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BACKGROUND: Support for relatives is highly important in the intensive care unit (ICU). During the first COVID-19 wave support for relatives had to be changed considerably. The alternative support could have decreased the quality and sense of support. We aimed to evaluate how support for relatives in Dutch ICUs was organised during the first COVID-19 wave and how this was experienced by these relatives in comparison to relatives from pre-COVID-19 and the second wave. Additionally, we aimed to investigate which elements of support are associated with positive experiences. METHODS: We performed a cross-sectional multicentre cohort study in six Dutch ICUs in the Netherlands. Written questionnaires were distributed among relatives of ICU patients from pre-COVID-19, the first wave and the second wave. The questionnaire included questions on demographics, the organisation of support, and the experiences and satisfaction of relatives with the support. RESULTS: A total of 329 relatives completed the questionnaire (52% partner, 72% woman and 63% ICU stay of 11 days or longer). Support for relatives of ICU patients during the first COVID-19 wave differed significantly from pre-COVID-19 and the second wave. Differences were found in all categories of elements of support: who, when, how and what. Overall, relatives from the three time periods were very positive about the support. The only difference in satisfaction between the three time periods, was the higher proportion of relatives indicating that healthcare professionals had enough time for them during the first wave. Elements of support which were associated with many positive experiences and satisfaction were: fixed timeslot, receiving information (e.g. leaflets) on ≥ 2 topics, discussing > 5 topics with healthcare professionals, and being offered emotional support. CONCLUSIONS: Although, support for relatives in the ICU changed considerably during the COVID-19 pandemic, relatives were still positive about this support. The altered support gave insight into avenues for improvement for future comparable situations as well as for normal daily ICU practice: e.g. daily contact at a fixed timeslot, offering video calling between patients and relatives, and offering emotional support. ICUs should consider which elements need improvement in their practice.
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COVID-19 , Feminino , Humanos , COVID-19/epidemiologia , Estudos Transversais , Pandemias , Estudos de Coortes , Unidades de Terapia IntensivaRESUMO
INTRODUCTION: Advanced intraocular retinoblastoma can be cured by enucleation, but spread of retinoblastoma cells beyond the natural limits of the eye is related to a high mortality. Adjuvant therapy after enucleation has been shown to prevent metastasis in children with risk factors for extraocular retinoblastoma. However, histological criteria and adjuvant treatment regimens vary and there is no unifying consensus on the optimal choice of treatment. METHOD: Data on guidelines for adjuvant treatment in European retinoblastoma referral centres were collected in an online survey among all members of the European Retinoblastoma Group (EURbG) network. Extended information was gathered via personal email communication. RESULTS: Data were collected from 26 centres in 17 countries. Guidelines for adjuvant treatment were in place at 92.3% of retinoblastoma centres. There was a consensus on indication for and intensity of adjuvant treatment among more than 80% of all centres. The majority of centres use no adjuvant treatment for isolated focal choroidal invasion or prelaminar optic nerve invasion. Patients with massive choroidal invasion or postlaminar optic nerve invasion receive adjuvant chemotherapy, while microscopic invasion of the resection margin of the optic nerve or extension through the sclera are treated with combined chemo- and radiotherapy. CONCLUSION: Indications and adjuvant treatment regimens in European retinoblastoma referral centres are similar but not uniform. Further biomarkers in addition to histopathological risk factors could improve treatment stratification. The high consensus in European centres is an excellent foundation for a common European study with prospective validation of new biomarkers.
