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

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Non-medical prescribers: prescribing within practice

Since its inception in Ireland in 2007, the Nurse Prescribing Programme has prepared registered nurses and midwives to prescribe from a limited formulary in their area of clinical speciality. However, registration numbers have declined in recent years, prompting changes to the registration processes. This article present the findings of a study conducted on the prescribing behaviours, practices and confidence of registered nurse/midwife prescribers following these changes, reporting the findings from the qualitative arm of a larger mixed-method study. Interviews with participants (n=6) explored their prescribing behaviours, practices and confidence. The findings suggest that organisational and professional factors influence prescribing. Scope of practice and expert decision-making is seen to influence engagement with treatment. Interprofessional cooperation continues to develop in making prescribing decisions. There is a clear need for interprofessional education to increase cooperation between health professionals in making prescribing decisions and including national competencies for all prescribers

“Providing a complete episode of care”: a survey of registered nurse and registered midwife prescribing behaviours and practices

Aims and objectives: To describe the prescribing behaviours and practices of registered nurse and midwife prescribers and to explore experiences of enablers and barriers to prescribing practices. Background: The extension of prescriptive authority to nurses and midwives internationally has created new opportunities for them to expand their scope of practice and is of significant benefit to effective and efficient health service provision. Design: Cross‐sectional national survey of registered nurse and midwife prescribers. Methods: Data were collected through an online survey between April–July 2018. A total of 84 nurse and midwife prescribers participated. The STROBE checklist was applied as the reporting guideline for this study. Results: Respondents estimated that two‐fifths of their consultations involved an episode of prescribing. Nurse and midwife prescribers engaged in similar prescribing behaviours spanning the range of activities from initiating new medications to ceasing medicines. The most frequently selected criterion for prescribing was clinical effectiveness. Prescribing was viewed as essential to respondents\u27 clinical practice, allowing them to provide a complete episode of care and leading to a reduction in medication errors and reduced delays and waiting times for patients. Enablers of prescribing included knowledge, experience, education and access to continuous professional development, as well as support from colleagues and organisations. Conclusion: Little is known about the prescribing behaviours and practices of registered nurse and midwife prescribers. While prescribing authority enables nurse and midwife practitioners to deliver holistic care, there remain significant barriers and challenges including increased workloads, lack of continuous professional development, lack of support and overly restrictive rules and policies governing prescribing.Relevance to clinical practice: Addressing the barriers identified in this study could enable more nurse and midwife prescribers to work to their full scope of practice, enabling populations to fully capitalise on the contributions of registered nurse and midwife prescribing services

Body mass index and all-cause mortality in heart failure patients with normal and reduced ventricular ejection fraction - a dose-response meta-analysis

Background: For patients with heart failure, there is an inverse relation between body mass index (BMI) and mortality, sometimes called the obesity-paradox. However, the relationship might be either U- or J-shaped and might differ between patients with reduced (HFrEF) or preserved left ventricular ejection fraction (HFpEF). We sought to investigate this further in a dose-response meta-analysis of published studies. Methods: PubMed and Embase from June 1980 to April 2017 were searched for prospective cohort studies evaluating associations between BMI and all-cause mortality in patients with HFrEF (LVEF <40%) or HFpEF (LVEF ≥ 50%). Summary estimated effect sizes were obtained by using a random effects model. Potential non-linear relationships were evaluated by using random effects restricted cubic spline models. Results: Ten studies were identified that included 96,424 patients of whom 59,263 had HFpEF (mean age 68 years of whom 38% were women) and 37,161 had HFrEF (mean age 60 years of whom 17% were women). For patients with HFpEF, the summary hazard ratio (HR) for all-cause mortality was: 0.93 (95%CI: 0.89-0.97) per 5 units increase in BMI (I-squared = 75.8%, p for heterogeneity = 0.01 and Begg’s test, p = 1.0, Egger’s test, p = 0.29) but the association was U-shaped (p for nonlinearity <0.01) with the nadir of risk at a BMI of 32-33 kg/m². For patients with HFrEF, the summary HR for all-cause mortality was: 0.96 (95%CI: 0.92-0.99) (I-squared=95%, p for heterogeneity < 0.001 and Begg’s test, p=0.45, Egger’s test, p=0.01). The relationship was also U-shaped (p < 0.01), although ‘flatter’ than for HFpEF, with the nadir at a BMI of 33 kg/m². Conclusions: For patients with heart failure, the relation between BMI and mortality is U-shaped with a similar nadir of risk for HFpEF and HFrEF at a BMI of 32-33 kg/m². Whether interventions that alter weight in either direction can alter risk is unknown

Respiratory support in patients with severe COVID-19 in the International Severe Acute Respiratory and Emerging Infection (ISARIC) COVID-19 study: a prospective, multinational, observational study

