The Risk of Getting Worse: Predictors of Deterioration After Decompressive Surgery for Lumbar Spinal Stenosis: A Multicenter Observational Study

ObjectiveTo investigate the frequency and predictors of deterioration after decompressive surgery for single and 2-level lumbar spinal stenosis.MethodsProspectively collected data were retrieved from the Norwegian Registry for Spine Surgery. Clinically significant deterioration was defined as an 8-point increase in Oswestry disability index (ODI) between baseline and 12 months' follow-up.ResultsThere were 2181 patients enrolled in the study. Of 1735 patients with complete 12 months follow-up, 151 (8.7%) patients reported deterioration. The following variables were significantly associated with deterioration at 12 months' follow-up; decreasing age (odds ratio [OR] 1.02, 95% confidence interval [95% CI] 1.00–1.04, P = 0.046), tobacco smoking (OR 2.10, 95% CI 1.42–3.22, P = 0.000), American Society of Anesthesiologists grade ≥3 (OR 1.80, 95% CI 1.07–2.94, P = 0.025), decreasing preoperative ODI (OR 1.05, 95% CI 1.02–1.07, P = 0.000), previous surgery at the same level (OR 2.00, 95% CI 1.18–3.27, P = 0.009), and previous surgery at other lumbar levels (OR 2.10, 95% CI 1.19–3.53, P = 0.009).ConclusionsOverall risk of clinically significant deterioration in patient-reported pain and disability after decompressive surgery for lumbar spinal stenosis is approximately 9%. Predictors for deterioration are decreasing age, current tobacco smoking, American Society of Anesthesiologists grade ≥3, decreasing preoperative ODI, and previous surgery at same or different lumbar level. We suggest that these predictors should be emphasized and discussed with the patients before surgery

Would loss to follow-up bias the outcome evaluation of patients operated for degenerative disorders of the lumbar spine?: A study of responding and non-responding cohort participants from a clinical spine surgery registry

Loss to follow-up may bias the outcome assessments of clinical registries. In this study, we wanted to determine whether outcomes were different in responding and non-responding patients who were included in a clinical spine surgery registry, at two years of follow-up. In addition, we wanted to identify risk factors for failure to respond. 633 patients who were operated for degenerative disorders of the lumbar spine were followed for 2 years using a local clinical spine registry. Those who did not attend the clinic and those who did not answer a postal questionnaire—for whom 2 years of outcome data were missing—and who would be lost to follow-up according to the standard procedures of the registry protocols, were defined as non-respondents. They were traced and interviewed by telephone. Outcome measures were: improvement in health-related quality of life (EQ-5D), leg pain, and back pain; and also general state of health, employment status, and perceived benefits of the operation. We found no statistically significant differences in outcome between respondents (78% of the patients) and nonrespondents (22%). Receipt of postal questionnaires (not being summoned for a follow-up visit) was the strongest risk factor for failure to respond. Forgetfulness appeared to be an important cause. Older patients and those who had complications were more likely to respond. Interpretation A loss to follow-up of 22% would not bias conclusions about overall treatment effects and, importantly, there were no indications of worse outcomes in non-respondents

Identification and Characterization of Novel Mutations in the Human Gene Encoding the Catalytic Subunit Calpha of Protein Kinase A (PKA)

The genes PRKACA and PRKACB encode the principal catalytic (C) subunits of protein kinase A (PKA) Cα and Cβ, respectively. Cα is expressed in all eukaryotic tissues examined and studies of Cα knockout mice demonstrate a crucial role for Cα in normal physiology. We have sequenced exon 2 through 10 of PRKACA from the genome of 498 Norwegian donors and extracted information about PRKACA mutations from public databases. We identified four interesting nonsynonymous point mutations, Arg45Gln, Ser109Pro, Gly186Val, and Ser263Cys, in the Cα1 splice variant of the kinase. Cα variants harboring the different amino acid mutations were analyzed for kinase activity and regulatory (R) subunit binding. Whereas mutation of residues 45 and 263 did not alter catalytic activity or R subunit binding, mutation of Ser109 significantly reduced kinase activity while R subunit binding was unaltered. Mutation of Cα Gly186 completely abrogated kinase activity and PKA type I but not type II holoenzyme formation. Gly186 is located in the highly conserved DFG motif of Cα and mutation of this residue to Val was predicted to result in loss of binding of ATP and Mg2+, which may explain the kinetic inactivity. We hypothesize that individuals born with mutations of Ser109 or Gly186 may be faced with abnormal development and possibly severe disease

Outcome prediction in chronic unilateral lumbar radiculopathy: prospective cohort study

