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.

Association between serum estradiol and cardiovascular health among transgender adults using gender-affirming estrogen therapy.

Gender-affirming estrogen therapy (GAET) is commonly used for feminization in transgender and nonbinary (TNB) individuals, yet the optimal rate of change (ROC) in estradiol levels for cardiovascular health is unclear. We examined the association between serum estradiol levels and cardiovascular-related mortality, adverse events, and risk factors in TNB adults using GAET. Cochrane Central Register of Controlled Trials, EMBASE, MEDLINE, and Web of Science were systematically searched (inception-April 2023) for original articles reporting serum estradiol levels and cardiovascular-related mortality, adverse events, and risk factors in TNB adults using GAET. Data extraction was completed in duplicate following Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Stratified random effect meta-analyses using serum estradiol ROC (serum estradiolbaseline - serum estradiolfollow-up/study duration) was used to assess longitudinal studies (low, 0 < ROC ≤ 1 pg/mL/mo; moderate, 1 < ROC ≤ 3 pg/mL/mo; high, ROC ≥ 3 pg/mL/mo). Thirty-five studies (13 cross-sectional, 19 cohort, and 3 trials) were included. Two studies collectively reported 50 cardiovascular-related deaths, and four collectively reported 23 adverse cardiovascular events. Nineteen studies reporting cardiovascular risk factors were meta-analyzed by ROC stratum (low = 5; moderate = 6; high = 8), demonstrating an association between moderate [0.40, 95% confidence interval (CI): 0.22, 0.59 kg/m2, I2 = 28.2%] and high (0.46, 95% CI: 0.15, 0.78 kg/m2; I2 = 0.0%) serum estradiol ROC and increased body mass index. High (-6.67, 95% CI: -10.65, -2.68 mg/dL; I2 = 0.0%) serum estradiol ROC was associated with decreased low-density lipoproteins. Low (-7.05, 95% CI: -10.40, -3.70 mmHg; I2 = 0.0%) and moderate (-3.69, 95% CI: -4.93, -2.45 mmHg; I2 = 0.0%) serum estradiol ROCs were associated with decreases in systolic blood pressure. In TNB adults using GAET, serum estradiol ROC may influence cardiovascular risk factors, which may have implications for clinical cardiovascular outcomes.NEW & NOTEWORTHY In this systematic review and meta-analysis of 35 studies involving 7,745 participants, high rates of serum estradiol change were associated with small increases in body mass index. Moderate to high rates of change were associated with decreases in low-density lipoprotein. Low rates of change were associated with small decreases in systolic blood pressure. Rate of serum estradiol change in adults using gender-affirming estrogen therapy may influence cardiovascular risk factors, though further research is warranted.

ChatGPT vs Medical Professional: Analyzing Responses to Laboratory Medicine Questions on Social Media.

BACKGROUND: The integration of ChatGPT, a large language model (LLM) developed by OpenAI, into healthcare has sparked significant interest due to its potential to enhance patient care and medical education. With the increasing trend of patients accessing laboratory results online, there is a pressing need to evaluate the effectiveness of ChatGPT in providing accurate laboratory medicine information. Our study evaluates ChatGPT's effectiveness in addressing patient questions in this area, comparing its performance with that of medical professionals on social media. METHODS: This study sourced patient questions and medical professional responses from Reddit and Quora, comparing them with responses generated by ChatGPT versions 3.5 and 4.0. Experienced laboratory medicine professionals evaluated the responses for quality and preference. Evaluation results were further analyzed using R software. RESULTS: The study analyzed 49 questions, with evaluators reviewing responses from both medical professionals and ChatGPT. ChatGPT's responses were preferred by 75.9% of evaluators and generally received higher ratings for quality. They were noted for their comprehensive and accurate information, whereas responses from medical professionals were valued for their conciseness. The interrater agreement was fair, indicating some subjectivity but a consistent preference for ChatGPT's detailed responses. CONCLUSIONS: ChatGPT demonstrates potential as an effective tool for addressing queries in laboratory medicine, often surpassing medical professionals in response quality. These results support the need for further research to confirm ChatGPT's utility and explore its integration into healthcare settings.

