Responsiveness and minimal important change of specific and generic patient-reported outcome measures for back patients: the Norwegian Neck and Back Register.

PURPOSE: To evaluate responsiveness and minimal important change (MIC) of Oswestry Disability Index (ODI), pain during activity on a numeric rating scale (NRSa) and health related quality of life (EQ-5D) based on data from the Norwegian neck and back registry (NNRR). METHODS: A total of 1617 patients who responded to NNRR follow-up after both 6 and 12 months were included in this study. Responsiveness was calculated using standardized response mean and area under the receiver operating characteristic (ROC) curve. We calculated MIC with both an anchor-based and distribution-based method. RESULTS: The condition specific ODI had best responsiveness, the more generic NRSa and EQ-5D had lower responsiveness. We found that the MIC for ODI varied from 3.0 to 9.5, from 0.4 to 2.5 for NRSa while the EQ5D varied from 0.05 to 0.12 depending on the method for calculation. CONCLUSION: In a register based back pain population, the condition specific ODI was more responsive to change than the more generic tools NRSa and EQ5D. The variations in responsiveness and MIC estimates also indicate that they should be regarded as indicative, rather than fixed estimates.

Is radial extracorporeal shock wave therapy (rESWT), sham-rESWT or a standardised exercise programme in combination with advice plus customised foot orthoses more effective than advice plus customised foot orthoses alone in the treatment of plantar fasciopathy? A double-blind, randomised, sham-controlled trial.

OBJECTIVES: To assess whether radial extracorporeal shock wave therapy (rESWT), sham-rESWT or a standardised exercise programme in combination with advice plus customised foot orthoses is more effective than advice plus customised foot orthoses alone in alleviating heel pain in patients with plantar fasciopathy. METHODS: 200 patients with plantar fasciopathy were included in a four-arm, parallel-group, sham-controlled, observer-blinded, partly patient-blinded trial. At baseline, before randomisation, all patients received advice plus customised foot orthoses. Patients were randomised to rESWT (n=50), sham-rESWT (n=50), exercise (n=50) or advice plus customised foot orthoses alone (n=50). Patients in the rESWT and sham-rESWT groups received three treatments. The exercise programme comprised two exercises performed three times a week for 12 weeks, including eight supervised sessions with a physiotherapist. Patients allocated to advice plus customised foot orthoses did not receive additional treatment. The primary outcome was change in heel pain during activity in the previous week per Numeric Rating Scale (0-10) from baseline to 6-month follow-up. The outcome was collected at baseline, and 3, 6 and 12 months. RESULTS: The primary analysis showed no statistically significant between-group differences in mean change in heel pain during activity for rESWT versus advice plus customised foot orthoses (-0.02, 95% CI -1.01 to 0.96), sham-rESWT versus advice plus customised foot orthoses (0.52, 95% CI -0.49 to 1.53) and exercise versus advice plus customised foot orthoses (-0.11, 95% CI -1.11 to 0.89) at 6 months. CONCLUSION: In patients with plantar fasciopathy, there was no additional benefit of rESWT, sham-rESWT or a standardised exercise programme over advice plus customised foot orthoses in alleviating heel pain. TRIAL REGISTRATION NUMBER: NCT03472989.

Comparison of Patients Operated for Lumbar Spinal Stenosis with and without Spondylolisthesis - A Secondary Analysis of the NORDSTEN Trials.

STUDY DESIGN: Observational cohort study (secondary analysis of two randomized trials). OBJECTIVE: To investigate whether function, disability, pain and quality of life before surgery and patient-reported outcome as well as complication and reoperation rates up to two years after surgery differ between lumbar spinal stenosis patients with and without spondylolisthesis. SUMMARY OF BACKGROUND DATA: Lumbar spinal stenosis is a degenerative condition of the spine, which appears with or without degenerative spondylolisthesis often presenting similar signs and symptoms. METHOD: This study is a secondary analysis of two randomized trials on patients with lumbar spinal stenosis with and without spondylolisthesis conducted at 16 public Norwegian hospitals. Disability, function, back pain, leg pain, quality of life, complication and reoperation rates up to two years after surgery were compared between the two cohorts. RESULTS: A total of 704 patients were included in this study, 267 patients with spondylolisthesis (median age 67.0 years [IQR 61.0-72.0]; 68.7% female) and 437 patients without spondylolisthesis (median age 68.0 years IQR 62.0-73.0]; 52.9% female). In the linear mixed model analysis there were no significant differences in disability, function, back pain, leg pain and quality of life scores between the two cohorts of patient with and without spondylolisthesis before surgery or at two years follow-up. The complication rate was 22.9% in patients with spondylolisthesis and 12.1% in patients without spondylolisthesis (P<0.001). There were no significant differences in reoperation rates. CONCLUSION: In patients with lumbar spinal stenosis the symptom burden before surgery and the clinical outcome up to two years after surgery were similar independently of a concomitant spondylolisthesis.

