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Modelo estándar de manual de procedimientos y calidad para la implementación del test rápido dual de VIH y sífilis / Standard model of procedures and quality manual for the implementation of the dual rapid test for HIV and syphilis

El presente manual es un documento base cuyo fin es ser adaptado por cada centro para normalizar los procedimientos atinentes al proceso de realización del test rápido dual para VIH y sífilis (TR). Es recomendable que esté completo antes de iniciar la realización sistemática de este estudio. Como todo manual de procedimiento, deberá ser actualizado cada vez que se produzca una modificación en alguna/s de sus secciones, detallando la fecha, versión y responsable de los estudios en ese centro. Este manual está organizado en tres partes: los Procedimientos operativos, el Circuito de atención y entrega de resultados, y el Control de calidad externo. (AU)

CRISPR Approaches for the Diagnosis of Human Diseases.

CRISPR/Cas is a prokaryotic self-defense system, widely known for its use as a gene-editing tool. Because of their high specificity to detect DNA and RNA sequences, different CRISPR systems have been adapted for nucleic acid detection. CRISPR detection technologies differ highly among them, since they are based on four of the six major subtypes of CRISPR systems. In just 5 years, the CRISPR diagnostic field has rapidly expanded, growing from a set of specific molecular biology discoveries to multiple FDA-authorized COVID-19 tests and the establishment of several companies. CRISPR-based detection methods are coupled with pre-existing preamplification and readout technologies, achieving sensitivity and reproducibility comparable to the current gold standard nucleic acid detection methods. Moreover, they are very versatile, can be easily implemented to detect emerging pathogens and new clinically relevant mutations, and offer multiplexing capability. The advantages of the CRISPR-based diagnostic approaches are a short sample-to-answer time and no requirement of laboratory settings; they are also much more affordable than current nucleic acid detection procedures. In this review, we summarize the applications and development trends of the CRISPR/Cas13 system in the identification of particular pathogens and mutations and discuss the challenges and future prospects of CRISPR-based diagnostic platforms in biomedicine.

Using social media to crowdsource collection of urine samples during a national pandemic.

The COVID-19 pandemic and subsequent lockdown had a substantial impact on normal research operations. Researchers needed to adapt their methods to engage at-home participants. One method is crowdsourcing, in which researchers use social media to recruit participants, gather data, and collect samples. We utilized this method to develop a diagnostic test for Interstitial Cystitis/Bladder Pain Syndrome (IC/BPS). Participants were recruited via posts on popular social-media platforms, and enrolled via a website. Participants received and returned a mail kit containing bladder symptom surveys and a urine sample cup containing room-temperature preservative. Using this method, we collected 1254 IC/BPS and control samples in 3 months from all 50 United States. Our data demonstrate that crowdsourcing is a viable alternative to traditional research, with the ability to reach a broad patient population rapidly. Crowdsourcing is a powerful tool for at-home participation in research, particularly during the lockdown caused by the COVID-19 pandemic.

Enjeux liés à l'implantation d'un système de soutien à la décision clinique visant la prescription d'un examen diagnostique / Issues pertaining to the implementation of a clinical decision support system for diagnostic test ordering

