Linear Mixed Effects Research Articles

Hepatotoxicity Patterns of Anidulafungin and Fluconazole in the Management of Candida Infections: A Comparative Study among Hospitalized Patients

Hepatotoxicity can potentially arise in hospitalized patients with Candida infections due to antifungal medications. Ongoing research has focused on the hepatotoxicity profiles of fluconazole and anidulafungin. Nevertheless, a limited number of studies have directly compared the hepatotoxicity of these two antifungals. This study compares the hepatotoxic effects of anidulafungin and fluconazole in patients hospitalized with Candida infections. This retrospective study was conducted at the Prince Mohamed Bin Abdelaziz Hospital in Saudi Arabia to compare the hepatotoxicity of fluconazole and anidulafungin in patients with Candida infection. The liver function test results were analyzed using linear mixed models, with adjustments made for confounding factors. The investigation comprised 202 cases, of which 85 (42%) were treated with fluconazole and 117 (58%) was treated with anidulafungin—mortality and prevalence of candidemia and septic shock in the Anidulafungin group (p 0.001). There was no significant difference between the two groups regarding age, gender, duration of treatment, or concomitant use of hepatotoxic drugs. Analyses utilizing Linear Mixed-Effects Models revealed higher alanine aminotransferase (ALT) (p = 0.001) and aspartate aminotransferase (AST) (p = 0.001) levels in the Anidulafungin group initially; however, after adjusting for covariates, these differences were no longer statistically significant. The levels of alkaline phosphatase (ALP) and gamma-glutamyl transferase (GTT) did not differ significantly between groups after controlling for confounding variables. However, the Anidulafungin group had substantially higher bilirubin levels than the Fluconazole group, and this difference remained significant after adjusting for potential confounding variables (p = 0.022). In summary, this study contributes to understanding the relative hepatotoxicity of anidulafungin and fluconazole. After controlling for confounding variables, it was found that there were no significant differences in liver enzyme levels between the two groups. When assessing the hepatotoxicity of these antifungal agents, it is imperative to consider the individual patient characteristics, underlying health conditions, and concurrent administration of other hepatotoxic medications.

Choroid plexus volume as a novel candidate neuroimaging marker of the Alzheimer’s continuum

BackgroundEnlarged choroid plexus (ChP) volume has been reported in patients with Alzheimer’s disease (AD) and inversely correlated with cognitive performance. However, its clinical diagnostic and predictive value, and mechanisms by which ChP impacts the AD continuum remain unclear.MethodsThis prospective cohort study enrolled 607 participants [healthy control (HC): 110, mild cognitive impairment (MCI): 269, AD dementia: 228] from the Chinese Imaging, Biomarkers, and Lifestyle study between January 1, 2021, and December 31, 2022. Of the 497 patients on the AD continuum, 138 underwent lumbar puncture for cerebrospinal fluid (CSF) hallmark testing. The relationships between ChP volume and CSF pathological hallmarks (Aβ42, Aβ40, Aβ42/40, tTau, and pTau181), neuropsychological tests [Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Neuropsychiatric Inventory (NPI), and Activities of Daily Living (ADL) scores], and multimodal neuroimaging measures [gray matter volume, cortical thickness, and corrected cerebral blood flow (cCBF)] were analyzed using partial Spearman’s correlation. The mediating effects of four neuroimaging measures [ChP volume, hippocampal volume, lateral ventricular volume (LVV), and entorhinal cortical thickness (ECT)] on the relationship between CSF hallmarks and neuropsychological tests were examined. The ability of the four neuroimaging measures to identify cerebral Aβ42 changes or differentiate among patients with AD dementia, MCI and HCs was determined using receiver operating characteristic analysis, and their associations with neuropsychological test scores at baseline were evaluated by linear regression. Longitudinal associations between the rate of change in the four neuroimaging measures and neuropsychological tests scores were evaluated on the AD continuum using generalized linear mixed-effects models.ResultsThe participants’ mean age was 65.99 ± 8.79 years. Patients with AD dementia exhibited the largest baseline ChP volume than the other groups (P < 0.05). ChP volume enlargement correlated with decreased Aβ42 and Aβ40 levels; lower MMSE and MoCA and higher NPI and ADL scores; and lower volume, cortical thickness, and cCBF in other cognition-related regions (all P < 0.05). ChP volume mediated the association of Aβ42 and Aβ40 levels with MMSE scores (19.08% and 36.57%), and Aβ42 levels mediated the association of ChP volume and MMSE or MoCA scores (39.49% and 34.36%). ChP volume alone better identified cerebral Aβ42 changes than LVV alone (AUC = 0.81 vs. 0.67, P = 0.04) and EC thickness alone (AUC = 0.81 vs.0.63, P = 0.01) and better differentiated patients with MCI from HCs than hippocampal volume alone (AUC = 0.85 vs. 0.81, P = 0.01), and LVV alone (AUC = 0.85 vs.0.82, P = 0.03). Combined ChP and hippocampal volumes significantly increased the ability to differentiate cerebral Aβ42 changes and patients among AD dementia, MCI, and HCs groups compared with hippocampal volume alone (all P < 0.05). After correcting for age, sex, years of education, APOE ε4 status, eTIV, and hippocampal volume, ChP volume was associated with MMSE, MoCA, NPI, and ADL score at baseline, and rapid ChP volume enlargement was associated with faster deterioration in NPI scores with an average follow-up of 10.03 ± 4.45 months (all P < 0.05).ConclusionsChP volume may be a novel neuroimaging marker associated with neurodegenerative changes and clinical AD manifestations. It could better detect the early stages of the AD and predict prognosis, and significantly enhance the differential diagnostic ability of hippocampus on the AD continuum.

