Health-Related Quality of Life according to Renal Function: Results from a Nationwide Health Interview and Examination Survey.

BACKGROUND: Most studies on health-related quality of life (HRQoL) in chronic kidney disease (CKD) focus on patients with end-stage kidney disease although they represent a small proportion of patients with CKD. We aimed to analyze HRQoL according to glomerular filtration rate (GFR) categories in a population-based sample of adults living in Germany. METHODS: Data from the German health interview and examination survey conducted from 2008 to 2011 were used. Participants with valid interview and examination data aged 40-79 years were included (n = 5,159). Serum creatinine levels were used to calculate estimated GFR via the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. We classified kidney function in GFR categories according to the Kidney Disease Improving Global Outcomes Initiative (KDIGO) guidelines on CKD: G1 (high): ≥90 mL/min/1.73 m2, G2 (normal): 60-89 mL/min/1.73 m2, G3a (mildly decreased): 45-59 mL/min/1.73 m2, G3b (moderately decreased): 30-44 mL/min/1.73 m2, G4/5 (severely decreased/end-stage kidney disease): <30 mL/min/1.73 m2. HRQoL was evaluated with the Short Form Health Survey (SF-36). Different multivariate linear and logistic regression models were used to analyze the association of HRQoL with GFR categories. RESULTS: Overall, 5.9% had a GFR <60 mL/min/1.73 m2 (corresponding to categories G3a, G3b, and G4/5). Compared to category G2 linear regression showed a decline in physical HRQoL in categories G3a (-2.34, p = 0.004), G3b (-5.37, p = 0.009), and G4/5 (-4.82, p = 0.117). No decline in mental HRQoL was detected with increasing GFR categories. Categories G3a to G4/5 were significantly associated with a low perceived general state of health (G3a: odds ratio [OR] = 2.03, p = 0.001; G3b: OR = 3.01, p = 0.009; G4/5: OR = 8.70, p = 0.016) when compared to category G2. CONCLUSION: In a representative sample of adults living in Germany, both physical HRQoL and the perceived general state of health are already significantly reduced in category G3a.

Use of oral anticoagulants in German nursing home residents: drug use patterns and predictors for treatment choice.

AIMS: Information on utilization of oral anticoagulants (OACs) in nursing homes is scarce. This study aimed to (i) describe OAC use in German nursing home residents, (ii) examine factors influencing whether treatment is initiated with vitamin K antagonists (VKAs) or non-VKA oral anticoagulants (NOACs) and (iii) assess which conditions predict switching to NOAC instead of continuing VKA. METHODS: Using claims data (2010-2014), we studied a cohort of new nursing home residents aged ≥65 years receiving OAC. Further, OAC use in patients with atrial fibrillation (AF) was examined over the years. RESULTS: Overall, 16 804 patients (median age: 85 years, 75% female, 44% with renal disease) were included. The majority received phenprocoumon as first OAC (58.0%), followed by rivaroxaban (28.1%). Over the study period, NOAC use increased substantially. Initiating NOAC instead of VKA was predicted by a previous stroke (adjusted odds ratio: 1.76; 95% confidence interval: 1.49-2.08). In contrast, renal disease predicted VKA initiation (0.66; 0.59-0.75) as did the presence of a prosthetic heart valve. Switching from VKA to NOAC was predicted by a stroke (2.55; 2.00-3.24), bleeding events and a recent hospitalization. During 2010-2014, the proportion of AF patients with a CHADS2 score ≥2 receiving OAC increased from 27% to 46%. CONCLUSIONS: NOACs are increasingly used in German nursing homes, both for initial anticoagulation but also in VKA pre-treated patients. Switching from VKA to NOAC was substantially influenced by aspects such as intended higher effectiveness and safety but probably also practicability due to less blood monitoring.

Permanent Decline of Renal Function after Infrarenal Abdominal Aortic Aneurysm Repair-Frequency and Risk Factors.

