Primer Part 1 - Preparing a laboratory quality improvement project.

Quality in laboratory medicine encompasses multiple components related to total quality management, including quality control (QC), quality assurance (QA), quality indicators, and quality improvement (QI). Together, they contribute to minimizing errors (pre-analytical, analytical, or post-analytical) in clinical service delivery and improving process appropriateness and efficiency. In contrast to static quality benchmarks (QC, QA, quality indicators), the QI paradigm is a continuous approach to systemic process improvement for optimizing patient safety, timeliness, effectiveness, and efficiency. Healthcare institutions have placed emphasis on applying the QI framework to identify and improve healthcare delivery. Despite QI's increasing importance, there is a lack of guidance on preparing, executing, and sustaining QI initiatives in the field of laboratory medicine. This has presented a significant barrier for clinical laboratorians to participate in and lead QI initiatives. This three-part primer series will bridge this knowledge gap by providing a guide for clinical laboratories to implement a QI project that issuccessful and sustainable. In the first article, we introduce the steps needed to prepare a QI project with focus on relevant methodology and tools related to problem identification, stakeholder engagement, root cause analysis (e.g., fishbone diagrams, Pareto charts and process mapping), and SMART aim establishment. Throughout, we describe a clinical vignette of a real QI project completed at our institution focused on serum protein electrophoresis (SPEP) utilization. This primer series is the first of its kind in laboratory medicine and will serve as a useful resource for future engagement of clinical laboratory leaders in QI initiatives.

Pediatric reference intervals for hematology parameters in healthy infants and young children in Iran.

INTRODUCTION: Defining accurate age- and sex-specific reference intervals (RIs) for hematology parameters, especially for the pediatric population, is important for making an appropriate clinical diagnosis. To address gaps, we established age-specific RIs for 11 hematologic parameters in Iranian children younger than 30 months for the first time. METHODS: Fresh whole blood samples collected from a total of 344 participants (males: 158 and females: 186) ages 3 days to 30 months, with a mean age of 12.91 ± 7.15 months, were recruited from healthcare centers in Mashhad, Iran. Hematologic parameters, including complete blood count (CBC), were analyzed on the Sysmex auto-analyzer system (KX-21 N). RIs were calculated with 90% confidence intervals using the direct method based on CLSI Ep28-A3 and C28-A3 guidelines. RESULTS: None of the CBC parameters required sex partitioning. Of 11 CBC parameters, six required age partitions of 3 days-<4 months, 4-<10, 10-<15, and 4-<30 months. Five parameters (i.e., white blood cell count, mean corpuscular hemoglobin concentration, mean platelet volume, red cell distribution width, and platelet distribution width) did not demonstrate age-specific changes. RIs of red blood cell count and hematocrit, as well as hemoglobin, increased with age, while mean corpuscular volume, mean corpuscular hemoglobin, and platelet count, decreased with age. CONCLUSION: In this study, we established RIs for 11 hematology parameters in young children. Age partitioning was required for six parameters demonstrating marked changes during the early period of growth and development and necessitating the use of pediatric-specific reference standards.

Comparison of reference intervals for biochemical and hematology markers derived by direct and indirect procedures based on the Isfahan cohort study.

INTRODUCTION: Indirect methods for reference interval (RI) establishment apply statistical techniques to generate RIs for test result interpretation using stored laboratory data. They present unique advantages relative to traditional direct approaches such as fewer resource requirements; however, there is debate regarding their performance. Herein, we aimed to compare indirect and direct approaches for RI establishment by harnessing data from the Isfahan Cohort Study (ICS). This cohort includes both healthy individuals and those with a history of disease, enabling a direct comparison. METHODS: Participants were recruited as part of ICS, including 6504 adults aged 34 years and older. Sociodemographic characteristics, anthropometry, blood pressure, various biochemical indices, and hematology parameters were collected. The refineR method was used to establish indirect RIs (before applying exclusion criteria). Direct RIs were calculated using nonparametric methods per CLSI EP28-A3 guidelines (after applying exclusion criteria). Bias ratios were calculated for each parameter to assess significant differences in estimations. RESULTS: Direct and indirect RI estimations for most hematological and biochemical parameters were comparable. Statistically significant bias ratios between methods were observed for the upper limits of total cholesterol, triglycerides, high-density lipoprotein cholesterol (HDL-C), hemoglobin (female), and platelet count as well as the lower limits of mean corpuscular hemoglobin (female), mean corpuscular volume, hemoglobin, and hematocrit (female). CONCLUSION: Data presented indicate RIs derived from direct and indirect approaches are similar, but not identical. Further work should focus on the clinical significance of such differences as well as the investigation of necessary data-cleaning criteria before indirect method application.

