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Background: Childhood cancer survivors face high risks of adverse late health effects. Long-term follow-up care for childhood cancer survivors is crucial to improve their health and quality of life. However, implementation remains a challenge. To support implementation of high-quality long-term follow-up care, we explored expected barriers and facilitators for establishing this follow-up care among healthcare providers from four European clinics., Methods: A qualitative study was conducted using four focus groups comprising 30 healthcare providers in total. The semi-structured interview guide was developed based on the Grol and Wensing framework. Data was analyzed following a thematic analysis, combining both inductive and deductive approaches to identify barriers and facilitators across the six levels of Grol and Wensing: innovation, professional, patient, social, organizational and economic and political., Results: Most barriers were identified on the organizational level, including insufficient staff, time, capacity and psychosocial support. Other main barriers included limited knowledge of late effects among healthcare providers outside the long-term follow-up care team, inability of some survivors to complete the survivor questionnaire and financial resources. Main facilitators included motivated healthcare providers and survivors, a skilled hospital team, collaborations with important stakeholders like general practitioners, and psychosocial care facilities, utilization of the international collaboration and reporting long-term follow-up care results to convince hospital managers., Conclusion: This study identified several factors for successful implementation of long-term follow-up care for childhood cancer survivors. Our findings showed that specific attention should be given to knowledge, capacity, and financial issues, along with addressing psychosocial issues of survivors., (© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)

Purpose: Childhood cancer survivors, in particular those treated with radiation therapy, are at high risk of long-term iatrogenic events. The prediction of risk of such events is mainly based on the knowledge of the radiation dose received to healthy organs and tissues during treatment of childhood cancer diagnosed decades ago. We aimed to set up a standardized organ dose table to help former patients and clinicians in charge of long-term follow-up clinics., Methods and Materials: We performed whole body dosimetric reconstruction for 2646 patients from 12 European countries treated between 1941 and 2006 (median, 1976). Most plannings were 2- or 3-dimensional. A total of 46% of patients were treated using Cobalt 60, and 41%, using a linear accelerator. The median prescribed dose was 27.2 Gy (IQ1-IQ3, 17.6-40.0 Gy). A patient-specific voxel-based anthropomorphic phantom with more than 200 anatomic structures or substructures delineated as a surrogate of each subject's anatomy was used. The radiation therapy was simulated with a treatment planning system based on available treatment information. The radiation dose received by any organ of the body was estimated by extending the treatment planning system dose calculation to the whole body, by type and localization of childhood cancer., Results: The integral dose and normal tissue doses to most of the 23 considered organs increased between the 1950s and 1970s and decreased or plateaued thereafter. Whatever the organ considered, the type of childhood cancer explained most of the variability in organ dose. The country of treatment explained only a small part of the variability., Conclusions: The detailed dose estimates provide very useful information for former patients or clinicians who have only limited knowledge about radiation therapy protocols or techniques, but who know the type and site of childhood cancer, sex, age, and year of treatment. This will allow better prediction of the long-term risk of iatrogenic events and better referral to long-term follow-up clinics., (Copyright © 2024. Published by Elsevier Inc.)

Given the lack of attention on adolescent food insecurity, the primary objective of this study was to assess the association of household participation in federal food assistance programs with food security status among adolescents in Baltimore during the COVID-19 pandemic. Adolescents, ages 14-19 years, were invited to participate in two online surveys. The baseline was implemented between October 2020 and January 2021, while the follow-up took place one year later from November 2021 to January 2022 after schools had re-opened. We then matched survey participants with household participation in food nutrition assistance programs using data obtained from the Maryland Department of Social Services. We used logistic regression to examine the association between food assistance program participation status and food insecurity. Additionally, to examine whether the impact of program participation on food insecurity changed between the baseline survey and one year later at follow-up when schools re-opened, a difference-in-differences analysis was conducted. The results showed no significant associations between adolescent food security and participation in any of the federal nutrition assistance programs. Increased attention on how best to improve adolescent food security in low-income households that can respond to the unique needs of adolescents is clearly warranted.

Objective: The coronavirus pandemic impacted health-seeking behaviour and access to primary care in Australia. We investigated factors associated with intention-to-attend and attendance of cervical screening during the pandemic, mainly in Victoria, Australia., Methods: We used questionnaire and attendance data (Aug 2020-Nov 2022) from Compass-PLUS, a sub-study of the Compass randomized-controlled trial of Human Papillomavirus-based vs cytology-based screening. Data was restricted to the HPV-screening arm for comparability to the national program. We investigated associations overall and for younger (25-39 years) and older (≥40 years) cohorts, between intention-to-attend/attendance, and socio-demographics, anxiety-related scores, and agreement with beliefs about screening during the pandemic (e.g. importance of screening, increased workload, working from home, risk of infection)., Results: Among 2,226 participants, positive intention to attend screening was more likely among those with a family history of cancer (p = 0.030) or living outside major cities (p = 0.024). Increased attendance was associated with increasing age (p < 0.001), prior regular cervical screening history [adjusted relative risk (aRR) for 2 screens in 6 years vs none: 1.23 (95 %CI 1.09,1.40); p < 0.001], and part-time employment or retirement compared to full-time employment [aRR:1.08 (1.02,1.14); aRR:1.12 (1.03, 1.22); respectively]. Lower attendance was related to increased agreement with statements indicating screening de-prioritisation (p-trend < 0.05) and higher recent anxiety, specifically in the older cohort (p-trend = 0.002)., Conclusions: Reduced priority of screening and heightened recent anxiety may partly explain indications of lower-than-expected cervical screening rates during the pandemic. It is important that catch-up of missed HPV screens is performed to prevent a possible increase in cancer diagnoses in the long term., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: KC and MS are co-PIs of an investigator-initiated trial of cervical screening, (Compass; ACTRN12613001207707 and NCT02328872) run by the Australian Centre for the Prevention of Cervical Cancer (ACPCC), which is a government-funded not-for-profit charity; ACPCC has received equipment and a funding contribution from Roche Molecular Diagnostics. KC, MS and DB are also co-PIs on a major investigator-initiated implementation program Elimination of Cervical Cancer in the Western Pacific (ECCWP) which receives support from the Minderoo Foundation, and equipment donations from Cepheid Inc. Neither KC, MS, nor their institutions have received direct funding from industry for any project. MS holds NHMRC grants for 5 projects, is the Director for Cancer Council Australia and Co-chair of HPV test characteristics expert panel and consultant for Cancer Care Ontario. MS’s institution, ACPCC, received donated HPV testing equipment for research purposes from the following companies: Roche, Seegene, Abbott, Becton Dickinson, Cepheid, AusDiganostics, Copan, Qiagen and Atila Biosystems. MAS reports salary support via fellowship grants from the NHMRC of Australia and Cancer Institute NSW and contracts paid to her institution (the Daffodil Centre) with the Commonwealth Department of Health (Australia) and National Screening Unit (New Zealand). The remaining authors have no conflicts of interests to declare., (© 2024 The Authors. Published by Elsevier Inc.)

The role of diet in colorectal cancer prognosis is not well understood and specific lifestyle recommendations are lacking. We searched for randomised controlled trials (RCTs) and longitudinal observational studies on post-diagnosis dietary factors, supplement use and colorectal cancer survival outcomes in PubMed and Embase from inception until 28th February 2022. Random-effects dose-response meta-analyses were conducted when at least three studies had sufficient information. The evidence was interpreted and graded by the CUP Global independent Expert Committee on Cancer Survivorship and Expert Panel. Five RCTs and 35 observational studies were included (30,242 cases, over 8700 all-cause and 2100 colorectal cancer deaths, 3700 progression, recurrence, or disease-free events). Meta-analyses, including 3-10 observational studies each, were conducted for: whole grains, nuts/peanuts, red and processed meat, dairy products, sugary drinks, artificially sweetened beverages, coffee, alcohol, dietary glycaemic load/index, insulin load/index, marine omega-3 polyunsaturated fatty acids, supplemental calcium, circulating 25-hydroxyvitamin D (25[OH]D) and all-cause mortality; for alcohol, supplemental calcium, circulating 25(OH)D and colorectal cancer-specific mortality; and for circulating 25(OH)D and recurrence/disease-free survival. The overall evidence was graded as 'limited'. The inverse associations between healthy dietary and/or lifestyle patterns (including diets that comprised plant-based foods), whole grains, total, caffeinated, or decaffeinated coffee and all-cause mortality and the positive associations between unhealthy dietary patterns, sugary drinks and all-cause mortality provided 'limited-suggestive' evidence. All other exposure-outcome associations provided 'limited-no conclusion' evidence. Additional, well-conducted cohort studies and carefully designed RCTs are needed to develop specific lifestyle recommendations for colorectal cancer survivors., (© 2024 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

