The influence of femoral head size following total hip replacement and hip resurfacing on hip biomechanics during walking, stair use and sit-to-stand

Due to geometrical features, it is claimed that larger femoral heads in total hip replacement (THR) are superior in achieving normal biomechanics than smaller ones; and that hip resurfacing (RSF) is superior to THR. This has not been conclusively proven. Most studies have investigated level walking, which may not be demanding enough to highlight what could be small biomechanical differences between implants. Few biomechanical studies have compared more demanding tasks and not with patients with different femoral head sizes or RSF. This thesis aimed to address these omissions by investigating level walking, stair descent and sit-to-stand (STS) biomechanics between three groups (32mm THR, 36mm THR and RSF). Twenty-six osteoarthritis patients were recruited and tested pre-operatively, then three and twelve months post-operatively. Demographic differences between groups were expected due to patient considerations for different implants, so a study was performed to determine whether level walking biomechanics alter progressively during the aging process with a group of 63 healthy participants. Three matched sub-groups were extracted from this group as controls. There was no suggestion that gait deteriorates progressively with age. Hip reconstruction, irrespective of head size, can allow patients to return to the biomechanical levels of controls during level walking. Stair descent differences remained 12 months post-operatively in cadence (p=0.042) and peak hip power generated (p<0.001) compared to controls. The 32mm group exhibited vertical ground reaction force (vGRF) asymmetry pre-operatively (p<0.001) and 3 months post-operatively (p=0.013); and impulse asymmetry (p<0.001) pre-operatively during STS. The 36mm group exhibited impulse asymmetry (p=0.05)three months post-operatively. This thesis is the first biomechanical analysis of stair descent and STS of two THR groups and a RSF group. It has demonstrated stair descent differences at 12 months post-operatively and overloading of the healthy limb in some THR patients. The latter could be problematic for the healthy limb

Sit-to stand ground reaction force changes after hip resurfacing or total hip replacement: a pilot study

Two groups of osteoarthritis patients had their ground reaction forces measured during a sit-to-stand task at three months post-operation. One group had a 32mm femoral head fitted during a total hip replacement procedure and the other group had a hip resurfacing procedure. Three validated orthopaedic score questionnaires and an activity questionnaire were completed prior to surgery and at three months post-operation. This pilot study showed that there were no significant differences in the ground reaction forces in the operated and non-operated limb between the groups although both groups exhibited significantly higher ground reaction forces on the non-operated limb compared to the operated one. None of the orthopaedic scores showed any significant differences between the groups, despite the resurfacing group reporting higher levels of sporting activity at three months postoperation

Identifying car ingress movement strategies before and after total knee replacement

Background: Post-operative performance of knee bearings is typically assessed in activities of daily living by means of motion capture. Biomechanical studies predominantly explore common tasks such as walking, standing and stair climbing, while overlooking equally demanding activities such as embarking a vehicle. Aims: The aim of this work is to evaluate changes in the movement habits of patients after total knee arthroplasty surgery in comparison to healthy age-matched control participants. Methods: A mock-up car was fabricated based on the architecture of a common vehicle. Ten control participants and 10 patients with severe osteoarthritis of the knee attended a single- and three-motion capture session(s), respectively. Participants were asked to enter the car and sit comfortably adopting a driving position. Three trials per session were used for the identification of movement strategies by means of hierarchical clustering. Task completion time was also measured. Results: Patients’ movement behaviour didn’t change significantly following total knee arthroplasty surgery. Control participants favoured different movement strategies compared to patients post-operatively. Group membership, height and sidedness of the affected joint were found to be non-significant in task completion time. Conclusion: This study describes an alternative movement identification technique for the analysis of the ingress movement that may be used to clinically assess knee bearings and aid in movement simulations and vehicle design

Implant Design Affects Walking and Stair Navigation after Total Knee Arthroplasty:a double-blinded randomised controlled trial

Background: Dissimilar total knee arthroplasty implant designs offer different functional characteristics. This is the first work in the literature to fully assess the Columbus ultra-congruent mobile (UCR) system with a rotating platform. Methods: This is a double-blinded randomised controlled trial, comparing the functional performance of the low congruent fixed (CR DD), ultra-congruent fixed (UC) and UCR Columbus Total Knee Systems. The pre-operative and post-operative functional performance of twenty-four osteoarthritic patients was evaluated against nine control participants when carrying out everyday tasks. Spatiotemporal, kinematic and kinetic gait parameters in walking and stair navigation were extracted by means of motion capture. Results: The UC implant provided better post-operative function, closely followed by the UCR design. However, both the UC and UCR groups exhibited restricted post-operative sagittal RoM (walking, 52.1 ± 4.4° and 53.2 ± 6.6°, respectively), whilst patients receiving a UCR implant did not show an improvement in their tibiofemoral axial rotation despite the bearing’s mobile design (walking, CR DD 13.2 ± 4.6°, UC 15.3 ± 6.7°, UCR 13.5 ± 5.4°). Patients with a CR DD fixed bearing showed a statistically significant post-operative improvement in their sagittal RoM when walking (56.8 ± 4.6°). Conclusion: It was concluded that both ultra-congruent designs in this study, the UC and UCR bearings, showed comparable functional performance and improvement after TKA surgery. The CR DD group showed the most prominent improvement in the sagittal RoM during walking. Trial registration: The study is registered under the clinical trial registration number: NCT02422251. Registered on April 21, 2015

An electrochemical SARS-CoV-2 biosensor inspired by glucose test strip manufacturing processes

