Trainee burnout: Are there modifiable factors?

BACKGROUND: Burnout is a complex phenomenon and a major concern in graduate medical education as it directly impacts trainee well-being. Identifying modifiable lifestyle factors over which trainees have immediate control could support timely, actionable, individual and programme-level interventions to combat it. OBJECTIVE: The objective of this pilot study is to describe modifiable lifestyle factors that may limit the development of burnout in medical residents and fellows. METHODS: We performed a cross-sectional survey of residents and fellows at academic medical centre from September 2017 to October 2017. Participants completed the Maslach Burnout Inventory and a questionnaire designed to identify factors hypothesised to be protective against burnout. FINDINGS: A total of 205/805 (25%) trainees completed the survey with a mean (SD) age of 29.7 (2.6) years. 52% (n = 107) were female. Averaging at least 7 h of sleep per night was found to have a significant association with lower scores for the emotional exhaustion (24.8 [11, p = 0.04]) and depersonalisation (11.1 [6.4, p = 0.02]) dimensions of burnout. Additionally, self-identifying as a healthy eater was found to have a significant association with lower scores for emotional exhaustion (25 [11.5, p = 0.03]) and depersonalisation (11.5 [6.6, p = 0.04]) as well. Workouts, hobbies, identifying with organised religion, praying, meditation and mindfulness activities were not associated with a difference. CONCLUSIONS: Adequate sleep (7 or more hours per night) and healthy eating are modifiable individual-level lifestyle factors associated with lower burnout scores in trainees. These items could be a target for trainee education and programme level support initiatives.

Patient Experience of Women With Dense Breasts Undergoing Screening Contrast-Enhanced Mammography.

OBJECTIVE: We investigated patient experience with screening contrast-enhanced mammography (CEM) to determine whether a general population of women with dense breasts would accept CEM in a screening setting. METHODS: In this institutional review board-approved prospective study, patients with heterogeneous and extremely dense breasts on their mammogram were invited to undergo screening CEM and complete pre-CEM and post-CEM surveys. On the pre-CEM survey, patients were asked about their attitudes regarding supplemental screening in general. On the post-CEM survey, patients were asked about their experience undergoing screening CEM, including causes and severity of any discomfort and whether they would consider undergoing screening CEM again in the future or recommend it to a friend. RESULTS: One hundred sixty-three women were surveyed before and after screening CEM. Most patients, 97.5% (159/163), reported minimal or no unpleasantness associated with undergoing screening CEM. In addition, 91.4% (149/163) said they would probably or very likely undergo screening CEM in the future if it cost the same as a traditional screening mammogram, and 95.1% (155/163) said they would probably or very likely recommend screening CEM to a friend. Patients in this study, who were all willing to undergo CEM, more frequently reported a family history of breast cancer than a comparison cohort of women with dense breasts (58.2% vs 47.1%, P = .027). CONCLUSION: Patients from a general population of women with dense breasts reported a positive experience undergoing screening CEM, suggesting screening CEM might be well received by this patient population, particularly if the cost was comparable with traditional screening mammography.

Automated Versus Traditional Scoring Agreeability During the Balance Error Scoring System.

CONTEXT: The Balance Error Scoring System (BESS) is a commonly used clinical tool to evaluate postural control that is traditionally performed through visual assessment and subjective evaluation of balance errors. The purpose of this study was to evaluate an automated computer-based scoring system using an instrumented pressure mat compared to the traditional human-based manual assessment. DESIGN: A descriptive cross-sectional study design was used to evaluate the performance of the automated versus human BESS scoring methodology in healthy individuals. METHODS: Fifty-one healthy active participants performed BESS trials following standard BESS procedures on an instrumented pressure mat (MobileMat, Tekscan Inc). Trained evaluators manually scored balance errors from frontal and sagittal plane video recordings for comparison to errors scored using center of force measurements and an automated scoring software (SportsAT, version 2.0.2, Tekscan Inc). A linear mixed model was used to determine measurement discrepancies across the 2 methods. Bland-Altman analyses were conducted to determine limit of agreement for the automated and manual scoring methods. RESULTS: Significant differences between the automated and manual errors scored were observed across all conditions (P < .05), excluding bilateral firm stance. The greatest discrepancy between scoring methods was during the tandem foam stance, while the smallest discrepancy was during the tandem firm stance. CONCLUSION: The 2 methods of BESS scoring are different with wide limits of agreement. The benefits and risks of each approach to error scoring should be considered when selecting the most appropriate metric for clinical use or research studies.