Based on the World Cancer Research Fund Global Cancer Update Programme, we performed systematic reviews and meta-analyses to investigate the association of post-diagnosis adiposity, physical activity, sedentary behaviour, and dietary factors with colorectal cancer prognosis. We searched PubMed and Embase until 28th February, 2022. An independent expert committee and expert panel graded the quality of evidence. A total of 167 unique publications were reviewed, and all but five were observational studies. The quality of the evidence was graded conservatively due to the high risk of several biases. There was evidence of non-linearity in the associations between body mass index and colorectal cancer prognosis. The associations appeared reverse J-shaped, and the quality of this evidence was graded as limited (likelihood of causality: limited-no conclusion). The evidence on recreational physical activity and lower risk of all-cause mortality (relative risk [RR] highest vs. lowest: 0.69, 95% confidence interval [CI]: 0.62-0.77) and recurrence/disease-free survival (RR: 0.80, 95% CI: 0.70-0.92) was graded as limited-suggestive. There was limited-suggestive evidence for the associations between healthy dietary and/or lifestyle patterns (including diets that comprised plant-based foods), intake of whole grains and coffee with lower risk of all-cause mortality, and between unhealthy dietary patterns and intake of sugary drinks with higher risk of all-cause mortality. The evidence for other exposures on colorectal cancer outcomes was sparse and graded as limited-no conclusion. Analyses were conducted excluding cancer patients with metastases without substantial changes in the findings. Well-designed intervention and cohort studies are needed to support the development of lifestyle recommendations for colorectal cancer patients., (© 2024 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

The adiposity influence on colorectal cancer prognosis remains poorly characterised. We performed a systematic review and meta-analysis on post-diagnosis adiposity measures (body mass index [BMI], waist circumference, waist-to-hip ratio, weight) or their changes and colorectal cancer outcomes. PubMed and Embase were searched through 28 February 2022. Random-effects meta-analyses were conducted when at least three studies had sufficient information. The quality of evidence was interpreted and graded by the Global Cancer Update Programme (CUP Global) independent Expert Committee on Cancer Survivorship and Expert Panel. We reviewed 124 observational studies (85 publications). Meta-analyses were possible for BMI and all-cause mortality, colorectal cancer-specific mortality, and cancer recurrence/disease-free survival. Non-linear meta-analysis indicated a reverse J-shaped association between BMI and colorectal cancer outcomes (nadir at BMI 28 kg/m 2 ). The highest risk, relative to the nadir, was observed at both ends of the BMI distribution (18 and 38 kg/m 2 ), namely 60% and 23% higher risk for all-cause mortality; 95% and 26% for colorectal cancer-specific mortality; and 37% and 24% for cancer recurrence/disease-free survival, respectively. The higher risk with low BMI was attenuated in secondary analyses of RCTs (compared to cohort studies), among studies with longer follow-up, and in women suggesting potential methodological limitations and/or altered physiological state. Descriptively synthesised studies on other adiposity-outcome associations of interest were limited in number and methodological quality. All the associations were graded as limited (likelihood of causality: no conclusion) due to potential methodological limitations (reverse causation, confounding, selection bias). Additional well-designed observational studies and interventional trials are needed to provide further clarification., (© 2024 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

Low physical activity and high sedentary behaviour have been clearly linked with colorectal cancer development, yet data on their potential role in colorectal cancer survival is limited. Better characterisation of these relationships is needed for the development of post-diagnosis physical activity and sedentary behaviour guidance for colorectal cancer survivors. We searched PubMed and Embase through 28 February 2022 for studies assessing post-diagnosis physical activity, and/or sedentary behaviour in relation to all-cause and cause-specific mortality and recurrence after colorectal cancer diagnosis. Total and recreational physical activity were assessed overall and by frequency, duration, intensity, and volume using categorical, linear, and non-linear dose-response random-effects meta-analyses. The Global Cancer Update Programme (CUP Global) independent Expert Committee on Cancer Survivorship and Expert Panel interpreted and graded the likelihood of causality. We identified 16 observational studies on 82,220 non-overlapping patients from six countries. Physical activity was consistently inversely associated with colorectal cancer morbidity and mortality outcomes, with 13%-60% estimated reductions in risk. Sedentary behaviour was positively associated with all-cause mortality. The evidence had methodological limitations including potential confounding, selection bias and reverse causation, coupled with a limited number of studies for most associations. The CUP Global Expert panel concluded limited-suggestive evidence for recreational physical activity with all-cause mortality and cancer recurrence. Total physical activity and its specific domains and dimensions, and sedentary behaviour were all graded as limited-no conclusion for all outcomes. Future research should focus on randomised trials, while observational studies should obtain objective and repeated physical activity measures and better adjustment for confounders., (© 2024 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

Background: Medulloblastoma (MB) is the most common malignant pediatric brain tumor, with 5-year survival rates > 70%. Cranial radiotherapy (CRT) to the whole brain, with posterior fossa boost (PFB), underpins treatment for non-infants; however, radiotherapeutic insult to the normal brain has deleterious consequences to neurocognitive and physical functioning, and causes accelerated aging/frailty. Approaches to ameliorate radiotherapy-induced late-effects are lacking and a paucity of appropriate model systems hinders their development., Methods: We have developed a clinically relevant in vivo model system that recapitulates the radiotherapy dose, targeting, and developmental stage of childhood medulloblastoma. Consistent with human regimens, age-equivalent (postnatal days 35-37) male C57Bl/6J mice received computerized tomography image-guided CRT (human-equivalent 37.5 Gy EQD2, n  = 12) ± PFB (human-equivalent 48.7 Gy EQD2, n  = 12), via the small animal radiation research platform and were longitudinally assessed for > 12 months., Results: CRT was well tolerated, independent of PFB receipt. Compared to a sham-irradiated group ( n  = 12), irradiated mice were significantly frailer following irradiation (frailty index; P  = .0002) and had reduced physical functioning; time to fall from a rotating rod (rotarod; P  = .026) and grip strength ( P  = .006) were significantly lower. Neurocognitive deficits were consistent with childhood MB survivors; irradiated mice displayed significantly worse working memory (Y-maze; P  = .009) and exhibited spatial memory deficits (Barnes maze; P  = .029). Receipt of PFB did not induce a more severe late-effect profile., Conclusions: Our in vivo model mirrored childhood MB radiotherapy and recapitulated features observed in the late-effect profile of MB survivors. Our clinically relevant model will facilitate both the elucidation of novel/target mechanisms underpinning MB late effects and the development of novel interventions for their amelioration., Competing Interests: The authors have no conflicts of interest to declare., (© The Author(s) 2024. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.)

Background: Healthy behaviors are paramount in preventing long-term adverse health outcomes in childhood, adolescent, and young adult (CAYA) cancer survivors. We systematically reviewed and synthesized existing literature on barriers, facilitators, and other factors associated with health behaviors in this population., Methods: MEDLINE and PsycInfo were searched for qualitative and quantitative studies including survivors aged 16-50 years at study, a cancer diagnosis ≤25 years and ≥2 years post diagnosis. Health behaviors included physical activity, smoking, diet, alcohol consumption, sun exposure, and a combination of these behaviors (defined as health behaviors in general)., Results: Barriers, facilitators, and other factors reported in ≥2 two studies were considered relevant. Out of 4529 studies, 27 were included (n = 31,905 participants). Physical activity was the most frequently examined behavior (n = 12 studies), followed by smoking (n = 7), diet (n = 7), alcohol (n = 4), sun exposure (n = 4), and health behavior in general (n = 4). Relevant barriers to physical activity were fatigue, lack of motivation, time constraints, and current smoking. Relevant facilitators were perceived health benefits and motivation. Influence of the social environment and poor mental health were associated with more smoking, while increased energy was associated with less smoking. No relevant barriers and facilitators were identified for diet, alcohol consumption, and sun exposure. Barriers to healthy behavior in general were unmet information needs and time constraints whereas lifestyle advice, information, and discussions with a healthcare professional facilitated healthy behavior in general. Concerning other factors, women were more likely to be physically inactive, but less likely to drink alcohol and more likely to comply with sun protection recommendations than men. Higher education was associated with more physical activity, and lower education with more smoking., Conclusion: This knowledge can be used as a starting point to develop health behavior interventions, inform lifestyle coaches, and increase awareness among healthcare providers regarding which survivors are most at risk of unhealthy behaviors., (© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)