BACKGROUND: Permanent renal function decline, and development and deterioration of chronic kidney disease (CKD) are associated with serious complications. How frequent is renal function decline after infrarenal abdominal aortic aneurysm (iAAA) repair according to current definitions and what are its risk factors, especially potentially modifiable ones? METHODS: Retrospective observational study including all patients with elective or urgent iAAA repair from 2007 to 2011. The primary outcome was renal function decline in the first year after iAAA repair, defined as permanent reduction of estimated glomerular filtration rate (eGFR) ≥20% from baseline and/or end-stage renal disease (ESRD), all in the first year after iAAA repair. According to current Kidney Disease Improving Global Outcomes guidelines, CKD and periprocedural AKI were defined and classified. Multivariate Cox proportional hazards model was used to assess associations of the primary end point with potential risk factors. RESULTS: Two hundred sixty-eight patients with iAAA repair were studied, 61 patients (22.7%) developed declining eGFR ≥20% and/or ESRD. The primary end point was independently associated with preexisting CKD (hazard ratio [HR] 3.14 [1.61-6.09]), renal artery stenosis (RAS) ≥70% (HR 4.34 [1.49-12.67]), open aortic aneurysm repair (OAR) (HR 1.69 [1.14-2.68]), and periprocedural AKI (HR 15.25 [7.49-31.05]). When comparing the subsets of patients with and without OAR and periprocedural AKI, these 2 modifiable risk factors had an additive impact. Declining eGFR ≥20% and/or ESRD was most frequent in patients receiving OAR who developed AKI. CONCLUSIONS: A permanent decline of renal function 1 year after iAAA repair is frequent. Preexisting CKD, RAS ≥70%, OAR, and periprocedural AKI are independent risk factors, the latter 2 with additive effect.

Acute kidney injury prediction in cardiac surgery patients by a urinary peptide pattern: a case-control validation study.

BACKGROUND: Acute kidney injury (AKI) is a prominent problem in hospitalized patients and associated with increased morbidity and mortality. Clinical medicine is currently hampered by the lack of accurate and early biomarkers for diagnosis of AKI and the evaluation of the severity of the disease. In 2010, we established a multivariate peptide marker pattern consisting of 20 naturally occurring urinary peptides to screen patients for early signs of renal failure. The current study now aims to evaluate if, in a different study population and potentially various AKI causes, AKI can be detected early and accurately by proteome analysis. METHODS: Urine samples from 60 patients who developed AKI after cardiac surgery were analyzed by capillary electrophoresis-mass spectrometry (CE-MS). The obtained peptide profiles were screened by the AKI peptide marker panel for early signs of AKI. Accuracy of the proteomic model in this patient collective was compared to that based on urinary neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) ELISA levels. Sixty patients who did not develop AKI served as negative controls. RESULTS: From the 120 patients, 110 were successfully analyzed by CE-MS (59 with AKI, 51 controls). Application of the AKI panel demonstrated an AUC in receiver operating characteristics (ROC) analysis of 0.81 (95 % confidence interval: 0.72-0.88). Compared to the proteomic model, ROC analysis revealed poorer classification accuracy of NGAL and KIM-1 with the respective AUC values being outside the statistical significant range (0.63 for NGAL and 0.57 for KIM-1). CONCLUSIONS: This study gives further proof for the general applicability of our proteomic multimarker model for early and accurate prediction of AKI irrespective of its underlying disease cause.

[Medical services for nursing home residents : Results of the study on inappropriate medication in patients with renal insufficiency in nursing homes]. / Ärztliche Versorgung von Pflegeheimbewohnern : Ergebnisse der Studie "Inappropriate medication in patients with renal insufficiency in nursing homes".

