High Severity Group Research Articles

The rCAST score is useful for estimating the neurological prognosis in pediatric patients with post-cardiac arrest syndrome before ICU admission: External validation study using a nationwide prospective registry

IntroductionThe objective of this cohort study was to investigate whether the revised post-Cardiac Arrest Syndrome for Therapeutic hypothermia score (rCAST), which we previously developed as a prognostic score for adult patients with post-cardiac arrest syndrome (PCAS), is also applicable to pediatric patients. MethodsPediatric PCAS patients were included from an out-of-hospital cardiac arrest (OHCA) registry of the Japanese Association for Acute Medicine (JAAM). We validated the predictive accuracy of the rCAST for the neurological outcomes at 30 and 90 days. We also evaluated the probability of a good neurological outcome in each of the three specified severity categories based on the rCAST (low severity: ≤5.5; moderate severity: 6.0–14.0; high severity: ≥14.5). ResultsAmong the 737 pediatric patients with OHCA, the data of 179 pediatric PCAS patients in whom return of spontaneous circulation was achieved were analyzed. The areas under the curve (AUC) of the rCAST for predicting the neurological outcomes at 30 days and 90 days were 0.95 (95% CI: 0.90–0.99) and 0.96 (0.91–1.00), respectively. The proportions of patients with a good neurological outcome at 30 days were 100% (12/12) in the low severity group, 36.1% (13/36) in the moderate severity group, and 2.3% (3/131) in the high severity group. ConclusionsThe AUC of the rCAST for pediatric PCAS patients was found to be greater than 0.9 in the external validation, which corresponds to excellent predictive accuracy. There was no patient with good neurological outcome among the patients with more than 17.0 points (extremely high severity group).

Preterm refraction and ocular biometry in children with and without retinopathy of prematurity in the first year of life

To determine ocular biometric and refractive profiles of premature children at risk of retinopathy of prematurity (ROP), comparing those who did and did not require laser treatment.In this prospective study, premature infants underwent biometry and refraction with their first ROP examination. Study parameters were assessed again at 3 months, 6 months, and 1 year. The main outcome measures were spherical equivalent, axial length, and keratometry.A total of 122 infants (243 eyes) were included. At baseline, infants without ROP, those with ROP who never needed treatment, and those who later needed treatment had overall comparable axial length (P = 0.53) and myopia (P = 0.05); the highest severity group had higher corneal steepness and more myopia at baseline. At 1 year, children with laser-treated ROP had the shortest axial lengths, with the least decrease in keratometry, and the greatest increase in myopia (-2.0 D; P = 0.001). Anisometropia, if present initially, persisted through the 1-year examination. Mean refractive error was more myopic in zone 1 disease (P = 0.3) and in aggressive posterior ROP (P = 0.15).Severe ROP is associated with disruption of emmetropization, and steeper corneas and more myopia at the first ROP examination, before any intervention. In our study cohort, these differences became more marked over the course of 1 year after laser therapy. The myopia in these cases was not axial. Laser therapy did not induce new anisometropia.

Trajectories of Change in an Open-access Internet-Based Cognitive Behavior Program for Childhood and Adolescent Anxiety: Open Trial.

BackgroundAlthough evidence bolstering the efficacy of internet-based cognitive behavioral therapy (iCBT) for treating childhood anxiety has been growing continuously, there is scant empirical research investigating the timing of benefits made in iCBT programs (eg, early or delayed).ObjectiveThis study aims to examine the patterns of symptom trajectories (changes in anxiety) across an iCBT program for anxiety (BRAVE Self-Help).MethodsThis study’s participants included 10,366 Australian youth aged 7 to 17 years (4140 children aged 7-12 years; 6226 adolescents aged 12-17 years) with elevated anxiety who registered for the BRAVE Self-Help program. Participants self-reported their anxiety symptoms at baseline or session 1 and then at the commencement of each subsequent session.ResultsThe results show that young people completing the BRAVE Self-Help program tend to fall into two trajectory classes that can be reliably identified in terms of high versus moderate baseline levels of anxiety and subsequent reduction in symptoms. Both high and moderate anxiety severity trajectory classes showed significant reductions in anxiety, with the greatest level of change being achieved within the first six sessions for both classes. However, those in the moderate anxiety severity class tended to show reductions in anxiety symptoms to levels below the elevated range, whereas those in the high symptom group tended to remain in the elevated range despite improvements.ConclusionsThese findings suggest that those in the high severity group who do not respond well to iCBT on a self-help basis may benefit from the additional support provided alongside the program or a stepped-care approach where progress is monitored and support can be provided as necessary.

