Addressing the consequences of the corporatization of reproductive medicine.

In Australia and the UK, commercialization and corporatization of assisted reproductive technologies have created a marketplace of clinics, products, and services. While this has arguably increased choice for patients, 'choice', shaped by commercial imperatives may not mean better-quality care. At present, regulation of clinics (including clinic-corporations) and clinicians focuses on the doctor-patient dyad and the clinic-consumer dyad. Scant attention has been paid to the conflicts between the clinic-corporation's duty to its shareholders and investors, the medical profession's duty to the corporations within which they practice, and the obligations of both clinicians and corporations to patients and to health systems. Frameworks of regulation based in corporate governance and business ethics, such as stakeholder models and 'corporate social responsibility', have well-recognized limits and may not translate well into healthcare settings. This means that existing governance frameworks may not meet the needs of patients or health systems. We argue for the development of novel regulatory approaches that more explicitly characterize the obligations that both corporations and clinicians in corporate environments have to patients and to society, and that promote fulfilment of these obligations. We consider mechanisms for application in the multi-jurisdictional setting of Australia, and the single jurisdictional settings of the UK.

Pulmonary BRAF-driven Langerhans cell histiocytosis following selpercatinib use in metastatic medullary thyroid cancer.

Summary: RET mutations are implicated in 60% of medullary thyroid cancer (MTC) cases. The RET-selective tyrosine kinase inhibitor selpercatinib is associated with unprecedented efficacy compared to previous multi-kinase treatments. Langerhans cell histiocytosis (LCH) is a clonal histiocytic neoplasm usually driven by somatic BRAF mutations, resulting in dysregulated MAPK signalling. We describe a 22-year-old woman with metastatic MTC to regional lymph nodes, lung and liver. Tumour tissue harboured a somatic pathogenic RET variant p.(M918T) and selpercatinib was commenced. She experienced sustained clinical, biochemical and radiological responses. Two years later, she developed rapidly progressive apical lung nodules, prompting biopsy. Histopathology demonstrated LCH with a rare BRAF variant p.(V600_K601>D). The lung nodules improved with inhaled corticosteroids. We hypothesize that selective pressure from RET blockade may have activated a downstream somatic BRAF mutation, resulting in pulmonary LCH. We recommend continued vigilance for neoplasms driven by dysregulated downstream MAPK signalling in patients undergoing selective RET inhibition. Learning points: Patients with RET-altered MTC can experience rapid disease improvement and sustained disease stability with selective RET blockade (selpercatinib). LCH is a clonal neoplasm driven by MAPK activation, for which the most common mechanism is BRAF mutation. Both MTC and pulmonary LCH are driven by dysregulated MAPK signalling pathway activation. We hypothesise that the RET-specific inhibitor selpercatinib may have caused the activation of dormant LCH secondary to selective pressure and clonal proliferation.

A survey of Australian public opinion on using comorbidity to triage intensive care patients in a pandemic.

Objectives This study aimed to determine which method to triage intensive care patients using chronic comorbidity in a pandemic was perceived to be the fairest by the general public. Secondary objectives were to determine whether the public perceived it fair to provide preferential intensive care triage to vulnerable or disadvantaged people, and frontline healthcare workers. Methods A postal survey of 2000 registered voters randomly selected from the Australian Electoral Commission electoral roll was performed. The main outcome measures were respondents' fairness rating of four hypothetical intensive care triage methods that assess comorbidity (chronic medical conditions, long-term survival, function and frailty); and respondents' fairness rating of providing preferential triage to vulnerable or disadvantaged people, and frontline healthcare workers. Results The proportion of respondents who considered it fair to triage based on chronic medical conditions, long-term survival, function and frailty, was 52.1, 56.1, 65.0 and 62.4%, respectively. The proportion of respondents who considered it unfair to triage based on these four comorbidities was 31.9, 30.9, 23.8 and 23.2%, respectively. More respondents considered it unfair to preferentially triage vulnerable or disadvantaged people, than fair (41.8% versus 21.2%). More respondents considered it fair to preferentially triage frontline healthcare workers, than unfair (44.2% versus 30.0%). Conclusion Respondents in this survey perceived all four hypothetical methods to triage intensive care patients based on comorbidity in a pandemic disaster to be fair. However, the sizable minority who consider this to be unfair indicates that these triage methods could encounter significant opposition if they were to be enacted in health policy.