Efficacy of naproxen in patients with sciatica: multicentre, randomized, double-blind, placebo-controlled trial.

ABSTRACT: This trial assessed the efficacy of naproxen in patients with sciatica in outpatient clinics across 4 Norwegian hospitals. A total of 123 adults with radiating pain below the knee (≥4 on a 0-10 numeric rating scale) and signs consistent with nerve root involvement were included. Participants were randomized to receive either naproxen 500 mg or a placebo twice daily for 10 days. The primary outcome, daily leg pain intensity measured on a 0 to 10 numeric rating scale throughout the treatment period, revealed a statistically significant difference in favor of naproxen, with an adjusted mean difference of -0.5 (95% CI -0.8 to -0.1, P = 0.015). In the naproxen group, the treatment effect was significantly related to time, and over the whole 10-day period, the average adjusted difference was -0.6 (95% CI -0.8 to -0.5). Mean numbers needed to treat for 30% and 50% improvement were 9.9 (95% CI 4.7-15.0) and 20.7 (8.7-32.7), respectively. The adjusted mean difference for back pain was -0.4 (95% CI -0.8 to 0.0), and for Roland Morris Disability Questionnaire for Sciatica, it was -1.5 (95% CI -3.0 to 0.0). No differences were found for sciatica bothersomeness or consumption of rescue medication or opioids. Participants in the naproxen group exhibited an adjusted odds ratio of 4.7 (95% CI 1.3-16.2) for improvement by 1 level on the global perceived change scale. In conclusion, naproxen treatment showed small, likely clinically unimportant benefits compared with placebo in patients with moderate-to-severe sciatica.

Compliance with requirements for registration and reporting of results in trials of mesenchymal stromal cells for musculoskeletal disorders: a systematic review.

OBJECTIVE: To assess compliance with statutory requirements to register and report outcomes in interventional trials of mesenchymal stromal cells (MSCs) for musculoskeletal disorders and to describe the trials' clinical and design characteristics. DESIGN: A systematic review of published trials and trials submitted to public registries. DATA SOURCES: The databases Medline, Cochrane Library and McMaster; six public clinical registries. All searches were done until 31 January 2023. ELIGIBILITY CRITERIA: Trials submitted to registries and completed before January 2021. Prospective interventional trials published in peer-reviewed journals. DATA EXTRACTION AND SYNTHESIS: The first author searched for trials that had (1) posted trial results in a public registry, (2) presented results in a peer-reviewed publication and (3) submitted a pretrial protocol to a registry before publication. Other extracted variables included trial design, number of participants, funding source, follow-up duration and cell type. RESULTS: In total 124 trials were found in registries and literature databases. Knee osteoarthritis was the most common indication. Of the 100 registry trials, 52 trials with in total 2 993 participants had neither posted results in the registry nor published results. Fifty-two of the registry trials submitted a protocol retrospectively. Forty-three of the 67 published trials (64%) had registered a pretrial protocol. Funding source was not associated with compliance with reporting requirements. A discrepancy between primary endpoints in the registry and publication was found in 16 of 25 trials. In 28% of trials, the treatment groups used adjuvant therapies. Only 39% of controlled trials were double-blinded. CONCLUSIONS: A large proportion of trials failed to comply with statutory requirements for the registration and reporting of results, thereby increasing the risk of bias in outcome assessments. To improve confidence in the role of MSCs for musculoskeletal disorders, registries and medical journals should more rigorously enforce existing requirements for registration and reporting.

The Influence of Spinous Process Union on Clinical Outcomes After Spinous Process Osteotomy for Lumbar Spinal Stenosis After 2 Years: A Secondary Analysis From the NORDSTEN-Study.