Mental Health of Chinese People During the COVID-19 Pandemic: Associations With Infection Severity of Region of Residence and Filial Piety.

This study aims to investigate mental health among Chinese people living in areas with differing levels of infection severity during the COVID-19 outbreak. It also assesses the association between reciprocal and authoritarian filial piety and mental health in times of crises. A sample of 1,201 Chinese participants was surveyed between April and June 2020. Wuhan city (where 23.4% of participants resided), Hubei province outside Wuhan (13.4% of participants), and elsewhere in China (63.1% of participants) were categorized into high, moderate, and low infection severity areas, respectively. The Depression, Anxiety, and Stress Scale’s severity cut-points were used to categorize participants. In the overall sample, 20.9, 34.2, and 29.0% of the participants showed elevated (mild to extremely severe) levels of stress, anxiety, and depression. Those in the highest infection severity group were significantly more likely to be categorized as having elevated levels of stress, anxiety, and depression. General linear modeling was performed on a composite mental distress variable (taking into account stress, anxiety, and depression scores). This model indicated that, even after adjusting for group differences in age, gender, education, and filial piety, the high infection severity group displayed more mental distress than the low infection severity groups. The model also found reciprocal filial piety to have a negative association with mental distress. Conversely, authoritarian filial piety was found to be unrelated to mental distress when controlling for the other variables in the model. No evidence was found for an interaction between either authoritarian or reciprocal filial piety and infection severity, which suggests that the negative association observed between reciprocal filial piety and mental distress was relatively consistent across the three infection severity groups. The findings suggest that future public health programs may integrate the promotion of filial piety as a strategy to help Chinese people maintain good mental health in the face of pandemic crises.

A Machine-Learning Framework to Identify Distinct Phenotypes of Aortic Stenosis Severity

ObjectivesThe authors explored the development and validation of machine-learning models for augmenting the echocardiographic grading of aortic stenosis (AS) severity. BackgroundIn AS, symptoms and adverse events develop secondarily to valvular obstruction and left ventricular decompensation. The current echocardiographic grading of AS severity focuses on the valve and is limited by diagnostic uncertainty. MethodsUsing echocardiography (ECHO) measurements (ECHO cohort, n = 1,052), we performed patient similarity analysis to derive high-severity and low-severity phenogroups of AS. We subsequently developed a supervised machine-learning classifier and validated its performance with independent markers of disease severity obtained using computed tomography (CT) (CT cohort, n = 752) and cardiovascular magnetic resonance (CMR) imaging (CMR cohort, n = 160). The classifier’s prognostic value was further validated using clinical outcomes (aortic valve replacement [AVR] and death) observed in the ECHO and CMR cohorts. ResultsIn 1,964 patients from the 3 multi-institutional cohorts, 1,346 (68%) subjects had either nonsevere or discordant AS severity. Machine learning identified 1,117 (57%) patients as having high-severity and 847 (43%) as having low-severity AS. High-severity patients in CT and CMR cohorts had higher valve calcium scores and left ventricular mass and fibrosis, respectively than the low-severity group. In the ECHO cohort, progression to AVR and progression to death in patients who did not receive AVR was faster in the high-severity group. Compared with the conventional classification of disease severity, machine-learning–based severity classification improved discrimination (integrated discrimination improvement: 0.07; 95% confidence interval: 0.02 to 0.12) and reclassification (net reclassification improvement: 0.17; 95% confidence interval: 0.11 to 0.23) for the outcome of AVR at 5 years. For both ECHO and CMR cohorts, we observed prognostic value of the machine-learning classifications for subgroups with asymptomatic, nonsevere or discordant AS. ConclusionsMachine learning can integrate ECHO measurements to augment the classification of disease severity in most patients with AS, with major potential to optimize the timing of AVR.

Prediction and Feature Importance Analysis for Severity of COVID-19 in South Korea Using Artificial Intelligence: Model Development and Validation.

