Firefighting, per- and polyfluoroalkyl substances, and DNA methylation of genes associated with prostate cancer risk.

Prostate cancer is the leading incident cancer among men in the United States. Firefighters are diagnosed with this disease at a rate 1.21 times higher than the average population. This increased risk may result from occupational exposures to many toxicants, including per- and polyfluoroalkyl substances (PFAS). This study assessed the association between firefighting as an occupation in general or PFAS serum levels, with DNA methylation. Only genomic regions previously linked to prostate cancer risk were selected for analysis: GSTP1, Alu repetitive elements, and the 8q24 chromosomal region. There were 444 male firefighters included in this study, with some analyses being conducted on fewer participants due to missingness. Statistical models were used to test associations between exposures and DNA methylation at CpG sites in the selected genomic regions. Exposure variables included proxies of cumulative firefighting exposures (incumbent versus academy status and years of firefighting experience) and biomarkers of PFAS exposures (serum concentrations of 9 PFAS). Proxies of cumulative exposures were associated with DNA methylation at 15 CpG sites and one region located within FAM83A (q-value <0.1). SbPFOA was associated with 19 CpG sites (q < 0.1), but due to low detection rates, this PFAS was modeled as detected versus not detected in serum. Overall, there is evidence that firefighting experience is associated with differential DNA methylation in prostate cancer risk loci, but this study did not find evidence that these differences are due to PFAS exposures specifically.

Prevalence of frailty and pain in hospitalised cancer patients: implications for older adult care.

A hospital-wide point prevalence study investigated frailty and pain in patients with a cancer-related admission. Modifiable factors associated with frailty in people with cancer were determined through logistic regression. Forty-eight patients (19%) with cancer-related admissions were 2.65 times more likely to be frail and 2.12 more likely to have moderate pain. Frailty and pain were highly prevalent among cancer-related admissions, reinforcing the need for frailty screening and importance of pain assessment for patients with cancer.

Encouraging outcomes of stemless ceramic head anatomic shoulder arthroplasty in severe primary osteoarthritis (Walch type B glenoids).

Background: We report the radiological and functional outcomes at five years in patients with severe osteoarthritis of the glenohumeral joint and a Walch type B glenoid who have undergone stemless anatomic total shoulder replacement. Methods: A retrospective analysis of case notes, computed tomography scans and plain radiographs of patients undergoing anatomic total shoulder replacement for primary glenohumeral osteoarthritis were performed. Patients were grouped by the severity of their osteoarthritis using the modified Walch classification, glenoid retroversion and posterior humeral head subluxation. An evaluation was made using modern planning software. Functional outcomes were assessed using the American shoulder and elbow surgeons score, shoulder pain and disability index and visual analogue scale. Annual Lazarus scores were reviewed as regard to glenoid loosening. Results: Thirty patients were reviewed at 5 years. Analysis of all patient-reported outcome measures demonstrated significant improvement at 5-year review, American shoulder and elbow surgeons (p = <0.0001), shoulder pain and disability index (p = 0.0001), visual analogue scale (p = 0.0001). Radiological associations between Walch scores and Lazarus scores were not statistically significant (p = 0.1251) at 5 years. There were no associations between features of glenohumeral osteoarthritis and patient-reported outcome measures. Discussion: The severity of osteoarthritis did not show any association with glenoid component survivorship or with patient-reported outcome measures at 5 years review. Level of evidence: IV.

Frailty and pain in an acute private hospital: an observational point prevalence study.

