Search

Prof. Warren reports grants and personal fees from Abbvie, grants and personal fees from Celgene, grants and personal fees from Eli Lilly, grants and personal fees from Novartis, personal fees from Sanofi, grants and personal fees from UCB|, grants and personal fees from Almirall, grants and personal fees from Amgen, grants and personal fees from Janssen, grants and personal fees from Leo, grants and personal fees from Pfizer, personal fees from Arena, personal fees from Avillion, personal fees from Bristol Myers Squibb, personal fees from Boehringer Ingelheim, outside the submitted work. We are grateful to all the patients who have contributed to PsoProtect I Me i , the professional and patient organisations who supported or promoted PsoProtect I M i e and for the input of Prof Lars Iversen, Prof Nick Reynolds, Prof Joel Gelfand, Ms Christine Janus and Ms Melissa Sweeney through their vital contributions. Dr. Di Meglio reports grants and personal fees from UCB, personal fees from Novartis, personal fees from Janssen, outside the submitted work. [Extracted from the article]

Summary: Background: Registry data suggest that people with immune‐mediated inflammatory diseases (IMIDs) receiving targeted systemic therapies have fewer adverse coronavirus disease 2019 (COVID‐19) outcomes compared with patients receiving no systemic treatments. Objectives: We used international patient survey data to explore the hypothesis that greater risk‐mitigating behaviour in those receiving targeted therapies may account, at least in part, for this observation. Methods: Online surveys were completed by individuals with psoriasis (globally) or rheumatic and musculoskeletal diseases (RMDs) (UK only) between 4 May and 7 September 2020. We used multiple logistic regression to assess the association between treatment type and risk‐mitigating behaviour, adjusting for clinical and demographic characteristics. We characterized international variation in a mixed‐effects model. Results: Of 3720 participants (2869 psoriasis, 851 RMDs) from 74 countries, 2262 (60·8%) reported the most stringent risk‐mitigating behaviour (classified here under the umbrella term 'shielding'). A greater proportion of those receiving targeted therapies (biologics and Janus Kinase inhibitors) reported shielding compared with those receiving no systemic therapy [adjusted odds ratio (OR) 1·63, 95% confidence interval (CI) 1·35–1·97]. The association between targeted therapy and shielding was preserved when standard systemic therapy was used as the reference group (OR 1·39, 95% CI 1·23–1·56). Shielding was associated with established risk factors for severe COVID‐19 [male sex (OR 1·14, 95% CI 1·05–1·24), obesity (OR 1·37, 95% CI 1·23–1·54), comorbidity burden (OR 1·43, 95% CI 1·15–1·78)], a primary indication of RMDs (OR 1·37, 95% CI 1·27–1·48) and a positive anxiety or depression screen (OR 1·57, 95% CI 1·36–1·80). Modest differences in the proportion shielding were observed across nations. Conclusions: Greater risk‐mitigating behaviour among people with IMIDs receiving targeted therapies may contribute to the reported lower risk of adverse COVID‐19 outcomes. The behaviour variation across treatment groups, IMIDs and nations reinforces the need for clear evidence‐based patient communication on risk‐mitigation strategies and may help inform updated public health guidelines as the pandemic continues. What is already known about this topic? At the beginning of the coronavirus disease 2019 (COVID‐19) pandemic, patients with immune‐mediated inflammatory diseases (IMIDs) on targeted systemic therapies were considered to be at higher risk of severe COVID‐19.Subsequent clinician‐reported registry data suggest that targeted systemic therapy use is associated with fewer adverse COVID‐19 outcomes compared with no systemic therapy. What does this study add? We characterize shielding behaviour in 3720 patients with IMIDs from a global self‐report survey.Use of targeted systemic therapy associates with increased shielding behaviour, compared with standard systemics or no therapy, as do demographic risk factors for severe COVID‐19 including male sex and obesity.Greater risk‐mitigating behaviour among people with IMIDs receiving targeted therapies may contribute to the reported lower risk of adverse COVID‐19 outcomes.Behaviour variation across treatment groups reinforces the need for clear, evidence‐based patient communication on risk‐mitigation strategies.These data may help to inform updated public health guidelines as the pandemic continues. Linked Comment: G. Becher and A.D. Burden. Br J Dermatol 2021; 185:7–8. [ABSTRACT FROM AUTHOR]