Money matters: a critique of 'informed financial consent'.

In recent years, concerns about the financial burdens of health care and growing recognition of the relevance of cost to decision making and patient experience have increasingly focused attention on financial 'transparency' and disclosure of costs to patients. In some jurisdictions, there have been calls not only for timely disclosure of costs information, but also for 'informed financial consent'. However, simply putting the 'financial' into 'informed consent' and invoking an informed consent standard for cost information encounters several ethical, legal, and practical difficulties. This article will examine the viability and desirability of 'informed financial consent', and whether it is possible to derive ideas from traditional informed consent that may improve decision making and the patient experience. We argue that, while there are important legal, ethical, and practical challenges to consider, some of the principles of informed consent to treatment can usefully guide financial communication. We also argue that, while medical practitioners (and their delegates) have an important role to play in bridging the gap between disclosure and enabling informed (financial) decision making, this must be part of a multi-faceted approach to financial communication that acknowledges the influence of non-clinical providers and other structural forces on discharging such obligations.

Daratumumab, cyclophosphamide, bortezomib, and dexamethasone for transplant-ineligible myeloma: AMaRC 03-16.

ABSTRACT: In newly diagnosed transplant-ineligible patients with myeloma, daratumumab has improved outcomes when added to the standard-of-care regimens. In a randomized trial, we tested whether similar improvements would be observed when daratumumab was added to the bortezomib, cyclophosphamide, and dexamethasone (VCD) regimen. Transplant-ineligible patients with untreated myeloma were randomized to receive VCD or VCD plus daratumumab (VCDD). A total of 121 patients were randomized: 57 in the VCD arm and 64 in the VCDD arm. Baseline characteristics were balanced between the 2 arms. The median progression-free survival (PFS) was 16.8 months (95% confidence interval [CI], 15.3-21.7) and 25.8 months (95% CI, 19.9-33.5) in the VCD and VCDD arms, respectively (hazard ratio, 0.67; log-rank test P = .066). In a preplanned analysis, it was demonstrated that the daratumumab-containing arm showed a significant improvement in PFS from 18 months onward, based on estimates at fixed time points after randomization. The proportions of patients who were progression-free at the following time points were: 18 months, 48% vs 68% (P = .0002); 24 months, 36% vs 52% (P = .0001); and 30 months, 27% vs 41% (P < .0001) in the VCD and VCDD arms, respectively. The best overall response and very good partial response rate were significantly higher in the daratumumab arm compared with the VCD and VCDD arms, respectively (65% vs 86%, P = .007; and 28% vs 52%, P = .009). Seventy-two percent of the VCDD patients completed the 9 cycles of induction therapy with no grade 3 or 4 peripheral neuropathy adverse events. This study supports VCDD as an option for the initial treatment of transplant-ineligible patients with myeloma. This trial was registered at the Australian New Zealand Clinical Trials Registry (ACTRN12617000202369).

Medicine in the marketplace: clinician and patient views on commercial influences on assisted reproductive technology.

RESEARCH QUESTION: What are the views and experiences of patient and expert stakeholders on the positive and negative impacts of commercial influences on the provision of assisted reproductive technology (ART) services, and what are their suggestions for governance reforms? DESIGN: Semi-structured interviews were conducted with 31 ART industry experts from across Australia and New Zealand and 25 patients undergoing ART from metropolitan and regional Australia, between September 2020 and September 2021. Data were analysed using thematic analysis. RESULTS: Expert and patient participants considered that commercial forces influence the provision of ART in a number of positive ways - increasing sustainability, ensuring consistency in standards and providing patients with greater choice. Participants also considered commercial forces to have a number of negative impacts, including increased costs to government and patients; the excessive use of interventions that lack sufficient evidence to be considered part of standard care; inadequately informed consent (particularly with regard to financial information); and threats to patient-provider relationships and patient-centred care. Participants varied in whether they believed that professional self-regulation is sufficient. While recognizing the benefits of commercial investment in healthcare, many considered that regulatory reforms, as well as organizational cultural initiatives, are needed as means to ensure the primacy of patient well-being. CONCLUSIONS: The views expressed in this study should be systematically and critically examined to derive insights into how best to govern ART. These insights may also inform the design and delivery of other types of healthcare that are provided in the private sector.