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.

Reconsidering the use of race adjustments in maternal serum screening.

The use of race in maternal serum screening is problematic because race is a social construct rather than a distinct biological classifier. Nevertheless, laboratories offering this testing are encouraged to use race-specific cutoff values for maternal serum screening biomarkers to determine the risk of fetal abnormalities. Large cohort studies examining racial differences in maternal serum screening biomarker concentrations have yielded conflicting results, which we postulate may be explained by genetic and socioeconomic differences between racial cohorts in different studies. We recommend that the use of race in maternal serum screening should be abandoned. Further research is needed to identify socioeconomic and environmental factors that contribute to differences in maternal serum screening biomarker concentrations observed between races. A better understanding of these factors may facilitate accurate race-agnostic risk estimates for aneuploidy and neural tube defects.

Limited Evidence for Use of a Black Race Modifier in eGFR Calculations: A Systematic Review.

BACKGROUND: Commonly used estimated glomerular filtration rate (eGFR) equations include a Black race modifier (BRM) that was incorporated during equation derivation. Race is a social construct, and a poorly characterized variable that is applied inconsistently in clinical settings. The BRM results in higher eGFR for any creatinine concentration, implying fundamental differences in creatinine production or excretion in Black individuals compared to other populations. Equations without inclusion of the BRM have the potential to detect kidney disease earlier in patients at the greatest risk of chronic kidney disease (CKD), but also has the potential to over-diagnose CKD or impact downstream clinical interventions. The purpose of this study was to use an evidence-based approach to systematically evaluate the literature relevant to the performance of the eGFR equations with and without the BRM and to examine the clinical impact of the use or removal. CONTENT: PubMed and Embase databases were searched for studies comparing measured GFR to eGFR in racially diverse adult populations using the Modification of Diet in Renal Disease or the 2009-Chronic Kidney Disease Epidemiology Collaboration-creatinine equations based on standardized creatinine measurements. Additionally, we searched for studies comparing clinical use of eGFR calculated with and without the BRM. Here, 8632 unique publications were identified; an additional 3 studies were added post hoc. In total, 96 studies were subjected to further analysis and 44 studies were used to make a final assessment. SUMMARY: There is limited published evidence to support the use of a BRM in eGFR equations.

A Retrospective Analysis of Creatinine-Based Kidney Function With and Without Sex Assigned at Birth Among Transgender Adults.

BACKGROUND: Clinicians use sex-based kidney function estimating equations, but the appropriate sex modifier for transgender adults undergoing hormone therapy (HT) is undetermined. OBJECTIVES: Compare median estimated creatinine clearance (eCrCL; Cockcroft-Gault) and estimated glomerular filtration rates (eGFRs; Modification of Diet in Renal Disease [MDRD] and Chronic Kidney Disease Epidemiology Study [CKD-EPI]) before and during HT when estimated with and without sex assigned at birth. METHODS: Single-system retrospective cohort study of transgender adults (2007-2017) prescribed ≥90 days HT (index date = first order) and measured serum creatinine ≤6 months pre-index date (baseline) and ≤12 months post-index date. We grouped patients based on testosterone or estrogen treatment and compared eCrCL and eGFRs at baseline up to 6-12 months post-index date using equations based on sex assigned at birth (female or male modifier in testosterone or estrogen groups, respectively) or gender identity (male or female modifier in testosterone or estrogen groups, respectively). We used Wilcoxon signed-rank tests (Bonferroni correction) for all comparisons. RESULTS: In total, 29 (median age 26 years, follow-up 259 days) and 41 patients (29 years, 250 days) were prescribed testosterone or estrogen, respectively. In the testosterone group, the maximum eCrCL and eGFR changes based on sex assigned at birth were -14%, P = 0.0181; -18%; P = 0.0009, respectively, and based on gender identity were +5%, P > 0.025 and +11%, P = 0.0094, respectively. In the estrogen group, eCrCL or eGFRs based on sex assigned at birth did not change from baseline but based on gender identity were -17%, P < 0.0001 and -26%, P < 0.0001, respectively. CONCLUSION AND RELEVANCE: Female-based equations may underestimate kidney function in transgender adults undergoing testosterone or estrogen treatment. Prospective cohort studies are needed to confirm the clinical significance of these findings.

