Band 12, Heft 3

Coronary artery disease (CAD) is the leading cause of cardiovascular events and showed high prevalence and healthcare costs in 2019. However, CAD screening for cardiovascular event prevention is invasive and expensive. This study aims to estimate the ability of a noninvasive method, pulse wave velocity (PWV), to detect the presence or absence of coronary artery disease in patients with suspected CAD. A systematic review and meta-analysis of the available evidence was conducted, comparing PWV with the gold standard diagnostic method, angiography. The literature search was systematically performed in the PubMed, Scopus and Web of Science databases from inception to August 2024. Study quality assessment was performed using the Diagnostic Accuracy Study Quality Assessment Tool (QUADAS-2). Publication bias was assessed using the method proposed by Deeks. Statistical analyses were performed with the STATA SE software, version 15. The eight included studies had a cross-sectional design, in which the presence of CAD was measured simultaneously by PWV and angiography. To assess the accuracy of the tests, the overall sensitivity and specificity were combined into a single value, the diagnostic odds ratio (dOR), which provided a value of 3.61, indicating a high probability of detecting CAD by PWV. The implementation of PWV as a screening technique in healthcare centers could bring great benefits to patients with suspected CAD and increase efficiency in the use of healthcare resources.

Prenatal screening (PNS) can be a very effective strategy for identifying the individuals at-risk of genetic disorders. In contrast to prenatal genetic tests, which are very expensive, require special set-ups and expertise, PNS can be of great help in reducing the burden of genetic disorders, especially in the Indian context. During the last 10 years, several advanced PNS tests utilizing new platforms, with comparatively more sensitivity and specificity, have emerged. PNS tests for chromosomal aneuploidies, microdeletion syndromes, hemoglobinopathies, neural tube defects etc. are available. However, primary health care providers need to be made more aware about the availability of different tests, the time point at which these need to be used, appropriateness of these tests to various presentations and interpretation of the result. They need to be periodically informed about the availability, limitations, sensitivity and specificity of different platforms for PNS. Further, there is a need to develop uniform, updated and practical guidelines on PNS and disseminate these to health care providers so as to benefit the mass population. This article compiles information on different types of PNS and prenatal diagnostic tests, commonly required for different genetic conditions. These recommendations may help clinicians and primary healthcare providers in PNS.

Introduction The differential diagnosis of fever of unknown origin (FUO) resembles that of inflammation of unknown origin (IUO), but the concept and differential diagnosis of FUO with no inflammatory laboratory evidence (FUO-NIL) are unknown. The aim was to propose the concept of FUO-NIL and explore its differential diagnosis. Content The present study is a scoping review of FUO-NIL, defined as FUO with normal serum C-reactive protein (CRP). The PubMed, Embase, CENTRAL, Web of Science, and Google Scholar databases were searched for relevant information. A study was considered eligible for enrolment if the final diagnosis was definitive and the CRP value was clearly noted as normal in each case. The data extracted included the patients’ clinical information, final diagnosis, diagnostic tests performed, treatments, and outcomes. Summary and Outlook The full text of 342 of 3,084 articles were reviewed, and 17 articles met the inclusion criteria. The review identified 19 cases that were eligible for quantitative analysis. The disease categories were infection (n=10, 52.6 %), malignancy (n=3, 15.8 %), non-infectious, inflammatory disease (n=4, 21.1 %), and miscellaneous (n=2, 10.5 %). A more specific differential diagnosis included intracellular fungal infection, tuberculosis, malignancy, systemic lupus erythematosus, granulomatous diseases, Fabry disease, hemophagocytic lymphohistiocytosis, and functional hyperthermia. FUO-NIL may have a unique differential diagnosis and have a different etiology from that of inflammatory FUO. In addition to the standard diagnostic work-up for FUO, tailored diagnostic strategies, including checking for a history of animal contact, the presence of hypohidrosis, and psychosocial stressors may be warranted in cases of FUO-NIL.