Accurate and rapid diagnostic tests are critical to reducing the impact of SARS-CoV-2. This study presents early, but promising measurements of SARS-CoV-2 using the ACE2 enzyme as the recognition element to achieve clinically relevant detection. The test provides a scalable route to sensitive, specific, rapid and low cost mass testing

SARS-CoV-2 aptasensors based on electrochemical impedance spectroscopy and low-cost gold electrode substrates

SARS-CoV-2 diagnostic practices broadly involve either quantitative polymerase chain reaction (qPCR)-based nucleic amplification of viral sequences or antigen-based tests such as lateral flow assays (LFAs). Reverse transcriptase-qPCR can detect viral RNA and is the gold standard for sensitivity. However, the technique is time-consuming and requires expensive laboratory infrastructure and trained staff. LFAs are lower in cost and near real time, and because they are antigen-based, they have the potential to provide a more accurate indication of a disease state. However, LFAs are reported to have low real-world sensitivity and in most cases are only qualitative. Here, an antigen-based electrochemical aptamer sensor is presented, which has the potential to address some of these shortfalls. An aptamer, raised to the SARS-CoV-2 spike protein, was immobilized on a low-cost gold-coated polyester substrate adapted from the blood glucose testing industry. Clinically relevant detection levels for SARS-CoV-2 are achieved in a simple, label-free measurement format using sample incubation times as short as 15 min on nasopharyngeal swab samples. This assay can readily be optimized for mass manufacture and is compatible with a low-cost meter

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

Clinical characteristics, risk factors and outcomes in patients with severe COVID-19 registered in the International Severe Acute Respiratory and Emerging Infection Consortium WHO clinical characterisation protocol: a prospective, multinational, multicentre, observational study

Due to the large number of patients with severe coronavirus disease 2019 (COVID-19), many were treated outside the traditional walls of the intensive care unit (ICU), and in many cases, by personnel who were not trained in critical care. The clinical characteristics and the relative impact of caring for severe COVID-19 patients outside the ICU is unknown. This was a multinational, multicentre, prospective cohort study embedded in the International Severe Acute Respiratory and Emerging Infection Consortium World Health Organization COVID-19 platform. Severe COVID-19 patients were identified as those admitted to an ICU and/or those treated with one of the following treatments: invasive or noninvasive mechanical ventilation, high-flow nasal cannula, inotropes or vasopressors. A logistic generalised additive model was used to compare clinical outcomes among patients admitted or not to the ICU. A total of 40 440 patients from 43 countries and six continents were included in this analysis. Severe COVID-19 patients were frequently male (62.9%), older adults (median (interquartile range (IQR), 67 (55-78) years), and with at least one comorbidity (63.2%). The overall median (IQR) length of hospital stay was 10 (5-19) days and was longer in patients admitted to an ICU than in those who were cared for outside the ICU (12 (6-23) days versus 8 (4-15) days, p<0.0001). The 28-day fatality ratio was lower in ICU-admitted patients (30.7% (5797 out of 18 831) versus 39.0% (7532 out of 19 295), p<0.0001). Patients admitted to an ICU had a significantly lower probability of death than those who were not (adjusted OR 0.70, 95% CI 0.65-0.75; p<0.0001). Patients with severe COVID-19 admitted to an ICU had significantly lower 28-day fatality ratio than those cared for outside an ICU

Renal artery sympathetic denervation:observations from the UK experience

Background: Renal denervation (RDN) may lower blood pressure (BP); however, it is unclear whether medication changes may be confounding results. Furthermore, limited data exist on pattern of ambulatory blood pressure (ABP) response—particularly in those prescribed aldosterone antagonists at the time of RDN. Methods: We examined all patients treated with RDN for treatment-resistant hypertension in 18 UK centres. Results: Results from 253 patients treated with five technologies are shown. Pre-procedural mean office BP (OBP) was 185/102 mmHg (SD 26/19; n = 253) and mean daytime ABP was 170/98 mmHg (SD 22/16; n = 186). Median number of antihypertensive drugs was 5.0: 96 % ACEi/ARB; 86 % thiazide/loop diuretic and 55 % aldosterone antagonist. OBP, available in 90 % at 11 months follow-up, was 163/93 mmHg (reduction of 22/9 mmHg). ABP, available in 70 % at 8.5 months follow-up, was 158/91 mmHg (fall of 12/7 mmHg). Mean drug changes post RDN were: 0.36 drugs added, 0.91 withdrawn. Dose changes appeared neutral. Quartile analysis by starting ABP showed mean reductions in systolic ABP after RDN of: 0.4; 6.5; 14.5 and 22.1 mmHg, respectively (p &lt; 0.001 for trend). Use of aldosterone antagonist did not predict response (p &lt; 0.2). Conclusion: In 253 patients treated with RDN, office BP fell by 22/9 mmHg. Ambulatory BP fell by 12/7 mmHg, though little response was seen in the lowermost quartile of starting blood pressure. Fall in BP was not explained by medication changes and aldosterone antagonist use did not affect response

HLA-DQA1*05 carriage associated with development of anti-drug antibodies to infliximab and adalimumab in patients with Crohn's Disease

Anti-tumor necrosis factor (anti-TNF) therapies are the most widely used biologic drugs for treating immune-mediated diseases, but repeated administration can induce the formation of anti-drug antibodies. The ability to identify patients at increased risk for development of anti-drug antibodies would facilitate selection of therapy and use of preventative strategies.This article is freely available via Open Access. Click on Publisher URL to access the full-text