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Background Many interventional in-patient coronavirus disease 2019 (COVID-19) trials assess primary outcomes through day 28 post-randomization. Since a proportion of patients experience protracted disease or relapse, such follow-up period may not fully capture the course of the disease, even when randomization occurs a few days after hospitalization. Methods Among adults hospitalized with COVID-19 in eastern Denmark from 18 March 2020–12 January 2021 we assessed all-cause mortality, recovery, and sustained recovery 90 days after admission, and readmission and all-cause mortality 90 days after discharge. Recovery was defined as hospital discharge and sustained recovery as recovery and alive without readmissions for 14 consecutive days. Results Among 3386 patients included in the study, 2796 (82.6%) reached recovery and 2600 (77.0%) achieved sustained recovery. Of those discharged from hospital, 556 (19.9%) were readmitted and 289 (10.3%) died. Overall, the median time to recovery was 6 days (interquartile range [IQR]: 3–10), and 19 days (IQR: 11–33) among patients in intensive care in the first 2 days of admission. Conclusions Postdischarge readmission and mortality rates were substantial. Therefore, sustained recovery should be favored to recovery outcomes in clinical COVID-19 trials. A 28-day follow-up period may be too short for the critically ill.

Objectives: It is unclear whether recurrent sputum culture with Pseudomonas aeruginosa from patients with chronic obstructive pulmonary disease (COPD) is caused by intermittent airway carriage by different P. aeruginosa lineages or persistent carriage by the same lineage, and whether lineages genetically adapt during carriage. Methods: Whole-genome sequencing was performed for P. aeruginosa isolates sampled longitudinally from sputum cultures in patients with COPD who were enrolled in an ongoing randomized controlled trial (clinicaltrials.gov: NCT03262142). Results: A total of 153 P. aeruginosa isolates were sequenced for 23 patients during 365 days of follow-up. Recurrent presence of P. aeruginosa was seen in 19 patients (83%) and was caused by persistence of the same clonal lineage in all but one patient. We identified 38 genes mutated in parallel in two or more lineages, suggesting positive selection for adaptive mutations. Mutational enrichment analysis revealed genes important in antibiotic resistance and chronic infections to be more frequently mutated. Discussion: Recurrent P. aeruginosa was common and carried for a prolonged time after initial detection in the airways of patients with COPD. Recurrence was caused by persistence of the same clonal lineage and was associated with genetic adaptation. Trial data on possible clinical benefits of attempting antibiotic eradication of P. aeruginosa in COPD are warranted.

Many interventional in-patient COVID-19 trials assess primary outcomes through day 28 post-randomization. Since a proportion of patients experience protracted disease or relapse, such follow-up period may not fully capture the course of the disease, even when randomization occurs a few days after hospitalization.Among adults hospitalized with COVID-19 in Eastern Denmark from March 18, 2020 - January 12, 2021 we assessed: all-cause mortality, recovery and sustained recovery 90 days after admission, and readmission and all-cause mortality 90 days after discharge. Recovery was defined as hospital discharge and sustained recovery as recovery and alive without readmissions for 14 consecutive days.Among 3,386 patients included in the study 2,796 (82.6%) reached recovery and 2,600 (77.0%) achieved sustained recovery. Of those discharged from hospital, 556 (19.9%) were readmitted, and 289 (10.3%) died. Overall, the median time to recovery was 6 days (Interquartile range (IQR), 3-10), and 19 days (IQR, 11-33) among patients in intensive care in the first two days of admission.Post-discharge readmission and mortality rates were substantial. Therefore, sustained recovery should be favored to recovery outcomes in clinical COVID-19 trials. A 28-day follow-up period may be too short the critically ill.

Before introducing combination antiretroviral therapy (cART), a higher prevalence of emphysema in people living with HIV (PLWH) than in the background population was reported. This systematic literature review aimed to investigate the prevalence of emphysema in PLWH and to compare the prevalence between PLWH and controls in the current cART era. A systematic literature search was conducted in PubMed, EMBASE, Scopus, and Web of Science (WOS), searching for “human immunodeficiency virus (HIV)” and “emphysema” from January 1, 2000 to March 10, 2021. Eligible studies were published after the introduction of cART, included PLWH, and reported the prevalence of emphysema. A total of 17 studies were included, and nine studies also included controls. The weighted average prevalence of emphysema in PLWH was 23% (95% CI: 16–30). In studies including both PLWH and controls the weighted average prevalence were 22% (95% CI: 10–33) and 9.7% (95% CI: 2.3–17), respectively (p = 0.052). The prevalence of emphysema in never-smoking PLWH and controls was just reported in one study and was 18 and 4%, respectively (p < 0.01). Thirteen of the studies had a moderate risk of bias, mainly due to selection of patients. A tendency to higher prevalence of emphysema was found in PLWH in comparison to controls in the current cART era. However, in the included studies, the definition of emphysema varied largely. Thus, to have a clear overview of the prevalence, further studies with well-designed cohorts of PLWH and controls are warranted.

OBJECTIVE:: Use of antibiotics in critically ill patients may increase the risk of invasive Candida infection. The objective of this study was to determine whether increased exposure to antibiotics is associated with increased prevalence of invasive Candida infection.DESIGN:: Substudy using data from a randomized controlled trial, the Procalcitonin And Survival Study 2006-2010.SETTING:: Nine multidisciplinary ICUs across Denmark.PATIENTS:: A total of 1,200 critically ill patients.INTERVENTION:: Patients were randomly allocated to either a "high exposure" antibiotic therapy (intervention arm, n = 604) or a "standard exposure" guided by current guidelines (n = 596).MEASUREMENTS AND MAIN RESULTS:: Seventy-four patients met the endpoint, "invasive Candida infection," 40 in the high exposure arm and 34 in standard exposure arm (relative risk = 1.2; 95% CI, 0.7-1.8; p = 0.52). Among medical patients in the high exposure arm, the use of ciprofloxacin and piperacillin/tazobactam was 51% and 75% higher than in the standard exposure arm; no difference in antibiotic exposure was observed between the randomized arms in surgical patients. Among medical intensive care patients, invasive Candida infection was more frequent in the high exposure arm (6.2%; 27/437) than in standard exposure arm (3.3%; 14/424) (hazard ratio = 1.9; 95% CI, 1.0-3.6; p = 0.05). Ciprofloxacin used at study entry independently predicted invasive Candida infection (adjusted hazard ratio = 2.1 [1.1-4.1]); the risk gradually increased with duration of ciprofloxacin therapy: six of 384 in patients not exposed (1.6%), eight of 212 (3.8%) when used for 1-2 days (hazard ratio = 2.5; 95% CI, 0.9-7.3), and 31 of 493 (6.3%) when used for 3 days (hazard ratio = 3.8; 95% CI, 1.6-9.3; p = 0.002). Patients with any ciprofloxacin-containing antibiotic regimen the first 3 days in the trial had a higher risk of invasive Candida infection than did patients on any antibiotic regimen not containing ciprofloxacin (unadjusted hazard ratio = 3.7; 95% CI, 1.6-8.7; p = 0.003; adjusted hazard ratio, 3.4; 95% CI, 1.4-8.0; p = 0.006).CONCLUSIONS:: High exposure to antibiotics is associated to increased risk of invasive Candida infection in medical intensive care patients. Patients with ciprofloxacin-containing regimens had higher risk of invasive Candida infection. Other antibiotics, such as meropenem, piperacillin/tazobactam, and cefuroxime, were not associated with such a risk.