Introduction Dengue is a viral infection caused by any one of the four related dengue virus (DENV) serotypes, 1–4. DENV is a single-stranded RNA virus belonging to the genus Flavivirus . Dengue can cause a range of symptoms, from mild to severe life-threatening illness. Currently, treatment for DENV is limited to supportive care, with better outcomes achieved through early diagnosis. The WHO has suggested that dengue mortality can be reduced to nearly zero by implementing appropriate clinical management strategies, such as early laboratory diagnosis. This calls for diagnostic approaches that combine high sensitivity and specificity, while also being suitable for point-of-care testing (POCT) in remote locations with minimal staff training and low testing costs. Content In this paper, we outline the limitations of existing confirmatory dengue diagnostic methods, such as ELISA and RT-PCR, which are time-consuming, expensive, and require skilled personnel. We also highlight alternative strategies to overcome these challenges. Additionally, the paper emphasizes the growing clinical demand for diagnosing severe dengue to reduce the risk of death, which must be addressed by next-generation dengue diagnostic approaches. Summary We propose the adoption of alternative strategies, such as fluorescence immunoassay (FIA) and chemiluminescence immunoassay (CLIA), which have the potential to overcome the limitations of existing dengue diagnostic methods. Outlook Improvements in dengue diagnosis, with a specific focus on identifying severe dengue in POCT setting, can help achieve the goal of zero deaths from dengue.

Diagnostic error is a pervasive problem in healthcare with approximately one-third of adverse events in hospitals attributed to a failure in the diagnostic process. Cognitive biases are systematic, often unconscious, automatic patterns of thought that sometimes skew thinking and are considered a major contributor to diagnostic error. More than 100 different biases have been described that affect clinical decision-making, and the challenge for educators and clinicians is bringing the conceptual knowledge of cognitive bias to the bedside in an applicable and useful way to mitigate the effects of cognitive bias in diagnosis. The language that is commonly used around cognitive bias is technical in nature, often with complicated and nuanced descriptions, so developing a clear understanding of cognitive bias is a task that needs sophisticated language and memory skills as well as clinical reasoning skills. A novel language approach to learning and talking about biases in medicine is to use idioms, short phrases with a particular meaning that differs from the meaning of each word on their own, to simplify the terminology and improve recognition of cognitive bias at the frontline. We present ‘The Idiom’s Guide to Cognitive Bias’, a Table that lists 21 common cognitive biases in the diagnostic process, and defines each, offering a healthcare example and possible explanation for why each occurs. The benefit of The Guide is its practical approach to reinforcing cognitive and medical concepts through the synergy of language and imagery and to demystify cognitive bias in the diagnostic process.

Enhancing the resolution of patient history is crucial for accurate diagnosis and improving patient outcomes. This paper introduces the “GREAT PRISM” strategy, a framework to eliminate barriers to reconstructing comprehensive patient history. Grounded in Grid analysis, the analysis organizes patient information along temporal and symptomatic axes to achieve high-resolution narratives for reaching an accurate diagnosis. Techniques such as identifying missing information, uncovering hidden histories, and dissecting temporal patterns are explored. While emphasizing cognitive forcing strategies and practical applications, this method bridges the gap between traditional practices and modern diagnostic approaches, fostering precision in diagnostic excellence from the point-of-care perspective.

