Accelerometer-based daily physical activity monitoring in patients with postpartum sacroiliac joint dysfunction: a case-control study.

Patients with low back pain caused by sacroiliac joint (SIJ) dysfunction have an impaired quality of life, due to reported pain, disability and activity limitations. There is increasing evidence that minimally invasive sacroiliac joint fusion (MISJF) results in improvement in pain, disability and quality of life in these patients. Some studies have reported improvements in daily physical activity following MISJF but based on bias-prone self-reports. Our aim was to provide objective data on daily physical activity in patients with SIJ dysfunction. Daily physical activity in daily life of participants was measured using a triaxial accelerometer for seven consecutive days, before surgery and 3 months after surgery. Recorded daily activities were the daily number of events and total time spent sitting or lying, standing, walking, cycling, high-activity and number of steps and sit-to-stand transfers. The quality of life was assessed by the validated Dutch EQ-5D-5 L-questionnaire. No statistical differences were observed between daily physical activity in patients with SIJ dysfunction before and 3 months after MISJF. As compared to matched controls, high-intensity physical activity was lower in both the pre- and postoperative period (p = 0.007) for patients with SIJ dysfunction. The quality of life improved significantly in patients after MSIJF, from 0.418 to 0.797 (p = 0.021) but did not reach the level of controls (1.000). Daily physical activity in patients with postpartum SIJ dysfunction does not improve 3 months following MISJF, while quality of life does improve significantly. The discrepancy between these two observations is food for new research.

Effectiveness of intra-articular analgesia in reducing postoperative pain after minimally invasive sacroiliac joint fusion: a double-blind randomized controlled trial.

During the first postoperative days following minimally invasive sacroiliac joint fusion (MISJF), patients often report serious pain, which contributes to high utilization of painkillers and prevention of early mobilization. This prospective, double-blind randomized controlled trial investigates the effectiveness of intraoperative SIJ infiltration with bupivacaine 0.50% versus placebo (NaCl 0.9%) in 42 patients in reducing postoperative pain after MISJF. The primary outcome was difference in pain between bupivacaine and placebo groups, assessed as fixed factor in a linear mixed model. Secondary outcomes were opioid consumption, patient satisfaction, adverse events, and length of hospital stay. We found that SIJ infiltration with bupivacaine did not affect postoperative pain scores in comparison with placebo, neither as group-effect (p = 0.68), nor dependent on time (group*time: p = 0.87). None of the secondary outcome parameters were affected in the postoperative period in comparison with placebo, including opioid consumption (p = 0.81). To conclude, intra-articular infiltration of the SIJ with bupivacaine at the end of MISJF surgery is not effective in reducing postoperative pain. Hence, we do not recommend routine use of intraoperative SIJ infiltration with analgesia in MISJF.

Transforaminal versus posterior lumbar interbody fusion for symptomatic single-level spondylolisthesis (LIFT): a multicentre controlled, patient blinded, randomised non-inferiority trial.

Background: The effectiveness of transforaminal lumbar interbody fusion (TLIF) compared to posterior lumbar interbody fusion (PLIF) in patients with single-level spondylolisthesis has not been substantiated. To address the evidence gap, a well-powered randomized controlled non-inferiority trial comparing the effectiveness of TLIF with PLIF, entitled the Lumbar Interbody Fusion Trial (LIFT), was conducted. Methods: In a multicenter randomized controlled non-inferiority trial among five Dutch hospitals, 161 patients were randomly allocated to either TLIF or PLIF (1:1), stratified according to study site. Patients and statisticians were blinded for group assignment. All patients were over 18 years old with symptomatic single-level degenerative, isthmic or iatrogenic lumbar spondylolisthesis, and eligible for lumbar interbody fusion surgery through a posterior approach. The primary outcome was change in disability measured with the Oswestry Disability Index (ODI) from preoperative to one year postoperative. The non-inferiority limit was set to 7.0 points based on the MCID of ODI. Secondary outcomes were change in quality-adjusted life years (QALY) assessed with EuroQol 5 Dimensions, 5 Levels (EQ-5D-5L) and Short Form Health Survey (SF-36), as well as back and leg pain (Numerical rating scale, NRS), anxiety and depression (Hospital Anxiety Depression Scale; HADS), perioperative blood loss, duration of surgery, duration of hospitalization, and complications. Trial registration: Netherlands Trial Registry, number 5722 (registration date March 30, 2016), Lumbar Interbody Fusion Trial (LIFT): A randomized controlled multicenter trial for surgical treatment of lumbar spondylolisthesis. Findings: Patients were included between August 2017 and November 2020. The total study population was 161 patients. Total loss-to-follow-up after one year was 16 patients. Per-protocol analysis included 66 patients in each group. In the TLIF group (mean age 61.6, 36 females), ODI improved from 46.7 to 20.7, whereas in the PLIF group (mean age 61.9, 41 females), it improved from 46.0 to 24.9. This difference (-4.9, 90% CI -12.2 to +2.4) did not reach the non-inferiority limit of 7.0 points in ODI. A significant difference in the secondary outcome measurement, QALY (SF-36), was observed in favor of TLIF (P < 0.05). However, this was not clinically relevant. No difference was found for all other secondary outcome measurements; PROMs (EQ-5D, NRS leg/back, HADS), perioperative blood loss, duration of surgery, duration of hospitalization, and perioperative and postoperative complications. Interpretation: For patients with single-level spondylolisthesis, TLIF is non-inferior to PLIF in terms of clinical effectiveness. Disability (measured with ODI) did not differ over time between groups. Funding: No funding was received for this trial.

