Adjustment For Race Research Articles

Early Hyperchloremia is Independently Associated with Death or Disability in Patients with Intracerebral Hemorrhage.

On the basis of increased mortality associated with hyperchloremia among critically ill patients, we investigated the effect of occurrence of early hyperchloremia on death or disability at 90days in patients with intracerebral hemorrhage (ICH). We analyzed the data from Antihypertensive Treatment of Cerebral Hemorrhage 2 trial, which recruited patients with spontaneous ICH within 4.5h of symptom onset. Patients with increased serum chloride levels (110mmol/L or greater) at either baseline or 24, 48, or 72h after randomization were identified. We further graded hyperchloremia into one occurrence or two or more occurrences within the first 72h. Two logistic regression analyses were performed to determine the effects of hyperchloremia on (1) death within 90days and (2) death or disability at 90days after adjustment for potential confounders. Among the total of 1,000 patients analyzed, hyperchloremia within 72h was seen in 114 patients with one occurrence and in 154 patients with two or more occurrences. Patients with one occurrence of hyperchloremia (odds ratio [OR] 2.5, 95% confidence interval [CI] 1.1-5.5) and those with two or more occurrences (OR 2.6, 95% CI 1.3-5.0) had significantly higher odds of death within 90days after adjustment for age, race and ethnicity, National Institutes of Health Stroke Scale score strata, hematoma volume, presence or absence of intraventricular hemorrhage, cigarette smoking, previous stroke, and maximum hourly dose of nicardipine. Patients with two or more occurrences of hyperchloremia (OR 3.4, 95% CI 2.1-5.6) had significantly higher odds of death or disability at 90days compared with patients without hyperchloremia after adjustment for the abovementioned potential confounders. The independent association between hyperchloremia and death or disability at 90days suggests that avoidance of hyperchloremia may reduce the observed death or disability in patients with ICH. ClinicalTrials.gov: NCT01176565.

MO189: The Clinical Relevance of Measured GFR in Patients with Solitary Kidney after Radical Nephrectomy: The Estimation is not Enough

Abstract BACKGROUND AND AIMS Chronic kidney disease (CKD) represents the major postoperative long-term complication in patients who undergo radical nephrectomy (RN) for the presence of a renal mass. The development of a mild to severe grade of CKD can dramatically change the lifespan of this category of patients who can experience not only an augmented rate of cardiovascular diseases but also cancer recurrence and oncological therapies based on nephrotoxic agents. Therefore, preventive strategies for reducing the risk of CKD are strictly required. Among them, one of the most important tools is represented by the correct assessment of renal function. In fact, especially in the oncological scenario, there are various causes of factitious elevation or reduction of serum creatinine due to the frequent modification of body composition, measurement interference with the assay and altered tubular secretion. Nevertheless, the use of estimated GFR based on serum creatinine levels remains nowadays the most common method to define renal function in RN patients, both in the oncological and in the urological universe. The aim of this study was to determine the extent of the error of eGFR compared to the mGFR in a consecutive prospective cohort of RN patients who remained with a solitary kidney. METHOD A total consecutive cohort of 115 RN patients enrolled in a single tertiary institution between 2018 and 2021 was collected in order to compare the most common eGFR formulas used by physicians (Cockroft-Gault, MDRD, CKD-EPI based on serum creatinine and/or serum cystatin and the new eGFR equation based on creatinine and cystatin without race adjustment) with the most widespread mGFR method (Iohexol Plasma Clearance). The mGFR technique together with the serum creatinine/cystatin measurement was performed after 12 months from the operation in order to consider a steady state for the chronic renal function. All clinical variables were reported for each pt. CKD classification was defined accorded to K-DIGO 2012 guidelines. The agreement between eGFR and mGFR was evaluated using bias (as median of difference), precision (as interquartile range of difference-IQR), accuracy (as P30) and total deviation index (TDI). The differences between cohorts were evaluated with Fisher's exact test and Chi-squared test for ordinal characteristics and Wilcoxon rank sum test for continuous variables. Data analysis was performed using programming language R and Python. RESULTS Clinical data were as follows: median age 66 (IQR 27.66), M/F ratio 4.48, median BMI 24.6 (IQR: 0.003, 24.6). 51.3% of patients had hypertension, 10.4% were diabetics. The median creatinine level in the overall population was 1.49 mg/dL (IQR: 0.8, 1.49), the median cystatin level was 1.33 mg/dL (IQR: 0.55, 1.33). Based on iohexol plasma clearance, 0.87% patients were classified in CKD in stage 1, 17.39% in stage 2, 39.13% in stage 3a, 25.22% in stage 3b, 16.52% in stage 4 and 0.87% in stage 5. Surprisingly, a non-negligible error was reported in each CKD class with a huge discrepancy between the eGFR formulas and the gold standard method (Figures 1 and 2), suggesting the pivotal role of mGFR in the clinical decision-making algorithm for RN patients. CONCLUSION In daily clinical practice, an appropriate nephrological tailored follow-up based on mGFR is mandatory for RN patients with a solitary kidney. In fact, a simple renal evaluation using eGFR can only increase the risk of clinical errors, sometimes underestimating and sometimes overestimating the real renal function with important medical consequences.

