Volumetric assessment of traumatic intracranial hematomas: is ABC/2 reliable?

Accurate measurement of traumatic intracranial hematoma volume is important for assessing disease progression and prognosis, as well as serving as an important endpoint in clinical trials aimed at preventing hematoma expansion. While the ABC/2 formula has traditionally been used for volume estimation in spontaneous intracerebral hemorrhage, its adaptation to traumatic hematomas lacks validation. This study aimed to compare the accuracy of ABC/2 with computer-assisted volumetric analysis (CAVA) in estimating the volumes of traumatic intracranial hematomas. We performed a dual-center observational study that included adult patients with moderate-to-severe traumatic brain injury. Volumes of intracerebral (ICH), subdural (SDH), and epidural hematomas (EDH) from admission CT scans were measured using ABC/2 and CAVA, and compared using the Wilcoxon signed-rank test, Spearman's rank correlation, Lin's concordance correlation coefficient (CCC), and Bland-Altman plots. Prognostic significance for outcomes were evaluated through logistic and linear regression models. In total, 1,179 patients with 1,543 hematomas were included. Despite a high correlation (Spearman coefficients between 0.95 and 0.98) and excellent concordance (Lin's CCC from 0.89 to 0.96) between ABC/2 and CAVA, ABC/2 overestimated hematoma volumes compared to CAVA, in some instances exceeding 50 ml. Bland-Altman analysis highlighted wide limits of agreement, especially in SDH. While both methods demonstrated comparable accuracy in predicting outcomes, CAVA was slightly better at predicting craniotomies and midline shift. We conclude that while ABC/2 provides a generally reliable volumetric assessment suitable for descriptive purposes and as baseline variables in studies, CAVA should be the gold standard in clinical situations and studies requiring more precise volume estimations, such as those using hematoma expansion as an outcome.

Understanding the impact of distance and disadvantage on lung cancer care and outcomes: a study protocol.

BACKGROUND: Lung cancer is the third most common cancer in the UK and the leading cause of cancer mortality globally. NHS England guidance for optimum lung cancer care recommends management and treatment by a specialist team, with experts concentrated in one place, providing access to specialised diagnostic and treatment facilities. However, the complex and rapidly evolving diagnostic and treatment pathways for lung cancer, together with workforce limitations, make achieving this challenging. This place-based, behavioural science-informed qualitative study aims to explore how person-related characteristics interact with a person's location relative to specialist services to impact their engagement with the optimal lung pathway, and to compare and contrast experiences in rural, coastal, and urban communities. This study also aims to generate translatable evidence to inform the evidence-based design of a patient engagement intervention to improve lung cancer patients' and informal carers' participation in and experience of the lung cancer care pathway. METHODS: A qualitative cross-sectional interview study with people diagnosed with lung cancer < 6 months before recruitment (in receipt of surgery, radical radiotherapy, or living with advanced disease) and their informal carers. Participants will be recruited purposively from Barts Health NHS Trust and United Lincolnshire Hospitals NHS Trusts to ensure a diverse sample across urban and rural settings. Semi-structured interviews will explore factors affecting individuals' capability, opportunity, and motivation to engage with their recommended diagnostic and treatment pathway. A framework approach, informed by the COM-B model, will be used to thematically analyse facilitators and barriers to patient engagement. DISCUSSION: The study aligns with the current policy priority to ensure that people with cancer, no matter where they live, can access the best quality treatments and care. The evidence generated will be used to ensure that lung cancer services are developed to meet the needs of rural, coastal, and urban communities. The findings will inform the development of an intervention to support patient engagement with their recommended lung cancer pathway. PROTOCOL REGISTRATION: The study received NHS Research Ethics Committee (Ref: 23/SC/0255) and NHS Health Research Authority (IRAS ID 328531) approval on 04/08/2023. The study was prospectively registered on Open Science Framework (16/10/2023; https://osf.io/njq48 ).

Toward a Public Health Approach to Farmer Suicide Prevention: The Potential Power of Systems Change.

