Multivariable Linear Mixed-effects Models Research Articles

#2285 Potentially modifiable factors influencing longitudinal health-related quality of life for those with chronic kidney disease in the NURTuRE-CKD cohort

Abstract Background and Aims Factors affecting poor health-related quality of life (HRQoL) for people with chronic kidney disease (CKD) have been previously described in literature, and worse HRQoL is associated with CKD progression and death. Little emphasis has been placed on which factors may be potentially modifiable, and longitudinal HRQoL outcome analyses in non-dialysis dependent CKD cohorts are few in number. Baseline analysis of the NURTuRE-CKD cohort identified several associations between these factors and HRQoL and these associations can now be examined with longitudinal data. Method The NURTuRE-CKD cohort study recruited 2996 participants with non-dialysis dependent CKD between 2017-2019, collecting biochemical, anthropometric, sociodemographic, medical history and patient reported outcome measure (PROM) data. Face-to-face follow-up repeated these measures. Longitudinal worsening overall HRQoL was the main outcome of interest, represented by mapped EQ-5D-3L index value and visual analogue score (VAS). Multivariable linear mixed effects models were fitted in R using the lmer and lmerTest packages. Models for index value were fit separately for each independent variable of interest and collated, as well as fitting models with all variables of interest. Models were adjusted for available confounders, repeated measures and follow-up time. P-values were adjusted for multiple testing using false discovery rate correction. Results 2054/2996 (68.6%) had complete HRQoL data at follow-up, of whom most had CKD stage G3a-G4 (n = 1597, 77.8%). 1817 (88.5%) were white and 1196 (58.2%) were male. Mean age was 63.7 (SD ±14.5) years and the mean number of comorbidities was 3.7 (SD ±2.2). Median (IQR) time between baseline and follow-up was 518 (410) days. At follow-up, mean mapped EQ-5D-3L index value was 0.72 (SD ±0.3) and mean VAS score was 70.4/100 (SD ±20.6). 1595 (77.7%) reported problems in at least one EQ-5D-5L dimension, with 255 (12.4%) developing issues since baseline. 1203 (58.6%) reported worse HRQoL index values at follow up and 910 (44.3%) reported worse VAS. The dimension with the highest number of newly reported issues at follow-up was ‘usual activities’ with 301 (14.7%). Multivariable linear mixed methods models showed independent associations with worse HRQoL (Figs 1 and 2) for those on ten or more medications (β −0.118, CI −0.137 to −0.100, p < 0.001), current smokers (β −0.036, CI −0.067 to −0.006, p = 0.0.012), obesity (β-0.059, CI −0.080 to-0.039, p < 0.001), haemoglobin of <100g/L (β-0.044, CI −0.073 to-0.016, p = 0.014), hospital anxiety and depression scale scores of 8 or above for anxiety (β-0.146, CI −0.161 to-0.130, p < 0.001) and depression (β-0.202, CI-0.219 to −0.186, p < 0.001), worse health literacy (β −0.099, CI −0.136 to −0.063, p < 0.001), and pain (β −0.148, CI −0.161 to −0.135, p ≤ 0.001), weakness (β −0.106, CI −0.120 to −0.092, p < 0.001) and shortness of breath symptoms (β −0.074, CI −0.087 to −0.060, p < 0.001). Conclusion Potentially modifiable factors influencing longitudinal worsening of HRQoL for people with CKD include polypharmacy, smoking, obesity, anaemia, depression and anxiety, limited health literacy, pain, weakness and shortness of breath symptoms. This highlights the need for high quality randomised controlled trials to test interventions addressing these factors with reported HRQoL outcomes. Further work in this cohort is required, examining a third timepoint for HRQoL and linked clinical outcome data.

Evaluation Of Biomarker-Based GFR Estimating Equations in Glomerular Disease

Introduction: Glomerular filtration rate (GFR) is typically estimated with equations that use biomarkers such as serum creatinine and/or cystatin-C. The impact of these different biomarkers on GFR estimates in glomerular disease patients is unclear. In this study, we compared the different GFR estimating equations in the Cure Glomerulonephropathy (CureGN) cohort of children and adults with glomerular disease. Methods: All available cystatin-C measurements from CureGN study participants were matched to same-day serum creatinine measurements to estimate GFR. To explore the strength of agreement between eGFR values obtained from the "Under 25” (U25) and Chronic Kidney Disease Epidemiology Collaboration (CKD-Epi) equations, we used intraclass correlation coefficients. Multivariable linear mixed effects models were used to determine which factors were independently associated with differences in eGFR values. Results: A total of 928 cystatin-C measurements were matched to same-day serum creatinine measurements from N=332 CureGN study participants (58% male, 69% White/Caucasian, 20% Black/African American). Among 628 measurements collected while study participants were under 25 years old, there was moderate agreement (0.731) in serum creatinine vs. cystatin-C U25 equations. Models showed that higher eGFR values were associated with larger differences between the two equations (p <0.001). Among 253 measurements collected while study participants were at least 18 years old, there was excellent agreement (0.891-0.978) among CKD-Epi equations using serum creatinine alone, cystatin-C alone, or the combination of both. Younger age was associated with larger differences between CKD-Epi equations (p=0.06 to p=0.016). Conclusion: Excellent agreement between CKD-Epi equations indicates continued use of serum creatinine only for GFR estimation could be appropriate for adults. In contrast, only moderate agreement between U25 equations indicates a need for more frequent measurement of cystatin-C among children and young adults, especially as eGFR increases.

