COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P < 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Dinâmica da infecção por Rickettsia parkeri em galinhas domésticas

The aim of the present study was to investigate experimental infections by Rickettsia parkeri in domestic chickens (Gallus gallus domesticus) and to determine the dynamics of antibody production during acute and chronic infection. The animals (n = 64) were allocated into eight groups as follows: G1, inoculated intramuscularly (IM) with 2.5 × 105 Vero cells (1 mL) infected with R. parkeri; G2, inoculated IM with 5.0 × 105 Vero cells (2 mL) infected with R. parkeri; G3, received 1 mL of the inoculum subcutaneously (SC); G4, received 2 mL of inoculum SC; G5, received 1 mL of the inoculum intraperitoneally (IP); G6, injected with 2 mL of the inoculum IP; G7 and G8, received 1 mL and 2 mL of culture medium IM, respectively (negative control groups). All R. parkeri inocula were viable prior to inoculation in the birds. In order to assess the dynamics of antibody production in acute and chronic infection, sera of chickens were collected 3, 7, 14, and 21 d post infection (PI) and assessed using an immunofluorescence antibody test (IFAT). In addition, PCR (gltA gene) was performed using fragments of spleen and lung from euthanized chickens to detect the replication of R. parkeri in tissues during the experimental period. Animals from the G4 and G3 groups exhibited the highest mean antibody titers, with maximum levels observed at 7 and 14 d PI, respectively. Conversely, G2, G4 and G6 exhibited higher mean antibody titers than G1, G3 and G5, respectively. Antibody titers were dose-dependent. Rickettsial DNA was not detected in either spleen or lung tissue. The present study demonstrated that birds seroconvert after being challenged by R. parkeri. However, there was no replication of the agent in the tissues analyzed and rickettsemia was not observed.O objetivo deste estudo foi avaliar a infecção experimental por Rickettsia parkeri em galinhas domésticas (Gallus gallus domesticus) e investigar a dinâmica de anticorpos. Para tanto, foram utilizadas 64 galinhas criadas extensivamente divididas em oito grupos: G1 - inoculado com 2,5 x 105 células Vero (1 ml) infectadas por R. parkeri via intramuscular (IM); G2 – 5,0 x 105 células Vero (2 ml) infectadas por R. parkeri via IM; G3 - 1 ml do inóculo via subcutânea (SC); G4 - 2 ml de inóculo via SC; G5 – 1 ml do inóculo via intraperitoneal (IP); G6 - 2 ml de inóculo via IP, e G7 e G8 - 1 e 2 ml de meio de cultivo de células Vero via IM, respectivamente representando os grupos controles negativos. Ressaltase que todos os inóculos de R. parkeri estavam viáveis no momento da inoculação. Os soros das aves foram coletados aos 3, 7, 14 e 21 dias pós-infecção (PI) e testadas por reação de imunofluorescência indireta (RIFI) para avaliar a dinâmica de anticorpos na infecção aguda e crônica. A identificação da multiplicação de R. parkeri nos tecidos, no mesmo período PI, foi realizada por PCR, para um fragmento do gene gltA, em amostras de baço e pulmão provenientes das galinhas eutanasiadas. As aves do G4 e G3 apresentaram as maiores médias de anticorpos obtendo os níveis mais elevados aos sete e 14 dias PI, respectivamente. G2, G4 e G6 apresentaram médias de anticorpos superiores comparados aos G1, G3 e G5 respectivamente, sendo considerada a infecção dose-dependente. Não foi detectado DNA rickettsial nos tecidos avaliados. No presente trabalho foi possível demonstrar que as aves soroconverteram mediante o desafio da inoculação por R. parkeri, todavia não houve a identificação do agente nos tecidos analisados, bem como a presença de rickettsemia

Qualidade pós-colheita de melão 'Orange Flesh' minimamente processado armazenado sob refrigeração e atmosfera modificada Postharvest quality of fresh-cut 'Orange Flesh' melon stored under refrigeration and modified atmosphere

