Tunneled Hemodialysis Catheter Tip Design and Risk of Catheter Dysfunction: An Australian Nationwide Cohort Study.

RATIONALE & OBJECTIVE: Hemodialysis catheter dysfunction is an important problem for patients with kidney failure. The optimal design of the tunneled catheter tip is unknown. This study evaluated the association of catheter tip design with the duration of catheter function. STUDY DESIGN: Observational cohort study using data from the nationwide REDUCCTION trial. SETTING & PARTICIPANTS: 4,722 adults who each received hemodialysis via 1 or more tunneled central venous catheters in 37 Australian nephrology services from December 2016 to March 2020. EXPOSURE: Design of tunneled hemodialysis catheter tip, classified as symmetrical, step, or split. OUTCOME: Time to catheter dysfunction requiring removal due to inadequate dialysis blood flow assessed by the treating clinician. ANALYTICAL APPROACH: Mixed, 3-level accelerated failure time model, assuming a log-normal survival distribution. Secular trends, the intervention, and baseline differences in service, patient, and catheter factors were included in the adjusted model. In a sensitivity analysis, survival times and proportional hazards were compared among participants' first tunneled catheters. RESULTS: Among the study group, 355 of 3,871 (9.2%), 262 of 1,888 (13.9%), and 38 of 455 (8.4%) tunneled catheters with symmetrical, step, and split tip designs, respectively, required removal due to dysfunction. Step tip catheters required removal for dysfunction at a rate 53% faster than symmetrical tip catheters (adjusted time ratio, 0.47 [95% CI, 0.33-0.67) and 76% faster than split tip catheters (adjusted time ratio, 0.24 [95% CI, 0.11-0.51) in the adjusted accelerated failure time models. Only symmetrical tip catheters had performance superior to step tip catheters in unadjusted and sensitivity analyses. Split tip catheters were infrequently used and had risks of dysfunction similar to symmetrical tip catheters. The cumulative incidence of other complications requiring catheter removal, routine removal, and death before removal were similar across the 3 tip designs. LIMITATIONS: Tip design was not randomized. CONCLUSIONS: Symmetrical and split tip catheters had a lower risk of catheter dysfunction requiring removal than step tip catheters. FUNDING: Grants from government (Queensland Health, Safer Care Victoria, Medical Research Future Fund, National Health and Medical Research Council, Australia), academic (Monash University), and not-for-profit (ANZDATA Registry, Kidney Health Australia) sources. TRIAL REGISTRATION: Registered at ANZCTR with study number ACTRN12616000830493. PLAIN-LANGUAGE SUMMARY: Central venous catheters are widely used to facilitate vascular access for life-sustaining hemodialysis treatments but often fail due to blood clots or other mechanical problems that impede blood flow. A range of adaptations to the design of tunneled hemodialysis catheters have been developed, but it is unclear which designs have the greatest longevity. We analyzed data from an Australian nationwide cohort of patients who received hemodialysis via a tunneled catheter and found that catheters with a step tip design failed more quickly than those with a symmetrical tip. Split tip catheters performed well but were infrequently used and require further study. Use of symmetrical rather than step tip hemodialysis catheters may reduce mechanical failures and unnecessary procedures for patients.

Effect of a Multifaceted Intervention on the Incidence of Hemodialysis Catheter Dysfunction in a National Stepped-Wedge Cluster Randomized Trial.

Introduction: Effective strategies to prevent hemodialysis (HD) catheter dysfunction are lacking and there is wide variation in practice. Methods: In this post hoc analysis of the REDUcing the burden of dialysis Catheter ComplicaTIOns: a national (REDUCCTION) stepped-wedge cluster randomized trial, encompassing 37 Australian nephrology services, 6361 participants, and 9872 catheters, we investigated whether the trial intervention, which promoted a suite of evidence-based practices for HD catheter insertion and management, reduced the incidence of catheter dysfunction, which is defined by catheter removal due to inadequate dialysis blood flow. We also analyzed outcomes among tunneled cuffed catheters and sources of event variability. Results: A total of 873 HD catheters were removed because of dysfunction over 1.12 million catheter days. The raw incidence was 0.91 events per 1000 catheter days during the baseline phase and 0.68 events per 1000 catheter days during the intervention phase. The service-wide incidence of catheter dysfunction was 33% lower during the intervention after adjustment for calendar time (incidence rate ratio = 0.67; 95% confidence interval [CI], 0.50-0.89; P = 0.006). Results were consistent among tunneled cuffed catheters (adjusted incidence rate ratio = 0.68; 95% CI, 0.49-0.94), which accounted for 75% of catheters (n = 7403), 97.4% of catheter exposure time and 88.2% of events (n = 770). Among tunneled catheters that survived for 6 months (21.5% of tunneled catheters), between 2% and 5% of the unexplained variation in the number of catheter dysfunction events was attributable to service-level differences, and 18% to 36% was attributable to patient-level differences. Conclusion: Multifaceted interventions that promote evidence-based catheter care may prevent dysfunction, and patient factors are an important source of variation in events.

