The aim of the current study was to evaluate the innervation of the acetabular labrum in the various zones and to understand its potential role in nociception and proprioception in hips with labral pathology.
A total of twenty hip labrums were tagged and excised intraoperatively from patients undergoing a total hip replacement. After preparation, the specimens were cut to a thickness of 10 μm and divided into four quadrants (zones) using a clock face pattern. Neurosensory structure distribution was then evaluated using Hematoxylin and Eosin (H and E), and immunoreactivity to S-100.
All specimens had abundant free nerve endings (FNEs). These were seen predominantly superficially and on the chondral side of the labrum. In addition, predominantly three different types of nerve end organs (NEOs) were identified in all twenty specimens. FNEs and NEOs were more frequently seen in the antero-superior and postero-superior zones. Four specimens had abundant vascularity and disorganised architecture of FNEs in the deeper zones of the antero-superior quadrant suggestive of a healed tear. Myofibroblasts were present in abundance in all the labral specimens and were distributed uniformly throughout all labral zones and depth.
The current study shows that the human acetabular labrum has abundant FNEs and NEOs. These are more abundant in the antero-superior and postero-superior zones. The labrum, by virtue of its neural innervation, can potentially mediate pain as well as proprioception of the hip joint, and be involved in neurosecretion that can influence connective tissue repair.
Labrum; Innervation; Femoro-acetabular impingement; Hip arthroscopy; Labral tear
Fractures of the humeral shaft are associated with a profound temporary (and in the elderly sometimes even permanent) impairment of independence and quality of life. These fractures can be treated operatively or non-operatively, but the optimal tailored treatment is an unresolved problem. As no high-quality comparative randomized or observational studies are available, a recent Cochrane review concluded there is no evidence of sufficient scientific quality available to inform the decision to operate or not. Since randomized controlled trials for this injury have shown feasibility issues, this study is designed to provide the best achievable evidence to answer this unresolved problem. The primary aim of this study is to evaluate functional recovery after operative versus non-operative treatment in adult patients who sustained a humeral shaft fracture. Secondary aims include the effect of treatment on pain, complications, generic health-related quality of life, time to resumption of activities of daily living and work, and cost-effectiveness. The main hypothesis is that operative treatment will result in faster recovery.
The design of the study will be a multicenter prospective observational study of 400 patients who have sustained a humeral shaft fracture, AO type 12A or 12B. Treatment decision (i.e., operative or non-operative) will be left to the discretion of the treating surgeon. Critical elements of treatment will be registered and outcome will be monitored at regular intervals over the subsequent 12 months. The primary outcome measure is the Disabilities of the Arm, Shoulder, and Hand score. Secondary outcome measures are the Constant score, pain level at both sides, range of motion of the elbow and shoulder joint at both sides, radiographic healing, rate of complications and (secondary) interventions, health-related quality of life (Short-Form 36 and EuroQol-5D), time to resumption of ADL/work, and cost-effectiveness. Data will be analyzed using univariate and multivariable analyses (including mixed effects regression analysis). The cost-effectiveness analysis will be performed from a societal perspective.
Successful completion of this trial will provide evidence on the effectiveness of operative versus non-operative treatment of patients with a humeral shaft fracture.
The trial is registered at the Netherlands Trial Register (NTR3617).
Currently, Posterior Short Segment Pedicle Screw Fixation is a popular procedure for treating unstable thoracolumbar/lumbar burst fracture. But progressive kyphosis and a high rate of hardware failure because of lack of the anterior column support remains a concern. The efficacy of different methods remains debatable and each technique has its advantages and disadvantages.
A consecutive series of 20 patients with isolated thoracolumbar/lumbar burst fractures were treated by posterior short segment pedicle screw fixation and transforaminal thoracolumbar/lumbar interbody fusion (TLIF) between January 2005 and December 2007. All patients were followed up for a minimum of 2 years. Demographic data, neurologic status, anterior vertebral body heights, segmental Cobb angle and treatment-related complications were evaluated.
The mean operative time was 167 minutes (range, 150–220). Blood loss was 450 ~ 1200 ml, an average of 820 ml. All patients recovered with solid fusion of the intervertebral bone graft, without main complications like misplacement of the pedicle screw, nerve or vessel lesion or hard ware failure. The post-operative radiographs demonstrated a good fracture reduction and it was well maintained until the bone graft fusion. Neurological recovery of one to three Frankel grade was seen in 14 patients with partial neurological deficit, three grades of improvement was seen in one patient, two grades of improvement was observed in 6 patients and one grade of improvement was found in 6 patients. All the 6 patients with no paraplegia on admission remained neurological intact, and in one patient with Frankel D on admission no improvement was observed.
Posterior short-segment pedicle fixation in conjunction with TLIF seems to be a feasible option in the management of selected thoracolumbar/lumbar burst fractures, thereby addressing all the three columns through a single approach with less trauma and good results.
