Multivariable Mixed-effects Models Research Articles

#1429 Daily urinary potassium excretion is not a fixed percentage of daily potassium intake

Abstract Background and Aims High potassium intake is associated with a lower blood pressure and lower incidence of chronic kidney disease. Since a significant amount of potassium is lost via stool, the World Health Organization advices to multiply 24-hour renal potassium excretion by 1.3 for estimation of dietary intake. We analyzed whether this 1.3 factor for potassium intake varies in healthy volunteers and evaluated whether factors associated with tissue cation storage, namely sodium intake, aldosterone, cortisol and urine volume, affect the renal potassium excretion. Method We performed a post-hoc analysis of the long-term sodium balance studies Mars105 and Mars520. Ten healthy male participants consumed a fixed amount of salt (6, 9 and 12 grams/day for >29 days) and potassium (4 grams/day) for 105 (n = 4) and 205 days (n = 6). During the entire study period all urine was collected in 24-hour aliquots. We calculated the percentage of potassium intake that was excreted in the corresponding 24-hour urine collection during steady-state. We assessed whether this percentage was associated with sodium intake, potassium intake, urinary aldosterone, urinary cortisol and urine volume using a multivariable mixed-effects model. Results Overall, the median renal potassium excretion was 80% of potassium intake (IQR 65-97%; range 24-304%). This corresponds to a conversion factor of 1.25 (IQR 1.03-1.54). Within individual subjects we also observed a marked day-to-day variation in the percentage of renal potassium excretion: the average intraperson width of the IQR was 25%. A higher sodium intake was associated with an increased percentage of renal potassium excretion, whereas a higher potassium intake was associated with a decreased percentage of renal potassium excretion. A significant positive interaction between the effects of sodium and potassium intake was present (P < .001; Fig. A). Furthermore, urinary aldosterone (Fig. B), urinary cortisol (Fig. C) and urine volume (Fig. D) were positively associated with the percentage of renal potassium excretion. Conclusion The percentage of consumed potassium that is excreted via urine shows considerable intra- and inter-subject variability. During steady-state this percentage is independently affected by sodium intake, potassium intake, urinary aldosterone, urinary cortisol, and urine volume. Our results suggest that the WHO's fixed 1.3 conversion factor may lead to inaccurate estimations of potassium intake.

Risk factors for gingival invagination: A retrospective study.

This study aimed to identify the risk factors for gingival invagination during orthodontic treatment after premolar extraction. The medical records of 135 patients who had undergone interdental space closure after premolar extraction were collected, and cone beam computed tomography was performed to determine the presence of gingival invagination. The risk factors were examined using mixed-effects models and generalized propensity score weighting (GPSW) to develop a predictive model. Univariate analysis revealed that the extraction site, buccal bone thickness 4 mm apical to the cemento-enamel junction (MB1), mid-root buccal bone thickness (MB2) and vertical skeletal relationships were related to gingival invagination (p < .05). Furthermore, a subsequent multivariable mixed-effects model analysis indicated a significantly increased risk of gingival invagination at MB1 < 1 mm (p < .001; odds ratio [ORMB1≤0.5mm] = 29.304; 95% confidence interval [CI]: 8.986-93.807; OR0.5<MB1<1mm = 22.309; 95% CI: 9.890-50.320). Row mixing model analysis performed after balancing covariates using GPSW showed that MB1 and vertical skeletal relationships were associated with gingival invagination (p < .05) with an increase in ORs. Therefore, in addition to MB1, the risk of gingival invagination is higher in hyperdivergent and normodivergent patients. During the establishment and internal validation of the predictive model, the area under the curve for all three models exceeded 0.7. The risk of gingival invagination is higher in patients with MB1 < 1 mm and in normodivergent or hyperdivergent patients.

Association between long-term exposure to ambient ozone and sperm quality in Shandong Province

