Biobank donation in search of public benefits and the potential impact of intellectual property rights over access to health-technologies developed: A focus on the bioethical implications.

The availability of biomaterials is a key component of health research and the development of new health-technologies (including, diagnostics, medicines, and vaccines). People are often encouraged by biobanks to donate samples altruistically to such biobanks. While empirical evidence suggests many donors are motivated by the desire to contribute towards developing new health-technologies for society. However, a tension can arise as health-technologies whose development is contributed to by donors' biomaterials will often be protected by intellectual property rights (IPRs), including patents. Patents give rightsholders control over how patented technologies are used and can be used in a way that impedes public access to technologies developed. Yet, there are no binding European legal obligations mandating disclosure to donors of how IPRs can operate over downstream health-technologies and how they could impact access to health-technologies developed, nor are there legally binding obligations to ensure public accessibility of technologies developed. Focusing on the bioethical implications posed, this article argues that the current situation can impact donors' autonomy and dignity interests. A more holistic approach is needed for biobank donation, which embeds a consideration of donors' expectations/interests from the point of donation through to how such samples are used and how health-technologies developed are accessed. We put forward avenues that seek to address such issues.

Replacing Plain Radiograph with ultra-low dose CT thorax in cystic fibrosis (CF) in the era of CFTR modulation and its impact on cumulative effective dose.

BACKGROUND: Medical radiation exposure is of increasing concern in patients with cystic fibrosis (PWCF) due to improving life expectancy. We aimed to assess and quantify the cumulative effective dose (CED) in PWCF in the context of CFTR-modulator therapy and the advancement of dose reduction techniques. METHODS: We performed a retrospective observational study in a single University CF centre over a 11-year period. We included PWCF, aged over 18 years who exclusively attended our institution. Relevant clinical data (demographics, transplantation history and modulator status) and radiological data (modality, quantity, and radiation exposure measured as CED) were collected. For those on modulator therapy the quantified imaging and radiation data was dichotomised into pre-and-post therapy periods. RESULTS: The study included 181 patients: 139 on CFTR modulator therapy, 15 transplant recipients and 27 with neither exposure. 82% of patients received <25 mSv over the study period. Mean study duration was 6.9 ± 2.6 years pre-modulation and 4.2 ± 2.6 years post-modulation. Pre-modulation CT contributed 9.6% of total chest imaging (n = 139/1453) and 70.9% of the total CED. Post-modulation CT use increased contributing 42.7% of chest imaging (n = 444/1039) and comprised 75.8% of CED. Annual CED was 1.55 mSv pre and 1.36 mSv post modulation (p = 0.41). Transplant recipients had an annual CED of 64 ± 36.1mSv. CONCLUSION: Chest CT utilisation for PWCF is rising in our institution, replacing chest radiography amidst CFTR-modulation. Despite the increasing use of CT, no significant radiation dose penalty was observed with a reduction in mean annual CED, primarily due to the influence of CT dose reduction strategies.

Analysis of the institutional landscape and proliferation of proposals for global vaccine equity for COVID-19: too many cooks or too many recipes?

This article outlines and compares current and proposed global institutional mechanisms to increase equitable access to COVID-19 vaccines, focusing on their institutional and operational complementarities and overlaps. It specifically considers the World Health Organization's (WHO's) COVAX (COVID-19 Vaccines Global Access) model as part of the Access to COVID-19 Tools Accelerator (ACT-A) initiative, the WHO's COVID-19 Technology Access Pool (C-TAP) initiative, the proposed TRIPS (Trade-Related Aspects of Intellectual Property Agreement) intellectual property waiver and other proposed WHO and World Trade Organization technology transfer proposals. We argue that while various individual mechanisms each have their specific individual merits-and in some cases weaknesses-overall, many of these current and proposed mechanisms could be highly complementary if used together to deliver equitable global access to vaccines. Nonetheless, we also argue that there are risks posed by the proliferation of proposals in this context, including the potential to disperse stakeholder attention or to delay decisive action. Therefore, we argue that there is now a clear need for concerted global multilateral action to recognise the complementarities of specific models and to provide a pathway for collaboration in attaining global equitable access to vaccines. The institutional infrastructure or proposals to achieve this amply exist at this point in time-but much greater cooperation from industry and clear, decisive and coordinated action from states and international organisations are urgently needed.

