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.

Associations Between Epigenetic Age Acceleration and microRNA Expression Among U.S. Firefighters.

Epigenetic changes may be biomarkers of health. Epigenetic age acceleration (EAA), the discrepancy between epigenetic age measured via epigenetic clocks and chronological age, is associated with morbidity and mortality. However, the intersection of epigenetic clocks with microRNAs (miRNAs) and corresponding miRNA-based health implications have not been evaluated. We analyzed DNA methylation and miRNA profiles from blood sampled among 332 individuals enrolled across 2 U.S.-based firefighter occupational studies (2015-2018 and 2018-2020). We considered 7 measures of EAA in leukocytes (PhenoAge, GrimAge, Horvath, skin-blood, and Hannum epigenetic clocks, and extrinsic and intrinsic epigenetic age acceleration). We identified miRNAs associated with EAA using individual linear regression models, adjusted for sex, race/ethnicity, chronological age, and cell type estimates, and investigated downstream effects of associated miRNAs with miRNA enrichment analyses and genomic annotations. On average, participants were 38 years old, 88% male, and 75% non-Hispanic white. We identified 183 of 798 miRNAs associated with EAA (FDR q < 0.05); 126 with PhenoAge, 59 with GrimAge, 1 with Horvath, and 1 with the skin-blood clock. Among miRNAs associated with Horvath and GrimAge, there were 61 significantly enriched disease annotations including age-related metabolic and cardiovascular conditions and several cancers. Enriched pathways included those related to proteins and protein modification. We identified miRNAs associated with EAA of multiple epigenetic clocks. PhenoAge had more associations with individual miRNAs, but GrimAge and Horvath had greater implications for miRNA-associated pathways. Understanding the relationship between these epigenetic markers could contribute to our understanding of the molecular underpinnings of aging and aging-related diseases.

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.

Serum per- and polyfluoroalkyl substance concentrations in four municipal US fire departments.

BACKGROUND: Firefighters have occupational and environmental exposures to per- and polyfluoroalkyl substances (PFAS). The goal of this study was to compare serum PFAS concentrations across multiple United States fire departments to National Health and Nutrition Examination Survey (NHANES) participants. METHODS: Nine serum PFAS were compared in 290 firefighters from four municipal fire departments (coded A-D) and three NHANES participants matched to each firefighter on sex, ethnicity, age, and PFAS collection year. Only Departments A and C had sufficient women study participants (25 and six, respectively) to compare with NHANES. RESULTS: In male firefighters compared with NHANES, geometric mean perfluorohexane sulfonate (PFHxS) was elevated in Departments A-C, sum of branched perfluoromethylheptane sulfonate isomers (Sm-PFOS) was elevated in all four departments, linear perfluorooctane sulfonate (n-PFOS) was elevated in Departments B and C, linear perfluorooctanoate (n-PFOA) was elevated in Departments B-D, and perfluorononanoate (PFNA) was elevated in Departments B-D, but lower in A. In male firefighters compared with NHANES, perfluoroundecanoate (PFUnDA) was more frequently detected in Departments B and D, and 2-(N-methyl-perfluorooctane sulfonamido) acetate (MeFOSAA) was less frequently detected in Departments B-D. In female firefighters compared with NHANES, PFHxS and Sm-PFOS concentrations were elevated in Departments A and C. Other PFAS concentrations were elevated and/or reduced in only one department or not significantly different from NHANES in any department. CONCLUSIONS: Serum PFHxS, Sm-PFOS, n-PFOS, n-PFOA, and PFNA concentrations were increased in at least two of four fire departments in comparison to NHANES.

Maternal iron deficiency anaemia in pregnancy: Lessons from a national audit.

We describe the management and the prevalence of iron deficiency anaemia (IDA) during pregnancy by comparison to standards. A cross-sectional national cohort study of women who had given birth six weeks prior to data collection was conducted at maternity units in the UK and Ireland. Participating centres collected data from 10 consecutive pregnant women. Analysis was descriptive to define the prevalence of IDA in pregnancy and the puerperium, and to compare the outcomes in women who had IDA with women who did not have anaemia anytime during pregnancy. Eighty-six maternity units contributed data on 860 pregnancies and births. The overall prevalence of IDA during pregnancy was 30.4% and in the puerperium 20%. Anaemic women were more likely to be from ethnic minorities, odds ratio 2.23 (1.50, 3.32). Adherence to national guidance was suboptimal, and the prevalence of anaemia in pregnancy remains very high. There is pressing need to explore barriers to early identification and effective management of iron deficiency. IDA should be considered a major public health problem in the UK.

