Band 5, Heft 2

Laboratory services around the world are undergoing substantial consolidation and changes through mechanisms ranging from mergers, acquisitions and outsourcing, primarily based on expectations to improve efficiency, increasing volumes and reducing the cost per test. However, the relationship between volume and costs is not linear and numerous variables influence the end cost per test. In particular, the relationship between volumes and costs does not span the entire platter of clinical laboratories: high costs are associated with low volumes up to a threshold of 1 million test per year. Over this threshold, there is no linear association between volumes and costs, as laboratory organization rather than test volume more significantly affects the final costs. Currently, data on laboratory errors and associated diagnostic errors and risk for patient harm emphasize the need for a paradigmatic shift: from a focus on volumes and efficiency to a patient-centered vision restoring the nature of laboratory services as an integral part of the diagnostic and therapy process. Process and outcome quality indicators are effective tools to measure and improve laboratory services, by stimulating a competition based on intra- and extra-analytical performance specifications, intermediate outcomes and customer satisfaction. Rather than competing with economic value, clinical laboratories should adopt a strategy based on a set of harmonized quality indicators and performance specifications, active laboratory stewardship, and improved patient safety.

Therapeutic drug monitoring (TDM) is used to manage drugs with a narrow window between effective and toxic concentrations. TDM involves measuring blood concentrations of drugs to ensure effective therapy, avoid toxicity and monitor compliance. Common drugs for which TDM is used include aminoglycosides for infections, anticonvulsants to treat seizures, immunosuppressants for transplant patients and cardiac glycosides to regulate cardiac output and heart rate. An essential element of TDM is the provision of accurate and clinically relevant reference intervals. Unlike most laboratory reference intervals, which are derived from a healthy population, TDM reference intervals need to relate to clinical outcomes in the form of efficacy and toxicity. This makes TDM inherently more difficult to develop as healthy individuals are not on therapy, so there is no “normal value”. In addition, many of the aforementioned drugs are old and much of the information regarding reference intervals is based on small trials using methods that have changed. Furthermore, individuals have different pharmacokinetics and drug responses, particularly in the context of combined therapies, which exacerbates the challenge of universal TDM targets. This focused review examines the origins and limitations of existing TDM reference intervals for common drugs, providing targets where possible based on available guidelines.

Background: Diagnostic error can lead to increased morbidity, mortality, healthcare utilization and cost. The 2015 National Academy of Medicine report “Improving Diagnosis in Healthcare” called for improving diagnostic accuracy by developing innovative electronic approaches to reduce medical errors, including missed or delayed diagnosis. The objective of this article was to develop a process to detect potential diagnostic discrepancy between pediatric emergency and inpatient discharge diagnosis using a computer-based tool facilitating expert review. Methods: Using a literature search and expert opinion, we identified 10 pediatric diagnoses with potential for serious consequences if missed or delayed. We then developed and applied a computerized tool to identify linked emergency department (ED) encounters and hospitalizations with these discharge diagnoses. The tool identified discordance between ED and hospital discharge diagnoses. Cases identified as discordant were manually reviewed by pediatric emergency medicine experts to confirm discordance. Results: Our computerized tool identified 55,233 ED encounters for hospitalized children over a 5-year period, of which 2161 (3.9%) had one of the 10 selected high-risk diagnoses. After expert record review, we identified 67 (3.1%) cases with discordance between ED and hospital discharge diagnoses. The most common discordant diagnoses were Kawasaki disease and pancreatitis. Conclusions: We successfully developed and applied a semi-automated process to screen a large volume of hospital encounters to identify discordant diagnoses for selected pediatric medical conditions. This process may be valuable for informing and improving ED diagnostic accuracy.

Background: Clinical reasoning is an essential skill in physicians, required to address the challenges of accurate patient diagnoses. The goal of the study was to compare the diagnostic accuracy in Family Medicine residents, with and without the use of a clinical decision support tool (DXplain http://www.mghlcs.org/projects/dxplain). Methods: A total of 87 first-year Family Medicine residents, training at the National Autonomous University of Mexico (UNAM) Postgraduate Studies Division in Mexico City, participated voluntarily in the study. They were randomized to a control group and an intervention group that used DXplain. Both groups solved 30 clinical diagnosis cases (internal medicine, pediatrics, gynecology and emergency medicine) in a multiple-choice question test that had validity evidence. Results: The percent-correct score in the Diagnosis Test in the control group (44 residents) was 74.1±9.4 (mean±standard deviation) whereas the DXplain intervention group (43 residents) had a score of 82.4±8.5 (p<0.001). There were significant differences in the four knowledge content areas of the test. Conclusions: Family Medicine residents have appropriate diagnostic accuracy that can improve with the use of DXplain. This could help decrease diagnostic errors, improve patient safety and the quality of medical practice. The use of clinical decision support systems could be useful in educational interventions and medical practice.

Background: The circadian fluctuations in the blood levels of selected components of the complement system are ill-defined. Some authors found nadir serum levels of C4 and C3 components, together with C3a at nighttime, while others reported insomnia when pro-inflammatory components exhibited increased serum levels. In this study, we quantitatively estimate the morning and evening daytime serum levels of CH50, C4, C3, put into context with C-reactive protein (CRP), cortisol, parathyroid hormone (PTH) and 25(OH)vitamin D at 07:00 A.M. and at 07:00 P.M. Methods: Seven healthy adult women and 11 men who were voluntary participants agreed to a fasting venipuncture in the morning after having normally eaten through the day and in the evening. The C4 and C3 serum levels were measured on a Cobas (Roche Diagnostics, Switzerland) modular analyzer, CH50 was estimated using the COMPL300 enzyme-linked immunosorbent assay (ELISA) of Wieslab (Malmö, Sweden). CRP, 25(OH)vitamin D, PTH and cortisol concentrations were assessed with electro-chemiluminescence immunoassay (ECLIA) on the Roche Cobas 6000 platform; IgG was measured using nephelometry (Siemens, Germany). Results: With the exception of higher PTH levels in the evening [3.12–5.46, 95% confidence interval (CI)] compared to the morning (2.93–4.65, 95% CI), the mean and median values of C4, C3, CH50 as well as CRP, PTH and 25(OH)vitamin D fell within the established reference intervals. Cortisol levels were measured as an internal positive control for diurnal fluctuations (morning: 294–522 nmol/L, 95% CI; evening: 106–136 nmol/L, 95% CI). Conclusions: The concentrations of the assessed complement components C4 and C3 as well as CH50 surrogate assay did not yield significantly different values between early morning and evening. This does not exclude their participation in the circadian metabolome; this pilot study with healthy participants suggests that patients with an autoimmune disease in remission can give their blood samples independently during daytime with or without fasting.

Background: Virilism is a female disorder in which secondary male sexual characteristics develop, caused by an excessive adrenal or ovarian androgen secretion. Case presentation: Here, we report an unusual case of an ovarian steroid cell tumor, not otherwise specified (NOS), in a 68-year-old female who presented with androgenic alopecia, clitoromegaly and an increased muscle mass. Laboratory investigations revealed both ovarian and adrenal hyperandrogenism with an elevation of androgen precursors mimicking congenital adrenal hyperplasia. A left adnexal mass was confirmed by imaging techniques. A laparoscopic bilateral salpingo-oophorectomy was performed and histopathology confirmed the diagnosis of an ovarian steroid cell tumor NOS. After surgical intervention, circulating androgen levels and their precursors returned to normal values in the postmenopausal woman. Conclusions: A detailed anamnesis and physical examination are key to the correct diagnosis in a woman with hyperandrogenism independent of her circulating androgen profile.