Effectiveness of a Novel Video Game Platform in the Treatment of Pediatric Amblyopia.

PURPOSE: To test the non-inferiority of a novel game platform for the treatment of pediatric amblyopia compared to standard eye patching. METHODS: Forty participants (ages 4 to 18 years) across seven optometric clinics in the United States diagnosed as having amblyopia associated with anisometropia were randomly assigned to either 12 weeks of eye patching therapy (n = 19) or Barron Vision (Barron Associates, Inc) video game treatment (n = 21). Participants in the eye patching group with best corrected visual acuity (BCVA) worse than 20/200 in their amblyopic eye were prescribed 6 hours of patching daily, whereas those whose BCVA was 20/200 (1.00 logarithm of the minimum angle of resolution [logMAR]) or better were instructed to patch for 2 hours daily. Participants in the video game group, irrespective of the severity of their amblyopia, were instructed to play four different 5-minute mini-games five times a week for a total of 20 minutes a day. RESULTS: A mixed linear modeling analysis of before and after BCVA differences after 12 weeks showed the non-inferiority of video game treatment to eye patching using a 0.10 logMAR threshold while adjusting for the participant's age, sex, and baseline BCVA. CONCLUSIONS: The results of the study suggest that a 12-week home-based video game vision therapy intervention can provide equivalent treatment outcomes to eye patching for amblyopia in children ages 5 to 18 years. Video game-based vision therapy may be a more acceptable and time-efficient alternative to existing approaches. By incorporating elements of perceptual learning, approaches such as Barron Vision video game treatment may have additional long-term therapeutic benefits and may improve treatment compliance. [J Pediatr Ophthalmol Strabismus. 2024;61(1):20-29.].

Individualized Coordination and Empowerment for Care Partners of Persons with Dementia (ICECaP): Study rationale and protocol.

The majority of care for >10 million older adults with dementia (PWD) in the United States depends on at least on 11 million unpaid care partners (CPs). CPs are at greater risk of adverse physical, psychological, and cognitive health outcomes relative to non-caregiving peers. The goal of this paper is to establish the rationale, design, and protocol for a pilot randomized control trial to test the efficacy of the CP-focused intervention, ICECaP: Individualized Coordination and Empowerment for Care Partners of Persons with Dementia. ICECaP involves the assignment of a trained dementia care coordinator to a CP. The care coordinator maintains at least monthly contact with the CP with hybrid delivery (in-person, phone, e-mail, and video calls) and provides individualized support with care coordination for the CP navigating the PWD's care in a complex healthcare system, as well as supportive counseling, psychoeducation, and skills training for the CP. This trial will compare outcomes from baseline to 12-months among CPs who receive ICECaP versus routine care (controls). Outcomes include CP depression, burden, anxiety, and quality of life; CPs' reactions to the behavioral symptoms of dementia; and use of support services for the PWD. This trial will also assess mechanisms of intervention efficacy including changes in CP dementia knowledge, caregiving preparedness, self-efficacy, and optimism. Publication of this intervention protocol will benefit other dementia care teams seeking to support CPs and PWDs.

An intracellular isotropic diffusion signal is positively associated with pubertal development in white matter.

