Return to work and health-related quality of life up to 1 year in patients hospitalized for COVID-19: the CO-FLOW study.

BACKGROUND: Currently, evidence about the long-term consequences of COVID-19 on return to work and health-related quality of life (HRQoL) is limited. We evaluated return to work and its associations with baseline characteristics and physical and mental recovery over time in patients up to 1 year after hospitalization for COVID-19. Secondly, we aimed to evaluate the association between return to work and health-related quality of life (HRQoL). METHODS: CO-FLOW, a multicenter prospective cohort study, enrolled adult participants hospitalized for COVID-19, aged ≥ 18 years within 6 months after hospital discharge. Return to work and HRQoL were collected at 3, 6, and 12 months after hospital discharge using the iMTA Productivity Cost Questionnaire and the 36-Item Short Form Health Survey, respectively. Data were collected between July 1, 2020, and September 1, 2022. Generalized estimating equations with repeated measurements were used to assess outcomes over time. RESULTS: In the CO-FLOW study, 371 participants were employed pre-hospitalization. At 3, 6, and 12 months post-discharge, 50% (170/342), 29% (92/317), and 15% (44/295) of participants had not returned to work, and 21% (71/342), 21% (65/317), and 16% (48/295) only partially, respectively. ICU admission (adjusted odds ratio (95% confidence interval): 0.17 (0.10 to 0.30), p < 0.001), persistent fatigue (0.93 (0.90 to 0.97), p < 0.001), female sex (0.57 (0.36 to 0.90), p = 0.017), and older age (0.96 (0.93 to 0.98), p < 0.001) were independently associated with no return to work. ICU patients required a longer time to return to work than non-ICU patients. Patients who did not return or partially returned to work reported lower scores on all domains of HRQoL than those who fully returned. CONCLUSIONS: One year after hospitalization for COVID-19, only 69% of patients fully returned to work, whereas 15% did not return and 16% partially returned to work. No or partial return to work was associated with reduced HRQoL. This study suggests that long-term vocational support might be needed to facilitate return to work. TRIAL REGISTRATION: World Health Organization International Clinical Trials Registry Platform NL8710.

The smell of lung disease: a review of the current status of electronic nose technology.

There is a need for timely, accurate diagnosis, and personalised management in lung diseases. Exhaled breath reflects inflammatory and metabolic processes in the human body, especially in the lungs. The analysis of exhaled breath using electronic nose (eNose) technology has gained increasing attention in the past years. This technique has great potential to be used in clinical practice as a real-time non-invasive diagnostic tool, and for monitoring disease course and therapeutic effects. To date, multiple eNoses have been developed and evaluated in clinical studies across a wide spectrum of lung diseases, mainly for diagnostic purposes. Heterogeneity in study design, analysis techniques, and differences between eNose devices currently hamper generalization and comparison of study results. Moreover, many pilot studies have been performed, while validation and implementation studies are scarce. These studies are needed before implementation in clinical practice can be realised. This review summarises the technical aspects of available eNose devices and the available evidence for clinical application of eNose technology in different lung diseases. Furthermore, recommendations for future research to pave the way for clinical implementation of eNose technology are provided.

Urine and plasma metabolites predict the development of diabetic nephropathy in individuals with Type 2 diabetes mellitus.

AIMS: Early detection of individuals with Type 2 diabetes mellitus or hypertension at risk for micro- or macroalbuminuria may facilitate prevention and treatment of renal disease. We aimed to discover plasma and urine metabolites that predict the development of micro- or macroalbuminuria. METHODS: Patients with Type 2 diabetes (n = 90) and hypertension (n = 150) were selected from the community-cohort 'Prevention of REnal and Vascular End-stage Disease' (PREVEND) and the Steno Diabetes Center for this case-control study. Cases transitioned in albuminuria stage (from normo- to microalbuminuria or micro- to macroalbuminuria). Controls, matched for age, gender, and baseline albuminuria stage, remained in normo- or microalbuminuria stage during follow-up. Median follow-up was 2.9 years. Metabolomics were performed on plasma and urine. The predictive performance of a metabolite for albuminuria transition was assessed by the integrated discrimination index. RESULTS: In patients with Type 2 diabetes with normoalbuminuria, no metabolites discriminated cases from controls. In patients with Type 2 diabetes with microalbuminuria, plasma histidine was lower (fold change = 0.87, P = 0.02) and butenoylcarnitine was higher (fold change = 1.17, P = 0.007) in cases vs. controls. In urine, hexose, glutamine and tyrosine were lower in cases vs. controls (fold change = 0.20, P < 0.001; 0.32, P < 0.001; 0.51, P = 0.006, respectively). Adding the metabolites to a model of baseline albuminuria and estimated glomerular filtration rate metabolites improved risk prediction for macroalbuminuria transition (plasma integrated discrimination index = 0.28, P < 0.001; urine integrated discrimination index = 0.43, P < 0.001). These metabolites did not differ between hypertensive cases and controls without Type 2 diabetes. CONCLUSIONS: Type 2 diabetes-specific plasma and urine metabolites were discovered that predict the development of macroalbuminuria beyond established renal risk markers. These results should be confirmed in a large, prospective cohort.