Objectives Physicians rarely receive formal training on communicating diagnostic uncertainty to patients. Best practices in timing and educational strategies are not established. We aimed to develop, implement and assess a curriculum on communicating uncertainty for medical students. Methods This was a pseudorandomized and controlled study. Students on their Internal Medicine Clerkship during the study period from February to August 2023 were invited to participate and separated into control and intervention groups based on assigned rotation site. Students in the intervention group received a curriculum on communicating diagnostic uncertainty. All students completed a subscale of the Physicians’ Reaction to Uncertainty Scale (PRUS) at the beginning of their clerkship and at the end of week 4 and an Objective Structured Clinical Examination (OSCE) at the end of week 4. Results Fifty-four students participated in the curriculum (29 intervention, 25 control). Intervention group students scored 2.13 points higher than control group students on their skills assessment (mean OSCE for intervention group=14.3, control group=12.17, p<0.001). PRUS increased in both groups, indicating improved tolerance of uncertainty, with no significant difference in change in PRUS between groups (mean change in PRUS for intervention group=2.68, control group=4.82, p=0.33). 97.7 % of students agreed that a curriculum on uncertainty should be included in their medical training. Conclusions Students who participated in a curriculum on communication of uncertainty demonstrated superior skills in communicating uncertainty during their OSCE. There was a significant increase in PRUS indicating decreased stress associated with uncertainty for all students. This may reflect high levels of baseline stress associated with starting a clerkship, maturation, exposure to cases, or role-modeling by the clinical team.

Objectives Emergency department (ED) encounters carry high risk of diagnostic error. Understanding how providers process information and reach diagnostic conclusions may identify interventions to reduce diagnostic errors. We aimed to determine if pediatric ED notes documenting a simple inventory of alternative diagnoses (inventorial differential diagnosis (DDx)) increased the odds of subsequent diagnostic error compared to encounters where the DDx was explicitly linked to specific data elements in the encounter (synthesized). Methods This is a cohort study of children 0–22 years who experienced unplanned admission within 10 days of an index pediatric ED or urgent care visit. Documented DDx (inventorial vs. synthesized) in the index visit notes served as the predictor variable. The primary outcome was presence of diagnostic error. Propensity scores were created using patient demographics and complexity and visit acuity. Propensity score matched patients were compared with multivariable conditional logistic regression to assess association between documented DDx and diagnostic error. Results Propensity scores matched 303 patient pairs of inventorial and synthesized DDx from 869 charts screened in for review. The adjusted odds ratio for diagnostic error at a subsequent unplanned admission was 1.79 (95 % CI 1.17–2.75) when an inventorial DDx was documented relative to synthesized. This finding includes adjustments for the number of diagnostic tests, obtaining a subspecialty consult and number of hospitalizations in the prior 6 months. Conclusions An inventorial DDx in pediatric emergency medical decision making is associated with significantly higher odds of subsequent diagnostic error, offering an actionable, simple opportunity for all providers to improve patient care.

Objectives Diagnostic errors represent the most common and costly preventable patient safety events, with historically marginalized populations disproportionately impacted due to systemic inequities in healthcare. Addressing these disparities requires embedding equity into every facet of the diagnostic process. The aim was to develop, refine, and validate a competency framework for Equity-Driven Diagnostic Excellence (DxEqEx). Methods A modified Delphi method was used, involving transdisciplinary diverse healthcare system participants, including patient advocates, physicians, nurses, and other healthcare professionals. Participants were guided through multiple rounds of feedback and ratings, assessing the importance, disciplinary relevance, feasibility, skill acquisition level required, granularity, and representativeness of the DxEqEx framework. Results Sixteen essential competencies have been identified, categorized into three domains: Intrapersonal, Team-based, and Structural. Participants rated the framework with high importance and strong relevance to their respective disciplines. However, the feasibility of implementing the framework varied, largely due to broader challenges within the healthcare system. The competencies were assessed as requiring a proficient skill level according to Dreyfus’ model. The final round maintained strong ratings for granularity and representativeness, which supported the final version of the framework. Conclusions The DxEqEx framework holds significant potential to proactively address the needs of historically marginalized patients throughout the diagnostic process. Future research should focus on participatory, resource-efficient implementation.