BackgroundThe number of deaths from COVID-19 continues to surge worldwide. In particular, if a patient’s condition is sufficiently severe to require invasive ventilation, it is more likely to lead to death than to recovery.ObjectiveThe goal of our study was to analyze the factors related to COVID-19 severity in patients and to develop an artificial intelligence (AI) model to predict the severity of COVID-19 at an early stage.MethodsWe developed an AI model that predicts severity based on data from 5601 COVID-19 patients from all national and regional hospitals across South Korea as of April 2020. The clinical severity of COVID-19 was divided into two categories: low and high severity. The condition of patients in the low-severity group corresponded to no limit of activity, oxygen support with nasal prong or facial mask, and noninvasive ventilation. The condition of patients in the high-severity group corresponded to invasive ventilation, multi-organ failure with extracorporeal membrane oxygenation required, and death. For the AI model input, we used 37 variables from the medical records, including basic patient information, a physical index, initial examination findings, clinical findings, comorbid diseases, and general blood test results at an early stage. Feature importance analysis was performed with AdaBoost, random forest, and eXtreme Gradient Boosting (XGBoost); the AI model for predicting COVID-19 severity among patients was developed with a 5-layer deep neural network (DNN) with the 20 most important features, which were selected based on ranked feature importance analysis of 37 features from the comprehensive data set. The selection procedure was performed using sensitivity, specificity, accuracy, balanced accuracy, and area under the curve (AUC).ResultsWe found that age was the most important factor for predicting disease severity, followed by lymphocyte level, platelet count, and shortness of breath or dyspnea. Our proposed 5-layer DNN with the 20 most important features provided high sensitivity (90.2%), specificity (90.4%), accuracy (90.4%), balanced accuracy (90.3%), and AUC (0.96).ConclusionsOur proposed AI model with the selected features was able to predict the severity of COVID-19 accurately. We also made a web application so that anyone can access the model. We believe that sharing the AI model with the public will be helpful in validating and improving its performance.

Outcome Related to Level of Targeted Temperature Management in Postcardiac Arrest Syndrome of Low, Moderate, and High Severities: A Nationwide Multicenter Prospective Registry.

The optimal target temperature during targeted temperature management for patients after cardiac arrest remains under debate. The aim of this study was to evaluate the association between targeted temperature management at lower target temperatures and the neurologic outcomes among patients classified by the severity of postcardiac arrest syndrome. A multicenter observational study from the out-of-hospital cardiac arrest registry of the Japanese Association for Acute Medicine, which is a nationwide prospective registry of out-of-hospital cardiac arrest patients. A total of 125 critical care medical centers or hospitals with an emergency care department across Japan. A total of 1,111 out-of-hospital cardiac arrest patients who had received targeted temperature management. We divided all 1,111 postcardiac arrest syndrome patients treated with targeted temperature management into two groups: those who received targeted temperature management at a lower target temperature (33-34°C) and those who received targeted temperature management at a higher target temperature (35-36°C). In regard to classification of the patients, we divided the patients into three categories of severity (low, moderate, and high severities) using the risk classification tool, post-Cardiac Arrest Syndrome for Therapeutic hypothermia, which was previously validated. The primary outcome was the percentage of patients with a good neurologic outcome at 30 days, and the secondary outcome was the survival rate at 30 days. Multivariate analysis showed that targeted temperature management at 33-34°C was significantly associated with a good neurologic outcome and survival at 30 days in the moderate severity (odds ratio, 1.70 [95% CI, 1.03-2.83] and 1.90 [95% CI, 1.15-3.16], respectively), but not in the patients of low or high severity (pinteraction = 0.033). Propensity score analysis also showed that targeted temperature management at 33-34°C was associated with a good neurologic outcome in the moderate-severity group (p = 0.022). Targeted temperature management at 33-34°C was associated with a significantly higher rate of a good neurologic outcome in the moderate-severity postcardiac arrest syndrome group, but not in the low- or high-severity group.

Balance Problems, Paralysis, and Angina as Clinical Markers for Severity in Major Depression.

