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Background: Young to middle-aged U.S. adults are burdened by the obesity, opioid, and COVID-19 epidemics. However, the ability to detect cardiovascular disease (CVD) manifestations of population-wide changes in risk factors within contemporary cohorts in young to middle adulthood is unknown. Objective(s): To assess inter-rater reliability of death certificate (DC), obituary, coroner/medical examiner (CME) autopsy report, and hospital record ion in young to middle adulthood. Setting(s): The National Longitudinal Study of Adolescent to Adult Health (Add Health), a nationally representative school-based sample of 20,745 U.S. adolescents in grades 7-12 (1994-1995) followed for the last 26 years and aged 37-45 years in 2020. Method(s): We traced all participants, identified decedents, then collected DCs, obituaries, CME autopsy reports, and hospital records = 1 month before death dates. Among a random sample of 28 decedents and an oversample of 28 hospitalized decedents enriched 3:1 for CVD, two trained and certified staff used an electronic data entry system to data needed for outcome classification from the four information sources following standardized, item-by-item instructions. We measured item-specific reliability of categorical data ion as the agreement between ors (%) and prevalence- and bias-adjusted kappa coefficient (PABAK). We measured reliability of interval-scale data (e.g. creatinine;troponin;creatinine kinase;CK-MB;pro-BNP concentrations) as an intra-class correlation coefficient (ICC). Result(s): We identified 578 (2.8%) participants who were deceased through December 2020. Of those, 577 (99.8%) had high scoring National Death Index matches uniquely identifying decedents in 44 U.S. states. We collected and ed 531 (92%), 445 (77%), 178 (66%), and 95 (39%) of their DCs, obituaries, CME autopsy reports, and hospital records. CVD was the underlying cause of death in 10% (95% confidence interval [CI]: 8%-13%) of decedents. Mean, item-specific agreement (95% CI) was 0.86 (0.84-0.89), 0.90 (0.87-0.93), 0.93 (0.92-0.95), and 0.94 (0.92-0.95) for each source. The corresponding mean, item-specific PABAK (95% CI) was 0.83 (0.80-0.86), 0.86 (0.83-0.90), 0.92 (0.90-0.94) and 0.91 (0.89-0.93). The mean, biomarker-specific ICC (95% CI) was 0.96 (0.95-0.98). Conclusion(s): Overall, CVD was a major cause of mortality and reliability of ion was excellent across a range of measures. Ongoing investigation of deaths, and as needed, targeted staff retraining and improvement of ion protocol will enable high quality studies of CVD emergence within this large, nationally representative U.S. cohort. Such studies will provide generalizable insight into the biological mechanisms underlying cardiovascular manifestations and thereby inform understanding of changing CVD burden in the U.S. population.
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Background. Congregate military populations remain at risk of SARS-CoV-2 outbreaks and the optimal surveillance approach in such settings remains unclear. We enrolled midshipmen at the United States Naval Academy (USNA) in a setting of frequent PCR screening use of prevention strategies. Methods. Dried blood spots (DBS) and saliva were collected in August 2020, December 2020, February 2021 (saliva only) and April/May 2021 to measure anti-SARS-CoV-2 spike (S) and nucleoprotein (NP) IgG. COVID-19 vaccine history and records of SARS-CoV-2 PCR tests and routine asymptomatic screening assays were obtained from the USNA Brigade Medical Clinic. Attack rates were compared with cumulative frequencies of infections. Concordance of saliva and DBS anti-NP and anti-S IgG positivity was determined using Cohen's kappa coefficient. Results. The study enrolled 181 midshipmen. COVID-19 vaccinations were administered in March/April 2021. Samples were collected for 101 participants in August, 73 in December, 57 in February (saliva only), and 63 in April/May. In August, 17 (17%) participants showed evidence of SARS-CoV-2 infection based on anti-S IgG values from DBS and/or saliva. By December 2020, anti-S seroconversion was observed for 5 more based on DBS and/or saliva. By May 2021, 100% of participants were anti-S IgG seropositive after vaccination based on DBS and/or saliva;48% of participants had seroconverted to anti-NP IgG. Among participants with both DBS and saliva samples, a coefficient of 0.64 showed substantial agreement between anti-S IgG results in August and perfect agreement in December (Table 1). DBS and saliva results for anti-NP IgG were in perfect agreement through December and in substantial agreement in May (0.68, Table 2). Prior to vaccination in March/April 2021, 4/48 of participants had at least one documented SARS-CoV-2 PCR positive result (Table 3). Cumulative PCR test positivity concordance with DBS seroconversion was 37.5% and 60% for anti-S IgG and anti-NP IgG, respectively. Conclusion. There was a substantive SARS-CoV-2 attack rate before vaccination;all vaccinees mounted an anti-S IgG response in blood. We note high agreement between DBS and saliva for IgG measurement. Serology-based surveillance identified substantially more SARS-CoV-2 infections than PCR screening.
