The effectiveness of a protocol without routine radiographs for follow-up of adolescent idiopathic scoliosis patients (CURVE): a study protocol.

BACKGROUND AND PURPOSE: Current follow-up protocols for adolescent idiopathic scoliosis (AIS) are based on consensus and consist of regular full-spine radiographs to monitor curve progression and surgical complications. Consensus exists to avoid inappropriate use of radiographs in children. It is unknown whether a standard radiologic follow-up (S-FU) approach is necessary or if a patient-empowered follow-up (PE-FU) approach can reduce the number of radiographs without treatment consequences. METHODS AND ANALYSES: A nationwide multicenter pragmatic randomized preference trial was designed for 3 follow-up subgroups (pre-treatment, post-brace, post-surgery) to compare PE-FU and S-FU. 812 patients with AIS (age 10-18 years) will be included in the randomized trial or preference cohorts. Primary outcome is the proportion of radiographs with a treatment consequence for each subgroup. Secondary outcomes consist of the proportion of patients with delayed initiation of treatment due to non-routine radiographic follow-up, radiation exposure, societal costs, positive predictive value, and interrelation of clinical assessment, quality of life, and parameters for initiation of treatment during follow-up. Outcomes will be analyzed using linear mixed-effects models, adjusted for relevant baseline covariates, and are based on intention-to-treat principle. Study summary: (i) a national, multicenter pragmatic randomized trial addressing the optimal frequency of radiographic follow-up in patients with AIS; (ii) first study that includes patient-empowered follow-up; (iii) an inclusive study with 3 follow-up subgroups and few exclusion criteria representative for clinical reality; (iv) preference cohorts alongside to amplify generalizability; (v) first study conducting an economic evaluation comparing both follow-up approaches.

The economic and societal burden associated with adolescent idiopathic scoliosis: A burden-of-disease study protocol.

Background: Adolescent idiopathic scoliosis (AIS) has an estimated general population prevalence of 2% to 3%. The impact of adolescent idiopathic scoliosis (AIS) on the patients' experienced quality of life and psychological well-being and the resulting societal burden are increasingly recognized. However, there is limited knowledge on the economic burden of AIS. This cross-sectional, prevalence-based, bottom-up approach burden of disease study aims to determine the impact associated with adolescent idiopathic scoliosis in terms of the cost-of-illness and health-related quality of life from a societal perspective in the Netherlands. Methods: Persons diagnosed with AIS or parents of a child with AIS that are willing and able to answer the questionnaires will be eligible to participate. Patients will be included consecutively between June until January 2023. Costs and self-perceived health-related quality of life will be estimated using 3 steps: identification, measurement and valuation. To assess the costs associated with AIS the institute for Medical Technology Assessment - Medical Consumption Questionnaire and the institute for Medical Technology Assessment - Productivity Cost Questionnaire will be used. To assess the HRQoL of adult AIS patients the EuroQol 5-dimensions or EuroQol 5-dimensions Youth questionnaire for children under the age of 12 and the Scoliosis Research Society-22 revised questionnaire will be considered. Discussion: This is the first study in this field. It will help raise awareness for AIS and wider support for both the patient community and informal care takers among healthcare professionals and policymakers. Major strengths of this study will be the use of mostly validated, standardized questionnaires. Limitations include the cross-sectional and retrospective nature of the study design.

Effectiveness and cost-effectiveness of dynamic bracing versus standard care alone in patients suffering from osteoporotic vertebral compression fractures: protocol for a multicentre, two-armed, parallel-group randomised controlled trial with 12 months of follow-up.

INTRODUCTION: Patients with osteoporosis may suffer from a fracture after minimal trauma. Osteoporotic vertebral compression fractures (OVCFs) are among the most common fractures, often leading to substantial pain. There is a need for evidence-based conservative treatment to aid in the management of OVCFs. The objective of this randomised controlled trial (RCT) is to evaluate the effectiveness and cost-effectiveness of dynamic bracing in addition to standard care for improving quality of life (QoL) in patients suffering from an OVCF. METHODS AND ANALYSIS: Ninety-eight postmenopausal women from two academic and four community hospitals with a recent symptomatic thoracolumbar OVCF will be randomised into either the standard care or dynamic bracing group. In the dynamic bracing group, the Spinova Osteo orthosis will be used in addition to standard care. Standard care comprises pain control with analgesics, physical therapy and osteoporosis medication. The primary outcome parameter is QoL 1 year after inclusion, as measured by the Quality of Life Questionnaire of the European Foundation for Osteoporosis (QUALEFFO-41). Secondary outcome parameters are pain, pain medication used, functional disability, sagittal spinal alignment, recurrence rate of OVCFs and physical activity in daily life. A trial-based economic evaluation consisting of both cost-effectiveness analysis and cost-utility analysis will be performed based on empirical data obtained in the RCT. A process evaluation will assess the feasibility of dynamic bracing. All outcomes will be assessed at baseline, 6 weeks, 3 months, 6 months, 9 months and 12 months. ETHICS AND DISSEMINATION: Ethical approval has been granted by the Medical Ethics Committee, University Hospital Maastricht and Maastricht University (METC azM/UM) (NL74552.068.20/METC 20-055). Patients will be included only after verification of eligibility and obtaining written informed consent. Results will be disseminated via the Dutch National Osteoporosis Patient Society and via publications and conferences. TRIAL REGISTRATION NUMBER: NL8746.

