Multivariate General Linear Model Research Articles

Long-term adverse events of three COVID-19 vaccines as reported by vaccinated physicians and dentists, a study from Jordan and Saudi Arabia

ABSTRACT Assessment of safety of COVID-19 vaccines is an ongoing process. This study aims to explore long-term adverse events reported by physicians and dentists who received at least two COVID-19 vaccine doses. A group of physicians and dentists were invited to complete a validated questionnaire that was composed of items on: socio-demographics, medical history, administered vaccines, and long-term adverse events (LTAE). Data of a total of 498 practitioners were included. Age ranged from 22 to 71 years (mean age= 35.75 ± 11.74) with a female majority (N = 348, 69.9%). The most frequently administered vaccines were Pfizer-BioNtech, Sinopharm and AstraZeneca vaccines. A total of 80 (16.0%) participants reported LTAEs which were mainly fatigue, menstrual disturbances, myalgia, arthralgia, dizziness, and headache (N = 32, 15, 8, 6, 4, and 4, respectively). There was no statistically significant association between LTAEs and: age, gender, or medical history (P > .05). The collective symptoms of fatigue, myalgia, arthralgia, dizziness, and headache were significantly associated with Sinopharm vaccine (P = .04). This was further confirmed by general linear multivariate model analysis. Less than 20% of COVID-19 vaccine recipients may complain of LTAEs that are mostly fatigue-related. It seems that factors such as age, gender, and medical status play a negligible role in development of these AEs. On the other hand, Sinopharm vaccine showed the highest significant association with these AEs followed by AstraZeneca vaccine.

Impact of Plant Growth Regulators to Development of the Second Generation Energy Crop Miscanthus × giganteus Produced Two Years in Marginal Post-Military Soil

The impact of the plant growth regulators (PGRs) Stimpo, Regoplant, and Charkor on the production of the second-generation energy crop Miscanthus × giganteus on marginal post-military soil was investigated during two vegetation seasons. The land, previously a tank training polygon, has not been in use since 1990 and has become marginal. Biological parameters (stem, shoot, and root lengths) and dry biomass values were evaluated in relation to the applied treatments. The multivariate general linear model (M-GLM) results showed a positive influence of Charkor on M. × giganteus development; the effect was markedly higher in the second year of vegetation. The impact of Stimpo and Regoplant was less noticeable; nevertheless, certain combinations of treatments showed satisfactory results. The M-GLM approach detected the inter-influence of the main factors of the production process, i.e., PGRs, soil, and year of growing. The results showed the predominant influence of year, PGRs and combined factor PGRs × year on the biological parameters; the other studied factors and their combinations were not as effective. Further research should focus on verifying the field-scale results for the M. × giganteus plantation established in a post-military area and compare the lab and field studies.

Lifestyle Behaviors and Parents' Mental Well-Being Among Low-Income Families During COVID-19 Pandemic.

BackgroundThe coronavirus 2019 (COVID-19) pandemic has negatively altered many families’ lifestyles and the mental well-being of parents, especially those who have a low income and young children. To improve low-income parents’ mental well-being, especially during a pandemic, understanding parents’ and children’s lifestyle behaviors and the relationship between their lifestyle behaviors and parents’ mental well-being is essential.ObjectiveThis cross-sectional study examined relationships between lifestyle behaviors (sleep, physical activity, screen time, and eating behavior of parents and children) and low-income parents’ well-being (stress, anxiety, and depression) during COVID-19.MethodsParents were recruited from two Michigan Head Start organizations as well as across the United States; 408 parents completed an online survey. Demographic characteristics were assessed, along with parents’ sleep, physical activity, screen time, and dietary intake; stress, anxiety, and depression were also examined. Children’s sleep time, physical activity, screen time, and fruit/vegetable intake were assessed. Descriptive statistics, correlations, and the multivariate general linear model procedure were used.ResultsApproximately 69.4% of parents reported moderate stress levels, and 17.2% reported high levels. Most parents had sleep disturbances, attained minimal physical activity, and consumed <5 fruits/vegetables per day; average screen time was >2 hours per day. Only 41% of preschoolers were active 7 days a week and slept ≥10 hours per day. Two thirds had >2 hours per day of screen time, and less than one fifth consumed ≥5 fruits/vegetables per day. After adjusting for parents’ demographics and children’s lifestyle behaviors, parents’ sleep disturbance was positively correlated with their levels of stress, anxiety, and depression. After controlling for parents’ demographics and lifestyle behaviors, child sleep time was negatively associated with parents’ stress levels. Family demographics and parents’ and children’s lifestyle behaviors explained 33.4%, 29.8%, and 28.1% of the variances in parents’ stress, anxiety, and depression, respectively.DiscussionMost parents and preschoolers were not meeting many lifestyle behavior recommendations, indicating a need for interventions. Improving parents’ sleep quality and reducing bedtime challenges involving their preschoolers may be necessary for enhancing parental mental well-being.

