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The Bone & Joint Journal Jan 2017We performed a systematic review of the current literature regarding the outcomes of unconstrained metacarpophalangeal joint (MCPJ) arthroplasty. (Review)
Review
AIMS
We performed a systematic review of the current literature regarding the outcomes of unconstrained metacarpophalangeal joint (MCPJ) arthroplasty.
MATERIALS AND METHODS
We initially identified 1305 studies, and 406 were found to be duplicates. After exclusion criteria were applied, seven studies were included. Outcomes extracted included pre- and post-operative pain visual analogue scores, range of movement (ROM), strength of pinch and grip, satisfaction and patient reported outcome measures (PROMs). Clinical and radiological complications were recorded. The results are presented in three groups based on the design of the arthroplasty and the aetiology (pyrocarbon-osteoarthritis (pyro-OA), pyrocarbon-inflammatory arthritis (pyro-IA), metal-on-polyethylene (MoP)).
RESULTS
Results show that pyrocarbon implants provide an 85% reduction in pain, 144% increase of pinch grip and 13° improvements in ROM for both OA and IA combined. Patients receiving MoP arthroplasties had a reduction in pinch strength. Satisfaction rates were 91% and 92% for pyrocarbon-OA and pyrocarbon-IA groups, respectively. There were nine failures in 87 joints (10.3%) over a mean follow-up of 5.5 years (1.0 to 14.3) for pyro-OA. There were 18 failures in 149 joints (12.1%) over a mean period of 6.6 years (1.0 to 16.0) for pyro-IA. Meta-analysis was not possible due to the heterogeneity of the studies and the limited presentation of data.
CONCLUSION
We would recommend prospective data collection for small joint arthroplasties of the hand consisting of PROMs that would allow clinicians to come to stronger conclusions about the impact on function of replacing the MCPJs. A national joint registry may be the best way to achieve this. Cite this article: Bone Joint J 2017;99-B:100-6.
Topics: Arthroplasty; Carbon; Hand Strength; Humans; Metacarpophalangeal Joint; Musculoskeletal Pain; Osteoarthritis; Patient Satisfaction; Prospective Studies; Prostheses and Implants; Prosthesis Failure; Range of Motion, Articular; Treatment Outcome
PubMed: 28053264
DOI: 10.1302/0301-620X.99B1.37237 -
Pain Physician Feb 2024Chronic axial spinal pain is one of the major causes of disability. Literature shows that spending on low back and neck pain and musculoskeletal disorders continues to... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Chronic axial spinal pain is one of the major causes of disability. Literature shows that spending on low back and neck pain and musculoskeletal disorders continues to escalate, not only with disability, but also with increasing costs, accounting for the highest amount of various disease categories. Based on the current literature utilizing controlled diagnostic blocks, facet joints, nerve root dura, and sacroiliac joints have been shown as potential sources of spinal pain. Therapeutic facet joint interventional modalities of axial spinal pain include radiofrequency neurotomy, therapeutic facet joint nerve blocks, and therapeutic intraarticular injections.
OBJECTIVE
The objective of this systematic review and meta-analysis is to evaluate the effectiveness of facet joint nerve blocks as a therapeutic modality in managing chronic axial spinal pain of facet joint origin.
STUDY DESIGN
A systematic review and meta-analysis of randomized controlled trials (RCTs) and observational studies utilizing the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist.
METHODS
The available literature on facet joint nerve blocks in axial spinal pain was reviewed. The quality assessment criteria utilized were the Cochrane review criteria to assess risk of bias, the Interventional Pain Management Techniques - Quality Appraisal of Reliability and Risk of Bias Assessment (IPM-QRB) for randomized therapeutic trials, and the Interventional Pain Management Techniques - Quality Appraisal of Reliability and Risk of Bias Assessment for Nonrandomized Studies (IPM-QRBNR) for nonrandomized studies. The evidence was graded according to Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) assessment criteria. The level of evidence was based on best evidence synthesis with modified grading of qualitative evidence from Level I to Level V. A comprehensive literature search of multiple databases from 1966 to July 2023, including manual searches of the bibliography of known review articles was performed. Quality assessment of the included studies and best evidence synthesis were incorporated into qualitative and quantitative evidence synthesis.