Metabolic disease is epidemiologically linked to severe complications upon influenza virus infection, thus vaccination is a priority in this high-risk population. Yet, vaccine responses are less effective in these same hosts. Here we examined how the timing of diet switching from a high-fat diet to a control diet affected influenza vaccine efficacy in diet-induced obese mice. Our results demonstrate that the systemic meta-inflammation generated by high-fat diet exposure limited T cell maturation to the memory compartment at the time of vaccination, impacting the recall of effector memory T cells upon viral challenge. This was not improved with a diet switch post-vaccination. However, the metabolic dysfunction of T cells was reversed if weight loss occurred 4 weeks before vaccination, restoring a functional recall response. This corresponded with changes in the systemic obesity-related biomarkers leptin and adiponectin, highlighting the systemic and specific effects of diet on influenza vaccine immunogenicity., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Childhood, adolescent and young adult (CAYA) cancer survivors are vulnerable to adverse late-effects. For CAYA cancer survivors, tobacco smoking is the most important preventable cause of ill-health and early death. Yet, effective strategies to support smoking cessation in this group are lacking. The PRISM study aims to undertake multi-method formative research to explore the need for, and if appropriate, inform the future development of an evidence-based and theory-informed tobacco smoking cessation intervention for CAYA cancer survivors., Materials and Methods: PRISM involves three phases of: 1) an environmental scan using multiple strategies to identify and examine a) smoking cessation interventions for CAYA cancer survivors that are published in the international literature and b) current smoking cessation services in England that may be available to, or tailorable to, CAYA cancer survivors; 2) a qualitative study involving semi-structured interviews with CAYA cancer survivors (aged 16-29 years and who are current or recent ex-smokers and/or current vapers) to explore their views and experiences of smoking, smoking cessation and vaping; and 3) stakeholder workshops with survivors, healthcare professionals and other stakeholders to consider the potential for a smoking cessation intervention for CAYA cancer survivors and what such an intervention would need to target and change. Findings will be disseminated to patient groups, healthcare professionals and researchers, through conference presentations, journal papers, plain English summaries and social media., Discussion: PRISM will explore current delivery of, perceived need for, and barriers and facilitators to, smoking cessation advice and support to CAYA cancer survivors from the perspective of both survivors and healthcare professionals. A key strength of PRISM is the user involvement throughout the study and the additional exploration of survivors' views on vaping, a behaviour which often co-occurs with smoking. PRISM is the first step in the development of a person-centred, evidence- and theory-based smoking cessation intervention for CAYA cancer survivors who smoke, which if effective, will reduce morbidity and mortality in the CAYA cancer survivor population., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Brown et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Childhood cancer survivors are at risk of subsequent gliomas and meningiomas, but the risks beyond age 40 years are uncertain. We quantified these risks in the largest ever cohort., Methods: Using data from 69,460 5-year childhood cancer survivors (diagnosed 1940-2008), across Europe, standardized incidence ratios (SIRs) and cumulative incidence were calculated., Results: In total, 279 glioma and 761 meningioma were identified. CNS tumour (SIR: 16.2, 95% CI: 13.7, 19.2) and leukaemia (SIR: 11.2, 95% CI: 8.8, 14.2) survivors were at greatest risk of glioma. The SIR for CNS tumour survivors was still 4.3-fold after age 50 (95% CI: 1.9, 9.6), and for leukaemia survivors still 10.2-fold after age 40 (95% CI: 4.9, 21.4). Following cranial radiotherapy (CRT), the cumulative incidence of a glioma in CNS tumour survivors was 2.7%, 3.7% and 5.0% by ages 40, 50 and 60, respectively, whilst for leukaemia this was 1.2% and 1.7% by ages 40 and 50. The cumulative incidence of a meningioma after CRT in CNS tumour survivors doubled from 5.9% to 12.5% between ages 40 and 60, and in leukaemia survivors increased from 5.8% to 10.2% between ages 40 and 50., Discussion: Clinicians following up survivors should be aware that the substantial risks of meningioma and glioma following CRT are sustained beyond age 40 and be vigilant for symptoms., (© 2024. The Author(s).)

The aim of this review is to raise awareness and knowledge among healthcare professionals and policymakers about late adverse effects in survivors of childhood leukemia. With contemporary treatment, over 90% of children with acute lymphoblastic leukemia (ALL) and over 60% with acute myeloid leukemia (AML) are cured. Large cohort studies demonstrate that 20% of ALL and most AML survivors have at least one chronic health condition by 20-25 years after diagnosis. These are life-changing or threatening in some survivors and contribute to increased premature mortality. We describe the frequency, causes, clinical features, and natural history of the most frequent and severe late adverse effects in childhood leukemia survivors, including subsequent malignant neoplasms, metabolic toxicity, gonadotoxicity and impaired fertility, endocrinopathy and growth disturbances, bone toxicity, central and peripheral neurotoxicity, cardiotoxicity, psychosocial late effects, accelerated ageing and late mortality. The wide range of late effects in survivors of haemopoietic stem cell transplant is highlighted. Recent developments informing the approach to long-term survivorship care are discussed, including electronic personalized patient-specific treatment summaries and care plans such as the Survivor Passport (SurPass), surveillance guidelines and models of care. The importance of ongoing vigilance is stressed given the increasing use of novel targeted drugs with limited experience of long-term outcomes. CONCLUSION: It is vital to raise awareness of the existence and severity of late effects of childhood leukemia therapy among parents, patients, health professionals, and policymakers. Structured long-term surveillance recommendations are necessary to standardize follow-up care., (Copyright © 2024 Roganovic et al. This article is available under a Creative Commons License (Attribution 4.0 International).)

Childhood, adolescent, and young adult (CAYA) cancer survivors are at risk of pulmonary dysfunction. Current follow-up care guidelines are discordant. Therefore, the International Late Effects of Childhood Cancer Guideline Harmonization Group established and convened a panel of 33 experts to develop evidence-based surveillance guidelines. We critically reviewed available evidence regarding risk factors for pulmonary dysfunction, types of pulmonary function testing, and timings of surveillance, then we formulated our recommendations. We recommend that CAYA cancer survivors and healthcare providers are aware of reduced pulmonary function risks and pay vigilant attention to potential symptoms of pulmonary dysfunction, especially among survivors treated with allogeneic haematopoietic stem cell transplantation, thoracic radiotherapy, and thoracic surgery. Based on existing limited evidence and current lack of interventions, our panel recommends pulmonary function testing only for symptomatic survivors. Since scarce existing evidence informs our recommendation, we highlight the need for prospective collaborative studies to address pulmonary function knowledge gaps among CAYA cancer survivors., Competing Interests: -AC Dietz is employed by and has equity in Shape Therapeutics, Inc. and was employed by and has equity in bluebird bio, Inc., neither of which provided financial support or oversight of this work.-AB received fees for lectures and/or boards from Astra-Zeneca, Novartis, Enanta paid to her institution as well as travel grants from Boehringer and Astra-Zeneca.-CEK received grants from the Swiss National Science Foundation-MO received research support from the Swiss Pediatric Oncology Society (SPOG)-DJW received grants/contracts from Vertex pharmaceuticals, Cystic Fibrosis Foundation Therapeutic Development Network, payment or honoraria for lectures/presentations by Cystic Fibrosis Foundation and American Board of Pediatrics-GS and RK received support for the present manuscript by Bernische Krebsliga and Lungenliga Bern-LSC received support from University of Alabama for COG Survivorship guidelines, royalties or licenses from Springer and Wolters Kluwer, payment or honoraria for lectures/presentations from the American Society for Hematology and the University of Miami, travel support from the First International Pediatric Cardio-oncology meeting, and participates on the Data Safety Monitoring Board or Advisory Board of the NCI PDQ-MG received a grant from the Swiss National Science Foundation, support for attending meetings and/or travel from the European Respiratory Society, has a leadership role in the BEAT-PCD ERS clinical research collaboration-NW received general research support from CANSEARCH Research Foundation, payment/honoraria and support to attend an international meeting from Swedish Orphan Biovitrum (SOBI), participates on a Data Safety Monitoring Board or Advisory Board from SOBI-PL received grants/contracts from Vertex and OM Pharma, payments or honoraria for lectures/presentations by Vertex, Vifor and OM Pharma, participates on a Data Safety Monitoring Board or Advisory Board from Polyphor, Santhera, Vertex, OM Pharma, Vifor, Sanofi Aventis-UH received a grant and support for attending meetings from the German Childhood Cancer Foundation,, (© 2024 Published by Elsevier Ltd.)

Migraines are a common neurological disorder that generally affects young to middle-aged adults and females more than males. Various treatment options are available; however, these can cause undesirable side effects. Therefore, alternative treatments with minimal side effects are still being investigated. Palmitoylethanolamide (PEA) is a signalling lipid known to have anti-inflammatory and analgesic properties. Previous prophylactic research has reported PEA supplementation to decrease pain associated with migraines. Upon commencement of migraine symptoms, participants were supplemented with either 600 mg of PEA (Levagen+) or a placebo (maltodextrin). Once a dose was taken, participants recorded a visual analogue scale (VAS) for pain every 30 min for 4 h or until the migraine resolved. If the migraine had not resolved 2 h post-dose, participants were instructed to take a second dose. Levagen+ supplementation resolved more headaches after 2- and 8 h, had a lower VAS for pain score at 1.5 and 4 h, and reduced rescue medication use significantly more than a placebo. No adverse events were reported in either group. Overall, PEA was safe and effective in reducing migraine pain, duration, and medication use in an otherwise healthy adult population.

