Multivariable Mixed-effect Regression Models Research Articles

Culturally Adapted Lifestyle Intervention for South Asian Adults With Cardiovascular Risk Factors

South Asian adults in the US experience excess cardiovascular disease (CVD) compared with other racial and ethnic groups. The effectiveness and reach of guideline-recommended lifestyle interventions have not been evaluated in this population. To evaluate whether a culturally adapted, group lifestyle intervention will improve CVD risk factors more effectively than written health education materials among US South Asian adults. This single-blind randomized clinical trial was conducted from March 6, 2018, to February 11, 2023 at community sites in the Chicago, Illinois, metropolitan area. South Asian adults aged 18 to 65 years who were overweight or obese, had no history of CVD events, and had at least 1 additional CVD risk factor (hypertension, dyslipidemia, prediabetes, or diabetes) were eligible for inclusion. A 16-week, culturally adapted, group-based lifestyle intervention led by community health coaches. Lifestyle modification counseling was delivered in English, Gujarati, Hindi, and Urdu. Participants tracked their diet and physical activity (PA) and received 4 optional group maintenance sessions between months 5 and 11 of follow-up. The intervention was delivered in person prior to the onset of the COVID-19 pandemic and via videoconference starting in March 2020. The control group received written health education materials, delivered monthly. Primary outcomes were the between-group differences in CVD risk factor changes from baseline to 12 months, including weight, systolic blood pressure (SBP), diastolic blood pressure (DBP), glycated hemoglobin (HbA1c), and total cholesterol, estimated using multivariate mixed-effects regression models. Secondary outcomes were self-reported diet quality, PA, and self-efficacy, estimated using univariate mixed-effects regression models. Among 549 randomized participants, 318 (57.9%) were women, and mean (SD) participant age was 49.2 (9.5) years. Mean differences in CVD risk factor changes from baseline to 12 months in the intervention vs control group were calculated for weight (mean difference, -0.07 kg; 95% CI, -0.55 to 0.42), SBP (mean difference, 0.47 mm Hg; 95% CI, -1.85 to 2.79), DBP (mean difference, 0.44 mm Hg; 95% CI, -1.06 to 1.95), cholesterol (mean difference, -2.47 mg/dL; 95% CI, -8.51 to 3.57), and HbA1c (mean difference, -0.07%; 95% CI -0.20% to 0.07%). Intervention participation was associated with greater improvements in dietary quality, PA, and self-efficacy than control. In the SAHELI randomized clinical trial, a culturally adapted, group lifestyle intervention was not more effective than written health education materials for CVD risk factor reduction among US South Asian adults, but the intervention was associated with small improvements in self-reported health behaviors. Effective CVD prevention interventions for this elevated-risk population require further investigation. ClinicalTrials.gov Identifier: NCT03336255.

Understanding Opportunities for Prescribing Pre-exposure Prophylaxis (PrEP) at Two Academic Medical Centers in a High Priority Jurisdiction for Ending the HIV Epidemic.

Pre-exposure prophylaxis (PrEP) is an effective, yet underutilized tool for HIV prevention. We sought to understand practice patterns and opportunities for prescribing PrEP across two large, urban, academic healthcare institutions in Chicago, Illinois. We analyzed electronic medical record data from two institutions including encounters for persons ≥18 years of age with ≥1 negative HIV test between 1/1/2015-12/31/2021 who had indications for PrEP. Eligible encounters were those within a six-month window after STI diagnosis, or as long as injection drug use (IDU) was documented. We categorized encounters as inpatient, emergency department (ED), primary care, infectious disease (ID), obstetrics and gynecology/women's health (OBGYN) and other outpatient settings. We performed bivariable and multivariable mixed effects regression models to examine associations, reporting odds ratios (or adjusted odds ratios) and 95% confidence intervals (OR, aOR, 95% CI). In total, 9644 persons contributed 53031 encounters that resulted in 4653 PrEP prescriptions. The two healthcare institutions had differing patient demographics; institution A had more 18-24 year-olds (58.3% vs 31.3%), more African Americans (83.8% vs 27.9%), and more women (65.7% vs 46.3%). Institution B had more White (40.6% vs 7.1%) and Hispanic persons (14.0% vs 4.2%), and more men who have sex with men (MSM) (15.2% vs 3.3%). Institution A had more eligible encounters in the ED (30.8% vs 7.3%) as well as in infectious disease, inpatient, OBYGN, and primary care settings. Institution B accounted for the majority of PrEP prescriptions (97.0%).Adjusted models found lower odds of PrEP prescriptions in non-Hispanic Black (aOR 0.23 [0.16, 0.32]) and Latino (aOR 0.62 [0.44, 0.89]) patients, those with injection drug use (aOR 0.01 [0.00, 0.09]), men who have sex with women (aOR 0.36 [0.23, 0.56]), women who have sex with men (aOR 0.11 [0.06, 0.19]), and in the ED (ref) or OBGYN (0.11 [0.04, 0.27]) settings; while increased odds of PrEP prescription were associated with non-Hispanic White (ref) and MSM (aOR 24.87 [15.79, 39.15]) patients, and encounters at Institution B (aOR 1.78 [1.25, 2.53]) and in infectious disease (aOR [11.92 [7.65, 18.58]), primary care (aOR 2.76 [1.90, 4.01]), and other outpatient subspecialty settings (aOR 2.67 [1.84, 3.87]). Institution A contained persons historically underrepresented in PrEP prescriptions, while institution B accounted for most PrEP prescriptions. Opportunities exist to improve equity in PrEP prescribing and across ED and OBGYN settings.