After the 'dot-com bust' there is considerable evidence that multi-channel retailers are more successful than purely on-line retailers. We talked to the management team of one of the most successful multi-channel apparel and home-ware retailers in Australasia about the business and technology factors that enabled their growth. We found seven key business strategies enabled growth and expansion into new channels, including e-commerce: integrated operational functions, channel synergy, logistics management, presenting a consistent brand, effective customer management, learning from customers, and informed imitation. These strategies were supported by integrated information technology applications. At the time of our study, the recently added Internet channel was not fully integrated with the other core systems. This was being adequately managed through strong internal processes but had the potential to constrain future growth in this channel. We examine the factors that led to the firm's success and some of the issues and constraints they are experiencing. We then extract from their experiences the lessons that can be learned by other organisations. [ABSTRACT FROM AUTHOR]

Abstract Background Artemisinin-based combination therapy (ACT) is the first-line malaria treatment throughout most of the malaria-endemic world. Data on ACT availability, price and market share are needed to provide a firm evidence base from which to assess the current situation concerning quality-assured ACT supply. This paper presents supply side data from ACTwatch outlet surveys in Benin, the Democratic Republic of Congo (DRC), Madagascar, Nigeria, Uganda and Zambia. Methods Between March 2009 and June 2010, nationally representative surveys of outlets providing anti-malarials to consumers were conducted. A census of all outlets with the potential to provide anti-malarials was conducted in clusters sampled randomly. Results 28,263 outlets were censused, 51,158 anti-malarials were audited, and 9,118 providers interviewed. The proportion of public health facilities with at least one first-line quality-assured ACT in stock ranged between 43% and 85%. Among private sector outlets stocking at least one anti-malarial, non-artemisinin therapies, such as chloroquine and sulphadoxine-pyrimethamine, were widely available (> 95% of outlets) as compared to first-line quality-assured ACT (< 25%). In the public/not-for-profit sector, first-line quality-assured ACT was available for free in all countries except Benin and the DRC (US$1.29 [Inter Quartile Range (IQR): $1.29-$1.29] and $0.52[IQR: $0.00-$1.29] per adult equivalent dose respectively). In the private sector, first-line quality-assured ACT was 5-24 times more expensive than non-artemisinin therapies. The exception was Madagascar where, due to national social marketing of subsidized ACT, the price of first-line quality-assured ACT ($0.14 [IQR: $0.10, $0.57]) was significantly lower than the most popular treatment (chloroquine, $0.36 [IQR: $0.36, $0.36]). Quality-assured ACT accounted for less than 25% of total anti-malarial volumes; private-sector quality-assured ACT volumes represented less than 6% of the total market share. Most anti-malarials were distributed through the private sector, but often comprised non-artemisinin therapies, and in the DRC and Nigeria, oral artemisinin monotherapies. Provider knowledge of the first-line treatment was significantly lower in the private sector than in the public/not-for-profit sector. Conclusions These standardized, nationally representative results demonstrate the typically low availability, low market share and high prices of ACT, in the private sector where most anti-malarials are accessed, with some exceptions. The results confirm that there is substantial room to improve availability and affordability of ACT treatment in the surveyed countries. The data will also be useful for monitoring the impact of interventions such as the Affordable Medicines Facility for malaria.

