Lipid distributions in the Global Diagnostics Network across five continents.

AIMS: Lipids are central in the development of cardiovascular disease, and the present study aimed to characterize variation in lipid profiles across different countries to improve understanding of cardiovascular risk and opportunities for risk-reducing interventions. METHODS AND RESULTS: This first collaborative report of the Global Diagnostics Network (GDN) evaluated lipid distributions from nine laboratory organizations providing clinical laboratory testing in 17 countries on five continents. This cross-sectional study assessed aggregated lipid results from patients aged 20-89 years, tested at GDN laboratories, from 2018 through 2020. In addition to mean levels, the World Health Organization total cholesterol risk target (<5.00 mmol/L, <193 mg/dL) and proportions in guideline-based low-density lipoprotein cholesterol (LDL-C) categories were assessed. This study of 461 888 753 lipid results found wide variation by country/region, sex, and age. In most countries, total cholesterol and LDL-C peaked at 50-59 years in females and 40-49 years in males. Sex- and age-group adjusted mean total cholesterol levels ranged from 4.58 mmol/L (177.1 mg/dL) in the Republic of Korea to 5.40 mmol/L (208.8 mg/dL) in Austria. Mean total cholesterol levels exceeded the World Health Organization target in Japan, Australia, North Macedonia, Switzerland, Germany, Slovakia, and Austria. Considering LDL-C categories, North Macedonia had the highest proportions of LDL-C results >4.91 mmol/L (>190 mg/dL) for both females (9.9%) and males (8.7%). LDL-C levels <1.55 mmol/L (<60 mg/dL) were most common among females in Canada (10.7%) and males in the UK (17.3%). CONCLUSION: With nearly a half billion lipid results, this study sheds light on the worldwide variability in lipid levels, which may reflect inter-country differences in genetics, lipid testing, lifestyle habits, and pharmacologic treatment. Despite variability, elevated atherogenic lipid levels are a common global problem, and these results can help inform national policies and health system approaches to mitigate lipid-mediated risk of cardiovascular disease.

Chlamydia and Gonorrhea Testing in Pregnancy: Time to Improve Adherence and Update Recommendations.

OBJECTIVE: The aim of the study is to evaluate adherence to national recommendations for Chlamydia trachomatis (chlamydia) and Neisseria gonorrhoeae (gonorrhea) testing during pregnancy including tests for cure/clearance and for persistence/potential reinfection at time of delivery. MATERIALS AND METHOD: We evaluated results of chlamydia and gonorrhea nucleic acid amplification tests (NAAT) performed by major national reference laboratory from January 2010 through July 2022. RESULTS: Of 3,519,781 uniquely identified pregnant individuals, we identified 4,077,212 pregnancies. Among pregnancies that had chlamydia or gonorrhea testing, 3.7% (149,422/4,055,016) and 0.4% (15,858/ 4,063,948) were initially positive, respectively. Initial tests occurred in the first trimester for approximately 88%. Of those initially chlamydia test positive, 71% were retested; 15.8% in <4 weeks and 37.3% >8 weeks (similarly for gonorrhea). Among patients initially test positive in early/mid pregnancy, more than one-third had no evidence of late pregnancy retesting. Individuals who were initially test negative and subsequently retested positive were approximately 50% likely to have the last available result be positive. Among all whom initially tested positive and were retested, 6.8% and 4.0%, were positive for chlamydia and gonorrhea, respectively on their last test before estimated delivery. There was no subsequent negative test before estimated delivery for 35.1% and 36.9% chlamydia or gonorrhea infected patients, respectively. CONCLUSIONS: Adherence to current recommendations is suboptimal and may not be adequate to reduce disease burden. Professional societies and practice plans should work to encourage better adherence to existing guidelines to protect the health of women and their newborns. We propose recommendations that may be helpful in reducing disease burden.

Simplifying Treatment Criteria in Chronic Hepatitis B: Reducing Barriers to Elimination.

