Introduction Illnesses requiring hospitalization are known to negatively impact psychological well-being and health-related quality of life (HRQoL) after discharge. The impact of hospitalization during the Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) pandemic on psychological well-being and health-related quality of life is expected to be higher due to the exceptional circumstances within and outside the hospital during the pandemic surge. The objective of this study was to quantify psychological distress up to three months after discharge in patients hospitalized during the first coronavirus disease 2019 (COVID-19) pandemic wave. We also aimed to determine HRQoL, to explore predictors for psychological distress and HRQoL, and to examine whether psychological distress was higher in COVID-19 confirmed patients, and in those treated in Intensive Care Units (ICUs). Methods In this single-center, observational cohort study, adult patients hospitalized with symptoms suggestive of COVID-19 between March 16 and April 28, 2020, were enrolled. Patients were stratified in analyses based on SARS-CoV-2 PCR results and the necessity for ICU treatment. The primary outcome was psychological distress, expressed as symptoms of post-traumatic stress disorder (PTSD), anxiety, and depression, up to three months post-discharge. Health-related quality of life (HRQoL) was the secondary outcome. Exploratory outcomes comprised predictors for psychological distress and HRQoL. Results 294 of 622 eligible patients participated in this study (median age 64 years, 36% female). 16% and 13% of these patients reported probable PTSD, 29% and 20% probable anxiety, and 32% and 24% probabledepression at one and three months after hospital discharge, respectively. ICU patients reported less frequently probable depression, but no differences were found in PTSD, anxiety, or overall HRQoL. COVID-19 patients had a worse physical quality of life one month after discharge, and ICU patients reported a better mental quality of life three months after discharge. PTSD severity was predicted by time after discharge and being Caucasian. Severity of anxiety was predicted by time after discharge and being Caucasian. Depression severity was predicted by time after discharge and educational level. Conclusion COVID-19 suspected patients hospitalized during the pandemic frequently suffer from psychological distress and poor health-related quality of life after hospital discharge. Non-COVID-19 and non-ICU patients appear to be at least as affected as COVID-19 and ICU patients, underscoring that (post-)hospital pandemic care should not predominantly focus on COVID-19 infected patients.

IMPORTANCE Hyperoxemia may increase organ dysfunction in critically ill patients, but optimal oxygenation targets are unknown.OBJECTIVE To determine whether a low-normal PaO 2 target compared with a high-normal target reduces organ dysfunction in critically ill patients with systemic inflammatory response syndrome (SIRS).DESIGN, SETTING, AND PARTICIPANTS Multicenter randomized clinical trial in 4 intensive care units in the Netherlands. Enrollment was from February 2015 to October 2018, with end of follow-up to January 2019, and included adult patients admitted with 2 or more SIRS criteria and expected stay of longer than 48 hours. A total of 9925 patients were screened for eligibility, of whom 574 fulfilled the enrollment criteria and were randomized.INTERVENTIONS Target PaO 2 ranges were 8 to 12 kPa (low-normal, n = 205) and 14 to 18 kPa (high-normal, n = 195). An inspired oxygen fraction greater than 0.60 was applied only when clinically indicated.MAIN OUTCOMES AND MEASURES Primary end point was SOFA RANK , a ranked outcome of nonrespiratory organ failure quantified by the nonrespiratory components of the Sequential Organ Failure Assessment (SOFA) score, summed over the first 14 study days. Participants were ranked from fastest organ failure improvement (lowest scores) to worsening organ failure or death (highest scores). Secondary end points were duration of mechanical ventilation, in-hospital mortality, and hypoxemic measurements. RESULTS Among the 574 patients who were randomized, 400 (70%) were enrolled within 24 hours (median age, 68 years; 140 women [35%]), all of whom completed the trial. The median PaO 2 difference between the groups was −1.93 kPa (95% CI, −2.12 to −1.74; P < .001). The median SOFA RANK score was −35 points in the low-normal PaO 2 group vs −40 in the high-normal PaO 2 group (median difference, 10 [95% CI, 0 to 21]; P = .06). There was no significant difference in median duration of mechanical ventilation (3.4 vs 3.1 days; median difference, −0.15 [95% CI, −0.88 to 0.47]; P = .59) and in-hospital mortality (32% vs 31%; odds ratio, 1.04 [95% CI, 0.67 to 1.63]; P = .91). Mild hypoxemic measurements occurred more often in the low-normal group (1.9% vs 1.2%; median difference, 0.73 [95% CI, 0.30 to 1.20]; P < .001). Acute kidney failure developed in 20 patients (10%) in the low-normal PaO 2 group and 21 patients (11%) in the high-normal PaO 2 group, and acute myocardial infarction in 6 patients (2.9%) in the low-normal PaO 2 group and 7 patients (3.6%) in the high-normal PaO 2 group.CONCLUSIONS AND RELEVANCE Among critically ill patients with 2 or more SIRS criteria, treatment with a low-normal PaO 2 target compared with a high-normal PaO 2 target did not result in a statistically significant reduction in organ dysfunction. However, the study may have had limited power to detect a smaller treatment effect than was hypothesized.