MO155: The Importance of Measured GFR in Clinical Practice: An Old Knowledge for Nephrologists, a New Challenge for Oncologists and Surgeons

Abstract BACKGROUND AND AIMS In daily clinical practice, an accurate assessment of renal function is of paramount importance in several categories of patients where the adequate medical or surgical treatment depends on the values of glomerular filtration rate (GFR). In particular, both oncological and urological patients require a personalized medical approach able to avoid misleading errors which could dramatically shorten their lifespan. Unfortunately, the most used method to measure GFR in these groups of patients is represented by the estimated glomerular filtration rate (eGFR), which harbours a significant error in comparison to gold standards methods (mGFR). The aim of this study was to determine the extent of the error of eGFR compared to the mGFR in a consecutive prospective cohort of oncological patients affected by urological malignancies. METHOD A total consecutive cohort of 352 patients enrolled in a single tertiary institution between 2018 and 2021 was collected in order to compare the most common eGFR formulas used by physicians (Cockroft-Gault, MDRD, CKD-EPI based on serum creatinine and/or serum cystatin and the new eGFR equation based on creatinine and cystatin without race adjustment) with the most widespread mGFR method (Iohexol Plasma Clearance). The study cohort was composed by 188 oncological patients affected by different types of urological malignancies (cases) before surgical operation and/or medical treatment and 164 non-oncological patients (controls) matched for baseline clinical variables and GFR. The agreement between eGFR and mGFR was evaluated using bias (as median of difference), precision (as interquartile range of difference—IQR) accuracy (as P30) and total deviation index (TDI). The differences between cohorts were evaluated with Fisher's exact test and Chi-squared test for ordinal characteristics and Wilcoxon rank sum test for continuous variables. Data analysis was performed using programming language R and Python. RESULTS Clinical data were as follows: median age 68 (IQR: 20.68), M/F ratio 3.19, median BMI 24.9 (IQR: 0.003, 24.938). A total of 61.2% of patients had hypertension, and 14.3% were diabetics. The median creatinine value in the overall population was 1.48 mg/dL (IQR: 0.45, 1.48); the median cystatin value was 1.26 mg/dL (IQR: 0.42, 1.26). Based on iohexol plasma clearance, 3.13% of patients were classified in CKD stage 1, 23.30% in stage 2, 29.55% in stage 3a, 27.27% in stage 3b, 14.77% in stage 4 and 1.99% in stage 5. The two matched cohorts of oncological and non-oncological patients displayed no statistical differences in terms of clinical variables and agreement parameters (TDI, CCC and P30). Surprisingly, both groups harboured a non-negligible error in each CKD class with a huge discrepancy between the eGFR formulas and the gold standard method (Figures 1 and 2), suggesting the great relevance of mGFR in the clinical decision-making algorithm, both in oncological and in non-oncological patients. CONCLUSION We observed that the error in the classification of CKD stages using eGFR formulas was very common, both in oncological and in nephrological patients, with a poor agreement with mGFR in all CKD classes. Therefore, mGFR remains a crucial tool for a correct clinical decision in all onconephrological patients who require surgery or potential nephrotoxic agents.

MO265: Patients with Alport Syndrome from the Radar Registry: A Natural History Study

