Becoming confident about confidence intervals

A clear understanding of variability is at the heart of many of the articles published by the Bone and Joint Journal. The terms variability, dispersion, spread, distribution and variance amongst many others are used to simply refer to the range of values within the dataset. Statistics was essentially founded as the study of variability, with variability often regarded as a nuisance. Measures of variability can be difficult concepts to comprehend when reading papers. They range from the relatively simple to the more complex

Cost effectiveness of treatment with percutaneous Kirschner wires versus volar locking plate for adult patients with a dorsally displaced fracture of the distal radius: Analysis from the DRAFFT trial

We present an economic evaluation using data from the Distal Radius Acute Fracture Fixation Trial (DRAFFT) to compare the relative cost effectiveness of percutaneous Kirschner wire (K-wire) fixation and volar locking-plate fixation for patients with dorsally-displaced fractures of the distal radius. The cost effectiveness analysis (cost per quality-adjusted life year; QALY) was derived from a multi-centre, two-arm, parallel group, assessor-blind, randomised controlled trial which took place in 18 trauma centres in the United Kingdom. Data from 460 patients were available for analysis, which includes both a National Health Service cost perspective including costs of surgery, implants and healthcare resource use over a 12-month period after surgery, and a societal perspective, which includes the cost of time off work and the need for additional private care. There was only a small difference in QALYs gained for patients treated with locking-plate fixation over those treated with K-wires. At a mean additional cost of £714 (95% confidence interval 588 to 865) per patient, locking-plate fixation presented an incremental cost effectiveness ratio (ICER) of £89 322 per QALY within the first 12 months of treatment. Sensitivity analyses were undertaken to assess the ICER of locking-plate fixation compared with K-wires. These were greater than £30 000. Compared with locking-plate fixation, K-wire fixation is a 'cost saving' intervention, with similar health benefits

The experience of long-term opiate maintenance treatment and reported barriers to recovery: A qualitative systematic review

Background/Aim: To inform understanding of the experience of long-term opiate maintenance and identify barriers to recovery. Methods: A qualitative systematic review. Results: 14 studies in 17 papers, mainly from the USA (65%), met inclusion criteria, involving 1,088 participants. Studies focused on methadone prescribing. Participants reported stability; however, many disliked methadone. Barriers to full recovery were primarily ‘inward focused'. Conclusion: This is the first review of qualitative literature on long-term maintenance, finding that universal service improvements could be made to address reported barriers to recovery, including involving ex-users as positive role models, and increasing access to psychological support. Treatment policies combining harm minimisation and abstinence-orientated approaches may best support individualised recovery

The comprehensive cohort model in a pilot trial in orthopaedic trauma

Background: The primary aim of this study was to provide an estimate of effect size for the functional outcome of operative versus non-operative treatment for patients with an acute rupture of the Achilles tendon using accelerated rehabilitation for both groups of patients. The secondary aim was to assess the use of a comprehensive cohort research design (i.e. a parallel patient-preference group alongside a randomised group) in improving the accuracy of this estimate within an orthopaedic trauma setting. Methods: Pragmatic randomised controlled trial and comprehensive cohort study within a level 1 trauma centre. Twenty randomised participants (10 operative and 10 non-operative) and 29 preference participants (3 operative and 26 non-operative). The ge range was 22-72 years and 37 of the 52 patients were men. All participants had an acute rupture of their Achilles tendon and no other injuries. All of the patients in the operative group had a simple end-to-end repair of the tendon with no augmentation. Both groups then followed the same eight-week immediate weight-bearing rehabilitation programme using an off-the-shelf orthotic. The disability rating index (DRI; primary outcome), EQ-5D, Achilles Total Rupture Score and complications were assessed ed at two weeks, six weeks, three months, six months and nine months after initial injury. Results: At nine months, there was no significant difference in DRI between patients randomised to operative or non-operative management. There was no difference in DRI between the randomised group and the parallel patient preference group. The use of a comprehensive cohort of patients did not provide useful additional information as to the treatment effect size because the majority of patients chose non-operative management. Conclusions: Recruitment to clinical trials that compare operative and non-operative interventions is notoriously difficult; especially within the trauma setting. Including a parallel patient preference group to create a comprehensive cohort of patients has been suggested as a way of increasing the power of such trials. In our study, the comprehensive cohort model doubled the number of patients involved in the study. However, a strong preference for non-operative treatment meant that the increased number of patients did not significantly increase the ability of the trial to detect a difference between the two interventions