BACKGROUND: Early, sustained hepatitis B virus (HBV) DNA suppression reduces long-term risks of hepatocellular carcinoma. Chronic hepatitis B (CHB) treatment criteria are complex. Simplifying criteria will improve timely linkage to therapy. We evaluated treatment eligibility patterns among US patients with CHB and propose stepwise simplification of CHB treatment criteria. METHODS: Using 2016-2020 Quest Diagnostics data, we evaluated treatment eligibility among patients with CHB (2 positive HBV tests [HBV surface antigen, HBV e antigen, or HBV DNA] ≥6 months apart) using American Association for the Study of Liver Disease (AASLD), European Association for Study of the Liver (EASL), Asian Pacific Association for Study of the Liver (APASL), and Asian American Treatment Algorithm (AATA) criteria. RESULTS: Among 84 916 patients with CHB, 6.7%, 6.2%, 5.8%, and 16.4% met AASLD, EASL, APASL, and AATA criteria, respectively. Among treatment-ineligible patients with CHB, proportion with significant fibrosis (aspartate aminotransferase platelet ratio index >0.5) were 10.4%, 10.4%, 10.8%, and 7.7% based on AASLD, EASL, APASL, and AATA, respectively. In the proposed treatment simplification, the proportion of patients with CHB eligible for therapy increased from 10.3% for step 1 (HBV DNA >20 000 IU/mL, elevated alanine aminotransferase [ALT] level) to 14.1% for step 2 (HBV >2000 IU/mL, elevated ALT level), 33.5% for step 3 (HBV DNA >2000 IU/mL, any ALT level), and 87.2% for step 4 (detectable HBV DNA, any ALT level). CONCLUSIONS: A large proportion of patients with CHB not meeting established treatment criteria have significant fibrosis. Simplifying criteria to treat all patients with detectable HBV DNA will reduce complexity and heterogeneity in assessing treatment eligibility, improving treatment rates and progress toward HBV elimination.

Hepatitis C Virus Clearance Cascade - United States, 2013-2022.

Approximately 2.4 million adults were estimated to have hepatitis C virus (HCV) infection in the United States during 2013-2016 (1). Untreated, hepatitis C can lead to advanced liver disease, liver cancer, and death (2). The Viral Hepatitis National Strategic Plan for the United States calls for ≥80% of persons with hepatitis C to achieve viral clearance by 2030 (3). Characterizing the steps that follow a person's progression from testing to viral clearance and subsequent infection (clearance cascade) is critical for monitoring progress toward national elimination goals. Following CDC guidance (4), a simplified national laboratory results-based HCV five-step clearance cascade was developed using longitudinal data from a large national commercial laboratory throughout the decade since highly effective hepatitis C treatments became available. During January 1, 2013-December 31, 2021, a total of 1,719,493 persons were identified as ever having been infected with HCV. During January 1, 2013-December 31, 2022, 88% of those ever infected were classified as having received viral testing; among those who received viral testing, 69% were classified as having initial infection; among those with initial infection, 34% were classified as cured or cleared (treatment-induced or spontaneous); and among those persons, 7% were categorized as having persistent infection or reinfection. Among the 1.0 million persons with evidence of initial infection, approximately one third had evidence of viral clearance (cured or cleared). This simplified national HCV clearance cascade identifies substantial gaps in cure nearly a decade since highly effective direct-acting antiviral (DAA) agents became available and will facilitate the process of monitoring progress toward national elimination goals. It is essential that increased access to diagnosis, treatment, and prevention services for persons with hepatitis C be addressed to prevent progression of disease and ongoing transmission and achieve national hepatitis C elimination goals.

Low Performance of Hepatitis Delta Virus Testing Among 2 National Cohorts of Chronic Hepatitis B Patients in the United States.

INTRODUCTION: The purpose of this study was to evaluate hepatitis delta virus (HDV) testing patterns among US adults with chronic hepatitis B (CHB). METHODS: HDV testing was evaluated among CHB patients using Quest Diagnostics (2016-2020) and Veterans Affairs (2010-2020) data. RESULTS: Among 157,333 CHB patients (Quest), 6.7% received HDV testing, among which 2.2% were positive. HDV testing was higher in male patients, younger individuals, and patients with advanced liver disease. Among 12,002 CHB patients (Veterans Affairs), 19.7% received HDV testing, among which 3.1% were positive. HDV testing was higher in younger individuals and Asians. DISCUSSION: Low HDV testing was observed among 2 large US cohorts of adults with CHB.

