BACKGROUND:Causes of childhood cancer remain poorly understood. Using data from the case-control studies of the Childhood Cancer and Leukemia International Consortium (CLIC), we explored how maternal education as a key socioeconomic status (SES) indicator, varies across studies/countries and contributes to understanding of potential environmental and lifestyle risk factors. METHODS:Control group data from cancer-free children matched by diagnosis date of cases from 16 studies were included, using both interview-based and health registry sources. Maternal education, the primary SES measure used in previous analyses with pooled CLIC data, was categorized as low, medium, or high according to the International Standard Classification of Education. Multinomial logistic regression assessed associations between maternal education and perinatal/lifestyle factors, calculating crude and adjusted odds ratios (ORs) and 95 % confidence intervals (CIs) for high vs. low education. RESULTS:Maternal education levels varied across studies and over time, with the highest proportions of highly educated mothers in the U.S. and lowest in Costa Rica, Italy, and Egypt. Higher maternal education was generally positively associated with higher birthweight, breastfeeding, daycare attendance, and maternal prenatal alcohol consumption. Higher maternal education was generally inversely associated with lower birthweight, younger maternal age, paternal occupational pesticide exposure, maternal prenatal smoking, and having more siblings. The direction of associations for older maternal age and for caesarean delivery differed substantially across regions. Exclusion of mothers < 21 years at birth of the index child had little effect on the results. CONCLUSION:This multi-country analysis supports the use of maternal education for adjustment as a proxy for SES, showing largely consistent associations with various behaviors and exposures. While the direction of associations was generally consistent, the strengths varied sometimes considerably by geographical region. These findings support the inclusion of maternal education as a covariate in analyses of childhood cancer risk when pooling CLIC studies.

Childhood cancers are rare, but incidence has risen modestly in countries with robust registration, partly reflecting improved diagnosis. In high-income countries, cancer is the leading cause of disease-related death in children. Marked inequities in incidence, survival, and research capacity underscore the need for large-scale collaboration to identify environmental, genetic, and contextual determinants of risk. The Childhood Cancer and Leukemia International Consortium (CLIC) was established in 2007 to study the etiology of childhood leukemia and later expanded in 2019 to include other childhood cancers, principally solid tumors. CLIC pools harmonized, individual-level data from case-control and cohort studies, obtained through interviews, record linkage (insurance claims, registries), or geographic information systems, and integrates germline genomic data where available. Membership has grown from 13 studies in 9 countries to 57 studies in 21 countries; recruitment spans the early 1960s to the present and encompasses approximately 150,000 cases across all tumor types and 300,000 controls with clinical, demographic, and exposure data, centralized via harmonized data dictionaries at the Data Coordination Center, established in 2014 at the International Agency for Research on Cancer, and supported by a secure analysis platform. Pooled analyses across diverse populations have implicated parental age, prenatal vitamin or folic acid use, mode of delivery, fetal growth, selected congenital anomalies, occupational or household exposures (e.g., pesticides), paternal smoking, and markers of early-life immune modulation (e.g., breastfeeding, daycare attendance) in leukemia risk, informing carcinogen evaluation and prevention. The integration of genetic ancestry and germline susceptibility data is clarifying ancestry-related differences in leukemia biology and outcomes, while confirming risk loci with population-specific effects. CLIC is now adding polygenic risk scores and exposomic data to refine etiologic subtyping and identify modifiable pathways, while broadening representation from underserved regions through partnership-building and capacity-strengthening.

