Less restrictions in daily life: a clinical practice guideline for children with cancer.

PURPOSE: In current clinical practice, recommendations regarding restrictions in daily life for children with cancer are often lacking or not evidence-based. Critically reviewing the evidence and formulating recommendations are therefore of great importance as social restrictions (e.g., swimming, school attendance, sports) can impair the quality of life of these children severely. Therefore, our aim was to develop a clinical practice guideline for clinicians, children, and their parents regarding social restrictions in children with cancer. METHODS: A comprehensive multidisciplinary panel was assembled, comprising 21 professionals and patient representatives. A systematic literature review was performed, including dual appraisal of all citations. The GRADE methodology was used to extract, summarize, and assess the evidence. Multiple in-person meetings were held to rank outcomes, discuss evidence, complete evidence-to-decision frameworks, and formulate recommendations. Final recommendations were unanimously supported by all panel members. RESULTS: Six studies, including 758 children, formed the evidence base for the recommendations. Given the scarcity of the available evidence and various designs of studies in children with cancer, additional evidence was extracted from adult oncology guidelines, and shared expert opinions were utilized. In total, 14 recommendations were formulated of which multiple result in changes in current policy and standard of practice in the Netherlands. Topics covered in this guideline are swimming, having pets, visiting the zoo or farm, performing sports or high-velocity events, attending school or kindergarten, and use of public transport. This guideline is not intended to provide recommendations for patients after end of treatment, for palliative care settings, or for children undergoing a stem cell transplantation. CONCLUSIONS: In this clinical practice guideline, we provide recommendations regarding restrictions in daily life in children with cancer. These include evidence-based recommendations and, in the absence of sufficient evidence, recommendations based on expert evidence. With these recommendations, we provide guidance for clinicians, children, and parents and contribute to improving quality of life for children with cancer.

Fetal-neonatal exposure to antibiotics and NEC development: A systematic review and meta-analysis.

Background: Fetal and neonatal exposure to antibiotics may contribute to the development of necrotizing enterocolitis (NEC) in preterm infants. This systematic review and meta-analysis investigate whether exposure to third trimester maternal antibiotics (MAB) and/or prolongation of empirical antibiotics (PEAB) are associated with NEC development in preterms. Method: We included observational and randomized controlled studies, including those on preterm or very low birth weight (VLBW) infants, from MEDLINE and EMBASE, published between 1990 and June 2021. Exposure was defined as third trimester MAB and/or PEAB. The two reviewers independently performed study selection, data extraction, and quality assessment. Results: Three cohort studies compared third trimester MAB with no antibiotics. MAB was associated with lower NEC incidence, unadjusted pooled odds ratio (OR) is 0.57 (95% CI: 0.35-0.93). Twelve cohort studies showed that PEAB was associated with an increased risk of NEC. Ten observational cohort studies show an unadjusted OR of 2.72 (1.65-4.47), and two case-control studies show an unadjusted mean difference of 2.31 (0.94-3.68). Moderate to substantial heterogeneity was observed but decreased in studies with low risk of bias and large sample size. Conclusion: Evidence suggests an association between MAB and decreased risk of NEC and an association between PEAB and increased risk of NEC. Further studies should confirm these associations and explore causality. Systematic Review Registration: identifier [CRD42022304937].

Fertility preservation for female patients with childhood, adolescent, and young adult cancer: recommendations from the PanCareLIFE Consortium and the International Late Effects of Childhood Cancer Guideline Harmonization Group.

Female patients with childhood, adolescent, and young adult cancer are at increased risk for fertility impairment when treatment adversely affects the function of reproductive organs. Patients and their families desire biological children but substantial variations in clinical practice guidelines reduce consistent and timely implementation of effective interventions for fertility preservation across institutions. As part of the PanCareLIFE Consortium, and in collaboration with the International Late Effects of Childhood Cancer Guideline Harmonization Group, we reviewed the current literature and developed a clinical practice guideline for fertility preservation in female patients who were diagnosed with childhood, adolescent, and young adult cancer at age 25 years or younger, including guidance on risk assessment and available methods for fertility preservation. The Grading of Recommendations Assessment, Development and Evaluation methodology was used to grade the available evidence and to form the recommendations. This clinical practice guideline leverages existing evidence and international expertise to develop transparent recommendations that are easy to use to facilitate the care of female patients with childhood, adolescent, and young adult cancer who are at high risk for fertility impairment. A complete review of the existing evidence, including a quality assessment, transparent reporting of the guideline panel's decisions, and achievement of global interdisciplinary consensus, is an important result of this intensive collaboration.