Abstract BACKGROUND AND AIMS Alport Syndrome (AS) is the second most common genetic kidney disease and results from mutations in COL4A3, A4 or A5 genes. It is characterized by glomerulonephritis, CKD, hearing loss, and ocular lens defects. Estimated incidence is ∼ 1 in 50 000 live births with prevalence of 1 in 5000–10 000. About 80% patients reach ESKD by age 35 years. The UK Alport Registry, part of the National Registry of Rare Kidney Diseases (RaDaR), performs on-going collection of longitudinal data of AS patients. The aims of this study were to characterize demographic and lab data of AS patients and determine the proportion of AS patients at risk for rapid kidney function decline. METHOD Eligible patients had a clinical, histological or genetic diagnosis of ‘Alport syndrome’ or ‘thin basement membrane nephropathy’ by their physician and provided informed consent. Some data were entered manually, but most routine test results were collected by automatic link between RaDaR and renal IT systems. eGFR was calculated using CKD-EPI Cr equation without race adjustment (2021) or Schwartz equation for subjects ≤16 years of age at time of Cr measurement. For eGFR slope calculations, a minimum of four measurements over at least 2 years were required to be included in this analysis; subjects were censored if they reached ESKD, defined as maintenance dialysis, transplant, or ≥ 2 consecutive eGFR measurements of <15 mL/min/1.73 m2. Data are presented as percentages for categorical variables and mean ± SD for continuous variables. RESULTS Between 4 January 2013 and 29 November 2021, 887 patients were recruited. See Table 1 for summary of data stratified by age groups. Overall, 52% male versus 48% female, and in those with genotyping data, 54% had X-linked AS with a mean age of 25.8 years at diagnosis and a mean age of proteinuria onset of 29.6 years. Clinically meaningful Stage 2 CKD was already present at time of diagnosis (mean eGFR 72.7 mL/min/1.73 m2) in many of those ≥ 18 years of age. A total of 43% of this AS cohort have reached ESKD, at a mean age of 32.8 years. While 37% were on ACEi and 20% on ARB medications, only 4% were on dual RAAS blockade therapy. About 50% had documentation of eGFR loss ≥4 mL/min/1.73 m2 per year, 29% had UPCR > 2 g/g, and 50% of those age ≥ 18 years had reached ESKD. The proportion of patients with ≥1 risk factor for rapid progression of kidney failure (defined as eGFR decline ≥ 4 mL/min/1.73 m2 per year, UPCR > 2 g/g, UACR > 1 g/g or male 18–23 yrs with eGFR < 90 mL/min/1.73 m2 based on ATHENA natural history study) was 41%. CONCLUSION Demographic and genetic characteristics of AS patients in the RaDaR registry are generally comparable with previously reported data. Approximately 50% had eGFR decline ≥ 4 mL/min/1.73 m2 per year and 41% of patients had exhibited ≥ 1 risk factor for future rapid progression of kidney disease. Results should be interpreted with caution, however, in light of the considerable amount of missing data in a number of the analyses. On-going data collection in this open cohort should allow for further insights on the natural history over time as well as identify AS patients for potential enrollment into clinical trials.

Association of County Race and Ethnicity Characteristics With Number of Insurance Carriers and Insurance Network Breadth

While the Affordable Care Act (ACA) set out to eliminate insurer discrimination based on preexisting conditions, the ACA health exchanges allow insurers to select what markets to enter and afford them great freedom on how they design their physician networks. Strategic market participation and physician network design based on population race, ethnicity, and health characteristics may give rise to a present-day form of redlining within health insurance markets-ie, a systematic underprovision of insurance plans and in-network practitioners within areas that are populated with higher proportions of non-Hispanic Black residents. To examine if markets with relatively higher non-Hispanic Black populations have systematically fewer insurers and lower network inclusion of physicians residing within these areas. This cohort study conducted a regression analysis of the US ACA health insurance exchange marketplace across 34 states with federal exchanges and physicians located within the 500 most populous US cities in 2014. County-level data were sourced from individual market and issuer enrollment databases and county health rankings; census tract data came from a national database of physician networks in 2014 marketplace plans, US Census Bureau data, and the Centers for Disease Control and Prevention's PLACES database. Adjustment was made for a rich set of county (or census tract) controls and state fixed effects to capture broad market and/or policy differences across states. Analyses were performed in June 2021. The raw count of insurers within a county and the mean percentage of insurance networks that physicians participate in within each census tract. A total of 2270 counties were examined within our first analyses. In the counties analyzed, a mean (SD) of 23.0% (3.2%) of the population was aged 18 years or younger, and a mean (SD) of 11.0% (15.8%) of the population had non-Hispanic Black race and ethnicity. For the second analysis, 16 006 to 25 096 census tracts were examined (depending on physician specialty). With adjustment for population size, age, and race and ethnicity, a 1-SD increase in the county non-Hispanic Black population was associated with a 14.1% reduction in the number of insurers (mean [SE] marginal effect size, -2.18 [0.13]; P < .001). Accounting for additional county-level risk selection controls and state fixed effects, a 1-SD increase in the non-Hispanic Black population was associated with a 2.3% reduction in available insurers (marginal effect size, -0.36 [0.17]; P = .04). For practitioners network breadth inclusion, a 1-SD increase in the non-Hispanic Black population was associated with a 15.8% (marginal effect size, -0.32 [0.01]; P < .001) to 24.7% (marginal effect size, -0.14 [0.02]; P < .001) reduction in the physicians' network participation depending on their specialty. Adjusting for additional state fixed effects yielded estimates of 6% (marginal effect size, -0.08 [0.01]; P < .001) to 13.5% (marginal effect size, -0.12 [0.02]; P < .001) reductions in practitioner network participation. These findings suggest that strategic decisions by insurers may contribute toward markets with higher racial or ethnic minority populations having systematically fewer participating insurers, as well as a higher prevalence of local physicians not included in coverage networks. These findings call for further examination of potential insurance redlining within the ACA marketplaces.