Background Identification of prognostic factors for persistent pain and disability are important for better understanding of the clinical course of chronic unilateral lumbar radiculopathy and to assist clinical decision-making. There is a lack of scientific evidence concerning prognostic factors. The aim of this study was to identify clinically relevant predictors for outcome at 52 weeks. Methods 116 patients were included in a sham controlled clinical trial on epidural injection of glucocorticoids in patients with chronic unilateral lumbar radiculopathy. Success at follow-up was ≤17.5 for visual analogue scale (VAS) leg pain, ≤22.5 for VAS back pain and ≤20 for Oswestry Disability Index (ODI). Fifteen clinically relevant variables included demographic, psychosocial, clinical and radiological data and were analysed using a logistic multivariable regression analysis. Results At follow-up, 75 (64.7%) patients had reached a successful outcome with an ODI score ≤20, 54 (46.6%) with a VAS leg pain score ≤17.5, and 47 (40.5%) with a VAS back pain score ≤22.5. Lower age (OR 0.94 (CI 0.89–0.99) for each year decrease in age) and FABQ Work ≥34 (OR 0.16 (CI 0.04-0.61)) were independent variables predicting a successful outcome on the ODI. Higher education (OR 5.77 (CI 1.46–22.87)) and working full-time (OR 2.70 (CI 1.02–7.18)) were statistically significant (P <0.05) independent predictors for successful outcome (VAS score ≤17.5) on the measure of leg pain. Lower age predicted success on ODI (OR 0.94 (95% CI 0.89 to 0.99) for each year) and less back pain (OR 0.94 (0.90 to 0.99)), while higher education (OR 5.77 (1.46 to 22.87)), working full-time (OR 2.70 (1.02 to 7.18)) and muscle weakness at baseline (OR 4.11 (1.24 to 13.61) predicted less leg pain, and reflex impairment at baseline predicted the contrary (OR 0.39 (0.15 to 0.97)). Conclusions Lower age, higher education, working full-time and low fear avoidance beliefs each predict a better outcome of chronic unilateral lumbar radiculopathy. Specifically, lower age and low fear avoidance predict a better functional outcome and less back pain, while higher education and working full-time predict less leg pain. These results should be validated in further studies before being used to inform patients. Trial registration Current Controlled Trials ISRCTN12574253 . Registered 18 May 2005

Criteria for failure and worsening after surgery for lumbar spinal stenosis. A prospective national spine registry observational study

Background context: Criteria for success after surgical treatment of lumbar spinal stenosis (LSS) have been defined previously; however, there are no clear criteria for failure and worsening after surgery as assessed by patient-reported outcome measures (PROMs). Purpose: We aimed to quantify changes in standard PROMs that most accurately identified failure and worsening after surgery for LSS. Study design /setting: Retrospective analysis of prospective national spine registry data with 12-months follow-up. Patient sample: We analyzed 10,822 patients aged 50 years and older operated in Norway during a decade, and 8,258 (76%) responded 12 months after surgery. Outcome measures (proms): We calculated final scores, absolute changes, and percentage changes for Oswestry Disability Index (ODI), Numeric Rating Scale (NRS) for back and leg pain (0-10), and EuroQol-5D (EQ-5D). These 12 PROM derivates were compared to the Global Perceived Effect (GPE), a 7-point Likert scale. Methods: We used ODI, NRS back and leg pain, and EQ-5D 12 months after surgery to identify patients with failure (no effect) and worsening (clinical deterioration). The corresponding GPE at 12-months was graded as failure (GPE=4-7) and worsening (GPE=6-7) and used as an external criterion. To quantify the most accurate cut-off values corresponding to failure and worsening, we calculated areas under the curves (AUCs) of receiver operating characteristics (ROC) curves for the respective PROM derivates. Results: Mean (95% CI) age was 68.3 (68.1 - 68.5) years, and 52% were females. There were 1,683 (20%) failures, and 476 (6%) patients were worse after surgery. The mean (95% CI) pre- and postoperative ODIs were 39.8 (39.5 - 40.2) and 23.7 (23.3 - 24.1), respectively. At 12 months, the mean difference (95% CI) in ODI was 16.1 (15.7 - 16.4), and the mean (95% CI) percentage improvement 38.8% (37.8 - 38.8). The PROM derivates identified failure and worsening accurately (AUC>0.80), except for the absolute change in EQ-5D. The ODI derivates were most accurate to identify both failure and worsening. We found that less than 20% improvement in ODI most accurately identified failure (AUC=0.89 [95% CI: 0.88 to 0.90]), and an ODI final score of 39 points or more most accurately identified worsening (AUC =0.91 [95% CI: 0.90 - 0.92]). Conclusions: In this national register study, ODI derivates were most accurate to identify both failure and worsening after surgery for degenerative lumbar spinal stenosis. We recommend use of ODI percentage change and ODI final score for further studies of failure and worsening in elective spine surgery. Keywords: Cut-off; Failure; PROM; Spinal Stenosis; Spine registry; Worsening. Copyright © 2021. Published by Elsevier Inc. © 2021 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/