Impact on Glycemia Risk Index and other metrics in type 1 adult patients switching to Advanced Hybrid Closed-Loop systems: a one-year real-life experience

BackgroundAdvanced Hybrid Closed-Loop system (AHCL) has profoundly changed type 1 diabetes therapy. This study primarily aimed to assess the impact on Glycemia Risk Index (GRI) and other continuous glucose monitoring (CGM) metrics when switching from one of four insulin strategies to AHCL in type 1 adult patients.MethodsA single-center, retrospective pre/post observational study; 198 patients (age 44.4 ± 12.7 years, 115 females/83 males, diabetes duration 24.7 ± 11.6 years, HbA1c 7.4 ± 1%), treated with different insulin therapies (MDI, CSII, SAP with PLGS, HCL) were assessed before and after switching to an AHCL (MiniMed 780G, Diabeloop Roche, Tandem Control-IQ) at 1, 3, 6, and 12 months. Mixed-effects multivariable regression models were used to estimate the mean pre/post variations at different time points, adjusted for potential confounders.ResultsA month after the switch, there was an improvement in CGM metrics and HbA1c for all patients: GRI −10.7, GMI −0.27%, CV −2.1%, TAR>250 −3.7%, TAR180-250 −5.6%, TIR + 9.7%, HbA1c −0.54% (all p < 0.001). This improvement was maintained throughout the observational period (at 3, 6, and 12 months, with all p-values < 0.001). When improvements across the 780, Diabeloop, and Tandem CIQ devices were compared: Diabeloop demonstrated significantly better performance in terms of GRI, GMI, CV, TAR>250 at T1 (for all p < 0.01); 780 recorded highest average decrease in TAR180-250 (p = 0.020), while Tandem achieved the most significant reduction in TBR54-69 (p = 0.004).ConclusionsAdopting an AHCL leads to a rapid and sustained improvement in GRI and other parameters of metabolic control for up to a year, regardless of prior insulin therapies, baseline conditions or brands.

Comparative study of widefield swept-source optical coherence tomography angiography in eyes with concomitant age-related macular degeneration and diabetic retinopathy

Background/aimsWe sought to evaluate widefield swept-source optical coherence tomography angiography (WF SS-OCTA) among eyes with concomitant age-related macular degeneration (AMD) and diabetes mellitus or diabetic retinopathy (DM/DR).MethodsThis cross-sectional, comparative study...

Associations of quantitative contrast sensitivity with vascular metrics on widefield swept-source OCT angiography across stages of diabetic retinopathy

PurposeTo investigate structure–function associations between contrast sensitivity (CS) and widefield swept-source optical coherence tomography angiography (WF SS-OCTA) vascular metrics across stages of non-proliferative (NPDR) and proliferative diabetic retinopathy (PDR), 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.

Potentially modifiable factors associated with health-related quality of life among people with chronic kidney disease: baseline findings from the National Unified Renal Translational Research Enterprise CKD (NURTuRE-CKD) cohort.

