Characteristics and outcomes of COVID-19 patients admitted to hospital with and without respiratory symptoms.

Background: COVID-19 is primarily known as a respiratory illness; however, many patients present to hospital without respiratory symptoms. The association between non-respiratory presentations of COVID-19 and outcomes remains unclear. We investigated risk factors and clinical outcomes in patients with no respiratory symptoms (NRS) and respiratory symptoms (RS) at hospital admission. Methods: This study describes clinical features, physiological parameters, and outcomes of hospitalised COVID-19 patients, stratified by the presence or absence of respiratory symptoms at hospital admission. RS patients had one or more of: cough, shortness of breath, sore throat, runny nose or wheezing; while NRS patients did not. Results: Of 178,640 patients in the study, 86.4 % presented with RS, while 13.6 % had NRS. NRS patients were older (median age: NRS: 74 vs RS: 65) and less likely to be admitted to the ICU (NRS: 36.7 % vs RS: 37.5 %). NRS patients had a higher crude in-hospital case-fatality ratio (NRS 41.1 % vs. RS 32.0 %), but a lower risk of death after adjusting for confounders (HR 0.88 [0.83-0.93]). Conclusion: Approximately one in seven COVID-19 patients presented at hospital admission without respiratory symptoms. These patients were older, had lower ICU admission rates, and had a lower risk of in-hospital mortality after adjusting for confounders.

The burden and dynamics of hospital-acquired SARS-CoV-2 in England.

Hospital-based transmission had a dominant role in Middle East respiratory syndrome coronavirus (MERS-CoV) and severe acute respiratory syndrome coronavirus (SARS-CoV) epidemics1,2, but large-scale studies of its role in the SARS-CoV-2 pandemic are lacking. Such transmission risks spreading the virus to the most vulnerable individuals and can have wider-scale impacts through hospital-community interactions. Using data from acute hospitals in England, we quantify within-hospital transmission, evaluate likely pathways of spread and factors associated with heightened transmission risk, and explore the wider dynamical consequences. We estimate that between June 2020 and March 2021 between 95,000 and 167,000 inpatients acquired SARS-CoV-2 in hospitals (1% to 2% of all hospital admissions in this period). Analysis of time series data provided evidence that patients who themselves acquired SARS-CoV-2 infection in hospital were the main sources of transmission to other patients. Increased transmission to inpatients was associated with hospitals having fewer single rooms and lower heated volume per bed. Moreover, we show that reducing hospital transmission could substantially enhance the efficiency of punctuated lockdown measures in suppressing community transmission. These findings reveal the previously unrecognized scale of hospital transmission, have direct implications for targeting of hospital control measures and highlight the need to design hospitals better equipped to limit the transmission of future high-consequence pathogens.

Characteristics and outcomes of an international cohort of 600 000 hospitalized patients with COVID-19.

BACKGROUND: We describe demographic features, treatments and clinical outcomes in the International Severe Acute Respiratory and emerging Infection Consortium (ISARIC) COVID-19 cohort, one of the world's largest international, standardized data sets concerning hospitalized patients. METHODS: The data set analysed includes COVID-19 patients hospitalized between January 2020 and January 2022 in 52 countries. We investigated how symptoms on admission, co-morbidities, risk factors and treatments varied by age, sex and other characteristics. We used Cox regression models to investigate associations between demographics, symptoms, co-morbidities and other factors with risk of death, admission to an intensive care unit (ICU) and invasive mechanical ventilation (IMV). RESULTS: Data were available for 689 572 patients with laboratory-confirmed (91.1%) or clinically diagnosed (8.9%) SARS-CoV-2 infection from 52 countries. Age [adjusted hazard ratio per 10 years 1.49 (95% CI 1.48, 1.49)] and male sex [1.23 (1.21, 1.24)] were associated with a higher risk of death. Rates of admission to an ICU and use of IMV increased with age up to age 60 years then dropped. Symptoms, co-morbidities and treatments varied by age and had varied associations with clinical outcomes. The case-fatality ratio varied by country partly due to differences in the clinical characteristics of recruited patients and was on average 21.5%. CONCLUSIONS: Age was the strongest determinant of risk of death, with a ∼30-fold difference between the oldest and youngest groups; each of the co-morbidities included was associated with up to an almost 2-fold increase in risk. Smoking and obesity were also associated with a higher risk of death. The size of our international database and the standardized data collection method make this study a comprehensive international description of COVID-19 clinical features. Our findings may inform strategies that involve prioritization of patients hospitalized with COVID-19 who have a higher risk of death.