MDS and AML show elevated fractions of CD34-positive blast cell populations with a high anti-apoptotic versus proliferation ratio.

This study investigates the intertwined processes of (anti-)apoptosis and cell proliferation in myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). Utilizing antibodies to Bcl-2 and Ki-67, the CD34-positive blast cell compartments in bone marrow aspirates from 50 non-malignant cases, 25 MDS patients, and 25 AML patients were analyzed for their anti-apoptotic and proliferative cell fractions through ten-color flow cytometry. MDS patients exhibited a significantly increased anti-apoptotic (p=0.0014) and reduced proliferative cell fraction (p=0.0030) in their blast cell population as compared to non-malignant cases. AML patients showed an even more exacerbated trend than MDS patients. The resulting Bcl-2:Ki-67 cell fraction ratios in MDS and AML were significantly increased as compared to the non-malignant cases (p=0.0004 and p<0.0001, respectively). AML patients displayed, however, a high degree of variability in their anti-apoptotic and proliferation index, attributed to heterogeneity in maturation stage and severity of the disease at diagnosis. Using double-labeling for Bcl-2 and Ki-67 it could be shown that besides blast cells with a mutually exclusive Ki-67 and Bcl-2 expression, also blast cells concurrently exhibiting anti-apoptotic and proliferative marker expression were found. Integrating these two dynamic markers into MDS and AML diagnostic workups may enable informed conclusions about their biological behavior, facilitating individualized therapy decisions for patients.

A Randomized Controlled Trial Using Epidural Analgesia for Pain Relief After Lumbar Interlaminar Decompressive Spine Surgery: The RAPID trial.

STUDY DESIGN: Prospective, double-blind randomized controlled trial. OBJECTIVE: If an intraoperative single bolus of epidural bupivacaine can result in less postoperative pain following lumbar spinal decompression surgery. SUMMARY OF BACKGROUND DATA: Adequate postoperative pain management following lumbar spinal decompression surgery is important, as it will lead to early mobilization, less complications, and a shorter hospital stay. Opioid consumption should be limited due to their frequently accompanied side effects and their addictive nature. During the final phase of lumbar decompression surgery, the epidural space becomes easily accessible. This might be an ideal moment for surgeons to administer an epidural bolus of analgesia as a safe and effective method for postoperative pain relief. MATERIALS AND METHODS: In this trial, we compared a single intraoperative bolus of epidural analgesia using bupivacaine 0.25% to placebo (NaCl 0.9%) and its effect on postoperative pain following lumbar spinal decompression surgery. The primary outcome was the difference in Numeric (Pain) Rating Scale between the intervention and placebo groups during the first 48 hours after surgery. RESULTS: Both the intervention group and the placebo group consisted of 20 randomized patients (N=40). Statistically significant lower mean Numeric (Pain) Rating Scale pain scores were observed in the intervention group in comparison with the control group (main effect group: -2.35±0.77, P =0.004). The average pain score was lower in the intervention group at all postoperative time points. No study-related complications occurred. CONCLUSION: This randomized controlled trial shows that administrating a bolus of intraoperative epidural bupivacaine is a safe and effective method for reducing early postoperative pain following lumbar decompression surgery.

Impact of the gating strategy for Ki-67 and Bcl-2 on the determination of proliferation and anti-apoptosis data by flow cytometry in non-malignant bone marrow aspirates and aspirates from patients with myeloid malignancies.

