Forefoot pathology in rheumatoid arthritis identified with ultrasound may not localise to areas of highest pressure: cohort observations at baseline and twelve months

BackgroundPlantar pressures are commonly used as clinical measures, especially to determine optimum foot orthotic design. In rheumatoid arthritis (RA) high plantar foot pressures have been linked to metatarsophalangeal (MTP) joint radiological erosion scores. However, the sensitivity of foot pressure measurement to soft tissue pathology within the foot is unknown. The aim of this study was to observe plantar foot pressures and forefoot soft tissue pathology in patients who have RA.Methods A total of 114 patients with established RA (1987 ACR criteria) and 50 healthy volunteers were assessed at baseline. All RA participants returned for reassessment at twelve months. Interface foot-shoe plantar pressures were recorded using an F-Scan® system. The presence of forefoot soft tissue pathology was assessed using a DIASUS musculoskeletal ultrasound (US) system. Chi-square analyses and independent t-tests were used to determine statistical differences between baseline and twelve months. Pearson’s correlation coefficient was used to determine interrelationships between soft tissue pathology and foot pressures.ResultsAt baseline, RA patients had a significantly higher peak foot pressures compared to healthy participants and peak pressures were located in the medial aspect of the forefoot in both groups. In contrast, RA participants had US detectable soft tissue pathology in the lateral aspect of the forefoot. Analysis of person specific data suggests that there are considerable variations over time with more than half the RA cohort having unstable presence of US detectable forefoot soft tissue pathology. Findings also indicated that, over time, changes in US detectable soft tissue pathology are out of phase with changes in foot-shoe interface pressures both temporally and spatially.Conclusions We found that US detectable forefoot soft tissue pathology may be unrelated to peak forefoot pressures and suggest that patients with RA may biomechanically adapt to soft tissue forefoot pathology. In addition, we have observed that, in patients with RA, interface foot-shoe pressures and the presence of US detectable forefoot pathology may vary substantially over time. This has implications for clinical strategies that aim to offload peak plantar pressures

'Ain't it a Ripping Night': Alcoholism and the Legacies of Empire in Salman Rushdie's Midnight's Children.

In the era of decolonisation that followed the Second World War, various authors sought to engage with India and the Empire’s past anew throughout their novels, identifying medicine and illness as key parts of Imperial authority and colonial experience. Salman Rushdie’s approach to the Raj in Midnight’s Children (1981) focused on the broad sweep of colonial life, juxtaposing the political and the personal. This article argues that Rushdie explores the history of colonial India by employing alcohol and alcoholism as lenses through which to explore the cultural, political and medical legacies of Empire. Through analysis of Midnight’s Children as well as a range of medical sources related to alcohol and inebriation, it will illustrate how drinking is central to Rushdie’s approach to secular and religious identities in newly independent India, as well as a means of satirising and undermining the supposed benefit that Empire presented to India and Indians

Training the next generation of clinical researchers: Evaluation of a graduate podiatrist research internship in rheumatology

Background: The aim of this study was to evaluate the effectiveness of the Arthritis Research UK funded graduate internship scheme for podiatrists and to explore the experiences of interns and mentors. Methods: Nine new graduates completed the internship programme (July 2006-June 2010); six interns and two mentors participated in this study. The study was conducted in three phases. Phase 1: quantitative survey of career and research outcomes for interns. Phase 2 and 3: qualitative asynchronous interviews through email to explore the experiences of interns and mentors. Interpretive phenomenological analysis (IPA) of coded transcripts identified recurring themes. Results: Research outputs included ten peer reviewed publications with authorial contributions from interns, 23 conference abstract presentations and one subsequent 'Jewel in the Crown' award at the British Society for Rheumatology Conference. Career progression includes two National Institute for Health research (NIHR) PhD fellowships, two Arthritis Research UK PhD fellowships, one NIHR Master of Research fellowship and one specialist rheumatology clinical post. Two interns are members of NIHR and professional body committees. Seven important themes arose from the qualitative phases: perceptions of the internship pre-application; internship values; maximising personal and professional development; psychosocial components of the internship; the role of mentoring and networking; access to research career pathways; perceptions of future developments for the internship programme. The role of mentorship and the peer support network have had benefits that have persisted beyond the formal period of the scheme. Conclusions: The internship model appears to have been perceived to have been valuable to the interns' careers and may have contributed significantly to the broader building of capacity in clinical research in foot and ankle rheumatology. We believe the model has potential to be transferable across health disciplines and on national and international scales

