Real evidence to assess clinical testing interference risk (REACTIR): A strategy using real world data to assess the prevalence of interfering substances in patients undergoing clinical laboratory testing.

INTRODUCTION: Laboratory test interferences can cause spurious test results and patient harm. Knowing the frequency of various interfering substances in patient populations likely to be tested with a particular laboratory assay may inform test development, test utilization and strategies to mitigate interference risk. METHODS: We developed REACTIR (Real Evidence to Assess Clinical Testing Interference Risk), an approach using real world data to assess the prevalence of various interfering substances in patients tested with a particular type of assay. REACTIR uses administrative real world data to identify and subgroup patient cohorts tested with a particular laboratory test and evaluate interference risk. RESULTS: We demonstrate the application REACTIR to point of care (POC) blood glucose testing. We found that exposure to several substances with the potential to interfere in POC blood glucose tests, including N-acetyl cysteine (NAC) and high dose vitamin C was uncommon in most patients undergoing POC glucose tests with several key exceptions, such as burn patients receiving high dose IV-vitamin C or acetaminophen overdose patients receiving NAC. CONCLUSIONS: Findings from REACTIR may support risk mitigation strategies including targeted clinician education and clinical decision support. Likewise, adaptations of REACTIR to premarket assay development may inform optimal assay design and assessment.

A Multicenter Evaluation of a Point-of-Care Blood Glucose Meter System in Critically Ill Patients.

BACKGROUND: Our purpose was to evaluate the performance of the ACCU-CHEK® Inform II blood glucose monitoring system (Roche Diagnostics GmbH) compared with the perchloric acid hexokinase (PCA-HK) comparator method on the cobas® 6000 analyzer (Roche Diagnostics International Ltd) in critically ill patients. METHODS: Overall, 476 arterial (376 pediatric/adult, 100 neonate), 375 venous, and 100 neonatal heel-stick whole-blood samples were collected and evaluated from critical care settings at 10 US hospitals, including the emergency department, medical and surgical intensive care units (ICUs), and neonatal and pediatric ICUs. The ACCU-CHEK Inform II system was evaluated at 2 cutoff boundaries: boundary 1 was ≥95% of results within ±12 mg/dL of the reference (samples with blood glucose <75 mg/dL) or ±12% of the reference (glucose ≥75 mg/dL), and boundary 2 was ≥98% of results within ±15 mg/dL or ±15% of the reference. Clinical performance was assessed by evaluating sample data using Parkes error grid, Monte Carlo simulation, and sensitivity and specificity analyses to estimate clinical accuracy and implications for insulin dosing when using the ACCU-CHEK Inform II system. RESULTS: Proportions of results within evaluation boundaries 1 and 2, respectively, were 96% and 98% for venous samples, 94% and 97% for pediatric and adult arterial samples, 84% and 98% for neonatal arterial samples, and 96% and 100% for neonatal heel-stick samples. Clinical evaluation demonstrated high specificity and sensitivity, with low risk of potential insulin-dosing errors. CONCLUSIONS: The ACCU-CHEK Inform II system demonstrated clinically acceptable performance against the PCA-HK reference method for blood glucose monitoring in a diverse population of critically ill patients in US care settings.

Implementation of High-Sensitivity and Point-of-Care Cardiac Troponin Assays into Practice: Some Different Thoughts.

BACKGROUND: The primary role of the International Federation of Clinical Chemistry (IFCC) Committee on Clinical Application of Cardiac Bio-Markers (C-CB) is to provide educational materials about cardiac biomarker use, emphasizing high-sensitivity cardiac troponin assays. CONTENT: This mini-review, regarding high-sensitivity cardiac and point-of-care troponin assays, addresses 1) new IFCC C-CB/AACC Academy laboratory practice recommendations; 2) new and updated concepts from the Fourth Universal Definition of Myocardial Infarction; 3) the role of point-of-care assays in practice and research; 4) regulatory challenges concerning point-of-care assays; e) testing in the COVID-19 world. SUMMARY: Implementation of high-sensitivity cardiac troponin assays makes a difference now and into the future in clinical practice and research. Providing point-of-care high-sensitivity cardiac troponin assays and optimizing studies to allow clearance of these assays by regulatory agencies, in a timely fashion, may provide improved patient management and outcomes.

