Mediport use as an acceptable standard for CAR T cell infusion.

Introduction: Mediport use as a clinical option for the administration of chimeric antigen receptor T cell (CAR T cell) therapy in patients with B-cell malignancies has yet to be standardized. Concern for mediport dislodgement, cell infiltration, and ineffective therapy delivery to systemic circulation has resulted in variable practice with intravenous administration of CAR T cell therapy. With CAR T cell commercialization, it is important to establish practice standards for CAR T cell delivery. We conducted a study to establish usage patterns of mediports in the clinical setting and provide a standard of care recommendation for mediport use as an acceptable form of access for CAR T cell infusions. Methods: In this retrospective cohort study, data on mediport use and infiltration rate was collected from a survey across 34 medical centers in the Pediatric Real-World CAR Consortium, capturing 504 CAR T cell infusion routes across 489 patients. Data represents the largest, and to our knowledge sole, report on clinical CAR T cell infusion practice patterns since FDA approval and CAR T cell commercialization in 2017. Results: Across 34 sites, all reported tunneled central venous catheters, including Broviac® and Hickman® catheters, as accepted standard venous options for CAR T cell infusion. Use of mediports as a standard clinical practice was reported in 29 of 34 sites (85%). Of 489 evaluable patients with reported route of CAR T cell infusion, 184 patients were infused using mediports, with no reported incidences of CAR T cell infiltration. Discussion/Conclusion: Based on current clinical practice, mediports are a commonly utilized form of access for CAR T cell therapy administration. These findings support the safe practice of mediport usage as an accepted standard line option for CAR T cell infusion.

Expert consensus guidance on respiratory physiotherapy and rehabilitation of patients with rib fractures: An international, multidisciplinary e-Delphi study.

BACKGROUND: There is limited research supporting optimal respiratory physiotherapy or physical rehabilitation strategies for patients with rib fractures. The aim of this study was to develop key recommendations for the physiotherapy management of patients with rib fractures. METHODS: A three-round modified e-Delphi survey design, using an international Delphi panel including physiotherapy clinicians, researchers and lecturers, physician associates, trauma surgeons, and intensivists, was used in this study. The draft recommendations were developed by the Steering Group, based on available research. Over three rounds, panelists rated their agreement (using a Likert scale) with regard to recommendation for physiotherapists delivering respiratory physiotherapy and physical rehabilitation to patients following rib fractures. Recommendations were retained if they achieved consensus (defined as ≥70% of panelists ≥5/7) at the end of each round. RESULTS: A total of 121 participants from 18 countries registered to participate in the study, with 87 (72%), 77 (64%), and 79 (65%) registrants completing the three rounds, respectively. The final guidance document included 18 respiratory physiotherapy and rehabilitation recommendations, mapped over seven clinical scenarios for patients (1) not requiring mechanical ventilation, (2) requiring mechanical ventilation, (3) with no concurrent fracture of the shoulder girdle complex, (4) with a concurrent fracture of the shoulder girdle complex, (5) with/without concurrent upper limb orthopedic injuries, (6) undergoing surgical stabilization of rib fractures, and (7) at hospital discharge. CONCLUSION: This guidance provides key recommendations for respiratory physiotherapy and physical rehabilitation of patients with rib fractures. It could also be used to inform future research priorities in the field. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level IV.

Factors Influencing the Use of Control Measures to Reduce Occupational Exposure to Welding Fume in Australia: A Qualitative Study.

Background: Exposure to welding fume is associated with adverse effects on worker health. The use of various control measures can reduce levels of exposure and the resulting health effects. However, little is known about the factors that may influence workers' use of control measures in the workplace and their perceived intervention needs. This study aimed to investigate workers' and other stakeholders' views on ways to improve the use of welding fume control measures in Australian workplaces. Methods: We conducted a series of online focus group discussions and individual interviews with participants who have some occupational involvement in welding, whether as workers, employers or industry representatives, union representatives, or regulators. A semi-structured question guide was used, and all discussions and interviews were recorded and transcribed for analysis. Results: Five focus group discussions and five individual interviews were conducted with a total of 21 participants. Three major themes emerged. The first addressed the current awareness of welding fume harms and concern about exposure; the second focussed on the current use of control measures, and barriers and facilitators to their use; and the last centred around intervention needs and the contents of a potential effective intervention. Conclusion: Improving the use of control measures to prevent exposure to welding fume requires knowledge around the barriers and facilitators of control, use, and the intervention needs of stakeholders. This study has provided such knowledge, which will facilitate the design and implementation of an intervention to reduce welding fume exposure and ultimately protect the health of workers.

