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1.
Bone Joint J ; 105-B(9): 1007-1012, 2023 09 01.
Article in English | MEDLINE | ID: mdl-37652459

ABSTRACT

Aims: Patients with cauda equina syndrome (CES) require emergency imaging and surgical decompression. The severity and type of symptoms may influence the timing of imaging and surgery, and help predict the patient's prognosis. Categories of CES attempt to group patients for management and prognostication purposes. We aimed in this study to assess the inter-rater reliability of dividing patients with CES into categories to assess whether they can be reliably applied in clinical practice and in research. Methods: A literature review was undertaken to identify published descriptions of categories of CES. A total of 100 real anonymized clinical vignettes of patients diagnosed with CES from the Understanding Cauda Equina Syndrome (UCES) study were reviewed by consultant spinal surgeons, neurosurgical registrars, and medical students. All were provided with published category definitions and asked to decide whether each patient had 'suspected CES'; 'early CES'; 'incomplete CES'; or 'CES with urinary retention'. Inter-rater agreement was assessed for all categories, for all raters, and for each group of raters using Fleiss's kappa. Results: Each of the 100 participants were rated by four medical students, five neurosurgical registrars, and four consultant spinal surgeons. No groups achieved reasonable inter-rater agreement for any of the categories. CES with retention versus all other categories had the highest inter-rater agreement (kappa 0.34 (95% confidence interval 0.27 to 0.31); minimal agreement). There was no improvement in inter-rater agreement with clinical experience. Across all categories, registrars agreed with each other most often (kappa 0.41), followed by medical students (kappa 0.39). Consultant spinal surgeons had the lowest inter-rater agreement (kappa 0.17). Conclusion: Inter-rater agreement for categorizing CES is low among clinicians who regularly manage these patients. CES categories should be used with caution in clinical practice and research studies, as groups may be heterogenous and not comparable.


Subject(s)
Cauda Equina Syndrome , Surgeons , Humans , Cauda Equina Syndrome/diagnosis , Cauda Equina Syndrome/surgery , Reproducibility of Results , Decompression, Surgical
2.
J Virol ; 97(8): e0068423, 2023 08 31.
Article in English | MEDLINE | ID: mdl-37555663

ABSTRACT

With increasing resistance of SARS-CoV-2 variants to antibodies, there is interest in developing entry inhibitors that target essential receptor-binding regions of the viral Spike protein and thereby present a high bar for viral resistance. Such inhibitors could be derivatives of the viral receptor, ACE2, or peptides engineered to interact specifically with the Spike receptor-binding pocket. We compared the efficacy of a series of both types of entry inhibitors, constructed as fusions to an antibody Fc domain. Such a design can increase protein stability and act to both neutralize free virus and recruit effector functions to clear infected cells. We tested the reagents against prototype variants of SARS-CoV-2, using both Spike pseudotyped vesicular stomatitis virus vectors and replication-competent viruses. These analyses revealed that an optimized ACE2 derivative could neutralize all variants we tested with high efficacy. In contrast, the Spike-binding peptides had varying activities against different variants, with resistance observed in the Spike proteins from Beta, Gamma, and Omicron (BA.1 and BA.5). The resistance mapped to mutations at Spike residues K417 and N501 and could be overcome for one of the peptides by linking two copies in tandem, effectively creating a tetrameric reagent in the Fc fusion. Finally, both the optimized ACE2 and tetrameric peptide inhibitors provided some protection to human ACE2 transgenic mice challenged with the SARS-CoV-2 Delta variant, which typically causes death in this model within 7-9 days. IMPORTANCE The increasing resistance of SARS-CoV-2 variants to therapeutic antibodies has highlighted the need for new treatment options, especially in individuals who do not respond to vaccination. Receptor decoys that block viral entry are an attractive approach because of the presumed high bar to developing viral resistance. Here, we compare two entry inhibitors based on derivatives of the ACE2 receptor, or engineered peptides that bind to the receptor-binding pocket of the SARS-CoV-2 Spike protein. In each case, the inhibitors were fused to immunoglobulin Fc domains, which can further enhance therapeutic properties, and compared for activity against different SARS-CoV-2 variants. Potent inhibition against multiple SARS-CoV-2 variants was demonstrated in vitro, and even relatively low single doses of optimized reagents provided some protection in a mouse model, confirming their potential as an alternative to antibody therapies.