Obstetric comorbidity index and the odds of general vs. neuraxial anesthesia in women undergoing cesarean delivery: a retrospective cohort study

BackgroundMaternal and fetal concerns have prompted a significant reduction in general anesthesia (GA) use for cesarean delivery (CD). The obstetric comorbidity index (OB-CMI) is a validated, dynamic composite score of comorbidities encountered in an obstetric patient. We sought to estimate the association between OB-CMI and odds of GA vs. neuraxial anesthesia (NA) use for CD. MethodsIn this single-center, retrospective cohort study conducted at a large academic hospital in the United States of America, OB-CMI was calculated on admission and every 12 h for women undergoing CD at ≥23 weeks’ gestation (n=928). The CD urgency, anesthesia type, and most recent OB-CMI were extracted from the medical record. The association between OB-CMI and GA use was estimated by logistic regression, with and without adjustment for CD urgency, parity and race. ResultsEach one-point increase in OB-CMI was associated with a 32% (95% confidence interval [CI] 17% to 48%) increase in the odds of GA use (Model 1, area under the receiver operating characteristic curve [AUC] 0.708, 95% CI 0.610 to 0.805). The AUC improved to 0.876 (95% CI 0.815 to 0.937) with the addition of emergent CD (Model 2, P <0.001 vs. Model 1), but not parity and race (Model 3, AUC 0.880, 95% CI 0.824 to 0.935; P=0.616 vs. Model 2). ConclusionsThe OB-CMI is associated with increased odds of GA vs. NA use for CD, particularly when emergent. Collected in real time, the OB-CMI may enable prophylaxis (e.g. comorbidity modification, earlier epidural catheter placement, elective CD) or preparation for GA use.

Association of Neighborhood-Level Socioeconomic Measures With Cognition and Dementia Risk in Australian Adults

Up to 40% of dementia cases are potentially preventable; therefore, it is important to identify high-risk groups to whom resources could be targeted for maximal impact in preventing late-life dementia. The association of neighborhood-level socioeconomic status (SES) with cognition and dementia risk is not well known, particularly in midlife when late-life dementia may still be preventable through established interventions, such as blood pressure management. To examine whether neighborhood-level SES is associated with differences in cognitive performance and dementia risk scores. This cross-sectional study analyzed data collected between November 17, 2016, and April 14, 2020, from 4656 participants in the longitudinal population-based Healthy Brain Project cohort. This large online cohort comprised community-dwelling individuals geographically dispersed across Australia. Participants were aged 40 to 70 years without dementia or other major neurological conditions. Neighborhood-level SES was computed by matching participants' residential addresses to the Australian Bureau of Statistics Index of Relative Socio-economic Advantage and Disadvantage (IRSAD). Postcodes provided by each participant were used to derive an IRSAD score that ranked participants according to deciles of neighborhood-level SES (range, 1-10, with higher deciles indicating greater socioeconomic advantage); neighborhoods in deciles 1 to 7 were considered to have low or intermediate SES, and neighborhoods in deciles 8 to 10 were considered to have high SES. Dementia risk estimated using the dementia risk score from the Cardiovascular Risk Factors, Aging, and Incidence of Dementia (CAIDE) tool (n = 4656) and cognitive composite scores for memory and attention measured by the Cogstate Brief Battery (n = 2181). Of 4656 participants (mean [SD] age, 56.1 [7.2] years; 3445 women [74.0%]), 2688 individuals (57.7%) lived in areas with high neighborhood-level SES (IRSAD decile ≥8), and 1968 (42.3%) lived in areas with low or intermediate neighborhood-level SES (IRSAD decile <8), with 1263 individuals (27.1%) residing in rural or regional areas. A total of 6 participants (0.1%) identified as African, 121 (2.6%) as Asian, 57 (1.2%) as Indigenous Australian, 24 (0.5%) as Latin American, 9 (0.2%) as Pacific Islander, 3671 (78.8%) as White or European, and 768 (16.5%) indicated other race (not specified). Each decile unit increase in neighborhood-level SES was associated with a lower CAIDE dementia risk score after adjustment for race and rurality (β [SE] = -0.070 [0.019]; P = .004). Each decile unit increase was also associated with better memory (β [SE] = 0.022 [0.006]; P = .006) but not with better attention (β [SE] = 0.009 [0.007]; P = .34), as measured by Cogstate Brief Battery composite z scores after adjustment for age, sex, race, years of education, and rurality. When comparing memory performance between individuals with IRSAD scores higher and lower than decile 8, neighborhood-level SES interacted with age (F1-2171 = 6.33; P = .02) and CAIDE dementia risk scores (F1-2173 = 4.02; P = .08). Differences in memory between neighborhood-level SES categories were larger among participants who were older and had a higher risk of dementia. In this study, higher neighborhood-level SES was associated with better memory and lower dementia risk scores. These results suggest that efforts to lower dementia risk factors in disadvantaged areas are needed to curtail the increasing burden of dementia and that inclusion of individuals living in areas with lower SES in research on dementia is warranted to improve understanding and potential interventions.

