Protocol for the ProFHER (PROximal Fracture of the Humerus: Evaluation by Randomisation) trial: a pragmatic multi-centre randomised controlled trial of surgical versus non-surgical treatment for proximal fracture of the humerus in adults

<p>Abstract</p> <p>Background</p> <p>Proximal humeral fractures, which occur mainly in older adults, account for approximately 4 to 5% of all fractures. Approximately 40% of these fractures are displaced fractures involving the surgical neck. Management of this group of fractures is often challenging and the outcome is frequently unsatisfactory. In particular it is not clear whether surgery gives better outcomes than non-surgical management. Currently there is much variation in the use of surgery and a lack of good quality evidence to inform this decision.</p> <p>Methods/Design</p> <p>We aim to undertake a pragmatic UK-based multi-centre randomised controlled trial evaluating the effectiveness and cost-effectiveness of surgical versus standard non-surgical treatment for adults with an acute closed displaced fracture of the proximal humerus with involvement of the surgical neck. The choice of surgical intervention is left to the surgeon, who must use techniques that they are fully experienced with. This will avoid 'learning curve' problems. We will promote good standards of non-surgical care, similarly insisting on care-provider competence, and emphasize the need for comparable provision of rehabilitation for both groups of patients.</p> <p>We aim to recruit 250 patients from a minimum of 18 NHS trauma centres throughout the UK. These patients will be followed-up for 2 years. The primary outcome is the Oxford Shoulder Score, which will be collected via questionnaires completed by the trial participants at 6, 12 and 24 months. This is a 12-item condition-specific questionnaire providing a total score based on the person's subjective assessment of pain and activities of daily living impairment. We will also collect data for other outcomes, including general health measures and complications, and for an economic evaluation. Additionally, we plan a systematic collection of reasons for non-inclusion of eligible patients who were not recruited into the trial, and their baseline characteristics, treatment preferences and intended treatment.</p> <p>Discussion</p> <p>This article presents the protocol for a multi-centre randomised controlled trial. It gives extensive details of, and the basis for, the chosen methods, and describes the key measures taken to avoid bias and to ensure validity.</p> <p>Trial Registration</p> <p>Current Controlled Trials ISRCTN50850043</p

Making a Step Forward Towards Urban Resilience. The Contribution of Digital Innovation

Starting from 'wicked problem' theory as the landmark for framing disaster events in terms of policy issue for city governments, this paper highlights the contribution provided by Big Data analytics and digital innovation in dealing with disaster risks. The research aims at answering the following question: what is the role that 'smart technologies' play in strengthening urban resilience to disaster risks

Correlation versus Causation? Pharmacovigilance of the Analgesic Flupirtine Exemplifies the Need for Refined Spontaneous ADR Reporting

Annually, adverse drug reactions result in more than 2,000,000 hospitalizations and rank among the top 10 causes of death in the United States. Consequently, there is a need to continuously monitor and to improve the safety assessment of marketed drugs. Nonetheless, pharmacovigilance practice frequently lacks causality assessment. Here, we report the case of flupirtine, a centrally acting non-opioid analgesic. We re-evaluated the plausibility and causality of 226 unselected, spontaneously reported hepatobiliary adverse drug reactions according to the adapted Bradford-Hill criteria, CIOMS score and WHO-UMC scales. Thorough re-evaluation showed that only about 20% of the reported cases were probable or likely for flupirtine treatment, suggesting an incidence of flupirtine-related liver injury of 1∶ 100,000 when estimated prescription data are considered, or 0.8 in 10,000 on the basis of all 226 reported adverse drug reactions. Neither daily or cumulative dose nor duration of treatment correlated with markers of liver injury. In the majority of cases (151/226), an average of 3 co-medications with drugs known for their liver liability was observed that may well be causative for adverse drug reactions, but were reported under a suspected flupirtine ADR. Our study highlights the need to improve the quality and standards of ADR reporting. This should be done with utmost care taking into account contributing factors such as concomitant medications including over-the-counter drugs, the medical history and current health conditions, in order to avoid unjustified flagging and drug warnings that may erroneously cause uncertainty among healthcare professionals and patients, and may eventually lead to unjustified safety signals of useful drugs with a reasonable risk to benefit ratio

Research on Teaching and Learning Mathematics at the Tertiary Level:State-of-the-art and Looking Ahead

This topical survey focuses on research in tertiary mathematics education, a field that has experienced considerable growth over the last 10 years. Drawing on the most recent journal publication as well as the latest advances from recent high quality conference proceedings, our review culls out the following five emergent areas of interest: mathematics teaching at the tertiary level; the role of mathematics in other disciplines; textbooks, assessment and students’ studying practices; transition to the tertiary level; and theoretical-methodological advances. We conclude the survey with a discussion of some potential ways forward for future research in this new and rapidly developing domain of inquiry

A new era for understanding amyloid structures and disease

The aggregation of proteins into amyloid fibrils and their deposition into plaques and intracellular inclusions is the hallmark of amyloid disease. The accumulation and deposition of amyloid fibrils, collectively known as amyloidosis, is associated with many pathological conditions that can be associated with ageing, such as Alzheimer disease, Parkinson disease, type II diabetes and dialysis-related amyloidosis. However, elucidation of the atomic structure of amyloid fibrils formed from their intact protein precursors and how fibril formation relates to disease has remained elusive. Recent advances in structural biology techniques, including cryo-electron microscopy and solid-state NMR spectroscopy, have finally broken this impasse. The first near-atomic-resolution structures of amyloid fibrils formed in vitro, seeded from plaque material and analysed directly ex vivo are now available. The results reveal cross-β structures that are far more intricate than anticipated. Here, we describe these structures, highlighting their similarities and differences, and the basis for their toxicity. We discuss how amyloid structure may affect the ability of fibrils to spread to different sites in the cell and between organisms in a prion-like manner, along with their roles in disease. These molecular insights will aid in understanding the development and spread of amyloid diseases and are inspiring new strategies for therapeutic intervention