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Neoplasias da Retina/terapia , Retinoblastoma/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimioterapia Adjuvante/métodos , Criança , Pré-Escolar , Terapia Combinada/métodos , Europa (Continente) , Enucleação Ocular , Humanos , Prognóstico , Radioterapia Adjuvante/métodos , Neoplasias da Retina/patologia , Retinoblastoma/patologia , Fatores de Risco , Inquéritos e QuestionáriosRESUMO
BACKGROUND: During the first peak of the COVID-19 pandemic in the Netherlands, relatives of patients with COVID-19 admitted to Intensive Care Units (ICUs) were severely restricted in visiting their relatives and in communicating with treating physicians. Family communication is a core element of critical care, however, this pandemic forced medical ICU staff to arrange alternative family support for instance by Family Support Teams (FSTs), consisting of non-ICU affiliated staff who telephonically contacted relatives. This study aims to examine relatives' experiences with FSTs on two ICUs of a Dutch university medical centre, and to evaluate its working strategies. . METHODS: In a semi-structured interview study, relatives of patients with COVID-19 admitted to ICU's, who had been supported by the FSTs, were sampled purposively. Twenty-one interviews were conducted telephonically by three researchers. All interviews were topic list guided and audio-recorded. Data was analysed thematically. RESULTS: All participants indicated they went through a rough time. Almost all evaluated the FSTs positively. Four major themes were identified. First, three important pillars of the FSTs were providing relatives with transparency about the patients' situation, providing attention to relatives' well-being, and providing predictability and certainty by calling on a daily basis in a period characterised by insecurity. Second, relatives appeared to fulfil their information needs by calls of the FSTs, but also by calling the attending ICU nurse. Information provided by the FSTs was associated with details and reliability, information provided by nurses was associated with the patient's daily care. Third, being a primary family contact was generally experienced as both valuable and as an emotional burden. Last, participants missed proper aftercare. Family support often stopped directly after the patient died or had left the ICU. Relatives expressed a need for extended support after that moment since they had strong emotions after discharge or death of the patient. CONCLUSIONS: Family support in times of the extreme COVID-19 situation is important, as relatives are restricted in communication and have a strong need for information and support. Relatives feel encouraged by structure, frequency, support and understanding by FSTs. However, remote family support should be tailored to the needs of relatives. A fixed contact person on de ICU and video calling might be good extra options for family support, also in future post COVID-19 care, but cannot replace physical visits.
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COVID-19 , Pandemias , Humanos , Unidades de Terapia Intensiva , Reprodutibilidade dos Testes , SARS-CoV-2RESUMO
BACKGROUND: Venous thromboembolism (VTE) is a common and severe complication during treatment of acute lymphoblastic leukemia (ALL). An important cause is the intensive use of asparaginase. Prospective cohort studies in which prophylactic low-molecular-weight heparin (LMWH) was used to prevent VTE showed lower VTE risk than in historic control cohorts, with a negligible bleeding risk. However, the efficacy of thromboprophylaxis with LMWH during ALL treatment has never been investigated in a randomized design. Here, we present the protocol of a randomized controlled trial in which the efficacy and safety of thromboprophylaxis with high prophylactic dose LMWH versus no thromboprophylaxis will be assessed in children treated for primary ALL with asparaginase. METHODS/DESIGN: Thromboprophylaxis in Children treated for Acute Lymphoblastic Leukemia with Low-molecular-weight heparin (TropicALL) is a multicenter, randomized controlled open-label trial conducted in the Netherlands. Patients between 1 and 19 years of age with primary ALL, who are treated within the Dutch Childhood Oncology Group (DCOG) ALL-11 or 12 study will be randomized to thromboprophylaxis with LMWH once daily, (dose of 85 IU/kg (intervention arm A)), or to no thromboprophylaxis (arm B, standard of care) during asparaginase courses of ALL treatment. Primary efficacy endpoint is symptomatic objectified VTE during ALL treatment; secondary efficacy endpoints are overall survival and the composite of symptomatic and asymptomatic objectified VTE. Primary safety endpoints are major bleeding, clinically relevant non-major bleeding and minor bleeding. A total of 324 patients will be included to obtain a relative risk reduction of 75% with a power of 80%, using a two-sided test with significance level α = 0.05. DISCUSSION: This trial will be the first to assess efficacy and safety of thromboprophylaxis with LMWH during asparaginase treatment for ALL in children in a randomized design. TRAIL REGISTRATION: Nederlands Trial Register NTR4707 . Registered 30 July 2014.
