Improving diagnosis and treatment of hypomagnesemia.

Magnesium is one of the most abundant cations in the body and acts as a cofactor in more than 600 biochemical reactions. Hypomagnesemia is a highly prevalent condition, especially in subjects with comorbid conditions, but has received less attention than other electrolyte disturbances. This review will discuss magnesium physiology, absorption, storage, distribution across the body, and kidney excretion. After reviewing the regulation of magnesium homeostasis, we will focus on the etiology and clinical presentation of hypomagnesemia. The role of laboratory medicine in hypomagnesemia will be the main purpose of this review, and we will discuss the laboratory tests and different samples and methods for its measurement. Although free magnesium is physiologically active, total serum magnesium is the most commonly used measurement in laboratory medicine and is apt for clinical purposes; however, it is not appropriately used, and many patients with hypomagnesemia remain undiagnosed and not treated. Using information technologies, laboratory medicine can largely improve the diagnosis and treatment of hypomagnesemia through the design and establishment of automatic demand management and result management interventions by acting in the first and last steps of the laboratory cycle, test requests, and actions taken after test results, to unmask patients with hypomagnesemia and improve the number of patients undergoing treatment.

Clinical Decision Support System in laboratory medicine.

Clinical Decision Support Systems (CDSS) have been implemented in almost all healthcare settings. Laboratory medicine (LM), is one of the most important structured health data stores, but efforts are still needed to clarify the use and scope of these tools, especially in the laboratory setting. The aim is to clarify CDSS concept in LM, in the last decade. There is no consensus on the definition of CDSS in LM. A theoretical definition of CDSS in LM should capture the aim of driving significant improvements in LM mission, prevention, diagnosis, monitoring, and disease treatment. We identified the types, workflow and data sources of CDSS. The main applications of CDSS in LM were diagnostic support and clinical management, patient safety, workflow improvements, and cost containment. Laboratory professionals, with their expertise in quality improvement and quality assurance, have a chance to be leaders in CDSS.

The clinical laboratory: a decision maker hub.

OBJECTIVES: We aimed to share a new laboratory model based on laboratory knowledge, meaningful use of information technology, and partnership with clinicians, to lead the appropriate use of laboratory testing and clinical decision making in the diagnosis of as-yet-undiagnosed disease. More specifically, we evaluate the role of eight different opportunistic interventions to diagnose certain asymptomatic disorders, by means of the automatic registration of appropriate laboratory testing according to different scenarios. METHODS: This is a retrospective longitudinal study to evaluate the impact of laboratory interventions on the diagnosis of different diseases and on patient care, including data from January 2012 to September 2020. RESULTS: Overall, the above strategies have so far identified 2063 patients with clinically relevant as-yet-undiagnosed disorders who would have otherwise remained occult, such as for instance, primary hyperparathyroidism, diabetes, and hypomagnesemia. CONCLUSIONS: We are facing a new laboratory model, a leading laboratory rather than a passive traditional laboratory, not just to intervene in clinical decision-making, but to make the clinical decision, through the identification of patients with occult disease.

High frequency of anti-parietal cell antibody (APCA) and intrinsic factor blocking antibody (IFBA) in individuals with severe vitamin B12 deficiency - an observational study in primary care patients.

Background Vitamin B12 deficiency is common worldwide and is also linked to several diseases including autoimmune atrophic gastritis (AAG). The presence of anti-parietal cell antibodies (APCA) and/or intrinsic factor blocking antibodies (IFBA) is indicative of AAG that may develop into pernicious anemia. Both conditions are known to be associated with an increased risk of gastric carcinoma. The aim of this study was to estimate the frequency of individuals positive for APCA and IFBA antibodies in primary care patients with severe vitamin B12 deficiency. Methods An observational study was designed and 5468 consecutive patients from primary care with a request for vitamin B12 status were included and add-on testing for APCA and IFBA that were automatically registered if severe vitamin B12 deficiency was identified (<73.8 pmol/L). For patients included in the intervention, study demographic data, mean corpuscular volume (MCV) and hemoglobin values were collected. Results Seventy-seven patients with severe vitamin B12 deficiency were identified and out of these 44 (57%) presented with antibodies to APCA and 11 (14%) to IFBA, 25 (32.5%) had anemia, and 25 (32.5%) had macrocytosis. The majority of APCA and/or IFBA positive patients were found in the age group >70 years. Both anemia and macrocytosis were more common among APCA positive patients but the association was not statistically significant, neither was the correlation between IFBA status and anemia and/or macrocytosis. Among the patients with anemia, 10 (39%) had macrocytosis, although the rate of macrocytosis among patients with or without anemia did not differ significantly. Conclusions The automated analysis strategy of measuring antibodies to APCA and IFBA in patients with severe vitamin B12 deficiency, efficiently detected positivity in more than 60% the patients. The result point to the presence of a high rate of otherwise undetected AAG and the potential clinical utility of APCA and IFBA as markers in primary care.

