Multivariable Linear Mixed 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.

#2560 Intradialytic serum phosphate variations are associated with low PTH levels

Abstract Background and Aims Secondary hyperparathyroidism (SHPT) is one of the most common complications in patients with chronic kidney disease (CKD). The prevalence of SHPT progressively increases with the severity of CKD, affecting approximately 50-70% of patients on hemodialysis (HD). SHPT significantly impacts morbidity, mortality, hospitalization risks, healthcare costs, and the quality of life of CKD patients, making its management of paramount importance in this population. A positive serum phosphorus (P) balance is one of the critical determinants of SHPT, and the management of P levels in HD patients revolves around nutritional therapy, medications, and optimal kidney replacement therapy (KRT). Numerous studies have explored the role of KRT in P control among prevalent HD patients. However, whether the reduction of P achieved during KRT affects parathyroid hormone (PTH) levels is still a matter of debate. Currently, a direct evaluation of the relationship between intra-HD P reduction and PTH levels is lacking. Method We conducted a retrospective observational study on the prevalent HD population at the Division of Nephrology, University Hospital of Verona, from January to December 2022. We Included clinically stable adult patients undergoing HD for over 6 months, with multiple recorded visits during the follow-up. Demographic, clinical, laboratory, and medication data were collected. Time-varying variables were updated at each study visit. Food intake was assessed through a 3-day food record (HD day, non-HD day, and weekend day). Patients were instructed to maintain their usual ideally low-phosphate diet and to meticulously record and weigh all foods and preparations consumed. This assessment was conducted every 4 months during the observation period. From the 3-day food records, the dietary phosphorus intake was calculated using a national database and reported as mg of P per day. A dietitian evaluated dietary questionnaires. The primary outcome of interest was PTH levels. The absolute intra-HD change in P (intra-HD ∆P), defined as the difference between pre- and post-HD P levels, served as the main exposure. Multivariable adjusted linear mixed models were used to investigate the relationship between intra-HD ∆P and PTH levels. Potential confounders were included in the following three models of hierarchical adjustment: (i) Model 1, unadjusted; (ii) Model 2, adjusted for age and sex; (iii) Model 3, adjusted for all covariates in Model 2 plus URR, HD modality, active vitamin D, phosphate binders, calcimimetics, comorbidities. Since the relationship between intra-HD ∆P and PTH is influenced by the pre-HD P, all models were adjusted for pre-HD P. The association between PTH and intra-HD ∆P was also assessed in a subgroup of patients who provided a valid dietary diary. A multivariable linear mixed model adjusted for all covariates in Model 3 plus dietary phosphorus intake was used to assess this association. Results A total of 211 patients contributed to 904 study visits. A significant and positive relationship was observed between intra-HD ∆P and pre-HD P (β = 0.76, 95% CI 0.75, 0.78, p < 0.001) and urea reduction ratio (β = 0.38, 95% CI 0.35, 0.41; p < 0.001) (Figure). An increase in intra-HD ∆P was significantly and independently associated with low PTH levels (β = −0.17, 95% CI −0.30, −0.03; p = 0.016; Table). Overall, 86 out of 211 patients provided valid dietary data. The relationship between intra-HD ∆P and PTH levels was confirmed after additional adjustment for dietary P intake (p = 0.041). Conclusion The extent of intra-HD P reduction significantly correlates with low PTH levels. Strategies focused on optimizing or enhancing depurative efficiency in KRT can exert a substantial impact on managing positive phosphorus balance and secondary hyperparathyroidism (SHPT). The assessment of intra-HD P reduction may play a pivotal role in the management and follow-up of SHPT in HD patients.

A Visualization Tool to Study Dyadic Caregiving Health Profiles.

Guided by a life course perspective and fundamental cause theory, this study aims to visualize co-trajectories of health between partners and examine how changes in one spouse's cognitive status can cohesively impact the health of the other spouse along three dimensions (functional, mental, and cognitive). Drawing longitudinal data from the Health and Retirement Study 2000-2016 (N = 3582), we measure women's health profiles by functional limitation (physical health), depression (mental health), and cognitive function (cognitive health). We use multivariate linear mixed models to summarize these paths in the same visual representation. The approach provides a visualization tool that depicts data and model in the same spatial representation allowing assessment of model fit and comparison. This study advances the traditional life course studies by representing underlying processes as a multidimensional time vector of health outcomes. The described approach provides a blueprint for studying complex health profiles or trajectories.