BACKGROUND:Maternal prenatal infections may affect fetal development, increasing the immunological vulnerability of offspring to childhood leukaemia (CL). The role of maternal infections in CL is unclear and might vary by subtype (lymphoblastic, ALL; myeloid, AML) or other characteristics. Understanding this potentially modifiable risk factor could inform prevention strategies. METHODS:Seventeen hospital- and population-based case-control studies of children born in 1972-2019 within the Childhood Cancer and Leukemia International Consortium with self-questionnaires or health-registry data on maternal infection were included (13 638 cases; 26 870 controls). Meta-analyses assessed CL and maternal infection (overall, viral, bacterial, respiratory, influenza/cold, urinary, genital) stratified by subtype, infection timing, race and ethnicity, and diagnosis age. RESULTS:The adjusted meta-analysis odds ratio (OR) for any maternal prenatal infection was 1.13 [95% confidence interval (CI) 0.91-1.40], with similar estimates for ALL and AML. Infection-specific estimates varied. ORs for first-trimester infections were highest for CL and ALL, but not AML, although all CIs contained one. We found modest risk differences between White and Hispanic/Latino children, most notably for CL diagnosed at <2 years (White children: OR 1.25, 95% CI 1.02-1.53; Hispanic/Latino children: OR 0.79, 95% CI 0.34-1.81, subgroup difference P = .05), with similar differences for viral and respiratory/influenza/cold infections. CONCLUSION:Although findings only modestly support an association between maternal prenatal infections and CL, some infections might increase the risk more markedly in young White children compared with Hispanic/Latino children. Risk patterns across race and ethnicity, type, and timing of maternal prenatal infection merit further investigation, as do studies with documented exposure information.

Although recent studies have demonstrated associations between nonchromosomal birth defects and several pediatric cancers, less is known about their role on childhood leukemia susceptibility. Using data from the Childhood Cancer and Leukemia International Consortium, we evaluated associations between nonchromosomal birth defects and childhood leukemia. Pooling consortium data from 18 questionnaire-based and three registry-based case-control studies across 13 countries, we used multivariable logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between a spectrum of birth defects and leukemia. Our analyses included acute lymphoblastic leukemia (ALL, n = 13 115) and acute myeloid leukemia (AML, n = 2120) cases, along with 46 172 controls. We used the false discovery rate to account for multiple comparisons. In the questionnaire-based studies, the prevalence of birth defects was 5% among cases vs 4% in controls, whereas, in the registry-based studies, the prevalence was 11% among cases vs 7% in controls. In pooled adjusted analyses, there were several notable associations, including (1) digestive system defects and ALL (OR = 2.70, 95% CI: 1.46-4.98); (2) congenital anomalies of the heart and circulatory system and AML (OR = 2.86, 95% CI: 1.81-4.52) and (3) nervous system defects and AML (OR = 4.23, 95% CI: 1.50-11.89). Effect sizes were generally larger in registry-based studies. Overall, our results could point to novel genetic and environmental factors associated with birth defects that could also increase leukemia susceptibility. Additionally, differences between questionnaire- and registry-based studies point to the importance of complementary sources of birth defect phenotype data when exploring these associations.

INTRODUCTION:Inhalers are commonly used in the management of respiratory diseases. The propellants used in pressurised metered dose inhalers (pMDIs) are potent greenhouse gases and carry a substantial global warming potential. Dry powder inhalers (DPIs) are propellant-free alternatives that have fewer consequences on the environment, while being equally effective. In this study, we assessed patients' and clinicians' attitudes towards choosing inhalers that have a lesser environmental impact. METHODS:Surveys of patients and practitioners were undertaken in primary and secondary care settings in Dunedin and Invercargill. Fifty-three patient and 16 practitioner responses were obtained. RESULTS:Sixty-four percent of patients were using pMDIs, while 53% were using DPIs. Sixty-nine percent of patients believed that the environment is an important consideration when switching inhalers. Sixty-three percent of practitioners were aware of the global warming potential of inhalers. Despite this, 56% of practitioners predominantly prescribe or recommend pMDIs. The 44% of practitioners who mostly prescribe DPIs were more comfortable doing so based on environmental impact alone. CONCLUSION:Most respondents believe global warming is an important issue and would consider changing their inhaler to a more environmentally friendly type. Many people were not aware that pressurised metered dose inhalers have a substantial carbon footprint. Greater awareness of their environmental impacts may encourage the use of inhalers with lower global warming potential.

