Multivariable Mixed-effect Regression Models Research Articles

Substance use disorder treatment and technology access among people who use drugs in rural areas of the United States: A cross-sectional survey.

To evaluate how technology access affected substance use disorder (SUD) treatment prior to COVID-19 for people who use drugs in rural areas. The Rural Opioid Initiative (January 2018-March 2020) was a cross-sectional study of people with prior 30-day injection drug or nonprescribed opioid use from rural areas of 10 states. Using multivariable mixed-effect regression models, we examined associations between participant technology access and SUD treatment. Of 3,026 participants, 71% used heroin and 76% used methamphetamine. Thirty-five percent had no cell phone and 10% had no prior 30-day internet use. Having both a cell phone and the internet was associated with increased days of medication for opioid use disorder (MOUD) use (aIRR 1.29 [95% CI 1.11-1.52]) and a higher likelihood of SUD counseling in the prior 30 days (aOR 1.28 [95% CI 1.05-1.57]). Lack of cell phone was associated with decreased days of MOUD (aIRR 0.77 [95% CI 0.66-0.91]) and a lower likelihood of prior 30-day SUD counseling (aOR 0.77 [95% CI 0.62-0.94]). Expanding US rural SUD treatment engagement via telemedicine may require increased cell phone and mobile network access.

Tolvaptan treatment is associated with altered mineral metabolism parameters and increased bone mineral density in ADPKD patients.

Autosomal dominant polycystic kidney disease (ADPKD) is characterized by a unique bone and mineral phenotype. The impact of tolvaptan treatment on mineral metabolism and bone mineral density (BMD) is unknown. We conducted an analysis in the Bern ADPKD Registry, a prospective observational cohort study. Mineral metabolism parameters were measured at baseline and every 12months thereafter. BMD was determined by dual-energy X-ray absorptiometry at baseline and after 3years. Multivariable mixed-effects regression models were applied to assess changes in mineral metabolism parameters and BMD associated with tolvaptan treatment. A total of 189 participants (122 without and 67 with subsequent tolvaptan treatment) were included in the analysis. During follow-up, tolvaptan treatment was associated with increased BMD at the femoral neck {β=0.092 [95% confidence interval (CI) 0.001-0.183], P=.047}. In addition, tolvaptan treatment was associated with higher plasma magnesium [β=0.019 (95% CI 0.001-0.037), P=.037], bicarbonate [β=0.972 (95% CI 0.242-1.702), P=.009] and urine pH [β=0.214 (95% CI 0.056-0.372), P=.008] and lower parathyroid hormone [β=-0.191 (95% CI -0.328 to -0.053), P=.006], 1,25(OH)D3 [β=-0.126 (95% CI -0.235 to -0.164), P=.024] and fractional urinary magnesium excretion [β=-0.473 (95% CI -0.622 to -0.324), P<.001]. Chronic tolvaptan treatment is associated with increased femoral BMD and significant changes in both mineral metabolism and acid-base parameters in ADPKD patients.

The association between vacant housing demolition and safety and health in Baltimore, MD

We measured the association between vacant housing demolitions and changes in crime and emergency department (ED) visits in Baltimore, MD. We included 646 block groups in Baltimore, 224 of which experienced at least one demolition from 2012 to 2019. The exposure was the number of demolitions completed in a block group during the previous quarter. Crime (all, property, and violent) and ED visits (all, adults, children, and for specific causes) were examined as the change in the rate per 1000 people from the previous quarter to the current quarter and analyzed using multivariable mixed effects regression models. Demolitions were associated with a small decrease in total ED visits (difference = −0.068 per 1000 people from the previous quarter to the current quarter, 95% CI -0.119, −0.018) but no significant change in crime. For each demolition, the rate of total child ED visits was 0.452 lower compared to the previous quarter (95% CI -0.777, −0.127). Demolitions were associated with small decreases in adult injury-related ED visits in the short term.

The prevalence of MAFLD and its association with atrial fibrillation in a nationwide health check-up population in China.

