Objective Markers Research Articles

Exploring the potential of objective metabolite measures in dietary assessment: randomised cross over feeding study

Reliable dietary assessment is key to our understanding of diet-health interactions(1). Most current dietary assessment methods are self-reported, making them prone to a range of biases(2). Objective markers, such as certain metabolite concentrations in human tissue, may prove a more reliable method of dietary assessment in the future while reducing participant burden(2,3). An example of these metabolite markers are alkylresorcinols, a family of compounds found in the bran layer of common grains. High concentrations of alkylresorcinols reflect high wholegrain intakes, very low levels indicate only refined grain intake, while no alkylresorcinols would indicate a gluten-free diet. We conducted a randomised crossover feeding study of three interventions (one standardisation day followed by a feeding day where known amounts were consumed under observation). Each feeding day differed by which food groups were provided (e.g., chicken, legumes, and fruit) or entirely absent (e.g., grains, fish, and dairy). Participants provided 24-hour urine samples on all six days (standardisation days and feeding days), as well as a 24-recalls and fasted blood samples the morning after each day. Known metabolite markers of dietary intake (approximately 70) were identified in blood and urine with LC-MSqToF, and semi-quantified with a known standard. Twenty-four hour urine sodium content was also measured as the current best known objective marker of dietary intake(4). Twenty-four participants (74% female, age (SD) 24.8 (6.1), BMI 24.1 (4.0)) commenced the study, with 21 (88%) completing all three interventions. Mean energy intake on feeding days (11720 kJ (2943.01)) was higher than self-reported energy intake on standardisation days (9243.57 kJ (3582.92)). Meals were well tolerated, with mean (range) intakes of 9.8 (6.3 – 16.1) serves whole grains, 2.4 (1.6 – 4.8) serves fish, 3.1 (1.9 – 5.5) serves dairy, 5.6 (4.5 – 9.1) serves chicken, 8.2 (7.0 – 14.1) serves legumes, 3.1 (1.3 – 4.6) serves fruit, 3.9 (2.6 – 6.4) serves red meat, 1.7 (1.35 – 2.6) serves nuts and seeds, or 13.4 (9.4 – 19.5) serves vegetables on their respective feeding days. The three feeding days provided clearly identifiable clusters when assessing the overall metabolic profile, both in terms of what was measured on the feeding days, and the difference in metabolite concentrations between standardisation day and feeding day. The relative correlations between self-reported intakes and individual metabolite concentrations reflecting specific foods or food groups with the known dietary intakes from feeding days will be presented first at the conference.

Electroencephalogram monitoring during ketamine antidepressant treatment: a pilot study

Introduction Depression is a major cause of disability world-wide. Up to a third of patients have a treatment-resistant form (TRD), presenting a major challenge. Ketamine has been introduced as a novel rapid-acting antidepressant effective in this population. However, at present, ketamine treatment is not routinely informed by any objective neural markers. Basic research has shown promising electroencephalogram (EEG) changes including a decrease in alpha power. However, clinical translation is lacking.ObjectivesAssess the feasibility of identifying EEG correlates of ketamine infusions in a routine outpatient setting with a low-cost, easily usable system.MethodsThe study was carried out at the Oxford Health Foundation Trust Ketamine Clinic (ethics reference 22/EM/0226). N=18 EEG recordings from N=12 patients were collected (5 women, mean age 44, range 33-62, IV dose 0.5-1mg/kg over 40min). 4-channel EEG was collected with a Muse-S headband at 256Hz, from 5min before to 55min after infusion start. 5s epochs were rejected if gyroscope data indicated head movement above 10 deg/s or if amplitude was above 200μV. A spectrogram (4s window, 3s overlap) as well as band-limited power (theta: 4-8Hz, alpha: 8-13Hz, beta: 13-25Hz) were computed. Significance of changes was found with a repeated measures analysis of variance (RM-ANOVA) on power in 5min segments together with post-hoc Tukey’s P-values.ResultsAcross the ketamine infusion recordings, there was a significant effect of time (F=3.65, P=0.0105) and Channel*Time interaction (F=3.80, P<0.001) on the EEG spectrum. Effects were largest on temporal electrodes, particularly TP9 in the alpha and theta bands (Figure 1, Table 1).Table 1:Effect sizes (Cohen’s d) and FDR-corrected ANOVA P-values for ketamine effects on each EEG channel and frequency band. P<0.05 was considered significant (bold). n.s. = not significant (P>0.2). Channel / Band TP9AF7AF8TP10Theta1.16 (P=0.019)0.11 (n.s.)0.11 (n.s.)0.42 (P=0.113)Alpha1.41 (P<0.001)0.12 (n.s.)0.17 (n.s.)0.605 (P=0.113)Beta1.19 (P=0.112)0.03 (n.s.)0.08 (n.s.)0.21 (n.s.)Image:ConclusionsIn a routine outpatient setting, sub-anaesthetic ketamine infusions in TRD patients were associated with decreased fronto-temporal EEG alpha and theta power. Future work should assess the potential of low-cost routine EEG, and alpha desaturation specifically, to inform individualised ketamine treatment.Disclosure of InterestNone Declared

