Cystatin C- and Creatinine-based Estimated GFR Differences: Prevalence and Predictors in the UK Biobank.

Rationale & Objective: Large differences between estimated glomerular filtration rate (eGFR) based on cystatin C (eGFRcys) and creatinine (eGFRcr) occur commonly. A comprehensive evaluation of factors that contribute to these differences is needed to guide the interpretation of discrepant eGFR values. Study Design: Cohort study. Setting & Participants: 468,969 participants in the UK Biobank. Exposures: Candidate sociodemographic, lifestyle factors, comorbidities, medication usage, and physical and laboratory predictors. Outcomes: eGFRdiff, defined as eGFRcys minus eGFRcr, categorized into 3 levels: lower eGFRcys (eGFRdiff, less than -15 mL/min/1.73 m2), concordant eGFRcys and eGFRcr (eGFRdiff, -15 to < 15 mL/min/1.73 m2), and lower eGFRcr (eGFRdiff, ≥15 mL/min/1.73 m2). Analytical Approach: Multinomial logistic regression models were constructed to identify predictors of lower eGFRcys or lower eGFRcr. We developed 2 prediction models comprising 375,175 participants: (1) a clinical model using clinically available variables and (2) an enriched model additionally including lifestyle variables. The models were internally validated in an additional 93,794 participants. Results: Mean ± standard deviation of eGFRcys was 88 ± 16 mL/min/1.73 m2, and eGFRcr was 95 ± 13 mL/min/1.73 m2; 25% and 5% of participants were in the lower eGFRcys and lower eGFRcr groups, respectively. In the multivariable enriched model, strong predictors of lower eGFRcys were older age, male sex, South Asian ethnicity, current smoker (vs never smoker), history of thyroid dysfunction, chronic inflammatory disease, steroid use, higher waist circumference and body fat, and urinary albumin-creatinine ratio >300 mg/g. Odds ratio estimates for these predictors were largely inverse of those in the lower eGFRcr group. The model's area under the curve was 0.75 in the validation set, with good calibration (1.00). Limitations: Limited generalizability. Conclusions: This study highlights the multitude of demographic, lifestyle, and health characteristics that are associated with large eGFRdiff. The clinical model may identify individuals who are likely to have discrepant eGFR values and thus should be prioritized for cystatin C testing.

Estimated glomerular filtration rate (eGFR) based on cystatin C and creatinine may differ substantially within an individual. Although most clinicians are aware that creatinine is influenced by muscle mass, there are additional numerous lifestyle and health characteristics that may affect serum concentrations of either biomarker. Our analyses of 468,969 individuals in the UK Biobank identified independent predictors of large differences between eGFR based on cystatin C and eGFR based on creatinine, which may inform the interpretation of discrepant eGFR values within an individual. We developed models that may be implemented at a population level to help health systems identify individuals who are likely to have large differences between eGFR based on cystatin C and eGFR based on creatinine and thus should be prioritized for cystatin C testing.

Dual sensitivity-enhanced microring resonance-based integrated microfluidic biosensor for Aß42 detection.

Sensitive, accurate, and straightforward biosensors are pivotal in the battle against Alzheimer's disease, particularly in light of the escalating patient population. These biosensors enable early adjunctive diagnosis, thereby facilitating prompt intervention, alleviating socioeconomic burdens, and preserving individual well-being. In this study, we introduce the development of a highly sensitive add-drop dual-microring resonant microfluidic sensing chip boasting a sensitivity of 188.11 nm/RIU, marking a significant 20.7% enhancement over single microring systems. Leveraging ultra-thin Parylene C for streamlined antibody immobilization and non-destructive removal, this platform facilitates the precise quantification of the Alzheimer's disease biomarker Aß42. Employing an immune sensing strategy that amplifies and captures antigen signals using Au-labeled antibodies, we achieve an exceptional limit of detection of 9.02 pg/mL. The designed microring-based microfluidic biosensor chip exhibits outstanding specificity and sensitivity for Aß42 in serum samples, offering a promising avenue for the early adjunctive diagnosis of Alzheimer's disease.

Ultrasensitive Silicon Photonic Refractive Index Sensor Based on Hybrid Double Slot Subwavelength Grating Microring Resonator.

