Mixed-effects Linear Regression Research Articles

Correlations of Corneal Endothelial Morphology and Corneal Thickness With Anterior Segment Parameters in Healthy Individuals.

The purpose of this study was to investigate the associations between central corneal endothelial cell density (ECD), endothelial morphology, and corneal thickness (central corneal thickness) with the anterior chamber depth, corneal volume (CV), white-to-white (WTW) distance, mean anterior chamber angle (CAmean), and gender in healthy individuals. This observational study included 136 healthy volunteers. The ECD, coefficient of variation of cell area, and hexagonal cell appearance ratio (%Hex) were measured by means of specular microscopy. The central corneal thickness, anterior chamber depth, CV, WTW distance, and the angle width of 12 points were taken by the Pentacam HR Scheimpflug anterior segment imaging. The arithmetical mean of the 12 points was considered as the CAmean. We used mixed effect linear regression model for the statistical analysis of the data. ECD was positively correlated with CV ( P = 0.028), while after adjusting for age, it was negatively correlated with age ( P < 0.001). Coefficient of variation of cell area was positively correlated with CAmean ( P = 0.036), while after adjusting for age, it was positively correlated with age ( P < 0.001) and CAmean ( P = 0.005). Hex was negatively correlated with WTW ( P = 0.023) and CAmean ( P = 0.025), and after adjusting for age, this correlation remained the same ( P = 0.029 when correlated with WTW and P = 0.035 with CAmean). There were significant changes in the morphology of the corneal endothelial cells in eyes with wider anterior chamber angle. Greater pleomorphism and polymegethism of the corneal endothelium was observed in healthy patients with wider CAmean. Deepening of the anterior chamber as myopia progresses could render the corneal endothelium more fragile and susceptible to mechanical stress, which is an area worthy of further study.

What variables predict stigmatizing attitudes toward people with mental disorders and their treatment in Filipinos and Americans?

In the United States, Asian Americans express greater stigma toward those with mental disorders and report lower rates of seeking mental health treatment than do White Americans. However, research on these topics in Filipino cultural groups, especially Filipinos living in the Philippines (i.e., Filipino nationals), is sparse. To support the design of interventions to decrease stigma and improve rates of seeking treatment, we assessed attitudes toward mental disorders and help-seeking in Filipinos. U.S. national (i.e., American) and Filipino national participants completed an online survey containing the Mental Illness Stigma Scale, a Theory of Planned Behavior questionnaire measuring attitudes toward seeking treatment, and queries regarding demographic and psychosocial factors. Filipinos expressed significantly more stigma regarding relationship disruption, interpersonal anxiety, and poor hygiene, alongside increased perceived subjective norms opposing seeking treatment and decreased perceived behavioral control over getting treatment if necessary. We ran a linear mixed effects regression on each nationality separately to identify relationships between stigma and psychosocial factors. For Filipinos, increased parental education predicted decreased perceived relationship disruption and interpersonal anxiety; urbanization was associated with greater trust in mental health professionals, and having a close relative with a disorder led to decreased belief in patient recoverability. For Americans, increased participant education predicted decreased interpersonal anxiety, increased perceived recoverability, and improved perceived behavioral control over getting treatment if necessary, and having a close relative with a disorder predicted improved perceived treatability. The results guide programs for decreasing stigma and increasing treatment-seeking behavior. Limitations, future research directions, and possible interventions are discussed.

Serologic responses to the MVA-based JYNNEOS mpox vaccine in a cohort of participants from the District of Columbia (D.C.)

We assessed early antibody responses after two doses of JYNNEOS (IMVANEX) mpox vaccine in the District of Columbia (D.C.) in persons at high risk for mpox without characteristic lesions or rash. Participants with PCR mpox negative specimens (oral swab, blood, and/or rectal swab) on the day of receipt of the first vaccine dose and who provided a baseline (day 0) serum sample and at least one serum sample at ∼28, ∼42–56 days, or 180 days post vaccination were included in this analysis. Orthopoxvirus (OPXV)-specific IgG and IgM ELISAs and neutralizing antibody titers were performed, and longitudinal serologic responses were examined. Based on participants’ IgG and IgM antibody levels at baseline, they were categorized as naïve or non-naïve. Linear mixed effects regression models were conducted to determine if IgG antibody response over time varied by age, sex, HIV status, and route of administration for both naïve and non-naïve participants. Among both naïve and non-naïve participants IgG seropositivity rates increased until day 42–56, with 89.4 % of naïve and 92.1 % of non-naïve participants having detectable IgG antibodies. The proportion of naive participants with detectable IgG antibodies declined by day 180 (67.7 %) but remained high among non-naïve participants (94.4 %). Neutralizing antibody titers displayed a similar pattern, increasing initially post vaccination but declining by day 180 among naïve participants. There were no significant serologic response differences by age, sex, or HIV status. Serologic response did vary by route of vaccine administration, with those receiving a combination of intradermal and subcutaneous doses displaying significantly higher IgG values than those receiving both doses intradermally. These analyses provide initial insights into the immunogenicity of a two-dose JYNNEOS PEP regimen in individuals at high risk of mpox exposure in the United States.