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.

The role of environmental sensitivity in the mental health of Syrian refugee children: a multi-level analysis.

Individuals with high environmental sensitivity have nervous systems that are disproportionately receptive to both the protective and imperilling aspects of the environment, suggesting their mental health is strongly context-dependent. However, there have been few consolidated attempts to examine putative markers of sensitivity, across different levels of analysis, within a single cohort of individuals with high-priority mental health needs. Here, we examine psychological (self-report), physiological (hair hormones) and genetic (polygenic scores) markers of sensitivity in a large cohort of 1591 Syrian refugee children across two waves of data. Child-caregiver dyads were recruited from informal tented settlements in Lebanon, and completed a battery of psychological instruments at baseline and follow-up (12 months apart). Univariate and multivariate Bayesian linear mixed models were used to examine a) the interrelationships between markers of sensitivity and b) the ability of sensitivity markers to predict anxiety, depression, post-traumatic stress disorder, and externalising behaviour. Self-reported sensitivity (using the Highly Sensitive Child Scale) significantly predicted a higher burden of all forms of mental illness across both waves, however, there were no significant cross-lagged pathways. Physiological and genetic markers were not stably predictive of self-reported sensitivity, and failed to similarly predict mental health outcomes. The measurement of environmental sensitivity may have significant implications for identifying and treating mental illness, especially amongst vulnerable populations, but clinical utility is currently limited to self-report assessment.

Importance of the cervical paraspinal muscles in postoperative patient-reported outcomes and maintenance of sagittal alignment after anterior cervical discectomy and fusion.

The aim of this study was to investigate the influence of preoperatively assessed paraspinal muscle parameters on postoperative patient-reported outcomes and maintenance of cervical sagittal alignment after anterior cervical discectomy and fusion (ACDF). Patients with preoperative and postoperative standing cervical spine lateral radiographs and preoperative cervical MRI who underwent an ACDF between 2015 and 2018 were reviewed. Muscles from C3 to C7 were segmented into 4 functional groups: anterior, posteromedial, posterolateral, and sternocleidomastoid. The functional cross-sectional area and also the percent fat infiltration (FI) were calculated for all groups. Radiographic alignment parameters collected preoperatively and postoperatively included C2-7 lordosis and C2-7 sagittal vertical axis (SVA). Neck Disability Index (NDI) scores were recorded preoperatively and at 2 and 4-6 months postoperatively. To investigate the relationship between muscle parameters and postoperative changes in sagittal alignment, multivariable linear mixed models were used. Multivariable linear regression models were used to analyze the correlations between the changes in NDI scores and the muscles' FI. A total of 168 patients with NDI and 157 patients with sagittal alignment measurements with a median follow-up of 364 days were reviewed. The mixed models showed that a greater functional cross-sectional area of the posterolateral muscle group at each subaxial level and less FI at C4-6 were significantly associated with less progression of C2-7 SVA over time. Moreover, there was a significant correlation between greater FI of the posteromedial muscle group measured at the C7 level and less NDI improvement at 4-6 months after ACDF. The findings highlight the importance of preoperative assessment of the cervical paraspinal muscle morphology as a predictor for patient-reported outcomes and maintenance of C2-7 SVA after ACDF.

