Obesity increases the odds of intervertebral disc herniation and spinal stenosis; an MRI study of 1634 low back pain patients.

PURPOSE: The objective of this study was to examine the relationships between BMI and intervertebral disc degeneration (DD), disc herniation (DH) and spinal stenosis (SS) using a large, prospectively recruited and heterogeneous patient population. METHODS: Patients were recruited through the European Genodisc Study. An experienced radiologist scored MRI images for DD, DH and SS. Multivariate linear and logistic regression analyses were used to model the relationship between these variables and BMI with adjustment for patient and MRI confounders. RESULTS: We analysed 1684 patients with a mean age of 51 years and BMI of 27.2 kg/m2.The mean DD score was 2.6 (out of 5) with greater DD severity with increasing age (R2 = 0.44). In the fully adjusted model, a 10-year increase in age and a 5 kg/m2 increase in BMI were associated, respectively, with a 0.31-unit [95% CI 0.29,0.34] and 0.04-unit [CI 0.01,0.07] increase in degeneration. Age (OR 1.23 [CI 1.06,1.43]) and BMI (OR 2.60 [CI 2.28,2.96]) were positively associated with SS. For DH, age was a negative predictor (OR 0.70 [CI 0.64,0.76]) but for BMI (OR 1.19 [CI 1.07,1.33]), the association was positive. BMI was the strongest predictor of all three features in the upper lumbar spine. CONCLUSIONS: While an increase in BMI was associated with only a slight increase in DD, it was a stronger predictor for DH and SS, particularly in the upper lumbar discs, suggesting weight loss could be a useful strategy for helping prevent disorders associated with these pathologies.

External validation of the deep learning system "SpineNet" for grading radiological features of degeneration on MRIs of the lumbar spine.

BACKGROUND: Magnetic resonance imaging (MRI) is used to detect degenerative changes of the lumbar spine. SpineNet (SN), a computer vision-based system, performs an automated analysis of degenerative features in MRI scans aiming to provide high accuracy, consistency and objectivity. This study evaluated SN's ratings compared with those of an expert radiologist. METHOD: MRIs of 882 patients (mean age, 72 ± 8.8 years) with degenerative spinal disorders from two previous trials carried out in our spine center between 2011 and 2019, were analyzed by an expert radiologist. Lumbar segments (L1/2-L5/S1) were graded for Pfirrmann Grades (PG), Spondylolisthesis (SL) and Central Canal Stenosis (CCS). SN's analysis for the equivalent parameters was generated. Agreement between methods was analyzed using kappa (κ), Spearman correlation (ρ) and Lin's concordance correlation (ρc) coefficients and class average accuracy (CAA). RESULTS: 4410 lumbar segments were analyzed. κ statistics showed moderate to substantial agreement in PG between the radiologist and SN depending on spinal level (range κ 0.63-0.77, all levels together 0.72; range CAA 45-68%, all levels 55%), slight to substantial agreement for SL (range κ 0.07-0.60, all levels 0.63; range CAA 47-57%, all levels 56%) and CCS (range κ 0.17-0.57, all levels 0.60; range CAA 35-41%, all levels 43%). SN tended to record more pathological features in PG than did the radiologist whereas the contrary was the case for CCS. SL showed an even distribution between methods. CONCLUSION: SN is a robust and reliable tool with the ability to grade degenerative features such as PG, SL or CCS in lumbar MRIs with moderate to substantial agreement compared to the current gold-standard, the radiologist. It is a valuable alternative for analyzing MRIs from large cohorts for diagnostic and research purposes.

Consensus on a standardised treatment pathway algorithm for lumbar spinal stenosis: an international Delphi study.