Short segment fixation; Thoracic vertebrae; Lumbar vertebrae; Unstable burst fractures; Pedicle screw; TLIF
Evidence on the reliability of clinical tests used for the spinal screening of children and adolescents is currently lacking. The aim of this study was to determine the inter- and intra-rater reliability and measurement error of clinical tests commonly used when screening young spines.
Two experienced chiropractors independently assessed 111 adolescents aged 12–14 years who were recruited from a primary school in Denmark. A standardised examination protocol was used to test inter-rater reliability including tests for scoliosis, hypermobility, general mobility, inter-segmental mobility and end range pain in the spine. Seventy-five of the 111 subjects were re-examined after one to four hours to test intra-rater reliability. Percentage agreement and Cohen’s Kappa were calculated for binary variables, and interclass correlation (ICC) and Bland-Altman plots with Limits of Agreement (LoA) were calculated for continuous measures.
Inter-rater percentage agreement for binary data ranged from 59.5% to 100%. Kappa ranged from 0.06-1.00. Kappa ≥ 0.40 was seen for elbow, thumb, fifth finger and trunk/hip flexion hypermobility, pain response in inter-segmental mobility and end range pain in lumbar flexion and extension. For continuous data, ICCs ranged from 0.40-0.95. Only forward flexion as measured by finger-to-floor distance reached an acceptable ICC(≥ 0.75). Overall, results for intra-rater reliability were better than for inter-rater reliability but for both components, the LoA were quite wide compared with the range of assessments.
Some clinical tests showed good, and some tests poor, reliability when applied in a spinal screening of adolescents. The results could probably be improved by additional training and further test standardization. This is the first step in evaluating the value of these tests for the spinal screening of adolescents. Future research should determine the association between these tests and current and/or future neck and back pain.
Reliability; Measurement error; Scoliosis; Hypermobility; Intersegmental mobility; Spine; Adolescents; Mobility
Low-intensity pulsed ultrasound (LIPUS) regiment has been used to treat fractures with non-union and to promote bone union in general. The effect of LIPUS on articular cartilage metabolism has been characterized. Yet, the effect of LIPUS to repair articular cartilage injury remains unclear in vivo.
We designed a study to investigate the effect of LIPUS on articular cartilage repairing in a rabbit severe cartilage injury model. Eighteen rabbits were divided into three groups: Sham-operated group, operated group without-LIPUS-treatment, operated group with-LIPUS-treatment (a daily 20-minute treatment for 3 months). Full-thickness cartilage defects were surgically created on the right side distal femoral condyle without intending to penetrate into the subchondral bone, which mimicked severe chondral injury. MR images for experimental joints, morphology grading scale, and histopathological Mankin score were evaluated.
The preliminary results showed that the operated groups with-LIPUS-treatment and without-LIPUS-treatment had significantly higher Mankin score and morphological grading scale compared with the sham-operated group. However, there was no significant difference between the with-LIPUS-treatment and without-LIPUS-treatment groups. Cartilage defects filled with proliferative tissue were observed in the with-LIPUS-treatment group grossly and under MR images, however which presented less up-take under Alcian blue stain. Furthermore, no new deposition of type II collagen or proliferation of chondrocyte was observed over the cartilage defect after LIPUS treatment.
LIPUS has no significant therapeutic potential in treating severe articular cartilage injury in our animal study.
Low-intensity pulsed ultrasound; Cartilage; Injury
A previous genome-wide association study (GWAS) suggested a strong association between the single nucleotide polymorphism (SNP) rs10510181 in the proximity of the gene encoding a cell adhesion molecule with homology to L1CAM (CHL1) and adolescent idiopathic scoliosis (AIS) in Caucasians. To clarify the role of CHL1 in the etiopathogenesis of AIS, we performed a case-control replication study in a Han Chinese population.
Five hundred female AIS patients between 10 and 18 years of age, as well as 500 age- and sex-matched controls were included. This study was conducted as a 2-stage case-control analysis: initial screening for the association between AIS and SNPs in and around the CHL1 gene (186 cases and 169 controls) followed by a confirmation test (314 cases and 331 controls). rs10510181 and 4 SNPs (rs2055314, rs331894, rs2272522, and rs2272524) in the CHL1 gene were selected for genotyping.
Putative associations were shown between AIS and rs10510181, rs2055314, and rs2272522 in stage I. However, the associations were not confirmed in stage II. For rs10510181, the genotype frequencies were GG 28.8%, GA 46.2%, and AA 25.0% in AIS patients and GG 29.8%, GA 48.8%, and AA 21.4% in controls. No significant difference was found in genotype distribution between cases and controls (P = 0.39). Similarly, the genotype and allele distribution were comparable between case and control for rs2055314 and rs2272522.
There was no statistical association between polymorphisms of the CHL1 gene and idiopathic scoliosis in a Chinese population.
