Invasive Pulmonary Aspergillosis in Coronavirus Disease 2019 Patients Lights and Shadows in the Current Landscape.

Invasive pulmonary aspergillosis (IPA) presents a known risk to critically ill patients with SARS-CoV-2; quantifying the global burden of IPA in SARS-CoV-2 is extremely challenging. The true incidence of COVID-19-associated pulmonary aspergillosis (CAPA) and the impact on mortality is difficult to define because of indiscriminate clinical signs, low culture sensitivity and specificity and variability in clinical practice between centers. While positive cultures of upper airway samples are considered indicative for the diagnosis of probable CAPA, conventional microscopic examination and qualitative culture of respiratory tract samples have quite low sensitivity and specificity. Thus, the diagnosis should be confirmed with serum and BAL GM test or positive BAL culture to mitigate the risk of overdiagnosis and over-treatment. Bronchoscopy has a limited role in these patients and should only be considered when diagnosis confirmation would significantly change clinical management. Varying diagnostic performance, availability, and time-to-results turnaround time are important limitations of currently approved biomarkers and molecular assays for the diagnosis of IA. The use of CT scans for diagnostic purposes is controversial due to practical concerns and the complex character of lesions presented in SARS-CoV-2 patients. The key objective of management is to improve survival by avoiding misdiagnosis and by initiating early, targeted antifungal treatment. The main factors that should be considered upon selection of treatment options include the severity of the infection, concomitant renal or hepatic injury, possible drug interactions, requirement for therapeutic drug monitoring, and cost of therapy. The optimal duration of antifungal therapy for CAPA is still under debate.

Diagnostics of messenger ribonucleic acid (mRNA) severe acute respiratory syndrome-corona virus­2 (SARS-CoV­2) vaccination-associated myocarditis-A systematic review.

Background: During the recent pandemic with the severe acute respiratory syndrome-corona virus­2 the first messenger ribonucleic acid (mRNA) vaccines were approved. To facilitate mass vaccination, confidence of the general population in these new vaccines is mandatory, which is in turn strongly dependent on the availability of reliable data on complications. Objective: Summary of the current knowledge on mRNA vaccination-associated myocarditis as a potentially fatal side effect. Methods: Systematic literature review. Results: Diagnostic algorithm for the postmortem diagnosis of mRNA vaccination-associated myocarditis. Conclusion: Autopsy series of fatalities following mRNA SARS-CoV­2 vaccination up to 6 weeks with subsequent sophisticated and interdisciplinary work-up are necessary to complement clinical data on vaccination-associated myocarditis, especially regarding the incidence of fatal courses. Supplementary Information: The online version of this article (10.1007/s00194-022-00587-9) includes a PDF file with supplemental clinical features.

Fatigue syndrome after a viral illness. Post COVID-19 exanthema infection. Ichthyosis of the skin of the feet. (Clinical case)

The COVID-19 pandemic has posed many challenges to the medical community, a number of which will remain in the near future. Analysis of clinical cases helps to identify problems, to plan future research, which can change the understanding of the consequences of the disease. As the first year of the pandemic progresses, there is a better understanding of the pathophysiology of the virus and the varied results of imaging COVID-19 in affected organs, which is crucial for improving the treatment of this complex disease and improving health outcomes. It is described a clinical case of exanthema in an 11-year-old patient after COVID-19 Clinical and immunological methods of investigation are used. The child's condition was of the moderate severity, caused by skin and asthenovegetative syndromes. The child was diagnosed with COVID-19;fatigue syndrome after a viral illness;post COVID-19 exanthema infection crustal ichthyosis of the legs. A particular feature of this case is the occurrence of exanthema on the skin of the child after COVID-19. In these cases, the awareness of pediatricians should be raised to increase the level of knowledge of the correct diagnostic algorithm. © 2022 by the Author(s).

Respiratory Tract Infections and Laboratory Diagnostic Methods: A Review with A Focus on Syndromic Panel-Based Assays.

