Methods

A policy theory approach combining scientific evidence with governance principles in a pragmatic manner was undertaken. This entailed extracting evidence from a recent review of the system influences on work disability due to LBP* (focused specifically on the healthcare system) and appraising it alongside the most recent review evidence on the implementation of clinical guidance, and policy material aimed at developing work-focused healthcare.

Methods

GDF6 receptor expression in patient-matched BM-MSCs and Ad-MSCs (N=6) was profiled through western blot and immunocytochemistry (ICC). GDF6 signal transduction was investigated through stimulation with 100 ng ml⁻¹ GDF6 for defined time periods. Subsequently smad1/5/9 phosphorylation and alternative non-smad pathway activation (phospho-p38; phospho-Erk1/2) was analysed (western blot, ELISA). Their role in inducing NP-like gene expression in Ad-MSCs was examined through pathway specific inhibitors.

Methods

Semi-structured interviews were conducted with 30 low back pain patients who had recently consulted for spinal surgery and were advised that surgery is not indicated. Interview were audio recorded and transcribed, and then coded using NVIVO qualitative software and analysed using the Framework Analysis.

Methods

GDF6 release from PLGA-PEG-PLGA MPs over 14 days was determined using BCA and ELISA. The effect of MP loading density on collagen gel formation was assessed through SEM and histological staining. ASCs were cultured in collagen hydrogels for 14 days with GDF6 delivered exogenously or via microspheres. ASC differentiation was assessed by qPCR for NP markers, glycosaminoglycan production (DMMB) and immunohistochemistry.

Summary of methods used and the results

We describe the results of a prospective series of patients who completed open MRI scanning, indicated for lower back pain and positional sciatica. 40 open MRI scans were requested between March 2012 and March 2017. 31 patients were intolerant to conventional MRI Scanning due to either claustrophobia or the inability to lie flat. 9 patients were identified as having positional sciatica. All patients completed the Oswestry Disability Index as part of their clinical assessment. The MRI images and radiology report were reviewed to identify surgically relevant causes. Dynamic foraminal narrowing and a progressive disc protrusion were identified in 2 patients who presented with positional sciatica. 23% of patients who were scanned had positional sciatica. 5% of patients indicated for open MRI scanning demonstrated surgically relevant changes on dynamic MRI scanning. 22% of those with positional sciatica demonstrated surgically relevant pathology on dynamic scanning.

Methods and results

In this study 159 participants (73 males, mean age=41, SD=19.6) were presented with 16 images of individuals in pain (8 female, 8 male), and subsequently rated their empathy towards them. Participants then completed the fear of pain and health anxiety measures. Both fear of pain and health anxiety were positively associated with empathy for pain, but in the regression model only fear of pain was a significant positive predictor of empathy for pain (p< .001). Further analysis revealed that when controlling for the effects of fear of pain, the correlation between health anxiety and empathy became non-significant. The same results were found when the overall empathy for pain score was split into empathy for male and female images. Observers' sex and age were not significant predictors of empathy for pain.

Methods

Gene expression of all 13 AQPs, were investigated in 102 human NP samples using RT-qPCR. AQPs which were expressed at gene level were further investigated by Immunohistochemistry in human and canine IVD samples.

Methods and results

Intervertebral motion data of L2/3 to L4/5, from a previously published study was used. This examined 40 patients with NSLBP and 40 healthy controls, matched for gender, age and body mass index, who underwent passive recumbent QF in the coronal and sagittal planes. For each motion direction, principal components analysis was carried out and salient dimensions selected. Using a lower dimensional principal components (PC) representation, groups were compared using Hoteling's T test. Linear and quadratic discriminant analysis (LDA and QDA) was carried out using PC representations to examine group differences. The features most clearly distinguishing groups from the LDA was examined graphically. An analysis of the sensitivity of the results to the number of PC dimensions was carried out. The performance of the LDA and QDA classifiers were examined using leave-one-out cross-validation.

