Patient-directed self-management of pain (PaDSMaP) compared to treatment as usual following total knee replacement; a randomised controlled trial.

BACKGROUND: Self-administration of medicines by patients whilst in hospital is being increasingly promoted despite little evidence to show the risks and benefits. Pain control after total knee replacement (TKR) is known to be poor. The aim of the study was to determine if patients operated on with a TKR who self-medicate their oral analgesics in the immediate post-operative period have better pain control than those who receive their pain control by nurse-led drug rounds (Treatment as Usual (TAU)). METHODS: A prospective, parallel design, open-label, randomised controlled trial comparing pain control in patient-directed self-management of pain (PaDSMaP) with nurse control of oral analgesia (TAU) after a TKR. Between July 2011 and March 2013, 144 self-medicating adults were recruited at a secondary care teaching hospital in the UK. TAU patients (n = 71) were given medications by a nurse after their TKR. PaDSMaP patients (n = 73) took oral medications for analgesia and co-morbidities after two 20 min training sessions reinforced with four booklets. Primary outcome was pain (100 mm visual analogue scale (VAS)) at 3 days following TKR surgery or at discharge (whichever came soonest). Seven patients did not undergo surgery for reasons unrelated to the study and were excluded from the intention-to-treat (ITT) analysis. RESULTS: ITT analysis did not detect any significant differences between the two groups' pain scores. A per protocol (but underpowered) analysis of the 60% of patients able to self-medicate found reduced pain compared to the TAU group at day 3/discharge, (VAS -9.9 mm, 95% CI -18.7, - 1.1). One patient in the self-medicating group over-medicated but suffered no harm. CONCLUSION: Self-medicating patients did not have better (lower) pain scores compared to the nurse-managed patients following TKR. This cohort of patients were elderly with multiple co-morbidities and may not be the ideal target group for self-medication. TRIAL REGISTRATION: ISRCTN10868989 . Registered 22 March 2012, retrospectively registered.

Does pre-operative psychological distress affect patient satisfaction after primary total hip arthroplasty?

BACKGROUND: There are concerns that pre-operative psychological distress might be associated with reduced patient satisfaction after total hip replacement (THR). METHODS: We investigated this in a multi-centre prospective study between January 1999 and January 2002. We dichotomised the patients into the mentally distressed (MHS ≤ 56) and the not mentally distressed (MHS > 56) groups based on their pre-operative Mental Health Score (MHS) of SF36. RESULTS: 448 patients (340 not distressed and 108 distressed) completed the patient satisfaction survey. Patient satisfaction rate at five year was 96.66% (415/448). There was no difference in patient satisfaction or willingness to have the surgery between the two groups. None of pre-operative variables predicted five year patient satisfaction in logistic regression. CONCLUSIONS: Patient satisfaction after surgery may not be adversely affected by pre-operative psychological distress.

Accuracy of clinical diagnosis in patients undergoing knee arthroscopy.

A retrospective analysis of patients who underwent knee arthroscopy was undertaken to determine the accuracy of clinical diagnosis when compared with arthroscopic findings, and to see whether any specific pathologies were difficult to diagnose. The preoperative diagnosis was compared with the operative findings and the accuracy, sensitivity and specificity of the clinical diagnosis calculated. Six hundred ninety-eight patients were included. The overall accuracy, sensitivity and specificity of clinical diagnosis was 99%, 70% and 99%, respectively. Ninety percent of patients underwent a beneficial procedure, while 10% had a normal knee diagnosed at operation. Medial meniscal tear was the hardest pathology to diagnose with accuracy, sensitivity and specificity rates of 82%, 92% and 79%, respectively. Clinical examination remains an accurate method of assessing whether patients would benefit from an arthroscopy, although the correct diagnosis may not be determined preoperatively, particularly if pain was located in the medial tibio-femoral joint.

Cruciate ligament assessment in MRI scans: a pilot study of a static drawer technique.

Ten subjects with cruciate ligament rupture (five ACL and five PCL), and four normal subjects underwent magnetic resonance imaging (MRI) with a novel splint that stresses the knee. The splint acted as a fulcrum to translate the tibia in an anterior and posterior direction, depending on application. The MRI images showed that translation of the tibial plateaux occurred but not in a simple manner. The resultant images did not show marked anterior tibial translation in the ACL ruptured knee with an anterior drawer, nor posterior tibial translation for the PCL injured knee in posterior drawer. The medial plateau tended to move posteriorly in anterior drawer in the normal knees. The secondary MRI findings of ACL injury and associated meniscal injuries were enhanced. A further study with 50 subjects in each group, and arthroscopic confirmation of the findings, would be required to confirm these results.

