• Outbreaks in care homes may lead to substantial disease burden if not mitigated

      Hall, Ian; orcid: 0000-0002-3033-2335; email: ian.hall@manchester.ac.uk; Lewkowicz, Hugo; orcid: 0000-0002-8944-0365; Webb, Luke; orcid: 0000-0001-6263-0575; House, Thomas; orcid: 0000-0001-5835-8062; Pellis, Lorenzo; orcid: 0000-0002-3436-6487; Sedgwick, James; orcid: 0000-0002-7200-4559; Gent, Nick; orcid: 0000-0002-2605-7369; on behalf of the University of Manchester COVID-19 Modelling Group and the Public Health England Modelling Team (The Royal Society, 2021-05-31)
      The number of COVID-19 outbreaks reported in UK care homes rose rapidly in early March of 2020. Owing to the increased co-morbidities and therefore worse COVID-19 outcomes for care home residents, it is important that we understand this increase and its future implications. We demonstrate the use of an SIS model where each nursing home is an infective unit capable of either being susceptible to an outbreak (S) or in an active outbreak (I). We use a generalized additive model to approximate the trend in growth rate of outbreaks in care homes and find the fit to be improved in a model where the growth rate is proportional to the number of current care home outbreaks compared with a model with a constant growth rate. Using parameters found from the outbreak-dependent growth rate, we predict a 73% prevalence of outbreaks in UK care homes without intervention as a reasonable worst-case planning assumption. This article is part of the theme issue ‘Modelling that shaped the early COVID-19 pandemic response in the UK’.
    • Overexpression of transcription factor BLIMP1/prdm1 leads to growth inhibition and enhanced secretory capacity in Chinese hamster ovary cells.

      Torres, Mauro; Dickson, Alan J; email: alan.dickson@manchester.ac.uk (2021-07-13)
      Chinese hamster ovary (CHO) cells present inherent limitations for processing and secretion of large amounts of recombinant proteins, especially for those requiring complex post-translational processing. To tackle these limitations, we engineered CHO host cells (CHOK1 and CHOS) to overexpress the transcription factor BLIMP1/prdm1 (a master regulator of the highly-secreting phenotype of antibody-producing plasma cells), generating novel CHO cell lines (referred to as CHOB). The CHOB cell lines exhibited decreased cell densities, prolonged stationary phase and arrested cell cycle in G1/G0 phase but simultaneously had significantly greater product titre for recombinant IgG1 (> 2-fold increase) coupled with a significantly greater cell-specific productivities (> 3-fold increase). We demonstrated that the improved productive phenotype of CHOB cells resulted from a series of changes to cell physiology and metabolism. CHOB cells showed a significantly greater ER size and increased protein synthesis and secretion capacity compared to control cells. In addition, CHOB cells presented a metabolic profile that favoured energy production to support increased recombinant protein production. This study indicated that a cell engineering approach based on BLIMP1 expression offers great potential for improving the secretory capacity of CHO cell hosts utilised for manufacture of recombinant biopharmaceuticals. Our findings also provides a greater understanding of the relationship between cell growth and productivity, valuable generic information for improving productive phenotypes for CHO cell lines during industrial cell line development. [Abstract copyright: Copyright © 2021 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.]
    • Overwhelming Evidence for a Major Role for Herpes Simplex Virus Type 1 (HSV1) in Alzheimer’s Disease (AD); Underwhelming Evidence against

      Itzhaki, Ruth F.; email: ruth.itzhaki@manchester.ac.uk (MDPI, 2021-06-21)
      This review describes investigations of specific topics that lie within the general subject of HSV1’s role in AD/dementia, published in the last couple of years. They include studies on the following: relationship of HSV1 to AD using neural stem cells; the apparent protective effects of treatment of HSV1 infection or of VZV infection with antivirals prior to the onset of dementia; the putative involvement of VZV in AD/dementia; the possible role of human herpes virus 6 (HHV6) in AD; the seemingly reduced risk of dementia after vaccination with diverse types of vaccine, and the association shown in some vaccine studies with reduced frequency of HSV1 reactivation; anti-HSV serum antibodies supporting the linkage of HSV1 in brain with AD in APOE-ε4 carriers, and the association between APOE and cognition, and association of APOE and infection with AD/dementia. The conclusions are that there is now overwhelming evidence for HSV1’s role—probably causal—in AD, when it is present in brain of APOE-ε4 carriers, and that further investigations should be made on possible prevention of the disease by vaccination, or by prolonged antiviral treatment of HSV1 infection in APOE-ε4 carriers, before disease onset.
    • OVPSYCH2: A randomized controlled trial of psychological support versus standard of care following chemotherapy for ovarian cancer.

