Issues in assessing analytical performance specifications in healthcare systems assembling multiple laboratories and measuring systems.

Analytical performance specifications (APS) are usually compared to the intermediate reproducibility uncertainty of measuring a particular measurand using a single in vitro diagnostic medical device (IVD MD). Healthcare systems assembling multiple laboratories that include several IVD MDs and cater to patients suffering from long-term disease conditions mean that samples from a patient are analyzed using a few IVD MDs, sometimes from different manufacturers, but rarely all IVD MDs in the healthcare system. The reproducibility uncertainty for results of a measurand measured within a healthcare system and the components of this measurement uncertainty is useful in strategies to minimize bias and overall measurement uncertainty within the healthcare system. The root mean squares deviation (RMSD) calculated as the sample standard deviation (SD) and relative SD includes both imprecision and bias and is appropriate for expressing such uncertainties. Results from commutable stabilized internal and external control samples, from measuring split natural patient samples or using big-data techniques, are essential in monitoring bias and measurement uncertainties in healthcare systems. Variance component analysis (VCA) can be employed to quantify the relative contributions of the most influential factors causing measurement uncertainty. Such results represent invaluable information for minimizing measurement uncertainty in the interest of the healthcare system's patients.

Six Sigma - is it time to re-evaluate its value in laboratory medicine?

The Sigma metric is widely used in laboratory medicine.

Clot time ratio (CTR) and relation to treatment outcome in patients with atrial fibrillation treated with Rivaroxaban.

BACKGROUND: There are situations where information about the anticoagulant effects of Rivaroxaban could be clinically useful. Methods for measuring Rivaroxaban concentrations are not available at all medical laboratories while the test MRX PT DOAC for measuring the functional effects of Rivaroxaban, in CTR (Clot Time Ratio), can be made available around the clock. The objectives of this study were to investigate CTR in trough and peak samples during Rivaroxaban treatment of atrial fibrillation and to correlate the findings to bleeding episodes. METHODS: 3 trough- and 3 peak samples from 60 patients (30 on 20 mg daily and 30 on 15 mg daily) were analyzed with PT DOAC. Patients were monitored for 20 months, and bleeding and thrombotic events were documented. Descriptive statistics were used to summarize the data and non-parametric t-test for comparison between groups. ROC curves for the prediction of DOAC plasma levels > 50 ng/mL as determined with LC-MS/MS and anti-FXa methods were computed. RESULTS: There was a significant difference between trough and peak CTR (median CTR 1.33 vs. 3.57, p < 0.001). 28 patients suffered bleeds. Patients on 20 mg Rivaroxaban with bleeds had higher mean peak CTR than patients without bleeds (CTR 4.11 vs. CTR 3.47, p = 0.040). There was no significant difference in mean CTR between patients on 15 mg Rivaroxaban with or without bleeds (CTR 3.81 vs. 3.21, p = 0.803), or when considering all patients (CTR 3.63 vs. 3.56, p = 0.445). Five out of seven patients on Rivaroxaban 20 with mean peak CTR above the dose specific first to third quartile range (Q1-Q3) suffered bleeds, while 7/16 patients with mean peak CTR within, and 1/7 patients with mean peak CTR below the Q1-Q3 suffered bleeds. The area under the ROC curve was > 0.98 at the upper limit of the PT DOAC reference interval and the negative predictive value of PT DOAC for the prediction of DOAC plasma levels > 50 ng/mL was > 0.96. CONCLUSIONS: The sample size was too low to draw any firm conclusions but is seems that MRX PT DOAC might be a useful laboratory test in situations where the effect of Rivaroxaban needs evaluation.

Expression of calcitonin gene-related peptide in atopic dermatitis and correlation with distress.

BACKGROUND: Atopic dermatitis (AD) is a chronic, inflammatory, often severely itching skin disorder. It may worsen due to stress, depression, or anxiety. Calcitonin gene-related peptide (CGRP) may be involved in inflammation signaling. CGRP has also been suggested in relation to stress, depression, and anxiety. This study aimed to investigate the expression of CGRP in the skin of patients with AD. METHODS: Twenty-seven adult patients with AD, characterized with clinical and psychodemographic parameters, were investigated regarding CGRP expression in skin biopsies, using an immunohistochemical technique. RESULTS: The total number of CGRP-positive nerve-like fibers was found to be higher in lesional skin than in non-lesional skin. Moreover, more inflammatory cells of dendritic shape intruded into the epidermis in lesional skin compared to non-lesional skin. Keratinocytes showing expression of CGRP were also found in lesional skin. Interestingly, the number of CGRP-positive nerve-like fibers in lesional skin correlated with depressive and anxiety scores. Correlation with depressive score was also found for round CGRP-positive inflammatory cells in the epidermis. CONCLUSIONS: CGRP may have a role in both the inflammatory process and distress, in AD.