The role of chondrocyte senescence in osteoarthritis.

Replicative senescence occurs when normal somatic cells stop dividing. Senescent cells remain viable, but show alterations in phenotype, e.g. altered expression of matrix metalloproteinases (MMPs); these enzymes are known to be involved in cartilage destruction. It is assumed that cells deplete their replicative potential during aging, and age is a major risk factor for osteoarthritis (OA). Therefore, we hypothesized that chondrocytes in aging or diseased cartilage become senescent with associated phenotypic changes contributing to development or progression of OA. Articular cartilage was obtained from OA patients undergoing arthroplasty, with 'normal' cartilage from trauma surgery for hip fracture. Senescent cells were identified using the senescence-associated beta-galactosidase (SA-beta-gal) marker. Telomere length was assessed using Southern blot. MMP expression was measured at the mRNA level using Taqman RT-PCR. No SA-beta-gal staining was observed in control cartilage regardless of patient age. In contrast, SA-beta-gal staining was observed in damaged OA cartilage adjacent to the lesion. Cultured chondrocytes isolated from sites near a lesion contained a greater percentage of SA-beta-gal positive cells than cultures isolated from distal sites or normal cartilage. Mean telomere length was shorter in cells near the lesion compared to distal sites in the same joint; thus the former population has undergone cell division. The expression of collagenases MMP-1, -8 and -13 and tissue inhibitor of metalloproteinases (TIMP)-1 was altered in OA cartilage, but no difference was detected between lesion and distal sites in the same joint (i.e. no correlation was found between senescent cells and proteinase/ inhibitor expression).

Long stem cemented revision arthroplasty for aseptic loosening in elderly patients produces good results, despite significant bone loss.

We assessed the results of long cemented stems in patients over 65 undergoing a first time revision hip arthroplasty for aseptic loosening. 103 patients were followed up for a minimum of five years after revision surgery; 45% had EndoKlinik C grade preoperative bone loss. At final follow-up 31 patients had died, all but one with the prosthesis in situ. There were 71 revisions alive, one had been revised for a peri-prosthetic fracture. Of the 45 that had radiographs at a minimum of five years, three stems were probably or definitely loose according to the Harris classification. There was 92% patient satisfaction and a mean Oxford Hip Score (OHS) of 25/60 in the 59 patients that had not been revised and had full clinical follow-up. Long-stem cemented revisions for aseptic loosening in elderly patients allow immediate postoperative weight bearing and have good radiological and clinical outcomes.

Patient directed self management of pain (PaDSMaP) compared to treatment as usual following total knee replacement: study protocol for a randomized controlled trial.

BACKGROUND: In 2009, 665 patients underwent total knee replacements (TKRs) at the Norfolk and Norwich University Hospitals NHS Foundation Trust (NNUH), representing nearly 1% of the national total. Pain control following the operation can be poor, and this can cause poor mobilization and potential long-term adverse events. Although high levels of pain are not associated with patient dissatisfaction, brief periods of pain may lead to neuronal remodeling and sensitization. Patient controlled oral analgesia (PCOA) may improve pain relief; however, the evidence to date has been inconclusive. Patient directed self management of pain (PaDSMaP) is a single center randomized controlled trial, which aims to establish if patient self-medication improves, or is equivalent to, treatment as usual and to create an educational package to allow implementation elsewhere. METHODS/DESIGN: Patients eligible for a TKR will be recruited and randomized in the outpatient clinic. All patients will undergo their operations according to normal clinical practice but will be randomized into two groups. Once oral medication has commenced, one group will have pain relief administered by nursing staff in the usual way (treatment as usual; TAU), whilst the second group will self manage their pain medication (patient directed self management of pain; PaDSMaP). Those recruited for self-medication will undergo a training program to teach the use of oral analgesics according to the World Health Organization (WHO) pain cascade and how to complete the study documentation. The primary endpoint of the trial is the visual analogue scale (VAS) pain score at 3 days or discharge, whichever is sooner. The follow-up time is 6 weeks with a planned trial period of 3 years. The secondary objectives are satisfaction with the management of patient pain post-operatively whilst an inpatient after primary TKR; overall pain levels and pain on mobilization; satisfaction with pain management information provided; global outcomes, such as quality of life (QOL) and activities of daily living (ADLs); time to mobilization and whether time to mobilization is associated with frequency of adverse events, improvements in QOL, ADLs and pain at 6 weeks after the operation; incidence of adverse events; quantity and type of pain medications used whilst an inpatient; the acceptability of PaDSMaP and/or TAU protocols for patients and the healthcare professionals involved in their care; to investigate the health-related costs associated with a PaDSMaP system; and to estimate the cost-effectiveness of PaDSMaP compared to TAU. TRIAL REGISTRATION: Current Controlled Trials ISRCTN: 10868989.