      Frangou, E; Bertelli, G; Love, S; Mackean, M J; Glasspool, R M; Fotopoulou, C; Cook, A; Nicum, S; Lord, R; Ferguson, M; et al. (2021-05-28)
      Fear of disease progression (FOP) is a rational concern for women with Ovarian Cancer (OC) and depression is also common. To date there have been no randomized trials assessing the impact of psychological intervention on depression and FOP in this patient group. Patients with primary or recurrent OC who had recently completed chemotherapy were eligible if they scored between 5 and 19 on the PHQ-9 depression and were randomized 1:1 to Intervention (3 standardized CBT-based sessions in the 6-12 weeks post-chemotherapy) or Control (standard of care). PHQ-9, FOP-Q-SF, EORTC QLQ C30 and OV28 questionnaires were then completed every 3 months for up to 2 years. The primary endpoint was change in PHQ-9 at 3 months. Secondary endpoints were change in other scores at 3 months and all scores at later timepoints. 182 patients registered; 107 were randomized; 54 to Intervention and 53 to Control; mean age 59 years; 75 (70%) had completed chemotherapy for primary and 32 (30%) for relapsed OC and 67 patients completed both baseline and 3-month questionnaires. Improvement in PHQ-9 was observed for patients in both study arms at three months compared to baseline but there was no significant difference in change between Intervention and Control. A significant improvement on FOP-Q-SF scores was seen in the Intervention arm, whereas for those in the Control arm FOP-Q-SF scores deteriorated at 3 months (intervention effect = -4.4 (-7.57, -1.22), p-value = 0.008). CBT-based psychological support provided after chemotherapy did not significantly alter the spontaneously improving trajectory of depression scores at three months but caused a significant improvement in FOP. Our findings call for the routine implementation of FOP support for ovarian cancer patients. [Abstract copyright: Crown Copyright © 2021. Published by Elsevier Inc. All rights reserved.]
    • P-Rex1 Controls Sphingosine 1-Phosphate Receptor Signalling, Morphology, and Cell-Cycle Progression in Neuronal Cells

      Hampson, Elizabeth; email: Elizabeth.Hampson@babraham.ac.uk; Tsonou, Elpida; email: elpida.tsonou1@astrazeneca.com; Baker, Martin J.; orcid: 0000-0002-9743-6294; email: martin.baker@manchester.ac.uk; Hornigold, David C.; orcid: 0000-0002-3354-2768; email: David.Hornigold@astrazeneca.com; Hubbard, Roderick E.; email: r.hubbard@vernalis.com; Massey, Andrew; email: a.massey@vernalis.com; Welch, Heidi C. E.; orcid: 0000-0001-7865-7000; email: heidi.welch@babraham.ac.uk (MDPI, 2021-09-18)
      P-Rex1 is a guanine-nucleotide exchange factor (GEF) that activates Rac-type small G proteins in response to the stimulation of a range of receptors, particularly G protein-coupled receptors (GPCRs), to control cytoskeletal dynamics and other Rac-dependent cell responses. P-Rex1 is mainly expressed in leukocytes and neurons. Whereas its roles in leukocytes have been studied extensively, relatively little is known about its functions in neurons. Here, we used CRISPR/Cas9-mediated P-Rex1 deficiency in neuronal PC12 cells that stably overexpress the GPCR S1PR1, a receptor for sphingosine 1-phosphate (S1P), to investigate the role of P-Rex1 in neuronal GPCR signalling and cell responses. We show that P-Rex1 is required for the S1P-stimulated activation of Rac1 and Akt, basal Rac3 activity, and constitutive cAMP production in PC12-S1PR1 cells. The constitutive cAMP production was not due to increased expression levels of major neuronal adenylyl cyclases, suggesting that P-Rex1 may regulate adenylyl cyclase activity. P-Rex1 was required for maintenance of neurite protrusions and spreading in S1P-stimulated PC12-S1PR1 cells, as well as for cell-cycle progression and proliferation. In summary, we identified novel functional roles of P-Rex1 in neuronal Rac, Akt and cAMP signalling, as well as in neuronal cell-cycle progression and proliferation.
    • Palladium catalysed C-H arylation of pyrenes: access to a new class of exfoliating agents for water-based graphene dispersions.

