University of Salford

About: University of Salford is a education organization based out in Salford, Manchester, United Kingdom. It is known for research contribution in the topics: Population & Context (language use). The organization has 13049 authors who have published 22957 publications receiving 537330 citations. The organization is also known as: University of Salford Manchester & The University of Salford Manchester.

Total meniscectomy in adolescents

Abstract: We have carried out a prospective, longitudinal 30-year review of 95 adolescents who underwent total meniscectomy in one knee, and have compared the results with those observed 13 years earlier. All the medical records were scrutinised. Of the 63 patients reviewed clinically, 47 reported decreased sporting activity, although subjective satisfaction rose by 3% to 71%. The scores on the WOMAC osteoarthritis index differed significantly between patients grouped by subjective global assessment. Satisfactory function scores increased from 48% to 60%. In the 53 patients consenting to bilateral radiography of the knee, the incidence of narrowing of the articular cartilage in the operated knee increased significantly between the reviews (19% to 36%). Progression of degenerative change paralleled reduction in activity. Outcome measures were best after medial, intermediate after lateral and worst after double meniscectomy.

"Omics"-Informed Drug and Biomarker Discovery: Opportunities, Challenges and Future Perspectives.

Abstract: The pharmaceutical industry faces unsustainable program failure despite significant increases in investment. Dwindling discovery pipelines, rapidly expanding R&D budgets and increasing regulatory control, predict significant gaps in the future drug markets. The cumulative duration of discovery from concept to commercialisation is unacceptably lengthy, and adds to the deepening crisis. Existing animal models predicting clinical translations are simplistic, highly reductionist and, therefore, not fit for purpose. The catastrophic consequences of ever-increasing attrition rates are most likely to be felt in the developing world, where resistance acquisition by killer diseases like malaria, tuberculosis and HIV have paced far ahead of new drug discovery. The coming of age of Omics-based applications makes available a formidable technological resource to further expand our knowledge of the complexities of human disease. The standardisation, analysis and comprehensive collation of the “data-heavy” outputs of these sciences are indeed challenging. A renewed focus on increasing reproducibility by understanding inherent biological, methodological, technical and analytical variables is crucial if reliable and useful inferences with potential for translation are to be achieved. The individual Omics sciences—genomics, transcriptomics, proteomics and metabolomics—have the singular advantage of being complimentary for cross validation, and together could potentially enable a much-needed systems biology perspective of the perturbations underlying disease processes. If current adverse trends are to be reversed, it is imperative that a shift in the R&D focus from speed to quality is achieved. In this review, we discuss the potential implications of recent Omics-based advances for the drug development process.

Flexible trial design in practice - stopping arms for lack-of-benefit and adding research arms mid-trial in STAMPEDE: a multi-arm multi-stage randomized controlled trial

Abstract: Background: Systemic Therapy for Advanced or Metastatic Prostate cancer: Evaluation of Drug Efficacy (STAMPEDE) is a randomized controlled trial that follows a novel multi-arm, multi-stage (MAMS) design. We describe methodological and practical issues arising with (1) stopping recruitment to research arms following a pre-planned intermediate analysis and (2) adding a new research arm during the trial. Methods: STAMPEDE recruits men who have locally advanced or metastatic prostate cancer who are starting standard long-term hormone therapy. Originally there were five research and one control arms, each undergoing a pilot stage (focus: safety, feasibility), three intermediate ‘activity’ stages (focus: failure-free survival), and a final ‘efficacy’ stage (focus: overall survival). Lack-of-sufficient-activity guidelines support the pairwise interim comparisons of each research arm against the control arm; these pre-defined activity cut-off becomes increasingly stringent over the stages. Accrual of further patients continues to the control arm and to those research arms showing activity and an acceptable safety profile. The design facilitates adding new research arms should sufficiently interesting agents emerge. These new arms are compared only to contemporaneously recruited control arm patients using the same intermediate guidelines in a time-delayed manner. The addition of new research arms is subject to adequate recruitment rates to support the overall trial aims. Results: (1) Stopping Existing Therapy: After the second intermediate activity analysis, recruitment was discontinued to two research arms for lack-of-sufficient activity. Detailed preparations meant that changes were implemented swiftly at 100 international centers and recruitment continued seamlessly into Activity Stage III with 3 remaining research arms and the control arm. Further regulatory and ethical approvals were not required because this was already included in the initial trial design. (2) Adding New Therapy: An application to add a new research arm was approved by the funder, (who also organized peer review), industrial partner and regulatory and ethical bodies. This was all done in advance of any decision to stop current therapies.