Mistranslation of the genetic code by a new family of bacterial transfer RNAs.

The correct coupling of amino acids with transfer RNAs (tRNAs) is vital for translating genetic information into functional proteins. Errors during this process lead to mistranslation, where a codon is translated using the wrong amino acid. While unregulated and prolonged mistranslation is often toxic, growing evidence suggests that organisms, from bacteria to humans, can induce and use mistranslation as a mechanism to overcome unfavorable environmental conditions. Most known cases of mistranslation are caused by translation factors with poor substrate specificity or when substrate discrimination is sensitive to molecular changes such as mutations or posttranslational modifications. Here we report two novel families of tRNAs, encoded by bacteria from the Streptomyces and Kitasatospora genera, that adopted dual identities by integrating the anticodons AUU (for Asn) or AGU (for Thr) into the structure of a distinct proline tRNA. These tRNAs are typically encoded next to a full-length or truncated version of a distinct isoform of bacterial-type prolyl-tRNA synthetase. Using two protein reporters, we showed that these tRNAs translate asparagine and threonine codons with proline. Moreover, when expressed in Escherichia coli, the tRNAs cause varying growth defects due to global Asn-to-Pro and Thr-to-Pro mutations. Yet, proteome-wide substitutions of Asn with Pro induced by tRNA expression increased cell tolerance to the antibiotic carbenicillin, indicating that Pro mistranslation can be beneficial under certain conditions. Collectively, our results significantly expand the catalog of organisms known to possess dedicated mistranslation machinery and support the concept that mistranslation is a mechanism for cellular resiliency against environmental stress.

Likelihood-based deconvolution of bulk gene expression data using single-cell references.

Direct comparison of bulk gene expression profiles is complicated by distinct cell type mixtures in each sample that obscure whether observed differences are actually caused by changes in the expression levels themselves or are simply a result of differing cell type compositions. Single-cell technology has made it possible to measure gene expression in individual cells, achieving higher resolution at the expense of increased noise. If carefully incorporated, such single-cell data can be used to deconvolve bulk samples to yield accurate estimates of the true cell type proportions, thus enabling one to disentangle the effects of differential expression and cell type mixtures. Here, we propose a generative model and a likelihood-based inference method that uses asymptotic statistical theory and a novel optimization procedure to perform deconvolution of bulk RNA-seq data to produce accurate cell type proportion estimates. We show the effectiveness of our method, called RNA-Sieve, across a diverse array of scenarios involving real data and discuss extensions made uniquely possible by our probabilistic framework, including a demonstration of well-calibrated confidence intervals.

Provider Interaction With an Electronic Health Record Notification to Identify Eligible Patients for a Cluster Randomized Trial of Advance Care Planning in Primary Care: Secondary Analysis.

BACKGROUND: Advance care planning (ACP) improves patient-provider communication and aligns care to patient values, preferences, and goals. Within a multisite Meta-network Learning and Research Center ACP study, one health system deployed an electronic health record (EHR) notification and algorithm to alert providers about patients potentially appropriate for ACP and the clinical study. OBJECTIVE: The aim of the study is to describe the implementation and usage of an EHR notification for referring patients to an ACP study, evaluate the association of notifications with study referrals and engagement in ACP, and assess provider interactions with and perspectives on the notifications. METHODS: A secondary analysis assessed provider usage and their response to the notification (eg, acknowledge, dismiss, or engage patient in ACP conversation and refer patient to the clinical study). We evaluated all patients identified by the EHR algorithm during the Meta-network Learning and Research Center ACP study. Descriptive statistics compared patients referred to the study to those who were not referred to the study. Health care utilization, hospice referrals, and mortality as well as documentation and billing for ACP and related legal documents are reported. We evaluated associations between notifications with provider actions (ie, referral to study, ACP not documentation, and ACP billing). Provider free-text comments in the notifications were summarized qualitatively. Providers were surveyed on their satisfaction with the notification. RESULTS: Among the 2877 patients identified by the EHR algorithm over 20 months, 17,047 unique notifications were presented to 45 providers in 6 clinics, who then referred 290 (10%) patients. Providers had a median of 269 (IQR 65-552) total notifications, and patients had a median of 4 (IQR 2-8). Patients with more (over 5) notifications were less likely to be referred to the study than those with fewer notifications (57/1092, 5.2% vs 233/1785, 13.1%; P<.001). The most common free-text comment on the notification was lack of time. Providers who referred patients to the study were more likely to document ACP and submit ACP billing codes (P<.001). In the survey, 11 providers would recommend the notification (n=7, 64%); however, the notification impacted clinical workflow (n=9, 82%) and was difficult to navigate (n=6, 55%). CONCLUSIONS: An EHR notification can be implemented to remind providers to both perform ACP conversations and refer patients to a clinical study. There were diminishing returns after the fifth EHR notification where additional notifications did not lead to more trial referrals, ACP documentation, or ACP billing. Creation and optimization of EHR notifications for study referrals and ACP should consider the provider user, their workflow, and alert fatigue to improve implementation and adoption. TRIAL REGISTRATION: ClinicalTrials.gov NCT03577002; https://clinicaltrials.gov/ct2/show/NCT03577002.