Subject(s)
COVID-19 , HIV Fusion Inhibitors , Animals , Mice , Humans , SARS-CoV-2/genetics , Angiotensin-Converting Enzyme 2/genetics , Spike Glycoprotein, Coronavirus/genetics , Mice, Transgenic , Peptides/pharmacology
4.
Lancet Reg Health Eur ; 24: 100545, 2023 Jan.
Article in English | MEDLINE | ID: mdl-36426378

ABSTRACT

Background: Cauda equina syndrome (CES) results from nerve root compression in the lumbosacral spine, usually due to a prolapsed intervertebral disc. Evidence for management of CES is limited by its infrequent occurrence and lack of standardised clinical definitions and outcome measures. Methods: This is a prospective multi-centre observational cohort study of adults with CES in the UK. We assessed presentation, investigation, management, and all Core Outcome Set domains up to one year post-operatively using clinician and participant reporting. Univariable and multivariable associations with the Oswestry Disability Index (ODI) and urinary outcomes were investigated. Findings: In 621 participants with CES, catheterisation for urinary retention was required pre-operatively in 31% (191/615). At discharge, only 13% (78/616) required a catheter. Median time to surgery from symptom onset was 3 days (IQR:1-8) with 32% (175/545) undergoing surgery within 48 h. Earlier surgery was associated with catheterisation (OR:2.2, 95%CI:1.5-3.3) but not with admission ODI or radiological compression. In multivariable analyses catheter requirement at discharge was associated with pre-operative catheterisation (OR:10.6, 95%CI:5.8-20.4) and one-year ODI was associated with presentation ODI (r = 0.3, 95%CI:0.2-0.4), but neither outcome was associated with time to surgery or radiological compression. Additional healthcare services were required by 65% (320/490) during one year follow up. Interpretation: Post-operative functional improvement occurred even in those presenting with urinary retention. There was no association between outcomes and time to surgery in this observational study. Significant healthcare needs remained post-operatively. Funding: DCN Endowment Fund funded study administration. Castor EDC provided database use. No other study funding was received.

5.
Viruses ; 16(1)2023 12 29.
Article in English | MEDLINE | ID: mdl-38257760

ABSTRACT

BACKGROUND: SARS-CoV-2 is a respiratory virus with neurological complications including the loss of smell and taste, headache, and confusion that can persist for months or longer. Severe neuronal cell damage has also been reported in some cases. The objective of this study was to compare the infectivity of the wild-type virus, Delta (B.1.617.2) and Omicron (B.1.1.529) variants in transgenic mice that express the human angiotensin-converting enzyme 2 (hACE2) receptor under the control of the keratin 18 promoter (K18) and characterize the progression of infection and inflammatory response in the lungs, brain, medulla oblongata, and olfactory bulbs of these animals. We hypothesized that wild type, Delta and Omicron differentially infect K18-hACE2 mice, thereby inducing distinct cellular responses. METHODS: K18-hACE2 female mice were intranasally infected with wild-type, Delta, or Omicron variants and euthanized either at 3 days post-infection (dpi) or at the humane endpoint. None of the animals infected with the Omicron variant reached the humane endpoint and were euthanized at day 8 dpi. Virological and immunological analyses were performed in the lungs, brains, medulla oblongata and olfactory bulbs isolated from infected mice. RESULTS: At 3 dpi, mice infected with wild type and Delta displayed significantly higher levels of viral RNA in the lungs than mice infected with Omicron, while in the brain, Delta and Omicron resulted in higher levels of viral RNA than with the wild type. Viral RNA was also detected in the medulla oblongata of mice infected by all these virus strains. At this time point, the mice infected with wild type and Delta displayed a marked upregulation of many inflammatory markers in the lungs. On the other hand, the upregulation of inflammatory markers was observed only in the brains of mice infected with Delta and Omicron. At the humane endpoint, we observed a significant increase in the levels of viral RNA in the lungs and brains of mice infected with wild type and Delta, which was accompanied by the elevated expression of many inflammatory markers. In contrast, mice which survived infection with the Omicron variant showed high levels of viral RNA and the upregulation of cytokine and chemokine expression only in the lungs at 8 dpi, suggesting that infection and inflammatory response by this variant is attenuated in the brain. Reduced RNA levels and the downregulation of inflammatory markers was also observed in the medulla oblongata and olfactory bulbs of mice infected with Omicron at 8 dpi as compared with mice infected with wild-type and Delta at the humane end point. Collectively, these data demonstrate that wild-type, Delta, and Omicron SARS-CoV-2 induce distinct levels of infection and inflammatory responses in K18-hACE2 mice. Notably, sustained brain infection accompanied by the upregulation of inflammatory markers is a critical outcome in mice infected with wild type and Delta but not Omicron.