Assessment of need for hemostatic evaluation in patients taking valproic acid: A retrospective cross-sectional study.

INTRODUCTION: Valproic acid (VPA) is a frequently prescribed anti-epileptic drug. Since its introduction side effects on hemostasis are reported. However, studies show conflicting results, and the clinical relevance is questioned. We aimed to determine the coagulopathies induced by VPA in patients who undergo high-risk surgery. The study results warrant attention to this issue, which might contribute to reducing bleeding complications in future patients. METHODS: Between January 2012 and August 2020, 73 consecutive patients using VPA were retrospectively included. Extensive laboratory hemostatic assessment (including platelet function tests) was performed before elective high-risk surgery. Patient characteristics, details of VPA treatment, and laboratory results were extracted from medical records. RESULTS: 46.6% of the patients using VPA (n = 73) showed coagulopathy. Mainly, platelet function disorder was found (36.4%). Thrombocytopenia was seen in 9.6% of the patients. Data suggested that the incidence of coagulopathies was almost twice as high in children as compared to adults and hypofibrinogenemia was only demonstrated in children. No association was found between the incidence of coagulopathies and VPA dosage (mg/kg/day). CONCLUSION: A considerable number of patients using VPA were diagnosed with coagulopathy, especially platelet function disorder. Further prospective studies are needed to confirm the need for comprehensive laboratory testing before elective high-risk surgery in these patients.

The Impact of Chronic Discogenic Low Back Pain: Costs and Patients' Burden.

Introduction: Chronic discogenic low back pain (CDP) is frequently diagnosed in patients referred to specialized pain clinics for their back pain. The aim of this study is to assess the impact of CDP both on the individual patient and on society. Materials and Methods: Using the baseline records of 80 patients in a randomized trial assessing the effectiveness of a new intervention for CDP, healthcare and societal costs related to back pain are calculated. Furthermore, the impact of the condition on perceived pain, disability, health-related quality of life, Quality of life Adjusted Life Years (QALY), and QALY loss is assessed. Results: Using the friction costs approach, we found that the annual costs for society are €7,911.95 per CDP patient, 51% healthcare and 49% societal costs. When using the human capital approach, total costs were €18,940.58, 22% healthcare and 78% societal costs. Healthcare costs were mainly related to pain treatment. Mean pain severity was 6.5 (0-10), and 46% suffered from severe pain (≥7/10). Mean physical limitations rate was 43.7; 13.5% of the patients were very limited to disabled. QALY loss compared to a healthy population was 64%. Discussion: This study shows that in patients with CDP referred to a pain clinic, costs for society are high and the most used healthcare resources are pain therapies. Patients suffer severe pain, are physically limited, and experience a serious loss in quality of life.

Radiopaque UHMWPE sublaminar cables for spinal deformity correction: Preclinical mechanical and radiopacifier leaching assessment.

Polymeric sublaminar cables have a number of advantages over metal cables in the field of spinal deformity surgery, with decreased risk of neurological injury and potential for higher correction forces as the two most predominant. However, currently available polymer cables are radiolucent, precluding postoperative radiological assessment of instrumentation stability and integrity. This study provides a preclinical assessment of a woven UHMWPE cable made with radiopaque UHMWPE fibers. Our primary goal was to determine if the addition of a radiopacifier negatively affects the mechanical properties of UHMWPE woven cables. Tensile mechanical properties were determined and compared to suitable controls. Radiopacity was evaluated and radiopacifier leaching was assessed in vitro and in vivo. Finally, in vivo bismuth organ content was quantified after a 24-week implantation period in sheep. Results show that the mechanical properties of woven UHMWPE cables were not deleteriously affected by the addition of homogenously dispersed bismuth oxide particles within each fiber. Limited amounts of bismuth oxide were released in vitro, well below the toxicological threshold. Tissue concentrations lower than generally accepted therapeutic dosages for use against gastrointestinal disorders, well below toxic levels, were discovered in vivo. These results substantiate controlled clinical introduction of these radiopaque UHMWPE cables. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 771-779, 2018.