Objective: To evaluate the association between long-term exposure to ambient ozone (O3) and sperm quality. Methods: From January 1, 2014, to December 31, 2019, healthy sperm donors were recruited through the Human Sperm Bank of Shandong University Affiliated Reproductive Hospital. A total of 37 977 sperm donation data from 2 971 healthy volunteers were analyzed. The average annual O3 concentration (0.01°× 0.01°) was matched according to household address. A multivariate mixed-effect model was used to analyze the exposure-response relationship between the average O3 exposure concentration and sperm quality in the previous year, with each donor as a random intercept. All results were presented as % changes with 95% confidence intervals (CIs) for all sperm parameters associated with 10 μg/m3 increases in O3. The effects of individual characteristics on the association between O3 and sperm quality were evaluated by stratified analysis. Results: The average O3 concentration in the year before semen collection was (107.09±7.50) μg/m3. Each 10 μg/m3 increase in O3 was associated with declined sperm concentration (-3.12%, 95%CI:-4.55%, -1.67%), total sperm count (-5.21%, 95%CI:-7.28%, -3.09%), total sperm motility (-1.49%, 95%CI:-2.37%, -0.61%), progressive motility (-2.53%, 95%CI:-3.78%, -1.26%), total motile sperm count (-5.82%, 95%CI:-8.17%, -3.41%), and progressively motile sperm count (-6.22%, 95%CI:-8.73%, -3.64%). Men aged 30 and above, obese, and with lower education levels might be more susceptible to the influence of O3 on sperm quality, but the difference was not statistically significant (P>0.05). Conclusion: Long-term exposure to O3 in Shandong Province is associated with a decrease in sperm quality.

Resting state EEG relates to short- and long-term cognitive functioning after cardiac arrest

BackgroundApproximately half of cardiac arrest survivors have persistent cognitive impairment. Guidelines recommend early screening to identify patients at risk for cognitive impairment, but there is no consensus on the best screening method. We aimed to identify quantitative EEG measures relating with short- and long-term cognitive function after cardiac arrest for potential to cognitive outcome prediction. MethodsWe analyzed data from a prospective longitudinal multicenter cohort study designed to develop a prediction model for cognitive outcome after cardiac arrest. For the current analysis, we used twenty-minute EEG registrations from 80 patients around one week after cardiac arrest. We calculated power spectral density, normalized alpha-to-theta ratio (nATR), peak frequency, and center of gravity (CoG) of this peak frequency. We related these with global cognitive functioning (scores on the Montreal Cognitive Assessment (MoCA)) at one week, three and twelve months follow-up with multivariate mixed effect models, and with performance on standard neuropsychological examination at twelve months using Pearson correlation coefficients. ResultsEach individual EEG parameter related to MoCA at one week (βnATR=7.36; P<0.01; βpeak frequency=1.73, P<0.01; βCoG=-9.88, P <0.01). The nATR also related with the MoCA at three months ((βnATR=2.49; P 0.01). No EEG metrics significantly related to the MoCA score at twelve months. nATR and peak frequency related with memory performance at twelve months. Results were consistent in sensitivity analyses. ConclusionEarly resting-state EEG parameters relate with short-term global cognitive functioning and with memory function at one year after cardiac arrest. Additional predictive values in multimodal prediction models need further study.

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.

Bayesian analysis of joint quantile regression for multi-response longitudinal data with application to primary biliary cirrhosis sequential cohort study.

This article proposes a Bayesian approach for jointly estimating marginal conditional quantiles of multi-response longitudinal data with multivariate mixed effects model. The multivariate asymmetric Laplace distribution is employed to construct the working likelihood of the considered model. Penalization priors on regression parameters are incorporated into the working likelihood to conduct Bayesian high-dimensional inference. Markov chain Monte Carlo algorithm is used to obtain the fully conditional posterior distributions of all parameters and latent variables. Monte Carlo simulations are conducted to evaluate the sample performance of the proposed joint quantile regression approach. Finally, we analyze a longitudinal medical dataset of the primary biliary cirrhosis sequential cohort study to illustrate the real application of the proposed modeling method.

Impact of operative time on textbook outcome after minimally invasive esophagectomy, a risk-adjusted analysis from a high-volume center.

We aimed to study the impact of operative time on textbook outcome (TO), especially postoperative complications and length of postoperative stay in minimally invasive esophagectomy. Patients undergoing esophagectomy for curative intent within a prospectively maintained database from 2016 to 2022 were retrieved. Relationships between operative time and outcomes were quantified using multivariable mixed-effects models with medical teams random effects. A restricted cubic spline (RCS) plotting was used to characterize correlation between operative time and the odds for achieving TO. Data of 2210 patients were examined. Median operative time was 270 mins (interquartile range, 233-313) for all cases. Overall, 902 patients (40.8%) achieved TO. Among non-TO patients, 226 patients (10.2%) had a major complication (grade≥III), 433 patients (19.6%) stayed postoperatively longer than 14 days. Multivariable analysis revealed operative time was associated with higher odds of major complications (odds ratio 1.005, P<0.001) and prolonged postoperative stay (≥14 days) (odds ratio 1.003, P=0.006). The relationship between operative time and TO exhibited an inverse-U shape, with 298 mins identified as the tipping point for the highest odds of achieving TO. Longer operative time displayed an adverse influence on postoperative morbidity and increased lengths of postoperative stay. In the present study, the TO displayed an inverse U-shaped correlation with operative time, with a significant peak at 298 mins. Potential factors contributing to prolonged operative time may potentiate targets for quality metrics and risk-adjustment process.