Subject(s)
Angiotensin-Converting Enzyme 2 , COVID-19 , Animals , Female , Humans , Mice , Angiotensin-Converting Enzyme 2/genetics , COVID-19/pathology , Keratin-18 , Mice, Transgenic , RNA, Viral/genetics , SARS-CoV-2/genetics
6.
Front Cell Infect Microbiol ; 12: 958240, 2022.
Article in English | MEDLINE | ID: mdl-36072228

ABSTRACT

Suboptimal efficacy of the current antibiotic regimens and frequent emergence of antibiotic-resistant Mycobacterium tuberculosis (Mtb), an etiological agent of tuberculosis (TB), render TB the world's deadliest infectious disease before the COVID-19 outbreak. Our outdated TB treatment method is designed to eradicate actively replicating populations of Mtb. Unfortunately, accumulating evidence suggests that a small population of Mtb can survive antimycobacterial pressure of antibiotics by entering a "persister" state (slowly replicating or non-replicating and lacking a stably heritable antibiotic resistance, termed drug tolerance). The formation of drug-tolerant Mtb persisters is associated with TB treatment failure and is thought to be an adaptive strategy for eventual development of permanent genetic mutation-mediated drug resistance. Thus, the molecular mechanisms behind persister formation and drug tolerance acquisition are a source of new antibiotic targets to eradicate both Mtb persisters and drug-resistant Mtb. As Mtb persisters are genetically identical to antibiotic susceptible populations, metabolomics has emerged as a vital biochemical tool to differentiate these populations by determining phenotypic shifts and metabolic reprogramming. Metabolomics, which provides detailed insights into the molecular basis of drug tolerance and resistance in Mtb, has unique advantages over other techniques by its ability to identify specific metabolic differences between the two genetically identical populations. This review summarizes the recent advances in our understanding of the metabolic adaptations used by Mtb persisters to achieve intrinsic drug tolerance and facilitate the emergence of drug resistance. These findings present metabolomics as a powerful tool to identify previously unexplored antibiotic targets and improved combinations of drug regimens against drug-resistant TB infection.


Subject(s)
COVID-19 , Mycobacterium tuberculosis , Tuberculosis, Lymph Node , Tuberculosis, Multidrug-Resistant , Antitubercular Agents/pharmacology , Antitubercular Agents/therapeutic use , Carbon , Drug Resistance , Drug Tolerance , Humans , Tuberculosis, Multidrug-Resistant/drug therapy
7.
BMC Musculoskelet Disord ; 22(1): 896, 2021 Oct 21.
Article in English | MEDLINE | ID: mdl-34674677