This Data in Brief article displays a flow cytometric assay that was used for the acquisition and analyses of proliferative and anti-apoptotic activity in hematopoietic cells. This dataset includes analyses of the Ki-67 positive fraction (Ki-67 proliferation index) and Bcl-2 positive fraction (Bcl-2 anti-apoptotic index) of the different myeloid bone marrow (BM) cell populations in non-malignant BM, and in BM disorders, i.e. myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). The present dataset comprises 1) the percentage of the CD34 positive blast cells, erythroid cells, myeloid cells and monocytic cells, and 2) the determined Ki-67 positive fraction and Bcl-2 positive fraction of these cell populations in tabular form. This allows the comparison and reproduction of the data when these analyses are repeated in a different setting. Because gating the Ki-67 positive and Bcl-2 positive cells is a critical step in this assay, different gating approaches were compared to determine the most sensitive and specific approach. BM cells from aspirates of 50 non-malignant, 25 MDS and 27 AML cases were stained with 7 different antibody panels and subjected to flow cytometry for determination of the Ki-67 positive cells and Bcl-2 positive cells of the different myeloid cell populations. The Ki-67 or Bcl-2 positive cells were then divided by the total number of cells of the respective cell population to generate the Ki-67 positive fraction (Ki-67 proliferation index) or the Bcl-2 positive fraction (Bcl-2 anti-apoptotic index). The presented data may facilitate the establishment and standardization of flow cytometric analyses of the Ki-67 proliferation index and Bcl-2 anti-apoptotic index of the different myeloid cell populations in non-malignant BM as well as MDS and AML patients in other laboratories. Directions for proper gating of the Ki-67 positive and Bcl-2 positive fraction are crucial for achieving standardization among different laboratories. In addition, the data and the presented assay allows application of Ki-67 and Bcl-2 in a research and clinical setting and this approach can serve as the basis for optimization of the gating strategy and subsequent investigation of other cell biological processes besides proliferation and anti-apoptosis. These data can also promote future research into the role of these parameters in diagnosis of myeloid malignancies, prognosis of myeloid malignancies and therapeutic resistance against anti-cancer therapies in these malignancies. As specific populations were identified based on cell biological characteristics, these data can be useful for evaluating gating algorithms in flow cytometry in general by confirming the outcome (e.g. MDS or AML diagnosis) with the respective proliferation and anti-apoptotic profile of these malignancies. The Ki-67 proliferation index and Bcl-2 anti-apoptotic index may potentially be used for classification of MDS and AML based on supervised machine learning algorithms, while unsupervised machine learning can be deployed at the level of single cells to potentially distinguish non-malignant from malignant cells in the identification of minimal residual disease. Therefore, the present dataset may be of interest for internist-hematologists, immunologists with affinity for hemato-oncology, clinical chemists with sub-specialization of hematology and researchers in the field of hemato-oncology.

Advocating uniformity in spine surgery: a practical disease-specific guideline for trial-based economic evaluations.

OBJECTIVES: Despite the availability of general and national guidelines for the conduct and reporting of economic evaluations, there is heterogeneity in economic evolutions concerning spine surgery. This is partly the result of differing levels of adherence to the existing guidelines and the lack of disease-specific recommendations for economic evaluations. The extensive heterogeneity in study design, follow-up duration and outcome measurements limit the comparability of economic evaluations in spine surgery. This study has three objectives: (1) to create disease-specific recommendations for the design and conduct of trial-based economic evaluations in spine surgery, (2) to define recommendations for reporting economic evaluations in spine surgery as a complement to the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) 2022 checklist and (3) to discuss methodological challenges and defining the need for future research. DESIGN: A modified Delphi method according to the RAND/UCLA Appropriateness Method. SETTING: A four-step process was followed to create and validate disease-specific statements and recommendations for the conduct and reporting of trial-based economic evaluations in spine surgery. Consensus was defined as >75% agreement. PARTICIPANTS: A total of 20 experts were included in the expert group. Validation of the final recommendations was obtained in a Delphi panel, which consisted of 40 researchers in the field who were not included in the expert group. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome measure is a set of recommendations for the conduct and reporting, as a complement to the CHEERS 2022 checklist, of economic evaluations in spine surgery. RESULTS: A total of 31 recommendations are made. The Delphi panel confirmed consensus on all of the recommendations in the proposed guideline. CONCLUSION: This study provides an accessible and practical guideline for the conduct of trial-based economic evaluations in spine surgery. This disease-specific guideline is a complement to existing guidelines, and should aid in reaching uniformity and comparability.

A systematic review comparing the cost-effectiveness of the direct anterior, posterior, and straight lateral approach in total hip arthroplasty.

Background: Total hip arthroplasty is a reliable option to treat osteoarthritis. It reduces pain, increases quality of life, and restores function. The direct anterior approach (DAA), posterior approach (PA), and straight lateral approach (SLA) are mostly used. This systematic review evaluates current literature about costs and cost-effectiveness of DAA, PA, and SLA. Methods: A Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) systematic search, registered in the PROSPERO database (registration number: CRD42021237427), was conducted of databases PubMed, CINAHL, EMBASE, Cochrane, Clinical Trials, Current Controlled Trials, ClinicalTrials.gov, NHS Centre for Review and Dissemination, Econlit, and Web of Science. Eligible studies were randomized controlled trials (RCTs) or comparative cohort studies reporting or comparing costs or cost-effectiveness of either approach as the primary outcome. The risk of bias (RoB) was assessed. For comparison, all costs were converted to American Dollars (reference year 2016). Results: Six systematic review studies were included. RoB ranged from low to high, the level of evidence ranged from 2 to 4, and methodological quality was moderate. Costs ranged from $5313.85 to $15 859.00 (direct) and $1921.00 to $6364.30 (indirect) in DAA. From $5158.46 to $12 344.47 (direct) to $2265.70 to $5566.01 (indirect) for PA and from $3265.62 to $8501.81 (direct) and $2280.16 (indirect) for SLA. Due to heterogeneity of included costs, they were not directly comparable. Solid data about cost-effectiveness cannot be presented. Conclusions: Due to limited and heterogenous evidence about costs and cost-effectiveness, the effect of these in surgical approach is unknown. Further well-powered research to make undisputed conclusions is needed.

