Relative and absolute test-retest reliabilities of biomechanical risk factors for knee osteoarthritis progression: benchmarks for meaningful change.

OBJECTIVE: Biomechanical factors are important treatment targets in knee osteoarthritis. The knee adduction (KAM) and flexion (KFM) moments, quadriceps strength and power, load frequency, and body mass index (BMI) all have the potential to affect knee articular cartilage integrity by modulating forces across the joint. To identify clinically meaningful change, however, these measurements must be reliable and sensitive to change. This study estimated relative and absolute test-retest reliabilities over long periods of biomechanical risk factors for knee osteoarthritis progression. METHOD: Data from a longitudinal, observational study were analyzed for knee osteoarthritis patients with data at baseline, 6-month and 24-month follow-ups. Gait kinematics and kinetics, quadriceps strength and power, daily load frequency and BMI were collected. Relative and absolute test-retest reliabilities of these measures were estimated using intraclass correlation coefficients (ICCs) and standard errors of measurement (SEMs), respectively. Minimal detectable change at the 95% confidence level (MDC95) was also calculated. RESULTS: Data from 46 participants [36 women; age 61.0 (6.6) years] were included. Good-to-excellent relative reliabilities (ICC ≥ 0.80) indicated that KAM peak and impulse, quadriceps strength and power, and BMI had a strong ability to discriminate amongst participants. Absolute reliabilities were high for quadriceps strength and BMI, which demonstrated reasonable within-participant variability (SEMs ≤ 11% of the mean). The MDC95 values supported use of clinical interventions effective in reducing BMI and KAM, and increasing quadriceps strength. CONCLUSION: These data are useful in interpreting findings from interventional or longitudinal investigations by determining whether observed changes are beyond measurement error and interpretable as true change.

Reliability and measurement error of the Osteoarthritis Research Society International (OARSI) recommended performance-based tests of physical function in people with hip and knee osteoarthritis.

OBJECTIVE: To estimate the reliability and measurement error of performance-based tests of physical function recommended by the Osteoarthritis Research Society International (OARSI) in people with hip and/or knee osteoarthritis (OA). DESIGN: Prospective repeated measures between independent raters within a session and within-rater over a week interval. Relative reliability was estimated for 51 people with hip and/or knee OA (mean age 64.5 years, standard deviation (SD) 6.21 years; 47% females; 36 (70%) primary knee OA) on the 30s Chair Stand Test (30sCST), 40m Fast-Paced Walk Test (40mFPWT), 11-Stair Climb Test (11-step SCT), Timed Up and Go (TUG), Six-Minute Walk Test (6MWT), 10m Fast-Paced Walk Test (10mFPWT) and 20s Stair Climb Test (20sSCT) using intra-class correlation coefficients (ICC). Absolute reliability was calculated using standard error of measurement (SEM) and minimal detectable change (MDC). RESULTS: Measurement error was acceptable (SEM < 10%) for all tests. Between-rater reliability was: optimal (ICC > 0.9, lower 1-sided 95% CI > 0.7) for the 40mFPWT, 6MWT and 10mFPWT; sufficient (ICC >0.8, lower 1-sided 95% CI > 0.7) for 30sCST, 20sSCT; unacceptable (lower 1-side 95% CI < 0.7) for 11-step SCT and TUG. Within-rater reliability was optimal for 40mFPWT, and 6MWT; sufficient for 30sCST and 10mFPWT and unacceptable for 11-step SCT, TUG and 20sSCT. CONCLUSIONS: The 30sCST, 40mFPWT, 6MWT and 10mFPWT, demonstrated, at minimum, acceptable levels of both between and within-rater reliability and measurement error. All tests demonstrated sufficiently small measurement error indicating they are adequate for measuring change over time in individuals with knee/hip OA.

The incident tibiofemoral osteoarthritis with rapid progression phenotype: development and validation of a prognostic prediction rule.