Fertility preservation for male patients with childhood, adolescent, and young adult cancer: recommendations from the PanCareLIFE Consortium and the International Late Effects of Childhood Cancer Guideline Harmonization Group.

Male patients with childhood, adolescent, and young adult cancer are at an increased risk for infertility if their treatment adversely affects reproductive organ function. Future fertility is a primary concern of patients and their families. Variations in clinical practice are barriers to the timely implementation of interventions that preserve fertility. As part of the PanCareLIFE Consortium, in collaboration with the International Late Effects of Childhood Cancer Guideline Harmonization Group, we reviewed the current literature and developed a clinical practice guideline for fertility preservation in male patients who are diagnosed with childhood, adolescent, and young adult cancer at age 25 years or younger, including guidance on risk assessment and available methods for fertility preservation. The Grading of Recommendations Assessment, Development and Evaluation methodology was used to grade the available evidence and to form the recommendations. Recognising the need for global consensus, this clinical practice guideline used existing evidence and international expertise to rigorously develop transparent recommendations that are easy to use to facilitate the care of male patients with childhood, adolescent, and young adult cancer who are at high risk of fertility impairment and to enhance their quality of life.

Communication and ethical considerations for fertility preservation for patients with childhood, adolescent, and young adult cancer: recommendations from the PanCareLIFE Consortium and the International Late Effects of Childhood Cancer Guideline Harmonization Group.

Patients with childhood, adolescent, and young adult cancer who will be treated with gonadotoxic therapies are at increased risk for infertility. Many patients and their families desire biological children but effective communication about treatment-related infertility risk and procedures for fertility preservation does not always happen. The PanCareLIFE Consortium and the International Late Effects of Childhood Cancer Guideline Harmonization Group reviewed the literature and developed a clinical practice guideline that provides recommendations for ongoing communication methods for fertility preservation for patients who were diagnosed with childhood, adolescent, and young adult cancer at age 25 years or younger and their families. Moreover, the guideline panel formulated considerations of the ethical implications that are associated with these procedures. Grading of Recommendations Assessment, Development and Evaluation methodology was used to grade the evidence and recommendations. In this clinical practice guideline, existing evidence and international expertise are combined to develop transparent recommendations that are easy to use to facilitate ongoing communication between health-care providers and patients with childhood, adolescent, and young adult cancer who might be at high risk for fertility impairment and their families.

Reducing pain and distress related to needle procedures in children with cancer: A clinical practice guideline.

BACKGROUND: Children with cancer often undergo long treatment trajectories involving repeated needle procedures that potentially cause pain and distress. As part of a comprehensive effort to develop clinical practice guidelines (CPGs) to address pain prevention and management in children with cancer, we aimed to provide recommendations on the pharmacological and psychological management of procedure-related pain and distress. METHODS: Of the international inter-disciplinary CPG development panel (44 individuals), two working groups including 13 healthcare professionals focused on procedural pain and distress. Grading of Recommendations Assessment, Development and Evaluation methodology was used, including the use of systematic literature reviews to inform recommendations and the use of evidence to decision frameworks. At an in-person meeting in February 2018, the guideline panel discussed these frameworks and formulated recommendations which were then discussed with a patient-parent panel consisting of 4 survivors and 5 parents. RESULTS: The systematic reviews led to the inclusion of 48 randomised controlled trials (total number of participants = 2271). Quality of evidence supporting the recommendations ranged from very low to moderate. Strong recommendations were made for the use of topical anesthetics in all needle procedures, for offering deep sedation (DS)/general anesthesia (GA) to all children undergoing lumbar puncture, for the use of DS/ GA in major procedures in children of all ages, for the use of hypnosis in all needle procedures and for the use of active distraction in all needle procedures. CONCLUSION: In this CPG, an evidence-based approach to manage procedure-related pain and distress in children with cancer is presented. As children with cancer often undergo repeated needle procedures during treatment, prevention and alleviation of procedure-related pain and distress is of the utmost importance to increase quality of life in these children and their families.

Treatment-related mortality in children with cancer: Prevalence and risk factors.