Measuring attentional selection of object categories using hierarchical frequency tagging.

In the present study, we used Hierarchical Frequency Tagging (Gordon etal., 2017) to investigate in electroencephalography how different levels of the neural processing hierarchy interact with category-selective attention during visual object recognition. We constructed stimulus sequences of cyclic wavelet scrambled face and house stimuli at two different frequencies (f1 = 0.8Hz and f2 = 1Hz). For each trial, two stimulus sequences of different frequencies were superimposed and additionally augmented by a sinusoidal contrast modulation with f3 = 12.5Hz. This allowed us to simultaneously assess higher level processing using semantic wavelet-induced frequency-tagging (SWIFT) and processing in earlier visual levels using steady-state visually evoked potentials (SSVEPs), along with their intermodulation (IM) components. To investigate the category specificity of the SWIFT signal, we manipulated the category congruence between target and distractor by superimposing two sequences containing stimuli from the same or different object categories. Participants attended to one stimulus (target) and ignored the other (distractor). Our results showed successful tagging of different levels of the cortical hierarchy. Using linear mixed-effects modeling, we detected different attentional modulation effects on lower versus higher processing levels. SWIFT and IM components were substantially increased for target versus distractor stimuli, reflecting attentional selection of the target stimuli. In addition, distractor stimuli from the same category as targets elicited stronger SWIFT signals than distractor stimuli from a different category indicating category-selective attention. In contrast, for IM components, this category-selective attention effect was largely absent, indicating that IM components probably reflect more stimulus-specific processing.

Variance due to the examination conditions and factors associated with success in objective structured clinical examinations (OSCEs): first experiences at Paris-Saclay medical school

BackgroundWe aimed to measure the variance due to examination conditions during the first sessions of objective structured clinical examinations (OSCEs) performed at a French medical school and identify factors associated with student success.MethodsWe conducted a retrospective, observational study using data from the first three OSCEs sessions performed at Paris-Saclay medical school in 2021 and 2022. For all sessions (each organized in 5 parallel circuits), we tested a circuit effect using a linear mixed-effects model adjusted for sex and the average academic level of students (according to written tests). Then, we studied the factors associated with student success at one station using a multivariate linear mixed-effects model, including the characteristics of students, assessors, and standardized patients.ResultsThe study included three OSCEs sessions, with 122, 175, and 197 students and a mean (± SD) session score of 13.7(± 1.5)/20, 12.7(± 1.7)/20 and 12.7(± 1.9)/20, respectively. The percentage of variance due to the circuit was 6.5%, 18.2% (statistically significant), and 3.8%, respectively. For all sessions, the student’s average level and station scenario were significantly associated with the score obtained in a station. Still, specific characteristics of assessors or standardized patients were only associated with the student’s score in April 2021 (first session).ConclusionThe percentage of the variance of students’ performance due to the examination conditions was significant in one out of three of the first OSCE sessions performed at Paris-Saclay medical school. This result seems more related to individual behaviors rather than specific characteristics of assessors or standardized patients, highlighting the need to continue training teaching teams.National clinical trial numberNot applicable.

