Mixed Logistic Models Research Articles

Predictors of Healthcare Utilization in Family Caregivers of Persons With a Primary Malignant Brain Tumor.

BACKGROUND: Negative physical health results from the emotional stress of providing care to a family member with a primary malignant brain tumor; however, the downstream effects on caregivers' healthcare utilization (HCU) are unknown. This analysis examined associations between caregivers' emotional health and markers of HCU during the 6 months after patients' diagnoses. METHODS: Caregivers' self-report HCU data from a longitudinal study with 116 neuro-oncology caregivers were analyzed. Healthcare utilization was operationalized as number of prescription medications, reporting visits to primary care providers (PCPs), nature of PCP visit, number of comorbid conditions, and change in comorbid conditions. Potential predictors were caregivers' depressive symptoms (Center for Epidemiologic Studies-Depression Scale), hours providing care per day, mastery (Pearlin and Schooler), and burden (Caregiver Reaction Assessment). Logistic mixed effects modeling were used. RESULTS : Caregivers with higher levels of depressive symptoms ( P < .01), anxiety ( P = .02), burden related to schedule ( P = .02), and abandonment ( P < .01) were more likely to report worsening comorbid conditions. Those with higher mastery ( P = .02) were less likely to report worsening comorbid conditions. Caregivers who had a PCP visit and reported higher burden related to feelings of self-esteem ( P = .03) were more likely to report an illness-related visit. CONCLUSION : Findings suggest a relationship between neuro-oncology caregivers' emotional health and their HCU. Data highlight the importance of caregivers' PCPs identifying caregivers at risk for deteriorating health and increased HCU and intervene to ensure caregivers' self-care.

Relating the One-Parameter Logistic Diagnostic Classification Model to the Rasch Model and One-Parameter Logistic Mixed, Partial, and Probabilistic Membership Diagnostic Classification Models

Diagnostic classification models (DCMs) are statistical models with discrete latent variables (so-called skills) to analyze multiple binary variables (i.e., items). The one-parameter logistic diagnostic classification model (1PLDCM) is a DCM with one skill and shares desirable measurement properties with the Rasch model. This article shows that the 1PLDCM is indeed a latent class Rasch model. Furthermore, the relationship of the 1PLDCM to extensions of the DCM to mixed, partial, and probabilistic memberships is treated. It is argued that the partial and probabilistic membership models are also equivalent to the Rasch model. The fit of the different models was empirically investigated using six datasets. It turned out for these datasets that the 1PLDCM always had a worse fit than the Rasch model and mixed and partial membership extensions of the DCM.

Relationships of pregnancy and postpartum diet quality with offspring birth weight and weight status through 12 months.

This study examined relationships of maternal pregnancy and postpartum diet quality with infant birth size and weight status indicators through 12 months and tested whether breastfeeding duration modifies these associations. In the Pregnancy Eating Attributes Study (PEAS), dietary intake was assessed six times in 458 mothers who were followed from early pregnancy through 12 months postpartum (2014-2018). Logistic and linear mixed models estimated relationships of pregnancy and postpartum diet quality (Healthy Eating Index [HEI]) with offspring who were large-for-gestational-age (LGA) at birth, as well as BMI z score (BMIz) and weight-for-length z score (WFLz) at birth, 6 weeks, 6 months, and 12 months. Pregnancy HEI was inversely related to LGA (odds ratio [OR] = 0.95, 95% CI: 0.92 to 0.98); HEI was also inversely related to WFLz (β = -0.01, 95% CI: -0.02 to -0.002) and BMIz (β = -0.009, 95% CI: -0.02 to -0.0009) from birth through 12 months. Postpartum HEI was inversely related to WFLz (β = -0.01, 95% CI: -0.02 to -0.0009) and BMIz (β = -0.008, 95% CI: -0.02 to 0.0007) in infants who were breastfed for at least 6 months, but not in those who were breastfed for a shorter duration. Maternal diet quality during pregnancy (and during postpartum in mothers who breastfed for a longer duration) was inversely related to LGA and weight status indicators from birth through 12 months. Increasing maternal diet quality may have use for promoting healthy infant weight development.

Efficiency of the Cerebroplacental Ratio in Identifying High-Risk Late-Term Pregnancies.

