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The worldwide spread of coronavirus disease 2019 (COVID-19) has generated a global health crisis and more than a million deaths so far. Epidemiological and clinical characteristics of COVID-19 are increasingly reported, along with its potential relationship with overweight and/or obesity. Therefore, we aim here to review the current scientific literature on the impact of overweight and/or obesity among hospitalized patients who have developed severe or critical forms of COVID-19. Following PRISMA guidelines, our literature search identified over 300 scientific articles using the keywords “obesity” and “COVID-19”, 22 of which were finally selected for reporting useful information on the association between overweight/obesity and disease severity. In particular, in 11 out of the 14 studies (79%) which evaluated the association between obesity and disease severity providing also a risk estimate (i.e., the odd ratio; OR), the OR value was constantly >2. Although the studies were found to be heterogeneous in terms of design, population, sample size and endpoints, in most cases a significant association was found between obesity and the risk of progressing to severe COVID-19 illness, intensive care unit admission and/or death. We can hence conclude that an increased body mass index shall be considered a negative prognostic factor in patients with COVID-19, and more aggressive prevention or treatment shall hence be reserved to overweight and/or obese patients.

Background An increasing number of diagnostic evaluations incorporate genetic testing to facilitate accurate and timely diagnoses. The increasing number and complexity of genetic tests continue to pose challenges in deciding when to test, selecting the correct test(s), and using results to inform medical diagnoses, especially for medical professionals lacking genetic expertise. Careful consideration of a diagnostic workflow can be helpful in understanding the appropriate uses of genetic testing within a broader diagnostic workup. Content The diagnosis of long QT syndrome (LQTS), a life-threatening cardiac arrhythmia, provides an example for this approach. Electrocardiography is the preferred means for diagnosing LQTS but can be uninformative for some patients due to the variable presentation of the condition. Family history and genetic testing can augment physiological testing to inform a diagnosis and subsequent therapy. Clinical and laboratory professionals informed by peer- reviewed literature and professional recommendations constructed a generalized LQTS diagnostic workflow. This workflow served to explore decisions regarding the use of genetic testing for diagnosing LQTS. Summary and outlook Understanding the complexities and approaches to integrating genetic testing into a broader diagnostic evaluation is anticipated to support appropriate test utilization, optimize diagnostic evaluation, and facilitate a multidisciplinary approach essential for achieving accurate and timely diagnoses.

Although the most effective strategy for preventing or containing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreaks relies on early diagnosis, the paramount and unprecedented number of tests needed to fully achieve this target is overwhelming worldwide testing supply and capacity. Molecular detection of SARS-CoV-2 RNA in nasopharyngeal swabs is still considered the reference diagnostic approach. Nonetheless, identification of SARS-CoV-2 proteins in upper respiratory tract specimens and/or saliva by means of rapid (antigen) immunoassays is emerging as a promising screening approach. These tests have some advantages compared to molecular analysis, such as point of care availability, no need of skilled personnel and dedicated instrumentation, lower costs and short turnaround time. However, these advantages are counterbalanced by lower diagnostic sensitivity compared to molecular testing, which would only enable to identifying patients with higher SARS-CoV-2 viral load. The evidence accumulated to-date has hence persuaded us to develop a tentative algorithm, which would magnify the potential benefits of rapid antigen testing in SARS-CoV-2 diagnostics.

Clinical and laboratory tests in clinical medicine include a range of measurements that may be categorized as “normal range” tests, positive or negative tests, or contextual tests. Normal range test results are quantitative and are compared to a reference interval or range provided by the laboratory. Positive or negative tests are also quantitative tests and characteristically have a cutoff value that specifies the result. Contextual tests require a context, a physiological condition, to correctly interpret the result. A closer examination of reference intervals suggests that these also are contextual. The fact that there is a range of apparently normal values indicates the presence of cultural, biological, physiological and behavioral diversity in the population sampled to determine normality. As such, the reference interval describes the population from which it was determined and may have utility in this regard.

