Plasma steroid profiling combined with machine learning for the differential diagnosis in mild autonomous cortisol secretion from nonfunctioning adenoma in patients with adrenal incidentalomas.

BACKGROUND: To assess the diagnostic value of combining plasma steroid profiling with machine learning (ML) in differentiating between mild autonomous cortisol secretion (MACS) and nonfunctioning adenoma (NFA) in patients with adrenal incidentalomas. METHODS: The plasma steroid profiles data in the laboratory information system were screened from January 2021 to December 2023. EXtreme Gradient Boosting (XGBoost) was applied to establish diagnostic models using plasma 24-steroid panels and/or clinical characteristics of the subjects. The SHapley Additive exPlanation (SHAP) method was used for explaining the model. RESULTS: 76 patients with MACS and 86 patients with NFA were included in the development and internal validation cohort while the external validation cohort consisted of 27 MACS and 21 NFA cases. Among five ML models evaluated, XGBoost demonstrated superior performance with an AUC of 0.77 using 24 steroid hormones. The SHAP method identified five steroids that exhibited optimal performance in distinguishing MACS from NFA, namely dehydroepiandrosterone (DHEA), 11-deoxycortisol, 11ß-hydroxytestosterone, testosterone, and dehydroepiandrosteronesulfate (DHEAS). Upon incorporating clinical features into the model, the AUC increased to 0.88, with a sensitivity of 0.77 and specificity of 0.82. Furthermore, the results obtained through SHAP revealed that lower levels of testosterone, DHEA, LDL-c, BMI, and ACTH along with higher level of 11-deoxycortisol significantly contributed to the identification of MACS in the model. CONCLUSIONS: We have elucidated the utilization of ML-based steroid profiling to discriminate between MACS and NFA in patients with adrenal incidentalomas. This approach holds promise for distinguishing these two entities through a single blood collection.

Magnetically driven capsules with multimodal response and multifunctionality for biomedical applications.

Untethered capsules hold clinical potential for the diagnosis and treatment of gastrointestinal diseases. Although considerable progress has been achieved recently in this field, the constraints imposed by the narrow spatial structure of the capsule and complex gastrointestinal tract environment cause many open-ended problems, such as poor active motion and limited medical functions. In this work, we describe the development of small-scale magnetically driven capsules with a distinct magnetic soft valve made of dual-layer ferromagnetic soft composite films. A core technological advancement achieved is the flexible opening and closing of the magnetic soft valve by using the competitive interactions between magnetic gradient force and magnetic torque, laying the foundation for the functional integration of both drug release and sampling. Meanwhile, we propose a magnetic actuation strategy based on multi-frequency response control and demonstrate that it can achieve effective decoupled regulation of the capsule's global motion and local responses. Finally, through a comprehensive approach encompassing ideal models, animal ex vivo models, and in vivo assessment, we demonstrate the versatility of the developed magnetic capsules and their multiple potential applications in the biomedical field, such as targeted drug delivery and sampling, selective dual-drug release, and light/thermal-assisted therapy.

Asymmetric magnetic levitation for density-based measurement and analysis.

BACKGROUND: Magnetic levitation (MagLev) based on negative magnetophoresis represents a promising technology for density-based analysis and manipulation of nonmagnetic objects. This approach has garnered considerable interest across multiple fields, such as chemistry, materials science, and biochemistry, primarily due to its inherent simplicity, precision, and cost-effectiveness. However, it is essential to recognize that frequently used MagLev configurations, including standard MagLev and axial MagLev, are not without their limitations. These configurations often struggle to strike a balance between levitation performance, ease of operation, and visibility. Therefore, it is necessary to develop a new MagLev configuration to address the aforementioned issue. RESULTS: This work describes the development of an innovative MagLev, termed "asymmetric MagLev", achieved by combining a ring magnet and a cylinder magnet as up-down asymmetric magnetic field sources. The asymmetric design overcomes the physical obstacles along the centerline of the standard MagLev, offering unique open-structure advantages, including easy handling of samples, the ability to observe samples from the top or bottom, and no restrictions on the container height. Meanwhile, comparative analysis reveals a considerable enhancement in the working distance of the asymmetric MagLev without significantly sacrificing the measurement range compared to the axial MagLev. Notably, the asymmetric MagLev achieves a remarkable sensitivity of up to about 1.8 × 104 mm (g cm-3)-1, surpassing the axial MagLev by approximately 30 times. Furthermore, experimental results validate the successful application of the asymmetric MagLev in density measurement and quality detection of small-sized objects. SIGNIFICANCE: This pioneering configuration represents the first utilization of up-down asymmetric magnets in the field of MagLev. Through the integration of an axially magnetized ring magnet and a cylinder magnet, the asymmetric MagLev design overcomes the limitations associated with conventional MagLev configurations. This innovative design exhibits outstanding operational capabilities and levitation performance, making it suitable for a wide range of applications in density-based measurement and analysis.