Puberty is a key event in adolescent development that involves significant, hormone-driven changes to many aspects of physiology including the brain. Understanding how the brain responds during this time period is important for evaluating neuronal developments that affect mental health throughout adolescence and the adult lifespan. This study examines diffusion MRI scans from the cross-sectional ABCD Study baseline cohort, a large multi-site study containing thousands of participants, to describe the relationship between pubertal development and brain microstructure. Using advanced, 3-tissue constrained spherical deconvolution methods, this study is able to describe multiple tissue compartments beyond only white matter (WM) axonal qualities. After controlling for age, sex, brain volume, subject handedness, scanning site, and sibling relationships, we observe a positive relationship between an isotropic, intracellular diffusion signal fraction and pubertal development across a majority of regions of interest (ROIs) in the WM skeleton. We also observe regional effects from an intracellular anisotropic signal fraction compartment and extracellular isotropic free water-like compartment in several ROIs. This cross-sectional work suggests that changes in pubertal status are associated with a complex response from brain tissue that cannot be completely described by traditional methods focusing only on WM axonal properties.

Lung Volume Dependence and Repeatability of Hyperpolarized 129Xe MRI Gas Uptake Metrics in Healthy Volunteers and Participants with COPD.

Purpose: To assess the effect of lung volume on measured values and repeatability of xenon 129 (129Xe) gas uptake metrics in healthy volunteers and participants with chronic obstructive pulmonary disease (COPD). Materials and Methods: This Health Insurance Portability and Accountability Act-compliant prospective study included data (March 2014-December 2015) from 49 participants (19 with COPD [mean age, 67 years ± 9 (SD)]; nine women]; 25 older healthy volunteers [mean age, 59 years ± 10; 20 women]; and five young healthy women [mean age, 23 years ± 3]). Thirty-two participants underwent repeated 129Xe and same-breath-hold proton MRI at residual volume plus one-third forced vital capacity (RV+FVC/3), with 29 also undergoing one examination at total lung capacity (TLC). The remaining 17 participants underwent imaging at TLC, RV+FVC/3, and residual volume (RV). Signal ratios between membrane, red blood cell (RBC), and gas-phase compartments were calculated using hierarchical iterative decomposition of water and fat with echo asymmetry and least-squares estimation (ie, IDEAL). Repeatability was assessed using coefficient of variation and intraclass correlation coefficient, and volume relationships were assessed using Spearman correlation and Wilcoxon rank sum tests. Results: Gas uptake metrics were repeatable at RV+FVC/3 (intraclass correlation coefficient = 0.88 for membrane/gas; 0.71 for RBC/gas, and 0.88 for RBC/membrane). Relative ratio changes were highly correlated with relative volume changes for membrane/gas (r = -0.97) and RBC/gas (r = -0.93). Membrane/gas and RBC/gas measured at RV+FVC/3 were significantly lower in the COPD group than the corresponding healthy group (P ≤ .001). However, these differences lessened upon correction for individual volume differences (P = .23 for membrane/gas; P = .09 for RBC/gas). Conclusion: Dissolved-phase 129Xe MRI-derived gas uptake metrics were repeatable but highly dependent on lung volume during measurement.Keywords: Blood-Air Barrier, MRI, Chronic Obstructive Pulmonary Disease, Pulmonary Gas Exchange, Xenon Supplemental material is available for this article © RSNA, 2023.

Outcome in Pediatric Functional Tic Disorders Diagnosed During the COVID-19 Pandemic.

OBJECTIVES: The incidence of pediatric functional tics has surged during the COVID-19 pandemic with little known about prognosis. To address this knowledge gap, the investigators examined clinical courses of functional tics diagnosed during the pandemic and explored factors predicting prognosis. METHODS: Study personnel reviewed electronic medical records of 29 pediatric patients diagnosed as having functional tics between March 1, 2020, and December 31, 2021, and estimated Clinical Global Impression-Improvement (CGI-I) scores at follow-up encounters. Twenty patient-guardian dyads completed telephone interviews. Logistic regression models were used to identify possible predictors of clinical trajectories. RESULTS: Of the 29 patients, 21 (82%) reported at least some improvement since diagnosis at the time of the last follow-up, with a median CGI-I score of 2 (much improved). During the telephone interview, 11 of 20 patients noted ongoing interference from tics, and 16 of 20 agreed with the diagnosis of functional tics. Median time from symptom onset to diagnosis was 197 days, with most patients reporting at least a mild reduction of symptoms (CGI-I score <4) at a median of 21 days after diagnosis. At a median follow-up time of 198 days after diagnosis, patients reported significant but not complete improvement. Greater age and longer time to diagnosis decreased odds of improvement within 1 month of diagnosis. CONCLUSIONS: Most patients showed improvements in but not the resolution of functional tic symptoms after diagnosis. These data support the importance of early diagnosis for functional tics.