Machine Learning for Extraction of Image Features Associated with Progression of Geographic Atrophy

Background: Several studies have investigated various features and models in order to understand the growth and progression of the ocular disease geographic atrophy (GA). Commonly assessed features include age, sex, smoking, alcohol consumption, sedentary lifestyle, hypertension, and diabetes. There have been inconsistencies regarding which features correlate with GA progression. Chief amongst these inconsistencies is whether the investigated features are readily available for analysis across various ophthalmic institutions. Methods:In this study, we focused our attention on the association of fundus autofluorescence (FAF) imaging features and GA progression. Our method included feature extraction using radiomic processes and feature ranking by machine learning incorporating the algorithm XGBoost to determine the best-ranked features. This led to the development of an image-based linear mixed-effects model, which was designed to account for slope change based on within-subject variability and inter-eye correlation. Metrics used to assess the linear mixed-effects model included marginal and conditional R2, Pearson’s correlation coefficient (r), root mean square error (RMSE), mean error (ME), mean absolute error (MAE), mean absolute deviation (MAD), the Akaike Information Criterion (AIC), the Bayesian Information Criterion (BIC), and loglikelihood. Results: We developed a linear mixed-effects model with 15 image-based features. The model results were as follows: R2 = 0.96, r = 0.981, RMSE = 1.32, ME = −7.3 × 10−15, MAE = 0.94, MAD = 0.999, AIC = 2084.93, BIC = 2169.97, and log likelihood = −1022.46. Conclusions: The advantage of our method is that it relies on the inherent properties of the image itself, rather than the availability of clinical or demographic data. Thus, the image features discovered in this study are universally and readily available across the board.

Cardiovascular and Kidney Outcomes of Non-Diabetic CKD by Albuminuria Severity: Findings From the CRIC Study

The clinical trajectory of normoalbuminuric chronic kidney disease (CKD), particularly in the absence of diabetes, has not yet been well-studied. This study evaluated the association of kidney and cardiovascular outcomes with levels of albuminuria in a cohort of patients with nondiabetic CKD. Prospective cohort study. 1,463 adults with nondiabetic CKD without known glomerulonephritis and diagnosed with hypertensive nephrosclerosis or unknown cause of CKD participating in the Chronic Renal Insufficiency Cohort (CRIC) Study. Albuminuria stage at study entry. Primary outcome: Composite kidney (halving of estimated glomerular filtration rate [eGFR], kidney transplantation, or dialysis), Secondary outcomes: (1) eGFR slope, (2) composite cardiovascular disease events (hospitalization for heart failure, myocardial infarction, stroke, or all-cause death), (3) all-cause death. Linear mixed effects and Cox proportional hazards regression analyses. Lower levels of albuminuria were associated with female sex and older age. For the primary outcome, compared with normoalbuminuria, those with moderate and severe albuminuria had higher rates of kidney outcomes (adjusted hazard ratio [AHR], 3.3 [95% CI, 2.4-4.6], and AHR, 8.6 [95% CI, 6.0-12.0], respectively) and cardiovascular outcomes (AHR, 1.5 [95% CI, 1.2-1.9], and AHR, 1.5 [95% CI, 1.1-2.0], respectively). Those with normoalbuminuria (<30μg/mg; n=863) had a slower decline in eGFR (-0.46mL/min/1.73m2 per year) compared with those with moderate (30-300μg/mg, n=372; 1.41mL/min/1.73m2 per year) or severe albuminuria (>300μg/mg, n=274; 2.63mL/min/1.73m2 per year). In adjusted analyses, kidney outcomes occurred, on average, sooner among those with moderate (8.6 years) and severe (7.3 years) albuminuria compared with those with normoalbuminuria (9.3 years) whereas the average times to cardiovascular outcomes were similar across albuminuria groups (8.2, 8.1, and 8.6 years, respectively). Self-report of CKD etiology without confirmatory kidney biopsies; residual confounding. Participants with normoalbuminuric nondiabetic CKD experienced substantially slower CKD progression but only modestly lower cardiovascular risk than those with high levels of albuminuria. These findings inform the design of future studies investigating interventions among individuals with lower levels of albuminuria. Diabetes and hypertension are the leading causes of chronic kidney disease (CKD). Urine albumin levels are associated with cardiovascular and kidney disease outcomes among individuals with CKD. However, previous studies of long-term clinical outcomes in CKD largely included patients with diabetes. As well, few studies have evaluated long-term outcomes across different levels of urine albumin among people without diabetes. In this study, we found individuals with nondiabetic CKD and low urine albumin had much slower decline of kidney function but only a modestly lower risk of a cardiovascular events compared with those with high levels of urine albumin. Individuals with low urine albumin were much more likely to have a cardiovascular event than progression of their kidney disease. These findings inform the design of future studies investigating treatments among individuals with lower levels of albuminuria.

Association between serum cytokines and timeframe for conversion from clinical high-risk to psychosis.