Radial Magnetic Levitation and Its Application to Density Measurement, Separation, and Detection of Microplastics.

This work describes the development of radial magnetic levitation (MagLev) using two radially magnetized ring magnets to solve the problem of limited operational spaces in standard MagLev and the major shortcoming of a short working distance in axial MagLev. Interestingly and importantly, we demonstrate that for the same magnet size, this new configuration of MagLev doubles the working distance over the axial MagLev without significantly sacrificing the density measurement range, whether for linear or nonlinear analysis. Meanwhile, we develop a magnetic assembly method to fabricate the magnets for the radial MagLev, where multiple magnetic tiles with single-direction magnetization are used as assembly elements. On this basis, we experimentally demonstrate that the radial MagLev has good applicability in density-based measurement, separation, and detection and show its advantages in improving separation performance compared with the axial MagLev. The open structure of two-ring magnets and good levitation characteristics make the radial MagLev have great application potential, and the performance improvement brought by adjusting the magnetization direction of magnets provides a new perspective for the magnet design in the field of MagLev.

Development and clinical evaluation of an online automated quality control system for improving laboratory quality management.

BACKGROUND: We developed an efficient online automated quality control (AUTO QC) system and tested its feasibility on automatic laboratory assembly lines. METHODS: AUTO QC is based on developed quality control software (Smart QC) and designed adaptable consumables before. We applied the system to two assembly lines in our laboratory. Using third-party quality control samples, we evaluated the impact of the online AUTO QC system on out-of-control rate, biosecurity risk, turnaround time (TAT) and cost. RESULTS: AUTO QC significantly decreased the occurrence rate of the Westgard quality control rules 13S/22S/R4s and 12S, representing out-of-control and warning, respectively. The out-of-control rates were reduced by 58%, and the potential biosecurity risk of the samples decreased by 90%. The AUTO QC implementation also reduced the median TAT (by 7 min), the number of full-time employees and the cost of the quality control samples (by 45%). CONCLUSIONS: The total laboratory AUTO QC system can improve the quality and stability of QC testing and reduce cost.

UHPLC-MS/MS-Based Metabolomics and Clinical Phenotypes Analysis Reveal Broad-Scale Perturbations in Early Pregnancy Related to Gestational Diabetes Mellitus.

Gestational diabetes mellitus (GDM) is the most common metabolic disturbance during pregnancy, with adverse effects on both mother and fetus. The establishment of early diagnosis and risk assessment model is of great significance for preventing and reducing adverse outcomes of GDM. In this study, the broad-scale perturbations related to GDM were explored through the integration analysis of metabolic and clinical phenotypes. Maternal serum samples from the first trimester were collected for targeted metabolomics analysis by using ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). Statistical analysis was conducted based on the levels of the 184 metabolites and 76 clinical indicators from GDM women (n =60) and matched healthy controls (n =90). Metabolomics analysis revealed the down-regulation of fatty acid oxidation in the first trimester of GDM women, which was supposed to be related to the low serum level of dehydroepiandrosterone.While the significantly altered clinical phenotypes were mainly related to the increased risk of cardiovascular disease, abnormal iron metabolism, and inflammation. A phenotype panel established from the significantly changed serum indicators can be used for the early prediction of GDM, with the area under the receiver-operating characteristic curve (ROC) 0.83. High serum uric acid and C-reaction protein levels were risk factors for GDM independent of body mass indexes, with ORs 4.76 (95% CI: 2.08-10.90) and 3.10 (95% CI: 1.38-6.96), respectively. Predictive phenotype panel of GDM, together with the risk factors of GDM, will provide novel perspectives for the early clinical warning and diagnosis of GDM.

