Cancer knowledge and health-consciousness in childhood cancer survivors following transition into adult care-results from the ACCS project

BACKGROUND: Knowledge on chronic medical conditions in childhood cancer survivors (CCSs) is constantly growing and underlines that long-term follow-up (LTFU) care is often mandatory, also in adulthood. However, many CCSs discontinue follow-up care after transition to adult care. One reason might be that the current transition practices do not meet the needs of adolescent and young adult CCSs. We therefore aim to evaluate different transition models for Swiss CCSs by assessing their cancer knowledge, cancer worries, self-management skills, and expectations for LTFU care, following transition in two different hospital-based models. METHODS: Within the Aftercare of Childhood Cancer Survivors (ACCS) study, we performed a questionnaire-based survey with a cross-sectional and longitudinal part. We included 5-year CCSs aged >16 years at recruitment who were transitioned to adult care in two hospitals between 2014 and 2021. Here, we report the results of the cross-sectional part. We compared the survivors' cancer knowledge with medical record data and assessed cancer worries (6 questions), self-management skills (15 questions), and expectations (12 questions) by validated scales. We used descriptive statistics, chi-squared test, and t-tests to describe the results. RESULTS: We analyzed 57 CCSs (response rate 44%), 60% of those were female, had a median age of 9 years at diagnosis and 23 years at the questionnaire. Most CCSs recalled their diagnosis (95%) and exposure to treatment modalities (98%) correctly. CCSs worried the most about potential late effects (47%) and issues with having children in the future (44%). At least 75% of CCSs agreed to 12 of the 15 self-management questions, indicating high self-management skills. The top three expectations included that physicians know the survivors' cancer history, that visits start on time, and that physicians can always be called in case of questions. CONCLUSION: CCSs receiving hospital-based LTFU care have good cancer knowledge and high self-management skills. The identified worries and expectations will help to improve the LTFU care of CCSs who transition to adult care, to further inform and educate survivors and healthcare professionals about and might be relevant for other countries with a similar healthcare system

Body image in adolescent survivors of childhood cancer: The role of chronic health conditions.

BACKGROUND Cancer and its treatment may impair the body image of childhood cancer survivors during adolescence. We compared the body image between adolescent cancer survivors and their siblings, and determined whether survivors' body image is associated with socio-demographic characteristics, clinical characteristics and chronic health conditions. PROCEDURE As part of the nationwide Swiss Childhood Cancer Survivor Study, we sent questionnaires to adolescents (aged 16-19 years), who survived >5 years after having been diagnosed with childhood cancer between 1989 and 2010. Siblings received the same questionnaire. We assessed the level of agreement with three body image statements referring to body satisfaction and preferences for changes. Chronic health conditions were classified into cardiovascular, pulmonary, endocrine, musculoskeletal, renal/digestive, neurological and hearing or vision impairment. We used ordered logistic regression models to identify determinants of a more negative body image. RESULTS Our study included 504 survivors (48% female) with a median age at study of 17.7 years (interquartile range: 16.8-18.6) and 136 siblings. Survivors and siblings reported overall comparable levels of agreement with body image statements (all p > .05). Female survivors (all odds ratio [ORs] ≥1.7), survivors treated with haematopoietic stem cell transplantation (HSCT; all ORs ≥2.2), and survivors with ≥2 chronic health conditions (all ORs ≥1.4) reported a more negative body image. This was particularly pronounced for survivors suffering from musculoskeletal or endocrine conditions. CONCLUSION Female survivors, survivors treated with HSCT or with chronic health conditions are at risk of body image concerns during adolescence. Increased awareness among clinicians and targeted psychosocial support could mitigate such concerns

Bayesian spatial modelling of childhood cancer incidence in Switzerland using exact point data: a nationwide study during 1985-2015