Background and aimsThe epidemiological characteristics of MAFLD and its relationship with atrial fibrillation (AF) are limited in China. Therefore, we explored the epidemiological characteristics of MAFLD from adults along with the association of MAFLD and 12-ECG diagnosed AF in a nationwide population from health check-up centers.MethodsThis observational study used cross-sectional and longitudinal studies with 2,083,984 subjects from 2009 to 2017. Age-, sex-, and regional-standardized prevalence of MAFLD was estimated. Latent class analysis (LCA) was used to identify subclusters of MAFLD. Multivariable logistic regression and mixed-effects Cox regression models were used to analyze the relationship between MAFLD and AF.ResultsThe prevalence of MAFLD increased from 22.75% to 35.58% during the study period, with higher rates in males and populations with high BMI or resided in northern regions. The MAFLD population was clustered into three classes with different metabolic features by LCA. Notably, a high proportion of MAFLD patients in all clusters had overweight and prediabetes or diabetes. The MAFLD was significantly associated with a higher risk of AF in the cross-sectional study and in the longitudinal study. In addition, the coexistence of prediabetes or diabetes had the largest impact on subsequent AF.ConclusionOur findings suggested a high prevalence of MAFLD and a high prevalence of other metabolic diseases in the MAFLD population, particularly overweight and glucose dysregulation. Moreover, MAFLD was associated with a significantly higher risk for existing and subsequent subclinical AF in the Chinese population.

Effects of Proton Craniospinal Radiation on Vertebral Body Growth Retardation in Children

It is of great interest to physicians and patients/patients' families to be able to predict the amount of growth decrement after craniospinal irradiation (CSI). Little data exist on the effect of proton CSI. Our aim was to determine the effect of proton CSI on vertebral body (VB) growth retardation, and to identify factors associated with growth delay. We performed a retrospective outcome data analysis of 80 patients <16 years old with central nervous system tumors who received proton radiation therapy (PRT) at the Massachusetts General Hospital between 2002 and 2010 with available spinal magnetic resonance imaging. Forty-eight patients received CSI, and 32 patients with brain tumors who received focal cranial irradiation served as controls. VB height was measured midline using sagittal T1-weighted contrast or noncontrast enhanced magnetic resonance imaging of the spine. Measurements were repeated at multiple levels (C3, C3-C4, T4, T4-T5, C3-T6, T4-T7, L3, L1-L5) on available scans for the duration of follow-up. Data were fitted using a mixed-effects multivariable regression model, including follow-up time, CSI dose, age at CSI, and pretreatment VB percentile as parameters. Median follow-up was 69.6 months for patients treated with proton CSI and 52.9 months for the control group. There was a significant association of CSI dose, follow-up time, age at treatment, and pretreatment VB percentile with VB growth retardation. Growth retardation was shown to be independent of gender or growth hormone deficiency. Although the current practice of PRT CSI delivery allows for sparing of the organs anterior to the spine, the vertebral column receives radiation therapy because of its close proximity to the targeted spinal canal. In growing children, the whole VB has generally been included so that growth impairment is even across the VB. We present a quantitative model predicting the growth retardation of patients treated with PRT CSI based on age at treatment, CSI dose, follow-up time, and pretreatment growth percentile.

Impact of deceased organ donor injection drug use on donor culture positivity and recipient outcomes.

Due to the ongoing opioid epidemic in the United States, deceased organ donors increasingly have a history of injection drug use (IDU), raising concerns about infectious risks to solid organ transplant (SOT) recipients. We sought to determine how recent IDU among deceased organ donors impacted donor culture results and recipient outcomes. A retrospective cohort study was performed at three transplant centers. Exposed donors were those with "recent IDU" (in the prior 12 months). Primary outcomes included (1) positive donor cultures for bacteria or Candida species, (2) recipient bacterial or Candida infection within 3 months posttransplant, and (3) recipient graft failure or death within 12 months posttransplant. Mixed effects multivariable regression models were used to evaluate the relationship between recent donor IDU and each outcome. A total of 658 SOT recipients who received organs from 394 donors were included. Sixty-six (17%) donors had a history of recent IDU. Recent IDU in donors was associated with a significantly increased odds of donor culture positivity (aOR 3.65, 95% CI 1.06-12.60, p = .04) but was not associated with SOT recipient infection (aHR 0.98, 95% CI 0.71-1.36, p = .92) or graft failure or death (aHR 0.67, 95% CI 0.29-1.51, p = .33). Donors with recent IDU are more likely to have positive cultures, but their recipients' outcomes are unaffected, suggesting organs from donors with recent IDU may be safely utilized.