A urinary peptide biomarker set predicts worsening of albuminuria in type 2 diabetes mellitus.

AIMS/HYPOTHESIS: Microalbuminuria is considered the first clinical sign of kidney dysfunction and is associated with a poor renal and cardiovascular prognosis in type 2 diabetes. Detection of patients who are prone to develop micro- or macroalbuminuria may represent an effective strategy to start or optimise therapeutic intervention. Here we assessed the value of a urinary proteomic-based risk score (classifier) in predicting the development and progression of microalbuminuria. METHODS: We conducted a prospective case-control study. Cases (n = 44) and controls (n = 44) were selected from the PREVEND (Prevention of Renal and Vascular End-stage Disease) study and from the Steno Diabetes Center (Gentofte, Denmark). Cases were defined by transition from normo- to microalbuminuria or from micro- to macroalbuminuria over a follow-up of 3 years. Controls with no transitions in albuminuria were pair-matched for age, sex and albuminuria status. A model for the progression of albuminuria was built using a proteomic classifier based on 273 urinary peptides. RESULTS: The proteomic classifier was independently associated with transition to micro- or macroalbuminuria (OR 1.35 [95% CI 1.02, 1.79], p = 0.035). The classifier predicted the development and progression of albuminuria on top of albuminuria and estimated GFR (eGFR, area under the receiver operating characteristic [ROC] curve increase of 0.03, p = 0.002; integrated discrimination index [IDI]: 0.105, p = 0.002). Fragments of collagen and α-2-HS-glycoprotein showed significantly different expression between cases and controls. CONCLUSIONS/INTERPRETATION: Although limited by the relatively small sample size, these results suggest that analysis of a urinary biomarker set enables early renal risk assessment in patients with diabetes. Further work is required to confirm the role of urinary proteomics in the prevention of renal failure in diabetes.

Validity of biomarkers predicting onset or progression of nephropathy in patients with Type 2 diabetes: a systematic review.

Novel biomarkers predicting onset or progression of nephropathy in patients with Type 2 diabetes have been recently identified. We performed a systematic review to assess the validity of biomarkers predicting onset or progression of nephropathy in patients with Type 2 diabetes in longitudinal studies. The methodological quality of the studies was scored using Standards for Reporting of Diagnostic Accuracy (STARD) criteria and the independent predictive value of the biomarkers beyond conventional risk factors was scored according to the adjustment for these risk factors. Validity of the biomarkers was determined by summarizing the methodological quality and the adjustment score. We identified 15 studies describing 27 biomarkers. Six studies had sufficient methodological quality. These studies identified 13 valid and significant markers for nephropathy in diabetes: serum interleukin 18, plasma asymmetric dimethylarginine; and urinary ceruloplasmin, immunoglobulin G and transferrin were considered valid markers predicting onset of nephropathy. Plasma asymmetric dimethylarginine, vascular cell adhesion molecule 1, interleukin 6, von Willebrand factor and intercellular cell adhesion molecule 1 were considered valid biomarkers predicting progression of nephropathy. Plasma high-sensitivity C-reactive protein, E-selectin, tissue-type plasminogen activator, von Willebrand factor and triglycerides were considered valid markers predicting onset and progression of nephropathy. Several novel biomarkers for prediction of nephropathy in diabetes have been published, which can potentially be applied in clinical practice and research in future. Because of the heterogeneous quality of biomarker studies in this field, a more rigorous evaluation of these biomarkers and validation in larger trials are advocated.

Former smoking is a risk factor for chronic kidney disease after lung transplantation.

Chronic kidney disease (CKD) is a common complication after lung transplantation (LTx). Smoking is a risk factor for many diseases, including CKD. Smoking cessation for >6 months is required for LTx enlistment. However, the impact of smoking history on CKD development after LTx remains unclear. We investigated the effect of former smoking on CKD and mortality after LTx. CKD was based on glomerular filtration rate (GFR) ((125) I-iothalamate measurements). GFR was measured before and repeatedly after LTx. One hundred thirty-four patients never smoked and 192 patients previously smoked for a median of 17.5 pack years. At 5 years after LTx, overall cumulative incidences of CKD-III, CKD-IV and death were 68.5%, 16.3% and 34.6%, respectively. Compared to never smokers, former smokers had a higher risk for CKD-III (hazard ratio [HR] 95% confidence interval [95%CI]= 1.69 [1.27-2.24]) and IV (HR = 1.90 [1.11-3.27]), but not for mortality (HR = 0.99 [0.71-1.38]). Adjustment for potential confounders did not change results. Thus, despite cessation, smoking history remained a risk factor for CKD in LTx recipients. Considering the increasing acceptance for LTx of older recipients with lower baseline renal function and an extensive smoking history, our data suggest that the problem of post-LTx CKD may increase in the future.