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.

Weight, anthropometric and metabolic changes after discontinuing antiretroviral therapy containing tenofovir alafenamide (TAF) in people with HIV.

Antiretroviral therapy (ART)-related weight gain is of particular concern in people with HIV (PWH). While weight gain was observed among PWH receiving tenofovir alafenamide (TAF), little is known about the potential reversibility after TAF discontinuation. We evaluated weight and metabolic changes 12 months after TAF discontinuation in the Swiss HIV Cohort Study. We included participants who received at least six months of TAF-containing ART between January 2016 and March 2023. Using multivariable mixed-effect models, changes in weight and lipid levels were compared between individuals who continued TAF and those who switched to one of the following TAF-free regimens: TDF-based ART, dolutegravir/lamivudine (DTG/3TC), or long-acting cabotegravir/rilpivirine (CAB/RPV). Of 6555 participants (median age 54 years, 24.3% female, 13% Black), 5485 (83.7%) continued and 1070 (16.3%) stopped TAF. Overall, discontinuing TAF was associated with an adjusted mean weight change of -0.54 kg (95% CI -0.98 to -0.11) after 12 months. In stratified analyses, switching from TAF to TDF led to an adjusted mean weight decrease of -1.84 kg (CI -2.72 to -0.97), and to a decrease in mean total cholesterol (-0.44 mmol/L) and triglycerides (-0.38 mmol/L) after 12 months. Switching from TAF-based ART to DTG/3TC (-0.17 kg, CI -0.82 to 0.48) or long-acting CAB/RPV (-0.64 kg, CI -2.16 to 0.89) did not lead to reductions in weight. Replacing TAF with TDF in PWH led to a decrease in body weight and an improved lipid profile within one year. Weight changes were not observed among individuals who switched to DTG/3TC or long-acting CAB/RPV.

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.

Inflammatory and tissue injury marker dynamics in pediatric acute respiratory distress syndrome.

BACKGROUNDThe molecular signature of pediatric acute respiratory distress syndrome (ARDS) is poorly described, and the degree to which hyperinflammation or specific tissue injury contributes to outcomes is unknown. Therefore, we profiled inflammation and tissue injury dynamics over the first 7 days of ARDS, and associated specific biomarkers with mortality, persistent ARDS, and persistent multiple organ dysfunction syndrome (MODS).METHODSIn a single-center prospective cohort of intubated pediatric patients with ARDS, we collected plasma on days 0, 3, and 7. Nineteen biomarkers reflecting inflammation, tissue injury, and damage-associated molecular patterns (DAMPs) were measured. We assessed the relationship between biomarkers and trajectories with mortality, persistent ARDS, or persistent MODS using multivariable mixed effect models.RESULTSIn 279 patients (64 [23%] nonsurvivors), hyperinflammatory cytokines, tissue injury markers, and DAMPs were higher in nonsurvivors. Survivors and nonsurvivors showed different biomarker trajectories. IL-1α, soluble tumor necrosis factor receptor 1, angiopoietin 2 (ANG2), and surfactant protein D increased in nonsurvivors, while DAMPs remained persistently elevated. ANG2 and procollagen type III N-terminal peptide were associated with persistent ARDS, whereas multiple cytokines, tissue injury markers, and DAMPs were associated with persistent MODS. Corticosteroid use did not impact the association of biomarker levels or trajectory with mortality.CONCLUSIONSPediatric ARDS survivors and nonsurvivors had distinct biomarker trajectories, with cytokines, endothelial and alveolar epithelial injury, and DAMPs elevated in nonsurvivors. Mortality markers overlapped with markers associated with persistent MODS, rather than persistent ARDS.FUNDINGNIH (K23HL-136688, R01-HL148054).

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.

