Peter Fritzell

2001 Volvo Award Winner in Clinical Studies: Lumbar fusion versus nonsurgical treatment for chronic low back pain: a multicenter randomized controlled trial from the Swedish Lumbar Spine Study Group.

Study Design. A randomized controlled multicenter study with a 2-year follow-up by an independent observer. Objectives. To determine whether fusion of the lower lumbar spine could reduce pain and diminish disability more effectively when compared with nonsurgical treatment in patients with severe chronic low back pain (CLBP). Summary of Background Data. The reported results after fusion surgery on patients with CLBP vary considerably, and the evidence of treatment efficacy is weak in the absence of randomized controlled studies. Patients and Methods. A total of 294 patients referred to 19 spinal centers from 1992 through 1998 were randomized blindly into four treatment groups. Patients aged 25–65 years with CLBP for at least 2 years and with radiologic evidence of disc degeneration at L4–L5, L5-S1, or both were eligible to participate in the study. The surgical group (n=222) included three different fusion techniques, not analyzed separately in this study. Patients in the nonsurgical group (n=72) were treated with different kinds of physical therapy. The surgical group comprised 49.5% men, and the mean age was 43 years. The corresponding figures for the nonsurgical group were 48.6% and 44 years. The patients had suffered from low back pain for a mean of 7.8 and 8.5 years and been on sick leave due to back pain for a mean of 3.2 and 2.9 years, respectively. The Visual Analogue Scale (VAS) was used to measure pain. The Oswestry Low Back Pain Questionnaire, the Million Score and the General Function Score (GFS) were used to measure disability. The Zung Depression Scale was used to measure depressive symptoms. The overall result was assessed by the patient and by an independent observer. Records from the Swedish Social Insurance were used to evaluate work disability. Patients who changed groups were included in the analyses of significance according to the intention-to-treat principle. Results. At the 2-year follow-up 289 of 294 (98%) patients, including 25 who had changed groups, were examined. Back pain was reduced in the surgical group by 33% (64 to 43), compared with 7% (63 to 58) in the nonsurgical group (P =0.0002). Pain improved most during the first 6 months and then gradually deteriorated. Disability according to Oswestry was reduced by 25% (47 to 36) compared with 6% (48 to 46) among nonsurgical patients (P =0.015), according to Million by 28% (64 to 46) compared with 8% (66 to 60) (P =0.004), and accordingtoGFS by 31% (49 to 34) compared with 4% (48 to 46) (P =0.005). The depressive symptoms, according to Zung, were reduced by 20% (39 to 31) in the surgical group compared with 7% (39 to 36) in the nonsurgical group (P =0.123). In the surgical group 63% (122/195) rated themselves as “much better” or “better” compared with 29% (18/62) in the nonsurgical group (P <0.0001). The “net back to work rate” was significantly in favor of surgical treatment, or 36% vs. 13% (P =0.002). The early complication rate in the surgical group was 17%. Conclusion. Lumbar fusion in a well-informed and selected group of patients with severe CLBP can diminish pain and decrease disability more efficiently than commonly used nonsurgical treatment.

The clinical importance of changes in outcome scores after treatment for chronic low back pain