OBJECTIVES: No clinical prediction rules were found for estimating the likelihood of developing incident radiographic tibiofemoral osteoarthritis (OA) with rapid progression. Such a tool would enhance prognostic capability for clinicians and researchers. DESIGN: We used two longitudinal datasets to independently derive (Multicenter Osteoarthritis Study) and validate (Osteoarthritis Initiative) a prognostic clinical prediction rule for estimating the probability of incident rapidly progressing radiographic knee OA in the following 4-5 years. Eligible subjects had at least one knee with a Kellgren and Lawrence (K&L) graded tibiofemoral joint of 0 or 1. Several potential risk factors were examined including obesity, age, knee alignment, frequent knee symptoms, contralateral knee OA and knee injury history. Multiple logistic regression was used to identify significant predictors and area under the receiver operating characteristic curve (AUC) was used to assess discrimination. RESULTS: A total of 1690 subjects participated in the derivation and 2422 subjects participated in the validation of the clinical prediction rule. The multivariable model displayed good discrimination with AUC of 0.79 in the derivation dataset and 0.81 in the validation dataset. CONCLUSIONS: Persons with contralateral knee OA, a baseline index knee OA grade of 1, higher body mass index (BMI) and higher baseline Western Ontario and McMaster Universities arthritis index total scores were more likely to develop K&L grade of 3 or 4 within 5 years. Frequent knee symptoms at baseline were not a significant predictor. The prediction rule and nomogram can assist clinicians in estimating the probability of rapidly progressing radiographic knee OA and the nomogram can assist researchers conducting epidemiologic studies and clinical trials.

Pregabalin reduces postoperative opioid consumption and pain for 1 week after hospital discharge, but does not affect function at 6 weeks or 3 months after total hip arthroplasty.

BACKGROUND: This study examined whether a perioperative regimen of pregabalin added to celecoxib improved pain scores and functional outcomes postdischarge up to 3 months after total hip arthroplasty (primary outcome) and acute postoperative pain and adverse effects (secondary outcomes). METHODS: One hundred and eighty-four patients were enrolled in a randomized, double-blind, placebo-controlled study. Two hours before receiving a spinal anaesthetic and undergoing surgery, patients received celecoxib 400 mg p.o. and were randomly assigned to receive either pregabalin 150 mg p.o. or placebo p.o. After surgery, patients received pregabalin 75 mg or placebo twice daily in hospital and for 7 days after discharge. Patients also received celecoxib 200 mg every 12 h for 72 h and morphine i.v. patient-controlled analgesia for 24 h. Pain and function were assessed at baseline, 6 weeks, and 3 months after surgery. RESULTS: There was no difference between groups in physical function or incidence and intensity of chronic pain 3 months after total hip arthroplasty. The pregabalin group used less morphine [mean (sd): 39.85 (28.1) mg] than the placebo group [54.01 (31.2) mg] in the first 24 h after surgery (P<0.01). Pain scores were significantly lower in the pregabalin group vs the placebo group on days 1-7 after hospital discharge, and the pregabalin group required less adjunctive opioid medication (Percocet) 1 week after hospital discharge (P<0.05). CONCLUSIONS: Perioperative administration of pregabalin did not improve pain or physical function at 6 weeks or 3 months after total hip arthroplasty. Perioperative administration of pregabalin decreased opioid consumption in hospital and reduced daily pain scores and adjunct opioid consumption for 1 week after discharge.

Perioperative gabapentin reduces 24 h opioid consumption and improves in-hospital rehabilitation but not post-discharge outcomes after total knee arthroplasty with peripheral nerve block.