Elimination of race in estimates of kidney function to provide unbiased clinical management in Canada

KEY POINTS For many years, the universally used equation for estimating risk of kidney disease (the kidney function estimate, Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] equation), included an adjustment for Black race that led to an upward correction in estimated glomerular

The neutrophil percentage-to-albumin ratio is associated with all-cause mortality in critically ill patients with acute myocardial infarction

AimIn this study, we evaluated the utility of neutrophil percentage-to-albumin ratio (NPAR) in predicting in critically ill patients with acute myocardial infarction (AMI).MethodsThe information of patients were collected from Medical Information Mart for Intensive Care III database. Admission NPAR was calculated as neutrophil percentage divided by serum albumin. The endpoints of this study were 30-day, 90-day, 180-day, and 365-day all-cause mortality. Cox proportional hazards models and subgroup analyses were used to determine the relationship between admission NPAR and these endpoints.Results798 critically ill patients with AMI were enrolled in. After adjustments for age, race and gender, higher admission NPAR was associated with increased risk of 30-day, 90-day, 180-day, and 365-day all-cause mortality in critically ill patients with AMI. And after adjusting for possible confounding variables, two different trends have emerged. Stratified by tertiles, high admission NPAR was independently associated with 180-day and 365-day all-cause mortality in critically ill patients with AMI (tertile 3 vs. tertile 1: adjusted HR, 95% CI 1.71, 1.10–2.66, p < 0.05; 1.66, 1.10–2.51, p < 0.05). In other hand, stratified by quartiles, highest admission NPAR levels were independently associated with 90-day, 180-day and 365-day all-cause mortality (quartile 4 vs. quartile 1: adjusted HR, 95% CI 2.36, 1.32–4.23, p < 0.05; 2.58, 1.49–4.47, p < 0.05; 2.61, 1.56–4.37, p < 0.05). ROC test showed that admission NPAR had a moderate ability to predict all-cause mortality of critically ill patients with AMI. No obvious interaction was found by subgroup analysis in most subgroups.ConclusionsAdmission NPAR was an independent predictor for 180-day and 365-day all-cause mortality in critically ill patients with AMI.

Sedentary Behavior and Atrial Fibrillation in Older Women: The OPACH Study.

BackgroundSedentary behavior is associated with cardiovascular disease, but its association with incident atrial fibrillation is not well studied. Our aim was to measure the association between objectively measured sedentary behavior and incident atrial fibrillation.Methods and ResultsSedentary behavior was measured by a triaxial accelerometer worn on a belt for 1 week. Incident atrial fibrillation was ascertained from Medicare claims. The associations between total sedentary time (or patterns of sedentary behavior) and incident atrial fibrillation were assessed using Cox proportional hazards models adjusted for demographic and clinical covariates. Among 2675 participants (mean age, 78.2 years), there were 268 (10.0%) cases of incident atrial fibrillation at a rate of 31 cases per 1000 person‐years. Greater total sedentary time was associated with a higher risk of incident atrial fibrillation after adjustment for age, race and ethnicity, body mass index, education, smoking history, hypertension, diabetes, stroke, heart disease, and other chronic conditions (quartile 4 versus quartile 1: hazard ratio, 1.20, [95% CI, 0.81–1.78]; P for trend=0.05). After adjusting for physical function and self‐rated health, this was no longer statistically significant. Both longer mean sedentary bout duration and more continuous sedentary periods (versus frequent breaks in sedentary time) were also associated with higher risks of incident atrial fibrillation, but these associations were also attenuated with serial adjustment.ConclusionsTotal sedentary time and prolonged patterns of sedentary accumulation were associated with a higher risk of atrial fibrillation in this prospective study of community‐dwelling older women, but these associations were attenuated by adjustment for physical function and self‐reported health. This suggests that associations between sedentary behavior and atrial fibrillation may be attributable to global measures of overall function and health.

Abstract P008: Atherogenic Cholesterol Across The Lifespan And The Relationship With Midlife Global Cognitive Function: The Bogalusa Heart Study

