Education modalities for serious illness communication training: A scoping review on the impact on clinician behavior and patient outcomes.

BACKGROUND: Several clinician training interventions have been developed in the past decade to address serious illness communication. While numerous studies report on clinician attitudes and confidence, little is reported on individual education modalities and their impact on actual behavior change and patient outcomes. AIM: To examine what is known about the education modalities used in serious illness communication training and their impact on clinician behaviors and patient outcomes. DESIGN: A scoping review using the Joanna Briggs Methods Manual for Scoping Reviews was conducted to examine studies measuring clinician behaviors or patient outcomes. DATA SOURCES: Ovid MEDLINE and EMBASE databases were searched for English-language studies published between January 2011 and March 2023. RESULTS: The search identified 1317 articles: 76 met inclusion criteria describing 64 unique interventions. Common education modalities used were: single workshop (n = 29), multiple workshops (n = 11), single workshop with coaching (n = 7), and multiple workshops with coaching (n = 5); though they were inconsistently structured. Studies reporting improved clinician skills tended to be in simulation settings with neither clinical practice nor patient outcomes explored. While some studies reported behavior changes or improved patient outcomes, they did not necessarily confirm improvements in clinician skills. As multiple modalities were commonly used and often embedded within quality improvement initiatives, the impact of individual modalities could not be determined. CONCLUSION: This scoping review of serious illness communication interventions found heterogeneity among education modalities used and limited evidence supporting their effectiveness in impacting patient-centered outcomes and long-term clinician skill acquisition. Well-defined educational modalities and consistent measures of behavior change and standard patient-centered outcomes are needed.

Transcriptome deregulation of peripheral monocytes and whole blood in GBA-related Parkinson's disease.

BACKGROUND: Genetic mutations in beta-glucocerebrosidase (GBA) represent the major genetic risk factor for Parkinson's disease (PD). GBA participates in both the endo-lysosomal pathway and the immune response, two important mechanisms involved in the pathogenesis of PD. However, modifiers of GBA penetrance have not yet been fully elucidated. METHODS: We characterized the transcriptomic profiles of circulating monocytes in a population of patients with PD and healthy controls (CTRL) with and without GBA variants (n = 23 PD/GBA, 13 CTRL/GBA, 56 PD, 66 CTRL) and whole blood (n = 616 PD, 362 CTRL, 127 PD/GBA, 165 CTRL/GBA). Differential expression analysis, pathway enrichment analysis, and outlier detection were performed. Ultrastructural characterization of isolated CD14+ monocytes in the four groups was also performed through electron microscopy. RESULTS: We observed hundreds of differentially expressed genes and dysregulated pathways when comparing manifesting and non-manifesting GBA mutation carriers. Specifically, when compared to idiopathic PD, PD/GBA showed dysregulation in genes involved in alpha-synuclein degradation, aging and amyloid processing. Gene-based outlier analysis confirmed the involvement of lysosomal, membrane trafficking, and mitochondrial processing in manifesting compared to non-manifesting GBA-carriers, as also observed at the ultrastructural levels. Transcriptomic results were only partially replicated in an independent cohort of whole blood samples, suggesting cell-type specific changes. CONCLUSIONS: Overall, our transcriptomic analysis of primary monocytes identified gene targets and biological processes that can help in understanding the pathogenic mechanisms associated with GBA mutations in the context of PD.

The impact of the Caremongering social media movement: A convergent parallel mixed-methods study.

Public health responses to the COVID-19 pandemic, such as business restrictions, social distancing and lockdowns, had social and economic impacts on individuals and communities. Caremongering Facebook groups spread across Canada to support vulnerable individuals by providing a forum for sharing information and offering assistance. We sought to understand the specific impacts of Caremongering groups on individuals 1 year after the pandemic began. We used a convergent parallel mixed-methods approach that included semi-structured interviews with group moderators from 16 Caremongering groups and survey data from 165 group members. We used a constant comparative approach for thematic analysis of interview transcripts and open-ended text responses to the survey. We used source theme tables as joint displays to integrate interview and survey findings. Our results revealed five major themes: providing food, sharing information, supporting health and wellness, acquiring goods and services (non-food), and connecting communities. Respondents of our survey tended to be 35-65 years of age range, but reported helping adults of all ages. Our findings illustrate the potential of using a social media platform to connect with others and provide and access support. The Caremongering initiative demonstrates a community-driven, social media solution to issues such as isolation, loneliness and community health promotion.