BACKGROUND: In Germany approximately 800,000 people are living in nursing homes. Outpatient medical treatment is provided by general practitioners (GP) and a variety of medical specialists. While nearly all residents have regular contact with GPs, care by specialists differs between the various disciplines. AIM: In this study an assessment of medical treatment for nursing home residents by GPs and specialists was made and compared with the available diagnoses. MATERIAL AND METHODS: Between October 2014 and April 2015 a cross-sectional study was conducted in nursing homes in Bremen and the surrounding areas. Anonymized data based on residents' files were collated by nursing staff. Every contact with various specialists within the preceding 12 months was assessed and grouped into (a) no physician visit, (b) resident visited physician and (c) physician visited resident. Analyses were stratified for age, sex and level of care dependency as well as dementia and further comorbidities. RESULTS: A total of 852 residents in 21 nursing homes were included (mean age 83.5 years, 76.5 % female) in the study. Dementia was diagnosed in 57.7 %. Nearly all residents had had contact with their GP in the previous 12 months, mostly by home visits (96.9 %). The majority (54.5 %) had not seen a dentist in the preceding 12 months and 25.4 % had been visited by a dentist. Of the residents 47.4 % were visited by a neurologist or psychiatrist but only 4.5 % visited these specialists in their practice. Higher care dependency and younger age were associated with more frequent visits by neurologists and psychiatrists. Contact rates to ophthalmologists (29.3 %) and urologists (20.5 %) were less frequent. A diagnosis of diabetes mellitus had no influence on the contact rate with ophthalmologists. CONCLUSION: Medical care by specialists is characterized by huge variations. Besides a frequent contact rate with GPs there seems to be an undersupply regarding care by dentists and ophthalmologists.

Effects of fractionated plasma separation and adsorption on survival in patients with acute-on-chronic liver failure.

BACKGROUND & AIMS: Fractionated plasma separation and adsorption (FPSA) is an extracorporeal procedure that supports liver function by removing endogenous toxins that cause complications from acute-on-chronic liver failure (AOCLF). We performed a randomized trial to investigate survival of patients with AOCLF treated with FPSA. METHODS: Patients with AOCLF were randomly assigned to groups given a combination of FPSA and standard medical therapy (SMT) (FPSA group, n = 77) or only SMT (SMT group, n = 68). The Prometheus liver support system was used to provide 8 to 11 rounds of FPSA (minimum of 4 hours each) for 3 weeks. Primary end points were survival probabilities at days 28 and 90, irrespective of liver transplantation. RESULTS: Baseline clinical parameters and number of transplant patients were similar between study arms. Serum bilirubin level decreased significantly in the FPSA group but not in the SMT group. In an intention-to-treat analysis, the probabilities of survival on day 28 were 66% in the FPSA group and 63% in the SMT group (P = .70); on day 90, they were 47% and 38%, respectively (P = .35). Baseline factors independently associated with poor prognosis were high SOFA score, bleeding, female sex, spontaneous bacterial peritonitis, intermediate increases in serum creatinine concentration, and combination of alcoholic and viral etiology of liver disease. There were no differences between the 2 groups in the incidence of side effects. CONCLUSIONS: Among all patients with AOCLF, extracorporeal liver support with FPSA does not increase the probability of survival. Further studies are needed to assess whether therapy might be beneficial in specific subsets of patients.

Progressive chronic kidney disease in primary care: modifiable risk factors and predictive model.

OBJECTIVE: To determine the incidence and prevalence of CKD and of progressive GFR decline, to identify modifiable risk factors of and to develop a predictive risk model for progressive GFR decline in high risk primary care patients. METHODS: Retrospective observational study of 803 patients with or at high risk of CKD exclusively managed in primary care. Baseline data was collected in 2003, follow-up data in 2006. High risk was defined as inadequately controlled hypertension or diabetes, and GFR<60, progressive GFR decline as annual GFR decline >2.5mlmin(-1) 1.73m(-2). RESULTS: CKD was present in 25.4% at baseline and developed in further 13.7% during follow-up, 42.5% demonstrated progressive GFR decline. Obesity, proteinuria, heart failure, inadequate hypertension and diabetes control, lacking angiotensin-converting-enzyme-inhibitors or angiotensin-receptor-blockers, radio contrast, and dual renin-angiotensin-aldosterone-system blockade were identified as modifiable, independent risk factors of progressive GFR decline. The risk model, containing 7 readily obtainable variables, showed good discriminative ability. CONCLUSIONS: High risk primary care patients demonstrated high CKD prevalence and incidence, and rate of progressive GFR decline. Identified risk factors can be modified in primary care. Our risk model may aid primary care physicians to predict patients at high risk of progressive GFR decline.

