CAPAbility: Comparison of the JOURNEY II Bi-Cruciate Stabilised and GENESIS II total knee arthroplasty in performance and functional ability: protocol of a randomised controlled trial

Background: Osteoarthritis of the knee is a common condition that is expected to rise in the next two decades leading to an associated increase in total knee replacement (TKR) surgery. Although there is little debate regarding the safety and efficacy of modern TKR, up to 20% of patients report poor functional outcomes following surgery. This study will investigate the functional outcome of two TKRs; the JOURNEY II Bi-Cruciate Stabilised knee arthroplasty, a newer knee prosthesis designed to provide guided motion and improve knee kinematics by more closely approximating a normal knee, and the GENESIS II, a proven existing design. Aim: To compare the change in Patient-reported Outcome Measures (PROMs) scores of the JOURNEY II BCS and the GENESIS II from pre-operation to 6 months post operation. Methods: CAPAbility is a pragmatic, blinded, two-arm parallel, randomised controlled trial recruiting patients with primary osteoarthritis due to have unilateral TKR surgery across two UK hospitals. Eligible participants (n = 80) will be randomly allocated to receive either the JOURNEY II or the GENESIS II BCS knee prosthesis. Baseline measures will be taken prior to surgery. Patients will be followed at 1 week, 6 to 8 weeks and 6 months post-operatively. The primary outcome is the Oxford Knee Score (OKS) at 6 months post-operatively. Secondary outcomes include: Other PROMs, biomechanical, radiological (computerised tomography, (CT)), clinical efficacy and safety outcomes. An embedded qualitative study will also investigate patients' perspectives via interview pre and post surgery on variables known to affect the outcome of TKR surgery. A sub-sample (n = 30) will have additional in-depth interviews to explore the themes identified. The surgeons' perspectives on the operation will be investigated by a group interview after all participants have undergone surgery. Discussion: This trial will evaluate two generations of TKR using PROMS, kinematic and radiological analyses and qualitative outcomes from the patient perspective

Targeting the DNA Double Strand Break Repair Machinery in Prostate Cancer

Regardless of the achievable remissions with first line hormone therapy in patients with prostate cancer (CaP), the disease escapes the hormone dependent stage to a more aggressive status where chemotherapy is the only effective treatment and no treatment is curative. This makes it very important to identify new targets that can improve the outcome of treatment. ATM and DNA-PK are the two kinases responsible for signalling and repairing double strand breaks (DSB). Thus, both kinases are pertinent targets in CaP treatment to enhance the activity of the numerous DNA DSB inducing agents used in CaP treatment such as ionizing radiation (IR). Colony formation assay was used to assess the sensitivity of hormone dependent, p53 wt (LNCaP) and hormone independent p53 mutant (PC3) CaP cell lines to the cytotoxic effect of IR and Doxorubicin in the presence or absence of Ku55933 and NU7441 which are small molecule inhibitors of ATM and DNA-PK, respectively. Flow cytometry based methods were used to assess the effect of the two inhibitors on cell cycle, apoptosis and H2AX foci formation. Neutral comet assay was used to assess the induction of DNA DSBs. Ku55933 or NU7441 alone increased the sensitivity of CaP cell lines to the DNA damaging agents, however combining both inhibitors together resulted in further enhancement of sensitivity. The cell cycle profile of both cell lines was altered with increased cell death, DNA DSBs and H2AX foci formation. This study justifies further evaluation of the ATM and DNA-PK inhibitors for clinical application in CaP patients. Additionally, the augmented effect resulting from combining both inhibitors may have a significant implication for the treatment of CaP patients who have a defect in one of the two DSB repair pathways

Development of a toolkit to enhance care processes for people with a long-term neurological condition:A qualitative descriptive study

Objective To (A) explore perspectives of people with a long-term neurological condition, and of their family, clinicians and other stakeholders on three key processes: Two-way communication, self-management and coordination of long-term care; and (B) use these data to develop a Living Well Toolkit', a structural support aiming to enhance the quality of these care processes. Design This qualitative descriptive study drew on the principles of participatory research. Data from interviews and focus groups with participants (n=25) recruited from five hospital, rehabilitation and community settings in New Zealand were analysed using conventional content analysis. Consultation with a knowledge-user group (n=4) and an implementation champion group (n=4) provided additional operational knowledge important to toolkit development and its integration into clinical practice. Results Four main, and one overarching, themes were constructed: (1) tailoring care:referring to getting to know the person and their individual circumstances; (2) involving others: Representing the importance of negotiating the involvement of others in the person's long-term management process; (3) exchanging knowledge: Referring to acknowledging patient expertise; and (4) enabling: Highlighting the importance of empowering relationships and processes. The overarching theme was: Assume nothing. These themes informed the development of a toolkit comprising of two parts: One to support the person with the long-term neurological condition, and one targeted at clinicians to guide interaction and support their engagement with patients. Conclusion Perspectives of healthcare users, clinicians and other stakeholders were fundamental to the development of the Living Well Toolkit. The findings were used to frame toolkit specifications and highlighted potential operational issues that could prove key to its success. Further research to evaluate its use is now underway