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Purpose: Chest radiographs (CXRs) are an important tool for COVID-19 disease management and progression.1 A number of international thoracic/radiology societies have developed structured reporting templates to reduce interpretation variability and measure concordance.2 Recent research into COVID-19 templates have used small data sets, small numbers of radiologists and focused on predictive disease progression. The aim of this study is to evaluate the utility of three (Australian, British, Dutch) CXR qualitative reporting templates in a large Sydney teaching hospital. Methods and Materials: Twelve staff specialist radiologists were recruited to participate in the study. Retrospective CXRs between 2020-21 were collected and organized into test sets, containing the CXRs of 50 PCR-positive COVID-19 patients and classified as 'classic/ characteristic' for radiology signs of COVID-19 disease (30 cases) or 'indeterminate' for radiological signs (20 cases) by two expert radiologists. A further 10 CXRs of patients who were imaged for an 'alternative' diagnosis and 10 CXRs that had been reported 'normal' were included. Radiologists were assigned to one of three image sets, with the 70 images randomized and instructed to report the cases using three templates: the Royal Australian and New Zealand College of Radiology (RANZCR), British Society of Thoracic Imaging (BSTI) and modified Co-RADS (Dutch)3. Fleiss' Kappa Coefficient was used for agreement between radiologists on each template (inter-reader), and for radiologist's agreement within themselves using the three templates (intra-reader). Result(s): Inter-reader agreement between radiologists was highest for the BSTI template at 0.46 (moderate agreement), followed by RANZCR (0.36) and modified CO-RADS (0.31) (fair agreement). For all templates, agreement was highest for 'normal CXRs" and lowest for 'indeterminate', with moderate or fair agreement for the 'classic' COVID-19 cases (BSTI 0.44;RANZCR 0.31;mod-CO-RADS 0.31). The intra-reader agreement across the 3 templates for 'classic/characteristic' COVID cases was 0.61, for 'normal' cases 0.76 and 'alternative' 0.68 (all at substantial agreement), indicating that radiologists largely were consistent with classification of cases. Conclusion(s): The BSTI template yielded the highest agreement among radiologists for reporting COVID-19 CXRs as well as for 'normal' and 'alternative'. There was a large range of intra-reader agreement for all 4 types of patient presentations, however the level of agreement equal to or higher than 'moderate'. Structured reporting templates have yielded promising results for concordance between radiologists and reliability within radiologist's reporting of CXRs. Further investigation of radiology lexicon within templates is required to seek reasons for variation in concordance, as well as the demographics of readers.
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Background: COVID-19 is associated with an increased risk of venous thrombosis, even when patients are on standard-dose antithrombotic prophylaxis. Hence, the identification of biomarkers of thrombosis helps tailoring dosage of antithrombotic prophylaxis. D-dimer has been extensively employed as a biomarker and cut-off values at hospital admission have been proposed to stratify the risk of thrombosis and make decision on prophylaxis. However, D-dimer measurement is not standardized, and it is unknown if the cut-off values used for decision making can be used interchangeably between methods. Aim(s): To assess for concordance of results obtained with different commercially available laboratory methods measuring D-dimer. Method(s): Plasma samples collected from COVID-19 patients at the Hospital of Cremona were evaluated for D-dimer with three widely used immunoturbidimetric methods (Liatest D-di, Stago, Asnieres, France;D-dimer HS 500, Werfen, Orangeburg, NY;Innovance D-dimer, Siemens, Marburg, Germany). Result(s): A total of 87 COVID-19 patients [54 male and 33 female, median age of 73 years (range 28-98)] were enrolled in the study. No significant differences were found between mean D-dimer concentrations obtained with the three methods even when stratifying D-dimer levels in 4 groups (<1000, 1000-2000, 2000-5000, >5000 ng/mL) (Figure 1). The three methods showed substantial result agreement [Stago-vs- Werfen and Siemens-vs- Stago (Cohen's kappa coefficient of 0.760 and 0.699, respectively)] to an almost perfect agreement [Siemens-vs- Werfen (Cohen's kappa coefficient of 0.811)], with a p-value < 0.001. Results from the three methods showed a good linear correlation (Rho = 0.94) (Figure 2). Conclusion(s): The relatively good concordance of D-dimer results among the three investigated methods indicates that D-dimer cut-off values could be used interchangeably regardless of the method used for testing. The results pave the way to clinical trials aimed to assess the value of D-dimer as a biomarker to make decision on the intensity of antithrombotic prophylaxis in COVID-19 patients. (Figure Presented).
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Background. Salivary glands ultrasonography (SGUS) is an emerging tool to evaluate damages in primary sjogren patients (pSS). Up to date, SGUS has demonstrated its metric properties as an outcome measure for diagnosing pSS. As New therapeutics protocols are in developing it seems mandatory to use validated SGUS scoring systems. Objectives. The goal of our study was to evaluate international SGUS reliability exercise before beginning an international SGUS study to evaluate Modification Abnormalities of Salivary glands in pSS According to disease duration (MASAI study). Methods. Fourteen sonographers with different levels of SGUS participated in the exercise, evaluating 60 grey scale static images (30 parotid and 30 submandibular glands). Before the exercise, training was done by videoconferencing showing the different pathological SGUS findings and explaining the new OMERACT scoring system. We evaluated homogeneity (yes/no), location of hypoechogenity (0 to 3), hyperechoic band (0-3), comprehensive OMERACT scoring system (0-3), binary comprehensive OMERACT (0-1 versus 2-3) and diagnosis appreciation (No/yes). Intra-reader and interreader reliability were estimated by computing Cohen's kappa coefficients using SPSS 25.0 (SPSS Inc., Chicago, IL), and was interpreted as follows: slight, 0-0.20;fair, 0.21-0.40;moderate, 0.41-0.60;substantial, 0.61-0.80;and almost perfect, 0.81-1. The most experienced sonographer (P4) was considered as the gold standard. Results. Intra-reader reliability of the most experienced was perfect and substantial for the OMERACT scoring system. Intra-reader reliability of the other sonographers was fair to almost perfect for homogeneity and diagnosis whereas the reliability was fair to substantial for other items. Inter-reader reliability between the two most experienced sonographers (P4 and P12) was almost perfect for homogeneity, substantial for diagnosis and moderate for OMERACT scoring system. Changing OMERACT scoring system in binary items, the reliability of the most experienced sonographer was good 0.65 (9 images with homogeneity and low OMERACT, 42 had heterogeneity and high OMERACT, 9 had no homogeneity but low OMERACT and none had homogeneity with high OMERACT), clearly lower that of homogeneity. Compared to the most experienced sonographer, reliabilities of other sonographers were moderate to almost perfect for both homogeneity and diagnosis but only fair to moderate for OMERACT (Table I, II). Conclusions. According to the updated literature, we confirmed that homogeneity is the most reliable item, very close to diagnosis appreciation. Structural damages evaluations by the OMERACT scoring systems gave lower kappa values but remain still useful for diagnosing and particularly following parenchymal modifications. (Table Presented).
