Insights from semi-structured interviews on integrating artificial intelligence in clinical chemistry laboratory practices.

BACKGROUND: Artificial intelligence (AI) is gradually transforming the practises of healthcare providers. Over the last two decades, the advent of AI into numerous aspects of pathology has opened transformative possibilities in how we practise laboratory medicine. Objectives of this study were to explore how AI could impact the clinical practices of professionals working in Clinical Chemistry laboratories, while also identifying effective strategies in medical education to facilitate the required changes. METHODS: From March to August 2022, an exploratory qualitative study was conducted at the Section of Clinical Chemistry, Department of Pathology and Laboratory Medicine, Aga Khan University, Karachi, Pakistan, in collaboration with Keele University, Newcastle, United Kingdom. Semi-structured interviews were conducted to collect information from diverse group of professionals working in Clinical Chemistry laboratories. All interviews were audio recorded and transcribed verbatim. They were asked what changes AI would involve in the laboratory, what resources would be necessary, and how medical education would assist them in adapting to the change. A content analysis was conducted, resulting in the development of codes and themes based on the analyzed data. RESULTS: The interviews were analysed to identify three primary themes: perspectives and considerations for AI adoption, educational and curriculum adjustments, and implementation techniques. Although the use of diagnostic algorithms is currently limited in Pakistani Clinical Chemistry laboratories, the application of AI is expanding. All thirteen participants stated their reasons for being hesitant to use AI. Participants stressed the importance of critical aspects for effective AI deployment, the need of a collaborative integrative approach, and the need for constant horizon scanning to keep up with AI developments. CONCLUSIONS: Three primary themes related to AI adoption were identified: perspectives and considerations, educational and curriculum adjustments, and implementation techniques. The study's findings give a sound foundation for making suggestions to clinical laboratories, scientific bodies, and national and international Clinical Chemistry and laboratory medicine organisations on how to manage pathologists' shifting practises because of AI.

A framework for implementing best laboratory practices for non-integrated point of care tests in low resource settings.

The method we respond to pandemics is still inadequate for dealing with the point of care testing (POCT) requirements of the next large epidemic. The proposed framework highlights the importance of having defined policies and procedures in place for non-integrated POCT to protect patient safety. In the absence of a pathology laboratory, this paradigm may help in the supply of diagnostic services to low-resource centers. A review of the literature was used to construct this POCT framework for non-integrated and/or unconnected devices. It also sought professional advice from the Chemical Pathology faculty, quality assurance laboratory experts and international POCT experts from the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC). Our concept presents a comprehensive integrated and networked approach to POCT with direct and indirect clinical laboratory supervision, particularly for outpatient and inpatient care in low-resource health care settings.

Is HbA1c associated with birth weight? A multivariable analysis of Pakistani pregnant women.

AIM: Globally, one in seven infants is born with low birth weight and 3%-7% of infants are born with high birth weight, with the greatest burden noted in low- and middle-income countries. This study investigated the association between maternal prenatal glucose regulation and birth weight and the moderating effect of fetal sex among Pakistani women. METHODS: Secondary data from a prospective longitudinal study of healthy pregnant women from Pakistan (N = 189) was used. Participants provided a blood sample (12-19 weeks' gestational age) for the assessment of HbA1c (%). Birth weight (g) was collected following delivery. RESULTS: Higher maternal HbA1c was associated with higher birth weight (b = 181.81, t[189] = 2.15, p = 0.03), which was moderated by fetal sex (b = -326.27, t[189] = -2.47, p = 0.02), after adjusting for gestational age at birth, ethnicity, and pregnancy weight. Among women carrying a male fetus, every 1% increase in HbA1c predicted a 182 g increase in birth weight (b = 181.81, t[189] = 2.15, p = 0.03). CONCLUSIONS: Results extend research from high-income countries and indicate that fetal sex may have implications for glucose regulation in early to mid-pregnancy. Future research should examine sociocultural factors, which could elucidate potential mediating factors in the relation between HbA1c and birth weight in healthy pregnancies.

Reference Intervals of Serum TSH from Mixed Distributions Using Truncation Points and the Kolmogorov-Smirnov Distance.

