The ProFHER (PROximal Fracture of the Humerus: Evaluation by Randomisation) trial – a pragmatic multicentre randomised controlled trial evaluating the clinical effectiveness and cost-effectiveness of surgical compared with non-surgical treatment for proximal fracture of the humerus in adults

Background Proximal humeral fractures account for 5–6% of all fractures in adults. There is considerable variation in whether or not surgery is used in the management of displaced fractures involving the surgical neck. Objective To evaluate the clinical effectiveness and cost-effectiveness of surgical compared with non-surgical treatment of the majority of displaced fractures of the proximal humerus involving the surgical neck in adults. Design A pragmatic parallel-group multicentre randomised controlled trial with an economic evaluation. Follow-up was for 2 years. Setting Recruitment was undertaken in the orthopaedic departments of 33 acute NHS hospitals in the UK. Patient care pathways included outpatient and community-based rehabilitation. Participants Adults (aged ≥ 16 years) presenting within 3 weeks of their injury with a displaced fracture of the proximal humerus involving the surgical neck. Interventions The choice of surgical intervention was left to the treating surgeons, who used techniques with which they were experienced. Non-surgical treatment was initial sling immobilisation followed by active rehabilitation. Provision of rehabilitation was comparable in both groups. Main outcome measures The primary outcome was the Oxford Shoulder Score (OSS) assessed at 6, 12 and 24 months. Secondary outcomes were the 12-item Short Form health survey, surgical and other shoulder fracture-related complications, secondary surgery to the shoulder or increased/new shoulder-related therapy, medical complications during inpatient stay and mortality. European Quality of Life-5 Dimensions data and treatment costs were also collected. Results The mean age of the 250 trial participants was 66 years and 192 (77%) were female. Independent assessment using the Neer classification identified 18 one-part fractures, 128 two-part fractures and 104 three- or four-part fractures. OSS data were available for 215 participants at 2 years. We found no statistically or clinically significant differences in OSS scores between the two treatment groups (scale 0–48, with a higher score indicating a better outcome) over the 2-year period [difference of 0.75 points in favour of the surgery group, 95% confidence interval (CI) –1.33 to 2.84; p  = 0.479; data from 114 surgery and 117 non-surgery participants] or at individual time points. We found no statistically significant differences between surgical and non-surgical group participants in SF-12 physical or mental component summary scores; surgical or shoulder fracture-related complications (30 vs. 23 respectively); those undergoing further shoulder-related therapy, either surgery (11 vs. 11 respectively) or other therapy (seven vs. four respectively); or mortality (nine vs. five respectively). The base-case economic analysis showed that, at 2 years, the cost of surgical intervention was, on average, £1780.73 more per patient (95% CI £1152.71 to £2408.75) than the cost of non-surgical intervention. It was also slightly less beneficial in terms of utilities, although this difference was not statistically significant. The net monetary benefit associated with surgery is negative. There was only a 5% probability of surgery achieving the criterion of costing < £20,000 to gain a quality-adjusted life-year, which was confirmed by extensive sensitivity analyses. Conclusions Current surgical practice does not result in a better outcome for most patients with displaced fracture

Changing perspectives on the city of Cyrene, Libya: Remote sensing and the management of the buried archaeological resource

Cyrene, a designated UNESCO World Heritage Site (WHS) in eastern modern Libya, was the leading city of the Libyan Pentapolis. Settled by Greek colonists toward the end of the 7th century B.C., it remained an active Graeco-Roman city of distinctively Hellenic character until the time of the Islamic conquest (A.D. 643). Archaeological missions from America, Italy, and the United Kingdom have excavated in Cyrene for more than a century. As a result the city is well known from extensive excavatio..