Many non-modifiable factors are associated with poorer health-related quality of life (HRQoL) experienced by people with chronic kidney disease (CKD). We hypothesize that potentially modifiable factors for poor HRQoL can be identified among CKD patients, providing potential targets for intervention. The National Unified Renal Translational Research Enterprise Chronic Kidney Disease (NURTuRE-CKD) cohort study recruited 2996 participants from nephrology centres with all stages of non-dialysis-dependent CKD. Baseline data collection for sociodemographic, anthropometric, biochemical and clinical information, including Integrated Palliative care Outcome Scale renal, Hospital Anxiety and Depression score (HADS) and the 5-level EuroQol-5D (EQ-5D-5L) as HRQoL measure, took place between 2017 and 2019. EQ-5D-5L dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression) were mapped to an EQ-5D-3L value set to derive index value. Multivariable mixed effects regression models, adjusted for known factors affecting HRQoL with recruitment region as a random effect, were fit to assess potentially modifiable factors associated with index value (linear) and within each dimension (logistic). Among the 2958/2996 (98.7%) participants with complete EQ-5D data, 2201 (74.4%) reported problems in at least one EQ-5D-5L dimension. Multivariable linear regression identified independent associations between poorer HRQoL (EQ-5D-3L index value) and obesity (body mass index ≥30.0kg/m2, β -0.037, 95% CI -0.058 to -0.016, P=.001), HADS depression score ≥8 (β -0.159, -0.182 to -0.137, P<.001), anxiety score ≥8 (β -0.090, -0.110 to -0.069, P<.001), taking ≥10 medications (β -0.065, -0.085 to -0.046, P<.001), sarcopenia (β -0.062, -0.080 to -0.043, P<.001) haemoglobin <100g/L (β -0.047, -0.085 to -0.010, P=.012) and pain (β -0.134, -0.152 to -0.117, P<.001). Smoking and prescription of prednisolone independently associated with problems in self-care and usual activities respectively. Renin-angiotensin system inhibitor (RASi) prescription associated with fewer problems with mobility and usual activities. Potentially modifiable factors including obesity, pain, depression, anxiety, anaemia, polypharmacy, smoking, steroid use and sarcopenia associated with poorer HRQoL in this cohort, whilst RASi use was associated with better HRQoL in two dimensions.

Associations Between Weight-Loss Attempts, Weight-Related Stress, and Body Image During Childhood and Adolescence in Children With Parental Obesity.

Background: Few longitudinal studies have investigated the role of weight-loss attempts or weight-related stress on body image during childhood. We examined whether weight-loss attempts and weight-related stress are associated with weight misperception and body dissatisfaction across childhood and adolescence. Methods: Data were drawn from the Quebec Adipose and Lifestyle InvesTigation in Youth (QUALITY) cohort of Canadian children with parental obesity (8-10 years: n = 630; 10-12 years: n = 564; 15-17 years: n = 377). We assessed weight-loss attempts and weight-related stress at baseline and first follow-up, and perceived and desired silhouettes at first and second follow-up with questionnaires. Weight misperception consisted of the difference in BMI z-score (zBMI) from the perceived silhouette and the measured zBMI. Body dissatisfaction consisted of the discordance between perceived and desired silhouettes. We estimated multivariable mixed-effects regression models adjusting for age, sex, pubertal stage, parental BMI and education, and sport-based teasing. Results: Weight loss attempts were associated with a higher weight misperception score (ever tried, beta [95% confidence intervals; CI]: 0.13 [0.01-0.24]) and with 2.13 times higher desire to be thinner (95% CI: 1.39-3.26) at the subsequent follow-up. Similarly, children stressed by their weight had a higher misperception score (beta [95% CI]: 0.15 [0.02-0.27]) and greater desire to be thinner at the next follow-up (odds ratio [95% CI]: 1.73 [0.999-3.00]). Conclusions: Weight-loss attempts and weight-related stress in children and adolescents are associated with weight misperception and body dissatisfaction, supporting empowerment and counseling focusing on healthy eating behaviors and a positive body image. Clinical Trial Registration Number: NCT03356262.