BACKGROUND: This study was designed to determine whether a 4 day perioperative regimen of gabapentin added to celecoxib improves in-hospital rehabilitation and physical function on postoperative day 4 and 6 weeks and 3 months after total knee arthroplasty (TKA). METHODS: After Research Ethics Board approval and informed consent, 212 patients were enrolled in a randomized, double-blinded, placebo-controlled study. Two hours before surgery, patients received celecoxib 400 mg p.o. and were randomly assigned to receive either gabapentin 600 mg or placebo p.o. Two hours later, patients received femoral, sciatic nerve blocks, and spinal anaesthesia. After operation, patients received gabapentin 200 mg or placebo three times per day (TID) for 4 days. All patients also received celecoxib 200 mg q12 h for 72 h and i.v. patient-controlled analgesia for 24 h. Pain and function were assessed at baseline, during hospitalization, on postoperative day 4 (POD4), and 6 weeks and 3 months after surgery. RESULTS: The gabapentin group used less morphine in the first 24 h after surgery [G=38.3 (29.5 mg), P=48.2 (29.4 mg)] (P<0.0125) and had increased knee range of motion compared with the placebo group in-hospital (P<0.05). There were no differences between groups in favour of the gabapentin group for pain or physical function on POD 4 [95% confidence interval (CI): pain: -1.4, 0.5; function: -6.3, 2.0], 6 weeks (95% CI: pain: 0.1, 1.9; function: -0.2, 6.5) or 3 months (95% CI: pain: -0.2, 1.7; function: -2.2, 4.3) after TKA. CONCLUSIONS: In the context of celecoxib, spinal anaesthesia, femoral and sciatic nerve blocks, a dose of gabapentin 600 mg before operation followed by 4 days of gabapentin 200 mg TID decreased postoperative analgesic requirements and improved knee range of motion after TKA. Gabapentin provided no improvement in pain or physical function on POD4 and 6 weeks or 3 months after surgery.

OARSI recommended performance-based tests to assess physical function in people diagnosed with hip or knee osteoarthritis.

OBJECTIVES: To recommend a consensus-derived set of performance-based tests of physical function for use in people diagnosed with hip or knee osteoarthritis (OA) or following joint replacement. METHODS: An international, multidisciplinary expert advisory group was established to guide the study. Potential tests for consideration in the recommended set were identified via a survey of selected experts and through a systematic review of the measurement properties for performance-based tests. A multi-phase, consensus-based approach was used to prioritize and select performance-based tests by applying decision analysis methodology (1000Minds software) via online decision surveys. The recommended tests were chosen based on available measurement-property evidence, feasibility of the tests, scoring methods and expert consensus. RESULTS: Consensus incorporated the opinions of 138 experienced clinicians and researchers from 16 countries. The five tests recommended by the advisory group and endorsed by Osteoarthritis Research Society International (OARSI) were the 30-s chair-stand test, 40 m fast-paced walk test, a stair-climb test, timed up-and-go test and 6-min walk test. The first three were recommended as the minimal core set of performance-based tests for hip or knee OA. CONCLUSION: The OARSI recommended set of performance-based tests of physical function represents the tests of typical activities relevant to individuals diagnosed with hip or knee OA and following joint replacements. These tests are complementary to patient-reported measures and are recommended as prospective outcome measures in future OA research and to assist decision-making in clinical practice. Further research should be directed to expanding the measurement-property evidence of the recommended tests.

Interpreting change scores for pain and functional status in low back pain: towards international consensus regarding minimal important change.

STUDY DESIGN: Literature review, expert panel, and a workshop during the "VIII International Forum on Primary Care Research on Low Back Pain" (Amsterdam, June 2006). OBJECTIVE: To develop practical guidance regarding the minimal important change (MIC) on frequently used measures of pain and functional status for low back pain. SUMMARY OF BACKGROUND DATA: Empirical studies have tried to determine meaningful changes for back pain, using different methodologies. This has led to confusion about what change is clinically important for commonly used back pain outcome measures. METHODS: This study covered the Visual Analogue Scale (0-100) and the Numerical Rating Scale (0-10) for pain and for function, the Roland Disability Questionnaire (0-24), the Oswestry Disability Index (0-100), and the Quebec Back Pain Disability Questionnaire (0-100). The literature was reviewed for empirical evidence. Additionally, experts and participants of the VIII International Forum on Primary Care Research on Low Back Pain were consulted to develop international consensus on clinical interpretation. RESULTS: There was wide variation in study design and the methods used to estimate MICs, and in values found for MIC, where MIC is the improvement in clinical status of an individual patient. However, after discussion among experts and workshop participants a reasonable consensus was achieved. Proposed MIC values are: 15 for the Visual Analogue Scale, 2 for the Numerical Rating Scale, 5 for the Roland Disability Questionnaire, 10 for the Oswestry Disability Index, and 20 for the QBDQ. When the baseline score is taken into account, a 30% improvement was considered a useful threshold for identifying clinically meaningful improvement on each of these measures. CONCLUSION: For a range of commonly used back pain outcome measures, a 30% change from baseline may be considered clinically meaningful improvement when comparing before and after measures for individual patients. It is hoped that these proposals facilitate the use of these measures in clinical practice and the comparability of future studies. The proposed MIC values are not the final answer but offer a common starting point for future research.