Symptom-based case definitions for COVID-19: Time and geographical variations for detection at hospital admission among 260,000 patients.

Introduction: Case definitions are used to guide clinical practice, surveillance and research protocols. However, how they identify COVID-19-hospitalised patients is not fully understood. We analysed the proportion of hospitalised patients with laboratory-confirmed COVID-19, in the ISARIC prospective cohort study database, meeting widely used case definitions. Methods: Patients were assessed using the Centers for Disease Control (CDC), European Centre for Disease Prevention and Control (ECDC), World Health Organization (WHO) and UK Health Security Agency (UKHSA) case definitions by age, region and time. Case fatality ratios (CFRs) and symptoms of those who did and who did not meet the case definitions were evaluated. Patients with incomplete data and non-laboratory-confirmed test result were excluded. Results: A total of 263,218 of the patients (42%) in the ISARIC database were included. Most patients (90.4%) were from Europe and Central Asia. The proportions of patients meeting the case definitions were 56.8% (WHO), 74.4% (UKHSA), 81.6% (ECDC) and 82.3% (CDC). For each case definition, patients at the extremes of age distribution met the criteria less frequently than those aged 30 to 70 years; geographical and time variations were also observed. Estimated CFRs were similar for the patients who met the case definitions. However, when more patients did not meet the case definition, the CFR increased. Conclusions: The performance of case definitions might be different in different regions and may change over time. Similarly concerning is the fact that older patients often did not meet case definitions, risking delayed medical care. While epidemiologists must balance their analytics with field applicability, ongoing revision of case definitions is necessary to improve patient care through early diagnosis and limit potential nosocomial spread.

Prospective validation of the 4C prognostic models for adults hospitalised with COVID-19 using the ISARIC WHO Clinical Characterisation Protocol.

PURPOSE: To prospectively validate two risk scores to predict mortality (4C Mortality) and in-hospital deterioration (4C Deterioration) among adults hospitalised with COVID-19. METHODS: Prospective observational cohort study of adults (age ≥18 years) with confirmed or highly suspected COVID-19 recruited into the International Severe Acute Respiratory and emerging Infections Consortium (ISARIC) WHO Clinical Characterisation Protocol UK (CCP-UK) study in 306 hospitals across England, Scotland and Wales. Patients were recruited between 27 August 2020 and 17 February 2021, with at least 4 weeks follow-up before final data extraction. The main outcome measures were discrimination and calibration of models for in-hospital deterioration (defined as any requirement of ventilatory support or critical care, or death) and mortality, incorporating predefined subgroups. RESULTS: 76 588 participants were included, of whom 27 352 (37.4%) deteriorated and 12 581 (17.4%) died. Both the 4C Mortality (0.78 (0.77 to 0.78)) and 4C Deterioration scores (pooled C-statistic 0.76 (95% CI 0.75 to 0.77)) demonstrated consistent discrimination across all nine National Health Service regions, with similar performance metrics to the original validation cohorts. Calibration remained stable (4C Mortality: pooled slope 1.09, pooled calibration-in-the-large 0.12; 4C Deterioration: 1.00, -0.04), with no need for temporal recalibration during the second UK pandemic wave of hospital admissions. CONCLUSION: Both 4C risk stratification models demonstrate consistent performance to predict clinical deterioration and mortality in a large prospective second wave validation cohort of UK patients. Despite recent advances in the treatment and management of adults hospitalised with COVID-19, both scores can continue to inform clinical decision making. TRIAL REGISTRATION NUMBER: ISRCTN66726260.