Frailty and pain in hospitalised patients are associated with adverse clinical outcomes. However, there is limited data on the associations between frailty and pain in this group of patients. Understanding the prevalence, distribution and interaction of frailty and pain in hospitals will help to determine the magnitude of this association and assist health care professionals to target interventions and develop resources to improve patient outcomes. This study reports the point prevalence concurrence of frailty and pain in adult patients in an acute hospital. A point prevalence, observational study of frailty and pain was conducted. All adult inpatients (excluding high dependency units) at an acute, private, 860-bed metropolitan hospital were eligible to participate. Frailty was assessed using the self-report modified Reported Edmonton Frail Scale. Current pain and worst pain in the last 24 h were self-reported using the standard 0-10 numeric rating scale. Pain scores were categorised by severity (none, mild, moderate, severe). Demographic and clinical information including admitting services (medical, mental health, rehabilitation, surgical) were collected. The STROBE checklist was followed. Data were collected from 251 participants (54.9% of eligible). The prevalence of frailty was 26.7%, prevalence of current pain was 68.1% and prevalence of pain in the last 24 h was 81.3%. After adjusting for age, sex, admitting service and pain severity, admitting services medical (AOR: 13.5 95% CI 5.7-32.8), mental health (AOR: 6.3, 95% CI 1. 9-20.9) and rehabilitation (AOR: 8.1, 95% CI 2.4-37.1) and moderate pain (AOR: 3.9, 95% CI 1. 6-9.8) were associated with increased frailty. The number of older patients identified in this study who were frail has implications for managing this group in a hospital setting. This indicates a need to focus on developing strategies including frailty assessment on admission, and the development of interventions to meet the care needs of these patients. The findings also highlight the need for increased pain assessment, particularly in those who are frail, for more effective pain management.Trial registration: The study was prospectively registered (ACTRN12620000904976; 14th September 2020).

Assessing pain using facial recognition software among Aboriginal aged care residents with cognitive impairment: A retrospective cohort study.

OBJECTIVE: To assess the observed pain behaviours of Aboriginal residents with cognitive impairment in aged care facilities and compare these results with a matched national sample of non-Aboriginal residents. METHODS: Observed pain behaviours of Aboriginal residents (N = 87) with cognitive impairment in aged care facilities across the Northern Territory of Australia were assessed using PainChek® Adult and compared with data from a matched national sample of non-Aboriginal residents (N = 420). Pain scores were derived from inbuilt automated facial recognition and analysis software plus a series of digital checklists requiring manual input by care staff. RESULTS: The median total pain score for the Aboriginal residents was 2 (IQR 1-4) and for the matched external residents was 3 (IQR 2-5). In a multivariable negative binomial regression model, this difference in total pain score was statistically significant (p < 0.001). The pain score derived from the automated facial recognition and analysis component of the PainChek® Adult app was not statistically different between the two groups when adjusted for multiple observations and context of observation (odds ratio = 1.06, 95% confidence interval 0.97-1.16, p = 0.169). CONCLUSIONS: We found under-reporting of observed pain signs and behaviours for Aboriginal aged care residents by assessors. Further training in the assessment of pain in Aboriginal and Torres Strait Islander aged care residents may be necessary and a continuing shift in clinical practice to using technology and point-of-care assessment.

Occupational Years of Service and Leukocyte Epigenetic Aging: Relationships in United States Firefighters.

OBJECTIVE: The aim of the study is to examine associations between years of firefighting service and eight chronological age-adjusted measures of blood leukocyte epigenetic age acceleration: Horvath, Hannum, SkinBloodClock, Intrinsic, Extrinsic, PhenoAge, GrimAge, and DNAm telomere length. METHODS: The study used a repeated measures analysis of data from 379 incumbent firefighters from eight career departments and 100 recruit firefighters from two of the departments, across the United States. RESULTS: Incumbent firefighters had on average greater epigenetic age acceleration compared with recruit firefighters, potentially due to the cumulative effect of occupational exposures. However, among incumbent firefighters, additional years of service were associated with epigenetic age deceleration, particularly for GrimAge, a strong predictor of mortality. CONCLUSIONS: Long-term studies with more specific occupational exposure classification are needed to better understand the relationship between years of service and aging biomarkers.

Molecular modeling of lactoferrin for food and nutraceutical applications: insights from in silico techniques.