When Fathers Feel Socially Constrained to Assume a Role: A Negative Predictor of the Coparental Relationship in Switzerland

Role distribution is a central issue for parents in the transition to parenthood, but little is known about the motivations in fathers to assume a specific role. Differences in work-family balance in each parent may be motivated by an individual choice mutually shared by both partners; however, in many couples, the parents may feel forced to adopt a traditional role distribution, either for financial reasons, or to comply with social expectations about what men and women should do when they are parents. This feeling of being socially constrained to adopt a role distribution that is not congruent with intrinsic motivations can generate dissatisfaction and may jeopardize the development of the interparental relationship. Coparenting refers to the emotional and instrumental support parents bring to each other in their parental tasks. It has been shown to be central in family functioning and a powerful predictor of children’s emotional and cognitive development. In this study, we aimed to assess the extent to which different motivations for role distribution in fathers are predictive of the quality of the coparental relationship. A convenience sample of 144 fathers from the French-speaking part of Switzerland completed online questionnaires about their motivations, coparental relationship, and sociodemographic characteristics. Results showed that the reasons for role distribution were mainly economical, practical, and in order to meet personal expectations. Multivariate general linear modeling showed that role distribution that is constrained to meet social expectations and age were predictive of a less cohesive coparental relationship, whereas a deliberate choice in role distribution was linked to a more cohesive coparental relationship.

Expenditures in Young Adults with Hodgkin Lymphoma: NCI-Designated Comprehensive Cancer Centers versus Other Sites.

Outcomes among Hodgkin lymphoma (HL) patients diagnosed between 22 and 39 years are worse than among those diagnosed <21 years, and have not seen the same improvement over time. Treatment at an NCI-designated Comprehensive Cancer Center (CCC) mitigates outcome disparities, but may be associated with higher expenditures. We examined cancer-related expenditures among 22- to 39-year-old HL patients diagnosed between 2001 and 2016 using deidentified administrative claims data (OptumLabs Data Warehouse; CCC: n = 1,154; non-CCC: n = 643). Adjusting for sociodemographics, clinical characteristics, and months enrolled, multivariable general linear models modeled average monthly health-plan paid (HPP) expenditures, and incidence rate ratios compared CCC/non-CCC monthly visit rates. In the year following diagnosis, CCC patients had higher HPP expenditures ($12,869 vs. $10,688, P = 0.001), driven by higher monthly rates of CCC nontreatment outpatient hospital visits (P = 0.001) and per-visit expenditures for outpatient hospital chemotherapy ($632 vs. $259); higher CCC inpatient expenditures ($1,813 vs. $1,091, P = 0.001) were driven by 3.1 times higher rates of chemotherapy admissions (P = 0.001). Out-of-pocket expenditures were comparable (P = 0.3). Young adults with HL at CCCs saw higher health-plan expenditures, but comparable out-of-pocket expenditures. Drivers of CCC expenditures included outpatient hospital utilization (monthly rates of non-therapy visits and per-visit expenditures for chemotherapy). Higher HPP expenditures at CCCs in the year following HL diagnosis likely reflect differences in facility structure and comprehensive care. For young adults, it is plausible to consider incentivizing CCC care to achieve superior outcomes while developing approaches to achieve long-term savings.

Levels of Angiotensin-Converting Enzyme and Apolipoproteins Are Associated with Alzheimer's Disease and Cardiovascular Diseases.

Angiotensin-converting enzyme-1 (ACE1) and apolipoproteins (APOs) may play important roles in the development of Alzheimer’s disease (AD) and cardiovascular diseases (CVDs). This study aimed to examine the associations of AD, CVD, and endocrine-metabolic diseases (EMDs) with the levels of ACE1 and 9 APO proteins (ApoAI, ApoAII, ApoAIV, ApoB, ApoCI, ApoCIII, ApoD, ApoE, and ApoH). Non-Hispanic white individuals including 109 patients with AD, 356 mild cognitive impairment (MCI), 373 CVD, 198 EMD and controls were selected from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) dataset. Multivariable general linear model (GLM) was used to examine the associations. ApoE ε4 allele was associated with AD, as well as ApoAIV, ApoB and ApoE proteins, but not associated with CVD and EMD. Both AD and CVD were associated with levels of ACE1, ApoB, and ApoH proteins. AD, MCI and EMD were associated with levels of ACE1, ApoAII, and ApoE proteins. This is the first study to report associations of ACE1 and several APO proteins with AD, MCI, CVD and EMD, respectively, including upregulated and downregulated protein levels. In conclusion, as specific or shared biomarkers, the levels of ACE1 and APO proteins are implicated for AD, CVD, EMD and ApoE ε4 allele. Further studies are required for validation to establish reliable biomarkers for these health conditions.