Purpose: Childhood cancer survivors are at the risk of developing subsequent colorectal cancers (CRCs), but the absolute risks by treatment modality are uncertain. We quantified the absolute risks by radiotherapy treatment characteristics using clinically accessible data from a Pan-European wide case-control study nested within a large cohort of childhood cancer survivors: the PanCareSurFup Study., Methods: Odds ratios (ORs) from a case-control study comprising 143 CRC cases and 143 controls nested within a cohort of 69,460 survivors were calculated. These, together with standardized incidence ratios for CRC for this cohort and European general population CRC incidence rates and survivors' mortality rates, were used to estimate cumulative absolute risks (CARs) by attained age for different categories of radiation to the abdominopelvic area., Results: Overall, survivors treated with abdominopelvic radiotherapy treatment (ART) were three times more likely to develop a subsequent CRC than those who did not receive ART (OR, 3.1 [95% CI, 1.4 to 6.6]). For male survivors treated with ART, the CAR was 0.27% (95% CI, 0.17 to 0.59) by age 40 years, 1.08% (95% CI, 0.69 to 2.34) by age 50 years (0.27% expected in the general population), and 3.7% (95% CI, 2.36 to 7.80) by age 60 years (0.95% expected). For female survivors treated with ART, the CAR was 0.29% (95% CI, 0.18 to 0.62) by age 40 years, 1.03% (95% CI, 0.65 to 2.22) by age 50 years (0.27% expected), and 3.0% (95% CI, 1.91 to 6.37) by age 60 years (0.82% expected)., Conclusion: We demonstrated that by age 40 years survivors of childhood cancer treated with ART already have a similar risk of CRC as those age 50 years in the general population for whom population-based CRC screening begins in many countries. This information should be used in the development of survivorship guidelines for the risk stratification of survivors concerning CRC risk.

Purpose: Childhood, adolescent and young adult (CAYA) cancer survivors require ongoing surveillance for health problems from the end of cancer treatment throughout their lives. There is a lack of evidence-based guidelines on optimal surveillance strategies for the period from the end of treatment to 5 years after diagnosis. We aimed to address this gap by developing recommendations for short-term surveillance of health problems based on existing long-term follow-up (LTFU) care guidelines., Methods: The guideline working group, consisting of healthcare professionals, parents and survivor representatives from 10 countries, worked together to identify relevant health problems that may occur in survivors between the end of treatment and 5 years after diagnosis and to develop recommendations for short-term surveillance of health problems. The recommendations were drawn from existing LTFU guidelines and adapted where necessary based on clinical expertise., Results: The working group developed 44 recommendations for short-term surveillance of health problems, which were divided into four categories based on the level of surveillance required: awareness only (n = 11), awareness, history and/or physical examination without surveillance test (n = 15), awareness, history and/or physical examination with potential surveillance test (n = 1) and awareness, history and/or physical examination with surveillance test (n = 17)., Conclusion: The development of a guideline for short-term surveillance of health problems fills a critical gap in survivorship care for CAYA cancer survivors, providing much-needed support immediately after treatment up to 5 years after diagnosis., Implications for Cancer Survivors: This guideline will support healthcare professionals to provide appropriate follow-up care and improve the quality of life of CAYA cancer survivors., (© 2023. The Author(s).)

Introduction: Upper respiratory tract infections (URTIs) are caused by bacteria or viruses, with the most common causes being the common cold and influenza. The high occurrence of URTI means therapies that are effective with minimal side effects are in constant demand. Palmitoylethanolamide (PEA) is a signaling lipid previously shown to be effective in improving the incidence of URTIs. The aim of this study was to assess the effectiveness of PEA (Levagen+) on URTI incidence, duration, and severity., Methods: Participants ( n = 426) consumed either 300 mg of Levagen+ or a placebo (maltodextrin) twice daily for 12 weeks. Participants completed the Wisconsin Upper Respiratory Symptom Survey 24 questionnaire daily upon the commencement of symptoms until symptoms subsided., Results: The Levagen+ group reported fewer URTI episodes (39 vs. 64) compared to the placebo group. The Levagen+ group reported a significant reduction in the median severity score of URTI symptoms for scratchy throat (3 vs. 7) and cough (2 vs. 7) compared to the placebo group., Conclusions: The results of this study show Levagen+ to be safe and effective in reducing the incidence and symptoms associated with URTIs.

The water sector could play a major role towards a Net Zero greenhouse gas (GHG) future if Scope 3 emissions were embraced and operationalised. Significant opportunities and challenges exist in tackling Scope 3 emissions including those associated with customer hot water use. Present GHG emission reduction practices predominantly focus on Scope 1 "within utility" and Scope 2 "purchased energy" emissions. In the urban water cycle, Scope 3 "indirect" emissions dominate, and water use is only one example of Scope 3 emissions. Over 90% of all water cycle GHG emissions can be attributed to water use in residential, industrial and commercial premises, collectively some 7% of global GHG emissions. One possibility is for water utilities to actively support efficient hot water use such as new ultra-low flow shower heads. Scope 3 opportunities also offer a range of cost-effective emissions-reduction opportunities, particularly when the wider perspective of "community value" is considered and not just a "business financial perspective". Hot water efficiency is additionally essential to Net Zero carbon futures, even with decarbonised grids, because most major Net Zero roadmaps require energy efficiency gains. Scientific and management advance needed includes: accounting methodologies, clear roles, collaboration, new business models, and clear definitions. The water sector has the opportunity to play a significant role in achieving Net Zero cities. The decision how much is yet to be made., Competing Interests: All authors declare they have no financial or personal relationships with other people or organizations that could inappropriately influence (bias) their work. There are no interests to declare., (© 2023 The Authors. Published by Elsevier Ltd.)

Introduction: Adolescence is a period of major transition in physical, cognitive, social and emotional development, and the peak time for the onset of mental health conditions, substance use disorders and sexual and reproductive health risks. Prevention and treatment during this time can improve health and well-being now and into the future. However, despite clinical guidelines recommending annual preventive health assessments for young people, health professionals cite lack of consultation time and adequate funding as key barriers. This trial aims to determine whether a specific fee-for-service ('rebate payment') for a young person's health assessment, is effective and cost-effective at increasing the detection and management of health risk behaviours and conditions among young people., Methods and Analysis: This cluster randomised controlled trial will be conducted in Australian general practice. 42 general practices (clusters) will be randomly allocated 1:1 to either an intervention arm where general practitioners receive a rebate payment for each annual health assessment undertaken for 14-24-year-olds during a 2 year study period, or a control arm (no rebate). The rebate amount will be based on the Medical Benefits Schedule (Australia's list of health professional services subsidised by the Australian Government) currently available for similar age-based assessments. Our primary outcome will be the annual rate of risk behaviours and health conditions recorded in the patient electronic health record (eg, alcohol/drug use, sexual activity and mental health issues). Secondary outcomes include the annual rate of patient management activities related to health risks and conditions identified (eg, contraception prescribed, sexually transmitted infection tests ordered). A process evaluation will assess acceptability, adoption, fidelity and sustainability of the rebate; an economic evaluation will assess its cost-effectiveness. Analyses will be intention-to-treat., Ethics and Dissemination: Ethics approval has been obtained from University of Melbourne Human and Research Ethics Committee (2022-23435-29990-3). Findings will be published in peer-reviewed journals., Trial Registration Number: ACTRN12622000114741., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: Radiation to the bone and exposure to alkylating agents increases the risk of bone cancer among survivors of childhood cancer, but there is uncertainty regarding the risks of bone tissue radiation doses below 10 Gy and the dose-response relationship for specific types of chemotherapy., Methods: Twelve European countries contributed 228 cases and 228 matched controls to a nested case-control study within a cohort of 69,460 5-year survivors of childhood cancer. Odds ratios (ORs) of developing bone cancer for different levels of cumulative radiation exposure and cumulative doses of specific types of chemotherapy were calculated. Excess ORs were calculated to investigate the shape and extent of any dose-response relationship., Results: The OR associated with bone tissue exposed to 1-4 Gy was 4.8-fold (95% CI, 1.2 to 19.6) and to 5-9 Gy was 9.6-fold (95% CI, 2.4 to 37.4) compared with unexposed bone tissue. The OR increased linearly with increasing dose of radiation ( P trend < .001) up to 78-fold (95% CI, 9.2 to 669.9) for doses of ≥40 Gy. For cumulative alkylating agent doses of 10,000-19,999 and ≥20,000 mg/m 2 , the radiation-adjusted ORs were 7.1 (95% CI, 2.2 to 22.8) and 8.3 (95% CI, 2.8 to 24.4), respectively, with independent contributions from each of procarbazine, ifosfamide, and cyclophosphamide. Other cytotoxics were not associated with bone cancer., Conclusion: To our knowledge, we demonstrate-for the first time-that the risk of bone cancer is increased 5- to 10-fold after exposure of bone tissue to cumulative radiation doses of 1-9 Gy. Alkylating agents exceeding 10,000 mg/m 2 increase the risk 7- to 8-fold, particularly following procarbazine, ifosfamide, and cyclophosphamide. These substantially elevated risks should be used to develop/update clinical follow-up guidelines and survivorship care plans.

