ABSTRACT
BackgroundUpdatable understanding of the onset and progression of individuals COVID-19 trajectories underpins pandemic mitigation efforts. In order to identify and characterize individual trajectories, we defined and validated ten COVID-19 phenotypes from linked electronic health records (EHR) on a nationwide scale using an extensible framework. MethodsCohort study of 56.6 million people in England alive on 23/01/2020, followed until 31/05/2021, using eight linked national datasets spanning COVID-19 testing, vaccination, primary & secondary care and death registrations data. We defined ten COVID-19 phenotypes reflecting clinically relevant stages of disease severity using a combination of international clinical terminologies (e.g. SNOMED-CT, ICD-10) and bespoke data fields; positive test, primary care diagnosis, hospitalisation, critical care (four phenotypes), and death (three phenotypes). Using these phenotypes, we constructed patient trajectories illustrating the transition frequency and duration between phenotypes. Analyses were stratified by pandemic waves and vaccination status. FindingsWe identified 3,469,528 infected individuals (6.1%) with 8,825,738 recorded COVID-19 phenotypes. Of these, 364,260 (11%) were hospitalised and 140,908 (4%) died. Of those hospitalised, 38,072 (10%) were admitted to intensive care (ICU), 54,026 (15%) received non-invasive ventilation and 21,404 (6%) invasive ventilation. Amongst hospitalised patients, first wave mortality (30%) was higher than the second (23%) in non-ICU settings, but remained unchanged for ICU patients. The highest mortality was for patients receiving critical care outside of ICU in wave 1 (51%). 13,083 (9%) COVID-19 related deaths occurred without diagnoses on the death certificate, but within 30 days of a positive test while 10,403 (7%) of cases were identified from mortality data alone with no prior phenotypes recorded. We observed longer patient trajectories in the second pandemic wave compared to the first. InterpretationOur analyses illustrate the wide spectrum of severity that COVID-19 displays and significant differences in incidence, survival and pathways across pandemic waves. We provide an adaptable framework to answer questions of clinical and policy relevance; new variant impact, booster dose efficacy and a way of maximising existing data to understand individuals progression through disease states. Research in ContextO_ST_ABSEvidence before the studyC_ST_ABSWe searched PubMed on October 14, 2021, for publications with the terms "COVID-19" or "SARS-CoV-2", "severity", and "electronic health records" or "EHR" without date or language restrictions. Multiple studies explore factors associated with severity of COVID-19 infection, and model predictions of outcome for hospitalised patients. However, most work to date focused on isolated facets of the healthcare system, such as primary or secondary care only, was conducted in subpopulations (e.g. hospitalised patients) of limited sample size, and often utilized dichotomised outcomes (e.g. mortality or hospitalisation) ignoring the full spectrum of disease. We identified no studies which comprehensively detailed severity of infections while describing disease severity across pandemic waves, vaccination status, and patient trajectories. Added value of this studyTo our knowledge, this is the first study providing a comprehensive view of COVID-19 across pandemic waves using national data and focusing on severity, vaccination, and patient trajectories. Drawing on linked electronic health record (EHR) data on a national scale (56.6 million people alive and registered with GP in England), we describe key demographic factors, frequency of comorbidities, impact of the two main waves in England, and effect of full vaccination on COVID-19 severities. Additionally, we identify and describe patient trajectory networks which illustrate the main transition pathways of COVID-19 patients in the healthcare system. Finally, we provide reproducible COVID-19 phenotyping algorithms reflecting clinically relevant stages of disease severity i.e. positive tests, primary care diagnoses, hospitalisation, critical care treatments (e.g. ventilatory support) and mortality. Implications of all the available evidenceThe COVID-19 phenotypes and trajectory analysis framework outlined produce a reproducible, extensible and repurposable means to generate national-scale data to support critical policy decision making. By modelling patient trajectories as a series of interactions with healthcare systems, and linking these to demographic and outcome data, we provide a means to identify and prioritise care pathways associated with adverse outcomes and highlight healthcare system touch points which may act as tangible targets for intervention.
ABSTRACT
Objective To study the rule of lower-cervical lymphatic metastasis in thoracic esophageal carcinoma,and make evaluation about the reasonable extent of lymphadenectomy. Methods One hundred and eight cases of thoracic esophageal carcinoma through chromatic ultrasound and CT before operation were divided into different groups selectively,while three fields lymphadenectomy (3-FL) was adopted in 31 cases,and two fields lymphadenctomy (2-FL) was adopted in 77 cases. Results The rate of lower-cervical lymphatic metastasis was 87.1%(27/31) through chromatic ultrasound and CT,and that was 25.0%(27/108) before the two up-mentioned examinations (P<0.05). In all cases, the rate of lower-cervical lymphatic metastasis in the upper pectoral esophageal carcinoma was 47.6% (10/21),that in the middle pectoral esophageal carcinoma was 21.3%(13161),and that in the middle and lower pectoral esophageal carcinoma was 19.5%(17187) ,P<0.05. Through 3-FL, the rate of lower--cervical lymphatic metastasis in the upper pectoral esophageal eareinoma was 57.1%(12/21), that in the middle pectoral esophageal carcinoma was 23.0%(14/61), and that in the middle and lower pectoral esophageal carcinoma was 21.8%(19/87), P<0.05. Conclusions The regionality metastasis is the main fashion in thoracic esophageal carcinoma with lower-cervical lymphatic metastasis. It is feasible to judge lower-cervical lymphatic metastasis through chromatic ultrasound and CT before operation.The 3-FL of the upper pectoral esophageal carcinoma is recommended. The 3-FL is selectable in the middle and lower pectoral esophageal carcinoma according to the result of chromatic ultrasound and CT.