Development and assessment of a digital X-ray software tool to determine vertebral rotation in adolescent idiopathic scoliosis.

BACKGROUND CONTEXT: The amount of vertebral rotation in the axial plane is of key importance in the prognosis and treatment of adolescent idiopathic scoliosis (AIS). Current methods to determine vertebral rotation are either designed for use in analogue plain radiographs and not useful in digital images, or lack measurement precision and are therefore less suitable for the follow-up of rotation in AIS patients. PURPOSE: This study aimed to develop a digital X-ray software tool with high measurement precision to determine vertebral rotation in AIS, and to assess its (concurrent) validity and reliability. STUDY DESIGN/SETTING: In this study a combination of basic science and reliability methodology applied in both laboratory and clinical settings was used. METHODS: Software was developed using the algorithm of the Perdriolle torsion meter for analogue AP plain radiographs of the spine. Software was then assessed for (1) concurrent validity and (2) intra- and interobserver reliability. Plain radiographs of both human cadaver vertebrae and outpatient AIS patients were used. Concurrent validity was measured by two independent observers, both experienced in the assessment of plain radiographs. Reliability-measurements were performed by three independent spine surgeons. RESULTS: Pearson correlation of the software compared with the analogue Perdriolle torsion meter for mid-thoracic vertebrae was 0.98, for low-thoracic vertebrae 0.97 and for lumbar vertebrae 0.97. Measurement exactness of the software was within 5° in 62% of cases and within 10° in 97% of cases. Intraclass correlation coefficient (ICC) for inter-observer reliability was 0.92 (0.91-0.95), ICC for intra-observer reliability was 0.96 (0.94-0.97). CONCLUSIONS: We developed a digital X-ray software tool to determine vertebral rotation in AIS with a substantial concurrent validity and reliability, which may be useful for the follow-up of vertebral rotation in AIS patients.

UHMWPE Sublaminar Wires in Posterior Spinal Instrumentation: Stability and Biocompatibility Assessment in an Ovine Pilot Study.

STUDY DESIGN: An animal study. OBJECTIVE: To explore ultra-high molecular weight polyethylene (UHMWPE) sublaminar wires in spinal surgery and to assess stability and biocompatibility of the UHMWPE instrumentation in an ovine model. SUMMARY OF BACKGROUND DATA: Sublaminar wiring is a well-established technique in segmental scoliosis surgery. However, during introduction and/or removal of the metal sublaminar wires, neurological problems can occur. Abrasion after cutting metal wires for removal can lead to damage to the dural sac. Sublaminar wires have to withhold large forces and breakage of the wires can occur. Different types of sublaminar wires have been developed to address these problems. UHMWPE sublaminar wires can potentially substitute currently used metal sublaminar metal wires. In vivo testing and biocompatibility analysis of UHMWPE wires are recommended before clinical use in spinal surgery. MATERIALS AND METHODS: In 6 immature sheep, pedicle screws were instrumented at lumbar level L4 and attached with titanium rods to 4 thoracolumbar vertebrae using 3- and 5-mm-wide UHMWPE sublaminar wiring constructions in 5 animals. Titanium sublaminar wires were applied in 1 animal to function as a control subject. After a follow-up period of 16 weeks, the animals were sacrificed and the spines were isolated. Radiographs and computed tomography (CT) scans were made to assess stability of the instrumentation. The vertebrae were dissected for macroscopic and histologic evaluation. RESULTS: None of the wires had loosened and the instrumentation remained stable. CT scans and radiographs showed no signs of failure of the instrumentation and no neurological complications occurred. Although several bony bridges were seen on CT, growth was observed at the operated levels. Biocompatibility was assessed by macroscopical and histologic analysis, showing no signs of dural or epidural inflammation. CONCLUSIONS: This pilot animal study shows that UHMWPE sublaminar wiring is a safe technique. The UHMWPE wires are biocompatible and provide sufficient stability in spinal instrumentation. Heterotopic ossification because of periost reactions in the ovine spine led to some restrictions in this study.

Efficacy and cost-effectiveness of intradiscal methylene blue injection for chronic discogenic low back pain: study protocol for a randomized controlled trial.