BACKGROUND: Serum TSH reference intervals (RIs) are methodology, population, and age specific. However, the ethical and practical challenges restrict the establishment of pediatric RIs using conventional approaches and advocates the use of indirect data mining-based algorithms. This study was carried out to estimate the reference interval of neonatal serum TSH in Pakistani population using an indirect approach. METHODS: A data mining of serum TSH results of neonates (≤ 1 month of age) from 2013 - 2018 was done. Two subgroups on the basis of age from birth to 5 days and 6 - 30 days were assessed. The German study group's pre-validated indirect algorithm 'KOSMIC' was utilized for the statistical analysis. RESULTS: A total of non-duplicate 82,299 neonatal serum TSH tests were retrieved over a period of 6 years, including 88% (n = 70,788) aged 0 - 5 days and 12% (n = 11,511) ranging from 6 days to 1 month. The estimated RIs for the first age partition was 0.7 (90% CI 0.6 - 0.8) to 15.5 (90% CI 12.9 - 16.2) and for the second group 0.7 (90% CI 0.5 - 0.9) to 7.8 (90% CI 6.1 - 9.9) µIU/mL. CONCLUSIONS: This study revealed age related trends in serum TSH. The study advocates the need for population specific RIs owing to the significant variations noted on comparison with previously published literature. Precise RIs become vital particularly when serum TSH is undertaken as a confirmatory test for presumptive positive results on newborn screening for congenital hypothyroidism.

Development and validation of standard and real patient gallstone library using Fourier transform infra-red spectroscopy.

BACKGROUND: Analysis of the constituents of gallstones using various spectroscopic techniques assists in identification of the pathogenesis of gallstones. In the current study, using Fourier Transform Infra-Red (FTIR) Spectroscopy, a Gallstone Standard Library (GSL) and a Gallstone Real Patients' Library (GRPL) were developed and validated for gallstone composition analysis. METHODS: The study was conducted at the Department of Pathology & Laboratory Medicine, Aga Khan University, Pakistan. Pure standards (cholesterol, calcium carbonate, bilirubin and bile salts) and gallstone specimens were analyzed using FTIR Nicolet iS-5 Spectrometer from Thermo Fisher Scientific, USA. Thermo Scientific™ QCheck™ algorithm, embedded within the OMNIC™ software, was used to identify the unique spectral fingerprint of the patient samples to match with known, standard material. Matching of > 75% was considered acceptable. Validation for accuracy of the library was performed for twenty analyzed gallstones at an international reference lab. RESULTS: Concerted search analysis was performed against the developed GSL consisting of 71 "pure component" spectrum divided into 5 types to generate the library. For the Gallstone Real Patient Library (GRPL), 117 patient samples were analyzed. Ninety-eight gall stones (83.8%) out of 117 stones matched with the developed GSL. Majority stones were mixed stones (95.92%), with cholesterol being the primary component (91.83%). Results of the developed library were 100% in agreement with the reports received from the external reference lab. CONCLUSIONS: The library developed displayed good consistency and can be used for detection of gallstone composition in Pakistan and replace the traditional labor- and time-intensive chemical method of gallstone analysis.

Impact of COVID-19 on the pre and post analytical clinical laboratory testing processes- A performance evaluation study using six sigma.

BACKGROUND: The aim of this study was to determine the impact of COVID-19 pandemic on the total testing process using six sigma metrics based on a comparison of pre and during pandemic periods. MATERIAL & METHODS: The study duration was over 12 months, 6 months before and 6 months after the COVID-19 onset in Pakistan in March 2020 after the recognition of the first case, using quality indicators (QIs). QIs were chosen from a model of QIs recommended by the CAP. Analysis was performed using Six Sigma calculators and QIs were expressed in percentage (%) and Sigma value were computed. Three levels of performance quality i.e. 25th, 50th, and 75th percentile were derived, being best, common and worst performance respectively. Between-group differences were tested using the Mann-Whitney's U test. RESULTS: The median defect percentages of these QIs ranged from 0% to 0.27% for the pre-pandemic period and 0% to 0.13% for the during pandemic period. Meanwhile, sigma values of the majority of the QIs were all above 4.0σ during the pre and the pandemic times. For the pre-analytical phase, sigma scores declined for 1 QI, improved for 3 QIs and remained same for 2. In the post analytical phase, no change in sigma metrics was noted for critical values notification. Considerable increase in defect percentage of inappropriate turnaround times was noted. CONCLUSION: The emergency preparedness proved to be fruitful as depicted by exceptional performance on the sigma metrics for most Qis both prior to and during the pandemic. The pre-analytical and the post analytical phases, being the most error sensitive requires strict vigilance.