OBJECTIVE: Suicide among farmers has, over the past 20 years, garnered attention from scholars around the world. The purpose of this paper is twofold. First, this paper will present a framework for considering farmer suicide that builds upon the Interpersonal-Psychological Theory of Suicidal Behavior and extends our current explanations of suicide to include a multilevel, multifactorial focus on individual, interpersonal, community and systemic factors at the root of stressors contributing to suicide among farmers. Secondly, a blueprint for farmer suicide prevention, leveraging the Water of Systems Change Model, is proposed. METHOD: In the spirit of conveying multi-layered influence on farmer suicide while highlighting relevant levels for prevention a parsimonious, prevention-based model of farmer suicide is presented. RESULTS: The Water of Systems Change (WSC) model incorporates research to bring attention to the community, organizational, and societal conditions that keep a problem, such as farmer suicide, from being eradicated. CONCLUSION: Suicide is a societal issue that requires a multi-level response. Farmer suicide is a particular concern, as farmers provide for and support all of us. It is incumbent upon public health and the community-at-large to improve our policies, systems, and contexts to create an environment in which farmers are also provided for and supported.

Periodic orbits, pair nucleation, and unbinding of active nematic defects on cones.

Geometric confinement and topological constraints present promising means of controlling active materials. By combining analytical arguments derived from the Born-Oppenheimer approximation with numerical simulations, we investigate the simultaneous impact of confinement together with curvature singularity by characterizing the dynamics of an active nematic on a cone. Here, the Born-Oppenheimer approximation means that textures can follow defect positions rapidly on the timescales of interest. Upon imposing strong anchoring boundary conditions at the base of a cone, we find a rich phase diagram of multidefect dynamics, including exotic periodic orbits of one or two +1/2 flank defects, depending on activity and nonquantized geometric charge at the cone apex. By characterizing the transitions between these ordered dynamical states, we present detailed understanding of (i) defect unbinding, (ii) defect absorption, and (iii) defect pair nucleation at the apex. Numerical simulations confirm theoretical predictions of not only the nature of the circular orbits but also defect unbinding from the apex.

Impact of therapeutic inhibition of oncogenic cell signaling tyrosine kinase on cell metabolism: in vivo-detectable metabolic biomarkers of inhibition.

BACKGROUND: Inhibition of kinases is the ever-expanding therapeutic approach to various types of cancer. Typically, assessment of the treatment response is accomplished by standard, volumetric imaging procedures, performed weeks to months after the onset of treatment, given the predominantly cytostatic nature of the kinase inhibitors, at least when used as single agents. Therefore, there is a great clinical need to develop new monitoring approaches to detect the response to kinase inhibition much more promptly. Noninvasive 1H magnetic resonance spectroscopy (MRS) can measure in vitro and in vivo concentration of key metabolites which may potentially serve as biomarkers of response to kinase inhibition. METHODS: We employed mantle cell lymphoma (MCL) cell lines demonstrating markedly diverse sensitivity of inhibition of Bruton's tyrosine kinase (BTK) regarding their growth and studied in-depth effects of the inhibition on various aspects of cell metabolism including metabolite synthesis using metabolomics, glucose and oxidative metabolism by Seahorse XF technology, and concentration of index metabolites lactate, alanine, total choline and taurine by 1H MRS. RESULTS: Effective BTK inhibition profoundly suppressed key cell metabolic pathways, foremost pyrimidine and purine synthesis, the citrate (TCA) cycle, glycolysis, and pyruvate and glutamine/alanine metabolism. It also inhibited glycolysis and amino acid-related oxidative metabolism. Finally, it profoundly and quickly decreased concentration of lactate (a product of mainly glycolysis) and alanine (an indicator of amino acid metabolism) and, less universally total choline both in vitro and in vivo, in the MCL xenotransplant model. The decrease correlated directly with the degree of inhibition of lymphoma cell expansion and tumor growth. CONCLUSIONS: Our results indicate that BTK inhibition exerts a broad and profound suppressive effect on cell metabolism and that the affected index metabolites such as lactate, alanine may serve as early, sensitive, and reliable biomarkers of inhibition in lymphoma patients detectable by noninvasive MRS-based imaging method. This kind of imaging-based detection may also be applicable to other kinase inhibitors, as well as diverse lymphoid and non-lymphoid malignancies.

Factors associated with persistent sexual dysfunction and pain 12 months postpartum.