Distribution, cellular localization, and colocalization of several peptide neurotransmitters in the central nervous system of Aplysia.

Neuropeptides are widely used as neurotransmitters in vertebrates and invertebrates. In vertebrates, a detailed understanding of their functions as transmitters has been hampered by the complexity of the nervous system. The marine mollusk Aplysia, with a simpler nervous system and many large, identified neurons, presents several advantages for addressing this question and has been used to examine the roles of tens of peptides in behavior. To screen for other peptides that might also play roles in behavior, we observed immunoreactivity in individual neurons in the central nervous system of adult Aplysia with antisera raised against the Aplysia peptide FMRFamide and two mammalian peptides that are also found in Aplysia, cholecystokinin (CCK) and neuropeptide Y (NPY), as well as serotonin (5HT). In addition, we observed staining of individual neurons with antisera raised against mammalian somatostatin (SOM) and peptide histidine isoleucine (PHI). However, genomic analysis has shown that these two peptides are not expressed in the Aplysia nervous system, and we have therefore labeled the unknown peptides stained by these two antibodies as XSOM and XPHI There was an area at the anterior end of the cerebral ganglion that had staining by antisera raised against many different transmitters, suggesting that this may be a modulatory region of the nervous system. There was also staining for XSOM and, in some cases, FMRFamide in the bag cell cluster of the abdominal ganglion. In addition, these and other studies have revealed a fairly high degree of colocalization of different neuropeptides in individual neurons, suggesting that the peptides do not just act independently but can also interact in different combinations to produce complex functions. The simple nervous system of Aplysia is advantageous for further testing these ideas.

Sex Hormones and Adrenal Steroids: Biological Variation Estimated Using Direct and Indirect Methods.

BACKGROUND: Biological variation (BV) data may be used to develop analytical performance specifications (APS), reference change values (RCV), and support the applicability of population reference intervals. This study estimates within-subject BV (CVI) for several endocrine biomarkers using 3 different methodological approaches. METHODS: For the direct method, 30 healthy volunteers were sampled weekly for 10 consecutive weeks. Samples were analyzed in duplicate for 17-hydroxyprogesterone (17-OHP), androstenedione, cortisol, cortisone, estradiol, follicle-stimulating hormone (FSH), luteinizing hormone (LH), sex hormone-binding globulin (SHBG), and testosterone. A CV-ANOVA with outlier removal and a Bayesian model were applied to derive the CVI. For estradiol, FSH and LH, only the male subgroup was included. In the indirect method, using the same analytes and groups, pairs of sequential results were extracted from the laboratory information system. The total result variation for individual pairs was determined by identifying a central gaussian distribution in the ratios of the result pairs. The CVI was then estimated by removing the effect of analytical variation. RESULTS: The estimated CVI from the Bayesian model (µCVP(i)) in the total cohort was: 17-OHP, 23%; androstenedione, 20%; cortisol, 18%; cortisone, 11%; SHBG, 7.4%; testosterone, 16%; and for the sex hormones in men: estradiol, 14%; FSH, 8%; and LH, 26%. CVI-heterogeneity was present for most endocrine markers. Similar CVI data were estimated using the CV-ANOVA and the indirect method. CONCLUSIONS: Similar CVI data were obtained using 2 different direct and one indirect method. The indirect approach is a low-cost alternative ensuring implementation of CVI data applicable for local conditions.

Overcoming challenges regarding reference materials and regulations that influence global standardization of medical laboratory testing results.