Erratum to: Trachoma Prevalence After Discontinuation of Mass Azithromycin Distribution.

In "Trachoma Prevalence After Discontinuation of Mass Azithromycin Distribution [J Infect Dis. 2020 Feb 13, jiz691, https://doi.org/10.1093/infdis/jiz691]" by Godwin et al., the first sentence of the Results section includes a reference to "ITI database" that is incorrect and should read as "GET2020 Database". In addition, the authors note that major contributors to the GET2020 database include numerous Ministries of Health worldwide as well as the Global Trachoma Mapping Project (Solomon AW, Pavluck AL, Courtright P, et al. The Global Trachoma Mapping Project: Methodology of a 34-Country Population-Based Study. Ophthalmic Epidemiol 2015; 22(3):214 25). The authors regret the error

Successful recruitment to trials : findings from the SCIMITAR+ Trial

BACKGROUND: Randomised controlled trials (RCT) can struggle to recruit to target on time. This is especially the case with hard to reach populations such as those with severe mental ill health. The SCIMITAR+ trial, a trial of a bespoke smoking cessation intervention for people with severe mental ill health achieved their recruitment ahead of time and target. This article reports strategies that helped us to achieve this with the aim of aiding others recruiting from similar populations. METHODS: SCIMITAR+ is a multi-centre pragmatic two-arm parallel-group RCT, which aimed to recruit 400 participants with severe mental ill health who smoke and would like to cut down or quit. The study recruited primarily in secondary care through community mental health teams and psychiatrists with a smaller number of participants recruited through primary care. Recruitment opened in October 2015 and closed in December 2016, by which point 526 participants had been recruited. We gathered information from recruiting sites on strategies which led to the successful recruitment in SCIMITAR+ and in this article present our approach to trial management along with the strategies employed by the recruiting sites. RESULTS: Alongside having a dedicated trial manager and trial management team, we identified three main themes that led to successful recruitment. These were: clinicians with a positive attitude to research; researchers and clinicians working together; and the use of NHS targets. The overriding theme was the importance of relationships between both the researchers and the recruiting clinicians and the recruiting clinicians and the participants. CONCLUSIONS: This study makes a significant contribution to the limited evidence base of real-world cases of successful recruitment to RCTs and offers practical guidance to those planning and conducting trials. Building positive relationships between clinicians, researchers and participants is crucial to successful recruitment

Int J Geriatr Psychiatry

Objectives Hearing, vision, and cognitive impairment commonly co‐occur in older adults. Improving sensory function may positively impact outcomes in people with dementia (PwD). We developed a “sensory intervention” (SI) to support hearing and vision in PwD. Here, we report the findings of an international open‐label field trial, and nested case series, to explore the impact of the SI on dementia‐related outcomes. Methods This was a home‐based trial conducted in France, England, and Cyprus. Participants were people with mild‐to‐moderate dementia and hearing and/or vision impairment (n = 19) and their study partners (unpaid carers; n = 19). The “basic” SI included a hearing and vision assessment and provision of glasses and/or hearing aids. A subsample received the “extended” SI with additional weekly visits from a sensory support therapist (SST). Exploratory analyses of dementia‐related, health utility and resource utilisation outcomes were performed. Results Quality of life (QoL) and sensory functional ability improved. Change in QoL exceeded the threshold for a minimum clinically important difference. There was a modest improvement (in absolute terms) post intervention in behavioural disturbance, self‐efficacy, and relationship satisfaction. Study partner time assisting instrumental activities of daily living (iADL) and supervision decreased by about 22 and 38 hours per month, respectively, although time for personal ADL support increased. Qualitative data supported effectiveness of the intervention: PwD were more socially engaged, less isolated, less dependent on study partners, and had improved functional ability and communication. Conclusions These findings support the need for a definitive randomised controlled trial (RCT) to evaluate the effectiveness of the intervention