BACKGROUND: The aetiology of most childhood cancers is largely unknown. Spatially varying environmental factors such as traffic-related air pollution, background radiation and agricultural pesticides might contribute to the development of childhood cancer. This study is the first investigation of the spatial disease mapping of childhood cancers using exact geocodes of place of residence. METHODS: We included 5947 children diagnosed with cancer in Switzerland during 1985-2015 at 0-15 years of age from the Swiss Childhood Cancer Registry. We modelled cancer risk using log-Gaussian Cox processes and indirect standardisation to adjust for age and year of diagnosis. We examined whether the spatial variation of risk can be explained by modelled ambient air concentration of NO$_{2}$, modelled exposure to background ionising radiation, area-based socio-economic position (SEP), linguistic region, duration in years of general cancer registration in the canton or degree of urbanisation. RESULTS: For all childhood cancers combined, the posterior median relative risk (RR), compared to the national level, varied by location from 0.83 to 1.13 (min to max). Corresponding ranges were 0.96 to 1.09 for leukaemia, 0.90 to 1.13 for lymphoma, and 0.82 to 1.23 for central nervous system (CNS) tumours. The covariates considered explained 72% of the observed spatial variation for all cancers, 81% for leukaemia, 82% for lymphoma and 64% for CNS tumours. There was weak evidence of an association of CNS tumour incidence with modelled exposure to background ionising radiation (RR per SD difference 1.17; 0.98-1.40) and with SEP (1.6; 1.00-1.13). CONCLUSION: Of the investigated diagnostic groups, childhood CNS tumours showed the largest spatial variation. The selected covariates only partially explained the observed variation of CNS tumours suggesting that other environmental factors also play a role

Desire for biological parenthood and patient counseling on the risk of infertility among adolescents and adults with hemoglobinopathies.

BACKGROUND Both diagnosis and treatment of hemoglobinopathies have been associated with an increased risk of fertility impairment. German guidelines recommend annual monitoring of fertility parameters to enable early detection of fertility impairment and/or to offer fertility preservation (FP) when indicated. We explored the general desire for parenthood, the frequency of recalling fertility counseling and testing, and the utilization of FP in adolescents and adults with hemoglobinopathies. PROCEDURE In a cross-sectional study, patients aged 12-50 years, treated in Germany, Austria, or Switzerland, were surveyed on fertility-related aspects. Medical data, including fertility testing results, were collected from patient records. RESULTS Overall, 116/121 eligible patients, diagnosed with sickle cell disease (70.7%), thalassemia (27.6%), or other hemoglobinopathy (1.7%), participated in our study (57.8% female, median age 17.0 years, range 12-50 years). All participants required treatment of the underlying hemoglobinopathy: 68.1% received hydroxyurea, 25.9% required regular blood transfusions, and 6.0% underwent hematopoietic stem cell transplantation (HSCT). Most patients (82/108, 75.9%) stated a considerable to strong desire for (future) parenthood, independent of sex, education, diagnosis, or subjective health status. Fertility counseling was only recalled by 32/111 patients (28.8%) and least frequently by younger patients (12-16 years) or those treated with regular blood transfusions or hydroxyurea. While fertility testing was documented for 59.5% (69/116) in medical records, only 11.6% (13/112) recalled previous assessments. FP was only used by 5.4% (6/111) of patients. CONCLUSION Most patients with hemoglobinopathies wish to have biological children, yet only few recalled fertility counseling and testing. Adequate patient counseling should be offered to all patients at risk for infertility

Autoimmunity and immunodeficiency associated with monoallelic LIG4 mutations via haploinsufficiency

BACKGROUND: Biallelic mutations in LIG4 encoding DNA-ligase 4 cause a rare immunodeficiency syndrome manifesting as infant-onset life-threatening and/or opportunistic infections, skeletal malformations, radiosensitivity and neoplasia. LIG4 is pivotal during DNA repair and during V(D)J recombination as it performs the final DNA-break sealing step. OBJECTIVE: We explored whether monoallelic LIG4 missense mutations may underlie immunodeficiency and autoimmunity with autosomal dominant inheritance. METHODS: Extensive flow-cytometric immune-phenotyping was performed. Rare variants of immune system genes were analyzed by whole exome sequencing. DNA repair functionality and T cell-intrinsic DNA damage tolerance was tested with an ensemble of in vitro and in silico tools. Antigen-receptor diversity and autoimmune features were characterized by high-throughput sequencing and autoantibody arrays. Reconstitution of wild-type vs. mutant LIG4 were performed in LIG4 knock-out Jurkat T cells and DNA damage tolerance was subsequently assessed. RESULTS: A novel heterozygous LIG4 loss-of-function mutation (p.R580Q), associated with a dominantly inherited familial immune-dysregulation consisting of autoimmune cytopenias, and in the index patient with lymphoproliferation, agammaglobulinemia and adaptive immune cell infiltration into nonlymphoid organs. Immunophenotyping revealed reduced naïve CD4$^{+}$ T cells and low TCR-Vα7.2$^{+}$ T cells, while T/B-cell receptor repertoires showed only mild alterations. Cohort screening identified two other non-related patients with the monoallelic LIG4 mutation p.A842D recapitulating clinical and immune-phenotypic dysregulations observed in the index family and displaying T cell-intrinsic DNA damage intolerance. Reconstitution experiments and molecular dynamics simulations categorize both missense mutations as loss-of-function and haploinsufficient. CONCLUSION: We provide evidence that certain monoallelic LIG4 mutations may cause human immune dysregulation via haploinsufficiency