Procedural-Related Bleeding in Hospitalized Patients With Liver Disease (PROC-BLeeD): An International, Prospective, Multicenter Observational Study.

BACKGROUND & AIMS: Hospitalized patients with cirrhosis frequently undergo multiple procedures. The risk of procedural-related bleeding remains unclear, and management is not standardized. We conducted an international, prospective, multicenter study of hospitalized patients with cirrhosis undergoing nonsurgical procedures to establish the incidence of procedural-related bleeding and to identify bleeding risk factors. METHODS: Hospitalized patients were prospectively enrolled and monitored until surgery, transplantation, death, or 28 days from admission. The study enrolled 1187 patients undergoing 3006 nonsurgical procedures from 20 centers. RESULTS: A total of 93 procedural-related bleeding events were identified. Bleeding was reported in 6.9% of patient admissions and in 3.0% of the procedures. Major bleeding was reported in 2.3% of patient admissions and in 0.9% of the procedures. Patients with bleeding were more likely to have nonalcoholic steatohepatitis (43.9% vs 30%) and higher body mass index (BMI; 31.2 vs 29.5). Patients with bleeding had a higher Model for End-Stage Liver Disease score at admission (24.5 vs 18.5). A multivariable analysis controlling for center variation found that high-risk procedures (odds ratio [OR], 4.64; 95% confidence interval [CI], 2.44-8.84), Model for End-Stage Liver Disease score (OR, 2.37; 95% CI, 1.46-3.86), and higher BMI (OR, 1.40; 95% CI, 1.10-1.80) independently predicted bleeding. Preprocedure international normalized ratio, platelet level, and antithrombotic use were not predictive of bleeding. Bleeding prophylaxis was used more routinely in patients with bleeding (19.4% vs 7.4%). Patients with bleeding had a significantly higher 28-day risk of death (hazard ratio, 6.91; 95% CI, 4.22-11.31). CONCLUSIONS: Procedural-related bleeding occurs rarely in hospitalized patients with cirrhosis. Patients with elevated BMI and decompensated liver disease who undergo high-risk procedures may be at risk to bleed. Bleeding is not associated with conventional hemostasis tests, preprocedure prophylaxis, or recent antithrombotic therapy.

Early Brain Amyloid Accumulation at PET in Military Instructors Exposed to Subconcussive Blast Injuries.

Background Traumatic brain injury (TBI) is the leading cause of disability in young adults. Recurrent TBI is associated with a range of neurologic sequelae, but the contributing factors behind the development of such chronic encephalopathy are poorly understood. Purpose To quantify early amyloid ß deposition in the brain of otherwise healthy adult men exposed to repeated subconcussive blast injury using amyloid PET. Materials and Methods In this prospective study from January 2020 to December 2021, military instructors who were routinely exposed to repeated blast events were evaluated at two different points: baseline (before blast exposure from breacher or grenade) and approximately 5 months after baseline (after blast exposure). Age-matched healthy control participants not exposed to blasts and without a history of brain injury were evaluated at similar two points. Neurocognitive evaluation was performed with standard neuropsychologic testing in both groups. Analysis of PET data consisted of standardized uptake value measurements in six relevant brain regions and a whole-brain voxel-based statistical approach. Results Participants were men (nine control participants [median age, 33 years; IQR, 32-36 years] and nine blast-exposed participants [median age, 33 years; IQR, 30-34 years]; P = .82). In the blast-exposed participants, four brain regions showed significantly increased amyloid deposition after blast exposure: inferomedial frontal lobe (P = .004), precuneus (P = .02), anterior cingulum (P = .002), and superior parietal lobule (P = .003). No amyloid deposition was observed in the control participants. Discriminant analysis on the basis of regional changes of amyloid accumulation correctly classified the nine healthy control participants as healthy control participants (100%), and seven of the nine blast-exposed participants (78%) were correctly classified as blast exposed. Based on the voxel-based analysis, whole-brain parametric maps of early abnormal early amyloid uptake were obtained. Conclusion Early brain amyloid accumulation was identified and quantified at PET in otherwise healthy adult men exposed to repetitive subconcussive traumatic events. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Haller in this issue.