Background: Healthy behaviors, that is, engaging in regular physical activities, maintaining a healthy diet, limiting alcohol consumption, and avoiding tobacco and drug use, decrease the risk of developing late adverse health conditions in childhood cancer survivors. However, childhood cancer survivors may experience barriers to adopting and maintaining healthy behaviors. This study aimed to assess these barriers and facilitators to health behavior adoption and maintenance in childhood cancer survivors., Methods: A focus group ( n  = 12) and semi-structured telephone interviews ( n  = 20) were conducted with a selected sample of European and Dutch childhood cancer survivors, respectively. The Theoretical Domains Framework (TDF) was used to inform the topic guide and analysis. Inductive thematic analysis was applied to identify categories relating to barriers and facilitators of health behavior adoption and maintenance, after which they were deductively mapped onto the TDF., Results: Ten TDF domains were identified in the data of which "Knowledge," "Beliefs about consequences," "Environmental context and resources," and "Social influences" were most commonly reported. Childhood cancer survivors expressed a need for knowledge on the importance of healthy behaviors, possibly provided by healthcare professionals. They indicated physical and long-term benefits of healthy behaviors, available professional support, and a supporting and health-consciously minded work and social environment to be facilitators. Barriers were mostly related to a lack of available time and an unhealthy environment. Lastly, (social) media was perceived as both a barrier and a facilitator to healthy behaviors., Conclusion: This study has identified education and available professional support in health behaviors and the relevance of healthy behaviors for childhood cancer survivors as key opportunities for stimulating health behavior adoption in childhood cancer survivors. Incorporating health behavior support and interventions for this population should therefore be a high priority., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: Living in low-income countries often restricts the consumption of adequate protein and animal protein., Objectives: This study aimed to investigate the effects of feeding low-protein diets on growth and liver health using proteins recovered from animal processing., Methods: Female Sprague-Dawley rats (aged 28 d) were randomly assigned (n = 8 rats/group) to be fed standard purified diets with 0% or 10% kcal protein that was comprised of either carp, whey, or casein., Results: Rats that were fed low-protein diets showed higher growth but developed mild hepatic steatosis compared to rats that were fed a no-protein diet, regardless of the protein source. Real-time quantitative polymerase chain reactions targeting the expression of genes involved in liver lipid homeostasis were not significantly different among groups. Global RNA-sequencing technology identified 9 differentially expressed genes linked to folate-mediated 1-carbon metabolism, endoplasmic reticulum (ER) stress, and metabolic diseases. Canonical pathway analysis revealed that mechanisms differed depending on the protein source. ER stress and dysregulated energy metabolism were implicated in hepatic steatosis in carp- and whey-fed rats. In contrast, impaired liver one-carbon methylations, lipoprotein assembly, and lipid export were implicated in casein-fed rats., Conclusions: Carp sarcoplasmic protein showed comparable results to commercially available casein and whey protein. A better understanding of the molecular mechanisms in hepatic steatosis development can assist formulation of proteins recovered from food processing into a sustainable source of high-quality protein., (Published by Elsevier Inc.)

Physical activity (PA) is recommended for childhood cancer survivors (CCSs). However, many CCSs have low levels of activity. This review aimed to systematically identify, appraise and synthesise qualitative research evidence on the barriers and facilitators to PA from the perspective of CCSs. Six databases (MEDLINE, Embase, PsycINFO, CINAHL, SPORTDiscus, and Scopus) were searched to identify qualitative data on PA gathered from CCSs diagnosed ≤18 years of age and who had completed active treatment. An inductive thematic synthesis was undertaken to identify descriptive themes relating to barriers and facilitators to PA, before mapping these onto the Theoretical Domains Framework (TDF). Methodological quality was assessed using CASP, and confidence in review findings was assessed using the GRADE-CERQual approach. Eight original studies were eligible. A total of 45 descriptive themes (29 facilitators and 16 barriers) were mapped onto nine domains of the TDF; they were most commonly mapped onto the Environmental Context and Resources ( n  = 13 descriptive themes) and the Social Influences ( n  = 13) domains. Study quality was variable and overall confidence in review findings was low. Conclusive/strong evidence for the barriers and facilitators to PA is lacking, highlighting the need for further research on the perceived influences on PA in CCSs. PROSPERO Registration: CRD42019147829.

Objectives: Apple pomace, a waste byproduct of apple processing, is rich in nutrients (e.g. polyphenols and soluble fiber) with the potential to be neuroprotective. The aim of this study was to employ RNA-sequencing (RNASeq) technology to investigate diet-gene interactions in the hypothalamus of rats after feeding a Western diet calorically substituted with apple pomace., Methods: Adolescent (age 21-29 days) female Sprague-Dawley rats were randomly assigned ( n  = 8 rats/group) to consume either a purified standard diet, Western (WE) diet, or Western diet calorically substituted with 10% apple pomace (WE/AP) for 8 weeks. RNA-seq was performed ( n  = 5 rats/group) to determine global differentially expressed genes in the hypothalamus., Results: RNA-seq results comparing rats fed WE to WE/AP revealed 15 differentially expressed genes in the hypothalamus. Caloric substitution of WE diet with 10% apple pomace downregulated ( q  < 0.06) five genes implicated in brain aging and neurodegenerative disorders: synuclein alpha, phospholipase D family member 5, NADH dehydrogenase Fe-S protein 6, choline O-acetyltransferase, and frizzled class receptor 6., Discussion: Altered gene expression of these five genes suggests that apple pomace ameliorated synthesis of the neurotransmitter, acetylcholine, in rats fed a WE diet. Apple pomace, a rich source of antioxidant polyphenols and soluble fiber, has been shown to reverse nonalcoholic fatty liver disease (NAFLD). Diet-induced NAFLD decreases hepatic de novo synthesis of choline, a precursor to acetylcholine. Based on preclinical evidence, apple pomace has the potential to be a sustainable functional food for maintaining brain function and for reducing the risk of neurodegeneration.