Effects of indoor and outdoor temperatures on blood pressure and central hemodynamics in a wintertime longitudinal study of Chinese adults.

We aimed to estimate the effects of indoor and outdoor temperature on wintertime blood pressure (BP) among peri-urban Beijing adults. We enrolled 1279 adults (ages: 40-89 years) and conducted measurements in two winter campaigns in 2018-2019 and 2019-2020. Study staff traveled to participant homes to administer a questionnaire and measure brachial and central BP. Indoor temperature was measured in the 5 min prior to BP measurement. Outdoor temperature was estimated from regional meteorological stations. We used multivariable mixed-effects regression models to estimate the within-individual and between-individual effects of indoor and outdoor temperatures on BP. Indoor and outdoor temperatures ranged from 0.0 to 28 °C and -14.3 to 6.4 °C, respectively. In adjusted models, a 1 °C increase in indoor temperature was associated with decreased SBP [-0.4 mmHg, 95% confidence interval (CI): -0.7 to -0.1 (between-individual; brachial and central BP); -0.5 mmHg, 95% CI: -0.8 to -0.2 (within-individual, brachial BP); -0.4 mmHg, 95% CI: -0.7 to -0.2 (within-individual, central BP)], DBP [-0.2 mmHg, 95% CI:-0.4 to -0.03 (between-individual); -0.3 mmHg, 95% CI: -0.5 to -0.04 (within-individual)], and within-individual pulse pressure [-0.2 mmHg, 95% CI: -0.4 to -0.04 (central); -0.3 mmHg, 95% CI: -0.4 to -0.1 (brachial)]. Between-individual SBP estimates were larger among participants with hypertension. There was no evidence of an effect of outdoor temperature on BP. Our results support previous findings of inverse associations between indoor temperature and BP but contrast with prior evidence of an inverse relationship with outdoor temperature. Wintertime home heating may be a population-wide intervention strategy for high BP and cardiovascular disease in China.

Antiretroviral choice and severe disease predict poorer neuropsychological outcomes in HIV+ children from Africa.

BackgroundThe International Maternal Pediatric Adolescent AIDS Clinical Trials Network (IMPAACT) P1104s study evaluated neuropsychological outcomes over 96 weeks in children living with HIV (CLHIV) aged 5–11 years at 6 Sub-Saharan African sites to explore associations between HIV-illness related biomarkers and neuropsychological outcomes.MethodsChildren living with HIV had participated in IMPAACT P1060, which compared efficacy of nevirapine versus lopinavir/ritonavir in children initiating ART at <3 years of age. At age 5–11, neuropsychological evaluations of KABC cognitive ability, TOVA attention-impulsivity and BOT-2 motor domains were assessed and repeated after 48 and 96 weeks. Clinical, antiretroviral therapy (ART) and laboratory (immunological and virological) parameters were used to predict neuropsychological outcomes using linear mixed-effects multivariable regression models, controlling for child and caregiver characteristics.Results246 CLHIV (45% male, mean age at initial neuropsychological evaluation 7.1 yrs [SD 1.2]) began ART at a median age 14.9 months (IQR 8.2, 25.2). Nadir CD4 percentage was 14.7% (IQR 11.0, 19.5); the median peak viral load (VL) was 750 000 copies/ml (IQR 366 000, 750 000) and 63% had ≥WHO stage 3 clinical disease; 164 (67%) were on lopinavir/ritonavir, 71 (29%) were on nevirapine and 7 (3%) were on efavirenz. Other antiretrovirals were similar. Nevirapine at P1104s study start or later was associated with poorer neuropsychological scores across all domains except Global Executive Composite, even when controlling for nadir CD4 percent and time-varying HIV VL. Other predictors of poorer scores in KABC domains included low birth weight, WHO stage 4 disease and serious illness history and elevated VL was associated with worse BOT-2 scores.ConclusionChildren receiving nevirapine had poorer neuropsychological scores than those on lopinavir/ritonavir. Antiretroviral choice might adversely impact neuropsychological performance. In addition, low birth weight and markers of severe HIV disease: advanced WHO clinical HIV disease, history of serious illness and an elevated VL, were associated with lower neuropsychological scores.