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Anticoagulantes/uso terapêutico , Antineoplásicos/efeitos adversos , Asparaginase/efeitos adversos , Heparina de Baixo Peso Molecular/uso terapêutico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Tromboembolia Venosa/prevenção & controle , Adolescente , Antineoplásicos/uso terapêutico , Asparaginase/uso terapêutico , Criança , Pré-Escolar , Protocolos Clínicos , Esquema de Medicação , Feminino , Seguimentos , Humanos , Lactente , Masculino , Estudos Prospectivos , Resultado do Tratamento , Tromboembolia Venosa/induzido quimicamente , Adulto JovemRESUMO
BACKGROUND: Current treatment strategies in pediatric oncology are intensive and lead to high survival rates but also to treatment-related complications. Therefore, supportive care plays an increasingly important role. This study was designed to evaluate variations in supportive care practice in children with cancer in the Netherlands and adherence to selected existing international guidelines through an in-depth review of local guidelines and protocols at all 6 Dutch pediatric cancer centers. METHODS: Based on shared expert opinion, a questionnaire regarding current supportive care practice was compiled. For each center, the required information was extracted from local supportive care guidelines, and the list was sent to a pediatric oncologist of that center to verify its correspondence with local daily practice. Subsequently, it was determined whether clinical practice was concordant (same in ≥ 5 of 6 centers), partly concordant (highly overlapping in ≥ 5 of 6 centers), or discordant (same in < 5 of 6 centers). Local practices were compared with strong recommendations from high-quality, evidence-based guidelines. RESULTS: The questionnaire comprised 67 questions regarding supportive care practice. Concordance was observed for 11 of 67 practice items (16%), partial concordance was observed for 6 of 67 practice items (9%), and discordance was observed for 50 of 67 practice items (75%). Adherence to strong recommendations of 4 high-quality, evidence-based guidelines varied but was generally low. CONCLUSIONS: Large variations exist in pediatric oncology supportive care practice, and this could negatively influence care. Adherence to existing evidence-based guidelines and the development and implementation of new clinical practice guidelines have the potential of standardizing supportive care practice and thereby improving outcomes for children with cancer.
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Antineoplásicos/efeitos adversos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/prevenção & controle , Oncologia , Neoplasias/terapia , Manejo da Dor/métodos , Cuidados Paliativos/métodos , Padrões de Prática Médica , Lesões por Radiação/prevenção & controle , Radioterapia/efeitos adversos , Criança , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/diagnóstico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/terapia , Medicina Baseada em Evidências , Humanos , Países Baixos , Guias de Prática Clínica como Assunto , Lesões por Radiação/diagnóstico , Lesões por Radiação/terapia , Inquéritos e QuestionáriosRESUMO
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.
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Anticoagulantes/uso terapêutico , Cateterismo Venoso Central/efeitos adversos , Etanol/uso terapêutico , Heparina/uso terapêutico , Neoplasias/terapia , Trombose Venosa/epidemiologia , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Prevalência , Resultado do Tratamento , Trombose Venosa/prevenção & controleRESUMO
In the original publication, there was a mistake in Table 1 as published [...].