Silicon photonic-based refractive index sensors are of great value in the detection of gases, biological and chemical substances. Among them, microring resonators are the most promising due to their compact size and narrow Lorentzian-shaped spectrum. The electric field in a subwavelength grating waveguide (SWG) is essentially confined in the low-refractive index dielectric, favoring enhanced analyte-photon interactions, which represents higher sensitivity. However, it is very challenging to further significantly improve the sensitivity of SWG ring resonator refractive index sensors. Here, a hybrid waveguide blocks double slot subwavelength grating microring resonator (HDSSWG-MRR) refractive index sensor operating in a water refractive index environment is proposed. By designing a new waveguide structure, a sensitivity of up to 1005 nm/RIU has been achieved, which is 182 nm/RIU higher than the currently highest sensitivity silicon photonic micro ring refractive index sensor. Meanwhile, utilizing a unique waveguide structure, a Q of 22,429 was achieved and a low limit of detection of 6.86 × 10-5 RIU was calculated.

Associations of Lower Extremity Muscle Strength, Area, and Specific Force With Lower Urinary Tract Symptoms in Older Men: The Baltimore Longitudinal Study of Aging.

BACKGROUND: Lower urinary tract symptoms (LUTS) in older men are associated with an increased risk of mobility limitations. Lower extremity muscle quality may represent a novel shared mechanism of both LUTS and mobility limitations. METHODS: We evaluated associations of thigh skeletal muscle measures (strength, area, and specific force) with total LUTS severity (American Urologic Association Symptom Index; AUASI) and voiding and storage subscores among 352 men aged ≥60 years enrolled in the Baltimore Longitudinal Study of Aging. Thigh muscle strength (Nm) was defined as maximum concentric 30°/s knee extensor torque, area (cm2), and specific force (Nm/cm2) defined as strength/area. Associations with AUASI score were estimated using multivariable linear regression and linear mixed models. RESULTS: Mean thigh muscle strength at baseline was 139.7Nm. In cross-sectional multivariable models, each 39Nm increment in thigh muscle strength and 0.28Nm/cm2 increment in specific force was associated with -1.17 point (95% CI: -1.93 to -.41) and -0.95 point (95% CI: -1.63 to -0.27) lower AUASI score, respectively. Similar associations were observed for voiding and storage subscores, although somewhat attenuated. In longitudinal analyses, baseline muscle measures were not associated with annual change in AUASI, and current changes in muscle measures and AUASI were unrelated. CONCLUSIONS: Cross-sectionally, higher thigh muscle strength and specific force were associated with decreased LUTS severity in older men. However, we did not observe concurrent worsening LUTS severity with declining thigh muscle strength, area, or specific force in longitudinal analyses.

Frequency of Screening for Colorectal Cancer by Predicted Life Expectancy Among Adults 76-85 Years.

This study assesses whether colorectal cancer screening varied by predicted life expectancy in a national sample of Veterans Affairs patients aged 76 to 85 years.

Skeletal Muscle Health, Physical Performance, and Lower Urinary Tract Symptoms in Older Adults: the Study of Muscle, Mobility and Aging (SOMMA).

BACKGROUND: Lower urinary tract symptoms (LUTS) and mobility limitations are bidirectionally associated among older adults, but the role of skeletal muscle remains unknown. We evaluated cross-sectional associations of muscle health and physical performance with LUTS. METHODS: We used data from 377 women and 264 men age>70 years in the Study of Muscle, Mobility and Aging (SOMMA). LUTS and urinary bother were assessed using the LURN Symptom Index-10 (SI-10;higher=worse symptoms). Muscle mass and volume were assessed using D3-creatine dilution (D3Cr) and magnetic resonance imaging. Grip strength and peak leg power assessed upper/lower extremity physical performance. 400m walk, Short Physical Performance Battery (SPPB), and Four Square Step Test (FSST) assessed global physical performance. Mobility Assessment Tool-short form (MAT-sf) assessed self-reported mobility. We calculated Spearman correlation coefficients adjusted for age, BMI, multimorbidity, and polypharmacy, chi-square tests, and Fisher's Z-test to compare correlations. RESULTS: Among women, LURN SI-10 total scores were inversely correlated with FSST (rs=0.11,P=0.045), grip strength (rs=-0.15,P=0.006), and MAT-sf (rs=-0.18,P=0.001), but not other muscle and physical performance measures in multivariable models. LURN SI-10 was not associated with any of these measures among men. 44% of women in the lowest tertile of 400m walk speed versus 24% in the highest tertile reported they were at least "somewhat bothered" by urinary symptoms (P<0.001) whereas differences among men were not significant. CONCLUSIONS: Balance and grip strength were associated with LUTS severity in older women but not men. Associations with other muscle and physical performance measures varied by LUTS subtype but remained strongest among women.

