ASCVD risk score of 23.9%. The mean (SD) reduction in systolic BP at 3 months in the DIG IT arm was twice that of the controls (30.8 [17.3] mmHg vs 15.2 [21.2] mmHg; P <.001). The mean (SD) ASCVD risk score reduction in the DIG IT arm was also twice that of the controls (6.4% [7.4%] vs 3.1% [5.1%]; P = .003). CONCLUSIONS: The DIG IT was more effective than controls (receiving usual care). Twofold improvement in the BP readings and ASCVD scores in medically underserved patients were achieved with DIG IT.

Miliary coccidioidomycosis mimicking tuberculosis: Case report and review of literature.

Miliary coccidioidomycosis is a severe manifestation of diseases caused by Coccidioides immitis and Coccidioides posadasii that is endemic to the southwestern United States as well as Central and South America. While most cases of coccidioidomycosis present with pulmonary disease, certain risk factors increase the risk for disseminated disease. We present a case of miliary coccidioidomycosis in a 46-year-old patient with uncontrolled diabetes. Additionally, we review the features of thirty-seven cases of patients with miliary coccidioidomycosis.

Chitinase 3-like-1 Inhibits Innate Antitumor and Tissue Remodeling Immune Responses by Regulating CD47-SIRPα- and CD24-Siglec10-Mediated Phagocytosis.

Innate immune responses such as phagocytosis are critically linked to the generation of adaptive immune responses against the neoantigens in cancer and the efferocytosis that is essential for homeostasis in diseases characterized by lung injury, inflammation, and remodeling as in chronic obstructive pulmonary disease (COPD). Chitinase 3-like-1 (CHI3L1) is induced in many cancers where it inhibits adaptive immune responses by stimulating immune checkpoint molecules (ICPs) and portends a poor prognosis. CHI3L1 is also induced in COPD where it regulates epithelial cell death. In this study, we demonstrate that pulmonary melanoma metastasis inhibits macrophage phagocytosis by stimulating the CD47-SIRPα and CD24-Siglec10 phagocytosis checkpoint pathways while inhibiting macrophage "eat me" signals from calreticulin and HMGB1. We also demonstrate that these effects on macrophage phagocytosis are associated with CHI3L1 stimulation of the SHP-1 and SHP-2 phosphatases and inhibition of the accumulation and phosphorylation of cytoskeleton-regulating nonmuscle myosin IIa. This inhibition of innate immune responses such as phagocytosis provides a mechanistic explanation for the ability of CHI3L1 to stimulate ICPs and inhibit adaptive immune responses in cancer and diseases such as COPD. The ability of CHI3L1 to simultaneously inhibit innate immune responses, stimulate ICPs, inhibit T cell costimulation, and regulate a number of other oncogenic and inflammation pathways suggests that CHI3L1-targeted therapeutics are promising interventions in cancer, COPD, and other disorders.

Author language and communication preferences, and familiarity with global publication guidelines, for English-language industry-sponsored publications in Asia-Pacific: insights from a cross-sectional survey.

OBJECTIVE: To understand current practices and challenges for collecting author feedback for English-language, industry-sponsored publications in Asia-Pacific (APAC), and the implications for adherence to international publication guidelines. METHODS: A cross-sectional, internet-based survey of industry ('internal') authors (17 questions) and publication professionals (18 questions) supporting publications in APAC, conducted between November 18 and December 4, 2022. RESULTS: Overall, 142 survey responses were received, of which 94 (66%) were complete and included in the analysis (33 internal authors, 61 publication professionals). Almost half (45%) of internal authors preferred a non-English language for providing feedback on publications, and most (70%) would use this language whenever possible. Internal authors favored written (91%) versus spoken (73%) English, and email was the preferred mode of communication. Publication professionals said they have observed qualitative differences when authors provide feedback in a preferred non-English language versus English. Many agreed that authors tend to provide more substantive or critical feedback when they can respond in their preferred non-English language. Internal authors had low self-assessed familiarity with key publication guidelines, while most publication professionals had a moderate or high self-assessed familiarity. The main barriers to application of publication guidelines, as rated by publication professionals, were that external authors in APAC are not familiar with global publication guidelines and do not always provide feedback/responses in writing. CONCLUSION: It is important to consider the diverse language, cultural, and communication preferences of individuals involved in English-language publication development in APAC, and to ensure that authors are aware of current publication guidelines and best practices.