BACKGROUND: Lumbar spinal stenosis (LSS) is a common degenerative spinal condition in older adults associated with disability, diminished quality of life, and substantial healthcare costs. Individual symptoms and needs vary. With sparse and sometimes inconsistent evidence to guide clinical decision-making, variable clinical care may lead to unsatisfactory patient outcomes and inefficient use of healthcare resources. METHODS: A three-phase modified Delphi study comprising four consensus rounds was conducted on behalf of the International Taskforce for the Diagnosis and Management of LSS to develop a treatment algorithm based on multi-professional international expert consensus. Participants with expertise in the assessment and management of people with LSS were invited using an international distribution process used for two previous Delphi studies led by the Taskforce. Separate treatment pathways for patients with different symptom types and severity were developed and incorporated into a proposed treatment algorithm through consensus rounds 1 to 3. Agreement with the proposed algorithm was evaluated in the final consensus round. RESULTS: The final algorithm combines stratified and stepped approaches. When indicated, immediate investigation and surgery is advocated. Otherwise, a stepped approach is suggested when self-directed care is unsatisfactory. This starts with tailored rehabilitation, then more complex multidisciplinary care, investigations and surgery options if needed. Treatment options in each step depend on clinical phenotype and symptom severity. Treatment response guides pathway entrance and exit points. Of 397 study participants, 86% rated their agreement ≥ 4 for the proposed algorithm on a 0-6 scale, of which 22% completely agreed. Only 7% disagreed. Over 70% of participants felt that the algorithm would be useful for clinicians in public healthcare (both primary care and specialist settings) and in private healthcare settings, and that a simplified version would help patients in shared decision-making. CONCLUSIONS: International and multi-professional agreement was achieved for a proposed LSS treatment algorithm developed through expert consensus. The algorithm advocates different pathway options depending on clinical indications. It is not intended as a treatment protocol and will require evaluation against current care for clinical and cost-effectiveness. It may, however, serve as a clinical guide until evidence is sufficient to inform a fully stratified care model.

Correction to: Identifying Scoliosis in Population­Based Cohorts: Automation of a Validated Method Based on Total Body Dual Energy X­ray Absorptiometry Scans.

In the original version of the article, the co-author would like to add to the acknowledgements section to highlight their funding stream (EPSRC). The revised acknowledgements is given below.

Identifying Scoliosis in Population-Based Cohorts: Automation of a Validated Method Based on Total Body Dual Energy X-ray Absorptiometry Scans.

Scoliosis is a 3D-torsional rotation of the spine, but risk factors for initiation and progression are little understood. Research is hampered by lack of population-based research since radiographs cannot be performed on entire populations due to the relatively high levels of ionising radiation. Hence we have developed and validated a manual method for identifying scoliosis from total body dual energy X-ray absorptiometry (DXA) scans for research purposes. However, to allow full utilisation of population-based research cohorts, this needs to be automated. The purpose of this study was therefore to automate the identification of spinal curvature from total body DXA scans using machine learning techniques. To validate the automation, we assessed: (1) sensitivity, specificity and area under the receiver operator curve value (AUC) by comparison with 12,000 manually annotated images; (2) reliability by rerunning the automation on a subset of DXA scans repeated 2-6 weeks apart and calculating the kappa statistic; (3) validity by applying the automation to 5000 non-annotated images to assess associations with epidemiological variables. The final automated model had a sensitivity of 86.5%, specificity of 96.9% and an AUC of 0.80 (95%CI 0.74-0.87). There was almost perfect agreement of identification of those with scoliosis (kappa 0.90). Those with scoliosis identified by the automated model showed similar associations with gender, ethnicity, socioeconomic status, BMI and lean mass to previous literature. In conclusion, we have developed an accurate and valid automated method for identifying and quantifying spinal curvature from total body DXA scans.

Could automated machine-learned MRI grading aid epidemiological studies of lumbar spinal stenosis? Validation within the Wakayama spine study.

