Effect of Plasma and Blood Donations on Levels of Perfluoroalkyl and Polyfluoroalkyl Substances in Firefighters in Australia: A Randomized Clinical Trial.

Importance: Elevated levels of blood perfluoroalkyl and polyfluoroalkyl substances (PFASs) have been associated with a range of adverse health outcomes. Firefighters have been exposed to PFASs in firefighting foams and have previously been shown to have higher PFAS levels in blood samples than the general population. No interventions have been shown to reduce PFAS levels. Objective: To examine the effect of blood or plasma donations on PFAS levels in firefighters in Australia. Design, Setting, and Participants: This 52-week, open-label, randomized clinical trial enrolled participants from May 23 to August 23, 2019. Participants were 285 Fire Rescue Victoria staff or contractors with serum levels of perfluorooctane sulfonate (PFOS) of 5 ng/mL or more who were eligible to donate blood, had not donated blood in the 3 months prior to randomization, and were able to provide written informed consent. Analysis was performed on an intention-to-treat basis from May to July 2021. Interventions: Firefighters with baseline PFOS levels of 5 ng/mL or more were randomly assigned to donate plasma every 6 weeks for 12 months, donate blood every 12 weeks for 12 months, or be observed only. Main Outcomes and Measures: The primary end points were changes in the serum PFOS and perfluorohexane sulfonic acid (PFHxS) levels after 12 months of plasma or blood donations or after observation only. Secondary end points included changes in serum PFAS levels from week 52 to week 64, changes in other PFASs, and changes in complete blood count, biochemistry, thyroid function, and lipid profile from screening to week 52. Results: A total of 285 firefighters (279 men [97.9%]; mean [SD] age, 53.0 [8.4] years) were enrolled; 95 were randomly assigned to donate plasma, 95 were randomly assigned to donate blood, and 95 were randomly assigned to be observed. The mean level of PFOS at 12 months was significantly reduced by plasma donation (-2.9 ng/mL; 95% CI, -3.6 to -2.3 ng/mL; P < .001) and blood donation (-1.1 ng/mL; 95% CI, -1.5 to -0.7 ng/mL; P < .001) but was unchanged in the observation group. The mean level of PFHxS was significantly reduced by plasma donation (-1.1 ng/mL; 95% CI, -1.6 to -0.7 ng/mL; P < .001), but no significant change was observed in the blood donation or observation groups. Analysis between groups indicated that plasma donation had a larger treatment effect than blood donation, but both were significantly more efficacious than observation in reducing PFAS levels. Conclusions and Relevance: Plasma and blood donations caused greater reductions in serum PFAS levels than observation alone over a 12-month period. Further research is needed to evaluate the clinical implications of these findings. Trial Registration: anzctr.org.au Identifier: ACTRN12619000204145.

Study protocol for a randomised controlled trial examining the effect of blood and plasma donation on serum perfluoroalkyl and polyfluoroalkyl substance (PFAS) levels in firefighters.

INTRODUCTION: Perfluoroalkyl and polyfluoroalkyl substances (PFAS) are a diverse group of compounds that have been used in hundreds of industrial applications and consumer products including aqueous film-forming foam (AFFF) for many years. Multiple national and international health and environmental agencies have accepted that PFAS exposures are associated with numerous adverse health effects. Australian firefighters have been shown to have elevated levels of PFAS in their blood, specifically perfluorooctane sulfonic acid (PFOS) and perfluorohexane sulfonic acid (PFHxS), due to the historical use of AFFF. While PFAS concentrations decline over time once the source of exposure has been removed, their potential adverse health effects are such that it would be prudent to develop an intervention to lower levels at a faster rate than occurs via natural elimination rates. METHODS AND ANALYSIS: This is a randomised controlled trial of current and former Australian firefighters in the Metropolitan Fire Brigade/Fire Rescue Victoria, and contractors, with previous occupational exposure to PFAS and baseline elevated PFOS levels. The study is investigating whether whole blood donation every 12 weeks or plasma donation every 6 weeks will significantly reduce PFAS levels, compared with a control group. We have used covariate-adaptive randomisation to balance participants' sex and blood PFAS levels between the three groups and would consider a 25% reduction in serum PFOS and PFHxS levels to be potentially clinically significant after 12 months of whole blood or plasma donation. A secondary analysis of health biomarkers is being made of changes between screening and week 52 in all three groups. ETHICS AND DISSEMINATION: This trial has been approved by Macquarie University Human Research Ethics Committee (reference number: 3855), final protocol V.2 dated 12 June 2019. Study results will be disseminated via peer-reviewed publications and presentations at conferences. TRIAL REGISTRATION NUMBER: Australian New Zealand Clinical Trials Registry (ACTRN12619000204145).

Ethics in Surgical Innovations from the Patient Perspective.