Respiratory tract infections (RTIs) are the focus of developments in public health, given their widespread distribution and the high morbidity and mortality rates reported worldwide. The clinical spectrum ranges from asymptomatic or mild infection to severe or fatal disease. Rapidity is required in diagnostics to provide adequate and prompt management of patients. The current algorithm for the laboratory diagnosis of RTIs relies on multiple approaches including gold-standard conventional methods, among which the traditional culture is the most used, and innovative ones such as molecular methods, mostly used to detect viruses and atypical bacteria. The implementation of molecular methods with syndromic panels has the potential to be a powerful decision-making tool for patient management despite requiring appropriate use of the test in different patient populations. Their use radically reduces time-to-results and increases the detection of clinically relevant pathogens compared to conventional methods. Moreover, if implemented wisely and interpreted cautiously, syndromic panels can improve antimicrobial use and patient outcomes, and optimize laboratory workflow. In this review, a narrative overview of the main etiological, clinical, and epidemiological features of RTI is reported, focusing on the laboratory diagnosis and the potentialities of syndromic panels.

Home Telemonitoring and a Diagnostic Algorithm in the Management of Heart Failure in the Netherlands: Cost-effectiveness Analysis.

BACKGROUND: Heart failure is a major health concern associated with significant morbidity, mortality, and reduced quality of life in patients. Home telemonitoring (HTM) facilitates frequent or continuous assessment of disease signs and symptoms, and it has shown to improve compliance by involving patients in their own care and prevent emergency admissions by facilitating early detection of clinically significant changes. Diagnostic algorithms (DAs) are predictive mathematical relationships that make use of a wide range of collected data for calculating the likelihood of a particular event and use this output for prioritizing patients with regard to their treatment. OBJECTIVE: This study aims to assess the cost-effectiveness of HTM and a DA in the management of heart failure in the Netherlands. Three interventions were analyzed: usual care, HTM, and HTM plus a DA. METHODS: A previously published discrete event simulation model was used. The base-case analysis was performed according to the Dutch guidelines for economic evaluation. Sensitivity, scenario, and value of information analyses were performed. Particular attention was given to the cost-effectiveness of the DA at various levels of diagnostic accuracy of event prediction and to different patient subgroups. RESULTS: HTM plus the DA extendedly dominates HTM alone, and it has a deterministic incremental cost-effectiveness ratio compared with usual care of €27,712 (currency conversion rate in purchasing power parity at the time of study: €1=US $1.29; further conversions are not applicable in cost-effectiveness terms) per quality-adjusted life year. The model showed robustness in the sensitivity and scenario analyses. HTM plus the DA had a 96.0% probability of being cost-effective at the appropriate €80,000 per quality-adjusted life year threshold. An optimal point for the threshold value for the alarm of the DA in terms of its cost-effectiveness was estimated. New York Heart Association class IV patients were the subgroup with the worst cost-effectiveness results versus usual care, while HTM plus the DA was found to be the most cost-effective for patients aged <65 years and for patients in New York Heart Association class I. CONCLUSIONS: Although the increased costs of adopting HTM plus the DA in the management of heart failure may seemingly be an additional strain on scarce health care resources, the results of this study demonstrate that, by increasing patient life expectancy by 1.28 years and reducing their hospitalization rate by 23% when compared with usual care, the use of this technology may be seen as an investment, as HTM plus the DA in its current form extendedly dominates HTM alone and is cost-effective compared with usual care at normally accepted thresholds in the Netherlands.

An expert opinion of the Polish Cardiac Society Working Group on Pulmonary Circulation on screening for chronic thromboembolic pulmonary hypertension patients after acute pulmonary embolism: Update.

Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare complication of acute pulmonary embolism (APE). Both pharmacological and invasive treatments for CTEPH are available in Poland, and awareness of the disease among physicians is growing. It has been suggested that the COVID-19 pandemic may increase the incidence of CTEPH and facilitate disease detection during more advanced stages of the illness. Thus, the Polish Cardiac Society's Working Group on Pulmonary Circulation, in cooperation with independent experts in this field, launched the updated statement on the algorithm to guide a CTEPH diagnosis in patients with previous APE. CTEPH should be suspected in individuals after APE with dyspnea, despite at least 3 months of effective anticoagulation, particularly when specific risk factors are present. Echocardiography is the main screening tool for CTEPH. A diagnostic workup of patients with significant clinical suspicion of CTEPH and right ventricular overload evident on echocardiography should be performed in reference centers. Pulmonary scintigraphy is a safe and highly sensitive screening test for CTEPH. Computed tomography pulmonary angiography with precise detection of thromboembolic residues in the pulmonary circulation is important for the planning of a pulmonary thromboendarterectomy. Right heart catheterization definitively confirms the presence of pulmonary hypertension and direct pulmonary angiography allows for the identification of lesions suitable for thromboendarterectomy or balloon pulmonary angioplasty. In this document, we propose a diagnostic algorithm for patients with suspected CTEPH. With an individualized and sequential diagnostic strategy, each patient can be provided with suitable and tailored therapy provided by a dedicated CTEPH Heart Team.