Increased Frequency of Heterozygous Alpha-1-Antitrypsin Deficiency in Liver Explants From Nonalcoholic Steatohepatitis Patients.

Cirrhotic explanted livers occasionally have unexpected periodic acid-Schiff-diastase (PASD)-positive globules within the hepatocyte cytoplasm. It is often unclear whether this finding is a nonspecific consequence of cirrhosis or is indicative of an underlying alpha-1-antitrypsin deficiency (A1ATD) contributing to the cirrhosis. In this study, explanted livers were retrospectively evaluated for histopathology (including PASD status with confirmatory alpha-1-antitrypsin [A1AT] immunohistochemistry [IHC]), and chart review provided etiology of liver failure and general clinical parameters. Real-time polymerase chain reaction was used to detect A1AT genotype (SERPINA1 S and Z alleles) by melting curve analysis on liver explant tissue from selected cases. Of 196 explanted livers, 21 (11%) had PASD+ globules, which were significantly enriched in patients with a clinical diagnosis of nonalcoholic steatohepatitis (NASH; 47%) compared with other causes (P < 0.001). IHC confirmed all PASD+ globules were A1AT+, with 20 of 21 cases demonstrating diffuse A1AT staining. In an expanded NASH cohort, 42% (14/33) of explants had PASD+ globules, 92% of which were homozygous (n = 1) or heterozygous (n = 11) for the SERPINA1 Z allele, corresponding to nearly 40% of all NASH patients. Overall, the Z allele was present in 10% of all tested liver explants, with 85% of PASD+ cases genotyping homozygous (n = 2) or heterozygous (n = 20), which is far in excess of the estimated 2% in the general population. These results indicate PASD+ A1AT globules (with confirmatory genotyping showing at least 1 Z allele) are commonly observed in NASH, suggesting a synergistic relationship toward liver fibrosis. In addition, the high frequency of SERPINA1 Z alleles in liver transplantation patients supports the utility of pretransplant genotyping.

Data-driven quality assurance to prevent erroneous test results.

Increasing laboratory automation and efficiency requires quality assurance (QA) approaches to ensure that reported results are precise and accurate. Prerequisites for designing optimal QA strategies include an in-depth understanding of the laboratory processes, the expected results, and of the mechanisms that can cause erroneous results. Oftentimes, a laboratory's own data, extracted from the laboratory information system, electronic medical record, and/or clinical data warehouse are necessary to master the aforementioned requirements. Data-driven QA utilizes retrospective and/or prospective laboratory results to minimize errors in the clinical laboratory due to pre-analytical or analytical vulnerabilities. Additionally, exploitation of this data may improve result interpretation. The objective of this review is to illustrate specific examples of data-driven QA approaches for several areas of the clinical laboratory and for different phases of the testing cycle.

Venous Thrombotic Risk in Transgender Women Undergoing Estrogen Therapy: A Systematic Review and Metaanalysis.