OUTCOME MEASURES
The primary outcome measure was the proportion of patients with significant relief and functional improvement of greater than 50% of at least 3 months. Duration of relief was categorized as short-term (less than 6 months) and long-term (greater than 6 months).
RESULTS
This assessment identified 8 high-quality and one moderate quality RCTs and 8 high quality and 4 moderate quality non-randomized studies with application of spinal facet joint nerve blocks as therapeutic modalities. However, based on the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) assessment, only 3 of the 21 studies showed high levels of evidence and clinical applicability, with 11 studies showing moderate levels of GRADE evidence and clinical applicability.
LIMITATIONS
Despite the availability of multiple studies, the paucity of literature is considered as the major drawback. Based on Grading of Recommendations, Assessment Development, and Evaluations (GRADE) assessment, only 3 of the 21 studies showed high levels of evidence and clinical applicability.
CONCLUSION
Based on the present systematic review and meta-analysis with 9 RCTs and 12 non-randomized studies, the evidence is Level II with moderate to strong recommendation for therapeutic facet joint nerve blocks in managing spinal facet joint pain.
Topics: Humans; Pain Management; Zygapophyseal Joint; Chronic Pain; Spine; Nerve Block
PubMed: 38324785
DOI: No ID Found -
A Systematic Review of the Normal Sacroiliac Joint Anatomy and Adjacent Tissues for Pain Physicians.Pain Physician Jul 2019The sacroiliac joint (SIJ) forms a complex joint and has shown to be underappreciated in its involvement with lower back pain. Research efforts have intensified on SIJ...
BACKGROUND
The sacroiliac joint (SIJ) forms a complex joint and has shown to be underappreciated in its involvement with lower back pain. Research efforts have intensified on SIJ anatomy and biomechanics because of its predisposing position to pain and dysfunction in individuals suffering from lower back discomfort. Previous work has focused on SIJ anatomy including bone and joint structure, innervation, as well as biomechanics and the treatment of SIJ pain. However, to date, no review exists describing the range of 'normal' anatomic features of the SIJ.
OBJECTIVES
To describe the normal appearance of the SIJ and adjacent tissues, as opposed to 'abnormal' conditions involving SIJ morphology. It will also identify key areas that require further study because of lacking information or disagreement.
STUDY DESIGN
A systematic literature review.
SETTING
The research took place at the University of Otago, New Zealand. All published research on 'normal SIJ anatomy' available from MEDLINE, OVID, Scopus, Web of Science, PubMed, and Science Direct were included, available until December 2018, in English, French, and German. Subject areas included bony landmarks, joint type, bone morphology, ligamentous attachments, muscular and fascial relationships, blood supply, fatty infiltration, and morphologic variation.
METHODS
Articles met the selection criteria if they contained specific information on SIJ anatomy, including bone morphology and architecture, ligaments, muscle attachments, innervation, vasculature, and the presence of fat. Biomechanics and kinematics related keywords were used as the literature often couples these with the anatomy. Keywords of individual articles were named as 'structures of interest.'
RESULTS
A total of 88 primary and 101 secondary articles were identified in the time frame from 1851 to 2018. Primary articles provided quantitative data and detailed anatomic descriptions. Secondary articles did not focus specifically on the anatomy of the SIJ. Although research appeared to be in general agreement on bony landmarks, joint type, myofascial attachments, vasculature, and innervation of the SIJ, there was only part consensus on ligament attachments and cartilage structure. Information regarding bone density of the articulating surfaces of the SIJ is lacking. Despite its potential clinical significance, fatty infiltration within the joint lacks research to date.
LIMITATIONS
Only the given databases were used for the initial search. Keyword combinations used for this review may not have been inclusive of all articles relevant to the SIJ. Work in languages other than the ones listed or work that is not available via the internet may be missing.
CONCLUSIONS
This study provides an overview of normal SIJ structures, including all neuromusculoskeletal elements related to the joint. There is a lack of knowledge on the SIJ ligaments warranting further investigation. Furthermore, there are discrepancies in relation to the nomenclature, layers, attachment sites, and on the topographical relationships between ligamentous tissues and nerves. Subsequent studies on the quantification of fat and bone density in the SIJ have been suggested. These could be useful radiologic parameters to assess the condition of the joint clinically. This review may provide insight into the clinical signs and abnormal biomechanical features of the joint for the purposes of treating SIJ pain.