INTRODUCTION: Les examens diagnostiques, lorsque pertinents, jouent un rôle essentiel dans le processus de diagnostic, de traitement et de suivi d'une maladie. Ainsi, les professionnels de la santé doivent décider de prescrire ou non un examen diagnostique en se basant sur leur jugement clinique et une variété de renseignements complexes. Cela peut parfois représenter un défi important pour lequel une solution prometteuse est l'emploi des systèmes de soutien à la décision clinique (SSDC) dont l'efficacité a été démontrée dans plusieurs domaines de la santé. Le ministère de la Santé et des Services sociaux (MSSS) a donc demandé à l'INESSS d'identifier les obstacles et les facilitateurs liés à l'implantation d'un SSDC pour la prescription d'examens diagnostiques. MÉTHODOLOGIE: Le présent état des connaissances est basé sur une revue rapide de la littérature réalisée selon les normes de qualité méthodologique de l'INESSS. Les études à inclure devaient remplir les critères suivants : la population à l'étude incluait les patients et proches aidants, les professionnels de la santé et les gestionnaires; le facteur d'exposition incluait tout facilitateur ou obstacle associé à l'implantation d'un SSDC visant la prescription d'examens diagnostiques, que ce SSDC soit techniquement couplé à un prescripteur électronique ou non; les résultats de l'implantation incluaient acceptabilité, adoption, pertinence, faisabilité, adaptabilité, portée (penetration) et pérennisation. La recherche de la littérature a été effectuée en janvier 2022 dans MEDLINE (via Ovid), Embase, EBM Reviews et la littérature grise. L'évaluation de la qualité méthodologique des études a été faite en employant l'outil MMAT (Mixed methods appraisal tool). Les obstacles et facilitateurs ont été codés et classifiés selon les construits de Consolidated Framework for Implementation Research (CFIR). Une synthèse des données a été faite et structurée en employant un cadre conceptuel basé sur les construits du CFIR et les résultats de l'implantation. RÉSULTATS: Au total, 23 études, de qualité méthodologique acceptable, ont été retenues. Celles-ci étaient récentes en majorité (50 % publiées après 2017), conduites en Amérique du Nord (17/23) et en milieux de soins primaires (13/23). La méthodologie appliquée dans les études incluses était variée. Certaines études ont eu recours aux cadres conceptuels/modèles spécifiques pour l'évaluation des obstacles et facilitateurs (9/23). L'entrevue semi-structurée était la méthode de collecte de données la plus utilisée (11/23). Les analyses réalisées dans les études étaient qualitatives et/ou descriptives. Le profil des personnes participantes était varié avec toutefois la présence de médecins dans toutes les études. Les SSDC étudiés étaient en majorité multifonctionnels (19/23), couvraient surtout des domaines spécialisés de la santé (17/23) et étaient principalement destinés aux professionnels de la santé uniquement (20/23). Les SSDC étaient, pour la plupart, connectés à un dossier médical électronique (17/23) et leur contenu était fréquemment basé sur des données de patients et des lignes directrices de pratique ou des recommandations basées sur les données probantes (16/23). L'usage (16/23), l'adoption (5/23) et l'acceptation / acceptabilité (2/23) étaient les trois résultats analysés en lien avec les obstacles et les facilitateurs. Les obstacles et les facilitateurs de l'implantation d'un SSDC étaient multidimensionnels, ils couvraient tous les domaines du CFIR et provenaient des études des phases de préimplantation (10/23) et de postimplantation (13/23). CONCLUSION: La présente revue rapide a permis d'identifier et de faire un portrait structuré des obstacles et facilitateurs liés à l'implantation d'un SSDC visant la prescription des examens diagnostiques au regard de son acceptation, de son adoption et de son utilisation. Les déterminants identifiés couvrent tous les domaines du CFIR. Ces déterminants, même s'ils sont exploratoires et nécessitent une contextualisation au système de santé québécois, devraient guider le MSSS dans le développement, la planification, l'exécution et l'évaluation de l'implantation d'un SSDC visant la prescription d'examens d'imagerie médicale.