The yeast exoribonuclease Xrn1 and associated factors modulate RNA polymerase II processivity in 5' and 3' gene regions.

mRNA levels are determined by the balance between mRNA synthesis and decay. Protein factors that mediate both processes, including the 5'-3' exonuclease Xrn1, are responsible for a cross-talk between the two processes that buffers steady-state mRNA levels. However, the roles of these proteins in transcription remain elusive and controversial. Applying native elongating transcript sequencing (NET-seq) to yeast cells, we show that Xrn1 functions mainly as a transcriptional activator and that its disruption manifests as a reduction of RNA polymerase II (Pol II) occupancy downstream of transcription start sites. By combining our sequencing data and mathematical modeling of transcription, we found that Xrn1 modulates transcription initiation and elongation of its target genes. Furthermore, Pol II occupancy markedly increased near cleavage and polyadenylation sites in xrn1Δ cells, whereas its activity decreased, a characteristic feature of backtracked Pol II. We also provide indirect evidence that Xrn1 is involved in transcription termination downstream of polyadenylation sites. We noted that two additional decay factors, Dhh1 and Lsm1, seem to function similarly to Xrn1 in transcription, perhaps as a complex, and that the decay factors Ccr4 and Rpb4 also perturb transcription in other ways. Interestingly, the decay factors could differentiate between SAGA- and TFIID-dominated promoters. These two classes of genes responded differently to XRN1 deletion in mRNA synthesis and were differentially regulated by mRNA decay pathways, raising the possibility that one distinction between these two gene classes lies in the mechanisms that balance mRNA synthesis with mRNA decay.

Leaning In to Serious Illness Care Through Stories and Science.

This volume was planned prior to the COVID-19 pandemic as the North Carolina Institute of Medicine (NCIOM) completed a yearlong task force on serious illness. Beyond the task force report, we wanted to dedicate a special edition of the NCMJ to serious illness issues. We commissioned authors who could discuss the challenges, the current practices, and the extensive personal and professional skills needed to navigate these complicated medical diagnoses that often end in death. Little did we know how timely this would be in light of the current pandemic, and we can only speculate on how the world will look as this is published. Our pre-COVID planning reflected personal experiences we all face with the common denominator of serious illness impacting and shaping our lives. As guest editors, we considered how this NCMJ edition would address personal concerns for you, our reader, as well as ourselves. A physician, a social worker, and a nurse, we each have our stories and we want to invite you to lean in and bring both your head and your heart to this reading. We start by relating two very personal experiences that shaped not only life following loss, but also career choices, clinical practices, and scholarship. As you focus on this journal's content, we hope you will also reflect on the people you care for, as well as the issues we all inevitably face.

NosP Modulates Cyclic-di-GMP Signaling in Legionella pneumophila.