Pre-operative psychological distress does not adversely affect functional or mental health gain after primary total hip arthroplasty.

Preoperative psychological distress has been reported to predict poor outcome and patient dissatisfaction after total hip arthroplasty (THA). The purpose of this study was to investigate if pre-operative psychological distress was associated with adverse functional outcome after primary THR. We analysed the database of a prospective multi-centre study undertaken between January 1999 and January 2002. We recorded the Oxford Hip Score (OHS) and SF36 score preoperatively and up to five years after surgery for 1055 patients. We dichotomised the patients into the mentally distressed (Mental Health Scale score - MHS =56) and the not mentally distressed (MHS >56) groups based on their pre-operative MHS of the SF36. 762 (72.22%). Patients (595 not distressed and 167 distressed) were followed up at 5 years. Both pre and post-operative OHS and SF-36 scores were significantly worse in the distressed group (both p<0.001). However, both groups experienced statistically significant improvement in OHS and MHS, which was maximal at 1 year after surgery and was maintained over the follow up (p=0.00). There was a substantial improvement in mental distress in patients who reported mental distress prior to surgery. The results suggest that pre-operative psychological distress did not adversely compromise functional outcome gain after THA. Despite having worse absolute values both pre and post operatively, patients with mental distress did not have any less functional gain from THA as measured by improvement in OHS.

Community-based orthopaedic follow-up. Is it what doctors and patients want?

INTRODUCTION: The objective of this study was to investigate how patients, general practitioners (GPs) and orthopaedic trainees, feel about the proposed governmental changes to reduce orthopaedic out-patient clinics by having GPs and specialist nurses follow-up postoperative orthopaedic patients in the community. SUBJECTS AND METHODS: The design was a cross-sectional questionnaire study including a teaching hospital and general practitioners in the Norfolk primary care trust. Participants were 73 orthopaedic postoperative patients who attended out-patients over a 1-week period in July 2007 who all responded. Of 250 GPs, 239 responded. Of 38 orthopaedic trainees at the level of senior house officer (post MRCS) and specialist registrar (Eastern Deanery Rotation and Pott Rotation), 30 responded RESULTS: Of the 73 patients, 56 (77%) felt the surgeon was best suited to manage them postoperatively. Of these, 47 felt that it was very important that the surgical team saw them postoperatively. Also, 53 felt that their GP did not have sufficient knowledge and experience to deal with their current orthopaedic problem adequately. Only 12 GPs of 239 (5%) felt very confident assessing postoperative patients. Inadequate resources available to diagnose and treat postoperative complications was noted by 74% as the reason for not performing follow-up in primary care, and only 18% felt they should follow-up postoperative patients. All trainees felt that following up their own postoperative patients was important to their training. CONCLUSIONS: Most patients, GPs, and orthopaedic trainees had serious doubts about the proposed governmental changes to reduce orthopaedic out-patient clinics by having GPs and specialist nurses follow-up postoperative orthopaedic patients in the community.

Degradome expression profiling in human articular cartilage.

INTRODUCTION: The molecular mechanisms underlying cartilage destruction in osteoarthritis are poorly understood. Proteolysis is a key feature in the turnover and degradation of cartilage extracellular matrix where the focus of research has been on the metzincin family of metalloproteinases. However, there is strong evidence to indicate important roles for other catalytic classes of proteases, with both extracellular and intracellular activities. The aim of this study was to profile the expression of the majority of protease genes in all catalytic classes in normal human cartilage and that from patients with osteoarthritis (OA) using a quantitative method. METHODS: Human cartilage was obtained from femoral heads at joint replacement for either osteoarthritis or following fracture to the neck of femur (NOF). Total RNA was purified, and expression of genes assayed using Taqman low-density array quantitative RT-PCR. RESULTS: A total of 538 protease genes were profiled, of which 431 were expressed in cartilage. A total of 179 genes were differentially expressed in OA versus NOF cartilage: eight aspartic proteases, 44 cysteine proteases, 76 metalloproteases, 46 serine proteases and five threonine proteases. Wilcoxon ranking as well as the LogitBoost-NR machine learning approach were used to assign significance to each gene, with the most highly ranked genes broadly similar using each method. CONCLUSIONS: This study is the most complete quantitative analysis of protease gene expression in cartilage to date. The data help give direction to future research on the specific function(s) of individual proteases or protease families in cartilage and may help to refine anti-proteolytic strategies in OA.

