Diagnostic Performance of Individual Symptoms to Predict SARS-CoV-2 RT-PCR Positivity and Symptom Persistence among Suspects Presenting in Primary Care during the First Wave of COVID-19.

This study aimed to estimate the diagnostic performance of patient symptoms and to describe the clinical course of RT-PCR-positive compared with RT-PCR-negative patients in primary care. Symptomatic COVID-19 suspects were assessed clinically at the initial consultation in primary care between March and May 2020, followed by phone consultations over a span of at least 28 days. Sensitivity and specificity were estimated for each symptom using the initial RT-PCR result as a reference standard. The proportions of symptomatic patients according to the RT-PCR test results were compared over time, and time to recovery was estimated. Out of 883 patients, 13.9% had a positive RT-PCR test, and 17.4% were not tested. Most sensitive symptoms were cough, myalgia, and a history of fever, while most specific symptoms were fever for ≥4 days, hypo/anosmia, and hypo/ageusia. At the final follow up (median time 55 days, range 28-105 days), 44.7% of patients still reported symptoms in the RT-PCR-positive group, compared with 18.3% in the negative group (p < 0.001), mostly with hypo/anosmia (16.3%), dyspnea (12.2%), and fatigue (10.6%). The discriminative value of individual symptoms for diagnosing COVID-19 was limited. Almost half of the SARS-CoV-2-positive patients still reported symptoms at least 28 days after the initial consultation.

Broad-spectrum capture of clinical pathogens using engineered Fc-mannose-binding lectin enhanced by antibiotic treatment.

Background: Fc-mannose-binding lectin (FcMBL), an engineered version of the blood opsonin MBL that contains the carbohydrate recognition domain (CRD) and flexible neck regions of MBL fused to the Fc portion of human IgG1, has been shown to bind various microbes and pathogen-associated molecular patterns (PAMPs). FcMBL has also been used to create an enzyme-linked lectin sorbent assay (ELLecSA) for use as a rapid (<1 h) diagnostic of bloodstream infections. Methods: Here we extended this work by using the ELLecSA to test FcMBL's ability to bind to more than 190 different isolates from over 95 different pathogen species. Results: FcMBL bound to 85% of the isolates and 97 of the 112 (87%) different pathogen species tested, including bacteria, fungi, viral antigens and parasites. FcMBL also bound to PAMPs including, lipopolysaccharide endotoxin (LPS) and lipoteichoic acid (LTA) from Gram-negative and Gram-positive bacteria, as well as lipoarabinomannan (LAM) and phosphatidylinositol mannoside 6 (PIM 6) from Mycobacterium tuberculosis. Conclusions: The efficiency of pathogen detection and variation between binding of different strains of the same species could be improved by treating the bacteria with antibiotics, or mechanical disruption using a bead mill, prior to FcMBL capture to reveal previously concealed binding sites within the bacterial cell wall. As FcMBL can bind to pathogens and PAMPs in urine as well as blood, its broad-binding capability could be leveraged to develop a variety of clinically relevant technologies, including infectious disease diagnostics, therapeutics, and vaccines.

Vocal Fold Injection of Absorbable Materials: A Histologic Analysis With Clinical Ramifications.