Establishment of Reference Interval and Aging Model of Homocysteine Using Real-World Data.

Objective: The level of Homocysteine (Hcy) in males is generally higher than that of females, but the same reference interval (RI) is often used in clinical practice. This study aims to establish a sex-specific RI of Hcy using five data mining algorithms and compare these results. Furthermore, age-related continuous RI was established in order to show the relationship between Hcy concentration distribution and age. Methods: A total of 20,801 individuals were included in the study and Tukey method was used to identify outliers in subgroups by sex and age. Multiple linear regression and standard deviation ratio (SDR) was used to determine whether the RI for Hcy needs to be divided by sex and age. Five algorithms including Hoffmann, Bhattacharya, expectation maximization (EM), kosmic and refineR were utilized to establish the RI of Hcy. Generalized Additive Models for Location Scale and Shape (GAMLSS) algorithm was used to determine the aging model of Hcy and calculate the age-related continuous RI. Results: RI of Hcy needed to be partitioned by sex (SDR = 0.735 > 0.375). RIs established by Hoffmann, Bhattacharya, EM (for females) and kosmic are all within the 95% CI of reference limits established by refine R. The Sex-specific aging model of Hcy showed that the upper limits of the RI of Hcy declined with age beginning at age of 18 and began to rise approximately after age of 40 for females and increased with age for males. Conclusion: The RI of Hcy needs to be partitioned by sex. The RIs established by the five data mining algorithms showed good consistency. The dynamic sex and age-specific model of Hcy showed the pattern of Hcy concentration with age and provide more personalized tools for clinical decisions.

Water-based ferrofluid with tunable stability and its significance in nuclear wastewater treatment.

The treatment of nuclear wastewater is one of the most urgent and arduous tasks currently, but traditional adsorption materials are significantly limited in practice due to their high demands on auxiliary operations (e.g., shaking or centrifugation) caused by poor stability or recyclability. To tackle this challenge, a water-based ferrofluid composed of magnetic nanoparticles grown in polyethylenimine branches is reported and applied to nuclear wastewater treatment. It is demonstrated that the ferrofluid can keep stable spontaneously in a wide pH range (3-11) out of their ultra-small size, strong electropositivity as well as high charge buffering capacity to achieve shaker-free adsorption, and can be magnetically separated after the neutralization of their positive charge to achieve convenient recycle. Meanwhile, it is found that the ferrofluid shows wide pH/adsorbate applicability and strong ion selectivity in radionuclides absorption. Furthermore, it is anticipated to achieve maximum adsorption capacities for U(VI), Sr(II) and Co(II) as high as 331.5, 427.8 and 759.6 mg/g, respectively. With these characteristics, this ferrofluid outperforms other reported adsorbents. In conclusion, this work provides a practical and effective radioactive wastewater treatment strategy, and enlightens the development of materials for other applications facing the dilemma of incompatible stability and recyclability.

A robust method for simultaneous measurement of serum 25(OH)D, 1,25(OH)2 D, and 24,25(OH)2 D by liquid chromatography-tandem mass spectrometry with efficient separation of 3-epi analogs, 23R,25(OH)2 D3 , and 4ß,25(OH)2 D3.