ABSTRACT

BACKGROUND: There is a need to improve consultations between patients with persistent musculoskeletal low back pain and orthopaedic spine clinicians when surgery is not indicated. Poor communication and lack of education about self- management in these consultations have been shown to be associated with increased distress and higher subsequent health care seeking. AIM: To develop a standardised intervention to improve spine care consultations for patients for whom surgery is not beneficial. METHOD: The intervention was developed in six stages. The first three stages included: interviews with patients, an interactive workshop with clinicians from a mix of disciplines, and interviews with spine clinicians about their perspective of the recommendations, their perceived difficulties and potential improvements. Information from these stages was synthesised by an expert panel, creating a draft intervention structure and content. The main features of the intervention and the materials developed were then reviewed by patients and spine clinicians. Finally, the research team incorporated the recommended amendments to produce the intervention. RESULTS: In total, 36 patients and 79 clinicians contributed to the development of the intervention. The final intervention includes three components: a pre-consultation letter with information suggesting that surgery is one possible intervention amongst many, introducing the staff, and alerting patients to bring with them a potted history of interventions tried previously. The intervention includes short online training sessions to improve clinicians' communication skills, during the consultation, in reference to listening skills, validation of patients' pain, and use of appropriate language. Clinicians are also supplied with a list of evidence-based sources for advice and further information to share with patients. Finally, post consultation, a follow up letter includes a short summary of the patients' clinical journey, the results of their examination and tests, and a reminder of recommendations for self-management. CONCLUSION: The intervention includes aspects around patient education and enhanced clinician skills. It was developed with input from a multitude of stakeholders and is based on patients' perceptions of what they would find reassuring and empowering when surgery is excluded. The intervention has the potential to improve the patients care journey and might lead to changes in practice in spine clinicians.


Subject(s)
Low Back Pain , Orthopedics , Self-Management , Humans , Low Back Pain/diagnosis , Low Back Pain/therapy , Patient Acceptance of Health Care , Referral and Consultation
8.
BMJ Open ; 11(9): e052938, 2021 09 16.
Article in English | MEDLINE | ID: mdl-34531223

ABSTRACT

OBJECTIVE: This study aimed to explore the perceptions of orthopaedic clinicians about consultations for people with persistent musculoskeletal low back pain (PMLBP) in which surgery is not recommended. Surgery is not recommended for the majority of PMLBP consulting in secondary care settings. SETTING: Secondary care sector in the UK. PARTICIPANTS: Semi-structured qualitative interviews were conducted with 24 orthopaedic team clinicians from 17 different hospitals in the UK and Ireland. Interviews explored clinicians' perceptions of the challenges in consultations where surgery is not indicated. Interviews were transcribed verbatim and analysed using thematic analysis. RESULTS: Two meta-themes, Difficulties and Enablers, each consisting of several subthemes were identified. Difficulties included challenges around the choice of appropriate terminology and labels for PMLBP, managing patients' expectations, working with mentally vulnerable patients and explaining imaging findings. Enablers included early management of expectations, use of routine imaging, triaging, access to direct referral elsewhere, including other non-surgical practitioners in the team, training to improve communication skills and understanding of psychological issues. CONCLUSION: The findings highlight clinicians' perceived need for concordance in messages delivered across the care pathway and training of orthopaedic clinicians to deliver effective reassurance and address patients' needs in circumstances where surgery is not indicated.


Subject(s)
Ice Cream , Low Back Pain , Orthopedics , Humans , Perception , Qualitative Research , Referral and Consultation
9.
Asian Spine J ; 15(2): 224-233, 2021 Apr.
Article in English | MEDLINE | ID: mdl-32703922

ABSTRACT

STUDY DESIGN: Prospective study. PURPOSE: Yellow flags are psychosocial associated with a greater likelihood of progression to persistent pain and disability. These are referred to as obstacles to recovery. Despite their recognized importance, it is unknown how effective clinicians are in detecting them. The primary objective of this study was thus to determine the effectiveness of spine specialist clinicians in detecting the presence of yellow flags in patients presenting to an orthopedic outpatient clinic with low back-related disorders. OVERVIEW OF LITERATURE: Psychosocial factors have been previously studied as important predictors of prognosis in patients with low back pain. However, the ability of spinal specialist to identify them remains unknown. METHODS: A prospective, single-center, consecutive cohort study was conducted over a period of 30 months. All new patients with low back-related disorders regardless of pathology completed a Yellow Flag Questionnaire that was adapted from the psychosocial flags framework. Clinicians assessing these patients completed a standardized form to determine which and how many yellow flags they had identified during the consultation. RESULTS: A total of 130 patients were included in the analysis, and the clinicians reported an average of 5 flags (range, 0-9). Fear of movement or injury was the most frequently reported yellow flag, reported by 87.7% (n=114) of patients. Clinician sensitivity in detecting yellow flags was poor, correctly identifying only 2 flags, on average, of the 5 reported by patients, with an overall sensitivity of only 39%. CONCLUSIONS: The ability of spine specialists to identify yellow flags is poor and can be improved by asking patients to complete a simple screening questionnaire.