Biological and Methodological Variability in Retinal Nerve Fiber Layer OCT: The Framingham Heart Study

ObjectiveTo explore participant-level biological attributes and scan-level methodological attributes associated with retinal nerve fiber layer (RNFL) thickness variability in a population-based sample of elderly United States adults. DesignCross-sectional analysis using data from the Framingham Heart Study. Participants1,347 eyes from 825 participants with at least one optical coherence tomography (OCT) scan and axial length data were included. MethodsThree or more successive RNFL scans of each eye of each participant were obtained in a single session. Multivariable linear mixed models were employed to explore the associations between average RNFL thickness with participant-level biological attributes (age, gender, race, ethnicity, and axial length) and scan-level attributes (signal strength [SS]) as independent variables in the whole population as well as a sub-sample of adults with no self-reported history of glaucoma. Similar analyses were designed to assess methodological variability with average within-eye standard deviation (SD) for repeated scans as the dependent variable. Main Outcomes1) Biological variability: average RNFL thickness, 2) Methodological variability: average within- participant SD across repeated scans. ResultsAge (β= −0.19 microns/year, [95% CI: −0.29, −0.09]), female gender (β= +1.48 microns vs. male, [95% CI: 0.09,2.86]), axial length (β= −1.24 microns/mm of greater length, [95% CI: −1.80, −0.67]), and SS (β= +1.62 microns/1 unit greater SS, [95% CI: 1.16,2.09]) were significantly associated with RNFL thickness, while race and ethnicity were not (p>0.05). In analyses designed to assess methodological variability, higher RNFL thickness (β= +0.02 per micron increase, [95% CI: 0.01,0.03]), and lower SS (β= +0.19 per 1 unit lower SS, [95% CI: 0.10,0.27]) were significantly associated with greater RNFL variability. In adults with no self-reported history of glaucoma (n of eyes = 1165, n of participants = 712), female gender was not associated with RNFL, while African-American race was associated with thicker RNFL (β= +4.65 microns vs. Whites, [95% CI: 1.28,8.03]). ConclusionsRNFL thickness is lower with older age, male gender, greater axial length, lower signal strength, and Whites (as compared to African-Americans) without self-reported glaucoma. Measurement variability (SD) is higher with greater RNFL thickness and lower SS. Understanding these biological and methodological variations is important to aid in OCT interpretation.

Deciduous teeth from the New Hampshire Birth Cohort Study: Early life environmental and dietary predictors of dentin elements

BackgroundSparse research exists on predictors of element concentrations measured in deciduous teeth. ObjectiveTo estimate associations between maternal/child characteristics, elements measured in home tap water during pregnancy and element concentrations in the dentin of shed deciduous teeth. MethodsOur analysis included 152 pregnant person-infant dyads followed from the second trimester through the end of the first postnatal year from the New Hampshire Birth Cohort Study. During pregnancy and early infancy, we collected dietary and sociodemographic information via surveys, measured elements in home tap water, and later collected naturally exfoliated teeth from child participants. We measured longitudinal deposition of elements in dentin using LA-ICP-MS. Multivariable linear mixed models were used to estimate associations between predictors and dentin element concentrations. ResultsWe measured 12 elements in dentin including those previously reported (Ba, Mn, Pb, Sr, Zn) and less frequently reported (Al, As, Cd, Cu, Hg, Li, and W). A doubling of Pb or Sr concentrations in water was associated with higher dentin Pb or Sr respectively in prenatally formed [9% (95%CI: 3%, 15%); 3% (1%, 6%)] and postnatally formed [10% (2%, 19%); 6% (2%, 10%)] dentin. Formula feeding from birth to 6 weeks or 6 weeks to 4 months was associated with higher element concentrations in postnatal dentin within the given time period as compared to exclusive human milk feeding: Sr: 6 weeks: 61% (36%, 90%) and 4 months: 85% (54%, 121%); Ba: 6 weeks: 35% (3.3%, 77%) and 4 months: 42% (10%, 83%); and Li: 6 weeks: 61% (33%, 95%) and 4 months: 58% (31%, 90%). SignificanceThese findings offer insights into predictors of dentin elements and potential confounders in exposure-health outcome relationships during critical developmental periods.