BACKGROUND: Lumbar spinal stenosis is a prevalent and increasingly important cause of low back pain, leg pain, and walking impairment. Minimally invasive decompressive techniques such as spinous process (SP) osteotomy have become more common in recent years. The main aim of this study was to investigate the proportion of complete SP union and whether complete radiological healing after the osteotomy is associated with superior clinical outcome after 2 years. METHODS: In this retrospective cohort study, 149 patients were included from the Spinal Stenosis Trial, a part of the NORwegian Degenerative spondylolisthesis and spinal STENosis study. Computed tomography imaging was performed 2 years postoperatively. The number of osteotomies and the number of SP unions were recorded. Patients were divided into groups based on the degree of union: nonunion, partial union, and complete union. Rate of success (>30% improvement in Oswestry Disability Index [ODI]) and mean change in ODI were the primary outcome measures. We compared the differences between baseline and follow-up between the Degree of Union groups. RESULTS: The study included 102 of 149 eligible patients. Ten patients (9.8%) were classified as having nonunion, 15 (14.7%) as having partial union, and 77 (75.5%) as having complete union. Of the 155 osteotomies, there were 122 classified as union (77%). The success rate was 74%, with no influence of SP union. The mean change in the ODI was -20.1 (95% CI -37.0, 14.2) with no influence of SP union. CONCLUSIONS: We found no influence of SP union, classified by computed tomography, on clinical outcome 2 years after SP osteotomy in patients with lumbar spinal stenosis. CLINICAL RELEVANCE: Supplying useful information about SPO to assist surgeons in the choice of decompressive technique.

Symptom burden and follow-up of patients with neck and back complaints in specialized outpatient care: a national register study.

Back and neck pain are common in the population, especially among immigrants. In Norway's specialist care system, treating these patients typically involves a multidisciplinary approach based on the biopsychosocial model. However, language and cultural differences may create barriers to participation. Immigrants are often underrepresented in clinical studies, but a register-based approach can enhance their participation in research. This study aimed to compare both the symptom burden, and treatment, among Norwegians, non-Norwegians, and patients requiring translator service for back and neck pain within the Norwegian specialist care system. The Norwegian neck and back registry is a National Quality Register, established in 2012 and fully digitized in late 2020. The baseline data includes demographics and patient recorded outcome measures including Oswestry Disability Index, Fear-Avoidance Beliefs, pain rating on a numeric rating scale, Hopkins Symptom Checklist and EuroQol five-dimensional questionnaire on health related quality of life. During the two-year study period, a total of 14,124 patients were invited, and 10,060 (71%) participated. Norwegian patients reported less pain, better function assessed by Oswestry Disability Index, lower fear avoidance beliefs, less emotional distress, and higher health related quality of life compared to non-Norwegians. We found that patients with female gender, who were younger, more educated and exhibited fear-avoidance behavior were significantly more likely to receive multidisciplinary treatment. We found no difference in the proportion of Norwegian and non-Norwegian patients receiving multidisciplinary treatment [odds ratio (OR) 1.02 (95% confidence interval (CI) 0.90-1.16)]. However, patients needing a translator were less likely to receive multidisciplinary treatment compared to those who didn't require translation [OR 0.41 (95% CI (0.25-0.66)]. We found that non-Norwegian patients experience a higher symptom burden compared to Norwegian. We found that both non-Norwegians and patient in need of translator were to a greater extent recommended treatment in primary health care. The proportion of non-Norwegians patients receiving multidisciplinary treatment was similar to Norwegians, but those needing a translator were less likely to receive such treatment.

Do patients with lumbar spinal stenosis benefit from decompression of levels with adjacent moderate stenosis? A prospective cohort study from the NORDSTEN study.