BACKGROUND: This study aimed to establish a robust, simple method to detect 25-hydroxyvitamin D3 (25(OH)D3 ), 25-hydroxyvitamin D2 (25(OH)D2 ), 1,25-dihydroxyvitamin D3 (1,25(OH)2 D3 ), 1,25-dihydroxyvitamin D2 (1,25(OH)2 D2 ), 24,25-dihydroxyvitamin D3 (24,25(OH)2 D3 ), and 24,25-dihydroxyvitamin D2 (24,25(OH)2 D2 ) simultaneously with efficient separation of 3-epi 25(OH)D3 , 3-epi 24,25(OH)2 D3 , 23R,25(OH)2 D3 , and 4ß,25-dihydroxyvitamin D3 (4ß,25(OH)2 D3 ) by liquid chromatography-tandem mass spectrometry (LC-MS/MS). METHOD: This method was validated according to procedures established by Clinical and Laboratory Standards Institute (CLSI) and then applied in healthy population to determine the distribution of the vitamin D metabolites by LC-MS/MS. RESULTS: The total-run CV% of 25(OH)D3 , 25(OH)D2 , 24,25(OH)2 D3 , 24,25(OH)2 D2 , 1,25(OH)2 D3 , and 1,25(OH)2 D2 were 6.30%-8.40%, 5.00%-8.40%, 5.90%-9.00%, 5.60%-9.00%, 5.60%-8.00%, and 7.00%-9.70%, respectively. The linearity correlation coefficients r of these six vitamin D metabolites were >0.99. The matrix effects of 25(OH)D3 , 25(OH)D2 , 24,25(OH)2 D3 , 24,25(OH)2 D2 , 1,25(OH)2 D3 , and 1,25(OH)2 D2 were 90.6%-103.3%, 97.3%-106.3%, 90.7%-106.3%, 100.7%-114.5%, 97.9%-104.6%, and 97.0%-111.0%. The trueness values of 25(OH)D3 , 25(OH)D2 , and 24,25(OH)2 D3 were 93.8%-103.0%, 101.0%, and 96.3%-100%, respectively. CONCLUSION: This study successfully established an efficient, accurate, robust method for simultaneous measurement of serum 25(OH)D, 1,25(OH)2 D, and 24,25(OH)2 D by LC-MS/MS with efficient separation of 3-epi analogs, 23R,25(OH)2 D3 , and 4ß,25(OH)2 D3 .

Data mining: traditional spring festival associated with hypercholesterolemia.

BACKGROUND: Serum lipid concentrations are affected by long-term high-fat diets; thus, we hypothesize that lipid levels increase after the Spring Festival in China. METHOD: In total, 20,192 individuals (male: n=10,108, female: n=10,084) were enrolled in this retrospective cross-sectional study based on clinical data from the Laboratory Information System (LIS) and Hospital Information System (HIS) in Peking Union Medical College Hospital from 2014 to 2018. Total cholesterol (TC), triglycerides (TGs), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) were analyzed. RESULTS: The serum TC [male vs. female: (4.71 ± 0.90 vs. 4.56 ± 0.85) mmol/L], TG [male vs. female: (1.71 ± 1.56 vs. 1.02 ± 0.68) mmol/L], and LDL-C [male vs. female: (3.01 ± 0.77 vs. 2.73 ± 0.74) mmol/L] levels were significantly higher in males than in females (P < 0.001); serum HDL-C [male vs. female: (1.18 ± 0.28 vs. 1.50 ± 0.34) mmol/L] was significantly lower in males (P < 0.001). In February, the TC, TG, and LDL-C levels were 8.4%, 16.3%, and 9.3% higher than the lowest levels recorded, respectively. The prevalence of dyslipidemia of the two weeks before the Spring festival was significantly lower than that of the first week after the Spring festival (43.6% (168/385) vs. 54.1% (126/233), P=0.007). Additionally, the prevalence of dyslipidemia was statistically higher in the first week after the Spring Festival than in May-January. CONCLUSION: Higher TC, TG, and LDL-C in winter could be associated with high-fat diets during the Spring Festival. The Spring Festival was immediately followed by a higher lipid concentrations. Thus, we don't recommend lipid assessment or physical examination immediately after the holiday especially Spring festival.

Metabolic profiling in early pregnancy and associated factors of folate supplementation: A cross-sectional study.