The impact of diabetes and obesity on postoperative complications after cesarean delivery

Obesity and diabetes are risk factors for postoperative complications. Independent vs. additive effects on perioperative outcomes are understudied. We measured the association between obesity, diabetes, and both on postcesarean complications. Retrospective cohort study of patients who underwent cesarean delivery at 182 US hospitals in 2019 (NSQIP). Missing BMI or diabetes were excluded. Patients were categorized as neither obesity nor diabetes (referent), obesity alone, diabetes alone, or obesity and diabetes. Primary outcome was a composite of severe maternal morbidity (SMM), defined by the CDC. Secondary outcomes were operative time, surgical site infection (SSI), length of postop stay and other complications. Multivariable logistic regression and general linear models with poisson or gamma distribution and log link were used to estimate measures of association. Of 9727 patients, 32% had neither obesity nor diabetes, 61% obesity alone, 1% diabetes alone, and 6% obesity and diabetes. Groups differed by age, race, HTN, and bleeding disorders (Table). Insulin-dependence did not differ between those who had diabetes alone versus obesity and diabetes (p=0.99). SMM occurred in 2% and did not differ by obesity and/or diabetes (Figure). Odds of SSI was higher in those with obesity and diabetes as well as obesity alone. Obesity was associated with higher odds of readmission. Operative time was longer in those with obesity and diabetes (adjusted mean 56.8min, 95% CI 52.8-61.2) and obesity alone (55.3min, 95% CI 51.1-59.1) vs. neither obesity nor diabetes (53.7 min, 95% CI 50.2-57.0; p< 0.05 for both). Postoperative length of stay was longer in those with diabetes (3.1 days, 95% CI 2.7-3.6) vs. neither obesity nor diabetes (2.7 days, 95% CI 2.5-3.0; p< 0.05). There was no difference in SMM between groups. Differences in postop stay and operative times are small and may not be clinically significant. Increased SSI and readmission in obese patients should be considered when considering surgical bundles, perioperative protocols, and postoperative plans to optimize outcomes.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

The Impact of Maternal Anxiety on Early Child Development During the COVID-19 Pandemic.

Background: Maternal prenatal anxiety is among important public health issues as it may affect child development. However, there are not enough studies to examine the impact of a mother's anxiety on the child's early development, especially up to 1 year.Objective: The present prospective cohort study aimed to examine whether maternal trait anxiety, perceived social support, and COVID-19 related fear impacted speech-language, sensory-motor, and socio-emotional development in 12 months old Serbian infants during the COVID-19 pandemic.Methods: This follow-up study included 142 pregnant women (Time 1) and their children at 12 months (Time 2). Antenatal maternal anxiety and children's development were examined. Maternal anxiety was assessed using the State-Trait Anxiety Inventory (STAI). Child speech-language, sensory-motor, and socio-emotional development were assessed using the developmental scale in the form of an online questionnaire that examined the early psychophysiological child development. Information on socioeconomic factors, child and maternal demographics, clinical factors, and perceived fear of COVID-19 viral infection were collected. Multivariable General Linear Model analysis was conducted, adjusted for demographic, clinical, and coronavirus prenatal experiences, maternal prenatal anxiety levels, perceived social support, speech-language, motor skills, and cognitive and socio-emotional development at the infants' age of 12 months.Results: The study revealed the influence of the COVID-19 pandemic on maternal trait anxiety. The association between selected independent factors and infants' development was found in a demographically unified sample except for employment and the number of children. There was a correlation between all observed developmental functions. Univariate General Linear model statistical analysis indicated that linear models with selected independent factors and covariates could account for 30.9% (Cognition) up to 40.6% (Speech-language) of variability in developmental functions. It turned out that two-way and three-way interactions had a dominant role on models, and STAI-T Level and COVID-19 related fear were present in all interaction terms.Conclusion: Our findings reveal important determinants of child developmental outcomes and underline the impact of maternal anxiety on early child development. These findings lay the groundwork for the following interdisciplinary research on pregnancy and child development to facilitate and achieve positive developmental outcomes and maternal mental health.

Does a visitor of dark sites have a dark personality?