KEY WORDS
Bone density, bony landmarks, fat infiltration, innervation, ligaments morphology, muscles, sacroiliac joint, vasculature.
Topics: Biomechanical Phenomena; Humans; Sacroiliac Joint
PubMed: 31337164
DOI: No ID Found -
International Journal of Molecular... Mar 2023Temporomandibular disorders (TMDs) occur frequently within the general population and are the most common non-dental cause of orofacial pain. Temporomandibular joint... (Review)
Review
Temporomandibular disorders (TMDs) occur frequently within the general population and are the most common non-dental cause of orofacial pain. Temporomandibular joint osteoarthritis (TMJ OA) is a degenerative joint disease (DJD). There have been several different methods of treatment of TMJ OA listed, including pharmacotherapy among others. Due to its anti-aging, antioxidative, bacteriostatic, anti-inflammatory, immuno-stimulating, pro-anabolic and anti-catabolic properties, oral glucosamine seems to be a potentially very effective agent in the treatment of TMJ OA. The aim of this review was to critically assess the efficacy of oral glucosamine in the treatment of TMJ OA on the basis of the literature. PubMed and Scopus databases were analyzed with the keywords: (temporomandibular joints) AND ((disorders) OR (osteoarthritis)) AND (treatment) AND (glucosamine). After the screening of 50 results, eight studies have been included in this review. Oral glucosamine is one of the symptomatic slow-acting drugs for osteoarthritis. There is not enough scientific evidence to unambiguously confirm the clinical effectiveness of glucosamine supplements in the treatment of TMJ OA on the basis of the literature. The most important aspect affecting the clinical efficacy of oral glucosamine in the treatment of TMJ OA was the total administration time. Administration of oral glucosamine for a longer period of time, i.e., 3 months, led to a significant reduction in TMJ pain and a significant increase in maximum mouth opening. It also resulted in long-term anti-inflammatory effects within the TMJs. Further long-term, randomized, double-blind studies, with a unified methodology, ought to be performed to draw the general recommendations for the use of oral glucosamine in the treatment of TMJ OA.
Topics: Humans; Glucosamine; Osteoarthritis; Temporomandibular Joint; Anti-Inflammatory Agents; Facial Pain; Randomized Controlled Trials as Topic
PubMed: 36902359
DOI: 10.3390/ijms24054925 -
Journal of Orthopaedic Surgery and... Mar 2022Threshold to detect passive motion (TTDPM) tests of the knee joint are commonly implemented among individuals with anterior cruciate ligament (ACL) injury to assess... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Threshold to detect passive motion (TTDPM) tests of the knee joint are commonly implemented among individuals with anterior cruciate ligament (ACL) injury to assess proprioceptive acuity. Their psychometric properties (PMPs), i.e. reliability, validity and responsiveness, are however unclear. This systematic review aimed to establish the PMPs of existing knee joint TTDPM tests among individuals with ACL injury.
METHODS
The databases PubMed, AMED, CINAHL, SPORTDiscus, Web of Science, Scopus, CENTRAL and ProQuest were searched to identify studies that assessed the properties of knee joint TTDPM tests in individuals with ACL injury. The risk of bias for each included study was assessed at the outcome level for each test. Overall quality and levels of evidence for each property were rated according to established criteria. Meta-analyses with mean differences were conducted using random-effects models when adequate data were available.
RESULTS
Fifty-one studies covering 108 TTDPM tests and 1632 individuals with unilateral ACL injury were included. A moderate-to-strong level of evidence indicated insufficient quality for all of the following: convergent validity, known-groups validity, discriminative validity, responsiveness between subgroups, and responsiveness to intervention. Subgroup meta-analyses for known-groups validity did however find that a starting angle of 15° resulted in significantly worse TTDPM for knees with ACL injury compared to those of asymptomatic persons (mean difference 0.28°; 95% CI 0.03 to 0.53; P = 0.03), albeit based on only three studies. Due to the lack of evidence, it was not possible to estimate the quality of reliability, measurement error, and criterion validity, nor responsiveness from a criterion and construct approach.