Although many studies have explored the link between inflammatory markers and psychosis, there is a paucity of research investigating the temporal progression in individuals at clinical high-risk (CHR) who eventually develop full psychosis. To address this gap, we investigated the correlation between serum cytokine levels and Timeframe for Conversion to Psychosis (TCP) in individuals with CHR. We enrolled 53 individuals with CHR who completed a 5-year follow-up with a confirmed conversion to psychosis. Granulocyte macrophage-colony stimulating factor (GM-CSF), interleukin (IL)-1β, 2, 6, 8, 10, tumor necrosis factor-α (TNF-α), and vascular endothelial growth factor (VEGF) levels were measured at baseline and 1-year. Correlation and quantile regression analyses were performed. The median TCP duration was 14 months. A significantly shorter TCP was associated with higher levels of TNF-α (P = 0.022) and VEGF (P = 0.016). A negative correlation was observed between TCP and TNF-α level (P = 0.006) and VEGF level (P = 0.04). Quantile regression indicated negative associations between TCP and GM-CSF levels below the 0.5 quantile, IL-10 levels below the 0.3 quantile, IL-2 levels below the 0.25 quantile, IL-6 levels between the 0.65 and 0.75 quantiles, TNF-α levels below the 0.8 quantile, and VEGF levels below the 0.7 quantile. A mixed linear effects model identified significant time effects for IL-10 and IL-2, and significant group effects for changes in IL-2 and TNF-α. Our findings underscore that a more pronounced baseline inflammatory state is associated with faster progression of psychosis in individuals with CHR. This highlights the importance of considering individual inflammatory profiles during early intervention and of tailoring preventive measures for risk profiles.

Effects of COVID-19 on Living Standards of Households in the North East Region of Ghana: A Linear Mixed Effects Model Approach

Abstract The world was severely hit by the novel coronavirus (COVID-19) in the latter part of 2019. The coronavirus is an ongoing global pandemic caused by severe acute respiratory syndrome coronavirus (SARS-CoV-2) and was first identified in Wuhan, China. The pandemic has devastated every sector of Ghana's economy and has significantly affected the living standards of people in the country. This study seeks to investigate the effects of COVID-19 on the living standards of households in Ghana using the North East Region as a case study. A sample of 399 respondents was drawn from the six (6) districts/municipalities using a single-stage cluster sampling technique. A linear mixed-effects model was used to investigate the fixed effects and the random effects in the study. Results from the study showed that variables such as the marital status of respondents, highest educational level of respondents, dependents, and employment status of respondents had significant fixed effects on the living standard of households in the Region. Overall, the study results showed that COVID-19 had significantly affected most households which has resulted in deteriorating living standards making the overall living standards worse in the Region. It was recommended in the study that a similar investigation be carried out in other parts of the country to get a more holistic view of the effects of the pandemic.

Global epidemiology of severe fever with thrombocytopenia syndrome virus in human and animals: a systematic review and meta-analysis

Since the initial identification of the Severe Fever with Thrombocytopenia Syndrome (SFTS) in ticks in rural areas of China in 2009, the virus has been increasingly isolated from a diverse array of hosts globally, exhibiting a rising trend in incidence. This study aims to conduct a systematic analysis of the temporal and spatial distribution of SFTS cases, alongside an examination of the infection rates across various hosts, with the objective of addressing public concerns regarding the spread and impact of the disease. In this systematic review and meta-analysis, an exhaustive search was conducted across multiple databases, including PubMed, Web of Science, Embase, and Medline, CNKI, WanFang, and CQVIP. The literature search was confined to publications released between January 1, 2009, and May 29, 2023. The study focused on collating data pertaining to animal infections under natural conditions and human infection cases reported. Additionally, species names were unified using the National Center for Biotechnology Information (NCBI) database. The notification rate, notification death rate, case fatality rate, and infection rates (or MIR) were assessed for each study with available data. The proportions were pooled using a generalized linear mixed-effects model (GLMM). Meta-regressions were conducted for subgroup analysis. This research has been duly registered with PROSPERO, bearing the registration number CRD42023431010. We identified 5492 studies from database searches and assessed 238 full-text studies for eligibility, of which 234 studies were included in the meta-analysis. For human infection data, the overall pooled notification rate was 18.93 (95% CI 17.02-21.05) per ten million people, the overall pooled notification deaths rate was 3.49 (95% CI 2.97-4.10) per ten million people, and the overall pooled case fatality rate was 7.80% (95% CI 7.01%-8.69%). There was an increasing trend in notification rate and deaths rate, while the case fatality rate showed a significant decrease globally. Regarding animal infection data, among 94 species tested, 48 species were found to carry positive nucleic acid or antibodies. Out of these, 14 species were classified under Arthropoda, while 34 species fell under Chordata, comprising 27 Mammalia and 7 Aves. This systematic review and meta-analysis present the latest global report on SFTS. In terms of human infections, notification rates and notification deaths rates are on the rise, while the case fatality rate has significantly decreased. More SFTSV animal hosts have been discovered than before, particularly among birds, indicating a potentially broader transmission range for SFTSV. These findings provide crucial insights for the prevention and control of SFTS on a global scale. None.

Physician and informal care use explained by the Pediatric Quality of Life Inventory (PedsQL) in children with suspected genetic disorders.