Background and Objectives: Over the last few years, great interest has arisen in the role of the cerebroplacental ratio (CPR) to identify low-risk pregnancies at higher risk of adverse pregnancy outcomes. This study aimed to assess the predictive capacity of the CPR for adverse perinatal outcomes in all uncomplicated singleton pregnancies attending an appointment at 40-42 weeks. Materials and Methods: This is a retrospective cohort study including all consecutive singleton pregnancies undergoing a routine prenatal care appointment after 40 weeks in three maternity units in Spain and the United Kingdom from January 2017 to December 2019. The primary outcome was adverse perinatal outcomes defined as stillbirth or neonatal death, cesarean section or instrumental delivery due to fetal distress during labor, umbilical arterial cord blood pH < 7.0, umbilical venous cord blood pH < 7.1, Apgar score at 5 min < 7, and admission to the neonatal unit. Logistic mixed models and ROC curve analyses were used to analyze the data. Results: A total of 3143 pregnancies were analyzed, including 537 (17.1%) with an adverse perinatal outcome. Maternal age (odds ratio (OR) 1.03, 95% confidence interval (CI) 1.01 to 1.04), body mass index (OR 1.04, 95% CI 1.03 to 1.06), racial origin (OR 2.80, 95% CI 1.90 to 4.12), parity (OR 0.36, 95% CI 0.29 to 0.45), and labor induction (OR 1.79, 95% CI 1.36 to 2.35) were significant predictors of adverse perinatal outcomes with an area under the ROC curve of 0.743 (95% CI 0.720 to 0.766). The addition of the CPR to the previous model did not improve performance. Additionally, the CPR alone achieved a detection rate of only 11.9% (95% CI 9.3 to 15) when using the 10th centile as the screen-positive cutoff. Conclusions: Our data on late-term unselected pregnancies suggest that the CPR is a poor predictor of adverse perinatal outcomes.

Evaluating false positive rates of standard and hierarchical measures of metacognitive accuracy

A key aspect of metacognition is metacognitive accuracy, i.e., the degree to which confidence judgments differentiate between correct and incorrect trials. To quantify metacognitive accuracy, researchers are faced with an increasing number of different methods. The present study investigated false positive rates associated with various measures of metacognitive accuracy by hierarchical resampling from the confidence database to accurately represent the statistical properties of confidence judgements. We found that most measures based on the computation of summary-statistics separately for each participant and subsequent group-level analysis performed adequately in terms of false positive rate, including gamma correlations, meta-d′, and the area under type 2 ROC curves. Meta-d′/d′ is associated with a false positive rate even below 5%, but log-transformed meta-d′/d′ performs adequately. The false positive rate of HMeta-d depends on the study design and on prior specification: For group designs, the false positive rate is above 5% when independent priors are placed on both groups, but the false positive rate is adequate when a prior was placed on the difference between groups. For continuous predictor variables, default priors resulted in a false positive rate below 5%, but the false positive rate was not distinguishable from 5% when close-to-flat priors were used. Logistic mixed model regression analysis is associated with dramatically inflated false positive rates when random slopes are omitted from model specification. In general, we argue that no measure of metacognitive accuracy should be used unless the false positive rate has been demonstrated to be adequate.

A pilot genome-wide association study meta-analysis of gastroparesis.

Gastroparesis (GP) is characterized by delayed gastric emptying in the absence of mechanical obstruction. Genetic predisposition may play a role; however, investigation at the genome-wide level has not been performed. We carried out a genome-wide association study (GWAS) meta-analysis on (i) 478 GP patients from the National Institute of Diabetes and Digestive and Kidney Diseases Gastroparesis Clinical Research Consortium (GpCRC) compared to 9931 population-based controls from the University of Michigan Health and Retirement Study; and (ii) 402 GP cases compared to 48,340 non-gastroparesis controls from the Michigan Genomics Initiative. Associations for 5,811,784 high-quality SNPs were tested on a total of 880 GP patients and 58,271 controls, using logistic mixed models adjusted for age, sex, and principal components. Gene mapping was obtained based on genomic position and expression quantitative trait loci, and a gene-set network enrichment analysis was performed. Genetic associations with clinical data were tested in GpCRC patients. Protein expression of selected candidate genes was determined in full thickness gastric biopsies from GpCRC patients and controls. While no SNP associations were detected at strict significance (p≤5×10-8 ), nine independent genomic loci were associated at suggestive significance (p≤1×10-5 ), with the strongest signal (rs9273363, odds ratio=1.4, p=1×10-7 ) mapped to the human leukocyte antigen region. Computational annotation of suggestive risk loci identified 14 protein-coding candidate genes. Gene-set network enrichment analysis revealed pathways potentially involved in immune and motor dysregulation (pFDR ≤ 0.05). The GP risk allele rs6984536A (Peroxidasin-Like; PXDNL) was associated with increased abdominal pain severity scores (Beta=0.13, p=0.03). Gastric muscularis expression of PXDNL also positively correlated with abdominal pain in GP patients (r=0.8, p=0.02). Dickkopf WNT Signaling Pathway Inhibitor 1 showed decreased expression in diabetic GP patients (p=0.005 vs. controls). We report preliminary GWAS findings for GP, which highlight candidate genes and pathways related to immune and sensory-motor dysregulation. Larger studies are needed to validate and expand these findings in independent datasets.