Adolescent idiopathic scoliosis; CHL1; Chinese; Polymorphism
Carpal tunnel syndrome (CTS) is the most common neuropathy of the upper limb and a significant contributor to hand functional impairment and disability. Effective treatment options include conservative and surgical interventions, however it is not possible at present to predict the outcome of treatment. The primary aim of this study is to identify which baseline clinical factors predict a good outcome from conservative treatment (by injection) or surgery in patients diagnosed with carpal tunnel syndrome. Secondary aims are to describe the clinical course and progression of CTS, and to describe and predict the UK cost of CTS to the individual, National Health Service (NHS) and society over a two year period.
In this prospective observational cohort study patients presenting with clinical signs and symptoms typical of CTS and in whom the diagnosis is confirmed by nerve conduction studies are invited to participate. Data on putative predictive factors are collected at baseline and follow-up through patient questionnaires and include standardised measures of symptom severity, hand function, psychological and physical health, comorbidity and quality of life. Resource use and cost over the 2 year period such as prescribed medications, NHS and private healthcare contacts are also collected through patient self-report at 6, 12, 18 and 24 months. The primary outcome used to classify treatment success or failures will be a 5-point global assessment of change. Secondary outcomes include changes in clinical symptoms, functioning, psychological health, quality of life and resource use. A multivariable model of factors which predict outcome and cost will be developed.
This prospective cohort study will provide important data on the clinical course and UK costs of CTS over a two-year period and begin to identify predictive factors for treatment success from conservative and surgical interventions.
Although many studies on reliability and reproducibility of measurement have been performed on coronal Cobb angle, few results about reliability and reproducibility are reported on sagittal alignment measurement including the pelvis. We usually use SurgimapSpine software to measure the Cobb angle in our studies; however, there are no reports till date on its reliability and reproducible measurements.
Sixty-eight standard standing posteroanterior whole-spine radiographs were reviewed. Three examiners carried out the measurements independently under the settings of manual measurement on X-ray radiographies and SurgimapSpine software on the computer. Parameters measured included pelvic incidence, sacral slope, pelvic tilt, Lumbar lordosis (LL), thoracic kyphosis, and coronal Cobb angle. SPSS 16.0 software was used for statistical analyses. The means, standard deviations, intraclass and interclass correlation coefficient (ICC), and 95% confidence intervals (CI) were calculated.
There was no notable difference between the two tools (P = 0.21) for the coronal Cobb angle. In the sagittal plane parameters, the ICC of intraobserver reliability for the manual measures varied from 0.65 (T2–T5 angle) to 0.95 (LL angle). Further, for SurgimapSpine tool, the ICC ranged from 0.75 to 0.98. No significant difference in intraobserver reliability was found between the two measurements (P > 0.05). As for the interobserver reliability, measurements with SurgimapSpine tool had better ICC (0.71 to 0.98 vs 0.59 to 0.96) and Pearson’s coefficient (0.76 to 0.99 vs 0.60 to 0.97). The reliability of SurgimapSpine measures was significantly higher in all parameters except for the coronal Cobb angle where the difference was not significant (P > 0.05).
Although the differences between the two methods are very small, the results of this study indicate that the SurgimapSpine measurement is an equivalent measuring tool to the traditional manual in coronal Cobb angle, but is advantageous in spino-pelvic measurement in T2-T5, PT, PI, SS, and LL.
SurgimapSpine software; Manual tool; Sagittal parameters measurement; Differences
Many patients with cervical disc disease require leave from work, due to long-lasting, complex symptoms, including chronic pain and reduced levels of physical and psychological function. Surgery on a few segmental levels might be expected to resolve disc-specific pain and reduce neurological deficits, but not the non-specific neck pain and the frequent illness. No study has investigated whether post-surgery physiotherapy might improve the outcome of surgery. The main purpose of this study was to evaluate whether a well-structured rehabilitation programme might add benefit to the customary post-surgical treatment for cervical disc disease, with respect to function, disability, work capability, and cost effectiveness.
This study was designed as a prospective, randomised, controlled, multi-centre study. An independent, blinded investigator will compare two alternatives of rehabilitation. We will include 200 patients of working age, with cervical disc disease confirmed by clinical findings and symptoms of cervical nerve root compression. After providing informed consent, study participants will be randomised to one of two alternative physiotherapy regimes; (A) customary treatment (information and advice on a specialist clinic); or (B) customary treatment plus active physiotherapy. Physiotherapy will follow a standardised, structured programme of neck-specific exercises combined with a behavioural approach. All patients will be evaluated both clinically and subjectively (with questionnaires) before surgery and at 6 weeks, 3 months, 6 months, 12 months, and 24 months after surgery. The main outcome variable will be neck-specific disability. Cost-effectiveness will also be calculated.
We anticipate that the results of this study will provide evidence to support physiotherapeutic rehabilitation applied after surgery for cervical radiculopathy due to cervical disc disease.
ClinicalTrials.gov identifier: NCT01547611
Intervertebral disc; Spine; Neck; Rehabilitation; Physical therapy
A high degree of meniscal body extrusion on knee magnetic resonance imaging has been shown to be strongly associated with development of knee osteoarthritis. However, very little is known about meniscal position in the asymptomatic knee and its natural history. Hence our objective was to study meniscal body position and its change over 4 years in asymptomatic adults.
