The application, character, and effectiveness of person-centred care with service-users, and the community within the discipline of podiatry: a scoping review.

BACKGROUND: The concept of person-centred care is embedded within healthcare policy, focusing on long-term conditions and multimorbidity. The evidence that person-centred care is being operationalised effectively across all areas of healthcare is limited. The aim of this scoping review was to explore the application, features, and effectiveness of person-centred care with service-users, carers, and the community within podiatry. METHODS: The scoping review was based upon Arksey and Malley's five stage framework. The following databases were searched between January 2010 and March 2021: AMED, CINAHL, Embase, Cochrane library, SocINDEX, British Education Index, Business Source Complete, MEDLINE (EBSCO), and the EThOS 'Global electronic thesis and dissertation' repository, Prospero, and reference lists of included papers. Primary research articles were included if they reported on a person-centred care focused intervention with podiatry. Research terms were developed, appropriate databases identified, and an initial search resulted in 622 papers which, following removal of duplicates and critical appraisal, resulted in 18 eligible papers. Data extracted involved the types of person-centred care utilised, intervention details, motivations for engaging in person-centred care interventions, and intervention barriers and challenges. RESULTS: Eighteen articles were included in the review. The main type of person-centred care utilised was patient/carer activities around self-management. None of the studies considered the role of the podiatrist as a person-centred care agent. The data on interventions generated the following themes 'service facilitated person-centred care' where a change has been made to service delivery, 'direct clinician delivery' where the intervention is delivered by the clinician with the patient present and 'patient instigated participation' where patient motivation is required to engage with an activity beyond the consultation. Outcome measures associated with quality of care and effectiveness were absent. CONCLUSION: There is a lack of congruency between the concept of person-centred care and how it is operationalised. A whole system approach that considers commissioning, organisational leadership, the role of the practitioners and patients has not been considered. There is immense scope for the podiatrist to play an important part in the personalised-care agenda, but currently research that can evidence the effectiveness of person-centred care in podiatry is absent. REVIEW REGISTRATION: Open Science Framework ( osf.io/egjsd ).

In Vitro Priming of Human T Cells by Dendritic Cells Provides a Screening Tool for Candidate Vaccines for Burkholderia pseudomallei.

Murine dendritic cells, when pulsed with heat-killed Burkholderia pseudomallei and used to immunise naïve mice, have previously been shown to induce protective immunity in vivo. We have now demonstrated the in vitro priming of naïve human T cells against heat-killed B. pseudomallei, by co-culture with syngeneic B. pseudomallei-pulsed dendritic cells. Additionally, we have enriched the DC fraction such that a study of the differential response induced by pulsed DCs of either myeloid or plasmacytoid lineage in syngeneic human T cells was achievable. Whilst both mDCs and pDCs were activated by pulsing, the mDCs contributed the major response to B. pseudomallei with the expression of the migration marker CCR7 and a significantly greater secretion of the proinflammatory TNFα and IL1ß. When these DC factions were combined and used to prime syngeneic T cells, a significant proliferation was observed in the CD4+ fraction. Here, we have achieved human T cell priming in vitro with unadjuvanted B. pseudomallei, the causative organism of melioidosis, for which there is currently no approved vaccine. We propose that the approach we have taken could be used to screen for the human cellular response to candidate vaccines and formulations, in order to enhance the cell-mediated immunity required to protect against this intracellular pathogen and potentially more broadly against other, difficult-to-treat intracellular pathogens. To date, the polysaccharide capsule of B. pseudomallei, fused to a standard carrier protein, e.g., Crm, looks a likely vaccine candidate. Dendritic cells (DCs), providing, as they do, the first line of defence to infection, process and present microbial products to the immune system to direct downstream immune responses. Here, we have sought to use DCs ex vivo to identify immunogenic products from heat-killed B. pseudomallei. Using practical volumes of fresh human donor blood, we show that heat-killed B. pseudomallei activated and stimulated the expression of pro-inflammatory cytokines TNF-α, IL-1ß and IL-6 from both myeloid and plasmacytoid DCs. Furthermore, B. pseudomallei-pulsed DCs cultured with naïve syngeneic T cells ex vivo, induced the activation and proliferation of the CD4+ T-cell population, which was identified by cell surface marker staining using flow cytometry. Thus, both DC subsets are important for driving primary T helper cell responses to B. pseudomallei in healthy individuals and have the potential to be used to identify immunogenic components of B. pseudomallei for future therapies and vaccines.

Bacteroides thetaiotaomicron-derived outer membrane vesicles promote regulatory dendritic cell responses in health but not in inflammatory bowel disease.