Methodology of economic evaluations in spine surgery: a systematic review and qualitative assessment.

OBJECTIVES: The present study is a systematic review conducted as part of a methodological approach to develop evidence-based recommendations for economic evaluations in spine surgery. The aim of this systematic review is to evaluate the methodology and quality of currently available clinical cost-effectiveness studies in spine surgery. STUDY DESIGN: Systematic literature review. DATA SOURCES: PubMed, Web of Science, Embase, Cochrane, Cumulative Index to Nursing and Allied Health Literature, EconLit and The National Institute for Health Research Economic Evaluation Database were searched through 8 December 2022. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Studies were included if they met all of the following eligibility criteria: (1) spine surgery, (2) the study cost-effectiveness and (3) clinical study. Model-based studies were excluded. DATA EXTRACTION AND SYNTHESIS: The following data items were extracted and evaluated: pathology, number of participants, intervention(s), year, country, study design, time horizon, comparator(s), utility measurement, effectivity measurement, costs measured, perspective, main result and study quality. RESULTS: 130 economic evaluations were included. Seventy-four of these studies were retrospective studies. The majority of the studies had a time horizon shorter than 2 years. Utility measures varied between the EuroQol 5 dimensions and variations of the Short-Form Health Survey. Effect measures varied widely between Visual Analogue Scale for pain, Neck Disability Index, Oswestry Disability Index, reoperation rates and adverse events. All studies included direct costs from a healthcare perspective. Indirect costs were included in 47 studies. Total Consensus Health Economic Criteria scores ranged from 2 to 18, with a mean score of 12.0 over all 130 studies. CONCLUSIONS: The comparability of economic evaluations in spine surgery is extremely low due to different study designs, follow-up duration and outcome measurements such as utility, effectiveness and costs. This illustrates the need for uniformity in conducting and reporting economic evaluations in spine surgery.

Factors associated with an increased risk of developing postoperative symptomatic lumbar spondylolisthesis after decompression surgery: an explorative two-centre international cohort study.

PURPOSE: Symptomatic lumbar spinal stenosis can be treated with decompression surgery. A recent review reported that, after decompression surgery, 1.6-32.0% of patients develop postoperative symptomatic spondylolisthesis and may therefore be indicated for lumbar fusion surgery. The latter can be more challenging due to the altered anatomy and scar tissue. It remains unclear why some patients get recurrent neurological complaints due to postoperative symptomatic spondylolisthesis, though some associations have been suggested. This study explores the association between key demographic, biological and radiological factors and postoperative symptomatic spondylolisthesis after lumbar decompression. METHODS: This retrospective cohort study included patients who had undergone lumbar spinal decompression surgery between January 2014 and December 2016 at one of two Spine Centres in the Netherlands or Switzerland and had a follow-up of two years. Patient characteristics, details of the surgical procedure and recurrent neurological complaints were retrieved from patient files. Preoperative MRI scans and conventional radiograms (CRs) of the lumbar spine were evaluated for multiple morphological characteristics. Postoperative spondylolisthesis was evaluated on postoperative MRI scans. For variables assessed on a whole patient basis, patients with and without postoperative symptomatic spondylolisthesis were compared. For variables assessed on the basis of the operated segment(s), surgical levels that did or did not develop postoperative spondylolisthesis were compared. Univariable and multivariable logistic regression analyses were used to identify associations with postoperative symptomatic spondylolisthesis. RESULTS: Seven hundred and sixteen patients with 1094 surgical levels were included in the analyses. (In total, 300 patients had undergone multilevel surgery.) ICCs for intraobserver and interobserver reliability of CR and MRI variables ranged between 0.81 and 0.99 and 0.67 and 0.97, respectively. In total, 66 of 716 included patients suffered from postoperative symptomatic spondylolisthesis (9.2%). Multivariable regression analyses of patient-basis variables showed that being female [odds ratio (OR) 1.2, 95%CI 1.07-3.09] was associated with postoperative symptomatic spondylolisthesis. Higher BMI (OR 0.93, 95%CI 0.88-0.99) was associated with a lower probability of having postoperative symptomatic spondylolisthesis. Multivariable regression analyses of surgical level-basis variables showed that levels with preoperative spondylolisthesis (OR 17.30, 95%CI 10.27-29.07) and the level of surgery, most importantly level L4L5 compared with levels L1L3 (OR 2.80, 95%CI 0.78-10.08), were associated with postoperative symptomatic spondylolisthesis; greater facet joint angles (i.e. less sagittal-oriented facets) were associated with a lower probability of postoperative symptomatic spondylolisthesis (OR 0.97, 95%CI 0.95-0.99). CONCLUSION: Being female was associated with a higher probability of having postoperative symptomatic spondylolisthesis, while having a higher BMI was associated with a lower probability. When looking at factors related to postoperative symptomatic spondylolisthesis at the surgical level, preoperative spondylolisthesis, more sagittal orientated facet angles and surgical level (most significantly level L4L5 compared to levels L1L3) showed significant associations. These associations could be used as a basis for devising patient selection criteria, stratifying patients or performing subgroup analyses in future studies regarding decompression surgery with or without fusion.