BACKGROUND: Lumbar spinal stenosis (LSS) is characterized by pain that radiates to the buttocks and/or legs, aggravated by walking and relieved by forward flexion. There is poor correlation between clinical symptoms and severity of stenosis on MRI, and multilevel stenosis has not been described to present worse symptoms or treatment outcomes, compared with patients with single-level stenosis. In patients with one level with severe stenosis combined with an adjacent level with moderate stenosis, the surgeon must decide whether to decompress only the narrowest level or both, to achieve the best possible outcome. The potential benefits of performing surgery on an adjacent moderate stenosis is debated, and the scientific evidence in scarce. PURPOSE: The aim of the present study was to investigate whether patients with a level of adjacent moderate stenosis, along with an index stenosis, benefitted from a dual-level decompression (DLD) compared with a single-level decompression (SLD). Furthermore, to investigate whether DLD patients had longer duration of surgery and hospital stay, higher rates of complications and/or lower rate of reoperations compared with SLD patients. STUDY DESIGN: Prospective cohort study. PATIENT SAMPLE: We analyzed data from the Norwegian Degenerative Spondylisthesis and Spinal Stenosis study- Spinal Stenosis Trial (NORDSTEN-SST). In this randomized multicenter study, 437 patients were included, evaluating clinical outcomes of three different surgical treatment options for LSS. Patients with degenerative spondylolisthesis were excluded. METHOD: Based on preoperative MRI, the present analysis included all patients who had a moderate stenosis (defined as Schizas B or C) in addition to a predefined index stenosis (the level with the smallest cross-sectional area). We compared patients who, based on the surgeons` choice, received a dual-level decompression, with those receiving a single-level decompression. OUTCOME MEASURES: The primary outcome was mean change in the Oswestry Disability Index (ODI) score from baseline to 2-year follow up. Secondary outcomes were proportion of success (30% reduction in ODI score), the Numeric Rating Scales for back and leg pain (NRS), the EuroQol 5-dimensional questionnaire utility index (EQ-5D), the Zurich Claudication Questionnaire (ZCQ), the Global Perceived Effect (GPE)-scale, duration of surgery, duration of hospital stay, perioperative complications and reoperation rates. RESULTS: Among the 222 patients, included in the analysis, 108 underwent DLD and 114 underwent SLD. There was no difference in change scores for any of the investigated patient-reported outcomes between the groups after 2 years. However, the DLD group had longer duration of surgery and longer length of hospital stay. There was no difference in reoperation rates or perioperative complications. CONCLUSION: This study, alongside the NORDSTEN-LSS trial on patients with adjacent moderate stenosis as well as an index stenosis, showed no superior clinical effectiveness for dual-level surgery compared with single-level surgery.

Ultrasound guided lavage with corticosteroid injection versus sham lavage with and without corticosteroid injection for calcific tendinopathy of shoulder: randomised double blinded multi-arm study.

OBJECTIVE: To compare treatment effects between ultrasound guided lavage with corticosteroid injection and sham lavage with and without corticosteroid injection in patients with calcific tendinopathy of the shoulder. DESIGN: Pragmatic, three arm, parallel group, double blinded, sham controlled, randomised, superiority trial with repeated measurements over 24 months. SETTING: Six hospitals in Norway and Sweden. PARTICIPANTS: 220 adults with calcific tendinopathy of the shoulder, persistent for at least three months. INTERVENTIONS: Ultrasound guided deposit lavage plus subacromial injection of 20 mg triamcinolone acetonide and 9 mL 1% lidocaine hydrochloride (lavage+steroid); sham lavage plus subacromial injection of 20 mg triamcinolone acetonide and 9 mL 1% lidocaine hydrochloride (sham lavage+steroid); or sham lavage plus subacromial injection of 10 mL 1% lidocaine hydrochloride (sham). All patients received a physiotherapeutic treatment regimen consisting of four home exercises. MAIN OUTCOME MEASURES: The primary outcome was the result on the 48 point scale (0=worst; 48=best) of the Oxford Shoulder Score (OSS) at four month follow-up. Secondary outcomes included measurements on the short form of the Disabilities of the Arm, Shoulder and Hand questionnaire (QuickDASH) and of pain intensity up to 24 months. The influence of the size of the deposit at baseline and of the persistence or disappearance of the deposit was investigated. RESULTS: Data from 218 (99%) participants were included in the primary analysis. Differences between groups on the OSS at four months were not significant: lavage+steroid versus sham 0.2 (95% confidence interval -2.3 to 2.8; P=1.0); sham lavage+steroid versus sham 2.0 (-0.5 to 4.6; P=0.35); lavage+steroid versus sham lavage+steroid -1.8 (-4.3 to 0.7; P=0.47). After four months, 143 patients with insufficient treatment effect received supplementary treatment. At 24 months, none of the study procedures was superior to sham. No serious adverse events were reported. CONCLUSIONS: This study found no benefit for ultrasound guided lavage with a corticosteroid injection or for sham lavage with a corticosteroid injection compared with sham treatment in patients with calcific rotator cuff tendinopathy of the shoulder. TRIAL REGISTRATION: NCT02419040EudraCT 2015-002343-34; Ethical committee Norway 2015-002343-34; Ethical committee Sweden 2015/79-31; Clinicaltrials.gov NCT02419040.

Responsiveness of specific and generic patient-reported outcome measures in patients with plantar fasciopathy.