Supportive Care During Pediatric Hematopoietic Stem Cell Transplantation : Prevention of Infections. A Report From Workshops on Supportive Care of the Paediatric Diseases Working Party (PDWP) of the European Society for Blood and Marrow Transplantation (EBMT)

Specific protocols define eligibility, conditioning, donor selection, graft composition and prophylaxis of graft vs. host disease for children and young adults undergoing hematopoietic stem cell transplant (HSCT). However, international protocols rarely, if ever, detail supportive care, including pharmaceutical infection prophylaxis, physical protection with face masks and cohort isolation or food restrictions. Supportive care suffers from a lack of scientific evidence and implementation of practices in the transplant centers brings extensive restrictions to the child's and family's daily life after HSCT. Therefore, the Board of the Pediatric Diseases Working Party (PDWP) of the European Society for Blood and Marrow Transplantation (EBMT) held a series of dedicated workshops since 2017 with the aim of initiating the production of a set of minimal recommendations. The present paper describes the consensus reached within the field of infection prophylaxis.Peer reviewe

Welfare and performance of newborn and young dairy calves : a thesis presented in partial fulfilment of the requirements for the degree of Master of Science in Physiology at Massey University, Palmerston North, New Zealand

Physiological evaluation of newborn lambs at birth revealed four main causes of hypothermia and death: placental insufficiency, intrapartum hypoxaemia, inadequate heat production and starvation. No similar evidence seems to be available for calves and thus the present study measures parameters used in previous lamb studies to evaluate the physiological status of calves and the incidence of the four factors in newborn dairy calves. The study was carried out in the Manawatu region during spring 2001. Multiparous and primiparous cows about to calve were observed continuously. All dystocias were assisted. Within 30 minutes of birth the rectal temperature of each calf and a jugular blood sample were taken. Time to stand on all four feet and birth weight were also measured. The packed cell volume and plasma concentrations of glucose, fructose and lactate were analysed as indices of prenatal and intrapartum status. A subset of calves was then followed up after pick-up to 4 days of age taking rectal temperature twice daily and a jugular blood sample at approximately 24, 48, 72 and 96 hours after birth. Plasma was analysed for glucose, beta-hydroxybutyrate, urea and gamma-glutamyl transferase concentrations to determine energy status of the calves for the first four days after birth and to determine whether calves had sufficient colostrum intake indicative of passive immunity. The physiological status of calves at birth was fairly uniform. Calves born after dystocia had significantly higher plasma lactate concentrations, took significantly longer to stand and had significantly lower packed cell volumes than normally born calves. The higher plasma lactate concentrations and longer time to stand in these calves indicate hypoxia at birth and reduced vigour. As packed cell volume was not significantly elevated in calves with significantly elevated plasma lactate concentrations it is suggested that placental insufficiency was not a major problem. The majority of calves had relatively high rectal temperatures suggesting that thermogenesis was not impeded. The majority of calves followed up to 4 days of age were in good energy balance. Starvation and hypothermia were not major issues as judged by relatively high plasma urea and beta-hydroxybutyrate concentrations and rectal temperatures. The majority of calves had adequate gamma-glutamyl transferase concentrations suggesting effective passive uptake of immunoglobulins. However, all calves that died (n=8) had significantly lower concentrations than calves that became sick and subsequently recovered and those calves that remained healthy. Overall, the physiological status of the calves of the present study between birth and 4 days of age was adequate. However, immune status plays an important role for the health and welfare of the newborn calves as judged by the fact that all calves that died failed to take in colostrum before pick-up

Neurological development and the potential for conscious perception after birth : comparison between species and implications for animal welfare : a thesis presented in partial fulfilment of the requirements for the degree of Doctor of Philosophy in Physiology, Massey University, Palmerston North, New Zealand