Evaluating clinical characteristics studies produced early in the Covid-19 pandemic: A systematic review.

OBJECTIVES: Clinical characterisation studies have been essential in helping inform research, diagnosis and clinical management efforts, particularly early in a pandemic. This systematic review summarises the early literature on clinical characteristics of patients admitted to hospital, and evaluates the quality of evidence produced during the initial stages of the pandemic. METHODS: MEDLINE, EMBASE and Global Health databases were searched for studies published from January 1st 2020 to April 28th 2020. Studies which reported on at least 100 hospitalised patients with Covid-19 of any age were included. Data on clinical characteristics were independently extracted by two review authors. Study design specific critical appraisal tools were used to evaluate included studies: the Newcastle Ottawa scale for cohort and cross sectional studies, Joanna Briggs Institute checklist for case series and the Cochrane collaboration tool for assessing risk of bias in randomised trials. RESULTS: The search yielded 78 studies presenting data on 77,443 people. Most studies (82%) were conducted in China. No studies included patients from low- and middle-income countries. The overall quality of included studies was low to moderate, and the majority of studies did not include a control group. Fever and cough were the most commonly reported symptoms early in the pandemic. Laboratory and imaging findings were diverse with lymphocytopenia and ground glass opacities the most common findings respectively. Clinical data in children and vulnerable populations were limited. CONCLUSIONS: The early Covid-19 literature had moderate to high risk of bias and presented several methodological issues. Early clinical characterisation studies should aim to include different at-risk populations, including patients in non-hospital settings. Pandemic preparedness requires collection tools to ensure observational studies are methodologically robust and will help produce high-quality data early on in the pandemic to guide clinical practice and public health policy. REVIEW REGISTRATION: Available at https://osf.io/mpafn.

Development and validation of the ISARIC 4C Deterioration model for adults hospitalised with COVID-19: a prospective cohort study.

BACKGROUND: Prognostic models to predict the risk of clinical deterioration in acute COVID-19 cases are urgently required to inform clinical management decisions. METHODS: We developed and validated a multivariable logistic regression model for in-hospital clinical deterioration (defined as any requirement of ventilatory support or critical care, or death) among consecutively hospitalised adults with highly suspected or confirmed COVID-19 who were prospectively recruited to the International Severe Acute Respiratory and Emerging Infections Consortium Coronavirus Clinical Characterisation Consortium (ISARIC4C) study across 260 hospitals in England, Scotland, and Wales. Candidate predictors that were specified a priori were considered for inclusion in the model on the basis of previous prognostic scores and emerging literature describing routinely measured biomarkers associated with COVID-19 prognosis. We used internal-external cross-validation to evaluate discrimination, calibration, and clinical utility across eight National Health Service (NHS) regions in the development cohort. We further validated the final model in held-out data from an additional NHS region (London). FINDINGS: 74 944 participants (recruited between Feb 6 and Aug 26, 2020) were included, of whom 31 924 (43·2%) of 73 948 with available outcomes met the composite clinical deterioration outcome. In internal-external cross-validation in the development cohort of 66 705 participants, the selected model (comprising 11 predictors routinely measured at the point of hospital admission) showed consistent discrimination, calibration, and clinical utility across all eight NHS regions. In held-out data from London (n=8239), the model showed a similarly consistent performance (C-statistic 0·77 [95% CI 0·76 to 0·78]; calibration-in-the-large 0·00 [-0·05 to 0·05]); calibration slope 0·96 [0·91 to 1·01]), and greater net benefit than any other reproducible prognostic model. INTERPRETATION: The 4C Deterioration model has strong potential for clinical utility and generalisability to predict clinical deterioration and inform decision making among adults hospitalised with COVID-19. FUNDING: National Institute for Health Research (NIHR), UK Medical Research Council, Wellcome Trust, Department for International Development, Bill & Melinda Gates Foundation, EU Platform for European Preparedness Against (Re-)emerging Epidemics, NIHR Health Protection Research Unit (HPRU) in Emerging and Zoonotic Infections at University of Liverpool, NIHR HPRU in Respiratory Infections at Imperial College London.

