Ethical argument for establishing good manufacturing practice for phage therapy in the UK.

Antimicrobial resistance (AMR) poses an increasing threat to patient care and population health and there is a growing need for novel therapies to tackle AMR. Bacteriophage (phage) therapy is a re-emerging antimicrobial strategy with the potential to transform how bacterial infections are treated in patients and populations. Currently, in the UK, phages can be used as unlicensed medicinal products on a 'named-patient' basis. We make an ethical case for why it is crucially important for the UK to invest in Good Manufacturing Practice (GMP) for both ongoing unlicensed and future licensed phage therapy. Access to phages produced to GMP (GMP phages) will ensure effective patient care and better outcomes as well as health systems benefits. The UK also has the potential to become a global leader in the timely and cost-efficient manufacturing and supply of a therapy that meets internationally recognised standards.

One virus, many lives: a qualitative study of lived experiences and quality of life of adults from diverse backgrounds living in the UK during the COVID-19 pandemic.

OBJECTIVES: The coronavirus disease 2019 (COVID-2019) pandemic has had far-reaching consequences for people's lives. In the UK, more than 23 million have been infected and nearly 185 000 have lost their lives. Previous research has looked at differential outcomes of COVID-19, based on socio-demographic factors such as age, sex, ethnicity and deprivation. We conducted a qualitative study with a diverse sample of adults living in the UK, to understand their lived experiences and quality of life (QoL) during the pandemic. METHODS: Participants were recruited with the help of civil society partners and community organisations. Semi-structured interviews were conducted between May and July 2021. Interviews were recorded with permission and transcribed. Transcripts were analysed following an inductive analytical approach as outlined in the Framework Method. RESULTS: 18 participants (≥16 years) representing different ethnicities, sexes, migration and employment statuses and educational qualifications took part. Five key themes and 14 subthemes were identified and presented using the QoL framework. The five key themes describe how COVID-19 affected the following aspects of QoL: (1) financial and economic, (2) physical health, (3) social, (4) mental health and (5) personal fulfilment and affective well-being. The narratives illustrated inequities in the impact of COVID-19 for individuals with intersecting social, economic, and health disparities. CONCLUSION: Our findings demonstrate the multidimensional and differential impact of the pandemic on different population groups, with most of the negative economic impacts being borne by people in low-paid and insecure jobs. Similarly, adverse social, physical and mental health impacts particularly affected people already experiencing displacement, violence, physical and mental illnesses or even those living alone. These findings indicate that COVID-19 impacts have been influenced by intersecting health and socioeconomic inequalities, which pre-existed. These inequities should be taken into consideration while designing pandemic recovery and rebuilding packages.

The Future of Clinical Phage Therapy in the United Kingdom.

Bacteriophage (phage) therapy is a promising alternative antimicrobial strategy with the potential to transform the way bacterial infections are treated. In the United Kingdom, phages are classed as a biological medicine. Although no phages are licensed for UK use, they may be used as unlicensed medicinal products where licensed alternatives cannot meet a patient's clinical needs. In the last 2 years, 12 patients in the UK have received phage therapy, and there is burgeoning clinical interest. Currently, clinical phage provision in the UK is ad hoc and relies upon networking with international sources of phages. The provision of phage therapy in the UK will not progress beyond an increasing number of ad hoc cases until an onshore sustainable and scalable source of well-characterised phages manufactured in accordance with Good Manufacturing Practice (GMP) is established. Here, we present an exciting new collaboration between UK Phage Therapy, the Centre for Phage Research at University of Leicester, CPI, and Fixed Phage. These partners, and others as we develop, will establish sustainable, scalable, and equitable phage therapy provision in the UK. We set out a vision for how phage therapy will be integrated into the NHS and healthcare more broadly, including the complementarity between licensed (cocktail) and unlicensed (personalised) phage preparations. Key elements of phage therapy infrastructure in the UK will be GMP phage manufacturing, a national phage library, and a national clinical phage centre. Together, this infrastructure will support NHS microbiology departments to develop and oversee phage therapy provision across the UK. As it will take time to deliver this, we also describe considerations for clinicians seeking to use unlicensed phage therapy in the interim. In summary, this review sets out a roadmap for the delivery of clinical phage therapy to the UK, the benefits of which we hope will reverberate for patients for decades to come.