Progesterone profiles in postpartum dairy cows with inflammatory disorders

The objective of this prospective cohort study was to determine if progesterone (P4) profiles differed between dairy cows with or without inflammatory disorders early postpartum. A total of 708 cows from 2 commercial herds were enrolled 3 wk before parturition and examined for clinical health disorders (retained placenta, metritis, displaced abomasum, mastitis, or lameness) until 5 wk postpartum. Serum haptoglobin (Hp) was measured in blood at 2 and 6 (±2) DIM, metritis was assessed at 4, 8, 11, and 15 DIM, and purulent vaginal discharge and endometritis (≥6% polymorphonuclear cells in endometrial cytology sampled by cytobrush) were assessed at 35 ± 3 DIM. As Hp ≥0.8 g/L or endometritis were associated with ovarian dysfunction in previous studies, cows with serum Hp ≥0.8 g/L at either time point and endometritis, regardless of clinical disease, were classified as the cohort with inflammatory disorders (INFLAM; n = 139). Clinically healthy cows without difficult calving or twin birth, with Hp <0.8 g/L at both sampling times, without endometritis, and BCS ≥3.00 (1 to 5 scale) were classified as healthy (n = 133). Cows with only one of the 2 conditions (high Hp or endometritis) were excluded. Cohorts had serum P4 measured twice weekly from 35 to 70 (±3) DIM, and the first detected luteal phase (LP) during the sampling period was defined as the interval from onset of luteal activity (P4 increase to ≥1 ng/mL) until decline of P4 to <1 ng/mL. The odds of prolonged LP (≥21 d), average LP length, peak P4, and time to P4 decline (hazard rate) were analyzed using multivariable mixed logistic, linear, or Cox proportional hazard regression models including INFLAM status, parity, sampling day (when applicable), and herd as a random effect considering the covariates of season, milk yield at first DHIA test, and DIM at onset of cyclicity or LP length (when applicable). Cows with INFLAM had greater odds of prolonged LP (LSM ± SEM; 67% vs. 37% ± 7), greater average LP length (17 vs. 15 ± 2 d), lesser P4 at d 4 (4.6 vs. 5.5 ± 0.3 ng/mL) and d 7 (6.0 vs. 7.7 ± 0.3 ng/mL) of the LP, and lesser peak P4 (6.9 vs. 8.2 ± 0.3 ng/mL) during the LP than healthy cows. Status of INFLAM was associated with time to P4 decline in multiparous but not primiparous cows; the LP of INFLAM multiparous cows was less likely to have luteolysis (P4 decline) by d 14 [adjusted hazard ratio (AHR) and 95% CI: 0.54; 0.31 to 0.94] or by d 21 (AHR: 0.32; 0.12 to 0.84) than in healthy multiparous cows. In conclusion, postpartum cows with markers of systemic inflammation at wk 1 and uterine inflammation at wk 5 had altered luteal function (prolonged LP and lower P4 concentrations) before first breeding, which is a possible pathway linking postpartum health disorders and infertility.

Natural disease course modeling of achondroplasia to evaluate the efficacy of recifercept in the absence of a placebo control arm in phase II study.

While randomized, placebo-controlled, double-blinded clinical studies are the gold standard for evaluating the efficacy of investigational drugs, the use of placebo in children with achondroplasia should be limited because it provides no clinical benefit while exhausting study participants' treatment window. Recifercept is an investigational drug for treating children with achondroplasia aged 2-10 years. An alternative efficacy evaluation method, instead of a placebo control arm, was employed in the phase II study. Prior to participating in the phase II study, participants completed a natural history (NH) study. Based on the NH data, a multi-variate linear mixed effects natural disease course model of three anthropometric end points (standing height, sitting height, and arm span) was developed. The model was validated using published growth charts of children with achondroplasia. Subsequently, the model was used to simulate the natural growth trajectories (without any treatment) of the three anthropometric end points for the individuals enrolled in the phase II study. To quantify the efficacy of recifercept, the simulations were compared with the observations post-recifercept treatment in the phase II study. For all the tested doses of recifercept, at the individual level, the observations were comparable to the simulations at 6 and 12 months post-recifercept treatment, suggesting no treatment effect. The results contributed to the decision of terminating recifercept clinical development. This work delivers a framework that could eliminate the need for placebo in clinical trials yet provide sufficient evidence for evaluating the efficacy of an investigational drug.

Smoking Intensity is Associated with Progressive Optic Nerve Head Vessel Density loss in Glaucoma.