AIM To explore patient and staff views about the mixing of COVID-19 vaccinated and unvaccinated patients in multi-bed hospital rooms. METHODS We conducted a mixed methods study with paper surveys and structured interviews. Self-administered surveys were undertaken with inpatients on the general medicine, general surgery, orthopaedic and respiratory wards in Dunedin Public Hospital. Face-to-face interviews were conducted with ward staff including consultants, registrars, charge nurses, registered nurses and nurse managers. The study was undertaken in February 2022, at the start of the first New Zealand wave of the Omicron variant. RESULTS Of 118 eligible patients, 63 agreed to participate. Sixty (95%) of these patients were vaccinated for COVID-19. Most patients (59%) thought that vaccinated and unvaccinated people should be accommodated in separate hospital rooms. Vaccinated patients felt more comfortable sharing a multi-bed room with others of the same COVID-19 vaccination status as themselves than with unvaccinated patients. Participants who thought that they were at higher risk of severe illness from COVID-19 were more likely to support separation of patients based on vaccination status. Fifteen ward staff were interviewed: most would prefer the hospital to separate patients by vaccination status but were aware this would present practical and ethical problems and thought that current arrangements were adequate. CONCLUSION While most vaccinated patients and staff wanted patients to be separated according to their COVID-19 vaccination status, the current precautionary measures for COVID-19 were viewed by most staff members as adequate.

Studies report mixed findings regarding the association of breastfeeding with childhood brain tumors (CBT), the leading causes of cancer-related mortality in young people. Our objective was to determine whether breastfeeding is associated with CBT incidence. We pooled data on N = 2610 cases with CBT (including 697 cases with astrocytoma, 447 cases with medulloblastoma/primitive neuroectodermal tumor [PNET], 167 cases with ependymoma) and N = 8128 age- and sex-matched controls in the Childhood Cancer and Leukemia International Consortium. We computed unconditional logistic regression models to estimate the odds ratio (OR) and 95 Breastfeeding was reported by 64.8

Increasing evidence suggests that breastfeeding may protect from childhood acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). However, most studies have limited their analyses to any breastfeeding, and only a few data have examined exclusive breastfeeding, or other exposures such as formula milk. We performed pooled analyses and individual participant data metaanalyses of data from 16 studies (N = 17 189 controls; N = 10 782 ALL and N = 1690 AML cases) from the Childhood Leukemia International Consortium (CLIC) to characterize the associations of breastfeeding duration with ALL and AML, as well as exclusive breastfeeding duration and age at introduction to formula with ALL. In unconditional multivariable logistic regression analyses of pooled data, we observed decreased odds of ALL among children breastfed 4 to 6 months (0.88, 95% CI 0.81‐0.96) or 7 to 12 months (OR 0.85, 0.79‐0.92). We observed a similar inverse association between breastfeeding ≥4 months and AML (0.82, 95% CI 0.71‐0.95). Odds of ALL were reduced among children exclusively breastfed 4 to 6 months (OR 0.73, 95% CI 0.63‐0.85) or 7 to 12 months (OR 0.70, 95% CI 0.53‐0.92). Random effects metaanalyses produced similar estimates, and findings were unchanged in sensitivity analyses adjusted for race/ethnicity or mode of delivery, restricted to children diagnosed ≥1 year of age or diagnosed with B‐ALL. Our pooled analyses indicate that longer breastfeeding is associated with decreased odds of ALL and AML. Few risk factors for ALL and AML have been described, therefore our findings highlight the need to promote breastfeeding for leukemia prevention.

To explore the impacts of the 2020 New Zealand COVID‐19 lockdown on peer‐led Steady as You Go (SAYGO) fall prevention exercise classes and members, and to develop recommendations for mitigating impacts during future lockdowns.

BACKGROUND:There are significant implications for both patients and providers when patients do not attend outpatient specialist appointments. Nonattendance has an impact on the efficiency of health care, provider resources and patient health outcomes.AIMS:In this qualitative study we aimed to gather insights on how Dunedin Hospital notifies patients about their appointments, the implications for the hospital and for patients and how the system could be improved.METHODS:We interviewed 13 hospital staff members and nine patients who volunteered to participate because they had missed appointments as a result of communication problems. Interviews were transcribed and analysed thematically using NVivo software.RESULTS:Dunedin Hospital relies heavily on posted letters to inform people about their appointments, with some also receiving reminder texts closer to the time of the appointment. Frustration with the current system was a common theme among both patients and staff. Almost all patients had missed an appointment because of a letter not arriving. While most patients found that the text reminders were helpful, most said they were sent too late and did not allow enough time for arrangements to be made for their appointments. Almost all patients experienced treatment delays, which caused distress. Most patients believed a self-booking system would improve the ability to attend their appointments, and most of them wanted to be notified of appointments via email.CONCLUSIONS:We recommend that a patient-oriented approach to communication should be implemented, and alternative methods of communication should be explored.