Effect of computed tomography angiography prior to bronchial embolization on radiation dose and recurrent hemoptysis.

PURPOSE: To investigate whether pre-procedure Computed Tomography Angiography (CTA) improves radiation exposure, procedure complexity, and symptom recurrence after bronchial embolization for massive hemoptysis. MATERIAL AND METHODS: A single-center retrospective review of bronchial artery embolization (BAE) for massive hemoptysis was performed for procedures between 2008 and 2019. Multi-variate analysis was performed to determine the significance of pre-procedure CTA and etiology of hemoptysis on patient radiation exposure (reference point air kerma, RPAK) and rate of recurrent hemoptysis. RESULTS: There were 61 patients (mean age 52.5 years; SD = 19.2 years, and 57.3% male) and CTA was obtained for 42.6% (26/61). Number of vessels selected was a mean of 7.2 (SD = 3.4) in those without CTA and 7.4 (SD = 3.4) in those with CTA (p = 0.923). Mean procedure duration was 1.8 h (SD = 1.6 h) in those without CTA and 1.3 h (SD = 1.0 h) in those with CTA (p = 0.466). Mean fluoroscopy time and RPAK per procedure were 34.9 min (SD = 21.5 min) and 1091.7 mGy (SD = 1316.6 mGy) for those without a CTA and 30.7 min (SD = 30.7 min) and 771.5 mGy (SD = 590.0 mGy) for those with a CTA (p = 0.523, and p = 0.879, respectively). Mean total iodine given was 49.2 g (SD = 31.9 g) for those without a CTA and 70.6 g (SD = 24.9 g) for those with a CTA (p = 0.001). Ongoing hemoptysis at last clinical follow up was 13/35 (37.1%) in those without CTA and 9/26 (34.6%) in those with CTA (p = 0.794). CONCLUSIONS: Pre-procedure CTA did not improve radiation effective dose and symptom recurrence after BAE and is associated with significant increases in total iodine dose.

Progressive Cardiac Metabolic Defects Accompany Diastolic and Severe Systolic Dysfunction in Spontaneously Hypertensive Rat Hearts.

Background Cardiac metabolic abnormalities are present in heart failure. Few studies have followed metabolic changes accompanying diastolic and systolic heart failure in the same model. We examined metabolic changes during the development of diastolic and severe systolic dysfunction in spontaneously hypertensive rats (SHR). Methods and Results We serially measured myocardial glucose uptake rates with dynamic 2-[18F] fluoro-2-deoxy-d-glucose positron emission tomography in vivo in 9-, 12-, and 18-month-old SHR and Wistar Kyoto rats. Cardiac magnetic resonance imaging determined systolic function (ejection fraction) and diastolic function (isovolumetric relaxation time) and left ventricular mass in the same rats. Cardiac metabolomics was performed at 12 and 18 months in separate rats. At 12 months, SHR hearts, compared with Wistar Kyoto hearts, demonstrated increased isovolumetric relaxation time and slightly reduced ejection fraction indicating diastolic and mild systolic dysfunction, respectively, and higher (versus 9-month-old SHR decreasing) 2-[18F] fluoro-2-deoxy-d-glucose uptake rates (Ki). At 18 months, only few SHR hearts maintained similar abnormalities as 12-month-old SHR, while most exhibited severe systolic dysfunction, worsening diastolic function, and markedly reduced 2-[18F] fluoro-2-deoxy-d-glucose uptake rates. Left ventricular mass normalized to body weight was elevated in SHR, more pronounced with severe systolic dysfunction. Cardiac metabolite changes differed between SHR hearts at 12 and 18 months, indicating progressive defects in fatty acid, glucose, branched chain amino acid, and ketone body metabolism. Conclusions Diastolic and severe systolic dysfunction in SHR are associated with decreasing cardiac glucose uptake, and progressive abnormalities in metabolite profiles. Whether and which metabolic changes trigger progressive heart failure needs to be established.

