Accuracy of Computable Phenotyping Approaches for SARS-CoV-2 Infection and COVID-19 Hospitalizations from the Electronic Health Record

ObjectiveReal-world data have been critical for rapid-knowledge generation throughout the COVID-19 pandemic. To ensure high-quality results are delivered to guide clinical decision making and the public health response, as well as characterize the response to interventions, it is essential to establish the accuracy of COVID-19 case definitions derived from administrative data to identify infections and hospitalizations. MethodsElectronic Health Record (EHR) data were obtained from the clinical data warehouse of the Yale New Haven Health System (Yale, primary site) and 3 hospital systems of the Mayo Clinic (validation site). Detailed characteristics on demographics, diagnoses, and laboratory results were obtained for all patients with either a positive SARS-CoV-2 PCR or antigen test or ICD-10 diagnosis of COVID-19 (U07.1) between April 1, 2020 and March 1, 2021. Various computable phenotype definitions were evaluated for their accuracy to identify SARS-CoV-2 infection and COVID-19 hospitalizations. ResultsOf the 69,423 individuals with either a diagnosis code or a laboratory diagnosis of a SARS-CoV-2 infection at Yale, 61,023 had a principal or a secondary diagnosis code for COVID-19 and 50,355 had a positive SARS-CoV-2 test. Among those with a positive laboratory test, 38,506 (76.5%) and 3449 (6.8%) had a principal and secondary diagnosis code of COVID-19, respectively, while 8400 (16.7%) had no COVID-19 diagnosis. Moreover, of the 61,023 patients with a COVID-19 diagnosis code, 19,068 (31.2%) did not have a positive laboratory test for SARS-CoV-2 in the EHR. Of the 20 cases randomly sampled from this latter group for manual review, all had a COVID-19 diagnosis code related to asymptomatic testing with negative subsequent test results. The positive predictive value (precision) and sensitivity (recall) of a COVID-19 diagnosis in the medical record for a documented positive SARS-CoV-2 test were 68.8% and 83.3%, respectively. Among 5,109 patients who were hospitalized with a principal diagnosis of COVID-19, 4843 (94.8%) had a positive SARS-CoV-2 test within the 2 weeks preceding hospital admission or during hospitalization. In addition, 789 hospitalizations had a secondary diagnosis of COVID-19, of which 446 (56.5%) had a principal diagnosis consistent with severe clinical manifestation of COVID-19 (e.g., sepsis or respiratory failure). Compared with the cohort that had a principal diagnosis of COVID-19, those with a secondary diagnosis had a more than 2-fold higher in-hospital mortality rate (13.2% vs 28.0%, P<0.001). In the validation sample at Mayo Clinic, diagnosis codes more consistently identified SARS-CoV-2 infection (precision of 95%) but had lower recall (63.5%) with substantial variation across the 3 Mayo Clinic sites. Similar to Yale, diagnosis codes consistently identified COVID-19 hospitalizations at Mayo, with hospitalizations defined by secondary diagnosis code with 2-fold higher in-hospital mortality compared to those with a primary diagnosis of COVID-19. ConclusionsCOVID-19 diagnosis codes misclassified the SARS-CoV-2 infection status of many people, with implications for clinical research and epidemiological surveillance. Moreover, the codes had different performance across two academic health systems and identified groups with different risks of mortality. Real-world data from the EHR can be used to in conjunction with diagnosis codes to improve the identification of people infected with SARS-CoV-2.

Increased risk of lung cancer in patients with eczema: a nationwide cohort study in Taiwan.