Previous research on dark tourism in vulnerable post-conflict areas, such as South-Eastern Europe, has overlooked the nature of visitor personalities. Accordingly, the main purpose of the present study is to determine which personality traits (dark triad, sadistic impulse, and six personality traits) are related to preference for dark tourism sites. The sample consisted of 227 respondents from Serbia who completed an online questionnaire. Using a multivariate general linear model, it was found that respondents high in Machiavellianism tended to prefer dark exhibitions, while respondents high in psychopathy tended to prefer visiting conflict/battle sites. Visitors to fun factories as an additional type of dark tourism sites showed low levels of sadism, while narcissism showed no effect on preference for dark tourism sites. Hence, only agreeableness and honesty-humility showed a significant effect on preference for dark tourism sites (dark exhibitions and conflict/battle sites). These results show interesting differences in dark sites visitors’ personalities.

The Association Between Breast Density and Gut Microbiota Composition at 2 Years Post-Menarche: A Cross-Sectional Study of Adolescents in Santiago, Chile.

The gut microbiome has been linked to breast cancer via immune, inflammatory, and hormonal mechanisms. We examined the relation between adolescent breast density and gut microbial composition and function in a cohort of Chilean girls. This cross-sectional study included 218 female participants in the Growth and Obesity Cohort Study who were 2 years post-menarche. We measured absolute breast fibroglandular volume (aFGV) and derived percent FGV (%FGV) using dual energy X-ray absorptiometry. All participants provided a fecal sample. The gut microbiome was characterized using 16S ribosomal RNA sequencing of the V3-V4 hypervariable region. We examined alpha diversity and beta diversity across terciles of %FGV and aFGV. We used MaAsLin2 for multivariable general linear modeling to assess differential taxa and predicted metabolic pathway abundance (MetaCyc) between %FGV and aFGV terciles. All models were adjusted for potential confounding variables and corrected for multiple comparisons. The mean %FGV and aFGV was 49.5% and 217.0 cm3, respectively, among study participants. Similar median alpha diversity levels were found across %FGV and aFGV terciles when measured by the Shannon diversity index (%FGV T1: 4.0, T2: 3.9, T3: 4.1; aFGV T1: 4.0, T2: 4.0, T3: 4.1). %FGV was associated with differences in beta diversity (R2 = 0.012, p=0.02). No genera were differentially abundant when comparing %FGV nor aFGV terciles after adjusting for potential confounders (q > 0.56 for all genera). We found no associations between predicted MetaCyc pathway abundance and %FGV and aFGV. Overall, breast density measured at 2 years post-menarche was not associated with composition and predicted function of the gut microbiome among adolescent Chilean girls.

Food neophobia and its relationship with dietary variety and quality in Irish adults: Findings from a national cross-sectional study

Food neophobia is characterised by a reluctance to eat novel or unfamiliar foods and has been linked to reduced dietary variety and quality. However, this link has been primarily studied in children. Therefore, we aimed to explore the relationship between food neophobia and dietary variety and quality in adults using a sub-sample of the National Adults Nutrition Survey collected between 2008 and 2010 (n = 1088). Food and nutrient intakes were assessed using a 4-day semi-weighed food diary. Food neophobia was measured using the Food Neophobia Scale (FNS). Dietary variety was assessed in three ways; Total Dietary Variety (TDV), Food-Group Variety (FGV) and Fruit and Vegetable Variety (FVV). Diet quality was assessed using the Mean Adequacy Ratio (MAR) and Nutrient-Rich Food Index (NRF9.3). A multivariate general linear model was used to assess the linear relationships between FNS score and all dietary measures, controlling for age, sex, education level, social class, location and BMI. Food neophobia was found to be inversely associated with TDV, FGV and FVV. In addition, food neophobia was negatively associated with vitamin C, magnesium and fruit and vegetable intakes and positively associated with percentage energy from free sugars. However, food neophobia was not significantly associated with all other nutrients, MAR and NRF9.3. While these results suggest food neophobia may not be a particularly important risk factor for poor nutrient status, adherence to certain dietary recommendations remains low within the Irish population and food neophobia may further inhibit the adaption of healthy and sustainable diets. Future research should seek to understand the implications of food neophobia on dietary behaviour change.

Associations of dietary, lifestyle, other participant characteristics, and oxidative balance scores with plasma F2-isoprostanes concentrations in a pooled cross-sectional study.