Untangling the association between prostate-specific antigen and diabetes: a systematic review and meta-analysis.

Objectives: Several studies have shown an inverse association between diabetes mellitus and prostate cancer (PCa). Some researchers suggest that this relationship is due to reduced PCa detection in diabetics due to lower prostate-specific antigen (PSA) levels compared to non-diabetics. Our objective is to analyze the impact of diabetes on PSA in asymptomatic men without known prostate pathology and without prior prostate intervention. Methods: We searched Medline (via PubMed), Embase and Scopus. We included studies that reported the relationship between serum PSA levels and diabetes or diabetes treatment in asymptomatic adult men without known prostate pathology, and without prior prostate intervention. Pooled mean differences were compared between diabetics and non-diabetics. Results: Of 2,392 screened abstracts, thirteen studies met the inclusion criteria and 8 (62%) reported appropriate measures that could be included in a meta-analysis. Eleven (85%) examined the influence of diabetes on PSA levels and 8 (62%) evaluated the influence of diabetes treatments on PSA levels. Overall diabetics had a significantly lower PSA level compared to non-diabetics (mean difference: -0.07 ng/mL; 95% CI -0.10, -0.04). Conclusions: Diabetes and related factors (such as disease duration, severity and treatment) were significantly associated with lower PSA levels among asymptomatic men, yet differences were small and are unlikely to influence PCa detection in a screening setting.

Urinary albumin strip assay as a screening test to replace quantitative technology in certain conditions.

Background The clinical laboratory plays a crucial role in the diagnosis and monitoring of chronic kidney disease. The quantitative measurement of urine albumin in a spot sample, expressed as ratio per creatinine (ACR) is the most frequently used biomarker for such a purpose. Our aim was to evaluate the diagnostic performances of a strip for measuring ACR for differentiating patients who are candidates for subsequent albumin quantification, and to evaluate the economic effects of its implementation. Methods We systematically measured strip analysis when quantitative urinary albumin was requested. Semiquantitative urinary albumin was measured using a UC-3500 (Sysmex, Kobe, Japan), based on the protein error of a pH indicator. We collected and reviewed all the values of quantified urinary albumin and their corresponding results in ACR strip tests. We calculated the diagnostic indicators for ACR at different albumin and creatinine values using the quantitative ACR measurement as a "gold standard". We also studied the economic effects based on both tests prices (€1.31 for quantitative albumin plus creatinine, and €0.04 for an albumin strip). Results The study included 9148 patients (mean age 63, 46.3% men). The results at different albumin and creatinine cutoffs showed the best performance when 10 mg/L and above 50 mg/dL, respectively. Based on our results, we would have saved 3506 urine albumin and creatinine tests in the study period, corresponding to €4226.94. Conclusions The present study supports the use of the ACR strip test to identify pathological albuminuria values to be measured through quantitative methods. Considerable economic savings are possible.

Computer-assisted interventions in the clinical laboratory process improve the diagnosis and treatment of severe vitamin B12 deficiency.