Double-center observational study of minimally invasive sacroiliac joint fusion for sacroiliac joint dysfunction: one-year results.

BACKGROUND: For a substantial part of patients with chronic low back pain, the origin is located in the sacroiliac joint (SIJ). Minimally invasive sacroiliac joint fusion (MISJF) is increasingly being implemented as a treatment option in SIJ dysfunction. Despite remaining controversy, evidence continues to increase. This study evaluates the clinical results and safety of MISJF in a double-center consecutive case series in patients with SIJ dysfunction over a one-year observation period. METHODS: SIJ complaints were diagnosed after history taking, physical examination and least a 50% reduction of SIJ pain 30-60 min following image-guided injection. Primary outcome measures were patient reported outcome measurements (PROMs), consisting of Visual Analogue Scale (VAS) pain score and EuroQol 5-dimensions 3-levels (EQ-5D-3L). Patients' perspectives on the effects of surgery were collected through questionnaires. Secondary outcome measures were implant positioning and (serious) adverse events ((S)AE's). RESULTS: A total of 29 patients were included. In 44.8% of patients, SIJ dysfunction was of postpartum origin. The mean VAS-pain score improved from 7.83 (± 1.71) to 4.97 (± 2.63) postoperatively (p < 0.001). EQ-5D-3L score improved from 0.266 (± 0.129) to 0.499 (± 0.260) postoperatively (p < 0.001). Opioid consumption decreased from 44.8 to 24.1% postoperatively (p = 0.026). In 13.7% of patients, an (S)AE occurred. CONCLUSION: MISJF appears to be an effective and safe procedure in this cohort. Statistically significant and clinically relevant improvements in pain and quality of life were observed one-year postoperatively. Future studies should focus on the long-term outcomes to further evaluate the safety and effectiveness of MISJF.

Motion analysis in patients with postpartum sacroiliac joint dysfunction: A cross-sectional case-control study.

BACKGROUND: Patients with sacroiliac joint dysfunction are limited in daily life activities such as gait, climbing stairs and rising from a chair. It is well known that individuals with chronic low back pain have impaired balance compared to healthy individuals. This cross-sectional case-control study aims to investigate spatiotemporal parameters, center of pressure and mass, pelvic angles and other joint angles in patients with sacroiliac joint dysfunction in comparison with healthy controls. METHODS: Motion analysis existed of three tasks: (1) normal gait, (2) single-leg-stance, and (3) sit-to-stance. Spatiotemporal parameters, center of pressure, pelvic angles and other joint angles were measured using a twelve-camera, three-dimensional motion capture system and ground reaction force platforms. FINDINGS: Thirty subjects were recruited for this study; ten patients, ten matched controls and ten healthy student controls. For gait, patients had a lower cadence, longer double support phase, shorter step length and slower walking speed than controls. For single-leg-stance, patients had a smaller hip angle of the risen leg than controls. Also, variability in center of pressure was larger in patients. For sit-to-stance, the total time to perform the task was almost doubled for patients compared to controls. INTERPRETATION: This study demonstrates that patients with sacroiliac joint dysfunction have an impaired gait, more balance problems during standing and standing up compared to healthy controls. This novel information assists to further comprehend the pathology and disease burden of sacroiliac joint dysfunction, in addition, it may allow us to evaluate the effect of current therapies.

Minimally Invasive Sacroiliac Joint Fusion vs Conservative Management in Patients With Sacroiliac Joint Dysfunction: A Systematic Review and Meta-Analysis.

BACKGROUND: The sacroiliac joint (SIJ) is affected in 14% to 22% in individuals presenting with chronic low back or buttock pain. This percentage is even higher in patients who underwent lumbar fusion surgery: 32% to 42%. Currently, there is no standard treatment or surgical indication for SIJ dysfunction. When patients do not respond well to nonsurgical treatment, minimally invasive sacroiliac joint fusion (MISJF) seems to be a reasonable option. This systematic review and meta-analysis evaluates the current literature on the effectiveness of MISJF compared to conservative management in patients with SIJ dysfunction. METHODS: A systematic search of health-care databases was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Inclusion criteria were randomized controlled trials (RCTs) or prospective and retrospective comparative cohort studies that compared MISJF with conservative management. Primary outcome measures were pain, disability, and patient satisfaction measured by patient-reported outcome measures. Secondary outcomes were adverse events (AEs), serious AEs, financial benefits, and costs. RESULTS: Two RCTs and one retrospective cohort study were included comparing MISJF and conservative management with regard to pain and disability outcome, encompassing 388 patients (207 conservative and 181 surgical). In a pooled mean difference analysis, MISJF demonstrated greater reduction in visual analog scale-pain score compared to conservative management: -37.03 points (95%CI [-43.91, -30.15], P < 0.001). Moreover, MISJF was associated with a greater reduction in Oswestry Disability Index outcome: -21.14 points (95% CI [-24.93, -17.35], P < 0.001). AEs were low among the study groups and comparable across the included studies. One cost-effectiveness analysis was also included and reported that MISJF is more cost-effective than conservative management.001). AEs were low among the study groups and comparable across the included studies. One cost-effectiveness analysis was also included and reported that MISJF is more cost-effective than conservative management. CONCLUSIONS: This systematic review and meta-analysis suggest that MISJF, using cannulated triangular, titanium implants, is more effective and cost-effective than conservative management in reducing pain and disability in patients with SIJ dysfunction. Further well-powered, independent research is needed to improve the overall evidence.