Effectiveness of Enhanced Performance Feedback on Appropriate Use of Blood Transfusions: A Comparison of 2 Cluster Randomized Trials.

Importance: Auditing and feedback are frequently used to improve patient care. However, it remains unclear how to optimize feedback effectiveness for the appropriate use of treatments such as blood transfusion, a common but costly procedure that is more often overused than underused. Objective: To evaluate 2 theoretically informed feedback interventions to improve the appropriate use of blood transfusions. Design, Setting, and Participants: Two sequential, linked 2 × 2 cluster randomized trials were performed in hospitals in the UK participating in national audits of transfusion for perioperative anemia and management of hematological disorders. Data were collected for a surgical trial from October 1, 2014, to October 31, 2016, with follow-up completed on October 31, 2016. Data were collected for a hematological trial through follow-up from July 1, 2015, to June 30, 2017. Trial data were analyzed from November 1, 2016, to June 1, 2019. Interventions: Hospitals were randomized to standard content or enhanced content to improve feedback clarity and usability and to standard support or enhanced support for staff to act on feedback. Main Outcomes and Measures: The primary end point was appropriateness of transfusions audited at 12 months. Secondary end points included volume of transfusions (aiming for reductions at patient and cluster levels) and transfusion-related adverse events and reactions. Results: One hundred thirty-five of 152 eligible clusters participated in the surgical audit (2714 patients; mean [SD] age, 74.9 [14.0] years; 1809 women [66.7%]), and 134 of 141 participated in the hematological audit (4439 patients; median age, 72.0 [IQR, 64.0-80.0] years; 2641 men [59.5%]). Fifty-seven of 69 clusters (82.6%) in the surgical audit randomized to enhanced content downloaded reports compared with 52 of 66 clusters (78.8%) randomized to standard reports. Fifty-nine of 68 clusters (86.8%) randomized to enhanced support logged onto the toolkit. The proportion of patients with appropriate transfusions was 0.184 for standard content and 0.176 for enhanced content (adjusted odds ratio [OR], 0.91 [97.5% CI, 0.61-1.36]) and 0.181 for standard support and 0.180 for enhanced support (adjusted OR, 1.05 [97.5% CI, 0.68-1.61]). For the hematological audit, 53 of 66 clusters (80.3%) randomized to enhanced content downloaded the reports compared with 53 of 68 clusters (77.9%) randomized to standard content. Forty-nine of 67 clusters sites (73.1%) assigned to enhanced support logged into the toolkit at least once. The proportion of patients with appropriate transfusions was 0.744 for standard content and 0.714 for enhanced content (adjusted OR, 0.81 [97.5% CI, 0.56-1.12]), and 0.739 for standard support and 0.721 for enhanced support (adjusted OR, 0.96 [97.5% CI, 0.67-1.38]). Conclusions and Relevance: This comparison of cluster randomized trials found that interventions to improve feedback usability and guide local action were no more effective than standard feedback in increasing the appropriate use of blood transfusions. Auditing and feedback delivered at scale is a complex and costly program; therefore, effective responses may depend on developing robust local quality improvement arrangements, which can be evaluated using rigorous experimental designs embedded within national programs. Trial Registration: isrctn.org Identifier: ISRCTN15490813.

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.

Perceptions of Work-Related Health and Cancer Risks Among Women Firefighters: A Qualitative Study.

