Diagnostic Performance of Chest CT for SARS-CoV-2 Infection in Individuals with or without COVID-19 Symptoms.

Background The use of chest CT for coronavirus disease 2019 (COVID-19) diagnosis or triage in health care settings with limited severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) polymerase chain reaction (PCR) capacity is controversial. COVID-19 Reporting and Data System (CO-RADS) categorization of the level of COVID-19 suspicion might improve diagnostic performance. Purpose To investigate the value of chest CT with CO-RADS classification to screen for asymptomatic SARS-CoV-2 infections and to determine its diagnostic performance in individuals with COVID-19 symptoms during the exponential phase of viral spread. Materials and Methods In this secondary analysis of a prospective trial, from March 2020 to April 2020, parallel SARS-CoV-2 PCR and CT with categorization of COVID-19 suspicion was performed with CO-RADS for individuals with COVID-19 symptoms and control participants without COVID-19 symptoms admitted to the hospital for medical emergencies unrelated to COVID-19. CT with CO-RADS was categorized on a five-point scale from 1 (very low suspicion) to 5 (very high suspicion). Area under the receiver operating curve (AUC) was calculated in symptomatic versus asymptomatic individuals to predict positive SARS-CoV-2 PCR, and likelihood ratios for each CO-RADS score were used for rational selection of diagnostic thresholds. Results A total of 859 individuals (median age, 70 years; interquartile range, 52-81 years; 443 men) with COVID-19 symptoms and 1138 control participants (median age, 68 years; interquartile range, 52-81 years; 588 men) were evaluated. CT with CO-RADS had good diagnostic performance (P < .001) in both symptomatic (AUC, 0.89) and asymptomatic (AUC, 0.70) individuals. In symptomatic individuals (42% PCR positive), CO-RADS 3 or greater detected positive PCR with high sensitivity (89%, 319 of 358) and specificity of 73%. In asymptomatic individuals (5% PCR positive), a CO-RADS score of 3 or greater detected SARS-CoV-2 infection with low sensitivity (45%, 27 of 60) but high specificity (89%). Conclusion CT with Coronavirus Disease 2019 Reporting and Data System (CO-RADS) had good diagnostic performance in symptomatic individuals, supporting its application for triage. Sensitivity in asymptomatic individuals was insufficient to justify its use as a first-line screening approach. Incidental detection of CO-RADS 3 or greater in asymptomatic individuals should trigger testing for respiratory pathogens. © RSNA, 2020 Online supplemental material is available for this article.

PID in Disguise: Molecular Diagnosis of IRAK-4 Deficiency in an Adult Previously Misdiagnosed With Autosomal Dominant Hyper IgE Syndrome.

Autosomal recessive IL-1R-associated kinase 4 (IRAK-4) deficiency is a rare cause of recurrent pyogenic infections with limited inflammatory responses. We describe an adult female patient with severe lung disease who was phenotypically diagnosed as suffering from autosomal dominant Hyper IgE syndrome (AD HIES) because of recurrent skin infections with Staphylococcus aureus, recurrent pneumonia and elevated serum IgE levels. In contrast to findings in AD HIES patients, no abnormalities were found in the Th17 and circulating follicular helper T cell subsets. A panel-based sequencing approach led to the identification of a homozygous IRAK4 stop mutation (c.877C > T, p.Gln293*).

REM sleep obstructive sleep apnoea.

Obstructive sleep apnoea (OSA) can occur in both rapid eye movement (REM) and non-REM sleep or be limited to REM sleep, when the upper airway is most prone to collapse due to REM sleep atonia. Respiratory events are usually longer and more desaturating in REM than in NREM sleep. The prevalence of REM OSA is higher in women than in men and REM OSA usually occurs in the context of mild-moderate OSA based on the apnoea-hypopnoea index calculated for the entire sleep study. Studies have highlighted some detrimental consequences of REM OSA; for example, its frequent association with systemic hypertension and a degree of excessive daytime sleepiness similar to that found in nonsleep-stage-dependent OSA. Moreover, REM OSA could increase cardiometabolic risk. Continuous positive airway pressure (CPAP) treatment aimed at preventing REM OSA should be longer than the 4 h usually considered as good compliance, since REM sleep occurs mostly during the second half of the night. Unfortunately, patients with REM OSA show poor adherence to CPAP. Alternative non-CPAP treatments might be a good choice for REM OSA, but data are lacking. This review summarises the available data on REM OSA and critically examines the weaknesses and strengths of existing literature.

Azithromycin for treatment of hospitalised COVID-19 patients: a randomised, multicentre, open-label clinical trial (DAWn-AZITHRO).

BACKGROUND AND OBJECTIVES: Azithromycin was rapidly adopted as a repurposed drug to treat coronavirus disease 2019 (COVID-19) early in the pandemic. We aimed to evaluate its efficacy in patients hospitalised for COVID-19. METHODS: In a series of randomised, open-label, phase 2 proof-of-concept, multicentre clinical trials (Direct Antivirals Working against the novel coronavirus (DAWn)), several treatments were compared with standard of care. In 15 Belgian hospitals, patients hospitalised with moderate to severe COVID-19 were allocated 2:1 to receive standard of care plus azithromycin or standard of care alone. The primary outcome was time to live discharge or sustained clinical improvement, defined as a two-point improvement on the World Health Organization (WHO) ordinal scale sustained for at least 3 days. RESULTS: Patients were included between April 22 and December 17, 2020. When 15-day follow-up data were available for 160 patients (56% of preset cohort), an interim analysis was performed at request of the independent Data Safety and Monitoring Board. Subsequently, DAWn-AZITHRO was stopped for futility. In total, 121 patients were allocated to the treatment arm and 64 patients to the standard-of-care arm. We found no effect of azithromycin on the primary outcome with a hazard ratio of 1.044 (95% CI 0.772-1.413; p=0.7798). None of the predefined subgroups showed significant interaction as covariates in the Fine-Gray regression analysis. No benefit of azithromycin was found on any of the short- and longer-term secondary outcomes. CONCLUSION: Time to clinical improvement is not influenced by azithromycin in patients hospitalised with moderate to severe COVID-19.