Cohort study using data from the Osteoarthritis Initiative (OAI) involving four clinical sites in the United States (Baltimore, Maryland, Pawtucket, Rhode Island, Columbus, Ohio, and Pittsburgh, Pennsylvania). We studied both knees from 118 subjects (mean age 55 years, 61% women, mean body mass index 24.4) from the OAI “non-exposed” reference cohort free of knee pain, radiographic knee osteoarthritis and risk factors for knee osteoarthritis at baseline. We assessed mid-coronal intermediate-weighted 3-Tesla magnetic resonance images from baseline and the 2- and 4-year follow-up visit. One observer measured tibia plateau, meniscal body width and meniscal body extrusion in both compartments. We calculated meniscal overlap distance on the tibial plateau, % coverage, and extrusion index compared to tibia width. Potential trends in position over the 4-year period were evaluated using a linear mixed-effects regression model.
The mean (SD) values at baseline for medial meniscal body extrusion and overlap distance were 1.64 mm (0.92) and 10.1 mm (3.5), and coverage was 34.4% (11.9). The corresponding values for the lateral compartment were 0.63 mm (0.73), 9.8 mm (2.4), and 31.0% (7.7). Medial meniscus body extrusion index was greater in female knees (p = 0.03). There was slight increase in medial meniscal body extrusion over 4 years (0.040 mm/year [95% CI: 0.019-0.062]). The other variables were relatively stable.
In asymptomatic adults, the relative degree of meniscus body extrusion is more pronounced in female knees. Although a slight increase in extrusion over time was noted for the medial body, positions were relatively stable within subjects over time.
Knee; Meniscus; Magnetic resonance imaging; Osteoarthritis
The role of endogenous glucocorticoids (GC) in the initiation and maintenance of rheumatoid arthritis (RA) remains unclear. We demonstrated previously that disruption of GC signalling in osteoblasts results in a profound attenuation of K/BxN serum-induced arthritis, a mouse model of RA. To determine whether or not the modulation of the inflammatory response by osteoblasts involves T cells, we studied the effects of disrupted osteoblastic GC-signalling in the T cell-dependent model of antigen-induced arthritis (AIA).
Acute arthritis was induced in pre-immunised 11-week-old male 11β-hydroxysteroid dehydrogenase type 2 transgenic (tg) mice and their wild-type (WT) littermates by intra-articular injection of methylated bovine serum albumine (mBSA) into one knee joint. Knee diameter was measured every 1–2 days until euthanasia on day 14 post injection. In a separate experiment, arthritis was maintained for 28 days by weekly reinjections of mBSA. Tissues were analysed by histology, histomorphometry and microfocal-computed tomography. Serum cytokines levels were determined by multiplex suspension array.
In both short and long term experiments, arthritis developed in tg and WT mice with no significant difference between both groups. Histological indices of inflammation, cartilage damage and bone erosion were similar in tg and WT mice. Bone volume and turnover at the contralateral tibia and systemic cytokine levels were not different.
Acute murine AIA is not affected by a disruption in osteoblastic GC signalling. These data indicate that osteoblasts do not modulate the T cell-mediated inflammatory response via a GC-dependent pathway.
11-beta-hydroxysteroid dehydrogenase type 2; Disease models; Animal; Arthritis; Glucocorticoids; Osteoblasts
Injuries reported to workers’ compensation (WC) system are often used to estimate incidence of health outcomes and evaluate interventions in musculoskeletal epidemiology studies. However, WC claims represent a relatively small subset of all musculoskeletal disorders among employed individuals, and perhaps not a representative subset. This study determined the influence of workplace and individual factors on filing of workers’ compensation claims by nursing home employees with back pain.
Surveys were conducted in 18 skilled nursing facilities in four U.S. states. Self-administered questionnaires obtained information on demographic characteristics, working environment, and health behaviors/status. Employees who reported low back pain at least once in four questionnaire surveys were included. WC claims from the same facilities were obtained from the employer’s workers compensation insurer and matched by employee name. The dichotomous dependent variable was filing of back-related worker’s compensation claim. Association with predictors of interest, including pain severity, physical job demand, job strain, social support, schedule control, and safety climate, was assessed using multivariate regression modeling. Individual characteristics were tested as potential confounders.
Pain severity level was significantly associated with filing low-back related claims (odds ratio (OR) = 1.49, 95% CI = 1.18 – 1.87). Higher physical demands at work (OR = 1.07, 95% CI = 1.01 – 1.14) also increased the likelihood of claim filing. Higher job strain (OR = 0.83, 95% CI = 0.73 – 0.94), social support at work (OR = 0.90, 95% CI = 0.82 – 0.99), and education (OR = 0.79, 95% CI = 0.71 – 0.89) decreased the likelihood of claim filing.