National Kidney Foundation Laboratory Engagement Working Group Recommendations for Implementing the CKD-EPI 2021 Race-Free Equations for Estimated Glomerular Filtration Rate: Practical Guidance for Clinical Laboratories.

Recognizing that race is a social and not a biological construct, healthcare professionals and the public have called for removal of race in clinical algorithms. In response, the National Kidney Foundation and the American Society of Nephrology created the Task Force on Reassessing the Inclusion of Race in Diagnosing Kidney Diseases to examine the issue and provide recommendations. The final report from the Task Force recommends calculating estimated glomerular filtration rate (eGFR) without a race coefficient using the recently published CKD-EPI 2021 creatinine (cr) and creatinine-cystatin C (cr-cys) equations. The Task Force recommends immediately replacing older eGFRcr equations (MDRD Study and CKD-EPI 2009) with the new CKD-EPI 2021 equation. In a 2019 survey by the College of American Pathologists, 23% of 6200 laboratories reporting eGFRcr used an incorrect equation that is not suitable for use with standardized creatinine measurements, 34% used the CKD-EPI 2009 equation and 43% used the MDRD Study 2006 equation re-expressed for standardized creatinine measurement. Rapid transition to using the CKD-EPI 2021 equation is an opportunity for laboratories to standardize to a single equation to eliminate differences in eGFRcr due to different equations used by different laboratories, and to report eGFR without use of race. We provide guidance to laboratories for implementing the CKD-EPI 2021 equations for both eGFRcr and eGFRcr-cys.

Prevalence of Hepatitis B Virus and Latent Tuberculosis Coinfection in the United States.

CONTEXT: Underlying chronic hepatitis B virus (HBV) infection increases the risk of drug-induced liver injury (DILI) when receiving tuberculosis therapies. Prevalence of HBV and latent tuberculosis infection (LTBI) coinfection is not well reported and no studies have evaluated testing patterns for and prevalence of HBV-LTBI coinfection in the United States. OBJECTIVE: To evaluate patterns of HBV and LTBI testing and prevalence of HBV-LTBI coinfection in the United States. DESIGN: Retrospective cohort study. SETTING: Quest Diagnostics clinical laboratory data, 2014-2020. PATIENTS: Chronic HBV infection was defined as any combination of 2 positive HBV surface antigen, HBV e antigen, or detectable HBV DNA tests at least 6 months apart. LTBI was defined as a positive QuantiFERON-TB or T-SPOT.TB test without evidence of active tuberculosis infection. MAIN OUTCOME MEASUREMENTS: Testing patterns for chronic HBV infection and LTBI and prevalence of HBV-LTBI coinfection were evaluated from 2016 through 2020 and stratified by age, sex, and race and ethnicity. RESULTS: Among 89 259 patients with chronic HBV infection, 9508 (10.7%) were tested for LTBI, among whom prevalence of HBV-LTBI coinfection was 19.6%, more than twice the observed prevalence of LTBI in patients with no chronic HBV infection in our cohort. Among 394 817 LTBI patients, 127 414 (32.3%) were tested for HBV, among whom prevalence of HBV-LTBI coinfection was 1.5%, approximately 3 times higher than prevalence of HBV infection in patients with no LTBI. The HBV-LTBI coinfection prevalence was highest among Asian Americans and older individuals. LIMITATIONS: The HBV-LTBI coinfection prevalence was likely underestimated because of suboptimal awareness and testing among at-risk populations. CONCLUSION: Among US individuals with chronic HBV infection or LTBI, prevalence of HBV-LTBI coinfection is substantial and highlights the need of testing for HBV-LTBI coinfection to mitigate risk of DILI associated with tuberculosis medications in patients with chronic HBV infection.

Chlamydia trachomatis and Neisseria gonorrhoeae in Pregnancy: Trends in United States, 2010 to 2018.