BACKGROUND: Severe vitamin B12 deficiency can result in serious complications if undiagnosed or untreated. Our aim was to test the efficacy of interventions in the laboratory process to improve the detection and the treatment of severe vitamin B12 deficiency. METHODS: Quasi-experimental investigation with a retrospective 7-year pre-intervention period and 29-month post-intervention follow-up in a university hospital. Two interventions were designed to improve the detection and treatment of subjects with vitamin B12 deficiency: the laboratory information system (LIS) automatically added seru vitamin B12 (s-vitamin B12) based on certain conditions; and created a comment in the report and scheduled an appointment with the general practitioner (GP). We calculated the number of new diagnoses of severe vitamin deficiency (s-vitamin B12 <73.8 pmol/L) and the proportion of identified patients that were correctly treated in the pre- and post-intervention periods. We compared the number of tests needed to detect a new case when ordered by GPs vs. added by the strategy. Finally, we investigated the economic cost of each new case. RESULTS: The strategy added 699 s-vitamin B12 and detected 66 new cases of severe vitamin deficiency. The number of tests needed to identify a new case when s-vitamin B12 was ordered by GPs was 187, as opposed to 10 when added through the intervention (p<0.001). The intervention reagent cost was €26.7 per new case. In the post-intervention cohort, 88% of patients were correctly treated, as opposed to 52% in the pre-intervention (p<0.001). CONCLUSIONS: Interventions in the clinical laboratory process improved the diagnosis and treatment of severe vitamin B12 deficiency.

Request Pattern, Pre-Analytical and Analytical Conditions of Urinalysis in Primary Care: Lessons from a One-Year Large-Scale Multicenter Study.

BACKGROUND: To study the urinalysis request, pre-analytical sample conditions, and analytical procedures. METHODS: Laboratories were asked to provide the number of primary care urinalyses requested, and to fill out a questionnaire regarding pre-analytical conditions and analytical procedures. RESULTS: 110 laboratories participated in the study. 232.5 urinalyses/1,000 inhabitants were reported. 75.4% used the first morning urine. The sample reached the laboratory in less than 2 hours in 18.8%, between 2 - 4 hours in 78.3%, and between 4 - 6 hours in the remaining 2.9%. 92.5% combined the use of test strip and particle analysis, and only 7.5% used the strip exclusively. All participants except one performed automated particle analysis depending on strip results; in 16.2% the procedure was only manual. CONCLUSIONS: Urinalysis was highly requested. There was a lack of compliance with guidelines regarding time between micturition and analysis that usually involved the combination of strip followed by particle analysis.

Glycated hemoglobin: A powerful tool not used enough in primary care.

BACKGROUND: Glycated haemoglobin (HbA1c) is one of the most useful and relevant laboratory tests currently available. The aim of the actual research was to study the variability and appropriateness in the request of HbA1c in primary care, and differences between regions, to assess if there would be an opportunity to improve the request. METHODS: A cross-sectional study was conducted enrolling clinical Spanish laboratories. The number of HbA1c requested in 2014 by all general practitioners was reported by each participant. Test-utilization rate was expressed as tests per 1000 inhabitants. The index of variability was calculated, as the top decile divided by the bottom decile. HbA1c per 1000 inhabitants was compared between the different regions. To investigate whether HbA1c was appropriately requested to manage patients with diabetes, the real request was compared to the theoretically ideal number, according to prevalence of known diabetes mellitus in Spain and guideline recommendations. RESULTS: A total of 110 laboratories participated in the study, corresponding to a catchment area of 27 798 262 inhabitants (59.8% of the Spanish population) from 15 different autonomous communities (AACCs). 2 655 547 HbA1c were requested, a median of 93.9 (interquartile range (IQR): 33.4) per 1000 inhabitants. The variability index was 1.97. The HbA1c/1000 inhabitants was significantly different among the AACCs, ranging from 73.4 to 126.3. A total of 4 336 529 additional HbA1c would have been necessary to manage patients with diabetes according to guidelines, and 3 861 769 for diagnosis in asymptomatic patients. CONCLUSIONS: There was a high variability and significant differences between Spanish AACCs. Also a significant under-request of HbA1c was observed in Primary Care in Spain.

Temporal and regional variability in the request of vitamin D from general practitioners in Spain.