Trend analysis of lab tests requisitions of COVID-19 prognostic biomarkers at a clinical chemistry reference laboratory-an observational study.

BACKGROUND: Biochemical parameters, such as C-reactive protein (C-RP), Procalcitonin (PCT), Lactate dehydrogenase (LDH) and Ferritin are associated with COVID-19 severity and prognosis. This trend analysis of COVID-19 prognostic biomarker requisitions is aimed at providing a reflection of the clinical practices adopted amidst the peak of the pandemic. This knowledge of the prognostic biomarkers utilized, will further aid to classify patients based on their risk, for optimal resource allocation and improve outcomes. MATERIAL & METHODS: This cross-sectional study was conducted at the clinical chemistry laboratory at the Aga Khan University Hospital (AKUH), Karachi Pakistan. A team consisting of two clinical chemistry consultants reviewed the COVID-19 prognostic biomarkers tests performance data from March to July 2020 using the integrated laboratory information management system (ILMS). The test statistics of March to July 2020 when COVID-19 cases were on the rise in the country were compared with those of the same months from 2019. The changes in the test groups were expressed in percentages. Microsoft Excel for windows 2019 was used for data analysis. RESULTS: The total specimens received for testing in 2020 (n = 574,092) showed a percent decline of approximately (-) 33% compared to 2019 (n = 858,756). Contrary to the overall decline in volumes an upward surge was noted for the prognostic biomarkers. From March to July, the highest percent change was noted for LDH (+155.1%), followed by PCT (+66.7.1%), C-RP (+26.5%) and Ferritin (+22.1%) in 2020 compared to the same time frame in 2019. The highest percent change was noted in June. CONCLUSION: During the COVID 19 pandemic, a significant increase in utilization of laboratory services was seen for COVID-19 prognostic markers.

Fostering teaching-learning through workplace based assessment in postgraduate chemical pathology residency program using virtual learning environment.

BACKGROUND: The principle of workplace based assessment (WBA) is to assess trainees at work with feedback integrated into the program simultaneously. A student driven WBA model was introduced and perception evaluation of this teaching method was done subsequently by taking feedback from the faculty as well as the postgraduate trainees (PGs) of a residency program. METHODS: Descriptive multimethod study was conducted. A WBA program was designed for PGs in Chemical Pathology on Moodle and forms utilized were case-based discussion (CBD), direct observation of practical skills (DOPS) and evaluation of clinical events (ECE). Consented assessors and PGs were trained on WBA through a workshop. Pretest and posttest to assess PGs knowledge before and after WBA were conducted. Every time a WBA form was filled, perception of PGs and assessors towards WBA, time taken to conduct single WBA and feedback were recorded. Faculty and PGs qualitative feedback on perception of WBA was taken via interviews. WBA tools data and qualitative feedback were used to evaluate the acceptability and feasibility of the new tools. RESULTS: Six eligible PGs and seventeen assessors participated in this study. A total of 79 CBDs (assessors n = 7 and PGs n = 6), 12 ECEs (assessors n = 6 and PGs n = 5), and 20 DOPS (assessors n = 6 and PGs n = 6) were documented. PGs average pretest score was 55.6%, which was improved to 96.4% in posttest; p value< 0.05. Scores of annual assessment before and after implementation of WBA also showed significant improvement, p value 0.039, Overall mean time taken to evaluate PG's was 12.6 ± 9.9 min and feedback time 9.2 ± 7.4 min. Mean WBA process satisfaction of assessors and PGs on Likert scale of 1 to 10 was 8 ± 1 and 8.3 ± 0.8 respectively. CONCLUSION: Both assessors and fellows were satisfied with introduction and implementation of WBA. It gave the fellows opportunity to interact with assessors more often and learn from their rich experience. Gain in knowledge of PGs was identified from the statistically significant improvement in PGs' assessment scores after WBA implementation.

Challenges amid COVID-19 times - Review of the changing practices in a clinical chemistry laboratory from a developing country.