The sonographic quantitative assessment of the deltoid muscle to detect type 2 diabetes mellitus: a potential noninvasive and sensitive screening method?

BackgroundIn our previous published study, we demonstrated that a qualitatively assessed elevation in deltoid muscle echogenicity on ultrasound was both sensitive for and a strong predictor of a type 2 diabetes (T2DM) diagnosis. This study aims to evaluate if a sonographic quantitative assessment of the deltoid muscle can be used to detect T2DM.MethodsDeltoid muscle ultrasound images from 124 patients were stored: 31 obese T2DM, 31 non-obese T2DM, 31 obese non-T2DM and 31 non-obese non-T2DM. Images were independently reviewed by 3 musculoskeletal radiologists, blinded to the patient’s category. Each measured the grayscale pixel intensity of the deltoid muscle and humeral cortex to calculate a muscle/bone ratio for each patient. Following a 3-week delay, the 3 radiologists independently repeated measurements on a randomly selected 40 subjects. Ratios, age, gender, race, body mass index, insulin usage and hemoglobin A1c were analyzed. The difference among the 4 groups was compared using analysis of variance or chi-square tests. Both univariate and multivariate linear mixed models were performed. Multivariate mixed-effects regression models were used, adjusting for demographic and clinical variables. Post hoc comparisons were done with Bonferroni adjustments to identify any differences between groups. The sample size achieved 90% power. Sensitivity and specificity were calculated based on set threshold ratios. Both intra- and inter-radiologist variability or agreement were assessed.ResultsA statistically significant difference in muscle/bone ratios between the groups was identified with the average ratios as follows: obese T2DM, 0.54 (P < 0.001); non-obese T2DM, 0.48 (P < 0.001); obese non-T2DM, 0.42 (P = 0.03); and non-obese non-T2DM, 0.35. There was excellent inter-observer agreement (intraclass correlation coefficient 0.87) and excellent intra-observer agreements (intraclass correlation coefficient 0.92, 0.95 and 0.94). Using threshold ratios, the sensitivity for detecting T2DM was 80% (95% CI 67% to 88%) with a specificity of 63% (95% CI 50% to 75%).ConclusionsThe sonographic quantitative assessment of the deltoid muscle by ultrasound is sensitive and accurate for the detection of T2DM. Following further studies, this process could translate into a dedicated, simple and noninvasive screening method to detect T2DM with the prospects of identifying even a fraction of the undiagnosed persons worldwide. This could prove especially beneficial in screening of underserved and underrepresented communities.

Quantitative contrast sensitivity test to assess visual function in central serous chorioretinopathy

BackgroundTo characterise the contrast sensitivity function (CSF) in central serous chorioretinopathy (CSCR) compared with healthy controls using novel computerised contrast sensitivity (CS) testing with active learning algorithms.MethodsProspective observational study measuring...

Contributing factors to lymph node recovery with esophagectomy by thoracic surgeons: an analysis of the Society of Thoracic Surgeons General Thoracic Surgery Database.

Given the association between lymphadenectomy and survival after esophagectomy, and the ongoing development of effective adjuvant protocols for identified residual disease, we determined factors contributing to lymph node yield and effects on postoperative morbidity following esophagectomy by thoracic surgeons. Using the Society of Thoracic Surgeons General Thoracic Surgery Database, all patients who underwent esophagectomy for primary esophageal cancer with gastric conduit reconstruction from 2012 to 2016 were identified. Patient demographics, technical factors, and tumor characteristics associated with lymph node yield were determined using a multivariable multilevel mixed-effects regression model. Associations between lymph node yield and perioperative morbidity and mortality were similarly assessed. A total of 8480 patients were included. The median number of nodes harvested was 16 [Interquartile Range 11-22]. Factors associated with fewer nodes included female gender (b=-0.53, P=0.032), body mass index <18.5 (b=-1.46, P=0.012), prior cardiothoracic surgery (b=-0.73, P=0.015), intraoperative blood transfusion (b=-1.43, P<0.001), squamous cell histology (b=-0.86, P=0.006), and neoadjuvant treatment (b=-1.41, P<0.001). Operative approach significantly affected lymph node yield, with minimally invasive approaches demonstrating higher lymph node counts, and open transhiatal esophagectomy recovering the fewest nodes. Findings were independent of clinical center. There was no association of higher lymph node yield with 30-day mortality, with only slightly increased risk for chyle leak (odds ratio [OR] 1.02, P=0.012). In conclusion, several patient and tumor factors affect lymph node recovery with esophagectomy, independent of hospital center. Technical aspects, specifically minimally invasive approach, play a significant role in quantified lymph node yield. Higher operative lymph node yield was associated with minimal increased morbidity.