Assay Integrity of a PCR Influenza Point-of-Care Test Remains Following Artificial System Contamination.

BACKGROUND: Healthcare providers who have access to tests at the point of care (POC) are increasingly requesting the same performance from the POC test as they expect from the laboratory. With the introduction of the cobas® Liat instrument, highly sensitive molecular diagnostic testing can be performed closer to the patient in CLIA-waived, POC settings. As more sensitive tests become available, there is concern regarding contamination of instrumentation owing to improper handling, mistakes made when processing, or environmental contamination. Recent concerns were raised when a nurse performed environmental surveillance for flu A/B by inserting a dry swab into the cobas Liat instrument and then ran it as a sample on the instrument, generating a positive result. This finding stimulated questions about the possibility of system contamination contributing to false-positive results, ultimately leading to the possibility of providing incorrect treatment to patients. METHODS: To assess the likelihood of system contamination contributing to the generation of false-positive results, in this study we contaminated a cobas Liat System with flu A/B-positive control material. The system contamination was then assessed by swabbing exposed surfaces. Following confirmed system contamination, negative control samples were processed to determine whether system contamination had an impact on the expected negative results. RESULTS: Instrument contamination was confirmed, and no detectable flu A/B signal was observed for any of the negative control tubes run immediately following confirmation of system contamination. CONCLUSION: Environmental contamination of the Liat instrument does not have an impact on the integrity of the result.

Current evidence and future perspectives on the effective practice of patient-centered laboratory medicine.

BACKGROUND: Systematic evidence of the contribution made by laboratory medicine to patient outcomes and the overall process of healthcare is difficult to find. An understanding of the value of laboratory medicine, how it can be determined, and the various factors that influence it is vital to ensuring that the service is provided and used optimally. CONTENT: This review summarizes existing evidence supporting the impact of laboratory medicine in healthcare and indicates the gaps in our understanding. It also identifies deficiencies in current utilization, suggests potential solutions, and offers a vision of a future in which laboratory medicine is used optimally to support patient care. SUMMARY: To maximize the value of laboratory medicine, work is required in 5 areas: (a) improved utilization of existing and new tests; (b) definition of new roles for laboratory professionals that are focused on optimizing patient outcomes by adding value at all points of the diagnostic brain-to-brain cycle; (c) development of standardized protocols for prospective patient-centered studies of biomarker clinical effectiveness or extraanalytical process effectiveness; (d) benchmarking of existing and new tests in specified situations with commonly accepted measures of effectiveness; (e) agreed definition and validation of effectiveness measures and use of checklists for articles submitted for publication. Progress in these areas is essential if we are to demonstrate and enhance the value of laboratory medicine and prevent valuable information being lost in meaningless data. This requires effective collaboration with clinicians, and a determination to accept patient outcome and patient experience as the primary measure of laboratory effectiveness.

Pathology consultation on prostate-specific antigen testing.

OBJECTIVES: To provide clarity on the pros and cons of using prostate-specific antigen (PSA) as a screening tool for prostate cancer. METHODS: Case scenarios and a literature review of recently published clinical trial data are presented to provide evidence of the controversy. RESULTS: PSA is a sensitive biomarker for detecting diseases of the prostate, but it is limited in its ability to distinguish cancerous from noncancerous conditions or aggressive from indolent cancers and has resulted in a considerable amount of overdiagnosis and overtreatment. CONCLUSIONS: The analytical methodology for total PSA testing is both reliable and cost-effective, but patients should be encouraged to talk to their providers to understand the benefits and harms associated with this testing.