Stop COVID Cohort: An Observational Study of 3480 Patients Admitted to the Sechenov University Hospital Network in Moscow City for Suspected Coronavirus Disease 2019 (COVID-19) Infection.

BACKGROUND: The epidemiology, clinical course, and outcomes of patients with coronavirus disease 2019 (COVID-19) in the Russian population are unknown. Information on the differences between laboratory-confirmed and clinically diagnosed COVID-19 in real-life settings is lacking. METHODS: We extracted data from the medical records of adult patients who were consecutively admitted for suspected COVID-19 infection in Moscow between 8 April and 28 May 2020. RESULTS: Of the 4261 patients hospitalized for suspected COVID-19, outcomes were available for 3480 patients (median age, 56 years; interquartile range, 45-66). The most common comorbidities were hypertension, obesity, chronic cardiovascular disease, and diabetes. Half of the patients (n = 1728) had a positive reverse transcriptase-polymerase chain reaction (RT-PCR), while 1748 had a negative RT-PCR but had clinical symptoms and characteristic computed tomography signs suggestive of COVID-19. No significant differences in frequency of symptoms, laboratory test results, and risk factors for in-hospital mortality were found between those exclusively clinically diagnosed or with positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RT-PCR. In a multivariable logistic regression model the following were associated with in-hospital mortality: older age (per 1-year increase; odds ratio, 1.05; 95% confidence interval, 1.03-1.06), male sex (1.71; 1.24-2.37), chronic kidney disease (2.99; 1.89-4.64), diabetes (2.1; 1.46-2.99), chronic cardiovascular disease (1.78; 1.24-2.57), and dementia (2.73; 1.34-5.47). CONCLUSIONS: Age, male sex, and chronic comorbidities were risk factors for in-hospital mortality. The combination of clinical features was sufficient to diagnose COVID-19 infection, indicating that laboratory testing is not critical in real-life clinical practice.

Risk stratification of patients admitted to hospital with covid-19 using the ISARIC WHO Clinical Characterisation Protocol: development and validation of the 4C Mortality Score.

OBJECTIVE: To develop and validate a pragmatic risk score to predict mortality in patients admitted to hospital with coronavirus disease 2019 (covid-19). DESIGN: Prospective observational cohort study. SETTING: International Severe Acute Respiratory and emerging Infections Consortium (ISARIC) World Health Organization (WHO) Clinical Characterisation Protocol UK (CCP-UK) study (performed by the ISARIC Coronavirus Clinical Characterisation Consortium-ISARIC-4C) in 260 hospitals across England, Scotland, and Wales. Model training was performed on a cohort of patients recruited between 6 February and 20 May 2020, with validation conducted on a second cohort of patients recruited after model development between 21 May and 29 June 2020. PARTICIPANTS: Adults (age ≥18 years) admitted to hospital with covid-19 at least four weeks before final data extraction. MAIN OUTCOME MEASURE: In-hospital mortality. RESULTS: 35 463 patients were included in the derivation dataset (mortality rate 32.2%) and 22 361 in the validation dataset (mortality rate 30.1%). The final 4C Mortality Score included eight variables readily available at initial hospital assessment: age, sex, number of comorbidities, respiratory rate, peripheral oxygen saturation, level of consciousness, urea level, and C reactive protein (score range 0-21 points). The 4C Score showed high discrimination for mortality (derivation cohort: area under the receiver operating characteristic curve 0.79, 95% confidence interval 0.78 to 0.79; validation cohort: 0.77, 0.76 to 0.77) with excellent calibration (validation: calibration-in-the-large=0, slope=1.0). Patients with a score of at least 15 (n=4158, 19%) had a 62% mortality (positive predictive value 62%) compared with 1% mortality for those with a score of 3 or less (n=1650, 7%; negative predictive value 99%). Discriminatory performance was higher than 15 pre-existing risk stratification scores (area under the receiver operating characteristic curve range 0.61-0.76), with scores developed in other covid-19 cohorts often performing poorly (range 0.63-0.73). CONCLUSIONS: An easy-to-use risk stratification score has been developed and validated based on commonly available parameters at hospital presentation. The 4C Mortality Score outperformed existing scores, showed utility to directly inform clinical decision making, and can be used to stratify patients admitted to hospital with covid-19 into different management groups. The score should be further validated to determine its applicability in other populations. STUDY REGISTRATION: ISRCTN66726260.

