Predictive Factors of Inactive Patient Participation in an Inflammatory Bowel Disease Learning Health System: A Longitudinal Cohort Study.

Patient participation is crucial to learning health systems that leverage patient data to improve care practices. Age, history of anxiety or depression, and frequency of clinic visits were associated with inactive participation in an inflammatory bowel disease learning health system.

Clinical journey for patients with aortic regurgitation: A retrospective observational study from a multicenter database.

BACKGROUND: Data using real-world assessments of aortic regurgitation (AR) severity to identify rates of Heart Valve Team evaluation and aortic valve replacement (AVR), as well as mortality among untreated patients, are lacking. The present study assessed these trends in care and outcomes for real-world patients with documented AR. METHODS: Using a deidentified data set (January 2018-March 2023) representing 1,002,853 patients >18 years of age from 25 US institutions participating in the egnite Database (egnite, Inc.) with appropriate permissions, patients were classified by AR severity in echocardiographic reports. Rates of evaluation by the Heart Valve Team, AVR, and all-cause mortality without AVR were examined using Kaplan-Meier estimates and compared using the log-rank test. RESULTS: Within the data set, 845,113 patients had AR severity documented. For moderate-to-severe or severe AR, respectively, 2-year rates (95% confidence interval) of evaluation by the Heart Valve Team (43.5% [41.7%-45.3%] and 65.4% [63.3%-67.4%]) and AVR (19.4% [17.6%-21.1%] and 46.5% [44.2%-48.8%]) were low. Mortality at 2 years without AVR increased with greater AR severity, up to 20.7% for severe AR (p < 0.001). In exploratory analyses, 2-year mortality for untreated patients with left ventricular end-systolic dimension index > 25 mm/m2 was similar for moderate (34.3% [29.2%-39.1%]) and severe (37.2% [24.9%-47.5%]) AR. CONCLUSIONS: Moderate or greater AR is associated with poor clinical outcomes among untreated patients at 2 years. Rates of Heart Valve Team evaluation and AVR were low for those with moderate or greater AR, suggesting that earlier referral to the Heart Valve Team could be beneficial.

Screening for asymptomatic nephrolithiasis in primary hyperparathyroidism patients is warranted.

BACKGROUND: We aimed to investigate the prevalence, characteristics, and management of nephrolithiasis in primary hyperparathyroidism (PHPT) patients. METHODS: Medical records of patients who underwent parathyroidectomy at a tertiary care hospital in British Columbia from January 2016 to April 2023 were retrospectively reviewed. Demographic data, laboratory results, imaging reports, and urologic consultations were examined. Descriptive statistics and relevant statistical tests, including logistic regressions, were utilized for data analysis. RESULT: Of the 413 PHPT patients included in the study population, 41.9% harbored renal stones, and nearly half (48.6%) required urological interventions. Male sex, elevated preoperative serum ionized calcium (iCa) and 24-h urinary calcium (24 â€‹h urine Ca) levels were independent risk factors for stone formation. Additionally, male sex, younger age, and lower preoperative serum 25-hydroxyvitamin D (25(OH)D) level were associated with higher odds of requiring urological intervention for stones. CONCLUSIONS: This study identified significant prevalence of asymptomatic renal calcifications in PHPT patients, with a substantial proportion necessitating urological intervention. These findings emphasize the importance of incorporating screening and treatment of renal stones into the management of PHPT patients.

Increased Risks for Suicide, Self-Harm, Substance Use, and Psychiatric Disorders in Adults With Inflammatory Bowel Disease: A Nationwide Study in the United States From 2007 to 2017.

In an analysis of over 260 million emergency department visits across the United States from 2007 to 2017, inflammatory bowel disease conferred >10-fold risk for suicide deaths, self-harm, substance use, and psychiatric disorders, though the overall self-harm rates were low (<1% of all-cause inflammatory bowel disease emergency department visits; total 56 suicide deaths).

Post-stroke Everything.

