Measuring vincristine-induced peripheral neuropathy in children with cancer: validation of the Dutch pediatric–modified Total Neuropathy Score

Purpose: The aims were to evaluate the construct validity and reliability of the Dutch version of the pediatric-modified Total Neuropathy Score (ped-mTNS) for assessing vincristine-induced peripheral neuropathy (VIPN) in Dutch pediatric oncology patients aged 5–18 years. Methods: Construct validity (primary aim) of the ped-mTNS was determined by testing hypotheses about expected correlation between scores of the ped-mTNS (range: 0–32) and the Common Terminology Criteria for Adverse Events (CTCAE) (range: 0–18) for patients and healthy controls and by comparing patients and controls regarding their total ped-mTNS scores and the proportion of children identified with VIPN. Inter-rater and intra-rater reliability and measurement error (secondary aims) were assessed in a subgroup of study participants. Results: Among the 112 children (56 patients and 56 age- and gender-matched healthy controls) evaluated, correlation between CTCAE and ped-mTNS scores was as expected (moderate (r = 0.60)). Moreover, as expected, patients had significantly higher ped-mTNS scores and more frequent symptoms of VIPN compared with controls (both p <.001). Reliability as measured within the intra-rater group (n = 10) (intra-class correlation coefficient (ICCagreement) = 0.64, standard error of measurement (SEMagreement) = 2.92, and smallest detectable change (SDCagreement) = 8.1) and within the inter-rater subgroup (n = 10) (ICCagreement = 0.63, SEMagreement = 3.7, and SDCagreement = 10.26) indicates insuffi

Vincristine-induced peripheral neuropathy in pediatric oncology: A randomized controlled trial comparing push injections with one-hour infusions (the vinca trial)

Vincristine (VCR) is a frequently used chemotherapeutic agent. However, it can lead to VCR-induced peripheral neuropathy (VIPN). In this study we investigated if one-hour infusions of VCR instead of push-injections reduces VIPN in pediatric oncology patients. We conducted a multicenter randomized controlled trial in which participants received all VCR administrations through push injections or one-hour infusions. VIPN was measured at baseline and 1–5 times during treatment using Common Terminology Criteria of Adverse Events (CTCAE) and pediatric-modified Total Neuropathy Score. Moreover, data on co-medication, such as azole antifungals, were collected. Overall, results showed no effect of administration duration on total CTCAE score or ped-mTNS score. However, total CTCAE score was significantly lower in patients receiving one-hour infusions concurrently treated with azole antifungal therapy (β = −1.58; p = 0.04). In conclusion, generally VCR administration through one-hour infusions does not lead to less VIPN compared to VC

Prevalence of Symptomatic and Asymptomatic Thrombosis in Pediatric Oncology Patients With Tunneled Central Venous Catheters

Background. Pediatric oncology patients with tunneled central venous catheters (CVCs) are at increased risk to develop venous thromboembolic events (VTEs), but the true prevalence of (a) symptomatic VTE is unknown. Aim of this study was to evaluate the prevalence of (a) symptomatic VTE in pediatric oncology patients with tunneled CVCs. Procedure. All patients were included in the Aristocaths study: a randomized controlled multicenter trial investigating the prophylactic effect of 70% ethanol locks on CVC-associated bloodstream infections (CABSIs) were eligible for this study. We assessed the following outcomes: (i) symptomatic VTE and (ii) asymptomatic CVC-related VTE (using ultrasound [US]). Follow-up was 6 months, unless patients developed one of the following events: VTE, CABSI, CVC removal, or death. Results. We included 305 patients (hematologic malignancy, n = 148; solid tumor, n = 157), median age 9 years (range, 1-18 years). Symptomatic VTE was detected in 8 of 305 patients (2.6%; 95% confidence interval [CI]: 1.1-5.1%), which was related to the CVC in three patients. Patients (185/305) were evaluated with US: 11 of 185 (5.9%; 95% CI: 3.0-10.4%) patients had asymptomatic CVC-related VTE. Conclusions. Prevalence of both symptomatic VTE and asymptomatic CVC-related VTE was low compared to other studies, which may be explained by the inclusion of patients with solid tumors, reduction of CABSI by ethanol, use of tunneled CVCs, and use of US. (C) 2016 Wiley Periodicals, Inc