Accuracy of physical examination for chronic lumbar radiculopathy

Background Clinical examination of patients with chronic lumbar radiculopathy aims to clarify whether there is nerve root impingement. The aims of this study were to investigate the association between findings at clinical examination and nerve root impingement, to evaluate the accuracy of clinical index tests in a specialised care setting, and to see whether imaging clarifies the cause of chronic radicular pain. Methods A total of 116 patients referred with symptoms of lumbar radiculopathy lasting more than 12 weeks and at least one positive index test were included. The tests were the straight leg raising test, and tests for motor muscle strength, dermatome sensory loss, and reflex impairment. Magnetic resonance imaging (n = 109) or computer tomography (n = 7) were imaging reference standards. Images were analysed at the level of single nerve root(s), and nerve root impingement was classified as present or absent. Sensitivities, specificities, and positive and negative likelihood ratios (LR) for detection of nerve root impingement were calculated for each individual index test. An overall clinical evaluation, concluding on the level and side of the radiculopathy, was performed. Results The prevalence of disc herniation was 77.8%. The diagnostic accuracy of individual index tests was low with no tests reaching positive LR >4.0 or negative LR <0.4. The overall clinical evaluation was slightly more accurate, with a positive LR of 6.28 (95% CI 1.06–37.21) for L4, 1.74 (95% CI 1.04–2.93) for L5, and 1.29 (95% CI 0.97–1.72) for S1 nerve root impingement. An overall clinical evaluation, concluding on the level and side of the radiculopathy was also performed, and receiver operating characteristic (ROC) analysis with area under the curve (AUC) calculation for diagnostic accuracy of this evaluation was performed. Conclusions The accuracy of individual clinical index tests used to predict imaging findings of nerve root impingement in patients with chronic lumbar radiculopathy is low when applied in specialised care, but clinicians’ overall evaluation improves diagnostic accuracy slightly. The tests are not very helpful in clarifying the cause of radicular pain, and are therefore inaccurate for guidance in the diagnostic workup of the patients. The study population was highly selected and therefore the results from this study should not be generalised to unselected patient populations in primary care nor to even more selected surgical populations

Persistent Use of Prescription Opioids Before and After Lumbar Spine Surgery: Observational Study With Prospectively Collected Data From Two Norwegian National Registries

Study Design - Prospective pharmacoepidemiologic study. Objective - To investigate clinical and sociodemographic factors associated with persistent opioid use in the years following spine surgery among patients with persistent opioid use preceding lumbar spine surgery. Summary of Background Data - It is unknown whether successful spine surgery leads to a cessation of preoperative persistent opioid use. Materials and Methods - Data from the Norwegian Registry for Spine Surgery and the Norwegian Prescription Database were linked for patients operated for degenerative lumbar spine disorders between 2007 and 2017. The primary outcome measure was persistent opioid use in the second year after surgery. Functional disability was measured with the Oswestry Disability Index (ODI). Factors associated with persistent opioid use in the year before, and two years following, surgery were identified using multivariable logistic regression analysis. The variables included in the analysis were selected based on their demonstrated role in prior studies. Results - The prevalence of persistent opioid use was 8.7% in the year before surgery. Approximately two-thirds of patients also met the criteria for persistent opioid use the second year after surgery. Among patients who did not meet the criteria for persistent opioid use the year before surgery, 991 (3.3%) patients developed persistent opioid use in the second year following surgery. The strongest association was exhibited by high doses of benzodiazepines in the year preceding surgery (OR 1.7, 95% CI 1.26 to 2.19, P Conclusion - A substantial proportion of patients reported sustained opioid use after surgery. Patients with persistent opioid use before surgery should be supported to taper off opioid treatment. Special efforts appear to be required to taper off opioid use in patients using high doses of benzodiazepines. Level of Evidence - 2; Prospective observational study

Open discectomy vs microdiscectomy for lumbar disc herniation - a protocol for a pragmatic comparative effectiveness study [version 1; referees: 2 approved]

Introduction:  Since the introduction of lumbar microdiscectomy in the 1970’s, many studies have attempted to compare the effectiveness of this method with that of standard open discectomy with conflicting results. This observational study is designed to compare the relative effectiveness of microdiscectomy (MD) with open discectomy (OD) for treating lumbar disc herniation, -within a large cohort, recruited from daily clinical practice. Methods and analysis:   This study will include patients registered in the Norwegian Registry for Spine Surgery (NORspine). This clinical registry collects prospective data, including preoperative and postoperative outcome measures as well as individual and demographic parameters. The primary outcome is change in Oswestry disability index between baseline and 12 months after surgery. Secondary outcome measures are improvement of leg pain and changes in health related quality of life measured by the Euro-Qol-5D between baseline and 12 months after surgery, complications to surgery, duration of surgical procedures and length of hospital stay