Biofilms form when bacteria adhere to a surface and secrete an extracellular polymeric substance. Bacteria embedded within a biofilm benefit from increased resistance to antibiotics, host immune responses, and harsh environmental factors. Nitric oxide (NO) is a signaling molecule that can modulate communal behavior, including biofilm formation, in many bacteria. In many cases, NO-induced biofilm dispersal is accomplished through signal transduction pathways that ultimately lead to a decrease in intracellular cyclic-di-GMP levels. H-NOX (heme nitric oxide/oxygen binding domain) proteins are the best characterized bacterial NO sensors and have been implicated in NO-mediated cyclic-di-GMP signaling, but we have recently discovered a second family of NO-sensitive proteins in bacteria named NosP (NO sensing protein); to date, a clear link between NosP signaling and cyclic-di-GMP metabolism has not been established. Here we present evidence that NosP (Lpg0279) binds to NO and directly affects cyclic-di-GMP production from two-component signaling proteins Lpg0278 and Lpg0277 encoded within the NosP operon. Lpg0278 and Lpg0277 are a histidine kinase and cyclic-di-GMP synthase/phosphodiesterase, respectively, that have already been established as being important in regulating Legionella pneumophila cyclic-di-GMP levels; NosP is thus implicated in regulating cyclic-di-GMP in L. pneumophila.

Knowledge and Preferences of Primary Care Providers in Delivering Head and Neck Cancer Survivorship Care.

Long-term care for head and neck cancer (HNC) survivors is complex and requires coordination among multiple providers. Clinical practice guidelines highlight the role of primary care providers (PCPs) in screening for secondary cancer/recurrence, assessment of late/long-term side effects, and referrals for appropriate specialty management of toxicity. However, these responsibilities may be difficult to meet within the scope of primary care practice. We conducted this study to explore preferences, comfort, and knowledge of PCPs in the care of HNC survivors. We piloted a 40-item web-based survey developed with oncologist and PCP input targeted for family medicine and internal medicine providers. Responses were collected within a single university health system over 2 months. PCPs (n = 28; RR = 11.3%) were interested in learning about health promotion after cancer treatment (89%) and generally agree that their current practice patterns address healthy lifestyle behaviors (82%). However, only 32% of PCPs felt confident they could manage late/long-term side effects of chemotherapy, radiation, or surgery. Only 29% felt confident they could provide appropriate cancer screening. Looking at shared care responsibilities with oncology providers, PCPs perceived being responsible for 30% of care in the first year after treatment and 81% of care after 5 years. Seventy-one percent of PCPs agreed that oncologists provided them necessary information, yet 32% of PCPs found it difficult to coordinate with cancer providers. While these PCPs perceive increased care responsibility for long-term survivors, most are uncomfortable screening for recurrence and managing late/long-term side effects. Education and mutual coordination between PCPs and oncology providers may improve survivor care.

OPERATOR NORM INEQUALITIES BETWEEN TENSOR UNFOLDINGS ON THE PARTITION LATTICE.

Interest in higher-order tensors has recently surged in data-intensive fields, with a wide range of applications including image processing, blind source separation, community detection, and feature extraction. A common paradigm in tensor-related algorithms advocates unfolding (or flattening) the tensor into a matrix and applying classical methods developed for matrices. Despite the popularity of such techniques, how the functional properties of a tensor changes upon unfolding is currently not well understood. In contrast to the body of existing work which has focused almost exclusively on matricizations, we here consider all possible unfoldings of an order-k tensor, which are in one-to-one correspondence with the set of partitions of {1, …, k}. We derive general inequalities between the lp -norms of arbitrary unfoldings defined on the partition lattice. In particular, we demonstrate how the spectral norm (p = 2) of a tensor is bounded by that of its unfoldings, and obtain an improved upper bound on the ratio of the Frobenius norm to the spectral norm of an arbitrary tensor. For specially-structured tensors satisfying a generalized definition of orthogonal decomposability, we prove that the spectral norm remains invariant under specific subsets of unfolding operations.

615 fs pulses with 17 mJ energy generated by an Yb:thin-disk amplifier at 3 kHz repetition rate.

A combination of Er/Yb:fiber and Yb:thin-disk technology produces 615 fs pulses at 1030 nm with an average output power of 72 W. The regenerative amplifier allows variation of the repetition rate between 3 and 5 kHz with pulse energies from 13 to 17 mJ. A broadband and intense seed provided by the compact and versatile fiber front-end minimizes gain narrowing. The resulting sub-ps performance is ideal for nonlinear frequency conversion and pulse compression. Operating in the upper branch of a bifurcated pulse train, the system exhibits exceptional noise performance and stability.

The ability of renal ultrasound and ureteral jet evaluation to predict 30-day outcomes in patients with suspected nephrolithiasis.