Expression profiling of metalloproteinases and their inhibitors in synovium and cartilage.

Cartilage destruction in osteoarthritis (OA) is thought to be mediated by two main enzyme families; the matrix metalloproteinases (MMPs) are responsible for cartilage collagen breakdown, whereas enzymes from the 'a disintegrin and metalloproteinase domain with thrombospondin motifs' (ADAMTS) family mediate cartilage aggrecan loss. Tissue inhibitors of metalloproteinases (TIMPs) regulate the activity of these enzymes. Although cartilage destruction in OA might be driven by the chondrocyte, low-grade synovitis is reported in patients with all grades of this disease. Our earlier work profiling these gene families in cartilage identified a number of genes that are regulated in OA, which are hence implicated in the disease process. Because the synovium might contribute to cartilage-matrix destruction in OA, we have extended the screening in the current study. We have profiled MMP, ADAMTS and TIMP genes in both cartilage and synovium from patients with either OA of the hip or a fracture to the neck of femur (NOF), giving a more complete picture of proteolysis in this disease. The four most significantly upregulated genes (P < 0.0001) in OA synovium compared to the fractured NOF are MMP28, ADAMTS16, ADAMTS17 and TIMP2. For MMP9, MMP10, MMP12, MMP17, MMP23, MMP28, ADAMTS4, and ADAMTS9, there is a significant correlation between expression levels in the synovium and cartilage, suggesting similar mechanisms of regulation. Additionally, we have shown that in cartilage the median level of steady-state mRNA for MMP13 is approximately 20-fold higher than MMP28 and approximately 1,500-fold higher than ADAMTS16, with expression of this latter gene approximately 150-fold higher in synovium than cartilage. This study is the most comprehensive analysis of the metzincin family of proteinases in the joint to date and has identified several proteinase genes not previously reported to be expressed or regulated in synovium.

Long-term clinical, radiological and histopathological follow-up of a well-fixed Mckee-Farrar metal-on-metal total hip arthroplasty.

Metal-on-metal is one potential bearing option for total hip arthroplasty (THA). Proponents of the bearing have suggested that if the tribology is optimal, volumetric wear may occur at levels at least one order of magnitude lower than metal-on-polyethylene bearings. We present a unique postmortem case of a well fixed, metal-on-metal, McKee-Farrar total hip arthroplasty implanted 30 years previously that was clinically asymptomatic in life. Clinical and radiological examination is supplemented by tribological examination of the bearing and histopathological examination of the cement-bone interface.

Expression profiling of metalloproteinases and their inhibitors in cartilage.

OBJECTIVE: To profile the expression of all known members of the matrix metalloproteinase (MMP), ADAMTS, and tissue inhibitor of metalloproteinases (TIMP) gene families in normal cartilage and cartilage from patients with osteoarthritis (OA). METHODS: Human cartilage was obtained from femoral heads at joint replacement for OA or following fracture to the femoral neck. Total RNA was purified, and gene expression was assayed using quantitative real-time polymerase chain reaction. RESULTS: Several members of the above gene families were regulated in OA. Genes that showed increased expression in OA were MMP13, MMP28, and ADAMTS16 (all at P < 0.001), MMP9, MMP16, ADAMTS2, and ADAMTS14 (all at P < 0.01), and MMP2, TIMP3, and ADAMTS12 (all at P < 0.05). Genes with decreased expression in OA were MMP1, MMP3, and ADAMTS1 (all at P < 0.001), MMP10, TIMP1, and ADAMTS9 (all at P < 0.01), and TIMP4, ADAMTS5, and ADAMTS15 (all at P < 0.05). Correlation analysis revealed that groups of genes across the gene families were coexpressed in cartilage. CONCLUSION: This is the first comprehensive expression profile of all known MMP, ADAMTS, and TIMP genes in cartilage. Elucidation of patterns of expression provides a foundation with which to understand mechanisms of gene regulation in OA and potentially to refine the specificity of antiproteolytic therapies.