The power of language: how to bridge the gap between healthcare research and patients - a scoping review.

OBJECTIVE: The value of patient involvement to the design, conduct, and outcomes of healthcare research is increasingly being recognized. Patient involvement also provides greater patient accessibility and contribution to research. However, the use of inaccessible and technical language when communicating with patients is a barrier to effective patient involvement. METHODS: We analyzed peer-reviewed and gray literature on how language is used in communication between healthcare researchers and patients. We used this analysis to generate a set of recommendations for healthcare researchers about using more inclusive and accessible language when involving patients in research. This scoping review adheres to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) extension for Scoping Review (PRISMA-ScR) checklist. RESULTS: Four major themes about the use of language were developed from the literature analysis and were used to develop the set of recommendations. These recommendations include guidance on using standardized terminology and plain language when involving patients in healthcare research. They also discuss the implementation of co-development practices, patient support initiatives, and researcher training, as well as ways to improve emotional awareness and the need for greater equality, diversity, and inclusion. DISCUSSION AND CONCLUSION: The use of inclusive, empathetic, and clear language can encourage patients to be involved in research and, once they are involved, make them feel like equal, empowered, and valued partners. Working toward developing processes and guidelines for the use of language that enables an equal partnership between researchers and patients is critical.

Patient and public involvement is when patients, carers, and the public are included as partners in all stages of healthcare research. Patient involvement has been shown to have a positive impact on people and on research itself, but researchers often use language that is complicated, confusing, or unsuitable for patients. This can lead to less meaningful patient involvement in research.Our work looked at two areas: (1) how using unsuitable language can be a barrier to effective and meaningful patient involvement; and (2) what can be done to help improve communication between healthcare researchers and patients.We started by finding out what has already been researched and published in these areas. We looked in medical journal databases for articles that were relevant to the topic. We also searched Google and the websites of relevant organizations. From looking at these sources, we found four common themes. These themes are: (1) lack of standardized terminology for patients involved in research; (2) consistent overuse of technical, scientific, and medical language; (3) positive outcomes of using language to show emotional understanding; and (4) language as a powerful tool for promoting diversity, equality, and inclusion of patients involved in research.Using these themes, we then developed seven recommendations to help improve how healthcare researchers and patients communicate with each other. These recommendations are: (1) using standardized terminology; (2) using plain language; (3) co-developing patient information; (4) providing patient training, mentoring, and support; (5) introducing researcher training; (6) having emotional awareness; and (7) improving equality, diversity, and inclusion.A graphical plain language summary can be found as Supplementary material for this article.

FK506-binding protein 51 interacts with Clostridium botulinum C2 toxin and FK506 inhibits membrane translocation of the toxin in mammalian cells.

The binary Clostridium botulinum C2 toxin consists of the binding/translocation component C2IIa and the separate enzyme component C2I. C2IIa delivers C2I into the cytosol of eukaryotic target cells where C2I ADP-ribosylates actin. After receptor-mediated endocytosis of the C2IIa/C2I complex, C2IIa forms pores in membranes of acidified early endosomes and unfolded C2I translocates through the pores into the cytosol. Membrane translocation of C2I is facilitated by the activities of host cell chaperone Hsp90 and the peptidyl-prolyl cis/trans isomerase (PPIase) cyclophilin A. Here, we demonstrated that Hsp90 co-precipitates with C2I from lysates of C2 toxin-treated cells and identified the FK506-binding protein (FKBP) 51 as a novel interaction partner of C2I in vitro and in intact mammalian cells. Prompted by this finding, we used the specific pharmacological inhibitor FK506 to investigate whether the PPIase activity of FKBPs plays a role during membrane translocation of C2 toxin. Treatment of cells with FK506 protected cultured cells from intoxication with C2 toxin. Moreover, FK506 inhibited the pH-dependent translocation of C2I across membranes into the cytosol but did not interfere with the enzyme activity of C2I or binding of C2 toxin to cells. Furthermore, FK506 treatment delayed intoxication with the related binary actin ADP-ribosylating toxins from Clostridium perfringens (iota toxin) and Clostridium difficile (CDT) but not with the Rho-glucosylating Clostridium difficile toxin A (TcdA). In conclusion, our results support the hypothesis that clostridial binary actin-ADP-ribosylating toxins share a specific FKBP-dependent translocation mechanism during their uptake into mammalian cells.