Measurement properties of the WOMAC LK 3.1 pain scale.

OBJECTIVE: The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) is applied extensively to patients with osteoarthritis of the hip or knee. Previous work has challenged the validity of its physical function scale however an extensive evaluation of its pain scale has not been reported. Our purpose was to estimate internal consistency, factorial validity, test-retest reliability, and the standard error of measurement (SEM) of the WOMAC LK 3.1 pain scale. METHOD: Four hundred and seventy-four patients with osteoarthritis of the hip or knee awaiting arthroplasty were administered the WOMAC. Estimates of internal consistency (coefficient alpha), factorial validity (confirmatory factor analysis), and the SEM based on internal consistency (SEM(IC)) were obtained. Test-retest reliability [Type 2,1 intraclass correlation coefficients (ICC)] and a corresponding SEM(TRT) were estimated on a subsample of 36 patients. RESULTS: Our estimates were: internal consistency alpha=0.84; SEM(IC)=1.48; Type 2,1 ICC=0.77; SEM(TRT)=1.69. Confirmatory factor analysis failed to support a single factor structure of the pain scale with uncorrelated error terms. Two comparable models provided excellent fit: (1) a model with correlated error terms between the walking and stairs items, and between night and sit items (chi2=0.18, P=0.98); (2) a two factor model with walking and stairs items loading on one factor, night and sit items loading on a second factor, and the standing item loading on both factors (chi2=0.18, P=0.98). CONCLUSION: Our examination of the factorial structure of the WOMAC pain scale failed to support a single factor and internal consistency analysis yielded a coefficient less than optimal for individual patient use. An alternate strategy to summing the five-item responses when considering individual patient application would be to interpret item responses separately or to sum only those items which display homogeneity.

Protocol of the COSMIN study: COnsensus-based Standards for the selection of health Measurement INstruments.

BACKGROUND: Choosing an adequate measurement instrument depends on the proposed use of the instrument, the concept to be measured, the measurement properties (e.g. internal consistency, reproducibility, content and construct validity, responsiveness, and interpretability), the requirements, the burden for subjects, and costs of the available instruments. As far as measurement properties are concerned, there are no sufficiently specific standards for the evaluation of measurement properties of instruments to measure health status, and also no explicit criteria for what constitutes good measurement properties. In this paper we describe the protocol for the COSMIN study, the objective of which is to develop a checklist that contains COnsensus-based Standards for the selection of health Measurement INstruments, including explicit criteria for satisfying these standards. We will focus on evaluative health related patient-reported outcomes (HR-PROs), i.e. patient-reported health measurement instruments used in a longitudinal design as an outcome measure, excluding health care related PROs, such as satisfaction with care or adherence. The COSMIN standards will be made available in the form of an easily applicable checklist. METHOD: An international Delphi study will be performed to reach consensus on which and how measurement properties should be assessed, and on criteria for good measurement properties. Two sources of input will be used for the Delphi study: (1) a systematic review of properties, standards and criteria of measurement properties found in systematic reviews of measurement instruments, and (2) an additional literature search of methodological articles presenting a comprehensive checklist of standards and criteria. The Delphi study will consist of four (written) Delphi rounds, with approximately 30 expert panel members with different backgrounds in clinical medicine, biostatistics, psychology, and epidemiology. The final checklist will subsequently be field-tested by assessing the inter-rater reproducibility of the checklist. DISCUSSION: Since the study will mainly be anonymous, problems that are commonly encountered in face-to-face group meetings, such as the dominance of certain persons in the communication process, will be avoided. By performing a Delphi study and involving many experts, the likelihood that the checklist will have sufficient credibility to be accepted and implemented will increase.