The Effect of City-Level Sugar-Sweetened Beverage Taxes on Longitudinal HbA1c and Incident Diabetes in Adults With Prediabetes.

Prediabetes, which is a condition characterized by higher-than-normal blood glucose levels that are under the threshold for diabetes, impacts over one-third of U.S. adults. Excise taxes on sugar-sweetened beverages (SSBs) are a proposed policy intervention to lower population consumption of SSBs and generate revenue to support health-related programs, thus potentially delaying or preventing the development of diabetes in individuals with prediabetes. We leveraged data from Kaiser Permanente in California to examine the impact of SSB taxes in California on individual-level mean HbA1c levels and rates of incident diabetes. We compared two outcomes, mean HbA1c levels and rates of incident diabetes, among a matched cohort of adults with prediabetes who lived and did not live in SSB excise tax cities, using outcomes collected in the 6 years prior and 4 years following SSB tax implementation. We used multivariable linear mixed effects models to analyze longitudinal mean HbA1c and discrete-time survival models for incident diabetes. We included 68,658 adults in the analysis. In adjusted models, longitudinal mean HbA1c (percent) was 0.007 (95% CI 0.002, 0.011) units higher in the tax cities compared with controls; while the estimated difference was statistically significant, it was not clinically significant (HbA1c < 0.5%). There was no significant difference in the risk of incident diabetes between individuals living in tax and control cities. We found no clinically significant association between SSB taxes and either longitudinal mean HbA1c or incident diabetes among adults with prediabetes in the 4 years following SSB tax implementation.

Sociodemographic factors associated with vaccine hesitancy in the South Asian community in Canada.

South Asians represent the largest non-white ethnic group in Canada and were disproportionately impacted by the COVID-19 pandemic. We sought to determine the factors associated with vaccine hesitancy in South Asian Canadians. We conducted a cross-sectional analysis of vaccine hesitancy using data collected at the baseline assessment of a prospective cohort study, COVID CommUNITY South Asian. Participants (18 + years) were recruited from the Greater Toronto and Hamilton Area in Ontario (ON) and the Greater Vancouver Area in British Columbia (BC) between April and November 2021. Demographic characteristics and vaccine attitudes measured by the Vaccine Attitudes Examination (VAX) scale were collected. Each item is scored on a 6-point Likert scale, and higher scores reflect greater hesitancy. A multivariable linear mixed effects model was used to identify sociodemographic factors associated with vaccine hesitancy, adjusting for multiple covariates. A total of 1496 self-identified South Asians (52% female) were analyzed (mean age = 38.5years; standard deviation (SD): 15.3). The mean VAX score was 3.2, SD: 0.8 [range: 1.0‒6.0]. Factors associated with vaccine hesitancy included: time since immigration (p = 0.04), previous COVID-19 infection (p < 0.001), marital status (p < 0.001), living in a multigenerational household (p = 0.03), age (p = 0.02), education (p < 0.001), and employment status (p = 0.001). Among South Asians living in ON and BC, time since immigration, prior COVID-19 infection, marital status, living in a multigenerational household, age, education, and employment status were associated with vaccine hesitancy. This information can be used to address vaccine hesitancy in the South Asian population in future COVID-19 waves or pandemics.

Reduction of Optic Disc Microvasculature and Retinal Nerve Fiber Layer Thinning in Patients with Glaucoma

PurposeTo assess the relationship between the change of optic disc vessel density (ODVD) and retinal nerve fiber layer (RNFL) thinning in primary open-angle glaucoma (POAG) patients. DesignRetrospective case series. MethodsFor 105 POAG patients, ≥ 5 consecutive optical coherence tomography (OCT) and OCT angiography (OCTA) images were obtained during ≥ 2 years of follow-up.Based on enface OCTA imaging, ODVD was calculated as the ratio of pixels occupied by vessels below the internal limiting membrane within the temporal area of the optic cup, and ODVD reduction was determined when there was a statistically significant negative slope (P < 0.05) for any of the global, superior, or inferior sectors. The association between the rates of ODVD change and RNFL thinning was assessed by multivariable longitudinal linear mixed-effects model vs. time. ResultsDuring 2.9 ± 0.3 years of follow-up on the 105 participants with visual field mean deviation at baseline of 5.7 ± 4.8 dB, 46 (43.8%) showed ODVD reduction. Faster global RNFL thinning was associated with the smaller Bruch's membrane opening area (ß = 0.381; 95% confidence interval (CI), 0.120 to 0.646; P = 0.006), optic disc hemorrhage (ß = -0.567; 95% CI, -0.909 to -0.228; P = 0.002) and faster rate of global ODVD change (ß = -0.090; 95% CI, -0.139 to -0.042; P = 0.001). ConclusionsReduction of optic disc microvasculature was associated with rapid RNFL thinning in POAG. This suggests a role for deep ONH circulation in the glaucoma pathogenesis.