Clinical utility of C-reactive protein-to-albumin ratio in the management of patients with inflammatory bowel disease.

C-reactive protein (CRP)-to-albumin ratio (CAR) is a novel score with prognostic value in inflammatory conditions. This study assessed the performance of CAR as an objective marker of disease activity and prediction of subtherapeutic infliximab trough levels in patients with inflammatory bowel disease (IBD). A retrospective study was conducted on three different patient cohorts with IBD: patients who had (i) fecal calprotectin (FC) measurements; (ii) Mayo Endoscopic Scores; and (iii) infliximab trough levels available. The relative performances of CAR, albumin, and CRP were compared in predicting disease activity (based on FC or Mayo Endoscopic Score) and infliximab trough levels. In both the FC (n = 289) and endoscopy (n = 65) cohorts, albumin and CAR correlated with objective disease activity. CAR (area under the curve [AUC] 0.70) was only marginally better at detecting active disease, measured by FC, compared to CRP (AUC 0.68). A CAR >0.15 was able to detect Mayo 3 disease (AUC 0.83, sensitivity 81%, specificity 89%). Albumin (r = 0.38) and CAR (r = -0.42) correlated with infliximab trough levels (n = 204). The optimal CAR for detecting subtherapeutic infliximab trough levels was >0.08 (AUC 0.70, sensitivity 66%, specificity 64%). Both albumin and CAR were independent predictors of subtherapeutic infliximab trough levels but correlated poorly with infliximab trough levels longitudinally in the same patient. CAR was only a modest discriminator of subtherapeutic infliximab levels and offers little more than CRP in detecting active disease. CAR has potential to detect severe Mayo 3 disease and could be calculated in patients admitted with suspected acute severe ulcerative colitis.

DNA Ploidy as a Potential Adjunct Prognostic Marker of Low-Risk Prostate Cancer Progression after Radical Prostatectomy.

Post prostatectomy PSA kinetics and General Grade Groups (GGG) are the strongest prognostic markers of biochemical recurrence (BCR) and prostate cancer (PCa)-specific mortality after radical prostatectomy. Despite having low-risk PCa, some patients will experience BCR, for some, clinically significant BCR. There is a need for an objective prognostic marker at the time of prostatectomy to improve risk stratification within this population. In this study, we investigated the prognostic potential of DNA ploidy. Prostatectomy samples from 97 patients with GGG1 and GGG2 with a low-risk CAPRA-S score were included in this study. PCa tissue with the worst Gleason pattern underwent tissue disaggregation, cell isolation and staining with a DNA stoichiometric stain. Using image cytometry, DNA ploidy was measured and a Ploidy Score (PS) was generated. Among the 97 patients, 79 had no BCR, 18 experienced BCR, of which 14 had a PSA doubling time (PSA-DT) >1 year (low-risk group) and 4 had a PSA-DT of <1 year (high-risk group). Using Logistic regression analysis, only pathological T stage (pT) and PS independently predicted BCR with PS being the most significant (p = 0.001). The number of aneuploid cells was significantly higher in the high-risk group compared to the other groups (p = 1.7x10-11). PS combined with GGG diagnosis further stratified risk groups of biochemical recurrence free survival within CAPRA-S low-risk cohort. DNA ploidy is an independent prognostic marker of BCR in low-risk PCa after radical prostatectomy, which could early on identify potentially aggressive PCa recurrences and introduce a more personalized approach to salvage treatments.

Intensive Longitudinal Social Sensing in Patients With Psychosis Spectrum Disorders: An Exploratory Pilot Study.