Should states restrict recipient choice amongst relevant and available COVID-19 vaccines?

Several COVID-19 vaccinations have been authorised worldwide. Whilst some vaccines are contraindicated for certain age groups or health conditions, there are often multiple clinically suitable authorised vaccine brands available. Few states have allowed recipients to choose amongst them, though there are multiple reasons why choice would be valued. We consider the policy justifications for state controls on recipient choice amongst COVID-19 vaccine brands, focusing on European countries and drawing on the UK context as an example. We contrast justifications for not offering choice at the height of the early pandemic crisis, and as some states seek to de-escalate their response and transition towards living with COVID-19. We argue that in the latter context public expectations of choice between available vaccine brands and platforms may rise, but that several considerations may justify continued restrictions on choice. A key factor which states should continue to take into consideration is the global nature of the pandemic. Insofar as offering recipient choice at a national level might exacerbate global inequity in vaccine distribution, states retain a normative and legal justification for restricting choice amongst available and clinically suitable vaccine brands.

Analysis of supervisory interventions in a transdisciplinary youth mental health service.

Heron's six category intervention framework, delineating key intervention styles within helping relationships, was developed to guide therapeutic work but has also been applied to supervisory work. Some previous research has investigated this framework's relevance for practice but there has been no previous research analyzing its application to supervision. Following a longitudinal, naturalistic, observational case study design, this study aimed to analyze and illustrate the usefulness of the six category intervention framework as a guide for supervisory practice. Individual meetings of five supervisory dyads in an Irish transdisciplinary, brief-intervention, public youth mental health service were recorded for 6 months. A codebook applying Heron's intervention framework to supervision was developed inductively and deductively, good interrater reliability was established, and transcripts of 20 of the dyads' supervision meetings were coded and analyzed. Informative interventions were found to be most dominant, followed by supportive and prescriptive interventions. Catalytic interventions were seldom used, and confronting and cathartic interventions were rare. It is concluded that the high use of informative interventions fitted the needs of early-career supervisees and the high pace of a brief-intervention service. However, a greater balance of interventions is recommended in supervisory practice, particularly more catalytic, cathartic, and confronting interventions, in order to foster supervisee autonomy and capability. Detailed illustrations of seldom-used interventions are presented and analyzed, and opportunities for their greater use are considered. It is concluded that the six category intervention framework offers a useful guide for supervisor training and ongoing development of supervisory practice in workplace settings. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Research engagement by British early-career practitioners in nephrology: a multidisciplinary survey.

OBJECTIVES: To establish barriers and motivators underlying research engagement among early-career practitioners in nephrology across the UK, in order to guide potential interventions to enhance research involvement in renal units. DESIGN: Cross-sectional online survey employing a range of free-text, Likert scale and binomial/multiple-choice responses, distributed via mailing lists and social media. Topics covered research experience, research involvement and barriers, impact of COVID-19 and strategies to improve research engagement. Thematic analysis was used to assess free-text responses. SETTING: Renal units throughout the UK. PARTICIPANTS: Non-consultant healthcare staff self-identifying as working in nephrology were included (n=211), with responses from non-UK respondents or consultant nephrologists excluded (n=12). RESULTS: Responses were received from across the multidisciplinary team (physicians (n=83) and nurses (n=83)) and other allied health professionals (n=45). Most were aware of ongoing local research, but under half of them were actively involved. Multivariate analysis indicated employment as a physician, protected time for research activity and provision of appropriate training were associated with greater research experience and output. There was general enthusiasm to undertake research, but perceived barriers included insufficient staffing, lack of time, funding and encouragement. COVID-19 was felt to have further impacted negatively upon opportunities. Among the suggested strategies to promote engagement, mentorship and an online research resource were felt to be of most interest. CONCLUSIONS: In the first survey of this type in nephrology, we demonstrate differences across the multidisciplinary spectrum in perceived research experience and accessibility, which have been worsened by COVID-19. Our findings will guide strategies to broaden engagement in early-career practitioners and serve as a baseline to assess the impact of these interventions.