Enhanced recovery following hip and knee arthroplasty: a systematic review of cost-effectiveness evidence.

OBJECTIVES: To assess cost-effectiveness of enhanced recovery pathways following total hip and knee arthroplasties. Secondary objectives were to report on quality of studies and identify research gaps for future work. DESIGN: Systematic review of cost-utility analyses. DATA SOURCES: Ovid MEDLINE, Embase, the National Health Service Economic Evaluations Database and EconLit, January 2000 to August 2019. ELIGIBILITY CRITERIA: English-language peer-reviewed cost-utility analyses of enhanced recovery pathways, or components of one, compared with usual care, in patients having total hip or knee arthroplasties for osteoarthritis. DATA EXTRACTION AND SYNTHESIS: Data extracted by three reviewers with disagreements resolved by a fourth. Study quality assessed using the Consensus on Health Economic Criteria list, the International Society for Pharmacoeconomics and Outcomes Research and Assessment of the Validation Status of Health-Economic decision models tools; for trial-based studies the Cochrane Collaboration's tool to assess risk of bias. No quantitative synthesis was undertaken. RESULTS: We identified 17 studies: five trial-based and 12 model-based studies. Two analyses evaluated entire enhanced recovery pathways and reported them to be cost-effective compared with usual care. Ten pathway components were more effective and cost-saving compared with usual care, three were cost-effective, and two were not cost-effective. We had concerns around risk of bias for all included studies, particularly regarding the short time horizon of the trials and lack of reporting of model validation. CONCLUSIONS: Consistent results supported enhanced recovery pathways as a whole, prophylactic systemic antibiotics, antibiotic-impregnated cement and conventional ventilation for infection prevention. No other interventions were subject of more than one study. We found ample scope for future cost-effectiveness studies, particularly analyses of entire recovery pathways and comparison of incremental changes within pathways. A key limitation is that standard practices have changed over the period covered by the included studies. PROSPERO REGISTRATION NUMBER: CRD42017059473.

Relationship of anxiety with joint pain and its management: A population survey.

OBJECTIVES: The aims of the present study was to examine the associations between the severity of pain and anxiety in a community population reporting joint pain, and to investigate the management of joint pain in the presence of comorbid anxiety. METHODS: A population survey was carried out of people aged ≥45 years, registered with eight general practices in Cheshire, Shropshire and Staffordshire, UK. Respondents were asked to report pain intensity in their hands, hips, knees and feet (on a numerical rating scale), anxiety symptoms (Generalized Anxiety Disorder seven-item [GAD-7] scale) and guideline-recommended treatments used to manage pain. Clinical anxiety was defined by a GAD-7 score of 10 or more. RESULTS: A total of 11,222 respondents with joint pain were included in the analysis, with 1,802 (16.1%) reporting clinical anxiety. Respondents reporting more severe pain were more likely to report clinical anxiety (severe versus mild pain, odds ratio [OR] 5.36, 95% confidence interval [CI] 4.56 to 6.31). The number of pain sites was also positively associated with clinical anxiety (four versus one site; OR 3.64, 95% CI 3.09 to 4.30). Those with clinical anxiety were less likely to undertake general fitness exercises (OR 0.60, 95% CI 0.52 to 0.70), but more likely to diet (OR 1.43, 95% CI 1.21 to 1.69), use walking aids (OR 1.53, 95% CI 1.32 to 1.77) and assistive devices (OR 1.24, 95% CI 1.04 to 1.49), and more likely to use opioids (OR 1.34, 95% CI 1.18 to1.52). CONCLUSIONS: Anxiety is common among patients presenting to primary care with joint pain. Patients with anxiety are likely to manage their joint pain differently to those without. Case-finding to identify and treat anxiety would be appropriate in this population, with caution about opioid prescribing and consideration of exercise as an intervention.