OBJECTIVES: We use a qualitative method to gain further insight into women firefighters' experiences, perceptions of cancer, health, and safety risks in the fire service. METHODS: We conducted six focus groups with U.S. women firefighters. Participants engaged in a 60 to 75-minute, semi-structured discussion and completed a sociodemographic questionnaire. A qualitative descriptive approach was used to inductively create themes. Data collection concluded when saturation was met. RESULTS: Forty-nine women firefighters participated. Qualitative results indicated the main health concerns include: occupational cancer risks including, risks related to hazardous exposures, sleep disruption and stress; and women's health concerns including, cancer, pregnancy and breastfeeding, and lack of resources. CONCLUSIONS: Women firefighters are concerned about their risk for cancer due to their occupation and identify a lack of resources specific to health and safety needs of women firefighters.

Repeated analyses of national clinical audit reports demonstrate improvements in feedback methods.

BACKGROUND: There is growing interest in the impact of national clinical audit programmes on the quality of healthcare. There is also an evolving evidence-base for enhancing the design and delivery of audit and feedback. We assessed the extent to which a sample of UK national clinical audit feedback reports met a set of good practice criteria over three time points. METHODS: We undertook three cross-sectional content analyses. We developed good practice criteria for the content and delivery of feedback based upon evidence, behavioural theory and expert opinion. We applied these to a feedback reports from 23 national audits listed on the Healthcare Quality Improvement Partnership (HQIP) website in November 2015. We repeated our assessments in January 2017 for 20 repeat feedback reports, after HQIP had published reporting guidance for national audits, and in August 2019 for a further 14 repeat feedback reports. We verified our assessments, where possible, with audit leads. RESULTS: Feedback reports consistently included strengths at baseline, including past or planned repeated audit cycles (21; 91%), stating the importance of the topic in relation to patient care (22; 93%), using multi-modal data presentation (23; 100%), and summarising key findings (23; 100%). We observed improvements over subsequent assessments, so that by 2019, at least 13 out of 14 (93%) feedback reports presented easily identifiable key findings and recommendations, linked recommendations to audit standards, and proposed easily identifiable action plans. Whilst the use of regional comparators did not improve, audit leads highlighted that programmes now provide local data via additional means. The main shortcoming was the time lag between data collection and feedback; none of the 14 reports assessed in 2019 presented performance data less than 6 months old. Audit leads highlighted that some of these data might be available via programme websites. CONCLUSION: We identified increased adherence to good practice in feedback by national clinical audit programmes that may enhance their impact on service delivery and outcomes. There is scope for improvement, especially in the recency of performance data. With further refinements, a criterion-based assessment offers an efficient means of monitoring the quality of national clinical audit feedback reports.

Fire Service Organizational-Level Characteristics Are Associated With Adherence to Contamination Control Practices in Florida Fire Departments: Evidence From the Firefighter Cancer Initiative.

OBJECTIVES: To characterize the types of contamination control practices followed by Florida fire departments and examine the association between fire department organizational-level characteristics and adherence to contamination control practices. METHODS: Using a cross-sectional study design, a survey was administered to 142 Florida firefighters. Validated survey measures assessed organizational level characteristics and 32 recommended national contamination control practices. RESULTS: An average of 18.9 contamination control practices (standard deviation = 5.54; min = 3; max = 30) were reported by fire departments of which, wearing personal protective equipment (PPE) according to manufacturer instructions (98.9%) and access to special machine for cleaning (91%) were most cited. Fire departments with one or more health and safety officers had significantly higher implementation of contamination control practices (P = 0.032). CONCLUSION: Health and safety officers may have a positive impact on the number of contamination control practices followed in Florida fire departments.

International Survey of Trials of Convalescent Plasma to Treat COVID-19 Infection.

The collection and clinical use of COVID-19 convalescent plasma (CCP) as a therapy for COVID-19 infection is under development and early use in many centers worldwide. We conducted an international survey of centers undertaking studies of CCP to provide understanding of the common themes and differences between them. Sixty-four studies in 22 countries were identified from clinical trial registries and personal contacts of the authors. Twenty of the 64 centers (31%) from 12 of 22 countries (55%) responded to the survey. Of the 20 studies, 11 were randomized controlled trials (RCTs), and 9 were case series. Only 4 of the RCTs plan to recruit 400 patients or more, and only 3 RCTs were blinded. The majority of studies will study the effect of CCP on sick patients requiring hospitalization and those requiring critical care, and none is examining the role of CCP in non-infected at-risk individuals. A wide variety of primary and secondary outcomes are being used. The donor eligibility criteria among the studies are very similar, and the use of plasmapheresis for the collection of CCP is almost universal. The planned dose of CCP ranges from as little as 200 mL to well over 1 L, but is 400 to 800 mL or 4 mL/kg or greater in all the RCTs. There is considerable variability in donor antibody testing with no consistency regarding the cut-off for antibody titer for acceptance as CCP or the use of pathogen-inactivation. Our survey provides an understanding of the similarities and differences among the studies of CCP, and that by virtue of their design some studies may be more informative than others.