Perioperative Management of the Fontan Patient for Cardiac and Noncardiac Surgery.

The Fontan circulation is the single-ventricle approach to surgical palliation of complex congenital heart disease wherein biventricular separation and function cannot be safely achieved. Incremental improvements in this surgical technique, along with improvements in the long-term medical management of these patients, have led to greater survival of these patients and a remarkably steady increase in the number of adults living with this unusual circulation and physiology. This has implications for healthcare providers who now have a greater chance of encountering Fontan patients during the course of their practice. This has particularly important implications for anesthesiologists because the effects of their interventions on the finely balanced Fontan circulation may be profound. The American Heart Association and American College of Cardiology recommend that, when possible, elective surgery should be performed in an adult congenital heart disease center, although this may not be feasible in the provision of true emergency care. This review article summarizes the pathophysiology pertinent to the provision of anesthesia in this complex patient group and describes important modifications to anesthetic technique and perioperative management.

Kidney disease risk factors do not explain impacts of low dietary protein on kidney function and structure.

The kidneys balance many byproducts of the metabolism of dietary components. Previous studies examining dietary effects on kidney health are generally of short duration and manipulate a single macronutrient. Here, kidney function and structure were examined in C57BL/6J mice randomized to consume one of a spectrum of macronutrient combinations (protein [5%-60%], carbohydrate [20%-75%], and fat [20%-75%]) from weaning to late-middle age (15 months). Individual and interactive impacts of macronutrients on kidney health were modeled. Dietary protein had the greatest influence on kidney function, where chronic low protein intake decreased glomerular filtration rates and kidney mass, whereas it increased kidney immune infiltration and structural injury. Kidney outcomes did not align with cardiometabolic risk factors including glucose intolerance, overweight/obesity, dyslipidemia, and hypertension in mice with chronic low protein consumption. This study highlights that protein intake over a lifespan is an important determinant of kidney function independent of cardiometabolic changes.

Development and implementation of an ultralow-dose CT protocol for the assessment of cerebrospinal shunts in adult hydrocephalus.

BACKGROUND: Cerebrospinal fluid shunts in the treatment of hydrocephalus, although associated with clinical benefit, have a high failure rate with repeat computed tomography (CT) imaging resulting in a substantial cumulative radiation dose. Therefore, we sought to develop a whole-body ultralow-dose (ULD) CT protocol for the investigation of shunt malfunction and compare it with the reference standard, plain radiographic shunt series (PRSS). METHODS: Following ethical approval, using an anthropomorphic phantom and a human cadaveric ventriculoperitoneal shunt model, a whole-body ULD-CT protocol incorporating two iterative reconstruction (IR) algorithms, pure IR and hybrid IR, including 60% filtered back projection and 40% IR was evaluated in 18 adult patients post new shunt implantation or where shunt malfunction was suspected. Effective dose (ED) and image quality were analysed. RESULTS: ULD-CT permitted a 36% radiation dose reduction (median ED 0.16 mSv, range 0.07-0.17, versus 0.25 mSv (0.06-1.69 mSv) for PRSS (p = 0.002). Shunt visualisation in the thoracoabdominal cavities was improved with ULD-CT with pure IR (p = 0.004 and p = 0.031, respectively) and, in contrast to PRSS, permitted visualisation of the entire shunt course (p < 0.001), the distal shunt entry point and location of the shunt tip in all cases. For shunt complications, ULD-CT had a perfect specificity. False positives (3/22, 13.6%) were observed with PRSS. CONCLUSIONS: At a significantly reduced radiation dose, whole body ULD-CT with pure IR demonstrated diagnostic superiority over PRSS in the evaluation of cerebrospinal fluid shunt malfunction.

Patents, Governance and Control: Ethics and the Patentability of Novel Beings and Advanced Biotechnologies in Europe.