OBJECTIVE: Identify factors associated with persistent sexual dysfunction and pain 12-months postpartum in an underserved population. METHODS: Extending Maternal Care After Pregnancy (eMCAP) is a program addressing health needs/disparities of patients at risk for worse perinatal outcomes. Participants completed the Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire (PISQ-12) and Urinary Distress Index (UDI-6) 12-months postpartum. The PISQ-12 was dichotomized with scores < 32.5 indicating sexual dysfunction. Urinary incontinence (UI) was defined as at-least-somewhat bothersome (vs. none or not-at-all bothersome) urgency urinary incontinence (UUI) or stress urinary incontinence (SUI). Screening for anxiety and depression was completed using Generalized Anxiety Disorder-7 (GAD-7) and Edinburgh Postnatal Depression Scale (EPDS). Bivariate and multivariable logistic regression analyses were performed for sexual dysfunction vs. normal-function, and pain vs. no-pain, using demographic, peri/postpartum, and social-determinant-of-health variables as correlating factors. RESULTS: 328 sexually active patients provided data. On bivariate analysis, sexual dysfunction (n = 31, 9.5%) vs. normal function (n = 297, 90.5%) groups showed no differences in age, BMI, parity, mode of delivery, episiotomy/laceration types, or breastfeeding. Sexual dysfunction was significantly associatedwith both UUI and SUI: 12 (39%) vs. 46 (15%) had UUI, p = 0.001, and 20 (65%) vs. 97 (33%) had SUI, P < 0.001; the dysfunction group also had higher GAD-7 and EPDS scores and greater overall stress levels. On multivariable analysis, SUI and stress remained significantly associated: OR (95% CI) 2.45 (1.02-6.03) and 1.81 (1.32-2.49), respectively. Comparing pain (n = 45, 13.7%) vs. no-pain (n = 283, 86.2%), dyspareunia patients endorsed greater stress levels. CONCLUSION: The interplay between sexual health, incontinence, and mental health deserves further study, and all three should be routinely addressed in postpartum care.

Multivariate Analysis of Factors Associated with Feeding Mother's Own Milk at Discharge in Preterm Infants: A Retrospective Cohort Study.

OBJECTIVE: This study aimed to develop a predictive model of feeding mother's own milk (MOM) at discharge using social determinants of health (SDOH), maternal and neonatal factors after deliveries at <33 weeks of gestational age (GA), or birth weight <1,500 g. STUDY DESIGN: Secondary analysis of a retrospective cohort in an inner-city hospital before (Epoch-1, 2018-2019) and after (Epoch-2, 2020-2021) implementing a donor human milk (DHM) program. RESULTS: Among 986 neonates, 495 were born in Epoch-1 (320 Hispanic White, 142 Non-Hispanic Black, and 33 Other) and 491 in Epoch-2 (327, 137, and 27, respectively). Feeding any MOM was less frequent in infants of non-Hispanic Black mothers than in those of Hispanic mothers (p < 0.05) but did not change with epoch (p = 0.46). Among infants who received any MOM, continued feeding MOM to the time of discharge was less frequent in infants of non-Hispanic Black mothers versus those of Hispanic mothers, 94/237 (40%) versus 339/595 (57%; p < 0.05), respectively. In multivariate analysis including SDOH and maternal variables, the odds of feeding MOM at discharge were lower with SDOH including neighborhoods with higher poverty levels, multiparity, substance use disorder, non-Hispanic Black versus Hispanic and young maternal age and increased with GA but did not change after implementing DHM. The predictive model including SDOH, maternal and early neonatal variables had good discrimination (area under the curve 0.85) and calibration and was internally validated. It showed the odds of feeding MOM at discharge were lower in infants of non-Hispanic Black mothers and with feeding DHM, higher need for respiratory support and later initiation of feeding MOM. CONCLUSION: Feeding MOM at discharge was associated with SDOH, and maternal and neonatal factors but did not change after implementing DHM. Disparity in feeding MOM at discharge was explained by less frequent initiation and shorter duration of feeding MOM but not by later initiation of feeding MOM. KEY POINTS: · In this cohort study of preterm infants, factors of feeding MOM at discharge included (1) SDOH; (2) postnatal age at initiation of feeding MOM; and (3) maternal and neonatal factors.. · Feeding MOM at the time of discharge was less frequent in infants of non-Hispanic Black mothers versus those of Hispanic mothers.. · Disparity in feeding MOM at discharge was explained by less frequent initiation and shorter duration of MOM feeding but not by later postnatal age at initiation of feeding MOM..

Modular Synthesis of Azines Bearing a Guanidine Core from N-Heterocyclic Carbene (NHC)-Derived Selenoureas and Diazo Reagents.

