Understanding the patterns and health impact of indoor air pollutant exposures in Bradford, UK: a study protocol.

INTRODUCTION: Relative to outdoor air pollution, there is little evidence examining the composition and concentrations of indoor air pollution and its associated health impacts. The INGENIOUS project aims to provide the comprehensive understanding of indoor air pollution in UK homes. METHODS AND ANALYSIS: 'Real Home Assessment' is a cross-sectional, multimethod study within INGENIOUS. This study monitors indoor air pollutants over 2 weeks using low-cost sensors placed in three rooms in 300 Born in Bradford (BiB) households. Building audits are completed by researchers, and participants are asked to complete a home survey and a health and behaviour questionnaire, in addition to recording household activities and health symptoms on at least 1 weekday and 1 weekend day. A subsample of 150 households will receive more intensive measurements of volatile organic compound and particulate matter for 3 days. Qualitative interviews conducted with 30 participants will identify key barriers and enablers of effective ventilation practices. Outdoor air pollution is measured in 14 locations across Bradford to explore relationships between indoor and outdoor air quality. Data will be analysed to explore total concentrations of indoor air pollutants, how these vary with building characteristics, and whether they are related to health symptoms. Interviews will be analysed through content and thematic analysis. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the NHS Health Research Authority Yorkshire and the Humber (Bradford Leeds) Research Ethics Committee (22/YH/0288). We will disseminate findings using our websites, social media, publications and conferences. Data will be open access through the BiB, the Open Science Framework and the UK Data Service.

A scoping review on the impact of austerity on healthcare access in the European Union: rethinking austerity for the most vulnerable.

BACKGROUND: There is consensus that the 2008 financial and economic crisis and related austerity measures adversely impacted access to healthcare. In light of the growing debt caused by the COVID-19 crisis, it is uncertain whether a period of austerity will return. OBJECTIVE: This study aims to provide a structured overview of the impact of austerity policies in the EU-28 zone, applied in response to the Great Recession, on access to health care for the adult population, using the five access dimensions by Levesque et al. (2013). METHODS: This study followed the PRISMA extension for Scoping Reviews guideline. Medline (PubMed) and Web of Science were searched between February 2021 and June 2021. Primary studies in the English language published after the 1st of January 2008 reporting on the possible change in access to the healthcare system for the adult population induced by austerity in an EU28 country were included. RESULTS: The final search strategy resulted in 525 articles, of which 75 studies were reviewed for full-text analysis, and a total of 21 studies were included. Results revealed that austerity policy has been primarily associated with a reduction in access to healthcare, described through four main categories: i) Increase in rates of reported unmet needs (86%); ii) Affordability (38%); iii) Appropriateness (38%); iv) and Availability and Accommodation (19%). Vulnerable populations were more affected by austerity measures than the general population when specific safeguards were not in place. The main affected adult vulnerable population groups were: patients with chronic diseases, elderly people, (undocumented) migrants, unemployed, economically inactive people and individuals with lower levels of education or socioeconomic status. CONCLUSION: Austerity measures have led to a deterioration in access to healthcare in the vast majority of the countries studied in the EU-28 zone. Findings should prompt policymakers to rethink the fiscal agenda across all policies in times of economic crisis and focus on the needs of the most vulnerable populations from the health perspective.

Increasing the Reuse of Protein Non-Naïve Nonhuman Primates in Pharmaceutical Drug Discovery and Development: An Overview and Industry Position on the Challenges and Benefits.

The IQ Consortium NHP Reuse Working Group (WG) comprises members from 15 pharmaceutical and biotechnology companies. In 2020, the WG developed and distributed a detailed questionnaire on protein non-naïve NHP reuse to the WG member companies. The WG received responses from key stakeholders including principal investigators, facility managers, animal welfare officers and research scientists. This paper's content reflects the consolidated opinion of the WG members and the questionnaire responses on the subject of NHP reuse within nonclinical programs at all stages of research and development. Many of the pharmaceutical companies represented in the working group or participating in the questionnaire have already achieved some level of NHP reuse in their nonclinical programs, but the survey results suggested that there is significant potential to increase NHP reuse further and a need to understand the considerations involved in reuse more clearly. The WG has also focused carefully on the inherent concerns and risks of implementing protein non-naive NHP reuse and has evaluated the best methods of risk assessment and decision-making. This paper presents a discussion on the challenges and opportunities surrounding protein non-naïve NHP reuse and aims to stimulate further industry dialogue on the subject and provide guidance for pharmaceutical companies to establish roadmaps and decision trees enabling increased protein non-naïve NHP reuse. In addition, this paper represents a solid basis for collaborative engagement between pharmaceutical and biotechnology companies with contract research organizations (CROs) to discuss how the availability of protein non-naïve NHP within CROs can be better leveraged for their use within nonclinical studies.