Psychosis spectrum disorders are characterized by significant alterations in social functioning, which is a major factor for patient recovery. Despite its importance, objectively quantifying the complex day-to-day social behavior in real-life settings has rarely been attempted. Here, we conducted a pilot study with wearable sensors that passively and continuously register interactions with other participants. We hypothesized that the amount and pattern of social interaction was associated with the severity of psychotic symptoms. We recruited 7 patients with psychosis spectrum disorders and 18 team members from a Soteria-style ward. Each participant wore a radio frequency identification badge, sending and receiving signals from nearby badges, allowing passive quantification of social interactions. In addition, symptom severity was assessed weekly by the Positive and Negative Syndrome Scale (PANSS). During an 11-week period, we identified 17970 interactions among patients and staff. On average, patients spent 2.6h per day interacting, capturing relevant aspects of daily social life. Relative daily interaction time, average interaction duration, and clustering coefficient, a measure of local network integration, were significantly associated with lower PANSS scores. Self-reported interaction time did not correlate with measured interaction time or with PANSS, indicating the importance of objective markers. This pilot study demonstrates the feasibility of passively recording social interaction of patients and staff at high resolution and for a long observation period in a real-life setting in a psychiatric department. We show links between quantified social interaction and psychopathology that may facilitate development and personalization of targeted treatments.

Prediction of psychotic disorder in individuals with clinical high-risk state by multimodal machine-learning: A preliminary study

Objective markers which can reliably predict psychosis transition among individuals with at-risk mental state (ARMS) are warranted. In this study, sixty-five ARMS subjects [of whom 17 (26.2%) later developed psychosis] were recruited, and we performed supervised linear support vector machine (SVM) with a variety of combinations of.modalities (clinical features, cognition, structural magnetic resonance imaging, eventrelated.potentials, and polyunsaturated fatty acids) to predict future psychosis onset. While single-modality SVMs showed a poor to fair accuracy, multi-modal SVMs revealed better predictions, up to 0.88 of the balanced accuracy, suggesting the advantage of multi-modal machine-learning methods for forecasting psychosis onset in ARMS.

Heart Rate Variability (HRV) serves as an objective correlate of distress and symptom burden in multiple sclerosis

BackgroundAutonomic nervous system (ANS) dysfunction is frequently seen in people living with multiple sclerosis (MS). Heart rate variability (HRV) is an easy and objective index for evaluating ANS functioning, and it has been previously used to explore the association between ANS and the experience of symptom burden in other chronic diseases. Given ANS functioning can be influenced by physical and psychological factors, this study investigated whether emotional distress and/or the presence of ANS dysfunction is associated with symptom severity in people living with MS. MethodsParticipants with MS and healthy controls (HC) with no history of cardiac conditions were recruited to self-collect HR data sampled from a chest strap HR monitor (PolarH10). Short-term HR signal was collected for five minutes, and time and frequency HRV analyses were performed and compared between groups. HRV values were then compared to self-reported distress (Kessler Psychological Distress Scale) and MS participants’ self-reported measures of symptom burden (SymptoMScreen). ResultsA total of n = 23 adults with MS (51 ± 12 years, 65 % female, median Patient Determined Disease Steps [PDDS]: 3.0) and n = 23 HCs (43 ± 18 years, 40 % female) completed the study procedures. All participants were able to complete the chest strap placement and HR data capture independently. Participants with MS, compared to the HC participants, had a significantly lower parasympathetic activation as shown by lower values of the root mean square of successive differences between normal heartbeats (RMSSD: 21.86 ± 9.84 vs. 43.13 ± 20.98 ms, p = 0.002) and of high-frequency (HF) power band (HF-HRV: 32.69 ± 12.01 vs. 42.39 ± 7.96 nu, p = 0.016), indicating an overall lower HRV in the MS group. Among individuals with MS, HF-HRV was significantly correlated with the severity of self-reported MS symptoms (r = -0.548, p = 0.010). Participants with MS also reported higher levels of distress compared to HC participants (18.32 ± 6.05 vs. 15.00 ± 4.61, p = 0.050), and HRV correlated with the severity of distress in MS participants (r = -0.569, p = 0.007). A significant mediation effect was also observed, with emotional distress fully mediating the association between HRV and symptom burden. ConclusionsThese findings suggest the potential for ANS dysfunction, as measured by HRV (i.e., lower value of HF power), to be utilized as an objective marker of symptom burden in people living with MS. Moreover, it is apparent that the relationship between HRV and symptom burden is mediated by emotional distress.