Assessing the Effect of Unit Champion-Initiated Audits on Fall Rates: Improving Awareness.

BACKGROUND: Inpatient falls remain challenging with repercussions that can include patient injury and increased hospital expense. Fall rates were consistently above the national benchmark. An initiative to reduce fall rates was use of Fall Champion Audits (FCAs). PURPOSE: The aim of this study was to assess the effect of FCAs on patient fall rates. METHODS: FCAs were piloted on a medical-oncology unit. An interrupted time series design was used to assess the effect of FCAs on fall rates. INTERVENTION: FCA is an audit conducted by the unit fall champion that assesses fall risk, interventions, and barriers among staff and patients. RESULTS: Analysis suggested a significant decrease in fall rates from pre- (3.75) to postimplementation (1.62). FCAs worked in conjunction with a division-wide fall program in reducing fall rate. CONCLUSIONS: FCAs, in conjunction with a fall program, are a feasible intervention in reducing fall rates.

National Comparative Audit of Blood Transfusion: report on the 2014 audit of patient information and consent.

OBJECTIVES: The aim of this study was to assess current practices around obtaining consent for blood transfusion and provision of patient information in hospitals across the UK and identify areas for improvement. BACKGROUND: Recommendations from the Advisory Committee on the Safety of Blood, Tissues and Organs (SaBTO) (2011) state that valid consent should be obtained for blood transfusion and documented in clinical records. A standardised source of information should be available to patients. Practices in relation to this have historically been inconsistent. METHODS: The consent process was studied in hospitals across the UK over a 3-month period in 2014 by means of an audit of case notes and simultaneous surveys of patients and staff. RESULTS: In total, 2784 transfusion episodes were reviewed across 164 hospital sites. 85% of sites had a policy on consent for transfusion. Consent was documented in 43% of case notes. 68% of patients recalled being given information on benefits of transfusion, 38% on risks and 8% on alternatives and 28% reported receiving an information leaflet. In total, 85% of staff stated they had explained the reason for transfusion, but only 65% had documented this. 41% of staff had received training specifically on transfusion consent in the last 2 years. CONCLUSIONS: There is a need to improve clinical practice in obtaining valid consent for transfusion in line with existing national guidelines and local Trust policies, with emphasis on documentation within clinical records. Provision of patient information is an area particularly highlighted for action, and transfusion training for clinicians should be strengthened.

Patient blood management knowledge and practice among clinicians from seven European university hospitals: a multicentre survey.

BACKGROUND AND OBJECTIVES: The aim of this survey was to evaluate the knowledge about Patient Blood Management (PBM) principles and practices amongst clinicians working in seven European hospitals participating in a European Blood Alliance (EBA) project. MATERIALS AND METHODS: A web-based questionnaire was sent to 4952 clinicians working in medical, surgery and anaesthesiology disciplines. The responses were analysed, and the overall results as well as a comparison between hospitals are presented. RESULTS: A total of 788 responses (16%) were obtained. About 24% of respondents were not aware of a correlation between preoperative anaemia (POA) and perioperative morbidity and mortality. For 22%, treatment of POA was unlikely to favourably influence morbidity and mortality even before surgery with expected blood loss. More than half of clinicians did not routinely treat POA. 29%, when asked which is the best way to treat deficiency anaemia preoperatively, answered that they did not have sufficient knowledge and 5% chose to 'do nothing'. Amongst those who treated POA, 38% proposed red cell transfusion prior to surgery as treatment. Restrictive haemoglobin triggers for red blood cell transfusion, single unit policy and reduction of number and volumes of blood samples for diagnostic purposes were only marginally implemented. CONCLUSION: Overall, the responses indicated poor knowledge about PBM. Processes to diagnose and treat POA were not generally and homogeneously implemented. This survey should provide further impetus to implement programmes to improve knowledge and practice of PBM.