To investigate the relationship of smoking and smoking intensity, with the rate of optic nerve head (ONH) whole image capillary density (wiCD) loss in primary open angle glaucoma (POAG) and glaucoma suspect patients. In this longitudinal study, POAG patients who had at least 2 years of follow-up and optical coherence tomography angiography (OCTA) performed at a minimum of 4 visits were selected for study. The smoking intensity was calculated as the pack-year at the baseline OCTA. Univariable and multivariable linear mixed models were used to determine the effect of each parameter on the rates of wiCD loss over time. Nonlinear least-squares estimation with piecewise regression model was used to investigate the cutoff point for the relationship between wiCD loss and smoking intensity. 164 eyes (69 glaucoma suspect and 95 POAG) of 110 patients were included with a mean (95% CI) follow-up of 4.0 (3.9 to 4.1) years. Of the 110 patients, 50 (45.5%) had a reported history of smoking. Greater smoking intensity was associated with faster wiCD loss (-0.11 (-0.23 to 0.00)) %/year per 10 pack-year higher; P=0.048) after adjusting for covariates. The wiCD thinning became significantly faster when smoking intensity was greater than 22.2 pack-years. Smoking had no effect on the rate of wiCD thinning in patients who smoked < 22.2 pack-years during their lifetime. A history of greater smoking consumption was associated with faster vessel density loss, suggesting smoking intensity as a potential risk factor for glaucoma.

Social history and glaucoma progression: the effect of body mass index, tobacco and alcohol consumption on the rates of structural change in patients with glaucoma

Background/aimsAlthough obesity, tobacco and alcohol consumption were linked to the progression of numerous chronic diseases, an association of these social history aspects with glaucoma progression is not yet determined. This...

Short-term data suggests cognitive benefits in the elderly with single-implant overdentures.

This study was an extension of a randomized crossover clinical trial approved by the institutional ethics committee (approval number: D2014-148) and adhered to the CONSORT guidelines. The original study juxtaposed patient contentment with single-implant overdentures (1-IODs) against conventional complete dentures (CCDs), with patient satisfaction being the primary focus. In this follow-up study, the cognitive function of edentulous patients receiving 1-IODs was assessed, specifically monitoring for the emergence of mild cognitive impairment (MCI) throughout a three-year period. Patient outcomes were systematically recorded at predetermined intervals: initially, two months post-1-IOD placement, after one year (with groups alternated between denture types at eight-month marks), then after two and three years. A prosthodontist with a decade of expertise performed all denture-related procedures. This follow-up emphasized the cognitive outcomes using the Montreal Cognitive Assessment (MoCA-J), considering it alongside previously documented results on masticatory function, bone resorption, survival rates, and patient-reported outcomes. Between 2015 and 2016, a follow-up study enrolled edentulous patients over 50 years of age who were proficient in Japanese, had sufficient mandibular bone for implants, and were free of systemic health issues and habits that could impact oral health. The participants were randomly divided into two groups after receiving a central mandibular implant. Group 1 initially used 1-IODs, and Group 2 used unloaded CCDs. After two months and subsequent periods, they swapped denture types. Eventually, all patients chose 1-IODs for continued use. Implant success was monitored over three years. The design featured block randomization and accounted for a sample size of 22, determined to be sufficient for evaluating the primary outcome of patient satisfaction. All patients underwent careful allocation and received customized dental interventions, with detailed radiographic planning and surgical precision guiding the implantation process. Multivariable linear mixed models were used to assess within-group changes in both overall and specific cognitive function scores across five timepoints. Age, assessment interval, and upper jaw denture status were incorporated as consistent variables, while individual participants were considered variable elements in the analysis. SPSS software version 22.0 was utilized to conduct the statistical tests, and a p value threshold of 0.05 was predetermined to establish statistical significance. Twenty-two patients with edentulous mandibles received 1-IODs. Memory and executive functions saw significant score increases at multiple timepoints over the three-year period, with statistical significance. Though one participant dropped out and another passed away, and two did not complete the 3-year follow-up, the remaining 18 participants provided comprehensive data. Age and type of maxillary denture were significant factors, influencing MoCA-J scores with older participants and those with fixed dentures showing lower scores in certain domains. Overall, the findings illustrated the positive correlation between 1-IODs and cognitive function in older adults. Older adults with no natural teeth left in their mandible showed improved cognitive function after one and three years of using 1-IODs, as reflected by their total and specific cognitive domain scores. The study suggests that such implant therapy may offer protective benefits against cognitive decline, demonstrating clinical relevance for patient care, regardless of the maxillary arch (antagonist) condition.