Microglial activation persists beyond clinical recovery following sport concussion in collegiate athletes.

Introduction: In concussion, clinical and physiological recovery are increasingly recognized as diverging definitions. This study investigated whether central microglial activation persisted in participants with concussion after receiving an unrestricted return-to-play (uRTP) designation using [18F]DPA-714 PET, an in vivo marker of microglia activation. Methods: Eight (5 M, 3 F) current athletes with concussion (Group 1) and 10 (5 M, 5 F) healthy collegiate students (Group 2) were enrolled. Group 1 completed a pre-injury (Visit1) screen, follow-up Visit2 within 24 h of a concussion diagnosis, and Visit3 at the time of uRTP. Healthy participants only completed assessments at Visit2 and Visit3. At Visit2, all participants completed a multidimensional battery of tests followed by a blood draw to determine genotype and study inclusion. At Visit3, participants completed a clinical battery of tests, brain MRI, and brain PET; no imaging tests were performed outside of Visit3. Results: For Group 1, significant differences were observed between Visits 1 and 2 (p < 0.05) in ImPACT, SCAT5 and SOT performance, but not between Visit1 and Visit3 for standard clinical measures (all p > 0.05), reflecting clinical recovery. Despite achieving clinical recovery, PET imaging at Visit3 revealed consistently higher [18F]DPA-714 tracer distribution volume (VT) of Group 1 compared to Group 2 in 10 brain regions (p < 0.001) analyzed from 164 regions of the whole brain, most notably within the limbic system, dorsal striatum, and medial temporal lobe. No notable differences were observed between clinical measures and VT between Group 1 and Group 2 at Visit3. Discussion: Our study is the first to demonstrate persisting microglial activation in active collegiate athletes who were diagnosed with a sport concussion and cleared for uRTP based on a clinical recovery.

Concurrent Validity of Measures of Upper Extremity Function Derived from Videogame-Based Motion Capture for Children with Hemiplegia.

Objective: Pediatric hemiplegia is associated with wide-ranging deficits in arm and hand motor function, neg-atively impacting participation in daily occupations and quality of life. This study investigated whether performance measures generated during therapy videogame play by children with hemiplegia can be valid indicators of upper extremity motor function. Materials and Methods: Ten children with hemiplegia used a custom therapy game system alternatively using their affected and non-affected hand to provide motion capture data that spans a wide range of motor function status. The children also completed a series of standardized outcome measure assessments with each hand, including the Quality of Upper Extremity Skills Test, the Jebsen Taylor Hand Function Test, and the Wolf Motor Function Test. Results: Statistical analysis using the nonparametric Spearman rank correlation revealed high and significant correlation between videogame-derived motion capture measures, characterizing the speed and smoothness of movements, and the standardized outcome measure assessments. Conclusion: The results suggest that a low-cost motion capture system can be used to monitor a child's motor function status and progress during a therapy program.

Sleep Disturbances Predict Cognitive Decline in Cognitively Healthy Adults.