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Purpose : In the COVID-19 era, tele-retinal technologies are rising to the forefront of contactless ophthalmic care. Point-of-care Optical Coherence Tomography (OCT) and fundus photography remotely analyzed by an off-site retina specialist (tele-R) must be validated for screening retinal disorders. This study assesses the feasibility of tele-R as a screening tool for diabetic retinopathy (DR) in an outpatient clinical setting. Methods : A retrospective study was conducted on 16 patients (32 eyes, 28 with DR, and 4 controls) presenting to the retina clinic (RC) of an urban academic medical center. Automated OCT-B and 45 fundus photographs of the posterior pole were taken using a Topcon Maestro 3D OCT-1 unit, and 3D topographical maps of the macula were generated. Images were transmitted to a remote retina specialist (blinded to patient history and demographics) who assessed severity of DR and diabetic macular edema (DME). Primary outcomes included grading of DR and DME with fundus and OCT-B images, respectively, using the International Clinical Diabetic Retinopathy classification scale. The secondary outcome was identifying the severity grade of DME using the 3D macular map. Concordance was tested between diagnoses obtained from tele-R assessment and in-person examination by the retina specialist (gold standard) using Cohen's Kappa statistic (κ). Eyes that could not be assessed were removed from analysis. Results : 30 of 32 eyes with sufficient data for analysis were included. The average age was 57.9 (±11.2) years. 37% of patients were male, 69% were Hispanic, and 94% had Type 2 diabetes. The κ±standard error (SE) for DR severity was 0.738±0.099 (p<0.001), for DME severity was 0.588±0.122 (p<0.001), and for presence of DME was 0.727±0.122 (p<0.001). The retina specialist was able to grade the DME severity in only 10/14 (71%) eyes using the 3D macular map alone, but in 93% (13/14) eyes with OCT-B images. Conclusions : Tele-R is a reliable modality for diagnosis of DR severity;there was substantial agreement on identifying DR severity using tele-R vs in-person examination. There was substantial agreement in discerning DME using tele-R vs in-person while only moderate agreement on determining the severity of DME, which suggests that tele-R may useful in identifying presence of DME but not determining the severity of edema.
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Purpose : In recent years, innovations in tele-ophthalmology have shown promise in providing quality ophthalmic care to patients in low-access settings and high-risk environments such as the COVID-19 pandemic. Emergency departments and urgent centers may benefit from tele-ophthalmology applications;the tele-images can be sent to the covering ophthalmologist or, to another ED for evaluation of images prior to transferring the patient. In this study, we aimed to assess the ability of resident physicians to identify features of posterior-pole retinal pathology using teleophthalmology. Methods : Retrospective study on 16 patients (32 eyes;30 with retinal pathology and 2 controls) who presented to a retina clinic at an academic medical center. Automated OCT-B images with 3D topographic maps and fundus photographs of the posterior pole using a Topcon Maestro 3D OCT-1 unit were taken. Images were transmitted remotely to a resident physician who attempted to identify retina pathology using fundus photography and OCT. The same images were consequently evaluated by a retina specialist for grading. We then tested the concordance between diagnoses rendered via tele-OCT by the resident physician and the gold standard clinical examination (performed by the retina specialist) using Cohen's Kappa statistic (κ). Results : An overall average of 79.9% concordance for 69 potential findings was obtained between the retina attending's diagnosis with clinical examination and the resident physician's diagnosis using tele-OCT/fundus images based on Cohen's Kappa statistic (κ). The concordance was lower in eyes with vitreous hemorrhage most likely due to the inferior quality fundus and OCT-B images. The resident exam also identified the presence of any macular pathology in all 30 eyes with macular pathology and correctly identified the controls, indicating 100% sensitivity for identifying abnormal findings using tele OCT/fundus images. Conclusions : This study verifies the utility of resident screening of tele-OCT fundus and OCT-B images to identify retinal pathology. Tele-ophthalmology likely has a useful role in triaging retinal pathology whose outcomes could be affected by timely intervention. Many unnecessary emergency transfers may be avoided if the on-call ophthalmology residents are able to review the fundus and OCT images before hand.