Analysis of a phosphorylcholine-based polymer coating on a coronary stent pre- and post-implantation.

There has been a move towards surface treatments for metallic coronary stents in an effort to improve their compatibility within the body and to provide a vehicle for the delivery of therapeutics. The Biodiv Ysio range of stents is characterised by a biocompatible coating comprised of a crosslinked phosphorylcholine (PC)-based polymer. In addition to a review of some of the data collected to support safety and efficacy of this device, this paper also describes a number of techniques that have been employed to both visualise and quantify the coating on the stent. Explantation of both coated and uncoated stents from porcine coronary arteries revealed that both coated and uncoated stents were >90% endothelialised after 5 days. Typical histological analysis of stented vessel sections after 4 and 12 weeks implantation showed the presence of cell types characteristic of the inflammatory response associated with the trauma caused by stent placement, with no evidence for any additional coating-related adverse inflammatory sequelae. Finally, it was demonstrated by AFM and SEM that both the thickness and force required to remove the coating were essentially unchanged after 6 months implantation. Thus, both the long-term stability and relative biological inertness of the coating has been confirmed in vivo, supporting its use as a vehicle for local drug delivery.

A novel phosphorylcholine-coated contact lens for extended wear use.

The preparation and characterisation of a new phosphorylcholine (PC)-coated silicone hydrogel contact lens for use in extended wear is described. The Michael-type addition of amines to acrylates forms the basis of the synthesis of a novel silicone-based macromer with hydrophilic functionality. It is demonstrated that this macromer can be combined with other silicone-based monomers, hydrophilic monomers and crosslinker to produce a contact lenses formulation. Examples of lenses with water contents of 33% and 46% are illustrated and their properties compared to other commercially available lenses. Materials with comparatively low modulus (<0.3 MPa) and adequate tear strength (>2-4MPa) with excellent elongation to break (>200%) can be obtained using this technology. In addition to the mechanical aspects. both the oxygen and solute permeabilities of the material can be controlled by the hydrophilic: hydrophobic monomer balance in the formulation. to obtain materials with attributes suitable for extended wear use. The PC coating is achieved by means of an in-mould coating (IMC) technique that produces a uniform and stable surface as determined by staining and XPS. The coating imparts both improved lens wettability (advancing contact angle of approximately 50 with virtually no hysteresis) and lower protein adsorption relative to the uncoated lens.

Use of SF-36 and SF-12 health status measures: a quantitative comparison for groups versus individual patients.

BACKGROUND: The extent to which SF-12 scores reflect SF-36 scores has not been well studied. OBJECTIVES: One purpose was to compare the sensitivity to change of the SF-36 Physical Function sub-score, and the Physical Component Summary Scores (PCS) of the SF-36 and SF-12 on patients with low back pain (LBP). A second purpose was to determine if the SF-12 could serve as a surrogate measure for the SF-36 when making decisions about individual patients. SUBJECTS: The sample consisted of 101 consecutive patients. MEASURES: SF-36 questionnaires were completed by patients at both initial and discharge examinations. SF-12 scores were calculated from the completed SF-36 questionnaires. Therapists' judgments of whether patients were judged to have returned to premorbid function served as the construct for meaningful clinical change. ANALYSIS: Receiver Operating Characteristic (ROC) curve analysis and repeated measures MANCOVA were used to assess sensitivity to change. Linear regression and 95% prediction bands described the extent to which SF-12 scores predict individual SF-36 scores. RESULTS: No significant differences were found between the ROC curve areas for the Physical Function sub-scale, the PCS-36 and PCS-12. No significant differences were found for the comparison of change scores between PF-36, PCS-36 and PCS-12 scores. CONCLUSION: The findings suggest that Physical Function sub-scores, SF-36 and SF-12 PCS scores are equally sensitive to change. SF-12 PCS scores do not adequately predict SF-36 PCS scores for individual patients. The PCS-12 should probably not be used to make judgments about the health status of individual patients with LBP.