Abstract. When measuring treatment effect in chronic low back pain with multi-item outcome instruments, it is necessary, both for clinical decision-making and research purposes, to understand the clinical importance of the outcome scores. The aims of the present study were three-fold. Firstly, it aimed to estimate the minimal clinically important difference of three multi-item outcome instruments (the Oswestry Disability Index, the General Function Score and the Zung Depression Scale) and of the visual analogue scale (VAS) of back pain. Secondly, it aimed to estimate the error of measurement of these instruments; and its third aim was to describe the clinical meaning of score change. The study population consisted of 289 patients treated surgically or non-surgically in a randomised controlled trial. The minimal clinically important difference was estimated with patient global assessment as the external criterion. It was compared with the standard error of measurement of the instruments. The individual items of the instruments were compared for score changes related to improvement and deterioration. The standard error of measurement of the Oswestry Disability Index, the General Function Score and the Zung Depression Scale was 4, 6 and 3 units, respectively. The 95% tolerance interval was 10, 16 and 8 units, respectively. The minimal clinically important difference was 10, 12 and 8–9 units, respectively, thus not significantly exceeding the tolerance interval. The minimal clinically important difference of VAS back pain was 18–19 units, well exceeding the 95% tolerance interval, which was 15 units. Improvement after treatment for chronic low back pain tends to occur to a greater extent in sleep disturbance, ability to do usual things and psychological irritability, but to a lesser extent in the ability to sit, stand and lift. We conclude that the VAS of back pain is responsive enough to detect the minimal clinically important difference, whereas the smallest acceptable score changes of the Oswestry Disability Index, the General Function Score and the Zung Depression Scale may require an increase to exceed the 95% tolerance interval when used for clinical decision making and for power calculation. Despite improvement after treatment, the ability to sit, stand and lift, remain notable problems.

Chronic low back pain and fusion: a comparison of three surgical techniques: a prospective multicenter randomized study from the Swedish lumbar spine study group.

Study Design. A multicenter randomized study with a 2-year follow-up period and an independent observer was conducted. Objective. To compare three commonly used surgical techniques to achieve lumbar fusion primarily in terms of their ability to reduce pain and decrease disability in patients with severe chronic low back pain. Summary of Background Data. Lumbar fusion can be used to reduce pain and decrease disability in patients with chronic low back pain, and different surgical techniques are available. The reported results after fusion surgery vary considerably, but most studies are retrospective and/or performed on heterogeneous patient groups. Spine surgeons commonly use the techniques presented in this report. However, in the absence of randomized trials it is difficult to know whether any one of them is better than the others for these patients. Methods. From 1992 through 1998, 294 patients referred to 19 spinal centers were blindly randomized into four treatment groups: three surgical groups (n = 222) and one nonsurgical group (n = 72). The sociodemographic and clinical characteristics did not differ among the groups. Eligibility included patients 25 to 65 years of age with therapy-resistant chronic low back pain that had persisted for at least 2 years and radiologic evidence of disc degeneration (spondylosis) at L4–L5, L5–S1, or both. Only patients randomized to one of three surgical groups were analyzed in the current study: Group 1 (posterolateral fusion; n = 73), Group 2 (posterolateral fusion combined with variable screw placement, an internal fixation device; n = 74), and Group 3 (posterolateral fusion combined with variable screw placement and interbody fusion; n = 75). The “circumferential fusion” in Group 3 was performed either as an anterior lumbar interbody fusion (n = 56) or as a biomechanically similar posterior lumbar interbody fusion (n = 19). The groups were composed of 51%, 58%, and 40% men respectively, and the respective mean ages were 44, 43, and 42 years. The patients had experienced low back pain for at least 2 years (mean, ≈8 years). They had been on sick leave for approximately 3 years. Pain was measured by a visual analog scale, and disability was assessed by the Oswestry Low Back Pain Questionnaire, the Million Visual Analogue Score, and the General Function Score. Depressive symptoms were measured by the Zung Depression Scale. The global overall rating of the result was assessed by the patient and an independent observer after 2 years. Hospitalization data including operation time, blood loss, blood transfusion, and days of hospitalization in connection with surgery were reported, along with complications and the fusion rate. Records from the Swedish Social Insurance Board providing information on sick leave and economic compensation for Swedish residents were used to evaluate the patients’ work status. Results. An independent observer examined 201 (91%) of 222 patients after 2 years, after 18 “group changers” and 3 dropouts had been excluded from the analyses. All surgical techniques were found to reduce pain and decrease disability substantially, but no significant differences were found among the groups. In all three groups, the patients rated the overall outcome similarly, as did the independent observer. The more demanding techniques in Groups 2 and 3 consumed significantly more resources in terms of operation time, blood transfusions, and days in hospital after surgery. The early complication rate was 6% in Group 1, 16% in Group 2, and 31% in Group 3. The fusion rate, as evaluated by plain radiograph, was 72% in Group 1, 87% in Group 2, and 91% in Group 3. Conclusions. All the fusion techniques used in the study could reduce pain and improve function in this selected group of patients with severe chronic low back pain. There was no obvious disadvantage in using the least demanding surgical technique of posterolateral fusion without internal fixation.