Effect of neighborhood and individual-level socioeconomic factors on breast cancer screening adherence in a multi-ethnic study

BackgroundAlthough mammography can significantly reduce breast cancer mortality, many women do not receive their annual breast cancer screening. Differences in screening adherence exist by race/ethnicity, socioeconomic status (SES), and insurance status. However, more detailed investigations into the impact of neighborhood disadvantage and access to resources on screening adherence are lacking.MethodsWe comprehensively examined the effect of individual social, economic, and demographic factors (n = 34 variables), as well as neighborhood level SES (nSES) indicators (n = 10 variables) on breast cancer screening adherence across a multi-ethnic population (n = 472). In this cross-sectional study, participants were surveyed from 2017 to 2018. The data was analyzed using univariate regression and LASSO for variable reduction. Significant predictors were carried forward into final multivariable mixed-effect logistic regression models where odds ratios (OR), 95% confidence intervals and p-values were reported.ResultsNineteen percent of participants were non-adherent to breast screening guidelines. Race/ethnicity was not associated with adherence; however, increasing age (OR = 0.97, 95%CI = 0.95–0.99, p = 0.01), renting a home (OR = 0.53, 95%CI = 0.30–0.94, p = 0.04), food insecurity (OR 0.46, 95%CI = 0.22–0.94, p = 0.01), and overcrowding (OR = 0.58, 95% CI = 0.32–0.94, p = 0.01) were significantly associated with lower breast cancer screening adherence.ConclusionSocioeconomic indicators at the individual and neighborhood levels impact low breast cancer screening adherence and may help to inform future screening interventions.

Self-reported and measured adherence to hepatitis C direct-acting antiviral therapy and sustained virologic response among people who inject drugs: The HERO study

BackgroundObjective adherence measures, such as electronic blister pack (BP), for direct-acting antivirals (DAAs) for hepatitis C virus (HCV) treatment have high accuracy, but their use is limited in real practice settings. We examined the association of self-reported adherence using a visual analogue scale (VAS) with objective BP adherence and sustained virologic response (SVR) among people who inject drugs. MethodsWe conducted secondary analyses using a subset of participants (N = 493) from the per-protocol sample of the HERO study, a pragmatic randomized trial of HCV treatment interventions that used both VAS and BP to measure adherence to a 12-week sofosbuvir/velpatasvir DAA regimen. Multivariable mixed-effects regression models tested the association of self-report adherence level with longitudinal weekly objective adherence. Multivariable logistic regression tested the association of self-report adherence with SVR. ResultsThe average VAS and BP adherences were 95.1 % (SD = 8.9 %) and 76.0 % (16.0 %), respectively, and the proportion of the participants achieving SVR was 92.9 %. The estimated adjusted mean objective adherence was significantly different (−16 %; 95 % CI: −22 %, −11 %, p < .001) between participants with 100 % and <80 % VAS adherence. The likelihood of SVR was significantly lower for those with <80 % VAS adherence [adjusted OR = 0.07; 95 % CI: 0.02, 0.24; p < .001] compared to those with 100 %. ConclusionSelf-reported adherence overestimated objective adherence. However, higher self-report adherence was significantly associated with higher objective adherence. Also, self-reported adherence ≥80 % was significantly associated with SVR. Thus, the self-report measure has utility as a monitoring tool for adherence during DAA treatment.

Haematological dynamics following treatment of visceral leishmaniasis: a protocol for systematic review and individual participant data (IPD) meta-analysis

IntroductionVisceral leishmaniasis (VL) is a parasitic disease with an estimated 30 000 new cases occurring annually. Despite anaemia being a common haematological manifestation of VL, the evolution of different haematological...

Exposure to ambient air pollutants, serum miRNA networks, lipid metabolism, and non-alcoholic fatty liver disease in young adults

Background and AimAmbient air pollution (AAP) exposure has been associated with altered blood lipids and liver fat in young adults. MicroRNAs regulate gene expression and may mediate these relationships. This work investigated associations between AAP exposure, serum microRNA networks, lipid profiles, and non-alcoholic fatty liver disease (NAFLD) risk in young adults. MethodsParticipants were 170 young adults (17–22 years) from the Meta-AIR cohort of the Children’s Health Study (CHS). Residential AAP exposure (PM2.5, PM10, NO2, 8-hour maximum O3, redox-weighted oxidative capacity [Oxwt]) was spatially interpolated from monitoring stations via inverse-distance-squared weighting. Fasting serum lipids were assayed. Liver fat was imaged by MRI and NAFLD was defined by ≥ 5.5% hepatic fat fraction. Serum microRNAs were measured via NanoString and microRNA networks were constructed by weighted gene correlation network analysis. The first principal component of each network represented its expression profile. Multivariable mixed effects regression models adjusted for sociodemographic, behavioral, and clinical covariates; baseline CHS town code was a random effect. Effects estimates are scaled to one standard deviation of exposure. Mediation analysis explored microRNA profiles as potential mediators of exposure-outcome associations. DIANA-mirPATH identified overrepresented gene pathways targeted by miRNA networks. ResultsPrior-month Oxwt was associated with NAFLD (OR=3.45; p = 0.003) and inversely associated with microRNA Network A (β = −0.016; p = 0.026). Prior-year NO2 was associated with non-HDL-cholesterol (β = 7.13; p = 0.01) and inversely associated with miRNA Network A (β = −0.019; p = 0.022). Network A expression was inversely associated with NAFLD (OR=0.35; p = 0.010) and non-HDL-C (β = −6.94 mg/dL; p = 0.035). Network A members miR-199a/b-3p and miR-130a, which both target fatty acid synthase, mediated 21% of the association between prior-month Oxwt exposure with NAFLD (p = 0.048) and 23.3% of the association between prior-year NO2 exposure and non-HDL-cholesterol (p = 0.026), respectively. ConclusionsExposure to AAP may contribute to adverse lipid profiles and NAFLD risk among young adults via altered expression of microRNA profiles.