In order for animals to experience pain and to suffer from it, they have to be capable of conscious perception. Recent evidence suggests that the fetus is maintained in a sleeplike unconscious state and that conscious perception therefore only occurs after birth. The timing of the onset of conscious perception depends on the maturation of underlying neurological processes and is anticipated to be species dependent. Painspecific electroencephalographic (EEG) responses of lightly anaesthetised young of three species born at different levels of neurological development were investigated. The results of the present thesis are in agreement with published data on general neurological, EEG and behavioural development. This information, in addition to the present results, has been used to estimate the approximate time of the onset of conscious perception in tammar wallaby joeys, rat pups and newborn lambs. In wallaby joeys (extremely immature at birth), the EEG remained isoelectric until about 100-120 days of in-pouch age and became continuous by about 150-160 days, with electroencephalographic and behavioural signs of conscious perception apparent by about 160-180 days. In rat pups (immature at birth), the absence of a differentiated EEG suggests that the ability for conscious perception in pups younger than 10-12 days is doubtful. The marginal EEG responses to noxious stimulation in 12-14 day-old pups and the pronounced EEG responses in pups 18-20 days suggest that rats may be capable of conscious perception from 12-14 days onwards. In lambs (mature at birth), full conscious perception is probably not apparent before 5 minutes after birth and may take up to several hours or days to become fully established. Its modulation by the residual neuroinhibitor allopregnanolone, if that occurs, would be highest over the first 12 hours after birth. Overall, the onset of conscious perception does not seem to follow an “on-off phenomenon”, but seems to develop gradually, even in species born neurologically mature. Although conscious perception, and hence pain experience, may be qualitatively different in younger animals, on the basis of the precautionary principle, when significantly invasive procedures are planned, pain relief should be provided from those postnatal ages when pain may first be perceived – i.e. from about 120 days in the tammar wallaby joey, about 10 days in the rat pup and from soon after birth in the lamb

Bayesian spatial modelling of childhood cancer incidence in Switzerland using exact point data: a nationwide study during 1985-2015.

BACKGROUND The aetiology of most childhood cancers is largely unknown. Spatially varying environmental factors such as traffic-related air pollution, background radiation and agricultural pesticides might contribute to the development of childhood cancer. This study is the first investigation of the spatial disease mapping of childhood cancers using exact geocodes of place of residence. METHODS We included 5947 children diagnosed with cancer in Switzerland during 1985-2015 at 0-15 years of age from the Swiss Childhood Cancer Registry. We modelled cancer risk using log-Gaussian Cox processes and indirect standardisation to adjust for age and year of diagnosis. We examined whether the spatial variation of risk can be explained by modelled ambient air concentration of NO2, modelled exposure to background ionising radiation, area-based socio-economic position (SEP), linguistic region, duration in years of general cancer registration in the canton or degree of urbanisation. RESULTS For all childhood cancers combined, the posterior median relative risk (RR), compared to the national level, varied by location from 0.83 to 1.13 (min to max). Corresponding ranges were 0.96 to 1.09 for leukaemia, 0.90 to 1.13 for lymphoma, and 0.82 to 1.23 for central nervous system (CNS) tumours. The covariates considered explained 72% of the observed spatial variation for all cancers, 81% for leukaemia, 82% for lymphoma and 64% for CNS tumours. There was weak evidence of an association of CNS tumour incidence with modelled exposure to background ionising radiation (RR per SD difference 1.17; 0.98-1.40) and with SEP (1.6; 1.00-1.13). CONCLUSION Of the investigated diagnostic groups, childhood CNS tumours showed the largest spatial variation. The selected covariates only partially explained the observed variation of CNS tumours suggesting that other environmental factors also play a role

Moving Beyond the Friend-Foe Myth: A Scoping Review of the Use of Social Media in Adolescent and Young Adult Oncology

Purpose: Adolescents and young adults (AYA) with cancer present a unique challenge to health care institutions. Their cancer diagnosis and treatment have a profound impact upon their health and well-being. Despite the various support services aimed at improving their quality of life, their needs and preferences are often underestimated or misjudged. Recent studies show that patients are empowered by the knowledge and support they receive online. Given the extensive use of social media among AYA, we aim to identify promises, challenges, and recommendations for integrating these platforms in AYA cancer care. Methodology: We systematically searched seven databases systematically: Scopus, PubMed, PsycInfo, Web of Science, CINAHL, SocINDEX, and Media. We placed no restriction on the type of methodology used in the studies. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses was used to frame the research. Results: Many studies argued that health care professionals need to integrate social media in their clinical practice to engage with patients' lifeworld. Social media were considered important allies in optimizing cancer care at all levels of support, ranging from information provision, treatment adherence, diet and exercise interventions, to professional, peer, and psychosocial self-care. Lack of research on the efficacy of social media in the context of psychosocial support was a commonly cited problem. A small number of publications paid attention to the inherent risks of promoting self-care online. Conclusion: Future studies should continue to pursue empirical research on the efficacy of online psychosocial care, while not neglecting the ethical challenges of social media research