Background: Higher levels of non-atherogenic cholesterol (HDL) may be protective against vascular risk and inflammation, mechanisms accompanying cognitive impairment in late life. However, the role of atherogenic lipoproteins remains controversial. Evidence suggests that CV risk burden in middle age may be more closely associated with late-life brain health. Therefore, we aimed to explore the relationship between atherogenic cholesterol (non-HDL) in a community-based cohort of midlife adults. Methods: A total of 1,266 adult participants (58.9% Woman, 34.5% African American) from the Bogalusa Heart Study, with cognitive function assessment at age 48 ± 5 years and at least 3 observations of lipoproteins since childhood. A standardized global cognitive score (GCS) was obtained from a battery of tests covering major neuropsychological domains. Non-HDL trajectories were created using latent class trajectory modeling. Linear regression models were used to determine the association between non-HDL trajectories and GCS in midlife. Results: The mean follow-up for non-HDL and other traditional cardiovascular (CV) risk factors was 41.8 ± 3.4 years. Four distinct trajectory classes were identified: class 1 (n= 451 [ 36%]), class 2(n=168 [13.2%]), class 3 (n=530 [41.8%]), and class 4 (n=117 [9 %] (Figure 1). With class 1 as reference, and after adjustment for sex, race, education, cholesterol medication, hypertension, and diabetes comorbidities. Class 2 and class 4 trajectories were associated with lower GCS (Beta= -0.65 [SE 0.28]; p =0.022, and Beta = -0.06 [0.31]; p=0.057, respectively). (Table 1) Conclusions: These findings suggest that highly-increasing atherogenic cholesterol trajectories over time, particularly from early adulthood to middle age, may adversely affect cognitive performance in midlife, independent of other dementia risk factors. This underscores the importance of addressing CV risk factors earlier in the life course, as their cumulative burden could have a detrimental impact on brain health.

Abstract P033: Higher Ambulatory Sbp Is Associated With Increasing Number Of Target Organ Abnormalities In Youth: The Ship Ahoy Study

Hypertension is associated with elevated left ventricular mass index (LVMI), cardiac dysfunction and increased arterial stiffness in adults which predict cardiovascular (CV) events. The extent to which elevated BP in youth is associated with subclinical CV target organ damage (TOD) is not known. We explored the relation between BP level and number of TOD abnormalities (nTOD). We measured clinic and ambulatory BP (ABP), anthropometrics, and nTOD in 244 adolescents (mean 15.5 + 1.8 years, 67% white, 60% male). Subjects were recruited as low-risk (L=98, SBP%&lt;80 th %), mid-risk (Mid=60, SBP% 80-&lt;90 th %); and high-risk (H=86, SBP% &gt;=90 th %) based on mean of 6 aneroid clinic BPs by age-, sex- and height-specific cut-points. 24-hour ABP was measured with an oscillometric device per pediatric guidelines. Four measures of TOD were: LVMI &gt; 38.6 g/m 2.7 ; LV systolic strain (Strain %) &gt; -18; LV diastolic function (E/e’) &gt; 8; pulse wave velocity (PWV) &gt; 5.8 m/sec. ANOVA was used to evaluate differences in CV risk factors and chi square for differences in nTOD across groups. Logistic regression models were used to determine if clinic and/or ABP was an independent predictor of nTOD after adjustment for age, sex, race, and BMI z-score. BP groups did not differ in BMI z-score. Clinic and ABP systolic and diastolic BP increased across BP groups. The distribution of nTOD was shifted towards higher BP group with most nTOD= 0 (47%) in the L and all (100%) nTOD = 4 in the H group (X 2 = 0.08) and became significant when L (clinic SBP&lt;75 th %) was compared to M+H (clinic SBP &gt; 80 th %; X 2 =0.04). Daytime ABP index (subject daytime systolic ABP/95 th % for daytime systolic ABP) and BMI z-score (both p &lt; 0.003) were significantly associated with nTOD in a model containing clinic SBP, age, sex and race (other covariates NS; full model p &lt; 0.0001, R 2 =0.22). We conclude that higher ABP is associated with a greater number of cardiac and vascular abnormalities in youth. ABP should be applied in youth with elevated BP to evaluate need for intensification of therapy to prevent CV TOD.

Annals for Educators - March 2022.

Annals for Educators - March 2022.

The association between fluoride in water and blood pressure in children and adolescents.

The objective of this study was to determine the association between water and plasma fluoride and blood pressure (BP) among children and adolescents. Our study population was individuals of 8-18 years in the 2013-2016 National Health and Nutrition Examination Survey. We performed a multivariable linear and logistic regression analysis to examine the relationship between fluoride and BP. In a linear regression analysis for systolic BP (SBP) (mmHg) adjusting for age, sex, race, and poverty, fluoride in water (mg/L) was significant with a coefficient of -0.44 (p = 0.046) among adolescents (12-18 years). Additional adjustments for race, poverty, serum levels of cotinine, and BMI remained significant. While an inverse relationship was found in children (8-11 years), none were significant. Fluoride in plasma was not significant across all ages. The odds ratio of high BP for an increase in water fluoride also was not significant. Higher concentrations of fluoride in water were associated with low SBP only among adolescents. Fluoride alone cannot be responsible for BP as several biological metabolic processes may influence its physiological effects. Fluoride consumption should be considered in conjunction with these processes. The high fluoride in drinking water was statistically significantly associated with low systolic BP in children and adolescents. The odds ratio of high BP for an increase in fluoride in drinking water was not significant. Our study contributes to the existing literature by providing individualized data and results on an individual level.