First Nations status and emergency department triage scores in Alberta: a retrospective cohort study.

Background:Previous studies have found that race is associated with emergency department triage scores, raising concerns about potential health care inequity. As part of a project on quality of care for First Nations people in Alberta, we sought to understand the relation between First Nations status and triage scores.Methods:We conducted a population-based retrospective cohort study of health administrative data from April 2012 to March 2017 to evaluate acuity of triage scores, categorized as a binary outcome of higher or lower acuity score. We developed multivariable multilevel logistic mixed-effects regression models using the levels of emergency department visit, patient (for patients with multiple visits) and facility. We further evaluated the triage of visits related to 5 disease categories and 5 specific diagnoses to better compare triage outcomes of First Nations and non–First Nations patients.Results:First Nations status was associated with lower odds of receiving higher acuity triage scores (odds ratio [OR] 0.93, 95% confidence interval [CI] 0.92–0.94) compared with non–First Nations patients in adjusted models. First Nations patients had lower odds of acute triage for all 5 disease categories and for 3 of 5 diagnoses, including long bone fractures (OR 0.82, 95% CI 0.76–0.88), acute upper respiratory infection (OR 0.90, 95% CI 0.84–0.98) and anxiety disorder (OR 0.67, 95% CI 0.60–0.74).Interpretation:First Nations status was associated with lower odds of higher acuity triage scores across a number of conditions and diagnoses. This may reflect systemic racism, stereotyping and potentially other factors that affected triage assessments.

Neighborhood racial/ethnic segregation and cognition in older adults

AbstractBackgroundSocial determinants of health, including neighborhood factors, play a key role in the health of diverse older adults. Yet few longitudinal studies have examined the role of neighborhood racial/ethnic segregation on cognitive function and cognitive decline in both Latinos and Blacks, two populations at greater risk for Alzheimer’s disease and related dementias. We examined how one measure of residential segregation is associated with cognitive outcomes in a diverse cohort.MethodsWe evaluated older non‐Hispanic White (NHW), Black, and Latino participants evaluated at the UC Davis Alzheimer’s Disease Research Center. Individual level addresses were geocoded at the initial visit and appended to U.S. Census 2010 data. Residential segregation was measured using the Getis‐Ord Gi* statistic; this spatial measure of clustering was created for Latino and Black clustering separately. Cognitive outcomes included validated measures of episodic memory, semantic memory, and executive function. We used mixed effects multivariate regression models to evaluate associations between segregation and cognitive function and decline, controlling for age, sex, education, cognitive status at initial visit, clinic versus community recruited, site, vascular risk score, number of visits, neighborhood SES, and population density.ResultsThe sample included 452 participants (mean age=75, SD = 7), 64% female, and 46% NHW, 26% Black, and 21% Latino, in 309 census tracts/neighborhoods. In race‐stratified adjusted analyses, Blacks demonstrated worse episodic memory at baseline among those living in neighborhoods with a higher clustering of Blacks (ß = ‐0.046; 95% CI: ‐0.075, ‐0.016) and worse executive function at baseline among those living in neighborhoods with a higher clustering of Latinos (ß = ‐0.025; 95% CI: ‐0.042, ‐0.008). Latinos demonstrated slower annual declines on episodic memory when living in neighborhoods with a greater clustering of Blacks (ß = 0.008; 95% CI: 0.004, 0.011) and/or Latinos (ß = 0.003; 95% CI: 0.001, 0.005). NHWs had slower annual declines on semantic memory when living in neighborhoods with a greater clustering of Latinos (ß = 0.005; 95% CI: 0.001, 0.008).ConclusionsThere may be some benefit for Latinos and NHWs living in ethnically clustered neighborhoods. Future research is needed to further investigate these findings.