INTRODUCTION: Diagnostic tests, when relevant, play a key role in the process of disease diagnosis, treatment and follow-up. Thus, health professionals must decide whether or not to order a diagnostic test based on their clinical judgment and a variety of complex information. This can sometimes pose a important challenge, for which one promising solution is the use of clinical decision support systems (CDSSs), which have been shown to be effective in many areas of health. The Ministère de la Santé et des Services sociaux (MSSS) therefore asked INESSS to identify the barriers and facilitators related to implementing a CDSS for diagnostic test ordering. METHODOLOGY: This state-of-knowledge report is based on a rapid literature review conducted in accordance with INESSS's methodological standards. To be included, studies had to meet the following criteria: the study population had to include patients and caregivers, health professionals, and health managers; the exposure factor had to include any facilitators of or barriers to implementing a CDSS for diagnostic test ordering, whether the CDSS was technically linked to an electronic prescriber or not; and the implementation outcomes had to include acceptability, adoption, relevance, feasibility, adaptability, penetration and sustainability. The literature search was conducted in January 2022 in MEDLINE (via Ovid), Embase, EBM Reviews and in the grey literature. The studies' methodological quality was assessed using the MMAT (Mixed Methods Appraisal Tool). Barriers and facilitators were coded and classified according to the Consolidated Framework for Implementation Research (CFIR) constructs. Data synthesis was performed and was structured using a conceptual framework based on the CFIR constructs and the implementation outcomes. RESULTS: A total of 23 studies with acceptable methodological quality were included. Most of them were recent (50% published after 2017) and were conducted in North America (17/23) and in primary care settings (13/23). The methodology used in the selected studies varied. Some used specific conceptual frameworks/models for assessing barriers and facilitators (9/23). The semi-structured interview was the most commonly used data collection method (11/23). The analyses performed in the studies were qualitative and/or descriptive. The participants' profile varied as well, although physicians were included in all the studies. Most of the CDSSs studied were multifunctional (19/23), mainly covered specialized areas of health (17/23) and were mainly intended for health professionals only (20/23). For the most part, the CDSSs were linked to an electronic health record (17/23), and their content was often based on patient data and evidence-based practice guidelines or recommendations (16/23). Use (16/23), adoption (5/23) and acceptance/acceptability (2/23) were the three outcomes analyzed in relation to the barriers and facilitators. The CDSS implementation barriers and facilitators were multidimensional, covered all the CFIR domains and were from the studies of the preimplementation (10/23) and post-implementation phases (13/23). CONCLUSION: This rapid review has identified and provided a structured portrait of the barriers to and facilitators of implementing a CDSS for diagnostic test ordering in terms of its acceptance, adoption and use. The determinants identified cover all the CFIR domains. Although these determinants are exploratory and require contextualization in Québec's health system, they should guide the MSSS in the development, planning, execution and evaluation of the implementation of a CDSS for the ordering of medical imaging tests.

Practice Patterns and Patient Outcomes After Widespread Adoption of Remote Heart Failure Care.

BACKGROUND: An unprecedented shift to remote heart failure outpatient care occurred during the coronavirus disease 2019 (COVID-19) pandemic. Given challenges inherent to remote care, we studied whether remote visits (video or telephone) were associated with different patient usage, clinician practice patterns, and outcomes. METHODS: We included all ambulatory cardiology visits for heart failure at a multisite health system from April 1, 2019, to December 31, 2019 (pre-COVID) or April 1, 2020, to December 31, 2020 (COVID era), resulting in 10 591 pre-COVID in-person, 7775 COVID-era in-person, 1009 COVID-era video, and 2322 COVID-era telephone visits. We used multivariable logistic and Cox proportional hazards regressions with propensity weighting and patient clustering to study ordering practices and outcomes. RESULTS: Compared with in-person visits, video visits were used more often by younger (mean 64.7 years [SD 14.5] versus 74.2 [14.1]), male (68.3% versus 61.4%), and privately insured (45.9% versus 28.9%) individuals (P<0.05 for all). Remote visits were more frequently used by non-White patients (35.8% video, 37.0% telephone versus 33.2% in-person). During remote visits, clinicians were less likely to order diagnostic testing (odds ratio, 0.20 [0.18-0.22] video versus in-person, 0.18 [0.17-0.19] telephone versus in-person) or prescribe ß-blockers (0.82 [0.68-0.99], 0.35 [0.26-0.47]), mineralocorticoid receptor antagonists (0.69 [0.50-0.96], 0.48 [0.35-0.66]), or loop diuretics (0.67 [0.53-0.85], 0.45 [0.37-0.55]). During telephone visits, clinicians were less likely to prescribe ACE (angiotensin-converting enzyme) inhibitor/ARB (angiotensin receptor blockers)/ARNIs (angiotensin receptor-neprilysin inhibitors; 0.54 [0.40-0.72]). Telephone visits but not video visits were associated with higher rates of 90-day mortality (1.82 [1.14-2.90]) and nonsignificant trends towards higher rates of 90-day heart failure emergency department visits (1.34 [0.97-1.86]) and hospitalizations (1.36 [0.98-1.89]). CONCLUSIONS: Remote visits for heart failure care were associated with reduced diagnostic testing and guideline-directed medical therapy prescription. Telephone but not video visits were associated with increased 90-day mortality.