This article focuses primarily on to what extent novel beings, and particularly, beings which display something akin to human consciousness or agency would be (or should be) patentable under current European patent law. Patents grant the patent holder a right to exclude others from using the patented invention for the period of patent grant (usually 20 years). This allows the patent holder to control how that invention can or cannot be used by others downstream, granting patent holders a governance like function over the patented technology for the duration of the patent. Accordingly, the potential for patentability of novel beings gives rise to a myriad of ethical issues including: to what extent is it appropriate for patent holders to retain and exercise patents over "novel beings"; how issues of "agency" displayed by any "novel beings" would fit within the current patent framework, if at all; and to what extent existing exclusions from patentability might exclude patents on "novel beings" or whether changes within patent law may be needed if patents in relation to "novel beings" are deemed ethically problematic. This article focuses on such issues, and in doing so, also sheds light on the role of ethical issues within the patenting of advanced biotechnologies more generally.

A Review of Heart Transplantation for Adults With Congenital Heart Disease.

As techniques for corrective and palliative surgery in congenital heart disease improve, the number of patients surviving to become adults with congenital heart disease (ACHD) has increased. A significant proportion of these patients will progress to develop advanced heart failure, the symptoms of which vary, complicating prediction of life expectancy. Unlike acquired heart failure, there is a lack of evidence-based treatments with which to relieve symptoms and prolong survival. As a result, a number of ACHD patients will proceed to heart transplantation. Referral for transplantation should be considered early, given the difficulties with prognostication, and should take place in a center with surgical and medical expertise in the management of ACHD patients and transplantation. In addition to assessing contraindications to heart transplantation for the general population, factors specific to ACHD should be considered. These include pulmonary hypertension, cyanosis, liver disease, previous surgeries, and the degree of allosensitization. Once listed for transplantation, ACHD patients spend longer on the waitlist, and are more likely to die or be delisted than their non-ACHD counterparts. Mechanical circulatory support is used less commonly as a bridge to transplantation given the difficulties with implantation and unfamiliarity of use. Recent evidence suggests that with increased experience and early consideration, mechanical circulatory support can be used successfully as a bridging therapy. Despite a higher early mortality, long-term survival is greater for ACHD patients after transplant due to younger age and relative lack of comorbidities. With early referral, careful assessment of each individual's unique anatomy and physiology, and care in a center experienced with ACHD patients and transplantation, outcomes will continue to improve.

Global equitable access to vaccines, medicines and diagnostics for COVID-19: The role of patents as private governance.

In June 2020, Gilead agreed to provide the USA with 500 000 doses of remdesivir-an antiviral drug which at that time was percieved to show promise in reducing the recovery time for patients with COVID-19. This quantity represented Gilead's then full production capacity for July and 90% of its capacity for August and September. Similar deals are evident around access to proposed vaccines for COVID-19, and such deals are only likely to increase. These attempts to secure preferential access to medicines and vaccines, so-called vaccine/treatment nationalism, jeopardise supplies of life-saving treatments and vaccines available elsewhere, and jeopardise global equitable distribution of such vaccines/treatments more generally. Much of the focus to date has been on States' role in negotiating such deals. However, such developments also demonstrate the power patent holders have in controlling access to life-saving healthcare, determining who obtains access first and at what price. This article argues that the extent of control currently given to patent holders for COVID-19 must be questioned. This article demonstrates that patents have significant implications for healthcare acting as private governance tools over patented inventions. It is only by greater probing of patent holders' role in delivering access to medicines, diagnostics and vaccines for COVID-19 that equitable global equitable access can be achieved.

Comparing erector spinae plane block with serratus anterior plane block for minimally invasive thoracic surgery: a randomised clinical trial.

