The best solution down the line: an observational study on taurolidine- versus citrate-based lock solutions for central venous catheters in hemodialysis patients

Introduction To prevent infection and thrombosis of central venous catheters (CVCs) in hemodialysis patients, different CVC lock solutions are available. Taurolidine-based solutions and citrate in different concentrations are frequently used, but no definite conclusions with regard to superiority have been drawn. Methods In this retrospective, observational, multicenter study, we aimed to assess the risk for removal of CVC due to infection or catheter malfunction in hemodialysis patients with CVC access for different lock solutions: taurolidine, high-concentrated citrate (46.7%) and low-concentrated citrate (4 or 30%). A multivariable Cox-regression model was used to calculate hazard ratio's (HR). Results We identified 1514 patients (median age 65 years, 59% male). In 96 (6%) taurolidine-based lock solutions were used. In 1418 (94%) citrate-based lock solutions were used (high-concentrated 73%, low-concentrated 20%). Taurolidine-based lock solutions were associated with a significantly lower hazard for removal of CVC due to infection or malfunction combined (HR 0.34, 95% CI 0.19-0.64), and for removal of CVC due to infection or malfunction separately (HR 0.36, 95% CI 0.15-0.88 and HR0.33, 95% CI 0.14-0.79). High-concentrated citrate lock solutions were not associated with a decreased hazard for our outcomes, compared to low-concentrated citrate lock solutions. Conclusion Removal of CVC due to infection or catheter malfunction occurred less often with taurolidine-based lock solutions. We present the largest cohort comparing taurolidine- and citrate-based lock solutions yet. However, due to the retrospective observational nature of this study, conclusions with regard to superiority should be drawn with caution.Clinical epidemiolog

Precurved non-tunnelled catheters for haemodialysis are comparable in terms of infections and malfunction as compared to tunnelled catheters: A retrospective cohort study

Background: The main limitations of central venous catheters for haemodialysis access are infections and catheter malfunction. Our objective was to assess whether precurved non-tunnelled central venous catheters are comparable to tunnelled central venous catheters in terms of infection and catheter malfunction and to assess whether precurved non-tunnelled catheters are superior to straight catheters. Materials and methods: In this retrospective, observational cohort study, adult patients in whom a central venous catheter for haemodialysis was inserted between 2012 and 2016 were included. The primary endpoint was a combined endpoint consisting of the first occurrence of either an infection or catheter malfunction. The secondary endpoint was a combined endpoint of the removal of the central venous catheter due to either an infection or a catheter malfunction. Using multivariable analysis, cause-specific hazard ratios for endpoints were calculated for tunnelled catheter versus precurved non-tunnelled catheter, tunnelled catheter versus non-tunnelled catheter, and precurved versus straight nontunnelled catheter. Results: A total of 1603 patients were included. No difference in reaching the primary endpoint was seen between tunnelled catheters, compared to precurved non-tunnelled catheters (hazard ratio, 0.91; 95% confidence interval, 0.70– 1.19, p=0.48). Tunnelled catheters were removed less often, compared to precurved non-tunnelled catheters (hazard ratio, 0.65; 9

Recovery of dialysis patients with COVID-19 : health outcomes 3 months after diagnosis in ERACODA

Background. Coronavirus disease 2019 (COVID-19)-related short-term mortality is high in dialysis patients, but longer-term outcomes are largely unknown. We therefore assessed patient recovery in a large cohort of dialysis patients 3 months after their COVID-19 diagnosis. Methods. We analyzed data on dialysis patients diagnosed with COVID-19 from 1 February 2020 to 31 March 2021 from the European Renal Association COVID-19 Database (ERACODA). The outcomes studied were patient survival, residence and functional and mental health status (estimated by their treating physician) 3 months after COVID-19 diagnosis. Complete follow-up data were available for 854 surviving patients. Patient characteristics associated with recovery were analyzed using logistic regression. Results. In 2449 hemodialysis patients (mean ± SD age 67.5 ± 14.4 years, 62% male), survival probabilities at 3 months after COVID-19 diagnosis were 90% for nonhospitalized patients (n = 1087), 73% for patients admitted to the hospital but not to an intensive care unit (ICU) (n = 1165) and 40% for those admitted to an ICU (n = 197). Patient survival hardly decreased between 28 days and 3 months after COVID-19 diagnosis. At 3 months, 87% functioned at their pre-existent functional and 94% at their pre-existent mental level. Only few of the surviving patients were still admitted to the hospital (0.8-6.3%) or a nursing home (∼5%). A higher age and frailty score at presentation and ICU admission were associated with worse functional outcome. Conclusions. Mortality between 28 days and 3 months after COVID-19 diagnosis was low and the majority of patients who survived COVID-19 recovered to their pre-existent functional and mental health level at 3 months after diagnosis