Lactoferrin is a protein, primarily found in milk that has attracted the interest of the food industries due to its health properties. Nevertheless, the instability of lactoferrin has limited its commercial application. Recent studies have focused on encapsulation to enhance the stability of lactoferrin. However, the molecular insights underlying the changes of structural properties of lactoferrin and the interaction with protectants remain poorly understood. Computational approaches have proven useful in understanding the structural properties of molecules and the key binding with other constituents. In this review, comprehensive information on the structure and function of lactoferrin and the binding with various molecules for food purposes are reviewed, with a special emphasis on the use of molecular dynamics simulations. The results demonstrate the application of modeling and simulations to determine key residues of lactoferrin responsible for its stability and interactions with other biomolecular components under various conditions, which are also associated with its functional benefits. These have also been extended into the potential creation of enhanced lactoferrin for commercial purposes. This review provides valuable strategies in designing novel nutraceuticals for food science practitioners and those who have interests in acquiring familiarity with the application of computational modeling for food and health purposes.

Molecular insights into the interaction of apo-lactoferrin with the receptor binding domain of the SARS-CoV-2 spike protein: a molecular dynamics simulation study.

LF is a bioactive protein, derived from colostrum and milk that has been found to possess various immunomodulatory, iron chelating, and antimicrobial properties, especially in its apo-form. Recent studies have demonstrated the functionality of LF in attaching to the S proteins of SARS-CoV-2, thereby preventing it from interacting with the ACE-2 receptor. However, the molecular mechanism mediating the process is poorly understood. In this study, molecular docking and MD simulations coupled with free energy calculations were applied to elucidate the key interaction of apo-LF and its N-lobe and C-lobe derivative forms with the RBD of coronavirus S proteins. This has also been extended into evaluating the L452R mutant, which is associated with the delta variant of SARS-CoV-2. The results demonstrate the efficacy of the apo-LF C-lobe in binding to the RBD of both variants, primarily through electrostatic attractions between the acidic residues of the former and the basic residues of each RBD. Furthermore, due to the additional arginine in the L452R variant, the interaction between the C-lobe and the latter is stronger, resulting in a more favourable binding and tightly bound structure. The simulations highlight that the C-lobe, followed by full-length apo-LF can form a multimeric complex with the RBD of SARS-CoV-2, indicating their potential use as novel therapeutics, particularly the cleaved C-lobe of apo-LF to disrupt the S proteins from binding to the host ACE-2 receptor.Communicated by Ramaswamy H. Sarma.

Ligament Reconstruction and Interposition Arthroplasty of the Acromioclavicular Joint.

Distal clavicle excision (DCE) for acromioclavicular (AC) joint primary osteoarthritis and post-traumatic arthritis has been shown to have good to excellent outcomes. However, there are studies that report significant rates of residual AC joint pain and distal clavicle instability after open and arthroscopic techniques. We describe a surgical technique for management of AC joint primary osteoarthritis, post-traumatic arthritis, and revision DCE that involves DCE with ligament reconstruction and tendon interposition arthroplasty. It provides distal clavicle stability and can theoretically reduce residual AC joint pain secondary to acromial abutment after DCE.

A Retrospective, Longitudinal External Study of the robustness and reproducibility of National Antibacterial Prescribing Survey Data.

BACKGROUND: Point prevalence surveys are used internationally to audit antibacterial use as well as the impact of interventions on improving prescribing and resistance rates. The annual National Antibacterial Prescribing Survey provides data on the appropriateness of antibacterial agent prescribing in Australian hospitals. Assessing the survey's robustness and result reproducibility is essential to its role in improving antibacterial prescribing practice. AIM: To evaluate the reproducibility of internal assessments of antibacterial agent prescribing of both guideline compliance and appropriateness from a Western Australian hospital. METHOD: Census data of 1051 prescriptions from 2013 to 2017 surveys were independently assessed for compliance based on Australian Therapeutic Guidelines - Antibiotics, and appropriateness, based on agent selection, therapy duration and microbiological test results. Concordance of these findings with internal hospital assessments was analysed. RESULTS: This external study did not reproduce internal hospital audit results for compliance with guideline parameters. Non-compliant prescribing rate was significantly (p < 0.001) higher externally at 50.7% (533/1051) than internal assessment at 34.9% (367/1051). External analysis also found a significantly smaller proportion of prescriptions to be appropriate (551/1051, 52.4%) compared to internal analysis (745/1051, 70.9%) p < 0.001. Cohen's Kappa analysis found a moderate agreement for compliance (0.49) and appropriateness (0.50) between the external and internal evaluations. CONCLUSION: The lack of adequate reproducibility of compliance and appropriateness assessments may limit the generalisability of the audit's results. Validating point prevalence surveys that assess antibacterial agent prescribing can increase confidence and improve reproducibility of their findings; as they provide important data for antimicrobial stewardship programs.

