Generalized Estimating Equations Models Research Articles

Urinary Vitamin D Binding Protein: A Marker of Kidney Tubular Dysfunction in Patients at Risk for Type 2 Diabetes.

Recent studies have reported elevated urinary vitamin D binding protein (uVDBP) concentrations in patients with diabetic kidney disease, although the utility of uVDBP to predict deterioration of kidney function over time has not been examined. Our objective was to assess the association of uVDBP with longitudinal changes in kidney function. Adults at-risk for type 2 diabetes from the Prospective Metabolism and Islet Cell Evaluation (PROMISE) study had 3 assessments over 6 years (n = 727). Urinary albumin-to-creatinine ratio (ACR) and estimated glomerular filtration rate (eGFR) were used as measures of kidney function. Measurements of uVDBP were performed with enzyme-linked immunosorbent assay and normalized to urine creatinine (uVDBP:cr). Generalized estimating equations (GEEs) evaluated longitudinal associations of uVDBP and uVDBP:cr with measures of kidney function, adjusting for covariates. Renal uVDBP loss increased with ACR severity at baseline. Individuals with normoalbuminuria, microalbuminuria, and macroalbuminuria had median log uVDBP:cr concentrations of 1.62 μg/mmol, 2.63 μg/mmol, and 2.48 μg/mmol, respectively, and ACR positively correlated with uVDBP concentrations (r = 0.37; P < .001). There was no significant association between uVDBP and eGFR at baseline. Adjusted longitudinal GEE models indicated that each SD increase both in baseline and longitudinal uVDBP:cr was significantly associated with higher ACR over 6 years (β = 30.67 and β = 32.91, respectively). Conversely, neither baseline nor longitudinal uVDBP:cr measures showed a significant association with changes in eGFR over time. These results suggest that loss of uVDBP:cr over time may be a useful marker for predicting renal tubular damage in individuals at risk for diabetes.

Prenatal and childhood lead exposure is prospectively associated with biological markers of aging in adolescence

Few studies have related early life lead exposure to adolescent biological aging, a period characterized by marked increases in maturational tempo. We examined associations between prenatal and childhood lead exposure and adolescent biological age (mean 14.5 years) utilizing multiple epigenetic clocks including: intrinsic (IEAA), extrinsic (EEAA), Horvath, Hannum, PhenoAge, GrimAge, Skin-Blood, Wu, PedBE, as well as DNA methylation derived telomere length (DNAmTL). Epigenetic clocks and DNAmTL were calculated via adolescent blood DNA methylation measured by Infinium MethylationEPIC BeadChips. We constructed general linear models (GLMs) with individual lead measures predicting biological age. We additionally examined sex-stratified models and lead by sex interactions, adjusting for adolescent age and lead levels, maternal smoking and education, and proportion of cell types. We also estimated effects of lead exposure on biological age using generalized estimating equations (GEE). First trimester blood lead was positively associated with a 0.14 increase in EEAA age in the GLMs though not the GEE models (95%CI 0.03, 0.25). First and 2nd trimester blood lead levels were associated with a 0.02 year increase in PedBE age in GLM and GEE models (1st trimester, 95%CI 0.004, 0.03; 2nd trimester, 95%CI 0.01, 0.03). Third trimester and 24 month blood lead levels were associated with a −0.06 and −0.05 decrease in Skin-Blood age, respectively, in GLM models. Additionally, 3rd trimester blood lead levels were associated with a 0.08 year decrease in Hannum age in GLM and GEE models (95%CI -0.15, −0.01). There were multiple significant results in sex-stratified models and significant lead by sex interactions, where males experienced accelerated biological age, compared to females who saw a decelerated biological age, with respect to IEAA, EEAA, Horvath, Hannum, and PedBE clocks. Further research is needed to understand sex-specific relationships between lead exposure and measures of biological aging in adolescence and the trajectory of biological aging into young adulthood.

Patients with longstanding psoriatic arthritis can achieve DAPSA remission or low disease activity and it correlates to better functional outcomes: results from a Latin-American real-life cohort