Sunproofed study protocol: A mixed-methods scoping study of sun safety policies in primary schools in Wales.

BACKGROUND: Skin cancer, including melanoma and non-melanoma (keratinocyte), is increasing in incidence in the UK. Accounting for half of all cancers in England and Wales, the disease significantly impacts overstretched dermatology services. Research suggests that 86% of melanoma is preventable with modified sun exposure. Educating children about sun safety in schools can help prevent skin cancer and is recommended by major health organisations. In England, teaching sun safety in primary schools is compulsory, while in Wales this is left to school discretion. AIMS: Understand how primary schools in Wales are responding to growing skin cancer rates and explore the effectiveness of sun safety policies in schools on knowledge and behaviour. METHODS: Sunproofed is a mixed-methods scoping study comprising 5 work packages (WP) using survey and routine electronic health record (EHR) data supplemented by qualitative case studies. Objective(s) are to: WP1: Discover if primary schools in Wales have sun safety policies; policy characteristics; determine factors that may influence their presence and identify areas where schools need support. WP2: Determine what EHR data is available regarding the incidence of sunburn in primary school children and the feasibility of using this data to evaluate the impact of sun safety policies. WP3: Understand the impact of sun safety policies on sun-safe knowledge and behaviour amongst children, parents, teachers, and school management; identify barriers and facilitators to schools implementing sun safety policies. WP4: Co-produce guidance regarding sun safety policies and best methods for implementation in schools. WP5: Disseminate guidance and findings widely to ensure impact and uptake. DISCUSSION: Skin cancer rates are increasing in the UK, straining limited resources. Sunproofed has the potential to inform the development of future prevention activities, both in Wales and beyond. This could reduce the number of skin cancer cases in the future and keep people healthier for longer.

Ruxolitinib for the treatment of steroid refractory pediatric chronic graft-versus-host disease.

Chronic graft-versus-host disease (cGVHD) of the skin is a serious cause of long-term morbidity and mortality among patients who receive hematopoietic stem cell transplants. Systemic corticosteroids remain first-line treatment for cutaneous cGVHD; however, there is currently no consensus on second-line therapy for steroid-refractory disease. We herein present a case of a pediatric patient with severe cGVHD of the skin, nonresponsive to corticosteroids, who was successfully treated with a prolonged course of ruxolitinib with minimal side effects.

Randomised feasibility study of prehospital recognition and antibiotics for emergency patients with sepsis (PhRASe).

Severe sepsis is a time critical condition which is known to have a high mortality rate. Evidence suggests that early diagnosis and early administration of antibiotics can reduce morbidity and mortality from sepsis. The prehospital phase of emergency medical care may provide the earliest opportunity for identification of sepsis and delivery of life-saving treatment for patients. We aimed to assess the feasibility of (1) paramedics recognising and screening patients for severe sepsis, collecting blood cultures and administering intravenous antibiotics; and (2) trial methods in order to decide whether a fully-powered trial should be undertaken to determine safety and effectiveness of this intervention. Paramedics were trained in using a sepsis screening tool, aseptic blood culture collection and administration of intravenous antibiotics. If sepsis was suspected, paramedics randomly allocated patients to intervention or usual care using scratchcards. Patients were followed up at 90 days using linked anonymised data to capture length of hospital admission and mortality. We collected self-reported health-related quality of life at 90 days. We pre-specified criteria for deciding whether to progress to a fully-powered trial based on: recruitment of paramedics and patients; delivery of the intervention; retrieval of outcome data; safety; acceptability; and success of anonymised follow-up. Seventy-four of the 104 (71.2%) eligible paramedics agreed to take part and 54 completed their training (51.9%). Of 159 eligible patients, 146 (92%) were recognised as eligible by study paramedics, and 118 were randomised (74% of eligible patients, or 81% of those recognised as eligible). Four patients subsequently dissented to be included in the trial (3%), leaving 114 patients recruited to follow-up. All recruited patients were matched to routine data outcomes in the Secure Anonymised Information Linkage Databank. Ninety of the 114 (79%) recruited patients had sepsis or a likely bacterial infection recorded in ED. There was no evidence of any difference between groups in patient satisfaction, and no adverse reactions reported. There were no statistically significant differences between intervention and control groups in Serious Adverse Events (ICU admissions; deaths). This feasibility study met its pre-determined progression criteria; an application will therefore be prepared and submitted for funding for a fully-powered multi-centre randomised trial.Trial registration: ISRCTN36856873 sought 16th May 2017; https://doi.org/10.1186/ISRCTN36856873.

