Five decades of occupational cancer epidemiology.

OBJECTIVE: In this discussion paper, we provide a narrative review of past and present occupational cancer studies in the journal with a viewpoint towards future occupational cancer research. METHOD: We reviewed all references in the journal that mentioned cancer according to relevance to etiology, cancer type, agent type, study design, and study population. RESULTS: The Scandinavian Journal of Work, Environment & Health has published over 300 manuscripts on occupational cancer over the 50 past years. Although studies of cancer represent the primary health outcome in the journal overall, the relative ranking of cancer manuscripts has declined somewhat over time. A large body of evidence from studies of occupation and industry was apparent both in early research and continuing in recent years. There are several examples of the utility of pooled multi-country collaborative studies. Studies also took advantage of available high-quality national population and cancer registers in Nordic countries. There have been notable shifts in focus with regard to the cancer types examined, with increases in publications examining female breast cancer over the decades. The interplay of studies of occupational and environmental cancer has also been apparent. CONCLUSIONS: The journal offers a unique viewpoint to consider the evolution of occupational cancer evidence over time. Studies of occupational cancer have played a central role in global cancer hazard identification efforts. Although much has been gained, there remains a need for renewed global support for occupational cancer research. Concerted efforts will be needed to ensure a future robust evidence-base for occupational and environmental cancer worldwide.

Occupational exposure to radiofrequency electromagnetic fields and brain tumor risk: Application of the INTEROCC job-exposure matrix.

Radiofrequency electromagnetic fields (RF-EMF, 100 kHz to 300 GHz) are classified by IARC as possibly carcinogenic to humans (Group 2B). This study evaluates the potential association between occupational RF-EMF exposure and brain tumor risk, utilizing for the first time, a RF-EMF job-exposure matrix (RF-JEM) developed in the multi-country INTEROCC case-control study. Cumulative and time-weighted average (TWA) occupational RF-EMF exposures were estimated for study participants based on lifetime job histories linked to the RF-JEM using three different methods: (1) by considering RF-EMF intensity among all exposed jobs, (2) by considering RF-EMF intensity among jobs with an exposure prevalence ≥ the median exposure prevalence of all exposed jobs, and (3) by considering RF-EMF intensity of jobs of participants who reported RF-EMF source use. Stratified conditional logistic regression models were used, considering various lag periods and exposure time windows defined a priori. Generally, no clear associations were found for glioma or meningioma risk. However, some statistically significant positive associations were observed including in the highest exposure categories for glioma for cumulative and TWA exposure in the 1- to 4-year time window for electric fields (E) in the first JEM application method (odds ratios [ORs] = 1.36, 95% confidence interval [95% CI] 1.08, 1.72 and 1.27, 95% CI 1.01, 1.59, respectively), as well as for meningioma for cumulative exposure in the 5- to 9-year time window for electric fields (E) in the third JEM application method (OR = 2.30, 95% CI 1.11, 4.78). We did not identify convincing associations between occupational RF-EMF exposure and risk of glioma or meningioma.

Comparison of a radiofrequency electric and magnetic field source-based job-exposure matrix with personal radiofrequency exposure measurements.

OBJECTIVES: Assessing occupational exposure to radiofrequency electromagnetic fields (RF-EMF) presents significant challenges due to the considerable variability in exposure levels within and between occupations. This spatial and temporal variability complicates the reliable evaluation of potential health risks associated with RF-EMF exposure in the workplace. Accurate assessment methods are crucial to understand the extent of exposure and to evaluate potential health risks, especially given the potential for higher exposures in occupational settings compared to the general population. This study compares the historical RF-EMF exposure estimates in the INTEROCC RF-EMF job-exposure matrix (RF-JEM) with recent personal measurement data collected in 2 countries as part of the OccRF-Health study, to assess the broader applicability of the RF-JEM. METHODS: Weighted kappa (k  w) coefficients and Spearman rank correlation tests were performed to assess the alignment between RF-JEM estimates and measurements for 8 h time-weighted average exposure intensity and prevalence estimates across various occupations. The comparisons were mainly based on 22 jobs having ≥5 measured workers in the OccRF-Health study. RESULTS: Poor agreement was found for both exposure prevalence and intensity between both methods (k  w < 0.1). RF-JEM values likely overestimated exposure levels for both electric (E) and magnetic (H) fields (mean percentage difference >194%) compared to current personal measurements. CONCLUSIONS: Findings suggest that the INTEROCC-JEM likely overestimates current exposure intensity levels in the measured jobs. Adopting a semiquantitative JEM could also mitigate misclassification errors due to exposure variability, improving accuracy in exposure assessment. These findings indicate the need for more targeted personal measurements, including among highly exposed workers, and for potentially considering new exposure metrics to more accurately assess occupational RF-EMF exposures in occupational epidemiological research.