BACKGROUND: Pregnancy generally alters the balance of maternal metabolism, but the molecular profiles in early pregnancy and associated factors of folate supplementation in pregnant women remains incompletely understood. METHODS: Untargeted metabonomics based on high-performance liquid chromatography-high-resolution mass spectrometry integrated with multivariate metabolic pathway analysis were applied to characterize metabolite profiles and associated factors of folate supplements in early pregnancy. The metabolic baseline of early pregnancy was determined by metabolic analysis of 510 serum samples from 131 non-pregnant and 379 pregnant healthy Chinese women. The pathophysiology of adaptive reactions and metabolic challenges induced by folate supplementation in early pregnancy was further compared between pregnant women with (n = 168) and without (n = 184) folate supplements. RESULTS: Compared with non-pregnant participants, 106 metabolites, majority of which are related to amino acids and lysophosphatidylcholine/phosphatidylcholine, and 13 metabolic pathways were significantly changed in early pregnancy. The supplementation of folate in early pregnancy induced marked changes in N-acyl ethanolamine 22:0, N-acyl taurine 18:2, glycerophosphoserine 44:1 and 8,11,14-eicosatrienoate, proline, and aminoimidazole ribotide levels. CONCLUSIONS: During early pregnancy, the metabolism of amino acids significantly changes to meet the physiological requirements of pregnant women. Folate intake may change glucose and lipid metabolism. These findings provide a comprehensive landscape for understanding the basic characteristics and gestational metabolic networks of early pregnancy and folate supplementation. This study provides a basis for further research into the relationship between metabolic markers and pregnancy diseases. TRIAL REGISTRATION: This study protocol was registered on www.ClinicalTrials.gov, NCT03651934, on August 29, 2018 (prior to recruitment).

Establishment of Early Pregnancy Related Thyroid Hormone Models and Reference Intervals for Pregnant Women in China Based on Real World Data.

Thyroid hormone reference intervals are crucial for diagnosing and monitoring thyroid dysfunction during early pregnancy, and the dynamic change trend of thyroid hormones during pregnancy can assist clinicians to assess the thyroid function of pregnant women. This study aims to establish early pregnancy related thyroid hormones models and reference intervals for pregnant women. We established two derived databases: derived database* and derived database#. Reference individuals in database* were used to establish gestational age-specific reference intervals for thyroid hormones and early pregnancy related thyroid hormones models for pregnant women. Individuals in database# were apparently healthy non-pregnant women. The thyroid hormones levels of individuals in database# were compared with that of individuals in database* using nonparametric methods and the comparative confidence interval method. The differences in thyroid stimulating hormone and free thyroxine between early pregnant and non-pregnant women were statistically significant (p<0.0001). The reference intervals of thyroid stimulating hormone, free thyroxine and free triiodothyronine for early pregnant women were 0.052-3.393 µIU/ml, 1.01-1.54 ng/dl, and 2.51-3.66 pg/ml, respectively. Results concerning thyroid stimulating hormone and free thyroxine reference intervals of early pregnancy are comparable with those from other studies using the same detection platform. Early pregnancy related thyroid hormones models showed various change patterns with gestational age for thyroid hormones. Early pregnancy related thyroid hormones models and reference intervals for pregnant women were established, so as to provide accurate and reliable reference basis for the diagnosing and monitoring of maternal thyroid disfunction in early pregnancy.

Effect of sample size and the traditional parametric, nonparametric, and robust methods on the establishment of reference intervals: Evidence from real world data.

Sample size and statistical methods are critical for establishing reference intervals (RIs) but they tend to be overlooked. In this study, we used R (3.6.3) to stratify the reference individuals by sex, and then stratified them using the random sampling method. Fourteen sub-data sets with a sample size of 40, 80, 120, 160, 200, 500, 800, 1000, 1500, 2000, 2500, 3000, 3500, and 4000 were extracted, respectively. The sex ratios of all sub-data sets were 1:1. Transformed parametric (using log transformation), nonparametric, and robust approaches as described in the Clinical and Laboratory Standards Institute guidelines were adopted to establish the RIs and the 90% confidence interval of the thyroid-stimulating hormone (TSH) using data from the sub-data sets. The Bland-Altman plot was used to evaluate the consistency of the upper and lower limits of the RIs established using the three methods. The upper and lower limits of TSH RI tended to be stable starting from the data set with a sample size of 1500. The RIs established using the three methods were more consistent when using a sample size greater than or equal to 2000.