Perspectives on non-financial conflicts of interest in health-related journals: A scoping review.

The objective of this scoping review was to systematically review the literature on how non-financial conflicts of interest (nfCOI) are defined and evaluated, and the strategies suggested for their management in health-related and biomedical journals. PubMed, Embase, Scopus and Web of Science were searched for peer reviewed studies published in English between 1970 and December 2023 that addressed at least one of the following: the definition, evaluation, or management of non-financial conflicts of interest. From 658 studies, 190 studies were included in the review. nfCOI were discussed most commonly in empirical (22%; 42/190), theoretical (15%; 29/190) and "other" studies (18%; 34/190) - including commentary, perspective, and opinion articles. nfCOI were addressed frequently in the research domain (36%; 68/190), publication domain (29%; 55/190) and clinical practice domain (17%; 32/190). Attitudes toward nfCOI and their management were divided into two distinct groups. The first larger group claimed that nfCOI were problematic and required some form of management, whereas the second group argued that nfCOI were not problematic, and therefore, did not require management. Despite ongoing debates about the nature, definition, and management of nfCOI, many articles included in this review agreed that serious consideration needs to be given to the prevalence, impact and optimal mitigation of non-financial COI.

A Case Report of Quinine-Induced Thrombotic Microangiopathy Successfully Treated With Eculizumab.

Drug-induced thrombotic microangiopathy (DITMA) is a life-threatening condition which may be immune or nonimmune mediated. Quinine is the most implicated drug in immune-mediated DITMA. However, the optimal treatment is unclear. Complement inhibition by eculizumab has demonstrated success in many DITMA (e.g., carfilzomib, gemcitabine, and tacrolimus), but there are limited data in DITMA, including quinine-associated cases. A 55-year-old female was diagnosed with quinine-associated thrombotic microangiopathy (TMA), as confirmed by a positive quinine-dependent platelet-associated antibody. This was successfully treated with eculizumab with complete resolution of thrombocytopenia and anemia by 1 and 6 weeks. She required hemodialysis for a month and gained full recovery of renal function. We discuss various challenges with the diagnosis and management of DITMA. We also review published data on the use of eculizumab in various DITMA. Our case demonstrates successful treatment of quinine-induced TMA with eculizumab. We recommend further studies to assess the efficacy of complement inhibition in quinine and other DITMA.

Attitudes to End-of-Life Care and Voluntary Assisted Dying Amongst Members of the Australian Jewish community.

The implementation of voluntary assisted dying (VAD) in the Australian State of Victoria in 2019 has stimulated discussions about end-of-life care and dying in many communities. Various attempts have been made to represent the attitudes of the Jewish community, a distinct culturally and linguistically diverse (CALD) group, in terms that suggest a unified set of opinions that opposes VAD policies. This research aimed to explore attitudes to VAD in the context of end-of-life care held by members of the Victorian Jewish community. A descriptive qualitative methodological design was employed. Ten Victorians who identify as Jewish were recruited and participated in in-depth, semi-structured interviews. Reflexive thematic analysis was carried out on the transcripts to identify key themes, attitudes and preferences in relation to end-of-life care, death and dying, and VAD. Three themes were identified: "complexity and variation", "similarities", and "factors influencing attitudes to VAD and end-of-life care". A significant degree of diversity was apparent, ranging from highly supportive of VAD to advocacy for a total repeal of the policy. The results indicate that images of how Victorian Jewish individuals feel towards VAD based on essentialised notions about the community and belief systems are not supported by the evidence. In reality, considerable diversity of attitudes exists towards VAD and end-of-life care. We conclude that it is important that policymakers and members of the broader society avoid stereotypes that falsely characterise this specific community and, by implication, other CALD groups, particularly in terms that ignore internal diversity regarding belief systems, social attitudes and ethical perspectives.