PURPOSE: To evaluate and compare responsiveness characteristics for the Foot Function Index revised short form (FFI-RS), RAND-12 Health Status Inventory (RAND-12), and Numeric Rating Scale (NRS), in patients with plantar fasciopathy receiving non-surgical treatment. MATERIALS AND METHODS: This study was conducted on a sub-group of patients from an ongoing randomised controlled trial. One-hundred fifteen patients were included. The patient-reported outcome measures (PROMs) were applied at baseline and after 6 months. Responsiveness was calculated using standardised response mean and area under the receiver operating characteristic (ROC) curve. ROC curves were used to compute the minimal important change (MIC) for the outcome measures. RESULTS: The region specific FFI-RS had best responsiveness and the NRS at rest had lowest responsiveness. CONCLUSION: FFI-RS were marginally more responsive than the other PROMs. Responsiveness and MIC estimates should be regarded as indicative rather than fixed estimates.

The region-specific Foot Function Index Revised Short Form could, based on responsiveness perspectives, be recommended as an outcome measurement for patients with plantar fasciopathy.Responsiveness and minimal important change estimates are indicative and should be interpreted with caution.

The Norwegian registry for spine surgery (NORspine): cohort profile.

PURPOSE: To review and describe the development, methods and cohort of the lumbosacral part of the Norwegian registry for spine surgery (NORspine). METHODS: NORspine was established in 2007. It is government funded, covers all providers and captures consecutive cases undergoing operations for degenerative disorders. Patients' participation is voluntary and requires informed consent. A set of baseline-, process- and outcome-variables (3 and 12 months) recommended by the International Consortium for Health Outcome Measurement is reported by surgeons and patients. The main outcome is the Oswestry disability index (ODI) at 12 months. RESULTS: We show satisfactory data quality assessed by completeness, timeliness, accuracy, relevance and comparability. The coverage rate has been 100% since 2016 and the capture rate has increased to 74% in 2021. The cohort consists of 60,647 (47.6% women) cases with mean age 55.7 years, registered during the years 2007 through 2021. The proportions > 70 years and with an American Society of Anaesthesiologists' Physical Classification System (ASA) score > II has increased gradually to 26.1% and 19.3%, respectively. Mean ODI at baseline was 43.0 (standard deviation 17.3). Most cases were operated with decompression for disc herniation (n = 26,557, 43.8%) or spinal stenosis (n = 26,545, 43.8%), and 7417 (12.2%) with additional or primary fusion. The response rate at 12 months follow-up was 71.6%. CONCLUSION: NORspine is a well-designed population-based comprehensive national clinical quality registry. The register's methods ensure appropriate data for quality surveillance and improvement, and research.

The reliability and validity of the Norwegian version of the Victorian Institute of Sports Assessment for gluteal tendinopathy questionnaire (VISA-G-Norwegian) for patients with greater trochanteric pain syndrome.

BACKGROUND: Greater Trochanteric Pain Syndrome (GTPS) is a common chronic musculoskeletal condition that may affect physical function, quality of life and sleep. The Victorian Institute of Sport Assessment-Gluteal questionnaire (VISA-G) has been developed as a Patient-Reported Outcome Measurement (PROM) to address pain, everyday activities, physical activities, and difficulty with weight bearing activities. The aim of the study was to test the reliability, validity and floor and ceiling effects of the Norwegian version of the VISA-G (VISA-G-Norwegian) in a population with GTPS in a specialist health care setting. METHODS: This psychometric evaluation of the VISA-G-Norwegian questionnaire were conducted with a prospective observational design. The VISA-G was translated into Norwegian following recommended guidelines. A subgroup repeated the VISA-G-Norwegian a week after the initial submission. For the reliability, the Intraclass Correlation Coefficient (ICC2.1), Standard Error of the Measurement (SEM) and the Smallest Detectable Change (SDC95%) were calculated. Internal consistency was measured using a Cronbach´s alpha. Floor and ceiling effects were evaluated, and construct validity was assessed with three a priori hypotheses. RESULTS: 78 participants were included in the study of which 47 stable participants undertook the test-retest reliability arm of the study. The ICC2.1 for the total score was 0.85 (95% CI 0.68, 0.92), SEM was 6.6 points and SDC95% 18.4 points. Cronbach`s alpha was 0.77 (95% CI 0.69, 0.84). No floor or ceiling effects were found in the total score, but ceiling effect was found in three of the eight items. For construct validity, one of the three hypotheses were confirmed. VISA-G-Norwegian correlated to the modified Harris Hip Score (mHHS), Oswestry Disability Questionnaire (ODI) and Numeric Pain Rating Scale (NPRS), 0.64, -0.75 and - 0.63 respectively. CONCLUSION: The VISA-G-Norwegian has acceptable reliability and validity, despite ceiling effect of individual items. The large SDC95% should be considered when measuring change in similar cohorts with GTPS. For a potential future version, it would be recommended to consider response options for questions with ceiling effect and the comprehensibility of question eight. TRIAL REGISTRATION: Registered at ClinicalTrials.gov the 28/02/2020 (NCT04289922).