Social class stigma and poorer health behaviors: Evidence from the eating in America study

Although the association between objective markers of low socioeconomic status (SES) and poor health is well established, one underexamined possibility is that over and above objective SES, social class stigma—experiences and anticipation of discrimination based on social class—might undermine people's ability to engage in healthy behaviors. Participants (N = 2022) were recruited between December 2019 and January 2020 via a national Qualtrics panel that was census-matched to the U.S. population in age, gender, income, race/ethnicity, and census region. Participants completed measures of class stigma, alcohol use, disordered eating, comfort eating, sleep disturbance, physical activity, and demographics. Controlling for objective SES and demographics, generalized linear regression models indicated that class stigma was associated with significantly greater alcohol use, disordered eating, greater comfort eating, and sleep disturbance but not less physical activity. Class stigma was not associated with health behaviors after full adjustment for weight/racial discrimination and psychological factors. Results from this investigation suggest that beyond one's objective SES, the stigma associated with having low class may also contribute to poorer health behaviors.

Quantum dots-based multiplexed immunosensors for accurate diagnosis of attention deficit hyperactivity disorder in childhood

Attention-deficit/hyperactivity disorder (ADHD) lacks objective diagnostic markers. In clinical settings, reliance on subjective judgments can often lead to missed or misdiagnoses. Some biomarkers have been reported to be associated with ADHD, but using one biomarker alone is not enough. To address this, we developed a fluorescent immunoassay platform based on quantum dots (QDs) to detect assay capable of detecting and quantifying multiple biomarkers simultaneously. Specifically, we were able to the simultaneously detect brain-derived neurotrophic factor, tumor necrosis factor-alpha, interleukin-6 and ferritin using different emission spectra QDs. The QD-based multiplexed immunoassay displayed a low detection of limit in the range of 0.021−0.068 pg/mL, and the assay showed satisfactory reproducibility and precision. We then quantified all four targets from ADHD patient’s plasma samples, where it showed remarkable consistency with clinical test for ADHD diagnosis. This methodological comparison supports the diagnosis of ADHD using our assay.

TARC/CCL17 reflects the severity of pemphigus (pemphigus vulgaris and pemphigus foliaceus) at the initial presentation

AbstractBackgroundPemphigus vulgaris (PV) and pemphigus foliaceus (PF) are autoimmune blistering diseases targeting desmoglein 3 (Dsg3) or desmoglein 1 (Dsg1). The current scoring system, pemphigus disease area index (PDAI), has limitations including inter‐ and intra‐evaluator variability, as well as a time‐consuming evaluation process.ObjectivesTo identify objective and quantitative surrogate markers for assessing disease severity in PV and PF.MethodsEleven PV and PF patients were included. PDAI scores and candidate biomarkers [anti‐Dsg3 antibody, anti‐Dsg1 antibody, thymus and activation‐regulated chemokine (TARC)/CCL17, immunoglobulin E (IgE) levels and eosinophil counts] were measured before oral corticosteroid treatment. Pearson's correlation coefficient was used for correlations between PDAI and candidate biomarkers.ResultsSerum TARC/CCL17 levels significantly correlated with PDAI scores in PV and PF (R = 0.72, p = 0.02), while anti‐Dsg3 antibody levels correlated with PDAI scores for PV (R = 0.86, p = 0.012). No significant correlations were observed for anti‐Dsg1 antibody, eosinophil counts or IgE levels.ConclusionsSerum TARC/CCL17 may be a quantitative and unbiased disease biomarker in pemphigus patients, although further studies involving larger patient cohorts are needed.

Oral vancomycin is associated with improved inflammatory bowel disease clinical outcomes in primary sclerosing cholangitis-associated inflammatory bowel disease (PSC-IBD): A matched analysis from the Paediatric PSC Consortium.