In Situ Simulation and Clinical Outcomes in Infants Born Preterm

To evaluate impact of a multihospital collaborative quality improvement project implementing in situ simulation training for neonatal resuscitation on clinical outcomes for infants born preterm. Twelve neonatal intensive care units were divided into 4 cohorts; each completed a 15-month long program in a stepped wedge manner. Data from California Perinatal Quality Care Collaborative were used to evaluate clinical outcomes. Infants with very low birth weight between 22 through 31weeks gestation were included. Primary outcome was survival without chronic lung disease (CLD); secondary outcomes included intubation in the delivery room, delivery room continuous positive airway pressure, hypothermia (<36°C) upon neonatal intensive care unit admission, severe intraventricular hemorrhage, and mortality before hospital discharge. A mixed effects multivariable regression model was used to assess the intervention effect. Between March 2017 and December 2020, a total of 2626 eligible very low birth weight births occurred at 12 collaborative participating sites. Rate of survival without CLD at participating sites was 74.1% in March to August 2017 and 76.0% in July to December 2020 (risk ratio 1.03; [0.94-1.12]); no significant improvement occurred during the study period for both participating and nonparticipating sites. The effect of in situ simulation on all secondary outcomes was stable. Implementation of a multihospital collaborative providing in situ training for neonatal resuscitation did not result in significant improvement in survival without CLD. Ongoing in situ simulations may have an impact on unit practice and unmeasured outcomes.

Dynamics of inflammatory responses after SARS-CoV-2 infection by vaccination status in the USA: a prospective cohort study

Cytokines and chemokines play a critical role in the response to infection and vaccination. We aimed to assess the longitudinal association of COVID-19 vaccination with cytokine and chemokine concentrations and trajectories among people with SARS-CoV-2 infection. In this longitudinal, prospective cohort study, blood samples were used from participants enrolled in a multi-centre randomised trial assessing the efficacy of convalescent plasma therapy for ambulatory COVID-19. The trial was conducted in 23 outpatient sites in the USA. In this study, participants (aged ≥18 years) were restricted to those with COVID-19 before vaccination or with breakthrough infections who had blood samples and symptom data collected at screening (pre-transfusion), day 14, and day 90 visits. Associations between COVID-19 vaccination status and concentrations of 21 cytokines and chemokines (measured using multiplexed sandwich immunoassays) were examined using multivariate linear mixed-effects regression models, adjusted for age, sex, BMI, hypertension, diabetes, trial group, and COVID-19 waves (pre-alpha or alpha and delta). Between June 29, 2020, and Sept 30, 2021, 882 participants recently infected with SARS-CoV-2 were enrolled, of whom 506 (57%) were female and 376 (43%) were male. 688 (78%) of 882 participants were unvaccinated, 55 (6%) were partly vaccinated, and 139 (16%) were fully vaccinated at baseline. After adjusting for confounders, geometric mean concentrations of interleukin (IL)-2RA, IL-7, IL-8, IL-15, IL-29 (interferon-λ), inducible protein-10, monocyte chemoattractant protein-1, and tumour necrosis factor-α were significantly lower among the fully vaccinated group than in the unvaccinated group at screening. On day 90, fully vaccinated participants had approximately 20% lower geometric mean concentrations of IL-7, IL-8, and vascular endothelial growth factor-A than unvaccinated participants. Cytokine and chemokine concentrations decreased over time in the fully and partly vaccinated groups and unvaccinated group. Log10 cytokine and chemokine concentrations decreased faster among participants in the unvaccinated group than in other groups, but their geometric mean concentrations were generally higher than fully vaccinated participants at 90 days. Days since full vaccination and type of vaccine received were not correlated with cytokine and chemokine concentrations. Initially and during recovery from symptomatic COVID-19, fully vaccinated participants had lower concentrations of inflammatory markers than unvaccinated participants suggesting vaccination is associated with short-term and long-term reduction in inflammation, which could in part explain the reduced disease severity and mortality in vaccinated individuals. US Department of Defense, National Institutes of Health, Bloomberg Philanthropies, State of Maryland, Mental Wellness Foundation, Moriah Fund, Octapharma, HealthNetwork Foundation, and the Shear Family Foundation.