Corona Virus Disease 2019 (COVID-19) pandemic is the defining global health crisis of our time. Compared with its neighbors China and Iran, which were rated as epi-centers of the outbreak, Pakistan has lower standards of health care, unstable economy and dearth of financial resources to tackle the outbreak. Like other institutes and industries in the country, clinical laboratories were succumbed to a variety of challenges. This article is based on the experience and adapted workflow measures from the Clinical Chemistry laboratory at the Aga Khan University Hospital (AKUH), Karachi, which serves as a national referral center with its widespread network of satellite laboratories and phlebotomy centers across the country. It highlights the challenges faced and the appropriate responses to ensure the provision of diagnostic facilities during the COVID-19 outbreak. Furthermore, the lessons acquired and necessary preparations for the post crisis situation are also incorporated.

Vitamin D and bone metabolism in breast cancer patients in Karachi, Pakistan.

Breast cancer is one of the common types of malignancy worldwide and in Pakistan. The heterogeneous disease itself and its complex treatment leads to various bone-affecting complications that make breast cancer patients more vulnerable to bone fractures. Vitamin D deficiency among these women worsens the condition and promotes breast cancer growth. Thus, the purpose of the study was to assess serum levels of 25-hydroxyvitamin D (25OHD) and bone markers in women suffering from breast cancer. Serum levels of 25OHD, alkaline phosphatase (ALP), bone specific ALP, calcium (Ca), phosphorus (P), magnesium (Mg), albumin (Alb) and beta carboxyl terminal collagen crosslink (ß-CTx) were analyzed in 201 histological diagnosed patient volunteers from breast cancer clinic. Vitamin D insufficiency was present among the total study population and deficiency was particularly observed among women with metastases. These patients had significantly increased serum levels of ß-CTx and bone specific ALP when compared with the non-metastatic group. No significant difference was observed in other biochemical parameters. A weak correlation between serum levels of 25OHD and ß-CTx was observed. Therefore, monitoring of serum levels of 25OHD and bone markers at the time of diagnosis and during the course of treatment will endeavor a better overall health status.

The utility of neutrophil gelatinase-associated Lipocalin (NGAL) as a marker of acute kidney injury (AKI) in critically ill patients.

In current clinical practice, Serum Creatinine (SCr) is a commonly used marker for the diagnosis of acute kidney injury (AKI). Unfortunately, due to a delayed increase in SCr, it is unable to accurately estimate the timing of the injury. The purpose of this study was to assess the ability of plasma neutrophil gelatinase-associated lipocalin (pNGAL) to predict AKI in critically ill adult patients. The study was conducted at the Section of Chemical Pathology, Department of Pathology& Laboratory Medicine in collaboration with Department of Anesthesiology, at Aga Khan University Hospital in Karachi, Pakistan. Subjects in the age groups of18 to 60, that were admitted into the intensive care unit (ICU) with suspected sepsis were enrolled in this study.AKI was labeled by using Risk-Injury-Failure-loss-End Stage (RIFLE) criteria. Forty-eight patients, mean age being 46.5 ± 16.3, were recruited over a nine-month period. Multiple blood samples were collected from each patient at 12 h, 24 h, and 48 h. A total of 52.1% (n = 24) of ICU patients suspected of sepsis had developed AKI. Baseline characteristics of subjects with AKI were compared to those without AKI. Statistically significant difference was noted in gender (p-value< 0.05) and pNGAL (p-value< 0.001). However, no significant differences were seen with respect to age, in patients with and without AKI. The area under the curve (AUC) at12hr was 0.82 (95% CI 0.68-0.96) with a sensitivity of 70.8% and specificity of 90.9%.While AUCs at 24 h was 0.86(95% CI 0.74-0.97) with a sensitivity of 78.5% and specificity of 88.8%. Furthermore, there was a positive correlation between pNGAL and the length of ICU stay (r = 0.98). Non-survivors or expired patients had higher median pNGAL170 (202-117) ng/ml as compared to survivors 123(170-91) ng/ml. In conclusion, pNGAL is an early predictor of AKI in a heterogeneous adult ICU population. Plasma NGAL allows the diagnosis of AKI 48 h prior to a clinical diagnosis based on RIFLE criteria. Early identification of high-risk AKI in patients may allow earlier initiation of therapies and improve patient outcome.

Prospective evaluation of serum procalcitonin in critically ill patients with suspected sepsis- experience from a tertiary care hospital in Pakistan.