Influence of two collection frequency intervals on sperm quality of standard and miniature bull Terriers during short breeding periods: A clinical field study.

The quality of canine sperm can be influenced by many factors, such as breed, body weight, age, ejaculatory frequency, nutrition, and environment. In the UK, it is common practice for standard Bull Terriers (SBT) and miniature Bull Terriers (MBT) to require male donors during a short breeding period. The aim of this study was to evaluate the effect of semen collection frequency on ejaculate volume and nine sperm parameters in SBT and MBT males, considering age and body condition score (BCS). Ejaculates from six adult SBTs and four MBTs were collected 5 times at two consecutive intervals (Time Series [TS]1, 24 h vs. TS2, 48 h), 1 week apart. Ejaculate volume, concentration, total output, viability (live sperm), subjective total motility, vigor, and total morphological defects, including head, midpiece, and tail defects of sperm, were evaluated. A multivariable mixed linear model for repeated measures was used to analyze the effects of semen collection frequency, age, breed, and BCS on ejaculate volume and sperm parameters. Semen collection frequency, age, and, to a lesser extent, breed, and BCS significantly affected sperm parameters. Semen collection frequency affected all sperm parameters (p < 0.05) but not ejaculate volume (p > 0.05). Total sperm output, sperm vigor, total motility, and tail defects decreased (p < 0.05) at the end of TS1. However, sperm parameters remained relatively constant (p > 0.05) in TS2 between semen collection sessions. Overall, poorer sperm parameters were observed in older dogs (aged 5-8 years) than in younger dogs (aged 4 years). MBT produced less (p < 0.001) ejaculate volume (3.2 ± 0.2 mL vs. 4.3 ± 0.2 mL: Least Squares Mean ± Standard Error of Mean), lower total sperm output (221.8 ± 19.2 × 106 vs. 348.6 ± 19.2 × 106) and lower total morphological defects (25.0 ± 1.1% vs. 31.3 ± 0.9%), and a higher percentage of live sperm (77.0 ± 1.4% vs. 71.7 ± 1.1%) than SBT. In addition, a BCS of 4 positively influenced (p < 0.05) viability, vigor, and total sperm motility. Despite differences in age, breed, and BCS, better sperm parameter values were observed in all semen collection sessions. However, intensive semen collection (TS1) appears to be less effective in maintaining good sperm quality. For breeding or artificial insemination purposes, a 48-h interval between collection sessions is recommended for both breeds. The results of this study could be used to further optimize assisted reproductive technologies in both breeds.

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.

Genotype- and sex-specific changes in vital parameters during isoflurane anesthesia in a mouse model of Alzheimer's disease.

The prevalence of neurodegenerative diseases is increasing as is life expectancy with Alzheimer's disease accounting for two-thirds of dementia cases globally. Whether general anesthesia and surgery worsen cognitive decline is still a matter of debate and most likely depending on the interplay of various influencing factors. In order to account for this complexity, Alzheimer's disease animal models have been developed. The Tg2576 model of Alzheimer's disease is a well-established mouse model exhibiting amyloidopathy and age-dependent sex-specific differences in Alzheimer's disease symptomology. Yet, data on anesthesia in this mouse model is scarce and a systematic comparison of vital parameters during anesthesia with wild-type animals is missing. In order to investigate the safety of general anesthesia and changes in vital parameters during general anesthesia in Tg2576 mice, we did a secondary analysis of vital parameters collected during general anesthesia in aged Tg2576 mice. After governmental approval (General Administration of the Free State of Bavaria, file number: 55.2-1-54-2532-149-11) 60 mice at 10-12 months of age were exposed to isoflurane (1.6 Vol%) for 120 min, data of 58 mice was analyzed. During general anesthesia, heart rate, respiratory rate, temperature, isoflurane concentration and fraction of inspired oxygen were monitored and collected. Data were analyzed using univariate and multivariate linear mixed regression models. During general anesthesia, heart rate decreased in a sex-specific manner. Respiratory rate decreased and body temperature increased dependent on genotype. However, the changes were limited and all vital parameters stayed within physiological limits. Isoflurane anesthesia in the Tg2576 mouse model is safe and does not seem to influence experimental results by interacting with vital parameters. The present study provides information on appropriate anesthesia in order to advance research on anesthesia and AD and could contribute to improving laboratory animal welfare.