Musculoskeletal tuberculosis in Bradford : 12 years of outcomes and observations in a high-incidence region of the UK.

AIMS: Tuberculosis (TB) is one of the biggest communicable causes of mortality worldwide. While incidence in the UK has continued to fall since 2011, Bradford retains one of the highest TB rates in the UK. This study aims to examine the local disease burden of musculoskeletal (MSK) TB, by analyzing common presenting factors within the famously diverse population of Bradford. METHODS: An observational study was conducted, using data from the Bradford Teaching Hospitals TB database of patients with a formal diagnosis of MSK TB between January 2005 and July 2017. Patient data included demographic data (including nationality/date of entry to the UK), disease focus, microbiology, and management strategies. Disease incidence was calculated using population data from the Office for National Statistics. Poisson confidence intervals were calculated to demonstrate the extent of statistical error. Disease incidence and nationality were also analyzed, and correlation sought, using the chi-squared test. RESULTS: Between January 2005 and July 2017, 109 cases of MSK TB were diagnosed in Bradford. Mean incidence was 1.65 per 100,000 population, per calendar year (SD 0.75). A total of 38 cases required surgical intervention. Low rates of antimicrobial resistance were encountered. A low rate of loss to follow-up was observed (four patients; 3.7%). Overall, 94.5% of patients (n = 103) were successfully treated. 67% of patients (n = 73) reported their country of origin as either India, Pakistan, or Bangladesh. These ethnicities account for around 25% of the local population. CONCLUSION: Bradford maintains a high prevalence of MSK TB infection relative to national data; the prevalence within the local immigrant population remains grossly disproportionate. Typical associated factors (HIV/hepatitis coinfection, drug resistance), have only modest prevalence in our dataset. However, local socioeconomic factors such as deprivation and poverty appear germane as suggested by global literature. We advocate a high degree of suspicion in treatment of atypical infection in any area with similar population factors to ensure timely diagnosis. Cite this article: Bone Jt Open 2022;3(5):432-440.

Perceptions of collective and other unjust punishment in Swiss prisons: a qualitative exploration.

PURPOSE: This paper aims to describe and analyse Swiss prisoners' and experts' views on collective punishment, the practice where a group is punished for one person's transgression. DESIGN/METHODOLOGY/APPROACH: A series of qualitative interviews with prisoners and stakeholders are reported following thematic analysis. FINDINGS: Despite being forbidden by the Geneva Convention and other international instruments, participants from this study expressed the view that collective punishment continues to be practiced in some form in prisons in Switzerland, violating the rights of prisoners via unjust and arbitrary decision-making, unjust rules, inequalities in prison structures and continuation of incarceration based on the behaviour of others. Families can also be both victims and vectors of collective punishment, and prolonging the detention of prisoners who would otherwise have been released because of rare high-profile cases of reoffending can also be considered a form of collective punishment. ORIGINALITY/VALUE: These significant findings suggest that collective punishment in various forms continues to be used in Swiss prisons.

The Cost of Coronavirus Obligations: Respecting the Letter and Spirit of Lockdown Regulations.

We all now know that the novel coronavirus is anything but a common cold. The pandemic has created many new obligations for all of us, several of which come with serious costs to our quality of life. But in some cases, the guidance and the law are open to a degree of interpretation, leaving us to decide what is the ethical (or unethical but desired) course of action. Because of the high cost of some of the obligations, a conflict of interest can arise between what we want to do and what it is right to do. And so, some people choose to respect only the letter of the law, but not the spirit, or not to respect even the spirit of the guidelines. This paper identifies and describes the new obligations imposed on us all by the pandemic, considers their costs in terms of the good life, and provides an ethical analysis of two personal and two public cases in terms of the letter and spirit of the guidance and legislation.