N-Heterocyclic carbene (NHC)-derived selenoureas comprise a fundamentally important class of NHC derivatives, with key applications in coordination chemistry and the determination of NHC electronic properties. Considering the broad reactivity of chalcogen-containing compounds, it is surprising to note that the use of NHC-derived selenoureas as organic synthons remains essentially unexplored. The present contribution introduces a novel, straightforward transformation leading to azines bearing a guanidine moiety, through the reaction of a wide range of NHC-derived selenoureas with commercially available diazo compounds, in the presence of triphenylphosphine. This transformation offers a new approach to such products, having biological, materials chemistry, and organic synthesis applications. The guanidine-bearing azines are obtained in excellent yields, with all manipulations taking place in air. A reaction mechanism is proposed, based on both experimental mechanistic findings and density functional theory (DFT) calculations. A one-pot, multicomponent transesterification reaction between selenoureas, α-diazoesters, alcohols, and triphenylphosphine was also developed, providing highly functionalized azines.

1H and 31P Magnetic Resonance Spectroscopic Metabolomic Imaging: Assessing Mitogen-Activated Protein Kinase Inhibition in Melanoma.

The MAPK signaling pathway with BRAF mutations has been shown to drive the pathogenesis of 40-60% of melanomas. Inhibitors of this pathway's BRAF and MEK components are currently used to treat these malignancies. However, responses to these treatments are not always successful. Therefore, identifying noninvasive biomarkers to predict treatment responses is essential for personalized medicine in melanoma. Using noninvasive 1H magnetic resonance spectroscopy (1H MRS), we previously showed that BRAF inhibition reduces lactate and alanine tumor levels in the early stages of effective therapy and could be considered as metabolic imaging biomarkers for drug response. The present work demonstrates that these metabolic changes observed by 1H MRS and those assessed by 31P MRS are also found in preclinical human melanoma models treated with MEK inhibitors. Apart from 1H and 31P MRS, additional supporting in vitro biochemical analyses are described. Our results indicate significant early metabolic correlations with response levels to MEK inhibition in the melanoma models and are consistent with our previous study of BRAF inhibition. Given these results, our study supports the potential clinical utility of noninvasive MRS to objectively image metabolic biomarkers for the early prediction of melanoma's response to MEK inhibition.

Critical thresholds of long-pressure reactivity index and impact of intracranial pressure monitoring methods in traumatic brain injury.

BACKGROUND: Moderate-to-severe traumatic brain injury (TBI) has a global mortality rate of about 30%, resulting in acquired life-long disabilities in many survivors. To potentially improve outcomes in this TBI population, the management of secondary injuries, particularly the failure of cerebrovascular reactivity (assessed via the pressure reactivity index; PRx, a correlation between intracranial pressure (ICP) and mean arterial blood pressure (MAP)), has gained interest in the field. However, derivation of PRx requires high-resolution data and expensive technological solutions, as calculations use a short time-window, which has resulted in it being used in only a handful of centers worldwide. As a solution to this, low resolution (longer time-windows) PRx has been suggested, known as Long-PRx or LPRx. Though LPRx has been proposed little is known about the best methodology to derive this measure, with different thresholds and time-windows proposed. Furthermore, the impact of ICP monitoring on cerebrovascular reactivity measures is poorly understood. Hence, this observational study establishes critical thresholds of LPRx associated with long-term functional outcome, comparing different time-windows for calculating LPRx as well as evaluating LPRx determined through external ventricular drains (EVD) vs intraparenchymal pressure device (IPD) ICP monitoring. METHODS: The study included a total of n = 435 TBI patients from the Karolinska University Hospital. Patients were dichotomized into alive vs. dead and favorable vs. unfavorable outcomes based on 1-year Glasgow Outcome Scale (GOS). Pearson's chi-square values were computed for incrementally increasing LPRx or ICP thresholds against outcome. The thresholds that generated the greatest chi-squared value for each LPRx or ICP parameter had the highest outcome discriminatory capacity. This methodology was also completed for the segmentation of the population based on EVD, IPD, and time of data recorded in hospital stay. RESULTS: LPRx calculated with 10-120-min windows behaved similarly, with maximal chi-square values ranging at around a LPRx of 0.25-0.35, for both survival and favorable outcome. When investigating the temporal relations of LPRx derived thresholds, the first 4 days appeared to be the most associated with outcomes. The segmentation of the data based on intracranial monitoring found limited differences between EVD and IPD, with similar LPRx values around 0.3. CONCLUSION: Our work suggests that the underlying prognostic factors causing impairment in cerebrovascular reactivity can, to some degree, be detected using lower resolution PRx metrics (similar found thresholding values) with LPRx found clinically using as low as 10 min-by-minute samples of MAP and ICP. Furthermore, EVD derived LPRx with intermittent cerebrospinal fluid draining, seems to present similar outcome capacity as IPD. This low-resolution low sample LPRx method appears to be an adequate substitute for the clinical prognostic value of PRx and may be implemented independent of ICP monitoring method when PRx is not feasible, though further research is warranted.