The results suggest that the WC system captured the most severe occupational injuries. Workplace factors had additional influence on workers’ decision to file claims, after adjusting for low back pain severity. Education was correlated with worker’s socioeconomic status; its influence on claim filing is difficult to interpret because of the possible mixed effects of working conditions, self-efficacy, and content knowledge.
Workers’ compensation; Healthcare worker; Work environment; Back pain; Under-reporting
Recent qualitative research has shown that stiffness is an important symptom for patients to identify remission. However, it is unclear how to measure stiffness in low disease activity. This systematic review aims to summarise the existing literature on validity of patient reported outcomes to measure stiffness in RA low disease activity states, to aid the choice for a measurement instrument.
An extensive pubmed-search was undertaken, identifying measurement instruments for patient perceived stiffness used in low disease activity. Eligible studies reported on 1) stiffness as an outcome in relation to other core set measures, 2) development of a patient reported tool to measure stiffness, or 3) comparison of two different tools to measure aspects of stiffness, all in low disease activity.
Of 788 titles, only two studies report on validity of stiffness measures within low disease activity. Morning stiffness (MS) is reported in 44 to 80% of patients in low disease activity. A difference of 40 to 60 minutes in duration until maximum improvement is observed between active and inactive patients. Severity of MS might discriminate better between high and low disease activity compared to measurement of duration of MS.
There is insufficient data on measurement of stiffness in the spectrum of low disease activity or remission.
Rheumatoid arthritis; Remission; Morning stiffness; Outcome assessment; Systematic review
Nonsteroidal anti-inflammatory drugs (NSAIDs) are a standard treatment for osteoarthritis (OA), but the use of oral NSAIDs has been linked to an elevated risk for cardiovascular and gastrointestinal adverse events and renal toxicity. Topical NSAIDs are thought to afford efficacy that is comparable to oral formulations while reducing widespread systemic drug exposure, which may provide a benefit in terms of safety and tolerability. As a result, European treatment guidelines have, for many years, recommended the use of topical NSAIDs as a safe and effective treatment option for OA. Following the recent approval of several topical NSAID formulations by the US Food and Drug Administration, US treatment guidelines are increasingly recommending the use of topical NSAIDs as an alternative therapy and, in some cases, as a first-line option for OA. This commentary summarizes OA treatment guidelines that are currently available and discusses their potential evolution with regard to the increased inclusion of topical NSAIDs.
Osteoarthritis; Pain; NSAIDs; Topical; Guidelines
Previously was found that sonography is a reliable method to measure a capsular distance in total hip arthroplasty hips. The aim of our current study was to investigate the relation between the implanted size of the cup and the anterior capsular distance, as measured with ultrasound one year after THA.
50 osteoarthritis (OA) patients operated on with total hip arthroplasty one year before were included in the study and the anterior capsular distance was measured sonographically. Patients were grouped with respect to cup size. The correlation between the implanted cup size and capsular distance was determined.
The mean capsular distance in the whole group was 1.37 (SD 0.19) cm. The mean capsular distance in the group with small cups was 1.27 (SD 0.13) cm, in large cups it was 1.45 (SD 0.20) cm, p = 0.02. Spearman correlation analysis showed a statistically significant correlation between a greater capsular distance and the larger size of the cup (r = 0.5, p < 0.0001).
The greater capsular distance in successful THA hips is affected by cup size. We propose that this should be considered when evaluating sonography of the anterior capsular distance after THA.
Sonography; Cup size; Capsular distance; THA
The economic assessment of treatment options in a chronic and severe disease like Psoriatic Arthritis (PsA) is crucial to estimate the burden of costs. In particular, the impact of new costly medications such as biologic agents have been studied to figure this important aspect of a multifaceted disease. In a previous observational, longitudinal multicentre cost evaluation study, the results showed that biologic agents are cost-effective. This study was obtained from the real clinical practice and encompassed PsA patients refractory to traditional treatments. Similar data were also obtained from reviews analysis of Randomized Controlled Trials (RCTs). Recently, Cawson et al. performed a systematic review, network meta-analysis and economic evaluation of biological therapy for the management of active PsA. The review was conducted to identify relevant, recently published studies and the new trial data were synthesized, via a Bayesian network meta-analysis (NMA), to estimate the relative efficacy of the TNF-α inhibitors in terms of Psoriatic Arthritis Response Criteria (PsARC) response, Health Assessment Questionnaire (HAQ) scores and Psoriasis Area and Severity Index (PASI). In particular the analysis showed that, on average, etanercept was the most cost-effective treatment and, at the National Institute for Health and Care Excellence willingness-to-pay threshold of between £20,000 to £30,000, etanercept is the preferred option. This study, as a systematic review, has been focused on main RCTs on active PsA treated by biological DMARDs and limitations to this analysis arise from a paucity of data on long-term follow up, as well as radiological progression and long-term safety. These interesting results reflected the important role of biologic agents in the management of PsA, highlighting their efficacy and cost-effectiveness. However, there are some unmet needs for pharmacoeconomic considerations based on prospective and/or on real clinical practice studies, as well as considering all the intriguing aspects of this challenging disease.