10.
BMJ Open ; 8(12): e025230, 2018 12 14.
Article in English | MEDLINE | ID: mdl-30552283

ABSTRACT

INTRODUCTION: Cauda equina syndrome (CES) is a potentially devastating condition caused by compression of the cauda equina nerve roots. This can result in bowel, bladder and sexual dysfunction plus lower limb weakness, numbness and pain. CES occurs infrequently, but has serious potential morbidity and medicolegal consequences. This study aims to identify and describe the presentation and management of patients with CES in the UK. METHODS AND ANALYSIS: Understanding Cauda Equina Syndrome (UCES) is a prospective and collaborative multicentre cohort study of adult patients with confirmed CES managed at specialist spinal centres in the UK. Participants will be identified using neurosurgical and orthopaedic trainee networks to screen referrals to spinal centres. Details of presentation, investigations, management and service usage will be recorded. Both patient-reported and clinician-reported outcome measures will be assessed for 1 year after surgery. This will establish the incidence of CES, current investigation and management practices, and adherence to national standards of care. Outcomes will be stratified by clinical presentation and patient management. Accurate and up to date information about the presentation, management and outcome of patients with CES will inform standards of service design and delivery for this important but infrequent condition. ETHICS AND DISSEMINATION: UCES received a favourable ethical opinion from the South East Scotland Research Ethics Committee 02 (Reference: 18/SS/0047; IRAS ID: 233515). All spinal centres managing patients with CES in the UK will be encouraged to participate in UCES. Study results will be published in medical journals and shared with local participating sites. TRIAL REGISTRATION NUMBER: ISRCTN16828522; Pre-results.


Subject(s)
Cauda Equina Syndrome/diagnosis , Cauda Equina Syndrome/surgery , Adolescent , Cauda Equina Syndrome/complications , Cauda Equina Syndrome/epidemiology , Child , Guideline Adherence , Humans , Incidence , Interdisciplinary Communication , Neurosurgical Procedures , Orthopedic Procedures , Outcome Assessment, Health Care , Prospective Studies , Standard of Care , Treatment Outcome , United Kingdom/epidemiology
13.
Spine J ; 16(4 Suppl): S3-4, 2016 Apr.
Article in English | MEDLINE | ID: mdl-26996055
14.
J Biol Chem ; 290(16): 10472-85, 2015 Apr 17.
Article in English | MEDLINE | ID: mdl-25759386

ABSTRACT

In this study, we used gene targeting in mice to identify the in vivo functions of PKD1. In addition to phenotypically characterizing the resulting knock-out animals, we also used mouse embryonic fibroblasts to investigate the associated signaling pathways in detail. This study is the first to use genetic deletion to reveal that PKD1 is a key regulator involved in determining the threshold of mitochondrial depolarization that leads to the production of reactive oxygen species. In addition, we also provide clear evidence that PKCδ is upstream of PKD1 in this process and acts as the activating kinase of PKD1. Therefore, our in vivo data indicate that PKD1 functions not only in the context of aging but also during nutrient deprivation, which occurs during specific phases of tumor growth.