Evolution of Symbiotic Bacteria in the Distal Human Intestine

The adult human intestine contains trillions of bacteria, representing hundreds of species and thousands of subspecies. Little is known about the selective pressures that have shaped and are shaping this community's component species, which are dominated by members of the Bacteroidetes and Firmicutes divisions. To examine how the intestinal environment affects microbial genome evolution, we have sequenced the genomes of two members of the normal distal human gut microbiota, Bacteroides vulgatus and Bacteroides distasonis, and by comparison with the few other sequenced gut and non-gut Bacteroidetes, analyzed their niche and habitat adaptations. The results show that lateral gene transfer, mobile elements, and gene amplification have played important roles in affecting the ability of gut-dwelling Bacteroidetes to vary their cell surface, sense their environment, and harvest nutrient resources present in the distal intestine. Our findings show that these processes have been a driving force in the adaptation of Bacteroidetes to the distal gut environment, and emphasize the importance of considering the evolution of humans from an additional perspective, namely the evolution of our microbiomes

Effects of Increased Nitrogen Deposition and Precipitation on Seed and Seedling Production of Potentilla tanacetifolia in a Temperate Steppe Ecosystem

The responses of plant seeds and seedlings to changing atmospheric nitrogen (N) deposition and precipitation regimes determine plant population dynamics and community composition under global change.In a temperate steppe in northern China, seeds of P. tanacetifolia were collected from a field-based experiment with N addition and increased precipitation to measure changes in their traits (production, mass, germination). Seedlings germinated from those seeds were grown in a greenhouse to examine the effects of improved N and water availability in maternal and offspring environments on seedling growth. Maternal N-addition stimulated seed production, but it suppressed seed mass, germination rate and seedling biomass of P. tanacetifolia. Maternal N-addition also enhanced responses of seedlings to N and water addition in the offspring environment. Maternal increased-precipitation stimulated seed production, but it had no effect on seed mass and germination rate. Maternal increased-precipitation enhanced seedling growth when grown under similar conditions, whereas seedling responses to offspring N- and water-addition were suppressed by maternal increased-precipitation. Both offspring N-addition and increased-precipitation stimulated growth of seedlings germinated from seeds collected from the maternal control environment without either N or water addition. Our observations indicate that both maternal and offspring environments can influence seedling growth of P. tanacetifolia with consequent impacts on the future population dynamics of this species in the study area.The findings highlight the importance of the maternal effects on seed and seedling production as well as responses of offspring to changing environmental drivers in mechanistic understanding and projecting of plant population dynamics under global change

Oral abstracts 3: RA Treatment and outcomesO13. Validation of jadas in all subtypes of juvenile idiopathic arthritis in a clinical setting