      Just-Baringo, Xavier; orcid: 0000-0003-2182-5960; Shin, Yuyoung; orcid: 0000-0003-4359-5406; Panigrahi, Adyasha; Zarattini, Marco; Nagyte, Vaiva; orcid: 0000-0003-0835-6039; Zhao, Ling; Kostarelos, Kostas; orcid: 0000-0002-2224-6672; Casiraghi, Cinzia; orcid: 0000-0001-7185-0377; Larrosa, Igor; orcid: 0000-0002-5391-7424 (2020-01-28)
      A new and diverse family of pyrene derivatives was synthesised <i>via</i> palladium-catalysed C-H <i>ortho</i>-arylation of pyrene-1-carboxylic acid. The strategy affords easy access to a broad scope of 2-substituted and 1,2-disubstituted pyrenes. The C1-substituent can be easily transformed into carboxylic acid, iodide, alkynyl, aryl or alkyl functionalities. This approach gives access to arylated pyrene ammonium salts, which outperformed their non-arylated parent compound during aqueous Liquid Phase Exfoliation (LPE) of graphite and compare favourably to state-of-the-art sodium pyrene-1-sulfonate <b>PS1</b>. This allowed the production of concentrated and stable suspensions of graphene flakes in water.
    • Palladium-doped hierarchical ZSM-5 for catalytic selective oxidation of allylic and benzylic alcohols

      Ding, Shengzhe; orcid: 0000-0003-2822-3882; Ganesh, Muhammad; Jiao, Yilai; Ou, Xiaoxia; Isaacs, Mark A.; orcid: 0000-0002-0335-4272; S'ari, Mark; Torres Lopez, Antonio; orcid: 0000-0001-7378-1811; Fan, Xiaolei; orcid: 0000-0002-9039-6736; email: xiaolei.fan@manchester.ac.uk; Parlett, Christopher M. A.; orcid: 0000-0002-3651-7314; email: christopher.parlett@manchester.ac.uk (The Royal Society, 2021-10-20)
      Hierarchical zeolites have the potential to provide a breakthrough in transport limitation, which hinders pristine microporous zeolites and thus may broaden their range of applications. We have explored the use of Pd-doped hierarchical ZSM-5 zeolites for aerobic selective oxidation (selox) of cinnamyl alcohol and benzyl alcohol to their corresponding aldehydes. Hierarchical ZSM-5 with differing acidity (H-form and Na-form) were employed and compared with two microporous ZSM-5 equivalents. Characterization of the four catalysts by X-ray diffraction, nitrogen porosimetry, NH3 temperature-programmed desorption, CO chemisorption, high-resolution scanning transmission electron microscopy, X-ray photoelectron spectroscopy and X-ray absorption spectroscopy allowed investigation of their porosity, acidity, as well as Pd active sites. The incorporation of complementary mesoporosity, within the hierarchical zeolites, enhances both active site dispersion and PdO active site generation. Likewise, alcohol conversion was also improved with the presence of secondary mesoporosity, while strong Brønsted acidity, present solely within the H-form systems, negatively impacted overall selectivity through undesirable self-etherification. Therefore, tuning support porosity and acidity alongside active site dispersion is paramount for optimal aldehyde production.
    • Pandemic Drones