Reducing decisional conflict in decisions about prenatal genetic testing: the impact of a dyadic intervention at the start of prenatal care.

Decisional conflict and regret about prenatal genetic screening and diagnostic tests may have important consequences in the current pregnancy and for future reproductive decisions. Identifying mechanisms that reduce conflict associated with the decision to use or decline these options is necessary for optimal patient counseling. We conducted a cluster-randomized controlled trial of a shared decision-making tool (NEST) at the beginning of prenatal care. Enrolled patients completed follow-up surveys at the time of testing (QTT) and in the second-third trimester (QFF), including the Decision Conflict Scale (DCS). Total DCS scores were analyzed using a multivariate linear mixed-effect model. Of the total number of participants (n=502) enrolled, 449 completed the QTT and QFF surveys. The mean age of participants was 31.6±3.8, with most parous at the time of study participation (n=321; 71.7 %). Both the NEST (the intervention) and control groups had lower median total DCS scores at QFF (NEST 13.3 [1.7, 25.0] vs. control 16.7 [1.7, 25.0]; p=0.24) compared to QTT (NEST 20.8 [5.0, 25.0] vs. control 18.3 [3.3, 26.7]; p=0.89). Participants exposed to NEST had lower decisional conflict at QFF compared to control (β-3.889; [CI-7.341,-0.437]; p=0.027). Using a shared decision-making tool at the start of prenatal care decreased decisional conflict regarding prenatal genetic testing. Such interventions have the potential to provide an important form of decision-making support for patients facing the unique type of complex and preference-based choices about the use of prenatal genetic tests.

Dynamic assessment of prealbumin for nutrition support effectiveness in critically ill patients

Background & AimsSerum prealbumin is considered to be a sensitive predictor of clinical outcomes and a quality marker for nutrition support. However, its susceptibility to inflammation restricts its usage in critically ill patients according to current guidelines. We assessed the performance of the initial value of prealbumin and dynamic changes for predicting the ICU mortality and the effectiveness of nutrition support in critically ill patients. MethodsThis monocentric study included patients admitted to the ICU between 2009-2016, having at least one initial prealbumin value available. Prospectively recorded data were extracted from the electronic ICU charts. We used both univariable and multivariable logistic regressions to estimate the performance of prealbumin for the prediction of ICU mortality. Additionally, the association between prealbumin dynamic changes and nutrition support was assessed via a multivariable linear mixed-effects model and multivariable linear regression. Performing subgroup analysis assisted in identifying patients for whom prealbumin dynamic assessment holds specific relevance. ResultsWe included 3136 patients with a total of 4942 prealbumin levels available. Both prealbumin measured at ICU admission (adjusted odds-ratio (aOR) 0.04, confidence interval (CI) 95% 0.01-0.23) and its change over the first week (aOR 0.02, CI95 0.00-0.19) were negatively associated with ICU mortality. Throughout the entire ICU stay, prealbumin dynamic changes were associated with both cumulative energy (estimate: 33.2, standard error (SE) 0.001, p < 0.01) and protein intakes (1.39, SE 0.001, p<0.01). During the first week of stay, prealbumin change was independently associated with mean energy (6.03e-04, SE 2.32e-04, p<0.01) and protein intakes (1.97e-02, SE 5.91e-03, p<0.01). Notably, the association between prealbumin and energy intake was strongest among older or malnourished patients, those suffering from increased inflammation and those with high disease severity. Finally, prealbumin changes were associated with a positive mean nitrogen balance at day 7 only in patients with SOFA<4 (p=0.047). ConclusionPrealbumin measured at ICU admission and its change during the first-week serve as an accurate predictor of ICU mortality. Prealbumin dynamic assessment may be a reliable tool to estimate the effectiveness of nutrition support in the ICU, especially among high-risk patients.

Effects of different sizes of ambient particulate matter and household fuel use on physical function: National cohort study in China

BackgroundImpact of outdoor and household air pollution on physical function remains unelucidated. This study examined the influence of various ambient particulate sizes (PM1, PM2.5, and PM10) and household fuel usage on physical function. MethodsData from the China Health and Retirement Longitudinal Study (CHARLS) spanning 2011 and 2015 were utilized. The physical functional score was computed by summing scores from four tests: grip strength, gait speed, chair stand test, and balance. Multivariate linear and linear mixed-effects models were used to explore the separate and combined effects of PM1, PM2.5, PM10 and household fuel use on physical function in the cross-sectional and longitudinal analyses, respectively, and to further observe the effects of fuel cleanup on physical function in the context of air pollution exposure. ResultsBoth cross-sectional and longitudinal analyses revealed negative correlations between PM1 (β = −0.044; 95% CI: −0.084, −0.004), PM2.5 (β = −0.024; 95% CI: −0.046, −0.001), PM10 (β = −0.041; 95% CI: −0.054, −0.029), and physical function, with a more pronounced impact observed for fine particulate matter (PM1). Cleaner fuel use was associated with enhanced physical function compared to solid fuels (β = 0.143; 95% CI: 0.070, 0.216). The presence of air pollutants and use of solid fuels had a negative impact on physical function, while cleaner fuel usage mitigated the adverse effects of air pollutants, particularly in areas with high exposure. ConclusionThis study underscores the singular and combined detrimental effects of air pollutants and solid fuel usage on physical function. Addressing fine particulate matter, specifically PM1, and prioritizing efforts to improve household fuel cleanliness in regions with elevated air pollution levels are crucial for preventing physical disability.