To examine associations between Pediatric Quality of Life Inventory (PedsQL) 4.0 Generic Core Scales and PedsQL Infant Scales with formal health care resource utilization (HCRU) and informal caregiver burden. We studied a pediatric cohort of 837 patients (median age: 8.4 years) with suspected genetic disorders enrolled January 2019 through July 2021 in the NYCKidSeq program for diagnostic sequencing. Using linked ~ nine-month longitudinal survey and physician claims data collected through May 2022, we modeled the association between baseline PedsQL scores and post-baseline HCRU (median follow-up: 21.1 months) and informal care. We also assessed the longitudinal change in PedsQL scores with physician services using linear mixed-effects models. Lower PedsQL total and physical health scores were independently associated with increases in 18-month physician services, encounters, and weekly informal care. Comparing low vs. median total scores, increases were 10.6 services (95% CI: 1.0-24.6), 3.3 encounters (95% CI: 0.5-6.8), and $668 (95% CI: $350-965), respectively. For the psychosocial domain, higher scores were associated with decreased informal care. Based on adjusted linear mixed-effects modeling, every additional ten physician services was associated with diminished improvement in longitudinal PedsQL total score trajectories by 1.1 point (95% confidence interval: 0.6-1.6) on average. Similar trends were observed in the physical and psychosocial domains. PedsQL scores were independently associated with higher utilization of physician services and informal care. Moreover, longitudinal trajectories of PedsQL scores became less favorable with increased physician services. Adding PedsQL survey instruments to conventional measures for improved risk stratification should be evaluated in further research.

Beneficial Effects of Synbiotics on the Gut Microbiome in Individuals with Low Fiber Intake: Secondary Analysis of a Double-Blind, Randomized Controlled Trial.

Insufficient dietary fiber intake can negatively affect the intestinal microbiome and, over time, may result in gut dysbiosis, thus potentially harming overall health. This randomized controlled trial aimed to improve the gut microbiome of individuals with low dietary fiber intake (<25 g/day) during a 7-week synbiotic intervention. The metabolically healthy male participants (n = 117, 32 ± 10 y, BMI 25.66 ± 3.1 kg/m2) were divided into two groups: one receiving a synbiotic supplement (Biotic Junior, MensSana AG, Forchtenberg, Germany) and the other a placebo, without altering their dietary habits or physical activity. These groups were further stratified by their dietary fiber intake into a low fiber group (LFG) and a high fiber group (HFG). Stool samples for microbiome analysis were collected before and after intervention. Statistical analysis was performed using linear mixed effects and partial least squares models. At baseline, the microbiomes of the LFG and HFG were partially separated. After seven weeks of intervention, the abundance of SCFA-producing microbes significantly increased in the LFG, which is known to improve gut health; however, this effect was less pronounced in the HFG. Beneficial effects on the gut microbiome in participants with low fiber intake may be achieved using synbiotics, demonstrating the importance of personalized synbiotics.

Plasma oxytocin levels in response to glucagon in patients with arginine vasopressin deficiency (central diabetes insipidus) and healthy controls

PurposeWe recently demonstrated an additional oxytocin (OT) deficiency in patients with arginine vasopressin (AVP) deficiency (central diabetes insipidus) by using 3,4-methylenedioxy-methamphetamine (MDMA) as a novel provocation test. However, the implication of the MDMA provocation test in clinical practice might be challenging. Glucagon effectively stimulates vasopressinergic neurons with a strong increase in plasma copeptin. We therefore hypothesized that this provocation test might also stimulate OT.MethodsThis is a predefined secondary analysis of a prospective double-blind, randomised, placebo-controlled cross-over trial involving ten patients with AVP deficiency and ten sex- and body-mass index-matched healthy participants at the University Hospital Basel, Switzerland. Each participant underwent the glucagon test (s.c. injection of 1 mg glucagon) and placebo test (s.c. injection of 0.9% normal saline). Plasma OT levels were measured at baseline, 60, 120 and 180 min after injection. The primary objective was to determine whether glucagon stimulates OT and whether OT levels differ between patients with AVP deficiency and healthy participants. The primary outcome (maximum change in OT within 180 min) was compared between groups and conditions using a linear mixed effects model.ResultsIn healthy participants, the median OT at baseline was 82.7 pg/ml [62.3–94.3] and slightly increased to a maximum of 93.3 pg/ml [87.2–121.1] after injection of glucagon, resulting in a change increase of 24.9 pg/ml [5.1–27.8]. Similarly, in patients with AVP deficiency, the median OT at baseline was 73.9 pg/ml [65.3–81.6] and slightly increased after glucagon injection to 114.9 pg/ml [70.9–140.9], resulting in a change increase of 36.8 pg/ml [–2.2 to 51.2]. The results from the mixed model showed no effect between glucagon compared to placebo on OT (difference: –0.5 pg/ml; 95%-CI [–25, 24]; p = 0.97) and no significant treatment-by-group interaction effect between patients compared to healthy participants (interaction: 28 pg/ml; 95%-CI [–7, 62]; p = 0.13).ConclusionWe found no effect of glucagon on plasma OT levels and no difference between patients with AVP deficiency and healthy participants.

