Identifying hepatic genes regulating the ovine response to gastrointestinal nematodes using RNA-Sequencing.

Gastrointestinal nematode (GIN) infections are considered the most important disease of grazing sheep and due to increasing anthelmintic resistance, chemical control alone is inadequate. Resistance to Gastrointestinal nematode infection is a heritable trait, and through natural selection many sheep breeds have higher resistance. Studying the transcriptome from GIN-exposed and GIN-unexposed sheep using RNA-Sequencing technology can provide measurements of transcript levels associated with the host response to Gastrointestinal nematode infection, and these transcripts may harbor genetic markers that can be used in selective breeding programs to enhance disease resistance. The objective of this study was to compare liver transcriptomes of sheep naturally exposed to Gastrointestinal nematode s, with either high or low parasite burdens, to GIN-unexposed control sheep in order to identify key regulator genes and biological processes associated with Gastrointestinal nematode infection. Differential gene expression analysis revealed no significant differentially expressed genes (DEG) between sheep with a high or low parasite burden (p-value ≤0.01; False Discovery Rate (FDR) ≤ 0.05; and Fold-Change (FC) of > ±2). However, when compared to the control group, low parasite burden sheep showed 146 differentially expressed genes (64 upregulated and 82 downregulated in the low parasite burden group relative to the control), and high parasite burden sheep showed 159 differentially expressed genes (57 upregulated and 102 downregulated in the low parasite burden group relative to the control) (p-value ≤0.01; FDR ≤0.05; and FC of > ±2). Among these two lists of significant differentially expressed genes, 86 differentially expressed genes (34 upregulated, 52 downregulated in the parasited group relative to the control) were found in common between the two parasite burden groups compared to the control (GIN-unexposed sheep). Functional analysis of these significant 86 differentially expressed genes found upregulated genes involved in immune response and downregulated genes involved in lipid metabolism. Results of this study offer insight into the liver transcriptome during natural Gastrointestinal nematode exposure that helps provide a better understanding of the key regulator genes involved in Gastrointestinal nematode infection in sheep.

A 15 to 17-year follow-up of the Kinemax total knee replacement.

BACKGROUND: There is a paucity of long-term data concerning the pre- and postoperative patient reported function of total knee replacement. The aim of this study was to determine the mortality, implant survivorship, patient reported function and satisfaction in a cohort of 114 patients, from a single centre, who received a Kinemax total knee replacement more than 15 years ago. METHODS: Patients completed a questionnaire incorporating validated disease- and joint-specific scores, patient satisfaction and overall health preoperatively, at three months, one year, two years and a minimum of 15 years following surgery. NHS National Strategic Tracing Service, hospital and primary care records were used to establish mortality and for implant survivorship in deceased patients. RESULTS: Forty five patients were alive at final follow-up. The survivorship of the cohort with revision of the TKR as the endpoint was 84%. Four cases were revised for wear, three for loosening and one for peri-prosthetic fracture. There was a significant improvement in WOMAC Pain, Function and Stiffness Scores, Oxford Knee Score and Self-Administered Patient Satisfaction Scale between pre-operative and all post-operative time points, although patient satisfaction had decreased significantly by the time of final follow-up. CONCLUSION: In this cohort, the Kinemax TKR showed survivorship of 84% at 16.3 years with functional scores demonstrating a high level of patient satisfaction at all follow-up time points. LEVEL OF EVIDENCE: 2 - Prospective Cohort Study.

Comparison of group-based outpatient physiotherapy with usual care after total knee replacement: a feasibility study for a randomized controlled trial.

OBJECTIVE: To evaluate the feasibility of conducting a randomized controlled trial comparing group-based outpatient physiotherapy with usual care in patients following total knee replacement. DESIGN: A feasibility study for a randomized controlled trial. SETTING: One secondary-care hospital orthopaedic centre, Bristol, UK. PARTICIPANTS: A total of 46 participants undergoing primary total knee replacement. INTERVENTIONS: The intervention group were offered six group-based exercise sessions after surgery. The usual care group received standard postoperative care. Participants were not blinded to group allocation. OUTCOME MEASURES: Feasibility was assessed by recruitment, reasons for non-participation, attendance, and completion rates of study questionnaires that included the Lower Extremity Functional Scale and Knee Injury and Osteoarthritis Outcome Score. RESULTS: Recruitment rate was 37%. Five patients withdrew or were no longer eligible to participate. Intervention attendance was high (73%) and 84% of group participants reported they were 'very satisfied' with the exercises. Return of study questionnaires at six months was lower in the usual care (75%) than in the intervention group (100%). Mean (standard deviation) Lower Extremity Functional Scale scores at six months were 45.0 (20.8) in the usual care and 57.8 (15.2) in the intervention groups. CONCLUSION: Recruitment and retention of participants in this feasibility study was good. Group-based physiotherapy was acceptable to participants. Questionnaire return rates were lower in the usual care group, but might be enhanced by telephone follow-up. The Lower Extremity Functional Scale had high responsiveness and completion rates. Using this outcome measure, 256 participants would be required in a full-scale randomized controlled trial.