Differential Associations of Cystatin C Versus Creatinine-Based Kidney Function With Risks of Cardiovascular Event and Mortality Among South Asian Individuals in the UK Biobank.

Background South Asian individuals have increased cardiovascular disease and mortality risks. Reliance on creatinine- rather than cystatin C-based estimated glomerular filtration rate (eGFRcys) may underestimate the cardiovascular disease risk associated with chronic kidney disease. Methods and Results Among 7738 South Asian UK BioBank participants without prevalent heart failure (HF) or atherosclerotic cardiovascular disease, we investigated associations of 4 eGFRcys and creatinine-based estimated glomerular filtration rate categories (<45, 45-59, 60-89, and ≥90 mL/min per 1.73 m2) with risks of all-cause mortality, incident HF, and incident atherosclerotic cardiovascular disease. The mean age was 53±8 years; 4085 (53%) were women. Compared with creatinine, cystatin C identified triple the number of participants with estimated glomerular filtration <45 (n=35 versus n=113) and 6 times the number with estimated glomerular filtration 45 to 59 (n=80 versus n=481). After multivariable adjustment, the eGFRcys 45 to 59 category was associated with higher risks of mortality (hazard ratio [HR], 2.38 [95% CI, 1.55-3.65]) and incident HF (sub-HR [sHR], 1.87 [95% CI, 1.09-3.22]) versus the eGFRcys ≥90 category; the creatinine-based estimated glomerular filtration rate 45 to 59 category had no significant associations with outcomes. Of the 7623 participants with creatinine-based estimated glomerular filtration rate ≥60, 498 (6.5%) were reclassified into eGFRcys <60 categories. Participants who were reclassified as having eGFRcys <45 had higher risks of mortality (HR, 4.88 [95% CI, 2.56-9.31]), incident HF (sHR, 4.96 [95% CI, 2.21-11.16]), and incident atherosclerotic cardiovascular disease (sHR, 2.29 [95% CI, 1.14-4.61]) versus those with eGFRcys ≥90; those reclassified as having eGFRcys 45 to 59 had double the mortality risk (HR, 2.25 [95% CI, 1.45-3.51]). Conclusions Among South Asian individuals, cystatin C identified a high-risk chronic kidney disease population that was not detected by creatinine and enhanced estimated glomerular filtration rate-based risk stratification for mortality, incident HF, and incident atherosclerotic cardiovascular disease.

Trends in Healthcare Expenditures among Adults in the United States by Cancer Diagnosis Status, 2008-2016: A Cross-Sectional Study.

BACKGROUND: This study aims to assess trends in direct medical expenditures and indirect costs between adults with and without a prior cancer diagnosis from 2008 to 2016. METHODS: Nine years of data (2008-2016) from the Medical Expenditure Panel Survey (weighted N = 236,811,875) were used. The outcomes included medical expenditures (total expenditure, inpatient, office-based, medications, outpatient, dental, emergency room visits, home health, other) and health-related missed workdays. The predictor was prior cancer diagnosis. Covariates included demographic characteristics, comorbidities, and calendar year at time of survey completion. Two-part statistical modeling with a combination of binomial and positive distributions was used to estimate medical expenditures and missed workdays. Data were clustered into five timepoints: 2008 to 2009, 2010 to 2011, 2012 to 2013, 2014 to 2015, and 2016. RESULTS: Eleven percent of the sample (n = 25,005,230) had a prior cancer diagnosis. Compared with those without a prior cancer diagnosis, those with a prior cancer diagnosis had higher mean incremental total expenditures across all years. Between 2008 and 2016, the adjusted annual incremental total expenditures were $3,522 [95% confidence interval (CI), $3,072-$3,972]; office-based visits ($1,085; 95% CI, $990-$1180); inpatient hospitalizations ($810; 95% CI, $627-$992); outpatient appointments ($517; 95% CI, $434-$600); and medications ($409; 95% CI, $295-$523); and health-related missed workdays (0.75; 95% CI, 0.45-1.04) compared with adults without a prior cancer diagnosis. CONCLUSIONS: Adults with a prior cancer diagnosis had significantly increased healthcare expenditures and health-related missed workdays compared with those with no cancer diagnosis. IMPACT: Our findings highlight the need for increasing strategies to remedy the impact of increasing direct and indirect costs associated with cancer survivorship as the population grows and ages.