Background: Up to 30% of hospitalised patients with COVID-19 require advanced respiratory support, including high-flow nasal cannulas (HFNC), non-invasive mechanical ventilation (NIV), or invasive mechanical ventilation (IMV). We aimed to describe the clinical characteristics, outcomes and risk factors for failing non-invasive respiratory support in patients treated with severe COVID-19 during the first two years of the pandemic in high-income countries (HICs) and low middle-income countries (LMICs). Methods: This is a multinational, multicentre, prospective cohort study embedded in the ISARIC-WHO COVID-19 Clinical Characterisation Protocol. Patients with laboratory-confirmed SARS-CoV-2 infection who required hospital admission were recruited prospectively. Patients treated with HFNC, NIV, or IMV within the first 24 h of hospital admission were included in this study. Descriptive statistics, random forest, and logistic regression analyses were used to describe clinical characteristics and compare clinical outcomes among patients treated with the different types of advanced respiratory support. Results: A total of 66,565 patients were included in this study. Overall, 82.6% of patients were treated in HIC, and 40.6% were admitted to the hospital during the first pandemic wave. During the first 24 h after hospital admission, patients in HICs were more frequently treated with HFNC (48.0%), followed by NIV (38.6%) and IMV (13.4%). In contrast, patients admitted in lower- and middle-income countries (LMICs) were less frequently treated with HFNC (16.1%) and the majority received IMV (59.1%). The failure rate of non-invasive respiratory support (i.e. HFNC or NIV) was 15.5%, of which 71.2% were from HIC and 28.8% from LMIC. The variables most strongly associated with non-invasive ventilation failure, defined as progression to IMV, were high leukocyte counts at hospital admission (OR [95%CI]; 5.86 [4.83-7.10]), treatment in an LMIC (OR [95%CI]; 2.04 [1.97-2.11]), and tachypnoea at hospital admission (OR [95%CI]; 1.16 [1.14-1.18]). Patients who failed HFNC/NIV had a higher 28-day fatality ratio (OR [95%CI]; 1.27 [1.25-1.30]). Conclusions: In the present international cohort, the most frequently used advanced respiratory support was the HFNC. However, IMV was used more often in LMIC. Higher leucocyte count, tachypnoea, and treatment in LMIC were risk factors for HFNC/NIV failure. HFNC/NIV failure was related to worse clinical outcomes, such as 28-day mortality. Trial registration This is a prospective observational study; therefore, no health care interventions were applied to participants, and trial registration is not applicable

Respiratory support in patients with severe COVID-19 in the International Severe Acute Respiratory and Emerging Infection (ISARIC) COVID-19 study: a prospective, multinational, observational study

Background: Up to 30% of hospitalised patients with COVID-19 require advanced respiratory support, including high-flow nasal cannulas (HFNC), non-invasive mechanical ventilation (NIV), or invasive mechanical ventilation (IMV). We aimed to describe the clinical characteristics, outcomes and risk factors for failing non-invasive respiratory support in patients treated with severe COVID-19 during the first two years of the pandemic in high-income countries (HICs) and low middle-income countries (LMICs). Methods: This is a multinational, multicentre, prospective cohort study embedded in the ISARIC-WHO COVID-19 Clinical Characterisation Protocol. Patients with laboratory-confirmed SARS-CoV-2 infection who required hospital admission were recruited prospectively. Patients treated with HFNC, NIV, or IMV within the first 24 h of hospital admission were included in this study. Descriptive statistics, random forest, and logistic regression analyses were used to describe clinical characteristics and compare clinical outcomes among patients treated with the different types of advanced respiratory support. Results: A total of 66,565 patients were included in this study. Overall, 82.6% of patients were treated in HIC, and 40.6% were admitted to the hospital during the first pandemic wave. During the first 24 h after hospital admission, patients in HICs were more frequently treated with HFNC (48.0%), followed by NIV (38.6%) and IMV (13.4%). In contrast, patients admitted in lower- and middle-income countries (LMICs) were less frequently treated with HFNC (16.1%) and the majority received IMV (59.1%). The failure rate of non-invasive respiratory support (i.e. HFNC or NIV) was 15.5%, of which 71.2% were from HIC and 28.8% from LMIC. The variables most strongly associated with non-invasive ventilation failure, defined as progression to IMV, were high leukocyte counts at hospital admission (OR [95%CI]; 5.86 [4.83–7.10]), treatment in an LMIC (OR [95%CI]; 2.04 [1.97–2.11]), and tachypnoea at hospital admission (OR [95%CI]; 1.16 [1.14–1.18]). Patients who failed HFNC/NIV had a higher 28-day fatality ratio (OR [95%CI]; 1.27 [1.25–1.30]). Conclusions: In the present international cohort, the most frequently used advanced respiratory support was the HFNC. However, IMV was used more often in LMIC. Higher leucocyte count, tachypnoea, and treatment in LMIC were risk factors for HFNC/NIV failure. HFNC/NIV failure was related to worse clinical outcomes, such as 28-day mortality. Trial registration This is a prospective observational study; therefore, no health care interventions were applied to participants, and trial registration is not applicable