Associations of Metabolic and Obstetric Risk Parameters with Timing of Lactogenesis II.

Lactogenesis II is the onset of copious milk production following parturition. Delayed onset of lactogenesis II (DLII) often contributes to poorer lactation performance, which may adversely affect maternal and child health. The present study aims to identify the metabolic and obstetric risk factors for DLII in a secondary analysis of a prospective cohort study following pregnant women through postpartum. We defined the onset of lactogenesis II as delayed if it occurred ≥72 h postpartum. Multiple logistic regression analyses were conducted to evaluate the associations of metabolic and obstetric variables with DLII. Median onset of lactogenesis II was 72.4 h (IQR 60.4–91.6) postpartum, and 55.4% (98 of 177) of women experienced DLII. Time to first breast contact ≥ 2 h postpartum compared to ≤1 h postpartum was associated with DLII (OR 2.71 95% CI 1.12–6.53) with adjustment for age, race, pregravid BMI, primiparity, and mode of delivery, while metabolic variables were not significantly associated with DLII. In this comprehensive examination of potential metabolic and obstetric parameters, earlier timing of putting the infant to the breast remained significantly associated with earlier onset of milk coming in after consideration of the other potential risk factors. Obstetrical practices, including putting the baby to the breast later, may have an important impact on the timing of lactation, and interventions are needed to address this concern.

Deconstructing the Way We Use Pulmonary Function Test Race-Based Adjustments

Race is a social construct. It is used in medical diagnostic algorithms to adjust the readout for spirometry and other diagnostic tests. The authors review historic evidence about the origins of race adjustment in spirometry, and recent attention to the lack of scientific evidence for their continued use. Existing reference values imply that White patients have better lung function than non-White patients. They perpetuate the historical assumptions that human biological functions of the lung should be calculated differently on the basis of racial-skin color without considering the difficulty of using self-identified race. More importantly, they fail to consider the important effects of environmental exposures, socioeconomic differences, health care access, and prenatal factors on lung function. In addition, the use of "race adjustment" implies a White standard to which other non-White values need "adjustment." Because of the spirometric guidelines in place, the current diagnostic prediction adjustment practice may have untoward effects on patients not categorized as "White," including underdiagnosis in asthma and restrictive lung disease, undertreatment with lung transplant, undercompensation in workers compensation cases, and other unintended consequences. Individuals, institutions, national organizations, and policymakers should carefully consider the historic basis, and reconsider the current role of an automated, race-based adjustment in spirometry.

Hematologic malignancies magnify the effect of body mass index on insulin resistance in cancer survivors

AbstractCancer survivors are at increased risk of type 2 diabetes, which usually develops from obesity and insulin resistance. Whether diabetes susceptibility is due to shared risk factors for cancer and insulin resistance or directly related to cancer and its treatment is unknown. We investigated effect modification between malignancy and body mass index (BMI) as determinants of insulin sensitivity in patients with hematologic malignancies and controls without cancer. In a cross-sectional study of 43 individuals without diabetes (20 patients with treated hematologic malignancies; 23 controls without malignancies), we measured insulin-stimulated whole-body glucose use (M) by hyperinsulinemic euglycemic clamp. Insulin sensitivity index (ISI) was calculated by dividing M over steady-state plasma insulin. Inflammatory cytokines were measured in plasma. Controls were more obese and included more non-White individuals and women vs patients with hematologic malignancies. Patients with cancer exhibited greater insulin sensitivity (median ISI, 42.4 mg/kg/min/[μU/mL]; interquartile range [IQR], 33.9-67.2 vs 23.4 mg/kg/min/[μU/mL]; IQR, 12.9-29.2; P < .001) and higher interleukin-6 (IL-6) and monocyte chemoattractant protein-1 (MCP-1) concentrations vs controls. Patients with cancer demonstrated greater reduction in ISI with increasing BMI vs controls, which remained significant after adjustment for sex and race (β = −2.6 units; 95% confidence interval, −4.8 to −0.4; P interaction = .024). This interaction also remained significant after adjusting for log IL-6 (P interaction = .048) and log MCP-1 (P interaction = .021). Cancer survivors had disproportionately greater insulin resistance with increasing BMI vs controls without malignancies. Effect modification between cancer and BMI in determining insulin sensitivity implicated cancer-specific etiologies in glucose dysregulation and could partially explain excess diabetes diagnoses among oncology patients.