Outdoor air pollution and risk of incident adult haematologic cancer subtypes in a large US prospective cohort.

BACKGROUND: Outdoor air pollution and particulate matter (PM) are classified as Group 1 human carcinogens for lung cancer. Pollutant associations with haematologic cancers are suggestive, but these cancers are aetiologically heterogeneous and sub-type examinations are lacking. METHODS: The American Cancer Society Cancer Prevention Study-II Nutrition Cohort was used to examine associations of outdoor air pollutants with adult haematologic cancers. Census block group level annual predictions of particulate matter (PM2.5, PM10, PM10-2.5), nitrogen dioxide (NO2), ozone (O3), sulfur dioxide (SO2), and carbon monoxide (CO) were assigned with residential addresses. Hazard ratios (HR) and 95% confidence intervals (CI) between time-varying pollutants and haematologic subtypes were estimated. RESULTS: Among 108,002 participants, 2659 incident haematologic cancers were identified from 1992-2017. Higher PM10-2.5 concentrations were associated with mantle cell lymphoma (HR per 4.1 µg/m3 = 1.43, 95% CI 1.08-1.90). NO2 was associated with Hodgkin lymphoma (HR per 7.2 ppb = 1.39; 95% CI 1.01-1.92) and marginal zone lymphoma (HR per 7.2 ppb = 1.30; 95% CI 1.01-1.67). CO was associated with marginal zone (HR per 0.21 ppm = 1.30; 95% CI 1.04-1.62) and T-cell (HR per 0.21 ppm = 1.27; 95% CI 1.00-1.61) lymphomas. CONCLUSIONS: The role of air pollutants on haematologic cancers may have been underestimated previously because of sub-type heterogeneity.

Supporting a mentally healthy place of study: Examining the relationship between mental well-being, stress, and protective factors among university students.

INTRODUCTION: Students can expect to experience stressors associated with their studies that can have detrimental effects on their mental well-being if not properly managed. Drawing on a positive psychology paradigm, protective factors can help students to counter study-related stressors and contribute to their mental well-being and academic success. The relationship between protective factors, such as maintaining perspective and building networks, with stress severity and positive mental well-being was examined in a sample of Australian university students undertaking postgraduate coursework. METHODS: Students completed a survey measuring stress from the Depression, Anxiety and Stress Scale (DASS), positive mental well-being from the Short Warwick-Edinburgh Mental Well-being Scale (SWEMWBS), and seven protective factors from the Resilience at University (RAU) scale. Bivariate correlations were calculated for the RAU protective factors with stress and mental well-being. ANOVA examined the RAU protective factors in relation to mental well-being and stress severity groupings. RESULTS: All seven protective factors had a positive and significant relationship with positive mental well-being, and six of the seven protective factors had a negative and significant relationship with stress. A statistically significant difference was found for six of the seven RAU protective factors according to mental well-being group, and three of the seven RAU protective factors group according to stress severity group. A linear effect emerged between level of protective factor and mental well-being group, with participants in the high well-being group having the highest level of protective factors. CONCLUSION: Universities should focus on the development of protective factors to support students' well-being and help them to flourish in their studies.

Unmet Needs, Quality of Life, and Financial Toxicity Among Survivors of Lung Cancer.