OBJECTIVES:: Gels composed of carboxymethylcellulose (CMC) and cross-linked hyaluronic acid are commonly used as temporary or resorbable injectable materials for vocal fold medialization. However, there is limited information about tissue injection patterns, soft tissue reaction, degradation, and residence time, particularly for the newer CMC gels. STUDY DESIGN:: Prospective, laboratory. METHODS:: Ten canines underwent paraglottic (deep to the vocal ligament) microlaryngoscopic injection with about 100 µL (0.1 mL) of cross-linked hyaluronic acid (Restylane) in the right vocal fold and about 100 µl (0.1 mL) of CMC gel in the left vocal fold. Two commercial CMC gels of similar formulation (Prolaryn Gel and Renú Gel) were used in 5 animals each. Two subjects were sacrificed for histologic analysis at 3, 13, 29, 42, and 55 days. RESULTS:: Histology showed that injected Restylane formed cohesive ovoid-shaped aggregated implants with minimal dispersion, inflammation, or cellular invasion in all subjects. Approximately 86% of Restylane injected remained at 8 weeks, as estimated from postmortem, high-resolution magnetic resonance imaging scans. In contrast, histology showed that both CMC gels dispersed widely through fascial planes during and after injection within and outside the thyroarytenoid muscle fascicles. There was a robust macrophage and histiocyte phagocytic response, with moderate to severe inflammation noted around residual CMC gel at early time points, and at 6 to 8 weeks, very little free gel was observed. CONCLUSIONS:: None of the studied materials induced a clinical inflammatory reaction on laryngoscopy such that they would be considered problematic or dangerous. Restylane demonstrated superior injection localization, tissue compatibility, and residence time. Both CMC gels did not localize well in the paraglottic region, and there was a robust inflammatory response, with clearance by macrophages and short residence time. These results suggest that CMC gels may have a more limited application than previously thought for vocal fold medialization in patients in whom the injection is being used to achieve voice enhancement while awaiting reinnervation. Level of Evidence: NA.

Glottic Stenosis: An Anatomic Analysis and New Treatment With a Self-Retaining Interarytenoid Spring.

INTRODUCTION:: Endotracheal (ET) intubation is a common cause of acquired glottic stenosis. Severe cases often require an irreversible arytenoidectomy/cordectomy, which typically results in poor voice quality. Adult human cadaver larynges were studied to gain insights about ET tube-induced posterior glottic injuries, hoping to create a less invasive remedy. STUDY DESIGN:: Human cadaver investigation and case reports. METHODS:: Microlaryngeal assessments were done on 10 human cadaver larynges (5 men, 5 women) with and without ET tubes. After supracricoid soft tissue resection, measurements were obtained, including the distance between the outer diameter of the ET tube and the medial aspect of the cricoarytenoid joint facet. Additionally, measurements of the circumferential arc of differently sized ET tubes were made alongside both cricoarytenoid joint capsules. This information was used to design a silastic stent that would function as a self-retaining interarytenoid spring to treat posterior glottic stenosis in 5 patients. Four of 5 patients included in the clinical study were tracheotomy dependent, primarily because of glottic stenosis. The human surgical technique is described in detail. RESULTS:: The shortest distance between the outer diameter of the ET tube to the medial cricoid facet averaged 5.02 mm in men and 3.62 mm in women. On the basis of the diameter of the intralaryngeal component of the initially round stent, and the position of the cricoarytenoid joint facets, the interarytenoid spring would have a subtended arc between 110° and 175°. These data helped fashion parameters for modifying a conventional T-tube to form a new self-retaining silastic interarytenoid spring. The first 5 human cases have been successful, allowing effective tracheotomy tube decannulation and excellent voice quality. CONCLUSIONS:: The anatomic investigation herein provided key insights into ET tube-induced glottic stenosis and facilitated a new straightforward procedure to surgically improve the airway yet preserve excellent vocal function in patients with acquired glottic stenosis. Level of Evidence: NA.

The fundamental association between mental health and life satisfaction: results from successive waves of a Canadian national survey.