BACKGROUND: Standardized results for laboratory tests are particularly important when their interpretation depends on fixed medical practice guidelines or common reference intervals. The medical laboratory community has developed a roadmap for an infrastructure to achieve standardized test results described in the International Organization for Standardization standard 17511:2020 In vitro diagnostic medical devices - Requirements for establishing metrological traceability of values assigned to calibrators, trueness control materials and human samples. Among the challenges to implementing metrological traceability are the availability of fit-for-purpose matrix-based certified reference materials (CRMs) and requirements for regulatory review that differ among countries. A workshop in December 2021 focused on these two challenges and developed recommendations for improved practices. DISCUSSION: The participants agreed that prioritization of measurands for standardization should be based on their impact on medical decisions in a clinical pathway. Ensuring that matrix-based CRMs are globally available for more measurands will enable fit-for-purpose calibration hierarchies for more laboratory tests. Regulation of laboratory tests is important to ensure safety and effectiveness for the populations served. Because regulations are country or region specific, manufacturers must submit recalibration changes intended to standardize results for regulatory review to all areas in which a measuring system is marketed. RECOMMENDATIONS: A standardization initiative requires collaboration and planning among all interested stakeholders. Global collaboration should be further developed for prioritization of measurands for standardization, and for coordinating the production and supply of CRMs worldwide. More uniform regulatory submission requirements are desirable when recalibration is implemented to achieve internationally standardized results.

The LEAP checklist for laboratory evaluation and analytical performance characteristics reporting of clinical measurement procedures.

Reporting a measurement procedure and its analytical performance following method evaluation in a peer-reviewed journal is an important means for clinical laboratory practitioners to share their findings. It also represents an important source of evidence base to help others make informed decisions about their practice. At present, there are significant variations in the information reported in laboratory medicine journal publications describing the analytical performance of measurement procedures. These variations also challenge authors, readers, reviewers, and editors in deciding the quality of a submitted manuscript. The International Federation of Clinical Chemistry and Laboratory Medicine Working Group on Method Evaluation Protocols (IFCC WG-MEP) developed a checklist and recommends its adoption to enable a consistent approach to reporting method evaluation and analytical performance characteristics of measurement procedures in laboratory medicine journals. It is envisioned that the LEAP checklist will improve the standardisation of journal publications describing method evaluation and analytical performance characteristics, improving the quality of the evidence base that is relied upon by practitioners.

The LEAP checklist for Laboratory Evaluation and Analytical Performance Characteristics reporting of clinical measurement procedures.

Reporting a measurement procedure and its analytical performance following method evaluation in a peer-reviewed journal is an important means for clinical laboratory practitioners to share their findings. It also represents an important source of evidence base to help others make informed decisions about their practice. At present, there are significant variations in the information reported in laboratory medicine journal publications describing the analytical performance of measurement procedures. These variations also challenge authors, readers, reviewers, and editors in deciding the quality of a submitted manuscript.The International Federation of Clinical Chemistry and Laboratory Medicine Working Group on Method Evaluation Protocols (IFCC WG-MEP) developed a checklist and recommends its adoption to enable a consistent approach to reporting method evaluation and analytical performance characteristics of measurement procedures in laboratory medicine journals. It is envisioned that the LEAP checklist will improve the standardisation of journal publications describing method evaluation and analytical performance characteristics, improving the quality of the evidence base that is relied upon by practitioners.

Prenatal stress, anxiety and depression alter transcripts, proteins and pathways associated with immune responses at the maternal-fetal interface†.

During pregnancy, the immune system is modified to allow developmental tolerance of the semi-allogeneic fetus and placenta to term. Pregnant women suffering from stress, anxiety, and depression show dysfunctions of their immune system that may be responsible for fetal and/or newborn disorders, provided that placental gene regulation is compromised. The present study explored the effects of maternal chronic self-perceived stress, anxiety, and depression during pregnancy on the expression of immune-related genes and pathways in term placenta. Pregnancies were clinically monitored with the Beck Anxiety Inventory (BAI) and Edinburgh Postnatal Depression Scale (EPDS). A cutoff threshold for BAI/EPDS of 10 divided patients into two groups: Index group (>10, n = 11) and a Control group (<10, n = 11), whose placentae were sampled at delivery. The placental samples were subjected to RNA-Sequencing, demonstrating that stress, anxiety, and depression during pregnancy induced a major downregulation of placental transcripts related to immune processes such as T-cell regulation, interleukin and cytokine signaling, or innate immune responses. Expression differences of main immune-related genes, such as CD46, CD15, CD8α & ß ILR7α, and CCR4 among others, were found in the Index group (P < 0.05). Moreover, the key immune-like pathway involved in humoral and cellular immunity named "Primary immunodeficiency" was significantly downregulated in the Index group compared with Controls. Our results show that mechanisms ruling immune system functions are compromised at the maternal-fetal interface following self-perceived depressive symptoms and anxiety during pregnancy. These findings may help unveil mechanisms ruling the impact of maternal psychiatric symptoms and lead to new prevention/intervention strategies in complicated pregnancies.