Reference Intervals for Thyroid-Associated Hormones and the Prevalence of Thyroid Diseases in the Chinese Population.

BACKGROUND: Thyroid diseases are highly prevalent worldwide, but their diagnosis remains a challenge. We established reference intervals (RIs) for thyroid-associated hormones and evaluated the prevalence of thyroid diseases in China. METHODS: After excluding outliers based on the results of ultrasound screening, thyroid antibody tests, and the Tukey method, the medical records of 20,303 euthyroid adults, who visited the Department of Health Care at Peking Union Medical College Hospital from January 2014 to December 2018, were analyzed. Thyroid-associated hormones were measured by the Siemens Advia Centaur XP analyzer. The RIs for thyroid-associated hormones were calculated according to the CLSI C28-A3 guidelines, and were compared with the RIs provided by Siemens. The prevalence of thyroid diseases over the five years was evaluated and compared using the chi-square test. RESULTS: The RIs for thyroid stimulating hormone (TSH), free thyroxine (FT4), free triiodothyronine (FT3), total thyroxine (TT4), and total triiodothyronine (TT3) were 0.71-4.92 mIU/L, 12.2-20.1 pmol/L, 3.9-6.0 pmol/L, 65.6-135.1 nmol/L, and 1.2-2.2 nmol/L, respectively. The RIs of all hormones except TT4 differed significantly between males and females. The RIs of TSH increased with increasing age. The prevalence of overt hypothyroidism, overt hyperthyroidism, subclinical hypothyroidism, and subclinical hyperthyroidism was 0.5% and 0.8%, 0.2% and 0.6%, 3.8% and 6.1%, and 3.3% and 4.7% in males and females, respectively, which differed from those provided by Siemens. CONCLUSIONS: Sex-specific RIs were established for thyroid-associated hormones, and the prevalence of thyroid diseases was determined in the Chinese population.

LC-MS/MS quantification of progesterone in ovariectomized miniature swine and its application for preliminary pharmacokinetic study of a novel vaginal sustained release system.

OBJECTIVE: We here established a simple, fast, robust and sensitive LC-MS/MS method and validated as well for the quantitative analysis of progesterone (PGT) in ovariectomized (OVX) miniature swine plasma. The method was successfully applied to characterize the pharmacokinetics of a progesterone vaginal drug delivery system. METHODS: Megestrol acetate was utilized as an internal standard (IS). The separation and detection of PGT from endogenous interference was performed successfully by liquid chromatography with gradient elution and mass spectrometry equipped with positive ESI source using MRM mode. The EVA intravaginal rings (IVRs) were manufactured by hot-melt extrusion (HME), afterward were administrated vaginally to OVX minipigs to evaluate PK study. RESULTS: The calibration curve for swine plasma samples across the concentration ranged between 0.25 ng/mL and 100 ng/mL. The intra- and inter-assay accuracy and precision were lower than ±5% and 5.88%, respectively. Recoveries of PGT and IS were ranging from 114-119% and 96.5-112%, respectively. In vitro study showed that the EVA IVRs release 18 mg/day of PGT continuously over 7 days, and corresponding mean PGT plasma concentration in OVX minipigs (CAVG) was 4.892 ng/mL. CONCLUSION: All the study produced reliable results for the measurement of PGT concentration in miniature swine plasma and the method was successfully applied to a PK study for PGT vaginal ring in miniature pigs, which may lay the foundation for further research on the progesterone preparations intended for in assisted reproductive technology.

An evaluation of urine and serum iodine status in the population of Tibet, China: No longer an iodine-deficient region.