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INTRODUCTION: Vincristine is an integral component of treatment for children with cancer. Its main dose-limiting side effect is vincristine-induced peripheral neuropathy (VIPN). The VINCA trial was a randomized controlled trial that explored the effect of 1-hour infusion compared with push injection of vincristine on the development of VIPN in children with cancer. The short-term outcomes (median follow-up 9 months) showed that there was no difference in VIPN between the randomization groups. However, 1-hour infusion was less toxic in children who also received azoles. We now report the results of the final analyses (median follow-up 20 months), which includes treatment outcome as a secondary objective (follow-up 3 years). METHODS: VIPN was measured 1-7 times per participant using the Common Terminology Criteria for Adverse Events (CTCAE) and the pediatric-modified total neuropathy score. Poisson mixed model and logistic generalized estimating equation analysis for repeated measures were performed. RESULTS: Forty-five participants per randomization group were included. There was no significant effect of 1-hour infusion compared with push injection on VIPN. In participants receiving concurrent azoles, the total CTCAE score was significantly lower in the one-hour group (rate ratio 0.52, 95% confidence interval 0.33-0.80, p = 0.003). Four patients in the one-hour group and one patient in the push group relapsed. Two patients in the one-hour group died. CONCLUSION: 1-hour infusion of vincristine is not protective against VIPN. However, in patients receiving concurrent azoles, 1-hour infusion may be less toxic. The difference in treatment outcome is most likely the result of differences in risk profile.
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Antineoplásicos Fitogênicos , Neoplasias , Doenças do Sistema Nervoso Periférico , Criança , Humanos , Vincristina/efeitos adversos , Antineoplásicos Fitogênicos/efeitos adversos , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Neoplasias/complicações , Neoplasias/tratamento farmacológico , Azóis/efeitos adversosRESUMO
Vincristine (VCR) is an important component of curative chemotherapy for many childhood cancers. Its main side effect is VCR-induced peripheral neuropathy (VIPN), a dose limiting toxicity. Some children are more susceptible to VIPN, which is at least partially dependent on genetic factors and pharmacokinetics (PK). In this study, we identify and replicate genetic variants associated with VCR PK and VIPN. Patient samples from a randomized clinical trial studying the effect of administration duration of VCR on VIPN in 90 patients were used. PK sampling was conducted on between one and five occasions at multiple time points. A linear two-compartment model with first-order elimination was used, and targeted next-generation DNA sequencing was performed. Genotype-trait associations were analyzed using mixed-effect models or logistic regression analysis for repeated measures, or Poisson regression analysis in which the highest VIPN score per patient was included. Nine single-nucleotide polymorphisms (SNPs) in seven genes (NDRG1, GARS, FIG4, FGD4, SEPTIN9, CEP72, and ETAA1) were associated with VIPN. Furthermore, three SNPs in three genes (MTNR1B, RAB7A and SNU13) were associated with PK of VCR. In conclusion, PK of VCR and VIPN are influenced by SNPs; upfront identification of those that lead to an altered susceptibility to VIPN or VCR exposure could help individualize VCR treatment.
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BACKGROUND: Monitoring of renal function is crucial in pediatric oncology. The use of creatinine to estimate glomerular filtration rate (GFR) is hampered by its dependency on muscle mass. Muscle wasting is common in children with cancer, leading to overestimation of GFR. Data on cystatin C are sparse in pediatric oncology, although this marker could be particularly useful in this population. PROCEDURE: Inulin clearance, estimated GFR using serum cystatin C according to Filler (eGFRcys) and serum creatinine according to Schwartz (eGFRcrea) were measured in 68 children with malignancy and 121 controls. We analyzed the difference between measured and estimated GFR and performance, bias and accuracy. RESULTS: Multiple linear regression analysis showed overestimation of GFR by eGFRcrea in females (B = -21.18; P = 0.001), and in patients with malignancy (B = -21.77; P = 0.014). eGFRcys overestimated GFR in females (B = -10.47; P = 0.001), but was independent of treatment for malignancy. Agreement with gold standard in detecting GFR below 90 ml/min/1.73 m(2) is better for eGFRcys (AUC 0.854) than for eGFRcrea (AUC 0.675) in the group with cancer. They performed comparably in the control group. Bland-Altman analysis showed considerable bias for eGFRcrea compared to eGFRcys (-14.3 ml/min/1.73 m(2) vs. -7.3 ml/min/1.73 m(2)). The proportion of estimates within 30% of true GFR for eGFRcrea (72.1%) was lower than for eGFRcys (82.4%) in the group with cancer. In the control group eGFRcrea (84.3%) outperformed eGFRcys (76.0%). When using the 50% limits of agreement, eGFRcys outperformed eGFRcrea in both groups. CONCLUSION: Cystatin C more accurately detects mildly impaired renal function than creatinine in children receiving treatment for malignancy.