Data on oral vancomycin for primary sclerosing cholangitis (PSC)-associated inflammatory bowel disease (IBD) are limited. Using data from the Paediatric PSC Consortium, to examine the effect of vancomycin on IBD activity. In this retrospective multi-centre cohort study, we matched vancomycin-treated and untreated patients (1:3) based on IBD duration at the time of primary outcome assessment. The primary outcome was Physician Global Assessment (PGA) of IBD clinical activity after 1 year (±6 months) of vancomycin. We used generalised estimating equations (GEE) to examine the association between vancomycin and PGA remission, adjusting for IBD type, severity and medication exposures. Secondary outcomes included serum labs and endoscopic remission (global rating of no activity) among those with available data and also analysed with GEE. 113 PSC-IBD patients received vancomycin (median age 12.7 years, 63% male). The matched cohort included 70 vancomycin-treated and 210 untreated patients. Vancomycin was associated with greater odds of IBD clinical remission (odds ratio [OR] 3.52, 95% CI 1.97-6.31; adjusted OR [aOR] 5.24, 95% CI 2.68-10.22). Benefit was maintained in sensitivity analyses restricted to non-transplanted patients and those with baseline moderate-severe PGA. Vancomycin was associated with increased odds of endoscopic remission (aOR 2.76, 95% CI 1.002-7.62; N = 101 with data), and with lower CRP (p = 0.03) and higher haemoglobin and albumin (both p < 0.01). Vancomycin was associated with greater odds of IBD clinical and endoscopic remission. Additional, preferably randomised, controlled studies are needed to characterise efficacy using objective markers of mucosal inflammation, and to examine safety and define optimal dosing.

Skeletal muscle estimation: A review of techniques and their applications.

Quantifying skeletal muscle size is necessary to identify those at risk for conditions that increase frailty, morbidity, and mortality, as well as decrease quality of life. Although muscle strength, muscle quality, and physical performance have been suggested as important assessments in the screening, prevention, and management of sarcopenic and cachexic individuals, skeletal muscle size is still a critical objective marker. Several techniques exist for estimating skeletal muscle size; however, each technique presents with unique characteristics regarding simplicity/complexity, cost, radiation dose, accessibility, and portability that are important factors for assessors to consider before applying these modalities in practice. This narrative review presents a discussion centred on the theory and applications of current non-invasive techniques for estimating skeletal muscle size in diverse populations. Common instruments for skeletal muscle assessment include imaging techniques such as computed tomography, magnetic resonance imaging, peripheral quantitative computed tomography, dual-energy X-ray absorptiometry, and Brightness-mode ultrasound, and non-imaging techniques like bioelectrical impedance analysis and anthropometry. Skeletal muscle size can be acquired from these methods using whole-body and/or regional assessments, as well as prediction equations. Notable concerns when conducting assessments include the absence of standardised image acquisition/processing protocols and the variation in cut-off thresholds used to define low skeletal muscle size by clinicians and researchers, which could affect the accuracy and prevalence of diagnoses. Given the importance of evaluating skeletal muscle size, it is imperative practitioners are informed of each technique and their respective strengths and weaknesses.

Annatto-Enriched Egg Improves the Perception of Satiety in Healthy Adults-Randomized Clinical Trial: EGGANT Study.

This study evaluated the effects of egg and annatto-enriched egg consumption on satiety markers and CVD risk factors in healthy adults from Colombia. A parallel randomized clinical trial was conducted, where one hundred and five (n = 105) men and women, divided into three groups, consumed daily for 8 weeks: (a) two eggs (egg group), or (b) two eggs with annatto (egg + annatto group), or (c) two egg whites (placebo group). The three groups were similar in gender distribution. No significant changes were found over time (before vs. after) in any of the groups nor between the groups in anthropometric variables, physical activity, eating profile, and ghrelin as an objective marker of satiety. In the egg + annatto group, subjective satiety increased (effect size 0.431; p < 0.05) after consumption. In healthy adults, the intake of two eggs, or two eggs with annatto daily for 8 weeks, did not result in significant changes in ghrelin; but eggs with annatto tend to increase the perception of satiety.

Comparative study of sleep and circadian rhythms in patients presenting unipolar or bipolar major depressive episodes

Currently, there is a major challenge in distinguishing between unipolar and bipolar major depressive episode. A significant body of research has been dedicated to identifying biomarkers that can aid in this differentiation due to its crucial implications, particularly for therapeutic and prognostic purposes. Among the biomarkers of interest, markers related to sleep and circadian rhythms show promise and could potentially aid in making this distinction. Nevertheless, no study has simultaneously examined sleep-wake disorders, circadian rhythms, and seasonal patterns using both subjective and objective measures. This study aims to characterize and compare the sleep-wake and rhythm disorders including patients with unipolar major depressive episode (n = 72) and with bipolar major depressive episode (n = 43) using both subjective markers (using self-report questionnaires and sleep complaints) and objective markers (using actigraphy). Patients with unipolar major depressive episode seem to experience significantly poorer quality of sleep, more symptoms of insomnia and lower sleep efficiency compared to patients with bipolar major depressive episode. On the other hand, patients with bipolar major depressive episode exhibit significantly more symptoms of motor retardation and hypersomnia compared to patients with unipolar disorder. These results hold significant implications for identifying individuals with unipolar major depressive episode or bipolar major depressive episode using sleep and circadian markers, and for developing recommended and personalized therapeutic strategies.