Effectiveness of nurse-led volunteer support and technology-driven pain assessment in improving the outcomes of hospitalised older adults: protocol for a cluster randomised controlled trial.

INTRODUCTION: Hospitalised older adults are prone to functional deterioration, which is more evident in frail older patients and can be further exacerbated by pain. Two interventions that have the potential to prevent progression of frailty and improve patient outcomes in hospitalised older adults but have yet to be subject to clinical trials are nurse-led volunteer support and technology-driven assessment of pain. METHODS AND ANALYSIS: This single-centre, prospective, non-blinded, cluster randomised controlled trial will compare the efficacy of nurse-led volunteer support, technology-driven pain assessment and the combination of the two interventions to usual care for hospitalised older adults. Prior to commencing recruitment, the intervention and control conditions will be randomised across four wards. Recruitment will continue for 12 months. Data will be collected on admission, at discharge and at 30 days post discharge, with additional data collected during hospitalisation comprising records of pain assessment and volunteer support activity. The primary outcome of this study will be the change in frailty between both admission and discharge, and admission and 30 days, and secondary outcomes include length of stay, adverse events, discharge destination, quality of life, depression, cognitive function, functional independence, pain scores, pain management intervention (type and frequency) and unplanned 30-day readmissions. Stakeholder evaluation and an economic analysis of the interventions will also be conducted. ETHICS AND DISSEMINATION: Ethical approval has been granted by Human Research Ethics Committees at Ramsay Health Care WA|SA (number: 2057) and Edith Cowan University (number: 2021-02210-SAUNDERS). The findings will be disseminated through conference presentations, peer-reviewed publications and social media. TRIAL REGISTRATION NUMBER: ACTRN12620001173987.

The role of the clinical pharmacist in mental health hospital-in-the-home: A scoping review.

BACKGROUND: The concept of integrating a clinical pharmacist (CP) within a Hospital-in-the-Home (HiTH) program is relatively new. Little is known about the role of a pharmacist in HiTH programs focused on mental health (MH). OBJECTIVES: To describe the role of a CP within an MH-HiTH program, focusing on the specific tasks performed by a pharmacist in this position, their benefits and limitations. METHODS: MEDLINE, CINAHL, EMBASE, Cochrane Database of Systematic Reviews, PsycINFO, Web of Science and the grey literature were searched without any date limits for references in English that included 2 or more of the following key terms (or their synonyms): "HiTH", "clinical pharmacist" and "mental health". Two reviewers independently screened and analysed the data. RESULTS: Of 60,482 screened references, 6 included all 3 key terms: 2 were HiTH guideline documents, 2 were conference abstracts and 2 were journal articles. These papers discussed MH-HiTH programs or similar home-care services where a CP was incorporated in the treating team to address medication management and adherence during a home visit. There is evidence that MH-HiTH CPs identify and resolve medication-related problems (MRPs), as well as improve medication adherence, patient care, hospital admission rates and emergency department presentations. An additional 54 references including 2 key terms provided corroborating evidence of an MH-HiTH CP role focused on improving patient care via 4 key groups of tasks: clinical pharmacy, mental healthcare, home medicines review and facilitation of care transition through medication reconciliation and follow-up. CONCLUSIONS: Although there is currently a paucity of literature describing the incorporation of a CP in an MH-HiTH program, preliminary evidence shows it can improve medication management. This has potential to improve patient outcomes as has been seen in similar home-based settings, but limitations such as time constraints are notable barriers. More robust studies are needed to evaluate these outcomes.