OBJECTIVES: Iodine is a critical trace element for the synthesis of thyroid-related hormones, and either low or high iodine status can lead to thyroid dysfunction. This study aimed to evaluate the iodine status of the Tibetan population. METHODS: From September 2016 to August 2018, we enrolled 1499 healthy adults from three areas of varying altitudes in Tibet. Urine iodine concentrations (UICs), adjusted UICs, and serum iodine concentrations (SICs) were measured using inductively coupled plasma mass spectrometry. RESULTS: The median UIC, adjusted UIC, and SIC was 137.9 µg/L, 118.4 µg/gCr, and 58.3 µg/L, respectively. Of the participants, 30.4% had UICs <100 µg/L, 63.0% had UICs ranging from 100 to 300 µg/L, and 9.6% had UICs >300 µg/L. The correlation between UIC, adjusted UIC, and SIC was good (r > 0.65, P < 0.01). The SICs were more stable than the UICs, and were not associated with age or sex. The prevalence of clinical hyperthyroidism, clinical hypothyroidism, subclinical hyperthyroidism, subclinical hypothyroidism, positive thyroid peroxide antibody, positive thyroglobulin antibody, either positive and both positive was 0.5%, 1.3%, 1.7% and 17.9%, 9.3%, 6.5%, 12.5%, and 2.5%, respectively. The prevalence of almost all thyroid disorders was higher in women than in men. CONCLUSION: This multicenter cross-sectional study found that the human iodine status of adults in Tibet was considered adequate, based on the World Health Organization's criteria.

Effects of calcium dobesilate (CaD) interference on serum creatinine measurements: a national External Quality Assessment (EQA)-based educational survey of drug-laboratory test interactions.

Objectives: Drug-laboratory test interactions (DLTIs) are one of the major sources of laboratory errors. Calcium dobesilate (CaD) interference on serum creatinine testing is a widespread problem that has long been ignored in China. A national EQA-based survey was launched to investigate the current status of CaD interference on creatinine routine methods used in China and enhance the education of CaD interference in clinical laboratories. Methods: A descriptive survey was developed to characterize the status quo of Chinese laboratory professionals' cognition to CaD interference. Four of survey samples which were spiked with/without interference additive were shipped to 175 participant laboratories. The target reference values from a reference measurement procedure were compared against the results from participating laboratories to evaluate the CaD interference on serum creatinine measurements using enzymatic method or Jaffé method. Results: The lack of knowledge of DLTIs and the barriers to collect information from pharmacological and laboratory data systems had become the main problems on implementing DLTIs education in China. A significant negative influence of CaD on enzymatic method was observed regardless of measurement platforms. Jaffé method was generally free from interaction with CaD but showed poor precision and accuracy at low creatinine concentrations. Conclusions: More efforts should be made to enhance the education of DLTIs in clinical laboratories in China.

Real-world big-data studies in laboratory medicine: Current status, application, and future considerations.

With the recent developments in information technology, real world big data studies (RWBDSs) have attracted increasing attention in the field of medicine. In RWBDSs, clinical laboratory data is an important part of the wider scope of real-world medical data, and its standardized use is critical for the generation of high-quality real-world evidence. To improve the core functioning and competitiveness of clinical laboratories as well as provide high-quality medical services for patients, it is important to construct an information analysis model and perform RWBDSs. However, among the majority of developing countries, as well as in some developed countries, due to the poorly developed neglect of data formatting standards information construction and the lack of consideration for, and experience with, the ideas and methods of RWBDSs, many clinical laboratories are unable to make use of the vast amount of data stored in their systems. Additionally, in the literature, there remain many areas that require improvements, such as the correct misuse of research methods, appropriate unreasonable data presentation methods, and optimal opaque methods for data cleaning, storage, and mining. In this review, we describe both the advantages and disadvantages of RWBDSs in laboratory medicine. In addition, we summarize the current application and methods of RWBDS in laboratory medicine from seven different perspectives: the establishment of a reference interval, patient data-based real time quality control, diagnostic or prognostic modeling, epidemiological investigation, laboratory management, analysis of sources of variations for analytes, and external quality assessment. Finally, we discuss the future prospects of this research. This review can provide the basis for clinical laboratories to carry out real world research; additionally, it promotes and standardizes RWBDS in laboratory medicine.