Learning control-ready forecasters for Blood Glucose Management.

Type 1 diabetes (T1D) presents a significant health challenge, requiring patients to actively manage their blood glucose (BG) levels through regular bolus insulin administration. Automated control solutions based on machine learning (ML) models could reduce the need for manual patient intervention. However, the accuracy of current models falls short of what is needed. This is due in part to the fact that these models are often trained on data collected using a basal bolus (BB) strategy, which results in substantial entanglement between bolus insulin and carbohydrate intake. Under standard training approaches, this entanglement can lead to inaccurate forecasts in a control setting, ultimately resulting in poor BG management. To address this, we propose a novel algorithm for training BG forecasters that disentangles the effects of insulin and carbohydrates. By exploiting correction bolus values and leveraging the monotonic effect of insulin on BG, our method accurately captures the independent effects of insulin and carbohydrates on BG. Using an FDA-approved simulator, we evaluated our approach on 10 individuals across 30 days of data. Our approach achieved on average higher time in range compared to standard approaches (81.1% [95% confidence interval (CI) 80.3,81.9] vs 53.6% [95%CI 52.7,54.6], p<0.001), indicating that our approach is able to reliably maintain healthy BG levels in simulated individuals, while baseline approaches are not. Utilizing proxy metrics, our approach also demonstrates potential for improved control on three real world datasets, paving the way for advancements in ML-based BG management.

Development, Acceptability, and Initial Implementation of an Interactive Text-Messaging Program for Fathers with Low Income.

OBJECTIVES: This study describes the development, acceptability, and implementation of an interactive text messaging program to engage fathers enrolled in home visitation programs. METHODS: We used an iterative development approach that integrated rapid testing of intervention content with acceptability feedback from program participants to examine the processes of implementation. In Study 1, we describe the rapid testing framework and present data from 171 men who provided feedback on Text4Dad content via three online surveys. In Study 2, a case study, we use administrative data from 108 fathers with whom we pilot-tested Text4Dad in three community-based home visiting programs, with the program implemented by fatherhood program community health workers (F-CHWs). Content analysis of exchanges between F-CHWs and fathers describes the specific use of Text4Dad. RESULTS: Across all three online surveys, fathers reported positive reviews of the Text4Dad content. The F-CHWs used Text4Dad mainly to push out information, especially that related to home visit scheduling and local events, instead of engaging in bidirectional interactions with fathers. CONCLUSIONS FOR PRACTICE: We conclude with a set of recommendations for social service and maternal and child health providers regarding the feasibility of implementing text messaging to support home visiting in community-based settings.

2023 American College of Rheumatology (ACR)/American College of Chest Physicians (CHEST) Guideline for the Screening and Monitoring of Interstitial Lung Disease in People with Systemic Autoimmune Rheumatic Diseases.

OBJECTIVE: We provide evidence-based recommendations regarding screening for interstitial lung disease (ILD) and the monitoring for ILD progression in people with systemic autoimmune rheumatic diseases (SARDs), specifically rheumatoid arthritis, systemic sclerosis, idiopathic inflammatory myopathies, mixed connective tissue disease, and Sjögren disease. METHODS: We developed clinically relevant population, intervention, comparator, and outcomes questions related to screening and monitoring for ILD in patients with SARDs. A systematic literature review was performed, and the available evidence was rated using the Grading of Recommendations, Assessment, Development, and Evaluation methodology. A Voting Panel of interdisciplinary clinician experts and patients achieved consensus on the direction and strength of each recommendation. RESULTS: Fifteen recommendations were developed. For screening people with these SARDs at risk for ILD, we conditionally recommend pulmonary function tests (PFTs) and high-resolution computed tomography of the chest (HRCT chest); conditionally recommend against screening with 6-minute walk test distance (6MWD), chest radiography, ambulatory desaturation testing, or bronchoscopy; and strongly recommend against screening with surgical lung biopsy. We conditionally recommend monitoring ILD with PFTs, HRCT chest, and ambulatory desaturation testing and conditionally recommend against monitoring with 6MWD, chest radiography, or bronchoscopy. We provide guidance on ILD risk factors and suggestions on frequency of testing to evaluate for the development of ILD in people with SARDs. CONCLUSION: This clinical practice guideline presents the first recommendations endorsed by the American College of Rheumatology and American College of Chest Physicians for the screening and monitoring of ILD in people with SARDs.