OBJECTIVE: Surgical innovation (SI) can place patients at risk. We sought to explore what clinical information is readily available to patients who have been offered innovative surgical procedures, using two examples drawn from our recent experience: one a surgical technique, and the other a prosthetic material. We wanted to determine from our review the extent to which information available on the Internet might augment the medical literature and help satisfy the ethical requirements for patients to be adequately informed before they proceed with innovative surgery. METHODS: A scoping review of the medical literature was performed to look for studies addressing the review aims; targeted searches on Google, YouTube, and patient websites were carried out to find readily available patient information on two chosen innovative surgical procedures. We conducted a content analysis of the selected references to determine the availability, relevance, and the utility of the published information to a layperson. RESULTS: Medical database searches identified 614 records, 91 were screened and only six were relevant. The Internet searches returned thousands of results; however, we limited our screening to the first five pages of results for those sources. From both types of searches, 348 references were excluded because they did not meet the inclusion criteria and 51 were included in the analysis. The findings are presented in four themes: safety and feasibility of the technique, availability and accessibility to a layperson, relevance and utility to a layperson, and commercial information. CONCLUSION: The review has shown that lay people seeking to find out more about the two innovations would get very little useful information from Google, YouTube, or patient websites. Practitioners offering SI should provide sufficient information to allow their patients to make an autonomous decision about whether to proceed. For major SI, we encourage innovators to develop a plain language statement that would be made available on the Internet to the mutual advantage of both innovators and patients.

Experiences of women with cardiac disease in pregnancy: a systematic review and metasynthesis.

OBJECTIVE: Cardiac disease in pregnancy is a leading cause of maternal death in high-income countries. Evidence-based guidelines to assist in planning and managing the healthcare of affected women is lacking. The objective of this research was to produce the first qualitative metasynthesis of the experiences of pregnant women with existing or acquired cardiac disease to inform improved healthcare services. METHOD: We conducted a systematic search of peer-reviewed publications in five databases to investigate the decision-making processes, supportive strategies and healthcare experiences of pregnant women with existing or acquired cardiac disease, or of affected women contemplating pregnancy. Identified publications were screened for duplication and eligibility against selection criteria, following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We then undertook a thematic analysis of the data relating to women's experiences extracted from each publication to inform new healthcare practices and communication. RESULTS: Eleven studies from six countries were included in our meta-synthesis. Four themes were revealed. Women with congenital and acquired heart disease identified situations where they had either taken charge of decision-making, lacked control or experienced emotional uncertainty when making decisions. Some women were risk aware and determined to take care of themselves in pregnancy while others downplayed the risks. Women with heart disease acknowledged the importance of specific social support measures during pregnancy and after child birth, and reported a spectrum of healthcare experiences. CONCLUSIONS: There is a lack of integrated and tailored healthcare services and information for women with cardiac disease in pregnancy. The experiences of women synthesised in this research has the potential to inform new evidence-based guidelines to support the decision-making needs of women with cardiac disease in pregnancy. Shared decision-making must consider communication across the clinical team. However, coordinated care is challenging due to the different specialists involved and the limited clinical evidence concerning effective approaches to managing such complex care.

Advance care planning in 21st century Australia: a systematic review and appraisal of online advance care directive templates against national framework criteria.

OBJECTIVES: A drive to promote advance care planning at a population level has led to a proliferation of online advance care directive (ACD) templates but little information to guide consumer choice. The current study aimed to appraise the quality of online ACD templates promoted for use in Australia. METHODS: A systematic review of online Australian ACD templates was conducted in February 2014. ACD templates were identified via Google searches, and quality was independently appraised by two reviewers against criteria from the 2011 report A National Frameworkfor Advance Care Directives. Bias either towards or against future medical treatment was assessed using criteria designed to limit subjectivity. RESULTS: Fourteen online ACD templates were included, all of which were available only in English. Templates developed by Southern Cross University best met the framework criteria. One ACD template was found to be biased against medical treatment--the Dying with Dignity Victoria Advance Healthcare Directive. CONCLUSIONS: More research is needed to understand how online resources can optimally elicit and record consumers' individual preferences for future care. Future iterations of the framework should address online availability and provide a simple rating system to inform choice and drive quality improvement.

Routine use of clinical management guidelines in Australian general practice.

Significant gaps remain between recommendations of evidence-based guidelines and primary health care practice in Australia. This paper aims to evaluate factors associated with the use of guidelines reported by Australian GPs. Secondary analysis was performed on a survey of primary care practitioners which was conducted by the Commonwealth Fund in 2009: 1016 general practitioners responded in Australia (response rate 52%). Two-thirds of Australian GPs reported that they routinely used evidence-based treatment guidelines for the management of four conditions: diabetes, depression, asthma or chronic obstructive pulmonary disease and hypertension - a higher proportion than in most other countries. Having non-medical staff educating patients about self-management, and a system of GP reminders to provide patients with test results or guideline-based intervention or screening tests, were associated with a higher probability of guidelines use. Older GP age was associated with lower probability of guideline usage. The negative association with age of the doctor may reflect a tendency to rely on experience rather than evidence-based guidelines. The association with greater use of reminders and self-management is consistent with the chronic illness model.

Preventive evidence into practice (PEP) study: implementation of guidelines to prevent primary vascular disease in general practice protocol for a cluster randomised controlled trial.