Estimating Analytical Errors of Glomerular Filtration Rate Measurement.

BACKGROUND: Few studies are available on how to optimize time points for sampling and how to estimate effects of analytical uncertainty when glomerular filtration rate (GFR) is calculated. METHODS: We explored the underlying regression mathematics of how analytical variation of a kidney filtration marker affects 1-compartment, slope-and-intercept GFR calculations, using 2 or 3 time points following a bolus injection, and used this to examine the results from 731 routine 3-point iohexol plasma clearance measurements. RESULTS: GFR calculations inflated analytical uncertainty if the time points were taken too late after the bolus injection and too close after each other. The uncertainty in GFR calculation was, however, the same as the analytical uncertainty if optimal time points were used. The middle of the 3 samples was of little value. The first sample should be taken as early as possible after the distribution phase. Sampling before the patient specific half-life of the kidney filtration marker resulted in an exponential error inflation whereas no error inflation was seen when sampling occurred later than 2 half-lives. Theoretical GFR uncertainty could be lowered 2.6-fold if individually optimized time points for sampling had been used in our 731 clearance measurements. Using Taylor expansions to approximate the moments of transformed random variables, the uncertainty of an individual GFR measurement could be calculated in a simple enough way to be applicable by laboratory software. CONCLUSIONS: We provide a theoretical foundation to select patient-optimal time points that may both limit errors and allow calculation of GFR uncertainty.

Pre-traumatic conditions can influence cortisol levels before and after a brain injury.

OBJECTIVE: Satisfactory anabolic reactions, including the activation of the hypothalamic-pituitary-adrenal (HPA) axis, are essential following severe traumatic brain injury (TBI) and aneurysmal subarachnoid hemorrhage (SAH). Many factors may influence this activation. This study aimed to investigate whether individuals who reported chronic diseases, psychosocial afflictions, or stressful events before a severe brain injury display a different pattern regarding cortisol levels retrospectively and up to three months compared with those who did not report stressful experiences. MATERIALS AND METHODS: Fifty-five patients aged 16-68 years who were admitted to the neurointensive care unit (NICU) were included. Hair cortisol measurements offer a unique opportunity to monitor cortisol levels retrospectively and after the trauma. Hair strands were collected as soon as possible after admission to the NICU and every month until three months after the injury/insult. The participants/relatives were asked about stressful events, psychosocial afflictions and recent and chronic diseases. RESULTS: The group who reported chronic diseases and/or stressful events before the brain injury had more than twice as high median hair cortisol levels before the brain injury compared with those who did not report stress, but the difference was not statistically significant (P = .12). Those who reported stress before the brain injury had statistically significantly lower hair cortisol values after the brain injury and they remained until three months after the injury. CONCLUSIONS: Stressful events and/or chronic disease before brain injury might affect mobilization of adequate stress reactions following the trauma. However, the large variability in cortisol levels in these patients does not allow firm conclusions and more studies are needed.

Stress and perceived health among primary care visitors in two corners of Europe: Scandinavia and Greece.

BACKGROUND: The global financial crisis emerging in 2008 struck Greece especially hard, whereas Scandinavian countries were less affected. This has created a unique opportunity to study the long-term effect of community stress on populations. Increasing frequencies of mental health issues and poorer perceived health among the Greek population have been reported. The physiological marker of long-term stress, cortisol in hair, is applied in this study together with measures of perceived health and stress, depression and anxiety. Our aim was to study self-reported and physiological stress, perceived health, including mental health, in the general population of Greece compared to Scandinavia, in order to assess long-term effects of the economic crisis on these parameters. METHODS: A cross-sectional comparative study of adult (18-65 years) Primary Health Care visitors from semi-rural areas in Greece (n = 84) and Scandinavia (n = 140). Data collection was performed in 2012, and encompassed a questionnaire with a variety of health and stress indicators as well as hair samples for analyzes of cortisol levels. RESULTS: The Greek sample reported significantly poorer overall health (p < 0.0001) than the Scandinavians and a significantly higher perceived stress (p < 0.0001). The Greeks were also less hopeful of the future (p < 0.0001), and to a larger extent fulfilled the HAD criteria for depression (p < 0.0001) and anxiety (p = 0.002). The strongest predictors explaining ill health in logistic regressions were being Greek (p = 0.001) and feeling hopeless about the future p = 0.001, OR = 6.00 (CI 2.10-14.88). Strong predictors in logistic regressions for high perceived stress were anxiety: high (p < 0.0001) and medium (p = 0.0001), as well as medium depression (p = 0.02). CONCLUSIONS: Greek adult Primary Health Care visitors perceived their health more negatively than the Scandinavians, including a higher presence of depression, anxiety, and a lower hope for the future. The Greeks also reported higher perceived stress, but this was not reflected in higher cortisol levels. The findings presented here, identify possible adverse long-term effects of the economic crisis in the examined Greek population that are not seen in the Scandinavian cohort. These differences may also be interpreted against the background of socio-cultural differences in the northern and south-eastern corners of Europe.