Determinants and practice variability of oxygen administration during surgery in the U.S., a retrospective cohort study.

The best approaches to supplemental oxygen administration during surgery remain unclear, which may contribute to variation in practice. We aimed to assess determinants of oxygen administration and its variability during surgery. Using multivariable linear mixed-effects regression, we measured the associations between intraoperative fraction of inspired oxygen and patient, procedure, medical center, anesthesiologist, and in-room anesthesia provider factors in surgical cases of 120 minutes or longer in adult patients who received general anesthesia with tracheal intubation and were admitted to the hospital after surgery between January 2016 and January 2019 at 42 medical centers across the U.S. participating in the Multicenter Perioperative Outcomes Group data registry. The sample included 367,841 cases (median [25 th, 75 th] age, 59 [47, 69] years; 51.1% women; 26.1% treated with nitrous oxide) managed by 3,836 anesthesiologists and 15,381 in-room anesthesia providers. Median (25 th, 75 th) fraction of inspired oxygen was 0.55 (0.48, 0.61), with 6.9% of cases <0.40 and 8.7% >0.90. Numerous patient and procedure factors were statistically associated with increased inspired oxygen, notably advanced ASA classification, heart disease, emergency surgery, and cardiac surgery, but most factors had little clinical significance (<1% inspired oxygen change). Overall, patient factors only explained 3.5% (95% CI, 3.5 to 3.5) of the variability in oxygen administration and procedure factors 4.4% (4.2 to 4.6). Anesthesiologist explained 7.7% (7.2 to 8.2) of the variability in oxygen administration, in-room anesthesia provider 8.1% (7.8 to 8.4), medical center 23.3% (22.4 to 24.2), and 53.0% (95% CI, 52.4 to 53.6) was unexplained. Among adults undergoing surgery with anesthesia and tracheal intubation, supplemental oxygen administration was variable and appeared arbitrary. Most patient and procedure factors had statistical but minor clinical associations with oxygen administration. Medical center and anesthesia provider explained significantly more variability in oxygen administration than patient or procedure factors.

Primary Care Organizational Support for Nurse Practitioner Practice and Emotional Health Care Delivery.

Nurse practitioners (NPs) are key to delivery of primary care services. However, poor organizational support for independent NP practice, such as lack of access to clinic resources, may lead to prioritizing patient physical health over emotional health. We investigated the relationship between organizational support for independent NP practice and emotional health care delivery. This was a secondary analysis of cross-sectional survey data collected from 397 NPs in 2017. We measured organizational support for independent NP practice using the independent practice and support subscale of the NP Primary Care Organizational Climate Questionnaire. Emotional health care delivery was measured by asking NPs how frequently they addressed emotional concerns of patients. We utilized multilevel mixed effects linear regression models, adjusting for NP and practice covariates. Controlling for NP age, gender, marital status, race, and ethnicity, along with practice setting and size, as the independent practice and support score increased, NPs reported addressing emotional concerns of patients more frequently (beta = 0.34, 95% confidence interval = 0.02-0.66, P = 0.04). This indicates that as organizations provided more support for independent NP practice, NPs were able to more frequently address emotional concerns of patients. Organizational support for independent NP practice is associated with addressing emotional concerns of patients. To support NP practice, primary care organizations should ensure that NPs manage patients independently and have access to ancillary staff and support for care management.

Psychological distress over 12 months post-diagnosis in an early inflammatory arthritis cohort.