Pooled safety analysis of tisagenlecleucel in children and young adults with B cell acute lymphoblastic leukemia.

BACKGROUND: Tisagenlecleucel, an anti-CD19 chimeric antigen receptor T cell therapy, has demonstrated efficacy in children and young adults with relapsed/refractory B cell acute lymphoblastic leukemia (B-ALL) in two multicenter phase 2 trials (ClinicalTrials.gov, NCT02435849 (ELIANA) and NCT02228096 (ENSIGN)), leading to commercialization of tisagenlecleucel for the treatment of patients up to age 25 years with B-ALL that is refractory or in second or greater relapse. METHODS: A pooled analysis of 137 patients from these trials (ELIANA: n=79; ENSIGN: n=58) was performed to provide a comprehensive safety profile for tisagenlecleucel. RESULTS: Grade 3/4 tisagenlecleucel-related adverse events (AEs) were reported in 77% of patients. Specific AEs of interest that occurred ≤8 weeks postinfusion included cytokine-release syndrome (CRS; 79% (grade 4: 22%)), infections (42%; grade 3/4: 19%), prolonged (not resolved by day 28) cytopenias (40%; grade 3/4: 34%), neurologic events (36%; grade 3: 10%; no grade 4 events), and tumor lysis syndrome (4%; all grade 3). Treatment for CRS included tocilizumab (40%) and corticosteroids (23%). The frequency of neurologic events increased with CRS severity (p<0.001). Median time to resolution of grade 3/4 cytopenias to grade ≤2 was 2.0 (95% CI 1.87 to 2.23) months for neutropenia, 2.4 (95% CI 1.97 to 3.68) months for lymphopenia, 2.0 (95% CI 1.87 to 2.27) months for leukopenia, 1.9 (95% CI 1.74 to 2.10) months for thrombocytopenia, and 1.0 (95% CI 0.95 to 1.87) month for anemia. All patients who achieved complete remission (CR)/CR with incomplete hematologic recovery experienced B cell aplasia; however, as nearly all responders also received immunoglobulin replacement, few grade 3/4 infections occurred >1 year postinfusion. CONCLUSIONS: This pooled analysis provides a detailed safety profile for tisagenlecleucel during the course of clinical trials, and AE management guidance, with a longer follow-up duration compared with previous reports.

Patient-reported quality of life after tisagenlecleucel infusion in children and young adults with relapsed or refractory B-cell acute lymphoblastic leukaemia: a global, single-arm, phase 2 trial.

BACKGROUND: The ELIANA trial showed that 61 (81%) of 75 paediatric and young adult patients with relapsed or refractory B-cell acute lymphoblastic leukaemia achieved overall remission after treatment with tisagenlecleucel, a chimeric antigen receptor targeted against the CD19 antigen. We aimed to evaluate patient-reported quality of life in these patients before and after tisagenlecleucel infusion. METHODS: ELIANA, a global, single-arm, open-label, phase 2 trial, was done in 25 hospitals across Australia, Austria, Belgium, Canada, France, Germany, Italy, Japan, Norway, Spain, and the USA. Patients with B-cell acute lymphoblastic leukaemia aged at least 3 years at the time of screening and 21 years or younger at the time of initial diagnosis who were in second or greater bone marrow relapse, chemorefractory, relapsed after allogeneic stem-cell transplantation, or were otherwise ineligible for allogeneic stem-cell transplantation were enrolled. Patients received a single intravenous administration of a target dose of 0·2-5 × 106 transduced viable T cells per kg for patients weighing 50 kg or less or 0·1-2·5 × 108 transduced viable T cells for patients weighing more than 50 kg. The primary outcome, reported previously, was the proportion of patients who achieved remission. A prespecified secondary endpoint, reported here, was patient-reported quality of life measured with the Pediatric Quality of Life Inventory (PedsQL) and European Quality of Life-5 Dimensions questionnaire (EQ-5D). Patients completed the questionnaires at baseline, day 28, and months 3, 6, 9, and 12 after treatment. The data collected were summarised using descriptive statistics and post-hoc mixed models for repeated measures. Change from baseline response profiles were illustrated with cumulative distribution function plots. The proportion of patients achieving the minimal clinically important difference and normative mean value were reported. Analysis was per protocol. This study is registered with ClinicalTrials.gov, NCT02435849. FINDINGS: Between April 8, 2015, and April 25, 2017, 107 patients were screened, 92 were enrolled, and 75 received tisagenlecleucel. 58 patients aged 8-23 years were included in the analysis of quality of life. At baseline, 50 (86%) patients had completed the PedsQL questionnaire and 48 (83%) had completed the EQ-5D VAS. Improvements in patient-reported quality-of-life scores were observed for all measures at month 3 after tisagenlecleucel infusion (mean change from baseline to month 3 was 13·3 [95% CI 8·9-17·6] for the PedsQL total score and 16·8 [9·4-24·3] for the EQ-5D visual analogue scale). 30 (81%) of 37 patients achieved the minimal clinically important difference at month 3 for the PedsQL total score and 24 (67%) of 36 patients achieved this for the EQ-5D visual analogue scale. INTERPRETATION: These findings, along with the activity and safety results of ELIANA, suggest a favourable benefit-risk profile of tisagenlecleucel in the treatment of paediatric and young adult patients with relapsed or refractory B-cell acute lymphoblastic leukaemia. FUNDING: Novartis.