Peri-zygomatic complications on zygomatic implants with or without penetrating the external surface of zygoma: A 2-year retrospective study.

The main purpose of this retrospective study was to assess the difference in the incidence of peri-zygomatic complications (PZCs) when zygomatic implants (ZIs) penetrate or do not penetrate the external surface of zygoma. This study included 32 patients with edentulous maxillae or potentially edentulous maxillae undergo zygomatic implantation. The patients were divided into the penetration group (P-group) and the non-penetration group (N-group) according to whether the apex of implants penetrated the external surface of zygoma in postoperative CBCT. The extension length, the penetration section of the implants, and the skin thickness at the corresponding position were simultaneously measured. Clinical follow-up was conducted regularly until 2 years after surgery. The occurrence of PZCs (including peri-zygomatic infection, skin numbness, non-infectious pain, and foreign body sensation) was recorded. A mixed effect logistic model was used to compare the difference of complication rate between the P-group and the N-group, and odds ratio (OR) was calculated. Then identify the impact of the extension length, penetration section and skin thickness in P-group with the same model. A total of 71 ZIs were implanted in 32 patients, including 37 implants in the P-group and 34 implants in the N-group. During the 2-year follow-up, a total of 13 implants occurred PZCs, with an overall complication rate of 18.3%. Thereinto, the incidence rate was 29.7% in the P-group, and 5.9% in the N-group (OR = 6.77). In P-group, there was a significant difference in complication rate of different extension lengths, while the penetration section and skin thickness had no statistical significance on the complication rate. Under the limitation of this study, to minimize the risk of PZCs, ZI should be placed in a manner that avoids the apex penetrating the external surface of the zygoma.

Prognosis and prediction of antibiotic benefit in adults with clinically diagnosed acute rhinosinusitis: an individual participant data meta-analysis

BackgroundA previous individual participant data meta-analysis (IPD-MA) of antibiotics for adults with clinically diagnosed acute rhinosinusitis (ARS) showed a marginal overall effect of antibiotics, but was unable to identify patients that are most likely to benefit from antibiotics when applying conventional (i.e. univariable or one-variable-at-a-time) subgroup analysis. We updated the systematic review and investigated whether multivariable prediction of patient-level prognosis and antibiotic treatment effect may lead to more tailored treatment assignment in adults presenting to primary care with ARS.MethodsAn IPD-MA of nine double-blind placebo-controlled trials of antibiotic treatment (n=2539) was conducted, with the probability of being cured at 8–15 days as the primary outcome. A logistic mixed effects model was developed to predict the probability of being cured based on demographic characteristics, signs and symptoms, and antibiotic treatment assignment. Predictive performance was quantified based on internal-external cross-validation in terms of calibration and discrimination performance, overall model fit, and the accuracy of individual predictions.ResultsResults indicate that the prognosis with respect to risk of cure could not be reliably predicted (c-statistic 0.58 and Brier score 0.24). Similarly, patient-level treatment effect predictions did not reliably distinguish between those that did and did not benefit from antibiotics (c-for-benefit 0.50).ConclusionsIn conclusion, multivariable prediction based on patient demographics and common signs and symptoms did not reliably predict the patient-level probability of cure and antibiotic effect in this IPD-MA. Therefore, these characteristics cannot be expected to reliably distinguish those that do and do not benefit from antibiotics in adults presenting to primary care with ARS.