BACKGROUND: Our main goal is to study the inter-practice regional variability and the temporal evolution in the request of 25-hydroxyvitamin D (25[OH]D) by general practitioners (GPs) in Spain. METHODS: Clinical laboratories in different autonomic communities (AACCs) were invited to report the number of 25(OH)D test requested by GPs during 2012 and 2014. The number of 25(OH)D requested per 1000 inhabitants and the index of variability were calculated, and compared between regions and time periods. We calculated the number of tests that could have been potentially saved in regions where 25(OH)D could be requested from primary care without restrictions taking into account the request in those where it is restricted, and the potential economical savings. RESULTS: Seventy-six laboratories participated in the 2012 edition, and 110 in 2014, corresponding to 17,679,195 and 27,798,262 inhabitants (59.8% Spanish population). The number of 25(OH)D requested per 1000 inhabitants increased from 1.1 in 2012 to 3.4 in 2014 (p<0.001). The variability index also increased from 51.7 to 68. There was a significantly variability among the different AACCs, ranging from 0.94 to 21.24 (p=0.002). 173,885 tests could have been not measured from primary care in regions without ordering restrictions, resulting in potential 886,813.5€ savings. CONCLUSIONS: There was a high variability in the request of 25(OH)D by GPs in Spain, which significantly increased in a 2 year period. The demand was higher in areas where the request of 25(OH)D was not restricted in primary care, with potential savings if the request would approach to regions with ordering restrictions.

Uncritical Request of Thyroid Laboratory Tests May Result in a Major Societal Economic Burden: Results from a Large Population Study in Spain.

BACKGROUND: Our aim is to study the regional variability in the request of thyroid laboratory tests from primary care facilities in Spain and to investigate a potential inappropriate request and its economic societal impact. METHODS: Spain is divided into 17 autonomous communities (AACCs) which are in turn divided in Health Departments that cover a geographic area and its population and a laboratory that attends the needs of every inhabitant. Each participating laboratory was required to report the number of thyroid tests requested from primary care during year 2014 and to provide organizational data. The request of every test per 1000 inhabitants and ratio of related tests (free thyroxine (FT4)/thyrotropin (TSH), triiodothironine (FT3)/TSH, antithyroglobulin antibody (ATG)/antiperoxidase antibody (TPO)) were calculated and compared in different AACCs with more than 4 participants. The economic costs taking into account reagent cost were calculated. RESULTS: 110 laboratories participated (27,798,262 inhabitants). Close to 6 million TSH tests were requested, representing an expense of more than 10 million euros. That corresponds to 18 million euros when extrapolating for the whole Spanish population, only in reagent cost. The number of TSH requests per 1000 inhabitants in the different AACCs ranged from 198 to 289. FT4 was ordered more than twice as frequently in some regions compared to others. TPO request per 1000 inhabitants ranged from 0.2 to 11.2. CONCLUSIONS: There was a significant over-request and regional variability of thyroid laboratory tests in primary care in Spain, resulting in a high economic impact on society.

Requests of laboratory tests for the diagnosis and management of calcium-phosphate disorders in Spain.

BACKGROUND: Knowledge about the variability in the request of calcium-phosphate metabolism laboratory tests in primary care is important to design strategies to improve health system efficiency. AIM: To compare the inter-practice variability in calcium-phosphate metabolism laboratory tests requested by general practitioners from diverse regions across Spain. MATERIAL AND METHODS: One hundred and forty one clinical laboratories were invited to participate in an observational cross-sectional study. They informed the number of serum calcium, phosphate, parathyroid hormone and 25-hydroxyvitamin D requested by general practitioners. Appropriateness indicators were calculated as number of test requests per 1,000 inhabitants and ratio of related tests requests. The differences according to hospital setting, region and type of management were analyzed. RESULTS: We recruited 76 laboratories (17,679,195 inhabitants). General practitioners requested 3,260,894 calcium-phosphate metabolism tests. The rate of request ranged from 2.97 per 1,000 inhabitants for 25-hydroxyvitamin D to 98.89 per 1,000 inhabitants for calcium. The rates of request for calcium, phosphate, parathyroid hormone in some areas were 30, 100 and 340 times higher than in other areas. Parathyroid hormone and 25-hydroxyvitamin D were highly requested in private management areas. There were also differences in phosphate, parathyroid hormone and 25-hydroxyvitamin D requesting between regions across Spain. CONCLUSIONS: The high variability observed is difficult to explain by differences in patient case mix between regions. Depending on the area, calcium could be under requested to detect primary hyperparathyroidism.