BackgroundPatients with psoriatic arthritis (PsA) experience reduced physical function and impaired quality of life. Better patient-reported functional outcomes are found when lower disease activity is achieved.ObjectivesTo evaluate the variation of physical function by HAQ-DI over time in PsA patients treated with standard therapy in a real-life setting: to verify predictors of achieving a minimum clinically important difference (MCID) in function by HAQ-DI (ΔHAQ-DI ≤ − 0.35) and to measure the impact of achieving REM/LDA on long-term function by HAQ-DI.MethodsThis is a longitudinal analysis of a real-life retrospective cohort. Data from PsA patients with at least 4 years of follow-up in the PsA clinic from 2011 to 2019 were extracted from electronic medical records. The variations of physical function by HAQ-DI and disease activity by DAPSA over time were calculated. A multivariate hierarchical regression model was applied to verify predictors of MCID in HAQ-DI. A comparison of HAQ-DI variation between patients with DAPSA REM, LDA, moderate and high disease activity was made using the generalized estimating equation model (GEE), adjusted by Bonferroni test. The Spearman correlation method was applied to verify the correlation of ΔDAPSA and ΔHAQ-DI over time. Statistical analysis was performed in SPSS program version 21.0.ResultsSeventy-three patients were included in the analysis. Physical function measured by HAQ-DI was determined by PsA disease activity measured by DAPSA (p < 0.000). A moderate and statistically significant correlation between ΔDAPSA and ΔHAQ-DI was observed (rs = 0.60; p < 0.001). Only patients in DAPSA REM demonstrated a constant decline in HAQ-DI scores during the follow-up. White ethnicity and older age at baseline were predictors for not achieving MCID in HAQ-DI [RR 0.33 (0.16–0.6795% CI p = 0.002) and RR 0.96 (0.93–0.9895% CI p < 0.000), respectively, while higher scores of HAQ-DI at baseline were predictors of achieving MCID [RR 1.71 (1.12–2.6095%CI p = 0.013)].ConclusionsIn PsA, patients who maintained DAPSA REM/LDA over time had better long-term functional outcomes. Higher HAQ-DI scores at baseline, non-white ethnicity and younger age were predictors for achieving a clinical meaningful improvement of HAQ-DI.

Impact of HIV-1 genetic diversity on disease progression: a prospective cohort study in Guangxi.

The high proportion of AIDS cases and mortality rates in Guangxi underscores the urgency to investigate the influence of HIV-1 genetic diversity on disease progression in this region. Newly diagnosed HIV-1 patients were enrolled from January 2016 to December 2021, and the follow-up work and detection of CD4+T lymphocytes were carried out every six months until December 2022. Multivariate logistic regression was used to analyze the factors affecting pre-treatment CD4+T lymphocyte counts, while local weighted regression models (LOESS) and generalized estimating equation models (GEE) were conducted to assess factors influencing CD4+T Lymphocyte Recovery. Cox regression analysis was utilized to examine the impact of subtypes on survival risk. Additionally, HIV-1 env sequences were utilized for predicting CXCR4 and CCR5 receptors. The study encompassed 1867 individuals with pol sequences and 281 with env sequences. Our findings indicate that age over 30, divorced/widowed, peasant, heterosexual infection, CRF01_AE, long-term infection, and Pre-treatment Viral load >10000 copies/ml were factors associated with higher risk for pre-treatment CD4+T lymphocyte decline. Specifically, male gender, age over 30, heterosexual infection (HETs), long-term infection, CRF01_AE, and Pre-treatment CD4 T cell counts below 350/µL were identified as risk factors impeding CD4+T lymphocyte recovery. Pre-treatment CD4+T lymphocyte counts and recovery in individuals infected with CRF01_AE were lower compared to CRF07_BC and CRF55_01B. Additionally, CRF01_AE and CRF08_BC subtypes exhibited higher mortality rates than CRF07_BC, CRF55_01B, and other subtypes. Notably, CRF01_AE demonstrated the highest percentage of CXCR4 affinity ratios. This research unveils the intricate influence of HIV-1 gene diversity on CD4+T lymphocyte dynamics and clinical outcomes. It highlights the multifaceted nature of HIV infection in Guangxi, providing novel insights into subtype-specific disease progression among HIV-infected individuals in this region.

Patient-Centered Positive Factors Influencing Glycemic Control in Adolescents with Type 1 Diabetes Mellitus in China: A Cross-Sectional and Longitudinal Study.

This study aimed to explore the stable longitudinalpatient-centered self-protectivefactors of glycosylated hemoglobin (HbA1c) in adolescents with type 1 diabetesmellitus(T1DM). We used both cross-sectional and longitudinal datasets at the Diabetes Education Center and National Endocrine and Metabolism Centre of a university hospital in China from April 2020 to July 2022. Participants were assessed using the Adolescent Diabetic Behavior Rating Scale (DBRS), Diabetes Strengths and Resilience Measure for Adolescents (DSTAR-Teen). HbA1c and other clinical variables were obtained from the medical record at the same time. 266 adolescents (131 male, age 14.1±3.9 years) completed the cross-sectional assessments and 131 (62 male, age 14.6±3.3 years) participated in a follow-up at a 1-year visit interval. Logistic regression analysis of cross-sectional data of 266 cases showed that there were significant positive effects between pump treatment (β=0.090, OR 2.460, P=0.005), DBRS scores (β=2.593, OR 13.366, P=0.002) and the meeting of standard HbA1c (<7.5%, 58 mmol/mol). Disease duration (β=-0.071, OR 0.932, P=0.033) was negatively correlated with it. The longitudinal multivariate generalized estimation equation model showed that DBRS scores (β=3.165, OR 23.681, P=0.009) and DSTAR-Teen scores (β=0.050, OR 1.051, P=0.012) had a positive influence on the meeting of standard HbA1c over one year time of 131 cases. Self-care and resilience had higher cross-temporal stability in influencing glycemic control over time. To reach a better glycemic control and improve long-term health outcomes, attention should be paid to the detection and enhancement of these patient-centered promoters.