Concentrations of per- and polyfluoroalkyl substances (PFAS) in human placental tissues and associations with birth outcomes

Per- and polyfluoroalkyl substances (PFAS) are ubiquitous environmental contaminants commonly detected in human serum. Previous studies have observed associations between maternal serum PFAS and adverse pregnancy and birth outcomes such as lower birth weight or pre-eclampsia; however, few studies have explored these associations with birth outcomes and placental tissue PFAS concentration. The placenta is a vital contributor to a healthy pregnancy and may be involved in the mechanism of PFAS reproductive toxicity. Our goal was to measure placental PFAS concentrations and examine associations with birth outcomes (e.g., birth weight, gestational duration). Placenta samples (n = 120) were collected during delivery from women enrolled in the Healthy Pregnancy, Healthy Baby cohort (HPHB) in Durham, North Carolina. All placenta samples contained detectable PFAS, with perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), and perfluorodecanoic acid (PFDA) being the most abundant and most frequently detected (all >96% detection frequency). While placental PFAS concentrations did not differ by infant sex, higher PFAS levels were observed in placenta from nulliparous women, suggesting that parity influences the accumulation of PFAS in the placenta. We used linear regression models to examine associations between placental PFAS and birth outcomes. After adjustment for parity, tobacco use, maternal age, and maternal race, we found that placental PFOS was associated with lower birth weight for gestational age in male infants and higher birth weight for gestational age in female infants. Similar findings were seen for PFNA for birth weight for gestational age. These differences in birth outcomes based on infant sex highlight a need to explore mechanistic differences in PFAS toxicity during gestation for male and female infants.

Sex Differences in the Risk of Dementia in Older Veterans.

Studies have demonstrated women to have a higher prevalence of dementia compared to men. However, sex differences in dementia incidence are controversial with conflicting reports showing women with higher, lower, or similar incidence. Source of difference may be due to clinical setting and lack of consideration of competing risk of death. We examined dementia incidence in a sample of the national Veteran population to determine differences by sex. We examined data from the Veterans Health Administration (VHA), the largest integrated health care system in the United States. We studied 947 797 Veterans aged ≥55 years (mean age: 69.9 ± 8.4, 3% female) evaluated in the VHA from October 1, 1999 to September 30, 2019. We estimated age-adjusted incidence rates of dementia (International Classification of Diseases, 9th and 10th Edition codes) by sex, and used Fine-Gray proportional hazards models with age as time scale to examine time to diagnosis, accounting for competing risk of death. During the follow-up (mean 8.4 years), 11.3% (n = 106 977, 11.4% men and 8.0% women) of Veterans developed dementia. Age-adjusted incidence was 12.6/1 000 person-years for men and 12.7/1 000 person-years for women. Compared to male Veterans, risk dementia was slightly higher among females (hazard ratio = 1.15; 95% confidence interval: 1.10-1.20), and on average, female Veterans developed dementia 0.2 years earlier than male Veterans. After additional adjustment for race, education, medical, and psychiatric conditions, results were similar. Among older Veterans in a national cohort, women had a slightly increased risk for developing dementia compared to men after accounting for competing risk of death.

Abstract WP131: Radiation For Head And Neck Cancer And Risk Of Intracranial Hemorrhage

Introduction: Radiation therapy in head and neck cancers has previously been associated with cerebrovascular complications such as aneurysm formation, atherosclerosis, and ischemic stroke. Radiation is also associated with extradural cranial hemorrhagic complications due to weakening of vessel walls and labile hypertension from baroreflex failure. We hypothesized radiation therapy in head and neck cancers would also be associated with intracranial hemorrhage. Methods: We performed a retrospective cohort study using inpatient and outpatient claims between 2008-2018 from a nationally representative 5% sample of Medicare beneficiaries. We included patients ≥65 years old with cancer of the oral cavity, nasal cavity, pharynx, or larynx, defined by ICD-9-CM and ICD-10-CM diagnosis codes, who underwent either radiation therapy or surgical tumor excision, defined by CPT codes. Intracranial hemorrhage was defined using ICD-9-CM and ICD-10-CM diagnosis codes for subarachnoid hemorrhage, intracerebral hemorrhage, and subdural hemorrhage. Cox proportional hazards regression was used to determine the association between radiation therapy and intracranial hemorrhage after adjustment for age, race, atrial fibrillation, coronary artery disease, hypertension, diabetes mellitus, congestive heart failure, chronic kidney disease, tobacco use, and alcohol use. Results: Of 15,990 eligible patients, 5,316 (33%) underwent radiation therapy. A total of 568 (3.5%) patients had an intracranial hemorrhage. In unadjusted analysis, radiation therapy was associated with an increased risk of intracranial hemorrhage (HR, 1.72, 95% CI, 1.40-2.10). This association was present after adjustment for age, race, and vascular risk factors (HR, 1.29; 95% CI, 1.04-1.59). Conclusions: In a nationally representative cohort of Medicare beneficiaries, radiation therapy for head and neck cancer was associated with an increased risk of intracranial hemorrhage.