An updated economic evaluation was conducted to compare the cost-effectiveness of the four tumour necrosis factor (TNF)-α inhibitors adalimumab, etanercept, golimumab and infliximab in active, progressive psoriatic arthritis (PsA) where response to standard treatment has been inadequate.
A systematic review was conducted to identify relevant, recently published studies and the new trial data were synthesised, via a Bayesian network meta-analysis (NMA), to estimate the relative efficacy of the TNF-α inhibitors in terms of Psoriatic Arthritis Response Criteria (PsARC) response, Health Assessment Questionnaire (HAQ) scores and Psoriasis Area and Severity Index (PASI). A previously developed economic model was updated with the new meta-analysis results and current cost data. The model was adapted to delineate patients by PASI 50%, 75% and 90% response rates to differentiate between psoriasis outcomes.
All four licensed TNF-α inhibitors were significantly more effective than placebo in achieving PsARC response in patients with active PsA. Adalimumab, etanercept and infliximab were significantly more effective than placebo in improving HAQ scores in patients who had achieved a PsARC response and in improving HAQ scores in PsARC non-responders. In an analysis using 1,000 model simulations, on average etanercept was the most cost-effective treatment and, at the National Institute for Health and Care Excellence willingness-to-pay threshold of between £20,000 to £30,000, etanercept is the preferred option.
The economic analysis agrees with the conclusions from the previous models, in that biologics are shown to be cost-effective for treating patients with active PsA compared with the conventional management strategy. In particular, etanercept is cost-effective compared with the other biologic treatments.
Up to 30% of patients suffer from long-term functional restrictions following conservative treatment of distal radius fractures. Whether duration of cast immobilisation influences functional outcome remains unclear.
The aim of the study is to evaluate whether the duration of immobilization of non or minimally displaced distal radial fractures can be safely reduced. We will compare three weeks of plaster cast immobilization with five weeks of plaster cast immobilization in adult patient with non or minimally displaced distal radial fractures.
Study design: a prospective randomized clinical trial.
Study population: adult (>18 years) (independent in activities of daily living) patients with a non/minimal displaced distal radius fracture (dorsal angulation <15°, volar tilt <20°, radial inclination >15°, ulnar positive variance <5 mm and an articular step off <2 mm).
Intervention: three weeks of plaster cast immobilization versus five weeks of plaster cast immobilization.
Main study parameters: primary outcome parameters: Patient related wrist evaluation (PRWE) Quick Disability of Arm, Shoulder and Hand (QUICKDASH) score after a one year follow-up, and secondary parameters: range of motion, pain level (VAS) and complications.
The expectation of this study is that shorter duration of plaster cast immobilisation is beneficial for the patient with a distal radius fracture. This risk of specific complications is low and generally similar in both treatment options. Moreover, the burden of the study is not much higher compared to standard treatment. Follow-up is standardized according to current trauma guidelines. Literature indicates that both treatment options from the study are accepted for displaced distal radius fractures. No clear advantage for one treatment options is found at present in the literature, although there is no level I evidence present. This trial will provide level-1 evidence for the comparison of consolidation and functional outcome between two treatment options for non-displaced distal radial fractures. The gathered data may support the development of a clinical guideline for conservative treatment of distal radial fractures.
Netherlands National Trial Register NTR3552.
The projected demand for total knee arthroplasty is staggering. At its root, the solution involves increasing supply or decreasing demand. Other developed nations have used rationing and wait times to distribute this service. However, economic impact and cost-effectiveness of waiting for TKA is unknown.
A Markov decision model was constructed for a cost-utility analysis of three treatment strategies for end-stage knee osteoarthritis: 1) TKA without delay, 2) a waiting period with no non-operative treatment and 3) a non-operative treatment bridge during that waiting period in a cohort of 60 year-old patients. Outcome probabilities and effectiveness were derived from the literature. Costs were estimated from the societal perspective with national average Medicare reimbursement. Effectiveness was expressed in quality-adjusted life years (QALYs) gained. Principal outcome measures were average incremental costs, effectiveness, and quality-adjusted life years; and net health benefits.
In the base case, a 2-year wait-time both with and without a non-operative treatment bridge resulted in a lower number of average QALYs gained (11.57 (no bridge) and 11.95 (bridge) vs. 12.14 (no delay). The average cost was $1,660 higher for TKA without delay than wait-time with no bridge, but $1,810 less than wait-time with non-operative bridge. The incremental cost-effectiveness ratio comparing wait-time with no bridge to TKA without delay was $2,901/QALY. When comparing TKA without delay to waiting with non-operative bridge, TKA without delay produced greater utility at a lower cost to society.
TKA without delay is the preferred cost-effective treatment strategy when compared to a waiting for TKA without non-operative bridge. TKA without delay is cost saving when a non-operative bridge is used during the waiting period. As it is unlikely that patients waiting for TKA would not receive non-operative treatment, TKA without delay may be an overall cost-saving health care delivery strategy. Policies aimed at increasing the supply of TKA should be considered as savings exist that could indirectly fund those strategies.