Long-term analysis of infections and associated risk factors in patients with multiple sclerosis treated with ocrelizumab: pooled analysis of 13 interventional clinical trials

Background: Patients with multiple sclerosis (PwMS) have an increased risk of infections. Objectives: To characterize incidence, clinical characteristics, outcomes and risk factors of infections, and serious infections (SIs) in ocrelizumab (OCR)-treated PwMS. Design: Post-hoc analysis of pooled data from 6155 patients in 13 clinical trials. Methods: Descriptive analyses of clinical characteristics and outcomes were reported over ⩽14 years. A Poisson Generalized Estimating Equation model was constructed to examine risk factors in a subgroup of patients with longer exposure to OCR ( n = 2092). Results: Over a median (max) treatment period of 3.7 (13.9) years, 420/6155 patients (6.8%) experienced 583 SIs, excluding coronavirus disease 2019. Incidence rates in relapsing multiple sclerosis (RMS; 1.50 per 100 patient years [95% confidence interval (CI): 1.34–1.68]) and progressive multiple sclerosis (PMS; 3.70 [95% CI: 3.27–4.17]) remained stable over this period. Lower respiratory tract, urinary tract, abdominal and gastrointestinal, and skin infections were the most commonly reported SIs. Most SIs (~90%) resolved, and treatment with OCR was continued in &gt;80% of cases. The presence of 1 or ⩾2 comorbidities (rate ratio = 1.66, 2.73, respectively), recent relapse activity (2.06), and Expanded Disability Status Scale (EDSS) score ⩾6.0 (2.02) were significant risk factors for SIs in patients with RMS treated over a median (max) period of 8.3 (11.2) years. In patients with primary PMS treated over a median (max) period of 7.1 (11.8) years, an EDSS score ⩾6.0 was associated with the greatest risk of SIs, a 4-fold increase (rate ratio, 4.31), followed by abnormal immunoglobulin (Ig)M levels (1.89), the presence of ⩾2 comorbidities (1.80), and having overweight/obesity (1.46). Time on OCR and abnormal IgG levels were not significantly associated with an increased SI risk. Conclusion: Continuous long-term treatment with OCR is associated with a manageable infection risk profile. Optimal disease control and addressing modifiable risk factors may reduce the risk of infections.

Pharmaceutical industry-sponsored meals are associated with increased prescriptions and Medicare spending for dupilumab among dermatologists in the United States.

Healthcare industry sometimes make large marketing payments to physicians. Previous studies have demonstrated that there are significant associations between industry marketing practices and physicians' prescribing behaviours in several specialties. Given the current increasing introduction of many novel biologics for atopic dermatitis and increasing payments to dermatologists, the industry payments to dermatologists for atopic dermatitis drugs could be associated with their prescribing patterns in the United States. This study aims to evaluate association between dermatologists' dupilumab prescription behaviours and manufacturer's sponsored meal payments to dermatologists in the United States. Using the Centers for Medicare and Medicaid Services and the Open Payments Database, this cross-sectional analysis evaluated associations between manufacturer's sponsored meal payments to dermatologists related to dupilumab and dermatologists' dupilumab prescriptions between 2017 and 2021. Associations were evaluated using logistic generalised estimating equations (GEE) and negative binomial regression GEE models at individual dermatologist level. Among 2852 dermatologists prescribing dupilumab, 74.5% received meal payments amounting to $1,083,919 between 2017 and 2021. Dermatologists receiving meal payments were more likely to prescribe dupilumab (odds ratio 1.50, 95% confidence interval [CI]: 1.37-1.65). There were also consistent dose-response associations between meal payments and total claims as well as Medicare spending. Dermatologists who received 1, 2-5, 6-10, and 11-15 meal payments per year reported 1.13 (95% CI: 1.03-1.24, p < 0.05), 1.35 (95% CI: 1.24-1.46, p < 0.001), 1.64 (95% CI: 1.48-1.82, p < 0.001), and 2.10 (95% CI: 1.78-2.47, p < 0.001) times more dupilumab-related claims in the year when they received the payments than those who did not receive the payments, respectively. This study found that significant associations between industry-sponsored meal payments and increased dupilumab prescriptions, shedding light on the potential influence of financial relationships on clinical practice. The findings call for heightened awareness among dermatologists, patients, and policymakers regarding the impact of these relationships on healthcare expenditures and decision-making in the United States. Future research is warranted to further explore these associations longitudinally.