Investigating the water availability hypothesis of pot binding: small pots and infrequent irrigation confound the effects of drought stress in potato (Solanum tuberosum L.).

To maximise the throughput of novel, high-throughput phenotyping platforms, many researchers have utilised smaller pot sizes to increase the number of biological replicates that can be grown in spatially limited controlled environments. This may confound plant development through a process known as "pot binding", particularly in larger species including potato (Solanum tuberosum), and under water-restricted conditions. We aimed to investigate the water availability hypothesis of pot binding, which predicts that small pots have insufficient water holding capacities to prevent drought stress between irrigation periods, in potato. Two cultivars of potato were grown in small (5 L) and large (20 L) pots, were kept under polytunnel conditions, and were subjected to three irrigation frequencies: every other day, daily, and twice daily. Plants were phenotyped with two Phenospex PlantEye F500s and canopy and tuber fresh mass and dry matter were measured. Increasing irrigation frequency from every other day to daily was associated with a significant increase in fresh tuber yield, but only in large pots. This suggests a similar level of drought stress occurred between these treatments in the small pots, supporting the water availability hypothesis of pot binding. Further increasing irrigation frequency to twice daily was still not sufficient to increase yields in small pots but it caused an insignificant increase in yield in the larger pots, suggesting some pot binding may be occurring in large pots under daily irrigation. Canopy temperatures were significantly higher under each irrigation frequency in the small pots compared to large pots, which strongly supports the water availability hypothesis as higher canopy temperatures are a reliable indicator of drought stress in potato. Digital phenotyping was found to be less accurate for larger plants, probably due to a higher degree of self-shading. The research demonstrates the need to define the optimum pot size and irrigation protocols required to completely prevent pot binding and ensure drought treatments are not inadvertently applied to control plants.

Clusters Based on Within-Treatment Symptom Trajectories as Predictors of Dropout in Treatment for Posttraumatic Stress Disorder and Substance Use Disorder.

Objective: Dropout rates are high in treatments for co-occurring posttraumatic stress disorder (PTSD) and substance use disorders (SUDs). We examined dropout predictors in PTSD-SUD treatment. Methods: Participants were 183 veterans receiving integrated or phased motivational enhancement therapy and prolonged exposure. Using survival models, we examined demographics and symptom trajectories as dropout predictors. Using latent trajectory analysis, we incorporated clusters based on symptom trajectories to improve dropout prediction. Results: Hispanic ethnicity (integrated arm), Black or African American race (phased arm), and younger age (phased arm) predicted dropout. Clusters based on PTSD and substance use trajectories improved dropout prediction. In integrated treatment, participants with consistently-high use and low-and-improving use had the highest dropout. In phased treatment, participants with the highest and lowest PTSD symptoms had lower dropout; participants with the lowest substance use had higher dropout. Conclusions: Identifying within-treatment symptom trajectories associated with dropout can help clinicians intervene to maximize outcomes. ClinicalTrials.gov Identifier: NCT01211106.

Factors Associated With Persistent Bothersome Urinary Symptoms and Leakage After Pregnancy.