Cast versus functional brace in the rehabilitation of patients treated non-operatively for a rupture of the Achilles tendon : protocol for UK Study of Tendo Achilles Rehabilitation (UK STAR)

Introduction Achilles tendon rupture affects over 11,000 people yearly in the UK, and the incidence is increasing. Controversy remains with regards the best rehabilitation strategy for these patients. In operatively treated patients, functional bracing provides better outcomes compared with plaster casts. However, the role of functional bracing in non-operatively managed patients is unclear. This is the protocol for a multi-centre randomised trial of plaster cast immobilisation versus functional bracing for patients with a non-operatively managed Achilles tendon rupture. Methods and analysis All adults presenting with a primary rupture of the Achilles tendon will be screened. Non-operatively treated patients will be eligible to take part in the trial. Broad eligibility criteria will ensure that the results of the study can be generalised to the wider patient population. Randomisation will be on a 1:1 basis. Both rehabilitation strategies are widely used within the NHS. Standardised protocols will be followed, but details of plaster material and brace will be as per the site’s usual practice. A minimum of 330 patients will be randomised to obtain 90% power to detect a difference of 8 points in Achilles Tendon Rupture Score (ATRS) at 9 months. Quality of life and resource use will also be collected at 3, 6 and 9 months. The differences between treatment groups will be assessed on an intention-to-treat basis. Results are expected to be available in the summer of 2019. Ethics and dissemination. National Research Ethic Committee approved this study on the 18th of March 2016 (16/SC/0109). The NIHR Health Technology Assessment monograph and a manuscript to a peer-reviewed journal will be submitted upon completion of the trial. The results of this trial will substantially inform clinical practice on the clinical and cost effectiveness of the treatment of this injury

Designing clinical trials in trauma surgery: overcoming research barriers.

The surgical community is plagued with a reputation for both failing to engage and to deliver on clinical research. This is in part due to the absence of a strong research culture, however it is also due to a multitude of barriers encountered in clinical research; particularly those involving surgical interventions. 'Trauma' amplifies these barriers, owing to the unplanned nature of care, unpredictable work patterns, the emergent nature of treatment and complexities in the consent process. This review discusses the barriers to clinical research in surgery, with a particular emphasis on trauma. It considers how barriers may be overcome, with the aim to facilitate future successful clinical research

Stellar Coronal and Wind Models: Impact on Exoplanets

Surface magnetism is believed to be the main driver of coronal heating and stellar wind acceleration. Coronae are believed to be formed by plasma confined in closed magnetic coronal loops of the stars, with winds mainly originating in open magnetic field line regions. In this Chapter, we review some basic properties of stellar coronae and winds and present some existing models. In the last part of this Chapter, we discuss the effects of coronal winds on exoplanets.Comment: Chapter published in the "Handbook of Exoplanets", Editors in Chief: Juan Antonio Belmonte and Hans Deeg, Section Editor: Nuccio Lanza. Springer Reference Work

Differential cargo mobilisation within Weibel-Palade bodies after transient fusion with the plasma membrane.