Comparison of four diagnostic criteria for invasive pulmonary aspergillosis-A diagnostic accuracy study in critically ill patients.

BACKGROUND: In the absence of lung biopsy, there are various algorithms for the diagnosis of invasive pulmonary aspergillosis (IPA) in critically ill patients that rely on clinical signs, underlying conditions, radiological features and mycology. The aim of the present study was to compare four diagnostic algorithms in their ability to differentiate between probable IPA (i.e., requiring treatment) and colonisation. METHODS: For this diagnostic accuracy study, we included a mixed ICU population with a positive Aspergillus culture from respiratory secretions and applied four different diagnostic algorithms to them. We compared agreement among the four algorithms. In a subgroup of patients with lung tissue histopathology available, we determined the sensitivity and specificity of the single algorithms. RESULTS: A total number of 684 critically ill patients (69% medical/31% surgical) were included between 2005 and 2020. Overall, 79% (n = 543) of patients fulfilled the criteria for probable IPA according to at least one diagnostic algorithm. Only 4% of patients (n = 29) fulfilled the criteria for probable IPA according to all four algorithms. Agreement among the four diagnostic criteria was low (Cohen's kappa 0.07-0.29). From 85 patients with histopathological examination of lung tissue, 40% (n = 34) had confirmed IPA. The new EORTC/MSGERC ICU working group criteria had high specificity (0.59 [0.41-0.75]) and sensitivity (0.73 [0.59-0.85]). CONCLUSIONS: In a cohort of mixed ICU patients, the agreement among four algorithms for the diagnosis of IPA was low. Although improved by the latest diagnostic criteria, the discrimination of invasive fungal infection from Aspergillus colonisation in critically ill patients remains challenging and requires further optimization.

Diagnosing Chronic Obstructive Airway Disease on a Smartphone Using Patient-Reported Symptoms and Cough Analysis: Diagnostic Accuracy Study

Background: Rapid and accurate diagnosis of chronic obstructive pulmonary disease (COPD) is problematic in acute care settings, particularly in the presence of infective comorbidities. Objective: The aim of this study was to develop a rapid smartphone-based algorithm for the detection of COPD in the presence or absence of acute respiratory infection and evaluate diagnostic accuracy on an independent validation set. Methods: Participants aged 40 to 75 years with or without symptoms of respiratory disease who had no chronic respiratory condition apart from COPD, chronic bronchitis, or emphysema were recruited into the study. The algorithm analyzed 5 cough sounds and 4 patient-reported clinical symptoms, providing a diagnosis in less than 1 minute. Clinical diagnoses were determined by a specialist physician using all available case notes, including spirometry where available. Results: The algorithm demonstrated high positive percent agreement (PPA) and negative percent agreement (NPA) with clinical diagnosis for COPD in the total cohort (N=252;PPA=93.8%, NPA=77.0%, area under the curve [AUC]=0.95), in participants with pneumonia or infective exacerbations of COPD (n=117;PPA=86.7%, NPA=80.5%, AUC=0.93), and in participants without an infective comorbidity (n=135;PPA=100.0%, NPA=74.0%, AUC=0.97). In those who had their COPD confirmed by spirometry (n=229), PPA was 100.0% and NPA was 77.0%, with an AUC of 0.97. Conclusions: The algorithm demonstrated high agreement with clinical diagnosis and rapidly detected COPD in participants presenting with or without other infective lung illnesses. The algorithm can be installed on a smartphone to provide bedside diagnosis of COPD in acute care settings, inform treatment regimens, and identify those at increased risk of mortality due to seasonal or other respiratory ailments. Trial Registration: Australian New Zealand Clinical Trials Registry ACTRN12618001521213;http://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=375939

