A Holistic Framework for the Evaluation of Kidney Function in a Gender-Diverse Landscape.

The most commonly used equations to estimate glomerular filtration rate incorporate a binary male-female sex coefficient, which has important implications for the care of transgender, gender-diverse, and nonbinary (TGD) people. Whether "sex assigned at birth" or a binary "gender identity" is most appropriate for the computation of estimated glomerular filtration rate (eGFR) is unknown. Furthermore, the use of gender-affirming hormone therapy (GAHT) for the development of physical changes to align TGD people with their affirmed gender is increasingly common, and may result in changes in serum creatinine and cystatin C, the biomarkers commonly used to estimate glomerular filtration rate. The paucity of current literature evaluating chronic kidney disease (CKD) prevalence and outcomes in TGD individuals on GAHT makes it difficult to assess any effects of GAHT on kidney function. Whether alterations in serum creatinine reflect changes in glomerular filtration rate or simply changes in muscle mass is unknown. Therefore, we propose a holistic framework to evaluate kidney function in TGD people. The framework focuses on kidney disease prevalence, risk factors, sex hormones, eGFR, other kidney function assessment tools, and the mitigation of health inequities in TGD people.

Optimizing the data in direct access testing: information technology to support an emerging care model.

Direct access testing (DAT) is an emerging care model that provides on-demand laboratory services for certain preventative, diagnostic, and monitoring indications. Unlike conventional testing models where health care providers order tests and where sample collection is performed onsite at the clinic or laboratory, most interactions between DAT consumers and the laboratory are virtual. Tests are ordered and results delivered online, and specimens are frequently self-collected at home with virtual support. Thus, DAT depends on high-quality information technology (IT) tools and optimized data utilization to a greater degree than conventional laboratory testing. This review critically discusses the United States DAT landscape in relation to IT to highlight digital challenges and opportunities for consumers, health care systems, providers, and laboratories. DAT offers consumers increased autonomy over the testing experience, cost, and data sharing, but the current capacity to integrate DAT as a care option into the conventional patient-provider model is lacking and will require innovative approaches to accommodate. Likewise, both consumers and health care providers need transparent information about the quality of DAT laboratories and clinical decision support to optimize appropriate use of DAT as a part of comprehensive care. Interoperability barriers will require intentional approaches to integrating DAT-derived data into the electronic health records of health systems nationally. This includes ensuring the laboratory results are appropriately captured for downstream data analytic pipelines that are used to satisfy population health and research needs. Despite the data- and IT-related challenges for widespread incorporation of DAT into routine health care, DAT has the potential to improve health equity by providing versatile, discreet, and affordable testing options for patients who have been marginalized by the current limitations of health care delivery in the United States.

AACC/NKF Guidance Document on Improving Equity in Chronic Kidney Disease Care.

BACKGROUND: Kidney disease (KD) is an important health equity issue with Black, Hispanic, and socioeconomically disadvantaged individuals experiencing a disproportionate disease burden. Prior to 2021, the commonly used estimated glomerular filtration rate (eGFR) equations incorporated coefficients for Black race that conferred higher GFR estimates for Black individuals compared to non-Black individuals of the same sex, age, and blood creatinine concentration. With a recognition that race does not delineate distinct biological categories, a joint task force of the National Kidney Foundation and the American Society of Nephrology recommended the adoption of the CKD-EPI 2021 race-agnostic equations. CONTENT: This document provides guidance on implementation of the CKD-EPI 2021 equations. It describes recommendations for KD biomarker testing, and opportunities for collaboration between clinical laboratories and providers to improve KD detection in high-risk populations. Further, the document provides guidance on the use of cystatin C, and eGFR reporting and interpretation in gender-diverse populations. SUMMARY: Implementation of the CKD-EPI 2021 eGFR equations represents progress toward health equity in the management of KD. Ongoing efforts by multidisciplinary teams, including clinical laboratorians, should focus on improved disease detection in clinically and socially high-risk populations. Routine use of cystatin C is recommended to improve the accuracy of eGFR, particularly in patients whose blood creatinine concentrations are confounded by processes other than glomerular filtration. When managing gender-diverse individuals, eGFR should be calculated and reported with both male and female coefficients. Gender-diverse individuals can benefit from a more holistic management approach, particularly at important clinical decision points.

Design of a pragmatic randomized controlled trial of home-based human papillomavirus (HPV) self-sampling for increasing cervical cancer screening uptake in a U.S. healthcare system: The STEP trial.