Predictors of PCSK9 (Proprotein Convertase Subtilisin/Kexin Type 9) Inhibitor Prescriptions for Secondary Prevention of Clinical Atherosclerotic Cardiovascular Disease.

Little is known about patterns of PCSK9i (proprotein convertase subtilisin/kexin type 9 inhibitor) use among patients with established clinical atherosclerotic cardiovascular disease. This study's objective was to describe PCSK9i prescribing patterns among patients with atherosclerotic cardiovascular disease. We used a national outpatient clinic registry linked to zip-code level on household income from the US Census to assess characteristics of patients with atherosclerotic cardiovascular disease and LDL-C (low-density lipoprotein cholesterol) <190 mg/dL between September 1, 2015, and September 30, 2019, who did and did not receive PCSK9i prescriptions and practice-level and temporal variation in PCSK9i prescriptions. We assessed predictors of PCSK9i prescription with a multivariable mixed effects regression model which included patient covariates as fixed effects and the cardiology practice as a random effect. Adjusted practice-level variation in PCSK9i prescribing was evaluated with median odds ratio (OR). Of 2 148 100 patients meeting study inclusion criteria, 27 249 (1.3%) received PCSK9i prescriptions. Receiving a PCSK9i prescription was associated with White race (versus non-White: OR, 1.78 [95% CI, 1.55-1.83]); high estimated household income (versus low income: OR, 1.18 [95% CI, 1.08-1.29]), and urban or suburban (versus rural) practice location (urban: OR, 1.47 [95% CI, 1.32-1.64]; suburban: OR, 1.25 [95% CI, 1.13-1.39]). Hispanics had lower odds of receiving PCSK9i prescriptions (OR, 0.66 [95% CI, 0.57-0.76]). The adjusted median odds ratio was 2.68 (95% CI, 2.46-2.94), consistent with clinically significant practice-level variation in PCSK9i prescriptions. No differences in quarterly PCSK9i prescription rates were observed before and after price reductions for evolocumab and alirocumab initiated during the fourth quarter of 2018 and first quarter of 2019, respectively. This study highlights racial, socioeconomic, geographic, and practice-level variations in early PCSK9i prescriptions which persist despite adjustment for clinical and demographic factors. After adjustment, 2 randomly selected practices would differ in likelihood of PCSK9i prescription by a factor of >2.

Effects of indoor and outdoor temperatures on blood pressure and central hemodynamics in a wintertime panel of peri-urban Chinese adults

BACKGROUND AND AIM: Excess wintertime cardiovascular mortality has been observed in populations globally and is partly attributed to cold-induced elevated blood pressure (BP). An inverse relationship between outdoor temperature and BP is well documented. The influence of indoor environmental conditions (e.g., heating, insulation) and indoor temperature on BP is less clear. We examined the effects of indoor and outdoor temperature on wintertime BP and central hemodynamics among older adults in peri-urban Beijing, China. METHODS: We enrolled 1,285 older adults into a panel study conducted in two winter seasons (2018-19 and 2019-2020). Staff traveled to participant homes to administer a questionnaire and measure their brachial and central systolic and diastolic BPs, pulse pressures, and pulse pressure amplification. Indoor temperature was measured within the 5-minutes prior to BP measurements for all participants and 12-month indoor temperature measurements were obtained in a 37% (1st season) and 32% (2nd season) random subsample. Village-level outdoor temperature was estimated from regional meteorological stations. Multivariable mixed-effects regression models were used to estimate the within- and between-individual effects of indoor and outdoor temperature on BP, allowing for effect measure modification. RESULTS:Indoor and outdoor winter temperatures ranged from 0.0 to 28.0˚C and -14.3 to 6.4˚C, respectively. Those in colder homes had a lower wealth score and less home insulation. We observed an inverse linear relationship between indoor temperature and BP (mmHg per 1˚C increase in temperature: −0.4 to −0.5 systolic, −0.3 diastolic, and −0.2 pulse pressure). We found little evidence of any effect of outdoor temperature with BP, or that outdoor temperature modified the effect of indoor temperature. CONCLUSIONS:We found an inverse association between indoor temperature and BP, but no relationship of BP with outdoor temperature. This suggests a stronger effect on BP of indoor compared to outdoor temperature. Improving insulation and household heating may help lower BP and prevent excess winter mortality. KEYWORDS: Cardiovascular diseases, Epidemiology, Socio-economic factors, Temperature

Health-Related Outcomes 3-15 Years Following Ankle Sprain Injury in Youth Sport: What Does the Future Hold?