BACKGROUND: Sepsis is the leading cause of mortality in critically ill patients. Procalcitonin (PCT) is a promising marker for identification of bacterial sepsis. The aim of this study was to determine the diagnostic accuracy of serum PCT concentration in patients with suspected sepsis admitted to mixed medical-surgical Intensive care unit (ICU). MATERIAL AND METHODS: A cross-sectional study conducted at section of Chemical Pathology, Department of Pathology and Laboratory Medicine and ICU. Patients with suspected sepsis were included, serum PCT cut off ≥0.5 ng/ml was taken for diagnosing sepsis. Diagnostic accuracy was measured in terms of sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) taking blood culture as gold standard. Furthermore, different cut offs were compared by using receiver operating characteristic curves (ROC). Data analysis was done on SPSS version 20. RESULTS: Median age of the study group (n = 103) was 48 years (IQR: 22), 60% being males. Out of the 103 patients included 82 patients had PCT levels above the optimal cut off. At a serum PCT cutoff of 0.5 µg/L, the sensitivity and specificity for the diagnosis of sepsis was found to be 93.75% and 43.59% respectively. NPV was higher compared to PPV making PCT a reliable marker to for the screening out of sepsis patients. Furthermore, it was revealed that PCT having an AUC = 0.70 outperformed WBC (AUC = 0.5) and CRP (AUC = 0.6). CONCLUSION: Elevated PCT concentration is a promising indicator of sepsis in newly admitted critically ill patients capable of complementing clinical signs and routine laboratory parameters.

High Burden of Subclinical Lead Toxicity after Phase Out of Lead from Petroleum in Pakistan.

OBJECTIVE: To evaluate the frequency of subclinical lead toxicity. STUDY DESIGN: Cross-sectional study. PLACE AND DURATION OF STUDY: Department of Pathology and Laboratory Medicine, The Aga Khan University Hospital, Karachi, from January 2011 to December 2014. METHODOLOGY: Analysis of laboratory data for blood lead levels (BLL) was performed. Lead was tested by atomic absorption spectrometer. For all subjects, only initial test results were included while the results of repeated testing were excluded. Exemption was sought from institutional ethical review committee. BLL of 2-10 ug/dl and 10-70 ug/dl in children and adults, respectively were taken as subclinical lead toxicity. RESULTS: Amongst the total number of subjects tested (n=524), 26.5% (n=139) were children (<16 years) while rest were adults. Overall median BLLs was 6.4 ug/dl (20.9-3.1). The median BLL was 4 ug/dl (6.7-2.6) in children and 8.3 ug/dl (27.9-3.4) in adults, respectively. The BLL increased with age; higher levels were observed in age range 21-30 years of subjects [median lead level 16.9 ug/dl (36.1-4)] and lower level [4.2 ug/dl (6.8-2.6)] in children with <10 years of age. Only 16% (n=22) children had desirable lead levels while most had either subclinical (76%, n=106) or toxic lead levels (8%, n=11). In adults, (55%, n=212) subjects had desired lead levels, and 40% (n=154) and 4.99% (n=19) had subclinical and toxic lead levels. CONCLUSION: Presence of subclinical lead poisoning even after phasing out of lead petroleum in Pakistanis is alarming, especially in children. A national population-based study to determine the lead status and targeted intervention to identify potential sources is need of the time.

Burden of Zinc (Zn) deficiency: A high volume clinical laboratory data analysis.

A cross-sectional survey was done at the Section of Chemical Pathology, Department of Pathology and Laboratory Medicine, AKUH, Karachi, to determine frequency of Zn deficiency, the second major micronutrient deficiency in developing countries, in subjects coming for investigations. Data of plasma Zn, from Jan 2013 to Dec 2014 was analyzed and deficiency was labeled at <65ug/dl. Total 469 subjects were tested for plasma Zn levels over the period of 24 months and complete information was available for 422 subjects, included in final analysis. Median age of subjects was 13 yrs (IQR 7-35) and 57% were male. Mean plasma Zn levels of the total subjects were 105±42.6ug/dl. Out of the total subjects 13.5% (n=57) had Zn deficiency (mean plasma Zn 52±11 ug/dl), and most of them were of age group 6-16yrs. These findings advocate that diet of Pakistani children should be revised in order to provide sufficient amounts of Zn.

Frequency of Thyroid Peroxidase Antibody and its Association with Miscarriages Among Pregnant Women.