Abstract Background Access to artemisinin-based combination therapy (ACT) remains limited in high malaria-burden countries, and there are concerns that the poorest people are particularly disadvantaged. This paper presents new evidence on household treatment-seeking behaviour in six African countries. These data provide a baseline for monitoring interventions to increase ACT coverage, such as the Affordable Medicines Facility for malaria (AMFm). Methods Nationally representative household surveys were conducted in Benin, the Democratic Republic of Congo (DRC), Madagascar, Nigeria, Uganda and Zambia between 2008 and 2010. Caregivers responded to questions about management of recent fevers in children under five. Treatment indicators were tabulated across countries, and differences in case management provided by the public versus private sector were examined using chi-square tests. Logistic regression was used to test for association between socioeconomic status and 1) malaria blood testing, and 2) ACT treatment. Results Fever treatment with an ACT is low in Benin (10%), the DRC (5%), Madagascar (3%) and Nigeria (5%), but higher in Uganda (21%) and Zambia (21%). The wealthiest children are significantly more likely to receive ACT compared to the poorest children in Benin (OR = 2.68, 95% CI = 1.12-6.42); the DRC (OR = 2.18, 95% CI = 1.12-4.24); Madagascar (OR = 5.37, 95% CI = 1.58-18.24); and Nigeria (OR = 6.59, 95% CI = 2.73-15.89). Most caregivers seek treatment outside of the home, and private sector outlets are commonly the sole external source of treatment (except in Zambia). However, children treated in the public sector are significantly more likely to receive ACT treatment than those treated in the private sector (except in Madagascar). Nonetheless, levels of testing and ACT treatment in the public sector are low. Few caregivers name the national first-line drug as most effective for treating malaria in Madagascar (2%), the DRC (2%), Nigeria (4%) and Benin (10%). Awareness is higher in Zambia (49%) and Uganda (33%). Conclusions Levels of effective fever treatment are low and inequitable in many contexts. The private sector is frequently accessed however case management practices are relatively poor in comparison with the public sector. Supporting interventions to inform caregiver demand for ACT and to improve provider behaviour in both the public and private sectors are needed to achieve maximum gains in the context of improved access to effective treatment.

Rising numbers of individuals receiving psoriasis biologics achieve clear/nearly clear skin (disease control). Trial data indicate some maintain control with lower doses, especially those with higher serum drug concentrations. This indicates potential for Model-Informed Precision Dosing (MIPD), an advanced therapeutic drug monitoring technique, in guiding dose minimisation. We developed, validated, and user-tested a precision dosing dashboard. We applied a MIPD approach leveraging Bayesian estimation to predict individual pharmacokinetic (PK) parameters for personalised dosing recommendations. A PK model of the exemplar biologic risankizumab, derived from phase I-III psoriasis trial data (13123 observations/1899 patients), was externally validated using real-world UK psoriasis data. The Bayesian model (posterior prediction: mean absolute error 0.89 mg/L; mean percentage error 19.55%; root mean square error 1.24 mg/L; R 2 0.86) had superior predictive power to the basic PK model (prior prediction). The model was incorporated into an interactive dashboard, enabling input of individual patient data (serum drug concentrations, model covariates). UK healthcare professionals rated the dashboard user-friendly and acceptable. Mean time to generate a dosing interval was 2 minutes. Our dashboard has potential to incorporate other biologics and extend across disease contexts (non-response, other inflammatory diseases) for optimal real-world impact of precision dosing on health and cost outcomes., (Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Lifestyle changes have meant that it is problematic for many people across the globe to maintain adequate vitamin D concentrations. As UV-catalysed production in the skin, which uses vitamin D-binding protein to facilitate systemic absorption, is the primary source of vitamin D, it is questionable if oral supplementation of this vitamin is the optimal means to replace it. However, supplementing an oil-soluble vitamin via the skin is problematic as it gets stuck in the stratum corneum after topical application. This clinical study will test if a new vitamin D ester, vitamin D phosphate, which is more water-soluble compared to vitamin D, administered via a transdermal patch, can be used to improve vitamin D status., Method: This is a two-part study comprising a dose-escalation with the vitamin D phosphate transdermal patch followed by a randomised, double-blind, placebo-controlled, multiarmed, multistage clinical trial. It is a single-centred, 12-week study that will enrol a maximum of 100 participants. The dose escalation study will monitor safety and tolerability using serum calcium and 25(OH)D 3 levels. The