Characterising meaningful patient and public involvement in the pharmaceutical industry research setting: a retrospective quality assessment.

OBJECTIVES: Patient and public involvement (PPI) in clinical research has a well-established infrastructure in the UK, and while there has been good progress within pharmaceutical-industry-sponsored research, further improvements are still needed. This review aims to share learnings from quality assessments of historical PPI projects within Pfizer UK to inform future projects and drive PPI progress in the pharmaceutical industry. DESIGN AND SETTING: Internal assessments of Pfizer UK PPI projects were conducted to identify all relevant projects across the medicines development continuum between 2017 and 2021. Five sample projects were developed into case studies. OUTCOME MEASURE: Retrospective quality assessments were performed using the Patient Focused Medicines Development (PFMD) Patient Engagement Quality Guidance (PEQG) tool. Recommendations for improvement were developed. RESULTS: Retrospective case study analysis and quality framework assessment revealed benefits of PPI to both Pfizer UK and to external partners, as well as challenges and learnings to improve future practice. Recommendations for improvement based on these findings focused on processes and procedures for PPI, group dynamics and diversity for PPI activities, sharing of expertise, the importance of bidirectional and timely feedback, and the use of understandable language in materials. CONCLUSIONS: PPI in medicines development is impactful and beneficial but is still being optimised in the pharmaceutical industry. Using the PFMD PEQG tool to define gaps, share learnings and devise recommendations for improvement helps to ensure that PPI is genuine and empowering, rather than tokenistic. Ultimately, these recommendations should be acted on to further embed PPI as an integral part of medicines development and health research within the pharmaceutical industry. This article includes a plain language summary in the supplement.

The Challenges of Outcomes-Based Contract Implementation for Medicines in Europe.

OBJECTIVES: The aim was to outline the challenges of implementing outcomes-based contracts (OBCs) in Europe. METHODS: A scoping review was conducted, building on the searches of a previous systematic review and updating them for December 2017 until May 2021. The combined results were screened, based on inclusion and exclusion criteria. All identified studies published in the English language that described specific OBC schemes for medicines in European countries were included. Insights into the challenges of OBCs were extracted and analysed to develop a conceptual framework. RESULTS: Ten articles from the previous systematic review matched our inclusion criteria, along with 14 articles from electronic searches. Analysis of these 24 articles and classification of the challenges revealed that there are multiple barriers that must be overcome if OBCs that benefit all stakeholders are going to be adopted widely across Europe. These challenges were grouped according to five key themes: negotiation framework; outcomes; data; administration and implementation; and laws and regulation. CONCLUSIONS: If the promise of OBCs is to be fully realised in Europe, there remain major challenges that need to be overcome by all stakeholders working in partnership. The overlapping and interconnected nature of these challenges highlights the complexity of OBC arrangements.

Living with Ulcerative Colitis Study (LUCY) in England: a retrospective study evaluating healthcare resource utilisation and direct healthcare costs of postoperative care in ulcerative colitis.

OBJECTIVE: Ulcerative colitis (UC) is a lifelong, relapsing-remitting disease. Patients non-responsive to pharmacological treatment may require a colectomy. We estimated pre-colectomy and post-colectomy healthcare resource utilisation (HCRU) and costs in England. DESIGN/METHOD: A retrospective, longitudinal cohort study indexing adult patients with UC undergoing colectomy (2009-2015), using linked Clinical Practice Research Datalink/Hospital Episode Statistics data, was conducted. HCRU, healthcare costs and pharmacological treatments were evaluated during 12 months prior to and including colectomy (baseline) and 24 months post-colectomy (follow-up; F-U), comparing baseline/F-U, emergency/elective colectomy and subtotal/full colectomy using descriptive statistics and paired/unpaired tests. RESULTS: 249 patients from 26 165 identified were analysed including 145 (58%) elective and 184 (74%) full colectomies. Number/cost of general practitioner consultations increased post-colectomy (p<0.001), and then decreased at 13-24 months (p<0.05). From baseline to F-U, the number of outpatient visits, number/cost of hospitalisations and total direct healthcare costs decreased (all p<0.01). Postoperative HCRU was similar between elective and emergency colectomies, except for the costs of colectomy-related hospitalisations and medication, which were lower in the elective group (p<0.05). Postoperative costs were higher for subtotal versus full colectomies (p<0.001). At 1-12 month F-U, 30%, 19% and 5% of patients received aminosalicylates, steroids and immunosuppressants, respectively. CONCLUSION: HCRU/costs increased for primary care in the first year post-colectomy but decreased for secondary care, and varied according to the colectomy type. Ongoing and potentially unnecessary pharmacological therapy was seen in up to 30% of patients. These findings can inform patients and decision-makers of potential benefits and burdens of colectomy in UC.