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Purpose : The COVID-19 pandemic exposed the need for increased mobilization of teleophthalmology resources. Artificial intelligence (AI) may serve as a tool to assist physicians in triaging highest need patients if the AI's assessment of disease is comparable to the physician's assessment. This study assesses the ability of AI software to diagnose diabetic retinopathy (DR) as compared to Tele-ophthalmology and in-person examination by a retina specialist. Methods : Records of forty patients (average age 55.1±10.9 years) presenting to an urban retina clinic were reviewed retrospectively for factors including demographics, retinal photos taken by Canon CR-2 Plus AF Retinal Imaging camera (Tokyo, Japan), and diagnosis of DR based on the International Clinical Diabetic Retinopathy (ICDR) classification scale during an in-person clinic visit in which a fundus exam was performed. Retinal photos were graded by AI software, EyeArt (EyeNuk, CA), as Normal, Mild DR, or More than Mild DR. Retinal images were also graded remotely by a retina specialist using the ICDR classification scale via TeamViewer software (Tele). Agreement between Tele, AI, and inperson DR diagnosis was assessed using Cohen's Kappa (κ) coefficient using IBM® SPSS® Statistics software. Results : Among 80 eyes, 33 were diagnosed in-person with no DR, 5 with mild nonproliferative DR (NPDR), 9 with moderate NPDR, 3 with severe NPDR, 7 with proliferative diabetic retinopathy (PDR), and 23 with regressed PDR. Eleven and 26 eyes could not be graded by Tele or AI, respectively. κ±SE for in-Person diagnosis vs Tele was 0.859±0.058 (p<.001), in-person vs AI was 0.751±0.082 (p<.001), and Tele vs AI was 0.883±0.063 (p<.001). Conclusions : AI is a reliable tool for screening patients for DR and referring them for physician evaluation since AI had a substantial rate of agreement with the in-person diagnosis and near perfect agreement with Tele. Tele grading was in near perfect agreement with the in-person diagnosis, showing that Tele is a reliable option for a physician to remotely screen patients that may be ungradable by AI. However, improvements are needed due to the high number of images that are ungradable via Tele and AI. Further studies should assess ways to reduce the number of ungradable images via Tele and AI and create a trend analysis for multiple visits for a given patient.
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Purpose : During the Covid-19 era, understanding the benefits and limitations of tele-ophthalmology has become increasingly important. In this study, we aim to assess the accuracy of tele-ophthalmic diagnosis of diabetic retinopathy (DR) and diabetic macular edema (DME) when performed by resident physicians. Methods : Retrospective study on 16 patients (32 eyes;28 DR and 4 controls) who presented to a retina clinic at an academic medical center. Automated OCT-B images with 3D topographic maps and fundus photographs of the posterior pole using a Topcon Maestro 3D OCT-1 unit were taken. Images were transmitted remotely to a resident physician who assessed the severity of the DR and DME on the basis of the fundus photographs and OCT. The same images were transmitted to a retina specialist for grading. Primary outcomes included DR and DME grade as defined by the International Clinical Diabetic Retinopathy classification scale. We then tested the concordance between diagnoses rendered via tele-OCT by the resident compared to the retina attending's remote diagnosis and the gold standard retina specialist's clinical examination using Cohen's Kappa statistic (κ). Results : Agreement between ophthalmology residents and attendings on tele-OCT diagnosis of DR was substantial (78% concordance on presence and 75% on severity), while agreement on identifying and grading edema was moderate (60% concordance on DME presence and 52% concordance on overall DME severity). Detection of DR by residents via tele-retinal imaging is highly sensitive (100% sensitivity), while detection of DME is highly specific (79-95% specificity). Discordance between residents and attendings on DME grading may owe to differences in opinion regarding what constitutes mild edema versus no edema;however, both concordance and predictive accuracy increase when identifying patients with moderate to severe DME. Conclusions : This study provides proof of principle for the sensitivity and specificity for remote diagnosis of DR via tele-OCT fundus and OCT-B images. This technology may be useful in identifying patients at risk of severe vision loss and enable early detection of patients who need referral for prompt treatment. These findings may be particularly relevant to training programs looking to implement tele-retinal diabetic screening or using tele-OCT where prompt access to a retina specialist may not be possible.
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Introduction/ Background: RT-PCR testing remains the gold standard for the diagnosis of infections. There are limited resources for SARS-CoV-2 RT-PCR, which affects capacity for screening large populations. To meet such demands and reduce transmission, antigen-based methods are being considered. We assess antigen tests performance for large population screening compared to RT-PCR. Methods: The evaluation was conducted on 4146 participants in Senegal and tested at IRESSEF (Institut de Recherche en Sante de Surveillance Epidemiologique et de Formations. Oropharyngeal and nasopharyngeal swaps were collected from each participant into 2 mL of viral transport medium (VTM). We used 400ul of VTM to assess the performance of LumiraDx SARSCoV- 2 antigen assay compared to RT-PCR. Sensibilities and specificities LumiraxDx were computed and compared to those of RT-PCR. Results: Prevalence of SARS-CoV-2 was 4.5% with RT-PCR and 4.1% with LumiraDx. Compared to the RT-PCR, the specificity and specificity of the LumiraDx test in large-scale population were 82.7% [95% CI 74,1-89,7] and 99.9% [95% CI 99,6-99,9] respectively. Based on the threshold cycle range, sensitivity and specificity were 92,1% [95% CI 84,6-96,3] and 99.9 % [95% CI 99,6-99,9], respectively when Ct value was below or equal 33 cycles, and 38.1% [95% CI 18,9-61,3] and 100% [95%CI 99,7-100] respectively when it was above 33. The kappa coefficient was 0.88 when considering all the patients and 0.94 for Ct values below 30 cycles. Impact: The results confirm that antigen-based tests could be used instead of PCR-based test in resource limited settings. Indeed, RT- PCR may not be feasible for large populations screening in resource limited countries and antigen-based testing could be an alternative to quickly diagnose, isolate and treat positive cases. Conclusion: Our data have shown that the LumiraDx SARS-CoV-2 antigen test using oropharyngeal and nasopharyngeal swap samples collected in viral transport elicited comparable prevalence, high sensitivity and good agreement in large scale screening of SARS-CoV-2, when compared to the RTPCR.