People with inflammatory arthritis (IA) experience worsened mental wellbeing alongside disease progression. Using the National Early Inflammatory Arthritis Audit (NEIAA), we assessed trends in psychological distress during 12-months following IA diagnosis, mapping these against clinical outcomes to identify associations. This is a prospective study of people recruited to NEIAA receiving an IA diagnosis and completing the baseline patient survey. Patient reported outcomes (PROs) at baseline, 3-months and 12-months were collected, including psychological distress (assessed using Patient Health Questionnaire Anxiety and Depression Screener (PHQ4ADS)). Mixed effects linear regression models estimated associations between predictor variables with psychological distress at baseline and over time. Of 6,873 eligible patients, 3,451 (50.2%) showed psychological distress at baseline. Of those completing follow-ups, 30.0% and 24.1% were distressed at 3-months and 12-months, respectively. Higher psychological distress at diagnosis was more commonly reported by younger, female, and non-white patients. Clinical factors, including higher counts of comorbidities, prior depression, and higher disease activity at diagnosis were associated with higher distress. Higher distress at baseline was associated with poorer outcomes over time in quality of life, disability, work performance, disease activity, as well as reduced likelihood of achieving good treatment response by EULAR criteria. Half of patients with IA show significant mental health comorbidity at presentation, which associated with worse disease outcomes and quality of life. Screening for anxiety and depression should be a universal standard, and access to effective mood therapies alongside arthritis treatments is essential. Strategies should be culturally valid and consider multi-morbidities.

A phase I/II clinical trial of ex-vivo expanded human bone marrow derived allogeneic mesenchymal stromal cells in adult patients with perianal fistulizing Crohn’s Disease

BackgroundPerianal fistulas (PF) affect one-third patients with Crohn’s disease (CD) with limited therapeutic options. There is dearth of literature on safety and efficacy of bone marrow-derived mesenchymal stromal cells (BMSCs) in this population.MethodsAn open-label, phase I/II, single-arm study was conducted involving local administration of human allogeneic bone marrow-derived mesenchymal stromal cells in perianal fistula of patients with Crohn’s disease refractory to standard therapies. Clinical severity and biomarkers were assessed at baseline and periodically until week 104 , and MRI at week 24 and 104. Primary and secondary objectives were to assess safety and efficacy respectively. Fistula remission was complete closure of fistula openings with < 2 cm perianal collection on MRI, and fistula response was decrease in drainage by ≥ 50%. Change in perianal disease activity index, quality-of-life and Van Assche index on MRI over time was assessed using mixed-effect linear regression model.ResultsTen patients (male:8, mean age:27.4 ± 12.0years) were recruited. Self-resolving procedure-related adverse events occurred in three patients, with no follow-up adverse events. In intention to treat analysis at week 24, two patients (20%) achieved fistula remission and seven (70%) had fistula response. At week 52, two (20%) patients were in remission and seven (70%) maintained response. At 104 weeks, two (20%) patients maintained response and one (10%) was in remission. Statistically significant decrease in perianal disease activity index (P = 0.008), Van Assche Index (P = 0.008) and improvement in quality-of-life (P = 0.001) were observed over time.ConclusionsAllogeneic BMSCs are safe and effective for the treatment of perianal fistulizing CD with significant improvement in clinical severity and radiological healing.Trial registrationThe study was prospectively registered on Clinical trials registry – India (CTRI), CTRI/2020/01/022743 on 14 January 2020, http://ctri.nic.in.

Long-term sustained effects of the Look AHEAD lifestyle intervention on body composition among adults with type 2 diabetes.

The objective of the study was to test whether there are sustained effects of the Look AHEAD intensive lifestyle intervention (ILI), versus diabetes support and education (DSE), on weight and body composition 12 to 16 years after randomization. Participants were a subset of enrollees in the Look AHEAD dual-energy x-ray absorptiometry substudy who completed the final visit, composed of men (DSE = 99; ILI = 94) and women (DSE = 134; ILI = 135) with type 2 diabetes and mean (SD) age 57.2 (6.4) years and BMI 34.9 (5.1) kg/m2 at randomization. Dual-energy x-ray absorptiometry measured total and regional fat and lean masses at randomization, at Years 1, 4, and 8, and at the final visit. Linear mixed-effects regressions were applied with adjustment for group, clinic, sex, age, race/ethnicity, and baseline body composition. Weight and most body compartments were reduced by 2% to 8% (and BMI 4%) in ILI versus DSE in men but not women. ILI-induced loss of lean tissue did not show a lower percent lean mass versus DSE at 16 years after randomization. ILI-related changes in weight, fat, and lean mass were detectable 12 to 16 years after randomization in men but, for unknown reasons, not in women. There was no evidence that the intervention led to a disproportionate loss of lean mass by the end of the study.

Associations Between Midlife Anticholinergic Medication Use and Subsequent Cognitive Decline: A British Birth Cohort Study.