A Look Into the Future: Are We Ready for an Approved Therapy in Celiac Disease?

As it appears that we are currently at the cusp of an era in which drugs that are new, re-purposed or as “supplements”, will be introduced to the management of celiac disease, we need to reflect if the framework is set for celiac disease to be increasingly treated by pharmaceuticals as well as diet. This refers to reflecting on the rigor of current diagnostic practices, the limitations of the current standard of care that is gluten-free diet, and that we lack objective markers of disease severity. Interrogating these issues will help us to identify gaps in technology and practices that could be critical for selecting patients with a well-defined need for an improved or alternative treatment. Both aspects, circumscribed limitations of the gluten-free diet and diagnostics helping to define celiac disease target groups, together with the guiding requirements by the responsible regulatory authorities will contribute to defining the subgroups of patients with confirmed celiac disease eligible for distinct pharmacological strategies. Because many celiac disease patients are diagnosed in childhood, these aspects need to be differentially discussed for the pediatric setting.In this perspective, we aim to describe these contextual issues and then look ahead to the future. What might be the major challenges in celiac disease clinics in the coming years once drugs are an option alongside the diet? And what will be future objectives for researchers who further decipher the mucosal immunology of celiac disease? Speculating on the answers to these questions is as stimulating as it is fascinating to be part of this turning point.

The Role of Concussion History and Biological Sex on Pupillary Light Reflex Metrics in Adolescent Rugby Players: A Cross-Sectional Study.

Background: Concussion examination is based primarily on clinical evaluation and symptomatic reporting. Pupillary light reflex (PLR) metrics may provide an objective physiological marker to inform concussion diagnosis and recovery, but few studies have assessed PLR, and normative data are lacking, particularly for adolescents. Aim: To capture PLR data in adolescent rugby players and examine the effects of concussion history and biological sex. Design: Cross-sectional. Methods: Male and female adolescent rugby union players aged 16 to 18 years were recruited at the start of the 2022-2023 playing season. PLR was recorded using a handheld pupillometer which provided seven different metrics relating to pupil diameter, constriction/dilation latency, and velocity. Data were analysed using a series of 2 × 2 ANOVAs to examine the main effects of independent variables: biological sex, concussion history, and their interactions, using adjusted p-values (p < 0.05). Results: 149 participants (75% male) were included. A total of 42% reported at least one previous concussion. Most metrics were unaffected by the independent variables. There were however significant main effects for concussion history (F = 4.11 (1); p = 0.05) and sex (F = 5.42 (1); p = 0.02) in end pupil diameters, and a main effect for sex in initial pupil diameters (F = 4.45 (1); p = 0.04). Although no significant interaction effects were found, on average, females with a concussion history presented with greater pupillary diameters and velocity metrics, with many pairwise comparisons showing large effects (SMD > 0.8). Conclusions: Pupillary diameters in adolescent athletes were significantly affected by concussion history and sex. The most extreme PLR metrics were recorded in females with a history of concussion (higher pupillary diameters and velocities). This highlights the importance of establishing baseline PLR metrics prior to interpretation of the PLR post-concussion. Long-standing PLR abnormalities post-concussion may reflect ongoing autonomic nervous system dysfunction. This warrants further investigation in longitudinal studies.

Gender and Pathways to Leadership in Academic Anesthesiology: A Qualitative Content Analysis of US Chairpersons' Curricula Vitae.