BACKGROUND: The effect of nighttime behaviors on cognition has not been studied independently from other neuropsychiatric symptoms. OBJECTIVE: We evaluate the following hypotheses that sleep disturbances bring increased risk of earlier cognitive impairment, and more importantly that the effect of sleep disturbances is independent from other neuropsychiatric symptoms that may herald dementia. METHODS: We used the National Alzheimer's Coordinating Center database to evaluate the relationship between Neuropsychiatric Inventory Questionnaire (NPI-Q) determined nighttime behaviors which served as surrogate for sleep disturbances and cognitive impairment. Montreal Cognitive Assessment scores defined two groups: conversion from 1) normal to mild cognitive impairment (MCI) and 2) MCI to dementia. The effect of nighttime behaviors at initial visit and covariates of age, sex, education, race, and other neuropsychiatric symptoms (NPI-Q), on conversion risk were analyzed using Cox regression. RESULTS: Nighttime behaviors predicted earlier conversion time from normal cognition to MCI (hazard ratio (HR): 1.09; 95% CI: [1.00, 1.48], p = 0.048) but were not associated with MCI to dementia conversion (HR: 1.01; [0.92, 1.10], p = 0.856). In both groups, older age, female sex, lower education, and neuropsychiatric burden increased conversion risk. CONCLUSION: Our findings suggest that sleep disturbances predict earlier cognitive decline independently from other neuropsychiatric symptoms that may herald dementia.

Telehealth-Guided Virtual Reality for Recovery of Upper Extremity Function Following Stroke.

This rater-blinded, randomized control trial (RCT) investigated the effectiveness of a Glove Rehabilitation Application for Stroke Patients (GRASP) virtual reality home exercise program (HEP) for upper extremity (UE) motor recovery following stroke. The GRASP system facilitates the use of the affected UE in simulated instrumental activities of daily living (IADLs). Participants were asked to use the system at home in asynchronous telehealth sessions 4 times per week over 8 weeks. A non-blinded occupational therapist (OT) provided synchronous telehealth visits biweekly. Analysis comparing pre- and post-assessment results for the Fugl-Meyer UE assessment (FMUE) shows a clinically important and statistically significant between-group difference for participants completing the GRASP HEP protocol compared with usual and customary care controls. Statistically significant and clinically important differences were also found in Motor Activity Log (MAL) scores. This evidence provides support for the effectiveness of home-based, IADL-focused, virtual reality therapy with telehealth support.

Further evidence of a type 2 inflammatory signature in chronic obstructive pulmonary disease or emphysema.

BACKGROUND: There is increasing recognition of a type 2 (T2) inflammatory pattern in a subset of patients with chronic obstructive pulmonary disease (COPD) or emphysema, characterized by blood and airway eosinophilia. The mechanism underlying this is not well established. The recognition that CD125 (interleukin [IL]-5 receptor alpha) is expressed on some lung neutrophils and eosinophils in patients with asthma led us to speculate that CD125 may also be expressed on lung neutrophils in patients with COPD or emphysema. OBJECTIVE: To interrogate the expression of CD125 on lung neutrophils (and, when present, eosinophils) in patients with COPD/emphysema and identify a meaningful biomarker to predict neutrophil CD125 expression, including other markers of T2 inflammation. METHODS: We obtained blood and bronchoalveolar lavage (BAL) samples from patients with physician-diagnosed COPD/emphysema undergoing a clinically indicated bronchoscopy. RESULTS: We found that a highly variable percentage of BAL neutrophils indeed expressed surface CD125 (0%-78.7%), with obvious clustering of CD125high and CD125low patterns. No correlation was found with clinical characteristics, blood or BAL eosinophil or neutrophil counts, BAL cytokines, or BAL eosinophil CD125 expression. CONCLUSION: We conclude that, similar to asthma, lung neutrophils from patients with COPD display interleukin-5 receptor alpha (CD125) on their surface. This along with the frequent presence of IL-4 and IL-5 in airway fluid further suggests a possible role of the T2 pathway in contributing to COPD severity. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03984799.

Association between Cystic Fibrosis exacerbations, lung function, T2 inflammation and microbiological colonization.