Importance: Despite a growing population of survivors of lung cancer, there is limited understanding of the survivorship journey. Survivors of lung cancer experience unmet physical, social, emotional, and medical needs regardless of stage at diagnosis or treatment modalities. Objective: To investigate the association of unmet needs with quality of life (QOL) and financial toxicity (FT) among survivors of lung cancer. Design, Setting, and Participants: This survey study was conducted at Johns Hopkins Sidney Kimmel Comprehensive Cancer Center thoracic oncology clinics between December 1, 2020, and September 30, 2021, to assess needs (physical, social, emotional, and medical), QOL, and FT among survivors of lung cancer. Patients had non-small cell lung cancer of any stage and were alive longer than 1 year from diagnosis. A cross-sectional survey was administered, which consisted of an adapted needs survey developed by the Mayo Survey Research Center, the Comprehensive Score for Financial Toxicity measure, and the European Organization for Research and Treatment of Cancer QLQ-C30 QOL scale. Demographic and clinical information was obtained through retrospective medical record review. Data analysis was performed between May 9 and December 8, 2022. Main Outcomes and Measures: Separate multiple linear regression models, treating QOL and FT as dependent variables, were performed to assess the adjusted association of total number of unmet needs and type of unmet need (physical, emotional, social, or medical) with QOL and FT. Results: Of the 360 survivors of lung cancer approached, 232 completed the survey and were included in this study. These 232 respondents had a median age of 69 (IQR, 60.5-75.0) years. Most respondents were women (144 [62.1%]), were married (165 [71.1%]), and had stage III or IV lung cancer (140 [60.3%]). Race and ethnicity was reported as Black (33 [14.2%]), White (172 [74.1%]), or other race or ethnicity (27 [11.6%]). A higher number of total unmet needs was associated with lower QOL (ß [SE], -1.37 [0.18]; P < .001) and higher FT (ß [SE], -0.33 [0.45]; P < .001). In the context of needs domains, greater unmet physical needs (ß [SE], -1.24 [0.54]; P = .02), social needs (ß [SE], -3.60 [1.34]; P = .01), and medical needs (ß [SE], -2.66 [0.98]; P = .01) were associated with lower QOL, whereas only greater social needs was associated with higher FT (ß [SE], -3.40 [0.53]; P < .001). Conclusions and Relevance: The findings of this survey study suggest that among survivors of lung cancer, unmet needs were associated with lower QOL and higher FT. Future studies evaluating targeted interventions to address these unmet needs may improve QOL and FT among survivors of lung cancer.

A Baker's Dozen of Top Antimicrobial Stewardship Intervention Publications in 2022.

Keeping abreast of the antimicrobial stewardship-related articles published each year is challenging. The Southeastern Research Group Endeavor identified antimicrobial stewardship-related, peer-reviewed literature that detailed an actionable intervention during 2022. The top 13 publications were selected using a modified Delphi technique. These manuscripts were reviewed to highlight actionable interventions used by antimicrobial stewardship programs to capture potentially effective strategies for local implementation.

AllergoOncology: Biomarkers and refined classification for research in the allergy and glioma nexus-A joint EAACI-EANO position paper.

Epidemiological studies have explored the relationship between allergic diseases and cancer risk or prognosis in AllergoOncology. Some studies suggest an inverse association, but uncertainties remain, including in IgE-mediated diseases and glioma. Allergic disease stems from a Th2-biased immune response to allergens in predisposed atopic individuals. Allergic disorders vary in phenotype, genotype and endotype, affecting their pathophysiology. Beyond clinical manifestation and commonly used clinical markers, there is ongoing research to identify novel biomarkers for allergy diagnosis, monitoring, severity assessment and treatment. Gliomas, the most common and diverse brain tumours, have in parallel undergone changes in classification over time, with specific molecular biomarkers defining glioma subtypes. Gliomas exhibit a complex tumour-immune interphase and distinct immune microenvironment features. Immunotherapy and targeted therapy hold promise for primary brain tumour treatment, but require more specific and effective approaches. Animal studies indicate allergic airway inflammation may delay glioma progression. This collaborative European Academy of Allergy and Clinical Immunology (EAACI) and European Association of Neuro-Oncology (EANO) Position Paper summarizes recent advances and emerging biomarkers for refined allergy and adult-type diffuse glioma classification to inform future epidemiological and clinical studies. Future research is needed to enhance our understanding of immune-glioma interactions to ultimately improve patient prognosis and survival.

Impact of a Nurse-Led Palliative Care Screening Tool on Medical Oncology Units.

There is a lack of early integration of palliative care in patients with advanced cancer, which has been shown to result in suboptimal quality of life across their disease continuum. Standardized palliative care screening too.

Lung Cancer Survivorship: Physical, Social, Emotional, and Medical Needs of NSCLC Survivors.