BACKGROUND: MRI scanning has revolutionized the clinical diagnosis of lumbar spinal stenosis (LSS). However, there is currently no consensus as to how best to classify MRI findings which has hampered the development of robust longitudinal epidemiological studies of the condition. We developed and tested an automated system for grading lumbar spine MRI scans for central LSS for use in epidemiological research. METHODS: Using MRI scans from the large population-based cohort study (the Wakayama Spine Study), all graded by a spinal surgeon, we trained an automated system to grade central LSS in four gradings of the bone and soft tissue margins: none, mild, moderate, severe. Subsequently, we tested the automated grading against the independent readings of our observer in a test set to investigate reliability and agreement. RESULTS: Complete axial views were available for 4855 lumbar intervertebral levels from 971 participants. The machine used 4365 axial views to learn (training set) and graded the remaining 490 axial views (testing set). The agreement rate for gradings was 65.7% (322/490) and the reliability (Lin's correlation coefficient) was 0.73. In 2.2% of scans (11/490) there was a difference in classification of 2 and in only 0.2% (1/490) was there a difference of 3. When classified into 2 groups as 'severe' vs 'no/mild/moderate'. The agreement rate was 94.1% (461/490) with a kappa of 0.75. CONCLUSIONS: This study showed that an automated system can "learn" to grade central LSS with excellent performance against the reference standard. Thus SpineNet offers potential to grade LSS in large-scale epidemiological studies involving a high volume of MRI spine data with a high level of consistency and objectivity.

Leptin and the intervertebral disc: a biochemical link exists between obesity, intervertebral disc degeneration and low back pain-an in vitro study in a bovine model.

PURPOSE: The aim of this study was to identify the effects of leptin upon the intervertebral disc (IVD) and to determine whether these responses are potentiated within an environment of existing degeneration. Obesity is a significant risk factor for low back pain (LBP) and IVD degeneration. Adipokines, such as leptin, are novel cytokines produced primarily by adipose tissue and have been implicated in degradative and inflammatory processes. Obese individuals are known to have higher concentrations of serum leptin, and IVD cells express leptin receptors. We hypothesise that adipokines, such as leptin, mediate a biochemical link between obesity, IVD degeneration and LBP. METHODS: The bovine intervertebral disc was used as a model system to investigate the biochemical effects of obesity, mediated by leptin, upon the intervertebral disc. Freshly isolated cells, embedded in 3D alginate beads, were subsequently cultured under varying concentrations of leptin, alone or together with the pro-inflammatory cytokines TNF-α, IL-1ß or IL-6. Responses in relation to production of nitric oxide, lactate, glycosaminoglycans and expression of anabolic and catabolic genes were analysed. RESULTS: Leptin influenced the cellular metabolism leading particularly to greater production of proteases and NO. Addition of leptin to an inflammatory environment demonstrated a marked deleterious synergistic effect with greater production of NO, MMPs and potentiation of pro-inflammatory cytokine production. CONCLUSIONS: Leptin can initiate processes involved in IVD degeneration. This effect is potentiated in an environment of existing degeneration and inflammation. Hence, a biochemical mechanism may underlie the link between obesity, intervertebral disc degeneration and low back pain. These slides can be retrieved under Electronic Supplementary Material.

Systematic review of the complications associated with magnetically controlled growing rods for the treatment of early onset scoliosis.

PURPOSE: To analyse the complication profile of magnetically controlled growing rods (MCGRs) in early onset scoliosis (EOS). METHODS: This is a systematic review using PUBMED, Medline, Embase, Google Scholar and the Cochrane Library (keywords: MAGEC, Magnetically controlled growing rods and EOS) of all studies written in English with a minimum of five patients and a 1-year follow-up. We evaluated coronal correction, growth progression (T1-S1, T1-T12) and complications. RESULTS: Fifteen studies (336 patients) were included (42.5% male, mean age 7.9 years, average follow-up 29.7 months). Coronal improvement was achieved in all studies (pre-operative 64.8°, latest follow-up 34.9° p = 0.000), as was growth progression (p = 0.001). Mean complication rate was 44.5%, excluding the 50.8% medical complication rate. The unplanned revision rate was 33%. The most common complications were anchor pull-out (11.8%), implant failure (11.7%) and rod breakage (10.6%). There was no significant difference between primary (39.8%) and conversion (33.3%) procedures (p = 0.462). There was a non-statistically significant increased complication rate with single rods (40 vs. 27% p = 0.588). CONCLUSIONS: MCGRs improve coronal deformity and maintain spinal growth, but carry a 44.5% complication and 33% unplanned revision rate. Conversion procedures do not increase this risk. Single rods should be avoided. These slides can be retrieved under Electronic Supplementary material.