Multifaceted intervention to reduce haemodialysis catheter related bloodstream infections: REDUCCTION stepped wedge, cluster randomised trial.

OBJECTIVE: To identify whether multifaceted interventions, or care bundles, reduce catheter related bloodstream infections (CRBSIs) from central venous catheters used for haemodialysis. DESIGN: Stepped wedge, cluster randomised design. SETTING: 37 renal services across Australia. PARTICIPANTS: All adults (age ≥18 years) under the care of a renal service who required insertion of a new haemodialysis catheter. INTERVENTIONS: After a baseline observational phase, a service-wide, multifaceted intervention bundle that included elements of catheter care (insertion, maintenance, and removal) was implemented at one of three randomly assigned time points (12 at the first time point, 12 at the second, and 13 at the third) between 20 December 2016 and 31 March 2020. MAIN OUTCOMES MEASURE: The primary endpoint was the rate of CRBSI in the baseline phase compared with intervention phase at the renal service level using the intention-to-treat principle. RESULTS: 1.14 million haemodialysis catheter days of use were monitored across 6364 patients. Patient characteristics were similar across baseline and intervention phases. 315 CRBSIs occurred (158 in the baseline phase and 157 in the intervention phase), with a rate of 0.21 per 1000 days of catheter use in the baseline phase and 0.29 per 1000 days in the intervention phase, giving an incidence rate ratio of 1.37 (95% confidence interval 0.85 to 2.21; P=0.20). This translates to one in 10 patients who undergo dialysis for a year with a catheter experiencing an episode of CRBSI. CONCLUSIONS: Among patients who require a haemodialysis catheter, the implementation of a multifaceted intervention did not reduce the rate of CRBSI. Multifaceted interventions to prevent CRBSI might not be effective in clinical practice settings. TRIAL REGISTRATION: Australia New Zealand Clinical Trials Registry ACTRN12616000830493.

REDUcing the burden of dialysis Catheter ComplicaTIOns: a National approach (REDUCCTION) - design and baseline results.

Background: Patients with hemodialysis central venous catheters (HD CVCs) are susceptible to health care-associated infections, particularly hemodialysis catheter-related bloodstream infection (HD-CRBSI), which is associated with high mortality and health care costs. There have been few systematic attempts to reduce this burden and clinical practice remains highly variable. This manuscript will summarize the challenges in preventing HD-CRBSI and describe the methodology of the REDUcing the burden of dialysis Catheter ComplicaTIOns: a National approach (REDUCCTION) trial. Methods: The REDUCCTION trial is a stepped-wedge cluster randomized trial of a suite of clinical interventions aimed at reducing HD-CRBSI across Australia. It clusters the intervention at the renal-service level with implementation randomly timed across three tranches. The primary outcome is the effect of this intervention upon the rate of HD-CRBSI. Patients who receive an HD CVC at a participating renal service are eligible for inclusion. A customized data collection tool allows near-to-real-time reporting of the number of active catheters, total exposure to catheters over time, and rates of HD-CRBSI in each service. The interventions are centered around the insertion, maintenance, and removal of HD CVC, informed by the most current evidence at the time of design (mid-2018). Results: A total of 37 renal services are participating in the trial. Data collection is ongoing with results expected in the last quarter of 2020. The baseline phase of the study has collected provisional data on 5385 catheters in 3615 participants, representing 603,506 days of HD CVC exposure. Conclusions: The REDUCCTION trial systematically measures the use of HD CVCs at a national level in Australia, accurately determines the rate of HD-CRBSI, and tests the effect of a multifaceted, evidence-based intervention upon the rate of HD-CRBSI. These results will have global relevance in nephrology and other specialties commonly using CVCs.

Interventions to improve gross motor performance in children with neurodevelopmental disorders: a meta-analysis.