The introduction of cardiac troponin (cTn) testing in clinical practice has been one of the most important breakthroughs that have occurred in the recent history of laboratory medicine. Although it is now uncontestable that cTn values are essential for diagnosing acute coronary syndrome (ACS), solid evidence is also emerging that assessment of either cardiac troponin I (cTnI) or T (cTnT) may provide valuable prognostic information in the general healthy population, as well as in patients with a vast array of cardiac and extra-cardiac diseases. We have hence performed a critical review of the scientific literature for identifying meta-analyses which have investigated the potential contribution of cTns in predicting the risk of death in health and disease. According to the articles identified with our research, we can conclude that increased cTn values may be considered independent risk factors for all-cause mortality in the general population, as well as in patients with ACS, in those undergoing revascularization procedures, or with stable coronary artery disease (CAD), heart failure (HF) and atrial fibrillation (AF). Measurement of cTn may then be helpful for stratifying the mortality risk in non-cardiac hospitalized patients, in those with critical illness or sepsis, syncope, stroke, acute aortic dissection, pulmonary diseases, brain injury, renal failure, vascular and non-cardiac surgery. Although this evidence has notable clinical implications, the cost-effectiveness of population screening with high-sensitivity (hs) cTn immunoassays has not been proven so far.

Reducing the incidence of diagnostic errors is increasingly a priority for government, professional, and philanthropic organizations. Several obstacles to measurement of diagnostic safety have hampered progress toward this goal. Although a coordinated national strategy to measure diagnostic safety remains an aspirational goal, recent research has yielded practical guidance for healthcare organizations to start using measurement to enhance diagnostic safety. This paper, concurrently published as an Issue Brief by the Agency for Healthcare Research and Quality, issues a “call to action” for healthcare organizations to begin measurement efforts using data sources currently available to them. Our aims are to outline the state of the science and provide practical recommendations for organizations to start identifying and learning from diagnostic errors. Whether by strategically leveraging current resources or building additional capacity for data gathering, nearly all organizations can begin their journeys to measure and reduce preventable diagnostic harm.

Background Missed vascular events, infections, and cancers account for ~75% of serious harms from diagnostic errors. Just 15 diseases from these “Big Three” categories account for nearly half of all serious misdiagnosis-related harms in malpractice claims. As part of a larger project estimating total US burden of serious misdiagnosis-related harms, we performed a focused literature review to measure diagnostic error and harm rates for these 15 conditions. Methods We searched PubMed, Google, and cited references. For errors, we selected high-quality, modern, US-based studies, if available, and best available evidence otherwise. For harms, we used literature-based estimates of the generic (disease-agnostic) rate of serious harms (morbidity/mortality) per diagnostic error and applied claims-based severity weights to construct disease-specific rates. Results were validated via expert review and comparison to prior literature that used different methods. We used Monte Carlo analysis to construct probabilistic plausible ranges (PPRs) around estimates. Results Rates for the 15 diseases were drawn from 28 published studies representing 91,755 patients. Diagnostic error (false negative) rates ranged from 2.2% (myocardial infarction) to 62.1% (spinal abscess), with a median of 13.6% [interquartile range (IQR) 9.2–24.7] and an aggregate mean of 9.7% (PPR 8.2–12.3). Serious misdiagnosis-related harm rates per incident disease case ranged from 1.2% (myocardial infarction) to 35.6% (spinal abscess), with a median of 5.5% (IQR 4.6–13.6) and an aggregate mean of 5.2% (PPR 4.5–6.7). Rates were considered face valid by domain experts and consistent with prior literature reports. Conclusions Diagnostic improvement initiatives should focus on dangerous conditions with higher diagnostic error and misdiagnosis-related harm rates.

Background Pyoderma gangrenosum (PG) is a chronic, ulcerative neutrophilic dermatosis. PG presents a diagnostic challenge, largely due to the many mimicking diseases, the lack of confirmatory laboratory or biological markers, and the absence of widely accepted diagnostic criteria. In particular, PG is often mistaken for necrotizing soft tissue infections (NSTI). Methods We reviewed four major textbooks each in general surgery, plastic surgery, trauma surgery, vascular surgery, emergency medicine, and dermatology. We also performed a search of review articles addressing NSTI and necrotizing fasciitis (NF). Results Ten out of the 20 non-dermatology textbooks did not list PG anywhere, and only two listed a differential diagnosis for PG. None of the non-dermatology textbooks indicated PG in the NSTI differential diagnosis, while three of the dermatology textbooks included PG in the NSTI differential diagnosis. PG was listed in all of the dermatology textbooks. Only one of the NSTI and NF articles mentioned PG in the differential diagnosis. Conclusions There is an underrepresentation in major textbooks of surgery and emergency medicine and in NSTI and NF review articles when it comes to diagnosing PG. This might be leading to trainees and advanced providers in these fields being uninstructed on PG, and likely contributes to PG misdiagnosis and mismanagement. We recommend PG be included in the differential diagnosis of chronic ulcers and NSTI in non-dermatology textbooks. We also suggest adding identification and diagnosis of inflammatory mimickers of NSTI (e.g. PG) in teaching modules in surgical and emergency specialties to address this knowledge gap.