Childhood cancer survival has improved significantly in the past few decades, reaching rates of 80% or more at 5 years. However, with improved survival, early- and late-occurring complications of chemotherapy and radiotherapy exposure are becoming progressively more evident. Cardiovascular diseases represent the leading cause of non-oncological morbidity and mortality in this highly vulnerable population. Therefore, the necessity of reliable, noninvasive screening tools able to early identify cardiac complications early is now pre-eminent in order to implement prevention strategies and mitigate disease progression. Echocardiography, may allow identification of myocardial dysfunction, pericardial complications, and valvular heart diseases. However, additional imaging modalities may be necessary in selected cases. This manuscript provides an in-depth review of noninvasive imaging parameters studied in childhood cancer survivors. Furthermore, we will illustrate brief surveillance recommendations according to available evidence and future perspectives in this expanding field., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Survivors of childhood, adolescent, and young adult cancer, previously treated with anthracycline chemotherapy (including mitoxantrone) or radiotherapy in which the heart was exposed, are at increased risk of cardiomyopathy. Symptomatic cardiomyopathy is typically preceded by a series of gradually progressive, asymptomatic changes in structure and function of the heart that can be ameliorated with treatment, prompting specialist organisations to endorse guidelines on cardiac surveillance in at-risk survivors of cancer. In 2015, the International Late Effects of Childhood Cancer Guideline Harmonization Group compiled these guidelines into a uniform set of recommendations applicable to a broad spectrum of clinical environments with varying resource availabilities. Since then, additional studies have provided insight into dose thresholds associated with a risk of asymptomatic and symptomatic cardiomyopathy, have characterised risk over time, and have established the cost-effectiveness of different surveillance strategies. This systematic Review and guideline provides updated recommendations based on the evidence published up to September, 2020., Competing Interests: Declaration of interests AN reports research support from Amgen; a research contract with Bristol Myers Squibb; consulting fees from AstraZeneca, Boehringer Ingelheim, and Bantam Pharmaceuticals; and participation on a data safety monitoring board for Takeda Oncology. CP reports personal honoraria and expenses for presentation at education meetings from Amgen, Incyte, Ipsen, Novartis, and Servier. LSC reports grant funding from the University of Alabama for the Children's Oncology Group Guidelines, payment or honoraria for lectures or presentations from the American Society of Hematology and the University of Miami, and participation in the National Cancer Institute PDQ Pediatric Oncology Board. EJC is the Principal Investigator on a research grant to his institution from Abbott Laboratories. All other authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Childhood cancer survivors (CCSs) have an increased risk of developing chronic health conditions. Evidence suggests that poor health behaviors further increase health risks. Healthcare professionals (HCPs) involved in survivorship care have a key role in providing health behavior support (HBS) but can feel limited in their ability to do so. This study aims to explore European HCPs perceived facilitators and barriers to providing HBS to CCSs., Methods: Five focus groups with 30 HCPs from survivorship care clinics across Europe were conducted. Topic guides were informed by the Theoretical Domains Framework (TDF) to capture domains that may influence provision of HBS. Focus groups were analyzed with thematic analysis. Transcripts were inductively coded, after which axial coding was applied to organize codes into categories. Finally, categories were mapped onto the TDF domains., Results: Nine TDF domains were identified in the data. The most commonly reported TDF domains were "Knowledge", "Skills", and "Environmental context and resources". HCPs indicated that their lack of knowledge of the association between late effects and health behaviors, besides time restrictions, were barriers to HBS. Facilitators for HBS included possession of skills needed to pass on health behavior information, good clinic organization, and an established network of HCPs., Conclusions: This study identified education and training of HCPs as key opportunities to improve HBS. Survivorship care clinics should work towards establishing well-integrated structured care with internal and external networks including HBS being part of routine care. Proper understanding of facilitators and barriers should lead to better survivorship care for CCSs., (© 2022 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: Survivors of Hodgkin lymphoma (HL) are at risk of developing non-Hodgkin lymphoma (NHL) after treatment; however, the risks of developing subsequent primary lymphomas (SPLs), including HL and NHL, after different types of childhood cancer are unknown. The authors quantified the risk of SPLs using the largest cohort of childhood cancer survivors worldwide., Methods: The Pan-European Network for Care of Survivors After Childhood and Adolescent Cancer (PanCare) Survivor Care and Follow-Up Studies (PanCareSurFup) cohort includes 69,460 five-year survivors of childhood cancer, diagnosed during 1940 through 2008, from 12 European countries. Risks of SPLs were quantified by standardized incidence ratios (SIRs) and relative risks (RRs) using multivariable Poisson regression., Results: Overall, 140 SPLs, including 104 NHLs and 36 HLs, were identified. Survivors were at 60% increased risk of an SPL compared with the general population (SIR, 1.6; 95% confidence interval [CI], 1.4-1.9). Survivors were twice as likely to develop NHL (SIR, 2.3; 95% CI, 1.9-2.8), with the greatest risks among survivors of HL (SIR, 7.1; 95% CI, 5.1-10.0), Wilms tumor (SIR, 3.1; 95% CI, 1.7-5.7), leukemia (SIR, 2.8; 95% CI, 1.8-4.4), and bone sarcoma (SIR, 2.7; 95% CI, 1.4-5.4). Treatment with chemotherapy for any cancer doubled the RR of NHL (RR, 2.1; 95% CI, 1.2-3.9), but treatment with radiotherapy did not (RR, 1.2; 95% CI, 0.7-2.0). Survivors were at similar risk of developing a subsequent HL as the general population (SIR, 1.1; 95% CI, 0.8-1.5)., Conclusions: In addition to HL, the authors show here for the first time that survivors of Wilms tumor, leukemia, and bone sarcoma are at risk of NHL. Survivors and health care professionals should be aware of the risk of NHL in these survivors and in any survivors treated with chemotherapy., (© 2022 The Authors. Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.)

Aim: Schools are a key platform for health promotion and a point of connection to local health-care services, with an almost universal reach across the child and adolescent population. This study sought to determine whether validated psychosocial assessment tools exist for a school-based nursing program that would assist in providing an initial health assessment to identify and understand the needs of children and young people referred to the nurse, with the outcome of appropriate connection to external health and wellbeing services., Methods: Rapid evidence assessment methodology was utilised to identify validated tools that could identify psychosocial concerns in children and young people aged 5-18 years. We identified articles from peer-reviewed journals via three electronic bibliographic databases (PubMed, Embase and CINAHL). We then extended the search for evidence through a search of the grey literature., Results: From 3963 peer-reviewed articles found in the database search, 10 relevant peer-reviewed publications met inclusion criteria. In combination with 12 grey literature sources, 33 tools were identified. These included self-report tools (typically for children aged 11 years and older), parent-report and teacher-report tools. We identified the six most promising psychosocial assessment tools. However, there was limited description about implementation within school-based nursing programs., Conclusions: Several tools exist that show promise in assisting school-based nursing programs to conduct preliminary psychosocial assessments for children and young people. The introduction of any tools into practice would require implementation guidance and evaluation, including how and when they should be used, and when referral and follow-up is required., (© 2023 Paediatrics and Child Health Division (The Royal Australasian College of Physicians).)

Purpose: Heart failure (HF) is a potentially life-threatening complication of treatment for childhood cancer. We evaluated the risk and risk factors for HF in a large European study of long-term survivors. Little is known of the effects of low doses of treatment, which is needed to improve current treatment protocols and surveillance guidelines., Methods: This study includes the PanCareSurFup and ProCardio cohort of ≥ 5-year childhood cancer survivors diagnosed between 1940 and 2009 in seven European countries (N = 42,361). We calculated the cumulative incidence of HF and conducted a nested case-control study to evaluate detailed treatment-related risk factors., Results: The cumulative incidence of HF was 2% (95% CI, 1.7 to 2.2) by age 50 years. The case-control study (n = 1,000) showed that survivors who received a mean heart radiation therapy (RT) dose of 5 to < 15 Gy have an increased risk of HF (odds ratio, 5.5; 95% CI, 2.5 to 12.3), when compared with no heart RT. The risk associated with doses 5 to < 15 Gy increased with exposure of a larger heart volume. In addition, the HF risk increased in a linear fashion with higher mean heart RT doses. Regarding total cumulative anthracycline dose, survivors who received ≥ 100 mg/m 2 had a substantially increased risk of HF and survivors treated with a lower dose showed no significantly increased risk of HF. The dose-response relationship appeared quadratic with higher anthracycline doses., Conclusion: Survivors who received a mean heart RT dose of ≥ 5 Gy have an increased risk of HF. The risk associated with RT increases with larger volumes exposed. Survivors treated with < 100 mg/m 2 total cumulative anthracycline dose have no significantly increased risk of HF. These new findings might have consequences for new treatment protocols for children with cancer and for cardiomyopathy surveillance guidelines.

Background: Survivors of childhood cancer are at risk of subsequent primary malignant neoplasms (SPNs), but the risk for rarer types of SPNs, such as oral cancer, is uncertain. Previous studies included few oral SPNs, hence large-scale cohorts are required to identify groups at risks., Methods: The PanCareSurFup cohort includes 69,460 5-year survivors of childhood cancer across Europe. Risks of oral SPNs were defined by standardised incidence ratios (SIRs), absolute excess risks and cumulative incidence., Results: One hundred and forty-five oral SPNs (64 salivary gland, 38 tongue, 20 pharynx, 2 lip, and 21 other) were ascertained among 143 survivors. Survivors were at 5-fold risk of an oral SPN (95% CI: 4.4-5.6). Survivors of leukaemia were at greatest risk (SIR = 19.2; 95% CI: 14.6-25.2) followed by bone sarcoma (SIR = 6.4, 95% CI: 3.7-11.0), Hodgkin lymphoma (SIR = 6.2, 95% CI: 3.9-9.9) and soft-tissue sarcoma (SIR = 5.0, 95% CI: 3.0-8.5). Survivors treated with radiotherapy were at 33-fold risk of salivary gland SPNs (95% CI: 25.3-44.5), particularly Hodgkin lymphoma (SIR = 66.2, 95% CI: 43.6-100.5) and leukaemia (SIR = 50.5, 95% CI: 36.1-70.7) survivors. Survivors treated with chemotherapy had a substantially increased risk of a tongue SPN (SIR = 15.9, 95% CI: 10.6-23.7)., Conclusions: Previous radiotherapy increases the risk of salivary gland SPNs considerably, while chemotherapy increases the risk of tongue SPNs substantially. Awareness of these risks among both health-care professionals and survivors could play a crucial role in detecting oral SPNs early., (© 2022. The Author(s).)