Cost-effectiveness of enhanced recovery in hip and knee replacement: a systematic review protocol.

INTRODUCTION: Hip and knee replacement represents a significant burden to the UK healthcare system. 'Enhanced recovery' pathways have been introduced in the National Health Service (NHS) for patients undergoing hip and knee replacement, with the aim of improving outcomes and timely recovery after surgery. To support policymaking, there is a need to evaluate the cost-effectiveness of enhanced recovery pathways across jurisdictions. Our aim is to systematically summarise the published cost-effectiveness evidence on enhanced recovery in hip and knee replacement, both as a whole and for each of the various components of enhanced recovery pathways. METHODS AND ANALYSIS: A systematic review will be conducted using MEDLINE, EMBASE, Econlit and the National Health Service Economic Evaluations Database. Separate search strategies were developed for each database including terms relating to hip and knee replacement/arthroplasty, economic evaluations, decision modelling and quality of life measures.We will extract peer-reviewed studies published between 2000 and 2017 reporting economic evaluations of preoperative, perioperative or postoperative enhanced recovery interventions within hip or knee replacement. Economic evaluations alongside cohort studies or based on decision models will be included. Only studies with patients undergoing elective replacement surgery of the hip or knee will be included. Data will be extracted using a predefined pro forma following best practice guidelines for economic evaluation, decision modelling and model validation.Our primary outcome will be the cost-effectiveness of enhanced recovery (entire pathway and individual components) in terms of incremental cost per quality-adjusted life year. A narrative synthesis of all studies will be presented, focussing on cost-effectiveness results, study design, quality and validation status. ETHICS AND DISSEMINATION: This systematic review is exempted from ethics approval because the work is carried out on published documents. The results of the review will be disseminated in a peer-reviewed academic journal and at conferences. PROSPERO REGISTRATION NUMBER: CRD42017059473.

Long-term results following polydioxanone sling fixation technique in unstable lateral clavicle fracture.

Neer type II (Edinburgh type 3B) fractures of the lateral clavicle are unstable fractures. The optimal management of these fractures remains controversial with many surgical techniques described in the literature. Our study reports the long-term results of a modified suture (1.5-mm polydioxanone cord) and sling technique for these fractures to avoid complications associated with current techniques in the literature. Over a 5-year period, 23 patients who were (12 males, 11 females; 14 left, 9 right) with a mean age of 42 years were treated with this technique. At last follow-up, the mean Oxford score was 45.1 (range 36-48); the mean SPADI score was 7.4 (range 0-32.3); and the mean Constant score was 91.5 (range 71-100). There were one non-union and no malunion. All patients in our series, except one, returned to their pre-injury activity level. This modified suture fixation technique is safe, technically simple to perform and cheap. It achieves excellent rates of fracture union without the complications associated with other fixation methods in the literature.

Methicillin-resistant Staphylococcus aureus infection of the subacromial bursa: an unusual complication following subacromial corticosteroid injection (a report of two cases).

Subacromial corticosteroid injections are frequently used for both diagnostic and therapeutic purposes in shoulder pain. Subacromial septic bursitis is a recognized but rare complication. There have been no reports of methicillin-resistant Staphylococcus aureus infections of the subacromial bursa after subacromial injections in the literature. We describe case reports of two patients who presented with subacromial methicillin-resistant Staphylococcus aureus septic bursitis following subacromial corticosteroid injections in the community and highlight the diagnostic and management challenges of this condition.