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.

Proliferative and anti-apoptotic fractions in maturing hematopoietic cell lineages and their role in homeostasis of normal bone marrow.

Recent developments in clinical flow cytometry allow the simultaneous assessment of proliferative and anti-apoptotic activity in the different hematopoietic cell lineages and during their maturation process. This can further advance the flow cytometric diagnosis of myeloid malignancies. In this study we established indicative reference values for the Ki-67 proliferation index and Bcl-2 anti-apoptotic index in blast cells, as well as maturing erythroid, myeloid, and monocytic cells from normal bone marrow (BM). Furthermore, the cell fractions co-expressing both proliferation and anti-apoptotic markers were quantified. Fifty BM aspirates from femoral heads of patients undergoing hip replacement were included in this study. Ten-color/twelve-parameter flow cytometry in combination with a software-based maturation tool was used for immunophenotypic analysis of Ki-67 and Bcl-2 positive fractions during the erythro-, myelo-, and monopoiesis. Indicative reference values for the Ki-67 and Bcl-2 positive fractions were established for different relevant hematopoietic cell populations in healthy BM. Ki-67 and Bcl-2 were equally expressed in the total CD34 positive blast cell compartment and 30% of Ki-67 positive blast cells also showed Bcl-2 positivity. The Ki-67 and Bcl-2 positive fractions were highest in the more immature erythroid, myeloid and monocytic cells. Both fractions then gradually declined during the subsequent maturation phases of these cell lineages. We present a novel application of an earlier developed assay that allows the simultaneous determination of the Ki-67 proliferative and Bcl-2 anti-apoptotic indices in maturing hematopoietic cell populations of the BM. Their differential expression levels during the maturation process were in accordance with the demand and lifespan of these cell populations. The indicative reference values established in this study can act as a baseline for further cell biological and biomedical studies involving hematological malignancies.

Process Evaluation of Lumbar Interbody Fusion Surgeries in Five Dutch Hospitals: A Qualitative Analysis.

Background and Objectives: Only limited qualitative research concerning instrumented spine surgeries has been published, despite the increasing number of these surgeries and the evident importance of qualitative analysis of the processes surrounding these complex interventions. Current qualitative research is mainly limited to the experiences, emotions and expectations of patients. Insight into the full process, including experiences from the perspective of informal caregivers and healthcare professionals, remains scarce. Materials and Methods: Data were gathered by means of semi-structured face-to-face interviews. In total, there were 27 participants, including 11 patients, 7 informal caregivers and 9 healthcare professionals. The interview process was audiotaped, and each interview was transcribed verbatim. To systematically analyse the gathered data, software for qualitative analysis (NVivo) was used. After immersion in the raw data of transcripts and field notes, a list of broad categories for organising the data into meaningful clusters for analysis was developed. All interviews were coded by the first author, and 25% was independently assessed by the second author. Results: The results of our study describe several promoting and limiting factors concerning the process of lumbar fusion surgery from the perspective of patients, informal caregivers and healthcare providers. The most frequently mentioned promoting factors were: information and opportunities to ask questions during consultations; multidisciplinary consultations; good communication and guidance during hospitalization; and follow-up appointments. The most frequently mentioned limiting factors were: lack of educational material; lack of guidance and communication prior to, during and after hospitalisation. Conclusion: Overall, participants were satisfied with the current healthcare-process in lumbar fusion surgery. However, we found that lack of educational material and guidance during the process led to insecurity about complaints, surgery and recovery. To improve the process of lumbar interbody fusion and to increase patient satisfaction, healthcare providers should focus on guiding and educating patients and informal caregivers about the pre-operative trajectory, the surgery and the recovery. From the healthcare providers' perspective, the process could be improved by multidisciplinary consultations and a dedicated spine team in the operation room. Although this study focusses on lumbar fusion surgery, results could be translated to other fields of spine surgery and surgery in general.

Study protocol for a randomised controlled trial on the effect of local analgesia for pain relief after minimal invasive sacroiliac joint fusion: the ARTEMIS study.