Strategies to improve clinical management of community-acquired pneumonia

Despite advances during the last few decades in the prevention, diagnosis and treatment of community-acquired pneumonia (CAP), its incidence remains high. In this thesis, strategies are described for improvement of the quality of clinical management in patients with pneumonia and for the reduction of the healthcare burden. The focus is on the prevention of pneumonia, a better understanding of the immune response in CAP, further development of biomarkers, and adjunctive therapies. Recent studies have suggested that gastric acid-suppressive medication may increase the risk of CAP. In Chapter 2, a population-based case-control study is presented on the relationship between proton pump inhibitor (PPI) treatment and CAP. In Chapter 3, the cytokine response in a cohort of 201 non-immunocompromised patients with CAP is described. In addition to the inflammatory response as discussed in Chapter 3, the complement system is an important component of the innate immune system. In Chapter 4, the role of polymorphisms in the genes of these two lectins in patients with S. aureus peritonitis on continuous ambulatory peritoneal dialysis (CAPD) is studied. This led to the study described in Chapter 5 in which binding to the pneumococci of MBL, ficolin-2 and subsequently MASP-2 was explored. This study showed that pneumococci can bind MASP-2 and that ficolin-2 seems to be the overriding MASP-2 activator.In Chapter 6, a quantitative multiplex immunoassay for the measurement of serotype-specific antibody concentrations after the onset of CAP is described. The estimated contribution of the pneumococcus in patients with an unidentified causative agent of CAP was calculated to be 57%. In Chapter 7, the usefulness of serum angiotensin I-converting enzyme (ACE) activity at the time of hospital admission as a prognostic marker is assessed. Serum ACE activity can become useful for the identification of bacteremia before the outcome of blood cultures is known. In Chapter 8, the incidence and predictive value of proteinuria as a biomarker for outcome in patients with CAP is presented. Proteinuria on admission was independently associated with increased length of hospital stay in CAP patients.In Chapter 9, the current literature concerning the various options for supportive therapy of patients treated with otherwise effective antibiotics is reviewed. In Chapter 10, a randomised placebo-controlled trial (RCT) using corticosteroids as an adjunctive treatment to antibiotics in patients with CAP is described. The median length of stay was 6.5 days for patients in the dexamethasone group and 7.5 days in the placebo group (p= 0.048).To further elucidate which patients benefit most from corticosteroids, the cytokine response of 304 patients in an RCT was evaluated in Chapter 11. The overall decrease in cytokine levels was more rapid in patients with CAP treated with dexamethasone in addition to antibiotic treatment than in patients without dexamethasone. In Chapter 12, it is shown that in patients with CAP, a cortisol level <10 µg/dL was not found to be associated with poor outcomes. Furthermore, patients with high cytokine responses and unexpectedly low cortisol levels (<50% of the patients with high cytokine responses) were shown to benefit more from dexamethasone therapy

Systemic cytokine response in patients with community-acquired pneumonia

The role of individual cytokines and polymorphisms in pneumonia has been described, but the relationship between different cytokines and polymorphisms in relation to causative microorganisms, antibiotics, corticosteroids and clinical course has not. This study questions the relationship between cytokines, polymorphisms and clinical characteristics of pneumonia.Patients diagnosed with pneumonia were included in the study. Serum cytokine levels were measured during hospital stay, genotyping was performed, causative microorganisms were identified and patients were monitored throughout the hospital stay.In 201 patients with pneumonia interleukin (IL)-1 receptor antagonist (IL-1RA), IL-6, IL-8 and IL-10 acted as acute phase proteins. After admission, the levels of these cytokines decreased rapidly. Single nucleotide polymorphisms did not influence cytokine production and were not associated with clinical outcome. Cytokine serum levels were significantly higher in patients with pneumococcal pneumonia. The decrease in levels of cytokines was independently influenced by the start of corticosteroid therapy.IL-1RA, IL-6, IL-8 and IL-10 are acute phase proteins, independent of genotype. Their levels are influenced by the nature of the causative microorganism and the start of corticosteroids therapy