STUDY OBJECTIVE: We sought to identify findings on bedside renal ultrasound that predicted need for hospitalization in patients with suspected nephrolithiasis. METHODS: A convenience sample of patients with suspected nephrolithiasis was prospectively enrolled and underwent bedside ultrasound of the kidneys and bladder to determine the presence and degree of hydronephrosis and ureteral jets. Sonologists were blinded to any other laboratory and imaging data. Patients were followed up at 30 days by phone call and review of medical records. RESULTS: Seventy-seven patients with suspected renal colic were included in the analysis. Thirteen patients were admitted. Reasons for admission included intractable pain, infection, or emergent urologic intervention. All 13 patients requiring admission had hydronephrosis present on initial bedside ultrasound. Patients with moderate hydronephrosis had a higher admission rate (36%) than those with mild hydronephrosis (24%), P<.01. Of patients without hydronephrosis, none required admission within 30 days. The sensitivity and specificity of hydronephrosis for predicting subsequent hospitalization were 100% and 44%, respectively. Loss of the ipsilateral ureteral jet was not significantly associated with subsequent hospital admission and did not improve the predictive value when used in combination with the degree of hydronephrosis. CONCLUSIONS: No patients with suspected renal colic and absence of hydronephrosis on bedside ultrasound required admission within 30 days. Ureteral jet evaluation did not help in prediction of 30-day outcomes and may not be useful in the emergency department management of renal colic.

Understanding ethical dilemmas in the emergency department: views from medical students' essays.

BACKGROUND: For medical students, the emergency department (ED) often presents ethical problems not encountered in other settings. In many medical schools there is little ethics training during the clinical years. The benefits of reflective essay writing in ethics and professionalism education are well established. OBJECTIVES: The purpose of this study was to determine and categorize the types of ethical dilemmas and scenarios encountered by medical students in the ED through reflective essays. METHODS: During a 4(th)-year emergency medicine rotation, all medical students wrote brief essays on an ethical situation encountered in the ED, and participated in an hour debriefing session about these essays. Qualitative analysis was performed to determine common themes from the essays. The frequency of themes was calculated. RESULTS: The research team coded 173 essays. The most common ethical themes were autonomy (41%), social justice (32.4%), nonmaleficence (31.8%), beneficence (26.6%), fidelity (12%), and respect (8.7%). Many of the essays contained multiple ethical principles that were often in conflict with each other. In one essay, a student grappled with the decision to intubate a patient despite a preexisting do-not-resuscitate order. This patient encounter was coded with autonomy, beneficence, and nonmaleficence. Common scenarios included ethical concerns when caring for critical patients, treatment of pain, homeless or alcoholic patients, access to care, resource utilization, and appropriateness of care. CONCLUSION: Medical students encounter patients with numerous ethically based issues. Frequently, they note conflicts between ethical principles. Such essays constitute an important resource for faculty, resident, and student ethics training.

The initial response to the Boston marathon bombing: lessons learned to prepare for the next disaster.

OBJECTIVE: We discuss the strengths of the medical response to the Boston Marathon bombings that led to the excellent outcomes. Potential shortcomings were recognized, and lessons learned will provide a foundation for further improvements applicable to all institutions. BACKGROUND: Multiple casualty incidents from natural or man-made incidents remain a constant global threat. Adequate preparation and the appropriate alignment of resources with immediate needs remain the key to optimal outcomes. METHODS: A collaborative effort among Boston's trauma centers (2 level I adult, 3 combined level I adult/pediatric, 1 freestanding level I pediatric) examined the details and outcomes of the initial response. Each center entered its respective data into a central database (REDCap), and the data were analyzed to determine various prehospital and early in-hospital clinical and logistical parameters that collectively define the citywide medical response to the terrorist attack. RESULTS: A total of 281 people were injured, and 127 patients received care at the participating trauma centers on that day. There were 3 (1%) immediate fatalities at the scene and no in-hospital mortality. A majority of the patients admitted (66.6%) suffered lower extremity soft tissue and bony injuries, and 31 had evidence for exsanguinating hemorrhage, with field tourniquets in place in 26 patients. Of the 75 patients admitted, 54 underwent urgent surgical intervention and 12 (22%) underwent amputation of a lower extremity. CONCLUSIONS: Adequate preparation, rapid logistical response, short transport times, immediate access to operating rooms, methodical multidisciplinary care delivery, and good fortune contributed to excellent outcomes.