      Hildebrand, Julia M.; email: hildebjm@eckerd.edu; Sodero, Stephanie; email: stephanie.sodero@manchester.ac.uk (Berghahn Books, 2021-03-01)
      When the novel coronavirus moved around the planet in early 2020, reconfiguring, slowing down, or halting everyday mobilities, another transport mode was mobilized: the pandemic drone. We highlight the increasing prominence of this aerial device by surveying international media coverage of pandemic drone use in the spring of 2020. To address a range of pandemic drone affordances and applications, we organize manifold cases under two broad categories: sensing and moving with the pandemic drone. Here we ask: what roles do, and could, drones play during the pandemic? Following the empirical examples and related mobilities research, we theorize the drone versus virus and the drone as virus. As such, the work identifies avenues for mobilities research into pandemic drones as a growing mobility domain. Moreover, in thinking through the pandemic drone, we demonstrate creative extensions of mobilities thinking that bridge biological and technological, as well as media and mobility frameworks when multiple public health and safety crises unfolded and intersected.
    • Pandemics, Protests, and Pronouns: The Changing Landscape of Biomedical Visualisation and Education.

      Finn, Gabrielle M; email: gabrielle.finn@manchester.ac.uk; Quinn, Rebecca; Sanders, Katherine; Ballard, William; Balogun-Katung, Abisola; Dueñas, Angelique N (2021)
      Events in early 2020 changed the landscape of education for the foreseeable future, perhaps permanently. Three events had a significant impact; (1) the Coronavirus disease 2019 (COVID-19) pandemic, (2) the death of George Floyd, which resulted in the most recent Black Lives Matter (BLM) protests, and (3) the Twitter storm, the resultant societal fallout and freedom of speech campaigns, following comments made by author JK Rowling which many deemed transphobic. These events had a differential impact on biomedical sciences, when compared to other sectors. COVID-19 resulted in a global lockdown, with higher education institutions closing campuses and moving to online-only delivery. This rapid change required radical shifts in the use of technology, with mass delivery of teaching at short notice. The BLM protests further raised awareness of the inequalities within society, particularly those experienced by Black people and other oppressed groups. As a result, there have been calls for the decolonisation of the curriculum. The implications of these three key events have led institutions to rethink their policies, teaching delivery, assessment, curricula, and physical environments. This chapter considers (1) the implications of a swift change in the primary mode of curriculum delivery within Higher Education to online formats and (2) how recent adverse events have resulted in calls for much-needed changes in visual representations within biomedical sciences. Finally, we consider (3) the role of the hidden curriculum and the potential impact of visual representations in curricula on the delivery of healthcare and the fight against health inequalities, which are often as a result of implicit biases. The year 2020 has proven timely in presenting the opportunity for change, provided through the power of imagery. [Abstract copyright: © 2021. The Author(s), under exclusive license to Springer Nature Switzerland AG.]
    • Panel Adjustment and Error Analysis for a Large Active Main Reflector Antenna by Using the Panel Adjustment Matrix

      Lian, Peiyuan; Wang, Congsi; Xue, Song; Xu, Qian; Wang, Na; Xiang, Binbin; Shi, Yu; Jia, Yu (Institute of Electrical and Electronics Engineers (IEEE), 2021)
    • Paranoia and negative schema about the self and others: A systematic review and meta-analysis.

      Humphrey, Charlotte; Bucci, Sandra; Varese, Filippo; Degnan, Amy; Berry, Katherine; email: katherine.berry@manchester.ac.uk (2021-08-30)
      Negative self and negative other schema have been implicated in the development of paranoia. The current study provides a meta-analysis, narrative review and quality appraisal of quantitative studies investigating the relationship between negative self and negative other schema and paranoia across the paranoia continuum. A systematic search identified 43 eligible studies; 25 were included in the meta-analysis. Meta-analytic findings demonstrated a medium to large relationship between paranoia and negative self-schema (r = 0.46, 95% CI 0.39 to 0.53) and negative other schema (r = 0.48, 95% CI 0.38 to 0.56). The magnitude of associations was similar across people with and without psychosis. Findings demonstrated that associations between negative self-schema and paranoia were not always statistically significant when controlling for confounding variables, particularly depression. The association between negative other schema and paranoia tended to remain significant when controlling for confounding variables. Findings also demonstrated that negative schema may mediate relationships between adverse experiences in childhood and paranoia. Overall, findings support theoretical proposals that both negative self and negative other schema are associated with paranoia. Longitudinal studies are required to confirm the direction of effects. Findings provide support for incorporating and targeting negative self and negative other schema in psychological formulations and therapeutic work. [Abstract copyright: Copyright © 2021. Published by Elsevier Ltd.]
    • Parental Licensing as Harm Reduction