Subject(s)
Fibroblasts/metabolism , Membrane Potential, Mitochondrial/genetics , Mitochondria/metabolism , Protein Kinase C-delta/genetics , Signal Transduction/genetics , TRPP Cation Channels/genetics , Animals , Embryo, Mammalian , Female , Fibroblasts/drug effects , Fibroblasts/pathology , Gene Expression Regulation , Hydrogen Peroxide/pharmacology , Male , Membrane Potential, Mitochondrial/drug effects , Mice , Mice, Knockout , Mitochondria/drug effects , Mitochondria/pathology , Oxidative Stress , Primary Cell Culture , Protein Kinase C-delta/metabolism , Reactive Oxygen Species/metabolism , TRPP Cation Channels/deficiency
15.
J Spinal Disord Tech ; 28(3): 80-8, 2015 Apr.
Article in English | MEDLINE | ID: mdl-22820280

ABSTRACT

STUDY DESIGN: Prospective cohort study. OBJECTIVE: Prospectively compare patient-reported as well as clinical and radiologic outcomes after anterior or posterior surgery for right thoracic adolescent idiopathic scoliosis (AIS) in a single center by the same surgeons. SUMMARY OF BACKGROUND DATA: Anterior and posterior spinal instrumentation and arthrodesis are both well-established treatments of thoracic AIS. The majority of studies comparing the 2 approaches have focused on radiographic outcomes. There remains a paucity of prospectively gathered patient-reported outcomes comparing surgical approaches. METHODS: Forty-two consecutive patients with right thoracic AIS were treated in a single center by one of 2 surgeons with either anterior (n=18) or posterior (n=24) approaches and followed up for over 2 years. Radiographic, clinical, and patient-reported outcomes of the Modified Scoliosis Research Society Outcome Instrument were gathered and analyzed by an independent surgeon. RESULTS: Patients reported significant improvements in all areas of the Modified Scoliosis Research Society Outcome Instrument, especially pain and self-image domains. There were no significant differences in the degree of improvement in any domains between the groups. Posterior and anterior surgery corrected rib hump by 53% and 61%, respectively (P=0.4). The Main thoracic curve Cobb angle was corrected from 69 to 26 degrees (62%) by posterior surgery and 61 to 23 degrees (64%) by anterior surgery (P=0.6). Posterior surgery significantly reduced kyphosis and lumbosacral lordosis. Anterior surgery had no overall affect of sagittal alignment but seemed able to correct those hypokyphotic preoperatively. Complications differed and were largely approach-related--intrathoracic in anterior and wound-related in posterior surgery. CONCLUSIONS: Patients with right thoracic AIS of differing curve types but otherwise similar preoperatively demonstrated that anterior and posterior surgery are largely equivalent. Patient-reported outcomes are improved similarly by either approach. Both offer excellent radiographic and trunk deformity correction. Differences in the effect of sagittal alignment, operative time, and complications should be considered when selecting approach.


Subject(s)
Patient Satisfaction , Scoliosis/surgery , Spinal Fusion/methods , Thoracic Vertebrae/surgery , Adolescent , Female , Humans , Kyphosis/diagnostic imaging , Kyphosis/surgery , Length of Stay , Lordosis/diagnostic imaging , Lordosis/surgery , Male , Postoperative Complications , Prospective Studies , Radiography , Scoliosis/diagnostic imaging , Scoliosis/physiopathology , Spinal Fusion/instrumentation , Thoracic Vertebrae/diagnostic imaging , Thoracic Vertebrae/physiopathology , Treatment Outcome
16.
Eur Spine J ; 22(3): 515-20, 2013 Mar.
Article in English | MEDLINE | ID: mdl-23179974