AIMS We aimed to assess the use of and attitudes towards cannabis use (medicinal and recreational) by people with IBD in New Zealand. METHODS People with IBD were invited to complete an anonymous online questionnaire. Participants were recruited via postal mail using a hospital database of patients with IBD (developed by the Gas-troenterology Department at Dunedin Public Hospital) and via online recruitment (advertised on the Crohn's and Colitis New Zealand website, Facebook page and e-mail list). Inclusion criteria were ages 18+ and self-reported confirmed IBD diagnosis. RESULTS In total, 378 participants completed the questionnaire, with 334 eligible responses. Partici-pants were predominantly New Zealand European (84%) and female (71%). Sixty-one percent of re-spondents had CD and 34% UC. Overall, 51% of respondents reported having ever used cannabis. Of those, 63% reported use as recreational and 31% for reduction of IBD symptoms. Users were more likely to be younger (on average by 6.4 years), with on-going symptoms, unemployed or self-employed and current or ex-smokers. There were no differences by disease status or severity. Symp-toms most reported as improved by cannabis use were abdominal pain/cramping, nausea/vomiting and loss of appetite. Fifty-four percent of participants reported that if cannabis were legal, they would request it for medicinal use to help manage their symptoms. CONCLUSIONS Overall, our research aligns with previous observational research that reports im-provements in symptoms of IBD with cannabis use. Studies of a higher evidence level (eg, RCTs) would be needed to guide prescribing. In the meantime, this research provides useful background to clini-cians about patients' views and experiences.

Objective To assess changes in presentations to EDs during the COVID-19 pandemic lockdown in the Southern Region of New Zealand. Methods We conducted a retrospective audit of patients attending EDs in the Southern District Health Board (SDHB), from 1 March to 13 May 2020. We made comparisons with attendances during the same period in 2019. The 2020 study period included 'pre-lockdown' (1 March-25 March), 'level 4 (strict) lockdown' (26 March-27 April) and 'level 3 (eased) lockdown' (28 April-13 May). Results Patient volumes reduced in all SDHB EDs during levels 4 and 3, mostly representing a loss of low acuity patients (Australasian Triage Scale 3, 4 and 5), although high-acuity presentations also declined. Average patient age increased by 5 years; however, the proportions of sexes and ethnicities did not change. Presentations of cerebrovascular accidents and appendicitis did not change significantly. Trauma, mental health, acute coronary syndrome and infectious respiratory presentations decreased significantly during level 4, and infectious respiratory presentations decreased further in level 3. Conclusions Within the SDHB, patient volumes reduced during levels 4 and 3 of our lockdown, with reduced low-acuity presentations. High-acuity patient numbers also declined. Trauma, mental health, alcohol-related, infectious respiratory and acute coronary syndrome presentations declined while cerebrovascular accident and appendicitis numbers showed little to no change.

To assess changes in presentations to EDs during the COVID-19 pandemic lockdown in the Southern Region of New Zealand. We conducted a retrospective audit of patients attending EDs in the Southern District Health Board (SDHB), from 1 March to 13 May 2020. We made comparisons with attendances during the same period in 2019. The 2020 study period included ‘pre-lockdown’ (1 March–25 March), ‘level 4 (strict) lockdown’ (26 March–27 April) and ‘level 3 (eased) lockdown’ (28 April–13 May). Patient volumes reduced in all SDHB EDs during levels 4 and 3, mostly representing a loss of low acuity patients (Australasian Triage Scale 3, 4 and 5), although high-acuity presentations also declined. Average patient age increased by 5 years; however, the proportions of sexes and ethnicities did not change. Presentations of cerebrovascular accidents and appendicitis did not change significantly. Trauma, mental health, acute coronary syndrome and infectious respiratory presentations decreased significantly during level 4, and infectious respiratory presentations decreased further in level 3. Within the SDHB, patient volumes reduced during levels 4 and 3 of our lockdown, with reduced low-acuity presentations. High-acuity patient numbers also declined. Trauma, mental health, alcohol-related, infectious respiratory and acute coronary syndrome presentations declined while cerebrovascular accident and appendicitis numbers showed little to no change.