IMPORTANCE: Urinary incontinence is a common postpartum morbidity that negatively affects quality of life. OBJECTIVE: This study aimed to identify factors associated with persistent (ie, 12 months postpartum) bothersome urinary symptoms, including stress urinary incontinence (SUI) and urgency urinary incontinence (UUI), and explore their association with mental health in medically underserved communities. STUDY DESIGN: This was a cross-sectional analysis of a prospective study of individuals enrolled into "extending Maternal Care After Pregnancy," a program providing 12 months of postpartum care to individuals with health disparities. Patients were screened at 12 months for urinary dysfunction, anxiety, and depression using the Urinary Distress Index-6, Generalized Anxiety Disorder-7, and Edinburgh Postnatal Depression Scale, respectively. Bivariate and multivariable logistic regression analyses were performed for at-least-somewhat-bothersome SUI versus no-SUI, UUI versus no-UUI, and for bothersome versus asymptomatic urinary symptoms, using demographic and peripartum and postpartum variables as associated factors. RESULTS: Four hundred nineteen patients provided data at median 12 months postpartum. Patients were 77% Hispanic White and 22% non-Hispanic Black. After multivariable analysis, SUI (n = 136, 32.5%) was significantly associated with increasing body mass index at the time of delivery and greater depression screening scores. Fetal birthweight, mode of delivery, degree of laceration, and breastfeeding status were not associated. Urgency urinary incontinence (n = 69, 16.5%) was significantly associated with increasing parity and higher anxiety screening scores. Similarly, participants with urinary symptom bother had significantly greater parity and higher anxiety screening scores. CONCLUSIONS: At 12 months postpartum, bothersome urinary symptoms and incontinence were quite common. Since these are treatable, postpartum screening for urinary complaints-and associated anxiety and depression-is essential, as is assisting patients in achieving a healthy weight.

Structure-Function Analysis of the Essential Mycobacterium tuberculosis P450 Drug Target, CYP121A1.

Cytochrome P450 CYP121A1 is a well-known drug target against Mycobacterium tuberculosis, the human pathogen that causes the deadly disease tuberculosis (TB). CYP121A1 is a unique P450 enzyme because it uses classical and non-classical P450 catalytic processes and has distinct structural features among P450s. However, a detailed investigation of CYP121A1 protein structures in terms of active site cavity dynamics and key amino acids interacting with bound ligands has yet to be undertaken. To address this research knowledge gap, 53 CYP121A1 crystal structures were investigated in this study. Critical amino acids required for CYP121A1's overall activity were identified and highlighted this enzyme's rigid architecture and substrate selectivity. The CYP121A1-fluconazole crystal structure revealed a novel azole drug-P450 binding mode in which azole heme coordination was facilitated by a water molecule. Fragment-based inhibitor approaches revealed that CYP121A1 can be inhibited by molecules that block the substrate channel or by directly interacting with the P450 heme. This study serves as a reference for the precise understanding of CYP121A1 interactions with different ligands and the structure-function analysis of P450 enzymes in general. Our findings provide critical information for the synthesis of more specific CYP121A1 inhibitors and their development as novel anti-TB drugs.

Two Methods of Measuring Cryptococcus neoformans Fungal Burden in Macrophages.

The ability of C. neoformans to survive and replicate within host phagocytes enables it to evade the immune system and allows for persistence of the infection. As such, measuring fungal burden of C. neoformans strains-and indeed how drug treatments can influence fungal burden-provides important information about C. neoformans pathogenesis. In this chapter, we describe two methods that may be used to appraise fungal burden: a standard end-point colony-formation assay for calculating the average number of yeast per host cell and a fluorescence microscopy-based method that may be used to measure changes in fungal burden in individual living macrophages in real time.

Quantification of C. neoformans Capsule Diameter.

The polysaccharide capsule of Cryptococcus neoformans is the primary virulence factor and one of the most commonly studied aspects of this pathogenic yeast. Capsule size varies widely between strains, has the ability to grow rapidly when introduced to stressful or low-nutrient conditions, and has been positively correlated with strain virulence. For these reasons, the size of the capsule is of great interest to C. neoformans researchers. Inducing the growth of the C. neoformans capsule is used during phenotypic testing to help understand the effects of different treatments on the yeast or size differences between strains. Here, we describe one of the standard methods of capsule induction and detail two accepted methods of staining: (i) India ink, a negative stain, used in conjunction with conventional light microscopy and (ii) co-staining with fluorescent dyes of both the cell wall and capsule followed by confocal microscopy. Finally, we outline how to measure capsule diameter manually and offer a protocol for automated diameter measurement of India ink-stained samples using computational image analysis.

Obesity and metabolic syndrome in patients with heart failure with preserved ejection fraction: a cross-sectional analysis of the Veradigm Cardiology Registry.