Reduced contrast sensitivity function is correlated with changes to cone photoreceptors in simple high myopia.

To investigate the contrast sensitivity function (CSF) changes in simple high myopia (SHM) and evaluate the correlations between these changes with the early changes in the retinal microstructure. This prospective study comprised 81 subjects, 20 with emmetropia (EM), 26 with low myopia and moderate myopia (LM/MM), and 35 with SHM. The area under the log CSF curve (AULCSF) and the cut-off spatial frequency (Cut-off SF) were employed as measures of CSF. Adaptive optics (AO) was employed to quantify the cone density, spacing, and regularity. The thickness and blood flow of the retinal sublayers were determined from vertical and horizontal optical coherence tomography angiography (OCTA) A-scans. Swept-source optical coherence tomography (SS-OCT) was employed to analyze the choroidal thickness (CT) and choroidal vascularity using a custom algorithm. Differences in the retinal and choroidal parameters, cone distribution, AULCSF, and Cut-off SF were compared among the three groups. Multivariate linear mixed models were used to elucidate the associations between photoreceptor morphological alterations, retinal and choroidal parameters, and AULCSF. The AULCSF and Cut-off SF were significantly lower in the SHM group compared to the EM and LM groups (p < 0.05). The SHM group had less cone density, larger cone spacing, and lower cone regularity than the EM and LM/MM groups (p < 0.05). Moreover, the thickness of the inner segment of photoreceptors (IS), retinal pigment epithelium (RPE) layer and choroid were reduced, and the outer segment of photoreceptors (OS) was thicker in the SHM group compared to the EM and LM/MM groups (all p < 0.05). A longer axial length (AL) was correlated with decreased AULCSF, cone density, and cone spacing (r = -0.800 to 0.752, all p < 0.050). Additionally, decreased CSF was correlated with lower cone density (r = 0.338, p = 0.035). Decreased contrast sensitivity was observed in patients with SHM and cone density was significantly correlated with reduced AUCSF.

Stability of parallel evolution in shell traits between the littoral and sublittoral ecotypes of the Antarctic limpet Nacella concinna along a 17-year time series

Abstract Ecotypes constitute valuable markers for understanding the phenotypic responses influenced by evolutionary forces and environmental variations. Assessing the role of these processes in establishing and maintaining ecotype divergence is essential for anticipating evolutionary responses to future climate shifts. We studied the evolutionary dynamics of phenotypic population structure between Nacella concinna ecotypes through a morphometric and temporal analysis (2004–2021) in Antarctica. This approach enables the assessment of contemporary evolutionary dynamics in the presence of biotic and abiotic factors, facilitating the inference of interactions between the acting forces. Using generalized Procrustes analysis, ecotypes were successfully discriminated by their lateral shell traits consistently persisting over the analysed period. Multivariate linear and univariate mixed models revealed a significant temporal effect on shell phenotypic variation, surpassing the effect of inter-ecotype differences. However, according to phenotypic trajectory analysis, this temporal effect did not alter the direction of the phenotypic trajectory of ecotype shell shape, which evolved in parallel during the time series. Despite the environmental variation, the evidence of parallel evolution might indicate the incidence of natural selection in ecotype divergence rather than relying solely on phenotypic plasticity. This work enhances our understanding of ecotype temporal changes and microevolution, underscoring the importance of long-term phenotypic monitoring.