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Antineoplásicos/efeitos adversos , Cistatina C/sangue , Monitoramento de Medicamentos/métodos , Taxa de Filtração Glomerular , Neoplasias/tratamento farmacológico , Insuficiência Renal/prevenção & controle , Biomarcadores/sangue , Estudos de Casos e Controles , Criança , Pré-Escolar , Creatinina/sangue , Feminino , Humanos , Lactente , Inulina , Modelos Lineares , Masculino , Análise Multivariada , Neoplasias/sangue , Insuficiência Renal/induzido quimicamente , Sensibilidade e EspecificidadeRESUMO
Renal function-based carboplatin dosing using measured glomerular filtration rate (GFR) results in more consistent drug exposure than anthropometric dosing. We aimed to validate the Newell dosing equation using estimated GFR (eGFR) and study which equation most accurately predicts carboplatin clearance in children with retinoblastoma. In 13 children with retinoblastoma 38 carboplatin clearance values were obtained from individual fits using MWPharm++. Carboplatin exposure (AUC) was calculated from administered dose and observed carboplatin clearance and compared to predicted AUC calculated with a carboplatin dosing equation (Newell) using different GFR estimates. Different dosing regimens were compared in terms of accuracy, bias and precision. All patients had normal eGFR. Carboplatin exposure using cystatin C-based eGFR equations tended to be more accurate compared to creatinine-based eGFR (30% accuracy 76.3-89.5% versus 76.3-78.9%, respectively), which led to significant overexposure, especially in younger (aged ≤ 2 years) children. Of all equations, the Schwartz cystatin C-based equation had the highest accuracy and lowest bias. Although anthropometric dosing performed comparably to many of the eGFR equations overall, we observed a weight-dependent change in bias leading to underdosing in the smallest patients. Using cystatin C-based eGFR equations for carboplatin dosing in children leads to more accurate carboplatin-exposure in patients with normal renal function compared to anthropometric dosing. In children with impaired kidney function, this trend might be more pronounced. Anthropometric dosing is hampered by a weight-dependent bias.
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PURPOSE: Vincristine (VCR) is a chemotherapeutic agent used in the treatment of pediatric oncology patients, but its main toxicity is VCR-induced peripheral neuropathy (VIPN). However, whether VIPN has an effect on health-related quality of life (HR-QoL) in children during treatment is unknown. Therefore, the aim of our study was to investigate the association between VIPN and HR-QoL in children starting treatment for cancer. METHODS: Measurements of VIPN were performed using two tools: Common Terminology Criteria for Adverse Events (CTCAE) and pediatric-modified Total Neuropathy Score (ped-mTNS). Assessment of HR-QoL was done with self- and proxy assessment of the Cancer and Generic module of the Pediatric Cancer Quality of Life Inventory™ (PedsQL). RESULTS: In total, N = 86 children were included. HR-QoL of children with VIPN (n = 67%, 76%) was significantly lower in comparison with children without VIPN: estimated Total score of PedsQL Generic (proxy) 84.57; ß = -8.96 and 95% confidence interval (CI) -14.48 to -3.43; p = 0.002, estimated PedsQL Generic Total score (self-reported): 85.16, ß = -8.38 (95% CI: -13.76 to -3.00); p = 0.003. Similar results were found in the Pain and Hurt domain of the PedsQL Cancer (pain: estimated score [proxy]: 85.28, ß = -9.94 [95%CI: -16.44 to -3.45], p = 0.003; hurt: estimated score [self-report] 97.57, ß = -19.15 [95%CI: -26.82 to -11.48], p < 0.001). CONCLUSION: VIPN results in a significant reduction of HR-QoL in children under treatment for a malignancy, which means that VIPN is important for the well-being of pediatric oncology patients. Therefore, this study underlines the importance of optimizing treatment with VCR, thereby aiming to reduce VIPN while maintaining efficacy.