BACKGROUND: The association between lung cancer and eczema remains controversial. Previous studies have yielded conflicting results. This retrospective population-based cohort study is aimed at clarifying the risk of lung cancer associated with eczema. PATIENTS AND METHODS: By using the Taiwan National Health Insurance Research Database, we identified 43,719 patients who had been newly diagnosed with eczema in the years 2000 to 2010. The comparison cohort included 87,438 randomly selected, age-matched patients without eczema. The cases of these two cohorts were followed until 2011. The Cox proportional hazard regression model was used to calculate the risk of lung cancer in eczema patients. The database did not contain any information regarding smoking, alcohol consumption, socioeconomic status, or family history. RESULTS: After adjusting for age and comorbidity, the population with eczema had a 2.80-fold greater risk of developing lung cancer compared with the population in the comparison cohort (adjusted hazard ratio 2.80, 95 % confidence interval 2.59-3.03). Eczema patients with comorbid diseases including asthma, chronic obstructive -pulmonary disease, alcoholic liver damage, or diabetes were at a higher risk of lung cancer compared with the non-eczema patients without comorbidity. CONCLUSIONS: Eczema is associated with a greater risk for the development of lung cancer. Further studies with more comprehensive information on potential confounders are warranted.

Erhöhtes Lungenkrebs-Risiko bei Ekzempatienten: eine landesweite Kohortenstudie in Taiwan.

HINTERGRUND: Der Zusammenhang zwischen Lungenkrebs und Ekzemen bleibt umstritten. Frühere Studien haben zu widersprüchlichen Ergebnissen geführt. Diese retrospektive populationsbasierte Kohortenstudie zielt darauf ab, das Risiko von Lungenkrebs im Zusammenhang mit Ekzemen abzuklären. PATIENTEN UND METHODEN: In der Forschungsdatenbank der taiwanesischen nationalen Krankenversicherung identifizierten wir 43719 Patienten, bei denen in den Jahren 2000 bis 2010 ein Ekzem neu diagnostiziert wurde. Die Vergleichskohorte bildeten 87438 zufällig ausgewählte, altersangepasste Patienten ohne Ekzem. Die Fälle aus diesen beiden Kohorten wurden bis 2011 verfolgt. Zur Kalkulation des Lungenkrebsrisikos bei Ekzempatienten wurde die Cox-Regression verwendet. Die Datenbank enthielt keine Informationen über Raucherstatus, Alkoholkonsum, sozioökonomischen Status oder Familienanamnese. ERGEBNISSE: Nach der Bereinigung um Alter und Komorbidität hatte die Population mit Ekzemen ein um 2,80 erhöhtes Risiko für die Entwicklung von Lungenkrebs gegenüber der Vergleichskohorte (bereinigte Hazard-Ratio 2,80, 95 % Konfidenzinterval 2,59-3,03). Ekzempatienten mit Begleiterkrankungen, darunter Asthma, chronisch obstruktive Lungenerkrankungen, alkoholbedingten Leberschäden oder Diabetes, hatten ein höheres Lungenkrebsrisiko als Patienten ohne Ekzeme oder Komorbidität. SCHLUSSFOLGERUNGEN: Ekzeme gehen mit einem höheren Risiko für die Entwicklung von Lungenkrebs einher. Weitere Studien mit umfassenderen Informationen über weitere potentielle Einflussfaktoren sind sinnvoll.

Electrochemical detection of oligonucleotide by attaching redox probes onto its backbone.

An approach was demonstrated to detect oligonucleotide by attaching redox probes onto its backbone. First, peptide nucleic acid (PNA) with a neutral backbone was immobilized onto a gold (Au) electrode surface as a capture. Second, when the PNA capture hybridized with a target oligonucleotide (a short DNA), an assembly of Au-PNA-DNA formed and phosphate groups were thus brought into the assembly from the DNA's backbone. The linker ion of Zr(4+) exhibits a strong coordination interaction with the phosphate group and the carboxylic group. The hybridized target DNA provides the phosphate group while a derivatized redox probe of ferrocene (Fc) carboxyl acid offers the carboxylic group. Therefore, the redox probe can be attached to the phosphate group by the linker to form an assembly of Au-PNA-DNA-Zr-Fc. Its redox process was studied and the detection conditions of oligonucleotide were optimized. A limit of detection of 1.0×10(-12) M or ∼2 attomol was reached.