BACKGROUND: Bacteroides thetaiotaomicron (Bt) is a prominent member of the human intestinal microbiota that, like all gram-negative bacteria, naturally generates nanosized outer membrane vesicles (OMVs) which bud off from the cell surface. Importantly, OMVs can cross the intestinal epithelial barrier to mediate microbe-host cell crosstalk involving both epithelial and immune cells to help maintain intestinal homeostasis. Here, we have examined the interaction between Bt OMVs and blood or colonic mucosa-derived dendritic cells (DC) from healthy individuals and patients with Crohn's disease (CD) or ulcerative colitis (UC). RESULTS: In healthy individuals, Bt OMVs stimulated significant (p < 0.05) IL-10 expression by colonic DC, whereas in peripheral blood-derived DC they also stimulated significant (p < 0.001 and p < 0.01, respectively) expression of IL-6 and the activation marker CD80. Conversely, in UC Bt OMVs were unable to elicit IL-10 expression by colonic DC. There were also reduced numbers of CD103+ DC in the colon of both UC and CD patients compared to controls, supporting a loss of regulatory DC in both diseases. Furthermore, in CD and UC, Bt OMVs elicited a significantly lower proportion of DC which expressed IL-10 (p < 0.01 and p < 0.001, respectively) in blood compared to controls. These alterations in DC responses to Bt OMVs were seen in patients with inactive disease, and thus are indicative of intrinsic defects in immune responses to this commensal in inflammatory bowel disease (IBD). CONCLUSIONS: Overall, our findings suggest a key role for OMVs generated by the commensal gut bacterium Bt in directing a balanced immune response to constituents of the microbiota locally and systemically during health which is altered in IBD patients. Video Abstract.

Deficient Resident Memory T Cell and CD8 T Cell Response to Commensals in Inflammatory Bowel Disease.

BACKGROUND AND AIMS: The intestinal microbiota is closely associated with resident memory lymphocytes in mucosal tissue. We sought to understand how acquired cellular and humoral immunity to the microbiota differ in health versus inflammatory bowel disease [IBD]. METHODS: Resident memory T cells [Trm] in colonic biopsies and local antibody responses to intraepithelial microbes were analysed. Systemic antigen-specific immune T and B cell memory to a panel of commensal microbes was assessed. RESULTS: Systemically, healthy blood showed CD4 and occasional CD8 memory T cell responses to selected intestinal bacteria, but few memory B cell responses. In IBD, CD8 memory T cell responses decreased although B cell responses and circulating plasmablasts increased. Possibly secondary to loss of systemic CD8 T cell responses in IBD, dramatically reduced numbers of mucosal CD8+ Trm and γδ T cells were observed. IgA responses to intraepithelial bacteria were increased. Colonic Trm expressed CD39 and CD73 ectonucleotidases, characteristic of regulatory T cells. Cytokines/factors required for Trm differentiation were identified, and in vitro-generated Trm expressed regulatory T cell function via CD39. Cognate interaction between T cells and dendritic cells induced T-bet expression in dendritic cells, a key mechanism in regulating cell-mediated mucosal responses. CONCLUSIONS: A previously unrecognised imbalance exists between cellular and humoral immunity to the microbiota in IBD, with loss of mucosal T cell-mediated barrier immunity and uncontrolled antibody responses. Regulatory function of Trm may explain their association with intestinal health. Promoting Trm and their interaction with dendritic cells, rather than immunosuppression, may reinforce tissue immunity, improve barrier function, and prevent B cell dysfunction in microbiota-associated disease and IBD aetiology.

British Society of Gastroenterology consensus guidelines on the management of inflammatory bowel disease in adults.

Ulcerative colitis and Crohn's disease are the principal forms of inflammatory bowel disease. Both represent chronic inflammation of the gastrointestinal tract, which displays heterogeneity in inflammatory and symptomatic burden between patients and within individuals over time. Optimal management relies on understanding and tailoring evidence-based interventions by clinicians in partnership with patients. This guideline for management of inflammatory bowel disease in adults over 16 years of age was developed by Stakeholders representing UK physicians (British Society of Gastroenterology), surgeons (Association of Coloproctology of Great Britain and Ireland), specialist nurses (Royal College of Nursing), paediatricians (British Society of Paediatric Gastroenterology, Hepatology and Nutrition), dietitians (British Dietetic Association), radiologists (British Society of Gastrointestinal and Abdominal Radiology), general practitioners (Primary Care Society for Gastroenterology) and patients (Crohn's and Colitis UK). A systematic review of 88 247 publications and a Delphi consensus process involving 81 multidisciplinary clinicians and patients was undertaken to develop 168 evidence- and expert opinion-based recommendations for pharmacological, non-pharmacological and surgical interventions, as well as optimal service delivery in the management of both ulcerative colitis and Crohn's disease. Comprehensive up-to-date guidance is provided regarding indications for, initiation and monitoring of immunosuppressive therapies, nutrition interventions, pre-, peri- and postoperative management, as well as structure and function of the multidisciplinary team and integration between primary and secondary care. Twenty research priorities to inform future clinical management are presented, alongside objective measurement of priority importance, determined by 2379 electronic survey responses from individuals living with ulcerative colitis and Crohn's disease, including patients, their families and friends.

The Effect of Vitamin D on Intestinal Inflammation and Faecal Microbiota in Patients with Ulcerative Colitis.