The evaluation of enhanced feedback interventions to reduce unnecessary blood transfusions (AFFINITIE): protocol for two linked cluster randomised factorial controlled trials.

BACKGROUND: Blood for transfusion is a frequently used clinical intervention, and is also a costly and limited resource with risks. Many transfusions are given to stable and non-bleeding patients despite no clear evidence of benefit from clinical studies. Audit and feedback (A&F) is widely used to improve the quality of healthcare, including appropriate use of blood. However, its effects are often inconsistent, indicating the need for coordinated research including more head-to-head trials comparing different ways of delivering feedback. A programmatic series of research projects, termed the 'Audit and Feedback INterventions to Increase evidence-based Transfusion practIcE' (AFFINITIE) programme, aims to test different ways of developing and delivering feedback within an existing national audit structure. METHODS: The evaluation will comprise two linked 2×2 factorial, cross-sectional cluster-randomised controlled trials. Each trial will estimate the effects of two feedback interventions, 'enhanced content' and 'enhanced follow-on support', designed in earlier stages of the AFFINITIE programme, compared to current practice. The interventions will be embedded within two rounds of the UK National Comparative Audit of Blood Transfusion (NCABT) focusing on patient blood management in surgery and use of blood transfusions in patients with haematological malignancies. The unit of randomisation will be National Health Service (NHS) trust or health board. Clusters providing care relevant to the audit topics will be randomised following each baseline audit (separately for each trial), with stratification for size (volume of blood transfusions) and region (Regional Transfusion Committee). The primary outcome for each topic will be the proportion of patients receiving a transfusion coded as unnecessary. For each audit topic a linked, mixed-method fidelity assessment and cost-effectiveness analysis will be conducted in parallel to the trial. DISCUSSION: AFFINITIE involves a series of studies to explore how A&F may be refined to change practice including two cluster randomised trials linked to national audits of transfusion practice. The methodology represents a step-wise increment in study design to more fully evaluate the effects of two enhanced feedback interventions on patient- and trust-level clinical, cost, safety and process outcomes. TRIAL REGISTRATION: http://www.isrctn.com/ISRCTN15490813.

Study protocol: first nationwide comparative audit of acute lower gastrointestinal bleeding in the UK.

INTRODUCTION: Acute lower gastrointestinal bleeding (LGIB) is a common indication for emergency hospitalisation worldwide. In contrast to upper GIB, patient characteristics, modes of investigation, transfusion, treatment and outcomes are poorly described. There are minimal clinical guidelines to inform care pathways and the use of endoscopy, including (diagnostic and therapeutic yields), interventional radiology and surgery are poorly defined. As a result, there is potential for wide variation in practice and clinical outcomes. METHODS AND ANALYSIS: The UK Lower Gastrointestinal Bleeding Audit is a large nationwide audit of adult patients acutely admitted with LGIB or those who develop LGIB while hospitalised for another reason. Consecutive, unselected presentations with LGIB will be enrolled prospectively over a 2-month period at the end of 2015 and detailed data will be collected on patient characteristics, comorbidities, use of anticoagulants, transfusion, timing and modalities of diagnostic and therapeutic procedures, clinical outcome, length of stay and mortality. These will be audited against predefined minimum standards of care for LGIB. It is anticipated that over 80% of all acute hospitals in England and some hospitals in Scotland, Wales and Northern Ireland will participate. Data will be collected on the availability and organisation of care, provision of diagnostic and therapeutic GI endoscopy, interventional radiology, surgery and transfusion protocols. ETHICS AND DISSEMINATION: This audit will be conducted as part of the national comparative audit programme of blood transfusion through collaboration with specialists in gastroenterology, surgery and interventional radiology. Individual reports will be provided to each participant site as well as an overall report and disseminated through specialist societies. Results will also be published in peer-reviewed journals. The study has been funded by National Health Services (NHS) Blood and Transplant and the Bowel Disease Research Foundation and endorsed by the Association of Coloproctology of Great Britain and Ireland.