Structural racism in precision medicine: leaving no one behind.

BACKGROUND: Precision medicine (PM) is an emerging approach to individualized care. It aims to help physicians better comprehend and predict the needs of their patients while effectively adopting in a timely manner the most suitable treatment by promoting the sharing of health data and the implementation of learning healthcare systems. Alongside its promises, PM also entails the risk of exacerbating healthcare inequalities, in particular between ethnoracial groups. One often-neglected underlying reason why this might happen is the impact of structural racism on PM initiatives. Raising awareness as to how structural racism can influence PM initiatives is paramount to avoid that PM ends up reproducing the pre-existing health inequalities between different ethnoracial groups and contributing to the loss of trust in healthcare by minority groups. MAIN BODY: We analyse three nodes of a process flow where structural racism can affect PM's implementation. These are: (i) the collection of biased health data during the initial encounter of minority groups with the healthcare system and researchers, (ii) the integration of biased health data for minority groups in PM initiatives and (iii) the influence of structural racism on the deliverables of PM initiatives for minority groups. We underscore that underappreciation of structural racism by stakeholders involved in the PM ecosystem can be at odds with the ambition of ensuring social and racial justice. Potential specific actions related to the analysed nodes are then formulated to help ensure that PM truly adheres to the goal of leaving no one behind, as endorsed by member states of the United Nations for the 2030 Agenda for Sustainable Development. CONCLUSION: Structural racism has been entrenched in our societies for centuries and it would be naïve to believe that its impacts will not spill over in the era of PM. PM initiatives need to pay special attention to the discriminatory and harmful impacts that structural racism could have on minority groups involved in their respective projects. It is only by acknowledging and discussing the existence of implicit racial biases and trust issues in healthcare and research domains that proper interventions to remedy them can be implemented.

Cost effectiveness of treatment models of care for hepatitis C: the South Australian state-wide experience.

AIM: The objective was to study the long-term (lifetime) cost effectiveness of four different hepatitis C virus (HCV) treatment models of care (MOC) with directly acting antiviral drugs. METHODS: A cohort Markov model-based probabilistic cost-effectiveness analysis (CEA) was undertaken extrapolating to up to 30 years from cost and outcome data collected from a primary study involving a real-life Australian cohort. In this study, noncirrhotic patients treated for HCV from 1 March 2016 to 28 February 2017 at four major public hospitals and liaising sites in South Australia were studied retrospectively. The MOC were classified depending on the person providing patient workup, treatment and monitoring into MOC1 (specialist), MOC2 (mixed specialist and hepatitis nurse), MOC3 (hepatitis nurse) and MOC4 (general practitioner, GP). Incremental costs were estimated from the Medicare perspective. Incremental outcomes were estimated based on the quality-adjusted life years (QALY) gained by achieving a sustained virological response. A cost-effectiveness threshold of Australian dollar 50 000 per QALY gained, the implicit criterion used for assessing the cost-effectiveness of new pharmaceuticals and medical services in Australia was assumed. Net monetary benefit (NMB) estimates based on this threshold were calculated. RESULTS: A total of 1373 patients, 64% males, mean age 50 (SD ±11) years, were studied. In the CEA, MOC4 and MOC2 clearly dominated MOC1 over 30 years with lower costs and higher QALYs. Similarly, NMB was the highest in MOC4, followed by MOC2. CONCLUSION: Decentralized care using GP and mixed consultant nurse models were cost-effective ways of promoting HCV treatment uptake in the setting of unrestricted access to new antivirals.

Stay fit or get bit - ethical issues in sharing health data with insurers' apps.