BackgroundRecovery of thymopoiesis after allogeneic hematopoietic stem cell transplantation is considered pivotal for full immune competence. However, it is still unclear to what extent insufficient recovery of thymopoiesis predicts for subsequent opportunistic infections and non-relapse mortality. Design and MethodsA detailed survey of all post-engraftment infectious complications, non-relapse mortality and overall survival during long-term follow-up was performed in 83 recipients of allogeneic stem cell grafts after myeloablative conditioning. Recovery of thymopoiesis was assessed using analysis of signal joint T-cell receptor rearrangement excision circles. The impact of recovery of thymopoiesis at 2, 6, 9 and 12 months post-transplantation on clinical outcome beyond those time points was evaluated by univariate and multivariate Cox regression analyses. ResultsThe cumulative incidence of severe infections at 12 months after transplantation was 66% with a median number of 1.64 severe infectious episodes per patient. Patients in whom thymopoiesis did not recover were at significantly higher risk of severe infections according to multivariable analysis. Hazard ratios indicated 3-and 9-fold increases in severe infections at 6 and 12 months, respectively. Impaired recovery of thymopoiesis also translated into a higher risk of non-relapse mortality and outweighed pre-transplant risk factors including age, donor type, and disease risk-status. ConclusionsThese results indicate that patients who fail to recover thymopoiesis after allogeneic hematopoietic stem cell transplantation are at very high risk of severe infections and adverse clinical outcome.Key words: thymopoiesis, opportunistic infections, transplantation outcome, TREC. Haematologica 2011;96(12):1846-1854. doi:10.3324/haematol.2011 This is an open-access paper. Citation: Wils E-J, van der Holt B, Broers AEC, Posthumus-van Sluijs SJ, Gratama J-W, Braakman E and Cornelissen JJ. Insufficient recovery of thymopoiesis predicts for opportunistic infections in allogeneic hematopoietic stem cell transplant recipients. Insufficient recovery of thymopoiesis predicts for opportunistic infections in allogeneic hematopoietic stem cell transplant recipients

Obesity is an established risk factor for severe coronavirus disease 2019 , but the contribution of overweight and/or diabetes remains unclear. In a multicenter, international study, we investigated if overweight, obesity, and diabetes were independently associated with COVID-19 severity and whether the BMIassociated risk was increased among those with diabetes. RESEARCH DESIGN AND METHODSWe retrospectively extracted data from health care records and regional databases of hospitalized adult patients with COVID-19 from 18 sites in 11 countries. We used standardized definitions and analyses to generate site-specific estimates, modeling the odds of each outcome (supplemental oxygen/noninvasive ventilatory support, invasive mechanical ventilatory support, and in-hospital mortality) by BMI category (reference, overweight, obese), adjusting for age, sex, and prespecified comorbidities. Subgroup analysis was performed on patients with preexisting diabetes. Sitespecific estimates were combined in a meta-analysis. RESULTSAmong 7,244 patients (65.6% overweight/obese), those with overweight were more likely to require oxygen/noninvasive ventilatory support (random effects adjusted odds ratio [aOR], 1.44; 95% CI 1.15-1.80) and invasive mechanical ventilatory support (aOR, 1.22; 95% CI 1.03-1.46). There was no association between overweight and in-hospital mortality (aOR, 0.88; 95% CI 0.74-1.04). Similar effects were observed in patients with obesity or diabetes. In the subgroup analysis, the aOR for any outcome was not additionally increased in those with diabetes and overweight or obesity. CONCLUSIONSIn adults hospitalized with COVID-19, overweight, obesity, and diabetes were associated with increased odds of requiring respiratory support but were not associated with death. In patients with diabetes, the odds of severe COVID-19 were not increased above the BMI-associated risk.

Purpose: Individualising drug dosing using model-informed precision dosing (MIPD) of beta-lactam antibiotics and ciprofloxacin has been proposed as an alternative to standard dosing to optimise antibiotic efficacy in critically ill patients. However, randomised clinical trials (RCT) on clinical outcomes have been lacking. Methods:This multicentre RCT, including patients admitted to the intensive care unit (ICU) who were treated with antibiotics, was conducted in eight hospitals in the Netherlands. Patients were randomised to MIPD with dose and interval adjustments based on monitoring serum drug levels (therapeutic drug monitoring) combined with pharmacometric modelling of beta-lactam antibiotics and ciprofloxacin. The primary outcome was ICU length of stay (LOS). Secondary outcomes were ICU mortality, hospital mortality, 28-day mortality, 6-month mortality, delta sequential organ failure assessment (SOFA) score, adverse events and target attainment. Results:In total, 388 (MIPD n = 189; standard dosing n = 199) patients were analysed (median age 64 ). We found no significant differences in ICU LOS between MIPD compared to standard dosing (10 MIPD vs 8 standard dosing; IRR = 1.16; 95% CI 0.96-1.41; p = 0.13). There was no significant difference in target attainment before intervention at day 1 (T1) (55.6% MIPD vs 60.9% standard dosing; p = 0.24) or at day 3 (T3) (59.5% vs 60.4%; p = 0.84). There were no significant differences in other secondary outcomes. Conclusions:We could not show a beneficial effect of MIPD of beta-lactam antibiotics and ciprofloxacin on ICU LOS in critically ill patients. Our data highlight the need to identify other approaches to dose optimisation.