AIM: Intensive treatment regimens have contributed to a marked increase in childhood cancer survival rates. Death due to treatment-related adverse effects becomes an increasingly important area to further improve overall survival. In this study, we examined 5-year survival in children with cancer to identify risk factors for treatment-related mortality (TRM). METHODS: All children (aged <18 years at diagnosis) diagnosed with cancer in 2 Dutch university hospitals between 2003 and 2013 were included, survival status was determined and causes of death were analysed. Various demographic and treatment factors were evaluated, for which a multivariable competing risks analysis was performed. RESULTS: A total of 1764 patients were included; overall 5-year survival was 78.6%. Of all 378 deaths, 81 (21.4%) were treatment-related, with infection being responsible for more than half of these deaths. Forty percent of TRM occurred in the first three months after initial diagnosis. Factors associated with TRM in the multivariable competing risks analysis were diagnosis of a haematological malignancy, age at diagnosis <1 year and receipt of allogeneic haematopoietic stem cell transplantation. In children suffering from haematological malignancies, TRM accounted for 56.3% of 103 deaths. CONCLUSION: Over one in five deaths in children with cancer death was related to treatment, mostly due to infection. In children suffering from a haematological malignancy, more children died due to their treatment than due to progression of their disease. To further increase overall survival, clinical and research focus should be placed on lowering TRM rates without compromising anti-tumour efficacy. The findings presented in this study might help identifying areas for improvement.

Reducing pain in children with cancer: Methodology for the development of a clinical practice guideline.

Although pain is one of the most prevalent and bothersome symptoms children with cancer experience, evidence-based guidance regarding assessment and management is lacking. With 44 international, multidisciplinary healthcare professionals and nine patient representatives, we aimed to develop a clinical practice guideline (following GRADE methodology), addressing assessment and pharmacological, psychological, and physical management of tumor-, treatment-, and procedure-related pain in children with cancer. In this paper, we present our thorough methodology for this development, including the challenges we faced and how we approached these. This lays the foundation for our clinical practice guideline, for which there is a high clinical demand.

Measurement properties of instruments to assess pain in children and adolescents with cancer: a systematic review protocol.

BACKGROUND: Pain in children and adolescents with cancer has been identified as an area where many healthcare professionals seek guidance. This protocol details a systematic review whose aim is to explore current knowledge regarding measurement instruments to assess pain (and pain-related distress) in children and adolescents with cancer. After completion of the review, the information will be used in the development of a clinical practice guideline. METHODS: We will search four electronic databases (MEDLINE via PubMed, CINAHL, PsycINFO and HaPI). Additional relevant studies will be identified by reference checking and expert consultation. All citations will be screened independently by two reviewers in a three-step approach: first selection based on title, second selection based on abstract, third selection based on full-text. Studies in children and adolescents with cancer that aimed to evaluate the clinimetric properties of an existing pain measurement instrument or to develop a new pain measurement instrument and that include at least one relevant outcome (reliability, validity, responsiveness, interpretability, clinical utility) are eligible for inclusion. For all steps of evidence selection, a detailed list with eligibility criteria will be determined a priori. Data extraction and quality assessment of included studies (according to the COnsensus-based Standards for the selection of health Measurement INstruments, COSMIN criteria) will be conducted independently by two authors. DISCUSSION: This systematic review will provide an overview of the current literature regarding measurement instruments to assess pain in children and adolescents with cancer. This knowledge synthesis will be used to formulate recommendations for clinical practice. Also, by synthesizing existing evidence, knowledge gaps will be identified. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42017072879.

Development of pediatric oncology supportive care indicators: Evaluation of febrile neutropenia care in the north of the Netherlands.

INTRODUCTION: Febrile neutropenia (FN) is a common complication of the intensive treatment strategies used in pediatric oncology. By close adherence to high-quality guidelines, which can be evaluated by indicators, the burden of FN can potentially be reduced. OBJECTIVES: The aims of this study were tripartite-(1) to develop structure, process, and outcome indicators, (2) to evaluate the implementation of the Dutch Childhood Oncology Group (DCOG) guideline on FN, and (3) to produce baseline measures on local quality of FN care (in the north of the Netherlands). METHODS: Seven indicators derived from the DCOG guideline were developed. Regarding structure indicators, we gathered information from all local centers providing care for children with cancer (n = 9). Regarding process and outcome indicators, we collected individual patient data from one academic and two shared-care hospitals. Children (<18 years) were included if they had been diagnosed with cancer in 2014 or 2015 and had suffered from FN. RESULTS: Six out of nine hospitals used the DCOG guideline on FN and three hospitals used an outdated supportive care handbook. Regarding individual patient data, we included 119 FN episodes in 59 patients. All FN episodes without focus were initially treated with guideline-based antibiotics. Of all FN episodes, 18.5% resulted in intensive care unit (ICU) admittance. Cumulative incidence of death during FN was 1.74%. CONCLUSION: Adherence to the DCOG guideline at the individual patient level was excellent. However, indicators concerning mortality and ICU admittances showed that FN still has devastating consequences. Subsequently, we will implement these indicators nationwide in order to improve FN care.