Anticholinergic medication use is associated with cognitive decline and incident dementia. Our study, a prospective birthcohortanalysis, aimed to determine if repeated exposure to anticholinergic medicationswas associated with greater decline, and whether decline was reversed with medication reduction. From the Medical Research Council (MRC) National Survey of Health and Development, a British birth cohort with all participants born in a single week of March 1946, we quantified anticholinergic exposure between ages 53 and 69 years using the Anticholinergic Cognitive Burden Scale (ACBS). We used multinomial regression to estimate associations with global cognition, quantified bythe Addenbrooke's Cognitive Examination, 3rd Edition (ACE-III). Longitudinal associations between ACBS and cognitive test results (Verbal memory quantifiedby theWord Learning Test [WLT], and processing speed quantified by theTimed Letter Search Task [TLST]) at three time points (age 53, 60-64 and 69) were assessed using mixed and fixed effects linear regression models. Analyses were adjusted for sex, childhood cognition, education, chronic disease count and severity, and mental health symptoms. Anticholinergic exposure was associated cross-sectionally with lower ACE-III scores at age 69, with the greatest effects in those with high exposure at ages 60-64 (mean difference - 2.34, 95% confidence interval [CI] - 3.51 to - 1.17). Longitudinally, both mild-moderate and high ACBS scores were linked to lower WLT scores, again with high exposure showing larger effects (mean difference with contemporaneous exposure - 0.90, 95% CI - 1.63 to - 0.17; mean difference with lagged exposure - 1.53, 95% CI - 2.43 to - 0.64). Associations remained in fixed effects models (mean difference with contemporaneous exposure -1.78, 95% CI -2.85 to - 0.71; mean difference with lagged exposure - 2.23, 95% CI - 3.33 to - 1.13). Associations with TLST were noted only in isolated contemporaneous exposure (mean difference - 13.14, 95% CI - 19.04 to - 7.23; p<0.01). Anticholinergic exposure throughout mid and later life was associated with lower cognitive function. Reduced processing speed was associated only with contemporaneous anticholinergic medication use, and not historical use. Associations with lower verbal recall were evident with both historical and contemporaneous use of anticholinergic medication, and associations with historical use persisted in individuals even when their anticholinergic medication use decreased over the course of the study.

Comparison of nursing staffing ratio in selected safety net and non-safety net hospitals in the United States

Comparison of nursing staffing ratio in selected safety net and non-safety net hospitals in the United States

Occurrence and characteristics of suicidal ideation in psychiatrically healthy individuals based on ecological momentary assessment.

Decedents with no known mental disorder comprise 5-40% of suicides, suggesting that suicide ideation (SI) and behavior may occur in the psychiatrically healthy with important implications for suicide risk screening. Healthy Volunteers (HV) and patients with Major Depressive Disorder (MDD) provided 7 days of Ecological Momentary Assessment (EMA) data about SI and stressors. Longitudinal mixed effects logistic regression models compared HV and patient SI and stressors. Mixed effects linear regression models compared HVs' and patients' SI score change from the previous epoch's SI score when each stressor occurred. HVs (n = 42) reported less frequent (p < 0.001) and less intense SI (p < 0.003) than patients (n = 80), yet did endorse SI and/or SI-related items in 44% of EMA epochs, endorsing SI items in 25% of epochs with non-zero SI scores. For 7 of 8 stressors, patients reported stressors more often than HVs (all p < 0.001) responding to them with increased SI (0.0001 < p < 0.0472). HVs were relatively resilient to stressors, reporting SI increases only in response to neglect (p < 0.0147). Although SI and SAs are documented among psychiatrically healthy individuals, scientific attention to these observations has been scant. Real-time SI measurement showed that HVs' SI was less pronounced than MDD patients', but was endorsed, nonetheless. Patients were more likely to report stressors than HVs, perhaps due to greater sensitivity to the environment, and reported SI in response to stressors, which was less common in HVs. Both MDD patients and HVs most often manifested passive SI (viz, "decreased wish to live"). However, passive SI (viz, "desire for death"), may predict suicide, even absent SI per se (thinking about killing yourself). This study validates the utility of real-time SI assessment, showing that HVs endorse SI items in 11% of epochs, which implies that suicide risk screening focused on those with mental disorders may be too narrow an approach.

Mitral Annular Disjunction and Its Progression during Childhood in Marfan Syndrome.