The Norwegian degenerative spondylolisthesis and spinal stenosis (NORDSTEN) study: study overview, organization structure and study population.

PURPOSE: To provide an overview of the The Norwegian Degenerative spondylolisthesis and spinal stenosis (NORDSTEN)-study and the organizational structure, and to evaluate the study population. METHODS: The NORDSTEN is a multicentre study with 10 year follow-up, conducted at 18 public hospitals. NORDSTEN includes three studies: (1) The randomized spinal stenosis trial comparing the impact of three different decompression techniques; (2) the randomized degenerative spondylolisthesis trial investigating whether decompression surgery alone is as good as decompression with instrumented fusion; (3) the observational cohort tracking the natural course of LSS in patients without planned surgical treatment. A range of clinical and radiological data are collected at defined time points. To administer, guide, monitor and assist the surgical units and the researchers involved, the NORDSTEN national project organization was established. Corresponding clinical data from the Norwegian Registry for Spine Surgery (NORspine) were used to assess if the randomized NORDSTEN-population at baseline was representative for LSS patients treated in routine surgical practice. RESULTS: A total of 988 LSS patients with or without spondylolistheses were included from 2014 to 2018. The clinical trials did not find any difference in the efficacy of the surgical methods evaluated. The NORDSTEN patients were similar to those being consecutively operated at the same hospitals and reported to the NORspine during the same time period. CONCLUSION: The NORDSTEN study provides opportunity to investigate clinical course of LSS with or without surgical interventions. The NORDSTEN-study population were similar to LSS patients treated in routine surgical practice, supporting the external validity of previously published results. TRIAL REGISTRATION: ClinicalTrials.gov; NCT02007083 10/12/2013, NCT02051374 31/01/2014 and NCT03562936 20/06/2018.

Surgery in degenerative spondylolisthesis: does fusion improve outcome in subgroups? A secondary analysis from a randomized trial (NORDSTEN trial).

BACKGROUND CONTEXT: Patients with spinal stenosis and degenerative spondylolisthesis are treated surgically with decompression alone or decompression with fusion. However, there is debate regarding which subgroups of patients may benefit from additional fusion. PURPOSE: To investigate possible treatment effect modifiers and prognostic variables among patients operated for spinal stenosis and degenerative spondylolisthesis. DESIGN: A secondary exploratory study using data from the Norwegian Degenerative Spondylolisthesis and Spinal Stenosis (NORDSTEN-DS) trial. Patients were randomized to decompression alone or decompression with instrumented fusion. PATIENT SAMPLE: The sample in this study consists of 267 patients from a randomized multicenter trial involving 16 hospitals in Norway. Patients were enrolled from February 12, 2014, to December 18, 2017. The study did not include patients with degenerative scoliosis, severe foraminal stenosis, multilevel spondylolisthesis, or previous surgery. OUTCOME MEASURES: The primary outcome was an improvement of ≥ 30% on the Oswestry Disability Index score (ODI) from baseline to 2-year follow-up. METHODS: When investigating possible variables that could modify the treatment effect, we analyzed the treatment arms separately. When testing for prognostic factors we analyzed the whole cohort (both treatment groups). We used univariate and multiple regression analyses. The selection of variables was done a priori, according to the published trial protocol. RESULTS: Of the 267 patients included in the trial (183 female [67%]; mean [SD] age, 66 [7.6] years), complete baseline data for the variables required for the present analysis were available for 205 of the 267 individuals. We did not find any clinical or radiological variables at baseline that modified the treatment effect. Thus, none of the commonly used criteria for selecting patients for fusion surgery influenced the chosen primary outcome in the two treatment arms. For the whole cohort, less comorbidity (American Society of Anesthesiologists Classification [ASA], OR = 4.35; 95% confidence interval (CI [1.16-16.67]) and more preoperative leg pain (OR = 1.23; CI [1.02-1.50]) were significantly associated with an improved primary outcome. CONCLUSIONS: In this study on patients with degenerative spondylolisthesis, neither previously defined instability criteria nor other pre-specified baseline variables were associated with better clinical outcome if fusion surgery was performed. None of the analyzed variables can be applied to guide the decision for fusion surgery in patients with degenerative spondylolisthesis. For both treatment groups, less comorbidity and more leg pain were associated with improved outcome 2 years after surgery. TRIAL REGISTRATION: NORDSTEN-DS ClinicalTrials.gov, NCT02051374.

