How can trial designs better serve the needs of children and young people with juvenile idiopathic arthritis?

In juvenile idiopathic arthritis we have seen remarkable progress in the number of available licensed biological and small molecule treatments in the past two decades, leading to improved outcomes for patients. Designing clinical trials for these therapeutics is fraught with ethical, legislative, and practical challenges. However, many aspects of current clinical trial design in juvenile idiopathic arthritis do not meet the needs of patients and clinicians. Commonly used withdrawal trial designs raise substantial ethical concerns for patients and families who believe that they do not enable evidence-based and patient-centred decisions around medication choices. In this Viewpoint, we present the personal views of a patient and parent network that is of the opinion that current trial design in juvenile idiopathic arthritis is failing children and young people with juvenile idiopathic arthritis and set out the need for change informed by lived experience.

Identifying early indicators of secondary peritonitis in critically ill patients with cirrhosis.

Ascitic fluid infection (AFI) is a life-threatening complication of cirrhosis. We aimed to identify early indicators of secondary peritonitis (SP), which requires emergency surgery, and to describe the outcomes of SP and spontaneous bacterial/fungal peritonitis (SBFP). Adults with cirrhosis and AFI admitted to 16 university or university-affiliated ICUs in France between 2002 and 2017 were studied retrospectively. Cases were identified by searching the hospital databases for relevant ICD-10 codes and hospital charts for AFI. Logistic multivariate regression was performed to identify factors associated with SP. Secondary outcomes were short- and long-term mortality and survivors' functional outcomes. Of 178 included patients (137 men and 41 women; mean age, 58 ± 11 years), 21 (11.8%) had SP, confirmed by surgery in 16 cases and by abdominal computed tomography in 5 cases. Time to diagnosis exceeded 24 h in 7/21 patients with SP. By multivariate analysis, factors independently associated with SP were ascitic leukocyte count > 10,000/mm3 (OR 3.70; 95%CI 1.38-9.85; P = 0.009) and absence of laboratory signs of decompensated cirrhosis (OR 4.53; 95%CI 1.30-15.68; P = 0.017). The 1-year mortality rates in patients with SBFP and SP were 81.0% and 77.5%, respectively (Log-rank test, P = 0.92). Patients with SP vs. SBFP had no differences in 1-year functional outcomes. This multicenter retrospective study identified two indicators of SP as opposed to SBFP in patients with cirrhosis. Using these indicators may help to provide early surgical treatment.

Outliers from national audits: their analysis and use by the Care Quality Commission in quality assurance and regulation of healthcare services in England.

The Care Quality Commission (CQC) is the independent regulator of health and adult social care in England. As part of the intelligence-driven approach to regulation, the CQC works closely with national clinical audit bodies to identify key metrics which reflect quality of care and track the performance of providers against these metrics. Where outliers on national audits are identified that may reflect risks to patients, the CQC encourages the hospital to identify any learning points and implement changes to improve patient care.In this article, we describe the role of national audit outcomes in the regulatory process and how providers can use national audits to inform both quality assurance and quality improvement processes, with two illustrative case studies. We discuss the ongoing challenges with using audit data in the regulatory process and how these could be addressed.

Oxygen reserve index for non-invasive early hypoxemia detection during endotracheal intubation in intensive care: the prospective observational NESOI study.

BACKGROUND: To evaluate the ability of the oxygen reserve index (ORI) to predict the occurrence of mild hypoxemia (defined as SpO2 < 97%) during endotracheal intubation (ETI) of patients in the intensive care unit (ICU). METHODS: This observational single-centre study included patients without hypoxemia (defined as SpO2/FiO2 > 214) who required ETI in the ICU. Patients were followed during preoxygenation and ETI then until hospital discharge and/or day 28. We recorded cases of mild hypoxemia, moderate (SpO2 < 90%) and severe (SpO2 < 80%) hypoxemia, moderate arterial hypotension (systolic arterial pressure < 90 mmHg), oesophageal intubation, aspiration, cardiac arrest, and death. RESULTS: Between January 2019 and July 2020, 56 patients were included prospectively and 51 patients were analysed. Twenty patients had mild hypoxemia between the end of preoxygenation and the end of intubation; in 10 of these patients, the decrease in SpO2 below 97% was preceded by an ORI < 0.4, the median time difference being 81 s [interquartile range, 34-146]. By multivariable analysis, a higher ORI (by 0.1 increase) value during preoxygenation was associated with absence of hypoxemia (odds ratio, 0.76; 95% confidence interval, 0.61;0.95; P = 0.0141). CONCLUSION: In non-hypoxemic patients, the 81-s [34-146] median time between the ORI decrease below 0.4 and the SpO2 decrease below 97% during apnoea may allow preventive action. A higher ORI value during preoxygenation was independently protective against hypoxemia. Whether these findings also apply to hypoxemic patients, and the clinical impact of a preoxygenation strategy based on ORI monitoring, remain to be evaluated prospectively. Trial Registration ClinicalTrial.gov, #NCT03600181.

Severe manifestations of chikungunya virus in critically ill patients during the 2013-2014 Caribbean outbreak.

OBJECTIVES: A chikungunya epidemic occurred in 2013-2014 in the Caribbean and Americas. Although the disease is usually benign, some patients required admission to the intensive care unit (ICU). The characteristics and outcomes of patients with chikungunya virus (CHIKV) infection admitted to an ICU during this epidemic are reported. METHODS: An observational study of consecutive patients with confirmed CHIKV infection admitted to ICUs in Martinique and Guadeloupe, French West Indies, between January and November 2014, was performed. In addition, patients with CHIKV-related manifestations were compared with those whose manifestations were not specifically related to CHIKV infection. RESULTS: Sixty-five patients were admitted to the ICU with CHIKV infection. Fifty-four (83%) had a pre-existing underlying disease and 27 (41.5%) were admitted due to exacerbation of a comorbidity. Thirty-seven (57%) patients were mechanically ventilated. ICU and hospital mortality rates were 26% and 27%, respectively. CHIKV-related manifestations were observed in 28 (18%) patients and were mainly encephalitis, Guillain-Barré syndrome, and severe sepsis. These patients less frequently had chronic arterial hypertension and diabetes and more frequently had autoimmune diseases compared with patients without CHIKV-related manifestations. CONCLUSIONS: Most patients admitted to the ICU with CHIKV infection had a pre-existing comorbidity. However, severe manifestations such as Guillain-Barré syndrome, encephalitis, and severe sepsis could be specifically related to CHIKV.