Intractable lateral epicondilytis: A differential diagnosis algorithm for a correct clinical interpretation

The epicondylalgia is the most frequent upper extremity pathology in adults and it can become an “intractable lateral epicondylitis” when patients do not improve with the treatment received. This is a complex entity that includes several musculo-tendinous, articular and neural syndromes than can coexist and they can also be confused with each other. For this reason, it is necessary to do a systematized and exhaustive evaluation where all the dysfunctions capable of generating the symptoms are precisely and independently analyzed. On this basis, a 7 steps assessment algorithm is proposed on this paper to enable the clinician to perform a complete and organized evaluation of these patients, to achieve a correct clinical interpretation. (AU)

Application of Full-Spectrum Rapid Clinical Genome Sequencing Improves Diagnostic Rate and Clinical Outcomes in Critically Ill Infants in the China Neonatal Genomes Project.

OBJECTIVES: To determine the diagnostic and clinical utility of trio-rapid genome sequencing in critically ill infants. DESIGN: In this prospective study, samples from critically ill infants were analyzed using both proband-only clinical exome sequencing and trio-rapid genome sequencing (proband and biological parents). The study occurred between April 2019 and December 2019. SETTING: Thirteen member hospitals of the China Neonatal Genomes Project spanning 10 provinces were involved. PARTICIPANTS: Critically ill infants (n = 202), from birth up until 13 months of life were enrolled based on eligibility criteria (e.g., CNS anomaly, complex congenital heart disease, evidence of metabolic disease, recurrent severe infection, suspected immune deficiency, and multiple malformations). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of the 202 participants, neuromuscular (45%), respiratory (22%), and immunologic/infectious (18%) were the most commonly observed phenotypes. The diagnostic yield of trio-rapid genome sequencing was higher than that of proband-only clinical exome sequencing (36.6% [95% CI, 30.1-43.7%] vs 20.3% [95% CI, 15.1-26.6%], respectively; p = 0.0004), and the average turnaround time for trio-rapid genome sequencing (median: 7 d) was faster than that of proband-only clinical exome sequencing (median: 20 d) (p < 2.2 × 10-16). The metagenomic analysis identified pathogenic or likely pathogenic microbes in six infants with symptoms of sepsis, and these results guided the antibiotic treatment strategy. Sixteen infants (21.6%) experienced a change in clinical management following trio-rapid genome sequencing diagnosis, and 24 infants (32.4%) were referred to a new subspecialist. CONCLUSIONS: Trio-rapid genome sequencing provided higher diagnostic yield in a shorter period of time in this cohort of critically ill infants compared with proband-only clinical exome sequencing. Precise and fast molecular diagnosis can alter medical management and positively impact patient outcomes.

Nanobodies for Medical Imaging: About Ready for Prime Time?

Recent advances in medical treatments have been revolutionary in shaping the management and treatment landscape of patients, notably cancer patients. Over the last decade, patients with diverse forms of locally advanced or metastatic cancer, such as melanoma, lung cancers, and many blood-borne malignancies, have seen their life expectancies increasing significantly. Notwithstanding these encouraging results, the present-day struggle with these treatments concerns patients who remain largely unresponsive, as well as those who experience severely toxic side effects. Gaining deeper insight into the cellular and molecular mechanisms underlying these variable responses will bring us closer to developing more effective therapeutics. To assess these mechanisms, non-invasive imaging techniques provide valuable whole-body information with precise targeting. An example of such is immuno-PET (Positron Emission Tomography), which employs radiolabeled antibodies to detect specific molecules of interest. Nanobodies, as the smallest derived antibody fragments, boast ideal characteristics for this purpose and have thus been used extensively in preclinical models and, more recently, in clinical early-stage studies as well. Their merit stems from their high affinity and specificity towards a target, among other factors. Furthermore, their small size (~14 kDa) allows them to easily disperse through the bloodstream and reach tissues in a reliable and uniform manner. In this review, we will discuss the powerful imaging potential of nanobodies, primarily through the lens of imaging malignant tumors but also touching upon their capability to image a broader variety of nonmalignant diseases.

Closing the translation gap: AI applications in digital pathology.