Determinants of Hispanic and non-Hispanic Workers' Intent to Work Past Age 65: An Analysis From the Life Course Perspective.

Background: The average retirement age in the United States (U.S.) has increased over the past few decades. However, the rate of increase for Hispanics is lower than that for non-Hispanics. For Hispanics, the decision to retire later may be more influenced by their migration history and context rather than health or finances. Objective: This study aims to explore the differences in the determinants of intentions to delay retirement (i.e., work beyond the age of 65) between Hispanics and non-Hispanic Whites in the U.S. Methods: A pooled sample was generated from all waves of the Health and Retirement Study (1992-2014), including a unique record for each non-institutionalized individual aged 55-61 who was employed. All eligible Hispanics (n = 3,663) were included, while a random sample of non-Hispanic Whites (n = 3,663) was selected. Logistic mixed models were conducted for each group, and a Two-fold Oaxaca-Blinder decomposition analysis was used to explore differences between the groups. Results: The results indicate that non-Hispanic Whites are more likely to plan to postpone retirement. Furthermore, significant differences were found between Hispanics and non-Hispanic Whites regarding their intentions to delay retirement, specifically related to socioeconomic indicators such as individual earnings, amount of debt, level of education, and parents' level of education. The differences between the groups were primarily influenced by the amount of debt, having a defined benefit plan, and parents' level of education, reflecting the cumulative disadvantage experienced by Hispanics over their life course. Conclusion: Most existing research on the topic has focused on middle-class Whites, while few studies have examined race or ethnicity as the primary focus or explored the extent to which commonly identified predictors of delayed retirement apply to different ethno-racial groups. This is significant because Hispanics and other disadvantaged groups tend to experience financial insecurity during retirement, which directly impacts their health and well-being.

Evidence for an association between allostatic load and multisensory integration in middle-aged and older adults

Multisensory integration, the ability of the brain to integrate information from different sensory modalities, is critical for responding to environmental stimuli. While older adults show changes in multisensory integration with age, the impact of allostatic load (AL) (i.e., the effect of exposure to chronic stress, which can accelerate ageing) on multisensory perception remains understudied. We explored the relationship between multisensory integration and AL in 1,358 adults aged 50+ from The Irish Longitudinal Study on Ageing by performing a Sound Induced Flash Illusion (SIFI) task at multiple audio-visual temporal asynchronies. The AL score was created using a battery of biomarkers representing the activity of four major physiological systems: immunological, cardiovascular, metabolic, and renal. The number of biomarkers for which a participant was categorised in the highest risk quartile using sex-specific cutoffs was used to produce an overall AL score. We accounted for medication use when calculating our AL score. We analysed the accuracy of illusion trials on a SIFI task using generalised logistic mixed effects regression models adjusted for a number of covariates. Observation of cross-sectional and longitudinal results revealed that lower accuracy in integration (i.e., higher SIFI susceptibility with larger temporal asynchronies) was associated with higher AL. This confirmed the distinct patterns of multisensory integration in ageing.

Malaria Infections and Placental Blood Flow: A Doppler Ultrasound Study From a Preconception Cohort in Benin.

Malaria in pregnancy (MiP) has been associated with fetal growth restriction, the underlying pathogenic mechanisms of which remain poorly understood. Malaria in pregnancy is suspected to induce abnormalities in placental vascularization, leading to impaired placental development. Our study evaluated MIP's effect on uterine artery (UtA) and umbilical artery (UA) blood flow. The analysis included 253 Beninese women followed throughout pregnancy and screened monthly for submicroscopic and microscopic malaria. Uterine artery Doppler measurement was performed once between 21 and 25 weeks' gestation (wg), and UA Doppler measurement was performed 1-3 times from 28 wg. Linear and logistic regression models were used to assess the effect of malaria infections on UtA Doppler indicators (pulsatility index and presence of a notch), whereas a logistic mixed model was used to assess the association between malaria infections and abnormal UA Doppler (defined as Z-score ≥2 standard deviation or absent/reversed UA end-diastolic flow). Primigravidae represented 7.5% of the study population; 42.3% of women had at least 1 microscopic infection during pregnancy, and 29.6% had at least 1 submicroscopic infection (and no microscopic infection). Both microscopic and submicroscopic infections before Doppler measurement were associated with the presence of a notch (adjusted odds ratio [aOR] 4.5, 95% confidence interval [CI] = 1.2-16.3 and aOR 3.3, 95% CI = .9-11.9, respectively). No associations were found between malaria before the Doppler measurement and abnormal UA Doppler. Malaria infections in the first half of pregnancy impair placental blood flow. This highlights the need to prevent malaria from the very beginning of pregnancy.