BACKGROUND: Minimally invasive thoracic surgery causes significant postoperative pain. Erector spinae plane (ESP) block and serratus anterior plane (SAP) block promise effective thoracic analgesia compared with systemically administered opioids, but have never been compared in terms of terms of quality of recovery and overall morbidity after minimally invasive thoracic surgery. METHODS: Sixty adult patients undergoing minimally invasive thoracic surgery were randomly assigned to receive either single-shot ESP or SAP block before surgery using levobupivacaine 0.25%, 30 ml. The primary outcome was quality of patient recovery at 24 h, using the Quality of Recovery-15 (QoR-15) scale. Secondary outcomes included area under the curve (AUC) of pain verbal rating scale (VRS) over time, time to first opioid analgesia, postoperative 24 h opioid consumption, in-hospital comprehensive complication index (CCI) score and hospital stay. RESULTS: The QoR-15 score was higher among ESP patients compared with those in the SAP group, mean (standard deviation): 114 (16) vs 102 (22) (P=0.02). Time (min) to first i.v. opioid analgesia in recovery was 32.6 (20.6) in ESP vs 12.7 (9.5) in SAP (P=0.003). AUC at rest was 92 (31) mm h-1vs 112 (35) in ESP and SAP (P=0.03), respectively, whereas AUC on deep inspiration was 107 mm h-1 (32) vs 129 (32) in ESP and SAP (P=0.01), respectively. VRS pain on movement in ESP and SAP at 24 h was, median (25-75% range): 4 (2-4) vs 5 (3-6) (P=0.04), respectively. Opioid consumption at 24 h postoperatively was 29 (31) vs 39 (34) (P=0.37). Median (25-75%) CCI in ESP and SAP was 1 (0-2) vs 4 (0-26) (P=0.03), whereas hospital stay was 3 (2-6) vs 6 (3-9) days (P=0.17), respectively. CONCLUSION: Compared with SAP, ESP provides superior quality of recovery at 24 h, lower morbidity, and better analgesia after minimally invasive thoracic surgery. CLINICAL TRIAL REGISTRATION: NCT03862612.

Responsiveness and the Role of Rights in Medical Law: Lessons from Montgomery†.

Over time, medical law has moved away from paternalism in favour of an approach grounded in patients' rights. Using Montgomery v Lanarkshire Health Board (2015) as a case study, we offer a deeper analysis of this emerging approach. We argue that patients' rights should be evaluated in terms of their contribution to making medical law more socially responsive, by developing it to give effect to social needs and aspirations pertaining to health care. Although rights can play an important role in achieving social responsiveness, they also carry the risk of entrenching approaches unrepresentative of patients' actual needs and empirical realities. This is evident in Montgomery, where the law, despite being derived from General Medical Council (GMC) guidance, has effects that differ significantly from the GMC's goals. Drawing on socio-legal literature, we outline a new approach for guiding the use of rights in medical law focused on the functional consequences of rights in facilitating patients' aspirations, and the capacity of rights to respond to social and institutional contexts in which medical interaction occurs. We conclude by showing how this approach, applied to informed consent, would produce a different and arguably a superior duty, providing a sounder basis for responding to patient needs.

Big Data Governance Needs More Collective Responsibility: The Role of Harm Mitigation in the Governance of Data Use in Medicine and Beyond.

Harms arising from digital data use in the big data context are often systemic and cannot always be captured by linear cause and effect. Individual data subjects and third parties can bear the main downstream costs arising from increasingly complex forms of data uses-without being able to trace the exact data flows. Because current regulatory frameworks do not adequately address this situation, we propose a move towards harm mitigation tools to complement existing legal remedies. In this article, we make a normative and practical case for why individuals should be offered support in such contexts and how harm mitigation tools can achieve this. We put forward the idea of 'Harm Mitigation Bodies' (HMBs), which people could turn to when they feel they were harmed by data use but do not qualify for legal remedies, or where existing legal remedies do not address their specific circumstances. HMBs would help to obtain a better understanding of the nature, severity, and frequency of harms occurring from both lawful and unlawful data use, and they could also provide financial support in some cases. We set out the role and form of these HMBs for the first time in this article.

Ionizing Radiation Dose Exposure to the Ocular Region of Pain Physicians During C-arm Guided Pain Interventions.