Impact of a clinical pharmacist on medication safety in mental health Hospital-in-the-Home: a retrospective analysis.

BACKGROUND: Integration of clinical pharmacists into multidisciplinary Mental Health Hospital-in-the-Home teams is increasing but little is known about the medication safety contribution these pharmacists make. AIM: To evaluate whether clinical pharmacist involvement in a Mental Health Hospital-in-the-Home service improved medication safety key performance indicators. METHOD: Medical records were retrospectively reviewed of all patients admitted to 2 Western Australian Mental Health Hospital-in-the-Home services from September to November 2015. SITE 1: was a 16-bed service incorporating a clinical pharmacist as part of its multidisciplinary team. SITE 2: was a similarly structured 18-bed service but without clinical pharmacist involvement. The primary outcome measure was completion of medication safety key performance indicators obtained from the Western Australian Government Pharmaceutical Review Policy and mental health-specific best practice guidelines. RESULTS: Key performance indicators from Site 1 (n = 75 records), which incorporated a clinical pharmacist, demonstrated significantly (p < 0.001) higher rates of completion of medication reconciliation [65 (87%) versus 17 (29%)], accurate adverse drug reaction list [73 (97%) versus 34 (58%)], accurate discharge medication list [51 (74%) versus 18 (45%)], accurate medication profile [74 (99%) versus 40 (68%)] and medication chart review [74 (99%) versus 0 (0%)] than Site 2 (n = 59). CONCLUSION: Integrating a clinical pharmacist into a Mental Health Hospital-in-the-Home program significantly improved achievement of medication safety key performance indicators.

Establishment and evolution of a clinical pharmacy mental health hospital-in-the-home service: An autoethnography.

BACKGROUND: Hospital-in-the-Home (HiTH) services provide "inpatient-style" care for patients at home. While relatively well known in non-psychiatric settings, little is known about mental health (MH)-HiTH services, with even less known about the role of a clinical pharmacist (CP) within a MH-HiTH multidisciplinary team (MDT). OBJECTIVE: The aim of this paper is to describe the evolution of the first MH-HiTH MDT in Western Australia and the various facets of the CP's role integrated within the service. METHOD: The integration of a CP into a non-traditional practice setting represents a cultural change in the pharmacy profession. Hence, this paper utilised a descriptive-realistic style of the autoethnographic method, with the narrative written in the first-person point of view of the first author (M.F.). It specifically focused on the tasks performed by the team's CP. A narrative analysis approach was used to reflect on the reason these tasks are performed, the potential benefits and limitations of integrating a CP into the team and subsequent cultural influence on the pharmacy profession. FINDINGS: The service commenced in 2014, consisting of an MDT of a consultant psychiatrist, a psychiatric registrar, clinical nurses, an occupational therapist, a social worker and a CP. Starting with 4 then 8 "virtual beds", it was gradually increased to 16 virtual beds. The MH-HiTH CP combined hospital clinical tasks - e.g. medication reconciliation and therapeutic drug monitoring - with home medication reviews as part of the MH-HiTH MDT. Lessons learnt include proactively integrating and flexibly adapting into a novel practice setting. CONCLUSION: There is scope to embed a CP within an MH-HiTH MDT; the major advantage is the inclusion of a comprehensive medication management service. While this is a promising new area where the pharmacy profession is becoming engaged, more studies are needed to quantify and confirm the stated benefits of such service.

Mid-term outcomes of a stemless ceramic head anatomic total shoulder replacement.