Women are underrepresented in medicine and academic anesthesiology, and especially in leadership positions. We sought to characterize career achievement milestones of female versus male academic anesthesiology chairs to understand possible gender-related differences in pathways to leadership. We conducted a retrospective observational cross-sectional analysis. In November 2019, curricula vitae (CVs) were requested from then-current members of the US Association of Academic Anesthesiology Chairs. Data reflecting accomplishments up to the time of chair appointment were systematically extracted from CVs and analyzed using a mixed methods approach with qualitative content analysis supplemented by descriptive statistics and bivariate statistical testing. Missing data were not imputed. Seventy-two CVs were received from eligible individuals (response rate 67.3%). The respondent sample was 12.5% women (n = 9), 87.5% men (n = 63), and no transgender or nonbinary people; this is similar to the known gender balance in anesthesiology chairs in the United States. No statistically significant differences in objective markers of academic achievement at the time of chair appointment were evident for female versus male chairs, including time elapsed between the first faculty appointment and assumption of the chair role (median 25 vs 18 years, P = .06), number of publications at the time the chair was assumed (101 vs 69, P = .28), or proportion who had ever held a National Institutes of Health (NIH) grant as principal investigator (44.4% vs 25.4%, 0.25). Four phenotypes of career paths were discernible in the data: the clinician-administrator, the educator, the investigator, and the well-rounded scholar; these did not differ by gender. Female chairpersons who were members of the Association of Academic Anesthesiology Chairs in the United States demonstrated similar patterns of academic achievement as compared to male chairpersons at the time the position of chair was assumed, suggesting that they were equally qualified for the role as compared to men. Four patterns of career achievements were evident in the chairperson group, suggesting multiple viable pathways to this leadership position.

Psychological, cognitive, and physiological impact of hazards casualties' trainings on first responders: the example of a chemical and radiological training. An exploratory study.

First responders are among the first to respond to hazards casualties. They might operate in volatile, uncertain, complex, and ambiguous (VUCA) environments. While they have underlined the need to improve their knowledge and training to face these environments, there are few data regarding the stress induced by these trainings. Chemical, biological, radiological, and nuclear (CBRN) hazards casualties' trainings seem to be a good model of "in vivo" stress. First responders must operate in a hostile and encountered environment with a CBRN protective equipment that places demand on their psychological, cognitive, and physiological capacities. Current research recognizes that the activity of the parasympathetic system (PSS) can be used as an objective marker of stress adaptation, measured as heart rate variability (HRV). To compare between baseline and simulation the evolution of the parasympathetic activity (primary outcome), anxiety, emotions, cognitive load, and body posture awareness (secondary outcomes). A total of 28 first responders attended to three simulated scenarios requiring CBRN management of casualties. One day before simulation, we collected HRV data (baseline). The simulations' day (pre-, post-simulation) we collected anxiety score (STAI-Y B), emotions (SPANE), cognitive load (NASA TLX), body posture awareness (PAS) and HRV. The morning after we collected the PAS score (recovery). We compare data' evolution between different times of the simulation. (i) A high level of anxiety at baseline [Median 51 (46; 56)] which decreased between pre- and post-simulation (p = 0.04; F = 2.93); (ii) a post-simulation decrease in negative feelings (p = 0.03); (iii) a decrease in body awareness after simulation which returned to the initial level at recovery (p = 0.03; F = 3.48); (iv) a decrease in mean RR between baseline, pre- and post-simulation (p = 0.009; F = 5.11). There were no significant difference between times on others analysis of HRV. Prior to simulation, participants experienced anticipatory anxiety. Simulations training practiced regularly could be one way to combat anticipatory anxiety.

PATTERNS AND ASSOCIATED FACTORS OF OBJECTIVE INFLAMMATION ASSESSMENT TO TREAT-TO-TARGET: DATA FROM THE IBD QORUS COLLABORATIVE