Balloon Kyphoplasty and Vertebroplasty for Vertebral Compression Fractures : A Comparative Systematic Review of Efficacy and Safety

Study Design. Systematic review and meta-regression. Objectives. To compare the efficacy and safety of balloon kyphoplasty and vertebroplasty for the treatment of vertebral compression fractures, and to examine the prognostic factors that predict outcome. Summary of Background Data. A previous systematic review of vertebroplasty by Levine et al in 2000 identified seven case series studies and no controlled studies. Methods. A number of electronic databases were searched through March 1, 2004. Citation searches of included studies were undertaken and contact was made with experts in the field. No language restrictions were applied. All controlled and uncontrolled studies were included with the exception of case reports. Prognostic factors responsible for pain relief and cement leakage were examined using meta-regression. Results. The following studies were included: balloon kyphoplasty (three nonrandomized comparative studies against conventional medical therapy and 13 case series), vertebroplasty (one nonrandomized comparative study against conventional medical care and 57 cases series), balloon kyphoplasty versus vertebroplasty (one nonrandomized comparative study). The majority of studies were undertaken in older women with osteoporotic vertebral compression fractures with long-term pain that was refractory to medical treatment. At this time, there is no good quality direct comparative evidence of balloon kyphoplasty versus vertebroplasty. From indirect comparison of case series evidence, the procedures appear to provide similar gains in pain relief while for balloon kyphoplasty there is better documentation of gains in patient functionality and quality of life. The level of cement leakage and number of reported adverse events (pulmonary emboli and neurologic injury) in balloon kyphoplasty was significantly lower than for vertebroplasty. These findings were confirmed by meta-regression analysis. Conclusions. There is Level III evidence to support balloon kyphoplasty and vertebroplasty as effective therapies in the management of patients with symptomatic osteoporotic vertebral compression fractures refractory to conventional medical therapy. Although there was a good ratio of benefit to harm for both procedures, balloon kyphoplasty appears to offer the better adverse event profile. These conclusions need to be updated on the basis of the findings of ongoing randomized controlled trials.

Balloon kyphoplasty in the management of vertebral compression fractures: an updated systematic review and meta-analysis

This systematic review updates the understanding of the evidence base for balloon kyphoplasty (BKP) in the management of vertebral compression fractures. Detailed searches of a number of electronic databases were performed from March to April 2006. Citation searches of included studies were undertaken and no language restrictions were applied. All controlled and uncontrolled studies were included with the exception of case reports. Prognostic factors responsible for pain relief and cement leakage were examined using meta-regression. Combined with previous evidence, a total of eight comparative studies (three against conventional medical therapy and five against vertebroplasty) and 35 case series were identified. The majority of studies were undertaken in older women with osteoporotic vertebral compression fractures with long-term pain that was refractory to medical treatment. In direct comparison to conventional medical management, patients undergoing BKP experienced superior improvements in pain, functionality, vertebral height and kyphotic angle at least up to 3-years postprocedure. Reductions in pain with BKP appeared to be greatest in patients with newer fractures. Uncontrolled studies suggest gains in health-related quality of life at 6 and 12-months following BKP. Although associated with a finite level of cement leakage, serious adverse events appear to be rare. Osteoporotic vertebral compression fractures appear to be associated with a higher level of cement leakage following BKP than non-osteoporotic vertebral compression fractures. In conclusion, there are now prospective studies of low bias, with follow-up of 12 months or more, which demonstrate balloon kyphoplasty to be more effective than medical management of osteoporotic vertebral compression fractures and as least as effective as vertebroplasty. Results from ongoing RCTs will provide further information in the near future.