2023 American College of Rheumatology (ACR)/American College of Chest Physicians (CHEST) Guideline for the Treatment of Interstitial Lung Disease in People with Systemic Autoimmune Rheumatic Diseases.

OBJECTIVE: We provide evidence-based recommendations regarding the treatment of interstitial lung disease (ILD) in adults with systemic autoimmune rheumatic diseases (SARDs). METHODS: We developed clinically relevant population, intervention, comparator, and outcomes questions. A systematic literature review was then performed, and the available evidence was rated using the Grading of Recommendations, Assessment, Development, and Evaluation methodology. A panel of clinicians and patients reached consensus on the direction and strength of the recommendations. RESULTS: Thirty-five recommendations were generated (including two strong recommendations) for first-line SARD-ILD treatment, treatment of SARD-ILD progression despite first-line ILD therapy, and treatment of rapidly progressive ILD. The strong recommendations were against using glucocorticoids in systemic sclerosis-ILD as a first-line ILD therapy and after ILD progression. Otherwise, glucocorticoids are conditionally recommended for first-line ILD treatment in all other SARDs. CONCLUSION: This clinical practice guideline presents the first recommendations endorsed by the American College of Rheumatology and American College of Chest Physicians for the treatment of ILD in people with SARDs.

Effect of Antifibrotic Use on Mortality in Patients with Idiopathic Pulmonary Fibrosis.

Rationale: Observational studies report a significant protective effect of antifibrotics on mortality among patients with idiopathic pulmonary fibrosis (IPF). Many of these studies, however, were subject to immortal time bias because of the mishandling of delayed antifibrotic initiation. Objectives: To evaluate the antifibrotic effect on mortality among patients with IPF using appropriate statistical methods that avoid immortal time bias. Methods: Using a large administrative database, we identified 10,289 patients with IPF, of whom 2,300 used antifibrotics. Treating delayed antifibrotic initiation as a time-dependent variable, three statistical methods were used to control baseline characteristics and avoid immortal time bias. Stratified analysis was performed for patients who initiated antifibrotics early and those who initiated treatment late. For comparison, methods that mishandle immortal time bias were performed. A simulation study was conducted to demonstrate the performance of these models in a wide range of scenarios. Results: All three statistical methods yielded nonsignificant results for the antifibrotic effect on mortality, with the stratified analysis for patients with early antifibrotic initiation suggesting evidence for reduced mortality risk (for all patients, hazard ratio, 0.89; 95% confidence interval, 0.79-1.01; P = 0.08; for patients who were 65 years or older, hazard ratio, 0.85; 95% confidence interval, 0.73-0.98; P = 0.03). Methods that mishandle immortal time bias demonstrated significantly lower mortality risk for antifibrotic users. Bias of these methods was evident in the simulation study, where appropriate methods performed well with little to no bias. Conclusions: Findings in this study did not confirm an association between antifibrotics and mortality, with a stratified analysis showing support for a potential treatment effect with early treatment initiation.

Nutrition counsellors' recommended eating patterns for individuals with type 2 diabetes in the USA.

Introduction: Multiple eating patterns can promote glycaemic control and weight loss among patients with type 2 diabetes mellitus (T2D). Clinical practice guidelines for T2D management encourage health professionals to guide patients' selection of a patient-centred eating pattern. This study aims to characterise beliefs about and recommendations for and against practice guideline-concordant eating patterns among registered dietitians (RDs) and other healthcare professionals who provide nutrition counselling to patients with T2D. Methods: This was a cross-sectional online survey. We invited 82 RDs affiliated with an academic health system in the midwestern USA to participate. We also invited health professionals who provide nutrition counselling to patients with T2D and are affiliated with 264 primary care practices within the Michigan Collaborative for Type 2 Diabetes. Participants were asked to select the eating pattern(s) that they commonly recommend or avoid for patients with T2D and why. Results: Survey respondents (n=81) most commonly recommend low-carbohydrate (77.8%); Mediterranean-style (52.8%) and energy-modified/calorie-restricted (36.1%) eating patterns. Survey respondents most commonly recommend avoiding very low-carbohydrate (51.0%) and very low-calorie (49.0%) eating patterns. Respondents who did not recommend very low-carbohydrate were most concerned about the eating pattern being too restrictive (93.0%). Conclusions: Survey respondents recommend a range of guideline-adherent eating patterns to patients with T2D but tend to recommend against very low-carbohydrate and very low-calorie eating patterns. Additional strategies are needed to increase patient-centred use of these evidence-based options in clinical practice settings.