Major depressive disorder (MDD) is a heterogeneous disorder. Our hypothesis is that neurological symptoms correlate with the severity of MDD symptoms. One hundred eighty-four outpatients with MDD completed a self-report questionnaire on past and present medical history. Patients were divided into three roughly equal depression severity levels based on scores from the APA Severity Measure for Depression—Adult (n = 66, 58, 60, for low, medium, high severity, respectively). We saw a significant and gradual increase in the frequency of “muscular paralysis” (1.5–5.2–16.7%) and “balance problems” (21.2–36.2–46.6%) from low to medium to high severity groups. We repeated the analysis using only the two most extreme severity categories: low severity (66 samples) vs. high severity (60 samples). High severity patients were also found to experience more “angina” symptoms than low severity patients (27.3 vs. 50%). The three significant clinical variables identified were introduced into a binary logistic regression model as the independent variables with high or low severity as the dependent variable. Both “muscular paralysis” and “balance problems” were significantly associated with increased severity of depression (odds ratio of 13.5 and 2.9, respectively), while “angina” was associated with an increase in severity with an odds ratio of 2.0, albeit not significantly. We show that neurological exam or clinical history could be useful biomarkers for depression severity. Our findings, if replicated, could lead to a simple clinical scale administered regularly for monitoring patients with MDD.

White matter texture abnormalities are associated with delusional severity in a cognitively mixed sample of older adults

AbstractBackgroundDelusions in older adults correlate with white matter lesion burden [1], though the relationship with white matter texture (WMT) is unclear. White matter texture is the tissue organization in normal‐appearing brain matter (NABM) related to overall diffusion capabilities.MethodUsing NPI‐Q scores from the ADNI data set, a cognitively mixed sample of patients with delusions was extracted. Delusional severity was ranked from 1‐3 (1 being the lowest severity) based on the NPI‐Q scores along with downloads of FLAIR MRI volumes for each subject. Subjects and volumes were analyzed in each severity group. Normal‐appearing brain matter of FLAIR images were extracted with validated in‐house brain extraction and intensity standardization algorithms [2]. Volume texture maps representing the correlation in the NABM for each FLAIR image were generated as per Khademi et. al [3].ResultBoxplots for the NABM texture measures are shown for groups 1, 2 and 3 in Figure 1. Subjects with high delusional severity (group 3) had the most noticeable change in WMT relative to lowest delusional severity (group 1). Group 3 had a higher spatial correlation value of 6.0947 e+03 +/‐ 592.6178 than group 1 with values of 5.7630 e+03 +/‐ 832.5040. A higher value indicates more spatial correlation among pixels. This suggests that there are larger regions that are smooth in Group 3 compared to Group 1, indicating less WM “structure” in the more severe delusion group.ConclusionThe severity of delusions in a cognitively diverse sample of older adults correlates with abnormalities in white matter texture, though further research is required to further validate our findings.

Perfectionism and Pain Intensity in Women with Fibromyalgia: Its Influence on Activity Avoidance from The Contextual Perspective.

Given the scarcity of studies regarding perfectionism from a contextual perspective, this study aims to analyze its role in the relationship between pain and activity avoidance and its differential effect among patients with different fibromyalgia severity. A cross-sectional study with 228 women with fibromyalgia classified into two disease severity groups (low/moderate vs. high) was carried out. Moderation analyses were conducted; perfectionism was used as moderator, pain (in high and low pain situations) as independent variable, and activity avoidance as the outcome. Among the high disease severity group, analyses showed direct contributions of perfectionism (p < 0.001) but not of pain (p > 0.05); moderation effects were found in high pain situations (p = 0.002) (for low levels of perfectionism, a positive association was found between pain intensity and avoidance). Among the low severity group, direct effects of perfectionism (p < 0.05) and pain intensity (p = 0.04) were found (although the latter only for high pain situations); moderation effects were found in high pain situations (p = 0.018) (for high levels of perfectionism a positive and significant association was found between pain intensity and avoidance). Perfectionism has been found to be a key variable in the differential relationship between pain intensity (in high pain situations) and activity avoidance in groups with high and low disease severity.