Repeatability imprecision from analysis of duplicates of patient samples and control materials.

Measurement imprecision is usually calculated from measurement results of the same stabilized control material(s) obtained over time, and is therefore, principally, only valid at the concentration(s) of the selected control material(s). The resulting uncertainty has been obtained under reproducibility conditions and corresponds to the conventional analytical goals. Furthermore, the commutability of the control materials used determines whether the imprecision calculated from the control materials reflects the imprecision of measuring patient samples. Imprecision estimated by measurements of patient samples uses fully commutable samples, freely available in the laboratories. It is commonly performed by calculating the results of routine patient samples measured twice each. Since the duplicates are usually analysed throughout the entire concentration interval of the patient samples processed in the laboratory, the result will be a weighted average of the repeatability imprecision measured in the chosen measurement intervals or throughout the entire interval of concentrations encountered in patient care. In contrast, the uncertainty derived from many measurements of control materials over periods of weeks is usually made under reproducibility conditions. Consequently, the repeatability and reproducibility imprecision play different roles in the inference of results in clinical medicine. The purpose of the present review is to detail the properties of the imprecision calculated by duplicates of natural samples, to explain how it differs from imprecision calculated from single concentrations of control materials, and to elucidate what precautions need to be taken in case of bias, e.g. due to carry-over effects.

An experimental study of methods for the analysis of variance components in the inference of laboratory information.

Measurement uncertainty (MU) can be estimated and calculated by different procedures, representing different aspects and intended use. It is appropriate to distinguish between uncertainty determined under repeatability and reproducibility conditions, and to distinguish causes of variation using analysis of variance components. The intra-laboratory MU is frequently determined by repeated measurements of control material(s) of one or several concentrations during a prolonged period of time. We demonstrate, based on experimental results, how such results can be used to identify the repeatability, 'pure' reproducibility and intra-laboratory variance as the sum of the two. Native patient material was used to establish repeatability using the Dahlberg formula for random differences between measurements and an expanded Dahlberg formula if a non-random difference, e.g. bias, was expected. Repeatability and reproducibility have different clinical relevance in intensive care compared to monitoring treatment of chronic diseases, comparison with reference intervals or screening.

Measurement repeatability profiles of eight frequently requested measurands in clinical chemistry determined by duplicate measurements of patient samples.

Measurement uncertainties in clinical chemistry are commonly regarded as heteroscedastic - having a constant relative standard deviation irrespective of the concentration of the measurand. The uncertainty is usually determined at two concentrations using stabilized control materials and assumed to represent the analytical goal. The purpose of the present study was to use duplicates of unselected patient samples to calculate the absolute and relative repeatability component of the intra-laboratory measurement uncertainty from duplicates, using the Dahlberg formula and analysis of variance components. Estimates were made at five different concentration intervals of ALT, AST, Calcium, Cholesterol, Creatinine, CRP, Triglycerides and TSH covering the entire concentration interval of the patient cohort. This partioning allows detailing their repeatability profiles. The calculations of the profiles were based on randomly selected results from sets of duplicates ranging from 12,000 to 65,000 pairs. The repeatability of the measurands showed substantial variability within the measuring interval. Therefore, characterizing imprecision profiles as purely homo- or heteroscedastic or by a single number may not be optimal for the intended use. The present data make a case for nuancing the evaluation of analytical goals and minimal differences of measurement results by establishing uncertainty profiles under repeatability conditions, using natural patient samples.

Self-reported mental health and cortisol activity at 27-28 years of age in individuals born with very low birthweight.