The Impact of Social Vulnerability on Structural and Functional Glaucoma Severity, Worsening, and Variability

To determine the association between social vulnerability index (SVI) and baseline severity, worsening, and variability of glaucoma, as assessed by visual field (VF) and optical coherence tomography (OCT). Retrospective longitudinal cohort study. Adults with glaucoma or glaucoma suspect status in one or both eyes. VFs were derived from 7,897 eyes from 4,482 patients, while OCTs were derived from 6,271 eyes from 3,976 patients. All eyes had a minimum of 5 tests over follow-up using either the Humphrey Field Analyzer or the Cirrus HD-OCT. SVI, which measures neighborhood-level environmental factors, was linked to patient addresses at the census tract level. Rates of change in mean deviation (MD) and retinal nerve fiber layer (RNFL) thickness were computed using linear regression. The slope of the regression line was used to assess worsening, while the standard deviation (SD) of residuals was used as a measure of variability. Multivariable linear mixed-effects models were used to investigate the impact of SVI on baseline, worsening, and variability in both MD and RNFL. We further explored the interaction effect of mean IOP and SVI on worsening in MD and RNFL. Glaucoma severity defined based on baseline MD and RNFL thickness. Worsening defined as MD and RNFL slope. Variability defined as the SD of the residuals obtained from MD and RNFL slopes. Increased (worse) SVI was significantly associated with worse baseline MD (β = -1.07 dB, 95% CI: [-1.54, -0.60]), thicker baseline RNFL (β = 2.46 μm, 95% CI: [0.75, 4.17]), greater rates of RNFL loss (β = -0.12 μm, 95% CI: [-0.23, -0.02]), and greater VF variability (β = 0.16 dB, 95% CI: [0.07, 0.24]). Having worse SVI was associated with worse RNFL loss with increases in IOP (βinteraction = -0.07, [95% CI: -0.12, -0.02]). Increased social vulnerability index score is associated with worse functional (VF) loss at baseline, higher rates of structural (OCT) worsening over time, higher VF variability, and a greater effect of IOP on RNFL loss. Further studies are needed to enhance our understanding of these relationships and establish their cause.

Efficacy of microwave ablation in the treatment of large benign thyroid nodules: a multi-center study.

To evaluate the efficacy, safety, and improvement of symptoms by ultrasound-guided microwave ablation (MWA) for patients with large benign thyroid nodules (BTNs). Eighty-seven patients with 87 BTNs (≥ 4cm) treated with MWA between April 2015 and March 2021 were enrolled in this retrospective multicenter study, with clinical and ultrasound examinations performed at the 1st, 3rd, 6th, and 12th months. A multivariable linear mixed effects model was employed to explore the alterations in volume and volume reduction ratio (VRR), as well as the potential factors associated with VRR. The mean age of the 87 patients was 45.69 ± 14.21years (range 18-76years), and the ratio of men to women was 1:4.8. The mean volumes were much decreased at the 12th month after ablation compared to the initial volumes (p < .001). The mean VRR was 76.09% at the 12th month. The technique efficacy (VRR > 50%) was 90.80% at the 12th month. A multivariate analysis revealed that VRR was related to the initial volume (p = .015), annular flow (p = .010), and nodule composition (p = .024). The mean symptomatic score decreased from 4.40 ± 0.28 to 0.26 ± 0.06 at the 12th month (p < .001). At the same time, the mean cosmetic score decreased from 3.22 ± 0.10 to 1.31 ± 0.08 (p < .001). MWA could serve as a safe and effective therapy for large BTNs, significantly reducing the volume of BTNs and significantly improving compressive symptoms and appearance problems. Microwave ablation could serve as a safe and effective therapy for large benign thyroid nodules, leading to significant volume reduction and satisfied symptom and cosmetic alleviation period. • This multicenter study investigated the feasibility and safety of microwave ablation for large benign thyroid nodules. • After ablation, the nodule volume was significantly reduced, and patients' symptoms and appearance problems were significantly improved. • Microwave ablation is feasible for large benign thyroid nodules and has been a supplement treatment.

Having More Tender Than Swollen Joints is Associated With Worse Function and Work Impairment in Patients With Early Rheumatoid Arthritis.