The relationship between adverse childhood experiences, the frequency and acuity of emergency department utilization and primary care engagement.

INTRODUCTION: A history of adverse child experiences (ACEs) is associated with increased high-risk adult behaviors, morbidity, mortality, and use of the emergency department. This study was designed to understand the relationship between ACEs and the characteristics of emergency department use and primary care engagement. METHODS: An in-person survey was conducted at an academic emergency department (ED) assessing ACE score, emergency department utilization and acuity, and primary care engagement. RESULTS: The prevalence of ACEs was 71.1% with 1+ ACE and 32.5% with 4+ ACE. ACE scores of four or more were associated with three or more ED visits in the past year compared those with an ACE score of zero (OR 3.22; p < 0.05) and when adjusted for sociodemographic factors (OR 3.22; p < 0.10). Higher ACE scores were associated with lower acuity presentations as indicated by the Emergency Severity Index before (ACE score 1 OR 3.91 p < 0.05; ACE score 2-3 OR 2.35 p < 0.05; ACE score 4+ OR 3.95 p < 0.05) and after adjustment (ACE score 1 OR 3.80 p < 0.10; ACE 2-3 OR 3.50 p < 0.10; ACE 4+ OR 4.36 p < 0.05). There was no association between ACE score and having a primary care provider (PCP), frequency of PCP visits, or PCP rating. CONCLUSION: Higher ACE scores were associated with higher emergency department utilization and lower acuity presentations but not associated with levels of primary care engagement. Additional investigations are needed to adequately characterize the discrete causal mechanisms behind these current findings.

Lower urinary tract symptoms and incident functional limitations among older community-dwelling men.

BACKGROUND: Lower urinary tract symptoms (LUTS) are associated with frailty phenotype, a risk factor for functional decline. Our objective was to determine the association between baseline LUTS and 2-year risk of new functional limitation among older men. METHODS: We analyzed data from the Osteoporotic Fractures in Men (MrOS) study with baseline at Year 7 and follow-up through Year 9. Participants included 2716 community-dwelling men age ≥ 71 years without any baseline self-reported functional limitation. LUTS severity (American Urologic Association Symptom Index) was classified as none/mild (score 0-7), moderate (8-19), and severe (20-35). At baseline and follow-up, men reported their ability to complete several mobility, activities of daily living (ADLs), and cognition-dependent tasks. Risk was estimated for 3 incident functional limitation outcomes: (1) mobility (any difficulty walking 2-3 blocks or climbing 10 steps), (2) ADL (any difficulty bathing, showering, or transferring), and (3) cognition-dependent (any difficulty managing money or medications). We used Poisson regression with a robust variance estimator to model adjusted risk ratios (ARR) and 95% CIs controlling for age, site, and comorbidities; other demographic/lifestyle factors did not meet criteria for inclusion. RESULTS: Overall, the 2-year risk was 15% for mobility, 10% for ADLs, and 4% for cognition-dependent task limitations. Compared to none/mild LUTS, risk of incident mobility limitations was increased for moderate (ARR = 1.35, 95% CI: 1.12, 1.63) and severe LUTS (ARR = 1.98, 95% CI: 1.48, 2.64). Men were also at higher risk for incident ADL limitations if they reported moderate (ARR = 1.32, 95% CI: 1.05, 1.67) and severe LUTS (ARR = 1.62, 95% CI: 1.07,2.43). Results were somewhat attenuated after adjusting for the frailty phenotype but remained statistically significant. LUTS were not associated with incident cognition-dependent task limitations. CONCLUSIONS: LUTS severity is associated with incident mobility and ADL limitations among older men. Increased clinical attention to risk of functional limitations among older men with LUTS is likely warranted.