In the framework of digital health, mobile applications with health-related content are increasing in number and importance. Many of these apps are targeted at the general public and, although they differ in features and purposes, their functions are often based on the promotion of health and the monitoring of customers’ lifestyle data. Apps of this type have also recently been developed by health insurance companies. In many cases, insurers’ apps do not simply offer health-related recommendations to the users, but also provide economic incentives to those customers who agree to share their behavioural data through the applications. Although such apps may contribute to the adoption of a health-conscious lifestyle, the fact that they require the sharing of dense individual data with the companies responsible for insurance coverage raises some relevant ethical issues. This paper investigates the phenomenon of insurers’ apps permitting customers to share their data in exchange for monetary rewards currently available in Switzerland. After describing the features and functioning of the apps, we present some ethically relevant aspects related to their use. More specifically, we discuss the issues of transparency of data-sharing purposes, potential discrimination amongst insured people, “quantification” of the users and, finally, the potential tension generated between solidarity and responsibility. We conclude by emphasising that these apps are becoming a new paradigm for insurers in many countries and that a thorough assessment of their ethical and societal implications is required.  .

Aging Prisoners' Views on Healthcare Services in Swiss Prisons.

OBJECTIVE: Due to the higher morbidity prevalent in the increasing older population, prisons are facing new challenges on a structural, ethical, and financial level. This study's goal was to explore older prisoners' views and experiences regarding the quality of medical services. METHOD: In this qualitative study, 35 semi-structured interviews were conducted with older inmates aged 50 years and above in 12 different prisons in the German-speaking (23 interviews) and the French-speaking parts (12 interviews) of Switzerland. RESULTS: The majority of older prisoners in this sample expressed concerns about quality of treatment throughout incarceration. Topics addressed reached from quality of the entrance to routine examinations, quality of the treatment received, and delays in care and services provided. CONCLUSION: This study's findings suggest that healthcare in prison is often perceived as insufficient and inadequate by older inmates.

AMEND study protocol: a case-control study to assess the long-term impact of invasive meningococcal disease in Australian adolescents and young adults.

INTRODUCTION: Invasive meningococcal disease (IMD) primarily causes disease in young children and adolescents and can cause long-term disability. Many countries are considering implementation of meningococcal B and/or meningococcal ACWY vaccines to control meningococcal disease. Estimating the cost-effectiveness of meningococcal vaccine programme is hampered due to a lack of good quality costing and burden of disease data. This study aims to address this evidence gap by assessing the clinical, physical, neurocognitive, economic and societal impact of IMD on adolescents and young adults. METHODS AND ANALYSIS: A case-control study of 64 participants with confirmed IMD (15-24 years 11 months at time of disease) and 64 control participants (17-34 years 11 months) will be conducted in Australia from 2016 to 2020. All participants will undergo a neurocognitive assessment, full medical examination, pure tone audiometry assessment and complete quality of life and behavioural questionnaires. Meningococcal cases will be assessed 2-10 years posthospitalisation and a subset of cases will be interviewed to explore in depth their experiences of IMD and its impact on their life. Primary outcome measures include general intellectual functioning from the Wechsler Adult Intelligence Scale and overall quality of life from the Health Utilities Index. Secondary outcome measures include academic achievement, executive functioning, behaviour, hearing, psychological and physical functioning. Outcome measures will be compared between cases and controls using independent t-tests or ORs, or if any significant confounders are identified, adjusted analyses (analysis of covariance or adjusted ORs) will be conducted. Thematic analysis will be used to analyse transcribed interviews and a costing model will be used to project lifetime costs. ETHICS AND DISSEMINATION: The Adolescent MENingococcal Disease (AMEND) study has been approved by the Human Research Ethics Committee of the Women's and Children's Health Network (HREC/14/WCHN/024). The results will be disseminated via peer-reviewed publications, conference presentations, study participants, and meningococcal and meningitis foundations. TRIAL REGISTRATION NUMBER: NCT03798574.

Unethical Aspects of Open Access.

In this article, we identify and discuss several ethically problematic aspects of open access scientific publishing. We conclude that, despite some positive effects, paid open access has at least three unethical aspects: it discriminates against researchers, creates an editorial conflict of interest, and diverts funding from the actual conduct of research. To be truly open access, all researchers must be able to access its benefits.

Nonclinical Safety Assessment of CFZ533, a Fc-Silent Anti-CD40 Antibody, in Cynomolgus Monkeys.