CONCLUSIONS
Among persons with ACL injury, existing tests of knee joint TTDPM lack either sufficient quality or evidence for their reliability, validity and responsiveness. Significantly worse thresholds for ACL-injured knees compared to those of asymptomatic controls from a 15° starting angle and trends towards significance for some validity measures nevertheless encourage the development of standardised tests. Further research investigating the influence of modifiable test components (e.g. starting angle and motion direction) on the PMPs of knee joint TTDPM tests following ACL injury is warranted.
Topics: Anterior Cruciate Ligament Injuries; Humans; Kinesthesis; Knee Joint; Proprioception; Range of Motion, Articular; Reproducibility of Results
PubMed: 35246192
DOI: 10.1186/s13018-022-03033-4 -
Osteoarthritis and Cartilage Feb 2016To review the association between patellofemoral joint (PFJ) imaging features and patellofemoral pain (PFP). (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
To review the association between patellofemoral joint (PFJ) imaging features and patellofemoral pain (PFP).
DESIGN
A systematic review of the literature from AMED, CiNAHL, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, PEDro, EMBASE and SPORTDiscus was undertaken from their inception to September 2014. Studies were eligible if they used magnetic resonance imaging (MRI), computed tomography (CT), ultrasound (US) or X-ray (XR) to compare PFJ features between a PFP group and an asymptomatic control group in people <45 years of age. A pooled meta-analysis was conducted and data was interpreted using a best evidence synthesis.
RESULTS
Forty studies (all moderate to high quality) describing 1043 people with PFP and 839 controls were included. Two features were deemed to have a large standardised mean difference (SMD) based on meta-analysis: an increased MRI bisect offset at 0° knee flexion under load (0.99; 95% CI: 0.49, 1.49) and an increased CT congruence angle at 15° knee flexion, both under load (1.40 95% CI: 0.04, 2.76) and without load (1.24; 95% CI: 0.37, 2.12). A medium SMD was identified for MRI patella tilt and patellofemoral contact area. Limited evidence was found to support the association of other imaging features with PFP. A sensitivity analysis showed an increase in the SMD for patella bisect offset at 0° knee flexion (1.91; 95% CI: 1.31, 2.52) and patella tilt at 0° knee flexion (0.99; 95% CI: 0.47, 1.52) under full weight bearing.
CONCLUSION
Certain PFJ imaging features were associated with PFP. Future interventional strategies may be targeted at these features.
PROSPERO REGISTRATION NUMBER
CRD 42014009503.
Topics: Humans; Magnetic Resonance Imaging; Patellofemoral Joint; Patellofemoral Pain Syndrome; Tomography, X-Ray Computed; Ultrasonography
PubMed: 26471209
DOI: 10.1016/j.joca.2015.09.004 -
Annals of the Royal College of Surgeons... Mar 2023Isolated volar dislocations of the distal radioulnar joint are reported as rare. We observed three such cases over a 12-month period. Literature to date consists of... (Review)
Review
INTRODUCTION
Isolated volar dislocations of the distal radioulnar joint are reported as rare. We observed three such cases over a 12-month period. Literature to date consists of multiple case reports and case series with no structured reviews. There is debate as to incidence, mechanism, investigation, treatment and prognosis.
METHODS
A case series and formal systematic review was performed. This included an analysis of the demographics, mechanism, presentation, investigation, treatment and outcome of the cases identified from the wider published series.
FINDINGS
In total 99 cases of this injury were identified from 59 papers, with a further 9 cases having an associated ulna styloid fracture.
CONCLUSIONS
This is a rare injury, representing up to 0.02% of all bony injuries, which is diagnosed late in 36% of cases. Inability to obtain a true lateral radiograph may contribute to the diagnosis being missed. Computed tomography scans are useful in suspected cases without radiographic confirmation. Acute cases are successfully treated with closed reduction in 78% of cases; however associated soft tissue injuries may need to be surgically addressed. Delayed presentation is more likely to require open surgery and preoperative MRI scans are indicated to aid surgical planning. Chronic instability rarely occurs and may need treatment with reconstruction or salvage. A good, subjective, result is reported in the majority of patients.