Predictors of outcome in fusion surgery for chronic low back pain. A report from the Swedish Lumbar Spine Study.

Abstract. Despite the continuous development of surgical techniques and implants, a substantial number of patients still undergo surgery for chronic low back pain (CLBP) without any benefit, or even become worse. With the aim of finding predictors of functional and work status outcome, 264 patients with severe CLBP of long duration, randomised to surgical or non-surgical treatment, were characterized by socio-demographic, clinical, radiological and psychological variables. The variables were estimated as predictors of outcome at the 2-year follow-up. Univariate and multiple logistic regression analyses were used in both treatment groups. We found that a personality characterized by low neuroticism and low disc height were significant predictors of functional improvement after surgical treatment. Depressive symptoms predicted functional improvement after non-surgical treatment. Work resumption was predicted by low age and short sick leave in the surgical group, and by short sick leave in the non-surgical group. We conclude that improved selection of successful surgical candidates with CLBP seems to be promoted by attention to severe disc degeneration, evaluation of personality traits and shortening of preoperative sick leave.

A Randomized, Controlled Trial of Fusion Surgery for Lumbar Spinal Stenosis

BACKGROUND The efficacy of fusion surgery in addition to decompression surgery in patients who have lumbar spinal stenosis, with or without degenerative spondylolisthesis, has not been substantiated in controlled trials. METHODS We randomly assigned 247 patients between 50 and 80 years of age who had lumbar spinal stenosis at one or two adjacent vertebral levels to undergo either decompression surgery plus fusion surgery (fusion group) or decompression surgery alone (decompression-alone group). Randomization was stratified according to the presence of preoperative degenerative spondylolisthesis (in 135 patients) or its absence. Outcomes were assessed with the use of patient-reported outcome measures, a 6-minute walk test, and a health economic evaluation. The primary outcome was the score on the Oswestry Disability Index (ODI; which ranges from 0 to 100, with higher scores indicating more severe disability) 2 years after surgery. The primary analysis, which was a per-protocol analysis, did not include the 14 patients who did not receive the assigned treatment and the 5 who were lost to follow-up. RESULTS There was no significant difference between the groups in the mean score on the ODI at 2 years (27 in the fusion group and 24 in the decompression-alone group, P=0.24) or in the results of the 6-minute walk test (397 m in the fusion group and 405 m in the decompression-alone group, P=0.72). Results were similar between patients with and those without spondylolisthesis. Among the patients who had 5 years of follow-up and were eligible for inclusion in the 5-year analysis, there were no significant differences between the groups in clinical outcomes at 5 years. The mean length of hospitalization was 7.4 days in the fusion group and 4.1 days in the decompression-alone group (P<0.001). Operating time was longer, the amount of bleeding was greater, and surgical costs were higher in the fusion group than in the decompression-alone group. During a mean follow-up of 6.5 years, additional lumbar spine surgery was performed in 22% of the patients in the fusion group and in 21% of those in the decompression-alone group. CONCLUSIONS Among patients with lumbar spinal stenosis, with or without degenerative spondylolisthesis, decompression surgery plus fusion surgery did not result in better clinical outcomes at 2 years and 5 years than did decompression surgery alone. (Funded by an Uppsala institutional Avtal om Läkarutbildning och Forskning [Agreement concerning Cooperation on Medical Education and Research] and others; Swedish Spinal Stenosis Study ClinicalTrials.gov number, NCT01994512.).

Cost-effectiveness of lumbar fusion and nonsurgical treatment for chronic low back pain in the Swedish Lumbar Spine Study: a multicenter, randomized, controlled trial from the Swedish Lumbar Spine Study Group.