Objectives Autopsy plays an essential role in detecting diagnostic errors and the findings from autopsies have the potential to reduce future errors. However, there are few reports from Japan on diagnostic errors based on autopsy diagnoses. This study aimed to detail diagnostic errors in autopsy reports in Japan. Methods This descriptive study utilized the case report abstract database of the Japanese Society of Internal Medicine chapter meetings. Autopsy cases from 2002 to 2022 were included. We defined diagnostic errors as discrepancies in the primary cause of death between autopsy and clinical diagnosis. Diagnostic error cases were also categorized according to the 10th revision of the International Statistical Classification of Diseases and Related Health Problems (ICD-10). To observe trends, a chi-square test was conducted by dividing the 20 years of data into four groups. Results Among 1,213 autopsied cases, diagnostic errors occurred in 435 cases (35.9 %; 95 % confidence interval, 33.2–38.6 %). The most frequent category of autopsy-detected diagnostic error cases was neoplasms (147, 33.8 %), followed by infections (131, 30.1 %), and cardiovascular diseases (49, 11.3 %). Over the 20 years, the incidence of diagnostic errors neither increased nor decreased. Conclusions Diagnostic errors detected in 35.8 % of autopsy cases in Japan. Autopsy is an important quality indicator for identifying diagnostic error.

Objectives Context specificity occurs when a health professional sees two patients with identical signs and symptoms yet arrives at two different diagnoses due to other existing factors. For example, one patient speaks English as a first language, while the other patient has limited English proficiency. It is not known if context specificity extends beyond diagnosis and also affects management reasoning. Our study explored whether reduced sleep and other distracting contextual factors (e.g., limited English proficiency) lead to context specificity, resulting in suboptimal management reasoning. Methods Seventeen medical residents participated in a two-month study (consisting of one outpatient and one inpatient rotation), in which their sleep was tracked. After each rotation, participants watched two clinical encounter videos–one with and one without distracting contextual factors–and completed think-aloud interviews for each video discussing their management plans. Interviews were transcribed and assessed for management reasoning themes. Results Residents (n=17) on outpatient rotations received more sleep than those on inpatient rotations (450.5 min ± 7.13 vs. 425.6 min ± 10.78, p=0.023). Five management reasoning themes were identified: organized knowledge, disorganized knowledge, uncertainty, addressing non-pharmacologic interventions, and addressing patient needs and concerns. There was essentially no difference in the prevalence of utterances of organized knowledge themes between residents with more or less sleep (25 vs. 27 times, p=0.78) or those exposed to contextual factors vs. not exposed (24 vs. 28 times, p=0.58). However, disorganized knowledge themes were observed significantly more frequently in participants exposed to contextual factors (33 vs. 18 times, p=0.036). Conclusions Residents slept more during outpatient rotations. While sleep alone was not associated with the prevalence of management reasoning themes, residents exposed to videos with distracting contextual factors displayed significantly more instances of disorganized knowledge, supporting the phenomenon of context specificity in management reasoning.

Objectives Although cognitive biases are one of the most frequent causes of diagnostic errors, their influence remains underestimated in allied health professions, especially in osteopathy. Yet, a part of osteopathic clinical reasoning and diagnosis rely on the practitioner’s intuition and subjective haptic perceptions. The aim of this study is to highlight links between the cognitive biases perceived by the practitioner to understand cognitive patterns during osteopathic diagnosis, and to suggest debiasing strategies. Methods A mixed method based on an explanatory sequential type is used. (QUAN→QUAL). A quantitative cross-sectional survey of 272 French osteopaths and three focus groups including 24 osteopaths were carried out. The quantitative analysis includes multinominal logistic regression models and multiple correspondence analysis. The qualitative analysis is based on the framework method (within thematic analysis) and followed a step-by-step guide (Gale et al.). Results Among 19 selected biases, osteopaths feel to be affected by 9.4 ± 0.28 biases (range [1−19], median=9). Some presumed biases would be associated, and socio-demographic (gender, age) and professional (experience and types of practice) factors would modify how practitioners perceive the presence of biases. Main debiasing solutions are supervision and transcultural clinical competences. Conclusions Osteopaths believe their diagnosis is impaired by the presence of cognitive biases as observed in clinical reality. Some biases are shared with medical doctors, but others are more specific to osteopaths, such as confirmation bias. To reduce their effect, the practitioner needs to be aware of these cognitive patterns of clinical reasoning, understand the patient and himself better, and use objective tests.