Age- and sex-specific reference intervals for superoxide dismutase enzyme and several minerals in a healthy adult cohort.

INTRODUCTION: The aim of this study was to establish RIs for clinically important markers including superoxide dismutase (SOD), serum copper, zinc, calcium, magnesium, and phosphate in a cohort of healthy Iranian adults. MATERIALS: A subsample from MASHAD cohort study was used to assess serum SOD, copper, zinc, calcium, magnesium and phosphate. Serum SOD was measured according to its inhibitory potential of pyrogallol oxidation. Micro- and macro-minerals were measured using flame atomic absorption spectrometry and a BT3000 autoanalyzer, respectively. Sex- and age-specific RIs were then calculated based on CLSI Ep28-A3 guidelines. RESULTS: Reference value distributions for studied parameters did not demonstrate any age-specific differences that were statistically significant. In addition, sex partitioning was not required for all parameters, apart from serum magnesium, which showed a wider range in females (0.81-1.26 mg/dl) compared with males (0.82-1.23 mg/dl). CONCLUSION: The RIs established in this study can be expected to improve mineral assessment and clinical decision-making in the Iranian adult population.

Comprehensive laboratory reference intervals for routine biochemical markers and pro-oxidant-antioxidant balance (PAB) in male adults.

BACKGROUND: Reference values of biochemical markers are influenced by various parameters including age, sex, region, and lifestyle. Hence, we aimed to determine age- and BMI-specific reference intervals (RIs) for important clinical biomarkers in a healthy adult male population from northeastern Iran. This is also the first study to investigate reference values for pro-oxidant-antioxidant balance (PAB). METHODS: Seven hundred and twenty (720) healthy men, aged 20-60 years, were recruited from Sarakhs in the northeast region of Iran. Reference values for lipid profiles (total cholesterol, triglyceride, HDL-C and LDL-C), fasting blood glucose, inflammatory factors (hs-CRP and PAB), minerals (zinc and copper), uric acid, and blood pressure were measured and statistically analyzed to establish accurate age- and BMI-specific RIs in alignment with CLSI Ep28-A3 guidelines. RESULTS: RIs for lipid profiles, inflammatory factors, minerals, and uric acid required no age partitioning with the exception of fasting blood glucose and blood pressure, which demonstrated significantly higher values in subjects aged 50 years and older. Among these biomarkers, only uric acid, blood pressure, and triglycerides demonstrated statistically significant increases in reference value concentrations with increasing BMI. CONCLUSION: In this study, age- and BMI-specific RIs for several biochemical markers were determined in healthy adult Iranian men. Partitioning by age and BMI was only required for a few analytes with most demonstrating no statistically significant changes with these covariates. These data can be useful to monitor various diseases in male adults with varying BMI in this region and others.

Comprehensive hematological reference intervals in a healthy adult male population.

Reference intervals (RIs) are important tools for improving medical decision-making. Hematology reference values can be influenced by important covariates such as genetic and environmental factors, rendering it essential to define RIs for specific populations. Therefore, we aimed to establish accurate and robust RIs for hematological markers in a healthy adult male Iranian population. This cross-sectional study was conducted in a population of 723 males aged 20-60 years old. Hematological parameters were routinely measured using a Sysmex auto analyser system (KX-21 N). The quality of assays was monitored using commercial quality control samples. The nonparametric rank method, as recommended by the Clinical and Laboratory Standards Institute (CLSI) guidelines, was used to calculate the 2.5th and 97.5th percentiles as the lower and upper reference limits, respectively. Of the 12 hematological parameters assessed, only mean platelet volume (MPV) demonstrated significant age-specific differences, requiring two partitions from 20 to 35 years (8.7-12.2 fL) and 35 to 65 years (8.5-11.5 fL). The remaining hematological parameters (e.g. leukocyte, erythrocyte, and platelet parameters) could be defined by one age range. This study established RIs for 12 routinely used hematological parameters in a healthy male population living in the northeastern region of Iran. Established RIs differed from those previously reported by other cohorts, highlighting the importance of population-specific RIs.