Study Design. A cost-effectiveness study was performed from the societal and health care perspectives. Objective. To evaluate the costs-effectiveness of lumbar fusion for chronic low back pain (CLBP) during a 2-year follow-up. Summary of Background Data. A full economic evaluation comparing costs related to treatment effects in patients with CLBP is lacking. Patients and Methods. A total of 284 of 294 patients with CLBP for at least 2 years were randomized to either lumbar fusion or a nonsurgical control group. Costs for the health care sector (direct costs), and costs associated with production losses (indirect costs) were calculated. Societal total costs were identified as the sum of direct and indirect costs. Treatment effects were measured using patient global assessment of improvement, back pain (VAS), functional disability (Owestry), and return to work. Results. The societal total cost per patient (standard deviations) in the surgical group was significantly higher than in the nonsurgical group: Swedish kroner (SEK) 704,000 (254,000) vs. SEK 636,000 (208,000). The cost per patient for the health care sector was significantly higher for the surgical group, SEK 123,000 (60,100) vs. 65,200 (38,400) for the control group. All treatment effects were significantly better after surgery. The incremental cost-effectiveness ratio (ICER), illustrating the extra cost per extra effect unit gained by using fusion instead of nonsurgical treatment, were for improvement: SEK 2,600 (600–5,900), for back pain: SEK 5,200 (1,100–11,500), for Oswestry: SEK 11,300 (1,200–48,000), and for return to work: SEK 4,100 (100–21,400). Conclusion. For both the society and the health care sectors, the 2-year costs for lumbar fusion was significantly higher compared with nonsurgical treatment but all treatment effects were significantly in favor of surgery. The probability of lumbar fusion being cost-effective increased with the value put on extra effect units gained by using surgery.

Simplifying outcome measurement: evaluation of instruments for measuring outcome after fusion surgery for chronic low back pain.

Study Design. A comparative evaluation of outcome instruments and global assessment was performed. Objective. To test patient global assessment as a substitute for the use of more comprehensive outcome instruments in treatment trials of chronic low back pain. Summary of Background Data. Treatment outcome can be measured with pain scales and functional instruments. In the absence of a gold standard, the patient him- or herself is the basic reference for outcome, for which the instruments give a more or less exact measurement. Global assessment, which is a retrospective recording, may overestimate improvement as a result of recall or motivational bias. Methods. In this study, 294 patients treated for chronic low back pain were evaluated with a visual analog scale for back pain, the Oswestry Disability Index, the Million Score and general function score for disease-specific disability, and the Zung Depression Scale for depressive symptoms. The correlation between the pretreatment and posttreatment scores for the outcome instruments (&Dgr; scores) and the global assessment scores was calculated; effect sizes were compared; sensitivity and specificity with receiver operating characteristics (ROC) curves were estimated; and associations of global assessment with pretreatment and posttreatment scores were determined. Results. All the &Dgr; scores showed significant correlations with patient global assessment and with each other. The effect size of global assessment tended to be greater than that of the outcome instruments. The specificity and sensitivity of the disability instruments and pain scale were approximately 75%, whereas they were lower for depression. The associations between global assessment and outcome instrument scores did not produce evidence that global assessment was biased. Conclusion. Patient global assessment is a valid and responsive descriptor of overall effect in randomized controlled trials of treatment for chronic low back pain.

The Swedish Spine Register: development, design and utility

The Swedish Spine Register enables monitoring of surgical activities focusing on changes in trends over time, techniques utilized and outcome, when implemented in general clinical practice. Basic requirements for a prosperous register are unity within the profession, mainly patient-based documentation and a well functioning support system. This presentation focuses on the development and design of the register protocol, problems encountered and solutions found underway. Various examples on how the results can be presented and utilized are given as well as validation. Register data demonstrate significant gender differences in lumbar disc herniation surgery with females having more pain, lower quality of life and more pronounced disability preoperatively while improvement after surgery is similar between genders. Quality of life after surgery for degenerative disorders is significantly improved for disc herniation, stenosis, spondylolisthesis and disc degenerative disorders. Over the last 10 years, surgical treatment for spinal stenosis has increased gradually while disc herniation surgery decreases regarding yearly number of procedures. An added function to the register enables more complex prospective clinical studies to include register data together with data suitable for the individual study. A common core set of demographic, surgical and outcome parameters would enable comparisons of clinical studies within and between nations.