Introduction: On April 25, 2020, Veterans’ Affairs in New Zealand (NZ) contacted approximately 3,000 of 8,000 known military Veterans by phone during the SARS-CoV-2 pandemic to ensure they were safe during the government-imposed lockdown. The impetus to this initiative were the findings of a cross-sectional quantitative survey of NZ Veterans, followed by the qualitative survey reported here, both carried out in 2019. The former report found 33% of 89 respondents were lonely and reported barriers to seeking support, and over half of Veterans felt uncomfortable accessing it. Methods: To understand the factors underlying loneliness, a qualitative survey was developed based on the barriers previously identified and a literature review. A purposeful sample based on gender, age, and ethnicity identified 20 respondents from the initial survey: 10 lonely and 10 non-lonely. Interviews were followed by an inductive thematic analysis, and themes and sub-themes were developed. Results: Ten of the 20 potential participants responded: 6 lonely and 4 non-lonely. Social and geographic isolation, problems with re-integration into the civilian community, and health problems were found to contribute to Veteran loneliness. Social connectedness, particularly to service peers, was the primary mitigating factor. Barriers included stoicism and perceptions of ineffective and inaccessible services. Inequity in the Veteran support system also emerged as a barrier for Veterans who had not deployed on operational missions. Discussion: During the pandemic, social connectedness will have decreased, and loneliness increased. Designing interventions with these factors in mind, and ensuring equity of access to support, should help combat Veteran loneliness.

Aim: Evidence for an association of foetal growth with acute myeloid leukaemia (AML) is inconclusive. AML is a rare childhood cancer, relatively more frequent in girls, with distinct features in infancy. In the context of the Childhood Leukemia International Consortium (CLIC), we examined the hypothesis that the association may vary by age, sex and disease subtype using data from 22 studies and a total of 3564 AML cases. Methods: Pooled estimates by age, sex and overall for harmonised foetal growth markers in association with AML were calculated using the International Fetal and Newborn Growth Consortium for the 21st Century Project for 17 studies contributing individual-level data; meta-analyses were, thereafter, conducted with estimates provided ad hoc by five more studies because of administrative constraints. Subanalyses by AML subtype were also performed. Results: A nearly 50% increased risk was observed among large-for-gestational-age infant boys (odds ratio [OR]: 1.49, 95% confidence interval [CI]: 1.03-2.14), reduced to 34% in boys aged <2 years (OR: 1.34, 95% CI: 1.05-1.71) and 25% in boys aged 0-14 years (OR: 1.25, 95% CI: 1.06-1.46). The association of large for gestational age became stronger in boys with M0/M1subtype (OR: 1.80, 95% CI: 1.15-2.83). Large birth length for gestational age was also positively associated with AML (OR: 1.38, 95% CI: 1.00-1.92) in boys. By contrast, there were null associations in girls, as well as with respect to associations of decelerated foetal growth markers. Conclusions: Accelerated foetal growth was associated with AML, especially in infant boys and those with minimally differentiated leukaemia. Further cytogenetic research would shed light into the underlying mechanisms. (C) 2020 Elsevier Ltd. All rights reserved.

AIMS:To describe health conditions in New Zealand nuclear veterans and their offspring, and examine the utility of tests to assess their heritability.METHOD:An online survey, open to all veterans and offspring, with questions on health conditions, the GHQ12 to measure psychological distress, the Euroquol-5D visual analogue scale (EQ5D VAS) to measure health state, and free text items on veteran support.RESULTS:Eighty-three responses (56%) were from veterans, 65 (44%) from offspring. Anxiety and depression were prevalent in both groups, with cancers (n=31, 37%) and joint conditions common in veterans (n=26, 31%). Few offspring reported cancer, rather problems with fertility (n=18, 40%). The free text themes fell into four domains, official commitment, health, emotional and information support; however, little support had been sought.CONCLUSION:Cancers have utility in assessing heritability, but a low prevalence and lack of diagnostic data rules this out. Psychological conditions may be heritable, but the techniques to assess this are still developing. Chromosomal damage in veterans and offspring can be detected, but with present knowledge cannot explain health outcomes. Future work should assemble a veteran and family register with linkage to routine data-sets. Veterans and offspring should be encouraged to seek support.