Antioxidant treatment and outcome of Cortinarius orellanus poisoning: a case series.

OBJECTIVES: To study the frequency, severity, and long-term outcome of renal injury in Cortinarius orellanus poisoning, to evaluate the association between the ingested amount of C. orellanus and outcome, and to evaluate the effect of N-acetylcysteine and corticosteroid treatment on outcome. METHODS: Case series of eight patients. Diagnosis and severity of acute kidney injury (AKI) and chronic kidney disease (CKD) were classified according to current AKI and CKD definitions. N-acetylcysteine and corticosteroids were administered to six patients, former according to the standard for paracetamol poisoning. MAIN FINDINGS: All patients developed AKI, six in the most severe stage and four required renal replacement therapy (RRT). After 12 months, seven patients presented with CKD, of whom three required chronic RRT and further two were in advanced CKD. AKI and CKD severity highly correlated with the consumed amounts of Cortinarius orellanus (r = 0.98, p < 0.001 and r = 0.78, p = 0.02, respectively) but not with N-acetylcysteine and corticosteroid treatment. CONCLUSIONS: AKI and CKD by current definitions and classifications are frequent and severe after Cortinarius orellanus poisoning. The ingested amount of Cortinarius orellanus correlates with the severity of both AKI and CKD. N-acetylcysteine and corticosteroid treatment do not seem to have a beneficial effect on either AKI or CKD.

Effect of stress hyperglycaemia on acute kidney injury in non-diabetic critically ill patients?

BACKGROUND: Stress hyperglycaemia (SH) and acute kidney injury (AKI) occur frequently in critically ill patients, and particularly non-diabetics are associated with adverse outcome. Data is scarce on the effect of SH on AKI. We assessed whether SH (i) preceded AKI, (ii) was a risk factor of subsequent AKI, and (iii) how SH and tubular injury interacted in AKI development in critically ill, non-diabetics. METHODS: Case-control study of 82 patients each with and without SH matched by propensity score for multiple demographic characteristics. AKI was defined by KDIGO criteria, SH either as blood glucose (BG) > 140 mg/dl (BG140), > 200 mg/dl (BG200), or stress hyperglycemia rate (SHR) ≥ 1.47 (SHR1.47) as measured 2 days before AKI. Urinary cystatin C and neutrophil gelatinase-associated lipocalin (NGAL) indicated tubular injury. RESULTS: In AKI, SH rates were frequent using all 3 definitions applied, but highest when BG140 was applied. SH by all 3 definitions was consistently associated with AKI. This was independent of established risk factors of AKI such as sepsis and shock. Increments of BG, urinary NGAL or cystatin C, and its products, were independently associated with the likelihood of subsequent AKI, demonstrating their reciprocal potentiating effects on AKI development. CONCLUSIONS: SH is frequent in critically ill, non-diabetics with AKI. SH was identified as an independent risk factor of AKI. Higher BG combined with tubular injury may potentiate their adverse effects on AKI.

Definition and risk factors of rapidly declining residual renal function in peritoneal dialysis: an observational study.

BACKGROUND: It is critical to preserve residual renal function (RRF) in peritoneal dialysis (PD), as RRF is associated with lower morbidity and mortality. There is no uniform definition of RRF, and rapidly declining RRF has rarely been studied and predominately limited to single factor analysis and not corrected for lead-time bias. METHODS: An observational study in 71 incident PD patients. RRF was defined as urine output (UO) ≥500 ml/day and renal glomerular filtration rate (rGFR) ≥2 ml/min/1.73 m(2), rapid declining RRF as UO <500 ml/day and rGFR <2 ml/min/1.73 m(2) occurring within 6 months which were separately evaluated. Independent risk factors associated with rapid RRF decline were identified while correcting for lead-time bias. RESULTS: RRF declined rapidly by both definitions in 65% patients 2.5 years after PD start. Both definitions of RRF decline were consistent in 96%. Nephrotoxic drugs, renal transplant failure and absent angiotensin-converting enzyme inhibitors (ACEI) or angiotensin II receptor blockers (ARB) were independent risk factors associated with rapidly declining RRF defined both by definitions, intravascular radiocontrast additionally for UO decline. CONCLUSIONS: Most PD patients demonstrated rapid RRF decline, independent of its definition. Both definitions are highly consistent and interchangeable. Nephrotoxic drugs and radiocontrast were identified as risk factors of acute, absent ACEI or ARB, and renal transplant failure of chronic renal injury.