Haematopoietic stem cell transplant (HSCT) recipients have deficiencies in their adaptive immunity against vaccine preventable diseases. National and International guidance recommends that HSCT recipients are considered 'never vaccinated' and offered a comprehensive course of revaccination. This position statement aims to draw upon the current evidence base and existing guidelines, and align this with national vaccine availability and licensing considerations in order to recommend a pragmatic and standardised re-vaccination schedule for adult and paediatric HSCT recipients in the UK., Competing Interests: Declaration of Competing Interest JS – Honoraria for educational events from Jazz, Gilead, Janssen. Advisory board membership from Medac, and trial IDMC membership from Kiadis Pharma. Other authors have no conflicts of interest to declare., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Physical inactivity and unhealthy dietary habits are known to be disadvantageous for the development of late adverse effects in survivors of childhood, adolescent, and young adult cancer. To make interventions, aimed at improving lifestyle, fit into the daily life of survivors, interventions should be designed and delivered in a person-centred way with a limited time burden. As part of the European PanCareFollowUp project, an eHealth intervention was developed to support sustainable changes to physical activity levels and/or diet of childhood, adolescent, and young adult cancer survivors. This feasibility study aims to gain insight into the feasibility and potential effect sizes of the PanCareFollowUp lifestyle intervention., Methods: The PanCareFollowUp lifestyle intervention consists of person-centred 3-6 screen-to-screen sessions with a certified lifestyle coach. The intervention will be evaluated with a single-arm pre-post feasibility study conducted at two survivorship care clinics in the Netherlands. A total of 60 participants who are (i) diagnosed with cancer <25 years, (ii) ≥ 5 years post-treatment, (iii) aged 16-55 years, and (iv) have a low physical activity level and/or unhealthy dietary intake manifested by overweight will be recruited. Using reports, hospital records, and questionnaires for survivors, coaches, and late effect doctors, feasibility will be based on (i) adherence to intervention, (ii) acceptability, (iii) practicality, (iv) integration/implementation, (v) demand, and (vi) attrition. The potential effect sizes of the intervention will be explored by determining the percentage of survivors that reach the personalized lifestyle goals that were set with the coach. Physical activity level, dietary intake, BMI, general self-efficacy, self-management, and motivation level will be assessed at three time points with questionnaires, reports, and/or an accelerometer., Discussion: Data of this study will be gathered to assess the feasibility and potential effect sizes. This will allow for further intervention refinement as needed as well as to inform a future large-scale intervention study and a manual for implementation at other centres., Trial Registration: International Clinical Trial Registry Platform (ICTRP) number: NL8932 (ICTRP Search Portal (who.int)). Registered on September 29, 2020., (© 2022. The Author(s).)

Survivors of childhood cancer are at risk of anthracycline-induced cardiotoxicity, which might be prevented by dexrazoxane. However, concerns exist about the safety of dexrazoxane, and little guidance is available on its use in children. To facilitate global consensus, a working group within the International Late Effects of Childhood Cancer Guideline Harmonization Group reviewed the existing literature and used evidence-based methodology to develop a guideline for dexrazoxane administration in children with cancer who are expected to receive anthracyclines. Recommendations were made in consideration of evidence supporting the balance of potential benefits and harms, and clinical judgement by the expert panel. Given the dose-dependent risk of anthracycline-induced cardiotoxicity, we concluded that the benefits of dexrazoxane probably outweigh the risk of subsequent neoplasms when the cumulative doxorubicin or equivalent dose is at least 250 mg/m 2 (moderate recommendation). No recommendation could be formulated for cumulative doxorubicin or equivalent doses of lower than 250 mg/m 2 , due to insufficient evidence to determine whether the risk of cardiotoxicity outweighs the possible risk of subsequent neoplasms. Further research is encouraged to determine the long-term efficacy and safety of dexrazoxane in children with cancer., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Purpose: Long-term follow-up (LTFU) care is essential to optimise health outcomes in childhood cancer survivors (CCS). We aimed to assess the impact of the COVID-19 pandemic on LTFU services and providers., Methods: A COVID-19 working group within the International Late Effects of Childhood Cancer Guideline Harmonization Group (IGHG) distributed a questionnaire to LTFU service providers in 37 countries across Europe, Asia, North America, Central/South America, and Australia. The questionnaire assessed how care delivery methods changed during the pandemic and respondents' level of worry about the pandemic's impact on LTFU care delivery, their finances, their health, and that of their family and friends., Results: Among 226 institutions, providers from 178 (79%) responded. Shortly after the initial outbreak, 42% of LTFU clinics closed. Restrictions during the pandemic resulted in fewer in-person consultations and an increased use of telemedicine, telephone, and email consultations. The use of a risk assessment to prioritise the method of LTFU consultation for individual CCS increased from 12 to 47%. While respondents anticipated in-person consultations to remain the primary method for LTFU service delivery, they expected significantly increased use of telemedicine and telephone consultations after the pandemic. On average, respondents reported highest levels of worry about psychosocial well-being of survivors., Conclusions: The pandemic necessitated changes in LTFU service delivery, including greater use of virtual LTFU care and risk-stratification to identify CCS that need in-person evaluations., Implications for Cancer Survivors: Increased utilisation of virtual LTFU care and risk stratification is likely to persist post-pandemic., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: Long-term survival after childhood cancer often comes at the expense of late, adverse health conditions. However, survivorship care is frequently not available for adult survivors in Europe. The PanCareFollowUp Consortium therefore developed the PanCareFollowUp Care Intervention, an innovative person-centred survivorship care model based on experiences in the Netherlands. This paper describes the protocol of the prospective cohort study (Care Study) to evaluate the feasibility and the health economic, clinical and patient-reported outcomes of implementing PanCareFollowUp Care as usual care in four European countries., Methods and Analysis: In this prospective, longitudinal cohort study with at least 6 months of follow-up, 800 childhood cancer survivors will receive the PanCareFollowUp Care Intervention across four study sites in Belgium, Czech Republic, Italy and Sweden, representing different healthcare systems. The PanCareFollowUp Care Intervention will be evaluated according to the Reach, Effectiveness, Adoption, Implementation and Maintenance framework. Clinical and research data are collected through questionnaires, a clinic visit for multiple medical assessments and a follow-up call. The primary outcome is empowerment, assessed with the Health Education Impact Questionnaire. A central data centre will perform quality checks, data cleaning and data validation, and provide support in data analysis. Multilevel models will be used for repeated outcome measures, with subgroup analysis, for example, by study site, attained age, sex or diagnosis., Ethics and Dissemination: This study will be conducted in accordance with the guidelines of Good Clinical Practice and the Declaration of Helsinki. The study protocol has been reviewed and approved by all relevant ethics committees. The evidence and insights gained by this study will be summarised in a Replication Manual, also including the tools required to implement the PanCareFollowUp Care Intervention in other countries. This Replication Manual will become freely available through PanCare and will be disseminated through policy and press releases., Trial Registration Number: Netherlands Trial Register (NL8918; https://www.trialregister.nl/trial/8918)., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)

This study explored strategies to improve adolescent food security using semi-structured in-depth interviews with 9 policy advocates, 12 parents and 15 adolescents aged between 17 and 20 years, living in households who were eligible for the Supplemental Nutrition Assistance Program in 2020. This study was part of a larger evaluation of adolescent food insecurity conducted in Baltimore, Maryland, USA during the COVID-19 pandemic. Three key strategies arose during analysis-improving federal nutrition assistance programs for households, federal nutrition assistance programs for individual adolescents, and leveraging school programs and resources. Respondents described concordant views regarding the role of the Supplemental Nutrition Assistance Program in supporting households but held discordant views about the role of other federal programs, such as the school nutrition programs and Pandemic Electronic Benefit Transfer program. The results of this study provide important insights about policy and programmatic supports that may assist adolescents to acquire food for themselves and their families. Future research should test how federal programs and policies specifically impact food security and nutrition for adolescents.

The fusion gene MLL/AF4 defines a high-risk subtype of pro-B acute lymphoblastic leukemia. Relapse can be associated with a lineage switch from acute lymphoblastic to acute myeloid leukemia, resulting in poor clinical outcomes caused by resistance to chemotherapies and immunotherapies. In this study, the myeloid relapses shared oncogene fusion breakpoints with their matched lymphoid presentations and originated from various differentiation stages from immature progenitors through to committed B-cell precursors. Lineage switching is linked to substantial changes in chromatin accessibility and rewiring of transcriptional programs, including alternative splicing. These findings indicate that the execution and maintenance of lymphoid lineage differentiation is impaired. The relapsed myeloid phenotype is recurrently associated with the altered expression, splicing, or mutation of chromatin modifiers, including CHD4 coding for the ATPase/helicase of the nucleosome remodelling and deacetylation complex. Perturbation of CHD4 alone or in combination with other mutated epigenetic modifiers induces myeloid gene expression in MLL/AF4+ cell models, indicating that lineage switching in MLL/AF4 leukemia is driven and maintained by disrupted epigenetic regulation., (© 2022 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Introduction: Global climate change (global warming) has been identified as the primary factor responsible for the observed increase in frequency and severity of wildfires (also known as bushfires in some countries) throughout the majority of the world's vegetated environments. This trend is predicted to continue, causing significant adverse health effects to nearby residential populations and placing a potential strain on local emergency departments (EDs)., Study Objective: The aim of this literature review was to identify papers relating to wildfires and their impact on EDs, specifically patient presentation characteristics, resource utilization, and patient outcomes., Method: This integrative literature review was guided by the Preferred Reporting Items of Systematic Reviews and Meta-Analysis (PRISMA) guidelines for data collection, and Whittemore and Knafl's framework for data analysis. Data were collected from OvidSP, MEDLINE, DARE, CINAHL, PubMed, and Scopus databases. Various Medical Subject Headings (MeSH) and keywords identified papers relevant to wildfires/bushfires and EDs., Results: Literature regarding the relationship between ED presentations and wildfire events, however, is primarily limited to studies from the United States and Australia and indicates particulate matter (PM) is principally linked to adverse respiratory and cardiovascular outcomes. Observable trends in the literature principally included a significant increase in respiratory presentations, primarily with a lag of one to two days from the initial event. Respiratory and cardiovascular studies that stratified results by age indicated individuals under five, over 65, or those with pre-existing conditions formed the majority of ED presentations., Conclusion: Key learnings from this review included the need for effective and targeted community advisory programs/procedures, prior to and during wildfire events, as well as pre-event planning, development, and robust resilience strategies for EDs.