Laboratory utilization improvement through a computer-aided algorithm developed with general practitioners.

BACKGROUND: One of the main duties of healthcare workers is to get an appropriate use of diagnostic and therapeutic tools. The aim of this study was to show how strategies can be designed and established in consensus with general practitioners (GPs) to reach an optimal laboratory test request. METHODS: The laboratory serves a population of approximately 235,000 inhabitants, including nine primary care centers. GPs could request every test in profiles and individually. In meetings between the laboratory and GPs our request patterns were compared to other geographic regions, and we investigated the appropriateness of test requesting. The group devised strategies that consisted of removing tests from profiles [aspartate aminotransferase (AST), γ-glutamyltranspeptidase (GGT) and phosphate], removing tests from GPs requests (iron and transferrin), substituting tests (IgA antigliadin antibody), and measuring total bilirubin (tBil) only when the icteric index value was above 34.2 mmol/L (2 mg/dL). We analyzed every test request in the post- (years 2012-2013) and pre-intervention period (years 2010-2011), and the tBil measured in the post-intervention period. We studied if AST/alanine aminotransferase (ALT) and GGT/ALT achieved indicators targets and calculated the economic savings in the post-intervention period. RESULTS: There was a significant drop in every test request in the post-intervention period. AST/ALT achieved the indicator target. GGT/ALT, never achieved the indicator goal. The strategies resulted in a savings of more than €34,000. CONCLUSIONS: The strategies designed between the laboratory and the requesting clinicians and automatically established by using our laboratory information system were successful.

Primary care use of laboratory tests in Spain: measurement through appropriateness indicators.

BACKGROUND: To compare the inter-practice and inter-regional variability in laboratory test requests by general practitioners in Spain, through the measure of appropriateness indicators. METHODS: A call for data was posted on the Redconlab website. We obtained production statistics for 2010 from laboratories in 37 different hospitals from diverse Spanish regions. The following appropriateness indicators were calculated: test requests per 1000 inhabitants, ratios of related tests requests and index of variability. The results obtained in the laboratories in the region of authors were compared to the rest of the participating laboratories in order to establish whether there were regional differences in the test requesting patterns. RESULTS: The rate of request of the tests ranged from 31.5 per 1000 inhabitants for vitamin B12 to 372.6 per 1000 inhabitants for glucose. The index of variability ranged from 1.53 for glucose and triglycerides to 7.4 for alkaline phosphatase. Regarding the ratios of related test requests, the variability index ranged from 1.24 for folic acid/vitamin B12 to 26.38 for lactate dehydrogenase/alanine transaminase. The most frequently ordered tests were the ones with less variability, except for uric acid and urinalysis. No significant differences were identified between the results of the laboratories in the region of authors and the rest, except for urinalysis (p < 0.001), folic acid/vitamin B12 (p = 0.030), and transferrin/ferritin (p = 0.018). CONCLUSIONS: A considerable variability exists in laboratory test ordering patterns by general practitioners across Spanish regions. Local habits must have been decisive as shown by the regional differences in the results of indicators of some tests. The study results bring out the need to accomplish interventions to improve appropriate use of laboratory tests.

Management of procalcitonin test overuse in an emergency department through a computer algorithm.

OBJECTIVES: To show the procalcitonin (PCT) test demand from an emergency department (ED) over several years, to decrease PCT measurement via a computerized algorithm based on C-reactive protein (CRP) value, and to evaluate the subsequent economic savings. STUDY DESIGN: A cross-sectional study was performed from January 1, 2018, to May 31, 2019, to evaluate an intervention to avoid PCT measurement in the ED of Hospital Universitario San Juan in Alicante in Spain, when CRP values are low. METHODS: A PCT result of at least 1.5 ng/mL was agreed upon with ED providers in our study as the value for clinical decision-making, with values less than 1.5 ng/mL considered negative. We retrospectively reviewed all PCT and CRP values for ED patients and calculated the diagnostic indicators for PCT at 4 different CRP cutoffs using the PCT quantification as the gold standard. From July 1, 2019, to April 30, 2021, the agreed-upon strategy was implemented, and we counted the PCT tests avoided and calculated the savings. RESULTS: PCT was not measured when CRP values were less than the selected CRP cutoff of 0.8 mg/dL, at which false-negative results were 1% and the 99th percentile of PCT was 1.5 ng/mL. In the postintervention period, 1091 PCT values were not measured and $11,553.69 was saved. CONCLUSIONS: An intervention to decrease PCT measurement in the ED designed by the clinical laboratory staff in consensus with requesting clinicians and based on CRP values decreased PCT testing and generated significant economic savings.