Objectives To compare proportions of pediatric emergency department (PED) patients with missed opportunities for diagnostic excellence (MODEs) by patient race and ethnicity, defined as either White non-Hispanic/Latino (WNH), or non-WNH. In addition, to assess the thoroughness of the PED patient evaluation by patient race and ethnicity. Methods Electronic trigger (E-trigger) followed by manual screening identified children with unplanned admission within 10 days of an index PED or pediatric urgent care (PUC) encounter from January 2018 through July 2022. Cases with disparate diagnoses at index encounter and hospital discharge were reviewed using the Revised Safer Dx tool to determine the presence of a MODE. Patient race and ethnicity were abstracted from the electronic record. The primary outcome was proportion of MODEs by race and ethnicity, analyzed using univariate comparisons; the secondary outcome was the completeness of the diagnostic evaluation. Independent predictors of MODEs were identified following multivariable logistic regression analysis. Results A total of 816 patients were screened in for Revised Safer Dx review, and a total of 183 potential MODEs were identified. Non-WNH populations did not differ significantly by proportion of potential MODEs when compared to WNH patients. WNH patients received a higher median number of diagnostic tests (p=0.02), more diagnostic workup (p=0.03), and more frequently had the eventual correct diagnosis initially considered (p=0.02) than non-WNH patients. Race and ethnicity did not significantly affect the odds of a MODE. Conclusions While race and ethnicity did not predict higher odds of a MODE, non-WNH PED/PUC populations received disparate levels of diagnostic consideration.

Objectives Fundoscopy can be challenging for non-ophthalmologists. For emergency physicians, non-mydriatic fundus photography is superior to other forms of ophthalmoscopy in sensitivity, specificity, and inter-examination agreement. We report on a prospective cross-sectional study evaluating the use of non-mydriatic photography as a triage and telemedicine tool for patients with vision loss in a Canadian emergency setting. Methods Images of both eyes were obtained by a non-ophthalmologist using a handheld, non-mydriatic fundus camera and shared with a fellowship-trained ophthalmologist without patient context. The reviewer was asked to (1) select the best photo obtained for each eye and rate image quality on a Likert scale, (2) comment on the presence or absence of fundus abnormalities and (3) provide an opinion on whether findings would have changed patient disposition if available at the time of the initial Emergency Department (ED) exam. Results Of 57 patients evaluated in the ED for vision loss, 22.8 % had a documented fundus examination. 86.8 % of images were deemed to have acceptable quality (Likert scale≥2). Factors limiting image quality included media opacity, pupillary miosis, photosensitivity, and eyelid/periorbital abnormalities. Of patients with relevant abnormalities, 0 % were identified by emergency physicians. In contrast, 37.5 % of patients with relevant findings were identified on review of images alone (specificity=100 %). Conclusions Fundoscopy is infrequently performed in the emergency setting in patients presenting with vision loss. Non-mydriatic fundus photography is a cost-effective method of fundus examination for non-expert examiners and can be reliably used as a telemedicine tool for remote ophthalmology consultation.

Objectives The MR imaging lesion burden described as “innumerable” is rare, and can present a diagnostic challenge. Brain MR imaging with this descriptive term has not been systematically studied. We determine risk factors and MR imaging sequences helpful in a diagnostic algorithm for innumerable brain MR lesions. Methods Twelve thousand four hundred ninety-five brain MR imaging studies done at our institution from July 1, 2013 to June 30, 2016 were surveyed for the term “innumerable”. Inclusion criteria included 50 or more parenchymal lesions. Patients were classified into active and chronic groups, based on MR characteristics and clinical features. Results One hundred and twenty three reports contained the term “innumerable”. Thirty-one met inclusion criteria and 19 showed active, and 12 chronic brain process. The active group included 9 metastasis, 6 infarction, 2 microbleeds, and one each, foreign body granulomatous reaction and fungal abscesses. The MR feature accompanied or heralded onset of illness in eight patients. Malignancy was a risk factor in nine patients with metastasis and in 2 with infarct from cancer-associated hypercoagulation. Other risk factors included immunosuppression, endocarditis, long bone fracture and aortic dissection. Conclusions MR defined active innumerable brain lesions occurred in 0.25 % of studies. Fifteen of 19 in the active group were due to metastasis or infarction, defined by T1-weighted gadolinium enhancement and restricted-diffusion respectively. A diagnostic algorithm based on MR imaging features and risk factors can guide critical decision for brain biopsy.