PURPOSE OF REVIEW: This review aims at providing updates on selected post-stroke complications. We examined recent advances in diagnosing and treating the following post-stroke complications: cognitive impairment, epilepsy, depression, fatigue, tremors, dysphagia, and pain. RECENT FINDINGS: Advances in understanding the mechanisms of post-stroke complications, in general, are needed despite advances made in understanding, treating, and preventing these complications. There are growing progresses in integrating new tools to diagnose post-stroke cognitive impairment. The potential role of acute stroke reperfusion treatment in post-stroke epilepsy and its impact on other stroke complications is getting more transparent. Post-stroke depression remains underestimated and new tools to diagnose depression after stroke are being developed. New promising pharmacological approaches to treating post-stroke pain are emerging. Tremors related to stroke are poorly understood and under-evaluated, while treatment towards post-stroke dysphagia has benefited from new non-pharmacological to pharmacological approaches. CONCLUSIONS: An integrative approach to stroke complications and collaborations between providers across specialties are more likely to improve stroke outcomes.

The Mortality Burden of Untreated Aortic Stenosis.

BACKGROUND: The American College of Cardiology/American Heart Association guidelines recommend the assessment and grading of severity of aortic stenosis (AS) as mild, moderate, or severe, per echocardiogram, and recommend aortic valve replacement (AVR) when the AS is severe. OBJECTIVES: The authors sought to describe mortality rates across the entire spectrum of untreated AS from a contemporary, large, real-world database. METHODS: We analyzed a deidentified real-world data set including 1,669,536 echocardiographic reports (1,085,850 patients) from 24 U.S. hospitals (egnite Database, egnite). Patients >18 years of age were classified by diagnosed AS severity. Untreated mortality and treatment rates were examined with Kaplan-Meier (KM) estimates, with results compared using the log-rank test. Multivariate hazards analysis was performed to assess associations with all-cause mortality. RESULTS: Among 595,120 patients with available AS severity assessment, the KM-estimated 4-year unadjusted, untreated, all-cause mortality associated with AS diagnosis of none, mild, mild-to-moderate, moderate, moderate-to-severe, or severe was 13.5% (95% CI: 13.3%-13.7%), 25.0% (95% CI: 23.8%-26.1%), 29.7% (95% CI: 26.8%-32.5%), 33.5% (95% CI: 31.0%-35.8%), 45.7% (95% CI: 37.4%-52.8%), and 44.9% (95% CI: 39.9%-49.6%), respectively. Results were similar when adjusted for informative censoring caused by treatment. KM-estimated 4-year observed treatment rates were 0.2% (95% CI: 0.2%-0.2%), 1.0% (95% CI: 0.7%-1.3%), 4.2% (95% CI: 2.0%-6.3%), 11.4% (95% CI: 9.5%-13.3%), 36.7% (95% CI: 31.8%-41.2%), and 60.7% (95% CI: 58.0%-63.3%), respectively. After adjustment, all degrees of AS severity were associated with increased mortality. CONCLUSIONS: Patients with AS have high mortality risk across all levels of untreated AS severity. Aortic valve replacement rates remain low for patients with severe AS, suggesting that more research is needed to understand barriers to diagnosis and appropriate approach and timing for aortic valve replacement.

Wearable sensor and machine learning estimate tendon load and walking speed during immobilizing boot ambulation.

The purpose of this study is to develop a wearable paradigm to accurately monitor Achilles tendon loading and walking speed using wearable sensors that reduce subject burden. Ten healthy adults walked in an immobilizing boot under various heel wedge conditions (30°, 5°, 0°) and walking speeds. Three-dimensional motion capture, ground reaction force, and 6-axis inertial measurement unit (IMU) signals were collected. We used a Least Absolute Shrinkage and Selection Operator (LASSO) regression to predict peak Achilles tendon load and walking speed. The effects of altering sensor parameters were also explored. Walking speed models (mean absolute percentage error (MAPE): 8.81 ± 4.29%) outperformed tendon load models (MAPE: 34.93 ± 26.3%). Models trained with subject-specific data performed better than models trained without subject-specific data. Removing the gyroscope, decreasing the sampling frequency, and using combinations of sensors did not change the usability of the models, having inconsequential effects on model performance. We developed a simple monitoring paradigm that uses LASSO regression and wearable sensors to accurately predict (MAPE ≤ 12.6%) Achilles tendon loading and walking speed while ambulating in an immobilizing boot. This paradigm provides a clinically implementable strategy to longitudinally monitor patient loading and activity while recovering from Achilles tendon injuries.