The effect of supine versus upright patient positioning on inferior vena cava metrics.

BACKGROUND: Ultrasound of the inferior vena cava (IVC) is a noninvasive and rapidly obtainable method of intravascular volume assessment; however not all patients can lie supine for this procedure. In this study we assess whether patient positioning affects IVC diameter metrics. METHODS: This was a prospective convenience sample of patients in an in-patient dialysis unit at an urban tertiary care center. IVC metrics taken in the supine patient, and then at 45o semi-upright position, pre and post dialysis. Measurements were taken in M-mode in longitudinal plane roughly 2 cm below the level of the diaphragm. IVC-maximum and IVC-minimum diameter measurements were used to determine the IVC collapse index (IVC Max - IVC Min)/IVC Max). Statistics such as means, frequencies and percentages, intraclass correlation coefficient and Bland Altman summary statistics were calculated. RESULTS: Forty-five patients were enrolled. Average age was 57 years, 69% were male, 73% were African American, 82% had hypertension, 42% had diabetes. There was good to excellent agreement between supine and upright IVC measurements. Both the IVC minimum and maximum measurements had similar coefficient correlation (ri) measurements (0.917 and 0.890 respectively), whereas agreement in the collapse index was lower (ri = 0.813). Bland Altman analysis demonstrated excellent agreement and small 95% limits of agreement (±6 mm) with minimal mean bias for both the minimum and maximum measurements. CONCLUSION: IVC metrics do not change significantly based on patient position. For those patients who are unable to lay completely supine, a semi-upright measurement of the IVC for volume status may be an accurate alternative.

Emotional regulation and suicidal ideation-Mediating roles of perceived social support and avoidant coping.

Introduction: Recent research has uncovered a wide prevalence variation of suicidal ideation in university students ranging from 9.7% to 58.3%. India has witnessed a 4.5% increase in suicide rates in the year 2021. The interplay between cognitive reappraisal of a stressful situation, suppression of emotional expression, and coping strategies for suicidal ideation of Indian University students is yet to be explored. We aim to determine whether suicidal ideation would differ across different types of family units, and to predict the extent to which perceived social support and avoidant coping could mediate the relation between emotion regulation processes and suicidal ideation. Methods: Two hundred randomly selected University students (Mean age = 19.9, SD = 1.43) participated. Kruskal-Wallis, Pearson's product-moment correlation, and GLM mediation model were computed. Results and discussion: Lifetime suicidal ideation significantly differed between those who stay alone and those who live in a nuclear family (p < 0.01), and also those who stay in a joint family (p < 0.05). Cognitive reappraisal predicted a reduction in suicidal ideation mediated by perceived social support (B = -0.06, p < 0.05) and avoidant coping (B = -0.07, p < 0.05). Whereas, expressive suppression predicted induced levels of suicidal ideation through perceived social support (B = 0.05, p < 0.05), and avoidant coping (B = 0.06, p < 0.05) as mediators. Conclusion: Though our sample size restricts the generalization, our findings implied the importance of regular psychological consultation regarding the efficacy of the said coping processes in dealing with suicidal ideation.

Design and pilot test of an implicit bias mitigation curriculum for clinicians.

Introduction: Clinician implicit racial bias (IB) may lead to lower quality care and adverse health outcomes for Black patients. Educational efforts to train clinicians to mitigate IB vary widely and have insufficient evidence of impact. We developed and pilot-tested an evidence-based clinician IB curriculum, "REACHing Equity." Methods: To assess acceptability and feasibility, we conducted an uncontrolled one-arm pilot trial with post-intervention assessments. REACHing Equity is designed for clinicians to: (1) acquire knowledge about IB and its impact on healthcare, (2) increase awareness of one's own capacity for IB, and (3) develop skills to mitigate IB in the clinical encounter. We delivered REACHing Equity virtually in three facilitated, interactive sessions over 7-9 weeks. Participants were health care providers who completed baseline and end-of-study evaluation surveys. Results: Of approximately 1,592 clinicians invited, 37 participated, of whom 29 self-identified as women and 24 as non-Hispanic White. Attendance averaged 90% per session; 78% attended all 3 sessions. Response rate for evaluation surveys was 67%. Most respondents agreed or strongly agreed that the curriculum objectives were met, and that REACHing Equity equipped them to mitigate the impact of implicit bias in clinical care. Participants consistently reported higher self-efficacy for mitigating IB after compared to before completing the curriculum. Conclusions: Despite apparent barriers to clinician participation, we demonstrated feasibility and acceptability of the REACHing Equity intervention. Further research is needed to develop objective measures of uptake and clinician skill, test the impact of REACHing Equity on clinically relevant outcomes, and refine the curriculum for uptake and dissemination.ClinicalTrials.gov ID: NCT03415308.