Background Despite growing positive evidence supporting the potential utility of differential diagnostic generator (DDX) tools, uptake has been limited in terms of geography and settings and calls have been made to test such tools in wider routine clinical settings. This study aims to evaluate the feasibility and utility of clinical use of Isabel, an electronic DDX tool, in a United Kingdom (UK) general practice setting. Methods Mixed methods. Feasibility and utility were assessed prospectively over a 6-month period via: usage statistics, survey as well as interview data generated from clinicians before and after Isabel was available for clinical use. Normalisation process theory (NPT) was utilised as a sensitising concept in the data collection and analysis of the qualitative data. Results Usage was extremely limited (n = 18 searches). Most potential users did not utilise the program and of those that did (n = 6), usage was restricted and did not alter subsequent patient management. Baseline interview findings indicated some prior awareness of DDX tools and ambivalent views with regards to potential utility. Post-use interviews supported analytic data and indicated low usage due to a range of endogenous (professional) and exogenous (organisational) factors. Conclusions In its current form, this small exploratory study suggests that Isabel is a tool that is unlikely to be utilised on a routine basis in primary care, but may have potential utility for diagnostic support in (1) education/training and (2) rare and diagnostically complex cases.

Background Feedback based on direct observation of the physical examination (PE) is associated with enhanced educational outcomes, yet attending physicians do not frequently observe graduate trainees performing the PE. Methods We recruited volunteer patients (VPs), each with an abnormality of the cardiovascular, respiratory, or neurological system. Interns examined each VP, then presented a differential diagnosis and management plan to two clinician educators, who, themselves, had independently examined the VPs. The clinician educators assessed interns along five domains and provided post-examination feedback and teaching. We collected data on intern performance, faculty inter-rater reliability, correlation with a simulation-based measure of clinical skill, and resident and VP perceptions of the assessment. Results A total of 72 PGY-1 interns from a large academic training program participated. Performance on the cardiovascular and respiratory system was superior to performance on the neurologic exam. There was no correlation between results of an online test and directly observed cardiovascular skill. Interns preferred feedback from the direct observation sessions. VPs and faculty also rated the experience highly. Inter-rater reliability was good for the respiratory exam, but poor for the cardiovascular and neurologic exams. Conclusions Direct observation of trainees provides evidence about PE skill that cannot be obtained via simulation. Clinician educators’ ability to provide reliable PE assessment may depend on the portion of the PE being assessed. Our experience highlights the need for ongoing training of clinician educators in direct observation, standard setting, and assessment protocols. This assessment can inform summative or formative assessments of physical exam skill in graduate medical education.

Background Laboratory tests are an essential aspect of current medical practice and their use has grown exponentially. Several studies however have demonstrated inappropriate use of laboratory testing. This inappropriateness can lead to delayed or wrong diagnosis, negatively impacting patient safety and an increase in health care expenditure. The aim of the present small-scale survey was to obtain information on the current status of demand management in European laboratories, as well as the opinions of laboratory and clinical professionals in this regard. Methods Two surveys were developed, one for laboratory specialists and one for clinicians, covering information on current use, knowledge and opinions on the possible impact of different demand management strategies on patient outcome and health care costs. Additionally, we asked for the current state and willingness on collaboration of laboratory specialists and clinicians. Results One hundred and fifty responses, 72 laboratory specialists and 78 clinicians, from nine countries were received. Developing local ordering protocols/profiles in collaboration with clinicians was the most used strategy (80.3% of laboratories). Of clinicians, 85.6% considered measures to ensure appropriate use of tests necessary and 100% were interested in advice/information about their indication. Of the laboratory specialists 97.2% were either already participating or willing to participate in multidisciplinary groups on the appropriateness of test demand as were 60.3% of clinicians, and 85.9% of clinicians were interested in attending activities about laboratory test demand management. Conclusions The results of our survey show that tools to improve the appropriate use of laboratory tests are already regularly used today. Laboratory medicine specialists as well as clinicians are willing to undertake additional shared activities aimed at improving patient-centered laboratory diagnostic workup.