Clinical and radiographic outcomes of a combined surgery approach to treat peri-implantitis

Peri-implant infra-bony defects are difficult to treat, and data on the management of peri-implantitis are lacking. The aim of this study was to evaluate the effect of a combined surgical approach to manage peri-implantitis: implantoplasty with xenogeneic bone grafting and a concentrated growth factor membrane. Two independent examiners analysed the medical records and radiographs taken before surgery and at the last follow-up. Data were analysed at the implant level; some patient-level data (age, sex, smoking habit) were also considered. Linear regression analysis with generalized estimating equations (GEE) was used to explore the effect of variables of interest (including marginal bone level (MBL)) on implantitis treatment success and resolution rates. The effect of the prosthesis type on postoperative clinical and radiographic parameters was also explored by GEE, with adjustment for age, sex, tooth site, location, follow-up duration, and implant length (model IV including all). Thirty patients with 72 implants were investigated. The implant survival rate was 100% over a mean observation period of 3.3 years (range 2–11 years). The treatment success rate (bone loss <0.5 mm, no bleeding on probing (BOP), no suppuration, probing depth (PD) < 5 mm) was higher in females than males (50% vs 19.0%; P = 0.008). At the last postoperative follow-up, the MBL (1.51 ± 1.07 vs 4.01 ± 1.13 mm), PD (3.61 ± 0.84 vs 6.54 ± 1.01 mm), and BOP (23.38 ± 23.18% vs 79.17 ± 15.51%) were significantly reduced when compared to pre-surgery values (all P < 0.001). Furthermore, a significantly higher PD reduction (β = −1.10 mm, 95% confidence interval −1.97 to −0.23 mm, P = 0.014) was observed for implants with a single crown than a full-arch prosthesis (GEE model IV). Preliminary clinical and radiographic data indicate that implantoplasty in combination with surgery could be an effective treatment option for peri-implantitis.

Perinatal outcomes and long-term infectious morbidity of offspring born to mothers with familial Mediterranean fever.

To investigate perinatal outcomes and long-term infectious morbidity in children of mothers with familial Mediterranean fever (FMF). A population-based cohort study comparing perinatal outcomes and long-term infectious morbidity of offspring of mothers with and without FMF was conducted. All singleton deliveries between the years 1991-2021 in a tertiary medical center were included. The study groups were followed until 18years of age for long-term infectious morbidity. A Kaplan-Meier survival curve was used to compare the cumulative incidence of long-term infectious morbidity, and generalized estimation equation (GEE) models as well as Cox proportional hazards models were constructed to control for confounders. During the study period, 356,356 deliveries met the inclusion criteria. 411 of them were women with FMF. The mean follow-up period interval was 9.7years (SD = 6.2) in both study groups. Using GEE models, preterm delivery, cesarean delivery, and low birth weight were independently associated with maternal FMF. The total infectious-related hospitalization rate was significantly higher in offspring born to mothers with FMF compared to the comparison group (Kaplan-Meier survival curve, log-rank p < 0.001). Using a Cox proportional hazards model, controlling for gestational age, maternal age, diabetes mellitus, cesarean delivery, and hypertensive disorders, being born to a mother with FMF was found to be an independent risk factor for long-term infection-related hospitalization of the offspring. Maternal FMF was found to be independently associated with long-term infection-related hospitalization of the offspring. This positive correlation may reflect an intra-uterine pro-inflammatory environment which may result in the offspring's long-term susceptibility to infection.

Longitudinal changes in crystalline lens thickness and power in children aged 6-12 years old.

To determine the three-year changes in crystalline lens power (LP) and thickness (LT) in children and their associated factors. Schoolchildren aged 6-12 years living in Shahroud, northeast Iran were examined in 2015 and 2018. The Bennett formula was used to calculate LP. Multiple generalized estimating equations (GEE) analysis was used for data analysis. Among the 8089 examined eyes, the mean LP in Phase 1 and 2, and the three-year change were 21.61 ± 1.47D, 21.00 ± 1.42D, and -0.61 ± 0.52D, respectively. The GEE model showed that negative shifts in LP were less pronounced with increasing age (β = 0.176; p < 0.001), and were also less noticeable in hyperopes compared to emmetropes (β = 0.120; p < 0.001). The changes in LP decreased when outdoor activity increased among urban residents (β = 0.013; p = 0.039), while it increased in rural area (β = -0.020; p = 0.047). Mean three-year change in LT was 0.002 ± 0.13 mm. Female sex and aging by one year increased the LT by 0.022 mm (P < 0.001). However, LT decreased in 6-8-year-olds, while it increased in 10-12-year-old children, both in a linear fashion. The change in LT was less in myopes than in emmetropes (β = -0.018, P-value = 0.010). LP decreases after three years in 6 to 12-year-old children. LT increases slightly after three years in 6 to 12-year-old children. The changes in LP and LT were associated with the refractive errors, place of residence, age and gender and outdoor activity time.