BACKGROUND: The Cystic Fibrosis Foundation Patient Registry (CFFPR) reports a high prevalence of asthma (34.6%) in people with Cystic Fibrosis (PwCF). While our current understanding of this relationship is limited, a type 2 inflammatory (T2) phenotype has often been identified in CF patients. RESEARCH QUESTION: This study aimed to evaluate the relationship between the eosinophilic CF T2 inflammatory phenotype and CF-related pulmonary outcomes and microbiological data. STUDY DESIGN AND METHODS: We conducted a retrospective chart review of adult patients with CF (18 and older; n = 93) receiving their care at University of Virginia Medical Center adult program from January, 2013 through December, 2018. Data collected included demographic data, CFTR (CF transmembrane conductance regulator) mutation, CF comorbidities, medications, Absolute Eosinophil Counts (AEC) in cells/µL and Immunoglobulin E (IgE) levels in IU/mL. RESULTS: Of 93 patients screened for study eligibility, 74 were included in the final analysis; 19 patients were excluded due to lack of longitudinal data across the study timeline. Lung function decline correlated with increased AEC (p < 0.001) and IgE (p < 0.001) even when adjusting for covariates: age, gender, presence of Pseudomonas spp., MRSA, other bacterial spp., Aspergillus spp., and other fungi (p < 0.001). Univariate analysis demonstrated that people with CF who experienced more than 2 exacerbations requiring hospitalizations and/or intravenous antibiotics a year were more likely to have high AEC (p = 0.018). Logistic regression showed that as AEC increases, the probability that the measurement was taken during a CF exacerbation increases (p = 0.0039). A linear mixed model showed that each additional annual exacerbation event increased on average the log IgE by 0.04. (p = 0.015). This finding remained stable in a multivariate model (p = 0.0145). When adjusted for atopy, log IgE increases as the number of exacerbation events increases (p = 0.022). There was no association between AEC and IgE and microbiological colonization. INTERPRETATION: This study has shown that in CF patients, T2 inflammation based on serum AEC and IgE correlated with pulmonary exacerbations requiring hospitalizations and/or intravenous antibiotics, independent of bacterial airway colonization. In addition, lung function decline correlated with increased IgE and AEC. Further studies are needed to explore these correlations and potential impact on treatment.

Depression differentially affects patient and caregiver perceptions of neuropsychiatric symptoms in Parkinson's disease.

OBJECTIVE: The aims of this study were twofold. First, we examined the relationship between patient and caregiver ratings of neuropsychiatric symptoms in Parkinson's disease (PD). Second, we examined if the severity of depressive symptoms affects patient and caregiver perceptions of other neuropsychiatric symptoms and contributes to discrepancies between their perceptions. METHOD: We examined data from a retrospective clinical cohort of 209 patients with PD and their caregivers. We used intra-class correlation coefficients and the Bland Altman method to assess intra-respondent (retrospective versus current) and inter-respondent (patient versus caregiver) agreement between Frontal Systems Behavior Scales (FrSBe) subscale scores. We then used generalized estimating equation models to examine FrSBe subscale scores and the magnitude of the intra- and inter-respondent discrepancies in FrSBe subscale scores, as a function of Beck Depression Inventory-2nd Edition scores, with patient demographic variable adjustments. RESULTS: There was low agreement between patient and caregiver ratings on all three subscales, at both time points, and high response variability within and between raters. Patients generally reported more severe neuropsychiatric symptoms than caregivers. Depression severity predicted patients' perceptions at both time points, but was more strongly associated with current perceptions. Depression severity predicted caregivers' current perceptions only. The inter-respondent discrepancy in perceived apathy and disinhibition, but not executive dysfunction, increased as a function of depression severity. CONCLUSIONS: There are differences in how patients with PD and caregivers perceive neuropsychiatric behaviors and the extent to which depressive symptoms influence their perceptions. Shared neuropathology and negative response biases likely contribute to these relationships.