Clinical implementation of value based healthcare: Impact on outcomes for lung cancer patients.

Value based Healthcare (VBHC) focuses on patient centered outcomes, by incorporating Patient Reported Outcome Measures (PROMS). Expectations on the benefits of VBHC are high, but few data are available that validate its routine use. We wanted to investigate if VBHC is feasible and beneficial for lung cancer patients in clinical practice. METHOD: We developed a digital transmural care pathway for lung cancer patients. During systemic therapy, patients digitally reported side effects weekly. Every six weeks, quality of life was reported trough EORTC questionnaires. Case-mix variables, treatment approaches and outcome indicators were systematically collected. We evaluated the compliance of the patients with the digitally reporting system and the impact of the care pathway on patient centered outcomes such as emergency department (ED) visits, time spent on the oncology day clinic, survival and quality of death. RESULTS: 221 lung cancer patients were included in the care pathway. 3091 weekly questionnaires were digitally collected. Compliance with the weekly digital follow-up was 92%: 2835 of 3091 questionnaires were completed. Patients in the care pathway had significantly less ED visits (3.5% vs 4.8%, p 0.04) and a shorter length of stay at the day clinic (2.5 h vs 4.1 h, p < 0,05) compared to routine clinical care. In stage IV lung cancer patients, overall survival was significantly higher in the care pathway (447 days (95% CI 379-663)) compared to routine care (286 days (95% CI 191-400)) (p = 0,025). CONCLUSION: Implementation of value based healthcare is feasible and beneficial in daily clinical care for lung cancer patients.

Benefits of intensive insulin therapy on neuromuscular complications in routine daily critical care practice: a retrospective study.

INTRODUCTION: Intensive insulin therapy (IIT) reduced the incidence of critical illness polyneuropathy and/or myopathy (CIP/CIM) and the need for prolonged mechanical ventilation (MV >or= 14 days) in two randomised controlled trials (RCTs) on the effect of IIT in a surgical intensive care unit (SICU) and medical intensive care unit (MICU). In the present study, we investigated whether these effects are also present in daily clinical practice when IIT is implemented outside of a study protocol. METHODS: We retrospectively studied electrophysiological data from patients in the SICU and MICU, performed because of clinical weakness and/or weaning failure, before and after routine implementation of IIT. CIP/CIM was diagnosed by abundant spontaneous electrical activity on electromyography. Baseline and outcome variables were compared using Student's t-test, Chi-squared or Mann-Whitney U-test when appropriate. The effect of implementing IIT on CIP/CIM and prolonged MV was assessed using univariate analysis and multivariate logistic regression analysis (MVLR), correcting for baseline and ICU risk factors. RESULTS: IIT significantly lowered mean (+/- standard deviation) blood glucose levels (from 144 +/- 20 to 107 +/- 10 mg/dl, p < 0.0001) and significantly reduced the diagnosis of CIP/CIM in the screened long-stay patients (125/168 (74.4%) to 220/452 (48.7%), p < 0.0001). MVLR identified implementing IIT as an independent protective factor (p < 0.0001, odds ratio (OR): 0.25 (95% confidence interval (CI): 0.14 to 0.43)). MVLR confirmed the independent protective effect of IIT on prolonged MV (p = 0.002, OR:0.40 (95% CI: 0.22-0.72)). This effect was statistically only partially explained by the reduction in CIP/CIM. CONCLUSIONS: Implementing IIT in routine daily practice in critically ill patients evoked a similar beneficial effect on neuromuscular function as that observed in two RCTs. IIT significantly improved glycaemic control and significantly and independently reduced the electrophysiological incidence of CIP/CIM. This reduction partially explained the beneficial effect of IIT on prolonged MV.

Intensive insulin therapy in mixed medical/surgical intensive care units: benefit versus harm.

Intensive insulin therapy (IIT) improves the outcome of prolonged critically ill patients, but concerns remain regarding potential harm and the optimal blood glucose level. These questions were addressed using the pooled dataset of two randomized controlled trials. Independent of parenteral glucose load, IIT reduced mortality from 23.6 to 20.4% in the intention-to-treat group (n = 2,748; P = 0.04) and from 37.9 to 30.1% among long stayers (n = 1,389; P = 0.002), with no difference among short stayers (8.9 vs. 10.4%; n = 1,359; P = 0.4). Compared with blood glucose of 110-150 mg/dl, mortality was higher with blood glucose >150 mg/dl (odds ratio 1.38 [95% CI 1.10-1.75]; P = 0.007) and lower with <110 mg/dl (0.77 [0.61-0.96]; P = 0.02). Only patients with diabetes (n = 407) showed no survival benefit of IIT. Prevention of kidney injury and critical illness polyneuropathy required blood glucose strictly <110 mg/day, but this level carried the highest risk of hypoglycemia. Within 24 h of hypoglycemia, three patients in the conventional and one in the IIT group died (P = 0.0004) without difference in hospital mortality. No new neurological problems occurred in survivors who experienced hypoglycemia in intensive care units (ICUs). We conclude that IIT reduces mortality of all medical/surgical ICU patients, except those with a prior history of diabetes, and does not cause harm. A blood glucose target <110 mg/day was most effective but also carried the highest risk of hypoglycemia.