Naturally occurring human urinary peptides for use in diagnosis of chronic kidney disease.

Because of its availability, ease of collection, and correlation with physiology and pathology, urine is an attractive source for clinical proteomics/peptidomics. However, the lack of comparable data sets from large cohorts has greatly hindered the development of clinical proteomics. Here, we report the establishment of a reproducible, high resolution method for peptidome analysis of naturally occurring human urinary peptides and proteins, ranging from 800 to 17,000 Da, using samples from 3,600 individuals analyzed by capillary electrophoresis coupled to MS. All processed data were deposited in an Structured Query Language (SQL) database. This database currently contains 5,010 relevant unique urinary peptides that serve as a pool of potential classifiers for diagnosis and monitoring of various diseases. As an example, by using this source of information, we were able to define urinary peptide biomarkers for chronic kidney diseases, allowing diagnosis of these diseases with high accuracy. Application of the chronic kidney disease-specific biomarker set to an independent test cohort in the subsequent replication phase resulted in 85.5% sensitivity and 100% specificity. These results indicate the potential usefulness of capillary electrophoresis coupled to MS for clinical applications in the analysis of naturally occurring urinary peptides.

Current equations estimating glomerular filtration rate in primary care: comparison and determinants.

OBJECTIVE: The aims of this study were to compare estimated glomerular filtration rate (eGFR) by Modification of Diet in Renal Disease (MDRD) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations, to assess the classification of chronic kidney disease (CKD) stages by both equations, and to identify factors associated with differences between both equations in patients with or at high risk of CKD managed in primary care. MATERIAL AND METHODS: This was an observational study of 803 patients with CKD, long-standing, severe hypertension and diabetes exclusively managed in primary care. Bias and precision between the two equations used to calculate eGFR were quantified as proposed by Bland and Altman. RESULTS: In 1534 eGFR calculations, mean eGFR(MDRD) was 0.8 ± 3.6 ml/min/1.73 m(2) higher than eGFR(CKD-EPI). Precision between the two equations was ±7.1 ml/min/1.73 m(2). Classification of CKD stages by MDRD or CKD-EPI equations agreed in 93.3% of cases. Age above 70 years, eGFR below 60 and above 120 ml/min/1.73 m(2) were associated with higher eGFR(MDRD) values; and age below 50 years and inadequately controlled hypertension with higher eGFR(CKD-EPI) values. CONCLUSIONS: Comparison of eGFR calculated by MDRD and CKD-EPI equations demonstrated no clinically relevant difference. In addition, CKD classification by both equations agreed highly. As both equations performed equally well, the simpler and more established MDRD equation should be preferred in patients with or at high risk of CKD managed in primary care. Patients' characteristics seem to account for previously reported differences in the performance of CKD-EPI and MDRD equations.

Incidence, severity, risk factors and outcomes of acute kidney injury in older adults: systematic review and meta-analysis.