ISSLS PRIZE IN BIOENGINEERING SCIENCE 2017: Automation of reading of radiological features from magnetic resonance images (MRIs) of the lumbar spine without human intervention is comparable with an expert radiologist.

STUDY DESIGN: Investigation of the automation of radiological features from magnetic resonance images (MRIs) of the lumbar spine. OBJECTIVE: To automate the process of grading lumbar intervertebral discs and vertebral bodies from MRIs. MR imaging is the most common imaging technique used in investigating low back pain (LBP). Various features of degradation, based on MRIs, are commonly recorded and graded, e.g., Modic change and Pfirrmann grading of intervertebral discs. Consistent scoring and grading is important for developing robust clinical systems and research. Automation facilitates this consistency and reduces the time of radiological analysis considerably and hence the expense. METHODS: 12,018 intervertebral discs, from 2009 patients, were graded by a radiologist and were then used to train: (1) a system to detect and label vertebrae and discs in a given scan, and (2) a convolutional neural network (CNN) model that predicts several radiological gradings. The performance of the model, in terms of class average accuracy, was compared with the intra-observer class average accuracy of the radiologist. RESULTS: The detection system achieved 95.6% accuracy in terms of disc detection and labeling. The model is able to produce predictions of multiple pathological gradings that consistently matched those of the radiologist. The model identifies 'Evidence Hotspots' that are the voxels that most contribute to the degradation scores. CONCLUSIONS: Automation of radiological grading is now on par with human performance. The system can be beneficial in aiding clinical diagnoses in terms of objectivity of gradings and the speed of analysis. It can also draw the attention of a radiologist to regions of degradation. This objectivity and speed is an important stepping stone in the investigation of the relationship between MRIs and clinical diagnoses of back pain in large cohorts. LEVEL OF EVIDENCE: Level 3.

Age and pro-inflammatory gene polymorphisms influence adjacent segment disc degeneration more than fusion does in patients treated for chronic low back pain.

PURPOSE: Does lumbar fusion lead to accelerated adjacent segment disc degeneration (ASDD) or is it explained by genetics and aging? The influence of genetics on ASDD remains to be explored. This study assesses whether the disc space height adjacent to a fused segment is associated with candidate gene single nucleotide polymorphisms (SNPs). METHODS: Patients with low back pain from four RCTs (N = 208 fusion; 77 non-operative treatment) underwent standing plain radiography and genetic analyses at 13 ± 4 years follow-up. Disc space height was measured using a validated computer-assisted distortion-compensated roentgen analysis technique and reported in standard deviations from normal values. Genetic association analyses included 34 SNPs in 25 structural, inflammatory, matrix degrading, apoptotic, vitamin D receptor and OA-related genes relevant to disc degeneration. These were analysed for their association with disc space height (after adjusting for age, gender, smoking, duration of follow-up and treatment group) first, separately, and then together in a stepwise multivariable model. RESULTS: Two SNPs from the IL18RAP gene (rs1420106 and rs917997) were each associated with a lower disc space height at the adjacent level (B = -0.34, p = 0.04 and B = -0.35, p = 0.04, respectively) and the MMP-9 gene SNP rs20544 was associated with a greater disc space height (B = 0.35, p = 0.04). Age (p < 0.001) and fusion (p < 0.008) were also significant variables in each analysis. The total explained variance in disc space height was for each SNP model 13-14 %, with 11-12 % of this being accounted for by the given SNP, 64-67 % by age and 19-22 % by fusion. In the multivariable regression analysis (with nine SNPs selected for entry, along with the covariates) the total explained variance in disc space height was 23 %, with the nine SNPs, age and fusion accounting for 45, 45 and 7 % of this, respectively. CONCLUSIONS: Age was the most significant determinant of adjacent segment disc space height followed by genetic factors, specifically inflammatory genes. Fusion explained a statistically significant but small proportion of the total variance. Much of the variance remained to be explained.