CRISIS DIAGNOSIS IN CROSS-BORDER REGIONS: LESSONS FROM THE PANDEMIC

In the article, methods and tools for diagnosing crisis phenomena in the conditions of the COVID-19 pandemic, based on the example of border regions of the Baltic Sea countries and the Northwestern Federal District of the Russian Federation, were presented. Governmental measures and restrictions on the functioning of the economic subjects introduced in the border regions caused some shock and stress situation, which are of great importance for the course of the crisis conditions and the way out of the crisis. The purpose of the diagnosis is to establish a specific recognition of the research object, to provide a specific description and to formulate a final document or a conclusion about the condition of this object within a specified research completion date. In other words, the diagnosis allows the determination of the state of the research object and the development of a conclusion from these results, which can be based on indicators, coefficients, standards, in order to propose real positive changes up to the definition of the strategy and development tactics. The study uses the methods of systemic, structural, factor and comparative analysis, considering common and available parameters. A qualitative diagnosis of the object is carried out based on the algorithm and research stages. Specific problems are investigated on the basis of indicators and characteristics that are comparable in studies of corona crisis phenomena. Currently, the frontier economy is facing new challenges that test the basic mechanisms of functioning in crisis conditions. All these processes imply measures to eliminate the consequences of post-pandemic phenomena. This research can be used by the public administration units in diagnosing the processes of cross-border cooperation in the period of recovering from the post-pandemic crisis.

Active Case Finding for Tuberculosis in India: A Syntheses of Activities and Outcomes Reported by the National Tuberculosis Elimination Programme.

India launched a national community-based active TB case finding (ACF) campaign in 2017 as part of the strategic plan of the National Tuberculosis Elimination Programme (NTEP). This review evaluated the outcomes for the components of the ACF campaign against the NTEP's minimum indicators and elicited the challenges faced in implementation. We supplemented data from completed pretested data proformas returned by ACF programme managers from nine states and two union territories (for 2017-2019) and five implementing partner agencies (2013-2020), with summary national data on the state-wise ACF outcomes for 2018-2020 published in annual reports by the NTEP. The data revealed variations in the strategies used to map and screen vulnerable populations and the diagnostic algorithms used across the states and union territories. National data were unavailable to assess whether the NTEP indicators for the minimum proportions identified with presumptive TB among those screened (5%), those with presumptive TB undergoing diagnostic tests (>95%), the minimum sputum smear positivity rate (2% to 3%), those with negative sputum smears tested with chest X-rays or CBNAAT (>95%) and those diagnosed through ACF initiated on anti-TB treatment (>95%) were fulfilled. Only 30% (10/33) of the states in 2018, 23% (7/31) in 2019 and 21% (7/34) in 2020 met the NTEP expectation that 5% of those tested through ACF would be diagnosed with TB (all forms). The number needed to screen to diagnose one person with TB (NNS) was not included among the NTEP's programme indicators. This rough indicator of the efficiency of ACF varied considerably across the states and union territories. The median NNS in 2018 was 2080 (interquartile range or IQR 517-4068). In 2019, the NNS was 2468 (IQR 1050-7924), and in 2020, the NNS was 906 (IQR 108-6550). The data consistently revealed that the states that tested a greater proportion of those screened during ACF and used chest X-rays or CBNAAT (or both) to diagnose TB had a higher diagnostic yield with a lower NNS. Many implementation challenges, related to health systems, healthcare provision and difficulties experienced by patients, were elicited. We suggest a series of strategic interventions addressing the implementation challenges and the six gaps identified in ACF outcomes and the expected indicators that could potentially improve the efficacy and effectiveness of community-based ACF in India.

Coronavirus Disease 2019 (COVID-19) Diagnostic Clinical Decision Support: A Pre-Post Implementation Study of CORAL (COvid Risk cALculator).