BACKGROUND: Mailing HPV self-sampling kits to overdue individuals increases cervical cancer screening adherence; offering self-sampling to previously adherent individuals has not been evaluated in the U.S. Given heterogeneity of the U.S. health system and population, data are needed to optimize how HPV self-sampling is offered to individuals who are overdue, due after successful past screening, or have an unknown screening history. METHODS: STEP is a pragmatic randomized controlled trial set within a U.S. integrated healthcare delivery system, designed to compare different outreach approaches for offering HPV self-sampling in populations defined by prior screening behavior (previously-adherent, overdue, or unknown screening history). Over 14 months, eligible individuals were identified through electronic medical record (EMR) data and randomized to Usual Care (UC), Education (UC + educational materials about cervical cancer screening), Direct-Mail (UC + Education + a mailed self-sampling kit) or Opt-In (UC + Education + option to request a kit), depending on screening history. The primary objective is to compare screening completion by outreach approach and screening history. Secondary objectives include evaluating incremental cost-effectiveness of outreach approaches, and identifying patient preference for, and satisfaction with, HPV self-screening, and barriers to abnormal results follow-up (measured through interviews and focus groups). CONCLUSIONS: The trial was designed to generate data that U.S. health systems can use to inform primary HPV screening implementation strategies that incorporate HPV self-sampling options to improve screening access, adherence, and patient satisfaction. The objective of this report is to describe the rationale and design of this pragmatic trial.

Cannabis Legalization Does Not Influence Patient Compliance with Opioid Therapy.

BACKGROUND: Prescription opioid use and opioid related deaths continue to increase nationwide. Several states have adopted legislation allowing for recreational use of cannabis. Little is known about how recreational cannabis laws impact compliance in chronic pain patients who have been prescribed opioid therapy. The goals of this study were to (1) retrospectively assess the effect of cannabis use on compliance with opioid therapy in a high-risk patient population and (2) determine the impact of legalization of recreational cannabis on patients prescribed therapeutic opioids. METHODS: We conducted a retrospective cohort study on results from a "high-risk" urine drug testing panel. Results from 1 year before and 1 year after initiation of recreational cannabis legislation were analyzed. This testing panel included qualitative assays for cannabinoids and 9 other common drugs of abuse in addition to a quantitative LC-MS/MS assay for 23 different opioids and metabolites. Opioid compliance was assigned by reviewing pathologists' interpretations. RESULTS: In the pre-legalization period, 1776 panels were performed, and in the post-legalization, 1648 panels were performed. An increase (6%) in the rate of positive cannabinoids screening results was observed after legalization of recreational cannabis; however, the overall compliance rate was consistent. CONCLUSIONS: The results of this study suggest that legalization of recreational cannabis does not affect compliance rate in patients treated with opioid therapy for chronic pain.

Biotin Interference in Clinical Immunoassays.

BACKGROUND: Shifts in consumer behavior and clinical practice have increased reports of biotin interference in immunoassays that incorporate biotin-streptavidin linkages in their design. This rise has significant implications because immunoassays are used to measure a wide range of analytes across medical specialties. The objective of this article was to review the mechanisms of biotin interference, define the scope of affected immunoassays, and summarize strategies for identifying and minimizing biotin interference in clinical samples. CONTENT: The literature was reviewed for reports of biotin interference and sorted by manufacturer. Abstracts from recent scientific meetings and manufacturer-provided data were also reviewed. SUMMARY: Immunoassays across a range of different manufacturer platforms are subject to interference by exogenous biotin supplementation. Providers and laboratorians must be aware of this potential interference to avoid patient harm.

Pseudohypophosphatemia associated with high-dose liposomal amphotericin B therapy.

BACKGROUND: Hypophosphatemia is commonly observed in critically ill patients. Inorganic phosphorus is quantified by spectrophotometric measurement of a phosphomolybdate complex, a method with multiple documented interferents. Our clinical laboratory was contacted to investigate a case of asymptomatic hypophosphatemia in a patient receiving high-dose liposomal amphotericin B therapy (L-AMB). METHODS: In vitro experiments were performed by spiking L-AMB into residual plasma specimens. Phosphate was measured on the Beckman Coulter AU and Ortho Diagnostics Vitros instruments. RESULTS: When measured on the AU, phosphate in plasma with approximately 250mcg/mL of L-AMB demonstrated a median negative bias of 3.45mg/dL relative to unspiked samples. In contrast, Vitros phosphate measurements demonstrated excellent agreement for specimens with and without L-AMB (median bias -0.2mg/dL). CONCLUSIONS: High L-AMB concentrations induced a significant negative bias on phosphate measured by the AU assay, but did not affect the Vitros assay. Laboratorians and clinicians should be aware of this phenomenon in patients receiving L-AMB who develop unexplained hypophosphatemia.

Association Between Laboratory Calibration of a Serum Bilirubin Assay, Neonatal Bilirubin Levels, and Phototherapy Use.