Disc herniations in astronauts: What causes them, and what does it tell us about herniation on earth?

PURPOSE: Recent work showed an increased risk of cervical and lumbar intervertebral disc (IVD) herniations in astronauts. The European Space Agency asked the authors to advise on the underlying pathophysiology of this increased risk, to identify predisposing factors and possible interventions and to suggest research priorities. METHODS: The authors performed a narrative literature review of the possible mechanisms, and conducted a survey within the team to prioritize research and prevention approaches. RESULTS AND CONCLUSIONS: Based on literature review the most likely cause for lumbar IVD herniations was concluded to be swelling of the IVD in the unloaded condition during spaceflight. For the cervical IVDs, the knowledge base is too limited to postulate a likely mechanism or recommend approaches for prevention. Basic research on the impact of (un)loading on the cervical IVD and translational research is needed. The highest priority prevention approach for the lumbar spine was post-flight care avoiding activities involving spinal flexion, followed by passive spinal loading in spaceflight and exercises to reduce IVD hyper-hydration post-flight.

What Value Can Qualitative Research Add to Quantitative Research Design? An Example From an Adolescent Idiopathic Scoliosis Trial Feasibility Study.

Using an example of qualitative research embedded in a non-surgical feasibility trial, we explore the benefits of including qualitative research in trial design and reflect on epistemological challenges. We interviewed 18 trial participants and used methods of Interpretive Phenomenological Analysis. Our findings demonstrate that qualitative research can make a valuable contribution by allowing trial stakeholders to see things from alternative perspectives. Specifically, it can help to make specific recommendations for improved trial design, generate questions which contextualize findings, and also explore disease experience beyond the trial. To make the most out of qualitative research embedded in quantitative design it would be useful to (a) agree specific qualitative study aims that underpin research design, (b) understand the impact of differences in epistemological truth claims, (c) provide clear thematic interpretations for trial researchers to utilize, and (d) include qualitative findings that explore experience beyond the trial setting within the impact plan.

Catechol-O-methyltransferase (COMT) gene polymorphisms are associated with baseline disability but not long-term treatment outcome in patients with chronic low back pain.

PURPOSE: To examine the association between COMT and OPRM1 gene polymorphisms and pain and disability at baseline and long-term follow-up in patients treated for chronic low back pain (LBP). METHODS: 371 of 767 unrelated European patients recruited from four randomised trials underwent genetic analyses at mean 11.4 years follow-up. 274 patients had fusion and 97 had non-operative treatment. Association analyses included disability, pain, five single nucleotide polymorphisms (SNPs) in the COMT gene, and one SNP in the OPRM1 gene. Analyses were adjusted for age, gender, smoking, analgesics and treatment. RESULTS: Disability at baseline was significantly associated with COMT SNPs rs4818 (p = 0.02), rs6269 (p = 0.007), rs4633 (p = 0.04) rs2075507 (p = 0.009), two haplotypes (p < 0.002), age, gender and smoking (p ≤ 0.002). No significant associations with clinical variables were observed for OPRM1, or for COMT at long-term follow-up. CONCLUSIONS: Results suggest that genetic factors are partly responsible for the variation in disability levels in patients presenting with chronic LBP being considered for surgery; in contrast, genetics has no influence on the long-term outcome of treatment.

A proposed set of metrics for standardized outcome reporting in the management of low back pain.