Laboratory reflex testing strategy for the early identification of primary care patients with multiple myeloma.

OBJECTIVES: Our objective was to shorten the screen for multiple myeloma (MM), through reflex testing. DESIGN AND METHODS: The clinical laboratory in the public University Hospital of San Juan (Alicante, Spain), serves 234,551 inhabitants. Through an intervention agreed with general practitioners, the Laboratory Information System (LIS) automatically registered serum immunoglobulins (Ig) when serum total proteins (STP) > 80 g/L for the first time in primary care patients. When concomitantly one Ig presented a value above and one below its reference interval, the LIS automatically registered a serum protein electrophoresis (SPEP). When a monoclonal peak in SPEP, immunofixation electrophoresis (IFE) for the typification of monoclonal bands (MB) was performed. If MB were present, a comment in the report explained the intervention. The number of additionally registered Ig, SPEP, IFE, and new diagnosis of MM were counted. The number of days elapsed from the report of elevated STP result to the final MM diagnosis was also counted as median and interquartile range (IQR), and compared to a pre intervention period. RESULTS: 2071 cases of hyperproteinemia were identified, and had 91 a monoclonal peak, confirmed by IFE. In 35 patients it was a new finding, and 9 were diagnosed with MM, 3 Waldestrom macroglobulinemia, 2 lymphoplasmacytic lymphoma and 21 monoclonal gammopathy of undetermined significance. The number of days elapsed from hyperproteinemia to diagnosis was lower in the intervention period (21.5 vs 119.4) (P < 0.01). As our results show, in addition to shortening the time to diagnosis, an increased rate of detection of plasma cell disorders was observed when using our algorithm. CONCLUSIONS: The above laboratory interventions agreed with clinicians, making use of laboratory technology resulted in early identification of MM.

Knowledge and practices regarding prostate cancer screening in Spanish men: The importance of personal and clinical characteristics (PROSHADE study).

INTRODUCTION: Patients' decisions on prostate cancer (PCa) opportunistic screening may vary. This study aimed to assess how demographic and health-related characteristics may influence knowledge and decisions regarding PCa screening. METHODS: A cross-sectional survey was conducted among men aged over 40, randomly sampled from the Spanish population, 2022. The survey underwent development and content validation using a modified Delphi method and was administered via telephone. Binomial logistic regression was used to explore the relationship between respondents' characteristics and participants' knowledge and practices concerning PCa and the PSA test. RESULTS: Out of 1,334 men, 1,067 (80%) respondents were interviewed with a mean age of 58.6 years (sd 11.9). Most had secondary or university studies (787, 73.8%) and 61 (5.7%) self-reported their health status as bad or very bad. Most of the respondents (1,018, 95.4%) had knowledge regarding PCa with nearly 70% expressed significant concern about its potential development (720, 70.8%), particularly among those under 64 years (p = 0.001). Out of 847 respondents, 573 (67.7%) reported that they have knowledge regarding the PSA test: 374 (65.4%) reported receiving information from a clinicians, 324 (86.6%) information about the benefits of the test and 189 (49,5%) about its risks, with differences based on educational background. In a multivariable analysis (adjusted for age, educational level and previous prostate problems), respondents with higher levels of education were more likely to have higher knowledge regarding the PSA test (OR 1.75, 95%CI 1.24-2.50, p<0.001). CONCLUSIONS: Although most of the patients reported to have knowledge regarding PCa, half of the interviewed men reported knowledge about PSA test. Differences in knowledge prostate cancer screening and undesirable consequences highlight the need to develop and provide tailored information for patients.