Healthcare Resource Utilization and Cost Associated with Allogeneic Hematopoietic Stem Cell Transplantation: A Scoping Review.

This scoping review summarizes the evidence regarding healthcare resource utilization (HRU) and costs associated with allogeneic hematopoietic stem cell transplantation (allo-HSCT). This study was conducted in accordance with the Joanne Briggs Institute methodology for scoping reviews. The PubMed, Embase, and Health Business Elite Electronic databases were searched, in addition to grey literature. The databases were searched from inception up to November 2022. Studies that reported HRU and/or costs associated with adult (≥18 years) allo-HSCT were eligible for inclusion. Two reviewers independently screened 20% of the sample at each of the 2 stages of screening (abstract and full text). Details of the HRU and costs extracted from the study data were summarized, based on the elements and timeframes reported. HRU measures and costs were combined across studies reporting results defined in a comparable manner. Monetary values were standardized to 2022 US Dollars (USD). We identified 43 studies that reported HRU, costs, or both for allo-HSCT. Of these studies, 93.0% reported on costs, 81.4% reported on HRU, and 74.4% reported on both. HRU measures and cost calculations, including the timeframe for which they were reported, were heterogeneous across the studies. Length of hospital stay was the most frequently reported HRU measure (76.7% of studies) and ranged from a median initial hospitalization of 10 days (reduced-intensity conditioning [RIC]) to 73 days (myeloablative conditioning). The total cost of an allo-HSCT ranged from $63,096 (RIC) to $782,190 (double umbilical cord blood transplantation) at 100 days and from $69,218 (RIC) to $637,193 at 1 year (not stratified). There is heterogeneity in the reporting of HRU and costs associated with allo-HSCT in the literature, making it difficult for clinicians, policymakers, and governments to draw definitive conclusions regarding the resources required for the delivery of these services. Nevertheless, to ensure that access to healthcare meets the necessary high cost and resource demands of allo-HSCT, it is imperative for clinicians, policymakers, and government officials to be aware of both the short- and long-term health resource requirements for this patient population. Further research is needed to understand the key determinants of HRU and costs associated with allo-HSCT to better inform the design and delivery of health care for HSCT recipients and ensure the quality, safety, and efficiency of care.

Choreographing a good death: Carers' experiences and practices of enacting assisted dying.

The proliferation of assisted dying legislative reforms globally is a significant change in the social and medico-legal landscape of end-of-life care. Understanding the impacts of these legislative reforms on family members who care for a dying person is vital, yet under-theorised in research. In this article, drawing on semi-structured interviews with 42 carers for a person who has sought assisted dying in Australia, and extending ideas of ontological choreography we explore the new and complex choreographies enacted by carers in their endeavour to arrange a 'good death' for the dying person. We find that desires to fulfil the dying person's wishes are often accompanied by normative pressures, affective tensions and complexities in bereavement. Enacting assisted dying requires carers to perform a repertoire of highly-staged practices. Yet, institutional obstacles and normative cultural scripts of dying can constrain carer assisted dying practices. Understanding the nuances of carers' experiences and how they navigate this new end-of-life landscape, we argue, provides critical insights about how assisted dying legislation is producing new cultural touchpoints for caring at the end of life. Moreover, we show how emerging cultural scripts of assisted dying are impacting in the lives of these carers.

Moral justification for the use of 'add-ons' in assisted reproductive technology: experts' views and experiences.