BACKGROUND AND PURPOSE: Outcome measurement has been shown to improve performance in several fields of healthcare. This understanding has driven a growing interest in value-based healthcare, where value is defined as outcomes achieved per money spent. While low back pain (LBP) constitutes an enormous burden of disease, no universal set of metrics has yet been accepted to measure and compare outcomes. Here, we aim to define such a set. PATIENTS AND METHODS: An international group of 22 specialists in several disciplines of spine care was assembled to review literature and select LBP outcome metrics through a 6-round modified Delphi process. The scope of the outcome set was degenerative lumbar conditions. RESULTS: Patient-reported metrics include numerical pain scales, lumbar-related function using the Oswestry disability index, health-related quality of life using the EQ-5D-3L questionnaire, and questions assessing work status and analgesic use. Specific common and serious complications are included. Recommended follow-up intervals include 6, 12, and 24 months after initiating treatment, with optional follow-up at 3 months and 5 years. Metrics for risk stratification are selected based on pre-existing tools. INTERPRETATION: The outcome measures recommended here are structured around specific etiologies of LBP, span a patient's entire cycle of care, and allow for risk adjustment. Thus, when implemented, this set can be expected to facilitate meaningful comparisons and ultimately provide a continuous feedback loop, enabling ongoing improvements in quality of care. Much work lies ahead in implementation, revision, and validation of this set, but it is an essential first step toward establishing a community of LBP providers focused on maximizing the value of the care we deliver.

Disc cell therapies: critical issues.

BACKGROUND: Disc cell therapies, in which cells are injected into the degenerate disc in order to regenerate the matrix and restore function, appear to be an attractive, minimally invasive method of treatment. Interest in this area has stimulated research into disc cell biology in particular. However, other important issues, some of which are discussed here, need to be considered if cell-based therapies are to be brought to the clinic. PURPOSE: Firstly, a question which is barely addressed in the literature, is how to identify patients with 'degenerative disc disease' who would benefit from cell therapy. Pain not disc degeneration is the symptom which drives patients to the clinic. Even though there are associations between back pain and disc degeneration, many people with even severely degenerate discs, with herniated discs or with spinal stenosis, are pain-free. It is not possible using currently available techniques to identify whether disc repair or regeneration would remove symptoms or prevent symptoms from occurring in future. Moreover, the repair process in human discs is very slow (years) because of the low cell density which can be supported nutritionally even in healthy human discs. If repair is necessary for relief of symptoms, questions regarding quality of life and rehabilitation during this long process need consideration. Also, some serious technical issues remain. Finding appropriate cell sources and scaffolds have received most attention, but these are not the only issues determining the feasibility of the procedure. There are questions regarding the safety of implanting cells by injection through the annulus whether the nutrient supply to the disc is sufficient to support implanted cells and whether, if cells are able to survive, conditions in a degenerate human disc will allow them to repair the damaged tissue. CONCLUSIONS: If cell therapy for treatment of disc-related disorders is to enter the clinic as a routine treatment, investigations must examine the questions related to patient selection and the feasibility of achieving the desired repair in an acceptable time frame. Few diagnostic tests that examine whether cell therapies are likely to succeed are available at present, but definite exclusion criteria would be evidence of major disc fissures, or disturbance of nutrient pathways as measured by post-contrast MRI.

Predictive factors for successful clinical outcome 1 year after an intensive combined physical and psychological programme for chronic low back pain.

PURPOSE: The aim of this longitudinal study is to determine the factors which predict a successful 1-year outcome from an intensive combined physical and psychological (CPP) programme in chronic low back pain (CLBP) patients. METHODS: A prospective cohort of 524 selected consecutive CLBP patients was followed. Potential predictive factors included demographic characteristics, disability, pain and cognitive behavioural factors as measured at pre-treatment assessment. The primary outcome measure was the oswestry disability index (ODI). A successful 1-year follow-up outcome was defined as a functional status equivalent to 'normal' and healthy populations (ODI ≤22). The 2-week residential programme fulfills the recommendations in international guidelines. For statistical analysis we divided the database into two equal samples. A random sample was used to develop a prediction model with multivariate logistic regression. The remaining cases were used to validate this model. RESULTS: The final predictive model suggested being 'in employment' at pre-treatment [OR 3.61 (95 % CI 1.80-7.26)] and an initial 'disability score' [OR 0.94 (95 % CI 0.92-0.97)] as significant predictive factors for a successful 1-year outcome (R (2) = 22 %; 67 % correctly classified). There was no predictive value from measures of psychological distress. CONCLUSION: CLBP patients who are in work and mild to moderately disabled at the start of a CPP programme are most likely to benefit from it and to have a successful treatment outcome. In these patients, the disability score falls to values seen in healthy populations. This small set of factors is easily identified, allowing selection for programme entry and triage to alternative treatment regimes.

