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.

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.

Reporting age-adjusted D-dimer cut-off values reduces radiology overuse in emergency department patients with suspected deep venous thrombosis.

INTRODUCTION: Venous thromboembolism (VTE) is a leading cause of death, associated with substantial morbidity in the absence of treatment. Our aim was, first, to compare the diagnostic performance of D-dimer for the diagnosis of VTE in the emergency department (ED), when reporting conventional cut-off point versus when additionally reporting age-adjusted values. Second, we explored the ordering pattern of Doppler ultrasound (US) and computerized tomographic pulmonary angiogram (CTPA), before and after reporting of the aforementioned age-adjusted cut-off value. MATERIALS AND METHODS: We conducted a cross-sectional study to compare the diagnostic performance of D-dimer as a screening for VTE when reporting the conventional cut-off value versus when additionally including the age-adjusted metrics, and a quasi-experimental study to explore the ordering of Doppler US and CTPA before the age-specific metrics were shared in the report in ED patients between 50 and 100 years-old with D-dimer ordering. RESULTS: The cross-sectional study included 392 patients, 25 with VTE. The specificity using an age-adjusted cut-off value was significantly higher (0.51) compared to a single absolute cut-off (0.42), and the negative likelihood ratio was lower as well (0.08 vs. 0.19), but again not statistically significant. In the quasi-experimental study, there was a decrease in the rate of use of both CTPA and Doppler US (P < 0.05). CONCLUSION: The intervention improved the use of the D-dimer result in the ED and helped improve the request for imaging tests.

Clinical Decision Support systems: A step forward in establishing the clinical laboratory as a decision maker hubA CDS system protocol implementation in the clinical laboratory.

Background: New tools for health information technology have been developed in recent times, such as Clinical Decision Support (CDS) systems, which are any digital solutions designed to help healthcare professionals when making clinical decisions. The study aimed to show how we have adopted a CDS system in the San Juan de Alicante Clinical Laboratory and facilitate the implementation of our protocol in other clinical laboratories. We have user experience and the motivation to improve healthcare tools. The improvement, measurement, and monitoring of interventions and laboratory tests has been our motto for years. Materials and methods: A descriptive research was conducted. All stages in the design of the project are as follows: 1. Set up a multidisciplinary workgroup. 2. Review patients' data. 3. Identify relevant data from main sources. 4. Design the likely outcomes. 5. Define a complete integration scenario. 6. Monitor and track the impact. To set up this protocol, two new software systems were implemented in our laboratory: AlinIQ CDS v8.2 as Rule Engine, and AlinIQ AIP Integrated Platform v1.6 as Business Intelligence (BI) tool. Results: Our protocol shows the workflow and actions that can be done with a CDS system and also how it could be integrated with other monitoring systems, as well as some examples of KPIs and their outcomes. Conclusions: CDS could be a great strategic asset for clinical laboratories to improve the integration of care, optimize the use of laboratory tests, and add more clinical value to physicians in the interpretation of results.

Reply to Jue, J.S.; Alameddine, M. Role of PSA Density and MRI in PSA Interpretation. Comment on "Lumbreras et al. Variables Associated with False-Positive PSA Results: A Cohort Study with Real-World Data. Cancers 2023, 15, 261".

We thank you and your co-authors for the comment [...].

Laboratory Strategies to Improve Allergy First-Line Screening in Primary Care.

BACKGROUND: There are nonestablished protocols in use for first-line allergy screening based on IgE testing. These protocols attempt to address an unmet need for sustainability of clinical laboratories, at a time when demand is increasing. OBJECTIVE: To present a novel protocol for first-line allergy screening and to evaluate the implementation benefits for patients, the health care system, and payers. METHODS: We carried out an observational retrospective study analyzing 4359 interventions on primary care testing requests. Interventions included overriding redundant serum IgE (sIgE) testing for allergen mixes, extracts included in mixes, low-prevalence extracts, and milk and egg molecular components without previous positive results when exposed to extracts. We also added prevalent allergen testing. RESULTS: The strategy saved 683 tests from being performed unnecessarily. Test volume decline was primarily driven by the cancelation of 2186 egg and milk components tests; 561 tests were added for mixes, together with 942 allergen extracts tests. DISCUSSION: The results of this study show how the allergy laboratory plays a key role in actively managing demand for sIgE testing, leading to optimized diagnosis.

PROSHADE Protocol: Designing and Evaluating a Decision Aid for Promoting Shared Decision Making in Opportunistic Screening for Prostate Cancer: A Mix-Method Study.