Endocrine disorders in survivors of childhood, adolescent, and young adult (CAYA) cancers are associated with substantial adverse physical and psychosocial effects. To improve appropriate and timely endocrine screening and referral to a specialist, the International Late Effects of Childhood Cancer Guideline Harmonization Group (IGHG) aims to develop evidence and expert consensus-based guidelines for healthcare providers that harmonize recommendations for surveillance of endocrine disorders in CAYA cancer survivors. Existing IGHG surveillance recommendations for premature ovarian insufficiency, gonadotoxicity in males, fertility preservation, and thyroid cancer are summarized. For hypothalamic-pituitary (HP) dysfunction, new surveillance recommendations were formulated by a guideline panel consisting of 42 interdisciplinary international experts. A systematic literature search was performed in MEDLINE (through PubMed) for clinically relevant questions concerning HP dysfunction. Literature was screened for eligibility. Recommendations were formulated by drawing conclusions from quality assessment of all evidence, considering the potential benefits of early detection and appropriate management. Healthcare providers should be aware that CAYA cancer survivors have an increased risk for endocrine disorders, including HP dysfunction. Regular surveillance with clinical history, anthropomorphic measures, physical examination, and laboratory measurements is recommended in at-risk survivors. When endocrine disorders are suspected, healthcare providers should proceed with timely referrals to specialized services. These international evidence-based recommendations for surveillance of endocrine disorders in CAYA cancer survivors inform healthcare providers and highlight the need for long-term endocrine follow-up care in subgroups of survivors and elucidate opportunities for further research., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Many long-term childhood cancer survivors suffer from treatment-related late effects, which may occur in any organ and include a wide spectrum of conditions. Long-term follow-up (LTFU) is recommended to facilitate early diagnosis and to ensure better health outcomes. Due to the heterogeneity of these sequelae, different specialists work together in the diagnosis and treatment of these conditions. Experts from both pediatric and internal medicine are involved in age-appropriate care by providing a transition process. Hence, LTFU of childhood cancer survivors is a prototypic example of multidisciplinary care for patients with complex needs treated in a specialized setting. International collaborations of healthcare professionals and scientists involved in LTFU of childhood cancer survivors, such as the International Guideline Harmonization Group, compile surveillance recommendations that can be clinically adopted all over the world. These global networks of clinicians and researchers make a joint effort to address gaps in knowledge, increase visibility and awareness of cancer survivorship and provide an excellent example of how progress in clinical care and scientific research may be achieved by international and multidisciplinary collaboration.

Objective: To evaluate the clinical features of Canadian adolescents admitted to the intensive care unit (ICU) for medically serious self-harm., Methods: 2700 Canadian paediatricians were surveyed monthly over two years (January 2017 to December 2018) through the Canadian Paediatric Surveillance Program to ascertain data from eligible cases., Results: Ninety-three cases (73 female; age 15.2 ± 1.5) met the case definition. Four provinces reported the majority of cases: Quebec (n = 27), Ontario (n = 26), Alberta (n = 21), and British Columbia (n = 8). There were 10 deaths, 9 by hanging. Overdose and hanging were the most frequently reported methods of self-harm (74.2% and 19.4%, respectively). Overdose was more common in females (80.8% females vs. 50% males; χ 2  = 7.8 (1), p  = .005), whereas hanging was more common in males (35% males vs. 15.1% females, χ 2  = 3.9 (1), p  = .04). More females than males had a past psychiatric diagnosis (79% vs. 58%; χ 2  = 4.1 (1), p  = .06), a previous suicide attempt (55.9% vs. 29.4%, χ 2  = 3.8 (1), p  = .05), and prior use of mental health service (69.7% vs. 27.8%, χ 2  = 10.4 (1), p  = .001). Family conflict was the most commonly identified precipitating factor (43%) of self-harm., Conclusions: Among Canadian adolescents admitted to the ICU with medically serious self-harm, females demonstrate a higher rate of suicide attempts and prior mental health care engagement, whereas males are more likely to die by suicide. These findings are consistent with data from other adolescent samples, as well as data from working-age and older adults. Therefore, a sex-specific approach to suicide prevention is warranted as part of a national suicide prevention strategy; family conflict may be a specific target for suicide prevention interventions among adolescents.

Background: Obesity increases the risk of type 2 diabetes, heart disease, stroke, mobility problems and some cancers, and its prevalence is rising. Men engage less than women in existing weight loss interventions. Game of Stones builds on a successful feasibility study and aims to find out if automated text messages with or without endowment incentives are effective and cost-effective for weight loss at 12 months compared to a waiting list comparator arm in men with obesity., Methods: A 3-arm, parallel group, assessor-blind superiority randomised controlled trial with process evaluation will recruit 585 adult men with body mass index of 30 kg/m 2 or more living in and around three UK centres (Belfast, Bristol, Glasgow), purposively targeting disadvantaged areas. Intervention groups: (i) automated, theory-informed text messages daily for 12 months plus endowment incentives linked to verified weight loss targets at 3, 6 and 12 months; (ii) the same text messages and weight loss assessment protocol; (iii) comparator group: 12 month waiting list, then text messages for 3 months. The primary outcome is percentage weight change at 12 months from baseline. Secondary outcomes at 12 months are as follows: quality of life, wellbeing, mental health, weight stigma, behaviours, satisfaction and confidence. Follow-up includes weight at 24 months. A health economic evaluation will measure cost-effectiveness over the trial and over modelled lifetime: including health service resource-use and quality-adjusted life years. The cost-utility analysis will report incremental cost per quality-adjusted life years gained. Participant and service provider perspectives will be explored via telephone interviews, and exploratory mixed methods process evaluation analyses will focus on mental health, multiple long-term conditions, health inequalities and implementation strategies., Discussion: The trial will report whether text messages (with and without cash incentives) can help men to lose weight over 1 year and maintain this for another year compared to a comparator group; the costs and benefits to the health service; and men's experiences of the interventions. Process analyses with public involvement and service commissioner input will ensure that this open-source digital self-care intervention could be sustainable and scalable by a range of NHS or public services., Trial Registration: ISRCTN 91974895 . Registered on 14/04/2021., (© 2022. The Author(s).)

Educational achievement and employment outcomes are critical indicators of quality of life in survivors of childhood, adolescent, and young adult (CAYA) cancer. This review is aimed at providing an evidence-based clinical practice guideline (CPG) with internationally harmonized recommendations for the surveillance of education and employment outcomes in survivors of CAYA cancer diagnosed before the age of 30 years. The CPG was developed by a multidisciplinary panel under the umbrella of the International Late Effects of Childhood Cancer Guideline Harmonization Group. After evaluating concordances and discordances of 4 existing CPGs, the authors performed a systematic literature search through February 2021. They screened articles for eligibility, assessed quality, and extracted and summarized the data from included articles. The authors formulated recommendations based on the evidence and clinical judgment. There were 3930 articles identified, and 83 of them, originating from 17 countries, were included. On a group level, survivors were more likely to have lower educational achievement and more likely to be unemployed than comparisons. Key risk factors for poor outcomes included receiving a primary diagnosis of a central nervous system tumor and experiencing late effects. The authors recommend that health care providers be aware of the risk of educational and employment problems, implement regular surveillance, and refer survivors to specialists if problems are identified. In conclusion, this review presents a harmonized CPG that aims to facilitate evidence-based care, positively influence education and employment outcomes, and ultimately minimize the burden of disease and treatment-related late adverse effects for survivors of CAYA cancers. LAY SUMMARY: A multidisciplinary panel has developed guidelines for the surveillance of education and employment outcomes among survivors of childhood, adolescent, and young adult cancer. On the basis of evidence showing that survivors are at risk for lower educational achievement and unemployment, it is recommended that all survivors receive regular screening for educational and employment outcomes., (© 2022 The Authors. Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.)