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Objective: Primary objective: To study the energy expenditure in a significant number of mechanically ventilated COVID-19 patients in ARDS. Secondary objective: 1. To compare the deviations seen with predictive equations based on actual and ideal body weight. 2. To compare the EE derived versus the VCO2 based estimation. Materials and methods: The Resting Energy expenditure (REE) of 60 patients was measured with the help of the ESCOVYX-module for indirect calorimetry using the GE CARESCAPE R860 ventilator. The steady-state was validated by ensuring a respiratory quotient of 0.7-0.8 and variation of 5% for VCO2 and VO2 for at least 30 minutes. It was ensured that for 60 minutes the patient was not disturbed by endotracheal tube suction, no ventilatory changes were performed, and no vasopressors alteration was done. The absence of a leak was ascertained on the ventilator. The calculation was done from day 2 onwards after mechanical ventilation and subsequently every 2nd day till the patient was on ventilator. The resting energy expenditure was also calculated by the simple predictive equations as per ESPEN COVID-19 guidelines, i.e., 25-30 kcal/kg of which the mean of 27 kcal/kg was chosen. Bodyweight was estimated by height equation 50 kg for 5 ft plus 2.3 kg for each inch >5 feet. The quantitative measures were studied by Bland and Altman plot to describe an agreement between the two by constructing a line of agreement. The limits were calculated by using the mean and standard deviation of the difference between the two measurements. Statistics: The EE derived from the two methods is compared by Bland and Altman plots. Reliability and adequacy between the methods are tested using ROC curves with kappa coefficient (reliability coefficient). For the coefficient of variation, ANOVA is used when applicable. IBM SPSS Statistics for Windows, version 24.0 (IBM Corporation, Chicago, USA) was used to perform analyses. MedCalc version 19 (MedCalc bv, Ostend, Belgium) was used to create BlandeAltman plots. Results: No 1: The estimated mean energy expenditure derived from weight-based calculations was 2576 ± 469 kcal/24 hours, which was significantly higher when compared with an estimation of EE from indirect calorimetry of 1507 ± 499 kcal/24 hours (15-20 kcal/kg/day). This correlation is significant but not useful for prediction (R = 0.345). No 2: The estimated mean EEVCO2 was 1388 ± 467 kcal/24 hours compared with an estimation of EE from indirect calorimetry of 1507 ± 499 kcal/24 hours. The Bias and precision, as visualized by the limits of agreement, are shown in the Bland-Altman plot where there was a significant bias of only 118 kcal/day (95% CI (-187 to 422 kcal);p < 0.001. The regression analysis reveals that for every one unit change in EEVCO2 value, there is one unit change in EE by IC. This correlation is significant (R = 0.951). Similarly, the Bland-Altman plot was tested between the estimated mean EEVCO2 and EE derived from weight-based calculations. The difference was wide with significant bias of 1187 kcal/day (95% CI (-2256 to (-118) kcal);p < 0.001). Conclusion: The ESPEN guidelines (30 kcal/kg through the disease state) for energy estimation may not be right in COVID-19 patients and the study calls for more personalisation of energy estimation by the correct use of indirect calorimetry.