OBJECTIVE: To measure the frequency of thyroid peroxidase antibody (TPO Ab) among clinically euthyroid pregnant women during first trimester and determine its association with pregnancy outcome as miscarriage or live birth by estimating the relative risk. STUDY DESIGN: Cohort study. PLACE AND DURATION OF STUDY: Section of Chemical Pathology, Department of Pathology and Laboratory Medicine and the Gynaecology and Obstetric outpatient clinics of the Aga Khan University Hospital, Karachi, from July to December 2012. METHODOLOGY: The study subjects comprised of apparently euthyroid pregnant women, who were tested for TPO Ab during first trimester of pregnancy and followed till pregnancy outcomes. Pregnancy outcome was noted and relative risk was determined. RESULTS: TPO Ab was found positive in 127 (13.5%) pregnant women from a cohort of 943 subjects. A2.03% increased risk of miscarriages was observed in TPO Ab positive subjects. CONCLUSION: There was a positive association of presence of TPO Ab with loss of pregnancy.

Bone Turnover Markers for Osteoporosis Status Assessment at Baseline in Postmenopausal Pakistani Females.

OBJECTIVE: To assess bone turnover status in osteopenic and osteoporotic postmenopausal females. STUDY DESIGN: Cross-sectional analytical study. PLACE AND DURATION OF STUDY: The Aga Khan University Hospital, Karachi, from January to December 2013. METHODOLOGY: Across-sectional study was conducted on 203 postmenopausal females undergoing bone mineral density testing (BMD) by DXAscan. Patients with clinical history of any disorder or medications affecting bone turnover were excluded. Bone turnover was assessed with osteocalcin and ß-CTx. Data was analyzed by SPSS version 19. RESULTS: Mean age of the participants was 54 ±4.66 years with a mean BMI of 28.7 ±5.5 kg/m2. Mean ß-CTx (0.28 ±0.24 ng/ml) and osteocalcin (21.5 ±10.6 ng/ml) levels were within the normal reference range. Subjects were grouped into normal (26.6%), osteopenic (44.8%), and osteoporotic (28.6%) based on the t-scores. Serum levels of osteocalcin and ß-CTx between normal, osteopenic, and osteoporotic groups were not significantly different. ß-CTx was negatively and significantly associated with only lumber spine BMD (r = -0.13, p=0.04). Positive association (< 0.0001) was noted between both markers in normal, osteopenic, and osteoporotic females. However, association of these markers with BMD in the 3 groups were not found. Multivariate linear regression showed a positive and significant effect of BMI on BMD (ß= 0.332, p= < 0.0001). ß-CTx had negative but significant effect on BMD (ß= -0.155, p= 0.018) of postmenopausal women. CONCLUSION: Association between baseline levels of BTM and rate of bone loss is variable and site dependent. ß-CTx correlates better with BMD. However, role of osteocalcin in postmenopausal osteoporosis is uncertain and needs further investigation.

Error identification in a high-volume clinical chemistry laboratory: Five-year experience.

INTRODUCTION: Quality indicators for assessing the performance of a laboratory require a systematic and continuous approach in collecting and analyzing data. The aim of this study was to determine the frequency of errors utilizing the quality indicators in a clinical chemistry laboratory and to convert errors to the Sigma scale. MATERIALS AND METHODS: Five-year quality indicator data of a clinical chemistry laboratory was evaluated to describe the frequency of errors. An 'error' was defined as a defect during the entire testing process from the time requisition was raised and phlebotomy was done until the result dispatch. An indicator with a Sigma value of 4 was considered good but a process for which the Sigma value was 5 (i.e. 99.977% error-free) was considered well controlled. RESULTS: In the five-year period, a total of 6,792,020 specimens were received in the laboratory. Among a total of 17,631,834 analyses, 15.5% were from within hospital. Total error rate was 0.45% and of all the quality indicators used in this study the average Sigma level was 5.2. Three indicators - visible hemolysis, failure of proficiency testing and delay in stat tests - were below 5 on the Sigma scale and highlight the need to rigorously monitor these processes. CONCLUSIONS: Using Six Sigma metrics quality in a clinical laboratory can be monitored more effectively and it can set benchmarks for improving efficiency.

B-type natriuretic peptide versus amino terminal pro-B type natriuretic peptide: selecting the optimal heart failure marker in patients with impaired kidney function.