The Relationship Between Patient Satisfaction and Healthcare Expenditures in Adults with Spine Related Disorders: An Analysis of the 2008 to 2015 Medical Expenditures Panel Survey (MEPS).

STUDY DESIGN: Cross-sectional study. OBJECTIVE: The aim of this study was to investigate the relationship between patient satisfaction (PS) and healthcare expenditures (HCE) in adults with spine related disorders (SRDs). SUMMARY OF BACKGROUND DATA: SRDs are widespread and pose a high cost to society. PS and HCE have yet to be studied in this population. METHODS: Fifteen thousand eight hundred fifty adults with SRDs from the Medical Expenditures Panel Survey (MEPS) (2008-2015) were analyzed. The MEPS medical conditions files were used to identify SRDs based on International Classification of Diseases-9 codes. Frequencies and percentages of sample demographics were calculated. HCE was measured as total direct payments for care provided during the survey year. A composite PS score was constructed using a 0 to 10 rating of their healthcare providers combined with the frequency in which patients felt they were listened to, were given understandable explanations, were respected, and were given enough time. Mean unadjusted HCE were calculated for each year and by quartile of PS. A two-part model consisting of a probit model and subsequent generalized linear model with gamma distribution was performed, adjusting for relevant covariates. Margins command was used to calculate incremental estimates of HCE. RESULTS: Mean unadjusted HCE increased annually from $7057 (95% confidence interval [CI], $6516, $7597) in 2008 to $9820 (95% CI, $8811, $10,830) in 2015 for adults with SRDs. Adjusting for predisposing factors, individuals in second, third, and fourth quartiles of PS were significantly different from the first quartile. Adjusting for predisposing and enabling factors, only fourth quartile was significantly different from first quartile. After adjusting for predisposing, enabling and need factors, second, third, and fourth quartiles were no longer significantly different from the first quartile. CONCLUSION: Expenditures have increased over time in adults with SRDs. PS is significantly associated with expenditures after controlling for predisposing and enabling factors, but not significant after controlling for need factors. Need factors appear to explain the relationship between lower levels of PS and higher HCE in adults with SRDs.Level of Evidence: 2.

Trends in Obesity and Medical Expenditure among Women with Diabetes, 2008-2016: Differences by Race/Ethnicity.

Objectives: Diabetes results in $327 billion in medical expenditures annually, while obesity, a risk factor for type 2 diabetes, leads to more than $147 billion in expenditure annually. The aims of this study were: 1) to evaluate racial/ethnic trends in obesity and medical expenditures; and 2) to assess incremental medical expenditures among a nationally representative sample of women with diabetes. Methods: Nine years of data (2008-2016) from the Medical Expenditure Panel Survey Full Year Consolidated File (unweighted = 11,755; weighted = 10,685,090) were used. The outcome variable was medical expenditure. The primary independent variable was race/ethnicity defined as non-Hispanic Black (NHB), Hispanic, or non-Hispanic White (NHW). Covariates included age, education, marital status, income, insurance, employment, region, comorbidity, and year. Cochran-Armitage tests determined statistical significance of trends in obesity and mean expenditure. Two-part modeling using Probit and gamma distribution was used to assess incremental medical expenditure. Data were clustered to 2008-2010, 2011-2013, 2014-2016. Results: Trends in medical expenditures differed significantly between NHB and NHW women between 2008-2016 (P<.001). Hispanic women paid $1,291 less compared with NHW women, after adjusting for relevant covariates. There were no significant differences in obesity trends from 2008-2016 between NHB (P=.989) or Hispanic women with diabetes (P=.938) compared with NHW women with diabetes. Conclusions: These findings suggest the need to further understand the factors associated with differences in trends for medical expenditures between NHB and NHW women with diabetes and incremental medical expenditures in Hispanic women with diabetes compared with NHW women with diabetes.