Development and validation of a clinical prediction model for patient-reported pain and function after primary total knee replacement surgery

To develop and validate a clinical prediction model of patient-reported pain and function after undergoing total knee replacement (TKR). We used data of 1,649 patients from the Knee Arthroplasty Trial who received primary TKR across 34 centres in the UK. The external validation included 595 patients from Southampton University Hospital, and Nuffield Orthopaedic Centre (Oxford). The outcome was the Oxford Knee Score (OKS) 12-month after TKR. Pre-operative predictors including patient characteristics and clinical factors were considered. Bootstrap backward linear regression analysis was used. Low pre-operative OKS, living in poor areas, high body mass index, and patient-reported anxiety or depression were associated with worse outcome. The clinical factors associated with worse outcome were worse pre-operative physical status, presence of other conditions affecting mobility and previous knee arthroscopy. Presence of fixed flexion deformity and an absent or damaged pre-operative anterior cruciate ligament (compared with intact) were associated with better outcome. Discrimination and calibration statistics were satisfactory. External validation predicted 21.1% of the variance of outcome. This is the first clinical prediction model for predicting self-reported pain and function 12 months after TKR to be externally validated. It will help to inform to patients regarding expectations of the outcome after knee replacement surgery

Cost-effectiveness of unicompartmental compared with total knee replacement: a population-based study using data from the National Joint Registry for England and Wales

Objectives: To assess the value for money of unicompartmental knee replacement (UKR) compared with total knee replacement (TKR). Design: A lifetime Markov model provided the framework for the analysis. Setting: Data from the National Joint Registry (NJR) for England and Wales primarily informed the analysis. Participants: Propensity score matched patients in the NJR who received either a UKR or TKR. Interventions: UKR is a less invasive alternative to TKR, where only the compartment affected by osteoarthritis is replaced. Primary outcome measures: Incremental quality-adjusted life years (QALYs) and healthcare system costs. Results: The provision of UKR is expected to lead to a gain in QALYs compared with TKR for all age and gender subgroups (male: <60 years: 0.12, 60–75 years: 0.20, 75+ years: 0.19; female: <60 years: 0.10, 60–75 years: 0.28, 75+ years: 0.44) and a reduction in costs (male: <60: £−1223, 60–75 years: £−1355, 75+ years: £−2005; female: <60 years: £−601, 60–75 years: £−935, 75+ years: £−1102 per patient over the lifetime). UKR is expected to lead to a reduction in QALYs compared with TKR when performed by surgeons with low UKR utilisation but an increase among those with high utilisation (<10%, median 6%: −0.04, ≥10%, median 27%: 0.26). Regardless of surgeon usage, costs associated with UKR are expected to be lower than those of TKR (<10%: £−127, ≥10%: £−758). Conclusions: UKR can be expected to generate better health outcomes and lower lifetime costs than TKR. Surgeon usage of UKR does, however, have a significant impact on the cost-effectiveness of the procedure. To achieve the best results, surgeons need to perform a sufficient proportion of knee replacements as UKR. Low usage surgeons may therefore need to broaden their indications for UKR

Minimization of phonon-tunneling dissipation in mechanical resonators

Micro- and nanoscale mechanical resonators have recently emerged as ubiquitous devices for use in advanced technological applications, for example in mobile communications and inertial sensors, and as novel tools for fundamental scientific endeavors. Their performance is in many cases limited by the deleterious effects of mechanical damping. Here, we report a significant advancement towards understanding and controlling support-induced losses in generic mechanical resonators. We begin by introducing an efficient numerical solver, based on the "phonon-tunneling" approach, capable of predicting the design-limited damping of high-quality mechanical resonators. Further, through careful device engineering, we isolate support-induced losses and perform the first rigorous experimental test of the strong geometric dependence of this loss mechanism. Our results are in excellent agreement with theory, demonstrating the predictive power of our approach. In combination with recent progress on complementary dissipation mechanisms, our phonon-tunneling solver represents a major step towards accurate prediction of the mechanical quality factor.Comment: 12 pages, 4 figure