Patients with early rheumatoid arthritis (RA) may present with more tender than swollen joints, which can persist. Elevated tender-swollen joint difference (TSJD) is often challenging, because there may be multiple causes and it may contribute to overestimating disease activity. Little is known about the phenotype and impact of TSJDs on patient function. Our objective was to evaluate the impact of TSJD on functional outcomes in early RA and to see whether associations vary by joint size. Data were from patients with active, early RA (≤12 months) enrolled in the Canadian Early Arthritis Cohort, who completed assessments of general function (Multidimensional Health Assessment Questionnaire [MDHAQ]), upper extremity (UE) function (Quality of Life in Neurological Disorders [Neuro-QoL] UE scale), and work/activity impairment (Work Productivity and Activity Impairment RA) over their first year of follow-up. A total of 28 joint counts were performed. TSJDs were calculated. Adjusted associations between TSJDs and functional outcomes were estimated in separate multivariable linear mixed effects models. Separate analyses were performed for large- versus small-joint TSJD. Patients (N=547) were 70% female, mean age 56 (SD 15) years, mean disease duration 5.3 (SD 2.9) months. At baseline, 287 (52%) had TSJD >0 (43% involved large joints and 34% small joints), decreasing to 32% at 12 months. A one-point increase in TSJD was significantly associated with worse function (MDHAQ: adjusted mean change 0.10, 95% confidence interval [CI] 0.08-0.13; Neuro-QoL UE function T score: adjusted mean change -0.59, 95% CI -0.76 to -0.43; and greater work impairment: adjusted mean change 1.95%, 95% CI 0.85%-3.05%). Higher large-joint TSJDs were associated with the worst functional outcomes. Having more tender than swollen joints is common in early RA and is associated with worse function, most notably when involving large joints. Early identification and targeted intervention strategies may be needed.

Associations between dietary indices and hearing status among middle-older aged adults – results from the Baltimore Longitudinal Study of Aging

BackgroundHearing loss, a public health issue in older populations, is closely related to functional decline. ObjectiveTo investigate the longitudinal associations between 4 dietary indices and hearing status. MethodsData from the Baltimore Longitudinal Study of Aging were used and included 882 participants ≥45 y of age. Dietary intake was assessed using a validated food frequency questionnaire, and 4 dietary scores (Mediterranean-Dietary Approaches to Stop Hypertension Intervention for Neurodegenerative Delay diet [MIND], Mediterranean style diet score [MDS], Alternative Healthy Eating Index [AHEI], and Healthy Eating Index [HEI]) were calculated as averages over time. Hearing status was examined using pure-tone audiometry, and pure-tone average (PTA) of hearing thresholds were calculated at speech-level (PTA(500, 1000, 2000, 4000 Hz)), low (PTA(500, 1000 Hz)), and high (PTA(4000, 8000 Hz)) frequencies, with lower thresholds indicating better hearing. Multivariable linear mixed-effect models were used to examine associations between dietary indices and hearing threshold change over time adjusted for confounders. ResultsAt baseline, the mean age of participants was 67 y and 55% were female. Over a median of 8 y of follow-up, MDS ≥7 was associated with 3.5 (95% CI: –6.5, –0.4) and 5.0 (95% CI: –9.1, –1.0) dB lower PTA(500, 1000, 2000, 4000 Hz) and PTA(4000, 8000 Hz), respectively, compared with MDS ≤3; the highest tertile of the AHEI was associated with 2.3 (95% CI: –4.6, –0.1) and 5.0 (95% CI: –8.0, –2.0) dB lower PTA(500, 1000, 2000, 4000 Hz) and PTA(4000, 8000 Hz); and each standard deviation increment in HEI was associated with 1.6 dB (95% CI: –2.7, –0.6), 1.1 dB (95% CI: –2.1, –0.1), and 2.1 dB (95% CI: –3.5, –0.6) lower PTA(500, 1000, 2000, 4000 Hz), PTA(500, 1000 Hz), and PTA(4000, 8000 Hz), respectively. ConclusionsAdherence to healthy dietary patterns was associated with better hearing status, with stronger associations at high frequencies. Am J Clin Nutr 20xx;x:xx.

Microperimetry and Structural Risk Factors on OCT in Intermediate Age-Related Macular Degeneration

PurposeTo determine the relationship between structural biomarkers on optical coherence tomography (OCT) that increases the risk of disease progression and microperimetric retinal sensitivity in patients with intermediate age-related macular degeneration (iAMD) DesignProspective cross-sectional, observational study ParticipantsForty-five eyes of 23 patients with iAMD MethodsPatients underwent OCT and microperimetry. OCT scans were evaluated for the risk factors intraretinal hyperreflective foci (HRF), hyporeflectivity within drusenoid lesions (HRDL), subretinal drusenoid deposits (SDD), double layer sign (DLS) and drusen volume. Microperimetric retinal sensitivity was analyzed with a 33-point grid covering the macula. With a novel method of determining what part of the retina corresponded to each microperimetry point, a Voronoi diagram was constructed, dividing the macula in cells consisting of the region nearer to each point than any other. The Voronoi diagram was superimposed on the OCT making it possible to determine the point-to-point location of the OCT risk factors. Univariable and multivariable linear mixed effects models were used for analysis Main Outcome MeasuresAssociation between microperimetric retinal sensitivity and OCT risk factors at individual measuring points Results1479 points of retinal sensitivity and corresponding structural area on OCT were included in this study. Retinal sensitivity was significantly decreased with presence of the OCT risk factors HRF, HRDL, DLS and drusen volume (all P < 0.001) when analyzed with the univariable linear mixed effects model. The multivariable model showed a significant decrease of retinal sensitivity with presence of HRF (P < 0.001), DLS (P = 0.025) and greater drusen volume (P < 0.001) ConclusionPresence of HRF, DLS, and greater drusen volume, all of which increase the risk of disease progression, are significantly and independently associated with decreased microperimetric retinal sensitivity in patients with iAMD.