Investigating the Relationships Between Three Important Functional Tasks Early After Stroke: Movement Characteristics of Sit-To-Stand, Sit-To-Walk, and Walking.

Background: Walking, sit-to-stand (STS) and sit-to-walk (STW) are all considered important functional tasks in achieving independence after stroke. Despite knowledge that sensitive measurement of movement patterns is crucial to understanding neuromuscular restitution, there is surprisingly little information available about the detailed biomechanical characteristics of, and relationships between, walking, sit-to-stand and sit-to-walk, particularly in the important time window early after stroke. Hence, here, the study aimed to: Identify the biomechanical characteristics of and determine any differences in both movement fluidity (hesitation, coordination and smoothness) and duration of movement phases, between sit-to-stand (STS) and sit-to-walk (STW) in people early after stroke.Determine whether measures of movement fluidity (hesitation, coordination, and smoothness) and movement phases during sit-to-stand (STS) and/or sit-to-walk (STW) are correlated strongly to commonly used measures of walking speed and/or step length ratio in people early after stroke. Methods: This study consisted of secondary data analysis from the SWIFT Cast Trial. Specifically, we investigated movement fluidity using established assessments of smoothness, hesitation and coordination and the time duration for specific movement phases in a group of 48 people after stroke. Comparisons were made between STS and STW and relationships to walking measures were explored. Results: Participants spent significantly more time in the initial movement phase, flexion momentum, during STS [mean time (SD) 1.74 ±1.45 s] than they did during STW [mean time (SD) 1.13 ± 1.03 s]. STS was also completed more smoothly but with more hesitation and greater coordination than the task of STW. No strong relationships were found between movement fluidity or duration with walking speed or step length symmetry. Conclusions: Assessment of movement after stroke requires a range of functional tasks and no one task should predominate over another. Seemingly similar or overlapping tasks such as STS and STW create distinct biomechanical characteristics which can be identified using sensitive, objective measures of fluidity and movement phases but there are no strong relationships between the functional tasks of STS and STW with walking speed or with step-length symmetry

Australasian Malignant PLeural Effusion (AMPLE)-3 trial: Study protocol for a multi-centre randomised study comparing indwelling pleural catheter (±talc pleurodesis) versus video-assisted thoracoscopic surgery for management of malignant pleural effusion

Introduction: Malignant pleural effusions (MPEs) are common. MPE causes significant breathlessness and impairs quality of life. Indwelling pleural catheters (IPC) allow ambulatory drainage and reduce hospital days and re-intervention rates when compared to standard talc slurry pleurodesis. Daily drainage accelerates pleurodesis, and talc instillation via the IPC has been proven feasible and safe. Surgical pleurodesis via video-assisted thoracoscopic surgery (VATS) is considered a one-off intervention for MPE and is often recommended to patients who are fit for surgery. The AMPLE-3 trial is the first randomised trial to compare IPC (±talc pleurodesis) and VATS pleurodesis in those who are fit for surgery. Methods and analysis: A multi-centre, open-labelled randomised trial of patients with symptomatic MPE, expected survival of ≥ 6 months and good performance status randomised 1:1 to either IPC or VATS pleurodesis. Participant randomisation will be minimised for (i) cancer type (mesothelioma vs non-mesothelioma); (ii) previous pleurodesis (vs not); and (iii) trapped lung, if known (vs not). Primary outcome is the need for further ipsilateral pleural interventions over 12 months or until death, if sooner. Secondary outcomes include days in hospital, quality of life (QoL) measures, physical activity levels, safety profile, health economics, adverse events, and survival. The trial will recruit 158 participants who will be followed up for 12 months. Ethics and dissemination: Sir Charles Gairdner and Osborne Park Health Care Group (HREC) has approved the study (reference: RGS356). Results will be published in peer-reviewed journals and presented at scientific meetings. Discussion: Both IPC and VATS are commonly used procedures for MPE. The AMPLE-3 trial will provide data to help define the merits and shortcomings of these procedures and inform future clinical care algorithms. Trial registration: Australia New Zealand Clinical Trial Registry ACTRN12618001013257. Registered on 18 June 2018. Protocol version: Version 3.00/4.02.1