Topics: Humans; Wrist Injuries; Joint Dislocations; Wrist Joint; Ulna Fractures; Radiography; Radius Fractures
PubMed: 35617051
DOI: 10.1308/rcsann.2022.0023 -
BioMed Research International 2022To provide available quantitative evidence of efficacy and safety of acupuncture treatments for improving sacroiliac joint malposition. (Comparative Study)
Comparative Study Meta-Analysis
AIM
To provide available quantitative evidence of efficacy and safety of acupuncture treatments for improving sacroiliac joint malposition.
METHODS
Databases such as the China National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database (CQVIP), Wanfang Database (Wanfang), China Biology Medicine disc (CBMdisc), PubMed, Web of Science, EMBASE, and Cochrane Library were searched by computer to collect the reports on acupuncture treatment of sacroiliac joint malposition from the database creation to July 20, 2021. The selection of included studies, data extraction and coding, and bias risk assessment were conducted independently by two reviewers. RevMan5.4 software was used for meta-analysis, and the results were expressed as mean difference (MD) or standardized mean difference (SMD), with a confidence interval (CI) of 95%.
RESULTS
A total of 10 randomized controlled clinical trials (RCTs) with 1019 participants were included. Their overall quality of methodology was not high, and there may be publication bias. Meta-analysis showed that the total effective rate of the treatment group was higher than that of the control group (OR = 2.74, 95% CI 2.00 to 3.74, < 0.00001). The treatment group was better than the control group in improving VAS score (WMD = -1.56, 95% CI -2.18 to -0.94, < 0.00001). The ODI score of the treatment group was lower than that of the control group (WMD = -6.04, 95% CI -7.05 to -5.02, < 0.00001). With the improvement of the JOA score, the difference of iliac transverse diameter of sacroiliac joint dislocation and the index of sacroiliac joint malposition in the treatment group were better than those in the control group ( < 0.05). There was no significant heterogeneity among the studies.
CONCLUSION
Acupuncture may have therapeutic advantages in improving sacroiliac joint malposition. Acupuncture and acupotomy provide a safe way to improve the related clinical symptoms and functional disorders in activity of sacroiliac joint dislocation. However, due to the low quality of the included literature, this conclusion still needs to be further verified by more high-quality and large-sample RCTs.
Topics: Acupuncture Therapy; Bone Malalignment; Humans; Sacroiliac Joint
PubMed: 35059467
DOI: 10.1155/2022/9485056 -
Journal of Orthopaedic Surgery and... Dec 2023To conduct a systematic review and meta-analysis to investigate the clinical efficacy of acupuncture combined with active exercise training in improving pain and... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To conduct a systematic review and meta-analysis to investigate the clinical efficacy of acupuncture combined with active exercise training in improving pain and function of knee osteoarthritis (KOA) individuals.
DATA SOURCES
PubMed, EMBASE, The Cochrane Library, Web of Science, China National Knowledge Infrastructure, Wan Fang Data, Technology Periodical Database and China Biology Medicine were searched from their inceptions to April 5, 2023.
REVIEW METHODS
We analyzed trials of acupuncture combined with active exercise training for KOA. The included studies were of high quality (Jadad ≥ 4) and RCTs. Study selection, data extraction, risk of bias and quality assessment were independently performed by two reviewers. We performed systematic analyses based on different outcome measures, including total efficiency rate, visual analogue scale (VAS), the Western Ontario and Mcmaster Universities Osteoarthritis Index (WOMAC), the Lysholm Knee Scale (LKS) and range of motion (ROM). We used Review Manager 5.3 and Stata/MP 14.0 to analyze the data. And it was verified by trial sequence analysis (TSA). If I > 50% and p < 0.05, we performed sensitivity analysis and subgroup analysis to find the source of heterogeneity. Publication bias was studied by funnel plot and Egger's test was used to verify it.