Methods

Two evaluations were performed that compared fusion rates between PEMF stimulation and a historical control (160 subjects) from the FDA investigational device exemption (IDE) study: a post hoc (PH) analysis of high-risk subjects from the FDA study (PH PEMF); and a multicentre, open-label (OL) study consisting of 274 subjects treated with PEMF (OL PEMF). Fisher’s exact test and multivariate logistic regression was used to compare fusion rates between PEMF-treated subjects and historical controls.

Methods and results

A systematic review and meta-analysis of pain and disability outcomes in prospective cohort studies after first time LSF for degenerative disorders. Two independent researchers searched key databases, determined study eligibility, extracted data and assessed risk of bias (modified Quality in Prognostic Studies tool). A third reviewer mediated at each stage. N weighted pooled estimates were calculated. Twenty-five articles (n=1,777 participants) were included. 17 studies were at unclear risk of bias and 8 at high risk. Back pain (12 studies) decreased modestly and irregularly at follow-up intervals. The n weighted mean VAS back pain decreased from 65.4 (±3.3) pre-surgery to 22.2 (±3.1) at 23 months, but then 45.0 (±not reported; 2 studies at risk of bias) at 42 months. In contrast, leg pain (12 studies) improved substantially short and long-term. Disability (20 studies) improved steadily over time with the exception of the 42-months and 48-months intervals.

Methods

A prospective observational study will recruit two temporally staggered cohorts (n=250 each cohort; 10 cases per candidate predictor) of consecutive acute musculoskeletal trauma patients aged ≥16 years, who are emergency admissions into a Major Trauma Centre in the United Kingdom, with an episode inception defined as the traumatic event. The first cohort will identify prognostic factors to develop a screening tool to predict development of chronic and disabling pain, and the second will allow evaluation of the predictive performance of the tool (validation). The outcome being predicted is an individual's absolute risk of poor outcome measured at 6-months follow-up using the Chronic Pain Grade Scale (poor outcome ≥Grade II). Candidate predictors encompass the four primary mechanisms of pain: nociceptive (e.g. injury characteristics), neuropathic (e.g. painDETECT), inflammatory (biomarkers), and central hypersensitivity (e.g. quantitative sensory testing). Concurrently, patient-reported outcome measures will assess general health and psychosocial factors. Risk of poor outcome will be calculated using multiple variable regression analysis.

Methods and Results

Data from 77 intervention participants was available (males = 43, females = 34) 37 control participants (males = 20, females = 17). Intervention participants all underwent 12wks of ILEX resistance training and changes in ILEX strength, pain (VAS) and disability (ODI) measured. True inter-individual response variability was examined through calculation of difference in the standard deviation of change scores for both control and intervention. Intervention participants were classified into using k-means cluster analysis for strength changes and using MCIC cut-offs for VAS and ODI. Analysis suggested true inter-individual responses to the intervention existed. Participants were classified for strength changes as low (n = 31), medium (n = 36), and high responders (n = 10). Participants were classified for VAS changes as negative (n = 3), non-responders (n = 34), responders (n = 15), and high responders (n = 19). Participants were classified for ODI changes as negative (n = 2), non-responders (n = 21), responders (n = 29), and high responders (n = 25).

Methods

hMSCs were incorporated within liquid NPgel and injected into bovine NP explants alongside controls. Explants were cultured for 6 weeks under hypoxia (5%) with ± calcium 5.0mM CaCl₂ or IL-1β individually or in combination to mimic the degenerate microenvironment. Cell viability was assessed by caspase 3 immunohistochemistry. Histological and immunohistochemical analysis was performed to investigate altered matrix synthesis and matrix degrading enzyme expression.

Methods

Thoracolumbar spine shape was characterised using statistical shape modelling on lateral dual-energy x-ray absorptiometry images, recorded for vertebral fracture analysis, of the spine from 1529 participants of the MRC National Survey of Health and Development, acquired at age 60–64 years. Associations between spine shape modes (SM) and 1) sex, 2) contemporaneous measures of overall and central adiposity (indicated by body mass index and waist circumference, respectively), 3) changes in total and central adiposity during earlier stages of adulthood and age at onset of overweight, were investigated.