Prevention of central venous catheter-associated bloodstream infections in paediatric oncology patients using 70% ethanol locks: A randomised controlled multi-centre trial

The prevention of central venous catheter (CVC) associated bloodstream infections (CABSIs) in paediatric oncology patients is essential. Ethanol locks can eliminate pathogens colonising CVCs and microbial resistance is rare. Aim of this study was to determine whether two hour 70% ethanol locks can reduce CABSI in paediatric oncology patients. We conducted a randomised, double blind, multi-centre trial in paediatric oncology patients (1-18 years) with newly inserted CVCs. Patients were randomly assigned to receive two hour ethanol locks (1.5 or 3 ml 70%) or heparin locks (1.5 or 3 ml 100 IU/ml), whenever it was needed to use the CVC, maximum frequency once weekly. Primary outcomes were time to CABSI or death due to CABSI. We recruited 307 patients (ethanol, n=153; heparin, n=154). In the ethanol group, 16/153 (10%) patients developed a CABSI versus 29/154 (19%) in the heparin group. The incidence of CABSI was 0.77/1000 and 1.46/1000 catheter days respectively (p=0.039). The number-needed-to-treat was 13. No patients died of CABSI. In particular, Gram-positive CABSIs were reduced (ethanol, n=8; heparin, n=21; p=0.012). Fewer CVCs were removed because of CABSI in the ethanol group (p=0.077). The ethanol lock patients experienced significantly more transient symptoms compared to the heparin lock patients (maximum grade 2) (nausea, p=0.030; taste alteration, p <0.001; dizziness, p=0.001; blushing, p <0.001), no suspected unexpected serious adverse reactions (SUSAR) occurred. This is the first randomised controlled trial to show that ethanol locks can prevent CABSI in paediatric oncology patients, in particular CABSI caused by Gram-positive bacteria. Implementation of ethanol locks in clinical practice should be considere

Risk-adapted approach for fever and neutropenia in paediatric cancer patients:: A national multicentre study

Background: In this national multicentre study, we examined the safety of reducing antibiotics in selected paediatric cancer patients with febrile neutropenia. Methods: Patients with signs of a bacterial infection and/or abnormal vital signs indicating sepsis were considered high risk and received antibiotic therapy. Remaining patients were allocated to low-or medium risk, depending on their interleukin-8 level. Low-risk patients did not receive any antibiotics and were discharged from the hospital after having been afebrile for 12 h. Medium-risk patients were re-evaluated after 72 h of antibiotic treatment and, in selected patients, antibiotics were stopped. Results: Two hundred thirty-three febrile neutropenic episodes in 141 paediatric cancer patients were included in the study. Sixty-four episodes were classified high risk (28%), 122 medium risk (52%), and 47 (20%) low risk. In the medium-risk group, antibiotics were stopped after 72 h in 50 in 122 episodes (41%). Median duration of antibiotic treatment and hospital admission was significantly lower in low-and medium-risk episodes with early discharge. No failures were observed in the medium-risk group with early discharge. In the low-risk group, six failures were observed (12.8%), due to coagulase-negative staphylococci-positive blood cultures and recurrent fever. Conclusion: We showed that it is safe to shorten antibiotic treatment to 72 h in selected medium-risk patients with febrile neutropenia, regardless of the neutrophil count. The safety of withholding antibiotics in selected low-risk paediatric cancer patients with febrile neutropenia requires further investigation, using more suitable definitions for safety. Reduction in hospital admissions allows children with cancer more time at home and consequently improves their quality of life. (C) 2015 Elsevier Ltd. All rights reserved