      Shields, Liam; orcid: 0000-0001-9272-1937; email: liam.shields@manchester.ac.uk (Springer US, 2020-10-17)
      Abstract: In this paper, I will argue that some prominent objections to parental licensing rely on dubious claims about the existence of a very stringent, if not indefeasible, right to parent, which would be violated by licensing. I claim that attaching such stringency to the right only makes sense if we make a number of idealising assumptions. Otherwise, it is deeply implausible. Instead, I argue that we should evaluate parental licensing policies in much the same way we would harm reduction policies. By adopting this critical perspective, we can see that there are powerful, but quite different, reasons to be cautious about parental licensing relating to our ability to minimize the harmful effects of mass-parenting in a world of minimal surveillance and intervention.
    • Pathogenic Intronic Splice-Affecting Variants in MYBPC3 in Three Patients with Hypertrophic Cardiomyopathy

      Wood, Katherine A.; orcid: 0000-0002-6459-2127; email: katherine.wood@manchester.ac.uk; Ellingford, Jamie M.; email: jamie.ellingford@manchester.ac.uk; Eden, James; email: james.eden@mft.nhs.uk; Thomas, Huw B.; orcid: 0000-0001-9626-9706; email: huw.thomas@manchester.ac.uk; O’Keefe, Raymond T.; email: rokeefe@manchester.ac.uk; Hopton, Claire; email: claire.hopton@manchester.ac.uk; Newman, William G.; email: william.newman@manchester.ac.uk (MDPI, 2021-06-02)
      Genetic variants in MYBPC3 are one of the most common causes of hypertrophic cardiomyopathy (HCM). While variants in MYBPC3 affecting canonical splice site dinucleotides are a well-characterised cause of HCM, only recently has work begun to investigate the pathogenicity of more deeply intronic variants. Here, we present three patients with HCM and intronic splice-affecting MYBPC3 variants and analyse the impact of variants on splicing using in vitro minigene assays. We show that the three variants, a novel c.927-8G>A variant and the previously reported c.1624+4A>T and c.3815-10T>G variants, result in MYBPC3 splicing errors. Analysis of blood-derived patient RNA for the c.3815-10T>G variant revealed only wild type spliced product, indicating that mis-spliced transcripts from the mutant allele are degraded. These data indicate that the c.927-8G>A variant of uncertain significance and likely benign c.3815-10T>G should be reclassified as likely pathogenic. Furthermore, we find shortcomings in commonly applied bioinformatics strategies to prioritise variants impacting MYBPC3 splicing and re-emphasise the need for functional assessment of variants of uncertain significance in diagnostic testing.
    • Pathogenic noncoding variants in the neurofibromatosis and schwannomatosis predisposition genes

      Perez‐Becerril, Cristina; orcid: 0000-0003-1630-1943; Evans, D. Gareth; orcid: 0000-0002-8482-5784; Smith, Miriam J.; orcid: 0000-0002-3184-0817; email: miriam.smith@manchester.ac.uk (2021-07-29)
      Abstract: Neurofibromatosis type 1 (NF1), type 2 (NF2), and schwannomatosis are a group of autosomal dominant disorders that predispose to the development of nerve sheath tumors. Pathogenic variants (PVs) that cause NF1 and NF2 are located in the NF1 and NF2 loci, respectively. To date, most variants associated with schwannomatosis have been identified in the SMARCB1 and LZTR1 genes, and a missense variant in the DGCR8 gene was recently reported to predispose to schwannomas. In spite of the high detection rate for PVs in NF1 and NF2 (over 90% of non‐mosaic germline variants can be identified by routine genetic screening) underlying PVs for a proportion of clinical cases remain undetected. A higher proportion of non‐NF2 schwannomatosis cases have no detected PV, with PVs currently only identified in around 70%–86% of familial cases and 30%–40% of non‐NF2 sporadic schwannomatosis cases. A number of variants of uncertain significance have been observed for each disorder, many of them located in noncoding, regulatory, or intergenic regions. Here we summarize noncoding variants in this group of genes and discuss their established or potential role in the pathogenesis of NF1, NF2, and schwannomatosis.
    • Patient engagement in melanoma research: from bench to bedside