Background

Low back pain (LBP) may worsen with time, making appropriate treatment important. In the NHS Physiotherapy services LBP patients may wait for 14–24 weeks for treatments. Many factors contribute to LBP, but it is predominantly initially viewed as a result of peripheral tissue damage. However, evidence show that persistent LBP is associated with amplification in pain processing in the central nervous system (central sensitisation). Sometimes, this may drive symptoms, resulting in poorer outcomes and requiring longer management. Timely assessment and appropriate management is therefore paramount.

Methods

Twenty male footballers were recruited (n: Injured- 9, Controls- 11). Isolated lumbar extension strength, low back pain, and the contraction time of muscles within the POS during a hip extension test were recorded. Participants were then grouped in either the injury or control group.

Methods

This was a pragmatic cluster randomised trial with a pre-intervention baseline period. Six primary care clinics were pair-randomised, three to an intensive stratified care quality improvement intervention and three as controls. LBP patients were invited to provide outcomes two weeks after their primary care visit, and two and six months later. Primary outcomes were physical function (RMDQ) and pain (0–10 NRS), and secondary outcomes including healthcare use and treatments provided received. Analysis was intention-to-treat.

Patients and Methods

The NERBPP is a clinical pathway based upon NICE guidelines (2009) for LBP. Patients with LBP referred onto the NERBPP by their General Practitioner (GP) between May 2015 and January 2017 were included in this evaluation. Data from 635 patients, who provided pre and post data for pain (Numerical rating scale [NRS]), function (Oswestry Disability Index [ODI]) and quality-of-life (EuroQol [EQ5D]), were analysed using a series of covariate adjusted models in SPSS. Patients were categorised into four groups based upon pain duration: <3months, ≥3 to <6months, ≥6months to <12months, ≥12months.

Methods

Rat sub-cut analysis was performed to investigate safety in vivo. A rat femur defect model was performed to evaluate efficacy. Four groups were investigated: sham operated controls; acellular L-pNIPAM-co-DMAc hydrogel; acellular L-pNIPAM-co-DMAc hydrogel with HAPna; L-pNIPAM-co-DMAc hydrogel with rat MSCs and HAPna. Following 4 weeks, defect site and organs were histologically examined to determine integration, repair and inflammatory response, as well as Micro-CT to assess mineralisation.

Methods

Nucleus pulposus cells were obtained from cows with no overt disc degeneration and patients following spine surgery (for herniations and/or degenerative disc disease) and cultured until confluent before maintaining with or without serum for 24h. Primary cilia were visualised with antibodies to the axoneme (acetylated α-tubulin and Arl13b) and/or the basal body (pericentrin) using fluorescent secondary antibodies and ≥200 cells per sample were counted.

Methods and results

In this qualitative study, based on the principles of interpretative phenomenological analysis, 14 participants with a clinical presentation of sciatica of likely nerve root origin, who had recently undergone investigations, were purposively recruited from an NHS, Primary Care Musculoskeletal Service in the UK. Individual, semi-structured interviews were used to collect data, which were audio-recorded and transcribed verbatim. Data were managed using a framework approach and analysed thematically.

Although patients reported wanting investigations to understand the cause of symptoms and inform management, access to them was difficult and protracted. When investigations revealed potentially relevant findings, patients experienced relief, validation, empowerment and decisive decision-making. Disappointment emerged, however, regarding treatment waiting times and options, and long-term prognosis. When investigations failed to identify relevant findings, patients were unable to make sense of their symptoms, move forward in their management or relinquish their search to identify the cause.

Summary of methods and results

This was a blinded parallel two-arm pilot randomised controlled trial. Adult patients referred to the pain and orthopaedic clinics at Barts Health NHS Trust with non-specific low back pain of at least three months' duration were considered for inclusion.

Participants who had a positive result following diagnostic single medial branch nerve blocks were randomised to receive either intra-articular lumbar facet-joint injections with steroid or a sham procedure. All participants were invited to attend a combined physical and psychological programme.

Questionnaires were used to assess a range of pain and disability-related issues. Healthcare utilisation and cost data were also assessed.

Of 628 participants screened for eligibility, 9 were randomised to receive the study intervention and 8 participants completed the study.