Reward Versus Nonreward Sensitivity of the Medial Versus Lateral Orbitofrontal Cortex Relates to the Severity of Depressive Symptoms

BackgroundThe orbitofrontal cortex (OFC) is implicated in depression. The hypothesis investigated was whether the OFC sensitivity to reward and nonreward is related to the severity of depressive symptoms. MethodsActivations in the monetary incentive delay task were measured in the IMAGEN cohort at ages 14 years (n = 1877) and 19 years (n = 1140) with a longitudinal design. Clinically relevant subgroups were compared at ages 19 (high-severity group: n = 116; low-severity group: n = 206) and 14. ResultsThe medial OFC exhibited graded activation increases to reward, and the lateral OFC had graded activation increases to nonreward. In this general population, the medial and lateral OFC activations were associated with concurrent depressive symptoms at both ages 14 and 19 years. In a stratified high-severity depressive symptom group versus control group comparison, the lateral OFC showed greater sensitivity for the magnitudes of activations related to nonreward in the high-severity group at age 19 (p = .027), and the medial OFC showed decreased sensitivity to the reward magnitudes in the high-severity group at both ages 14 (p = .002) and 19 (p = .002). In a longitudinal design, there was greater sensitivity to nonreward of the lateral OFC at age 14 for those who exhibited high depressive symptom severity later at age 19 (p = .003). ConclusionsActivations in the lateral OFC relate to sensitivity to not winning, were associated with high depressive symptom scores, and at age 14 predicted the depressive symptoms at ages 16 and 19. Activations in the medial OFC were related to sensitivity to winning, and reduced reward sensitivity was associated with concurrent high depressive symptom scores.

Patterns of autism symptoms: hidden structure in the ADOS and ADI-R instruments

We simultaneously revisited the Autism Diagnostic Interview-Revised (ADI-R) and Autism Diagnostic Observation Schedule (ADOS) with a comprehensive data-analytics strategy. Here, the combination of pattern-analysis algorithms and extensive data resources (n = 266 patients aged 7–49 years) allowed identifying coherent clinical constellations in and across ADI-R and ADOS assessments widespread in clinical practice. Our clustering approach revealed low- and high-severity patient groups, as well as a group scoring high only in the ADI-R domains, providing quantitative contours for the widely assumed autism subtypes. Sparse regression approaches uncovered the most clinically predictive questionnaire domains. The social and communication domains of the ADI-R showed convincing performance to predict the patients’ symptom severity. Finally, we explored the relative importance of each of the ADI-R and ADOS domains conditioning on age, sex, and fluid IQ in our sample. The collective results suggest that (i) identifying autism subtypes and severity for a given individual may be most manifested in the ADI-R social and communication domains, (ii) the ADI-R might be a more appropriate tool to accurately capture symptom severity, and (iii) the ADOS domains were more relevant than the ADI-R domains to capture sex differences.

MON-614 Degree of Diabetes Control Determines the Admission Severity of Diabetic Ketoacidosis

Objectives: To determine whether the degree of diabetes control correlates with the admission severity of diabetic ketoacidosis (DKA).Methods: A Retrospective chart review was performed for patients admitted with DKA to the medical ICU at Abington Memorial Hospital between January 1, 2017 and January 1, 2018. Laboratory Data required to determine an acute physiology and chronic health evaluation (APACHE) score, hemoglobin A1C, length of hospital stay was recorded. The APACHE score was used to determine the severity of disease at admission. Patients were divided into two groups: low severity (APACHE <15) and high severity (APACHE >15).Results: A total of 50 patients were included in the analysis. The mean age of the patients was 47 yrs (range 17-85 yrs). 52%(n=26) of the population were males. The overall mean APACHE II at admission was 15 (range 3-28). The low severity group (APACHE <=15) and high severity group (APACHE >15) were equally matched at 25 patients each. The mean APACHE scores were 9.9 and 18.7 for the low and high severity groups respectively. The mean hemoglobin A1C values for the low and high severity groups were 10.5 and 15 respectively. The average length of ICU/hospital stay was 1.6/3.65 and 1.54/3.61 days for the low and high severity groups respectively.Conclusions: According to our study, a higher severity of DKA (higher APACHE) was associated with a higher hemoglobin A1C level. However, the study did not find any difference in the average length of ICU/hospital stay between the two groups.