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Neoplasias/complicações , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Vincristina/uso terapêutico , Criança , Feminino , Humanos , Masculino , Neoplasias/tratamento farmacológico , Neoplasias/mortalidade , Estudos Prospectivos , Qualidade de Vida , Análise de Sobrevida , Vincristina/farmacologiaRESUMO
Vincristine (VCR) is frequently used in pediatric oncology and can be administered intravenously through push injections or 1 h infusions. The effects of administration duration on population pharmacokinetics (PK) are unknown. We described PK differences related to administration duration and the relation between PK and VCR-induced peripheral neuropathy (VIPN). PK was assessed in 1-5 occasions (1-8 samples in 24 h per occasion). Samples were analyzed using high-performance liquid chromatography/tandem mass spectrometry. Population PK of VCR and its relationship with administration duration was determined using a non-linear mixed effect. We estimated individual post-hoc parameters: area under the concentration time curve (AUC) and maximum concentration (Cmax) in the plasma and peripheral compartment. VIPN was assessed using Common Terminology Criteria for Adverse Events (CTCAE) and the pediatric-modified total neuropathy score (ped-mTNS). Overall, 70 PK assessments in 35 children were evaluated. The population estimated that the intercompartmental clearance (IC-Cl), volume of the peripheral compartment (V2), and Cmax were significantly higher in the push group. Furthermore, higher IC-Cl was significantly correlated with VIPN development. Administration of VCR by push led to increased IC-Cl, V2, and Cmax, but were similar to AUC, compared to 1 h infusions. Administration of VCR by 1 h infusions led to similar or higher exposure of VCR without increasing VIPN.
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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 (ß = -1.58; p = 0.04). In conclusion, generally VCR administration through one-hour infusions does not lead to less VIPN compared to VCR push injections in pediatric oncology patients. However, one-hour infusions lead to less severe VIPN compared to push-injections when azole therapy is administered concurrently with VCR. These results indicate that in children treated with VCR and requiring concurrent azole therapy, one-hour infusions might be beneficial over push injections, although larger trials are needed to confirm this association.
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OBJECTIVES: Comparison of the effect of corticosteroid therapy on the diagnostic performance of cystatin C (Cys) and beta-trace protein (bTP), two endogenous markers of GFR. DESIGN AND METHODS: Out of a total of 193 pediatric inulin clearance studies, a random sample of 85 steroid-free studies served to establish GFR prediction equations (eGFR), which were used to compare the remaining 76 steroid-free and 32 steroid-positive studies (median prednisone dose 33.0 mg m(-2) day(-1)). RESULTS: We found a positive relationship between prednisone dose and eGFR(betaTP) (b=0.414, p=0.0002) and a negative relationship with eGFR(cys) (b=-0.208, p=0.0091). Only Cys independently predicted GFR below 90 mL min(-1) 1.73 m(-2), both in steroid-positives (b=6.260, p=0.010) and steroid-negatives (b=6.845, p=0.012). Glucocorticoid therapy did not affect the accuracy in estimating GFR within 30% of measured GFR for Cys, while accuracy was lower with bTP (65.6% vs. 81.6%, p=0.08). CONCLUSION: Glucocorticoids have less impact on the diagnostic accuracy of Cys than bTP.