Abstract BACKGROUND A Treat-to-Target (T2T) strategy for inflammatory bowel disease (IBD) improves clinical outcomes. The cornerstone of T2T is the routine assessment of objective markers of inflammation to determine treatment efficacy. Despite this, objective testing is often delayed or not performed. This study aims to describe patterns and associated factors of intended assessment of objective markers of inflammation for patients with IBD within the multicenter quality improvement collaborative, IBD Qorus. METHODS Patient and provider survey data from IBD Qorus were prospectively collected from 6/2021 to 10/2022 across 35 academic and community practices during routine clinical care visits. Patients with unknown status of mucosal healing were excluded. The primary outcome of "timely assessment" was defined as provider-reported intent to obtain fecal calprotectin (FC), imaging, or endoscopy within 12 months. Factors associated with the primary outcome were assessed using univariate and multivariate logistic regression, adjusting for age, gender, IBD type, and clinical factors. RESULTS 4,831 encounter-level surveys from the study period were included for analysis. In 73.9% of encounters, providers reported an intent to assess inflammation within the next 6 months. Of these, 77.1% planned to use FC and 57.7% imaging or endoscopy. 89.3% of visits noted an intent to assess inflammation within 12 months. Providers reported in 29.8% of encounters that patients declined FC and in 8.3% that imaging or endoscopy were declined. In the primary univariate analysis, intent for timely assessment was associated with ulcerative colitis (UC), recent emergency department visit or hospitalization, lack of clinical remission, mild Provider Global Assessment, current steroid use, lack of immunomodulator use, lack of steroid-free mucosal healing, care at an academic site, and intent to change therapy. On multivariate analyses, UC (OR 1.38, 95% CI 1.11-1.71), steroid use (OR 2.1, 95% CI 1.1-4.6), and plans to change therapy (OR 1.84, 95% CI 1.2-2.9) remained significantly associated with higher odds of timely assessment. In contrast, steroid-free mucosal healing (OR 0.52, 95% CI 0.41-0.66) and care in community practice (OR 0.63, 95% CI 0.51-0.77) remained significantly associated with lower odds of timely assessment. CONCLUSION In IBD Qorus, there is a strong intent to assess objective markers of inflammation. However, lower odds of intended assessment were found among patients with Crohn’s, patients in steroid-free mucosal healing, and those receiving care in community practice, revealing potential care gaps. Interestingly, providers frequently reported that patients declined FC testing, and declined this at higher rates than that for endoscopy or imaging. This study identifies potential areas to improve testing for inflammation under a T2T strategy.

P740 Results at 52 weeks of Intravenous Ustekinumab as Maintenance Treatment in Patients with Loss of Response to Subcutaneous Doses: A Multicenter Retrospective Observational Study

Abstract Background Ustekinumab (UST) is indicated for the treatment of Crohn’s Disease (CD) and Ulcerative Colitis (UC). Despite having shown clinical effectiveness in the real world,some patients may lose response over time or need a higher dose to achieve it. In this context, UST intravenous (IV) maintenance has been proposed. The primary endpoint of our study was to evaluate the efficacy and safety of maintenance IV UST treatment in Inflammatory Bowel Disease (IBD) patients who present with partial response or loss of response to subcutaneous UST. Methods We performed a multicenter observational retrospective study including patients with active IBD on maintenance treatment with IV UST. The study conducted at 2 hospitals in Andalusia.The clinical response and remission was analyzed at week 12 and 52, defined as either Harvey-Bradshaw Index (HBI) ≤4 for CD or partial Mayo Score (pMS) ≤2 for UC. The reduction of objective markers of disease activity, fecal calprotectin (FCal) and C-reactive protein (CRP) was evaluated. Moreover, UST trough levels were measured pre-and post UST IV maintenance, drug persistence at the end of the follow-up and any adverse events were assessed. Results A total of 59 patients were included in the study, with a median age of 41 years [IQR32-52]. 84.7% (50/59) had Crohn's disease (CD). 91.5% (53/59) had previously received at least one biologic or JAK inhibitor treatment. 58.6% (34/59) werepreviously on subcutaneous UST every 4 weeks (Table 1). In patients with CD, the median baseline HBI value was 9 (IQR 6-12), which decreased to 5 (IQR 4-7) at week 12 and 4 (IQR 3-6) at week 52 (p&amp;lt;0.001) (Figure 2A). In patients with ulcerative colitis (UC), the median baseline pMayo value was 8.5 (IQR 6.5-9.0), which decreased to 5.5 (IQR 4.3-6.0) at week 12 and 3 (IQR 2.0-4.8) at week 52 (p=0.017) (Figure 2B). The median baseline FCal was 800.2 μg/g, which decreased to 520 μg/g at week 12 and 220 μg/g at week 52 (p&amp;lt;0.001). Regarding CRP, the median baseline was 7.1 mg/L, which decreased to 4 mg/L at week 12 and 3 mg/L at week 52 (p&amp;lt;0.001). The median UST levels with subcutaneous maintenance treatment were 3.1 mcg/mL (IQR 1.1-7.4) compared to 12 mcg/mL (IQR 9-20) with intravenous treatment (p&amp;lt;0.001) (Figure 2C). Clinical remission at week 12 and 52, was achieved by 47,5% and 64,3% of the patients respectively. At the end of the follow-up, 96.6% of the patients continued with intravenous UST (Figure 2D). No adverse events were recorded in any patient for the duration of the study. Conclusion Intravenous UST for maintenance is able to rescue up to 64% of patients who have failed on subcutaneous doses. 97% of patients continue intravenous UST treatment after one year with an excellent safety profile. UST levels increase fourfold.