Recent advances in artificial intelligence show tremendous promise to improve the accuracy, reproducibility, and availability of medical diagnostics across a number of medical subspecialities. This is especially true in the field of digital pathology, which has recently witnessed a surge in publications describing state-of-the-art performance for machine learning models across a wide range of diagnostic applications. Nonetheless, despite this promise, there remain significant gaps in translating applications for any of these technologies into actual clinical practice. In this review, we will first give a brief overview of the recent progress in applying AI to digitized pathology images, focusing on how these tools might be applied in clinical workflows in the near term to improve the accuracy and efficiency of pathologists. Then we define and describe in detail the various factors that need to be addressed in order to successfully close the "translation gap" for AI applications in digital pathology.

Magnetic Levitation Systems for Disease Diagnostics.

Magnetic levitation (MagLev) is a well-documented, robust technique for density measurements and separations. Although the potential of MagLev as an emerging tool in biotechnology has been recently investigated, the practical use of MagLev in diagnosis and disease detection merits further attention. This review highlights the diagnostic capacity of a simple and portable MagLev system and the possibilities and limitations of the MagLev technique for density-based separation, classification, and manipulation of soft matter and biological systems (e.g., cells, proteins), which in turn may pave the way for the discovery of disease-specific biomarkers.

Updates on Rapid Diagnostic Tests in Infectious Diseases.

In the last two decades there have been dramatic advances in development of rapid diagnostic tests. Turnaround time of the assays have significantly been shortened which led to reductions in time to appropriate antimicrobial therapy and improvement of patient clinical outcomes. Molecular-based assays generally have better sensitivity than conventional methods, but the cost is higher. The results need to be interpreted cautiously as detection of colonized organisms, pathogen detection in asymptomatic patients, and false negative/positive can occur. Indications and cost-effectiveness need to be considered for appropriate utilization of rapid diagnostic tests.

Modern diagnostic technologies for HIV.

Novel diagnostic technologies, including nanotechnology, microfluidics, -omics science, next-generation sequencing, genomics big data, and machine learning, could contribute to meeting the UNAIDS 95-95-95 targets to end the HIV epidemic by 2030. Novel technologies include multiplexed technologies (including biomarker-based point-of-care tests and molecular platform technologies), biomarker-based combination antibody and antigen technologies, dried-blood-spot testing, and self-testing. Although biomarker-based rapid tests, in particular antibody-based tests, have dominated HIV diagnostics since the development of the first HIV test in the mid-1980s, targets such as nucleic acids and genes are now used in nanomedicine, biosensors, microfluidics, and -omics to enable early diagnosis of HIV. These novel technologies show promise as they are associated with ease of use, high diagnostic accuracy, rapid detection, and the ability to detect HIV-specific markers. Additional clinical and implementation research is needed to generate evidence for use of novel technologies and a public health approach will be required to address clinical and operational challenges to optimise their global deployment.

[IgG4-related disease: Diagnostic criteria evolution toward the 2019 ACR/EULAR classification criteria]. / Maladie associée aux IgG4 : des critères « diagnostiques ¼ aux critères de classification ACR/EULAR 2019.

The concept of IgG4-related disease (IgG4-RD) has recently been individualized in the early 2000s, but most of the organ involvements are known since more than 100 years. IgG4-RD is a non-malignant fibroinflammatory disorder, characterized by peculiar immunological and pathological abnormalities, which can affect virtually all organs or tissues. Diagnostic criteria have been proposed and have evolved rapidly, with general or organ specific criteria. An international and multidisciplinary group assembled by the American College of Rheumatology (ACR) and the European League Against Rheumatism (EULAR) has recently developed and validated a set of classification criteria called 2019 ACR/EULAR classification criteria for IgG4-related disease. The objective of this review is to discuss the evolution from organ specific and general diagnostic criteria toward the 2019 ACR/EULAR classification criteria, as well as respective benefits and limits of these criteria. The use of the 2019 ACR/EULAR classification criteria will help to better define homogeneous group of IgG4-RD patients in future clinical, epidemiological and basic science research studies on the disease.

Pathologists should probably forget about kappa. Percent agreement, diagnostic specificity and related metrics provide more clinically applicable measures of interobserver variability.