Progressive worsening of posttraumatic stress symptoms in Syrian and Iraqi refugees associated with cumulative and victimization trauma: A longitudinal study.

War and forced migration expose refugees to trauma and ongoing stress, often contributing to long-term psychological consequences. Typically, trauma exposure is assessed cumulatively; yet, trauma type may better predict psychological outcomes. This study examined the differential impact of cumulative trauma and trauma subtypes (victimization, death threat, accidental/injury) on postmigration trajectories of posttraumatic stress and anxiety in refugees. Seventy-seven Syrian (88.3%) and Iraqi (9.1%) adult refugees self-reported prior trauma exposure and psychological symptoms at time of arrival in the United States and 2 years post. Linear mixed-effects modeling was performed to assess for associations between trauma variables and symptom trajectories. Models using cumulative trauma as a predictor were compared to models including the three trauma subtype variables as predictors, using pseudo-R² values to compare variance explained between the two methods of trauma measurement. Linear mixed-effects modeling indicated that prior exposure to victimization predicted progressively worsening posttraumatic stress disorder (PTSD) symptoms over time postmigration (b = .97, SE = .45, t = 2.14, p = .036). Cumulative trauma also predicted increasing PTSD symptoms (b = .124, SE = .06, t = 2.09, p = .041), but explained less variance than victimization (9% vs. 18.1%). Direct effects of cumulative trauma (p = .009) and victimization (p = .002) on anxiety severity emerged; however, anxiety symptoms did not change over time depending on prior trauma exposure. Accidents/injuries and death threats did not predict PTSD or anxiety. These findings can be leveraged toward focused identification of those at highest risk for progressive illness postmigration, thus providing empirical guidance for allocation of interventions and resources for refugees. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Lemann Index for Assessing Bowel Damage in Crohn’s Disease: A Real-world Study

Abstract Background and Aims The Lemann Index [LI], an endpoint to measure cumulative structural bowel damage in Crohn’s disease [CD], has been recently updated and validated. We applied this to investigate predictors of bowel damage in a real-world cohort. Methods We performed a retrospective study [2008–2022] involving two tertiary referral IBD centres in the USA. Magnetic resonance imaging [MR] or computed tomography [CT] enterographies were reviewed by study radiologists with endoscopy reports by study gastroenterologists, to calculate LI scores. Baseline and follow-up LI scores were calculated. We defined high bowel damage as LI ≥ 2. Factors associated with high LI were identified in patients with ≥ 2 LI scores, using multivariate logistic regression, and then assessed for a change in LI [increase vs no change/decrease], using a multivariate linear mixed-effects model. Results A total of 447 patients with CD had a median first LI of 7 (interquartile range [IQR], 1.25–14.55). Median LI scores were significantly different when categorised by disease duration; 2.0 [IQR, 0.6–5.9] for &amp;lt; 2 years, 2.6 [IQR, 0.6–9.6] for ≥ 2 and &amp;lt; 10 years, and 12.5 [IQR, 6.4–21.5] for ≥ 10 years, with a p &amp;lt; 0.01. Disease duration, presence of perianal disease, elevated C-reactive protein, and Harvey–Bradshaw index, were associated with a high LI at inclusion and increase in LI during follow-up [all p &amp;lt; 0.01]. Conclusions The updated LI quantified cross-sectional and longitudinal cumulative bowel damage in a real-world cohort of patients with CD, with predictors identified for a longitudinal increase in LI. Further studies for prospective validation of LI and identification of multi-omic predictors of bowel damage are needed.

Value of MRI - T2 Mapping to Differentiate Clinically Significant Prostate Cancer.