blinded, randomised trial will test different dose frequencies for 4 weeks compared to a placebo. Then, after an interim analysis, the best dosing frequency will be assessed against a placebo. The primary outcome for the multistage clinical study will be the percentage change in 25(OH)D 3 concentration in the serum (ng/mL) at weeks 4 and 8 compared to baseline. The secondary outcome measures include percentage change in serum vitamin D-binding protein levels, skin interstitial fluid biomarker concentrations, and nail appearance after 4 and 8 weeks compared to baseline., Discussion: This study will determine if a vitamin D phosphate transdermal patch can improve vitamin D status. In addition, it could provide a better understanding of how vitamin D is absorbed directly into the skin after application by measuring the serum vitamin D-binding protein and skin biomarker responses to transdermal supplementation., Trial Registration: Clinical Trials.gov NCT06098846, registered on 23rd October 2023., Competing Interests: Declarations. Ethics approval and consent to participate: Research ethics approval This clinical trial has been approved by the King’s College, London Research Ethics Committee (KCL-REC) [Reference Number: HR/DP-22/23-34078, Study Title: TransVitD]. Any protocol amendments will be submitted to King’s College REC for approval. The trial will comply with good clinical practice guidelines over the reporting of adverse events (AEs), serious adverse events (SAEs), and suspected serious adverse reactions (SUSARs) as well as providing the REC with progress reports and final study report. Patient or participant protocol involvement There was no patient or participant involvement in the study protocol design. Protocol amendments If amendments to this protocol are required, approval will be sought from the KCL-REC and updated protocol will be made available on request. This protocol version is 1.5, 10th October 2024. The PI will notify the trial sponsor, funders, and trial centre clinical teams of any protocol changes. In addition, a copy of the revised protocol will be added to the Investigator Site File and the consent forms and clinical trial registry entry will be amended to reflect the changes. Consent for publication: All participants have agreed to the publication of these results. Competing interests: SAJ is the inventor of the vitamin D phosphate patent WO2022084669A1. MAA and SAJ have received funding to develop and test the vitamin D patch in preclinical studies from Vitamax Patch Wholesaler LLC., (© 2025. The Author(s).)

Background: The main conventional systemic treatments for atopic dermatitis (AD) are methotrexate (MTX) and ciclosporin (CyA). Dupilumab was the first novel systemic agent to enter routine clinical practice. There are no head-to-head randomized controlled trials or real-world studies comparing these agents directly. Network meta-analyses provide indirect comparative efficacy and safety data and have shown strong evidence for dupilumab and CyA., Objectives: To compare the real-world clinical effectiveness and safety of CyA, dupilumab and MTX in AD., Methods: We compared the effectiveness and safety of these systemic agents in a prospective observational cohort study of adult and paediatric patients recruited into the UK-Irish Atopic eczema Systemic TherApy Register (A-STAR). Treatment effectiveness measures included Eczema Area and Severity Index (EASI), Patient-Oriented Eczema Measure (POEM), Peak Pruritus Numerical Rating Scale (PP-NRS), Dermatology Life Quality Index (DLQI) and children's DLQI (cDLQI). The minimum duration of treatment was 28 days and follow-up was 12 months. Adjusted Cox-regression analysis was used to compare the hazard ratios of achieving EASI-50, EASI-75 and EASI-90 over time, and linear mixed-effects models were used to estimate changes in efficacy scores. Treatment safety was assessed by examining adverse events (AEs) at follow-up visits., Results: We included 488 patients (311 adults and 177 children/adolescents) on dupilumab (n = 282), MTX (n = 149) or CyA (n = 57). CyA and MTX were primarily used as the first-line treatment, while dupilumab was mainly a second-line systemic treatment as per UK National Institute of Clinical and Care Excellence (NICE) recommendations. EASI-50, EASI-75 and EASI-90 were achieved more rapidly in the dupilumab and CyA groups compared with MTX. After adjustment for previous severity, the reduction in EASI, POEM, PP-NRS and DLQI was greater for patients treated with dupilumab compared with MTX. In patients with severe disease the reduction in EASI, POEM and PP-NRS was even greater with CyA. The incidence rates of AEs were similar across groups (734, 654 and 594 per 10 000 person-month on CyA, dupilumab and MTX, respectively)., Conclusions: This real-world comparison of CyA, dupilumab and MTX in AD suggests that dupilumab is consistently more effective than MTX and that CyA is most effective in very severe disease within 1 year of follow-up., Competing Interests: Conflicts of interest The full conflicts of interest statement is provided in Appendix 3., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Association of Dermatologists.)