OBJECTIVES: Old age was identified as a strong risk factor for acute kidney injury (AKI). Our objectives were to provide estimates of AKI, risk factors and outcomes in patients ≥ 75 years for whom data are scarce. METHODS: Observational studies and randomized controlled trials between 2005 and 2021 with patients of mean or median age ≥ 75 years, reporting AKI according to current definitions. Data on AKI incidence, risk factors and mortality were analyzed separately in unselected (UC) and acute heart failure (AHF) cohorts. RESULTS: Twenty-six observational studies and 4 randomized controlled trials with 51,111 UC and 25,414 AHF patients were included. Ages averaged 79.4 and 79.8 years, respectively. Pooled risk ratios (RRs) of AKI rates were 26.29% (95% confidence intervals (CI) 13.20-41.97) (UC) and 24.21% (95% CI 20.03-28.65) (AHF). In both cohorts, AKI was associated with decreased estimated glomerular filtration rate at baseline, chronic kidney disease (UC: RR 1.80 (95% CI 1.15-2.80), AHF: RR 1.51 (95% CI 1.26-1.95) and hypertension (UC: RR 1.30 (95% CI 1.09-1.56), AHF: RR 1.07 (95% CI 1.05-1.09). RRs of AKI in patients on renin-angiotensin-inhibitors were 0.87 (95% CI 0.78-0.97) and 0.88 (95% CI 0.78-0.98) in UC and AHF, respectively. AKI was consistently associated with increased risk of in-hospital mortality (UC: RR 3.15 (95% CI 2.28-4.35), AHF: RR 4.28 (95% CI 2.53-7.24). CONCLUSION: AKI is frequent in patients ≥ 75 years. While reduced renal function at baseline, CKD and hypertension were associated with AKI development, renin-angiotensin-inhibitors may be protective. Older AKI patients showed higher short-term mortality rates.

Does the euroSCORE equally well predict perioperative cardiac surgical risk for men and women?

The euroSCORE is a widely applied scoring system to estimate perioperative risk in patients undergoing cardiac surgery. It acknowledges an increased risk in women but does not apply a gender-specific weighing of individual risk indicators. We separately investigated the performance of the euroSCORE for men and women. Cardiac surgical patients operated in 2002 and 2003 (n = 1930) served as training group. Patients operated in 2004 served as validation group (n = 870). Using binary regression analysis, we developed a gender-specific model on the basis of the original euroSCORE risk indicators. The individual risk indicators were assigned gender-specific correlation coefficients. Applying ROC analysis to the validation group, the original euroSCORE performed well, with an area under curve (AUC) of 0.758, for men but poor, with an AUC 0.676, for women. After gender-specific re-weighing, ROC analysis revealed considerably improved predictive values of the modified euroSCORE. AUC for women increased to 0.755, AUC for men further increased to 0.772. The original euroSCORE failed to accurately predict perioperative mortality in women. A binary regression model, assigning a gender-specific weight to each of the risk indicators of the original euroSCORE, considerably improved the predictive power of the modified euroSCORE.

Tyrosine kinase inhibitors targeting vascular endothelial growth factor and the risk of aortic dissection-A pharmacovigilance analysis.

There are concerns by the United States Food and Drug Administration (FDA) regarding a potential link between tyrosine kinase inhibitors targeting vascular endothelial growth factor (VEGF-TKIs) and the risk of aortic dissection. Elevation of blood pressure induced by VEGF-TKIs has been discussed as part of the pathomechanism. To address this important safety issue, we conducted a large pharmacovigilance study assessing the risk of aortic dissection reporting associated with the use of VEGF-TKIs, thereby exploring the role of blood pressure. We queried the FDA Adverse Event Reporting System from 2004 to 2019 for reports including VEGF-TKIs and aortic dissection and estimated reporting odds ratios (RORs) and 95% confidence intervals (CIs) of aortic dissection associated with the use of VEGF-TKIs. Secondary analyses stratified by the strength of blood pressure elevation (≥10 mmHg vs. <10 mmHg increased systolic or diastolic bloods pressure) and pre-existing arterial hypertension. There were 81 reports of aortic dissection related to VEGF-TKIs during the study period. VEGF-TKIs were associated with an increased risk of aortic dissection reporting (ROR, 4.31; 95% CI, 3.43 to 5.42). The risk was higher among compounds strongly increasing blood pressure (ROR, 5.33; 95% CI, 3.88 to 7.32) than among compounds moderately increasing blood pressure (ROR, 2.79; 95% CI, 1.83 to 4.27). Pre-existing arterial hypertension did not modify the association. Overall, our study showed an increased risk of aortic dissection reporting associated with the use of VEGF-TKIs. Blood pressure elevation seems to play a role in the pathophysiology of this adverse effect.

SARS-CoV-2: Viral Loads of Exhaled Breath and Oronasopharyngeal Specimens in Hospitalized Patients with COVID-19.