Disparities in cardiovascular outcomes among emergency department patients with mental illness.

BACKGROUND: Patients with mental illness have been shown to receive lower quality of care and experience worse cardiovascular (CV) outcomes compared to those without mental illness. This present study examined mental health-related disparities in CV outcomes after an Emergency Department (ED) visit for chest pain. METHODS: This retrospective cohort included adult Medicaid beneficiaries in Washington state discharged from the ED with a primary diagnosis of unspecified chest pain in 2010-2017. Outcomes for patients with any mental illness (any mental health diagnosis or mental-health specific service use within 1 year of an index ED visit) and serious mental illness (at least two claims (on different dates of service) within 1 year of an index ED visit with a diagnosis of schizophrenia, other psychotic disorder, or major mood disorder) were compared to those of patients without mental illness. Our outcomes of interest were the incidence of major adverse cardiac events (MACE) within 30 days and 6 months of discharge of their ED visit, defined as a composite of death, acute myocardial infarction (AMI), CV rehospitalization, or revascularization. Secondary outcomes included cardiovascular diagnostic testing (diagnostic angiography, stress testing, echocardiography, and coronary computed tomography (CT) angiography) rates within 30 days of ED discharge. Only treat-and-release visits were included for outcomes assessment. Hierarchical logistic random effects regression models assessed the association between mental illness and the outcomes of interest, controlling for age, gender, race, ethnicity, Elixhauser comorbidities, and health care use in the past year, as well as fixed year effects. RESULTS: There were 98,812 treat-and-release ED visits in our dataset. At 30 days, enrollees with any mental illness had no differences in rates of MACE (AOR 0.96; 95% CI, 0.72-1.27) or any of the individual components. At 6 months, enrollees with any mental illness (AOR 1.86; 95% CI, 1.11-3.09) and serious mental illness (AOR 2.60; 95% CI 1.33-5.13) were significantly more likely to be hospitalized for a CV condition compared to those without mental illness. Individuals with any mental illness had higher rates of testing at 30 days (AOR 1.16; 95% CI 1.07-1.27). CONCLUSION: Patients with mental illness have similar rates of MACE, but higher rates of certain CV outcomes, such as CV hospitalization and diagnostic testing, after an ED visit for chest pain.

A Fyn biosensor reveals pulsatile, spatially localized kinase activity and signaling crosstalk in live mammalian cells.

Cell behavior is controlled through spatio-temporally localized protein activity. Despite unique and often contradictory roles played by Src-family-kinases (SFKs) in regulating cell physiology, activity patterns of individual SFKs have remained elusive. Here, we report a biosensor for specifically visualizing active conformation of SFK-Fyn in live cells. We deployed combinatorial library screening to isolate a binding-protein (F29) targeting activated Fyn. Nuclear-magnetic-resonance (NMR) analysis provides the structural basis of F29 specificity for Fyn over homologous SFKs. Using F29, we engineered a sensitive, minimally-perturbing fluorescence-resonance-energy-transfer (FRET) biosensor (FynSensor) that reveals cellular Fyn activity to be spatially localized, pulsatile and sensitive to adhesion/integrin signaling. Strikingly, growth factor stimulation further enhanced Fyn activity in pre-activated intracellular zones. However, inhibition of focal-adhesion-kinase activity not only attenuates Fyn activity, but abolishes growth-factor modulation. FynSensor imaging uncovers spatially organized, sensitized signaling clusters, direct crosstalk between integrin and growth-factor-signaling, and clarifies how compartmentalized Src-kinase activity may drive cell fate.

KMT1 family methyltransferases regulate heterochromatin-nuclear periphery tethering via histone and non-histone protein methylation.