Ethical considerations of using a single minor donor for three bone marrow harvests for three HLA-matched siblings with primary immunodeficiency.

Allogeneic hematopoietic stem cell transplantation is curative for primary immunodeficiencies. Bone marrow from an unaffected human leukocyte antigen (HLA)-identical sibling donor is the ideal graft source. For minor donors, meaningful consent or assent may not be feasible, and permission from parents or legal guardians is considered acceptable. Adverse events, albeit extremely small, can be associated with bone marrow harvest in pediatric donors. Donor safety concerns potentially increase with multiple bone marrow harvests. Very little is known about multiple bone marrow harvests from pediatric donors. We describe the ethical considerations and clinical decision-making in an unusual clinical situation where three patients with the same primary immunodeficiency were HLA identical to one another and their younger sibling, who underwent bone marrow harvests three times between 1.3 and 4 years of age, resulting in successful transplantation for all three patients. We hope that this experience will provide guidance to providers and families in a similar situation.

Interventions to Reduce Future Cancer Incidence from Diesel Engine Exhaust: What Might Work?

Exposure to diesel engine exhaust (DEE) contributes appreciably to the burden of occupational cancer. This study aims to estimate the potential impact of a range of interventions on the future burden of cancer from occupational exposure to DEE in Australia. The future excess fraction method, a novel method based on the lifetime risk approach, was used to model changes in the future burden of cancer among the Australian working age population exposed to DEE at work in 2012 under various intervention strategies. The interventions modeled were based on the widely accepted hierarchy of control model. At baseline, 600 (0.4%) future bladder and 4,450 (0.6%) future lung cancer cases over the lifetime of the cohort were estimated to be attributable to occupational exposure to DEE in those exposed in 2012. Up to 2,000 of these cases were estimated to be avoidable through the use of various interventions. Exhaust hoses (engineering controls) were estimated to be particularly effective. This study provides an indication of which intervention strategies may be most useful in reducing the future burden of cancer associated with occupational DEE exposure. These results show the potential effect of changing current exposure, rather than focusing on past exposures, and thus provide relevant information for policy planning.

Reduction in Mortality after Umbilical Cord Blood Transplantation in Children Over a 20-Year Period (1995-2014).