Plasma F2-isoprostanes (FiP) concentration, a reliably measured, valid, systemic oxidative stress biomarker, has been associated with multiple health-related outcomes; however, associations of most individual dietary and lifestyle exposures with FiP are unclear, and there is no reported oxidative balance score (OBS) comprising multiple dietary and/or lifestyle components weighted by their associations with FiP. To investigate cross-sectional associations of dietary and lifestyle characteristics with plasma FiP concentrations, we used multivariable general linear models to compare adjusted mean FiP concentrations across categories of dietary nutrient and whole-food intakes and lifestyle characteristics in two pooled cross-sectional studies (n = 386). We also developed equal-weight and weighted OBS (nutrient- and foods-based dietary OBS, lifestyle OBS, and total OBS), and compared adjusted mean FiP concentrations across OBS tertiles. Among men and women combined, adjusted mean FiP concentrations were statistically significantly, proportionately 28.1% higher among those who were obese relative to those who were normal weight; among those in the highest relative to the lowest total nutrient intake tertiles, FiP concentrations were statistically significantly lower by 9.8% for carotenes, 13.6% for lutein/zeaxanthin, 10.9% for vitamin C, 12.2% for vitamin E, 11.5% for glucosinolates, and 5% for calcium. Of the various OBS, the weighted OBS that combined total nutrient intakes and lifestyle exposures was most strongly associated with FiP concentrations: among those in the highest relative to the lowest total OBS, mean FiP concentrations were statistically significantly 29.7% lower (P < 0.001). Multiple dietary and lifestyle characteristics, individually, and especially collectively, may contribute to systemic oxidative stress.

Early effects of amyloid-β on structural and vascular brain changes in mid-life cognitively unimpaired individuals.

The apolipoprotein E (APOE) is the strongest genetic risk factor for late-onset Alzheimer's disease (AD). It has been shown that APOE ε4 allele (ε4) relates to early pathological accumulation of cerebral amyloid-β (Aβ), leading to decade earlier age-of-onset of AD. However vascular and anatomical brain changes in the presence of Aβ and ε4 gene have not yet been fully examined in middle age. We aim to investigate how ε4 and Aβ level influence MR neuroimaging biomarkers such as white-matter hyperintensities and hippocampus volume in mid-life (45-65 year old) cognitively unimpaired (CU) individuals. 149 middle age (44 to 66 years of age) CU adults (age 58.2±5.4, 115 Females, years of education 13.5±2.8) underwent 3T MRI and amyloid PET scans using 18 F-Florbetaben as part of the PISA study. Of this ε4 enriched cohort (N=78 ε4 carriers), 12 were classified as Aβ+ (Centiloid≥20). 5 participants with ε2ε4 genotypes were excluded due to the protective effect of the ε2 allele. Multivariable general linear models were implemented to study the association of ε4 and Aβ with structural neuroimaging markers including white-matter hyperintensity volume (WMHV) and Hippocampus volume (HV). Both volumes were normalised using total intracranial volume, and age, gender and years-of-education were used as independent covariates. There was no age difference between ε4+ and ε4- groups (Kruskal-Wallis test, p-value=0.8), but Aβ+ participants were older compared to Aβ- (p-value=0.005). There was no HV differences between ε4+ and ε4- groups when controlling for Centiloid (p-value=0.55). When comparing HV differences between groups based on joint ε4 and Aβ, Aβ+ε4+ had significantly lower HV compared to Aβ-ε4+ (p-value=0.01) and Aβ-ε4- (p-value=0.021) as shown in Figure 1. For WMHV differences, a trend towards significance exists for Aβ+ε4+ when compared to and Aβ+ε4- and Aβ-ε4- (p-value=0.069) as shown in Figure 2. In this study, we found that early signs of hippocampus degeneration may occur in the middle age in the presence of both high Aβ level and APOE ε4 allele. Future studies will investigate the effective age spread for middle-aged preclinical AD population which will be beneficial for participant recruitment for new clinical trials.

A Field Study Evaluating Humoral Immunity in Calves Vaccinated with Multivalent Bovine Respiratory Pathogen Vaccines