Kappa statistics have been widely used in the pathology literature to compare interobserver diagnostic variability (IOV) among different pathologists but there has been limited discussion about the clinical significance of kappa scores. Five representative and recent pathology papers were queried using clinically relevant specific questions to learn how IOV was evaluated and how the clinical applicability of results was interpreted. The papers supported our anecdotal impression that pathologists usually assess IOV using Cohen's or Fleiss' kappa statistics and interpret the results using some variation of the scale proposed by Landis and Koch. The papers did not cite or propose specific guidelines to comment on the clinical applicability of results. The solutions proposed to decrease IOV included the development of better diagnostic criteria and additional educational efforts, but the possibility that the entities themselves represented a continuum of morphologic findings rather than distinct diagnostic categories was not considered in any of the studies. A dataset from a previous study of IOV reported by Thunnissen et al. was recalculated to estimate percent agreement among 19 international lung pathologists for the diagnosis of 74 challenging lung neuroendocrine neoplasms. Kappa scores and diagnostic sensitivity, specificity, positive and negative predictive values were calculated using the majority consensus diagnosis for each case as the gold reference diagnosis for that case. Diagnostic specificity estimates among multiple pathologists were > 90%, although kappa scores were considerably more variable. We explain why kappa scores are of limited clinical applicability in pathology and propose the use of positive and negative percent agreement and diagnostic specificity against a gold reference diagnosis to evaluate IOV among two and multiple raters, respectively.

Coronaviruses: a challenge of today and a call for extended human postmortem brain analyses.

While there is abounding literature on virus-induced pathology in general and coronavirus in particular, recent evidence accumulates showing distinct and deleterious brain affection. As the respiratory tract connects to the brain without protection of the blood-brain barrier, SARS-CoV-2 might in the early invasive phase attack the cardiorespiratory centres located in the medulla/pons areas, giving rise to disturbances of respiration and cardiac problems. Furthermore, brainstem regions are at risk to lose their functional integrity. Therefore, long-term neurological as well as psychiatric symptomatology and eventual respective disorders cannot be excluded as evidenced from influenza-A triggered post-encephalitic Parkinsonism and HIV-1 triggered AIDS-dementia complex. From the available evidences for coronavirus-induced brain pathology, this review concludes a number of unmet needs for further research strategies like human postmortem brain analyses. SARS-CoV-2 mirroring experimental animal brain studies, characterization of time-dependent and region-dependent spreading behaviours of coronaviruses, enlightening of pathological mechanisms after coronavirus infection using long-term animal models and clinical observations of patients having had COVID-19 infection are calling to develop both protective strategies and drug discoveries to avoid early and late coronavirus-induced functional brain disturbances, symptoms and eventually disorders. To fight SARS-CoV-2, it is an urgent need to enforce clinical, molecular biological, neurochemical and genetic research including brain-related studies on a worldwide harmonized basis.

[Update on the diagnosis of parasitic and fungal infections]. / Actualités du diagnostic des infections parasitaires et fongiques.

The diagnosis of parasitic and fungal infections, historically based on the detection of these pathogens using direct diagnosis (macro/microscopic examination, culture) or serological methods, has considerably evolved in the last decades, especially with the development of molecular approaches and mass spectrometry. These techniques, as well as most analyses of parasitic and fungal serology, are mostly the preserve of Hospital University Centers Parasitology-Mycology laboratories. In 2016, the French association of medical parasitology and mycology teachers and hospital practitioners (Anofel) has provided a Catalogue of rare analyses, regularly updated and freely accessible on the Anofel website (https://anofel.net/). This tool, which hinges on 4 parts (parasitology, parasitic serology, mycology, and fungal serology), aims to provide information on all available analyses, and a list of hospital laboratories able to undertake them. It is complementary to the other reference works that were developed by our association, including the Guide of analyses and methods in parasitology and mycology, published in 2018, and the eANOFEL pictures and videos database, freely accessible online (http://www.eanofel.fr). In this article, we draw-up a state-of-the-art of the most specialized techniques available in the parasitology-mycology laboratories and presented in the Catalogue of rare analyses of the Anofel collegium, and their interest for the diagnosis of these infections.