Infections and graft-versus-host disease (GVHD) have historically resulted in high mortality among children undergoing umbilical cord blood transplantation (UCBT). However, recent advances in clinical practice have likely improved outcomes of these patients. We conducted a retrospective cohort study of children (<18years of age) undergoing UCBT at Duke University between January 1, 1995 and December 31, 2014. We compared 2-year all-cause and cause-specific mortality during 3 time periods based on year of transplantation (1995 to 2001, 2002 to 2007, and 2008 to 2014). We used multivariable Cox regression to identify demographic and UCBT characteristics that were associated with all-cause mortality, transplantation-related mortality, and death from invasive aspergillosis after adjustment for time period. During the 20-year study period 824 children underwent UCBT. Two-year all-cause mortality declined from 48% in 1995 to 2001 to 30% in 2008 to 2014 (P = .0002). White race and nonmalignant UCBT indications were associated with lower mortality. Black children tended to have a higher risk of death for which GVHD (18% versus 11%; P = .06) or graft failure (9% versus 3%; P = .01) were contributory than white children. Comparing 2008 to 2014 with 1995 to 2001, more than half (59%) of the reduced mortality was attributable to a reduction in infectious mortality, with 45% specifically related to reduced mortality from invasive aspergillosis. Antifungal prophylaxis with voriconazole was associated with lower mortality from invasive aspergillosis than low-dose amphotericin B lipid complex (hazard ratio, .09; 95% confidence interval, .01 to .76). With the decline in mortality from invasive aspergillosis, adenovirus and cytomegalovirus have become the most frequentinfectious causes of death in children after UCBT. Advances in clinical practice over the past 20years improved survival of children after UCBT. Reduced mortality from infections, particularly invasive aspergillosis, accounted for the largest improvement in survival and was associated with use of voriconazole for antifungal prophylaxis.

The Cat Flea (Ctenocephalides felis) Immune Deficiency Signaling Pathway Regulates Rickettsia typhi Infection.

Rickettsia species are obligate intracellular bacteria with both conserved and lineage-specific strategies for invading and surviving within eukaryotic cells. One variable component of Rickettsia biology involves arthropod vectors: for instance, typhus group rickettsiae are principally vectored by insects (i.e., lice and fleas), whereas spotted fever group rickettsiae are exclusively vectored by ticks. For flea-borne Rickettsia typhi, the etiological agent of murine typhus, research on vertebrate host biology is facilitated using cell lines and animal models. However, due to the lack of any stable flea cell line or a published flea genome sequence, little is known regarding R. typhi biology in flea vectors that, importantly, do not suffer lethality due to R. typhi infection. To address if fleas combat rickettsial infection, we characterized the cat flea (Ctenocephalides felis) innate immune response to R. typhi Initially, we determined that R. typhi infects Drosophila cells and increases antimicrobial peptide (AMP) gene expression, indicating immune pathway activation. While bioinformatics analysis of the C. felis transcriptome identified homologs to all of the Drosophila immune deficiency (IMD) and Toll pathway components, an AMP gene expression profile in Drosophila cells indicated IMD pathway activation upon rickettsial infection. Accordingly, we assessed R. typhi-mediated flea IMD pathway activation in vivo using small interfering RNA (siRNA)-mediated knockdown. Knockdown of Relish and Imd increased R. typhi infection levels, implicating the IMD pathway as a critical regulator of R. typhi burden in C. felis These data suggest that targeting the IMD pathway could minimize the spread of R. typhi, and potentially other human pathogens, vectored by fleas.

Children Receiving Hematopoietic Stem Cell Transplantation are at Increased Risk of Onychocryptosis Requiring Surgical Management.

PURPOSE: At our institution, a high proportion of children with onychocryptosis (ingrown toenail) requiring surgical intervention were noted to have a history of hematopoietic stem cell transplantation (HSCT). We analyzed the characteristics of patients who underwent surgical intervention for onychocryptosis and examined our institutional HSCT database to determine if an association exists between onychocryptosis and HSCT. MATERIALS AND METHODS: Surgical cases for onychocryptosis performed from 2000 to 2012 were identified. Nine demographic, clinical, and perioperative variables for both patients with and without prior HSCT were assessed. In a separate analysis, the institutional HSCT database was then queried to identify the prevalence and clinical characteristics associated with onychocryptosis after HSCT. RESULTS: We identified 17 children who had undergone surgical management of onychocryptosis, of which 8 (47.1%) had previous HSCT. Children who had undergone HSCT had an aggressive form of onychocryptosis with 50.0% having bilateral great toe and nail edge involvement and 37.5% having a recurrence. In HSCT cohort analysis of 1069 children, 91 (8.5%) had onychocryptosis. Male sex, non-black race, acute graft versus host disease, and increasing age at transplantation were independently associated with onychocryptosis. CONCLUSIONS: HSCT is strongly associated with onychocryptosis requiring surgical intervention. Children with a history of HSCT may also have more aggressive toenail disease, with higher rates of surgical intervention, bilateral ingrown toenails, recurrence, and need for return to the operating room. Clinicians should perform careful screening and early treatment in these patients.