BACKGROUND: There are significant gaps in the implementation and uptake of evidence-based guideline recommendations for cardiovascular disease (CVD) and diabetes in Australian general practice. This study protocol describes the methodology for a cluster randomised trial to evaluate the effectiveness of a model that aims to improve the implementation of these guidelines in Australian general practice developed by a collaboration between researchers, non-government organisations, and the profession. METHODS: We hypothesise that the intervention will alter the behaviour of clinicians and patients resulting in improvements of recording of lifestyle and physiological risk factors (by 20%) and increased adherence to guideline recommendations for: the management of CVD and diabetes risk factors (by 20%); and lifestyle and physiological risk factors of patients at risk (by 5%). Thirty-two general practices will be randomised in a 1:1 allocation to receive either the intervention or continue with usual care, after stratification by state. The intervention will be delivered through: small group education; audit of patient records to determine preventive care; and practice facilitation visits adapted to the needs of the practices. Outcome data will be extracted from electronic medical records and patient questionnaires, and qualitative evaluation from provider and patient interviews. DISCUSSION: We plan to disseminate study findings widely and directly inform implementation strategies by governments, professional bodies, and non-government organisations including the partner organisations.

A systematic review of interventions to enhance access to best practice primary health care for chronic disease management, prevention and episodic care.

BACKGROUND: Although primary health care (PHC) is a key component of all health care systems, services are not always readily available, accessible or affordable. This systematic review examines effective strategies to enhance access to best practice processes of PHC in three domains: chronic disease management, prevention and episodic care. METHODS: An extensive search of bibliographic data bases to identify peer and non-peer reviewed literature was undertaken. Identified papers were screened to identify and classify intervention studies that measured the impact of strategies (singly or in combination) on change in use or the reach of services in defined population groups (evaluated interventions). RESULTS: The search identified 3,148 citations of which 121 were intervention studies and 75 were evaluated interventions. Evaluated interventions were found in all three domains: prevention (n = 45), episodic care (n = 19), and chronic disease management (n = 11). They were undertaken in a number of countries including Australia (n = 25), USA (n = 25), and UK (n = 15). Study quality was ranked as high (31% of studies), medium (61%) and low (8%). The 75 evaluated interventions tested a range of strategies either singly (n = 46 studies) or as a combination of two (n = 20) or more strategies (n = 9). Strategies targeted both health providers and patients and were categorised to five groups: practice re-organisation (n = 43 studies), patient support (n = 29), provision of new services (n = 19), workforce development (n = 11), and financial incentives (n = 9). Strategies varied by domain, reflecting the complexity of care needs and processes. Of the 75 evaluated interventions, 55 reported positive findings with interventions using a combination of strategies more likely to report positive results. CONCLUSIONS: This review suggests that multiple, linked strategies targeting different levels of the health care system are most likely to improve access to best practice PHC. The proposed changes in the structure of PHC in Australia may provide opportunities to investigate the factors that influence access to best practice PHC and to develop and implement effective, evidence based strategies to address these.

Institutionalisation of Bulgarian ethics committees: history and current status.

This paper provides an overview of the institutionalisation of the ethics review process in Bulgaria in accordance with the worldwide trend in establishment of ethics committees. Historical and current politico-legal changes influencing the work of ethics committees are analysed. The paper focuses on ethics committees which review biomedical research involving humans, with an emphasis on their composition, functions, training of members, and decision-making processes. Recent positive changes addressing insufficient training of ethics committees'members are highlighted. Recommendations are made for enhancement of the ethics review process and improved transparency.

Preventing vascular disease - effective strategies for implementing guidelines in general practice.

BACKGROUND: Prevention of vascular disease is an important and challenging role for general practice. Various professional bodies in Australia have published best practice guidelines that address the major behavioural and physiological risk factors for vascular disease. Although these guidelines provide consistent advice and have been widely disseminated, they have not been systematically implemented. OBJECTIVE: This article presents findings from a literature review that identified effective strategies for implementing guidelines. DISCUSSION: Interventions that support guideline implementation are informed by theory, are multifaceted, tailored to barriers (at the patient, provider and practice levels) and the local context, and involve the entire primary healthcare team. Effective strategies include small group education, clinician prompts and decision aids, audit and feedback and external facilitation. The effectiveness of these strategies in different contexts varies. New systems or tools must fit well within the usual work routines if they are to be successful.

Research governance and change in research ethics practices at a major Australian university.

Recent revisions of the National Statement on Ethical Conduct in Human Research and the Australian Code for the Responsible Conduct of Research put a great emphasis on research governance. Institutional responsibility for the governance of the research is not limited only to the ethical review by the Human Research Ethics Committee (HREC), but also to the accountability for quality, safety, privacy, risk management and financial management of the research. Despite the development of proposed research governance frameworks, many Australian institutions do not have such structures in place and rely excessively on HRECs to perform administrative functions that are not their responsibility. In this paper we report on implementation of a research governance framework at University of New South Wales which led to reduced HREC workload and allowed more attention to its core functions. We present the approach undertaken by the university to separate the ethical review process by HREC from the research governance. We recommend that with proper research governance frameworks in place, the role of HRECs and the institutional responsibility of governance of the research can be defined clearly.