Metal and oxidative potential exposure through particle inhalation and oxidative stress biomarkers: a 2-week pilot prospective study among Parisian subway workers

ObjectiveIn this pilot study on subway workers, we explored the relationships between particle exposure and oxidative stress biomarkers in exhaled breath condensate (EBC) and urine to identify the most relevant biomarkers for a large-scale study in this field.MethodsWe constructed a comprehensive occupational exposure assessment among subway workers in three distinct jobs over 10 working days, measuring daily concentrations of particulate matter (PM), their metal content and oxidative potential (OP). Individual pre- and post-shift EBC and urine samples were collected daily. Three oxidative stress biomarkers were measured in these matrices: malondialdehyde (MDA), 8-hydroxy-2′deoxyguanosine (8-OHdG) and 8-isoprostane. The association between each effect biomarker and exposure variables was estimated by multivariable multilevel mixed-effect models with and without lag times.ResultsThe OP was positively associated with Fe and Mn, but not associated with any effect biomarkers. Concentration changes of effect biomarkers in EBC and urine were associated with transition metals in PM (Cu and Zn) and furthermore with specific metals in EBC (Ba, Co, Cr and Mn) and in urine (Ba, Cu, Co, Mo, Ni, Ti and Zn). The direction of these associations was both metal- and time-dependent. Associations between Cu or Zn and MDAEBC generally reached statistical significance after a delayed time of 12 or 24 h after exposure. Changes in metal concentrations in EBC and urine were associated with MDA and 8-OHdG concentrations the same day.ConclusionAssociations between MDA in both EBC and urine gave opposite response for subway particles containing Zn versus Cu. This diverting Zn and Cu pattern was also observed for 8-OHdG and urinary concentrations of these two metals. Overall, MDA and 8-OHdG responses were sensitive for same-day metal exposures in both matrices. We recommend MDA and 8-OHdG in large field studies to account for oxidative stress originating from metals in inhaled particulate matter.

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.

Utility of peripheral protein biomarkers for the prediction of incident interstitial features: a multicentre retrospective cohort study

Introduction/rationaleProtein biomarkers may help enable the prediction of incident interstitial features on chest CT.MethodsWe identified which protein biomarkers in a cohort of smokers (COPDGene) differed between those with and without...

Collaborative Integration of Community Health Workers in Hospitals and Health Centers to Reduce Pediatric Asthma Disparities: A Quality Improvement Program Evaluation.

To address pediatric asthma disparities on the South Side of Chicago, a community health worker (CHW) home visiting intervention was implemented collaboratively by academic institutions and community based health centers. This evaluation assessed the effectiveness of this longitudinal quality improvement CHW intervention in reducing asthma morbidity and healthcare utilization. All patients aged 2-18 who met the high-risk clinical criteria in outpatient settings or those who visited the ED due to asthma were offered the program. A within-subject study design analyzed asthma morbidity and healthcare utilization at baseline and follow-up. Multivariable mixed-effects regression models, adjusted for baseline demographic and asthma characteristics, were used to assess changes over time. Among 123 patients, the average age was 8.8 (4.4) years, and 89.3% were non-Hispanic black. Significant reductions were observed in the average daytime symptoms days (baseline 4.1 days and follow-up 1.6 days), night-time symptoms days (3.0 days and 1.2 days), and days requiring rescue medication (4.1 days and 1.6 days) in the past two weeks (all p < 0.001). The average number of emergency department visits decreased from 0.92 one year before to 0.44 one year after program participation, a 52% reduction (p < 0.001). No significant difference was found in hospital admissions. These results support the use of a collaborative approach to implement the CHW home visiting program as part of standard care for pediatric asthma patients in urban settings. This approach has the potential to reduce asthma disparities and underscores the valuable role of CHWs within the clinical care team.

The effect of dose-interval on antibody response to mRNA COVID-19 vaccines: a prospective cohort study.

Vaccination against COVID-19 is highly effective in preventing severe disease and hospitalization, but primary COVID mRNA vaccination schedules often differed from those recommended by the manufacturers due to supply chain issues. We investigated the impact of delaying the second dose on antibody responses to COVID mRNA-vaccines in a prospective cohort of health-care workers in Quebec. We recruited participants from the McGill University Health Centre who provided serum or participant-collected dried blood samples (DBS) at 28-days, 3 months, and 6 months post-second dose and at 28-days after a third dose. IgG antibodies to SARS-CoV2 spike (S), the receptor-binding domain (RBD), nucleocapsid (N) and neutralizing antibodies to the ancestral strain were assessed by enzyme-linked immunosorbent assay (ELISA). We examined associations between long (≤89 days) versus short (<89 days) between-dose intervals and antibody response through multivariable mixed-effects models adjusted for age, sex, prior covid infection status, time since vaccine dose, and assay batch. The cohort included 328 participants who received up to three vaccine doses (>80% Pfizer-BioNTech). Weighted averages of the serum (n=744) and DBS (n=216) cohort results from the multivariable models showed that IgG anti-S was 31% higher (95% CI: 12% to 53%) and IgG anti-RBD was 37% higher (95% CI: 14% to 65%) in the long vs. short interval participants, across all time points. Our study indicates that extending the covid primary series between-dose interval beyond 89 days (approximately 3 months) provides stronger antibody responses than intervals less than 89 days. Our demonstration of a more robust antibody response with a longer between dose interval is reassuring as logistical and supply challenges are navigated in low-resource settings.