Cytokine Patterns as Predictors of Antibiotic Treatment Effect in Chronic Low Back Pain with Modic Changes: Subgroup Analyses of a Randomized Trial (AIM Study).

Objective: Randomized trials testing the effect of antibiotics for chronic low back pain (LBP) with vertebral bone marrow changes on MRI (Modic changes) report inconsistent results. A proposed explanation is subgroups with low grade discitis where antibiotics are effective, but there is currently no method to identify such subgroups. The objective of the present study was to evaluate whether distinct patterns of serum cytokine levels predict any treatment effect of oral amoxicillin at one-year follow-up in patients with chronic low back pain and Modic changes at the level of a previous lumbar disc herniation. Design: We used data from an overpowered, randomized, placebo-controlled trial (the AIM study) that tested 100 days of oral 750 mg amoxicillin vs placebo three times daily in hospital outpatients with chronic (>6 months) LBP with pain intensity ≥5 on a 0-10 numerical rating scale and Modic changes type 1 (oedema type) or 2 (fatty type). We measured serum levels of 40 inflammatory cytokines at baseline and analysed six predefined potential predictors of treatment effect based on cytokine patterns in 78 randomized patients; three analyses with recursive partitioning, one based on cluster analysis and two based on principal component analyses. The primary outcome was the Roland-Morris Disability Questionnaire score at one-year follow-up in the intention to treat population. The methodology and overall results of the AIM study were published previously. Results: The 78 patients were 25-62 years old and 47 (60%) were women. None of the three recursive partitioning analyses resulted in any suggested subgroups. Of all main analyses, the largest effect estimate (mean difference between antibiotic and placebo groups) was seen in a subgroup not predefined as of main interest (Cluster category 3+4; -2.0, 95% CI: -5.2-1.3, RMDQ points; p-value for interaction 0.54). Conclusion: Patterns of inflammatory serum cytokine levels did not predict treatment effect of amoxicillin in patients with chronic LBP and Modic changes. Clinical Trial Registration Number: ClinicalTrials.gov (identifier: NCT02323412).

Factors correlated with pain after total knee arthroplasty: A systematic review and meta-analysis.

MAIN OBJECTIVE: Systematically review and synthesize preoperative and intraoperative factors associated with pain after total knee arthroplasty (TKA) in patients with osteoarthritis. METHODS: Based on a peer-reviewed protocol, we searched Medline, Embase, CINAHL, Cochrane Library, and PEDro for prospective observational studies (January 2000 to February 2023) investigating factors associated with pain after TKA. The primary outcome was pain twelve months after TKA. Pain at three and six months were secondary outcomes. Multivariate random-effects meta-analyses were used to estimate mean correlation (95% CIs) between factors and pain. Sensitivity analysis was performed for each risk of bias domain and certainty of evidence was assessed. RESULTS: Of 13,640 studies, 29 reports of 10,360 patients and 61 factors were analysed. The mean correlation between preoperative factors and more severe pain at twelve months was estimated to be 0.36 (95% CI, 0.24, 0.47; P < .000; moderate-certainty evidence) for more catastrophizing, 0.15 (95% CI; 0.08, 0.23; P < .001; moderate-certainty evidence) for more symptomatic joints, 0.13 (95% CI, 0.06, 0.19; P < .001; very low-certainty evidence) for more preoperative pain. Mean correlation between more severe radiographic osteoarthritis and less pain was -0.15 (95% CI; -0.23, -0.08; P < .001; low-certainty evidence). In sensitivity analysis, the estimated correlation coefficient for pain catastrophizing factor increased to 0.38 (95% CI 0.04, 0.64). At six and three months, more severe preoperative pain was associated with more pain. Better preoperative mental health was associated with less pain at six months. CONCLUSION AND RELEVANCE: More pain catastrophizing, more symptomatic joints and more pain preoperatively were correlated with more pain, while more severe osteoarthritis was correlated with less pain one year after TKA. More preoperative pain was correlated with more pain, and better mental health with less pain at six and three months. These findings should be further tested in predictive models to gain knowledge which may improve TKA outcomes.