BACKGROUND: SARS-CoV-2 seems mainly transmissible via respiratory droplets. We compared the time-dependent SARS-CoV-2 viral load in serial pharyngeal swab with exhaled breath (EB) samples of hospitalized COVID-19 patients. METHODS: In this prospective proof of concept study, we examined hospitalized patients who initially tested positive for SARS-CoV-2. Paired oronasopharyngeal swab and EB specimens were taken at different days of hospitalization. EB collection was performed through a simple, noninvasive method using an electret air filter-based device. SARS-CoV-2 RNA detection was determined with real-time quantitative reverse transcription polymerase chain reaction. RESULTS: Of 187 serial samples from 15 hospitalized patients, 87/87 oronasopharyngeal swabs and 70/100 EB specimens tested positive. Comparing the number of SARS-CoV-2 copies, the viral load of the oronasopharyngeal swabs was significantly higher (CI 99%, P<<0,001) than for EB samples. The mean viral load per swab was 7.97 × 106 (1.65 × 102-1.4 × 108), whereas EB samples showed 2.47 × 103 (7.19 × 101-2.94 × 104) copies per 20 times exhaling. Viral loads of paired oronasopharyngeal swab and EB samples showed no correlation. CONCLUSIONS: Assessing the infectiousness of COVID-19 patients merely through pharyngeal swabs might not be accurate. Exhaled breath could represent a more suitable matrix for evaluating infectiousness and might allow screening for superspreader individuals and widespread variants such as Delta.

Urinary excretion of twenty peptides forms an early and accurate diagnostic pattern of acute kidney injury.

Early and accurate detection of acute kidney injury (AKI) is needed to prevent the progression to chronic kidney disease and to improve outcome. Here we used capillary electrophoresis-mass spectrometry to identify urinary peptides predictive of AKI in a training set of 87 urine samples longitudinally collected from patients in an intensive care unit. Within this patient cohort, 16 developed AKI while 14 maintained normal renal function. The sequence of twenty peptides significantly associated with AKI was identified. They were found to be degradation products of six proteins. These formed a diagnostic pattern. Peptides of albumin, α-1-antitrypsin, and ß-2-microglobulin were upregulated but fragments of fibrinogen α and collagens 1 α(I) and 1 α(III) were downregulated in AKI. After cross-validation of the training set, a good diagnostic performance of the marker pattern was found with an area under the ROC curve of 0.91. This was confirmed in a blinded validation set of 20 patients in the intensive care unit and 31 allogeneic hematopoietic stem cell transplantation patients, of which 13 had and 18 had not experienced an episode of AKI. In comparison to more established markers of AKI such as serum cystatin C and urinary kidney injury molecule-1, interleukin-18, and neutrophil gelatinase associated-lipocalin, the proteomic marker pattern was found to be of superior prognostic value, detecting AKI up to 5 days in advance of the rise in serum creatinine.

Validation of the Clinical Frailty Scale for retrospective use in acute care.

PURPOSE: There is a considerable need to measure frailty retrospectively in clinical practice and research. We assessed agreement, accuracy, precision, and reliability of retrospectively compared with prospectively, and separately attained, retrospective Clinical Frailty Scale (CFS) scoring, respectively. METHODS: We studied 110 hospitalized patients aged ≥ 80 years, consisting of 70.9% females. Agreement was assessed by bias, accuracy by root mean square error (RMSE) and the percentages of one CFS scores within 20% and 30% of each other (P20 and P30), precision by interquartile ranges of the bias, and reliability by weighted Cohen's kappa (κ). RESULTS: Comparison of retrospective and prospective CFS scores demonstrated a modest bias of 0.26. Classification as robust, prefrail, or frail was generally correct in retrospectively compared to prospectively CFS scores. RMSE was low (0.28), while P20 and P30 values were high (90.0% and 96.6%, respectively). Precision of retrospective to predict prospective CFS scores was high with narrow interquartile ranges of 0 and 1. Reliability of retrospective with prospective CFS scores was high (κ = 0.89). Comparing two separately attained retrospective CFS scores demonstrated low bias (0.05) and RMSE (0.24), and a high P30 value (90.0%). Precision and interrater reliability of the comparison of retrospective CFS scores were high with narrow interquartile ranges and κ = 0.85. CONCLUSION: The retrospectively attained CFS score is a valid diagnostic instrument to measure frailty in older hospitalized patients with high agreement, accuracy, precision, and reliability compared to both prospective and separately attained CFS scores.