Breastfeeding Disparities During the COVID-19 Pandemic: Race/Ethnicity, Age, Education, and Insurance Payor.

There are well-documented disparities in rates of continued breastfeeding. Existing research regarding breastfeeding during COVID-19 has raised concerns that the pandemic may have exacerbated these disparities. The aim of this research was first to quantify disparities in any breastfeeding associated with the maternal factors of race/ethnicity, age, insurance payor, and zip code rates of education in North Carolina. Second, we aimed to investigate any changes in these disparities before and during the COVID-19 pandemic. This was an observational study, with a retrospective, longitudinal design. Participants included infants who were born in one of eight medical centers across North Carolina from either September 1, 2019 to October 31, 2019 (pre-COVID: n = 1,104) or from April 1, 2020 to May 31, 2020, (during COVID: n = 1,157), and whose caregivers reported whether they were breastfeeding at either a 3-month or 6-month postnatal follow-up (N = 2,261). Mixed effects logistic models, including random effects of zip code, assessed predictors associated with probability of breastfeeding cessation at 3- and 6-month child well-check. Overall, younger maternal age, being non-Hispanic Black, not having commercial insurance, and residing in a zip code with lower rates of higher education, were all independently associated with earlier breastfeeding cessation across both cohorts. Disparities did not significantly change during the COVID-19 pandemic. We did not find support for the hypothesis that the COVID-19 pandemic might have exacerbated breastfeeding disparities. Nevertheless, there is a continued need to eliminate existing disparities.

Malnutrition and protein energy wasting are associated with severity and progression of pediatric chronic kidney disease.

Protein energy wasting (PEW), a state of deficient protein storage, is not well understood in children and adolescents with chronic kidney disease (CKD). We aimed to re-define PEW using pediatric malnutrition guidelines from the Academy of Nutrition and Dietetics/American Society for Parenteral and Enteral Nutrition (AND/ASPEN), and to describe the relationship between PEW, malnutrition, and kidney function. This was a retrospective review of outpatients ≤ 20years old with a diagnosis of CKD from January 1, 2013, to August 31, 2018. Malnutrition was diagnosed by a licensed dietitian, and PEW was diagnosed using an updated definition incorporating AND/ASPEN malnutrition guidelines. Logistic regression and linear mixed effects modeling were performed on the relationship of malnutrition and PEW to estimated glomerular filtration rate (eGFR). The 142 patients included in this analysis had a median age of 11.1years and median eGFR of 57ml/min/1.73 m2 at initial visit. Malnutrition was diagnosed in 50% of patients in at least one visit, and 17.6% met ≥ 2 PEW criteria. Patients with eGFR < 30ml/min/1.73 m2 had significantly increased risk of malnutrition [OR 2.5, 95% CI 2.0-3.3] (p < 0.001) and PEW [OR 4.9, 95% CI 3.0-8.0] (p < 0.001). A diagnosis of malnutrition or PEW was associated with worse eGFR by logistic regression (p = 0.01 and p = 0.001, respectively) and more rapid eGFR decline by linear mixed effects model (p = 0.002 and p < 0.001, respectively) compared to those without these diagnoses. Malnutrition and PEW are prevalent in pediatric CKD and are associated with significantly lower eGFR and more rapid decline in eGFR, emphasizing the need to address nutritional status. A higher resolution version of the Graphical abstract is available as Supplementary information.

Stricter Blood Pressure Control Is Associated With Lower Left Ventricular Mass in Children After Kidney Transplantation: A Longitudinal Analysis of the 4C-T Study.