Associations of small vessel disease and acute symptomatic seizures in ischemic stroke patients.

BACKGROUND AND PURPOSE: Cerebral microbleeds (CMBs), markers of small vessel disease are frequent in ischemic stroke, yet the association with acute symptomatic seizures (ASS) has not been well characterized. METHODS: A retrospective cohort of hospitalized patients with anterior circulation ischemic stroke. The association of CMBs with acute symptomatic seizures was assessed using a logistic regression model and causal mediation analysis. RESULTS: Of 381 patients, 17 developed seizures. Compared with patients without CMBs, those with CMBs had a three-fold higher unadjusted odds of seizures (unadjusted OR: 3.84, 95% 1.16-12.71, p = 0.027). After adjusting for confounders such as stroke severity, cortical infarct location, and hemorrhagic transformation, the association between CMBs and ASS was attenuated (adjusted OR: 3.11, 95%CI: 0.74-11.03, p = 0.09). The association was not mediated by stroke severity. CONCLUSION: In this cohort of hospitalized patients with anterior circulation ischemic stroke, CMBs were more likely to be found in patients with ASS than those without ASS, an association that was attenuated when accounting for stroke severity, cortical infarct location, and hemorrhagic transformation. Evaluation of the long-term risk of seizures associated with CMBs and other markers of small vessel disease is warranted.

Wearable sensor and machine learning accurately estimate tendon load and walking speed during immobilizing boot ambulation.

Achilles tendon injuries are treated with progressive weight bearing to promote tendon healing and restore function. Patient rehabilitation progression are typically studied in controlled, lab settings and do not represent the long-term loading experienced during daily living. The purpose of this study is to develop a wearable paradigm to accurately monitor Achilles tendon loading and walking speed using low-cost sensors that reduce subject burden. Ten healthy adults walked in an immobilizing boot under various heel wedge conditions (30°, 5°, 0°) and walking speeds. Three-dimensional motion capture, ground reaction force, and 6-axis inertial measurement unit (IMU) signals were collected per trial. We used Least Absolute Shrinkage and Selection Operator (LASSO) regression to predict peak Achilles tendon load and walking speed. The effects of using only accelerometer data, different sampling frequency, and multiple sensors to train the model were also explored. Walking speed models outperformed (mean absolute percentage error (MAPE): 8.41 ± 4.08%) tendon load models (MAPE: 33.93 ± 23.9%). Models trained with subject-specific data performed significantly better than generalized models. For example, our personalized model that was trained with only subject-specific data predicted tendon load with a 11.5 ± 4.41% MAPE and walking speed with a 4.50 ± 0.91% MAPE. Removing gyroscope channels, decreasing sampling frequency, and using combinations of sensors had inconsequential effects on models performance (changes in MAPE < 6.09%). We developed a simple monitoring paradigm that uses LASSO regression and wearable sensors to accurately predict Achilles tendon loading and walking speed while ambulating in an immobilizing boot. This paradigm provides a clinically implementable strategy to longitudinally monitor patient loading and activity while recovering from Achilles tendon injuries.

Recurrent activity within microcircuits of macaque dorsolateral prefrontal cortex tracks cognitive flexibility.