5 Year Outcomes and Survivorship of the Triathlon Total Knee Replacement: a Cohort Study.

The aim of this study was to determine outcomes and survivorship of the Triathlon knee replacement up to 5 years post-operation. A cohort of 266 patients receiving a Triathlon knee replacement were assessed before surgery and at 3 months, 1 year, 2 years, 3 years and 5 years post-operation. Assessments included patient-reported outcome measures, American Knee Society Score, complications and survivorship. The largest improvements in pain, function, stiffness and knee-related quality of life occurred in the first 3 months post-operation. Further smaller improvements were reported between 3 and 12 months post-operation, and then a plateauing of outcomes was observed up to 5 years. A high percentage of patients (86%) were satisfied with their outcome at 5 years. Survivorship with revision as the endpoint was 96.6% (95% CI 93.2-98.1%) at 5 years post-operation. In conclusion, this study observed good mid-term patient outcomes and survivorship of the Triathlon knee replacement.

Fast Click Rate Electrocochleography and Auditory Brainstem Response in Normal-Hearing Adults Using Continuous Loop Averaging Deconvolution.

OBJECTIVES: Using the continuous loop averaging deconvolution (CLAD) technique for conventional electrocochleography (ECochG) and auditory brainstem response (ABR) recordings, the effects of testing at high stimulus rates may have the potential to diagnose disorders of the inner ear and auditory nerve. First, a body of normative data using the CLAD technique must be established. DESIGN: Extratympanic click ECochG and ABR to seven stimulus rates using CLAD were measured simultaneously from a tympanic membrane electrode and surface electrodes on the forehead and mastoid of 42 healthy individuals. RESULTS: Results showed that the compound action potential (AP) of the ECochG and waves I, III, and V of the ABR decreased in amplitude and increased in latency as stimulus rate was increased from standard 7.1 clicks/s up to 507.81 clicks/s, with sharp reduction in AP amplitude at 97.66 clicks/s and reaching asymptote at 292.97 clicks/s. The summating potential (SP) of the ECochG, however, stayed relatively stable, resulting in increased SP/AP ratios with increasing rate. The SP/AP amplitude ratio showed more stability than AP amplitude findings, thus it is recommended for use in evaluation of cochlear and neural response. CONCLUSIONS: Results of both amplitude and latency data from this normative neural adaptation function of the auditory pathway serves as guide for improving diagnostic utility of both ECochG and ABR using CLAD as a reliable technique in distinguishing inner ear and auditory nerve disorders.

Effectiveness and cost-effectiveness of outpatient physiotherapy after knee replacement for osteoarthritis: study protocol for a randomised controlled trial.

BACKGROUND: Primary total knee replacement is a common operation that is performed to provide pain relief and restore functional ability. Inpatient physiotherapy is routinely provided after surgery to enhance recovery prior to hospital discharge. However, international variation exists in the provision of outpatient physiotherapy after hospital discharge. While evidence indicates that outpatient physiotherapy can improve short-term function, the longer term benefits are unknown. The aim of this randomised controlled trial is to evaluate the long-term clinical effectiveness and cost-effectiveness of a 6-week group-based outpatient physiotherapy intervention following knee replacement. METHODS/DESIGN: Two hundred and fifty-six patients waiting for knee replacement because of osteoarthritis will be recruited from two orthopaedic centres. Participants randomised to the usual-care group (n = 128) will be given a booklet about exercise and referred for physiotherapy if deemed appropriate by the clinical care team. The intervention group (n = 128) will receive the same usual care and additionally be invited to attend a group-based outpatient physiotherapy class starting 6 weeks after surgery. The 1-hour class will be run on a weekly basis over 6 weeks and will involve task-orientated and individualised exercises. The primary outcome will be the Lower Extremity Functional Scale at 12 months post-operative. Secondary outcomes include: quality of life, knee pain and function, depression, anxiety and satisfaction. Data collection will be by questionnaire prior to surgery and 3, 6 and 12 months after surgery and will include a resource-use questionnaire to enable a trial-based economic evaluation. Trial participation and satisfaction with the classes will be evaluated through structured telephone interviews. The primary statistical and economic analyses will be conducted on an intention-to-treat basis with and without imputation of missing data. The primary economic result will estimate the incremental cost per quality-adjusted life year gained from this intervention from a National Health Services (NHS) and personal social services perspective. DISCUSSION: This research aims to benefit patients and the NHS by providing evidence on the long-term effectiveness and cost-effectiveness of outpatient physiotherapy after knee replacement. If the intervention is found to be effective and cost-effective, implementation into clinical practice could lead to improvement in patients' outcomes and improved health care resource efficiency. TRIAL REGISTRATION: ISRCTN32087234 , registered on 11 February 2015.

The colour of pain: can patients use colour to describe osteoarthritis pain?

OBJECTIVE: The aim of the present study was to explore patients' views on the acceptability and feasibility of using colour to describe osteoarthritis (OA) pain, and whether colour could be used to communicate pain to healthcare professionals. METHODS: Six group interviews were conducted with 17 patients with knee OA. Discussion topics included first impressions about using colour to describe pain, whether participants could associate their pain with colour, how colours related to changes to intensity and different pain qualities, and whether they could envisage using colour to describe pain to healthcare professionals. RESULTS: The group interviews indicated that, although the idea of using colour was generally acceptable, it did not suit all participants as a way of describing their pain. The majority of participants chose red to describe high-intensity pain; the reasons given were because red symbolized inflammation, fire, anger and the stop signal in a traffic light system. Colours used to describe the absence of pain were chosen because of their association with positive emotional feelings, such as purity, calmness and happiness. A range of colours was chosen to represent changes in pain intensity. Aching pain was consistently identified as being associated with colours such as grey or black, whereas sharp pain was described using a wider selection of colours. The majority of participants thought that they would be able to use colour to describe their pain to healthcare professionals, although issues around the interpretability and standardization of colour were raised. CONCLUSIONS: For some patients, using colour to describe their pain experience may be a useful tool to improve doctor-patient communication.