BACKGROUND: A self-reported life satisfaction question is routinely used as an indicator of societal well-being. Several studies support that mental illness is an important determinant for life satisfaction and improvement of mental healthcare access therefore could have beneficial effects on a population's life satisfaction. However, only a few studies report the relationship between subjective mental health and life satisfaction. Subjective mental health is a broader concept than the presence or absence of psychopathology. In this study, we examine the strength of the association between a self-reported mental health question and self-reported life satisfaction, taking into account other relevant factors. METHODS: We conducted this analysis using successive waves of the Canadian Community Health Survey (CCHS) collected between 2003 and 2012. Respondents included more than 400,000 participants aged 12 and over. We extracted information on self-reported mental health, socio-demographic and other factors and examined correlation with self-reported life satisfaction using a proportional ordered logistic regression. RESULTS: Life satisfaction was strongly associated with self-reported mental health, even after simultaneously considering factors such as income, general health, and gender. The poor-self-reported mental health group had a particularly low life satisfaction. In the fair-self-reported mental health category, the odds of having a higher life satisfaction were 2.35 (95% CI 2.21 to 2.50) times higher than the odds in the poor category. In contrast, for the "between 60,000 CAD and 79,999 CAD" household income category, the odds of having a higher life satisfaction were only 1.96 (95% CI 1.90 to 2.01) times higher than the odds in the "less than 19,999 CAD" category. CONCLUSIONS: Subjective mental health contributes highly to life satisfaction, being more strongly associated than other selected previously known factors. Future studies could be useful to deepen our understanding of the interplay between subjective mental health, mental illness and life satisfaction. This may be beneficial for developing public health policies that optimize mental health promotion, illness prevention and treatment of mental disorders to enhance life satisfaction in the general population.

Hemoglobin Levels and the Risk of Malaria in Papua New Guinean Infants: A Nested Cohort Study.

Studies are available that assess the risk of malaria in accordance to the body's iron store and the systematic iron supplementation of preschool children. However, only a few studies evaluated the temporal association between hemoglobin and malaria and their results are opposing. A total of 1,650 3-month-old Papua New Guinean infants were enrolled in this study and followed-up for 12 months. The risk of malaria was assessed in all children every 3 months and with each episode of fever. The incidence of clinical malaria between 3 and 15 months of age was 249 cases per 1,000 infants per year. After adjustment for potential confounding factors, a decrease of 1 g/dL of hemoglobin was associated with a nonsignificant increase of 11% for risk of malaria infection (hazard ratio, 1.11, 95% confidence interval; CI, 0.99-1.25, P = 0.076). Only children with severe anemia (hemoglobin < 8.0 g/dL) at baseline were at higher risk of malaria infection (hazard ratio, 1.72, 95% CI, 1.08-2.76, P = 0.023) during the follow-up year compared with the control group (Hemoglobin > 10.0 g/dL). This association was not statistically significant if only clinical malaria episodes were taken into account (hazard ratio, 1.42, 95% CI, 0.77-2.61, P = 0.26). Our study suggests that infants with lower hemoglobin levels are not protected against malaria infection. Further research that examines the risk of malaria in relation to both hemoglobin and iron store levels would be important to better understand this complex interaction.

A Broad-Spectrum Infection Diagnostic that Detects Pathogen-Associated Molecular Patterns (PAMPs) in Whole Blood.

BACKGROUND: Blood cultures, and molecular diagnostic tests that directly detect pathogen DNA in blood, fail to detect bloodstream infections in most infected patients. Thus, there is a need for a rapid test that can diagnose the presence of infection to triage patients, guide therapy, and decrease the incidence of sepsis. METHODS: An Enzyme-Linked Lectin-Sorbent Assay (ELLecSA) that uses magnetic microbeads coated with an engineered version of the human opsonin, Mannose Binding Lectin, containing the Fc immunoglobulin domain linked to its carbohydrate recognition domain (FcMBL) was developed to quantify pathogen-associated molecular patterns (PAMPs) in whole blood. This assay was tested in rats and pigs to explore whether it can detect infections and monitor disease progression, and in prospectively enrolled, emergency room patients with suspected sepsis. These results were also compared with data obtained from non-infected patients with or without traumatic injuries. RESULTS: The FcMBL ELLecSA was able to detect PAMPS present on, or released by, 85% of clinical isolates representing 47 of 55 different pathogen species, including the most common causes of sepsis. The PAMP assay rapidly (<1h) detected the presence of active infection in animals, even when blood cultures were negative and bacteriocidal antibiotics were administered. In patients with suspected sepsis, the FcMBL ELLecSA detected infection in 55 of 67 patients with high sensitivity (>81%), specificity (>89%), and diagnostic accuracy of 0·87. It also distinguished infection from trauma-related inflammation in the same patient cohorts with a higher specificity than the clinical sepsis biomarker, C-reactive Protein. CONCLUSION: The FcMBL ELLecSA-based PAMP assay offers a rapid, simple, sensitive and specific method for diagnosing infections, even when blood cultures are negative and antibiotic therapy has been initiated. It may help to triage patients with suspected systemic infections, and serve as a companion diagnostic to guide administration of emerging dialysis-like sepsis therapies.