While hostile attributional bias (a tendency to interpret others' behaviors as intentionally hostile) is associated with negative outcomes in romantic relationships, no measure has been developed specifically for this context. Here, we describe the development and validation of a self-report questionnaire across three studies, named Hostile Attribution in Romantic Relationships Test. Study 1 introduces the development and preliminary validation (N = 152). Study 2 tests the validity and test-retest stability of the modified version revised based on findings in Study 1 (N = 151). Study 3 reports the translation and validation of a Chinese version (N = 630). The final 9-vignette scale is the first to specifically measure hostile attribution bias in romantic relationships, with good internal reliability, test-retest stability, and convergent validity. Factor analysis reveals a three-factor structure reflecting direct hostile attribution, indirect hostile attribution, and benign attribution to partners' behaviors. Implications regarding couple dynamics and clinical therapeutic interventions are discussed., (© 2024 The Authors. Journal of Marital and Family Therapy published by Wiley Periodicals LLC on behalf of American Association for Marriage and Family Therapy.)

Objective: Monoclonal antibody (Mab) treatments have significantly improved the quality and quantity of life, but they are some of the most expensive treatments, resulting in a degree of hesitancy to introduce new Mab agents. A system for estimating the effect of Mab drugs, in general, would optimally inform health strategy and fully realize how a single scientific discovery can deliver health benefits. We evaluated such a method with several well-established Mab regimens., Methods: We selected five different Mab regimens in oncology and rheumatology in England. We carried out two systematic literature reviews and meta-analyses to assess health outcomes (Health Assessment Questionnaire-Disability Index for rheumatoid arthritis; overall mortality for melanoma) from real-world data and compared them to the outcomes from randomized control trials (RCTs). We applied economic modeling to estimate the net monetary benefits for health outcomes for the estimated patient population size for each Mab regimen., Results: Meta-analyses of 27 eligible real-world data (RWD) sets and 26 randomized controlled trial (RCT) sets found close agreement between the observed and expected health outcomes. A Markov model showed the net positive monetary benefit in three Mab regimens and the negative benefit in two regimens. However, because of limited access to NHS data, the economic model made several assumptions about the number of treated patients and the cost of treatment to the NHS, the accuracy of which may affect the estimation of the net monetary benefit., Conclusion: RCT results reliably inform the real-world experience of Mab treatments. Calculation of the net monetary benefit by the algorithm described provides a valuable overall measure of the health impact, subject to the accuracy of data inputs. This study provides a compelling case for building a comprehensive, systematized, and accessible database and related analytics, on all Mab treatments within health services., Competing Interests: MR has received honoraria from Lilly, Galapagos, Biogen and Menarini, and support for attending conferences from Lilly, Pfizer, Janssen and UCB. LM is author of multiple articles and a book on the history of Mabs. SS is Co-inventor with MRC of Mabs for ABO blood typing. LM receives royalties from Yale University Press for her book The Lock and Key of Medicine: Monoclonal antibodies and the transformation of healthcare (2015). She has also been a consultant for two documentary films about monoclonal antibodies, respectively produced by Holt Productions and Pulpo Films. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Lim, Ng, Balachandran, Russell, Boalch, Sinclair, Coker, Vinnakota, Mansoor, Douiri, Marks and Sacks.)