Data on mitral annular disjunction (MAD) in children with Marfan syndrome (MFS) are sparse. To investigate the diagnostic yield of MAD by echocardiography and cardiac magnetic resonance imaging (CMR), its prevalence and progression during childhood. We included patients <21 years old with MFS, defined by 2010 Ghent criteria and a pathogenic FBN1 variant or ectopia lentis. Two readers measured systolic separation between the mitral valve (MV) posterior hinge point and left ventricular (LV) myocardium on initial and subsequent imaging. MAD was defined as MV-LV separation ≥2 mm, MV prolapse (MVP) as atrial displacement ≥2 mm. Kappa coefficients evaluated echocardiogram-CMR agreement. Bland-Altman and intraclass correlation coefficients (ICC) assessed interrater and intermodality reliability. Univariable mixed-effects linear regression was used to evaluate longitudinal changes of MAD. MAD was detected in 60% (110/185) eligible patients. MVP was present in 48% (53/110) of MAD and MAD in 90% (53/59) of MVP. MAD detection by CMR and echocardiography had 96% overall agreement (Kappa = 0.89, p < 0.001) and a 0.32-mm estimate bias (95%CI 0.00, 0.65). ICC by echocardiography, CMR, and between modalities were 0.97 (95%CI 0.93, 0.98), 0.92 (95%CI 0.79, 0.97), and 0.91 (95%CI 0.85, 0.94), respectively. MAD was associated with aortic root dilation (p < 0.001). MAD was found in children of all ages, increased +0.18 mm/year (95%CI +0.14, + 0.22) during a median duration of 5.5 years (IQR 3.1, 7.5 years). MAD indexed by height yielded a constant value +0.0002 mm/m/year (95%CI -0.0002, + 0.0005 mm/m/year). MAD was common in pediatric MFS and was associated with aortic root dilation. MAD detection by echocardiography and CMR was highly reliable, suggesting that routine assessment in MFS is feasible. MAD was present in neonates and progressed over time but remained constant when indexing by height. Further studies are needed to evaluate MAD as a biomarker for clinical outcomes in pediatric MFS.

Acute Hyperglycemia Induced by Hyperglycemic Clamp Affects Plasma Amyloid-β in Type 2 Diabetes.

Individuals with type 2 diabetes (T2D) have an increased risk of cognitive symptoms and Alzheimer's disease (AD). Mis-metabolism with aggregation of amyloid-β peptides (Aβ) play a key role in AD pathophysiology. Therefore, human studies on Aβ metabolism and T2D are warranted. The objective of this study was to examine whether acute hyperglycemia affects plasma Aβ 1-40 and Aβ 1-42 concentrations in individuals with T2D and matched controls. Ten participants with T2D and 11 controls (median age, 69 years; range, 66-72 years) underwent hyperglycemic clamp and placebo clamp (saline infusion) in a randomized order, each lasting 4 hours. Aβ 1-40, Aβ 1-42, and insulin-degrading enzyme (IDE) plasma concentrations were measured in blood samples taken at 0 and 4 hours of each clamp. Linear mixed-effect regression models were used to evaluate the 4-hour changes in Aβ 1-40 and Aβ 1-42 concentrations, adjusting for body mass index, estimated glomerular filtration rate, and 4-hour change in insulin concentration. At baseline, Aβ 1-40 and Aβ 1-42 concentrations did not differ between the two groups. During the hyperglycemic clamp, Aβ decreased in the control group, compared to the placebo clamp (Aβ 1-40: p = 0.034, Aβ 1-42: p = 0.020), IDE increased (p = 0.016) during the hyperglycemic clamp, whereas no significant changes in either Aβ or IDE was noted in the T2D group. Clamp-induced hyperglycemia was associated with increased IDE levels and enhanced Aβ 40 and Aβ 42 clearance in controls, but not in individuals with T2D. We hypothesize that insulin-degrading enzyme was inhibited during hyperglycemic conditions in people with T2D.

Effectiveness of a mindfulness and acceptance-based intervention for improving the mental health of adolescents with HIV in Uganda: An open-label trial.

Adolescents with HIV (AWH) face the double burden of dealing with challenges presented by their developmental phase while coping with stigma related to HIV, affecting their mental health. Poor mental health complicates adherence to daily treatment regimens, requiring innovative psychosocial support strategies for use with adolescents. We assessed the effectiveness of a mindfulness and acceptance-based intervention on the mental health of AWH in Uganda. One hundred and twenty-two AWH, mean age 17 ±1.59 (range 15 to 19 years), 57% female, receiving care at a public health facility in Kampala were enrolled in an open-label randomized trial (ClinicalTrials.gov: NCT05010317) with assessments at pre-and post-intervention. The mindfulness and acceptance-based intervention involved weekly 90-minute group sessions for four consecutive weeks facilitated by two experienced trainers. Sessions involved clarifying values, skillfully relating to thoughts, allowing and becoming aware of experiences non-judgmentally, and exploring life through trial and error. The control group received the current standard of care. Three mental health domains (depression, anxiety, and internalized stigma) were compared between the intervention and control groups. A linear mixed effects regression was used to analyze the effect of the intervention across the two time points. Results showed that the intervention was associated with a statistically significant reduction in symptoms of depression (β = -10.72, 95%CI: 6.25, -15.20; p < .0001), anxiety (β = -7.55, 95%CI: 2.66, -12.43; p = .0003) and stigma (β = -1.40, 95%CI: 0.66 to -2.15; p = .0004) over time. Results suggest that mindfulness and acceptance-based interventions have the potential to improve the mental health of AWH.