ABSTRACT

INTRODUCTION: In traumatic injury there is a clear relationship between the dose of energy involved, structural tissue damage and resultant disability after recovery. This relationship is often absent in cases of non-specific chronic low back pain that is perceived by patients as attributed to a workplace injury. There are many studies assessing risk factors for non-specific low back pain. However, studies addressing causality of back pain are deficient. PURPOSE: To establish whether there exists a causal relationship between structural injury, low back pain and spinal disability. METHODS: Retrospective analysis of prospectively gathered validated spinal outcome measures [Oswestry disability index (ODI), low back outcome score (LBO), modified somatic perception (MSP), modified Zung depression index (MZD)] between patients with healed high energy thoracolumbar spinal fractures and patients with self-perceived work-related low back pain. Causality was established according to two of Bradford Hill's criteria of medical causality, temporal and dose-response relationships. RESULTS: Twenty-three patients with spinal fractures (group 1) of average age 44 years were compared to 19 patients with self-reported back pain in the workplace pursuing claims for compensation (group 2) of average age 48 years. Both groups were comparable in terms of age and sex. The average ODI in group 1 was 28 % (SD 19) compared to 42 % (SD 19) in group 2 (P < 0.05). Similarly, LBOS was 39.7 versus 24.3 (P < 0.05), MSP 4.3 versus 9.3 (P < 0.05) and MZD 20.2 versus 34.8 (P < 0.05) in groups 1 and 2, respectively. CONCLUSION: Despite high-energy trauma and significant structural damage to the spine, patients with the high energy injuries had better spinal outcome scores in all measures. There is no 'dose-response' relationship between structural injury, low back pain and spinal disability. This is the reverse of what would be anticipated if structural injury was the cause of disability in workplace reported onset of low back pain.


Subject(s)
Disability Evaluation , Disabled Persons , Low Back Pain/etiology , Lumbar Vertebrae/injuries , Spinal Injuries/complications , Adult , Female , Humans , Longitudinal Studies , Male , Middle Aged , Retrospective Studies
17.
Eur Spine J ; 20(12): 2247-51, 2011 Dec.
Article in English | MEDLINE | ID: mdl-21553339

ABSTRACT

Vitamin B12 deficiency can confound the clinical assessment of patients presenting with features of spinal disorders. Speciality practice within spinal surgery may lead the clinician to a focus upon spinal explanations for symptoms and that belief may be reinforced by supporting imaging. In the presence of mainly sensory symptoms consideration and exclusion of non surgical causes needs to occur. This study aimed at identifying the prevalence of vitamin B12 deficiency; the presence of dual pathology on imaging performed; the implementation of replacement therapy and their subsequent clinical response as perceived by patients. This was performed through a retrospective review of patients presenting to specialist spine out-patient clinics over a 4-year period via access to pathology reports followed by a telephone survey. 457 patients were investigated of which 8.5% were vitamin B12 deficient. 70% of patients had repeat levels and 31% continued to be deficient. 26% of these patients were not placed on any supplemental therapy. 72% of patients on treatment had self perceived improved outcomes as compared with 55% not on treatment. 73% of patients underwent MRI/CT imaging. 59% of which had evidence of spinal stenosis. In older patients with sensory symptoms, the coexistence of B12 deficiency should be considered. Detection of deficiency with consequent treatment results in better global outcomes than no treatment. Unless the correct blood test is done, the pathology will remain undetected, and patients may continue with their primary symptoms despite high-risk spinal surgical procedures.


Subject(s)
Spinal Stenosis/complications , Vitamin B 12 Deficiency/complications , Vitamin B 12/therapeutic use , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Retrospective Studies , Spinal Stenosis/drug therapy , Treatment Outcome , Vitamin B 12 Deficiency/drug therapy
19.
J Spinal Disord Tech ; 23(1): 74-7, 2010 Feb.
Article in English | MEDLINE | ID: mdl-20072036