Multimorbidity, Social Engagement, and Age-Related Cognitive Decline in Older Adults from the Rancho Bernardo Study of Healthy Aging.

Multimorbidity is associated with increased rate of cognitive decline with age. It is unknown whether social engagement, which is associated with reduced risk of dementia, modifies associations between multimorbidity and cognitive decline. To examine the associations of multimorbidity with longitudinal cognitive test performance among community-dwelling older adults, and to determine whether associations differed by levels of social engagement. We used data from the Rancho Bernardo Study of Healthy Aging, a community-based prospective cohort study. Starting in 1992-1996, participants completed a battery of cognitive function tests at up to 6 study visits over 23.7 (mean = 7.2) years. Multimorbidity was defined as≥2 of 14 chronic diseases. Social engagement was assessed using items based on the Berkman-Syme Social Network Index. Multivariable linear mixed-effects models were used to test associations of multimorbidity and cognitive performance trajectories. Effect measure modification by social engagement was evaluated. Among 1,381 participants (mean age = 74.5 years; 60.8% women; 98.8% non-Hispanic White), 37.1% had multimorbidity and 35.1% had low social engagement. Multimorbidity was associated with faster declines in Mini-Mental State Examination (MMSE; β= -0.20; 95% CI -0.35, -0.04), Trail-Making Test Part B (β= 10.02; 95% CI 5.77, 14.27), and Category Fluency (β= -0.42; 95% CI -0.72, -0.13) after adjustment for socio-demographic and health-related characteristics. Multimorbidity was associated with faster declines in MMSE among those with low compared to medium and high social engagement (p-interaction < 0.01). Multimorbidity was associated with faster declines in cognition among community-dwelling older adults. Higher social engagement may mitigate multimorbidity-associated cognitive decline.

Midterm Outcomes and Aneurysm Sac Dynamics Following Fenestrated Endovascular Aneurysm Repair after Previous Endovascular Aneurysm Repair

Fenestrated endovascular aneurysm repair (FEVAR) represents a feasible option for aortic repair after endovascular aneurysm repair (EVAR), due to improved peri-operative outcomes compared with open conversion. However, little is known regarding the durability of FEVAR as treatment of failed EVARs. Since aneurysm sac evolution is an important marker for success after aneurysm repair, the aim of the study was to examine mid-term outcomes and aneurysm sac dynamics of FEVAR after prior EVAR. Patients undergoing FEVAR for complex abdominal aortic aneurysms from 2008 to 2021 at two hospitals in The Netherlands were included. Patients were categorised into primary FEVAR and FEVAR after EVAR. Outcomes included five year mortality, one year aneurysm sac dynamics (regression/stable/expansion), sac dynamics over time, and five year aortic related procedures. Analyses were done using Kaplan-Meier methods, multivariable Cox regression analysis, chi-square tests, and linear mixed effect models. In total, 196 patients with FEVAR were identified, of whom 27% (n = 53) had a prior EVAR. Patients with prior EVAR were significantly older (78 ± 6.7 years vs. 73 ± 5.9 years, p < .001). There were no significant differences in mortality. FEVAR after EVAR was associated with higher risk of aortic related procedures within five years (hazard ratio [HR] 2.6; 95% confidence interval [CI] 1.1 - 6.5, p = .037). Sac dynamics were assessed in 154 patients with available imaging. Patients with a prior EVAR showed lower rates of sac regression and higher rates of sac expansion at one year compared with primary FEVAR (sac expansion 48%, n = 21/44, vs. 8%, n = 9/110, p < .001)). Sac dynamics over time showed similar results, sac growth for FEVAR after EVAR, and sac shrinkage for primary FEVAR (p < .001). FEVAR after EVAR showed high rates of sac expansion and needed more secondary procedures than patients with primary FEVAR, although this did not affect mid-term survival. Future studies will have to assess whether FEVAR after EVAR is a valid intervention, and the underlying process that drives aneurysm sac growth following successful FEVAR after EVAR.