BACKGROUND: Newer therapies prolong survival for patients with lung cancer. Beyond extending survival, the needs of lung cancer (LC) survivors are poorly described. METHODS: We conducted a single-institution needs assessment survey of LC survivors alive ≥1 year from diagnosis. Needs were rated on a 5-point Likert scale for 4 domains (physical, social, emotional, and medical). Multiple regression models identified demographic or treatment characteristics associated with more needs in each category. A subset analysis of survivors with metastatic LC was performed. RESULTS: Of 360 patients approached, 235 surveys were completed. Among completed survey respondents, the median age was 69 years; most were female (62%), married (71%), and White (74%); and 41% had stage IV cancer. Finding support resources (34%) was the most common medical need. Fatigue (70%), sleep disturbance (60%), memory and concentration (57.5%), weakness (54%), and trouble breathing (51%) were physical needs affecting more than half of respondents. The most common social need was managing daily activities (42%). Emotional needs were highly prevalent, with 79% of respondents reporting a fear of recurrence and 74.5% reporting living with uncertainty. Multiple regression analysis identified that receipt of multiple lines of systemic therapy and lower household income were associated with higher physical and social needs. Younger age was associated with having a greater number of social and emotional needs. Similar results were found in the subset of survivors with metastatic disease at diagnosis. CONCLUSIONS: The needs of LC survivors are diverse across multiple domains. Several clinical and demographic factors are independently associated with higher numbers of patient-reported needs. Our study identifies critical gaps in survivorship care for LC survivors with all stages of disease and highlights areas of future intervention.

Recognition of COVID-19 with occupational origin: a comparison between European countries.

OBJECTIVES: This study aims to present an overview of the formal recognition of COVID-19 as occupational disease (OD) or injury (OI) across Europe. METHODS: A COVID-19 questionnaire was designed by a task group within COST-funded OMEGA-NET and sent to occupational health experts of 37 countries in WHO European region, with a last update in April 2022. RESULTS: The questionnaire was filled out by experts from 35 countries. There are large differences between national systems regarding the recognition of OD and OI: 40% of countries have a list system, 57% a mixed system and one country an open system. In most countries, COVID-19 can be recognised as an OD (57%). In four countries, COVID-19 can be recognised as OI (11%) and in seven countries as either OD or OI (20%). In two countries, there is no recognition possible to date. Thirty-two countries (91%) recognise COVID-19 as OD/OI among healthcare workers. Working in certain jobs is considered proof of occupational exposure in 25 countries, contact with a colleague with confirmed infection in 19 countries, and contact with clients with confirmed infection in 21 countries. In most countries (57%), a positive PCR test is considered proof of disease. The three most common compensation benefits for COVID-19 as OI/OD are disability pension, treatment and rehabilitation. Long COVID is included in 26 countries. CONCLUSIONS: COVID-19 can be recognised as OD or OI in 94% of the European countries completing this survey, across different social security and embedded occupational health systems.

Global, regional and national burdens of non-melanoma skin cancer attributable to occupational exposure to solar ultraviolet radiation for 183 countries, 2000-2019: A systematic analysis from the WHO/ILO Joint Estimates of the Work-related Burden of Disease and Injury.

BACKGROUND: A World Health Organization (WHO) and International Labour Organization (ILO) systematic review reported sufficient evidence for higher risk of non-melanoma skin cancer (NMSC) amongst people occupationally exposed to solar ultraviolet radiation (UVR). This article presents WHO/ILO Joint Estimates of global, regional, national and subnational occupational exposures to UVR for 195 countries/areas and the global, regional and national attributable burdens of NMSC for 183 countries, by sex and age group, for the years 2000, 2010 and 2019. METHODS: We calculated population-attributable fractions (PAFs) from estimates of the population occupationally exposed to UVR and the risk ratio for NMSC from the WHO/ILO systematic review. Occupational exposure to UVR was modelled via proxy of occupation with outdoor work, using 166 million observations from 763 cross-sectional surveys for 96 countries/areas. Attributable NMSC burden was estimated by applying the PAFs to WHO's estimates of the total NMSC burden. Measures of inequality were calculated. RESULTS: Globally in 2019, 1.6 billion workers (95 % uncertainty range [UR] 1.6-1.6) were occupationally exposed to UVR, or 28.4 % (UR 27.9-28.8) of the working-age population. The PAFs were 29.0 % (UR 24.7-35.0) for NMSC deaths and 30.4 % (UR 29.0-31.7) for disability-adjusted life years (DALYs). Attributable NMSC burdens were 18,960 deaths (UR 18,180-19,740) and 0.5 million DALYs (UR 0.4-0.5). Men and older age groups carried larger burden. Over 2000-2019, attributable deaths and DALYs almost doubled. CONCLUSIONS: WHO and the ILO estimate that occupational exposure to UVR is common and causes substantial, inequitable and growing attributable burden of NMSC. Governments must protect outdoor workers from hazardous exposure to UVR and attributable NMSC burden and inequalities.