Methods

BMP receptor expression profile of non-degenerate and degenerate human NP cells was determined through western blot, immunofluorescence and qPCR. Phosphorylation statuses of Smad1/5/9 and non-canonical p38 MAPK and Erk1/2 were assessed in the presence/absence of pathway blockers. NP marker and matrix degrading enzyme gene expression was determined by qPCR following GDF6 stimulation. Glycosaminoglycan and collagen production were assessed through DMMB-assay and histochemical staining.

Methods and Results

In order to identify these complexities, a review of the background literature was undertaken in addition to a Patient and Public Involvement and Engagement (PPIE) session. The PPIE group consisted of eight older adults who experience chronic musculoskeletal pain. This session was used to discuss and explore what factors are important to consider in GP consultations for musculoskeletal pain for older adults, in addition to those identified through background literature. A number of factors were highlighted through these methods, including the difference in mood and aspirations for older adults; taking a holistic approach; the impact of comorbidities; whether the GP is listening and ‘on the same wavelength’, and older adults' expectations regarding their pain and the consultation.

Methods

Data were collected from 607 primary care patients consulting with LBLP and assessed by 7 physiotherapists, in the ATLAS cohort study. Following clinical assessment, physiotherapists documented whether he/she wanted the patient to have an MRI. Factors potentially associated with clinicians' preference for imaging were selected a priori, from patient characteristics and clinical assessment findings. A mixed-effect logistic regression model examined the associations between these factors and physiotherapists' preference for MRI.

Methods

We used recruitment data from the SCOPiC trial and its internal pilot, to show the differences between estimated and actual numbers of patients from consultation to participation in the trial. Patients were consented to the trial if they had a clinical diagnosis of sciatica (with at least 70% confidence) and met the trial eligibility criteria.

Methods and results

A qualitative research design with a constructivist grounded theory approach was used for semi-structured interviews and data collection/analysis. A purposive sample of eight physiotherapists practicing in Italy and having experience with patients presenting chronic musculoskeletal problems were recruited from private clinics.

Three main categories were constructed:

1)

Conceptions of the biopsychosocial model and its role in CLBP;

The study revealed partial identification of these factors, limited understanding of the role they play in CLBP and lack of standardization in this area within the manipulative physiotherapy profession.

Methods & Results

Porcine notochordal cells were isolated from 6 week post natal discs using dissection and enzymatic digestion and cultured in vitro under different conditions: (1)DMEM vs αMEM (2)laminin-521, fibronectin, gelatin and untreated tissue culture plastic (3)2% 02 vs normoxia (4)αMEM (300 mOsm/L) vs αMEM (400 mOsm/L). Notochordal cells were cultured in alginate beads as a control. Adherence, cell viability, morphology and expression of known notochordal markers (CD24, KRT8, KRT18, KRT19 and T) were assessed throughout the culture period. Use of αMEM media and laminin-521 coated surfaces displayed the greatest cell adherence, viability and retention of notochordal cell morphology and gene expression, which was further enhanced through culture in hypoxia and hyperosmolar media mimicking the intervertebral disc niche.

Background and pathway

Changes to back and neck pain commissioning by our CCG required GPs not to refer to manual therapy until six weeks and upgrade GP care beyond that previous.

100 consecutive patients requesting GP appointment reporting back/neck pain were directed to a pragmatic service provided by an experienced manual therapy practitioner. Cognitive Reassurance reflecting evidenced informed biopsychosocial and salutogenic thinking was given at initial consultation/assessment. Patients were contacted at 10 and 20 days to ascertain their status. One sub-group suggested an opportunity for long-term follow-up.

Pilot Objectives

Providing Cognitive Reassurance for achieving greater levels of patient engagement with self-management

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Outcomes 100 patients

Outcomes 36 patients decided at 20 days no further treatment needed

Methods & Results

The Steering Committee overseeing this project selected 17 potential core instruments for physical functioning, three for pain intensity, and five for HRQoL. Evidence on their measurement properties in nsLBP was synthesized in three systematic reviews using COSMIN methodology. Researchers, clinicians, and patients (n = 208) were invited in a Delphi survey to seek consensus on which instruments to endorse as core. Consensus was a-priori set at 67% of participants agreeing on endorsing an instrument. Two Delphi rounds were run (response rates = 44% and 41%). Agreement was reached on endorsing the Oswestry Disability Index (ODI 2.1a) for physical functioning, the Numeric Rating Scale (NRS) for pain intensity, but not on other instruments. Several participants demanded to have free of charge core instruments. Taking these results into account, the steering committee formulated the following recommendations: ODI 2.1a or 24-item Roland Morris Disability Questionnaire for physical functioning, NRS for pain intensity, Short-Form 12 or 10-item PROMIS Global Health for HRQoL.