IMPORTANCE: The American Academy of Pediatrics treatment recommendations for neonatal jaundice are based on age-specific total serum bilirubin (TSB) levels. In May 2012, Ortho Clinical Diagnostics adjusted the calibrator values for Vitros Chemistry Products BuBc Slides (Ortho Clinical Diagnostics), a widely used method to quantify TSB, after concerns of positively biased results. OBJECTIVE: To investigate the association between recalibration of a reflectance spectrophotometry serum bilirubin assay and TSB levels and phototherapy use among newborns. DESIGN, SETTING, AND PARTICIPANTS: Descriptive study comparing TSB levels and phototherapy use before and after recalibration at Kaiser Permanente Northern California, a large, integrated health care delivery system. The study evaluated live births at or after 35 weeks' gestation at 12 facilities that used universal serum bilirubin screening before (January 1, 2010, through April 30, 2012; n = 61 677) and after (July 1, 2012, through December 31, 2013; n = 42 571) recalibration. The analysis took place in December 2015. INTERVENTION: Recalibration of bilirubin testing instruments. MAIN OUTCOMES AND MEASURES: Proportions of newborns with (1) at least 1 TSB value at or above 15 mg/dL; (2) at least 1 TSB level exceeding the American Academy of Pediatrics phototherapy threshold; (3) phototherapy during the birth hospitalization; and (4) at least 1 readmission for phototherapy. RESULTS: In 104 420 infants (61 677 in the prerecalibration period and 42 511 in the postrecalibration period), a TSB was obtained in 99.2% of infants during birth and in 99.5% of infants within the first 30 days after birth. The postrecalibration period was associated with a 1.25 mg/dL (95% CI, 1.19-1.31; P < .001) decrease in mean maximum TSB, which led to a 39% relative reduction (from 20.4% to 12.4%) in infants with a TSB level of 15 mg/dL or more and a 51% relative reduction (from 9.3% to 4.5%) in infants with a TSB level that was at or above the American Academy of Pediatrics phototherapy threshold. Phototherapy during birth hospitalizations was reduced by 59% (absolute risk reduction, 5.5%; 95% CI, 4.7%-6.1%) and readmissions for phototherapy by 53% (absolute risk reduction, 1.8%; 95% CI, 1.4%-2.3%). CONCLUSIONS AND RELEVANCE: Modest recalibration-induced reductions in mean TSB concentrations was associated with a significant reduction in the percentage of infants with clinically significant hyperbilirubinemia. Current laboratory accuracy standards are insufficient to detect biases that can have significant clinical effect. These data underline the need for increased integration of laboratory expertise into clinical guidelines and to support international initiatives to standardize laboratory measurements.

Challenges in harmonizing integrated healthcare network laboratories: multi-center evaluation of the hCG5 assay.

BACKGROUND: Beckman Coulter recently introduced a new hCG assay manufactured for the Access 2 and DxI platforms. This assay is the first to use the 5th International Standard (5th IS) as its primary calibration material. Clinical laboratories are required to validate the method performance before testing and reporting patient results. METHODS: Beckman Coulter Access 2 instruments (n=41) across Kaiser Permanente Northern California were evaluated for their performance characteristics using the hCG5 reagent. Precision, linearity, dilution verification, and patient sample comparisons were performed on each instrument. RESULTS: The assay was linear up to 1350IU/L. Intra-day and inter-day precision ranged from 1.0%-3.3% and 1.8-7.3%, respectively, for the low QC material (mean concentration 4.6IU/L). Percent bias between the previous assay (hCG2) and the hCG5 assay was 3.2 to 22.7% for hCG concentrations <1000IU/L and -2.9 to 30% for concentrations >1000IU/L. On board and manual dilutions agreed within 15% following proper adjustment of the instrument dilution factor. CONCLUSIONS: Achieving Access 2 inter-instrument agreement on specimens needing dilutions (hCG>1350IU/L) requires validation of the on board dilution factor. Laboratories should use QC material above the linear range to monitor instrument dilution accuracy and precision.

Challenges in harmonizing integrated healthcare network laboratories: Multi-center evaluation of the AccuTnI+3 troponin assay.

BACKGROUND: Beckman Coulter has recently introduced a new troponin assay manufactured for the Access2 and DxI platforms, releasing it under the name AccuTnI+3. Clinical laboratories are required to validate method performance before testing and reporting patient results. METHODS: Beckman Coulter Access 2 instruments (n=42) across Kaiser Permanente Northern California were evaluated for their performance characteristics using the AccuTnI+3 reagent. Precision, linearity, and patient sample comparisons were performed on each instrument. Limit of the blank (LOB), limit of detection (LOD), limit of quantitation (LOQ), serum plasma comparisons, and specimen stability were evaluated using a single instrument. RESULTS: The assay was linear from 0-100,000ng/L. The LOB, LOD and LOQ were determined to be 5, 8 and 20ng/L, respectively. Interday precision on the low QC (mean concentration 41ng/L) ranged from 3.0% to 14.2%. The bias observed between the former assay (AccuTnI) and the AccuTnI+3 was comparable to the inter-instrument bias for either assay. Non-uniform distribution was observed in the precision and inter-instrument/inter-assay comparisons among the instruments evaluated. CONCLUSIONS: The AccuTnI and AccuTnI+3 troponin assays are equivalent across the analytical measuring range. There was no significant difference at the medical decision point. No changes in patient results are anticipated. However, the assay-independent inter-instrument bias observed is an important consideration for harmonization efforts.