Diesel exhaust particles exposure exacerbates pro-thrombogenic plasma features ex-vivo after cerebral ischemia and accelerates tPA-induced clot-lysis in hypertensive subjects.

The combustion of fossil fuels, mainly by diesel engines, generates Diesel Exhaust Particles (DEP) which are the main source of Particulate Matter (PM), a major air pollutant in urban areas. These particles are a risk factor for stroke with 5.6% of cases attributed to PM exposure. Our aim was to evaluate the effect of DEP exposure on clot formation and lysis in the context of stroke. An ex-vivo clot formation and lysis turbidimetric assay has been conducted in human and mouse plasma samples from ischemic stroke or control subjects exposed to DEP or control conditions. Experimental DEP exposure was achieved by nasal instillation in mice, or by ex-vivo exposure in human plasma. Results show consistent pro-thrombogenic features in plasma after human ischemic stroke and mouse cerebral ischemia (distal MCAo), boosted by the presence of DEP. Otherwise, thrombolysis times were increased after ischemia in chronically exposed mice but not in the DEP exposed group. Finally, subjects living in areas with high PM levels presented accelerated thrombolysis compared to those living in low polluted areas. Overall, our results point at a disbalance of the thrombogenic/lytic system in presence of DEP which could impact on ischemic stroke onset, clot size and thrombolytic treatment.

Research Recommendations for Selected IARC-Classified Agents: Impact and Lessons Learned.

BACKGROUND: The International Agency for Research on Cancer (IARC) Monographs program assembles expert working groups who publish a critical review and evaluation of data on agents of interest. These comprehensive reviews provide a unique opportunity to identify research needs to address classification uncertainties. A multidisciplinary expert review and workshop held in 2009 identified research gaps and needs for 20 priority occupational chemicals, metals, dusts, and physical agents, with the goal of stimulating advances in epidemiological studies of cancer and carcinogen mechanisms. Overarching issues were also described. OBJECTIVES: In this commentary we review the current status of the evidence for the 20 priority agents identified in 2009. We examine whether identified Research Recommendations for each agent were addressed and their potential impact on resolving classification uncertainties. METHODS: We reviewed the IARC classifications of each of the 20 priority agents and identified major new epidemiological and human mechanistic studies published since the last evaluation. Information sources were either the published Monograph for agents that have been reevaluated or, for agents not yet reevaluated, Advisory Group reports and literature searches. Findings are described in view of recent methodological developments in Monographs evidence evaluation processes. DISCUSSION: The majority of the 20 priority agents were reevaluated by IARC since 2009. The overall carcinogen classifications of 9 agents advanced, and new cancer sites with either "sufficient" or "limited" evidence of carcinogenicity were also identified for 9 agents. Examination of published findings revealed whether evidence gaps and Research Recommendations have been addressed and highlighted remaining uncertainties. During the past decade, new research addressed a range of the 2009 recommendations and supported updated classifications for priority agents. This supports future efforts to systematically apply findings of Monograph reviews to identify research gaps and priorities relevant to evaluation criteria established in the updated IARC Monograph Preamble. https://doi.org/10.1289/EHP12547.

Personal exposure to radiofrequency electromagnetic fields in various occupations in Spain and France.