Total knee arthroplasty; Cost-effectiveness analysis; Cost-utility analysis; Markov; Decision analysis; Healthcare economics
Advising patients about when they can drive after surgery is common practice after arthroplasty of the knee or hip. In the literature, the preoperative braking performance values of the patients are frequently taken as the “safe” landmark. We hypothesised that osteoarthritis (OA), the most frequent reason for arthroplasty, already compromises the ability to perform an emergency stop. We expected that both Reaction Time (RT) and Movement Time (MT) as components of the Total Brake Response Time (TBRT), would be prolonged in patients with OA of the knee or hip in comparison with healthy subjects. We also expected maximum pressure levels on the brake pedal to be reduced in such cases.
A real car cabin was equipped with pressure sensors on the accelerator and brake pedals to measure RT, MT, TBRT and maximum Brake Force (BF) under realistic spatial constraints. Patients with OA of the knee (right n = 18, left n = 15) or hip (right n = 20, left n = 19) were compared with a healthy control group (n = 21).
All measured values for TBRT in the control group remained below 600 ms. OA of the right hip or knee significantly prolonged the braking performance (right hip: TBRT p = 0.025, right knee: TBRT p < 0.001), whereas OA of the left hip did not impair driving ability (TBRT p = 0.228). Intriguingly, OA of the left knee prolonged RT and MT to the same degree as OA on the contralateral side (RT p = 0.001, MT p < 0.001).
This study demonstrates that depending on the localisation of OA, driving capability can be impaired; OA can significantly increase the total braking distance. To ensure safe traffic participation the safety margin for TBRT should be strictly set, under our experimental conditions, at around 600 ms. Moreover, therapeutic approaches to OA, such as physiotherapy, and patients receiving surgery of the left knee should take into account that left knee OA can also impair driving ability.
Clinical trial registration number: Project number of the ethics committee of the University of Tübingen: 268/2009BO2; 267/2009BO2.
Automobile driving; Reaction time; Osteoarthritis of the knee; Osteoarthritis of the hip; Total brake response time; Driver reaction time
The editors of BMC Musculoskeletal Disorders would like to thank all our reviewers who have contributed to the journal in Volume 14 (2013).
Femoral head osteonecrosis is frequently observed in patients treated with excessive corticosteroids. The objective of the current study was to establish a rat model to investigate the disruption of immune response in steroid-induced femoral head osteonecrosis via Toll-like receptor 4 (TLR4) signaling pathway.
Male SD rats were divided into the treatment group (group A) and the model group (group B) consisting of 24 rats each, and were injected intramuscularly with 20 mg/kg methylprednisolone (MP) for 8 weeks, once a week. The rats in group A were injected intravenously with 7.5 mg/kg TAK242 before each MP administration. A control group (group N) consisted of 12 rats were received saline injection. All animals were sacrificed 8, 10 and 12 weeks from the first MP injection, respectively. Histopathological analysis was performed and the concentration of tartrate-resistant acid phosphatase (TRAP) in serum was tested. The signaling molecules including TLR4, MyD88, NF-κB p65 and MCP-1 were detected by immunohistochemistry, quantitative real-time PCR and Western blot.
Femoral head osteonecrosis was observed in the model rats, and the concentration of TRAP and positive staining of all signaling molecules increased significantly in group B compared with that in group A and group N. Compare with the control group, the mRNA expressions and protein levels of all signaling molecules were enhanced significantly in group B, but no significant in group A.
Corticosteroids can induce femoral head osteonecrosis by disturbing the immune response via TLR4 signaling pathway. These findings suggest that the disruption of immune response play a role in the pathogenesis of osteonecrosis.
Osteonecrosis; Femoral head; Toll-like receptor 4; Corticosteroids; Rat
Head-eye movement control deficit is an identified problem in patients with chronic neck pain, particularly in cases of whiplash associated disorders (WAD). To date, there is no evidence concerning the reliability and validity of visually assessed active head-eye movement control tests. Therefore, the objectives of the present cross-sectional study were, a) to develop a test battery; and b) to investigate inter-observer reliability and discriminative validity in patients with chronic neck pain compared to healthy controls.
The study was conducted at two physiotherapy clinics in Switzerland. Ethics Committee approval was obtained. Ten active head-eye coordination tests, on 23 patients with chronic neck pain and associated symptoms and 19 healthy controls, were videotaped. The tests included eye movements in the neutral head position and 45° relative neck rotation, gaze stability and sequential head-eye movements. All tests were performed in the sitting and standing positions. Two blinded physiotherapists independently rated the randomized videos. Performance was rated as "negative", "moderately positive" or "clearly positive". Weighted kappa (wK) and 95% confidence intervals (CI) were calculated to investigate inter-observer reliability. Good reliability was defined as wK >0.5 with a lower boundary of 95% CI >0.2. Odds ratios (to define cut-off points) and the distribution of the classificator, numbers of positive tests, were calculated.