PanCareLIFE: The scientific basis for a European project to improve long-term care regarding fertility, ototoxicity and health-related quality of life after cancer occurring among children and adolescents.

AIMS: Survival after cancer diagnosed during childhood or adolescence continues to improve with new treatments and supportive therapies. Optimal long-term care requires that risks to vulnerable organs are clearly defined and translated into guidelines that are implemented into practice. PanCareLIFE is a pan-European consortium that addresses survivorship issues comprising fertility, hearing impairment and quality of life. This article describes the scientific basis of PanCareLIFE's studies. METHODS: PanCareLIFE involves 17 partner institutions from eight European countries, with additional 11 data providers from five other countries. Study designs and methods include molecular genetic, cohort and case-control studies, a longitudinal study and an intervention study. Ethics and data protection issues have been taken into account from the beginning. RESULTS: PanCareLIFE will investigate the way that treatment impairs female fertility, by evaluating anti-Müllerian hormone levels and the underlying genetic susceptibility to loss of fertility. For our fertility studies, more than 6000 survivors have completed questionnaires, more than 1500 provided serum samples and more than 400 case-control triads have been identified. Fertility preservation guidelines for boys and girls will be developed. More than 2000 survivors have contributed audiograms for the ototoxicity study. Almost 1000 samples were sent for genetic analysis related to ototoxicity and gonadal reserve. The SF-36 questionnaire will measure quality of life in more than 10,000 survivors. CONCLUSIONS: The large number of subjects enrolled in PanCareLIFE and the detailed information accumulated will allow in-depth evaluation of important outcomes. Fertility preservation guidelines will help patients and their families make informed decisions and contribute to their long-term well-being.

Predictive value of PCT and IL-6 for bacterial infection in children with cancer and febrile neutropenia.

PURPOSE: Only a third of children with cancer and febrile neutropenia (FN) have a proven bacterial infection; nevertheless, most children are hospitalized and treated with intravenous antibiotics. Several biomarkers have been proposed as predictive markers for bacterial infection in this population. We aimed to evaluate the role of interleukin-6 (IL-6) and procalcitonin (PCT) in diagnosing bacterial infection in children with cancer and FN. METHODS: The study population was derived from a prospective database (2006-2013, IL-8 study) comprising children with cancer who presented with FN. From stored plasma samples (taken at admission and/or at 12-24 h), we determined the PCT and IL-6 levels. Consequently, we explored their relation with the presence of bacterial infection (positive blood culture, radiologically documented infection or clinical bacterial focus). We predefined cutoff values at 60 ng/L for IL-6 and 0.25 ng/mL for PCT. RESULTS: Seventy-seven FN episodes in 55 children with cancer were included. In 18 episodes (23.4%), a bacterial infection was documented. Both at presentation and after 12-24 h, median values of IL-6 and PCT were significantly higher in patients with a bacterial infection compared to patients without a bacterial infection. With both biomarkers above cutoff values, sensitivity was 93% (with either one, this was even 100%). The identified group at low risk for bacterial infection comprised 41% of the population. CONCLUSION: PCT and IL-6 are promising markers in identifying bacterial infection in children with cancer and FN. In a subsequent project, we will incorporate these biomarkers in a risk assessment model that we will test prospectively in a clinical trial.

Individualised advance care planning in children with life-limiting conditions.

INTRODUCTION: In 2013, the Pediatric Association of the Netherlands launched an evidence-based guideline 'Palliative care for children'. To promote implementation in daily practice and hereby improve quality of paediatric palliative care, we aimed to develop a functional individualised paediatric palliative care plan (IPPCP) that covers physical, psychological, spiritual and social functioning, with great emphasis on the guideline's recommendations, advance care planning and patients' and parents' preferences and desires. METHODS: A Dutch working group (28 individuals) with a strong multidisciplinary character developed a draft IPPCP, which was piloted retrospectively and prospectively. In the pilots we completed, the IPPCPs for patients who were recently diagnosed with a life-threatening or life-limiting condition and evaluated completeness, usability and user-friendliness. RESULTS: The final IPPCP comprised five domains: (1) IPPCP data, (2) basics, (3) social, (4) psychosocial and spiritual and (5) physical care. Each domain covered various components. In both pilots, the IPPCP was considered a comprehensive document that covered all areas of paediatric palliative care and was experienced as an improvement to the present situation. However, the current form was regarded to lack user-friendliness. CONCLUSION: We propose a set of essential components of a comprehensive IPPCP for paediatric palliative care with extra attention for advance care planning and anticipatory action. Patients' and parents' preferences and desires are included next to the recommendations of the evidence-based guideline 'Palliative care for children'.