DELUSIONAL SEVERITY IN A COGNITIVELY MIXED SAMPLE OF OLDER ADULTS IS ASSOCIATED WITH ABNORMALITIES IN WHITE MATTER TEXTURE

Introduction Background: Delusions occur in older patients and may be a harbinger of later cognitive impairment. Studies to date have suggested a correlation with white matter lesion burden [2] [3] but the correlation between delusions and white matter texture (WMT) is not well understood. White matter texture refers to tissue organization in normal-appearing brain matter (NABM) related to the overall diffusion capabilities of brain tissue. There is growing interest in analyzing these regions of the brain since they may contain early signs of disease [4]. Whether delusion severity is correlated with WMT is not so clear. Knowing the relationship between delusional severity and WMT may provide insight into potential mechanisms. Objective: Using neuroimaging biomarkers measured from 212 FLAIR MRI volumes, we investigated the relationship between delusional level and texture of the NABM in a cognitively mixed cohort extracted from the Alzheimer's Disease Neuroimaging (ADNI) data set. Methods Method: We extracted a cognitively diverse sample of patients with delusions based on NPI-Q scores from the ADNI data set. The delusion group was organized according to severity (1, 2, 3) based on Neuropsychiatric Inventory-Quick (NPI-Q) scores, with 1 being the lowest severity, and FLAIR MRI volumes for each subject was downloaded. There were 32 subjects (130 volumes) in group 1, 11 subjects (49 volumes) in group 2 and 9 subjects (33 volumes) in group 3 for analysis. Using validated, in-house brain extraction and intensity standardization algorithms [5][6][7], the normal-appearing brain matter (NABM) of FLAIR images were extracted. Texture analysis was performed on the NABM with a 2D texture feature that measures spatial correlation among pixel intensities [1]. This 2D spatial correlation metric was extracted on a per pixel basis, using 3mm x 3mm windows to find local, microstructural texture differences. The spatial feature maps were averaged over all slices to find a volume representation and a slight erosion was applied to remove outliers caused by the large brain-background edge. From the volume's correlation histogram, the bottom 2% and top 98% of the features are removed to further improve robustness to outliers. The mean and median of these feature maps were statistically compared between delusion groups (1, 2, 3). High spatial correlation indicates neighboring pixels have similar intensities (and is more homogeneous). Results Results: Boxplots for the NABM texture measures are shown for groups 1, 2 and 3 in Figure 1. Subjects with high delusional severity (group 3) had the most noticeable change in WMT when compared to lowest delusional severity (group 1). Group 3 had a higher spatial correlation value of 6.0947 e+03 +/- 592.6178 than group 1 with values of 5.7630 e+03 +/- 832.5040. A higher value indicates more spatial correlation among pixels (i.e. local homogeneity since closer pixels are more likely to have similar intensity values). This suggests that there are larger regions that are smooth in Group 3 compared to Group 1, which could indicate less WM “structure” in the more severe delusions group. This effect is shown in Figure 2. T-test results in Table 1 shows the highest difference is between groups 1 and 3 when examining the mean and median values with p-values both Conclusions Discussion: This study provides the first evidence that severity of delusions in a cognitively diverse sample of older adults is correlated with abnormalities in white matter texture. This finding suggests that alterations in white matter texture may contribute to the development of delusions in older patients. There is a notable difference between an individual with mild symptoms and severe symptoms based on their white matter texture as shown. Due to the subjective nature of an individual being scored either NPI-Q 1 or 2, or, 2 or 3, differentiating between mild and moderate, or moderate and severe disease is often ill-defined. This may contribute to challenges in differentiating between these groups. Further study comparing our results to patients without delusions and controlling for severity of cognitive impairment is required to further validate our findings. This research was funded by: St. Michael's Hospital Foundation, Heather and Eric Donnelly endowment

Effect of force direction and tooth angulation during traction of palatally impacted canines: A finite element analysis

Treatment of a palatally impacted canine (PIC) is associated with demanding anchorage control, increased treatment duration, and undesirable side effects. Accurate PIC localization and force application impact treatment success. The objective of this research was to determine the stresses on the PIC when subjected to initial force activation in various directions (buccal, vertical, and distal) and relative to impaction severity. Thirty PICs from 21 scans underwent finite element modeling. A prototype 3D model was reconstructed and segmented into its anatomic components. Each PIC was precisely positioned in the prototype model according to impaction position. Stresses in response to a (1.0N) force in the distal, vertical, and buccal directions were evaluated at different levels of the root (apical, middle, and cervical). Distal and buccal forces yielded higher stress (6.64 and 6.41kPa, respectively) than the vertical force (5.97kPa) on the total PIC root and the apical and cervical root levels, but not at midroot. Statistically significant differences between severity groups were found mostly at the apical level among all force directions, except between distal and buccal forces in the higher severity group. In this group, stress was greatest at the cervical level with the buccal force significantly different from the stresses generated by either the distal or the vertical force. Vertical forces generated the lowest stresses. Differentially distributed stresses over the root reflected an initial tipping movement. Greater cervical stresses from the buccal force indicate resistance to movement, suggesting treatment initiation with vertical and distal forces over buccal forces, particularly with severely inclined canines.