Euchromatic histone methyltransferases (EHMTs), members of the KMT1 family, methylate histone and non-histone proteins. Here, we uncover a novel role for EHMTs in regulating heterochromatin anchorage to the nuclear periphery (NP) via non-histone methylation. We show that EHMTs methylate and stabilize LaminB1 (LMNB1), which associates with the H3K9me2-marked peripheral heterochromatin. Loss of LMNB1 methylation or EHMTs abrogates heterochromatin anchorage at the NP We further demonstrate that the loss of EHMTs induces many hallmarks of aging including global reduction of H3K27methyl marks and altered nuclear morphology. Consistent with this, we observe a gradual depletion of EHMTs, which correlates with loss of methylated LMNB1 and peripheral heterochromatin in aging human fibroblasts. Restoration of EHMT expression reverts peripheral heterochromatin defects in aged cells. Collectively, our work elucidates a new mechanism by which EHMTs regulate heterochromatin domain organization and reveals their impact on fundamental changes associated with the intrinsic aging process.

Mitochondrial DNA Mutations are Associated with Ulcerative Colitis Preneoplasia but Tend to be Negatively Selected in Cancer.

The role of mitochondrial DNA (mtDNA) mutations in cancer remains controversial. Ulcerative colitis is an inflammatory bowel disease that increases the risk of colorectal cancer and involves mitochondrial dysfunction, making it an ideal model to study the role of mtDNA in tumorigenesis. Our goal was to comprehensively characterize mtDNA mutations in ulcerative colitis tumorigenesis using Duplex Sequencing, an ultra-accurate next-generation sequencing method. We analyzed 46 colon biopsies from non-ulcerative colitis control patients and ulcerative colitis patients with and without cancer, including biopsies at all stages of dysplastic progression. mtDNA was sequenced at a median depth of 1,364x. Mutations were classified by mutant allele frequency: clonal > 0.95, subclonal 0.01-0.95, and very low frequency (VLF) < 0.01. We identified 208 clonal and subclonal mutations and 56,764 VLF mutations. Mutations were randomly distributed across the mitochondrial genome. Clonal and subclonal mutations increased in number and pathogenicity in early dysplasia, but decreased in number and pathogenicity in cancer. Most clonal, subclonal, and VLF mutations were C>T transitions in the heavy strand of mtDNA, which likely arise from DNA replication errors. A subset of VLF mutations were C>A transversions, which are probably due to oxidative damage. VLF transitions and indels were less abundant in the non-D-loop region and decreased with progression. Our results indicate that mtDNA mutations are frequent in ulcerative colitis preneoplasia but negatively selected in cancers. IMPLICATIONS: While mtDNA mutations might contribute to early ulcerative colitis tumorigenesis, they appear to be selected against in cancer, suggesting that functional mitochondria might be required for malignant transformation in ulcerative colitis.

Does Hypoxia-Inducible Factor -1 α (HIF-1α) C1772T polymorphism predict short-term prognosis in patients with oral squamous cell carcinoma (OSCC)?

BACKGROUND: Oral squamous cell carcinoma (OSCC) is a cancer of the oral cavity that is a major health problem in India. There is an urgent need to identify biomarkers that have prognostic significance. We studied HIF-1α levels as well as single-nucleotide polymorphism of HIF-1α gene in cancer and healthy controls. METHODS: Fifty newly diagnosed OSCC patients and 50 age and sex-matched healthy control were included in the study. Serum concentrations of HIF-1α were measured by sandwich ELISA; whereas HIF-1α gene polymorphism study was performed using restriction enzyme digestion by HpH I. RESULTS: The major genotype observed was CC genotype in both control (84%) and patients (86%) followed by CT genotype (control 16%, cases 14%). CT genotype led to more aggressive tumors. On subgroup analysis based on prognosis, the median overall survival of patients who were treatment responders was 488 days (16.2 months) and that of the patients with progressive disease was 365 days (12.1 months). The patients who expired during the study observation period had median survival of 330 days (11 months). CONCLUSION: Our study showed that CT genotype for C1772T polymorphism of HIF-1α predisposes to aggressive tumor phenotype in patients with OSCC. Moreover, patients with CT genotype had poor survival rate as compared to CC genotype. A cut-off value of 460 pg/mL of HIF-1α can help to segregate patients with OSCC from healthy controls.