ORCID Profile
0000-0002-6316-5692
Current Organisations
Centre Hospitalier Universitaire Vaudois
,
Sherwood Forest Hospitals NHS Foundation Trust
,
University of Nottingham
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Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 11-2021
Publisher: Rockefeller University Press
Date: 07-06-2019
DOI: 10.1084/JEM.20190301
Abstract: The generation of protective humoral immunity after vaccination relies on the productive interaction between antigen-specific B cells and T follicular helper (Tfh) cells. Despite the central role of Tfh cells in vaccine responses, there is currently no validated way to enhance their differentiation in humans. From paired human lymph node and blood s les, we identify a population of circulating Tfh cells that are transcriptionally and clonally similar to germinal center Tfh cells. In a clinical trial of vaccine formulations, circulating Tfh cells were expanded in Tanzanian volunteers when an experimental malaria vaccine was adjuvanted in GLA-SE but not when formulated in Alum. The GLA-SE–formulated peptide was associated with an increase in the extrafollicular antibody response, long-lived antibody production, and the emergence of public TCRβ clonotypes in circulating Tfh cells. We demonstrate that altering vaccine adjuvants is a rational approach for enhancing Tfh cells in humans, thereby supporting the long-lived humoral immunity that is required for effective vaccines.
Publisher: Elsevier BV
Date: 06-2023
Publisher: JMIR Publications Inc.
Date: 30-10-2023
DOI: 10.2196/51474
Publisher: National Institute for Health and Care Research
Date: 10-2017
DOI: 10.3310/HTA21600
Abstract: Biological treatments such as adalimumab (Humira ® AbbVie Ltd, Maidenhead, UK) are antibodies targeting tumour necrosis factor alpha, released from ruptured intervertebral discs, which might be useful in sciatica. Recent systematic reviews concluded that they might be effective, but that a definitive randomised controlled trial was needed. Usual care in the NHS typically includes a physiotherapy intervention. To test whether or not injections of adalimumab plus physiotherapy are more clinically effective and cost-effective than injections of saline plus physiotherapy for patients with sciatica. Pragmatic, parallel-group, randomised controlled trial with blinded participants and clinicians, and an outcome assessment and statistical analysis with concurrent economic evaluation and internal pilot. Participants were referred from primary care and musculoskeletal services to outpatient physiotherapy clinics. Adults with persistent symptoms of sciatica of 1–6 months’ duration and with moderate to high levels of disability. Eligibility was assessed by research physiotherapists according to clinical criteria for diagnosing sciatica. After a second eligibility check, trial participants were randomised to receive two doses of adalimumab (80 mg and then 40 mg 2 weeks later) or saline injections. Both groups were referred for a course of physiotherapy. Outcomes were measured at the start, and after 6 weeks’ and 6 months’ follow-up. The main outcome measure was the Oswestry Disability Index (ODI). Other outcomes: leg pain version of the Roland–Morris Disability Questionnaire, Sciatica Bothersomeness Index, EuroQol-5 Dimensions, 5-level version, Hospital Anxiety and Depression Scale, resource use, risk of persistent disabling pain, pain trajectory based on a single question, Pain Self-Efficacy Questionnaire, T a Scale of Kinesiophobia and adverse effects. To detect an effect size of 0.4 with 90% power, a 5% significance level for a two-tailed t -test and 80% retention rate, 332 participants would have needed to be recruited. The primary effectiveness analysis would have been linear mixed models for repeated measures to measure the effects of time and group allocation. An internal pilot study would have involved the first 50 participants recruited across all centres. The primary economic analysis would have been a cost–utility analysis. The internal pilot study was discontinued as a result of low recruitment after eight participants were recruited from two out of six sites. One site withdrew from the study before recruitment started, one site did not complete contract negotiations and two sites signed contracts shortly before trial closure. In the two sites that did recruit participants, recruitment was slow. This was partly because of operational issues, but also because of a low rate of uptake from potential participants. Although large numbers of invitations were sent to potential participants, identified by retrospective searches of general practitioner (GP) records, there was a low rate of uptake. Two sites planned to recruit participants during GP consultations but opened too late to recruit any participants. The main failure was attributable to problems with contracts. Because of this we were not able to complete the internal pilot or to test all of the different methods for primary care recruitment we had planned. A trial of biological therapy in patients with sciatica still needs to be done, but would require a clearer contracting process, qualitative research to ensure that patients would be willing to participate, and simpler recruitment methods. Current Controlled Trials ISRCTN14569274. This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment Vol. 21, No. 60. See the NIHR Journals Library website for further project information.