BACKGROUND: Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) case surveillance relies on reported positive laboratory results. Changes in reported cases may represent changes in testing practice or infection prevalence. This study evaluated changes over time for CT and NG positivity and testing rates of pregnant persons. METHODS: Prenatal testing results from persons aged 16 to 40 years tested by a national reference clinical laboratory were analyzed for CT and NG testing and positivity from 2010 to 2018 (n = 3,270,610). RESULTS: Testing rates increased among pregnant persons for CT (from 56.3% in 2010 to 64.1% in 2018, P < 0.001) and NG (from 55.6% to 63.2%, P < 0.001). Higher CT testing rates were found in Black non-Hispanic (adjusted odds ratio [AOR], 1.58; 95% confidence interval [CI], 1.57-1.60) and Hispanic (AOR, 1.19; 95% CI, 1.18-1.20) persons. NG and CT testing rates were virtually identical. Significant increasing trends in CT positivity were observed for each age group studied (P < 0.001 for all): 16-19 (from 11.7% to 13.0%), 20-24 (from 6.4% to 6.7%), 25-30 (from 1.9% to 2.4%), and 31-40 years (from 0.76% to 0.92%). Black non-Hispanic persons had the highest positivity for CT (AOR, 2.52; 95% CI, 2.46-2.57) and NG (AOR, 5.42; 95% CI, 5.05-5.82). CONCLUSIONS: Testing and adjusted positivity for both CT and NG among pregnant persons increased from 2010 to 2018. Higher testing rates were observed in Black non-Hispanic and Hispanic persons (even in persons younger than 25 years), suggesting some testing decisions may have been based on perceived risk, in contrast to many guidelines recommending screening all pregnant persons younger than 25 years.

Q fever: an under-reported reportable communicable disease.

The objective of this study was to provide real-world clinical laboratory-based data to supplement Centers for Disease Control and Prevention (CDC) reporting of Q fever. We analysed titre results of specimens submitted to a large US clinical laboratory for Coxiella burnetii IgG antibody testing from 2010 through 2016. Presumptive Q fever was defined as acute (phase II IgG titre ⩾1:128, phase I titre <1:1024) or chronic (phase I IgG titre ⩾1:1024), based on the results from a single serum specimen. During 2010-2016, an average of 328 presumptive acute Q fever cases were identified at Quest each year, nearly three times the annual average reported to the CDC (122). During the same period, the number of chronic cases identified annually at Quest Diagnostics (34) was similar to that reported to the CDC (29). These findings suggest that CDC data may underestimate the incidence of acute Q fever.

Predicted 25-hydroxyvitamin D in relation to incidence of breast cancer in a large cohort of African American women.

BACKGROUND: Vitamin D deficiency, which has been linked to an increased risk of colorectal cancer, is particularly common among African Americans. Previous studies of vitamin D status and breast cancer risk, mostly conducted in white women, have had conflicting results. We examined the relationship between predicted vitamin D status and incidence of breast cancer in a cohort of 59,000 African American women. METHODS: Participants in the Black Women's Health Study have been followed by biennial mail questionnaires since 1995, with self-reported diagnoses of cancer confirmed by hospital and cancer registry records. Repeated five-fold cross-validation with linear regression was used to derive the best 25-hydroxyvitamin D (25(OH)D) prediction model based on measured 25(OH)D in plasma specimens obtained from 2856 participants in 2013-2015 and questionnaire-based variables from the same time frame. In the full cohort, including 1454 cases of incident invasive breast cancer, Cox proportional hazards models were used to compute the incidence rate ratio (IRR) for each quartile of predicted vitamin D score relative to the highest quartile. Predicted vitamin D score for each two-year exposure period was a cumulative average of predicted scores from all exposure periods up to that time. RESULTS: Twenty-two percent of women with measured 25(OH)D were categorized as "deficient" (<20 ng/mL) and another 25 % as "insufficient" (20-29 ng/mL). The prediction model explained 25 % of variation in measured 25(OH)D and the correlation coefficient for predicted versus observed 25(OH)D averaged across all cross-validation runs was 0.49 (SD 0.026). Breast cancer risk increased with decreasing quartile of predicted 25(OH)D, p for trend 0.015; the IRR for the lowest versus highest quartile was 1.23 (95 % confidence interval 1.04, 1.46). CONCLUSIONS: In prospective data, African American women in the lowest quartile of cumulative predicted 25(OH)D were estimated to have a 23 % increased risk of breast cancer relative to those with relatively high levels. Preventing vitamin D deficiency may be an effective means of reducing breast cancer incidence in African American women.