BACKGROUND: In an anatomic shoulder replacement (aTSR) good results have been reported with the use of a stemless humeral prosthesis. In vitro a ceramic articulation with polyethylene has been shown to produce less polyethylene wear particles than with metal. This study aims to evaluate clinical and radiographic results of a stemless aTSR with a ceramic head articulating with a polyethylene glenoid component, with mid-term follow-up. METHODS: All patients (n = 92) in this prospective study had an aTSR utilizing a stemless humeral component with a ceramic head and a cemented double pegged cemented polyethylene glenoid component for glenohumeral osteoarthritis. Pre- and postoperative clinical evaluations at 2 years were performed using the ASES score, Constant score, SPADI score, DASH score, VAS pain score, patient satisfaction and range of motion. There was a 5-year evaluation of SPADI, ASES, pain, and satisfaction, plus radiographic assessment of glenoid component radiolucent lines and humeral osteolysis. RESULTS: Seventy-four cases (68.1 ± 7.1 years) had a five-year follow-up and demonstrated active elevation improvement from 91.3° preoperatively to 151.1° (p < 0.001). Further improvement was identified with the ASES from 41.6 to 94.3, the SPADI from 62.9 to 4.3, VAS pain from 5.6 to 0.4 (0-10), and satisfaction levels were at 96%. Sixty-two cases had no glenoid radiolucent lines with a maximum Lazarus score of 2 in one patient. Constant scores, available up to 2 years, improved significantly from 30.3 to 77.9 (p < 0.001). There was one case that required revision for glenoid loosening. CONCLUSIONS: Overall, the 5-year results of this ceramic head prosthesis demonstrated good radiographic and clinical outcomes. TRIAL REGISTRATION: ACTRN12613001183774 . Registered: 29 October 2013 - Retrospectively registered. Australian New Zealand Clinical Trials Registry (ANZCTR).

Proton pump inhibitors are associated with incident type 2 diabetes mellitus in a prospective population-based cohort study.

AIM: To investigate the association between proton pump inhibitors (PPIs) and risk of incident diabetes in a follow-up study and to investigate its potential mechanisms. METHODS: A total of 9531 individuals without type 2 diabetes (T2DM) at baseline were included from the Rotterdam Study, a prospective population-based cohort of 14 926 individuals aged 45 years or older. During the study period (1 April 1997 to 1 January 2012) all incident cases of T2DM were enrolled. We used multivariable linear regression analysis to investigate the associations of baseline PPI use and various serum biomarkers (eg, serum magnesium, insulin-like growth factor 1) which might modify the association. Thereafter, we excluded prevalent PPI users and performed a Cox proportional hazard regression analysis to explore the time-varying effect of incident PPI use on T2DM during follow-up. RESULTS: Baseline use of a PPI was associated with increased serum levels of fasting insulin (0.091 pmoL/L, 95% confidence interval [CI] 0.049, 0.133), homeostasis model assessment-insulin resistance (0.100, 95% CI 0.056, 0.145) and C-reactive protein (0.29 mg/L, 95% CI 0.198, 0.384), but decreased levels of magnesium (-0.009 mmol/L, 95% CI -0.014, -0.004) and IGF-1 (-0.805 nmoL/L, 95% CI -1.015, -0.595). After adjustment for risk factors such as physical activity and body mass index/waist-to-hip ratio, current use of PPI was associated with an increased risk of incident T2DM (hazard ratio [HR] 1.69, 95% CI 1.36-2.10). The effect was dose-dependent with the highest risk (HR 1.88, 95% CI 1.29-2.75) in those on more than one defined daily dose. CONCLUSION: New users of PPIs during follow-up had a significantly higher dose-dependent risk of incident diabetes. We suggest vigilance regarding their potential adverse effect on glucose homeostasis.

Per- and polyfluoroalkyl substances, epigenetic age and DNA methylation: a cross-sectional study of firefighters.