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.

Public health engagement in alcohol licensing in England and Scotland: the ExILEnS mixed-method, natural experiment evaluation.

International systematic reviews suggest an association between alcohol availability and increased alcohol-related harms. Alcohol availability is regulated through separate locally administered licensing systems in England and Scotland, in which local public health teams have a statutory role. The system in Scotland includes a public health objective for licensing. Public health teams engage to varying degrees in licensing matters but no previous study has sought to objectively characterise and measure their activity, examine their effectiveness, or compare practices between Scotland and England. To critically assess the impact and mechanisms of impact of public health team engagement in alcohol premises licensing on alcohol-related harms in England and Scotland. We recruited 39 diverse public health teams in England (n = 27) and Scotland (n = 12). Public health teams more active in licensing were recruited first and then matched to lower-activity public health teams. Using structured interviews (n = 66), documentation analysis, and expert consultation, we developed and applied the Public Health Engagement In Alcohol Licensing (PHIAL) measure to quantify six-monthly activity levels from 2012 to 2019. Time series of PHIAL scores, and health and crime outcomes for each area, were analysed using multivariable negative binomial mixed-effects models to assess correlations between outcome and exposure, with 18-month average PHIAL score as the primary exposure metric. In-depth interviews (n = 53) and a workshop (n = 10) explored public health team approaches and potential mechanisms of impact of alcohol availability interventions with public health team members and licensing stakeholders (local authority licensing officers, managers and lawyers/clerks, police staff with a licensing remit, local elected representatives). Nineteen public health team activity types were assessed in six categories: (1) staffing; (2) reviewing and (3) responding to licence applications; (4) data usage; (5) influencing licensing stakeholders/policy; and (6) public involvement. Usage and intensity of activities and overall approaches varied within and between areas over time, including between Scotland and England. The latter variation could be explained by legal, structural and philosophical differences, including Scotland's public health objective. This objective was felt to legitimise public health considerations and the use of public health data within licensing. Quantitative analysis showed no clear evidence of association between level of public health team activity and the health or crime outcomes examined, using the primary exposure or other metrics (neither change in, nor cumulative, PHIAL scores). Qualitative data suggested that public health team input was valued by many licensing stakeholders, and that alcohol availability may lead to harms by affecting the accessibility, visibility and norms of alcohol consumption, but that the licensing systems have limited power to act in the interests of public health. This study provides no evidence that public health team engagement in local licensing matters was associated with measurable downstream reductions in crime or health harms, in the short term, or over a 7-year follow-up period. The extensive qualitative data suggest that public health team engagement is valued and appears to be slowly reorienting the licensing system to better address health (and other) harms, especially in Scotland, but this will take time. A rise in home drinking, alcohol deliveries, and the inherent inability of the licensing system to reduce - or in the case of online sales, to contain - availability, may explain the null findings and will continue to limit the potential of these licensing systems to address alcohol-related harms. Further analysis could consider the relative success of different public health team approaches in terms of changing alcohol availability and retailing. A key gap relates to the nature and impact of online availability on alcohol consumption, harms and inequalities, alongside development and study of relevant policy options. A national approach to licensing data and oversight would greatly facilitate future studies and public health input to licensing. Our interview data and therefore PHIAL scores may be limited by recall bias where documentary evidence of public health activity was not available, and by possible variability in grading of such activity, though steps were taken to minimise both. The analyses would have benefited from additional data on licensing policies and environmental changes that might have affected availability or harms in the study areas. The study was registered with the Research Registry (researchregistry6162) on 26 October 2020. The study protocol was published in BMC Medical Research Methodology on 6 November 2018. This synopsis presents independent research funded by the National Institute for Health and Care Research (NIHR) Public Health Research programme as award number 15/129/11.