CFZ533 is a pathway blocking, nondepleting anti-CD40 antibody that is in clinical development for inhibition of transplant organ rejection and therapy for autoimmune diseases. A 26-week GLP toxicity study in sexually mature Cynomolgus monkeys was conducted in order to support chronic application of CFZ533. CFZ533 was subcutaneously administered at doses up to 150 mg/kg/week and was safe and generally well tolerated. CFZ533 showed no adverse effects for cardiovascular, respiratory, and neurobehavioral endpoints, and no changes were observed for blood lymphocyte and platelet counts or blood coagulation markers. In line with the nondepleting nature of CFZ533, CD20+ B cells in the blood were only marginally reduced. A complete suppression of germinal center (GC) development in lymph nodes and spleen was the most prominent result of post-mortem histological investigations. This was corroborated by an abrogated T-dependent antibody response (TDAR) to the antigen Keyhole Limpet Hemocyanin (KLH) as well as an absence of anti-drug antibodies (ADAs) in the absence of B cell depletion as seen with immunophenotyping and histology. When serum levels of CFZ533 in recovery animals dropped levels necessary for full CD40 occupancy on B cells, all animals were able to mount a TDAR to KLH. All histological changes also reverted to normal appearance after recovery. In summary, CFZ533 was shown to be well tolerated and safe in the 26-week toxicity study with a distinct pharmacodynamic profile in histology and immune function.

Assessment of decision-making capacity in patients requesting assisted suicide.

In this editorial, we argue that current attitudes toward terminally ill patients are generally too paternalistic, and that it is wrong to assume that patients suffering from mental health issues (including depression) cannot consent to assisted suicide.Declaration of interestNone.

Is failure to raise concerns about misconduct a breach of integrity? Researchers' reflections on reporting misconduct.

This article describes and discusses the views of researchers on the significance of raising concerns about scientific misconduct in their work environment and the reasons or circumstances that might deter them from doing so. In this exploratory qualitative research study, we conducted in-depth interviews with 33 researchers working in life sciences and medicine. They represent three seniority levels and five universities across Switzerland. A large majority of respondents in this research study argued that failure to raise concerns about scientific misconduct compromises research integrity. This is an encouraging result demonstrating that researchers try to adhere to high ethical standards. However, further interaction with respondents highlighted that this correct ethical assessment does not lead researchers to take the consequent action of raising concerns. The factors that discourage researchers from raising concerns need to be addressed at the level of research groups, institutions, and by setting a positive precedent which helps them to believe in the system's ability to investigate concerns raised in a timely and professional manner. Training of researchers in research integrity related issues will have limited utility unless it is coupled with the creation of research culture where raising concerns is a standard practice of scientific and research activities.

Implementation of Plate Imaging for Demonstration of Monoclonality in Biologics Manufacturing Development.

Monoclonality of mammalian cell lines used for production of biologics is a regulatory expectation and one of the attributes assessed as part of a larger process to ensure consistent quality of the biologic. Historically, monoclonality has been demonstrated through statistics generated from limiting dilution cloning or through verified flow cytometry methods. A variety of new technologies are now on the market with the potential to offer more efficient and robust approaches to generating and documenting a clonal cell line.Here we present an industry perspective on approaches for the application of imaging and integration of that information into a regulatory submission to support a monoclonality claim. These approaches represent the views of a consortium of companies within the BioPhorum Development Group and include case studies utilising imaging technology that apply scientifically sound approaches and efforts in demonstrating monoclonality. By highlighting both the utility of these alternative approaches and the advantages they bring over the traditional methods, as well as their adoption by industry leaders, we hope to encourage acceptance of their use within the biologics cell line development space and provide guidance for regulatory submission using these alternative approaches.LAY ABSTRACT: In the manufacture of biologics produced in mammalian cells, one recommendation by regulatory agencies to help ensure product consistency, safety, and efficacy is to produce the material from a monoclonal cell line derived from a single, progenitor cell. The process by which monoclonality is assured can be supplemented with single-well plate images of the progenitor cell. Here we highlight the utility of that imaging technology, describe approaches to verify the validity of those images, and discuss how to analyze that information to support a biologic filing application. This approach serves as an industry perspective to increased regulatory interest within the scope of monoclonality for mammalian cell culture-derived biologics.

Good collaborative practice: reforming capacity building governance of international health research partnerships.