Background: Nonadherence to immune-modifying therapy is a complex behaviour which, before the COVID-19 pandemic, was shown to be associated with mental health disorders in people with immune-mediated diseases. The COVID-19 pandemic has led to a rise in the global prevalence of anxiety and depression, and limited data exist on the association between mental health and nonadherence to immune-modifying therapy during the pandemic., Objectives: To assess the extent of and reasons underlying nonadherence to systemic immune-modifying therapy during the COVID-19 pandemic in individuals with psoriasis, and the association between mental health and nonadherence., Methods: Online self-report surveys (PsoProtectMe), including validated screens for anxiety and depression, were completed globally during the first year of the pandemic. We assessed the association between anxiety or depression and nonadherence to systemic immune-modifying therapy using binomial logistic regression, adjusting for potential cofounders (age, sex, ethnicity, comorbidity) and country of residence., Results: Of 3980 participants from 77 countries, 1611 (40.5%) were prescribed a systemic immune-modifying therapy. Of these, 408 (25.3%) reported nonadherence during the pandemic, most commonly due to concerns about their immunity. In the unadjusted model, a positive anxiety screen was associated with nonadherence to systemic immune-modifying therapy [odds ratio (OR) 1.37, 95% confidence interval (CI) 1.07-1.76]. Specifically, anxiety was associated with nonadherence to targeted therapy (OR 1.41, 95% CI 1.01-1.96) but not standard systemic therapy (OR 1.16, 95% CI 0.81-1.67). In the adjusted model, although the directions of the effects remained, anxiety was not significantly associated with nonadherence to overall systemic (OR 1.20, 95% CI 0.92-1.56) or targeted (OR 1.33, 95% CI 0.94-1.89) immune-modifying therapy. A positive depression screen was not strongly associated with nonadherence to systemic immune-modifying therapy in the unadjusted (OR 1.22, 95% CI 0.94-1.57) or adjusted models (OR 1.14, 95% CI 0.87-1.49)., Conclusions: These data indicate substantial nonadherence to immune-modifying therapy in people with psoriasis during the pandemic, with attenuation of the association with mental health after adjusting for confounders. Future research in larger populations should further explore pandemic-specific drivers of treatment nonadherence. Clear communication of the reassuring findings from population-based research regarding immune-modifying therapy-associated adverse COVID-19 risks to people with psoriasis is essential, to optimize adherence and disease outcomes., Competing Interests: Conflict of interests J.W. has presented talks for Abbott, AbbVie, Bayer, Boehringer Ingelheim, Chiesi, Merck and Roche. K.J.M. reports personal fees from LEO Pharma and Novartis, outside the submitted work. H.M. reports grants from AbbVie, Almirall, Celgene, Dermal Laboratories, Eli Lilly, Janssen, LEO Pharma, T & R Derma and UCB, outside the submitted work. D.U. reports grants from AbbVie, Almirall, Amgen, Celgene, Dermal Laboratories, Eli Lilly, Janssen, LEO Pharma, T & R Derma and UCB, outside the submitted work. L.M. reports personal fees from AbbVie, Celgene, Janssen, LEO Pharma, Novartis and UCB, outside the submitted work. Additional disclosures from L.M. include Almirall, BMS and Lilly. H.B. reports personal fees from AbbVie, Almirall, Biocad, Boehringer-Ingelheim, Janssen, Kyowa Kirin, LEO Pharma, Novartis, Pfizer and UCB, outside the submitted work. F.C. reports consultancy fees from AnaptysBio, grants from Boehringer Ingelheim, outside the submitted work. C.D.l.C. reports personal fees from Boehringer Ingelheim and UCB Pharma; grants from Janssen, Pfizer, Sandoz, Sanofi; grants and personal fees from AbbVie, Novartis, outside the submitted work. P.D.M. reports grants and personal fees from UCB; personal fees from Janssen and Novartis, outside the submitted work. P.G. reports personal fees from AbbVie, Amgen, Eli Lilly, Janssen, Novartis, Pierre Fabre, Sandoz and UCB, outside the submitted work. D.J. reports personal fees and nonfinancial support from AbbVie, Celgene, Janssen-Cilag, Lilly, LEO Pharma, MEDAC and Novartis; and personal fees from Amgen, outside the submitted work. L.P. reports grants and personal fees from AbbVie, Almirall, Amgen, Boehringer Ingelheim, Janssen, Lilly, Novartis and UCB; and personal fees from Bristol Myers Squibb, Fresenius-Kabi, Mylan, Pfizer, Samsung-Bioepis, Sandoz, Sanofi, outside the submitted work. P.S. has done consultancies in the past for Sanofi 111017 and