Background: Opportunistic prostate-specific antigen (PSA) screening may reduce prostate cancer mortality risk but is associated with false positive results, biopsy complications and overdiagnosis. Although different organisations have emphasised the importance of shared decision making (SDM) to assist men in deciding whether to undergo prostate cancer screening, recent evaluations show that the available decision aids fail to facilitate SDM, mainly because they do not consider the patients' perspective in their design. We aim to systematically develop and test a patient decision aid to promote SDM in prostate cancer screening, following the Knowledge to Action framework. Methods: (1) Feasibility study: a quantitative survey evaluating the population and clinician (urologists and general practitioners) knowledge of the benefits and risks derived from PSA determination and the awareness of the available recommendations. Focus groups to explore the challenges patients and clinicians face when discussing prostate cancer screening, the relevance of a decision aid and how best to integrate it into practice. (2) Patient decision aid development: Based on this data, an evidence-based multicomponent SDM patient decision aid will be developed. (3) User-testing: an assessment of the prototype of the initial patient decision aid through a user-testing design based on mix-methods (questionnaire and semi-structured review). The decision aid will be refined through several iterative cycles of feedback and redesign. (4) Validation: an evaluation of the patient decision aid through a cluster-randomised controlled trial. Discussion: The designed patient decision aid will provide balanced information on screening benefits and risks and should help patients to consider their personal preferences and to take a more active role in decision making. Conclusions: The well-designed patient decision aid (PDA) will provide balanced information on screening benefits and risks and help patients consider their personal preferences.

Stat Laboratory Interventions to Improve Patient Management in the Emergency Department and Resource Expenditure: A 10-Year Study.

OBJECTIVE: To illustrate the changes in stat laboratory procedures over a 10 year period. MATERIALS AND METHODS: We implemented 5 different interventions: reporting total bilirubin through the icteric index, replacing total proteins for albumin, reporting albumin-adjusted calcium in hyper- or hypocalcemia, using lipase as a first marker and amylase-selected scenario, and measuring magnesium in hypocalcemia, hypokalemia, or high lipase values. RESULTS: Only 9.9% of total bilirubin that was requested was measured, which resulted in savings of $22,492.83. There were 30,036 albumin tests measured, and $15,625.18 was saved replacing total protein. There was $41,374.38 spent to measure lipase and amylase; the difference in costs from the lipase establishment was $16,929.62. Finally, $382.30 was spent for magnesium: 717 magnesium levels were measured given hypocalcemia or hypokalemia (42.8% hypomagnesemia), and 123 tests were added because of high lipase (35% hypomagnesemia). Overall, $53,374.15 was saved. CONCLUSION: Progressive changes in stat laboratory procedures resulted in more efficient resources expenditures.

Variables Associated with False-Positive PSA Results: A Cohort Study with Real-World Data.

(1) Background: There are no real-world data evaluating the incidence of false-positive results. We analyzed the clinical and analytical factors associated with the presence of false-positive results in PSA determinations in practice. (2) Methods: A prospective cohort study of patients with a PSA test was performed in clinical practice. We followed the patients by reviewing their medical records for 2 years or until the diagnosis of PCa was reached, whichever came first. (3) Results: False-positive PSA rate was 46.8% (95% CI 44.2-49.2%) and false-negative PSA rate was 2.8% (95% CI 2-3.5%). Patients aged 61-70 years and those over 70 years were more likely to have a false-positive result than those under 45 years (aOR 2.83, 95% CI 1.06-7.55, p = 0.038, and aOR 4.62, 95% CI 1.75-12.22, p = 0.002, respectively). Patients with urinary tract infection were more likely to have a false-positive result (aOR 8.42, 95% CI 2.42-29.34, p = 0.001). Patients with diabetes mellitus were less likely to have a false-positive result (aOR 0.63, 95% CI 0.41-0.98, p = 0.038); (4) Conclusions: This study has generated relevant information that could be very useful for shared decision making in clinical practice.

Dealing with redundant gamma glutamyl transpeptidase in primary care, when requested along with alkaline phosphatase.

The use of gamma glutamyl transpeptidase (GGT) levels as screening test for liver function is controversial. The GGT main utility is in cases in which alkaline phosphatase (ALP) is elevated. We aimed to investigate the request over time for alanine amino transferase (ALT), ALP and GGT, study the effect of a new demand management (DM) intervention for optimal GGT measurement in primary care. Our descriptive study was conducted from January 2010 to December 2020. The intervention was established in November 2019 and consisted of the laboratory information system would automatically remove GGT, if the test had been ordered simultaneously with ALP and there was no prior pathological result on record. We counted the absolute number of measured ALT, ALP and GGT, and calculated the ratios for each of the three markers related to creatinine, and GGT related to ALT in a monthly basis. The number of measured GGT increased slightly and progressively along the study until October 2019, when a decrease was observed. The ALT and ALP request from primary care also increased slightly along years. However, the GGT/ALT ratio never reached the 0.2 goal. Out of the 57,614 GGT requested in primary care patients, 38,167 (66.2%) were not measured. 7633.4€ were saved in reagent. The DM intervention to reduce the measurement of GGT when requested redundantly with ALP in primary care was successful, and the results have been maintained over time as observed by monitoring the GGT/CREA and GGT/ALT indicator results.

Do the Prostate-Specific Antigen (PSA) Tests That Are Ordered in Clinical Practice Adhere to the Pertinent Guidelines?