Effects of remote dignity therapy on mental health among patients with hematologic neoplasms and their significant others: A randomized controlled trial

BackgroundFamilies of patients with hematologic neoplasms involved in dignity therapy have exhibited a remarkable improvement in psychological well-being and family functioning. However, the applicability and generalizability of family participatory dignity therapy are limited as it is influenced by factors such as intervention time, place, and participants. Whether remote support from significant others is feasible and effective remains unknown. ObjectivesThis study aimed to confirm the efficacy of significant others participating in remote dignity therapy (r-DT) on hope, dignity loss, meaning of life, and sense of stigma among patients with hematologic neoplasms as well as their significant others' depression and anxiety. DesignA randomized, single-blinded, two-arm, parallel-group controlled trial. Setting(s) and participantsParticipants included patients with hematologic neoplasms and their significant others, who were recruited from Fujian Medical University Union Hospital from May 2021 to January 2022. MethodsA total of 72 eligible participants (patients and significant others) agreed to participate, and were randomly assigned to an intervention group (n = 35) or a control group (n = 37). Each pair of participants in the intervention group participated in two or three conversations based on the online video function of the WeChat platform, performed by one therapist in accordance with a specific communication outline. To evaluate the effects of the intervention, we assessed the patients' degree of dignity loss, hope level, meaning of life, and sense of stigma, as well as their significant others' depression, anxiety, and intimacy at baseline (T0), 15 days (T1), 30 days (T2), and 60 days (T3), and compared the scores between the two groups after the completion of the intervention. The Generalized Estimation Equation Model (GEE) was used to examine the effects of time, group, and their interaction. ResultsThe intervention group statistically significantly differed in lower dignity loss (t = 2.190, p = 0.032), higher hope level (t = −2.010, p = 0.049), and higher meaning of life (t = −2.066, p = 0.043) than the control group at T1. Regarding their significant others, the results of the comparison between the two groups showed that significant others in the intervention group had reduced levels of anxiety and depression at T1 and T2 (p < 0.05). The majority of patients (84.38 %) and significant others (75.00 %) provided positive evaluations of the program. ConclusionsThe r-DT showed a short-term positive effect on decreasing patients' dignity loss and promoting patients' hope and meaning of life; among their significant others, it decreased anxiety and depression. Trial registrationRegistered in the China Clinical Trial Registry on 17 March 2021(ChiCTR2100044374). Tweetable abstractRemote dignity therapy decreased patients' dignity loss and promoted their hope and meaning of life; among their significant others, it decreased anxiety and depression.

Evaluating the sensitivity of Centiloid quantification to pipeline design and image harmonization

AbstractBackgroundThe Centiloid scale is a well‐established standardized metric for estimating amyloid load in clinical and research settings. In this study, we evaluated the stability of Centiloid to pipeline design options, tracer, and image harmonization.MethodA total of 670 participants of the AMYPAD DPMS and PNHS multicenter studies with either [18F]flutemetamol or [18F]florbetaben PET scans and T1‐weighted MRI were included (Table1). PET images were harmonized to achieve an 8 mm Full‐Width‐at‐Half‐Maximum(FWHM) effective image resolution. Using SPM12, 32 Centiloid pipelines were created, calibrated and validated, based on combinations of four reference regions (Whole Cerebellum[WCB], Cerebellar Gray[CG], Whole Cerebellum+Brainstem[WCB+BSTM], Pons), two target VOI types (standard GAAIN vs subject‐based), two reference region types (standard GAAIN vs subject‐based) and two analysis spaces (native vs MNI). Generalized Estimating Equations (GEE) were used to evaluate the impact of the different factors on Centiloid. First, a base model including only the pipeline design factors was defined. Then, harmonization status (original vs harmonized PET images), tracer, and grey matter volume, as a measure of cerebral atrophy, were added to the base GEE model. Analyses were performed in the two cohorts separately and changes &gt;5 Centiloid were considered relevant.ResultQuantification space, target VOI, and reference region type had a small impact on Centiloid. Selection of reference region had the largest impact on Centiloid as using the Pons resulted in ∆Centiloid∼‐12.00 compared with using the standard reference region, WCB (Table2). Harmonization status affected Centiloid only for some reference regions: CG and Pons were sensitive to harmonization status (∆Centiloid∼ 5.45 and ‐5.70 respectively). In contrast, Centiloid was minimally affected by harmonization when using WCB and WCB+BSTM (Table3). Tracer and atrophy had a minimal effect on Centiloid for both DPMS and PNHS cohorts.ConclusionCentiloid quantification is robust against differences in analysis space, reference region type, target VOI, tracer and the presence of atrophy. However, choice of reference region can significantly influence Centiloid, with the Pons having the largest impact on Centiloid relative to other reference regions. Centiloid is stable against harmonization status and image resolution heterogeneities while using WCB as reference region.

Evaluating the sensitivity of Centiloid quantification to pipeline design and image harmonization