P1203 Fecal transplantation for Ulcerative Colitis from diet conditioned donors followed by dietary intervention results in favorable gut microbial profile and decreased gut inflammation compared to fecal transplantation alone

Abstract Background Several fecal microbial transplantation (FMT) approaches for ulcerative colitis (UC) have been investigated with conflicting results. We have recently published the clinical outcomes from the CRAFT UC Trial using FMT with the UC Exclusion Diet (UCED), a novel diet for active UC, compared with FMT alone. Here we aimed to compare the two FMT strategies in terms of microbial profile and functional outcomes. Methods Subjects recruited to the CRAFT UC study with available pre- and post-intervention fecal samples were included. Seven donors received diet conditioning for 14 days in line with the UCED principles. Group 1 received single donor standard FMT by colonoscopy on Day 1 and rectal enemas on Days 2 and 14 without dietary conditioning of the donor (N=11). Group 2 received FMT as above but with dietary pre-conditioning of the donor and UCED for the patients (N=10). Pre- and post-intervention fecal samples were assessed by DNA shotgun metagenomic sequencing to obtain microbial compositional and functional data. Data was analyzed using a multivariable linear regression mixed effects model and spearman correlation. Benjamini-Hochberg correction was used for multiple testing with p-values&amp;lt;0.05 and q-values&amp;lt;0.2 considered significant. Results Following diet conditioning, donors had significant depletion in microbial metabolic pathways involved in the biosynthesis of sulfur-containing amino acids. Only patients in Group 2 receiving FMT from diet conditioned donors followed by the UCED showed significant shifts towards the donors’ microbial composition (ADONIS: R2=0.15, p=0.008). Eubacterium sp AF228LB was significantly increased post-intervention in Group 2 (β-coefficient 2.66, 95% CI 2.1 to 3.3) and was also inversely correlated with fecal calprotectin levels (rho=-0.52, p=0.035). Moreover, microbial metabolic pathways involved in gut inflammation and barrier function including ribonucleotides biosynthesis (β-coefficient 0.29, 95% CI 0.07 to 0.51) and branched chain amino acids (β-coefficient 0.44, 95% CI 0.16 to 0.72) were enriched post intervention only in Group 2 and were significantly correlated with decrease in fecal calprotectin (rho=-0.78, p=0.01 and rho=-0.58, p=0.09, respectively). Conclusion FMT from diet conditioned donors followed by the UCED diet led to microbial alterations associated with favorable microbial compositional and functional profile related to sulfur metabolic pathways, which translated to decreased gut inflammation. Our findings support further exploration of additive benefit of dietary intervention for both donors and patients undergoing FMT as a potential treatment of active UC.

Sjögren's Versus Non-Sjögren's Ocular Features: Similar Symptoms, But Significantly Worse Signs.

To examine the ocular signs and symptoms in participants of the Sjögren's International Collaborative Clinical Alliance cohort, and to compare them across Sjögren's disease (SjD) status. Our study population comprised 3380 Sjögren's International Collaborative Clinical Alliance participants who had no missing data relevant to this study. Participants' SjD status was assessed using the updated 2016 American College of Rheumatism/European League Against Rheumatism SjD classification criteria. Participants completed baseline questionnaires of ocular symptoms and underwent ocular examinations. Differences in the ocular signs and symptoms between SjD and non-SjD groups were assessed. We used multivariable linear and linear mixed-effects models to investigate the impact of SjD on Ocular Surface Disease Index-6 and OSS. Among 1532 participants classified as SjD, their Ocular Surface Disease Index-6 did not clinically differ from those classified as non-SjD (adjusted difference, -0.97; 95% confidence interval, -1.52 to -0.41). However, SjD participants exhibited an elevated ocular staining score (adjusted difference, 3.47; 95% confidence interval, 3.36-3.57; P<0.001) compared with non-SjD participants. In addition, SjD was associated with increased odds of ocular signs, such as reduced tear break-up time, abnormal Schirmer I test, and corneal abnormalities, and was strongly related to more intense corneal and conjunctival staining, as well as additional corneal staining points. SjD is associated with a higher risk of ocular signs and pathology compared with non-SjD, whereas ocular symptoms remain similar. In addition, corneal abnormalities and corneal staining patterns could serve as a potential biomarker in identifying SjD-related dry eye.

The Effect of β-Blocker Eye Drops on Pulse Rate, Ocular Blood Flow, and Glaucoma Progression: A Retrospective Longitudinal Study.

Our study was conducted to determine factors associated with the effectiveness of a β-blocker eye drop add-on in altering pulse rate (PR) in glaucoma patients. This retrospective study examined 236 eyes of 138 patients who received a β-blocker eye drop add-on during follow-up. Patients were included if at least one PR measurement was available both before and after the add-on was started. We collected data on ophthalmic parameters: longitudinal PR; longitudinal choroidal blood flow, represented by laser speckle flowgraphy-measured mean blur rate (MBR); and diacron-reactive oxygen metabolites (d-ROMs). We used a multivariable linear mixed-effects model to investigate the effectiveness of the β-blocker eye drop add-on in altering PR and examined factors contributing to a larger PR alteration after the add-on was started by analyzing the effect on PR of the interaction term between the add-on and clinical factors. We used the k-means method to classify the patients. The β-blocker eye drop add-on reduced PR (- 7.61bpm, P < 0.001). Female gender, higher PR when the add-on was started, lower central corneal thickness, and a higher d-ROM level were associated with greater reduction in PR (P < 0.05). In a cluster of patients with these clinical features, choroidal MBR increased by + 3.42% when we adjusted for change over time; MD slope, which represents the speed of glaucoma progression, improved by + 0.64dB/year (P < 0.05). We identified a glaucoma subgroup in which PR decreased, choroidal blood flow increased, and glaucoma progression slowed after a β-blocker eye drop add-on was started.