Objectives Cellulitis shares several clinical features with fulminant deep soft tissue infections, creating a diagnostic dilemma for which clinicians are increasingly using cross-sectional diagnostic imaging to resolve. However, the role of imaging in apparent cellulitis is poorly defined. In particular, the clinical utility of CT in extremity cellulitis is underexplored. The purpose of this study was to determine patient and clinical factors that increase likelihood for finding of deep infection on CT among patients with extremity cellulitis. Methods A retrospective observational study was performed of patients with cellulitis of the extremities who were examined with computed tomography from January 1, 2012 to December 31, 2021. Demographics, medical history, and clinical and laboratory characteristics were collected. The presence of positive findings on CT report was recorded. Repeated measures logistic regression was used to evaluate significant predictors of positive CT. Results There were 496 eligible patient encounters, and CT was positive for deep infection in 39 cases (7.9 %). Median patient age was 56 years of age, 58.1 % were male, and most patients had a history of diabetes mellitus, history of tobacco use, and/or obesity. Significant predictors for positive CT on multivariable analysis included gas on pre-CT radiographs, febrile leukopenic state, injection drug use, purulence on exam, and white blood cell count extremes. Elevated CRP was also a significant positive predictor on bivariate analysis. Conclusions Finding a deep infection on CT in a patient with extremity cellulitis is uncommon and is predominantly associated with a high-risk clinical picture, and/or with high index of suspicion based on pre-CT plain films. In the absence of these patient factors or compelling findings on radiographs, CT does not typically provide clinically actionable information for extremity cellulitis and should not be used as part of standard evaluation.

A bstract Objectives Diagnostic and management reasoning of neurological disorders may present unique challenges and uncertainty for clinicians, particularly in emergency department settings. This study aims to assess the level of uncertainty emergency department physicians experience when diagnosing neurological versus non-neurological conditions, and whether this uncertainty extends to the management of neurological conditions. Additionally, the study explores whether clinical experience is related to perceived diagnostic and/or management uncertainty. Methods Fifty-three emergency department physicians completed a survey measuring diagnostic uncertainty, management uncertainty, and associated anxiety. The survey included clinical vignettes depicting neurological and non-neurological cases, as well as items which assessed perceived diagnostic and management uncertainty across eight different specialties. Statistical analyses included paired samples t-test for comparing uncertainty between neurology and non-neurology cases and a general linear model to assess relationship between clinical experience and uncertainty. Results Emergency department physicians reported greater diagnostic uncertainty for neurological vignettes compared to non-neurological vignettes (Cohen’s d=1.37), as well as greater management uncertainty (Cohen’s d=1.41). They also reported greater anxiety when diagnosing neurological cases compared to non-neurological cases (Cohen’s d=1.33), as well as greater anxiety when managing them (Cohen’s d=0.69). Exploratory analyses indicated that with greater experience, management uncertainty of neurology cases decreased, while diagnostic uncertainty remained unchanged. Conclusions The results suggest unique diagnostic and management challenges posed by neurological cases in emergency departments, particularly for less experienced providers. Future research could focus on developing interventions to reduce diagnostic and management uncertainty in neurological conditions.