Durable Chimerism and Long-Term Survival after Unrelated Umbilical Cord Blood Transplantation for Pediatric Hemophagocytic Lymphohistiocytosis: A Single-Center Experience.

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening disorder of immune dysregulation characterized by fever, hepatosplenomegaly, cytopenias, central nervous system disease, increased inflammatory markers, and hemophagocytosis. Currently, allogeneic hematopoietic stem cell transplantation is the only curative approach for patients with HLH, with reported survival ranging from 50% to 70% with myeloablative conditioning (MAC) regimens. However, donor availability and transplantation-related mortality associated with conventional MAC are major barriers to success. Unrelated umbilical cord blood transplantation (UCBT) provides a readily available alternative donor source for patients lacking matched related donors. Accordingly, we report the results of UCBT in 14 children treated between 1998 and 2016. All children received standard HLH chemotherapy before UCBT. The median age at diagnosis was 2.7 months (range, .8 to 10.4) and at transplantation was 7.5 months (range, 3.8 to 17). Ten patients received MAC with busulfan/cyclophosphamide/etoposide /antithymocyte globulin (ATG) (n = 5), busulfan/cyclophosphamide /ATG (n = 4), or busulfan /melphalan/ATG (n = 1). Four patients received reduced-toxicity conditioning (RTC) with alemtuzumab/fludarabine/melphalan/hydroxyurea ± thiotepa. Cord blood units were mismatched at either 1 (n = 9) or 2 (n = 5) loci and delivered a median total nucleated cell dose of 11.9 × 107/kg (range, 4.6 to 27.9) and CD34+ dose of 3.1 × 105/kg (range, 1.1 to 6.8). The cumulative incidence of neutrophil engraftment by day 42 was 78.6% (95% confidence interval [CI], 42.9% to 93.4%) with a median of 19 days (range, 13 to 27), and that for platelet (50,000) engraftment by day 100 was 64.3% (95% CI, 28.2% to 85.7%) with a median of 51 days (range, 31 to 94). Six patients developed either grade II (n = 5) or grade IV (n = 1) acute graft-versus-host disease (GVHD); no extensive chronic GVHD was seen. Ten patients (71.4%) are alive and well at a median of 11.2 years after transplantation (range, .85 to 18.25), 9 of whom maintain sustained full donor chimerism after a single UCBT, whereas 1 patient with autologous recovery after first UCBT with RTC has achieved full donor chimerism after a second UCBT with MAC. This series demonstrates that, in combination with standard HLH therapy, UCBT after MAC or RTC conditioning can provide long-term survival with durable complete donor chimerism comparable to that of conventional donors. UCBT should be considered for patients with HLH lacking a fully matched related or unrelated adult donor.

The future excess fraction of occupational cancer among those exposed to carcinogens at work in Australia in 2012.

BACKGROUND: Studies in other countries have generally found approximately 4% of current cancers to be attributable to past occupational exposures. This study aimed to estimate the future burden of cancer resulting from current occupational exposures in Australia. METHODS: The future excess fraction method was used to estimate the future burden of occupational cancer (2012-2094) among the proportion of the Australian working population who were exposed to occupational carcinogens in 2012. Calculations were conducted for 19 cancer types and 53 cancer-exposure pairings, assuming historical trends and current patterns continued to 2094. RESULTS: The cohort of 14.6 million Australians of working age in 2012 will develop an estimated 4.8 million cancers during their lifetime, of which 68,500 (1.4%) are attributable to occupational exposure in those exposed in 2012. The majority of these will be lung cancers (n=26,000), leukaemias (n=8000), and malignant mesotheliomas (n=7500). CONCLUSIONS: A significant proportion of future cancers will result from occupational exposures. This estimate is lower than previous estimates in the literature; however, our estimate is not directly comparable to past estimates of the occupational cancer burden because they describe different quantities - future cancers in currently exposed versus current cancers due to past exposures. The results of this study allow us to determine which current occupational exposures are most important, and where to target exposure prevention.

The Australian Work Exposures Study: Prevalence of Occupational Exposure to Respirable Crystalline Silica.

