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Tolerogenic dendritic cell-based treatment for multiple sclerosis (MS): a harmonised study protocol for two phase I clinical trials comparing intradermal and intranodal cell administration

Por: Willekens · B. · Presas-Rodriguez · S. · Mansilla · M. · Derdelinckx · J. · Lee · W.-P. · Nijs · G. · De Laere · M. · Wens · I. · Cras · P. · Parizel · P. · Van Hecke · W. · Ribbens · A. · Billiet · T. · Adams · G. · Couttenye · M.-M. · Navarro-Barriuso · J. · Teniente-Serra · A. · Quira
Introduction

Based on the advances in the treatment of multiple sclerosis (MS), currently available disease-modifying treatments (DMT) have positively influenced the disease course of MS. However, the efficacy of DMT is highly variable and increasing treatment efficacy comes with a more severe risk profile. Hence, the unmet need for safer and more selective treatments remains. Specifically restoring immune tolerance towards myelin antigens may provide an attractive alternative. In this respect, antigen-specific tolerisation with autologous tolerogenic dendritic cells (tolDC) is a promising approach.

Methods and analysis

Here, we will evaluate the clinical use of tolDC in a well-defined population of MS patients in two phase I clinical trials. In doing so, we aim to compare two ways of tolDC administration, namely intradermal and intranodal. The cells will be injected at consecutive intervals in three cohorts receiving incremental doses of tolDC, according to a best-of-five design. The primary objective is to assess the safety and feasibility of tolDC administration. For safety, the number of adverse events including MRI and clinical outcomes will be assessed. For feasibility, successful production of tolDC will be determined. Secondary endpoints include clinical and MRI outcome measures. The patients’ immune profile will be assessed to find presumptive evidence for a tolerogenic effect in vivo.

Ethics and dissemination

Ethics approval was obtained for the two phase I clinical trials. The results of the trials will be disseminated in a peer-reviewed journal, at scientific conferences and to patient associations.

Trial registration numbers

NCT02618902 and NCT02903537; EudraCT numbers: 2015-002975-16 and 2015-003541-26.

Relationship between hospital or surgeon volume and outcomes in joint arthroplasty: protocol for a suite of systematic reviews and dose-response meta-analyses

Por: Wu · X.-D. · Liu · M.-M. · Sun · Y.-Y. · Zhao · Z.-H. · Zhou · Q. · Kwong · J. S. W. · Xu · W. · Tian · M. · He · Y. · Huang · W.
Introduction

Joint arthroplasty is a particularly complex orthopaedic surgical procedure performed on joints, including the hip, knee, shoulder, ankle, elbow, wrist and even digit joints. Increasing evidence from volume–outcomes research supports the finding that patients undergoing joint arthroplasty in high-volume hospitals or by high-volume surgeons achieve better outcomes, and minimum case load requirements have been established in some areas. However, the relationships between hospital/surgeon volume and outcomes in patients undergoing arthroplasty are not fully understood. Furthermore, whether elective arthroplasty should be restricted to high-volume hospitals or surgeons remains in dispute, and little is known regarding where the thresholds should be set for different types of joint arthroplasties.

Methods and analyses

This is a protocol for a suite of systematic reviews and dose–response meta-analyses, which will be amended and updated in conjunction with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols. Electronic databases, including PubMed and Embase, will be searched for observational studies examining the relationship between the hospital or surgeon volume and clinical outcomes in adult patients undergoing primary or revision of joint arthroplasty. We will use records management software for study selection and a predefined standardised file for data extraction and management. Quality will be assessed using the Newcastle-Ottawa Scale, and the meta-analysis, subgroup analysis and sensitivity analysis will be performed using Stata statistical software. Once the volume–outcome relationships are established, we will examine the potential non-linear relationships between hospital/surgeon volume and outcomes and detect whether thresholds or turning points exist.

Ethics and dissemination

Ethical approval is not required, because these studies are based on aggregated published data. The results of this suite of systematic reviews and meta-analyses will be submitted to peer-reviewed journals for publication.

PROSPERO registration number

CRD42017056639.

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