Abstract Bovine Respiratory Syncytial Virus (BRSV), Bovine Parainfluenza 3 (BPI3) and Mannheimia haemolytica (Mh) are major respiratory pathogens in the bovine respiratory disease complex. It is important to optimize passive and active immunity to these pathogens early in life to reduce clinical and subclinical productivity losses. The administration of inactivated, adjuvanted and multivalent vaccines, such as Bovilis® Bovipast RSP (Bovipast), and Bovalto® Respi 3 (Bovalto) to calves, may enhance cellular and humoral immunity against BRSV, BPI3 and Mh. A field trial evaluated the immune responses to these three agents in the first year of life in 12 Bovipast and 13 Bovalto vaccinated calves, and 5 negative control calves. Calves were vaccinated starting at 2 weeks of age and revaccinated 4 weeks later (primo vaccination). A booster vaccination was given at approximately 10 months of age. Serum samples were taken at time intervals up to 6 months after primo vaccination and up to 1 month after the booster vaccination. BRSV serum titres were evaluated using a serum neutralisation assay (SN), and BRSV, BPI3 and Mh titres were evaluated using a commercial enzyme linked immunosorbent assay (ELISA) test. Serum antibodies after primo and booster vaccinations in the individual calves were evaluated by calculating the areas under the curve (AUC) of the Log2 transformed BRSV SN titres and the optic density measures of the ELISA tests for BRSV, BPI3 and Mh. Multivariate general linear models were used to evaluate the influence of the vaccination on the AUC of the serum measures within 6 months after the primo vaccination. Similarly, models evaluated the AUC of the serum measures after the booster vaccination. The Bovipast vaccinated calves had significantly higher SN and ELISA titres AUC following the primo vaccination and booster vaccinations compared to the negative control calves and the Bovalto vaccinated calves. The Bovalto vaccinated calves did not have a significantly different BRSV SN and ELISA titres AUC response after the primo or booster vaccinations compared to the negative control calves. The serum antibody responses to BPI3 and Mh in the vaccinated calves were less pronounced than the Bovipast BRSV antibody response. Bovipast and Boval- to vaccinated calves mounted a significantly higher AUC ELISA OD for both BPI3 and Mh and the highest AUC was measured in the Bovipast vaccinated calves. This study indicated that early vaccinations of calves with multivalent adjuvanted inactivated BRD vaccines, such as Bovilis® Bovipast RSP can elicit a humoral response with a cellular-mediated memory effect as indicated by the booster vaccination.

Cortical microstructural changes in autosomal dominant Alzheimer’s disease

AbstractBackgroundAutosomal dominant Alzheimer's Disease (ADAD) is an important area of study to understand the pathogenesis of AD. Previous studies suggested that mutations in the genes coding for amyloid precursor protein cause early deposition of amyloid‐β peptide (Aβ), resulting in an amyloid‐induced inflammatory response and cortical microstructural changes during the cognitively asymptomatic phase, several years before clinical onset. The aim of this work was to investigate the cortical microstructural changes in an ADAD population, using novel diffusion tensor imaging (DTI) metrics that are correlated with specific neuropathology and disruption of cortical minicolumns.MethodA total of 270 individuals from families with known mutations in the PSEN1, PSEN2, and APP genes (168 mutation carriers and 102 non‐carriers) from the Dominantly Inherited Alzheimer’s Network (DIAN) were included in the study. 3DT1 and DTI scans at baseline were used to calculate the cortical grey matter fraction, cortical thickness, mean diffusivity (MD), and three novel cortical diffusivity measures, namely: the angle between the radial minicolumnar direction and the principal diffusion direction (AngleR); the diffusion components perpendicular to the minicolumns (PerpPD), and the principal diffusion component parallel with the minicolumns (ParlPD). A multivariate General Linear model (GLM) was used to investigate cross‐sectional differences. Mutation carrier status was added as a fixed factor, and “sex” and “age” as covariates. Differences across the clinical spectrum are evaluated with box‐plots of metrics grouped by clinical dementia rating (CDR) Figure 1.ResultDifferences in cortical diffusivity measures were found between mutation carriers and non‐carriers. The GLM results revealed a significant main effect of mutation carrier status (p&lt;0.05) as well as age (p&lt;0.001) and sex (p&lt;0.001). Between‐subjects effects revealed that PerpPD (p&lt;0.0001), ParlPD (p&lt;0.0001), and MD (p&lt;0.0001) were significantly higher in the mutation carrier group. As expected, the cortical grey matter fraction (p&lt;0.005) and cortical thickness (p&lt;0.01) were significantly lower in the mutation carrier group.ConclusionIn autosomal dominant (inherited) Alzheimer’s disease, differences emerge in several novel cortical diffusivity measures, years before the expected diagnosis based on parental age of onset. These findings support using cortical diffusivity measures as a surrogate of cortical microstructure quality for identification of the early stages of AD.

Nurse knowledge and confidence on peripheral intravenous catheter insertion and maintenance in pediatric patients: A multicentre cross-sectional study