INTRODUCTION: Chronic lower back pain is a common report in the general population. A dysfunctional sacroiliac joint (SIJ) is estimated to be responsible for one in five patients with lower back pain. Minimally invasive sacroiliac joint fusion (MISJF) is a surgical procedure to treat SIJ dysfunction. During the procedure, the SIJ is stabilised by implants inserted percutaneously under fluoroscopy guidance. Postoperatively, patients often report a lot of pain, which contributes to patients taking high doses of painkillers (opioids for example,) and preventing early mobilisation. In several orthopaedic procedures, intraoperative infiltration of the wound bed results in decreased consumption of analgesics, earlier mobilisation and shorter hospitalisation time. The aim of this study is to investigate the effectiveness of intraoperative SIJ infiltration with analgesia in reducing postoperative pain after MISJF. METHODS AND ANALYSIS: We will perform a two-centre, prospective, double-blind, randomised controlled trial to determine whether SIJ infiltration with 1.5-5 cc bupivacaine 0.50% is superior to 1.5-5 cc placebo (NaCl 0.9%) in reducing postoperative pain in patients after MISJF, and to determine whether bupivacaine significantly reduces opioid use in the direct postoperative period. Patients will be randomised with 1:1 allocation for either bupivacaine (intervention) or placebo SIJ infiltration. Postoperative pain will be measured by the Visual Analogue Scale pain score at entry and exit recovery, 2, 4, 6, 24 and 48 hours postoperatively. ETHICS AND DISSEMINATION: This is the first trial that investigates the effectiveness of intraoperative SIJ infiltration with bupivacaine 0.50% in reducing postoperative pain after MISJF. If intraoperative SIJ infiltration with bupivacaine 0.50% proves to be effective, this might have important clinical implications, such as postoperative analgesics (opioids for example,) consumption, earlier mobilisation and potentially shorter hospitalisation time. TRIAL REGISTRATION NUMBER: NL9151.

Evidence-based recommendations for economic evaluations in spine surgery: study protocol for a Delphi consensus.

INTRODUCTION: Considering the rising global healthcare expenses, economic evaluations are more important than ever. Even though the number of studies regarding costs and cost-effectiveness is increasing, the quality of these studies remains relatively low. This is mainly caused by abundant heterogeneity in methods used for determining, calculating and reporting cost data, despite current general guidelines for the conduct of economic evaluations. Disease-specific recommendations for the conduct of economic evaluations in the field of spine surgery, as complement to existing general guidelines, will ameliorate overall research quality, comparability and interpretability and thus, the overall quality. We aim to provide expert-based recommendations for the design, conduct, and reporting of economic evaluations in spine surgery. METHODS AND ANALYSIS: A modified Delphi study will be conducted to formulate expert-based recommendations. The following steps will be taken:(1) The conduct of a systematic review to identify relevant publications and identify relevant authors. Formation of an expert group and a Delphi-panel. (2) Drafting of statements based on articles included in the systematic literature review. Validation of drafted statements by the expert group. Step 2 can be repeated up to three times, statements can be discarded and adjusted in these rounds. Statements with more than 75% agreement will be accepted as consensus statements. (3) Validation of statements by the Delphi-panel. (4) Final recommendations. ETHICS AND DISSEMINATION: The underlying work is based on existing literature and published data and does not include participation of patients, and thus does not require ethical review approval. The final recommendations are intended for (clinical) researchers in the field of cost-effectiveness in spine surgery. The Delphi method ensures that the final output reflects the opinions of international participants and gives insight in the adherence level to the recommendations. The aim is to reach uniformity in design, conduct and reporting of these studies, as is currently lacking. This will provide a solid basis to determine cost-effectiveness of spine surgeries and consequently aid to limit the rising healthcare costs. The findings of this study and the final recommendations will be disseminated in conferences and seminars and will be published in an international peer-reviewed journal.

Comparison of (Partial) economic evaluations of transforaminal lumbar interbody fusion (TLIF) versus Posterior lumbar interbody fusion (PLIF) in adults with lumbar spondylolisthesis: A systematic review.