Inflammatory chemokines can be selectively released from Weibel-Palade bodies (WPBs) during kiss-and-run exocytosis. Such selectivity may arise from molecular size filtering by the fusion pore, however differential intra-WPB cargo re-mobilisation following fusion-induced structural changes within the WPB may also contribute to this process. To determine whether WPB cargo molecules are differentially re-mobilised, we applied FRAP to residual post-fusion WPB structures formed after transient exocytosis in which some or all of the fluorescent cargo was retained. Transient fusion resulted in WPB collapse from a rod to a spheroid shape accompanied by substantial swelling (>2 times by surface area) and membrane mixing between the WPB and plasma membranes. Post-fusion WPBs supported cumulative WPB exocytosis. To quantify diffusion inside rounded organelles we developed a method of FRAP analysis based on image moments. FRAP analysis showed that von Willebrand factor-EGFP (VWF-EGFP) and the VWF-propolypeptide-EGFP (Pro-EGFP) were immobile in post-fusion WPBs. Because Eotaxin-3-EGFP and ssEGFP (small soluble cargo proteins) were largely depleted from post-fusion WPBs, we studied these molecules in cells preincubated in the weak base NH4Cl which caused WPB alkalinisation and rounding similar to that produced by plasma membrane fusion. In these cells we found a dramatic increase in mobilities of Eotaxin-3-EGFP and ssEGFP that exceeded the resolution of our method (∼ 2.4 µm2/s mean). In contrast, the membrane mobilities of EGFP-CD63 and EGFP-Rab27A in post-fusion WPBs were unchanged, while P-selectin-EGFP acquired mobility. Our data suggest that selective re-mobilisation of chemokines during transient fusion contributes to selective chemokine secretion during transient WPB exocytosis. Selective secretion provides a mechanism to regulate intravascular inflammatory processes with reduced risk of thrombosis

Molecular and cellular mechanisms underlying the evolution of form and function in the amniote jaw.

The amniote jaw complex is a remarkable amalgamation of derivatives from distinct embryonic cell lineages. During development, the cells in these lineages experience concerted movements, migrations, and signaling interactions that take them from their initial origins to their final destinations and imbue their derivatives with aspects of form including their axial orientation, anatomical identity, size, and shape. Perturbations along the way can produce defects and disease, but also generate the variation necessary for jaw evolution and adaptation. We focus on molecular and cellular mechanisms that regulate form in the amniote jaw complex, and that enable structural and functional integration. Special emphasis is placed on the role of cranial neural crest mesenchyme (NCM) during the species-specific patterning of bone, cartilage, tendon, muscle, and other jaw tissues. We also address the effects of biomechanical forces during jaw development and discuss ways in which certain molecular and cellular responses add adaptive and evolutionary plasticity to jaw morphology. Overall, we highlight how variation in molecular and cellular programs can promote the phenomenal diversity and functional morphology achieved during amniote jaw evolution or lead to the range of jaw defects and disease that affect the human condition

Does pay for performance improve patient outcomes in a national health service? results from the WHiTE multicentre hip fracture cohort

Aims: The aim of this study was to determine whether national standards of best practice are associated with improved health-related quality of life (HRQoL) outcomes in hip fracture patients. Methods: This was a multicentre cohort study conducted in 20 acute UK NHS hospitals treating hip fracture patients. Patients aged ≥ 60 years treated operatively for a hip fracture were eligible for inclusion. Regression models were fitted to each of the “Best Practice Tariff” indicators and overall attainment. The impact of attainment on HRQoL was assessed by quantifying improvement in EuroQol five-dimension five-level questionnaire (EQ-5D-5L) from estimated regression model coefficients. Results: A total of 6,532 patients provided both baseline and four-month EQ-5D-5L, of whom 1,060 participants had died at follow-up. Best practice was achieved in the care of 57% of participants; there was no difference in age, cognitive ability, and mobility at baseline for the overall attainment and non-attainment groups. Attaining at least ‘joint care by surgeon and orthogeriatrician’, ‘delirium assessment’, and ‘falls assessment’ was associated with a large, clinically relevant increase in four months EQ-5D-5L of 0.094 (bootstrapped 95% confidence interval (CI) 0.046 to 0.146). Conclusion: National standards with enhanced remuneration in hip fracture care results in improvement in individual patients’ HRQoL