A prospective tool for risk assessment of sendout testing.

OBJECTIVE: Errors associated with laboratory testing can cause significant patient harm. Sendout testing refers to tests sent by a primary lab to a reference lab when testing is unavailable at the primary lab. Sendout testing is particularly high risk for patient harm, due to many factors including increased hand-offs, manual processes, and complexity associated with rare, low-volume tests. No published prospective tools exist for sendout risk assessment. METHODS: A novel prospective tool was developed to assess risk of diagnostic errors involving laboratory sendout testing. This tool was successfully piloted at nine sites. RESULTS: Marked diversity was noted among survey respondents, particularly in the sections on quality metrics and utilization management. Of note, most sites had committees who managed rules for test ordering, but few places reported enforcing these rules. Only one site claimed to routinely measure the frequency clinicians failed to retrieve test results. An evaluation of the tool indicated that it was both useful and easy to use. CONCLUSIONS: This tool could be used by other laboratories to identify the areas of highest risk to patients, which in turn may guide them in focusing their quality improvement efforts and resources.

Barriers to quality health care for the transgender population.

The transgender community is arguably the most marginalized and underserved population in medicine. A special issue focusing on men's health would be incomplete without mention of this vulnerable population, which includes those transitioning to and from the male gender. Transgender patients face many barriers in their access to healthcare including historical stigmatization, both structural and financial barriers, and even a lack of healthcare provider experience in treating this unique population. Historical stigmatization fosters a reluctance to disclose gender identity, which can have dire consequences for long-term outcomes due to a lack of appropriate medical history including transition-related care. Even if a patient is willing to disclose their gender identity and transition history, structural barriers in current healthcare settings lack the mechanisms necessary to collect and track this information. Moreover, healthcare providers acknowledge that information is lacking regarding the unique needs and long-term outcomes for transgender patients, which contributes to the inability to provide appropriate care. All of these barriers must be recognized and addressed in order to elevate the quality of healthcare delivered to the transgender community to a level commensurate with the general population. Overcoming these barriers will require redefinition of our current system such that the care a patient receives is not exclusively linked to their sex but also considers gender identity.

Dermal exposure to a compounded pain cream resulting in severely elevated clonidine concentration.

INTRODUCTION: Clonidine is an imidazoline derivative antihypertensive medication that is also used as adjunctive therapy for neuropathic pain disorders via topical administration. Clonidine overdose can manifest both central and peripheral alpha-adrenergic agonist effects. CASE REPORT: A 23-year-old man presented to an emergency department with altered mental status, bradycardia, and hypertension after suspected overdose. He had rubbed a specially compounded medicinal cream over his entire body containing clonidine 0.2 % (w/w), gabapentin 6 %, imipramine 3 %, ketamine 10 %, lidocaine 2 %, and mefenamic acid 1 %. The patient presented with severe hypertension, bradycardia, and altered mental status. He was found to have a subarachnoid hemorrhage and was treated for hypertensive emergency. Toxicological analysis of initial blood samples revealed a serum clonidine concentration of 5,200 ng/ml. At 6-month follow-up, the patient had made a full recovery. DISCUSSION: There are limited reports of topical clonidine toxicity, and to our knowledge, this case involves the highest concentration yet reported following clonidine overdose by any route of exposure. The severely elevated serum clonidine concentration found in our patient demonstrates the possibility of toxicity resulting from inappropriate use of such a product. At high serum concentrations, the pharmacodynamic effects of clonidine appear to cause significant peripheral alpha-1 adrenergic stimulation. Toxicologists should be aware of the increasing use of topical clonidine preparations for the treatment of neuropathic pain and the potential for toxicity.

Interpreting laboratory results in transgender patients on hormone therapy.