Impact of the number of previous lumbar operations on patient-reported outcomes after surgery for lumbar spinal stenosis or lumbar disc herniation.

Repeated lumbar spine surgery has been associated with inferior clinical outcomes. This study aimed to examine and quantify the impact of this association in a national clinical register cohort. This is a population-based study from the Norwegian Registry for Spine surgery (NORspine). We included 26,723 consecutive cases operated for lumbar spinal stenosis or lumbar disc herniation from January 2007 to December 2018. The primary outcome was the Oswestry Disability Index (ODI), presented as the proportions reaching a patient-acceptable symptom state (PASS; defined as an ODI raw score ≤ 22) and ODI raw and change scores at 12-month follow-up. Secondary outcomes were the Global Perceived Effect scale, the numerical rating scale for pain, the EuroQoL five-dimensions health questionnaire, occurrence of perioperative complications and wound infections, and working capability. Binary logistic regression analysis was conducted to examine how the number of previous operations influenced the odds of not reaching a PASS. The proportion reaching a PASS decreased from 66.0% (95% confidence interval (CI) 65.4 to 66.7) in cases with no previous operation to 22.0% (95% CI 15.2 to 30.3) in cases with four or more previous operations (p < 0.001). The odds of not reaching a PASS were 2.1 (95% CI 1.9 to 2.2) in cases with one previous operation, 2.6 (95% CI 2.3 to 3.0) in cases with two, 4.4 (95% CI 3.4 to 5.5) in cases with three, and 6.9 (95% CI 4.5 to 10.5) in cases with four or more previous operations. The ODI raw and change scores and the secondary outcomes showed similar trends. We found a dose-response relationship between increasing number of previous operations and inferior outcomes among patients operated for degenerative conditions in the lumbar spine. This information should be considered in the shared decision-making process prior to elective spine surgery.

The clinical impact of retears after repair of posterosuperior rotator cuff tears: a systematic review and meta-analysis.

BACKGROUND: Structural integrity after rotator cuff repair is frequently not achieved, but the clinical consequences of a retear remain disputed. The purpose of this meta-analysis was to analyze the relationships between postoperative cuff integrity and shoulder pain and function. METHODS: We searched the literature for studies of surgical repair of full-thickness rotator cuff tears published after 1999 describing rates of retear and clinical outcomes and providing sufficient data to estimate effect sizes (standardized mean differences [SMDs]). Baseline and follow-up data of healed and failed repairs were extracted, including shoulder-specific scores, pain, muscle strength, and health-related quality of life. Pooled SMDs, mean differences, and overall change from baseline to follow-up according to structural integrity at follow-up were calculated. Subgroup analysis was performed to assess the influence of study quality on differences. RESULTS: This analysis included 43 study arms with 3350 participants. The average age of the participants was 62 years (range, 52-78 years). The median number of participants per study was 65 (interquartile range, 39-108). At a median of 18 months' follow-up (interquartile range, 12-36 months), 844 repairs (25%) were described as retorn on imaging. The pooled SMD between healed repairs and retears at follow-up was 0.49 (95% confidence interval [CI], 0.37 to 0.61) for the Constant-Murley score, 0.49 (95% CI, 0.22 to 0.75) for the American Shoulder and Elbow Surgeons score, 0.55 (95% CI, 0.31 to 0.78) for other shoulder-specific outcomes combined, 0.27 (95% CI, 0.07 to 0.48) for pain, 0.68 (95% CI, 0.26 to 1.11) for muscle strength, and -0.001 (95% CI, -0.26 to 0.26) for health-related quality of life. The pooled mean differences were 6.12 (95% CI, 4.65 to 7.59) for the Constant-Murley score, 7.13 (95% CI, 3.57 to 10.70) for the American Shoulder and Elbow Surgeons score, and 0.49 (95% CI, 0.12 to 0.87) for pain, all below the commonly suggested minimal clinically important differences. The differences were not significantly affected by study quality and were generally modest compared with overall improvements from baseline to follow-up for both healed and failed repairs. CONCLUSIONS: The negative impact of retears on pain and function was statistically significant but judged to be of minor clinical importance. The results indicate that most patients may expect satisfactory outcomes despite retears.