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Introduction: Telemedicine, once of limited scope, has become common and widespread due to the present and ongoing SARSCoV- 2 pandemic. Center to home delivery, the most common model, allows for convenient and efficient care. Concurrent with this groundshift, there is increasing attention to disparities in medical services, and how these disparities may impact patient outcomes. Telemedicine could be used to help bridge barriers to timely quality care, however, patient access and longstanding institutional biases may limit the potential. Healthcare providers must actively develop systems to ensure that telemedicine is optimized for people across the income spectrum. This exploratory analysis examined how economic disparities in patients being evaluated for obstructive sleep apnea may be associated with providers clinical impressions. The objective was to study the inter-method reliability of pre-test probability of obstructive sleep apnea assessed via telemedicine and in-person evaluations, and to compare that reliability between income classes. Methods: This is a secondary analysis of a pre-pandemic interrater reliability study, conducted between March 2017 and January 2019. Our researchers completed a randomized, blinded study comparing the pre-test probability of obstructive sleep apnea between an in-person physician and a separate physician seeing the same patient via televideo conferencing. Patients referred to the University of Rochester (UR) Sleep Center were eligible for the study. Women and men 30-70 years old were invited to participate. The patients were not necessarily referred to the center for evaluation of sleep disordered breathing. Patients with dementia, hearing or visual loss, severe psychiatric or developmental illness, or not fluent in English were excluded. Patients had adequate computer literacy, access to high speed internet, and a computing device with appropriate video camera and microphone.The primary objective of the original study was to assess the interrater reliability between the in-person and telemedicine raters for pre-test probability of sleep apnea (high, moderate, or low). Providers used clinical judgement from the history and examination to determine pre-test probabilityFor this present analysis, we assessed the inter-method reliability separately for strata defined by reported annual income level: low income (< $50,000), middle income ($50,000-$100,000), and high income (> $100,000). Reliability was quantified for each stratum using weighted kappa statistics given the ordinal nature of the outcome variable, pre-test probability of obstructive sleep apnea (high, moderate, or low). Weighted kappa statistics were compared between the income strata (high vs. middle, high vs. low, middle vs. low). The operant statistic assumed an approximate standard normal distribution under the null hypothesis of equal kappa values in the two income strata. The Bonferroni method was used to adjust the p-values for the three pairwise comparisons performed among the three income strata. Results: Data from 53 patients were avaiable for this analysis. 11 of these patients were in the low income group, 22 in the middle income, and 16 were in the high income group. 9 patients did not include their income bracket, and were not included in the analysis. Inter-method reliabilities, assessed using weighted kappa, were 0.83 (low income), 0.24 (middle income), and 0.66 (high income). When comparing between the strata, the kappa statistics were significantly different (p=0.005) between the low and moderate income groups. There was a trend between the high and moderate income groups that did not meet statistical significance (p=0.07). Conclusion: The intermethod reliability was substantial in the low income stratum, moderate in the high income stratum, and slight in the middle income group based on the kappa statistic. There was a significant difference in the reliability values of telemedicine versus in-person assessments between the low and middle income brackets, and there was a trend between the high and mo er te groups. Since the raters were unaware of the patients income levels, this association might suggest possible unconscious bias in evaluating for OSA. It may also suggest that beyond access to telemedicine technology, the quality of the care may also be influenced by socioeconomic factors. With telemedicine in its early stages, it is important to develop this technology that will minimize biases that could result from patients economic fortunes.
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Background: Live virus micro-neutralization (MN) is the gold standard for quantifying the neutralizing titer (NT) of antibodies to SARS-CoV-2. However, performing MN is labor intensive and requires a biosafety level 3 laboratory. We assessed the performance of 8 immunoassays which measure SARS-CoV-2 NT and compared them to gold standard MN results. Methods: Samples from 269 individuals known to previously be SARS-CoV-2 PCR+ (i.e., convalescent individuals, <10% hospitalized) and 200 pre-pandemic individuals were evaluated on 3 lateral flow immunoassays (LFAs;Wondfo Colloidal Gold, Wondfo Colored Microsphere, Wondfo Finecare) and 5 enzyme-linked immunoassays (ELISAs;ImmunoRank, GenScript, Cusabio, Euroimmun NeutraLISA, Euroimmun QuantiVac). MN was performed on all samples from convalescent individuals;results were classified as undetectable vs any detection of MN NT (NT<20 vs. NT>20), as well as high and low MN NT (NT>80 vs. NT<80). Receiver operating curve analysis was used to assess accuracy for detecting levels of NT. The area under the curve (AUC) was calculated for the manufacturer's cut off and empirically to identify the best discriminatory cut off value. Cohen's kappa statistics were calculated to assess categorical agreement and Spearman's rank statistics were calculated to assess correlations. Results: Of the 269 convalescent plasma samples, 89 (33%) had MN NT values <20 (undetectable) and 117 (43%) >80 (high NT). Using the manufacturer's cutoffs, sensitivity for detection of samples with any NT ranged from 79% to 100%, and the false-positive rate (ie, classifying samples with undetectable NT as positive) was highest for LFAs (72% to 84%) and ranged from 14% to 69% for the ELISAs. For all assays except the ImmunoRank and NeutraLISA ELISAs, discrimination to identify samples with any NT was improved by raising the cut off values (Table). AUCs of ∼0.94 to discriminate high NT samples could be achieved for all quantifiable assays using an adjusted cut off value. Cohen's kappa statistic ranged from 0.20 to 0.69. Spearman's rank correlation between each assay and NT value ranged from 0.73 to 0.86. Using the manufacturer's cutoffs, specificity on pre-pandemic samples was ≥98% for all assays except for Cusabio which was 86%. Conclusion: The performance of immunoassays using manufacturer's cutoff to discriminate samples with any NT was accurate (AUC>0.83 for all assays), but could be improved by changing the cutoff. Identifying samples with high NT could be achieved using an alternative cutoff.
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BACKGROUND AND AIM: Zinc is a multifunctional trace element. Due to its positive effects on the immune system, the use of zinc supplements has become widespread during the COVID 19 pandemic Both zinc deficiency and excess intake can lead to significant health problems. In this study;we aimed to compare serum and intra-erythrocyte zinc levels to determine most appropriate matrice in requirement and follow-up of zinc replacement. METHODS: Simultaneously measured serum and intra-erythrocyte zinc levels obtained from 285 patients admitted to our laborotory between 2000-2021 were scanned retrospectively. Atomic absorption spectroscopy method had been used for measurements. Quantitative results of the two different matrices were analyzed by simple linear regression analysis. The agreement between the classifications obtained according to the reference interval was evaluated with kappa statistics. RESULTS: A very weak agreement was observed between intra-erythrocyte and serum zinc measurements according to classification agreement (Kappa statistic=0.000;p=0.994). 149 (59.6%) of 250 results in serum were normal, whereas low in intra-erythrocytes. 6 of results were low in intra-erythrocytes, whereas were high in serum and 2 of results were high in intra-erythrocytes whereas were low in serum samples. The relationship between the measurements of the two matrices was not significant in the linear regression analysis (B=0.011;r=0.106;p=0.073). CONCLUSIONS: These findings indicate that serum measurement may be insufficient to detect zinc deficiency. In the light of these findings, it was decided to study both matrices together in terms of functional target and to follow the clinical correlation in the follow-up of zinc replacement therapy in our laboratory.