BACKGROUND: A preliminary job-exposure matrix (JEM) for radiofrequency electromagnetic fields (RF-EMF) was created based on self-reported occupational information from a multi-country population-based study of approximately 10,000 participants combined with available measurement data compiled in a source-exposure matrix (spot measurements). In order to address the limited personal occupational RF-EMF measurement data available in the literature, we performed a measurement campaign among workers in various occupations in Spain and France. METHODS: Personal full-shift measurements were conducted using RadMan 2XT™ (Narda) devices. A worker diary was used to capture information on occupational and background sources of RF exposure during the shift. Inclusion of occupations to be measured was initially based on exposure prevalence and level information in the preliminary JEM and expert judgment. RESULTS: Personal full-shift measurements were conducted among 333 workers representing 46 ISCO88 occupations. Exposure to electric (E) and magnetic (H) fields was infrequent with >99% of measurements below the detection limit of the device (≥1% of the 1998 ICNIRP standards). A total of 50.2% and 77.2% of workers were ever exposed to E and H fields respectively (having at least one recorded 1-second measurement above the detection limit). Workers in elementary occupations, technicians and associate professionals, plant and machine operators and assemblers had somewhat greater numbers of measurements above the detection limit, higher maximum values and longer exposure durations. A small proportion of measurements were ≥100% of the standards, though these exceedances were brief (generally a few seconds in duration). Female workers and workers reporting use of any RF-EMF emitting source were more likely to have a measured exposure to E and H fields. CONCLUSION: We conducted personal RF-EMF measurements among workers in various occupations in Spain and France. Overall, RF-EMF exposure ≥1 % ICNIRP was infrequent, despite some intermittent exposures ≥100% observed among workers in some occupations.

Occupational exposure to extremely low-frequency magnetic fields and follicular lymphoma risk: a family case-control study.

OBJECTIVES: We aimed to examine the relationship between occupational exposure to extremely low-frequency magnetic fields (ELF-MFs) and follicular lymphoma (FL) risk. METHODS: We conducted a family case-control study between 2011 and 2016 in Australia and included 681 cases. Controls were either a family member of cases (related (n=294), unrelated (n=179)) or were unrelated recruited for a similarly designed Australian multiple myeloma study (n=711). We obtained detailed job histories using lifetime work calendars. We assigned exposure to ELF-MFs using an enhanced job exposure matrix, with a lag period of 10 years. We examined associations with FL risk using logistic regression accounting for relatedness between cases and controls. We performed sensitivity analyses including by control type, by sex, complete case analyses, ELF-MF exposure percentiles in addition to quartiles, ELF-MF exposure in the maximum exposed job, a shorter lag period (1 year) and the cumulative exposure in the most recent time period (1-9 years). RESULTS: We observed no association with the average intensity, duration or lifetime cumulative exposure to occupational ELF-MF exposure in the primary or sensitivity analyses. CONCLUSIONS: Our findings do not support an association between occupational ELF-MF exposure and FL risk. Although the inclusion of family members as part of the larger control group may have biased our risk estimates towards the null, findings were similar in sensitivity analyses restricted to cases and unrelated controls. Further research incorporating enhanced exposure assessment to ELF-MF is warranted to inform occupational safety regulations and any potential role in lymphomagenesis.

Mild matters: trial learnings and importance of community engagement in research for early identified bilateral mild hearing loss.

Introduction: Early identification of mild hearing loss has resulted in early hearing amplification without adequate evidence of effectiveness. This paper describes learnings from a pilot trial, combined with a qualitative study, to highlight the importance of community engagement in designing research studies to determine whether early amplification benefits young children with bilateral mild hearing loss. Methods: PART 1 of the study is a proof-of-concept non-blinded multi-centre randomised controlled trial (RCT) of hearing device fitting vs. no fitting aimed to gather preliminary data and determine its acceptability/feasibility in children <2 years old with bilateral mild hearing loss. Results: PART 2 is a qualitative study to understand the barriers/enablers to RCT participation. Of 40 potentially eligible families, nine (23%) declined, three were uncontactable (7%), 26 (65%) ineligible: of these, nine (35%) did not meet hearing threshold inclusion criteria, 11 (42%) were already fitted or had made decisions on fitting hearing device, two (7%) had conductive loss and four (16%) were ineligible for other reasons. Two of 11 (18%) eligible families were randomised. With the limited sample size, outcome measures were not compared between groups. Both participants completed the trial, reported the RCT to be acceptable, and neither changed group post-enrolment. Discussion: Whilst recruitment uptake could potentially be increased by altering the eligibility criteria, better communication with and reimbursement of clinicians as recruiters, and improving awareness of the study amongst external stakeholders, the RCT methodology does not conform to family-centred practice, and potentially raises ethical concerns regarding potential adverse consequences of not offering early amplification. Parental perception of losing control over choice of management due to randomisation is not an easily modifiable factor. Alternative methodological approaches without randomisation are required to determine whether hearing amplification benefits infants with mild hearing loss.Clinical Trial Registration: identifier [ACTRN12618001608257].