We assessed the effect of blood pressure (BP) control on left ventricular mass index (LVMI) and left ventricular hypertrophy (LVH). Ninety-six patients (64 males) ≥9 months post-kidney transplantation from the 4C-T (Cardiovascular Comorbidity in Children with Chronic Kidney Disease and Transplantation) study were analyzed longitudinally (mean follow-up, 2.6±1.3 years). Cumulative systolic blood pressure (SBP)/diastolic BP exposure was calculated as a time-averaged area under the curve and categorized: ≤50th, 50th to ≤75th, 75th to ≤90th, and >90th percentile (pct). We performed adjusted linear and logistic mixed models for LVMI and LVH, respectively. At baseline, LVMI was 49.7±12.7g/m2.16 with 64% (n=61) kidney transplantation recipients displaying LVH. Compared with patients with cumulative SBP exposure >90th pct, patients with cumulative SBP of 50th to ≤75th showed a significant LVMI reduction of -5.24g/m2.16 (P=0.007). A similar tendency was seen for cumulative SBP≤50th (β=-3.70 g/m2.16; P=0.067), but patients with cumulative SBP of 75th to ≤90th pct showed no reduction. A post hoc analysis in patients with cumulative SBP≤75th revealed that median SBP exposure was at 57.5th pct. For cumulative diastolic BP, a significant LVMI reduction was seen in all 3 categories ≤90th pct compared with patients >90th pct. Patients with cumulative SBP of ≤50th or 50th to ≤75th pct showed 79% or 83% lower odds of developing LVH, respectively. Patients with cumulative diastolic BP ≤50th showed a tendency of 82% lower odds for LVH (95% CI, 0.03-1.07). Stricter BP control led to regression of LVMI and LVH. Our data suggest a BP target below the 60th pct, which needs to be substantiated in a randomized controlled trial.

Subjective valuation of performance feedback is robust to trait cognitive fatigue in multiple sclerosis.

Performance feedback is vital to rehabilitation interventions that treat cognitive impairments from multiple sclerosis (MS). Optimal treatment relies on participants' motivation to learn from feedback throughout these interventions. Cognitive fatigue, a prevalent symptom of MS, is associated with aberrant reward processing, which necessitates research into how fatigue affects perceived reward value of feedback in these individuals. The current study investigated how trait fatigue influences subjective valuation of feedback and subsequent feedback-seeking behavior in people with MS. 33 MS and 32 neurotypical (NT) participants completed a willingness-to-pay associative memory paradigm that assessed feedback valuation via trial-by-trial decisions to either purchase or forego feedback in service of maximizing a performance-contingent monetary reward. Participant ratings of trait fatigue were also collected. Generalized logistic mixed modeling was used to analyze factors that influenced trial-wise feedback purchase decisions and task performance. Despite reporting greater trait fatigue, MS participants purchased comparable amounts of feedback as NT participants. Like NT participants, MS participants were more likely to purchase feedback when they were less confident about response accuracy. MS participants also performed comparably to NT participants, who both particularly benefited from purchase decisions that yielded negative feedback (i.e., indicating a response error). Trait cognitive fatigue may not impact performance feedback valuation in people with MS. Nonetheless, confidence in performance may drive their feedback-seeking behavior and may serve as a target for improving learning throughout cognitive rehabilitation and maximizing treatment success.

Admixture mapping implicates 13q33.3 as ancestry-of-origin locus for Alzheimer disease in Hispanic and Latino populations.

Alzheimer disease (AD) is the most common form of senile dementia, with high incidence late in life in many populations including Caribbean Hispanic (CH) populations. Such admixed populations, descended from more than one ancestral population, can present challenges for genetic studies, including limited sample sizes and unique analytical constraints. Therefore, CH populations and other admixed populations have not been well represented in studies of AD, and much of the genetic variation contributing to AD risk in these populations remains unknown. Here, we conduct genome-wide analysis of AD in multiplex CH families from the Alzheimer Disease Sequencing Project (ADSP). We developed, validated, and applied an implementation of a logistic mixed model for admixture mapping with binary traits that leverages genetic ancestry to identify ancestry-of-origin loci contributing to AD. We identified three loci on chromosome 13q33.3 associated with reduced risk of AD, where associations were driven by Native American (NAM) ancestry. This AD admixture mapping signal spans the FAM155A, ABHD13, TNFSF13B, LIG4, and MYO16 genes and was supported by evidence for association in an independent sample from the Alzheimer's Genetics in Argentina-Alzheimer Argentina consortium (AGA-ALZAR) study with considerable NAM ancestry. We also provide evidence of NAM haplotypes and key variants within 13q33.3 that segregate with AD in the ADSP whole-genome sequencing data. Interestingly, the widely used genome-wide association study approach failed to identify associations in this region. Our findings underscore the potential of leveraging genetic ancestry diversity in recently admixed populations to improve genetic mapping, in this case for AD-relevant loci.