Pharmacotherapy for the Prevention of Depression and Behavioral Side Effects in Hematopoietic Stem Cell Transplantation Patients

Depression and decreased quality of life (QoL) develop in approximately 30% of nondepressed hematopoietic stem cell transplantation (HSCT) recipients early after transplantation. To potentially prevent this complication, we conducted a prospective randomized trial to assess whether prophylaxis of nondepressed HSCT patients with the antidepressant sertraline (SER) in addition to supportive psychotherapy starting at admission for transplantation decreases the risk of depression and improves QoL. The primary objective of the study was to evaluate whether there was an added benefit of SER versus placebo along with routine supportive psychotherapy on the development of depression in patients receiving HSCT. A secondary objective was to analyze the impact on patient-reported QoL and survival. The study was conducted at a single-site academic medical center. We randomized 123 nondepressed HSCT recipients (1:1) in a phase III double-blind study to receive SER starting at a dose of 50 mg/day, with possible dose escalations to 200 mg per day, or placebo beginning on admission for HSCT and continuing for 12 weeks. Supportive psychotherapy was provided for both groups. Depression (Beck Depression Inventory II [BDI-II]) and QoL (Functional Assessment of Cancer Therapy-Bone Marrow Transplantation [FACT-BMT]) were assessed prior to HSCT and then weekly to week 12 post-HSCT. A multivariable linear mixed-effects model was used to estimate the mean change in BDI-II scores as a function of elapsed time since baseline, treatment assignment, and their interaction. The same process was used to assess treatment effects on all QoL scores from the FACT-BMT assessment. A Kaplan-Meier curve was used to estimate the probability of survival for each group following initiation of treatment. A follow-up Cox proportional hazards model was used to estimate the mortality rate in the 2 groups. Our results do not indicate a benefit of SER in either a diminished risk of depression or improved QoL or survival outcomes. Based on our findings, we can only recommend early evaluation of HSCT recipients for depression, with antidepressant use reserved for patients with evidence of clinical depression, unless additional randomized trials can confirm the effects of early antidepressant therapy on mood and QoL in this vulnerable group. Future research in this area would be improved by systematic monitoring of medication adherence, identification of the optimal dose of SER (or other antidepressant), and inclusion of psychotherapy outcomes when relevant, the absence of which are limitations of this study.

Life course neighborhood social determinants of health and longitudinal changes in cognition in three Alzheimer’s Disease Research Center cohorts

AbstractBackgroundSeminal studies on exposure to life course social determinants of health, such as neighborhood racial segregation and neighborhood poverty, suggest detrimental associations with poorer cognitive function. We aimed to test the opposite by examining the relationship between self‐reported exposure to health‐promoting neighborhood environments over the life course and cognitive function among older adults.MethodParticipants were persons living without dementia at three US Alzheimer’s Disease Research Centers (University of California, Davis in Sacramento (UCD); Washington University in Saint Louis (WU); and Wake Forest University in Winston‐Salem (WFU)). An ancillary study (K01AG063895, PI: Besser) included the Life Course Sociodemographics and Neighborhood Questionnaire (LSNEQ) comprised of indices like neighborhood measures of socioeconomic status (NSES), walking and biking frequency, and greenness from childhood, midlife, and late life. LSNEQ data were linked with late‐life cognitive test z‐scores (Animals and Vegetables Category Fluency, Trail Making Parts A and B) from the National Alzheimer’s Coordinating Center Uniform Data Set. Multivariable linear mixed effects models tested associations between the LSNEQ index scores (composite values over childhood and mid‐ and late‐life) and baseline and longitudinal change in cognitive function controlling for demographics, Center, and baseline global Clinical Dementia Rating (0 or 0.5).ResultThe sample (n = 322) included 65% women, 17% Black, 76% White, and 7% other/mixed racialized group participants and was, on average, 70±7 years old and followed for 2.5±3.2 years. Life Course NSES was lower for UCD (mean = 12.7, SD = 3.5) versus WU (mean = 13.9, SD = 3.2) and WFU (mean = 14.3, SD = 3.2). Life Course Neighborhood Walking and Biking frequency did not differ by Center. Life Course Neighborhood Greenness differed across Centers, and was lowest for WU (mean = 4.8, SD = 1.3) and highest for WFU (mean = 5.6; SD = 1.2). In multivariable analyses, greater Life Course Neighborhood Walking and Biking was associated with higher baseline Trail A scores (estimate = 0.83, 95% CI = 0.08‐1.58) and slower decline on Animals over time (estimate = 0.024, 95% CI = 0.002‐0.045). Greater Life Course Neighborhood Greenness was associated with slower decline on Vegetables over time (estimate = 0.035, 95% CI = 0.001‐0.069).ConclusionThese preliminary findings suggest self‐reported, life course neighborhood exposures and behaviors (i.e., greenness and neighborhood walking/biking) may be associated with better cognition and slower decline in later life.