Objectives Scandinavian evaluation of laboratory equipment for point of care testing (SKUP) provides objective and supplier-independent information about analytical quality and user-friendliness of point-of-care (POC) measuring systems. The evaluation reports are freely available online and are valuable tools when selecting fit-for-purpose POC equipment. In this study, we present an overview of the performance of four POC measuring systems for monitoring prothrombin time international normalized ratio (INR) assessed against updated analytical performance specifications (APSs). Methods Primary healthcare centres (PHCCs) in Sweden and Norway did the practical work under real-life conditions. In each evaluation, 2–4 PHCCs participated with at least 40 patients on Warfarin treatment per site. Capillary samples were measured on the POC INR systems (qLabs Q3 Plus PT-INR Owren, Xprecia Stride, microINR or ProTime InRhythm), with venous samples analysed at hospital laboratories for comparison (STA-R Evolution or Sysmex CS5100). In the current study, APSs from SKUP, ISO 17593:2022, and CLSI POCT14-Ed2 were used. User-friendliness was assessed by addressing operational facilities, user-manual, time factors, and quality control. Results Only microINR coagulometer met the APS for accuracy, while qLabs Q3 Plus PT-INR Owren and ProTime InRhythm met the repeatability criteria. Xprecia Stride scored highest on user-friendliness, whereas the other systems faced challenges with sample application and unclear error messages on the devices. Conclusions This study highlights the potential for improvements in POC INR measuring systems and underscores the importance of performing objective evaluations under real-life conditions.

Objectives This study reported a large cohort of fetal blood analysis of various hemoglobinopathies. Methods A total of 371 fetal blood specimens were recruited. Complete blood count and hemoglobin (Hb) analysis using capillary electrophoresis were performed. Genotypes were defined by DNA analysis. Results Among 371 fetuses, 36 were non-thalassemic and 29 thalassemia genotypes were identified in the remaining 335 fetuses. Fetuses with β-thalassemia and Hb E traits, homozygous Hb E, and Hb E-β 0 -thalassemia had similar hematological parameters as those of non-thalassemic. However, the levels of Hb A in β-thalassemia and Hb E traits were approximately half of that observed in the non-thalassemic fetuses. As for Hb E, fetuses with a single copy of the β E -globin gene in the Hb E trait and Hb E-β 0 -thalassemia had lower Hb E levels as compared to that of the homozygous Hb E. For α-thalassemia, fetuses with one or two α-globin gene defects had small changes in hematological parameters, but variable Hb Bart’s levels were observed. Fetuses with Hb H and Hb H-CS diseases had moderate anemia, whereas those with homozygous Hb CS and Hb Bart’s hydrops fetalis had severe anemia. Identification of the fetuses with Hb Bart’s hydrops fetalis with various genetic interactions allows the exact re-location of electrophoretic mobilities of various embryonic Hbs. Conclusions This study confirmed the genetic heterogeneity of hemoglobinopathies among the fetuses and fetal blood analysis are useful for presumptive diagnosis of hemoglobinopathies. The results should facilitate a prevention and control program of hemoglobinopathies in the region.

Objectives This study aimed to develop and implement autoverification (AV) system for routine coagulation assays, specifically prothrombin time (PT) and activated partial thromboplastin time (APTT), in tertiary care hospital. The efficiency, accuracy, and impact on turnaround time (TAT) were evaluated . Methods AV rules were developed using historical data from 70,865 coagulation test results. The rules included pre-analytical, analytical, and post-analytical checks. The system underwent validation through data simulations, pilot phase, go-live implementation. Performance metrics included sensitivity, specificity, predictive values, passing rates, error rates, TAT. Results The AV system achieved 63.3 % overall passing rate (analyzed from 159,183 data), with outpatient settings showing higher rate (69.2 %) than inpatient settings (56.3 %). Final performance evaluation showed sensitivity, specificity, PPV, and NPV of 93.0 , 65.0, 59.7, and 94.4 %, respectively. Manual verification was required for 36 % of cases, mainly due to defective sample volumes (21.5 %). False negatives, primarily from partial clots, occurred in 0.1 % of cases. Integrating CBC clot alerts into AV rules halved the errors. The system increased tests completed within guaranteed TAT of 90 min by 2.4 %, from 89.7 to 92.1 % and reduced median TAT by 5 min. Outpatient TAT improved significantly, with a reduction over 19 min. Conclusions The AV system for APTT and PT tests was successfully implemented, reducing manual verification, improving TAT, particularly in outpatient settings. This study highlights AV systems’ potential to enhance laboratory performance for routine coagulation panels, which rely only on APTT and PT assays. Ongoing rule refinement and monitoring remain crucial for enhancing system accuracy and effectiveness.