BACKGROUND: Respirable crystalline silica (RCS) is a biologically active dust that can accumulate in the lung and induce silicosis and lung cancer. Despite occupational exposure being the predominant source, no study has described current occupational RCS exposure on a national scale in Australia. The aim of this study is to estimate the characteristics of those exposed and the circumstances of RCS exposure in Australian workplaces. METHODS: A cross-sectional survey of the Australian working population (18-65 years old) was conducted. Information about the respondents' current job and their demographic characteristics was collected in a telephone interview. Occupational exposure to RCS was determined based on preprogrammed decision rules regarding potential levels of exposure associated with self-reported tasks. RESULTS: Overall, 6.4% of respondents were deemed exposed to RCS at work in 2012 (3.3% were exposed at a high level). The exposure varied with sex, state of residence, and socioeconomic status. Miners and construction workers were most likely to be highly exposed to RCS when performing tasks with concrete or cement or working near crushers that create RCS-containing dusts. When extrapolated to the entire Australian working population, 6.6% of Australian workers were exposed to RCS and 3.7% were highly exposed when carrying out tasks at work. CONCLUSION: This is the first study investigating occupational RCS exposure in an entire national working population. The information about occupational tasks that lead to high level RCS exposure provided by this study will inform the direction of occupational interventions and policies.

The Australian Work Exposures Study: Occupational Exposure to Lead and Lead Compounds.

INTRODUCTION: The aims of this study were to produce a population-based estimate of the prevalence of work-related exposure to lead and its compounds, to identify the main circumstances of exposures, and to collect information on the use of workplace control measures designed to decrease those exposures. METHODS: Data came from the Australian Workplace Exposures Study, a nationwide telephone survey which investigated the current prevalence and circumstances of work-related exposure to 38 known or suspected carcinogens, including lead, among Australian workers aged 18-65 years. Using the web-based tool, OccIDEAS, semi-quantitative information was collected about exposures in the current job held by the respondent. Questions were addressed primarily at tasks undertaken rather than about self-reported exposures. RESULTS: A total of 307 (6.1%) of the 4993 included respondents were identified as probably being exposed to lead in the course of their work. Of these, almost all (96%) were male; about half worked in trades and technician-related occupations, and about half worked in the construction industry. The main tasks associated with probable exposures were, in decreasing order: soldering; sanding and burning off paint while painting old houses, ships, or bridges; plumbing work; cleaning up or sifting through the remains of a fire; radiator-repair work; machining metals or alloys containing lead; mining; welding leaded steel; and working at or using indoor firing ranges. Where information on control measures was available, inconsistent use was reported. Applied to the Australian working population, approximately 6.3% [95% confidence interval (CI) = 5.6-7.0] of all workers (i.e. 631000, 95% CI 566000-704000 workers) were estimated to have probable occupational exposure to lead. CONCLUSIONS: Lead remains an important exposure in many different occupational circumstances in Australia and probably other developed countries. This information can be used to support decisions on priorities for intervention and control of occupational exposure to lead and estimates of burden of cancer arising from occupational exposure to lead.

The Australian Work Exposures Study: Occupational Exposure to Polycyclic Aromatic Hydrocarbons.

INTRODUCTION: The aims of this study were to produce a population-based estimate of the prevalence of work-related exposure to polycyclic aromatic hydrocarbons (PAHs), to identify the main circumstances of exposure and to describe the use of workplace control measures designed to decrease those exposures. METHODS: The analysis used data from the Australian Workplace Exposures Study, a nationwide telephone survey which investigated the current prevalence and exposure circumstances of work-related exposure to 38 known or suspected carcinogens, including PAHs, among Australian workers aged 18-65 years. Using the web-based tool OccIDEAS, semi-quantitative information was collected about exposures in the current job held by the respondent. Questions were addressed primarily at tasks undertaken rather than about self-reported exposures. RESULTS: Of the 4,993 included respondents, 297 (5.9%) were identified as probably being exposed to PAHs in their current job [extrapolated to 6.7% of the Australian working population-677 000 (95% confidence interval 605 000-757 000) workers]. Most (81%) were male; about one-third were farmers and about one-quarter worked in technical and trades occupations. In the agriculture industry about half the workers were probably exposed to PAHs. The main exposure circumstances were exposure to smoke through burning, fighting fires or through maintaining mowers or other equipment; cleaning up ash after a fire; health workers exposed to diathermy smoke; cooking; and welding surfaces with a coating. Where information on control measures was available, their use was inconsistent. CONCLUSION: Workers are exposed to PAHs in many different occupational circumstances. Information on the exposure circumstances can be used to support decisions on appropriate priorities for intervention and control of occupational exposure to PAHs, and estimates of burden of cancer arising from occupational exposure to PAHs.