RESULTS
Full 11 high-quality studies (Jadad ≥ 4) including 774 KOA individuals were included in this review for meta-analysis. The results showed that acupuncture combined with active exercise training (combined group) was superior to the acupuncture group in improving the total effective rate [RR = 1.13, 95%CI (1.05, 1.22), I = 0%, P = 0.70], reducing the pain level (VAS) [MD = - 0.74, 95%CI (- 1.04, - 0.43), I = 68%, P < 0.05], improving knee joint function (WOMAC) [MD = - 6.97, 95%CI (- 10.74, - 3.19), I = 76%, P < 0.05] and improving joint range of motion (ROM) [MD = 6.25, 95%CI (2.37, 10.04), I = 0%, P = 0.71]. Similarly, the combined group showed significant improvements in the total effective rate [RR = 1.31, 95% CI (1.18, 1.47), I = 48%, P = 0.10], pain (VAS) [MD = 1.42, 95% CI (- 1.85, - 1.00), I = 65%, P = 0.02] and knee function (WOMAC) [MD = 7.05, 95% CI (- 11.43, - 2.66), I = 86%, P < 0.05] compared with the non-acupuncture group.
CONCLUSION
The combined effect of all studies showed significant benefits of acupuncture combined with active exercise training in improving the total effective rate, reducing pain, promoting recovery of knee function and expanding range of motion. However, some evaluation indicators are highly subjective and need to be further confirmed by more objective and evidence-based high-quality RCTs in future.
SYSTEMATIC REVIEW REGISTRATION
[PROSPERO], identifier [No. CRD42023425823].
Topics: Humans; Osteoarthritis, Knee; Pain; Acupuncture Therapy; Knee Joint; Exercise
PubMed: 38042802
DOI: 10.1186/s13018-023-04403-2 -
Pain Physician 2015Spinal zygapophysial, or facet, joints are a source of axial spinal pain and referred pain in the extremities. Conventional clinical features and other noninvasive... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Spinal zygapophysial, or facet, joints are a source of axial spinal pain and referred pain in the extremities. Conventional clinical features and other noninvasive diagnostic modalities are unreliable in diagnosing zygapophysial joint pain.
STUDY DESIGN
A systematic review of the diagnostic accuracy of spinal facet joint nerve blocks.
OBJECTIVE
To determine the diagnostic accuracy of spinal facet joint nerve blocks in chronic spinal pain.
METHODS
A methodological quality assessment of included studies was performed using Quality Appraisal of Reliability Studies (QAREL). Only diagnostic accuracy studies meeting at least 50% of the designated inclusion criteria were utilized for analysis. The level of evidence was classified as Level I to V based on the grading of evidence utilizing best evidence synthesis. Data sources included relevant literature identified through searches of PubMed and other electronic searches published from 1966 through March 2015, Cochrane reviews, and manual searches of the bibliographies of known primary and review articles.
OUTCOME MEASURES
Studies must have been performed utilizing controlled local anesthetic blocks. The criterion standard must have been at least 50% pain relief from baseline scores and the ability to perform previously painful movements.
RESULTS
The available evidence is Level I for lumbar facet joint nerve blocks with the inclusion of a total of 17 studies with dual diagnostic blocks, with at least 75% pain relief with an average prevalence of 16% to 41% and false-positive rates of 25% to 44%. The evidence for diagnosis of cervical facet joint pain with cervical facet joint nerve blocks is Level II based on a total of 11 controlled diagnostic accuracy studies, with significant variability among the prevalence in a heterogenous population with internal inconsistency. The prevalence rates ranged from 36% to 67% with at least 80% pain relief as the criterion standard and a false-positive rate of 27% to 63%. The level of evidence for the diagnostic accuracy of thoracic facet joint nerve blocks is Level II with 80% or higher pain relief as the criterion standard with a prevalence ranging from 34% to 48% and false-positive rates ranging from 42% to 48%.
LIMITATIONS
The shortcomings of this systematic review include a paucity of literature related to the thoracic spine, continued debate on an appropriate gold standard, appropriateness of diagnostic blocks, and utility.
CONCLUSION
The evidence is Level I for the diagnostic accuracy of lumbar facet joint nerve blocks, Level II for cervical facet joint nerve blocks, and Level II for thoracic facet joint nerve blocks in assessment of chronic spinal pain.
Topics: Back Pain; Humans; Injections; Nerve Block; Pain Management; Reproducibility of Results; Zygapophyseal Joint
PubMed: 26218947
DOI: No ID Found