Background Several nonbiological factors, including socioeconomic status indicators and other family characteristics, influence survival from childhood cancers. Our study explores the association between parental education and childhood cancer survival. Methods The specialized Childhood Cancer Registry of the Piedmont region in Italy provided data on all the cases (aged 0-14) diagnosed with cancer in the period 1976-2011 who resided in the city of Turin (capital of the Piedmont region) at least once since 1971. Information on parental education was extracted from the Turin Longitudinal Study by record linkage. The association between parental educational level and survival was estimated using Cox regression. Results The study included 949 children. We observed a disadvantage in the overall survival for children of less educated mothers. No such effect was observed for paternal education. The effect of maternal education was particularly strong for central nervous system tumors (hazard ratios, 2.9; 95% confidence interval, 1.1-8.0). A similar effect, though smaller in magnitude, was observed for leukemia and embryonal tumors, whereas the estimates for lymphoma were imprecise. Conclusions Our study shows an association between maternal educational level and survival in children with central nervous system tumors, a diagnosis that often requires long-lasting treatment and special care. Giving support to the families of affected children to provide them the optimal care has the potential to improve children's cancer treatment outcomes.

ObjectivesPreviously published studies on parental occupational exposure to extremely low-frequency magnetic fields (ELF-MF) and risk of acute lymphoblastic leukaemia (ALL) and acute myeloid leukaemia (AML) in their offspring were inconsistent. We therefore evaluated this question within the Childhood Leukemia International Consortium.MethodsWe pooled 11 case–control studies including 9723 childhood leukaemia cases and 17 099 controls. Parental occupational ELF-MF exposure was estimated by linking jobs to an ELF-MF job-exposure matrix (JEM). Logistic regression models were used to estimate ORs and 95% CIs in pooled analyses and meta-analyses.ResultsORs from pooled analyses for paternal ELF-MF exposure >0.2 microtesla (µT) at conception were 1.04 (95% CI 0.95 to 1.13) for ALL and 1.06 (95% CI 0.87 to 1.29) for AML, compared with ≤0.2 µT. Corresponding ORs for maternal ELF-MF exposure during pregnancy were 1.00 (95% CI 0.89 to 1.12) for ALL and 0.85 (95% CI 0.61 to 1.16) for AML. No trends of increasing ORs with increasing exposure level were evident. Furthermore, no associations were observed in the meta-analyses.ConclusionsIn this large international dataset applying a comprehensive quantitative JEM, we did not find any associations between parental occupational ELF-MF exposure and childhood leukaemia.

Background: Parental age has been associated with several childhood cancers, albeit the evidence is still inconsistent. Aim: To examine the associations of parental age at birth with acute myeloid leukemia (AML) among children aged 0-14 years using individual-level data from the Childhood Leukemia International Consortium (CLIC) and non-CLIC studies. Material/methods: We analyzed data of 3182 incident AML cases and 8377 controls from 17 studies [seven registry-based case-control (RCC) studies and ten questionnaire-based case-control (QCC) studies]. AML risk in association with parental age was calculated using multiple logistic regression, meta-analyses, and pooled-effect estimates. Models were stratified by age at diagnosis (infants < 1 year-old vs. children 1-14 years-old) and by study design, using five-year parental age increments and controlling for sex, ethnicity, birthweight, prematurity, multiple gestation, birth order, maternal smoking and education, age at diagnosis (cases aged 1-14 years), and recruitment time period. Results: Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) derived from RCC, but not from the QCC, studies showed a higher AML risk for infants of mothers >= 40-year-old (OR = 6.87; 95% CI: 2.12-22.25). There were no associations observed between any other maternal or paternal age group and AML risk for children older than one year. Conclusions: An increased risk of infant AML with advanced maternal age was found using data from RCC, but not from QCC studies; no parental age-AML associations were observed for older children.