Background: Juvenile Arthritis Disease Activity Score (JADAS) is a 4 variable composite disease activity (DA) score for JIA (including active 10, 27 or 71 joint count (AJC), physician global (PGA), parent/child global (PGE) and ESR). The validity of JADAS for all ILAR subtypes in the routine clinical setting is unknown. We investigated the construct validity of JADAS in the clinical setting in all subtypes of JIA through application to a prospective inception cohort of UK children presenting with new onset inflammatory arthritis. Methods: JADAS 10, 27 and 71 were determined for all children in the Childhood Arthritis Prospective Study (CAPS) with complete data available at baseline. Correlation of JADAS 10, 27 and 71 with single DA markers was determined for all subtypes. All correlations were calculated using Spearman's rank statistic. Results: 262/1238 visits had sufficient data for calculation of JADAS (1028 (83%) AJC, 744 (60%) PGA, 843 (68%) PGE and 459 (37%) ESR). Median age at disease onset was 6.0 years (IQR 2.6-10.4) and 64% were female. Correlation between JADAS 10, 27 and 71 approached 1 for all subtypes. Median JADAS 71 was 5.3 (IQR 2.2-10.1) with a significant difference between median JADAS scores between subtypes (p < 0.01). Correlation of JADAS 71 with each single marker of DA was moderate to high in the total cohort (see Table 1). Overall, correlation with AJC, PGA and PGE was moderate to high and correlation with ESR, limited JC, parental pain and CHAQ was low to moderate in the individual subtypes. Correlation coefficients in the extended oligoarticular, rheumatoid factor negative and enthesitis related subtypes were interpreted with caution in view of low numbers. Conclusions: This study adds to the body of evidence supporting the construct validity of JADAS. JADAS correlates with other measures of DA in all ILAR subtypes in the routine clinical setting. Given the high frequency of missing ESR data, it would be useful to assess the validity of JADAS without inclusion of the ESR. Disclosure statement: All authors have declared no conflicts of interest. Table 1Spearman's correlation between JADAS 71 and single markers DA by ILAR subtype ILAR Subtype Systemic onset JIA Persistent oligo JIA Extended oligo JIA Rheumatoid factor neg JIA Rheumatoid factor pos JIA Enthesitis related JIA Psoriatic JIA Undifferentiated JIA Unknown subtype Total cohort Number of children 23 111 12 57 7 9 19 7 17 262 AJC 0.54 0.67 0.53 0.75 0.53 0.34 0.59 0.81 0.37 0.59 PGA 0.63 0.69 0.25 0.73 0.14 0.05 0.50 0.83 0.56 0.64 PGE 0.51 0.68 0.83 0.61 0.41 0.69 0.71 0.9 0.48 0.61 ESR 0.28 0.31 0.35 0.4 0.6 0.85 0.43 0.7 0.5 0.53 Limited 71 JC 0.29 0.51 0.23 0.37 0.14 -0.12 0.4 0.81 0.45 0.41 Parental pain 0.23 0.62 0.03 0.57 0.41 0.69 0.7 0.79 0.42 0.53 Childhood health assessment questionnaire 0.25 0.57 -0.07 0.36 -0.47 0.84 0.37 0.8 0.66 0.4

Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced approaches

Extracellular vesicles (EVs), through their complex cargo, can reflect the state of their cell of origin and change the functions and phenotypes of other cells. These features indicate strong biomarker and therapeutic potential and have generated broad interest, as evidenced by the steady year-on-year increase in the numbers of scientific publications about EVs. Important advances have been made in EV metrology and in understanding and applying EV biology. However, hurdles remain to realising the potential of EVs in domains ranging from basic biology to clinical applications due to challenges in EV nomenclature, separation from non-vesicular extracellular particles, characterisation and functional studies. To address the challenges and opportunities in this rapidly evolving field, the International Society for Extracellular Vesicles (ISEV) updates its 'Minimal Information for Studies of Extracellular Vesicles', which was first published in 2014 and then in 2018 as MISEV2014 and MISEV2018, respectively. The goal of the current document, MISEV2023, is to provide researchers with an updated snapshot of available approaches and their advantages and limitations for production, separation and characterisation of EVs from multiple sources, including cell culture, body fluids and solid tissues. In addition to presenting the latest state of the art in basic principles of EV research, this document also covers advanced techniques and approaches that are currently expanding the boundaries of the field. MISEV2023 also includes new sections on EV release and uptake and a brief discussion of in vivo approaches to study EVs. Compiling feedback from ISEV expert task forces and more than 1000 researchers, this document conveys the current state of EV research to facilitate robust scientific discoveries and move the field forward even more rapidly