BACKGROUND: Clinical guidelines recommend laboratory monitoring of transgender persons on cross-sex hormone therapy, but gender-specific reference intervals leave clinicians with the dilemma of deciding what is "normal" for each patient. The goal of this study was to identify consistent changes in measurands with hormone therapy and determine which reference interval is appropriate. METHODS: Laboratory data were abstracted from the medical records of 55 male-to-female patients on hormone therapy and compared with 20 male and 20 female nontransgender subjects. RESULTS: Hemoglobin, hematocrit, and low-density lipoprotein resembled female values (P < .005), while alkaline phosphatase, potassium, and creatinine resembled male values (P < .05). Triglycerides were higher (P < .005) than either the male or female groups. The remainder of the measurands showed no differences. CONCLUSIONS: Use of correct reference intervals in interpreting laboratory results reduces the risk of testing-related diagnostic error. Preliminary data suggest that new reference intervals need to be established for transgender patients.

A comprehensive acute coronary syndrome algorithm for centers with percutaneous coronary intervention capability.

A comprehensive acute coronary syndrome (ACS) protocol was developed to improve the quality of care for patients admitted with definite or probable ACS. These protocols were constructed to streamline the practice for diverse clinicians who care for ACS patients across a variety of clinical settings. They are applicable in the emergency department, the cardiac catheterization laboratory, and the inpatient settings for hospitals with primary percutaneous coronary intervention capability. These protocols standardized the care by selecting the best therapy for each clinical scenario based on available established guidelines to insure the safest and highest value (quality/cost) medical care.

Using an algorithmic approach to secondary amenorrhea: Avoiding diagnostic error.

Secondary amenorrhea in women of reproductive age may be an indication of an undiagnosed, chronic condition and appropriate treatment is dependent upon accurate diagnosis of the underlying etiology. A thorough clinical assessment and a few common laboratory tests can easily identify the most frequent causes of secondary amenorrhea. However, once these have been ruled out, the more uncommon pathophysiologies can be difficult to diagnose due to similarities in presentation and appropriate laboratory testing and interpretation become critical. In these cases, misdiagnosis is unfortunately common and often the result of poor laboratory utilization in the form of a failure to employ indicated tests, the use of obsolete tests, or erroneous interpretation in the face of interfering factors or co-morbidities. Consequently, the algorithmic approach to laboratory evaluation in the context of secondary amenorrhea described in this review can minimize the risk of diagnostic error as well was decrease test volume, cost, and time to diagnosis.

Rate of detection of unsuspected pregnancies after implementation of mandatory point-of-care urine pregnancy testing prior to hysterosalpingography.

PURPOSE: The aim of this study was to determine the rate of detection of unsuspected pregnancies after the implementation of mandatory point-of-care urine pregnancy testing before hysterosalpingography (HSG). METHODS: At the authors' institution, HSGs are scheduled to occur during days 8 to 12 of the menstrual cycle. Upon arrival in the radiology department, all women undergo point-of-care urine pregnancy testing before HSG (at a cost of $1.25 per test). Urine pregnancy test results were retrospectively reviewed. RESULTS: Four hundred ten women (mean age, 25.9 years; range, 22-50 years) underwent point-of-care urine pregnancy testing before HSG between October 2010 and July 2012. Study indications were infertility evaluation (90.7% [372 of 410]) and tubal patency assessment after placement of tubal occlusive devices (9.3% [38 of 410]). Two positive urine pregnancy test results (0.5%) were recorded. One positive result was deemed a false-positive because the patient had received an intramuscular injection of ß-human chorionic gonadotropin before the scheduled HSG, and follow-up laboratory testing showed declining ß-human chorionic gonadotropin levels. The second positive result was a true-positive, and the patient was determined to be 4.5 weeks pregnant on the date of the scheduled HSG. CONCLUSIONS: One of 410 women presenting for HSG was found to have an unsuspected early pregnancy, which was detected with a point-of-care urine pregnancy test. Consideration should be given to routine pregnancy testing of women before HSG because scheduling on the basis of menstrual cycle dates can be unreliable.