Timescales of Massive Human Entrainment

The past two decades have seen an upsurge of interest in the collective behaviors of complex systems composed of many agents entrained to each other and to external events. In this paper, we extend concepts of entrainment to the dynamics of human collective attention. We conducted a detailed investigation of the unfolding of human entrainment - as expressed by the content and patterns of hundreds of thousands of messages on Twitter - during the 2012 US presidential debates. By time locking these data sources, we quantify the impact of the unfolding debate on human attention. We show that collective social behavior covaries second-by-second to the interactional dynamics of the debates: A candidate speaking induces rapid increases in mentions of his name on social media and decreases in mentions of the other candidate. Moreover, interruptions by an interlocutor increase the attention received. We also highlight a distinct time scale for the impact of salient moments in the debate: Mentions in social media start within 5-10 seconds after the moment; peak at approximately one minute; and slowly decay in a consistent fashion across well-known events during the debates. Finally, we show that public attention after an initial burst slowly decays through the course of the debates. Thus we demonstrate that large-scale human entrainment may hold across a number of distinct scales, in an exquisitely time-locked fashion. The methods and results pave the way for careful study of the dynamics and mechanisms of large-scale human entrainment.Comment: 20 pages, 7 figures, 6 tables, 4 supplementary figures. 2nd version revised according to peer reviewers' comments: more detailed explanation of the methods, and grounding of the hypothese

Effects of ecstasy/polydrug use on memory for associative information

Rationale Associative learning underpins behaviours that are fundamental to the everyday functioning of the individual. Evidence pointing to learning deficits in recreational drug users merits further examination. Objectives A word pair learning task was administered to examine associative learning processes in ecstasy/polydrug users. Methods After assignment to either single or divided attention conditions, 44 ecstasy/polydrug users and 48 non-users were presented with 80 word pairs at encoding. Following this, four types of stimuli were presented at the recognition phase: the words as originally paired (old pairs), previously presented words in different pairings (conjunction pairs), old words paired with new words, and pairs of new words (not presented previously). The task was to identify which of the stimuli were intact old pairs. Results Ecstasy/ploydrug users produced significantly more false-positive responses overall compared to non-users. Increased long-term frequency of ecstasy use was positively associated with the propensity to produce false-positive responses. It was also associated with a more liberal signal detection theory decision criterion value. Measures of long term and recent cannabis use were also associated with these same word pair learning outcome measures. Conjunction word pairs, irrespective of drug use, generated the highest level of false-positive responses and significantly more false-positive responses were made in the divided attention condition compared to the single attention condition. Conclusions Overall, the results suggest that long-term ecstasy exposure may induce a deficit in associative learning and this may be in part a consequence of users adopting a more liberal decision criterion value

The prevalence of hand and wrist osteoarthritis in elite former cricket and rugby union players

OBJECTIVES: This study aimed to determine the prevalence of hand and wrist osteoarthritis in former elite cricket and rugby union players, by sport and playing position, and to define the prevalence of severe hand injury, and its association with hand osteoarthritis. DESIGN: Cross-sectional. METHODS: Data from cross-sectional studies of former elite male cricket and rugby players were used to determine the prevalence of hand pain, physician-diagnosed osteoarthritis, and previous severe injury. Multivariable logistic regression was used to determine the association of previous injury with pain and osteoarthritis. RESULTS: Data from 200 cricketers and 229 rugby players were available. Complete case analysis resulted in 127 cricketers and 140 rugby players. Hand pain was more prevalent amongst cricketers (19.7%) than rugby players (10.0%). The prevalence did not differ between cricket and rugby players for hand osteoarthritis (2.4% and 3.6%), wrist osteoarthritis (1.6% and 2.1%), or previous severe hand injury (36.2% and 31.4%). No significant association between previous hand injury and pain or osteoarthritis was identified in either sport. CONCLUSIONS: Former elite cricketers reported more hand pain than rugby players. No significant association was found between self-reported severe injury and hand osteoarthritis in either cohort, potentially indicating that risk factors aside from injury may be more prominent in the development of hand osteoarthritis