BACKGROUND: The growth of interventional pain medicine in recent years has resulted in more procedures being carried out under fluoroscopic guidance. The proximity of the pain physician (PP) to ionization radiation (IR) potentially increases the risk of radiation exposure to the ocular region. A European directive has reduced the limits of occupational ocular dose 7.5-fold. OBJECTIVES: The objectives of this study are to quantify the typical IR exposure in the ocular region of PP and to compare it to recommended international guidelines. STUDY DESIGN: Three consultants involved in the pain unit service were enrolled in the study to reflect the dose implications involved with different caseloads, training obligations, and procedure types. All 3 consultants were experienced primary operators. SETTING: The study was undertaken at the pain management suite in the South Infirmary Victoria University Hospital (SIVUH). Annually, this unit performs 2,800 fluoroscopic guide pain procedures. METHODS: Thermoluminescent dosimeters (TLDs) calibrated to measure eye lens doses [Hp (0.07)] and whole-body doses (WBDs) were fitted to 3 pain consultants while they undertook imaging-guided pain procedures using mobile C-arm fluoroscopy over a 3-month period. The duration of radiation exposure, screening time (seconds), and procedure type were recorded. Radiation dose was calculated to estimate the effective radiation dose to the ocular region using (i) dose-area product (DAP) in milliGray per centimeter squared (mGycm2) and (ii) Air Kerma (AK) values in mGy. RESULTS: IR doses were effectively recorded in 682 cases over 3 months and the data extrapolated. The estimated annual lens dose experienced by pain physicians performing fluoroscopy-guided procedures is less than the recommended international guidelines. A significant linear relationship between screening time and IR exposure was estimated (rs = 0.93, P < 0.01). LIMITATIONS: In many centers, including our own, fluoroscopy procedures are undertaken by nonconsultant staff. Therefore, a small single-center cohort recruiting experienced consultant staff and not including pain fellows or registrars/residents with varying levels of experience is a limitation. CONCLUSION: While IR to the ocular region was significantly less than the recommended European safety guidelines, the annual dose needs to be confirmed in pain physicians with a lesser degree of clinical experience. KEY WORDS: Ionizing radiation, ocular, radiation protection, pain medicine, interventional.

The Relationship Between Dietary Macronutrients and Hepatic Telomere Length in Aging Mice.

Macronutrients and dietary energy influence aging, age-related health, and life span. Reduction in telomere length has been proposed as one mechanism for aging. Therefore, this study investigated the effects of varying ratios of dietary macronutrients and energy on telomere length in older adult mice. C57Bl/6 mice were fed ad libitum their entire life on one of 25 diets varying in protein, carbohydrates, fat, and energy. Average telomere length ratio (ATLR) was measured by polymerase chain reaction in livers of a subset of 161 mice aged 15 months. There was a significant positive relationship between ATLR and carbohydrate intake and a negative relationship with protein intake, but no relationships with fat or energy intake. Analysis using the Geometric Framework and Generalized Additive Models confirmed that carbohydrate intake was positively associated with ATLR, while the longest ATLR was achieved by mice restricted to low protein, high carbohydrate diets. ATLR distribution across the diets was parallel to median life-span results previously published. ATLR was associated with blood levels of some amino acids (asparagine, glutamate, taurine) but not with blood levels of fatty acids, hepatic mitochondrial function, or nutrient sensing pathways. In conclusion, mice on low protein, high carbohydrate diets have the longest hepatic telomeres and longest life span.

Long-term Dietary Macronutrients and Hepatic Gene Expression in Aging Mice.

Nutrition influences both hepatic function and aging, but mechanisms are poorly understood. Here, the effects of lifelong, ad libitum-fed diets varying in macronutrients and energy on hepatic gene expression were studied. Gene expression was measured using Affymetrix mouse arrays in livers of 46 mice aged 15 months fed one of 25 diets varying in protein, carbohydrates, fat, and energy density from 3 weeks of age. Gene expression was almost entirely influenced by protein intake. Carbohydrate and fat intake had few effects on gene expression compared with protein. Pathways and processes associated with protein intake included those involved with mitochondrial function, metabolic signaling (PI3K-Akt, AMPK, mTOR) and metabolism of protein and amino acids. Protein intake had variable effects on genes associated with regulation of longevity and influenced by caloric restriction. Among the genes of interest with expression that were significantly associated with protein intake are Cth, Gls2, Igf1, and Nnmt, which were increased with higher protein intake, and Igf2bp2, Fgf21, Prkab2, and Mtor, which were increased with lower protein intake. Dietary protein has a powerful impact on hepatic gene expression in older mice, with some overlap with genes previously reported to be involved with regulation of longevity or caloric restriction.