AbstractBackgroundThe Centiloid scale is a well‐established standardized metric for estimating amyloid load in clinical and research settings. In this study, we evaluated the stability of Centiloid to pipeline design options, tracer, and image harmonization.MethodA total of 670 participants of the AMYPAD DPMS and PNHS multicenter studies with either [18F]flutemetamol or [18F]florbetaben PET scans and T1‐weighted MRI were included (Table1). PET images were harmonized to achieve an 8 mm Full‐Width‐at‐Half‐Maximum(FWHM) effective image resolution. Using SPM12, 32 Centiloid pipelines were created, calibrated and validated, based on combinations of four reference regions (Whole Cerebellum[WCB], Cerebellar Gray[CG], Whole Cerebellum+Brainstem[WCB+BSTM], Pons), two target VOI types (standard GAAIN vs subject‐based), two reference region types (standard GAAIN vs subject‐based) and two analysis spaces (native vs MNI). Generalized Estimating Equations (GEE) were used to evaluate the impact of the different factors on Centiloid. First, a base model including only the pipeline design factors was defined. Then, harmonization status (original vs harmonized PET images), tracer, and grey matter volume, as a measure of cerebral atrophy, were added to the base GEE model. Analyses were performed in the two cohorts separately and changes &gt;5 Centiloid were considered relevant.ResultQuantification space, target VOI, and reference region type had a small impact on Centiloid. Selection of reference region had the largest impact on Centiloid as using the Pons resulted in ∆Centiloid∼‐12.00 compared with using the standard reference region, WCB (Table2). Harmonization status affected Centiloid only for some reference regions: CG and Pons were sensitive to harmonization status (∆Centiloid∼ 5.45 and ‐5.70 respectively). In contrast, Centiloid was minimally affected by harmonization when using WCB and WCB+BSTM (Table3). Tracer and atrophy had a minimal effect on Centiloid for both DPMS and PNHS cohorts.ConclusionCentiloid quantification is robust against differences in analysis space, reference region type, target VOI, tracer and the presence of atrophy. However, choice of reference region can significantly influence Centiloid, with the Pons having the largest impact on Centiloid relative to other reference regions. Centiloid is stable against harmonization status and image resolution heterogeneities while using WCB as reference region.

Mortality related to HCV and other chronic liver diseases in Veneto (Italy), 2008-2021: Changes in trends and age-period-cohort effects.

The objective of this study was to assess the impact of the COVID-19 pandemic and direct-acting antiviral (DAA) agents on mortality related to chronic liver diseases (CLD). Age-standardized mortality rates were computed based on CLD as the underlying cause of death (UCOD) and as any mention in death certificates (multiple causes of death-MCOD). Time trends in age-standardized mortality rates were investigated using generalized estimation equation models. Additionally, we conducted age, period, and birth cohort (APC) analyses on CLD-related mortality associated with alcohol and hepatitis C virus (HCV). Between 2008 and 2021, among residents in the Veneto region (Northeastern Italy) aged ≥35 years, there were 20 409 deaths based on the UCOD and 30 069 deaths based on MCOD from all CLD. We observed a 4% annual decline in age-standardized MCOD-based mortality throughout 2008-2021, with minor peaks corresponding to COVID-19 epidemic waves. Starting in 2016, the decline in HCV-related mortality accelerated further (p < .001). A peak in HCV-related mortality in the 1963-1967 birth cohort was observed, which levelled off by the end of the study period. Mortality related to alcoholic liver disease declined at a slower pace, becoming the most common aetiology mentioned in death certificates. The study demonstrates a significant decrease in HCV-related mortality at the population level in Italy with the introduction of DAAs. Continuous monitoring of MCOD data is warranted to determine if this favourable trend will continue. Further studies utilizing additional health records are needed to clarify the role of other CLD etiologies.

2006. The Impact of Race and Rurality on Healthcare-Associated Infections and Downstream Adverse Outcomes

Abstract Background There is limited information on racial disparities and healthcare-associated infections (HAIs). The objective of this study was to evaluate the impact of race and rurality on HAIs and outcomes of HAIs including death and intensive care unit (ICU) admission. Methods We established a retrospective cohort of adults ≥ 18 years admitted ≥ 48 hours from 1/1/2017–8/31/2020 at three Missouri hospitals. HAIs were defined as positive cultures from urine, blood, or respiratory specimens ≥ 48 hours after admission. The primary exposure was patient race and rurality defined as combinations of race (Black or white) and residence (urban vs. rural based on patient ZIP code and using the National Center for Health Statistics Urban-Rural classification). We used a generalized estimating equations (GEE) model to determine disparity-related (i.e., race/rurality, sex, Medicaid payer, census median income quartile) risk factors for HAI accounting for clustering of admissions at the patient-level and adjusting for other factors (e.g., comorbidities, age, transfer status). Among HAI admissions, similar GEE models examined in-hospital death and ICU admission after HAI. Results The cohort included 214,955 admissions (Table 1), with HAIs occurring during 6,699 (3.1%) of admissions (1,572 blood; 3,146 urine; 2,497 respiratory HAIs). HAIs developed during 3.1% of admissions among white urban patients, 3.9% among white rural patients, 2.7% among Black urban patients, and 4.1% among Black rural patients (Figure 1). White rural patients had an increased risk of HAI (adjusted relative risk [aRR] 1.13; 95% confidence interval [CI] 1.06, 1.20) while Black urban patients had a decreased risk of HAI (aRR 0.82; 95% CI 0.76, 0.88) compared to white urban patients. Among HAIs, adverse outcomes were more common in Black rural patients (Figure 2). Specifically, Black rural patients had an increased risk of ICU admission (aRR 1.35; 95% CI 1.15, 1.58) and in-hospital death (aRR 1.85; 95% CI 1.31, 2.60) while white rural and Black urban patients had similar outcomes compared to white urban patients.Table 1.Patient characteristicsFigure 1.Proportion of admissions with an HAI by race and ruralityFigure 2.Among HAIs, proportion of admissions with adverse outcomes by race and rurality Conclusion We identified disparities related to race and rurality in HAIs and adverse outcomes from HAIs. Future work to understand the reasons underpinning these differences is critical to identify targets for intervention. Disclosures All Authors: No reported disclosures

Sleep Quality and Self-Stigma Mediate the Association Between Problematic Use of Social Media and Quality of Life Among People With Schizophrenia in Taiwan: A Longitudinal Study.