      Tivey, Ann; Huddar, Prerana; Shotton, Rohan; Cheese, Imogen; Daniels, Susanna; Lorigan, Paul; orcid: 0000-0002-8875-2164; J Lee, Rebecca; orcid: 0000-0003-2540-2009; email: Rebecca.lee-3@manchester.ac.uk (Future Medicine Ltd, 2021-07-02)
      Advances in research have transformed the management of melanoma in the past decade. In parallel, patient advocacy has gained traction, and funders are increasingly prioritizing patient and public involvement. Here we discuss the ways in which patients and the public can be engaged in different stages of the research process, from developing, prioritizing and refining the research question to preclinical studies and clinical trials, then finally to ongoing research in the clinic. We discuss the challenges and opportunities that exist at each stage in order to ensure that a representative population of patients and the public contribute to melanoma research both now and in the future.
    • Patient engagement in melanoma research: from bench to bedside

      Tivey, Ann; Huddar, Prerana; Shotton, Rohan; Cheese, Imogen; Daniels, Susanna; Lorigan, Paul; orcid: 0000-0002-8875-2164; J Lee, Rebecca; orcid: 0000-0003-2540-2009; email: Rebecca.lee-3@manchester.ac.uk (Future Medicine Ltd, 2021-07-02)
      Advances in research have transformed the management of melanoma in the past decade. In parallel, patient advocacy has gained traction, and funders are increasingly prioritizing patient and public involvement. Here we discuss the ways in which patients and the public can be engaged in different stages of the research process, from developing, prioritizing and refining the research question to preclinical studies and clinical trials, then finally to ongoing research in the clinic. We discuss the challenges and opportunities that exist at each stage in order to ensure that a representative population of patients and the public contribute to melanoma research both now and in the future.
    • Patient insights on living with idiopathic inflammatory myopathy and the limitations of disease activity measurement methods – a qualitative study

      Oldroyd, Alexander; orcid: 0000-0001-5701-6490; email: alexander.oldroyd@manchester.ac.uk; Dixon, William; Chinoy, Hector; Howells, Kelly (BioMed Central, 2020-09-21)
      Abstract: Background: The idiopathic inflammatory myopathies (IIMs) are chronic autoimmune conditions, typically resulting in proximal muscle weakness and impacting upon quality of life. Accurate measurement of IIM disease activity is imperative for appropriate medical management and carrying out valid clinical trials. The International Myositis Assessment and Clinical Studies Group (IMACS) “Disease Activity Core Set Measures” are the current gold-standard of IIM disease activity assessment. Anecdotally, patients with an IIM report that the IMACS Core Set Measures and other available methods do not necessarily capture their perceived disease activity. Investigating the patient experiences of living with an IIM and their views on the accuracy of the IMACS Core Set Measures will provide valuable insights for both clinical and research purposes. Methods: Eighteen interviews with patients with an IIM were carried out and analysed thematically, using a grounded theory approach. Experiences on living with an IIM and perceptions on the accuracy of disease activity measurement methods were explored. Results: Interview analysis revealed four themes: 1) fatigue, 2) pain, 3) day-to-day symptom variation, 4) limitations of creatine kinase levels and manual muscle testing. Conclusions: This study has provided valuable insights into patient experiences of living with an IIM. Aspects of IIM disease activity perceived not to be wholly measured by the IMACS Core Set Measures have also been identified. These findings have implications for future IIM clinical care and research, in particular providing justification for research into pain, fatigue and symptom variation.
    • Patient preferences and priorities for haemophilia gene therapy in the US: A discrete choice experiment