Drug interactions with oral anticoagulants in German nursing home residents: comparison between vitamin K antagonists and non-vitamin K antagonist oral anticoagulants based on two nested case-control studies.

BACKGROUND: Vitamin K antagonists (VKAs) are susceptible to drug-drug interactions. Non-VKA oral anticoagulants (NOACs) have a decreased sensitivity to pharmacokinetic interactions and might be therefore considered superior in patients treated with multiple drugs. The objective of this study was to compare the risk of serious bleeding associated with interacting drugs in German nursing home residents treated with VKA or NOAC. METHODS: Using claims data of new nursing home residents aged ≥ 65 years (2010-2014) we conducted separate nested case-control analyses within two cohorts of patients treated with VKA or NOAC, respectively. Cases were defined as patients hospitalized for serious bleeding. For each case, up to 20 controls were selected by risk-set sampling. Conditional logistic regression was used to obtain confounder-adjusted odds ratios (aORs) and 95% confidence intervals (CI) for the risk of bleeding associated with VKA or NOAC use and interacting drugs compared with the use of the respective oral anticoagulant alone. RESULTS: Among 127,227 new nursing home residents, 16,804 patients received oral anticoagulation. Based on 372 cases and 7281 matched controls, the highest risk of bleeding in VKA users was observed for the concomitant use of antibiotics (aOR 3.00; CI 2.11-4.27) vs. VKA use alone, followed by non-steroidal anti-inflammatory drugs (1.66; 1.13-2.43). Among 243 NOAC cases and 4776 matched controls, elevated risks for bleeding were observed for the use of heparins (2.05; 1.25-3.36) and platelet inhibitors (1.92; 1.36-2.72). CONCLUSIONS: Concomitant medication needs to be prescribed cautiously and monitored closely in nursing home residents treated with oral anticoagulants.

Capnocytophaga canimorsus - a potent pathogen in immunocompetent humans - systematic review and retrospective observational study of case reports.

Purpose: Severe and fatal Capnocytophaga canimorsus infection has been described in immunocompromised patients. Data of C. canimorsus infection in immunocompetent and risk factors of severe courses are missing. Our aims were to describe the epidemiology of C. canimorsus infection and to identify potential risk factors of sepsis and fatal outcome.Methods: Observational study and systematic review of all cases reported in immunocompetent subjects between 2002 and 2019.Results: A total of 128 cases of C. canimorsus infection in immunocompetent individuals were reported. Male gender comprised 74.2%, the median age was 58 years and 47.7% were admitted with sepsis. Case-fatality rate was 29.7% and especially high in septic patients (55.7%). Transmission by bite (OR = 2.37, 95% CI: 1.05-6.52) and incubation time ≤3 d (OR = 7.98; 95% CI: 2.33-27.34) were identified as risk factors of sepsis on admission, and early wound cleansing as protective (OR = 0.42; 95% CI: 0.14-0.96). Sepsis (OR = 23.67; 95% CI: 2.85-197.89) and septic shock (OR = 45.50; 95% CI: 3.08-676.55) were risk factors of fatal outcome, whereas early wound cleansing (OR = 0.05; 95% CI: 0.01-0.72), initial penicillin therapy with beta-lactamase inhibitors (OR = 0.48; 95% CI: 0.16-0.92) and surgical removal of infectious focus (OR = 0.38; 95% CI: 0.06-0.95) were protective factors.Conclusions: Immunocompetent patients with C. canimorsus infection frequently develop sepsis. A shorter incubation period in cases of sepsis might be related to higher infectious dose. Fatal outcome may be prevented by early wound cleansing, initial use of penicillins in combination with beta-lactamase inhibitors and surgical removal of an infectious focus.