A grumbling concern: an international survey of gastrointestinal symptoms in cystic fibrosis in the modulator era [version 1; peer review: awaiting peer review]

Background: Gastrointestinal symptoms in cystic fibrosis (CF) are common and intrusive to daily life. Relieving gastrointestinal symptoms was identified as an important research priority and previously explored in an international survey in 2018. However, following the widespread introduction of cystic fibrosis transmembrane conductance regulator (CFTR) modulators in 2019, the landscape of CF treatment has changed. We repeated an online survey to further describe gastrointestinal symptoms and their effect on quality of life (QoL) in the CFTR modulator era. Methods: An electronic survey consisting of closed questions and free text responses was distributed via social media and professional networks for a period of one month between March - April 2022. People with CF (pwCF), their family and friends, and healthcare professionals (HCPs) were invited to take part. Results: There were 164 respondents: 88 pwCF (54%), 22 (13%) family, and 54 (33%) healthcare professionals (HCPs). A total of 89/110 (81%) pwCF or family members reported CFTR modulator treatment. The most commonly reported symptoms were wind / gas, rumbling stomach noises, loose motions (modulator) and bloating (no modulator). Abdominal pain and bloating had the greatest impact on QoL. For those on a CFTR modulator, the proportion of pwCF reporting “no change” or “worse” for all of the symptoms surveyed was greater than the proportion reporting an improvement. Following modulator introduction, dietary changes were recommended by 28/35 (80%) of HCPs and reported by 38/76 (50%) lay respondents. Changes in medication were recommended by 19/35 (54%) HCPs and reported by 44/76 (58%) of patients and family members. Conclusion This survey has shown that gastrointestinal symptoms remain prevalent in pwCF in the CFTR modulator era, though the nature of these symptoms may have changed. A better understanding of the underlying pathophysiology of these symptoms is essential. Future clinical studies should focus on improving symptoms and QoL

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

Establishing a large prospective clinical cohort in people with head and neck cancer as a biomedical resource: head and neck 5000

BACKGROUND: Head and neck cancer is an important cause of ill health. Survival appears to be improving but the reasons for this are unclear. They could include evolving aetiology, modifications in care, improvements in treatment or changes in lifestyle behaviour. Observational studies are required to explore survival trends and identify outcome predictors. METHODS: We are identifying people with a new diagnosis of head and neck cancer. We obtain consent that includes agreement to collect longitudinal data, store samples and record linkage. Prior to treatment we give participants three questionnaires on health and lifestyle, quality of life and sexual history. We collect blood and saliva samples, complete a clinical data capture form and request a formalin fixed tissue sample. At four and twelve months we complete further data capture forms and send participants further quality of life questionnaires. DISCUSSION: This large clinical cohort of people with head and neck cancer brings together clinical data, patient-reported outcomes and biological samples in a single co-ordinated resource for translational and prognostic research

Mapping the Deep Blue Oceans

The ocean terrain spanning the globe is vast and complex—far from an immense flat plain of mud. To map these depths accurately and wisely, we must understand how cartographic abstraction and generalization work both in analog cartography and digital GIS. This chapter explores abstraction practices such as selection and exaggeration with respect to mapping the oceans, showing significant continuity in such practices across cartography and contemporary GIS. The role of measurement and abstraction—as well as of political and economic power, and sexual and personal bias—in these sciences is illustrated by the biographies of Marie Tharp and Bruce Heezen, whose mapping of the Mid-Atlantic Ridge precipitated a paradigm shift in geology

Modelling Roman agricultural production in the Middle Tiber Valley, Central Italy

This thesis analyses the potential agricultural production of the regions of South Etruria and Sabina, north of Rome in the Middle Tiber Valley, Central Italy. Historical evidence from Roman authors is combined with archaeological evidence from field survey and geographical resource data, and modelled within a Geographical Information System. Farm size and location are investigated in order to determine any correlation with contemporary Roman recommendations. Multi-criteria evaluation is then used to create suitability maps, showing those regions within the study area best suited to different types of crops. A number of different models for agricultural production within the study area are presented. Many variables are utilised, each presenting a range of possibilities for the carrying capacity of the area, complementing previous studies of demography. Research into workload, nutrition and crop yields provides a basis for determining the supported population of the area. Urban provisioning is investigated also, showing how high yielding models could have supported a large urban population within the studied region, as well as its potential contribution to the food supply of Rome. This analysis showed which agricultural systems could adequately supply urban centres, and highlighted those models that would have led either to an urban dependency on larger scale trade networks or to decline