Abstract 106: Differential Effects of Mild Therapeutic Hypothermia Against Normothermia for Post-Cardiac Arrest Syndrome According to the Severity Scale

Introduction: There are few studies on the differential effects of mild therapeutic hypothermia (MTH) according to the risk class in post-cardiac arrest syndrome (PCAS) patients. Objective: The aim of this study was to evaluate the differential effects of MTH against therapeutic normothermia (TN) for PCAS patients according to our risk classification tool (rCAST). Methods: We used data from the out-of-hospital cardiac arrest (OHCA) registry of the Japanese Association for Acute Medicine (JAAM), which is a multi-center, prospective registry of OHCA patients who were transported to critical care medical centers or hospitals with an emergency care department across Japan. We classified eligible PCAS patients treated with MTH or TN on the basis of our rCAST score which was previously developed by us: low severity group (≤5.5), moderate severity group (6-14), and high severity group (≥14.5). The differential effects of MTH vs. TN for their neurological outcome in the 3 severity categories were evaluated by interaction analysis, and the effect of MTH vs. TN in each group was assessed by multivariate logistic regression analysis and propensity score analysis. The good neurological outcome was defined as a Cerebral Performance Categories score ≤2 at 30 days. Results: Among 12,024 OHCA patients in the registry, data of 460 PCAS patients treated by MTH or TN were analyzed (96 patients; the low score, 192; the moderate score, and 172; the high score group). There was a statistically significant interaction effect between MTH/TN and their neurological outcome at 30 days in the 3 categories (p = 0.022). MTH was significantly associated with good neurological outcome at 30 days in PCAS patients of moderate severity group both in the multivariate logistic regression analysis (adjusted odds ratio, 3.09; 95% confidence interval, 1.13-8.49; p = 0.029) and the propensity score analysis (p = 0.030), while it was not in low and high severity group. Conclusions: The effect of MTH in PCAS patients differed according to the severity of PCAS, and MTH was significantly associated with a good neurological outcome as compared to TN in the moderate severity group.

Red blood cell distribution width as a useful marker for severity in pediatric acute gastroenteritis.

Acute gastroenteritis (AGE) in children is still one of the most important causes of mortality and morbidity in developing countries. Therefore, it is very important for clinicians to detect the presence and severity of acute gastroenteritis. Red cell distribution width (RDW) is thought to have the potential for AGE evaluation in children. We sought to investigate the value of RDW for severity assessment in children with AGE. A total of 97 AGE patients were included in a prospective observational study. Complete blood count, serum C-reactive protein, and stool examinations were carried out. Modified Vesikari score (MVS) was evaluated to determine severity. Median age was 19months (min-max, 1-198months). The male/female ratio was 1.55 (59/38). Rotavirus was detected in 31 of 97 children (32%). median MVS was 9 points (min-max, 5-24 points). A total of 32 (33%), 43 (44%) and 22 patients (23%) were classified in the mild-, moderate-, and high-severity groups, respectively. There were no significant differences between rotavirus-positive and rotavirus-negative children. Hemoglobin, mean corpuscular volume, and RDW differed significantly according to severity. RDW had the highest area under the curve when the high-severity group was compared with the combination of low- and moderate-severity groups on receiver operating characteristic analysis. Red cell distribution width increased with the increase in severity of AGE. RDW may offer additional severity stratification in children with AGE.