Method

Qualitative, semi-structured interviews with NS-CLBP patients, physiotherapists, and doctors conducted using purposeful sampling of 6–11 people from each group. The interviews were recorded, transcribed and analysed using framework analysis. Validity was ensured by data triangulation with participants.

Background

The BeST programme is a group Cognitive Behavioural Approach (CBA) for people with persistent (≥6 weeks) low back pain (LBP). This intervention has been shown to be clinically and cost-effective in a large pragmatic trial. To aid implementation of the BeST programme, an online training intervention (iBeST) was developed.

Methods

A previously validated FE model of the human body in the driver-occupant position was used to investigate cervical hyperextension injury. The cervical spine was subjected to simulated whiplash exposure in accordance with Euro NCAP (the European New Car Assessment Programme) testing using the whole human FE model. The coupled motions between the cervical spine and lumbar spine were assessed by evaluating the biomechanical effects of simulated cervical fusion and lumbar fusion.

Purpose

To improve the management of atraumatic spinal pain patients admitted onto the emergency assessment unit (EAU) thus improving quality of care, reducing bed stay and facilitating appropriate discharge and follow-up within an interdisciplinary model.

Methods

The study population were 609 LBLP primary care consulters. Variables from clinical assessment were included in the LCA. Characteristics of the statistically identified clusters were described and compared to the clinically defined groups of LBLP patients.

Method

The spine was modelled according to easily identifiable anatomical landmarks, including upper thoracic (T1-T6), lower thoracic (T7-T12) and lumbar (L1-L5) segments. Pelvis, thigh, shank and foot segments were included. A 10-camera 3D motion capture system was used to track retro-reflective markers, which were used to define each segment of 10 healthy participants as they walked 3 times at a comfortable speed over a 6km walkway. The relative peak angles between each segment were calculated using the Joint Coordinate System convention and Intraclass Correlation Coefficients (ICCs) were used to determine intra-rater and inter-rater reliability (between an experienced clinician and biomechanical scientist).

Methods

A sample of 21 healthy, asymptomatic subjects participated (mean age 56.9 years). T2-weighted axial lumbar images were obtained (L3/L4 to L5/S1), with slices oriented through the centre of each disc. Scans were examined by a Consultant MRI specialist and divided into 2 groups dependent on Modic presence (M) or absence (NM). Bilateral measurements of the CSA and FCSA of the erector spinae, multifidus, psoas major and quadratus lumborum were made using Image-J software. Muscle composition was determined using the equation [(FCSA/CSA)*100] and asymmetry using the equation [(Largest FCSA-smallest FCSA)/largest FCSA*100]. Data were analysed using Mann-Whitney U tests (p value set at). Intrarater reliability was examined using Intraclass Correlations (ICCs).

Methods

hMSCs were encapsulated in NPgel and cultured for 4 weeks under hypoxia (5%) with ± calcium (2.5mM and 5.0mM CaCl₂), IL-1β and TNFα either individually or in combination to mimic the degenerate microenvironment. Cell viability was assessed by Alamar blue assay. Histological and immunohistochemical analysis investigated altered matrix and matrix degrading enzyme expression.

Methods

We included data from 4′940 patients documented in Eurospine's Spine Tango Registry from 2004 to 2015. Medical history and surgical details were documented on the Tango Surgery form, as were surgical and general medical complications arising between admission and discharge. Multiple logistic regression models were built to investigate the relationship between the number of any previous surgeries and the presence of a perioperative complication, controlling for other potential confounders (age, sex, smoking, BMI, comorbidity, number of vertebral levels affected).