BACKGROUND: Low back pain (LBP) is a common health problem and a substantial part of LBP is presumed to be attributable to degeneration of the intervertebral disc. For patients suffering from intractable discogenic LBP, there are few evidence-based effective interventional treatment options available. In 2010, the results of a randomized controlled trial (RCT) were published concerning "intradiscal methylene blue injection" (IMBI), in which this intervention appeared to be very successful in relieving discogenic pain. Therefore, we decided to repeat this study to investigate whether we could replicate the published results. The results of our preliminary feasibility study gave reason to set up an RCT. The aim of this RCT is to evaluate if IMBI is a more effective treatment of discogenic low back pain as an intradiscal placebo intervention, and furthermore, to assess the cost-effectiveness of this intervention. METHODS/DESIGN: Consecutive discogenic low back pain patients referred to four specialized pain treatment facilities are being screened for eligibility. After a positive standardized provocation discography and informed consent, patients are randomized into two groups. The treatment group receives an intradiscal injection with methylene blue, lidocaine, and contrast, and the control group receives intradiscal isotonic saline with lidocaine and contrast. Main outcome measures are pain at the 6-month follow-up, patient's global impression of change, cost-effectiveness, quality of life, disability, and analgesic intake. DISCUSSION: The importance of this study is emphasized by the fact that for intractable discogenic low back pain patients, evidence-based effective pain treatments are rare. If this study establishes clinical success and cost-effectiveness, IMBI could become the "pain treatment of choice" for a selected group of patients with chronic discogenic low back pain for whom noninvasive treatment options have failed. TRIAL REGISTRATION: National Trial register NTR2547 Registered at 29 September 2010 and 31 March 2014.

Assessment of the healing process in distal radius fractures by high resolution peripheral quantitative computed tomography.

In clinical practice, fracture healing is evaluated by clinical judgment in combination with conventional radiography. Due to limited resolution, radiographs don't provide detailed information regarding the bone micro-architecture and bone strength. Recently, assessment of in vivo bone density, architectural and mechanical properties at the microscale became possible using high resolution peripheral quantitative computed tomography (HR-pQCT) in combination with micro finite element analysis (µFEA). So far, such techniques have been used mainly to study intact bone. The aim of this study was to explore whether these techniques can also be used to assess changes in bone density, micro-architecture and bone stiffness during fracture healing. Therefore, the fracture region in eighteen women, aged 50 years or older with a stable distal radius fracture, was scanned using HR-pQCT at 1-2 (baseline), 3-4, 6-8 and 12weeks post-fracture. At 1-2 and 12 weeks post-fracture the distal radius at the contra-lateral side was also scanned as control. Standard bone density, micro-architectural and geometric parameters were calculated and bone stiffness in compression, torsion and bending was assessed using µFEA. A linear mixed effect model with time post-fracture as fixed effect was used to detect significant (p-value ≤0.05) changes from baseline. Wrist pain and function were scored using the patient-rated wrist evaluation (PRWE) questionnaire. Correlations between the bone parameters and the PRWE score were calculated by Spearman's correlation coefficient. At the fracture site, total and trabecular bone density increased by 11% and 20%, respectively, at 6-8 weeks, whereas cortical density was decreased by 4%. Trabecular thickness increased by 23-31% at 6-8 and 12 weeks and the intertrabecular area became blurred, indicating intertrabecular bone formation. Compared to baseline, calculated bone stiffness in compression, torsion and bending was increased by 31% after 12 weeks. A moderate negative correlation was found between the stiffness and the PRWE score. No changes were observed at the contra-lateral side. The results demonstrate that it is feasible to assess clinically relevant and significant longitudinal changes in bone density, micro-architecture and mechanical properties at the fracture region during the healing process of stable distal radius fractures using HR-pQCT.

Provocative discography and lumbar fusion: is preoperative assessment of adjacent discs useful?

STUDY DESIGN: A cohort study of clinical outcomes of lumbar fusion patients with preoperative assessment of adjacent levels by provocative discography. OBJECTIVE: To evaluate whether the preoperative status of the adjacent discs, as determined by provocative discography, has an impact on the clinical outcome of lumbar fusion in chronic low back pain (LBP) patients. SUMMARY OF BACKGROUND DATA: The results of lumbar fusion in chronic LBP patients vary considerably and are hard to predict. It is believed that degenerative levels adjacent to a fused spinal segment may be a cause of continuing pain. In this respect, it is important to know whether preoperative degenerative or symptomatic adjacent levels have an adverse effect on patient outcomes after lumbar fusion. METHODS: In 197 patients with an equivocal indication for lumbar fusion (two thirds were patients with prior spine surgery), the decision for either lumbar fusion or conservative management was determined by a temporary external transpedicular fixation trial. During the diagnostic workup, all patients had undergone provocative discography that included the assessment of the discs adjacent to the intended fusion levels. The individual changes in pain on a visual analog scale, assessed before treatment and at follow-up, and patient satisfaction were the measures of outcome. RESULTS: In the 82 patients who underwent a lumbar fusion, no difference in outcome was found between those patients with degenerative or symptomatic discs adjacent to the fusion and those with normal adjacent discs. CONCLUSION: In this cohort study of chronic LBP patients with an uncertain indication for lumbar fusion, the preoperative status of adjacent levels as assessed by provocative discography did not appear to be related to the clinical outcome after fusion.