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INTRODUCTION/HYPOTHESIS: By identifying patients most likely to survive with ventilator support, health systems could improve survival rates among those afflicted and increase ventilator availability for subsequent patients during resource poor pandemic situations. The goal of this study was to prospectively evaluate the utility and discerning power of two different ventilator triage models (Whit & Lo and New York guidelines). METHODS: Prospective observational study of consecutive patients (N=1076) admitted to the Medical Intensive Care Unit during the COVID-19 pandemic from May to August 2020. New York State triage criteria and those proposed by White and Lo were applied. Characteristics and outcomes of those meeting initial criteria for the lowest level of priority for mechanical ventilation (using both criteria) were assessed. Agreement was compared between the 2 sets of triage criteria RESULTS: Among 1076 patients who received mechanical ventilation, the mean (SD) age was 60.5 (15.6) years, 618 (57.4%) were males, 659 (61.5%) were Caucasian, the mean BMI (SD) 30.4 (10.0), 135 (12.5%) had COVID and their SOFA score on admission day was 6.4 (3.0). Comparing the White and Lo triage criteria vs New York guidelines, 159 patients (14.7%) were in the lowest priority category vs 76 patients (7.06%);the mean (SD) age of 63.5 (15.2) years vs 56.2 (15.0) years, 88 (55.3%) vs 42 (55.3%) were males, 104 (65.4%) vs 52 (68.4%) were Caucasian, the mean BMI (SD) 28.8 (7.3) vs30.9 (8.5), 17 (10.7%) vs 4 (5.3%) had COVID, the mean (SD) SOFA score on admission day was 10.2 (2.9) vs 12.9 (1.4), 103 (64.8%) vs 63 (82.9%) patient received MV, the mean (SD) day on MV was 3.7 (5.6) vs 5.5 (6.8), 85 (53.5%) vs 37 (48.7%) survived. Only 63 admissions (5%) were in the lowest priority category for both guidelines, with the κ statistic for agreement equal to 0.40 (95% CI, 0.36-0.45). CONCLUSIONS: Five percent of admissions were identified as having the lowest priority for ventilator allocation using proposed guidelines with moderate agreement. Approximately a third of these patients (low probability) in both triage criteria survived to discharge. Valid and equitable allocation of limited critical resources should be based on sound scrutiny of proposed triage criteria.
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Background: While no single policy is able to bring an end to the present COVID-19 pandemic, diagnostic testing plays an important role in the development and efficacy evaluation of public policy. In this regard, throughout the pandemic, the Food and Drug Administration has approved over 200 diagnostic tests for COVID-19. The natural question then is, which among the many tests should be used, and in what contexts or populations? Answering this requires expedient and complex clinical trials. In evaluating diagnostic test accuracy, key measures such as the sensitivity and specificity of a given test against baseline are often used. However, having several tests with tolerably comparable results is desired. A natural evaluation of the consistency of various substitutable (or competing tests), is how they all perform relative to a baseline, naturally quantified through the inter-rater agreement (IRA). However, a difficulty arises from the multitude of IRA statistics, not well studied in the multiple-raters context. Objectives: To evaluate the use of several key IRA statistics in the context of multiple raters (testing methods) with binary outcomes. Methods: We simulated the responses of several raters from a multi-variate normal distribution with a variable compound correlation matrix (spanning 0 to 1, with a step of 0.001). Responses were then dichotomized at a threshold (0 and 0.5, separately). The two distinct cut-offs provided approximately symmetric and asymmetric binary ratings, respectively. Simulations were done for 2, 3, 4, and 5 raters with 20, 50, 300, and 500 observations. For each number of rater/observations combinations, we estimated the expected value of each IRA statistic (Fleiss' Kappa, Light's Kappa, Conger's Kappa, and Gwet's AC1) for each correlation matrix, and the estimated variance of each statistic. Finally, we fitted linear regressions between each pair of statistics. Results: In the symmetric case, the estimated mean values (over the set of latent correlations) of all four statistics are asymptotically equal. In contrast, in the asymmetric case, only the mean values of the Kappa statistics are asymptotically equal as Gwet's AC1 provides a uniformly higher estimate of IRA. The variance of all four statistics decreases monotonically over each scenario (number of raters and observations). In the symmetric case, Fleiss' Kappa yielded a higher estimated variance than the other three statistics. Of the remaining three statistics, no difference in the estimated variances was appreciated;however, in the asymmetric case, Gwet's AC1 yielded a lower estimated variance than the three Kappa statistics for each scenario. Finally, from the linear regressions between the correlations, we observe a strong bijection between each pair of statistics (p < 10-15);however, the relationships between the Kappa statistics and AC1 had neither a slope of 1 nor an intercept of 0. Discussion: Since population-level prevalence of a set of outcomes may not be known a priori, and in the symmetric case, the four statistics provide similar estimated variances, to address the unknown prevalence, Gwet's AC1 statistic should be used. Moreover, for meaningful head-to-head comparisons between IRA measures (especially with AC1), linear transformations between the measures must be accounted for.