Problematic use of social media (PUSM) may affect sleep quality and self-stigma in people with schizophrenia and consequently reduce their quality of life (QoL). This longitudinal study investigated if sleep quality and self-stigma mediated relationships between PUSM and QoL. One-hundred-and-ninety-three outpatients with schizophrenia were recruited from a psychiatric center in Taiwan from April 2019 to August 2021 and participated in a longitudinal study at intervals of three months between measurements. QoL was assessed using the World Health Organization Quality of Life Questionnaire Brief Version; sleep quality using the Pittsburgh Sleep Quality Index; self-stigma using the Self-Stigma Scale-Short; and PUSM using the Bergen Social Media Addiction Scale. Via SPSS 20.0, general estimating equation models assessed temporal associations between variables. Via R software, mediating effects of self-stigma and sleep quality were examined through Monte Carlo simulations with 20,000 repetitions. Mean scores of physical, psychological, social and environmental QoL ranged from 11.86 to 13.02. Mean scores of sleep quality and self-stigma were 9.1±4.5 and 2.2±0.8, respectively. Sleep quality and self-stigma were directly related to QoL (p<0.001) and mediated indirect relationships between PUSM and all components of QoL with a range of 95% confidence intervals spanning from -0.0591 to -0.0107 for physical QoL; -0.0564 to -0.0095 for psychological QoL; -0.0292 to -0.0035 for social QoL; and -0.0357 to -0.0052 for environmental QoL. Sleep quality and self-stigma mediated relationships between PUSM and QoL in people with schizophrenia. Developing interventions targeting PUSM, sleep, and self-stigma may help improve QoL in people with schizophrenia.

Intra-patient analysis of individual weight gain or loss between IVF cycles: cycle now and transfer later.

What is the impact of clinically significant weight change on outcomes related to IVF cycle performance? While individual weight loss did not significantly impact ovarian response to stimulation or other cycle outcome parameters in our study, some positive associations were found for individual weight gain. The role of weight-change in patients undergoing IVF has been largely studied by comparing weight loss in different cohorts of patients stratified by a static BMI. Specifically, obesity has been extensively studied in relation to its negative effects on assisted or unassisted conception outcomes and ovulatory function. Previous research has shown conflicting results, while BMI, which is commonly used as a marker of obesity, may not accurately reflect the underlying factors affecting fertility in obese patients. This study utilized a retrospective within-patient repeated measurement analysis design to assess the impact of weight change on IVF outcomes in cycles where all embryos were cryopreserved at the blastocyst stage for transfer at a later date. The study was conducted at an academically affiliated fertility center. The data included 961 women who underwent at least two IVF cycles between December 2014 and June 2020, with documented short-term weight gain (n = 607) or weight loss (n = 354) within 1year from their initial IVF cycle. Multivariable generalized estimating equations (GEE) and generalized linear mixed models (GLMM) were employed to assess associations between weight change and outcomes across cycles. The multivariable models indicated that weight loss did not show any significant associations with the numbers of oocytes retrieved, or mature oocytes, the fertilization rate or the blastulation rate. However, weight gain demonstrated a minor positive association with the number of oocytes retrieved in both GEE models (coefficient: 0.01, 95% CI: 0.00-0.01) and GLMM models (0.01, 95% CI: 0.01-0.00). There was also a potential increase in the fertilization rate with weight gain, as indicated by a positive coefficient in both GEE models (coefficient: 0.01, 95% CI: 0.00-0.02) and GLMM models (coefficient: 0.01, 95% CI: 0.00-0.01). However, the association between weight gain and the embryo blastulation rate was not statistically significant in any model. This study focused on cycle performance parameters instead of reproductive outcomes, which restricted our ability to evaluate the impact of weight change on cumulative live birth rates. Additionally, the study did not account for variables such as stimulation protocols, potentially introducing confounding factors and limiting the generalizability of the results. Although obesity is associated with adverse obstetrical risks, there is less evidence of adverse reproductive outcomes in IVF cycles. We therefore recommend that an IVF cycle should not be delayed due to weight, so that the patient is not adversely affected by increasing age. The IVF cycle should aim to freeze all embryos, so that embryo transfer can then occur after weight loss, so as to limit the recognized obstetrical risks. The study was not funded and there were no competing interests. N/A.