2020 American College of Rheumatology Guideline for the Management of Gout

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/155484/1/art41247.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/155484/2/art41247_am.pd

Avian Influenza Virus Surveillance in Wild Birds in Georgia: 2009-2011

The Caucasus, at the border of Europe and Asia, is important for migration and over-wintering of wild waterbirds. Three flyways, the Central Asian, East Africa-West Asia, and Mediterranean/Black Sea flyways, converge in the Caucasus region. Thus, the Caucasus region might act as a migratory bridge for influenza virus transmission when birds aggregate in high concentrations in the post-breeding, migrating and overwintering periods. Since August 2009, we have established a surveillance network for influenza viruses in wild birds, using five sample areas geographically spread throughout suitable habitats in both eastern and western Georgia. We took paired tracheal and cloacal swabs and fresh feces samples. We collected 8343 swabs from 76 species belonging to 17 families in 11 orders of birds, of which 84 were real-time RT-PCR positive for avian influenza virus (AIV). No highly pathogenic AIV (HPAIV) H5 or H7 viruses were detected. The overall AIV prevalence was 1.6%. We observed peak prevalence in large gulls during the autumn migration (5.3-9.8%), but peak prevalence in Black-headed Gulls in spring (4.2-13%). In ducks, we observed increased AIV prevalence during the autumn post-moult aggregations and migration stop-over period (6.3%) but at lower levels to those observed in other more northerly post-moult areas in Eurasia. We observed another prevalence peak in the overwintering period (0.14-5.9%). Serological and virological monitoring of a breeding colony of Armenian Gulls showed that adult birds were seropositive on arrival at the breeding colony, but juveniles remained serologically and virologically negative for AIV throughout their time on the breeding grounds, in contrast to gull AIV data from other geographic regions. We show that close phylogenetic relatives of viruses isolated in Georgia are sourced from a wide geographic area throughout Western and Central Eurasia, and from areas that are represented by multiple different flyways, likely linking different host sub-populations

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Company for the ultra-high density, ultra-short period sub-Earth GJ 367 b: discovery of two additional low-mass planets at 11.5 and 34 days

GJ 367 is a bright (V $\approx$ 10.2) M1 V star that has been recently found to host a transiting ultra-short period sub-Earth on a 7.7 hr orbit. With the aim of improving the planetary mass and radius and unveiling the inner architecture of the system, we performed an intensive radial velocity follow-up campaign with the HARPS spectrograph -- collecting 371 high-precision measurements over a baseline of nearly 3 years -- and combined our Doppler measurements with new TESS observations from sectors 35 and 36. We found that GJ 367 b has a mass of $M_\mathrm{b}$ = 0.633 $\pm$ 0.050 M$_{\oplus}$ and a radius of $R_\mathrm{b}$ = 0.699 $\pm$ 0.024 R$_{\oplus}$, corresponding to precisions of 8% and 3.4%, respectively. This implies a planetary bulk density of $\rho_\mathrm{b}$ = 10.2 $\pm$ 1.3 g cm$^{-3}$, i.e., 85% higher than Earth's density. We revealed the presence of two additional non transiting low-mass companions with orbital periods of $\sim$11.5 and 34 days and minimum masses of $M_\mathrm{c}\sin{i_\mathrm{c}}$ = 4.13 $\pm$ 0.36 M$_{\oplus}$ and $M_\mathrm{d}\sin{i_\mathrm{d}}$ = 6.03 $\pm$ 0.49 M$_{\oplus}$, respectively, which lie close to the 3:1 mean motion commensurability. GJ 367 b joins the small class of high-density planets, namely the class of super-Mercuries, being the densest ultra-short period small planet known to date. Thanks to our precise mass and radius estimates, we explored the potential internal composition and structure of GJ 367 b, and found that it is expected to have an iron core with a mass fraction of 0.91$^{+0.07}_{-0.23}$. How this iron core is formed and how such a high density is reached is still not clear, and we discuss the possible pathways of formation of such a small ultra-dense planet.Comment: 28 pages, 11 figures. Accepted for publication in ApJ