BACKGROUND: The effect of impaired kidney function on B-type natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP) is vague. This study was performed to examine the effect of kidney dysfunction on the afore-mentioned markers and determine appropriate cutoffs for systolic heart failure (SHF). METHODS: In this cross sectional study adults with estimated glomerular filtration rate (eGFR) <60 ml/min for ≥3 months were identified in consulting clinics from June 2009 to March 2010. SHF was defined as documented by a cardiologist with ejection fraction of < 40% and assessed by New York Heart Association classification (NYHA). Plasma was assayed for creatinine (Cr), BNP and NT-proBNP. RESULTS: A total of 190 subjects were enrolled in the study, 95 with and 95 without SHF. The mean age of patients was 58 (±15) years, 67.4% being males. Mean BNP levels showed a 2.5 fold and 1.5 fold increase from chronic kidney disease (CKD) stage 3 to stage 5 in patients with and without SHF respectively. NT-proBNP levels in non-heart failure group were 3 fold higher in CKD stage 5 compared to stage 3. Mean NT-proBNP levels were 4 fold higher in CKD stage 5 compared to stage 3 in patients with SHF. Optimal BNP and NT-proBNP cutoffs of SHF diagnosis for the entire CKD group were 300 pg/ml and 4502 pg/ml respectively. CONCLUSION: BNP and NT-proBNP were elevated in kidney dysfunction even in the absence of SHF; however the magnitude of increase in NT-proBNP was greater than that of BNP. BNP and NT-proBNP can be useful in diagnosing SHF, nonetheless, by using higher cutoffs stratified according to kidney dysfunction. NT-proBNP appears to predict heart failure better than BNP.

Verification and Determination of the Thyroid Peroxidase Antibody Reference Interval: Insight Into the CLSI Guideline.

OBJECTIVE: To verify the upper reference limit and define the population-based reference interval (RI) for thyroid peroxidase antibody, according to Clinical and Laboratory Standards Institute (CLSI) guidelines. MATERIAL AND METHODS: We subjected serum samples from 146 subjects to thyroid-stimulating hormone (TSH) and TPO Ab analysis for verification and determination of RI. We verified an upper reference limit for thyroid peroxidase antibody (TPO Ab) and established an RI according to National Academy of Clinical Biochemistry (NACB) and CLSI guidelines. RESULTS: The manufacturer's suggested upper reference limit was not verified for use as a functional reference value. Rather, on defining the RI of TPO Ab by means of a full-scale study, we found a higher upper reference limit (13.8 vs 12.0). We calculated lower and upper reference limits of 3.3 and 13.8, with 90% confidence intervals (CIs) of 2.8 to 3.5 and 13.6 to 14.8, respectively. CONCLUSION: RIs provided by assay manufacturers are general data and may not always be appropriate for different locations and patient demographics. Verification of an RI is necessary before use in a given patient population.

Bone health status of premenopausal healthy adult females in Pakistani females.

UNLABELLED: Bone health status in healthy premenopausal females was assessed. We found high bone turnover in 36.8 % and vitamin D deficiency and insufficiency in 82.8 and 16.1 %, respectively, and secondary hyperparathyroidism in 25.9 % of the subjects. This is alarming as there is inability to achieve peak bone mass and predisposes to osteoporosis risk. PURPOSE: This study aimed to assess bone health status in healthy females by using biochemical markers of bone metabolism in blood [N-telopeptide of type I collagen (NTx), 25-hydroxyvitamin D (25OHD), and plasma intact parathyroid hormone (iPTH)]. MATERIAL AND METHODS: One hundred and seventy-four healthy premenopausal female volunteers were recruited from an urban residential area in Karachi. Demographic details were collected on a preformed questionnaire. Blood samples for the estimation of serum NTx, 25OHD, and plasma iPTH were taken in a fasting state. Data were analyzed using Statistical Package for Social Sciences 16.0. A p value of <0.05 was considered as significant. RESULTS: High bone turnover, as depicted by NTx, was seen in 36.8 % cases. Vitamin D deficiency, insufficiency, and sufficiency were seen in 82.8, 16.1, and 1.1 % respectively. Secondary hyperparathyroidism was present in 25.9 % of the subjects, while others had blunted PTH response. Significant correlates of bone health were serum 25OHD levels, duration of sun exposure, and the practice of wearing veil (p value < 0.001). CONCLUSION: Bone turnover is high with high prevalence of vitamin D deficiency in apparently healthy premenopausal females predisposing them to higher risk for development of osteoporosis.