Decrease in the prevalence of antimicrobial resistance in Escherichia coli isolates of Canadian turkey flocks driven by the implementation of an antimicrobial stewardship program.

The emergence of antimicrobial-resistant organisms at the human-animal-environment interface has raised global concern prompting governments and various stakeholders to take action. As a part of the stewardship initiative, Canadian turkey producers have implemented an antimicrobial use (AMU) strategy to manage antimicrobial resistance (AMR) in their sector. This study evaluated farm-level AMU and AMR data collected between 2016 and 2021 in major turkey-producing provinces/regions through the Canadian Integrated Program for Antimicrobial Resistance Surveillance to assess the progress of the strategy by characterizing the prevalence of homologous and multidrug resistance (MDR) in Escherichia coli isolated from turkeys. Multivariable mixed-effect logistic regression models assessed temporal and provincial/regional variations in AMR and MDR. Negative binomial regression models examined the temporal and regional variations in the total AMU. The total AMU (measured in mg/kg turkey biomass) significantly decreased in all provinces/regions in 2020 and 2021. Escherichia coli isolates from turkey flocks showed a significant decrease in resistance to gentamicin, sulfisoxazole, and tetracyclines during the six-year study period, consistent with the timing of the AMU reduction strategy. The prevalence of MDR isolates was significantly lower in 2020 and 2021 compared to 2016. Higher prevalence was observed in the Western region compared to Québec and Ontario. Two common AMR patterns were identified: ampicillin-streptomycin-tetracyclines and streptomycin-sulfisoxazole-tetracyclines. These AMR patterns indicate possible cross-resistances (same class), co-selection (unrelated classes) for resistance, or potential carryover of resistance determinants from previous production cycles. The decreasing prevalence of resistance to homologous antimicrobials, MDR, and AMU quantity are suggestive that the turkey sector's AMU strategy is achieving its desired impact. However, antimicrobials previously eliminated for preventive use in turkey flocks and the use of highly important antimicrobials in human medicine suggest that the AMU reduction strategy should be monitored and re-evaluated periodically to mitigate the emergence of MDR bacteria and safeguard animal and public health.

Serial deep gray nuclear DTI changes in Parkinson's disease over twelve years.

Deep gray nuclear pathology relates to motor deterioration in idiopathic Parkinson's disease (PD). Inconsistent deep nuclear diffusion tensor imaging (DTI) findings in cross-sectional or short-term longitudinal studies have been reported. Long-term studies in PD are clinically challenging; decade-long deep nuclear DTI data are nonexistent. We investigated serial DTI changes and clinical utility in a case-control PD cohort of 149 subjects (72 patients/77 controls) over 12 years. Participating subjects underwent brain MRI at 1.5T; DTI metrics from segmented masks of caudate, putamen, globus pallidus and thalamus were extracted from three timepoints with 6-year gaps. Patients underwent clinical assessment, including Unified Parkinson Disease Rating Scale Part 3 (UPDRS-III) and Hoehn and Yahr (H&Y) staging. A multivariate linear mixed-effects regression model with adjustments for age and gender was used to assess between-group differences in DTI metrics at each timepoint. Partial Pearson correlation analysis was used to correlate clinical motor scores with DTI metrics over time. MD progressively increased over time and was higher in the putamen (p < 0.001) and globus pallidus (p = 0.002). FA increased (p < 0.05) in the thalamus at year six, and decreased in the putamen and globus pallidus at year 12. Putaminal (p = 0.0210), pallidal (p = 0.0066) and caudate MD (p < 0.0001) correlated with disease duration. Caudate MD (p < 0.05) also correlated with UPDRS-III and H&Y scores. Pallido-putaminal MD showed differential neurodegeneration in PD over 12 years on longitudinal DTI; putaminal and thalamic FA changes were complex. Caudate MD could serve as a surrogate marker to track late PD progression.