Human and non-human primate data clearly implicate the dorsolateral prefrontal cortex (dlPFC) as critical for advanced cognitive functions 1,2 . It is thought that intracortical synaptic architectures within dlPFC are the integral neurobiological substrate that gives rise to these processes, including working memory, inferential reasoning, and decision-making 3-7 . In the prevailing model, each cortical column makes up one fundamental processing unit composed of dense intrinsic connectivity, conceptualized as the 'canonical' cortical microcircuit 3,8 . Each cortical microcircuit receives sensory and cognitive information from a variety of sources which are represented by sustained activity within the microcircuit, referred to as persistent or recurrent activity 4,9 . Via recurrent connections within the microcircuit, activity can propagate for a variable length of time, thereby allowing temporary storage and computations to occur locally before ultimately passing a transformed representation to a downstream output 4,5,10 . Competing theories regarding how microcircuit activity is coordinated have proven difficult to reconcile in vivo where intercortical and intracortical computations cannot be fully dissociated 5,9,11,12 . Here, we interrogated the intrinsic features of isolated microcircuit networks using high-density calcium imaging of macaque dlPFC ex vivo . We found that spontaneous activity is intrinsically maintained by microcircuit architecture, persisting at a high rate in the absence of extrinsic connections. Further, using perisulcal stimulation to evoke persistent activity in deep layers, we found that activity propagates through stochastically assembled intracortical networks, creating predictable population-level events from largely non-overlapping ensembles. Microcircuit excitability covaried with individual cognitive performance, thus anchoring heuristic models of abstract cortical functions within quantifiable constraints imposed by the underlying synaptic architecture.

Utilization of Mammography During the Last Year of Life Among Older Breast Cancer Survivors.

Background: Mammography is generally recommended for breast cancer survivors. However, discussion is ongoing about stopping surveillance mammography when life expectancy is <5-10 years as the benefit of screening might be diminished toward the end of life. The utilization pattern of mammography in the last year of life among this population has not been well studied. Methods: We identified 58,736 females diagnosed with breast cancer between January 2002 and December 2015, who died at the age of at least 67, from the SEER-Medicare database. We examined the utilization patterns of mammography during their last year of life and investigated factors associated with the use of mammography at the end of life using a multivariable logistic regression model. Results: Overall, 28.5% of the patients received mammography during the last year of life. Multivariable logistic regression showed that older age (OR = 0.31, 95% CI = 0.29-0.34, p < 0.001 for 95 vs. 85 years old), more advanced cancer stage (OR = 0.22, 95% CI = 0.20-0.24 p < 0.001 for distant vs. localized disease), and higher comorbidity score (OR = 0.92, 95% CI = 0.91-0.93, p < 0.001 for every 1-point increase) were associated with less mammography use. Age was nonlinearly associated with mammography use, with a steady proportion of patients receiving a mammography until approximately age 80 and then a sharp decrease thereafter. Conclusion: This population-based study found that a sizable proportion of older breast cancer survivors received mammography during the last year of life.

The Reliability of Patient Self-reported Utilization in an Inflammatory Bowel Diseases Learning Health System.

Background: Inflammatory bowel disease (IBD) care is beset with substantial practice variation. Learning health systems (LHSs) aim to learn from this variation and improve quality of care by sharing feedback and improvement strategies within the LHS. Obtaining accurate information on outcomes and quality of care is a priority for LHS, which often includes patients' self-reported data. While prior work has shown that patients can accurately report their diagnosis and surgical history, little is known about their ability to self-report recent healthcare utilization, medication use, and vaccination status. Methods: We compared patient self-reported data within the IBD Qorus LHS regarding recent IBD-related emergency department (ED) visits, hospitalizations, computerized tomography (CT) scans, corticosteroid use, opioid use, influenza vaccinations, and pneumococcal vaccinations with electronic health record (EHR) data. Results: We compared 328 patient self-reports to data extracted from the EHR. Sensitivity was moderate-to-high for ED visits, hospitalizations, and CT scans (76%, 87%, and 87%, respectively), sensitivity was lower for medication use with 71% sensitivity for corticosteroid use and only 50% sensitivity for self-reported use of opioids. Vaccinations were reported with high sensitivity, but overall agreement was low as many patients reported vaccinations that were not registered in the EHR. Conclusions: Self-reported IBD-related ED visits, hospitalizations, and CT scans are reported with high sensitivity and accuracy. Medication use, and in particular opioid use, is less reliably reported. Vaccination self-report is likely more accurate than EHR data as many vaccinations are not accurately registered.