Standardized reporting of multiparametric prostate MRI (mpMRI) is widespread and follows international standards (Pi-RADS). However, quantitative measurements from mpMRI are not widely comparable. Although T2 mapping sequences can provide repeatable quantitative image measurements and extract reliable imaging biomarkers from mpMRI, they are often time-consuming. We therefore investigated the value of quantitative measurements on a highly accelerated T2 mapping sequence, in order to establish a threshold to differentiate benign from malignant lesions. For this purpose, we evaluated a novel, highly accelerated T2 mapping research sequence that enables high-resolution image acquisition with short acquisition times in everyday clinical practice. In this retrospective single-center study, we included 54 patients with clinically indicated MRI of the prostate and biopsy-confirmed carcinoma (n = 37) or exclusion of carcinoma (n = 17). All patients had received a standard of care biopsy of the prostate, results of which were used to confirm or exclude presence of malignant lesions. We used the linear mixed-effects model-fit by REML to determine the difference between mean values of cancerous tissue and healthy tissue. We found good differentiation between malignant lesions and normal appearing tissue in the peripheral zone based on the mean T2 value. Specifically, the mean T2 value for tissue without malignant lesions was (151.7ms [95% CI: 146.9-156.5ms] compared to 80.9ms for malignant lesions [95% CI: 67.9-79.1ms]; p < 0.001). Based on this assessment, a limit of 109.2ms is suggested. Aditionally, a significant correlation was observed between T2 values of the peripheral zone and PI-RADS scores (p = 0.0194). However, no correlation was found between the Gleason Score and the T2 relaxation time. Using REML, we found a difference of -82.7ms in mean values between cancerous tissue and healthy tissue. We established a cut-off-value of 109.2ms to accurately differentiate between malignant and non-malignant prostate regions. The addition of T2 mapping sequences to routine imaging could benefit automated lesion detection and facilitate contrast-free multiparametric MRI of the prostate.

Traumatic Cervical Spinal Cord Injury and Income and Employment Status

Spinal cord injury (SCI) causes drastic changes to an individual's physical health that may be associated with the ability to work. To estimate the association of SCI with individual earnings and employment status using national administrative health databases linked to income tax data. This was a retrospective, national, population-based cohort study of adults who were hospitalized with cervical SCI in Canada between January 2005 and December 2017. All acute care hospitalizations for SCI of adults ages 18 to 64 years were included. A comparison group was constructed by sampling from individuals in the injured cohort. Fiscal information from their preinjury years was used for comparison. The injured cohort was matched with the comparison group based on age, sex, marital status, province of residence, self-employment status, earnings, and employment status in the year prior to injury. Data were analyzed from August 2022 to January 2023. The first outcome was the change in individual annual earnings up to 5 years after injury. The change in mean yearly earnings was assessed using a linear mixed-effects differences-in-differences regression. Income values are reported in 2022 Canadian dollars (CAD $1.00 = US $0.73). The second outcome was the change in employment status up to 5 years after injury. A multivariable probit regression model was used to compare proportions of individuals employed among those who had experienced SCI and the paired comparison group of participants. A total of 1630 patients with SCI (mean [SD] age, 47 [13] years; 1304 male [80.0%]) were matched to patients in a preinjury comparison group (resampled from the same 1630 patients in the SCI group). The mean (SD) of preinjury wage earnings was CAD $46 000 ($48 252). The annual decline in individual earnings was CAD $20 275 (95% CI, -$24 455 to -$16 095) in the first year after injury and CAD $20 348 (95% CI, -$24 710 to -$15 985) in the fifth year after injury. At 5 years after injury, 52% of individuals who had an injury were working compared with 79% individuals in the preinjury comparison group. SCI survivors had a decrease in employment of 17.1 percentage points (95% CI, 14.5 to 19.7 percentage points) in the first year after injury and 17.8 percentage points (14.5 to 21.1 percentage points) in the fifth year after injury. In this study, SCI was associated with a decline in earnings and employment up to 5 years after injury for adults aged 18 to 64 years in Canada.

Dissecting heritability, environmental risk, and air pollution causal effects using > 50 million individuals in MarketScan

Large national-level electronic health record (EHR) datasets offer new opportunities for disentangling the role of genes and environment through deep phenotype information and approximate pedigree structures. Here we use the approximate geographical locations of patients as a proxy for spatially correlated community-level environmental risk factors. We develop a spatial mixed linear effect (SMILE) model that incorporates both genetics and environmental contribution. We extract EHR and geographical locations from 257,620 nuclear families and compile 1083 disease outcome measurements from the MarketScan dataset. We augment the EHR with publicly available environmental data, including levels of particulate matter 2.5 (PM2.5), nitrogen dioxide (NO2), climate, and sociodemographic data. We refine the estimates of genetic heritability and quantify community-level environmental contributions. We also use wind speed and direction as instrumental variables to assess the causal effects of air pollution. In total, we find PM2.5 or NO2 have statistically significant causal effects on 135 diseases, including respiratory, musculoskeletal, digestive, metabolic, and sleep disorders, where PM2.5 and NO2 tend to affect biologically distinct disease categories. These analyses showcase several robust strategies for jointly modeling genetic and environmental effects on disease risk using large EHR datasets and will benefit upcoming biobank studies in the era of precision medicine.