This study examined the association between youth sport-related ankle sprain injury and health-related outcomes, 3-15 years postinjury. A historical cohort study in which uninjured controls were cluster-matched with injured cases. The primary outcome was self-reported Foot and Ankle Outcome Score (FAOS). Secondary outcomes included measures of adiposity, validated questionnaires for physical activity, athletic identity, fear of pain, and tests of strength, balance, and function. We recruited 86 participants (median age of 23 years; 77% female); 50 with a time-loss ankle sprain, median of 8 years postinjury, and 36 uninjured controls cluster-matched by sex and sport. Based on mixed effects multivariable regression models, previously injured participants demonstrated poorer outcomes than controls on all 5 FAOS subscales regardless of sex and time since injury, with the largest differences observed in symptoms (-20.9, 99% CI: -29.5 to -12.3) and ankle-related quality of life (-25.3, 99% CI: -34.7 to -15.9) subscales. Injured participants also had poorer unipedal dynamic balance (-1.9, 99% CI: 3.5 to -0.2) and greater fear of pain (7.2, 99% CI: 0.9-13.4) compared with controls. No statistically significant differences were found for other secondary outcomes. At 3-15 years following time-loss ankle sprain injury in youth sport, previously injured participants had more pain and symptoms, poorer self-reported function, ankle-related quality of life, reduced sport participation, balance, and greater fear of pain than controls. This underlines the need to promote the primary prevention of ankle sprains and secondary prevention of potential health consequences, including posttraumatic osteoarthritis. Level III, historical cohort study.

Neighborhood racial/ethnic segregation and cognitive decline in older adults

Social determinants of health, including neighborhood factors, play a key role in the health of diverse older adults. However, few longitudinal studies have examined the role of neighborhood racial/ethnic segregation on cognitive decline in diverse samples. We examined older non-Hispanic White (NHW), Black, and Latino participants evaluated at an Alzheimer's Disease Research Center. Neighborhood racial/ethnic segregation was measured using the Getis-Ord Gi* statistic, a spatial measure of clustering that was created for Latino and Black clustering separately. Cognitive outcomes included episodic memory, semantic memory, and executive function. We used mixed effects multivariable regression models to evaluate associations between segregation and cognitive function and decline. We had 452 individuals: 46% NHW, 26% Black, and 21% Latino in 309 census tracts with an average of 5.2 years of follow-up data (range 0.6–15.0). In analyses that adjusted for a variety of covariates (including neighborhood SES), individuals in neighborhoods with a higher clustering of Latino residents (higher Gi* statistic) had slower declines over time on semantic memory and those in neighborhoods with a higher clustering of Black residents had slower declines over time on episodic memory. In race/ethnicity-stratified adjusted analyses: for Black participants, the association between clustering and cognition was present for episodic memory and executive function, showing lower baseline scores in highly clustered Black and Latino neighborhoods, respectively. There was no association with cognitive change. Among Latino participants, highly clustered Latino neighborhoods were associated with lower baseline scores in semantic memory, but slower declines in episodic memory; Latinos living in neighborhoods with a greater clustering of Black residents also had slower declines in episodic memory. Among NHWs, residing in neighborhoods with a higher clustering of Latino residents was associated with slower declines over time on semantic memory. Segregated neighborhoods may be differentially associated with cognitive outcomes depending on individual race/ethnicity.

Effect of Neighborhood and Individual-Level Socioeconomic Factors on Colorectal Cancer Screening Adherence.