Improved treatment of systemic blood infections using antibiotics with extracorporeal opsonin hemoadsorption.

Here we describe development of an extracorporeal hemoadsorption device for sepsis therapy that employs commercially available polysulfone or polyethersulfone hollow fiber filters similar to those used clinically for hemodialysis, covalently coated with a genetically engineered form of the human opsonin Mannose Binding Lectin linked to an Fc domain (FcMBL) that can cleanse a broad range of pathogens and endotoxin from flowing blood without having to first determine their identity. When tested with human whole blood in vitro, the FcMBL hemoadsorption filter (FcMBL-HF) produced efficient (90-99%) removal of Gram negative (Escherichia coli) and positive (Staphylococcus aureus) bacteria, fungi (Candida albicans) and lipopolysaccharide (LPS)-endotoxin. When tested in rats, extracorporeal therapy with the FcMBL-HF device reduced circulating pathogen and endotoxin levels by more than 99%, and prevented pathogen engraftment and inflammatory cell recruitment in the spleen, lung, liver and kidney when compared to controls. Studies in rats revealed that treatment with bacteriocidal antibiotics resulted in a major increase in the release of microbial fragments or 'pathogen-associated molecular patterns' (PAMPs) in vivo, and that these PAMPs were efficiently removed from blood within 2 h using the FcMBL-HF; in contrast, they remained at high levels in animals treated with antibiotics alone. Importantly, cleansing of PAMPs from the blood of antibiotic-treated animals with the FcMBL-hemoadsorbent device resulted in reduced organ pathogen and endotoxin loads, suppressed inflammatory responses, and resulted in more stable vital signs compared to treatment with antibiotics alone. As PAMPs trigger the cytokine cascades that lead to development of systemic inflammatory response syndrome and contribute to septic shock and death, co-administration of FcMBL-hemoadsorption with antibiotics could offer a more effective approach to sepsis therapy.

The 'help' question doesn't help when screening for major depression: external validation of the three-question screening test for primary care patients managed for physical complaints.

BACKGROUND: Major depression, although frequent in primary care, is commonly hidden behind multiple physical complaints that are often the first and only reason for patient consultation. Major depression can be screened by two validated questions that are easier to use in primary care than the full Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV) criteria. A third question, called the 'help' question, improves the specificity without apparently decreasing the sensitivity of this screening procedure. We validated the abbreviated screening procedure for major depression with and without the 'help' question in primary care patients managed for a physical complaint. METHODS: This diagnostic accuracy study used data from the SODA (for 'SOmatisation Depression Anxiety') cohort study conducted by 24 general practitioners (GPs) in western Switzerland that included patients over 18 years of age with at least a single physical complaint at index consultation. Major depression was identified with the full Patient Health Questionnaire. GPs were asked to screen patients for major depression with the three screening questions 1 year after inclusion. RESULTS: Of 937 patients with at least a single physical complaint, 751 were eligible 1 year after index consultation. Major depression was diagnosed in 69/724 (9.5%) patients. The sensitivity and specificity of the two-question method alone were 91.3% (95% CI 81.4 to 96.4) and 65.0% (95% CI 61.2 to 68.6), respectively. Adding the 'help' question decreased the sensitivity (59.4%; 95% CI 47.0 to 70.9) but improved the specificity (88.2%; 95% CI 85.4 to 90.5) of the three-question method. CONCLUSIONS: The use of two screening questions for major depression was associated with high sensitivity and low specificity in primary care patients presenting a physical complaint. Adding the 'help' question improved the specificity but clearly decreased the sensitivity; when using the 'help' question, four out of ten patients with depression will be missed, compared to only one out of ten with the two-question method. Therefore, the 'help' question is not useful as a screening question, but may help discussing management strategies.