The association between kidney function, cognitive function, and structural brain abnormalities in community-dwelling individuals aged 50+ is mediated by age and biomarkers of cardiovascular disease.

Cognitive impairment has been associated with kidney function and chronic kidney disease. Whether this association is due to accelerated cardiovascular disease (CVD) or an independent specific kidney function effect related to toxins is unclear. We investigated the impact of an array of clinical factors, inflammatory biomarkers, and cardiovascular biomarkers on the association between kidney function, cognitive function, and structural brain abnormalities. We used data from the first and third waves of the TILDA Study, a population-representative prospective cohort of Irish adults aged 50 years and over, based on stratified random sampling (n = 3774). The MRI sub-study included participants who consented to MRI brain imaging in addition to the health assessment. Multivariable linear and mixed-effect longitudinal regression models were fitted separately for each kidney marker/estimated glomerular filtration rate (eGFR) equation after adjusting for baseline age and demographics, clinical vascular risk factors, and biomarkers. Unadjusted analyses showed an association between low eGFR, cognitive dysfunction, and cognitive decline (P < 0.001 for all kidney markers). Kidney function markers were also associated with white matter disease [OR = 3.32 (95% CI: 1.11, 9.98)], total grey matter volume (β = -0.17, 95% CI -0.27 to -0.07), and regional grey matter volumes within areas particularly susceptible to hypoxia (P < 0.001 for all). All the associations decreased after adjusting for age and were also diminished after adjusting for CVD biomarkers. Age and CVD-biomarker score were significant mediators of the adjusted associations between eGFR and cognitive status. These results remained consistent for cross-sectional and longitudinal outcomes and specific cognitive domains. Decreased kidney function was associated with cerebrovascular disease. The association appeared to be mediated predominantly by age and the combination of CVD markers [namely N-terminal pro-B-type natriuretic peptide (NT-proBNP) and Growth Differentiation Factor 15 (GDF15)], supporting the idea that shared biological pathways underline both diseases. Further mechanistic studies of the specific molecular mechanisms that lead to both kidney and cognitive decline are warranted.

FUNCTIONAL OUTCOMES FOLLOWING HIGH- AND LOW-ENERGY LISFRANC INJURIES: A LARGE REGISTRY-BASED STUDY

Lisfranc injuries account for 0.2% of all fractures and have been linked to poorer functional outcomes, in particular resulting in post-traumatic arthritis, midfoot collapse and chronic pain. This study assesses the longitudinal functional outcomes in patients with low and high energy Lisfranc injuries treated both operatively and non-operatively.Patients above 16 years with Lisfranc injuries from January 2008 and December 2017 were identified through the Victorian Orthopaedic Trauma Outcomes (VOTOR) registry. Follow-up performed at 6, 12 and 24 months through telephone interviews with response rate of 86.1%, 84.2% and 76.2% respectively. Longitudinal functional outcome data using Global Outcome Assessment, EQ-5D-5L, numerical pain scale, Short-Form 12, the WHO Disability Assessment Schedule and return to work status were collected. Univariate analysis was performed and variables showing a significant difference between groups (p &lt; 0.25) were analysed with multivariable mixed effects regression model.745 patients included in this retrospective cohort study. At 24 months, both the operative and non-operative groups demonstrated similar functional outcomes trending towards an improvement. Mixed effect regression models for the EQ items for mobility (OR 1.80, CI 0.91 – 3.57), self-care (OR 1.95, 95% CI 1.09-3.49), usual activities (OR 1.10, 95% CI 0.99-1.03), pain (OR 1.07, 95% CI 0.61-1.89), anxiety (OR 1.29, 95% CI 0.72-2.34) and pain scale (OR 1.07, 95% CI 0.51 – 2.22) and return to work (OR 1.28, 95% CI 0.56-2.91) between groups were very similar and not statistically significantly different.We concluded that there was no statistically significant difference between operative and non-operative patients with low and high energy Lisfranc injuries. Current clinical practices in Lisfranc injury management are appropriate and not inadvertently causing any further harm to patients. Future research comparing fracture patterns, fixation types and corresponding functional outcomes can help determine gold standard Lisfranc injury management.