Models to predict nitrogen excretion from beef cattle fed a wide range of diets compiled from South America.

The objective of this meta-analysis was to develop and evaluate models for predicting nitrogen (N) excretion in feces, urine, and manure in beef cattle in South America. The study incorporated a total of 1,116 individual observations of N excretion in feces and 939 individual observations of N excretion in feces and in urine (g/d), representing a diverse range of diets, animal genotypes, and management conditions in South America. The datasetalso included data on dry matter intake (DMI; kg/d) and nitrogen intake (NI; g/d), concentrations of dietary components, as well as average daily gain (ADG; g/d) and average body weight (BW; kg). Models were derived using linear mixed-effects regression with a random intercept for the study. Fecal N excretion was positively associated with DMI, NI, nonfibrous carbohydrates, average BW, and ADG and negatively associated with EE and CP concentration in the diet. The univariate model predicting fecal N excretion based on DMI (model 1) performed slightly better than the univariate model, which used NI as a predictor variable (model 2) with a root mean square error (RMSE) of 38.0 vs. 39.2%, the RMSE-observations SD ratio (RSR) of 0.81 vs. 0.84, and concordance correlation coefficient (CCC) of 0.53 vs. 0.50, respectively. Models predicting urinary N excretion were less accurate than those derived to predict fecal N excretion, with an average RMSE of 43.7% vs. 37.0%, respectively. Urinary and manure N excretion were positively associated with DMI, NI, CP, average BW, and ADG and negatively associated with neutral detergent fiber concentration in the diet. As opposed to fecal N excretion, the univariate model predicting urinary N excretion using NI (model 10) performed slightly better than the univariate model using DMI (model 9) as predictor variable with an RMSE of 36.0% vs. 39.7%, RSR 0.85 vs. 0.93, and CCC of 0.43 vs. 0.29, respectively. The models developed in this study are applicable for predicting N excretion in beef cattle across a broad spectrum of dietary compositions and animal genotypes in South America. The univariate model using DMI as a predictor is recommended for fecal N prediction, while the univariate model using NI is recommended for predicting urinary and manure N excretion because the use of more complex models resulted in little to no benefits. However, it may be more useful to consider more complex models that incorporate nutrient intakes and diet composition for decision-making when N excretion is a factor to be considered. Three extant equations evaluated in this study have the potential to be used in tropical conditions typical of South America to predict fecal N excretion with good precision and accuracy. However, none of the extant equations are recommended for predicting urine or manure N excretion because of their high RMSE, and low precision and accuracy.

Impact of deep learning image reconstruction on volumetric accuracy and image quality of pulmonary nodules with different morphologies in low-dose CT

BackgroundThis study systematically compares the impact of innovative deep learning image reconstruction (DLIR, TrueFidelity) to conventionally used iterative reconstruction (IR) on nodule volumetry and subjective image quality (IQ) at highly reduced radiation doses. This is essential in the context of low-dose CT lung cancer screening where accurate volumetry and characterization of pulmonary nodules in repeated CT scanning are indispensable.Materials and methodsA standardized CT dataset was established using an anthropomorphic chest phantom (Lungman, Kyoto Kaguku Inc., Kyoto, Japan) containing a set of 3D-printed lung nodules including six diameters (4 to 9 mm) and three morphology classes (lobular, spiculated, smooth), with an established ground truth. Images were acquired at varying radiation doses (6.04, 3.03, 1.54, 0.77, 0.41 and 0.20 mGy) and reconstructed with combinations of reconstruction kernels (soft and hard kernel) and reconstruction algorithms (ASIR-V and DLIR at low, medium and high strength). Semi-automatic volumetry measurements and subjective image quality scores recorded by five radiologists were analyzed with multiple linear regression and mixed-effect ordinal logistic regression models.ResultsVolumetric errors of nodules imaged with DLIR are up to 50% lower compared to ASIR-V, especially at radiation doses below 1 mGy and when reconstructed with a hard kernel. Also, across all nodule diameters and morphologies, volumetric errors are commonly lower with DLIR. Furthermore, DLIR renders higher subjective IQ, especially at the sub-mGy doses. Radiologists were up to nine times more likely to score the highest IQ-score to these images compared to those reconstructed with ASIR-V. Lung nodules with irregular margins and small diameters also had an increased likelihood (up to five times more likely) to be ascribed the best IQ scores when reconstructed with DLIR.ConclusionWe observed that DLIR performs as good as or even outperforms conventionally used reconstruction algorithms in terms of volumetric accuracy and subjective IQ of nodules in an anthropomorphic chest phantom. As such, DLIR potentially allows to lower the radiation dose to participants of lung cancer screening without compromising accurate measurement and characterization of lung nodules.