BACKGROUND: Gross motor skills are fundamental to childhood development. The effectiveness of current physical therapy options for children with mild to moderate gross motor disorders is unknown. The aim of this study was to systematically review the literature to investigate the effectiveness of conservative interventions to improve gross motor performance in children with a range of neurodevelopmental disorders. METHODS: A systematic review with meta-analysis was conducted. MEDLINE, EMBASE, AMED, CINAHL, PsycINFO, PEDro, Cochrane Collaboration, Google Scholar databases and clinical trial registries were searched. Published randomised controlled trials including children 3 to ≤18 years with (i) Developmental Coordination Disorder (DCD) or Cerebral Palsy (CP) (Gross Motor Function Classification System Level 1) or Developmental Delay or Minimal Acquired Brain Injury or Prematurity (<30 weeks gestational age) or Fetal Alcohol Spectrum Disorders; and (ii) receiving non-pharmacological or non-surgical interventions from a health professional and (iii) gross motor outcomes obtained using a standardised assessment tool. Meta-analysis was performed to determine the pooled effect of intervention on gross motor function. Methodological quality and strength of meta-analysis recommendations were evaluated using PEDro and the GRADE approach respectively. RESULTS: Of 2513 papers, 9 met inclusion criteria including children with CP (n = 2) or DCD (n = 7) receiving 11 different interventions. Only two of 9 trials showed an effect for treatment. Using the least conservative trial outcomes a large beneficial effect of intervention was shown (SMD:-0.8; 95% CI:-1.1 to -0.5) with "very low quality" GRADE ratings. Using the most conservative trial outcomes there is no treatment effect (SMD:-0.1; 95% CI:-0.3 to 0.2) with "low quality" GRADE ratings. Study limitations included the small number and poor quality of the available trials. CONCLUSION: Although we found that some interventions with a task-orientated framework can improve gross motor outcomes in children with DCD or CP, these findings are limited by the very low quality of the available evidence. High quality intervention trials are urgently needed.

The kynurenine pathway and inflammation in amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a progressive and fatal motor neuron disease of unknown pathogenesis. The kynurenine pathway (KP), activated during neuroinflammation, is emerging as a possible contributory factor in ALS. The KP is the major route for tryptophan (TRP) catabolism. The intermediates generated can be either neurotoxic, such as quinolinic acid (QUIN), or neuroprotective, such as picolinic acid (PIC), an important endogenous chelator. The first and inducible enzyme of the pathway is indoleamine 2,3-dioxygenase (IDO). The present study aimed to characterize the expression of the KP in cerebrospinal fluid (CSF), serum and central nervous system (CNS) tissue of ALS patients. Using high performance liquid chromatography, we analysed the levels of TRP and kynurenine (KYN), and, with gas chromatography/mass spectrometry, the levels of PIC and QUIN, in the CSF and serum of ALS patients and control subjects. Immunohistochemistry was employed to determine the expression of QUIN, IDO and human leukocyte antigen-DR (HLA-DR) in sections of brain and spinal cord from ALS patients. There were significantly increased levels of CSF and serum TRP (P < 0.0001), KYN (P < 0.0001) and QUIN (P < 0.05) and decreased levels of serum PIC (P < 0.05) in ALS samples. There was a significant increase in activated microglia expressing HLA-DR (P < 0.0001) and increased neuronal and microglial expression of IDO and QUIN in ALS motor cortex and spinal cord. We show the presence of neuroinflammation in ALS and provide the first strong evidence for the involvement of the KP in ALS. These data point to an inflammation-driven excitotoxic-chelation defective mechanism in ALS, which may be amenable to inhibitors of the KP.

Age and circadian influences on picolinic acid concentrations in human cerebrospinal fluid.

It has been suggested that picolinic acid (PIC), an endogenous metabolite of l-tryptophan, possesses neuro-protective and anti-proliferative effects within the CNS. However, the literature surrounding PIC is limited, and its exact endogenous function is not known. Picolinic acid is produced via the kynurenine pathway which has been implicated in the pathogenesis of a range of neuro-inflammatory diseases. Although not extensively studied, there have been reports of altered PIC production alongside other kynurenine metabolites in inflammatory disorders. In order to investigate whether PIC concentrations are altered with disease in the CNS, we analysed PIC levels in the CSF of 241 patients who underwent lumbar puncture as part of their standard clinical evaluation. In patients with no apparent CNS disease, CSF PIC levels were 10-fold higher in samples taken between 20:00 and 16:00 h compared with those collected between 04:00 and 12:00 h. This result suggests a diurnal variation in PIC synthesis within the CNS. In addition, we observed a direct correlation between a patient's age and their PIC concentration. No significant correlations were observed between CSF PIC levels and any specific disease state.