Melões 'Orange Flesh' minimamente processados foram armazenados por 8 dias sob refrigeração (6 &plusmn; 1ºC e 90 &plusmn; 5% UR) e atmosfera modificada (passiva e ativas: 5% O2 + 5% CO2 e 2% O2 + 10% CO2). As variáveis pH, acidez titulável, sólidos solúveis e acetaldeído não foram influenciadas pelas atmosferas estudadas. Aumentos na concentração de CO2 ocorreram ao logo do armazenamento, sendo que a atmosfera modificada ativa (2% O2 + 10% CO2) foi mais eficaz no controle da produção de CO2 até o quarto dia de armazenamento.<br>Fresh-cut 'Orange Flesh' melons were stored for 8 days under refrigeration (6 &plusmn; 1ºC e 90 &plusmn; 5% RH) and modified atmosphere (passive and active: 5% O2 + 5% CO2 and 2% O2 + 10% CO2). The variables pH, titratable acidity, soluble solids and acetaldehyde were not affected, differently, for the atmospheres studied. Increase in CO2 concentration occurred over the storage period. Active modified atmosphere (2% O2 + 10% CO2) was the most effective in controlling the CO2 production until the fourth day of storage

Intraoperative transfusion practices in Europe

Transfusion of allogeneic blood influences outcome after surgery. Despite widespread availability of transfusion guidelines, transfusion practices might vary among physicians, departments, hospitals and countries. Our aim was to determine the amount of packed red blood cells (pRBC) and blood products transfused intraoperatively, and to describe factors determining transfusion throughout Europe. We did a prospective observational cohort study enrolling 5803 patients in 126 European centres that received at least one pRBC unit intraoperatively, during a continuous three month period in 2013. The overall intraoperative transfusion rate was 1.8%; 59% of transfusions were at least partially initiated as a result of a physiological transfusion trigger- mostly because of hypotension (55.4%) and/or tachycardia (30.7%). Haemoglobin (Hb)- based transfusion trigger alone initiated only 8.5% of transfusions. The Hb concentration [mean (sd)] just before transfusion was 8.1 (1.7) g dl and increased to 9.8 (1.8) g dl after transfusion. The mean number of intraoperatively transfused pRBC units was 2.5 (2.7) units (median 2). Although European Society of Anaesthesiology transfusion guidelines are moderately implemented in Europe with respect to Hb threshold for transfusion (7-9 g dl), there is still an urgent need for further educational efforts that focus on the number of pRBC units to be transfused at this threshold

Safety and Outcome of Revascularization Treatment in Patients With Acute Ischemic Stroke and COVID-19: The Global COVID-19 Stroke Registry.

BACKGROUND AND OBJECTIVES COVID-19 related inflammation, endothelial dysfunction and coagulopathy may increase the bleeding risk and lower efficacy of revascularization treatments in patients with acute ischemic stroke. We aimed to evaluate the safety and outcomes of revascularization treatments in patients with acute ischemic stroke and COVID-19. METHODS Retrospective multicenter cohort study of consecutive patients with acute ischemic stroke receiving intravenous thrombolysis (IVT) and/or endovascular treatment (EVT) between March 2020 and June 2021, tested for SARS-CoV-2 infection. With a doubly-robust model combining propensity score weighting and multivariate regression, we studied the association of COVID-19 with intracranial bleeding complications and clinical outcomes. Subgroup analyses were performed according to treatment groups (IVT-only and EVT). RESULTS Of a total of 15128 included patients from 105 centers, 853 (5.6%) were diagnosed with COVID-19. 5848 (38.7%) patients received IVT-only, and 9280 (61.3%) EVT (with or without IVT). Patients with COVID-19 had a higher rate of symptomatic intracerebral hemorrhage (SICH) (adjusted odds ratio [OR] 1.53; 95% CI 1.16-2.01), symptomatic subarachnoid hemorrhage (SSAH) (OR 1.80; 95% CI 1.20-2.69), SICH and/or SSAH combined (OR 1.56; 95% CI 1.23-1.99), 24-hour (OR 2.47; 95% CI 1.58-3.86) and 3-month mortality (OR 1.88; 95% CI 1.52-2.33).COVID-19 patients also had an unfavorable shift in the distribution of the modified Rankin score at 3 months (OR 1.42; 95% CI 1.26-1.60). DISCUSSION Patients with acute ischemic stroke and COVID-19 showed higher rates of intracranial bleeding complications and worse clinical outcomes after revascularization treatments than contemporaneous non-COVID-19 treated patients. Current available data does not allow direct conclusions to be drawn on the effectiveness of revascularization treatments in COVID-19 patients, or to establish different treatment recommendations in this subgroup of patients with ischemic stroke. Our findings can be taken into consideration for treatment decisions, patient monitoring and establishing prognosis