BACKGROUND: Isolation of hospitalized persons under investigation (PUIs) for coronavirus disease 2019 (COVID-19) reduces nosocomial transmission risk. Efficient evaluation of PUIs is needed to preserve scarce healthcare resources. We describe the development, implementation, and outcomes of an inpatient diagnostic algorithm and clinical decision support system (CDSS) to evaluate PUIs. METHODS: We conducted a pre-post study of CORAL (COvid Risk cALculator), a CDSS that guides frontline clinicians through a risk-stratified COVID-19 diagnostic workup, removes transmission-based precautions when workup is complete and negative, and triages complex cases to infectious diseases (ID) physician review. Before CORAL, ID physicians reviewed all PUI records to guide workup and precautions. After CORAL, frontline clinicians evaluated PUIs directly using CORAL. We compared pre- and post-CORAL frequency of repeated severe acute respiratory syndrome coronavirus 2 nucleic acid amplification tests (NAATs), time from NAAT result to PUI status discontinuation, total duration of PUI status, and ID physician work hours, using linear and logistic regression, adjusted for COVID-19 incidence. RESULTS: Fewer PUIs underwent repeated testing after an initial negative NAAT after CORAL than before CORAL (54% vs 67%, respectively; adjusted odd ratio, 0.53 [95% confidence interval, .44-.63]; P < .01). CORAL significantly reduced average time to PUI status discontinuation (adjusted difference [standard error], -7.4 [0.8] hours per patient), total duration of PUI status (-19.5 [1.9] hours per patient), and average ID physician work-hours (-57.4 [2.0] hours per day) (all P < .01). No patients had a positive NAAT result within 7 days after discontinuation of precautions via CORAL. CONCLUSIONS: CORAL is an efficient and effective CDSS to guide frontline clinicians through the diagnostic evaluation of PUIs and safe discontinuation of precautions.

Idiosyncratic Drug-Induced Liver Injury (DILI) and Herb-Induced Liver Injury (HILI): Diagnostic Algorithm Based on the Quantitative Roussel Uclaf Causality Assessment Method (RUCAM).

Causality assessment in liver injury induced by drugs and herbs remains a debated issue, requiring innovation and thorough understanding based on detailed information. Artificial intelligence (AI) principles recommend the use of algorithms for solving complex processes and are included in the diagnostic algorithm of Roussel Uclaf Causality Assessment Method (RUCAM) to help assess causality in suspected cases of idiosyncratic drug-induced liver injury (DILI) and herb-induced liver injury (HILI). From 1993 until the middle of 2020, a total of 95,865 DILI and HILI cases were assessed by RUCAM, outperforming by case numbers any other causality assessment method. The success of RUCAM can be traced back to its quantitative features with specific data elements that are individually scored leading to a final causality grading. RUCAM is objective, user friendly, transparent, and liver injury specific, with an updated version that should be used in future DILI and HILI cases. Support of RUCAM was also provided by scientists from China, not affiliated to any network, in the results of a scientometric evaluation of the global knowledge base of DILI. They highlighted the original RUCAM of 1993 and their authors as a publication quoted the greatest number of times and ranked first in the category of the top 10 references related to DILI. In conclusion, for stakeholders involved in DILI and HILI, RUCAM seems to be an effective diagnostic algorithm in line with AI principles.

Challenges in the diagnostic approach of suspected pulmonary embolism in COVID-19 patients.

Accumulating studies on COVID-19 patients report high incidences of thrombotic complications, but guidance on the best diagnostic approach for suspected pulmonary embolism (PE) in COVID-19 patients is lacking. Diagnosing PE in these patients is challenging as signs and symptoms of PE and COVID-19 show wide overlap, D-dimer levels are often elevated in the absence of thrombosis and computed tomography pulmonary angiography (CTPA) may be unfeasible in the case of severe renal impairment and/or hemodynamic instability.This narrative review discusses available literature and guidelines on current diagnostic algorithms for suspected PE in special patient populations, in particular COVID-19. A special focus is on reviewing the literature aimed at identifying symptoms with a high suspicion for PE and on the diagnostic performance of diagnostic algorithms for suspected PE in the setting of COVID-19.Based on available literature, the index of suspicion for PE should be high in the case of unexplained abrupt worsening of respiratory status, typical symptoms of deep-vein thrombosis and/or acute unexplained right ventricular dysfunction. Despite the lack of prospective diagnostic management studies, we propose to adhere to current diagnostic algorithms applying assessment of pretest probability and D-dimer testing as available evidence suggests that these might be considered safe. Preferably, algorithms using adjusted D-dimer thresholds are recommended as it likely improves the yield of the clinical decision rule/D-dimer combination.