Longitudinal mental health trends in cystic fibrosis

BackgroundMental health screening in accordance with consensus guidelines became routine clinical practice in our cystic fibrosis (CF) Center in 2015. We hypothesized improvement in anxiety and depression symptoms over time and associations between elevated screening scores and disease severity. We aimed to observe the impact of the COVID-19 pandemic and modulator use on mental health symptoms. MethodsRetrospective chart reviews were conducted for people 12 years and older with at least one Generalized Anxiety Disorder-7 (GAD-7) or Patient Health Questionnaire-9 (PHQ-9) screening for six years. Descriptive statistics were used to summarize demographic variables and logistic regression and linear mixed models were used to evaluate the relationship between screening scores and clinical variables. ResultsAnalyses included 150 participants (ages 12–22 years). The percentage of minimal to no symptom scores increased over time for anxiety and depression. Increased mental health visits and CFRD were associated with higher PHQ-9 and GAD-7 scores. Higher FEV1pp was associated with lower GAD-7 and PHQ-9 scores. More effective modulator use was associated with lower PHQ-9 scores. Mean PHQ-9 and GAD-7 scores were not significantly different when comparing pre-pandemic and pandemic scores. ConclusionDisruptions in screening during the pandemic were minimal and symptom scores remained stable. Individuals with higher mental health screening scores were more likely to have CFRD and utilization of mental health services. Consistent mental health monitoring and support is needed so individuals with CF can endure anticipated and unanticipated stressors including changes in physical health, healthcare, and societal stressors such as COVID-19 pandemic.

Bayesian model selection for generalized linear mixed models.

We propose a Bayesian model selection approach for generalized linear mixed models (GLMMs). We consider covariance structures for the random effects that are widely used in areas such as longitudinal studies, genome-wide association studies, and spatial statistics. Since the random effects cannot be integrated out of GLMMs analytically, we approximate the integrated likelihood function using a pseudo-likelihood approach. Our Bayesian approach assumes a flat prior for the fixed effects and includes both approximate reference prior and half-Cauchy prior choices for the variances of random effects. Since the flat prior on the fixed effects is improper, we develop a fractional Bayes factor approach to obtain posterior probabilities of the several competing models. Simulation studies with Poisson GLMMs with spatial random effects and overdispersion random effects show that our approach performs favorably when compared to widely used competing Bayesian methods including deviance information criterion and Watanabe-Akaike information criterion. We illustrate the usefulness and flexibility of our approach with three case studies including a Poisson longitudinal model, a Poisson spatial model, and a logistic mixed model. Our proposed approach is implemented in the R package GLMMselect that is available onCRAN.

P-220 “Blame it on my youth”: when very young age appears to be associated with poorer embryo development in oocyte donors