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Introduction: The coexistence of heart failure (HF) and frailty leads to a worse prognosis. Frailty is generally diagnosed using the Fried criteria. To assess whether patients are frail according to the Fried scale, faceto-face physical examinations are required. However, with the COVID-19 pandemic, to avoid the spread of the virus in hospitals, it is important to screen hospitalized patients for frailty without contact. Therefore, noncontact measurement methods, such as questionnaires, should be used to screen for frailty in clinical practice. The FRAIL scale is a questionnaire used to screen for frailty. There are no studies regarding the consistency of the FRAIL scale with the Fried criteria, the impact on mortality, and physical dysfunction in elderly patients with HF. Purpose: We investigated whether the FRAIL scale questionnaire is consistent with the Fried criteria, predicts all-cause mortality, and reflects physical dysfunction in patients with HF. Methods: The present study was secondary analysis of FRAGILE-HF, a cohort study that enrolled participants from 2016 to 2018 and followed up for 1-year of discharge. A prospective multicenter cohort study in which 15 hospitals in Japan (8 university hospitals and 7 non-university teaching hospitals) participated. We prospectively enrolled 1332 consecutive hospitalized patients with HF ≥65 years old and analyzed 1028 patients after excluding 304 patients with missing data on the FRAIL scale. The FRAIL scale, the Fried model, and physical function were measured before discharge. The endpoint was all-cause mortality. Results: According to the FRAIL scale, 459 (44.6%) and 491 (47.8%) were classified as frail and pre-frail, respectively. The Kappa coefficient between the FRAIL scale and the Fried criteria were 0.39 (95% confidence interval [CI]: 0.34-0.44;P value: <0.001). The area under the receiver-operating characteristic curves for frailty diagnosed by the Fried criteria of the FRAIL scale was 0.74 (95% CI: 0.71-0.76;P value: <0.001). A total of 118 deaths occurred during 1 year of follow-up. After adjusting for the MAGGIC score and log-BNP, The FRAIL scale predicted all-cause mortality (hazard ratio: 1.17;95% CI: 1.01-1.36;P value = 0.035). The FRAIL scale was also associated with various physical dysfunction that correlated with poor prognosis. Conclusions: The FRAIL scale had moderate consistency with the Fried criteria, predicted all-cause mortality, and reflected clinically important physical dysfunction.
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Background: The COVID-19 pandemic has spread globally, infecting and killing millions. Those subjects with cardiovascular disease (CVD) are at higher risk of severe COVID-19 morbidity and mortality following SARSCoV- 2 infection. Purpose: To investigate the response to different treatments against COVID-19 in patients with a pre-existing CVD. Methods: We conducted a systematic review and meta-analysis following Cochrane, PRISMA and MOOSE guidelines (PROSPERO ref:CRD42020183057). Eligible articles reported in-hospital mortality rate in COVID-19 patients with CVD after testing specific treatments. Statistical concordance was performed by Cohen's kappa coefficient. The primary outcome was in-hospital mortality rate, secondary outcome was the length of hospital stay (LOS). The analysis utilised a random-effects model. Categorical variables were expressed as risk ratio (RR) and continuous variable with weighted mean difference (WMD) and standard deviation with 95% confidence interval (CI). I2 and Chi-tests were used to assess studies' heterogeneity. Publication bias was visualised by L'Abbe' plot and funnel plot with Egger's test. Subgroup analysis (pooling analysis) was also performed to compare the three groups' mortality differences: 'CVD treated' vs.'CVD untreated' vs.'no-CVD (treated and untreated)'. Meta-regression models were used to determine the effects of specific treatments and risk factors on the primary outcomes. R-studio used for analysis. Results: Of 1,673 articles retrieved, 46 studies included CVD patients from which 11 included control group, finally five were comparative studies and were included in the quantitative analysis. From those studies, the sample size was 130 (mean age 63.9±2.7 years;55.3% male). There was 100% concordance between reviewers equating to a Cohen's kappa coefficient of κ=1. The most frequent CV risk factor (CVRF) was hypertension (60%) followed by diabetes (28.5%). The most frequent CVD seen in patients was coronary artery disease at 9.09% and peripheral arterial disease at 5.4%. Mortality rate was significant higher in the CVD treated group (RR:1.52;95% CI [1.05,2.21], CVD treated vs overall population p=0.03). Meta-regression showed that no treatment was significant associated to mortality and systemic hypertension, but an independent risk factor for mortality. Pooled single analysis showed no difference between treated vs untreated CVD patients. There was certain degree of heterogeneity (I2 50%) across the studies. L'Abbe and funnel plot visualized not significant dispersion (Egger test, p=0.71). There was no difference in terms of LOS [0,79, 95% CI (-0.48, 2,05);p-value 0.22]. Conclusions: This quantitative analysis showed that CVD patients despite specific treatments were exposed to significant higher mortality when compared to the overall population. These results remark the clinical relevance to reduce CVD risk factors and ameliorate specific COVID-19 treatments to lower the risk of mortality in this group.