Modelling Patient Behaviour Using IoT Sensor Data: a Case Study to Evaluate Techniques for Modelling Domestic Behaviour in Recovery from Total Hip Replacement Surgery

The UK health service sees around 160,000 total hip or knee replacements every year and this number is expected to rise with an ageing population. Expectations of surgical outcomes are changing alongside demographic trends, whilst aftercare may be fractured as a result of resource limitations. Conventional assessments of health outcomes must evolve to keep up with these changing trends. Health outcomes may be assessed largely by self-report using Patient Reported Outcome Measures (PROMs), such as the Oxford Hip or Oxford Knee Score, in the months up to and following surgery. Though widely used, many PROMs have methodological limitations and there is debate about how to interpret results and definitions of clinically meaningful change. With the development of a home-monitoring system, there is opportunity to characterise the relationship between PROMs and behaviour in a natural setting and to develop methods of passive monitoring of outcome and recovery after surgery. In this paper, we discuss the motivation and technology used in long-term continuous observation of movement, sleep and domestic routine for healthcare applications, such as the HEmiSPHERE project for hip and knee replacement patients. In this case study, we evaluate trends evident in data of two patients, collected over a 3-month observation period post-surgery, by comparison with scores from PROMs for sleep and movement quality, and by comparison with a third control home. We find that accelerometer and indoor localisation data correctly highlight long-term trends in sleep and movement quality and can be used to predict sleep and wake times and measure sleep and wake routine variance over time, whilst indoor localisation provides context for the domestic routine and mobility of the patient. Finally, we discuss a visual method of sharing findings with healthcare professionals

An influenza virus-inspired polymer system for the timed release of siRNA

Small interfering RNA silences specific genes by interfering with mRNA translation, and acts to modulate or inhibit specific biological pathways; a therapy that holds great promise in the cure of many diseases. However, the naked small interfering RNA is susceptible to degradation by plasma and tissue nucleases and due to its negative charge unable to cross the cell membrane. Here we report a new polymer carrier designed to mimic the influenza virus escape mechanism from the endosome, followed by a timed release of the small interfering RNA in the cytosol through a self-catalyzed polymer degradation process. Our polymer changes to a negatively charged and non-toxic polymer after the release of small interfering RNA, presenting potential for multiple repeat doses and long-term treatment of diseases

Immunostimulatory Motifs Enhance Antiviral siRNAs Targeting Highly Pathogenic Avian Influenza H5N1

Highly pathogenic avian influenza (HPAI) H5N1 virus is endemic in many regions around the world and remains a significant pandemic threat. To date H5N1 has claimed almost 300 human lives worldwide, with a mortality rate of 60% and has caused the death or culling of hundreds of millions of poultry since its initial outbreak in 1997. We have designed multi-functional RNA interference (RNAi)-based therapeutics targeting H5N1 that degrade viral mRNA via the RNAi pathway while at the same time augmenting the host antiviral response by inducing host type I interferon (IFN) production. Moreover, we have identified two factors critical for maximising the immunostimulatory properties of short interfering (si)RNAs in chicken cells (i) mode of synthesis and (ii) nucleoside sequence to augment the response to virus. The 5-bp nucleoside sequence 5′-UGUGU-3′ is a key determinant in inducing high levels of expression of IFN -α, -β, -λ and interleukin 1- β in chicken cells. Positioning of this 5′-UGUGU-3′ motif at the 5′- end of the sense strand of siRNAs, but not the 3′- end, resulted in a rapid and enhanced induction of type I IFN. An anti-H5N1 avian influenza siRNA directed against the PB1 gene (PB1-2257) tagged with 5′-UGUGU-3′ induced type I IFN earlier and to a greater extent compared to a non-tagged PB1-2257. Tested against H5N1 in vitro, the tagged PB1-2257 was more effective than non-tagged PB1-2257. These data demonstrate the ability of an immunostimulatory motif to improve the performance of an RNAi-based antiviral, a finding that may influence the design of future RNAi-based anti-influenza therapeutics