Tofacitinib for the treatment of moderately to severely active ulcerative colitis: a systematic review, network meta-analysis and economic evaluation.

BACKGROUND AND AIMS: In the UK, treatments for patients with moderately to severely active ulcerative colitis who have an inadequate response to conventional therapies comprise four biological therapies-the tumour necrosis factor inhibitor (TNFi) agents adalimumab, golimumab and infliximab and the anti-integrin vedolizumab-and an orally administered small molecule therapy, tofacitinib. However, there have been few head-to-head studies of these therapies. This study aimed to compare the clinical and cost-effectiveness of tofacitinib with biological therapies. METHODS: A systematic literature review was conducted to identify all relevant randomised controlled trial (RCT) evidence. Clinical response, clinical remission and serious infection rates were synthesised using network meta-analysis (NMA). The results were used to compare the cost-effectiveness of tofacitinib and biologics with conventional therapy, using a Markov model, which incorporated lifetime costs and consequences of treatment from a UK National Health Service perspective. Analyses were conducted separately for TNFi-naïve and TNFi-exposed populations. RESULTS: Seventeen RCTs were used in the NMAs. There were no statistically significant differences among biological therapies and tofacitinib for either TNFi-naïve or TNFi-exposed patients. In TNFi-naïve patients, all therapies were more efficacious than placebo. In TNFi-exposed patients, only tofacitinib was significantly more efficacious than placebo as induction therapy, and only tofacitinib and vedolizumab were significantly more efficacious than placebo as maintenance therapies. There were no significant differences in serious infection rates among therapies. The incremental cost-effectiveness ratios for tofacitinib versus conventional therapy were £21 338 and £22 816 per quality-adjusted life year (QALY) in the TNFi-naïve and TNFi-exposed populations, respectively. TNFi therapies were dominated or extendedly dominated in both populations. Compared with vedolizumab, tofacitinib was associated with a similar number of QALYs, at a lower cost. CONCLUSION: Tofacitinib is an efficacious treatment for moderately to severely active ulcerative colitis and is likely to be a cost-effective use of NHS resources.

Using an epidemiological model to investigate unwarranted variation: the case of ventilation tubes for otitis media with effusion in England.

OBJECTIVES: To investigate unwarranted variation in ventilation tube insertions for otitis media with effusion in children in England. This procedure is known to be 'overused' from clinical audits, as only one in three ventilation tube insertions conforms to the appropriateness criteria of the National Institute for Health and Care Excellence (NICE); but audits cannot identify the scale of 'underuse' - i.e. patients who would benefit but are not treated. METHODS: To explore both 'underuse' and 'overuse' of ventilation tubes for otitis media with effusion, we developed an epidemiological model based on: definitions of children with otitis media with effusion expected to benefit from ventilation tubes according to NICE guidance; epidemiological and clinical information from a systematic review; and expert judgement. A range of estimates was derived using Monte Carlo simulation and compared with the number of ventilation tubes provided in the English National Health Service in 2010. RESULTS: About 32,200 children in England would be expected to benefit from ventilation tubes for otitis media with effusion per year (between 20,411 and 45,231 with 90% certainty). The observed number of ventilation tubes for otitis media with effusion-associated diagnoses was 16,824. CONCLUSIONS: The expected population capacity to benefit from ventilation tubes for otitis media with effusion based on NICE guidance appeared to exceed, by far, the number of ventilation tubes provided in the English National Health Service. So, while there is known 'overuse', there also may be substantial 'underuse' of ventilation tubes for otitis media with effusion if NICE criteria were applied. Future investigations of unwarranted variation should, therefore, not only focus on the patients who are treated but also consider the potential for benefit at the population level.