BACKGROUND: The proportion of heart failure patients with preserved ejection fraction has been rising over the past decades and has coincided with increases in the prevalence of obesity and metabolic syndrome. The relationship between these interconnected comorbidities and heart failure with preserved ejection fraction (HFpEF) is still poorly understood. This study characterized obesity and metabolic syndrome among real-world patients with HFpEF. METHODS: We identified adults with heart failure in the Veradigm Cardiology Registry, previously the PINNACLE Registry, with a left ventricular ejection fraction measurement ≥ 50% between 01/01/2016 and 12/31/2019. Patients were stratified by obesity diagnosis and presence of metabolic syndrome (≥ 3 of the following: diabetes, hypertension, hyperlipidemia, and obesity). We captured baseline demographic and clinical characteristics and used multivariable logistic regression to examine the odds of having cardiac (atrial fibrillation, coronary artery disease, coronary artery bypass surgery, myocardial infarction, and stroke/transient ischemic attack) and non-cardiac (chronic kidney disease, chronic liver disease, and peripheral artery disease) comorbidities of interest. The models adjusted for age and sex, and the main covariates of interest were obesity and metabolic burden score (0-3 based on the presence of diabetes, hypertension, and hyperlipidemia). The models were run with and without an obesity*metabolic burden score interaction term. RESULTS: This study included 264,571 patients with HFpEF, of whom 55.7% had obesity, 52.5% had metabolic syndrome, 42.5% had both, and 34.3% had neither. After adjusting for age, sex, and burden of other metabolic syndrome-associated diagnoses, patients with HFpEF with obesity had lower odds of a diagnosis of other evaluated comorbidities relative to patients without obesity. The presence of metabolic syndrome in HFpEF appears to increase comorbidity burden as each additional metabolic syndrome-associated diagnosis was associated with higher odds of assessed comorbidities except atrial fibrillation. CONCLUSION: Obesity was common among patients with HFpEF and not always co-occurring with metabolic syndrome. Multivariable analysis suggested that patients with obesity may develop HFpEF in the absence of other driving factors such as cardiovascular disease or metabolic syndrome.

Area Deprivation and Postpartum Readmission Facility Location and Timing.

This cohort study evaluates the role that community-level socioeconomic status plays in hypertension-related hospital readmission within 12 weeks after delivery.

Clinician Burnout and Effectiveness of Guideline-Recommended Psychotherapies.

Importance: Clinician burnout has been associated with clinician outcomes, but the association with patient outcomes remains unclear. Objective: To evaluate the association between clinician burnout and the outcomes of patients receiving of guideline-recommended trauma-focused psychotherapies for posttraumatic stress disorder (PTSD). Design, Setting, and Participants: This cohort study was set at the US Veterans Affairs Health Care System and included licensed therapists who provided trauma-focused psychotherapies and responded to an online survey between May 2 and October 8, 2019, and their patients who initiated a trauma-focused therapy during the following year. Patient data were collected through December 31, 2020. Data were analyzed from May to September 2023. Exposures: Therapists completing the survey reported burnout with a 5-point validated measure taken from the Physician Worklife Study. Burnout was defined as scores of 3 or more. Main Outcomes and Measures: The primary outcome was patients' clinically meaningful improvement in PTSD symptoms according to the PTSD Checklist for the Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition). Patient dropout, therapist adherence, and session spacing was assessed through electronic health records. Multivariable random-effects logistic regression examined the association of therapist burnout and clinically meaningful improvement, adjusted for case-mix. Results: In this study, 165 of 180 (91.7%) therapists (89 [53.9%] female) completed the burnout measure and provided trauma-focused psychotherapies to 1268 patients (961 [75.8%] male) with outcome data. Fifty-eight (35.2%) therapists endorsed burnout. One third of patients (431 [34.0%]) met criterion for clinically meaningful improvement. Clinically meaningful improvement in PTSD symptoms was experienced by 120 (28.3%) of the 424 patients seen by therapists who reported burnout and 311 (36.8%) of the 844 patients seen by therapists without burnout. Burnout was associated with lower odds of clinically meaningful improvement (adjusted odds ratio [OR],0.63; 95% CI, 0.48-0.85). The odds of clinically meaningful improvement were reduced for patients who dropped out (OR, 0.15; 95% CI, 0.11-0.20) and had greater session spacing (OR, 0.80; 95% CI, 0.70-0.92). Therapist adherence was not associated with therapy effectiveness. Adjusting for dropout or session spacing did not meaningfully alter the magnitude of the association between burnout and clinically meaningful improvement. Conclusions and Relevance: In this prospective cohort study, therapist burnout was associated with reduced effectiveness of trauma-focused psychotherapies. Studying when and how burnout affects patient outcomes may inform workplace interventions.