AIM: To assess mental health outcomes of very low birthweight (VLBW, <1500 g) subjects to adulthood and to examine salivary cortisol and hair cortisol levels and their relation to birth characteristics and mental health. METHODS: A Swedish regional cohort of 56 VLBW subjects and 55 full-term controls were assessed at the ages 27-28 with adult self-reported scales and the mean of 2 days diurnal salivary cortisol and hair cortisol. The cohorts had been assessed at 15 years of age with youth self-reported scales. RESULTS: There were no differences between the groups in youth self-reported scales and adult self-reported scores. The 24 participating VLBW girls scored lower on youth self-reported scales externalising and total problem scores than the control girls. In adulthood, the 21 participating VLBW women had significantly higher morning concentrations of salivary cortisol than control women, P = .014. No significant associations were found between cortisol concentrations and adult self-reported scales internalising, externalising and total scores. CONCLUSION: Self-reported mental health in VLBW subjects was comparable with normal birthweight controls indicating a satisfying transition from adolescence to adulthood. VLBW females had higher morning salivary cortisol concentrations, suggesting a gender difference. We found no correlations between cortisol and mental health.

Women born with very low birth weight have similar menstrual cycle pattern, pregnancy rates and hormone profiles compared with women born at term.

BACKGROUND: Individuals born very preterm or with very low birth weight (VLBW) have a reduced likelihood to reproduce according to population-based register studies. Extremely low-birth weight born adults had a lower reproduction rate for both men and women in a follow-up study. AIM: To investigate if being born with VLBW is associated with differences in the reproductive health, i.e. age of menarche, menstrual cycle pattern, pregnancy rates and hormone profile compared with women born at term. METHODS: A prospective long-term follow-up of a cohort of live-born VLBW children and their controls studied repeatedly since birth and now assessed at 26-28 years of age. Of the totally 80 girls enrolled from birth 49 women (24 VLBW women and 25 controls) participated in the current follow-up. The women's anthropometric data and serum hormone levels were analysed. RESULTS: The reproductive hormone levels, including Anti-Mullerian Hormone, did not differ significantly between VLBW women and their controls. Both groups reported menstrual cycle irregularities and pregnancies to the same extent but the VLBW women reported 1.5 years later age of menarche. The VLBW subjects had a catch-up growth within 18 months of birth but remained on average 5 cm shorter in adult height. There were no significant differences in BMI, sagittal abdominal diameter, blood pressure or in their answers regarding life style between the VLBW women and the controls. CONCLUSION: No differences in the reproductive hormone levels were found between VLBW women and their controls. Although age at menarche was somewhat higher in the VLBW group menstrual cycles and pregnancy rates were similar in the VLBW and control groups. Further follow-up studies are required to elucidate the health outcomes of being born VLBW.

Evaluation of commercial, wireless dermal thermometers for surrogate measurements of core temperature.

Extensive research has been devoted to developing methods for assessing core body temperature, and to determine which method is most accurate. A number of wireless dermal thermometers for home use are presently available, but their relation to core body temperature and suitability for use in clinical research has hitherto not been assessed. The current study aimed to evaluate such thermometers by comparing them to the results of a rectal thermometer. Four wireless dermal thermometers for home use (FeverSmart, iThermonitor, Quest Temp Sitter, and Thermochron iButton) were applied to 15 patients during 24 h, and rectal temperature was measured at four occasions. Pearson correlation revealed moderate correlation for the Feversmart (r = 0.75), iThermonitor (r = 0.79), and Thermochron iButton (r = 0.71) systems. The Quest Temp Sitter system malfunctioned repeatedly, and the correlation (r = 0.29) for this method should therefore be assessed with caution. All dermal thermometers rendered lower average temperatures than Terumo c405 (Feversmart -0.70 ± 0.65 °C; iThermonitor -0.77 ± 0.53 °C, Quest Temp Sitter -1.18 ± 0.66 °C, and Thermochron iButton -0.87 ± 0.65 °C). Sensitivity of the dermal thermometers for detecting core temperatures ≥38.0 °C was low, ranging from 0.33 to 0.6, but improved to 0.60 to 0.80 after adjusting temperatures by the methods' average deviation from rectal temperature. The results from the dermal thermometers tested here showed an insufficient correlation to core temperature to be used for core temperature monitoring in clinical research and practice. Unfortunately, other options for non-invasive temperature measurements are few. The two thermometers with the least unsatisfactory performance profile in our evaluations were the Feversmart and iThermonitor systems.