Effect of walnut consumption on neuropsychological development in healthy adolescents: a multi-school randomised controlled trial.

Background: Omega-3 fatty acids are critical for neuropsychological functioning. Adolescence is increasingly believed to entail brain vulnerability to dietary intake. The potential benefit on adolescent neurodevelopment of consuming walnuts, a source of omega-3 alpha-linolenic acid (ALA), remains unclear. Methods: We conducted a 6-month multi-school-based randomised controlled nutrition intervention trial to assess whether walnut consumption has beneficial effects on the neuropsychological and behavioural development of adolescents. The study took place between 04/01/2016 and 06/30/2017 in twelve different high schools in Barcelona, Spain (ClinicalTrials.gov Identifier: NCT02590848). A total of 771 healthy teenagers aged 11-16 years were randomised into two equal groups (intervention or control). The intervention group received 30 g/day of raw walnut kernels to be incorporated into their diet for 6 months. Multiple primary endpoints concerning neuropsychological (working memory, attention, fluid intelligence, and executive function) and behavioural (socio-emotional and attention deficit hyperactivity disorder [ADHD] symptoms) development were assessed at baseline and after intervention. Red blood cell (RBC) ALA status was determined at baseline and 6 months as a measure of compliance. Main analyses were based on intention-to-treat using a linear mixed-effects model. A per-protocol effect of the intervention was analysed using inverse-probability weighting to account for post-randomisation prognostic factors (including adherence) using generalised estimating equations. Findings: In intention-to-treat analyses, at 6 months there were no statistically significant changes between the intervention and control groups for all primary endpoints. RBC ALA (%) significantly increased only in the intervention group, coefficient = 0.04 (95% Confidence Interval (CI) = 0.03, 0.06; p < 0.0001). The per-protocol (adherence-adjusted) effect on improvement in attention score (hit reaction time variability) was -11.26 ms (95% CI = -19.92, -2.60; p = 0.011) for the intervention group as compared to the control group, improvement in fluid intelligence score was 1.78 (95% CI = 0.90, 2.67; p < 0.0001), and reduction of ADHD symptom score was -2.18 (95% CI = -3.70, -0.67; p = 0.0050). Interpretation: Our study suggested that being prescribed eating walnuts for 6 months did not improve the neuropsychological function of healthy adolescents. However, improved sustained attention, fluid intelligence, and ADHD symptoms were observed in participants who better complied with the walnut intervention. This study provides a foundation for further clinical and epidemiological research on the effect of walnuts and ALA on neurodevelopment in adolescents. Funding: This study was supported by Instituto de Salud Carlos III through the projects 'CP14/00108, PI16/00261, PI21/00266' (co-funded by European Union Regional Development Fund 'A way to make Europe'). The California Walnut Commission (CWC) has given support by supplying the walnuts for free for the Walnuts Smart Snack Dietary Intervention Trial.

Society for Immunotherapy of Cancer (SITC) consensus definitions for immune checkpoint inhibitor-associated immune-related adverse events (irAEs) terminology.

Immune-related adverse events (irAEs) associated with immune checkpoint inhibitor (ICI) therapy may vary substantially in their clinical presentation, including natural history, outcomes to treatment, and patterns. The application of clinical guidelines for irAE management can be challenging for practitioners due to a lack of common or consistently applied terminology. Furthermore, given the growing body of clinical experience and published data on irAEs, there is a greater appreciation for the heterogeneous natural histories, responses to treatment, and patterns of these toxicities, which is not currently reflected in irAE guidelines. Furthermore, there are no prospective trial data to inform the management of the distinct presentations of irAEs. Recognizing a need for uniform terminology for the natural history, response to treatment, and patterns of irAEs, the Society for Immunotherapy of Cancer (SITC) convened a consensus panel composed of leading international experts from academic medicine, industry, and regulatory agencies. Using a modified Delphi consensus process, the expert panel developed clinical definitions for irAE terminology used in the literature, encompassing terms related to irAE natural history (ie, re-emergent, chronic active, chronic inactive, delayed/late onset), response to treatment (ie, steroid unresponsive, steroid dependent), and patterns (ie, multisystem irAEs). SITC developed these definitions to support the adoption of a standardized vocabulary for irAEs, which will have implications for the uniform application of irAE clinical practice guidelines and to enable future irAE clinical trials.