      Witkop, Michelle; Morgan, George; orcid: 0000-0003-2014-3415; email: george.morgan@hcdeconomics.com; O'Hara, Jamie; Recht, Michael; Buckner, Tyler W.; Nugent, Diane; Curtis, Randall; orcid: 0000-0002-6859-6432; O'Mahony, Brian; orcid: 0000-0001-9780-6972; Skinner, Mark W.; orcid: 0000-0002-0934-0680; Mulhern, Brendan; et al. (2021-07-26)
      Abstract: Introduction: Gene therapy has shown promise in clinical trials for patients with haemophilia, but patient preference studies have focused on factor replacement treatments. Aim: We conducted a discrete choice experiment (DCE) to investigate the relative importance and differential preferences patients provide for gene therapy attributes. Methods: We surveyed male adults with haemophilia in the United States recruited from patient panels including the National Hemophilia Foundation Community Voices in Research platform using an online survey over 4 months in 2020/21. Participants indicated preferences for gene therapy attributes including dosing frequency/durability, effect on annual bleeding, uncertainty related to side effects, impact on daily activities, impact on mental health, and post‐treatment requirements. The relative importance of each attribute was analysed overall and for subgroups based on haemophilia type and severity. Results: A total of 183 males with haemophilia A (n = 120) or B (n = 63) were included. Half (47%) had severe haemophilia; most (75%) were White. Overall, participants gave effect on bleeding rate the greatest relative importance (31%), followed by dose frequency/durability (26%), uncertainty regarding safety issues (17%), and impact on daily activities (11%). Dose frequency/durability had the greatest importance for those with haemophilia B (35%). Conclusion: People with haemophilia prioritised reduced bleeding and treatment burden; the former was more important in haemophilia A and the latter in haemophilia B, followed by safety and impact on daily life in this DCE of gene therapy attributes. These findings and differences can inform clinical and health policy decisions to improve health equity for people with haemophilia.
    • Patient preferences for stratified medicine in psoriasis: a discrete choice experiment

      Dalal, G.; orcid: 0000-0002-4073-4215; Wright, S.J.; Vass, C.M.; Davison, N.J.; Vander Stichele, G.; Smith, C.H.; Griffiths, C.E.M.; orcid: 0000-0001-5371-4427; Payne, K.; orcid: 0000-0002-3938-4350; email: katherine.payne@manchester.ac.uk; the PSORT Consortium (2021-07-29)
      Summary: Background: New technologies have enabled the potential for stratified medicine in psoriasis. It is important to understand patients’ preferences to enable the informed introduction of stratified medicine, which is likely to involve a number of individual tests that could be collated into a prescribing algorithm for biological drug selection to be used in clinical practice. Objectives: To quantify patient preferences for an algorithm‐based approach to prescribing biologics (‘biologic calculator’) in psoriasis. Methods: An online survey comprising a discrete choice experiment (DCE) was conducted to elicit the preferences of two purposive samples of adults living with psoriasis in the UK, identified from a psoriasis patient organization (Psoriasis Association) and an online panel provider (Dynata). Respondents chose between two biologic calculators and conventional prescribing described using five attributes: treatment delay; positive predictive value; negative predictive value; risk of infection; and cost saving to the National Health Service. Each participant selected their preferred alternative from six hypothetical choice sets. Additional data, including sociodemographic characteristics, were collected. Choice data were analysed using conditional logit and fully correlated random parameters logit models. Results: Data from 212 respondents (67 from the Psoriasis Association and 145 from Dynata) were analysed. The signs of all estimated coefficients were consistent with a priori expectations. Respondents had a strong preference for a high predictive accuracy and avoiding serious infection, but there was evidence of systematic differences in preferences between the samples. Conclusions: This study indicates that individuals with psoriasis would value a biologic calculator and suggested that such a biologic calculator should have sufficient accuracy to predict future response and risk of serious infection from the biologic.
    • Patient‐relevant health outcomes for hemophilia care: Development of an international standard outcomes set

      Balen, Erna C.; orcid: 0000-0002-3678-6581; O'Mahony, Brian; Cnossen, Marjon H.; Dolan, Gerard; Blanchette, Victor S.; Fischer, Kathelijn; Gue, Deborah; O'Hara, Jamie; Iorio, Alfonso; orcid: 0000-0002-3331-8766; Jackson, Shannon; et al. (Wiley, 2021-03-06)