Sows and piglets adjust their use of an outdoor paddock with season and piglet age during the first weeks of life in an organic farm

Few studies have examined sows and piglets' use of outdoor access during their first weeks of life, when reared with access to a hut and a pasture as in the organic system. We studied whether the age of the piglets and the season of the year influenced the use of an outdoor area by piglets and the sow, and the use of indoor spaces. For this, the localisation of sows and their piglets inside and outside the hut was analysed on 16 sows and their litters during the summer and 16 others during the winter, by scan sampling, on days 2, 7 and 13 after parturition in an organic herd in Denmark. When inside the hut, the number of piglets in the creep area, next to the sow or other piglets was noted. All parameters were analysed by linear mixed-effects ANOVA models. Sows were less often observed outside the hut in the wintertime and during the mornings compared to later times of the day (P<0.001). Furthermore, the sows increased their outdoor use with the age of their litter (P<0.001). The season also influenced the piglet use of outdoor areas (winter < summer; P<0.001). Piglets that were observed outside for the first time were older (8.9±0.9 d) during winter than during summer (3.5±0.5 d). The proportion of piglets observed outside increased with age, with a significant Season x Age interaction (P<0.001). The proportion of observations where the sows and piglets were outdoors together increased with the piglets’ age (P < 0.001). Sows’ outing was correlated with summer (R=0.3) and winter (R=0.2) temperatures, unlike piglets, where outings were correlated only with summer temperatures (R=0.3, P<0.001). The proportion of piglets observed in the creep area was significantly affected by the age with a Season x Age interaction effect (P<0.001). Piglets were rarely observed lying alone inside the hut. The proportion of piglets in contact with the sow and other piglets inside the pen was influenced by a significant Age x Season interaction effect (P<0.001). We showed that piglets given access to an outside paddock gradually increase their use with age and don’t go outside right away. Their first exit and the proportion of piglets outside depended also on the season. In general, a higher proportion of sows and piglets were observed indoor during the wintertime. Thus, sows and piglets adjust their use of outdoor paddock with season and piglet age during the first weeks of life.

Just Keep Spinning? The Impact of Auditory and Somatosensory Cues on Rotary Chair Testing.

The purpose of this study was to determine whether providing realistic auditory or somatosensory cues to spatial location would affect measures of vestibulo-ocular reflex gain in a rotary chair testing (RCT) context. This was a fully within-subject design. Thirty young adults age 18-30 years (16 men, 14 women by self-identification) completed sinusoidal harmonic acceleration testing in a rotary chair under five different conditions, each at three rotational frequencies (0.01, 0.08, and 0.32 Hz). We recorded gain as the ratio of the amplitude of eye movement to chair movement using standard clinical procedures. The five conditions consisted of two without spatial information (silence, tasking via headphones) and three with either auditory (refrigerator sound, tasking via speaker) or somatosensory (fan) information. Two of the conditions also included mental tasking (tasking via headphones, tasking via speaker) and differed only in terms of the spatial localizability of the verbal instructions. We used linear mixed-effects modeling to compare pairs of conditions, specifically examining the effects of the availability of spatial cues in the environment. This study was preregistered on Open Science Framework (https://osf.io/2gqcf/). Results showed significant effects of frequency in all conditions (p < .05), but the only pairs of conditions that were significantly different were those including tasking in one condition but not the other (e.g., tasking via headphones vs. silence). Post hoc equivalence testing showed that the lack of significance in the other comparisons could be confirmed as not meaningfully different. These findings suggest that the presence of externally localizable sensory information, whether auditory or somatosensory, does not affect measures of gain in RCT to any relevant degree. However, these findings also contribute to the increasing body of evidence suggesting that mental engagement ("tasking") does increase gain whether or not it is provided via localizable instructions.

Social drivers of health in communicative outcomes of racially and ethnically minoritized autistic adolescents and adults.

Despite their importance, little is known about how social drivers of health shape communicative outcomes in autism. Even less is known when considering the intersection of race and language impairment. An understanding of factors in communicative outcomes is key for characterizing developmental trajectories and informing supports. This cross-sectional observational study examined the role of social drivers of health in communicative outcomes of racially and ethnically minoritized autistic adolescents and adults. Participants ages 13 to 30 (N = 73) completed a behavioral assessment protocol, including language and nonverbal cognitive skills, as well as social drivers of health (sense of community, unmet services, barriers to services). Correlational analyses revealed associations between social drivers of health on social communication impairment and real-world communication. Generalized linear mixed-effects modeling revealed that language predicted real-world communication, but sense of community predicted social communication impairment. Findings point to the importance of assessing both individual differences and social drivers of health in outcomes in autism research. Future work should focus on social drivers of health in larger-scale analyses of outcomes in minoritized autistic individuals during the transition to adulthood, considering supports that align with service eligibility and person-centered outcomes.