PurposeTo examine nursing knowledge and confidence of peripheral intravenous catheter insertion and maintenance in pediatric patients. Design and methodsAn online survey using validated questionnaires was conducted in ten (tertiary and district) hospitals in Indonesia from May to September 2020. Multivariable general linear models were used to investigate associations between nurses' characteristics and knowledge and confidence on the catheter insertion and maintenance score. ResultsA total of 413 out of 458 pediatric nurses completed the survey (a response rate of 90%). The mean score of the nurse knowledge on insertion was 18.9(±3.3) (maximum score: 21), and the maintenance score was 6.5(±2.0) (maximum score: 12). The median score of the nurse insertion and maintenance confidence was quite high: 44 (IQR = 7) out of 50 and 37 (IQR = 4) out of 45, respectively. Initial patient assessment, catheter securement, site assessment and management of complications are areas where nurse knowledge and confidence are still lacking. Adjusted analysis indicates that training and work experience were significantly associated with the knowledge and confidence score (p < 0.05). ConclusionPediatric nurses were largely confident in their skills but this was not reflected in their knowledge scores. Training and experience were important predictors for nursing knowledge and confidence in catheter insertion and maintenance. Practice implicationsThe results provide nursing and hospital managers and educational institutions to understand areas of intravenous catheter insertion and maintenance in which nurses lack of knowledge and confidence as well as to formulate tailored and ongoing training to improve nurse knowledge, confidence, practices and optimize patients' care.

Economic Burden of Hospitalizations for Patients with Newly Diagnosed Acute Myeloid Leukemia in Remission in the United States: Retrospective Analysis of an Administrative Claims Database

INTRODUCTION: Managing patients with acute myeloid leukemia (AML) requires extensive healthcare resource utilization and costs; hospitalization is the largest component of medical costs for AML. In the phase 3 QUAZAR AML-001 trial, oral azacitidine (Oral-AZA [CC-486]) was associated with significant improvements in overall survival and relapse-free survival (RFS) vs. placebo (Wei, 2020). Prolonged RFS with Oral-AZA may translate into substantial economic benefits, with lower hospitalization-related costs due to reduced rates of hospitalization and days in hospital (Oliva, ASH 2020). Real-world economic benefits of prolonged remission remain insufficiently studied.OBJECTIVE: This study aimed to examine the economic burden of hospitalizations among patients with newly diagnosed AML in remission from a retrospective analysis of real-world data from a US claims database.METHODS: Using a retrospective cohort design, adult patients were selected from the IBM MarketScan TM Commercial and Medicare Supplemental Databases, with ≥2 outpatient claims or 1 inpatient claim with a primary International Classification of Disease 9th/10th Revision (ICD-9/ICD-10) code for AML between July 1, 2012, and September 30, 2019. Patients were required to have 1) at least 6 months of continuous enrollment, with pharmacy benefits, prior to diagnosis, 2) received systemic induction therapy as first-line (1L) therapy for AML on or after the index diagnosis date, and 3) attained remission from 1L systemic therapy.Patients were followed from remission after systemic induction therapy, with or without consolidation, until the end of the follow-up period. Eligible patients were organized into cohorts based on their duration of remission (DOR): Cohort A included patients with < median DOR and Cohort B had patients with ≥ median DOR. Hospitalization incidence and duration during the follow-up period were calculated using a per-patient per-year (PPPY) metric. Hospitalization-related costs were compared using a generalized linear model (GLM) with gamma distribution and log-link function. Generalized estimating equations (GEE) clustered on the patient were used to compare incidence and duration of hospitalizations. All costs were adjusted for inflation and reported in 2019 US dollars (USD).RESULTS: In all, 693 patients met all selection criteria and were assessed for DOR. The median DOR for all patients was 167 days; cohorts A and B included 346 and 347 patients, respectively, with median times from remission to end of follow-up of 106.5 and 460 days. Baseline characteristics were comparable between cohorts; mean [SD] age was 55.1 [14.4] years, 49.4% of patients were male, and mean [SD] Charlson comorbidity index [CCI] was 0.8 [1.2]. The PPPY number of hospitalizations was higher in Cohort A than in Cohort B (4.56 vs 2.09, respectively), as was the PPPY total length of hospital stay (51.1 vs 19.7 days). The PPPY hospitalization-related costs were $345,728 in Cohort A and $125,018 in Cohort B; the cumulative hospitalization cost per patient was $148,430 higher in Cohort A at 12 months and $177,500 higher at 18 months (Figure). Multivariate GEE and GLM models with adjustment for patient characteristic covariates (eg, age, sex, CCI) identified prolonged remission was significantly associated with reduced number, duration, and cost of hospitalization (P < 0.001, all comparisons).CONCLUSIONS: In a real-world setting, prolonged AML remission was associated with significantly lower rates and durations of hospitalization, which were estimated to result in substantial cumulative cost savings. These data underscore the importance of active maintenance therapies that delay relapse for patients with AML. While the costs of long-term therapy face increasing scrutiny, these costs should be weighed relative to the potential economic benefit of prolonged remission and reduced burden of healthcare resource utilization. [Display omitted] DisclosuresChen: Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Papademetriou: SmartAnalyst Inc.: Current Employment. Potluri: Bristol Myers Squibb: Consultancy.