BACKGROUND AND AIMS: Vitamin D may be immunomodulatory and alter faecal microbiota, but results from clinical studies in humans to date have been inconclusive. This study aimed to assess the effect of vitamin D replacement in vitamin D-deficient patients with and without ulcerative colitis [UC] on inflammation and faecal microbiota. METHODS: Vitamin D was replaced over 8 weeks in patients with active UC [defined by faecal calprotectin ≥ 100 µg/g], inactive UC [faecal calprotectin < 100 µg/g] and non-inflammatory bowel disease [IBD] controls with baseline serum 25[OH] vitamin D <50 nmol/l, and markers of inflammation and faecal microbiota were analysed. RESULTS: Eight patients with active UC, nine with inactive UC and eight non-IBD controls received 40000 units cholecalciferol weekly for 8 weeks. Mean baseline 25[OH] vitamin D increased from 34 [range 12-49] to 111 [71-158] nmol/l [p < 0.001], with no difference across the groups [p = 0.32]. In patients with active UC, faecal calprotectin levels decreased from a median 275 to 111 µg/g [p = 0.02], platelet count decreased [mean 375 to 313 × 109/l, p = 0.03] and albumin increased [mean 43 to 45 g/l, p = 0.04]. These parameters did not change in patients with inactive UC or non-IBD controls. No changes in overall faecal bacterial diversity were noted although a significant increase in Enterobacteriaceae abundance was observed in patients with UC [p = 0.03]. CONCLUSIONS: Vitamin D supplementation was associated with reduced intestinal inflammation in patients with active UC, with a concomitant increase in Enterobacteriaceae but no change in overall faecal microbial diversity.

Anti-TNF drug and antidrug antibody level monitoring in IBD: a practical guide.

The antitumour necrosis factor (TNF) medications, adalimumab and infliximab, play an important role in the management of both Crohn's disease and ulcerative colitis. For those in whom anti-TNF is effective, the therapy is associated with fewer symptoms, improved quality of life and disease and surgery-free survival. Unfortunately, up to 30% of patients will fail to respond to anti-TNF drugs while up to 50% of those who do see an initial response will lose response at some point. The introduction of drug monitoring for anti-TNFs, including drug level and antidrug antibody level testing allows a more personalised management of patients and improves patient outcomes. This article reviews the data for the use of anti-TNF monitoring and presents a 'how to' guide for clinicians.

Republished curriculum based clinical review: IBD: reproductive health, pregnancy and lactation.

The peak incidence of inflammatory bowel diseases (IBD) occurs during the child-bearing years, and so questions about fertility, pregnancy and breast feeding are often asked by patients. It is known that patients with IBD receive twice as much information about pregnancy-related issues from gastroenterologists as from any other source (including the internet). Therefore, the role of the gastroenterologist in correctly educating patients to avoid misconceptions is paramount, and this should be done proactively prior to planning pregnancy so that the patient's health and medications can be optimised. A clear understanding of medication safety during pregnancy and lactation will improve clinical management.

IBD: reproductive health, pregnancy and lactation.

The peak incidence of inflammatory bowel diseases (IBD) occurs during the child-bearing years, and so questions about fertility, pregnancy and breast feeding are often asked by patients. It is known that patients with IBD receive twice as much information about pregnancy-related issues from gastroenterologists as from any other source (including the internet). Therefore, the role of the gastroenterologist in correctly educating patients to avoid misconceptions is paramount, and this should be done proactively prior to planning pregnancy so that the patient's health and medications can be optimised. A clear understanding of medication safety during pregnancy and lactation will improve clinical management.

Provision of service and training for small bowel endoscopy in the UK.

OBJECTIVE: To determine the location and use of small bowel endoscopy services in the UK and to analyse training uptake to assess future demand and shape discussions about training and service delivery. DESIGN: Surveys of British Society of Gastroenterology (BSG) members by web-based and personal contact were conducted to ascertain capsule endoscopy practice and numbers of procedures performed. This was compared with expected numbers of procedures calculated using BSG guidelines, hospital episode statistics and published data of capsule endoscopy in routine practice. Analysis of data from two national training courses provided information about training. RESULTS: 45% of UK gastroenterology services offered in-house capsule endoscopy. 91.3% of survey responders referred patients for capsule endoscopy; 67.7% felt that local availability would increase referrals. Suspected small bowel bleeding and Crohn's disease were considered appropriate indications by the majority. Demand is increasing in spite of restricted use in 21.6% of centres. Only two regions performed more than the minimum estimate of need of 45 procedures per 250 000 population. Eight centres perform regular device-assisted enteroscopy; 14 services are in development. 74% of trainees were interested in training and of those training in image interpretation, 67% are doctors and 28% are nurses. CONCLUSIONS: Capsule endoscopy is used by the majority of UK gastroenterologists but appears to be underused. Current demand for device-assisted enteroscopy seems likely to be matched if new services become established. Future demand is likely to increase, however, suggesting the need to formalise training and accreditation for both doctors and nurses.