Central venous catheter-related complications in older haemodialysis patients: A multicentre observational cohort study

Background: Central venous catheters (CVC) remain a commonly used vascular access option in haemodialysis, despite guidelines advising to preferably use arteriovenous fistulae. Compared to younger patients, the risk-benefit ratio of CVC in older patients might be more beneficial, but previous studies mainly focussed on catheter-related bacteraemia and/or assessed tunnelled CVC (TCVC) only. This study's aim was to compare all catheter-related infections and malfunctions in older patients with younger patients using all CVC subtypes. Materials and methods: We used data from DUCATHO, a multicentre observational cohort study in The Netherlands. All adult patients in whom a CVC was placed for haemodialysis between 2012 and 2016 were included. The primary endpoint was the occurrence of catheter-related infections, comparing patients aged > 70 years with patients aged 70 years. No statistically significant difference was found for the occurrence of catheter-related infections (adjusted HR 0.80-95% CI 0.62-1.02), catheter malfunction (adjusted HR 0.94-95% CI 0.75-1.17) and catheter removal due to infection or malfunction (adjusted HR 0.94-95% CI 0.80-1.11). Results were comparable when assessing NTCVC and TCVC separately. Conclusion: Patients aged > 70 to <70 years have a comparable risk for the occurrence of catheter-related infections and catheter malfunction. These findings may help when discussing treatment options with older patients starting haemodialysis and may inform the current debate on the best vascular access for these patients

Central venous catheter-related complications in older haemodialysis patients: A multicentre observational cohort study

Background: Central venous catheters (CVC) remain a commonly used vascular access option in haemodialysis, despite guidelines advising to preferably use arteriovenous fistulae. Compared to younger patients, the risk-benefit ratio of CVC in older patients might be more beneficial, but previous studies mainly focussed on catheter-related bacteraemia and/or assessed tunnelled CVC (TCVC) only. This study's aim was to compare all catheter-related infections and malfunctions in older patients with younger patients using all CVC subtypes. Materials and methods: We used data from DUCATHO, a multicentre observational cohort study in The Netherlands. All adult patients in whom a CVC was placed for haemodialysis between 2012 and 2016 were included. The primary endpoint was the occurrence of catheter-related infections, comparing patients aged > 70 years with patients aged 70 years. No statistically significant difference was found for the occurrence of catheter-related infections (adjusted HR 0.80-95% CI 0.62-1.02), catheter malfunction (adjusted HR 0.94-95% CI 0.75-1.17) and catheter removal due to infection or malfunction (adjusted HR 0.94-95% CI 0.80-1.11). Results were comparable when assessing NTCVC and TCVC separately. Conclusion: Patients aged > 70 to <70 years have a comparable risk for the occurrence of catheter-related infections and catheter malfunction. These findings may help when discussing treatment options with older patients starting haemodialysis and may inform the current debate on the best vascular access for these patients.Nephrolog

The position of renal denervation in treatment of hypertension: an expert consensus statement.

Hypertension is an important risk factor for cardiovascular disease. In the Netherlands, there are approximately 2.8 million people with hypertension. Despite treatment recommendations including lifestyle changes and antihypertensive drugs, most patients do not meet guideline-recommended blood pressure (BP) targets. In order to improve BP control and lower the risk of subsequent cardiovascular events, renal sympathetic denervation (RDN) has been introduced and studied as a non-pharmacological approach. While early data on the efficacy of RDN showed conflicting results, improvements in treatment protocols and study design resulted in robust new evidence supporting the potential of the technology to improve patient care in hypertensive subjects. Recently, 5 randomised sham-controlled trials demonstrated the safety and efficacy of the technology. Modelling studies have further shown that RDN is cost-effective in the Dutch healthcare setting. Given the undisputable disease burden along with the shortcomings of current therapeutic options, we postulate a new, clearly framed indication for RDN as an adjunct in the treatment of hypertension. The present consensus statement summarises current guideline-recommended BP targets, proposed workup and treatment for hypertension, and position of RDN for those patients with primary hypertension who do not meet guideline-recommended BP targets (see central illustration)

Precurved non-tunnelled catheters for haemodialysis are comparable in terms of infections and malfunction as compared to tunnelled catheters:A retrospective cohort study

Clinical epidemiolog