Topology and size optimization for a flexure hinge using an integration of SIMP, deep artificial neural network, and water cycle algorithm

This paper develops a multistage optimization method for designing a new flexure hinge (FH). The proposed method is a combination of the topology optimization, the deep artificial neural network (DANN)-based modeling, and the water cycle algorithm-based size optimization. Firstly, solid isotropic material with penalization is employed to topologize the FH. Then, the topological FH is modified to transform into a compliant configuration. Finite element method is used to collect the output datasets of the hinge. Subsequently, the architectures of DANN are optimized to formulate the objective functions and constraints of the hinge. The results showed that the prediction accuracy of the developed DANN is better than that of the multivariate general linear model. Lastly, the geometrical sizes of the hinge are optimized by hybridizing the optimal DANN and the water cycle algorithm. The results found that the optimal solutions found from the proposed method are greater than those obtained from the other metaheuristic algorithms. Based on the results of Wilcoxon, Friedman, and Post-hoc tests, the proposed method outperforms the other methods. Besides, the results indicated that the performances of the FH are superior to the conventional hinges. The proposed optimization framework can be considered as a systematic design method for compliant mechanisms and related engineering areas.

Genetic predisposition to impaired metabolism of the branched chain amino acids, dietary intakes, and risk of type 2 diabetes

Background and objectivesCirculating branched chain amino acids (BCAAs) increase the risk of type 2 diabetes (T2D). The genetic variants in the BCAA metabolic pathway influence the individual metabolic ability of BCAAs and may affect circulating BCAA levels together with dietary intakes. So, we investigated whether genetic predisposition to impaired BCAA metabolism interacts with dietary BCAA intakes on the risk of type 2 diabetes and related parameters.MethodsWe estimated dietary BCAA intakes among 434 incident T2D cases and 434 age-matched controls from The Harbin Cohort Study on Diet, Nutrition and Chronic Non-Communicable Diseases. The genetic risk score (GRS) was calculated on the basis of 5 variants having been identified in the BCAA metabolic pathway. Multivariate logistic regression models and general linear regression models were used to assess the interaction between dietary BCAAs and GRS on T2D risk and HbA1c.ResultsDietary BCAAs significantly interact with metabolism related GRS on T2D risk and HbA1c (p for interaction = 0.038 and 0.015, respectively). A high intake of dietary BCAAs was positively associated with diabetes incidence only among high GRS (OR 2.40, 95% CI 1.39, 4.12, P for trend = 0.002). Dietary BCAAs were associated with 0.14% elevated HbA1c (p = 0.003) and this effect increased to 0.21% in high GRS (p = 0.003). Furthermore, GRS were associated with 9.19 μmol/L higher plasma BCAA levels (p = 0.006, P for interaction = 0.015) only among the highest BCAA intake individuals.ConclusionsOur study suggests that genetic predisposition to BCAA metabolism disorder modifies the effect of dietary BCAA intakes on T2D risk as well as HbA1c and that higher BCAA intakes exert an unfavorable effect on type 2 diabetes risk and HbA1c only among those with high genetic susceptibility.

Effect of High-definition Transcranial Direct Current Stimulation on Conditioned Pain Modulation in Healthy Adults: A Crossover Randomized Controlled Trial

The disorder of the conditioned pain modulation (CPM) system is one of the main causes of pain perception in individuals. High-definition transcranial direct current stimulation (HD-tDCS) targeting specific brain areas was indicated to have an analgesic effect possibly by activating the endogenous pain inhibition pathway evident in CPM. However, discrepancies were found in previous limited studies of varied homogeneity and quality. Therefore, the present study applied 2 mA HD-tDCS (20 min) in the left primary motor cortex (M1) among 35 healthy adults with a blinded crossover study design, to investigate its effectiveness on optimizing the analgesic effect in healthy individuals through assessing changes of the CPM. The univariate and multivariate general linear models were used to evaluate the intervention effect between-group on the Δ-value (after-intervention minus before-intervention) during CPM (primary outcome), pressure pain threshold (PPT), and cold pressure threshold (CPT) (secondary outcome), respectively. A significant between-group difference in Δ-CPM was found for active stimulation. HD-tDCS significantly improved the analgesic efficiency of Δ-CPM, compared with the sham control, after adjusting the confounding factors including age, gender, psychological status, as well as the sequence effect. The changes of CPM were positively correlated with the total physical activity volume. In conclusion, our findings provide evidence support to the effectiveness of HD-tDCS on endogenous pain modulation among healthy adults. Further studies are required to explore the analgesic effect of tDCS among patients with chronic pain, thereby facilitating optimal chronic pain management.