INTRODUCTION: The demand for spinal fusion surgery has increased over the last decades. Health care providers should take costs and cost-effectiveness of these surgeries into account. Open transforaminal lumbar interbody fusion (TLIF) and posterior lumbar interbody fusion (PLIF) are two widely used techniques for spinal fusion. Earlier research revealed that TLIF is associated with less blood loss, shorter surgical time and sometimes shorter length of hospital stay, while effectiveness of both techniques on back and/or leg pain are equal. Therefore, TLIF could result in lower costs and be more cost-effective than PLIF. This is the first systematic review comparing direct and indirect (partial) economic evaluations of TLIF with PLIF in adults with lumbar spondylolisthesis. Furthermore, methodological quality of included studies was assessed. METHODS: Searches were conducted in eight databases for reporting on eligibility criteria; TLIF or PLIF, lumbar spondylolisthesis or lumbar instability, and cost. Costs were converted to United States Dollars with reference year 2020. Study quality was assessed using the bias assessment tool of the Cochrane Handbook for Systematic Reviews of Interventions, the Level of Evidence guidelines of the Oxford Centre for Evidence-based Medicine and the Consensus Health Economic Criteria (CHEC) list. RESULTS: Of a total of 693 studies, 16 studies were included. Comparison of TLIF and PLIF could only be made indirectly, since no study compared TLIF and PLIF directly. There was a large heterogeneity in health care and societal perspective costs due to different in-, and exclusion criteria, baseline characteristics and the use of costs or charges in calculations. Health care perspective costs, calculated with hospital costs, ranged from $15,867-$43,217 in TLIF-studies and $32,662 in one PLIF-study. Calculated with hospital charges, it ranged from $8,964-$51,469 in TLIF-studies and $21,838-$93,609 in two PLIF-studies. Societal perspective costs and cost-effectiveness, only mentioned in TLIF-studies, ranged from $5,702/QALY-$48,538/QALY and $50,092/QALY-$90,977/QALY, respectively. Overall quality of studies was low. CONCLUSIONS: This systematic review shows that TLIF and PLIF are expensive techniques. Moreover, firm conclusions about the preferable technique, based on (partial) economic evaluations, cannot be drawn due to limited studies and heterogeneity. Randomized prospective trials and full economical evaluations with direct TLIF and PLIF comparison are needed to obtain high levels of evidence. Furthermore, development of guidelines to perform adequate economic evaluations, specified for the field of interest, will be useful to minimize heterogeneity and maximize transferability of results. TRIAL REGISTRATION: Prospero-database registration number: CRD42020196869.

Cost-effectiveness of open transforaminal lumbar interbody fusion (OTLIF) versus minimally invasive transforaminal lumbar interbody fusion (MITLIF): a systematic review and meta-analysis.

BACKGROUND CONTEXT: The number of performed instrumented lumbar spine surgeries and associated health-care-related costs has increased over the last decades, and will increase further in the future. With the consistent growth of health-care-related costs, cost-effectiveness of surgical techniques is of major relevance. Common indications for instrumented lumbar spine surgery are spondylolisthesis and degenerative disease. A commonly used technique is the open transforaminal lumbar interbody fusion (OTLIF). Nowadays, there is an increasing interest in the minimally invasive variation of this technique (minimally invasive transforaminal lumbar interbody fusion [MITLIF]). Currently available literature describes that MITLIF has comparable or even better clinical results compared to OTLIF. Cost-effectiveness of MITLIF and OTLIF is important considering the growing health-care related costs, although no consensus has been reached regarding the most cost-effective technique. In this systematic review, previous literature concerning costs and cost-effectiveness of OTLIF was compared with MITLIF in patients with lumbar spondylolisthesis or degenerative disease. Furthermore, methodological quality of included studies was assessed. PURPOSE: This study aims to evaluate the current literature on cost-effectiveness of OTLIF compared MITLIF to in patients with lumbar spondylolisthesis or degenerative disease. STUDY DESIGN: This study is a systematic literature review and meta-analysis. STUDY SAMPLE: Clinical studies reporting costs or cost-effectiveness for either OTLIF or MITLIF in patients with spondylolisthesis, lumbar instability, or degenerative disease were included. OUTCOME MEASURES: The following data items were evaluated: study design, study population, utility measurement tool, gained quality adjusted life years (QALYs), cost sources, health care and societal perspective costs, total costs, costs per QALY (cost-effectiveness) and incremental cost-effectiveness ratio (ICER). METHODS: A systematic search was conducted using databases PubMed, CINAHL, EMBASE, Cochrane, Clinical Trials, Current Controlled Trials, ClinicalTrials.gov, NHS Centre for Review and Dissemination, Econlit and Web of Science on studies reporting OTLIF or MITLIF, spondylolisthesis or lumbar instability or degenerative disease, and costs. Relevant studies were selected and reviewed independently by two authors. For comparison, all costs were converted to American dollars with the reference year 2018. RESULTS: After duplicate removal, a total of 892 studies were identified. Eventually, 32 studies were included. Nine studies compared OTLIF and MITLIF directly. All studies mentioned health care perspective costs. Seven studies mentioned societal perspective costs. Cost-effectiveness of OTLIF was mentioned in five studies, ranging from $47,303/QALY to $218,766/QALY. Cost-effectiveness of MITLIF was mentioned in one study, $121,105/QALY. Meta-analysis of hospital perspective costs showed a significant overall effect in favor of MITLIF, with a mean difference of $2,650. There was great heterogeneity in health care and societal perspective costs due to different in-, and exclusion factors, baseline characteristics, and calculation methods. Overall quality of studies was low. CONCLUSIONS: OTLIF and MITLIF appear to be expensive interventions when using a threshold of $50,000/QALY. Results of this study and previous literature suggest that MITLIF is more cost-effective compared to OTLIF. Considering the increase in health care costs of instrumented spine surgery, cost-effectiveness could be one of the factors in surgical decision-making. Prospective randomized studies directly comparing cost-effectiveness of OTLIF and MITLIF from both hospital and societal perspectives are needed to obtain higher level of evidence.