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Corticosteroides/uso terapêutico , Cistatinas/sangue , Taxa de Filtração Glomerular/efeitos dos fármacos , Oxirredutases Intramoleculares/sangue , Lipocalinas/sangue , Adolescente , Corticosteroides/farmacologia , Criança , Pré-Escolar , Cistatina C , Feminino , Humanos , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/farmacocinética , Insulina/administração & dosagem , Insulina/farmacocinética , Testes de Função Renal , Masculino , Taxa de Depuração Metabólica/efeitos dos fármacos , Prednisona/farmacologia , Prednisona/uso terapêuticoRESUMO
Vincristine-induced peripheral neuropathy (VIPN) is a dose-limiting side effect of vincristine (VCR) treatment in children, leading to diminished quality of life. Much remains unknown about the underlying mechanisms of VIPN. This review systematically summarizes the available literature concerning contributing factors of VIPN development in children. Studied factors include patient characteristics, VCR dose, administration method, pharmacokinetics, and genetic factors. Furthermore, this review reports on currently available tools to assess VIPN in children. In total, twenty-eight publications were included. Results indicate that Caucasian race, higher VCR dose, older age and low clearance negatively influence VIPN, although results regarding the latter two factors were rather conflicting. Moreover, genetic pathways influencing VIPN were identified. Furthermore, the studied tools to assess VIPN seriously impairs comparability across study results. Studying the factors and their interactions that seem to influence VIPN in children, should aid in personalized VCR treatment, thereby increasing VCR effectiveness while minimizing toxicity.
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Antineoplásicos Fitogênicos/efeitos adversos , Neoplasias/tratamento farmacológico , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Vincristina/efeitos adversos , Criança , HumanosRESUMO
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.
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Antibacterianos/administração & dosagem , Neutropenia Febril Induzida por Quimioterapia/tratamento farmacológico , Neoplasias/tratamento farmacológico , Adolescente , Assistência Ambulatorial , Antineoplásicos/efeitos adversos , Bacteriemia/diagnóstico , Bacteriemia/tratamento farmacológico , Criança , Pré-Escolar , Esquema de Medicação , Feminino , Infecções por Bactérias Gram-Positivas/diagnóstico , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Hospitalização/estatística & dados numéricos , Humanos , Lactente , Recém-Nascido , Infusões Intravenosas , Masculino , Estudos Prospectivos , Medição de RiscoRESUMO
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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 considered.
Assuntos
Antibacterianos/administração & dosagem , Anticoagulantes/administração & dosagem , Infecções Relacionadas a Cateter/prevenção & controle , Cateterismo Venoso Central/efeitos adversos , Cateterismo Venoso Central/instrumentação , Cateteres Venosos Centrais/efeitos adversos , Etanol/administração & dosagem , Heparina/administração & dosagem , Neoplasias/tratamento farmacológico , Adolescente , Fatores Etários , Antibacterianos/efeitos adversos , Anticoagulantes/efeitos adversos , Infecções Relacionadas a Cateter/sangue , Infecções Relacionadas a Cateter/diagnóstico , Infecções Relacionadas a Cateter/microbiologia , Criança , Pré-Escolar , Método Duplo-Cego , Etanol/efeitos adversos , Feminino , Heparina/efeitos adversos , Humanos , Lactente , Masculino , Países Baixos , Resultado do TratamentoRESUMO
BACKGROUND: Over 90% of the population is infected with the Epstein-Barr virus (EBV). Following primary infection, the virus remains latent in B-lymphocytes. In isolated cases, especially in immunocompromised patients, the Epstein-Barr virus can result in a chronic active infection (CAEBV). CASE DESCRIPTION: We describe an 11-year-old boy with Down syndrome who was admitted because of fever of unknown origin during several periods. Serological findings (high VCA-IgG and absent EBNA-IgG) were suggestive of CAEBV, which was confirmed by the high circulating EBV viral load. During admission the clinical picture worsened and our patient developed pancytopenia, which led us to diagnose concurrent haemophagocytic lymphohistiocytosis and Hodgkin lymphoma. CONCLUSION: CAEBV is the result of deficiency in cellular immunity, which in this patient could possibly be attributed to deficiencies in the immune system associated with Down syndrome. CAEBV is difficult to treat, and it can come with life-threatening complications such as haemophagocytic lymphohistiocytosis.