Blood Lead Levels in Young Children: US, 2009-2015.

OBJECTIVES: To evaluate trends in blood lead levels in children <6 years of age, this Quest Diagnostics Health Trends report builds on previously reported National Health and Nutrition Examination Survey data with a much larger national group and adds more detail and novel assessments. STUDY DESIGN: This report describes the results from a 6-year retrospective study (May 2009-April 2015) based on >5 million blood lead level results (including >3.8 million venous results) from children <6 years old living in all 50 states and the District of Columbia. We evaluated yearly changes and examined demographic categories including sex, pre-1950s housing construction, poverty income ratios (PIRs), Medicaid enrollment status, and geographic regions. RESULTS: Among children <6 years old, 3.0% exhibited blood lead levels ≥5.0 µg/dL (high). There were significant differences in high blood lead levels based on sex, pre-1950s housing construction quintiles, and PIR <1.25 and PIR >5 (all P < .01). Health and Human Services regions, states, and 3-digit ZIP code areas exhibited drastically different frequencies of high blood lead levels and blood lead levels ≥10.0 µg/dL (very high). Generally, levels declined over time for all groups. CONCLUSION: Examination of more than 5 million venous blood lead level results in children younger than 6 years old allowed for a robust, detailed analysis of blood lead level group results by geography and other criteria that are prohibited with the narrower National Health and Nutrition Examination Survey database. Progress in reducing the burden of lead toxicity is a public health success story that is incomplete with some identified factors posing larger, ongoing challenges.

Neighborhood Socioeconomic Status in Relation to Serum Biomarkers in the Black Women's Health Study.

Lower neighborhood socioeconomic status (SES) is associated with higher cardiovascular disease (CVD) risk. Black women have a higher CVD risk and are more likely to live in poor neighborhoods than white women. We examined the association of neighborhood SES with several CVD biomarkers using data from the Black Women's Health Study (BWHS), a follow-up study of US black women reporting high levels of education and income. Blood specimens of 418 BWHS participants were assayed for C-reactive protein (CRP), hemoglobin A1C (hgA1C), and high-density lipoprotein (HDL) cholesterol. US Census block group data were linked to the women's addresses to reflect neighborhood SES. Multivariable-adjusted mixed linear regression models that adjusted for person-level SES and for cardiovascular risk factors were used to assess CRP, hgA1C, and HDL levels in relation to quintiles of neighborhood SES. Women living in the poorest neighborhoods had the least favorable biomarker levels. As neighborhood SES increased, CRP decreased (P for trend = 0.01), hgA1C decreased (P for trend = 0.07), and HDL increased (P for trend = 0.19). These associations were present within strata of individual educational level. The present findings suggest that neighborhood environments may affect physiological processes within residents independently of individual SES.

National assessment of warfarin anticoagulation therapy for stroke prevention in atrial fibrillation.

BACKGROUND: Anticoagulation control with warfarin, as assessed by the international normalized ratio (INR), is challenging. Time in the therapeutic range has been inversely correlated with major hemorrhage, thrombosis, and mortality. Quest Diagnostics offers standardized INR laboratory testing services to approximately half of US physician practices. To inform national stroke prevention strategies, we evaluated anticoagulation control in office-based community practices. METHODS AND RESULTS: We selected individuals with ≥2 months of INR data, INR results of >1.2, and an ICD-9 diagnosis code of atrial fibrillation. Frequency of INR testing and time in the therapeutic range were analyzed by age, sex, length of testing period, number of referred patients per provider, and median household income (based on home ZIP code). We identified 138 319 individuals referred by 37 939 physicians, yielding a total of 2 683 674 INR results. Patients had a mean age of 74 years; 81% were ≥65 years of age, and 55% were ≥75 years of age. The mean time in the therapeutic range was 53.7% overall and improved with time on treatment, increasing from 47.6% for patients with <6 months of testing to 57.5% for those with ≥6 months of testing (P<0.0001). The number of patients tested per physician practice was positively associated with time in the therapeutic range. Younger age, female sex, and lower income were also independently associated with poorer anticoagulant control. CONCLUSION: This study demonstrates widespread suboptimal anticoagulation control, suggesting an urgent need to improve oral anticoagulation care for most patient segments in the United States.