Long-read sequencing and optical genome mapping identify causative gene disruptions in noncoding sequence in two patients with neurologic disease and known chromosome abnormalities.

Despite advances in next generation sequencing (NGS), genetic diagnoses remain elusive for many patients with neurologic syndromes. Long-read sequencing (LRS) and optical genome mapping (OGM) technologies improve upon existing capabilities in the detection and interpretation of structural variation in repetitive DNA, on a single haplotype, while also providing enhanced breakpoint resolution. We performed LRS and OGM on two patients with known chromosomal rearrangements and inconclusive Sanger or NGS. The first patient, who had epilepsy and developmental delay, had a complex translocation between two chromosomes that included insertion and inversion events. The second patient, who had a movement disorder, had an inversion on a single chromosome disrupted by multiple smaller inversions and insertions. Sequence level resolution of the rearrangements identified pathogenic breaks in noncoding sequence in or near known disease-causing genes with relevant neurologic phenotypes (MBD5, NKX2-1). These specific variants have not been reported previously, but expected molecular consequences are consistent with previously reported cases. As the use of LRS and OGM technologies for clinical testing increases and data analyses become more standardized, these methods along with multiomic data to validate noncoding variation effects will improve diagnostic yield and increase the proportion of probands with detectable pathogenic variants for known genes implicated in neurogenetic disease.

Direct rotation from a fentanyl patch to a buprenorphine patch in a patient with chronic pain.

Transitioning a patient with chronic pain from a fentanyl patch to a buprenorphine patch has not been well described in the literature. Even after a patient removes their fentanyl patch, the residual fentanyl in the skin continues to be absorbed for hours. Due to the risk of precipitated withdrawal when initiating buprenorphine, this transition is a more challenging opioid rotation to plan safely. We report a case of a patient who had been using a fentanyl patch for over 10 years and was successfully rotated directly to a buprenorphine patch.

Modified blood cell GAP model as a prognostic biomarker in idiopathic pulmonary fibrosis.

Background: The Gender, Age and Physiology (GAP) model is a simple mortality prediction tool in patients with idiopathic pulmonary fibrosis that uses demographic and physiological variables available at initial evaluation. White blood cell variables may have associations with idiopathic pulmonary fibrosis outcomes. We evaluated whether incorporating blood cell counts in modified GAP (cGAP) models would improve outcome prediction in patients with idiopathic pulmonary fibrosis. Patients and methods: This retrospective analysis included pooled data from phase 3 randomised trials of pirfenidone in idiopathic pulmonary fibrosis (ASCEND, CAPACITY 004, CAPACITY 006). Study outcomes (disease progression, all-cause mortality, all-cause hospitalisation, respiratory-related hospitalisation) were evaluated during the initial 1-year period. Shared frailty models were used to evaluate associations between continuous and categorical baseline white and red blood cell parameters and study outcomes in a bivariate context, and to evaluate the impact of adding continuous monocyte count (cGAP1) or white and red blood cell parameters (cGAP2) to traditional GAP variables in a multivariable context based on C-statistics changes. Results: Data were pooled from 1247 patients (pirfenidone, n=623; placebo, n=624). Significant associations (bivariate analyses) were idiopathic pulmonary fibrosis progression with neutrophil and eosinophil counts; all-cause mortality with monocyte and neutrophil counts; all-cause hospitalisation with monocyte count, neutrophil count and haemoglobin level; and respiratory-related hospitalisation with monocyte count, neutrophil count and haemoglobin level. In multivariate analyses, C-statistics were highest for the cGAP2 model for each of the outcomes. Conclusion: Modified GAP models incorporating monocyte counts alone or plus other white and red blood cell variables may be useful to improve prediction of outcomes in patients with idiopathic pulmonary fibrosis.