BACKGROUND: Transgender women are female individuals who were recorded men at birth based on natal sex. Supporting a person's gender identity improves their psychological health, and gender-affirming hormones reduce gender dysphoria and benefit mental health. For transgender women, estrogen administration has clinically significant benefits. Previous reviews have reported conflicting literature on the thrombotic risk of estrogen therapy in transgender women and have highlighted the need for more high-quality research. CONTENT: To help address the gap in understanding thrombotic risk in transgender women receiving estrogen therapy, we performed a systematic literature review and metaanalysis. Two evaluators independently assessed quality using the Ottawa Scale for Cohort Studies. The Poisson normal model was used to estimate the study-specific incidence rates and the pooled incidence rate. Heterogeneity was measured using Higgins I 2 statistic. The overall estimate of the incidence rate was 2.3 per 1000 person-years (95% CI, 0.8-6.9). The heterogeneity was significant (I 2 = 74%; P = 0.0039). SUMMARY: Our study estimated the incidence rate of venous thromboembolism in transgender women prescribed estrogen to be 2.3 per 1000 person-years, but because of heterogeneity this estimate cannot be reliably applied to transgender women as a group. There are insufficient data in the literature to partition by subgroup for subgroup prohibiting the analysis to control for tobacco use, age, and obesity, which is a major limitation. Additional studies of current estrogen formulations, modes of administration, and combination therapies, as well as studies in the aging transgender population, are needed to confirm thrombotic risk and clarify optimal therapy regimens.

The Vaginal Microbiome of Transgender Men.

BACKGROUND: Hormonal changes influence the composition of vaginal flora, which is directly related to the health of an individual. Transgender men prescribed testosterone experience a vaginal hormone composition that differs from cisgender women. To the author's knowledge, there are no clinical studies evaluating the influence that testosterone administration has on the vaginal microbiome. METHODS: Vaginal swabs were self-collected by a cohort of self-identified healthy transgender men prescribed testosterone for at least 1 year (n = 28) and from cisgender women who were used as the comparator (n = 8). Participants completed a questionnaire to indicate the mode and dose of testosterone administration, sexual history, and vaginal health. Serum was collected for hormone analysis. Bacterial community profiles were assessed with broad-range PCR primers targeting the V3-V4 hypervariable region of the 16S bacterial rRNA, next-generation sequencing, and analysis by phylogenetic placement. RESULTS: Compared to cisgender women, the vaginal floras of transgender men were less likely to have Lactobacillus as their primary genus. Intravaginal estrogen administration was positively associated with the presence of Lactobacillus in transgender men (P = 0.045). Transgender men had a significantly increased relative abundance of >30 species and a significantly higher α diversity (P = 0.0003). The presence of Lactobacillus was significantly associated with a lower α diversity index (P = 0.017). CONCLUSIONS: The vaginal microbiome of transgender men who were assigned a female sex at birth and use testosterone may differ from that of cisgender women. Intravaginal estrogen administration may reduce these differences by promoting colonization with Lactobacillus species and decreasing α diversity.

Clinical Laboratory Practice Recommendations for the Use of Cardiac Troponin in Acute Coronary Syndrome: Expert Opinion from the Academy of the American Association for Clinical Chemistry and the Task Force on Clinical Applications of Cardiac Bio-Markers of the International Federation of Clinical Chemistry and Laboratory Medicine.

This document is an essential companion to the third iteration of the National Academy of Clinical Biochemistry [NACB,8 now the American Association for Clinical Chemistry (AACC) Academy] Laboratory Medicine Practice Guidelines (LMPG) on cardiac markers. The expert consensus recommendations were drafted in collaboration with the International Federation of Clinical Chemistry and Laboratory Medicine Task Force on Clinical Applications of Bio-Markers (IFCC TF-CB). We determined that there is sufficient clinical guidance on the use of cardiac troponin (cTn) testing from clinical practice groups. Thus, in this expert consensus document, we focused on clinical laboratory practice recommendations for high-sensitivity (hs)-cTn assays. This document utilized the expert opinion class of evidence to focus on the following 10 topics: (a) quality control (QC) utilization, (b) validation of the lower reportable analytical limits, (c) units to be used in reporting measurable concentrations for patients and QC materials, (d) 99th percentile sex-specific upper reference limits to define the reference interval; (e) criteria required to define hs-cTn assays, (f) communication with clinicians and the laboratory's role in educating clinicians regarding the influence of preanalytic and analytic problems that can confound assay results, (g) studies on hs-cTn assays and how authors need to document preanalytical and analytical variables, (h) harmonizing and standardizing assay results and the role of commutable materials, (i) time to reporting of results from sample receipt and sample collection, and (j) changes in hs-cTn concentrations over time and the role of both analytical and biological variabilities in interpreting results of serial blood collections.