Safety and Outcome of Revascularization Treatment in Patients With Acute Ischemic Stroke and COVID-19: The Global COVID-19 Stroke Registry

BACKGROUND AND OBJECTIVES: COVID-19 related inflammation, endothelial dysfunction and coagulopathy may increase the bleeding risk and lower efficacy of revascularization treatments in patients with acute ischemic stroke. We aimed to evaluate the safety and outcomes of revascularization treatments in patients with acute ischemic stroke and COVID-19. METHODS: Retrospective multicenter cohort study of consecutive patients with acute ischemic stroke receiving intravenous thrombolysis (IVT) and/or endovascular treatment (EVT) between March 2020 and June 2021, tested for SARS-CoV-2 infection. With a doubly-robust model combining propensity score weighting and multivariate regression, we studied the association of COVID-19 with intracranial bleeding complications and clinical outcomes. Subgroup analyses were performed according to treatment groups (IVT-only and EVT). RESULTS: Of a total of 15128 included patients from 105 centers, 853 (5.6%) were diagnosed with COVID-19. 5848 (38.7%) patients received IVT-only, and 9280 (61.3%) EVT (with or without IVT). Patients with COVID-19 had a higher rate of symptomatic intracerebral hemorrhage (SICH) (adjusted odds ratio [OR] 1.53; 95% CI 1.16-2.01), symptomatic subarachnoid hemorrhage (SSAH) (OR 1.80; 95% CI 1.20-2.69), SICH and/or SSAH combined (OR 1.56; 95% CI 1.23-1.99), 24-hour (OR 2.47; 95% CI 1.58-3.86) and 3-month mortality (OR 1.88; 95% CI 1.52-2.33).COVID-19 patients also had an unfavorable shift in the distribution of the modified Rankin score at 3 months (OR 1.42; 95% CI 1.26-1.60). DISCUSSION: Patients with acute ischemic stroke and COVID-19 showed higher rates of intracranial bleeding complications and worse clinical outcomes after revascularization treatments than contemporaneous non-COVID-19 treated patients. Current available data does not allow direct conclusions to be drawn on the effectiveness of revascularization treatments in COVID-19 patients, or to establish different treatment recommendations in this subgroup of patients with ischemic stroke. Our findings can be taken into consideration for treatment decisions, patient monitoring and establishing prognosis

Development of a prediction model for postoperative pneumonia A multicentre prospective observational study

BACKGROUND Postoperative pneumonia is associated with increased morbidity, mortality and costs. Prediction models of pneumonia that are currently available are based on retrospectively collected data and administrative coding systems. OBJECTIVE To identify independent variables associated with the occurrence of postoperative pneumonia. DESIGN A prospective observational study of a multicentre cohort (Prospective Evaluation of a RIsk Score for postoperative pulmonary COmPlications in Europe database). SETTING Sixty-three hospitals in Europe. PATIENTS Patients undergoing surgery under general and/or regional anaesthesia during a 7-day recruitment period. MAIN OUTCOME MEASURE The primary outcome was postoperative pneumonia. Definition: the need for treatment with antibiotics for a respiratory infection and at least one of the following criteria: new or changed sputum; new or changed lung opacities on a clinically indicated chest radiograph; temperature more than 38.3 degrees C; leucocyte count more than 12 000 mu l(-1). RESULTS Postoperative pneumonia occurred in 120 out of 5094 patients (2.4%). Eighty-two of the 120 (68.3%) patients with pneumonia required ICU admission, compared with 399 of the 4974 (8.0%) without pneumonia (P < 0.001). We identified five variables independently associated with postoperative pneumonia: functional status [odds ratio (OR) 2.28, 95% confidence interval (CI) 1.58 to 3.12], pre-operative SpO(2) values while breathing room air (OR 0.83, 95% CI 0.78 to 0.84), intra-operative colloid administration (OR 2.97, 95% CI 1.94 to 3.99), intra-operative blood transfusion (OR 2.19, 95% CI 1.41 to 4.71) and surgical site (open upper abdominal surgery OR 3.98, 95% CI 2.19 to 7.59). The model had good discrimination (c-statistic 0.89) and calibration (Hosmer-Lemeshow P = 0.572). CONCLUSION We identified five variables independently associated with postoperative pneumonia. The model performed well and after external validation may be used for risk stratification and management of patients at risk of postoperative pneumonia