ABSTRACT

STUDY DESIGN: Triple blind randomized controlled study. OBJECTIVE: To establish the treatment effect of etanercept in acute sciatica secondary to lumbar disc herniation. SUMMARY OF BACKGROUND DATA: Etanercept is a selective competitor of tumor necrosis factor-alpha which is a proinflammatory cytokine. It is currently used alone or in combination with other medication for the treatment of chronic inflammatory disease. METHODS: Inclusion criteria were acute unilateral radicular leg pain secondary to herniated nucleus pulposus confirmed on magnetic resonance imaging scan. Exclusions were previous back surgery, spinal stenosis and any contraindications to the use of etanercept such as immunosuppression. The patient, the injector, and assessor were blinded to the agent being used. Follow-up was at 6 weeks and 3 months posttreatment. Oswestry disability index and visual analog scores were among the assessment criteria. RESULTS: Fifteen patients were recruited in a 4 years period with a 3 months follow-up of 80%. The etanercept group had 8 patients whereas the placebo group had 7. The average Oswestry disability index for the etanercept group preintervention was higher than that in the placebo group (53.6 vs. 50.4) and this remained the same after 6 weeks (46.1 vs. 31.2) and 3 months of follow-up (37 vs. 35). Visual analog score was also higher in the etanercept group versus placebo; preinjection (8.6 vs. 7.4), 6 weeks (5.0 vs. 3.8), and 3 months (4.8 vs. 4.5). CONCLUSIONS: Small numbers of trial participants limited statistical analysis. The trend appears to show no benefit to the use of etanercept over placebo in the pharmacologic treatment of sciatica.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Immunoglobulin G/administration & dosage , Receptors, Tumor Necrosis Factor/administration & dosage , Sciatica/drug therapy , Tumor Necrosis Factor-alpha/antagonists & inhibitors , Anti-Inflammatory Agents, Non-Steroidal/adverse effects , Disability Evaluation , Double-Blind Method , Etanercept , Female , Humans , Immunoglobulin G/adverse effects , Inflammation/drug therapy , Inflammation/pathology , Inflammation/physiopathology , Intervertebral Disc Displacement/complications , Male , Pain Measurement , Placebos , Radiculopathy/drug therapy , Radiculopathy/pathology , Radiculopathy/physiopathology , Sample Size , Sciatica/etiology , Sciatica/physiopathology , Spinal Nerve Roots/drug effects , Spinal Nerve Roots/pathology , Spinal Nerve Roots/physiopathology , Spondylosis/complications , Treatment Failure , Tumor Necrosis Factor-alpha/metabolism
20.
Eur Spine J ; 19(2): 279-82, 2010 Feb.
Article in English | MEDLINE | ID: mdl-19727851

ABSTRACT

Self reported walking distance is a clinically relevant measure of function. The aim of this study was to define patient accuracy and understand factors that might influence perceived walking distance in an elective spinal outpatients setting. A prospective cohort study. 103 patients were asked to perform one test of distance estimation and 2 tests of functional distance perception using pre-measured landmarks. Standard spine specific outcomes included the patient reported claudication distance, Oswestry disability index (ODI), Low Back Outcome Score (LBOS), visual analogue score (VAS) for leg and back, and other measures. There are over-estimators and under-estimators. Overall, the accuracy to within 9.14 metres (m) (10 yards) was poor at only 5% for distance estimation and 40% for the two tests of functional distance perception. Distance: Actual distance 111 m; mean response 245 m (95% CI 176.3-314.7), Functional test 1 actual distance 29.2 m; mean response 71.7 m (95% CI 53.6-88.9) Functional test 2 actual distance 19.6 m; mean response 47.4 m (95% CI 35.02-59.95). Surprisingly patients over 60 years of age (n = 43) are twice as accurate with each test performed compared to those under 60 (n = 60) (average 70% overestimation compared to 140%; p = 0.06). Patients in social class I (n = 18) were more accurate than those in classes II-V (n = 85): There was a positive correlation between poor accuracy and increasing MZD (Pearson's correlation coefficient 0.250; p = 0.012). ODI, LBOS and other parameters measured showed no correlation. Subjective distance perception and estimation is poor in this population. Patients over 60 and those with a professional background are more accurate but still poor.


Subject(s)
Disability Evaluation , Gait Disorders, Neurologic/diagnosis , Gait Disorders, Neurologic/etiology , Mobility Limitation , Outcome Assessment, Health Care/methods , Spinal Stenosis/complications , Adult , Aged , Cohort Studies , Exercise Tolerance/physiology , Female , Gait Disorders, Neurologic/surgery , Humans , Lumbar Vertebrae/pathology , Lumbar Vertebrae/surgery , Male , Middle Aged , Outpatients/statistics & numerical data , Pain Measurement , Polyradiculopathy/complications , Polyradiculopathy/physiopathology , Polyradiculopathy/surgery , Predictive Value of Tests , Prospective Studies , Self-Assessment , Sensitivity and Specificity , Spinal Stenosis/surgery , Walking/physiology
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