Abstract Study question Is a very young donor’s age associated with different blastocyst usable rate and embryo quality? Summary answer Donors &amp;lt;20 years old have a significantly lower blastocyst usable rate but comparable average embryo quality than donors &amp;gt;25. What is known already Embryo development and quality in IVF cycles are affected by increasing female age. However, some authors also described a lower fertilization rate and reduced number of top-quality embryos in very young infertile patients &amp;lt;25 years old as compared to patients aged 25-35. It has even been reported that live birth rates are significantly lower in oocyte recipients when the donors’ age is &amp;lt; 25. Still, the mechanisms underlying these apparently poorer outcomes in very young women remain speculative given that data on embryo development and quality in vitro are scarce. Study design, size, duration Retrospective-observational study of 1274 oocyte donor’s and 1738 oocyte recipient’s cycles with blastocyst transfer carried out in 2016-2022 in the Fertility Unit of a tertiary University Hospital. Cycles with vitrified oocytes, severe male factor or cleavage-stage embryo transfer were excluded. The main parameters analyzed were blastocyst usable rate (% fertilized oocytes that became a blastocyst suitable for transfer/freezing) and blastocyst quality based on 2015 ASEBIR-scoring system (considering day of development and morphology):D5A, D5B, D5C, D6B, D6C. Participants/materials, setting, methods Cycles were categorized according to donor’s age (Group A: &amp;lt;20, Group B: 20-25, Group C: ≥26). Oocyte donors were aged 18-34. Recipients were aged 18-50. Blastocyst usable rate and embryo quality were compared across groups according to donor’s age. For multivariable analysis, a generalized logistic linear mixed model was applied to estimate the odds for every endpoint, taking Group C as a reference group. Donor and recipient were treated as random factors to avoid the repeated-observation effect. Main results and the role of chance A total of 1274 oocyte donor’s cycles and 1738 oocyte recipient’s cycles were analyzed. Mean age was 26.1 ± 4.3 years old for donors, 42.6 ± 3.8 for recipients, and 43.3 ± 5.7 for male partners. Mean donors’ AMH was 3.8 ± 2.1ng/ml, mean number of mature oocytes (MII) retrieved was 15.8 ± 7.7, and mean total dose of gonadotropins was 1413.1 ± 885.4 units. ICSI technique was used in 75.6% of the cycles. The distribution of cycles by donor age was Group A: n = 55 cycles (4.3%), Group B: n = 532 cycles (41.8%) and Group C: n = 687 cycles (53.9%). Blastocyst usable rate was significantly different according to donors’ age: 33.2% (176/530) for Group A, 42.9% (2580/6016) for Group B and 43.5% (3109/7147) for Group C. Regression analysis, adjusting for confounding factors (AMH, MII, gonadotropins total dose, male age, insemination technique), has shown a significantly lower blastocyst usable rate in very young donors Group A (OR: 0.63; CI 95%; 0.48-0.83) as compared to Group C. Although similar differences were observed in the proportion of top-quality blastocysts (D5A+D5B) in the bivariate analysis A: 19.2% (102/530), B: 24.6% (1480/6016) and C: 24.4% (1742/7147), no significant differences were found after adjustment for confounding factors. Limitations, reasons for caution The main limitation of this study is its retrospective design; still multiple adjustments for confounding factors have been performed in order to minimize the risk of confounding bias. Wider implications of the findings Our finding of a lower blastocyst usable rate in very young donors may be associated with a higher aneuploidy embryo rate in this group, previously reported, advocating for further studies with PGT-A and basic research to decipher the underlying molecular mechanisms. Trial registration number not applicable

Associations between adverse childhood experiences and early adolescent problematic screen use in the United States

BackgroundProblematic screen use, defined as an inability to control use despite private, social, and professional life consequences, is increasingly common among adolescents and can have significant mental and physical health consequences. Adverse Childhood Experiences (ACEs) are important risk factors in the development of addictive behaviors and may play an important role in the development of problematic screen use.MethodsProspective data from the Adolescent Brain Cognitive Development Study (Baseline and Year 2; 2018–2020; N = 9,673, participants who did not use screens were excluded) were analyzed in 2023. Generalized logistic mixed effects models were used to determine associations with ACEs and the presence of problematic use among adolescents who used screens based on cutoff scores. Secondary analyses used generalized linear mixed effects models to determine associations between ACEs and adolescent-reported problematic use scores of video games (Video Game Addiction Questionnaire), social media (Social Media Addiction Questionnaire), and mobile phones (Mobile Phone Involvement Questionnaire). Analyses were adjusted for potential confounders including age, sex, race/ethnicity, highest parent education, household income, adolescent anxiety, depression, and attention-deficit symptoms, study site, and participants who were twins.ResultsThe 9,673 screen-using adolescents ages 11–12 years old (mean age 12.0) were racially and ethnically diverse (52.9% White, 17.4% Latino/Hispanic, 19.4% Black, 5.8% Asian, 3.7% Native American, 0.9% Other). Problematic screen use rates among adolescents were identified to be 7.0% (video game), 3.5% (social media), and 21.8% (mobile phone). ACEs were associated with higher problematic video game and mobile phone use in both unadjusted and adjusted models, though problematic social media use was associated with mobile screen use in the unadjusted model only. Adolescents exposed to 4 or more ACEs experienced 3.1 times higher odds of reported problematic video game use and 1.6 times higher odds of problematic mobile phone use compared to peers with no ACEs.ConclusionsGiven the significant associations between adolescent ACE exposure and rates of problematic video and mobile phone screen use among adolescents who use screens, public health programming for trauma-exposed youth should explore video game, social media, and mobile phone use among this population and implement interventions focused on supporting healthy digital habits.