Methods

Patients over 70 years old who visited an outpatient clinic for back pain treatment and underwent a standing whole-body radiograph were enrolled. Falls were prospectively assessed for 12 months using a monthly fall diary, and patients were divided into fallers and non-fallers according to the history of falls. Radiological parameters from whole-body radiographs and clinical data were compared between the two groups.

Methods

185 pairs of twins were selected from the TwinsUK database having cervical MRI scans at baseline and at follow-up, after 10 years. Isolated disc degeneration (IDD) was diagnosed in subjects having severe loss in disc height (graded 3/3) in a single disc, whilst discs immediately adjacent manifested little or no degeneration (graded 0 or 1). The controls' ‘adjacent discs’ were considered at the same levels as their affected co-twins.

Methods

hMSCs were injected either alone or within NPgel, into bovine NP tissue explants and maintained at 5% O₂ for up to 6wks. Media alone and acellular NPgel were also injected into NP explants to serve as controls. Cell viability was assessed by Caspase 3 immunohistochemistry and the phenotype of injected hMSC was assessed by histology and immunohistochemistry. Mechanical properties were also assessed via dynamic mechanical analysis (DMA).

Background

The endplate is key in both the mechanics, anchoring and nutrition of the disc. Understanding the detailed structure of the normal and pathological endplate is important for understanding how it achieves its functions.

Advancements in imaging technology continually allow for greater understanding of biological structures. The development of two-photon fluorescence (TPF) combined with second harmonic generation (SHG), allows for the imaging of relatively thick, fresh samples without the need for staining.

Methods

A ‘best-evidence’ synthesis was conducted to collate the evidence on those ‘black flags’ proposed to be the most important: compensatory systems (worker's compensation and disability benefits), healthcare provider systems and ‘significant others’ (spouse/partner/close family members). A systematic search of scientific and grey literature databases was performed, and the validity and merit of the available evidence was assessed using a system adapted from previous large-scale policy reviews conducted in this field.

Method

Referral onto the programme occurred through triage and treat practitioners or consultant clinics. A total of 44 patients were referred, with 31 attending the programme. The programme was delivered as a 3 week residential programme, with patients present 9am-5pm Monday to Thursday. A MDT provided an intense programme consisting of education, physical exercise, practical coping strategies and group discussion. The work has received ethical approval from the School of Health and Social Care Research Ethics and Governance committee at Teesside University.

Objectives

Explore barriers and facilitators to engaging in PA in adults accessing pain services.

Methods

Rat MSCs were seeded onto fibronectin coated auxetic foams at a cell density of 6.4 × 10³ cells/mm³, and cultured for up to 3 weeks. Cell viability was assessed throughout culture and following culture scanning electron microscopy (SEM) was used to assess morphological characteristics. Histological assessment was performed to assess production of matrix proteins.

Conclusion

The findings of this research have been utilised, working with patients as partners, to establish clear, sensitive and understandable language to use during clinical questioning of potential CES patients. This patient choice of language for sensitive questions has been replicated on a clinical cue card to use during the consultation and on a credit card sized leaflet to give to patients. Working with patients, clear methods of communication have been developed surrounding potentially embarrassing but critical symptoms in order to assist ‘bringing the individual patient and the surgical team together at the earliest practical opportunity’

No conflicts of interest

Source of funding; Physiotherapy Research Foundation (Part of the CSP Charitable Trust registered charity 279882)

Methods and Results

Recruitment has taken place over 15 months. Invitation letters or emails were sent to individual practitioners identified using online search tools and professional networks. Recruitment rates were analysed descriptively. Within the private sector, response rates (number participating/number invited) are: acupuncturists 3% (49/1561), osteopaths 6% (53/912), physiotherapists 4% (40/1048). Private sector practitioners have each recruited on average 1, 4, and 2 patients into the study respectively. Within the NHS, the response rates are: acupuncturists 100% (2/2), osteopaths 8% (1/13), physiotherapists 63% (44/70). NHS practitioners have each recruited on average 4, 3, and 2 patients respectively.

Purpose of the study

The purpose of this study was to investigate the value of physiotherapy in the treatment of DHS by case series analysis.