Advances in the diagnosis of degenerated lumbar discs and their possible clinical application.

PURPOSE: One possible source of chronic low back pain is a degenerated intervertebral disc. In this review, various diagnostic methods for the assessment of the presence of degenerative changes are described. These include clinical MRI, a number of novel MRI techniques and nuclear magnetic resonance spectroscopy. METHODS: Non-systematic literature review. RESULTS: Clinical MRI is the most commonly employed technique to determine the general "health status" of the intervertebral disc. Novel MRI techniques, such as quantitative MRI, T1ρ MRI, sodium MRI and nuclear magnetic resonance spectroscopy, are more sensitive in quantifying the biochemical changes of disc degeneration, as measured by alteration in collagen structure, as well as water and proteoglycan loss. As potential future diagnostic alternatives, miniature sensors are currently being developed to measure parameters associated with the disc degeneration cascade, such as intradiscal pressure and PG concentration. However, none of the methods listed above show sufficient specificity to identify a degenerated disc as the actual source of the pain. Provocative discography is the only test aimed at a direct diagnosis of discogenic pain, but it has a high false positive rate and there is some evidence of long-term adverse effects. Imaging techniques have also been tested for this purpose, but their validity has not been confirmed and they do appear to be problematic. CONCLUSIONS: A reliable diagnostic tool that could help a clinician to determine if a disc is the source of the pain in patients with chronic LBP is still not available. New MRI techniques are under investigation that could result in a significant improvement over current methods, particularly as they can allow monitoring, not only of morphological but also of biochemical changes.

Disc degeneration-related clinical phenotypes.

The phenotype, or observable trait of interest, is at the core of studies identifying associated genetic variants and their functional pathways, as well as diagnostics. Yet, despite remarkable technological developments in genotyping and progress in genetic research, relatively little attention has been paid to the equally important issue of phenotype. This is especially true for disc degeneration-related disorders, and the concept of degenerative disc disease, in particular, where there is little consensus or uniformity of definition. Greater attention and rigour are clearly needed in the development of disc degeneration-related clinical phenotypes if we are to see more rapid advancements in knowledge of this area. When selecting phenotypes, a basic decision is whether to focus directly on the complex clinical phenotype (e.g. the clinical syndrome of spinal stenosis), which is ultimately of interest, or an intermediate phenotype (e.g. dural sac cross-sectional area). While both have advantages, it cannot be assumed that associated gene variants will be similarly relevant to both. Among other considerations are factors influencing phenotype identification, comorbidities that are often present, and measurement issues. Genodisc, the European research consortium project on disc-related clinical pathologies has adopted a strategy that will allow for the careful characterisation and examination of both the complex clinical phenotypes of interest and their components.

Rehabilitation following surgery for lumbar spinal stenosis.