AbbVie 041217 (unpaid); has received departmental independent research grants for TREAT NL registry from pharma companies since December 2019; is involved in performing clinical trials with many pharmaceutical industries that manufacture drugs used for the treatment of diseases such as psoriasis and atopic dermatitis, for which financial compensation is paid to the department/hospital; and is chief investigator of the systemic and phototherapy atopic eczema registry (TREAT NL) for adults and children, as well as one of the main investigators of the SECURE-AD registry. T.T. reports grants and personal fees from AbbVie, Almirall, Amgen, Arena Pharmaceuticals, Biocad, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Janssen, LEO Pharma, MSD, Novartis, Pfizer, Samsung-Bioepis and Sandoz, during the conduct of the study. R.B.W. reports grants from AbbVie, Almirall, Amgen, Celgene, Janssen, LEO, Lilly, Medac, Novartis, Pfizer and UCB. R.B.W. also reports consultancy fees from AbbVie, Almirall, Amgen, Arena, Astellas, Avillion, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, DiCE, GSK, Janssen, LEO, Lilly, Medac, Novartis, Pfizer, Sanofi, Sun Pharma, UCB and UNION. H.W. is on the Board of the International Federation of Psoriasis Associations who have received grants from AbbVie, Almirall, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Janssen, LEO Pharma, Novartis, Pfizer, Sun Pharma and UCB, outside the submitted work. J.B.G. reports personal fees from AbbVie, Eli Lilly, Janssen, Novartis, Pfizer, Sanofi and UCB, outside the submitted work. C.E.M.G. reports grants and personal fees from AbbVie, Janssen, Lilly and Novartis and UCB Pharma; and grants from Almirall, Amgen, BMS, LEO and Pfizer, outside the submitted work. J.N.B. reports grants and personal fees from AbbVie, J&J, Lilly and Novartis during the conduct of the study. J.N.B. has attended advisory boards, and/or received consultancy fees, and/or spoken at sponsored symposia, and/or received grant funding from AbbVie, Almirall, Amgen, Boehringer Ingelheim, Bristol Meyers Squibb, Celgene, Janssen, LEO Pharma, Lilly, Novartis, Pfizer, Samsung, Sun Pharma and UCB. C.H.S. reports grants from AbbVie, Novartis, Pfizer and Sanofi; and through consortia with multiple academic partners (psort.org.uk, BIOMAP-IMI.eu), outside the submitted work. S.K.M. reports departmental income from AbbVie, Almirall, Eli Lilly, Janssen-Cilag, Novartis, Sanofi and UCB, outside the submitted work., (© The Author(s) 2022. Published by Oxford University Press on behalf of British Association of Dermatologists.)

Background: Post-transplant glomerulonephritis (PTGN) has been associated with inferior long-term allograft survival, and its incidence varies widely in the literature., Methods: This is a cohort study of 7,623 patients transplanted between 2005 and 2016 at four major transplant UK centres. The diagnosis of glomerulonephritis (GN) in the allograft was extracted from histology reports aided by the use of text-mining software. The incidence of the four most common GN post-transplantation was calculated, and the risk factors for disease and allograft outcomes were analyzed., Results: In total, 214 patients (2.8%) presented with PTGN. IgA nephropathy (IgAN), focal segmental glomerulosclerosis (FSGS), membranous nephropathy (MN), and membranoproliferative/mesangiocapillary GN (MPGN/MCGN) were the four most common forms of post-transplant GN. Living donation, HLA DR match, mixed race, and other ethnic minority groups were associated with an increased risk of developing a PTGN. Patients with PTGN showed a similar allograft survival to those without in the first 8 years of post-transplantation, but the results suggest that they do less well after that timepoint. IgAN was associated with the best allograft survival and FSGS with the worst allograft survival., Conclusions: PTGN has an important impact on long-term allograft survival. Significant challenges can be encountered when attempting to analyze large-scale data involving unstructured or complex data points, and the use of computational analysis can assist., Competing Interests: MH-F is currently an employee of UCB Celltech, a pharmaceutical company. Her involvement in the conduct of this research was solely in her capacity as academic at King’s College London. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Aguiar, Bourmpaki, Bunce, Coker, Delaney, de Jongh, Oliveira, Weir, Higgins, Spiridou, Hasan, Smith, Mulla, Glampson, Mercuri, Montero, Hernandez-Fuentes, Roufosse, Simmonds, Clatworthy, McLean, Ploeg, Davies, Várnai, Woods, Lord, Pruthi, Breen and Chowdhury.)