Publisher: National Institute for Health and Care Research
Date: 05-2017
DOI: 10.3310/HTA21300
Abstract: The National Institute for Health and Care Excellence (NICE) 2009 guidelines for persistent low back pain (LBP) do not recommend the injection of therapeutic substances into the back as a treatment for LBP because of the absence of evidence for their effectiveness. This feasibility study aimed to provide a stable platform that could be used to evaluate a randomised controlled trial (RCT) on the clinical effectiveness and cost-effectiveness of intra-articular facet joint injections (FJIs) when added to normal care. To explore the feasibility of running a RCT to test the hypothesis that, for people with suspected facet joint back pain, adding the option of intra-articular FJIs (local anaesthetic and corticosteroids) to best usual non-invasive care is clinically effective and cost-effective. The trial was a mixed design. The RCT pilot protocol development involved literature reviews and a consensus conference followed by a randomised pilot study with an embedded mixed-methods process evaluation. Five NHS acute trusts in England. Participants were patients aged ≥ 18 years with moderately troublesome LBP present ( 6 months), who had failed previous conservative treatment and who had suspected facet joint pain. The study aimed to recruit 150 participants (approximately 30 per site). Participants were randomised sequentially by a remote service to FJIs combined with ‘best usual care’ (BUC) or BUC alone. All participants were to receive six sessions of a bespoke BUC rehabilitation package. Those randomised into the intervention arm were, in addition, given FJIs with local anaesthetic and steroids (at up to six injection sites). Randomisation occurred at the end of the first BUC session. Process and clinical outcomes. Clinical outcomes included a measurement of level of pain on a scale from 0 to 10, which was collected daily and then weekly via text messaging (or through a written diary). Questionnaire follow-up was at 3 months. Fifty-two stakeholders attended the consensus meeting. Agreement informed several statistical questions and three design considerations: diagnosis, the process of FJI and the BUC package and informing the design for the randomised pilot study. Recruitment started on 26 June 2015 and was terminated by the funder (as a result of poor recruitment) on 11 December 2015. In total, 26 participants were randomised. Process data illuminate some of the reasons for recruitment problems but also show that trial processes after enrolment ran smoothly. No between-group analysis was carried out. All pain-related outcomes show the expected improvement between baseline and follow-up. The mean total cost of the overall treatment package (injection £419.22 and BUC £264.00) was estimated at £683.22 per participant. This is similar to a NHS tariff cost for a course of FJIs of £686.84. Poor recruitment was a limiting factor. This feasibility study achieved consensus on the main challenges in a trial of FJIs for people with persistent non-specific low back pain. Further work is needed to test recruitment from alternative clinical situations. EudraCT 2014-000682-50 and Current Controlled Trials ISRCTN93184143. This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment Vol. 21, No. 30. See the NIHR Journals Library website for further project information.
Publisher: Springer Science and Business Media LLC
Date: 31-07-2018
Publisher: Oxford University Press (OUP)
Date: 15-03-1993
Publisher: Springer Science and Business Media LLC
Date: 12-2015
Publisher: Wiley
Date: 11-05-2017
DOI: 10.1002/EJP.1027
Publisher: JMIR Publications Inc.
Date: 02-08-2023
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for David Walsh.