Transfusion support for transgender men of childbearing age.

BACKGROUND: To date, limited attention has been given to transgender recipients of blood components, particularly transgender men of childbearing age. Here, we highlight the essential information needed to provide transfusion support for this population. CASE REPORT: A 40-year-old transgender man, who retained his uterus and ovaries, presented with severe vaginal hemorrhage following biopsies for a cervical mass. He was admitted to the Gynecology unit and emergency blood was ordered. Because the patient was listed as male in the electronic health record (EHR), the transfusion service prepared uncrossmatched type O, RhD-positive red blood cells (RBC). After the sex/gender incongruence was recognized, the units were switched for Rh-negative. CONCLUSION: This case illustrates particular considerations when caring for transgender patients: gender/sex documentation, decision-making processes when gender/sex-specific care applies, and challenges to the pathology service.

When Gender Identity Doesn't Equal Sex Recorded at Birth: The Role of the Laboratory in Providing Effective Healthcare to the Transgender Community.

BACKGROUND: Transgender is an umbrella term used to describe individuals who identify with a gender incongruent to or variant from their sex recorded at birth. Affirming gender identity through a variety of social, medical, and surgical interventions is critical to the mental health of transgender individuals. In recent years, awareness surrounding transgender identities has increased, which has highlighted the health disparities that parallel this demographic. These disparities are reflected in the experience of transgender patients and their providers when seeking clinical laboratory services. CONTENT: Little is known about the effect of gender-affirming hormone therapy and surgery on optimal laboratory test interpretation. Efforts to diminish health disparities encountered by transgender individuals and their providers can be accomplished by increasing social and clinical awareness regarding sex/gender incongruence and gaining insight into the physiological manifestations and laboratory interpretations of gender-affirming strategies. This review summarizes knowledge required to understand transgender healthcare including current clinical interventions for gender dysphoria. Particular attention is paid to the subsequent impact of these interventions on laboratory test utilization and interpretation. Common nomenclature and system barriers are also discussed. SUMMARY: Understanding gender incongruence, the clinical changes associated with gender transition, and systemic barriers that maintain a gender/sex binary are key to providing adequate healthcare to transgender community. Transgender appropriate reference interval studies are virtually absent within the medical literature and should be explored. The laboratory has an important role in improving the physiological understanding, electronic medical system recognition, and overall social awareness of the transgender community.

Establishing consensus-based, assay-specific 99th percentile upper reference limits to facilitate proper utilization of cardiac troponin measurements.

Implementation of the 99th percentile as the upper reference limit for cardiac troponin (cTn) assays is a seemingly lucid recommendation, but, in reality, is incredibly complex. Lack of harmonization between cTn assays diminishes the ability to have a single medical decision point across manufacturer assay/instruments. Moreover, even within a single cTn assay there are several published values corresponding to the "99th percentile". Variability in the determined value is primarily a function of population selection including: sample size, age, sex, exclusion criteria, and statistical methods. Given the complexities associated with this value, some countries have taken an expert consensus approach to endorsing harmonized, assay-specific, cTn 99th percentile values. The purpose of this manuscript is to highlight the intricacies associated with selecting a cTn 99th percentile and to review the approach that Australia used to endorse a nationwide upper reference limit for the Architect STAT hs-cTnI assay.

Method-dependent Discrepancies in Fetal Hemoglobin Quantification in Patients With Hemoglobin S.

Hemoglobin F (HbF) concentration is used in the diagnosis of certain hemoglobinopathies and accurate quantification is central to treatment of patients with sickle cell disease. The 2 most commonly used methods to quantify HbF are high performance liquid chromatography and capillary zone electrophoresis. This study reports discrepancies in HbF quantification between these methods when hemoglobin S is present in the sample. Clinicians and investigators should be mindful of the method used for HbF quantification when evaluating and treating patients who produce hemoglobin S.