Is age discrimination a risk factor for frailty progression and frailty development among older adults? A prospective cohort analysis of the English Longitudinal Study of Ageing

BackgroundWith the increasing global burden of frailty on healthcare resources, it is important to understand the modifiable risk factors of frailty. This study examined perceived age discrimination as a potential risk factor for frailty progression and frailty development among older adults. MethodsProspective cohort study using data from Waves 5 to 9 of the English Longitudinal Study of Ageing (ELSA). Data on perceived age discrimination was collected only in Wave 5 of ELSA and analysed as baseline data in this study. Frailty was defined using the Frailty Index (FI) scores (0 to 1), calculated using the multidimensional deficits (scores ≥ 0.25 were considered frail). Binomial generalised estimating equation models (GEE) were fitted in R studio using perceived age discrimination as the main predictor with age, gender, long-standing illness, cognition, subjective social status status (SSS) and psychological wellbeing as covariates. Odd ratios were reported with 95 % confidence intervals (CI). ResultsA total sample of 2,385 ELSA participants were included in the analysis. 55.8 % (n = 1312) were female, mean age 71.9 (SD ± 5.27) years and baseline frailty prevalence was 12.1 % (n = 288). Perceived age discrimination was reported by 38.4 % (n = 916) of the participants. Both frailty progression (OR 1.50, CI [1.26- 1.70]) and frailty development (OR 1.39, CI [1.14–1.62]) were significantly associated with perceived age discrimination in the fully adjusted models. Age (80+ years) (OR 3.72, CI [2.84–4.86]) and long-standing illness (OR 5.45, CI [4.43–6.67]) had the strongest association with respondents’ frailty progression. ConclusionPerceived age discrimination significantly increased the risk of frailty progression and frailty development among ELSA participants.

Associations of social media use with smoking and e-cigarettes: a national longitudinal study

BackgroundSocial media use is high among children and young people and might influence health behaviours. We examined social media use and use of tobacco and e-cigarettes in the UK. MethodsWe used data from participants aged 10–25 years from the UK Household Longitudinal Study (January 2015–January 2022). Participants were asked: “On a normal weekday, that is Monday to Friday, how many hours do you spend chatting or interacting with friends through a social website or app like that?”. Specific social media platforms were not specified. Responses were none, less than 1 h, 1–3 h, 4–6 h, 7 h or more. Outcomes were current tobacco smoking and e-cigarette use. Generalised Estimating Equation (GEE) logistic regression models investigated associations of social media use with tobacco and e-cigarette use, and fixed effects analyses investigated changes in social media use with uptake of both products. Models included possible confounders such as age, sex, household income, ethnicity (White vs non-White) and use of tobacco or e-cigarettes by others within the home. All participants gave written informed consent. FindingsThe analytic sample included 10 808 participants with 27 962 observations (mean age 15·7 years [SD 3·8], 5080 [47%] male, 5728 [53%] female, and 7868 [73%] White). Current tobacco smoking was reported at one or more timepoints by 929 (8·6%) participants, and current e-cigarette use by 270 (2·5%) participants. In adjusted GEE models, all levels of social media use were associated with greater odds of current smoking than no use. This association was particularly apparent at higher levels of use adjusted odds ratio [aOR] 3·11, 95% CI 2·41–4·03 for ≥7 h use vs no use), with similar associations for e-cigarettes (aOR 3·04, 2·11–4·40 for ≥7 h use vs no use). Fixed effects analyses also found increased use of social media to be associated with increased uptake of both products (eg, changing to using social media for ≥7 h/day was associated with >2 times the odds of taking up tobacco smoking [aOR 2·33, 1·28–4·24]). InterpretationThese analyses suggest an association between social media use and e-cigarette and tobacco use. Potential pathways include promotion of these products on social media. Further research with details on specific platforms would be useful as well as with longer follow-up time. FundingCancer Research UK.

Association between Average Vitamin D Levels and COVID-19 Mortality in 19 European Countries—A Population-Based Study

Early epidemic reports have linked low average 25(OH) vitamin D levels with increased COVID-19 mortality. However, there has been limited updated research on 25(OH) vitamin D and its impact on COVID-19 mortality. This study aimed to update the initial report studying the link between vitamin D deficiency and COVID-19 mortality by using multi-country data in 19 European countries up to the middle of June 2023. COVID-19 data for 19 European countries included in this study were downloaded from Our World in Data from 1 March 2020, to 14 June 2023, and were included in the statistical analysis. The 25(OH) vitamin D average data were collected by conducting a literature review. A generalized estimation equation model was used to model the data. Compared to European countries with 25(OH) vitamin D levels of ≤50 nmol/L, European countries with 25(OH) vitamin D average levels greater than 50 nmol/L had lower COVID-19 mortality rates (RR = 0.794, 95% CI: 0.662–0.953). A statistically significant negative Spearman rank correlation was observed between 25(OH) vitamin D average levels and COVID-19 mortality. We also found significantly lower COVID-19 mortality rates in countries with high average 25(OH) vitamin D levels. Randomized trials on vitamin D supplementation are needed. In the meantime, the issue of vitamin D use should be debated in relation to the ongoing discussions of national post-COVID-19 resilience against future pandemics.