The duration of anthracycline infusion should be at least one hour in children with cancer: A clinical practice guideline.

We aimed to provide recommendations on the infusion duration of anthracycline chemotherapy agents in children with cancer. This study also serves as a practice example of the essential steps that need to be taken when using a previously published systematic review to develop a high-quality clinical practice guideline. Although evidence was scarce and included adult studies, the panel was able (using the Grading of Recommendations Assessment, Development and Evaluation evidence-to-decision framework) to recommend in favor of an anthracycline infusion duration of at least 1 hr (strong recommendation, very low to moderate quality of evidence). Recommending a precise optimal prolonged infusion duration was currently not possible.

Fertility preservation in children, adolescents, and young adults with cancer: Quality of clinical practice guidelines and variations in recommendations.

BACKGROUND: Fertility preservation care for children, adolescents, and young adults (CAYAs) with cancer is not uniform among practitioners. To ensure high-quality care, evidence-based clinical practice guidelines (CPGs) are essential. The authors identified existing CPGs for fertility preservation in CAYAs with cancer, evaluated their quality, and explored differences in recommendations. METHODS: A systematic search in PubMed (January 2000-October 2014); guideline databases; and Web sites of oncology, pediatric, and fertility organizations was performed. Two reviewers evaluated the quality of the identified CPGs using the Appraisal of Guidelines for Research and Evaluation II Instrument (AGREE II). From high-quality CPGs, the authors evaluated concordant and discordant areas among the recommendations. RESULTS: A total of 25 CPGs regarding fertility preservation were identified. The average AGREE II domain scores (scale of 0%-100%) varied from 15% on applicability to 100% on clarity of presentation. The authors considered 8 CPGs (32%) to be of high quality, which was defined as scores ≥60% in any 4 domains. Large variations in the recommendations of the high-quality CPGs were observed, with 87.2% and 88.6%, respectively, of discordant guideline areas among the fertility preservation recommendations for female and male patients with cancer. CONCLUSIONS: Only approximately one-third of the identified CPGs were found to be of sufficient quality. Of these CPGs, the fertility preservation recommendations varied substantially, which can be a reflection of inadequate evidence for specific recommendations, thereby hindering the ability of providers to deliver high-quality care. CPGs including a transparent decision process for fertility preservation can help health care providers to deliver optimal and uniform care, thus improving the quality of life of CAYAs with cancer and cancer survivors. Cancer 2016;122:2216-23. © 2016 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society.

Very early discharge versus early discharge versus non-early discharge in children with cancer and febrile neutropenia.