A Cadaveric Study: Does Ankle Positioning Impact the Quality of Anatomic Syndesmosis Reduction?

Objective: To compare the quality of syndesmotic reduction with the ankle in maximal dorsiflexion versus neutral plantarflexion (normal resting position). Methods: Baseline computed tomography (CT) imaging of 10 cadaveric ankle specimens from 5 donors was obtained with the ankles placed in normal resting position. Two fellowship-trained orthopaedic surgeons disrupted the syndesmosis of each ankle specimen. All ankles were then placed in neutral plantarflexion and were subsequently reduced with thumb pressure under direct visualization via an anterolateral approach and stabilized with one 0.062-inch K-wire placed from lateral to medial in a quadricortical fashion across the syndesmosis. Post-reduction CT scans were then obtained with the ankle in normal resting position. This process was repeated with the ankles placed in maximal dorsiflexion during reduction and stabilization. Post-reduction CT scans were then obtained with the ankles placed in normal resting position. All post-reduction CT scans were compared to baseline CT imaging using mixed-effects linear regression with significance set at p&lt;0.05. Results: Syndesmotic reduction and stabilization in maximal dorsiflexion led to increased external rotation of the fibula compared to baseline scans [13.0 degrees ± 5.4 degrees (mean ± SD) vs. 7.5 degrees ± 2.4 degrees, p=0.002]. There was a tendency towards lateral translation of the fibula with the ankle reduced in maximal dorsiflexion (3.3 mm ± 1.0 mm vs. 2.7 mm ± 0.7 mm, p=0.096). No other statistically significant differences between measurements of reduction with the ankle placed in neutral plantarflexion or maximal dorsiflexion compared to baseline were present (p&gt; 0.05). Conclusions: Reducing the syndesmosis with the ankle in maximal dorsiflexion may lead to malreduction with external rotation of the fibula. There was no statistically significant difference in reduction quality with the ankle placed in neutral plantarflexion compared to baseline. Future studies should assess the clinical implications of ankle positioning during syndesmotic fixation.

Smaller subcortical volume relates to greater weight gain in girls with initially healthy weight.

Among 3614 youth who were 9 to 12 years old and initially did not have overweight or obesity (12% [n = 385] developed overweight or obesity), we examined the natural progression of weight gain and brain structure development during a 2-year period with a high risk for obesity (e.g., pre- and early adolescence) to determine the following: 1) whether variation in maturational trajectories of the brain regions contributes to weight gain; and/or 2) whether weight gain contributes to altered brain development. Data were gathered from the Adolescent Brain Cognitive Development (ABCD) Study. Linear mixed-effects regression models controlled for puberty, caregiver education, handedness, and intracranial volume (random effects: magnetic resonance scanner [MRI] scanner and participant). Because pubertal development occurs earlier in girls, analyses were stratified by sex. For girls, but not boys, independent of puberty, greater increases in BMI were driven by smaller volumes over time in the bilateral accumbens, amygdala, hippocampus, and thalamus, right caudate and ventral diencephalon, and left pallidum (all p < 0.05). The results suggest a potential phenotype for identifying obesity risk because underlying differences among regions involved in food intake were related to greater weight gain in girls, but not in boys. Importantly, 2 years of weight gain may not be sufficient to alter brain development, highlighting early puberty as a critical time to prevent negative neurological outcomes.

Glycemic control during TB treatment among Filipinos: The Starting Anti-Tuberculosis Treatment Cohort Study.