Background: Antenatal detection and management of small for gestational age (SGA) is a strategy to reduce stillbirth. Large observational studies provide conflicting results on the effect of the Growth Assessment Protocol (GAP) in relation to detection of SGA and reduction of stillbirth; to the best of our knowledge, there are no reported randomised control trials. Our aim was to determine if GAP improves antenatal detection of SGA compared to standard care., Methods and Findings: This was a pragmatic, superiority, 2-arm, parallel group, open, cluster randomised control trial. Maternity units in England were eligible to participate in the study, except if they had already implemented GAP. All women who gave birth in participating clusters (maternity units) during the year prior to randomisation and during the trial (November 2016 to February 2019) were included. Multiple pregnancies, fetal abnormalities or births before 24+1 weeks were excluded. Clusters were randomised to immediate implementation of GAP, an antenatal care package aimed at improving detection of SGA as a means to reduce the rate of stillbirth, or to standard care. Randomisation by random permutation was stratified by time of study inclusion and cluster size. Data were obtained from hospital electronic records for 12 months prerandomisation, the washout period (interval between randomisation and data collection of outcomes), and the outcome period (last 6 months of the study). The primary outcome was ultrasound detection of SGA (estimated fetal weight <10th centile using customised centiles (intervention) or Hadlock centiles (standard care)) confirmed at birth (birthweight <10th centile by both customised and population centiles). Secondary outcomes were maternal and neonatal outcomes, including induction of labour, gestational age at delivery, mode of birth, neonatal morbidity, and stillbirth/perinatal mortality. A 2-stage cluster-summary statistical approach calculated the absolute difference (intervention minus standard care arm) adjusted using the prerandomisation estimate, maternal age, ethnicity, parity, and randomisation strata. Intervention arm clusters that made no attempt to implement GAP were excluded in modified intention to treat (mITT) analysis; full ITT was also reported. Process evaluation assessed implementation fidelity, reach, dose, acceptability, and feasibility. Seven clusters were randomised to GAP and 6 to standard care. Following exclusions, there were 11,096 births exposed to the intervention (5 clusters) and 13,810 exposed to standard care (6 clusters) during the outcome period (mITT analysis). Age, height, and weight were broadly similar between arms, but there were fewer women: of white ethnicity (56.2% versus 62.7%), and in the least deprived quintile of the Index of Multiple Deprivation (7.5% versus 16.5%) in the intervention arm during the outcome period. Antenatal detection of SGA was 25.9% in the intervention and 27.7% in the standard care arm (adjusted difference 2.2%, 95% confidence interval (CI) -6.4% to 10.7%; p = 0.62). Findings were consistent in full ITT analysis. Fidelity and dose of GAP implementation were variable, while a high proportion (88.7%) of women were reached. Use of routinely collected data is both a strength (cost-efficient) and a limitation (occurrence of missing data); the modest number of clusters limits our ability to study small effect sizes., Conclusions: In this study, we observed no effect of GAP on antenatal detection of SGA compared to standard care. Given variable implementation observed, future studies should incorporate standardised implementation outcomes such as those reported here to determine generalisability of our findings., Trial Registration: This trial is registered with the ISRCTN registry, ISRCTN67698474., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: NM reports personal fees from Takeda, personal fees from RSM Consulting, personal fees from Novartis, outside the submitted work. BT is the Clinical Director of the Tommy’s National Centre for Maternity Improvement based at the Royal College of Obstetrics and Gynaecology (RCOG); the Centre’s objective is to translate the latest evidence into clinical practice in the UK. DAL has received support from Medtronic Ltd and Roche Diagnostics for research unrelated to that presented here. LP is clinical advisor [and from Sept 2021 deputy clinical director] for Healthcare Safety Investigation Branch maternity investigation programme, President of the British Intrapartum Care Society (BICS), invited member of some RCOG working groups and co-opted member of the British Maternal and Fetal Medicine Society (BMFMS) committee; she also received support from Pharmacosmos for clinical consultancy in work unrelated to that presented here.