Association of seizure co-morbidity with early hospital readmission among traumatic brain injury patients.

OBJECTIVE: To assess the frequency of seizure co-morbidity and its independent association with 30-day readmission rate among patients hospitalized with traumatic brain injury (TBI) in the United States. METHODS: The data source was the 2014 Nationwide Readmission Database. We included adults (Age ≥18 years) with a primary discharge diagnosis of TBI, identified using the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes 800.0, 801.9, 803.0, 804.9, 850.0-854.1, and 959.01. Seizures were diagnosed using the ICD-9-CM codes of 345.x and 780.39. Overall and across pre-specified groups 30-readmission rate was computed. Logistic regression analysis was used to identify independent predictors of 30-day readmission. RESULTS: Among 76,062 unweighted adults discharged with a diagnosis of TBI, 7,776 (10.14%) had a secondary discharge diagnosis of seizures.A total of 1,751 (2.3%) patients with a primary discharge diagnosis of TBI were readmitted within 30 days. On multivariate logistic analysis, patients discharged with a secondary diagnosis of seizures were 18% more likely to be readmitted within 30 days compared to those without seizures (OR 1.18, 95% CI: 1.01-1.39, P = .42). CONCLUSION: One in 10 patients hospitalized with TBI in the US have a co-morbid seizure disorder. Seizure co-morbidity conferred 18% greater odds of being readmitted within 30 days.

A qualitative inquiry into patients' perspectives on individualized priorities for treatment outcomes in inflammatory bowel diseases.

PURPOSE: Patients with inflammatory bowel diseases (IBD) experience a variety of symptoms and limitations due to their condition. While many outcome measures are available to assess IBD symptom level and disease activity, individual patients' preferences are usually not accounted for. Individualized outcome measures allow individual patients to select and weigh outcomes based on their relative importance, and have been developed in other medical disciplines. In this study, we explored IBD patients' perspectives on different strategies to prioritize IBD-specific health outcomes. METHODS: Existing individualized measures were modified for relevance to IBD patients. We performed six focus groups, in which patients were asked to rate and weigh these measures in a series of exercises and to discuss the pros and cons of five different prioritization methods (Likert scale, ranking, selecting outcomes, distribute points, and using a rotating disk) using a semi-structured approach. A thematic analysis revealed key themes in the data. RESULTS: Patients' thoughts could be grouped into four key themes with 2-4 subthemes each: (1) prioritizing outcomes; (2) differences between methods; (3) outcomes to include; and (4) practical use. Overall, it was challenging for many patients to prioritize outcomes. Among the different prioritization methods, the rotating disk was perceived as the most intuitive. Patients anticipated that this visualization would also help them communicate with their physician. CONCLUSION: In a series of focus groups, a visual rotating disk was found to be an intuitive and holistic way to elicit the relative importance of different outcomes for individual IBD patients.

Stable calcium-free myocilin olfactomedin domain variants reveal challenges in differentiating between benign and glaucoma-causing mutations.