Managing Patient and Clinician Expectations of Phage Therapy in the United Kingdom.

Bacteriophage (phage) therapy is a promising alternative antimicrobial approach which has the potential to transform the way we treat bacterial infections. Phage therapy is currently being used on a compassionate basis in multiple countries. Therefore, if a patient has an antibiotic refractory infection, they may expect their clinician to consider and access phage therapy with the hope of improvement. The expectations of clinicians may be similar and may also include expectations around data collection. However, there are multiple biological and practical barriers to fulfilling patient and clinician expectations. While it is possible to access phage therapy, the path to acquisition is not straightforward and expectations therefore need to be managed appropriately to avoid raising false hope and undermining confidence in phage therapy. Phage scientists have an important contribution to make in educating clinicians and the broader public about phage therapy. However, it is clinicians that are responsible for managing the expectations of their patients and this relies on clear communication about the barriers and limitations.

The balancing of virtues-Muslim perspectives on palliative and end of life care: Empirical research analysing the perspectives of service users and providers.

In this paper, I will share findings from a qualitative study that offers a thematic analysis of 76 interviews with Muslim patients and families as well as doctors, nurses, allied health professionals, chaplains and community faith leaders across the United Kingdom. The data show that for many Muslims, Islam-its texts and lived practice-is of central importance when they are deliberating about death and dying . Central to these deliberations are virtues rooted within Islamic theology and ethics, the traditions of adab (virtue) and aqhlaq (proper conduct). Themes analysed include theological and moral understandings around the virtues of hope and acceptance. The study provides an analysis of these themes in relation to the experiences of Muslim patients and families arriving at meaning making around death and dying and how this interfaces with their interaction with biomedicine and healthcare. The study shows that the juxtaposition of different values and moral frameworks require careful negotiation when Muslim patients and families encounter the healthcare system. The study also describes how healthcare professionals and staff of other faiths and no faith encounter Muslim beliefs and practices, and the challenges they face in interpreting virtues and values rooted in faith, especially when these are perceived to be mutually opposed or inconsistent.

The practical, ethical and legal reasons why patients should not be transferred between NHS trusts for phage therapy.

Bacteriophages (phages) are naturally occurring viruses of bacteria that have a long history of use as antimicrobials, known as phage therapy. The antibiotic resistance crisis has driven renewed interest in phage therapy, which has been used on an unlicensed compassionate basis in various Western contexts. The option to use unlicensed medicines exists to allow clinicians to respond to genuine clinical needs arising in their own patients. However, in the UK some clinicians may, in the absence of suitable patients of their own, seek to transfer patients from other NHS trusts into their own Trust. This article sets out why patient transfer is not necessary and the practical, ethical and legal reasons why patients should not be transferred between NHS Trusts for phage therapy. Phage preparations should always be transported to the patient and the patient treated in the Trust in which they would have received care in the absence of phage. We enclose suggested best practice guidelines for adoption across the UK that will protect patient safety and safeguard clinicians and Trusts from potential litigation.

When can Muslims withdraw or withhold life support? A narrative review of Islamic juridical rulings.

When it is ethically justifiable to stop medical treatment? For many Muslim patients, families, and clinicians this ethical question remains a challenging one as Islamic ethico-legal guidance on such matters remains scattered and difficult to interpret. In light of this gap, we conducted a systematic literature review to aggregate rulings from Islamic jurists and juridical councils on whether, and when, it is permitted to withdraw and/or withhold life-sustaining care. A total of 16 fatwas were found, 8 of which were single-author rulings, and 8 represented the collective view of a juridical council. The fatwas are similar in that nearly all judge that Islamic law, provided certain conditions are met, permits abstaining from life-sustaining treatment. Notably, the justifying conditions appear to rely on physician assessment of the clinical prognosis. The fatwas differ when it comes to what conditions justify withdrawing or withholding life- sustaining care. Our analyses suggest that while notions of futility greatly impact the bioethical discourse regarding with holding and/or withdrawal of treatment, the conceptualization of futility lacks nuance. Therefore, clinicians, Islamic jurists, and bioethicists need to come together in order to unify a conception of medical futility and relate it to the ethics of withholding and/or withdrawal of treatment.