In uncontrolled diabetes, thyroid hormone and sympathetic activators induce thermogenesis without increasing glucose uptake in brown adipose tissue.

Recent advances in human brown adipose tissue (BAT) imaging technology have renewed interest in the identification of BAT activators for the treatment of obesity and diabetes. In uncontrolled diabetes (uDM), activation of BAT is implicated in glucose lowering mediated by intracerebroventricular (icv) administration of leptin, which normalizes blood glucose levels in streptozotocin (STZ)-induced diabetic rats. The potent effect of icv leptin to increase BAT glucose uptake in STZ-diabetes is accompanied by the return of reduced plasma thyroxine (T4) levels and BAT uncoupling protein-1 (Ucp1) mRNA levels to nondiabetic controls. We therefore sought to determine whether activation of thyroid hormone receptors is sufficient in and of itself to lower blood glucose levels in STZ-diabetes and whether this effect involves activation of BAT. We found that, although systemic administration of the thyroid hormone (TR)ß-selective agonist GC-1 increases energy expenditure and induces further weight loss in STZ-diabetic rats, it neither increased BAT glucose uptake nor attenuated diabetic hyperglycemia. Even when GC-1 was administered in combination with a ß(3)-adrenergic receptor agonist to mimic sympathetic nervous system activation, glucose uptake was not increased in STZ-diabetic rats, nor was blood glucose lowered, yet this intervention potently activated BAT. Similar results were observed in animals treated with active thyroid hormone (T3) instead of GC-1. Taken together, our data suggest that neither returning normal plasma thyroid hormone levels nor BAT activation has any impact on diabetic hyperglycemia, and that in BAT, increases of Ucp1 gene expression and glucose uptake are readily dissociated from one another in this setting.

Diagnosis of near-fatal pulmonary embolus-in-transit with focused echocardiography.

BACKGROUND: Among patients who die from pulmonary embolus (PE), approximately two-thirds succumb within an hour of presentation. Computed tomography can provide a definitive diagnosis but is associated with practical limitations. Echocardiography can increase diagnostic certainty of PE by visualizing signs of acute right ventricular (RV) strain. This case highlights a potentially lethal finding associated with PE and the role of clinician-performed bedside echocardiography in the timely management of this disease. OBJECTIVE: To describe a case of PE-in-transit diagnosed by clinician-performed focused echocardiography. CASE REPORT: A 78-year-old man with lymphoma presented to the Emergency Department with shortness of breath. His blood pressure was 95/53 mm Hg; his oxygen saturation was 84% on room air. A focused echocardiogram showed a highly mobile elongated mass traversing the right atrium and right ventricle, consistent with a PE-in-transit. Anticoagulation was initiated and Cardiovascular Surgery was consulted for emergent thrombectomy. Minutes after reviewing the ultrasound with the surgeons, the patient was transported to the operating room. Just before surgery, the patient had a cardiac arrest. Exploration of his heart failed to reveal thrombus; however, extensive clot burden was removed from the pulmonary arteries, with subsequent return of spontaneous circulation. CONCLUSION: The clinician performed a focused echocardiogram to evaluate the cause of the patient's critical state. PE-in-transit, a rare entity associated with large PEs, was identified, which obviated the need for further diagnostic evaluation and led to immediate aggressive therapy. Increased familiarity with the uses of bedside sonography in the evaluation of shock and respiratory distress may allow clinicians to become more proficient in managing these patients.

Using Design Thinking to Promote Goals of Care Conversations With Seriously Ill Patients.