Poor TB treatment outcomes are observed in patients with type 2 diabetes mellitus (DM) comorbidity and glycemic control throughout treatment may play a role. The objective of this study was to investigate glycemic control longitudinally among Filipino adults undergoing TB treatment using mixed-effects linear and logistic regression. Analyses were conducted in 188 DM-TB patients out of 901 enrolled in the Starting Anti-TB Treatment (St-ATT) cohort, with a median baseline glycosylated hemoglobin (HbA1c) of 8.2% (range 4.5-13.3%). Previous versus new DM diagnosis was associated with higher mean HbA1c (worse glycemic control) during treatment, with a smaller effect amongst those with central obesity (coefficient 0.80, 95% confidence interval [CI] 0.26, 1.57, P = 0.043) than amongst those without central obesity (coefficient 3.48, 95% CI 2.16, 4.80, P<0.001). In those with a new DM diagnosis, central obesity was associated with higher blood glucose (coefficient 1.62, 95% CI 0.72, 2.53, P = 0.009). Of 177 participants with ≥2 HbA1c results, 40% had uncontrolled glycemia (≥2 HbA1c results ≥8%). Of 165 participants with ≥3 HbA1c results, 29.9% had consistently-controlled glycemia, 15.3% had initially-uncontrolled glycemia, and 18.6% had consistently-uncontrolled glycemia. Previous versus new DM diagnosis and glucose-lowering medication use versus no use were associated with having uncontrolled versus controlled glycemia (adjusted odds ratio [aOR] 2.50 95%CI 1.61, 6.05, P = 0.042; aOR 4.78 95% CI 1.61,14.23, P<0.001) and more likely to have consistently-uncontrolled versus consistently-controlled glycemia (adjusted relative risk ratio [aRRR] 5.14 95% CI 1.37, 19.20, P = 0.015; aRRR 10.24 95% CI 0.07, 0.95, P = 0.003). Relapse cases of TB were less likely than new cases to have uncontrolled (aOR 0.20 95%CI 0.06, 0.63, P = 0.031) or consistently-uncontrolled (aRRR 0.25 95%CI 0.07, 0.95, P = 0.042) versus controlled glycemia. Those with long-term DM, suggested by previous diagnosis, glucose-lowering medication use and possibly central obesity, may require additional support to manage blood glucose during TB treatment.

Abstract PO4-12-08: Changes in peripheral immune cell composition in women who do and do not develop breast cancer

Abstract Background: Breast cancer survivors have higher age-specific rates of hypertension and other chronic diseases than women without a history of breast cancer. We and others have shown that alterations to the immune system are associated with risk of these conditions in the general population, leading to the hypothesis that the increased chronic disease risk in breast cancer survivors may be driven, in part, by lasting changes in immunity. Peripheral immune cell composition appears to become altered years before a breast cancer diagnosis, but little is currently known about the influence of different breast cancer treatments on subsequent changes to leukocyte composition and the persistence of these associations over time. Methods: Among 410 women enrolled in the Sister Study, paired blood samples collected an average of 7.6 years apart were analyzed for DNA methylation (DNAm). Deconvolution methods were applied to these DNAm data to estimate circulating percentages of 12 leukocyte subsets. Approximately half the women sampled were diagnosed and treated for breast cancer between the blood draws (n= 185) whereas the other half remained breast cancer-free (n= 225). Breast tumor characteristics and treatment information were abstracted from medical records. Mixed-effect linear regression models were used to estimate changes in leukocyte composition over time comparing women with breast cancer to those who remained breast cancer-free. A case-only analysis of breast cancer survivors was performed to examine the persistence of changes over time and to explore whether changes in leukocyte composition were associated with the types of therapies received (endocrine therapy, radiation therapy, chemotherapy). All models were adjusted for age and self-reported race. In the treatment analysis, because tumor characteristics can guide clinical decisions, tumor estrogen receptor status and stage at diagnosis were additionally included as model covariates. Results: At baseline, women who developed breast cancer between the blood draws had lower mean circulating percentages of CD8+ cytotoxic T cells than women who remained breast cancer-free (3.8% vs 4.6%; P-diff= 0.04). After accounting for differences in leukocyte composition at baseline, compared to women who remained breast cancer-free, women diagnosed and treated for breast cancer between the blood draws had decreases in total circulating CD4+ helper T cell percentage (adjusted mean difference [β]= -1.50, 95% CI: -2.56, -0.44, P= 0.006) and alterations to both naïve and memory B cell percentages (naïve B cells, β= 0.46, 95% CI: 0.17, 0.75, P= 0.002; memory B cells, β= -0.22, 95% CI: -0.34, -0.09, P= 0.001). Although associations did not vary by tumor characteristics or participant race, the changes in leukocyte composition appeared to persist over time as changes were not associated with time since diagnosis. In the case-only analysis of different breast cancer therapies, radiation was associated with decreases in CD4+ T cells (β= -2.56, 95% CI: -4.26, -0.88, P= 0.003) and chemotherapy was associated with increases in B cells (β= 0.62, 95% CI: 0.07, 1.16, P= 0.03). Surgery and endocrine therapy were not meaningfully associated with changes in leukocyte composition. Conclusions: Breast cancer survivors have lasting changes in peripheral leukocyte composition that may be related to the types of treatments received. These findings add to our understanding of the biological changes that underlie the long-term health of breast cancer survivors. Citation Format: Jacob Kresovich, Katie O'Brien, Zongli Xu, Clarice Weinberg, Dale Sandler, Jack Taylor. Changes in peripheral immune cell composition in women who do and do not develop breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-12-08.