Objectives Biomarkers are useful clinical tools but only a handful of them are used routinely for patient care. Despite intense efforts to discover new, clinically useful biomarkers, very few new circulating biomarkers were implemented in clinical practice in the last 40 years. This is mainly due to rather poor clinical performance. Here, our goal was to validate the performance of a group of newly discovered circulating biomarkers for glioma by comparing our data with data from a paper recently published in Science Advances. Methods We analyzed our own sets of clinical samples (gliomas (n=30), meningiomas (n=20)) and a different analytical assay (Proximity Extension Assay, OLINK Proteomics) to compare the results of Shen and colleagues. Results Despite the sophistication of the utilized discovery method by the original investigators, we found that the newly proposed biomarkers for glioma (the best one presumably being SERPINA6) did not perform as originally claimed. Conclusions Scientific irreproducibility has been extensively discussed in the literature. A large proportion of newly discovered candidate biomarkers likely represent “false discovery” and significantly contribute to the propagation of irreproducible results between investigators. One of the best ways to assess the value of any new biomarker is by independent and extensive validation. Based on our previous classification of irreproducible results, we believe that this new work likely represents another example of biomarker false discovery.

Objectives Published clinical reasoning curricula are limited, and measuring curricular impact has proven difficult. This study aims to evaluate the impact of a broad-reaching, multi-level reasoning curricula by measuring utilization of clinical reasoning terminology in published abstracts. Methods In 2014, the University of Pittsburgh Medical Center (UPMC) created a clinical reasoning curriculum with interventions at the student, resident, and faculty levels with the goal of bringing reasoning education to the forefront. This study was a retrospective analysis of published clinical vignettes of the Society of General Internal Medicine prior to local curricular intervention (2014), post-curricular intervention (2018), and on follow-up (2022). UPMC-affiliated abstracts were compared to abstracts containing reasoning terms from all other institutions, at each time point. Results There was a statistically significant increase in the use of clinical reasoning terms by UPMC-affiliated participants from 2014 to 2018. Non-UPMC submissions, saw a smaller, but still significant increase in the use of clinical reasoning terms. There was a decline in clinical reasoning term use from 2018 to 2022, both at UPMC and nationally. Conclusions This study demonstrates that widespread clinical reasoning curricula can increase interest in and use of clinical reasoning terminology. Further work is needed to develop creative assessment tools for reasoning curricula.

Objectives We performed a comparative evaluation of analytical performance between the novel bench-top Stago sthemO 301 hemostasis analyzer and the Werfen ACL TOP 750 coagulometer using routine plasma samples. Methods A minimum of 100 fresh plasma samples per test were analyzed using both analytical systems. The tests included prothrombin time (PT) expressed as international normalized ratio (INR) and seconds (s), activated partial thromboplastin time (APTT) in ratio and seconds, fibrinogen, antithrombin and D-dimer. Clotting assays were performed using mechanical clot detection on sthemO and optical detection on ACL TOP. The comparative evaluation included the calculation of Spearman’s correlation, Passing–Bablok regression and Bland–Altman plots. Results Correlation coefficients ranged between 0.76 for APTT to 0.98 for PT-INR and D-dimer, indicating a generally acceptable/good agreement. The regression slopes varied from 0.82 for D-dimer to 1.17 for APTT-s. A significant bias was observed for all tests except antithrombin, with differences for sthemO ranging between −31 % for D-dimer and 13.7 % for PT-s. Conclusions SthemO demonstrates acceptable global comparability with ACL TOP for routine coagulation testing. Nevertheless, reagent- and method-dependent bias has been observed, which highlight the need for additional harmonization efforts.