RESEARCH QUESTION: What factors do assisted reproductive terchnology (ART) providers take into account when they make decisions about offering 'add-ons'? DESIGN: A qualitative analysis of interviews with 31 ART professionals, focusing on their views and experiences in relation to add-ons, including the factors that are considered when doctors make decisions about their use. RESULTS: The participants reported that a range of considerations are taken into account when it comes to justifying the use of a particular add-on in a given circumstance, including the likelihood of benefit and harm, patients' perceived psychological needs and preferences, and organizational expectations. Importantly, patient preferences, psychological factors and low risk of harm appear to be stronger motivations than increasing the likelihood of a live birth or the desire to innovate. CONCLUSIONS: These findings suggest that it cannot be taken for granted that add-ons and innovation are closely linked. One possible response to this would be regulatory reform; for example, only allowing 'unproven' add-ons to be used in the context of formal scientific evaluation. Alternatively, it could be made clear that add-ons that are not undergoing formal evaluation have more in common with other therapies lacking a clear evidence base, such as complementary and alternative medicines, than with conventional medical practice. Practices in relation to add-ons may also require a focus on the responsibilities of corporations, and the standards applying to purveyors of consumer goods and services.

Repeated COVID-19 vaccination to maximum antibody response yields very low mortality and hospitalisation rates in patients with CLL and MBL.

We analysed COVID-19 infection outcomes of 129/241 chronic lymphocytic leukaemia (CLL) (53.9%) and 22/55 monoclonal B-lymphocytosis (MBL) (40.0%) patients following multiple vaccine doses aiming for maximum measured anti-spike antibody response. Throughout the pandemic to date, there were 8/129 CLL (6.2%) patients hospitalised, with one death (0.8%). No MBL patients were hospitalised or died. CLL patients with COVID-19 had lower anti-spike levels (3778.8 AU/mL) than those without (13 486.8 AU/mL; p = 0.0061). Anti-nucleocapsid antibody was detected in 29.8% within 2 months and 17.5% >6 months. Of COVID-19-infected CLL patients, 47.3% received anti-viral therapy. A multiple vaccine dosing strategy to achieve measured maximum antibody is highly effective in preventing severe COVID-19.

Therapeutic misunderstandings in modern research.

Clinical trials play a crucial role in generating evidence about healthcare interventions and improving outcomes for current and future patients. For individual trial participants, however, there are inevitably trade-offs involved in clinical trial participation, given that trials have traditionally been designed to benefit future patient populations rather than to offer personalised care. Failure to understand the distinction between research and clinical care and the likelihood of benefit from participation in clinical trials has been termed the 'therapeutic misconception'. The evolution of the clinical trials landscape, including greater integration of clinical trials into healthcare and development of novel trial methodologies, may reinforce the significance of the therapeutic misconception and other forms of misunderstanding while at the same time (paradoxically) challenging its salience. Using cancer clinical trials as an exemplar, we describe how methodological changes in early- and late-phase clinical trial designs, as well as changes in the design and delivery of healthcare, impact upon the therapeutic misconception. We suggest that this provides an impetus to re-examine the ethics of clinical research, particularly in relation to trial access, participant selection, communication and consent, and role delineation.

Clinician perspectives on voluntary assisted dying and willingness to be involved: a multisite, cross-sectional survey during implementation in New South Wales, Australia.

BACKGROUND: In the context of nationwide law reform, New South Wales (NSW) became the last state in Australia to legalise voluntary assisted dying (VAD) - commencing 28 November 2023. Clinicians have divergent views regarding VAD, with varying levels of understanding, support, and willingness to be involved, and these may have a significant impact on the successful implementation. AIMS: To understand levels of support, understanding and willingness to be involved in VAD among clinical staff across NSW during implementation of VAD. METHODS: A multisite, cross-sectional online survey of clinicians across four local health districts, assessing relevant demographics, awareness of and support for VAD legislation and willingness to be involved in different levels of VAD-related clinical activities. RESULTS: A total of 3010 clinical staff completed the survey. A majority of participants were aware of VAD legislation in NSW (86.35%) and supportive of it (76%), with nursing and allied health clinicians significantly more likely than medical specialists to express support. Among medical specialists, support was statistically more likely in those who did not care for patients at the end of life and those with limited knowledge of the legislation. Willingness of medical specialists to perform key roles was significantly lower, with 41.49% willing to act in coordinating or consulting roles, and only 23.21% as administering practitioners. CONCLUSIONS: The majority of clinical staff surveyed across NSW supported VAD legislation. While many eligible clinicians were reluctant to be actively involved, sufficient numbers appear willing to provide VAD services, indicating that successful implementation should be possible.