Health diplomacy: a new approach to the Muslim world?

Three years ago, the Lancet's frontispiece stated "Health is now the most important foreign policy issue of our time" and last year, the Director-General of WHO, Margaret Chan, in her opening address, to the Executive Board at its 132nd Session said "health diplomacy works". The nascent field of health diplomacy provides a political framework which aims to deliver the dual goals of improved health in target populations and enhanced governmental relations between collaborating countries. Any government that offered tangible health improvement as a component of aid to a nation with whom they wished to develop stronger diplomatic links would have an advantage in developing a deeper relationship with its citizens.Here we suggest several different mechanisms through which such links could be developed or enhanced, including: provision of relevant health solutions, applied research, cultural alignment and the development of collaborative networks. The Islamic tradition promotes the practice of medicine as a service to humanity. Physical and spiritual wellbeing are intimately related in popular Muslim consciousness. Thoughtful Health Diplomacy therefore has the potential to bridge the perceived divides between Western and predominantly Muslim nations.

Time trends over five decades, and recent geographical variation, in rates of childhood squint surgery in England.

AIMS: To study trends in rates of childhood squint surgery in England over five decades, and to study recent geographical variation in England. METHODS: Use of routine hospital statistics to analyse trends in squint surgery in the Oxford record linkage study area 1963-2010, and England 1968-2010; analysis of geographical variation in England 1999-2010. All rates, numerators and population denominators were restricted to people aged under 15 years. RESULTS: The study included 519 089 admissions for operations on squint. Annual admission rates for squint surgery in England fell from 188.8 episodes per 100 000 population (95% CI 180.9 to 196.8) in 1968 to 64.1 (62.4 to 65.7) episodes per 100 000 population in 2010. A similar decline was seen in the Oxford region, from 213.2 (181.3 to 245.2) episodes per 100 000 population in 1963 to 61.3 (54.8 to 67.9) episodes in 2010. There was wide variation across local authorities in annual rates of squint surgery from 28.2 (95% CI 22.7 to 34.8) admissions per 100 000 population to 138.6 (123.0 to 155.7) admissions per 100 000, a 4.9-fold difference between areas with the highest and lowest rates. CONCLUSIONS: Squint surgery rates have decreased substantially over time. The current wide geographical variation in rates raises questions about whether this scale of variation is clinically warranted, whether it reflects variation in needs for surgery and patient/parental choice, whether it is a result of inequalities in the availability of ophthalmic services, or whether it results from variation between clinicians in clinical decision making about the likely benefits of squint surgery.

Geographical variation in certification rates of blindness and sight impairment in England, 2008-2009.

OBJECTIVES: To examine and interpret the variation in the incidence of blindness and sight impairment in England by PCT, as reported by the Certificate of Vision Impairment (CVI). DESIGN: Analysis of national certification data. SETTING: All Primary Care Trusts, England. PARTICIPANTS: 23 773 CVI certifications issued from 2008 to 2009. MAIN OUTCOME MEASURES: Crude and Age standardised rates of CVI data for blindness and sight loss by PCT. METHODS: The crude and age standardised CVI rates per 100 000 were calculated with Spearman's rank correlation used to assess whether there was any evidence of association between CVI rates with Index of Multiple Deprivation (IMD) and the Programme Spend for Vision. RESULTS: There was high-level variation, almost 11-fold (coefficient of variation 38%) in standardised CVI blindness and sight impairment annual certification rates across PCTs. The mean rate was 43.7 and the SD 16.7. We found little evidence of an association between the rate of blindness and sight impairment with either the IMD or Programme Spend on Vision. CONCLUSIONS: The wide geographical variation we found raises questions about the quality of the data and whether there is genuine unmet need for prevention of sight loss. It is a concern for public health practitioners who will be interpreting these data locally and nationally as the CVI data will form the basis of the public health indicator 'preventable sight loss'. Poor-quality data and inadequate interpretation will only create confusion if not addressed adequately from the outset. There is an urgent need to address the shortcomings of the current data collection system and to educate all public health practitioners.