Nonsynonymous gene mutations can be beneficial, neutral, or detrimental to the stability, structure, and biological function of the encoded protein, but the effects of these mutations are often not readily predictable. For example, the ß-propeller olfactomedin domain of myocilin (mOLF) exhibits a complex interrelationship among structure(s), stability, and aggregation. Numerous mutations within mOLF are linked to glaucoma; the resulting variants are less stable, aggregation-prone, and sequestered intracellularly, causing cytotoxicity. Here, we report the first stable mOLF variants carrying substitutions in the calcium-binding site that exhibit solution characteristics indistinguishable from those of glaucoma variants. Crystal structures of these stable variants at 1.8-2.0-Å resolution revealed features that we could not predict by molecular dynamics simulations, including loss of loop structure, helix unwinding, and a blade shift. Double mutants that combined a stabilizing substitution and a selected glaucoma-causing single-point mutant rescued in vitro folding and stability defects. In the context of full-length myocilin, secretion of stable single variants was indistinguishable from that of the WT protein, and the double mutants were secreted to varying extents. In summary, our finding that mOLF can tolerate particular substitutions that render the protein stable despite a conformational switch emphasizes the complexities in differentiating between benign and glaucoma-causing variants and provides new insight into the possible biological function of myocilin.

Specific loss of adipocyte CD248 improves metabolic health via reduced white adipose tissue hypoxia, fibrosis and inflammation.

BACKGROUND: A positive energy balance promotes white adipose tissue (WAT) expansion which is characterized by activation of a repertoire of events including hypoxia, inflammation and extracellular matrix remodelling. The transmembrane glycoprotein CD248 has been implicated in all these processes in different malignant and inflammatory diseases but its potential impact in WAT and metabolic disease has not been explored. METHODS: The role of CD248 in adipocyte function and glucose metabolism was evaluated by omics analyses in human WAT, gene knockdowns in human in vitro differentiated adipocytes and by adipocyte-specific and inducible Cd248 gene knockout studies in mice. FINDINGS: CD248 is upregulated in white but not brown adipose tissue of obese and insulin-resistant individuals. Gene ontology analyses showed that CD248 expression associated positively with pro-inflammatory/pro-fibrotic pathways. By combining data from several human cohorts with gene knockdown experiments in human adipocytes, our results indicate that CD248 acts as a microenvironmental sensor which mediates part of the adipose tissue response to hypoxia and is specifically perturbed in white adipocytes in the obese state. Adipocyte-specific and inducible Cd248 knockouts in mice, both before and after diet-induced obesity and insulin resistance/glucose intolerance, resulted in increased microvascular density as well as attenuated hypoxia, inflammation and fibrosis without affecting fat cell volume. This was accompanied by significant improvements in insulin sensitivity and glucose tolerance. INTERPRETATION: CD248 exerts detrimental effects on WAT phenotype and systemic glucose homeostasis which may be reversed by suppression of adipocyte CD248. Therefore, CD248 may constitute a target to treat obesity-associated co-morbidities.

Leptin contributes to the beneficial effects of insulin treatment in streptozotocin-diabetic male mice.

It was long thought that the only hormone capable of reversing the catabolic consequences of diabetes was insulin. However, various studies have demonstrated that the adipocyte-derived hormone leptin can robustly lower blood glucose levels in rodent models of insulin-deficient diabetes. In addition, it has been suggested that some of the metabolic manifestations of insulin-deficient diabetes are due to hypoleptinemia as opposed to hypoinsulinemia. Because insulin therapy increases leptin levels, we sought to investigate the contribution of leptin to the beneficial effects of insulin therapy. To do this, we tested insulin therapy in streptozotocin (STZ) diabetic mice that were either on an ob/ ob background or that were given a leptin antagonist to determine if blocking leptin action would blunt the glucose-lowering effects of insulin therapy. We found that STZ diabetic ob/ ob mice have a diminished blood glucose-lowering effect in response to insulin therapy compared with STZ diabetic controls and exhibited more severe weight loss post-STZ injection. In addition, STZ diabetic mice administered a leptin antagonist through daily injection or plasmid expression respond less robustly to insulin therapy as assessed by both fasting blood glucose levels and blood glucose levels during an oral glucose tolerance test. However, leptin antagonism did not prevent the insulin-induced reduction in ß-hydroxybutyrate and triglyceride levels. Therefore, we conclude that elevated leptin levels can contribute to the glucose-lowering effect of insulin therapy in insulin-deficient diabetes.