Abstract A050: Evaluation of the effect of Medicare’s Oncology Care Model on racial disparities in patient receipt of novel cancer therapies

Abstract Introduction. Medicare’s Oncology Care Model (OCM) was a demonstration project that tied performance-based payments to cost and quality goals for participating oncology practices. A major concern about OCM regarded inclusion of high-cost cancer therapies which could potentially disincentivize oncologists from prescribing novel therapies and could exacerbate racial disparities in access to novel cancer technologies. Methods: This retrospective cohort study used SEER-Medicare data to identify patients who were eligible to receive one of 10 novel cancer therapies that received FDA approval in the 18 months leading up to implementation of OCM. The difference-in-differences cohort analysis matched patients treated by OCM-participating oncologists to non-OCM-participating oncologists and used a multivariable mixed effects regression model to evaluate whether OCM participation changed the likelihood that patients received novel therapies versus alternative treatments. A pre-planned triple difference-in-difference-in-differences analysis evaluated the impact of OCM on Black/White racial disparities in receipt of novel therapies. Results. The study included 2,839 matched patients (760 OCM, 2,079 non-OCM) who had a median age of 73 years and were 56% female, 85% White, 8% Black and 94% non-Hispanic. Among non-OCM patients, 33.2% and 39.9% received novel therapies before and after the start of OCM, respectively, vs 40.1% and 50.3% for OCM patients (adjusted difference-in-differences: 3.5 percentage points [95% CI -3.7 – 10.7 percentage points, p=0.34]). Overall, Black patients were 39% less likely to receive novel therapies compared to White patients (OR 0.61, 95% CI 0.42-0.89, p&amp;lt;0.01). Among patients of OCM clinicians, Black patients saw a larger increase in receipt of novel therapies after OCM implementation (27.8% pre-OCM to 54.1% post-OCM) compared to White patients (40.8% pre-OCM to 49.9% post-OCM) that erased the pre-OCM disparity. In contrast, among patients of non-OCM clinicians, Black patients saw a smaller increase in receipt of novel therapies (25.8% pre-OCM to 29.0% post-OCM) after OCM implementation than White patients (33.7% pre-OCM to 41.1% post-OCM). The difference-in-difference estimate for the effect of OCM was 23.0 percentage points (95% CI -2.4 – 48.5, p=0.08) for Black patients versus 1.8 percentage points (95% CI -6.0 – 9.5, p =0.66) for White patients. The triple difference-in-difference-in-differences analysis showed a large but not statistically-significant effect of OCM on this Black/White racial disparity (triple differences: 21.2 percentage points, 95% CI -5.5 – 48.0; p=0.12).Conclusion. OCM did not negatively affect patient receipt of novel therapies. OCM clinicians eliminated Black/White racial disparities in receipt of novel therapies after OCM implementation while non-OCM clinicians had an increase in this disparity. This triple-differences comparison was not statistically significant but had limited power – future analyses should evaluate the impact of payment models on disparities in receipt of novel therapies. Citation Format: Christopher R. Manz, Angela C. Tramontano, Hajime Uno, Ravi B. Parikh, Justin E. Bekelman, Deborah Schrag. Evaluation of the effect of Medicare’s Oncology Care Model on racial disparities in patient receipt of novel cancer therapies [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr A050.

Preference for online social interactions and support for violent radicalization among college and university students.

Young people are at increased risk of supporting violent radicalization (VR), and VR processes are increasingly happening online. Despite the important role that online socialization plays in the lives of digital natives as well as in VR processes, empirical research aimed to investigate the association between online socialization and support for VR among young people is scant. This article examines the association between preference for online social interactions and support for VR among students and investigates whether this association is moderated by social support and collective self-esteem and mediated by depressive symptoms. A total of 5,598 Canadian college and university students (Mage = 22.75, SDage = 7.45) responded to an online survey. We implemented multivariable mixed-effects regression models, stratified and mediation analyses. Greater preference for online social interactions was associated with stronger support for VR. Preference for online social interactions was a risk factor for VR, particularly at low levels of public self-esteem and social support as well as at high levels of importance attributed to one's group identity. Depressive symptoms partially mediated this association. Programs aimed to foster and value multiple identities and increase social support in educational settings are urgently needed to address the possible negative consequences of the online space on young people's mental health and support for violence. Prevention programs should address the provision of psychosocial support to students reporting depressive symptoms and help them build and maintain a supportive social network, as well as enhance inclusion at the societal level and across educational institutions. (PsycInfo Database Record (c) 2023 APA, all rights reserved).