BACKGROUND: Goals of care (GOC) conversations can improve serious illness outcomes such as pain and symptom management and patient satisfaction. PROBLEM: However, we recognized that very few Duke Health patients who died had a GOC conversation documented in the designated electronic health record (EHR) tab. Therefore, in 2020, we set a target that all Duke Health patients who died should have had a GOC conversation documented in a designated EHR tab in the last 6 months of life. INTERVENTION: In developing a strategy to promote GOC conversations, we used two interwoven approaches. The first was RE-AIM, a model for designing, reporting and evaluating health behavior research. The second was less of a model than a way of approaching problems, known as "design thinking." OUTCOMES: We employed both of these approaches in a system-wide effort that achieved a 50% prevalence of GOC conversations in the last 6 months of life. KEY MESSAGE: In combination, simple interventions can have a significant impact on behavior change in an academic health system. LESSONS LEARNED: We found that design thinking techniques offered a useful bridge between RE-AIM strategy and clinical.

Insomnia among community members in Florida: Associations with demographics, health conditions, and social support.

Objectives: To identify associations between demographics, social determinants of health, health conditions, and reported history of insomnia. A cross-sectional study including 11,960 adult community members recruited through HealthStreet, a community outreach program at University of Florida. Methods: Health assessments were conducted via interviews. Participants reported their demographic background, level of social support, history of health conditions, and insomnia. Logistic regression was used to understand associations between risk factors and history of insomnia. Results: The prevalence of self-reported insomnia was 27.3%. Adults aged ≥ 65 years (OR = 1.16) and women (OR = 1.18) reported higher rates of insomnia than their counterparts. Black/African American individuals reported lower rates of insomnia (OR = 0.72) than White individuals. Individuals with food insecurity (OR = 1.53), a military history (OR = 1.30), lower social support (OR = 1.24), living alone (OR = 1.14), anxiety (OR = 2.33), cardiometabolic disease (OR = 1.58), and attention-deficit hyperactivity disorder (ADHD) (OR = 1.44) were significantly more likely to endorse insomnia compared with their counterparts. Depression (OR = 2.57) had the strongest association with insomnia. Conclusions: This study provides evidence regarding who is at greater risk for insomnia among a large community-based sample. Our findings highlight the importance of screening for insomnia, particularly among patients who experience food insecurity, are military veterans, have anxiety, depression, ADHD, or cardiometabolic disease, as well as those who live alone or have lower levels of social support. Future public health campaigns should provide education on insomnia symptoms, treatments, and evidenced-based sleep-promotion strategies.

Machine learning functional impairment classification with electronic health record data.

BACKGROUND: Poor functional status is a key marker of morbidity, yet is not routinely captured in clinical encounters. We developed and evaluated the accuracy of a machine learning algorithm that leveraged electronic health record (EHR) data to provide a scalable process for identification of functional impairment. METHODS: We identified a cohort of patients with an electronically captured screening measure of functional status (Older Americans Resources and Services ADL/IADL) between 2018 and 2020 (N = 6484). Patients were classified using unsupervised learning K means and t-distributed Stochastic Neighbor Embedding into normal function (NF), mild to moderate functional impairment (MFI), and severe functional impairment (SFI) states. Using 11 EHR clinical variable domains (832 variable input features), we trained an Extreme Gradient Boosting supervised machine learning algorithm to distinguish functional status states, and measured prediction accuracies. Data were randomly split into training (80%) and test (20%) sets. The SHapley Additive Explanations (SHAP) feature importance analysis was used to list the EHR features in rank order of their contribution to the outcome. RESULTS: Median age was 75.3 years, 62% female, 60% White. Patients were classified as 53% NF (n = 3453), 30% MFI (n = 1947), and 17% SFI (n = 1084). Summary of model performance for identifying functional status state (NF, MFI, SFI) was AUROC (area under the receiving operating characteristic curve) 0.92, 0.89, and 0.87, respectively. Age, falls, hospitalization, home health use, labs (e.g., albumin), comorbidities (e.g., dementia, heart failure, chronic kidney disease, chronic pain), and social determinants of health (e.g., alcohol use) were highly ranked features in predicting functional status states. CONCLUSION: A machine learning algorithm run on EHR clinical data has potential utility for differentiating functional status in the clinical setting. Through further validation and refinement, such algorithms can complement traditional screening methods and result in a population-based strategy for identifying patients with poor functional status who need additional health resources.