BACKGROUND: Lumbar spinal stenosis is a common cause of back pain that can also give rise to pain in the buttock, thigh or leg, particularly when walking. Several possible treatments are available, of which surgery appears to be best at restoring function and reducing pain. Surgical outcome is not ideal, and a sizeable proportion of patients do not regain good function. No accepted evidence-based approach to postoperative care is known-a fact thathas prompted this review. OBJECTIVES: To determine whether active rehabilitation programmes following primary surgery for lumbar spinal stenosis have an impact on functional outcomes and whether such programmes are superior to 'usual postoperative care'. SEARCH METHODS: We searched the following databases from their first issues to March 2013: CENTRAL (The Cochrane Library, most recent issue), the Cochrane Back Review Group Trials Register, MEDLINE, EMBASE, CINAHL and PEDro. SELECTION CRITERIA: We considered randomised controlled trials (RCTs) that compared the effectiveness of active rehabilitation versus usual care in adults (> 18 years of age) with confirmed lumbar spinal stenosis who had undergone spinal decompressive surgery (with or without fusion) for the first time. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data from the included trials by using a predeveloped form. We contacted authors of original trials to request additional unpublished data as required. We recorded baseline characteristics of participants, interventions, comparisons, follow-up and outcome measures to enable assessment of clinical homogeneity. Clinical relevance was independently assessed by using the five questions recommended by the Cochrane Back Review Group (CBRG), and risk of bias within studies was determined by using CBRG criteria.We pooled individual study results in a meta-analysis when appropriate. For continuous outcomes, we calculated the mean difference (MD) when the same measurement scales were used in all studies and the standardised mean difference (SMD) when different measurement scales were used. Whenreported means and standard deviations of the outcomes showed that outcome data were skewed, we log-transformed data for all studies in the comparison and performed a meta-analysis on the log-scale. Results of analyses performed on the log-scale were converted back to the original scale. We used a fixed-effect inverse variance model to measure treatment effect when no substantial evidence of statistical heterogeneity was found. When we detected substantial statistical heterogeneity, we used a random-effects inverse variance model.The primary outcome measure was functional status as measured by a back-specific functional scale. Secondary outcomes included measures of leg pain, low back pain and global improvement/general health. We considered statistical significance and clinical relevance of outcomes. We used the GRADE approach to assess the overall quality of evidence for each outcome on the basis of five criteria, for which evidence was ranked from high to very low quality, depending on the number of criteria met. MAIN RESULTS: Our searches yielded 1,726 results, and a total of three studies (N = 373 participants) were included in the review and meta-analysis. All studies were deemed to have low risk of bias; no study had unacceptably high dropout rates. Also, no unacceptably unbalanced dropout rates, unacceptably low adherence rates or non-adherence to the protocol or clearly significant unbalanced baseline differences were noted for the primary outcome. Outcomes in the short term (within six months postoperative)Evidence of moderate quality from three RCTs (N = 340) shows that active rehabilitation is more effective than usual care for functional status (log SMD -0.22, 95% confidence interval (CI) -0.44 to 0.00, corresponding to an average percentage improvement (reduction in standardised functional score) of 20%, 95% CI 0% to 36%) and for reported low back pain (log MD -0.18, 95% CI-0.35 to -0.02, corresponding to an average percentage improvement (reduction in VAS score) of 16%, 95% CI 2% to 30%). In contrast, evidence of low quality suggests that rehabilitation is no more effective than usual care for leg pain (log MD -0.17, 95% CI -0.52 to 0.19, corresponding to an average percentage improvement (reduction in VAS score) of 16%, 95% CI 21% worsening to 41% improvement). Low-quality evidence from two RCTs (N = 238) indicates that rehabilitation has no additional benefit on general health status as compared to usual care (MD 1.30, 95% CI -4.45 to 7.06). Outcomes in the long term (at 12 months postoperative)Evidence of moderate quality from three RCTs (N = 373) shows that rehabilitation is more effective than usual care for functional status (log SMD -0.26, 95% CI -0.46 to -0.05, corresponding to an average percentage improvement (reduction in standardised functional score) of 23%, 95% CI 5% to 37%), for reported low back pain (log MD -0.20, 95% CI -0.36 to -0.05, corresponding to an average percentage improvement (reduction in VAS score) of 18%, 95% CI 5% to 30%]. Evidence of moderate quality (N = 373) and for leg pain (log MD -0.24, 95% CI -0.47 to -0.01, corresponding to an average percentage improvement (reduction in VAS score) of 21%, 95% CI 1% to 37%). In contrast, evidence of low quality from two studies (N = 273) suggests that rehabilitation is no more effective than usual care with respect to improvement in general health (MD -0.48, 95% CI -6.41 to 5.4).None of the included papers reported any relevant adverse events. AUTHORS' CONCLUSIONS: Evidence suggests that active rehabilitation is more effective than usual care in improving both short- and long-term (back-related) functional status. Similar findings were noted for secondary outcomes, including short-term improvement in low back pain and long-term improvement in both low back pain and leg pain, although limited impact was observed in relation to improvements in general health status. The clinical relevance of these effects is medium to small. Our evaluation is limited by the small number of relevant studies identified, and further research is required.