In line with the policy objectives of the United Nations Sustainable Development Goals, this commentary seeks to examine the extent to which provisions of international health research guidance promote capacity building and equitable partnerships in global health research. Our evaluation finds that governance of collaborative research partnerships, and in particular capacity building, in resource-constrained settings is limited but has improved with the implementation guidance of the International Ethical Guidelines for Health-related Research Involving Humans by The Council for International Organizations of Medical Sciences (CIOMS) (2016). However, more clarity is needed in national legislation, industry and ethics guidelines, and regulatory provisions to address the structural inequities and power imbalances inherent in international health research partnerships. Most notably, ethical partnership governance is not supported by the principal industry ethics guidelines - the International Conference on Harmonization Technical Requirements for Registration of Pharmaceutical for Human Use (ICH) Good Clinical Practice (ICH-GCP). Given the strategic value of ICH-GCP guidelines in defining the role and responsibility of global health research partners, we conclude that such governance should stipulate the minimal requirements for creating an equitable environment of inclusion, mutual learning, transparency and accountability. Procedurally, this can be supported by i) shared research agenda setting with local leadership, ii) capacity assessments, and iii) construction of a memorandum of understanding (MoU). Moreover, the requirement of capacity building needs to be coordinated amongst partners to support good collaborative practice and deliver on the public health goals of the research enterprise; improving local conditions of health and reducing global health inequality. In this respect, and in order to develop consistency between sources of research governance, ICH-GCP should reference CIOMS ethical guidelines as the established standard for collaborative partnership. Moreover, greater commitment and support should be given to co-ordinate, strengthen and enforce local laws requiring equitable research partnerships and health system strengthening.

Defining Health Research for Development: The perspective of stakeholders from an international health research partnership in Ghana and Tanzania.

OBJECTIVES: The study uses a qualitative empirical method to define Health Research for Development. This project explores the perspectives of stakeholders in an international health research partnership operating in Ghana and Tanzania. METHODS: We conducted 52 key informant interviews with major stakeholders in an international multicenter partnership between GlaxoSmithKline (GSK, Vaccine Developer) and the global health nonprofit organisation PATH and its Malaria Vaccine Initiative program (PATH/MVI, Funder-Development Partner), (RTS, S) (NCT00866619). The respondents included teams from four clinical research centres (two centres in Ghana and two in Tanzania) and various collaborating partners. This paper analyses responses to the question: What is Health Research for Development? RESULTS: Based on the stakeholders' experience the respondents offered many ways of defining Health Research for Development. The responses fell into four broad themes: i) Equitable Partnerships; ii) System Sustainability; iii) Addressing Local Health Targets, and iv) Regional Commitment to Benefit Sharing. CONCLUSION: Through defining Health Research for Development six key learning points were generated from the four result themes: 1) Ensure there is local research leadership working with the collaborative partnership, and local healthcare system, to align the project agenda and activities with local research and health priorities; 2) Know the country-specific context - map the social, health, legislative and political setting; 3) Define an explicit development component and plan of action in a research project; 4) Address the barriers and opportunities to sustain system capacity. 5) Support decentralised health system decision-making to facilitate the translation pathway; 6) Govern, monitor and evaluate the development components of health research partnerships. Overall, equity and unity between partners are required to deliver health research for development.

Accessibility of prison healthcare for elderly inmates, a qualitative assessment.

Aging in custody and the rising population of elderly prisoners are creating compelling challenges for criminal justice, prison and public healthcare systems. Geriatric syndrome and higher prevalence of co-morbidities amongst older inmates result in heightened vulnerability in prison environments. Empirical research addressing older adults' access to medical care in detention is scarce; therefore, this study assessed access to medical care in prison from the perspective of older prisoners in Switzerland. We interviewed a sample of 35 older inmates (average age 61 years) on their experience of healthcare accessibility in prison; data were qualitatively analysed and major themes regarding evaluation of their access to medical services were extracted. Our findings identified three barriers to accessing health services in prison including psychological obstacles, negative consequences of healthcare utilization, and environmental hurdles. We advocate facilitating older inmates' access to medical care in order to relieve the psychological burden of seeking health services in detention and adequately informing them of their right to demand these services, thereby lessening the negative consequences of their requests. We suggest further training of prison and medical staff for better management of age-related issues in prison can ease the environmental obstacles.