Background: Per- and polyfluoroalkyl substances (PFASs) are persistent chemicals that firefighters encounter. Epigenetic modifications, including DNA methylation, could serve as PFASs toxicity biomarkers. Methods: With a sample size of 197 firefighters, we quantified the serum concentrations of nine PFASs, blood leukocyte DNA methylation and epigenetic age indicators via the EPIC array. We examined the associations between PFASs with epigenetic age, site- and region-specific DNA methylation, adjusting for confounders. Results: Perfluorohexane sulfonate, perfluorooctanoate (PFOA) and the sum of branched isomers of perfluorooctane sulfonate (Sm-PFOS) were associated with accelerated epigenetic age. Branched PFOA, linear PFOS, perfluorononanoate, perfluorodecanoate and perfluoroundecanoate were associated with differentially methylated loci and regions. Conclusion: PFASs concentrations are associated with accelerated epigenetic age and locus-specific DNA methylation. The implications for PFASs toxicity merit further investigation.

Prevalence of frailty and pain in hospitalised adult patients in an acute hospital: a protocol for a point prevalence observational study.

INTRODUCTION: Frailty and pain are associated with adverse patient clinical outcomes and healthcare system costs. Frailty and pain can interact, such that symptoms of frailty can make pain assessment difficult and pain can exacerbate the progression of frailty. The prevalence of frailty and pain and their concurrence in hospital settings are not well understood, and patients with cognitive impairment are often excluded from pain prevalence studies due to difficulties assessing their pain. The aim of this study is to determine the prevalence of frailty and pain in adult inpatients, including those with cognitive impairment, in an acute care private metropolitan hospital in Western Australia. METHODS AND ANALYSIS: A prospective, observational, single-day point prevalence, cross-sectional study of frailty and pain intensity of all inpatients (excluding day surgery and critical care units) will be undertaken. Frailty will be assessed using the modified Reported Edmonton Frail Scale. Current pain intensity will be assessed using the PainChek smart-device application enabling pain assessment in people unable to report pain due to cognitive impairment. Participants will also provide a numerical rating of the intensity of current pain and the worst pain experienced in the previous 24 hours. Demographic and clinical information will be collected from patient files. The overall response rate of the survey will be reported, as well as the percentage prevalence of frailty and of pain in the sample (separately for PainChek scores and numerical ratings). Additional statistical modelling will be conducted comparing frailty scores with pain scores, adjusting for covariates including age, gender, ward type and reason for admission. ETHICS AND DISSEMINATION: Ethical approval has been granted by Ramsay Health Care Human Research Ethics Committee WA/SA (reference: 2038) and Edith Cowan University Human Research Ethics Committee (reference: 2020-02008-SAUNDERS). Findings will be widely disseminated through conference presentations, peer-reviewed publications and social media. TRIAL REGISTRATION NUMBER: ACTRN12620000904976.

Differential DNA Methylation by Hispanic Ethnicity Among Firefighters in the United States.

Firefighters are exposed to a variety of environmental hazards and are at increased risk for multiple cancers. There is evidence that risks differ by ethnicity, yet the biological or environmental differences underlying these differences are not known. DNA methylation is one type of epigenetic regulation that is altered in cancers. In this pilot study, we profiled DNA methylation with the Infinium MethylationEPIC in blood leukocytes from 31 Hispanic white and 163 non-Hispanic white firefighters. We compared DNA methylation (1) at 12 xenobiotic metabolizing genes and (2) at all loci on the array (>740 000), adjusting for confounders. Five of the xenobiotic metabolizing genes were differentially methylated at a raw P-value <.05 when comparing the 2 ethnic groups, yet were not statistically significant at a 5% false discovery rate (q-value <.05). In the epigenome-wide analysis, 76 loci exhibited DNA methylation differences at q < .05. Among these, 3 CpG sites in the promoter region of the biotransformation gene SULT1C2 had lower methylation in Hispanic compared to non-Hispanic firefighters. Other differentially methylated loci included genes that have been implicated in carcinogenesis in published studies (FOXK2, GYLTL1B, ZBTB16, ARHGEF10, and more). In this pilot study, we report differential DNA methylation between Hispanic and non-Hispanic firefighters in xenobiotic metabolism genes and other genes with functions related to cancer. Epigenetic susceptibility by ethnicity merits further study as this may alter risk for cancers linked to toxic exposures.