Three out of ten tests showed "excellent" (wK 0.82 to 0.86), five out of ten tests showed "substantial" (wK 0.69 to 0.79) and two out of ten tests showed "moderate" (wK 0.54 to 0.59) reliability. Results were comparable in the sitting and standing positions. On average, three out of five tests were rated positive in patients and one out of five tests was rated positive in healthy controls. An odds ratio of 13.3 to 18.6 was obtained using ≥2/5 tests as a cut-off point.
Visual assessment by physiotherapists of head-eye movement control tests is reliable. The test battery is able to discriminate between patients with chronic neck pain and healthy controls. There were no differences in performance between the sitting and standing positions. The test battery can therefore be reduced to five tests. Further research is needed to identify the test-retest stability and responsiveness.
Head-eye movement control; Chronic neck pain; Whiplash associated disorders; Reliability; Discriminative validity; Assessment
Group cognitive behavioural intervention (CBI) is effective in reducing low-back pain and disability in comparison to advice in primary care. The aim of this analysis was to investigate the impact of compliance on estimates of treatment effect and to identify factors associated with compliance.
In this multicentre trial, 701 adults with troublesome sub-acute or chronic low-back pain were recruited from 56 general practices. Participants were randomised to advice (control n = 233) or advice plus CBI (n = 468). Compliance was specified a priori as attending a minimum of three group sessions and the individual assessment. We estimated the complier average causal effect (CACE) of treatment.
Comparison of the CACE estimate of the mean treatment difference to the intention-to-treat (ITT) estimate at 12 months showed a greater benefit of CBI amongst participants compliant with treatment on the Roland Morris Questionnaire (CACE: 1.6 points, 95% CI 0.51 to 2.74; ITT: 1.3 points, 95% CI 0.55 to 2.07), the Modified Von Korff disability score (CACE: 12.1 points, 95% CI 6.07 to 18.17; ITT: 8.6 points, 95% CI 4.58 to 12.64) and the Modified von Korff pain score (CACE: 10.4 points, 95% CI 4.64 to 16.10; ITT: 7.0 points, 95% CI 3.26 to 10.74). People who were non-compliant were younger and had higher pain scores at randomisation.
Treatment compliance is important in the effectiveness of group CBI. Younger people and those with more pain are at greater risk of non-compliance.
Current Controlled Trials ISRCTN54717854
Compliance; CACE analysis; Low back pain; Cognitive behaviour therapy
Discontinuation of rheumatoid arthritis (RA) treatment for lack or loss of initial response, tolerability issues, or development of antibodies against the therapeutic agent remains a challenge in clinical practice. Here we present a 6-month interim analysis of a 2-year prospective observational trial in Europe and Canada aiming to assess the real-world effectiveness, safety, and tolerability of intravenous abatacept for the treatment of moderate-to-severe RA.
ACTION (AbataCepT In rOutiNe clinical practice) is a prospective, observational study assessing effectiveness, safety, and tolerability of abatacept in patients with RA enrolled in Europe and Canada between May 2008 and January 2011. The patient population was divided into two groups: biologic naïve (‘first-line’) patients and patients who had previously failed treatment with at least one biologic agent (‘second-line’). Retention rates were calculated using Kaplan–Meier curve estimates. Effectiveness was measured using European League Against Rheumatism (EULAR) response criteria, the 28-item Disease Activity Score, the Clinical Disease Activity Index (CDAI), and physical function, as assessed by the Health Assessment Questionnaire-Disability Index (HAQ-DI). Serious adverse events (SAEs) were reported for all enrolled patients.
Of 1138 consecutively enrolled patients, 1114 and 1079 patients were evaluable for retention and effectiveness, respectively. Overall, retention rates were 88.6% (95% confidence interval [CI]: 86.4, 90.4); 67.4% of patients achieved good/moderate EULAR response; 32.8% had a CDAI Low Disease Activity State (LDAS); and 44.7% a HAQ-DI response. Retention rates among first- and second-line patients were 93.0% (95% CI: 85.9, 96.6) and 88.1% (95% CI: 85.7, 90.0), respectively. The percentage of patients achieving CDAI LDAS was 40.0% (95% CI: 26.4, 53.6) for first- and 32.2% (95% CI: 28.4, 36.0) for second-line patients and the proportion achieving a HAQ-DI response was 60.3% (95% CI: 47.8, 72.9) versus 43.1% (95% CI: 39.0, 47.2), respectively. The incidence of SAEs was 4.7%.
Evidence from this 6-month interim analysis suggests that abatacept offers an effective and well-tolerated treatment option for patients with RA, including those who have previously failed anti-tumor necrosis factor treatment. In addition, higher retention rates and effectiveness outcomes were observed when abatacept treatment was initiated earlier in the course of the disease.
Rheumatoid arthritis; Biological agents; Abatacept; Effectiveness; Safety; Registries