Phosphorylcholine-based polymer coatings for stent drug delivery.

Phosphorylcholine-based polymers have been used commercially to improve the biocompatibility of coronary stents. In this study, one particular polymer is assessed for its suitability as a drug delivery vehicle. Membranes of the material are characterized in terms of water content and molecular weight cut-off, and the presence of hydrophilic and hydrophobic domains investigated by use of the hydrophobic probe pyrene. The in vitro loading and elution of a variety of drugs was assessed using stents coated with the polymer. The rate of a drug's release was shown not to be simply a function of its water solubility, but rather more closely related to the drug oil/water partition coefficient. This finding was explained in terms of the more hydrophobic drugs partitioning into, and interacting with, the hydrophobic domains of the polymer coating. The suitability of the coated stent as a drug delivery vehicle was assessed in vivo using a radiolabeled analog of one of the more rapidly eluting drugs, angiopeptin. Autoradiography showed that the drug was released locally to the wall of the stented artery, and could be detected up to 28 days after implantation.

Crosslinkable coatings from phosphorylcholine-based polymers.

2-Methacryloyloxyethyl phosphorylcholine (MPC) was synthesised and then used in the preparation of crosslinked polymer membranes with lauryl methacrylate, hydroxypropyl methacrylate and trimethoxysilylpropyl methacrylate (crosslinker) comonomers. Some physical aspects of the membrane properties were evaluated in order to establish the basis for the synthesis of a series of post-crosslinkable polymers. These materials were made by copolymerisation of the constituent monomers via a free radical method, and characterised using NMR, FT-IR, viscometry and elemental analysis. The optimum crosslink density and conditions required for curing coatings of these polymers were investigated using atomic force microscopy (AFM) and showed the inclusion of 5 mol% silyl crosslinking agent to be ideal. A nanoindentation technique was employed to determine if the coating developed elasticity upon crosslinking. The biological properties of the coatings were evaluated using a variety of protein adsorption assays and blood contacting experiments, and an enzyme immunoassay was developed to detect E. coli in order to assess the level of bacterial adhesion to these biomaterials. Polymers of this type were shown to be very useful as coating materials for improving the biocompatibility of, or reducing the levels of adherent bacteria to medical devices.

Development and initial validation of the back pain functional scale.

STUDY DESIGN: A prospective repeated-measures design was applied. OBJECTIVES: To examine the measurement properties of the Back Pain Functional Scale (BPFS) and the Roland-Morris Questionnaire (RMQ) and to formulate hypotheses and sample size estimates for a subsequent comparison study. SUMMARY OF BACKGROUND DATA: Although there are numerous functional status measures for patients with low back pain, most have been conceived of and validated with a group rather than an individual patient as the unit of interest. Also, little has been done to formally compare-this includes the generation of a priori hypotheses, followed by statistical hypotheses testing-the many competing measures. METHODS: Subjects were 77 patients with low back pain who were referred by physicians to 10 outpatient physical therapy clinics located in Canada and the United States. The questionnaires were administered at patients' initial visits, within 48 hours of the initial visit, and at 1-, 2-, and 3-week follow-up visits. Reliability, cross-sectional validity, and longitudinal validity (sensitivity to change) coefficients were calculated. RESULTS: Test-retest reliability estimates of 0.81 and 0. 88 were obtained for the RMQ and BPFS, respectively. The measures demonstrated similar levels of cross-sectional validity. Correlations of 0.56 and 0.65 were noted between a prognostic rating of change and the RMQ and BPFS, respectively. The RMQ demonstrated a ceiling effect. Approximately 180 patients are needed for a subsequent head-to-head comparison study of the measures. CONCLUSIONS: The BPFS appears to have sound measurement properties, and a formal head-to-head comparison study with the RMQ is warranted.