Scientific societies have provided guidelines to reduce PSA-specific harms. We studied the potential non-compliance of PSA testing with current guidelines in general practice. A cross-sectional study of a random sample of 1291 patients with a PSA test was performed between January and April 2018 in primary health care. Patients with a previous prostate cancer diagnosis or those who were being followed-up for previous high PSA values were excluded. Two independent researchers classified whether each test was potentially non-compliant with recommendations. We estimated frequencies of potentially non-compliant PSA determinations and calculated prevalence ratios (PR) to assess their relationship with possible explanatory variables. A total of 66% (95% CI: 62-69%) of PSA requests in asymptomatic patients were potentially non-compliant with the current guideline. This was associated with having a previous diagnosis of neoplasm (PR adjusted by age and life expectancy: 1.18; 95% CI: 1.02-1.37) as well as being a current consumer of tobacco, alcohol, or other drugs (PR: 0.80; 95% CI: 0.67-0.97). Real world data shows that patients are still frequently exposed to overdiagnosis risk with a PSA potentially non-compliant with recommendations. Patients diagnosed with another neoplasm or non-consumers of toxic substances were more exposed, probably due to increased contact with doctors or health-seeking behaviour.

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.

CONUT: a tool to assess nutritional status. First application in a primary care population.

OBJECTIVES: Malnutrition is an unfavorable prognostic factor associated with an increase in mortality, hospital stays, readmissions and resources consumption. The aim was to screen primary care patients for risk of malnutrition by using the control nutritional (CONUT) score, calculated through total lymphocytes count, serum albumin and total cholesterol, when the three markers were requested, and to compare results between primary care centers (PCC). METHODS: The clinical laboratory located in a 370-bed suburban University Community Hospital serves the Health Department inhabitants (2,34,551), attended in nine PCC. The laboratory information system (LIS) automatically calculated the CONUT score in every primary care patient over 18 years old, when all three laboratory markers were ordered by the General Practitioner. For all primary care patients, we collected demographic data, CONUT index and PCC. We classified results by PCC, and compared them. RESULTS: The clinical laboratory received 74,743 requests from primary care. The CONUT score was calculated in 7,155 (12.28%) patients. Nine hundred seventy-six (13.6%) were at risk of malnutrition according to the CONUT score, mainly male (p<0.01) and over 65 (p<0.01). Detected cases of malnutrition were all mild, except 48 patients (4.9%) with moderate, and one (0.1%) with severe risk. The percentage of patients at risk of malnutrition was not significantly different among PCC, with the exception of one with patients at lower malnutrition risk. CONCLUSIONS: It is possible to use CONUT score as a front-line population-wide laboratory marker to screen for the risk for malnutrition in primary care patients that was lower in one PCC.

Laboratory parameters in patients with COVID-19 on first emergency admission is different in non-survivors: albumin and lactate dehydrogenase as risk factors.

Prompt identification of the clinical status and severity of COVID-19 can be a challenge in the emergency department (ED), as the clinical severity of the disease is variable, real-time reverse-transcription PCR (RT-PCR) results may not be immediately available, and imaging findings appear approximately 10 days after the onset of symptoms. There is currently no set of simple, readily available and fast battery of tests that can be used in the ED as prognostic factors. The purpose was to study laboratory test results in patients with COVID-19 at hospital emergency admission and to evaluate the results in non-survivors and their potential prognostic value. A profile of laboratory markers was agreed with the ED providers based on the International Federation of Clinical Chemistry and Laboratory Medicine recommendation of its usefulness, which was made in 218 patients with COVID-19. Non-survivors were significantly older, and the percentage of patients with pathological values of creatinine, albumin, lactate dehydrogenase (LDH), C reactive protein, prothrombin time, D-dimer, and arterial blood gas, PaO2/FIO2 and satO2/FIO2 indices were significantly higher among the patients with COVID-19 who died than those who survived. Patients who died also presented higher neutrophil counts. Among all studied tests, albumin and LDH were independent prognostic factors for death. The results of the study show pathology in nine laboratory markers in patients with COVID-19 admitted in the ED, valuable findings to take into consideration for its prompt identification when there is no immediate availability of RT-PCR results.

Alopecia and Iron Deficiency: An Interventional Pilot Study in Primary Care to Improve the Request of Ferritin.

BACKGROUND: The aim was to study the demographic and laboratory pattern of primary care patients with alopecia undergoing laboratory testing, more specifically, the request of hemoglobin and ferritin and values showing anemia and iron deficiency, and to evaluate the effects of an intervention involving automatic ferritin registration and measurement when not requested. METHODS: Retrospective and prospective observational cross-sectional studies were conducted, as well as an intervention to automatically register and measure ferritin when not requested by the general practitioner. RESULTS: There were 343 and 1032 primary care laboratory requests prompted by alopecia in the retrospective and prospective studies. Hemoglobin was requested in almost every patient and ferritin in 88%. 5% of the cohort had anemia, and 25% had iron deficiency. The intervention registered and measured that 123 ferritin and 24 iron deficiencies were detected in patients with alopecia, all women, at a cost of 10.6€. CONCLUSION: Primary care patients with alopecia and laboratory tests request were mainly young female. Our intervention added ferritin when not requested, detecting iron deficiency in 27.9% of women, potentially avoiding the adverse effects of iron deficiency on hair loss.

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.