Patterns of polysubstance use and simultaneous co-use in high risk young adults

BackgroundPolysubstance use (PSU) is associated with worse prognosis and poorer physical and mental health compared to single substance use. The current study provides information about PSU patterns by examining a diverse range of alcohol/substance use behaviors ranging from low-level experimentation to indicators of severe abuse. In addition, the current study, for the first time, examines how simultaneous co-use of multiple substances cluster with other more commonly studied PSU behaviors. MethodsLatent Class Analysis was used to identify patterns of substance use, in a sample of young-adults (n = 2098), using 25 items from the Semi-Structured Assessment for the Genetics of Alcoholism (SSAGA-II) including: items assessing severity of problems with alcohol, cannabis, stimulants, opiates, and sedatives; items assessing # of lifetime uses; items assessing simultaneous co-use of all combinations of substances. Then the association of class membership and age, antisocial and impulsive personality, experience seeking, anxiety, and neuroticism was examined using Multinomial Regression. ResultsFit indices (i.e. AIC, SSABIC, and entropy) and interpretability of classes supported a five-class solution: “Low Problems” (32% of sample), “Alcohol Primary” (11%), “Alcohol and Cannabis” (25%), “Moderate PSU” (23%), and “Severe PSU” (9%). Simultaneous co-use behaviors discriminated between lower and higher severity groups. Externalizing personality constructs robustly predicted membership in the “Moderate” and “Severe” PSU classes compared to the “Alcohol Primary” class. ConclusionsPSU patterns followed an additive pattern of use with lower severity classes using alcohol/cannabis and more severe classes using other illicit substances in addition. Co-use items provided valuable information about PSU severity.

Differential Posttreatment Outcomes of Methylphenidate for Smoking Cessation for Individuals With ADHD

In a multisite, randomized study (CTN-0029), a 3-month course of Osmotic-Release Oral System Methylphenidate (OROS-MPH) improved smoking cessation in a group of patients with higher baseline severity in Attention-Deficit/Hyperactivity Disorder (ADHD). This treatment, however, worsened smoking cessation outcome in the group with lower baseline ADHD severity. We want to examine whether this differential treatment effect persisted after OROS-MPH was discontinued. We conducted a secondary analysis of the 1-month follow-up data from CTN-0029 after the discontinuation of OROS-MPH (N = 134). Nicotine patch was tapered during this month. We tested whether OROS-MPH had an effect on self-reported 7-day abstinence by week, as well as possible treatment by baseline ADHD severity interactions. Abstinence diminished overall in time after the end of the treatment. In the high baseline severity group, patients who received OROS-MPH had an advantage in 7-day abstinence at week 15 (40% for OROS-MPH vs 20% for placebo, odds ratio = 2.63, P = .028). In the lower severity group (n = 121), no difference was detected (29% for OROS-MPH vs 32% for placebo, P = 1.00) between the two treatment groups. There was also a significant treatment by baseline ADHD severity interaction (P = .03). OROS-MPH promotes abstinence beyond the course of treatment for patients with more severe ADHD, while the paradoxical effects in the lower baseline severity group is not persistent after medication discontinuation. Targeting ADHD in smoking cessation as a comorbidity therefore can have broader impact with more precise patient selection. (Am J Addict).

Intrathecal B-cell accumulation and axonal damage distinguish MRI-based benign from aggressive onset in MS.

ObjectiveWe explored the incremental value of adding multiple disease activity biomarkers in CSF and serum for distinguishing MRI-based benign from aggressive MS in early disease course.MethodsNinety-three patients diagnosed with clinically isolated syndrome (CIS) or early MS were divided into 3 nonoverlapping severity groups defined by objective MRI criteria. Ninety-seven patients with noninflammatory neurologic disorders and 48 patients with other inflammatory neurologic diseases served as controls. Leukocyte subsets in the CSF were analyzed by flow cytometry. CSF neurofilament light chain (NfL) and chitinase-3-like protein 1 (CHI3L1) levels were measured by ELISA. Serum NfL levels were examined using single molecule array technology.ResultsCSF CD20+/CD14+ ratios and NfL levels in CSF and serum were significantly different between high and low MRI severity groups, whereas no difference was found for CSF CHI3L1 levels. NfL levels in CSF and serum highly correlated. Receiver operating characteristic analysis demonstrated that the cumulative sums combining CSF CD20+/CD14+ ratios and NfL levels in serum or CSF considerably improved diagnostic accuracy. A composite score built from these 2 cumulative sums best distinguished MRI severity. These findings were validated by support vector machine analysis, which confirmed that the accuracy of the cumulative sums and composite score outperforms single biomarkers.ConclusionPatients with extreme manifestations of CIS or early MS defined by strict MRI parameters can be best distinguished by combining markers of intrathecal B-cell accumulation and axonal damage. This could stratify individual treatment decisions toward a more personalized immunotherapy.