BACKGROUND: Chemotherapy-induced neutropenia is a common adverse effect in children with cancer. Due to the high relative risk of infections and infectious complications, standard care for children with cancer and febrile neutropenia consists of routine hospitalization and parenteral administration of broad-spectrum antibiotics. However, there are less serious causes of febrile neutropenia; in a subgroup of these children, lengthy in-hospital treatment might be unnecessary. Various research groups have studied the adjustment of standard care to shorten in-hospital treatment for children with cancer and febrile neutropenia at low risk for bacterial infections. However, most of these studies were not done in a randomized matter. OBJECTIVES: To evaluate whether early discharge (mean/median of less than five days) from in-hospital treatment was not inferior to non-early discharge (mean/median of five days or more) and whether very early discharge (mean/median of less than 24 hours) was not inferior to early discharge, non-early discharge, or a combination of these, in children with cancer and febrile neutropenia. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (2015, issue 11), MEDLINE/PubMed (from 1945 to December 2015), EMBASE/Ovid (from 1980 to December 2015), the reference lists of relevant articles and review articles, and various conference proceedings (dependent on availability from 2005 to 2010 to 2013 to 2015). We scanned the International Standard Randomised Controlled Trials Number (ISRCTN) Register, the National Institute of Health Register for ongoing trials, and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) on 9 January 2016. SELECTION CRITERIA: We included all randomized controlled trials and controlled clinical trials in which children with cancer and febrile neutropenia were divided in groups with different times of discharge. DATA COLLECTION AND ANALYSIS: We used standard methods of Cochrane and its Childhood Cancer Group. Two independent review authors performed study selection, data extraction, and risk of bias assessment. We entered data extracted from the included studies into Review Manager 5 and undertook analyses according to the guidelines of the Cochrane Handbook for Systematic Reviews of Interventions. MAIN RESULTS: We included two randomized controlled trials assessing very early, early, non-early (or a combination of these) discharge in children with cancer and febrile neutropenia. We graded the evidence as low quality; we downgraded for risk of bias and imprecision. One study, Santolaya 2004, consisted of 149 randomized low-risk episodes and compared early discharge (mean/median of less than five days) to non-early discharge (mean/median of five days or more). This study found no clear evidence of difference in treatment failure (risk ratio (RR) 0.91, 95% confidence interval (CI) 0.24 to 3.50, P value = 0.89 for rehospitalization or adjustment of antimicrobial treatment, or both; Fischer's exact P value = 0.477 for death) or duration of treatment (mean difference -0.3 days, 95% CI -1.22 to 0.62, P value = 0.52 for any antimicrobial treatment; mean difference -0.5 days, 95% CI -1.36 to 0.36, P value = 0.25 for intravenous antimicrobial treatment; mean difference 0.2 days, 95% CI -0.51 to 0.91, P value = 0.58 for oral antimicrobial treatment). Costs were lower in the early discharge group (mean difference USD -265, 95% CI USD -403.14 to USD -126.86, P value = 0.0002). The second included study, Brack 2012, consisted of 62 randomized low-risk episodes and compared very early discharge (mean/median of less than 24 hours) to early discharge (mean/median of less than five days). This study also found no clear evidence of difference in treatment failure (RR 0.54, 95% CI 0.15 to 1.89, P value = 0.34 for rehospitalization or adjustment of antimicrobial treatment (or both); Fischer's exact P value = 0.557 for death). Regarding duration of treatment, median duration of intravenous antimicrobial treatment was shorter in the very early discharge group (Wilcoxon's P value ≤ 0.001, stated in the study) and median duration of oral antimicrobial treatment was shorter in the early discharge group (Wilcoxon's P ≤ 0.001, stated in the study) as compared to one another. However, there was no clear evidence of difference in median duration of any antimicrobial treatment (Wilcoxon's P value = 0.34, stated in the study). Costs were not assessed in this study. Neither of the included studies assessed quality of life. Meta-analysis was not possible as the included studies assessed different discharge moments and used different risk stratification models. AUTHORS' CONCLUSIONS: Very limited data were available regarding the safety of early discharge compared to non-early discharge from in-hospital treatment in children with cancer and febrile neutropenia and a low risk for invasive infection. The absence of clear evidence of differences in both studies could be due to lack of power.Evidently, there are still profound gaps regarding very early and early discharge in children with cancer and febrile neutropenia. Future studies that assess this subject should have a large sample size and aim to establish uniform and objective criteria regarding the identification of a low-risk febrile neutropenic episode.

Current variations in childhood cancer supportive care in the Netherlands.

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.

Skin autofluorescence is increased in patients with carotid artery stenosis and peripheral artery disease.

Advanced glycation end products (AGEs) have a pivotal role in atherosclerosis. We evaluated skin autofluorescence (SAF), a non-invasive measurement of tissue AGE accumulation, in patients with carotid artery stenosis with and without coexisting peripheral artery occlusive disease (PAOD). SAF was measured using the AGE Reader™ in 56 patients with carotid artery stenosis and in 56 age- and sex-matched healthy controls without diabetes, renal dysfunction or known atherosclerotic disease. SAF was higher in patients with carotid artery stenosis compared to the control group: mean 2.81 versus 2.46 (P = 0.002), but especially in the younger age group of 50-60 years old: mean 2.82 versus 1.94 (P = 0.000). Patients with carotid artery stenosis and PAOD proved to have an even higher SAF than patients with carotid artery stenosis only: mean 3.28 versus 2.66 (P = 0.003). Backward linear regression analysis showed that age, smoking, diabetes mellitus, renal function and the presence of PAOD were the determinants of SAF, but carotid artery stenosis was not. SAF is increased in patients with carotid artery stenosis and PAOD. The univariate and multivariate associations of SAF with age, smoking, diabetes, renal insufficiency and PAOD suggest that increased SAF can be seen as an indicator of widespread atherosclerosis.