Despite the effectiveness of screenings in reducing colorectal cancer (CRC) mortality, ~25% of US adults do not adhere to screening guidelines. Prior studies associate socioeconomic status (SES) with low screening adherence and suggest that neighborhood deprivation can influence CRC outcomes. We comprehensively investigated the effect of neighborhood SES circumstances (nSES), individual SES, and race/ethnicity on adherence to CRC screening in a multiethnic cross-sectional study. Participant surveys assessing 32 individual-level socioeconomic and healthcare access measures were administered from 2017 to 2018. Participant data were joined with nine nSES measures from the US Census at the census tract level. Univariate, LASSO, and multivariable mixed-effect logistic regression models were used for variable reduction and evaluation of associations. The total study population included 526 participants aged 50–85; 29% of participants were non-adherent. In the final multivariable model, age (p = 0.02) and Non-Hispanic Black race (p = 0.02) were associated with higher odds of adherence. Factors associated with lower adherence were home rental (vs. ownership) (p = 0.003), perception of low healthcare quality (p = 0.006), no routine checkup within two years (p = 0.002), perceived discrimination (p = 0.02), and nSES deprivation (p = 0.02). After comprehensive variable methods were applied, socioeconomic indicators at the neighborhood and individual level were found to contribute to low CRC screening adherence.

Semen quality and windows of susceptibility: A case study during COVID-19 outbreak in China

BackgroundTo evaluate the impact of air pollution exposure on semen quality parameters during COVID-19 outbreak in China, and to identify potential windows of susceptibility for semen quality. MethodsA retrospective observational study was carried out on 1991 semen samples collected between November 23, 2019 and July 23, 2020 (a period covering COVID-19 lock-down in China) from 781 sperm donor candidates at University-affiliated Sichuan Provincial Human Sperm Bank. Multivariate mixed-effects regression models were constructed to investigate the relationship between pollution exposure, windows of susceptibility, and semen quality, while controlling for biographic and meteorologic confounders. Result(s)The results indicated multiple windows of susceptibility for semen quality, especially sperm motility, due to ambient pollution exposure. Exposure to particulate matters (PM2.5 and PM10), O3 and NO2 during late stages of spermatogenesis appeared to have weak but positive association with semen quality. Exposure to CO late in sperm development appeared to have inverse relationship with sperm movement parameters. Exposure to SO2 appeared to influence semen quality throughout spermatogenesis. Conclusion(s)Potential windows of susceptibility for semen quality varied depending on air pollutants. Sperm motility was sensitive to pollution exposure. Findings from current study further elucidate the importance of sensitive periods during spermatogenesis and provide new evidence for the determinants of male fertility.

Apathy and Anxiety in De Novo Parkinson's Disease Predict the Severity of Motor Complications.

Neuropsychiatric and affective symptoms are prevalent in prodromal and clinical Parkinson's disease (PD). Some evidence suggests that they may also signify risk for motor complications (motor fluctuations and dyskinesias) of dopamine replacement therapy (DRT). To determine whether neuropsychiatric symptoms present in de novo PD (ie, before DRT initiation) predict the severity of eventual motor complications of DRT. We used clinical, demographic, neurobehavioral, and neuroimaging data from the Parkinson's Progression Markers Initiative (PPMI), a multicenter observational PD study. Participants were unmedicated at enrollment and 361 initiated DRT during PPMI follow-up. We used Cox proportional hazard and multivariate ordinal mixed-effects regression models to evaluate the relationship between baseline neuropsychiatric symptoms and motor complications as measured by the Movement Disorders Society-revised Unified Parkinson's Disease Rating Scale (MDS-UPDRS). The cumulative incidences of dyskinesias and motor fluctuations during follow-up (6.0 ± 1.5 years) were 34.3% and 59.9%, respectively. Both apathy and high trait-anxiety (top quartile) conveyed over two-fold increases in hazard for dyskinesia onset and for adverse impact on activities of daily living caused by both dyskinesias and motor fluctuations. The longitudinal severity of motor fluctuations and dyskinesias was significantly predicted by baseline trait-anxiety and apathy, but not depression. Models were adjusted for dimensionally related symptoms (eg autonomic dysfunction) and potential confounding variables (eg DRT dose). Apathy and anxiety levels in de novo PD may be neuropsychiatric biomarkers of vulnerability to earlier and more disabling motor complications of DRT.