Review Article The mild Procedure: A Systematic Review of the Current Literature

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1 bs_bs_banner Pain Medicine 2014; 15: Wiley Periodicals, Inc. SPINE SECTION Review Article The mild Procedure: A Systematic Review of the Current Literature D. Scott Kreiner, MD,* John MacVicar, MB ChB, MPainMed, Belinda Duszynski, BS, and Devi E. Nampiaparampil, MD *Ahwatukee Sport and Spine, Phoenix, Arizona; International Spine Intervention Society, San Rafael, California; NYU School of Medicine, Anesthesiology and Rehabilitation Medicine, New York, New York, USA; St Georges Medical Centre, Southern Rehabilitation Institute, Christchurch, New Zealand Reprint requests to: Belinda Duszynski, BS, International Spine Intervention Society, 161 Mitchell Boulevard, Suite 103, San Rafael, CA 94903, USA. Tel: ; Fax: ; bduszynski@spinalinjection.org. Disclosures: D. S. K.: None. J. M.: None. B. D.: None. D. N.: Expert witness for Kline Specter one time; ProStrakan Medical Research Advisory Panel in June 2011 one time. Abstract Objectives. This study s objective was to determine if the literature supports use of the Minimally Invasive Lumbar Decompression (mild ) procedure (Vertos Medical, Aliso Viejo, CA, USA) to reduce pain and improve function in patients with symptomatic degenerative lumbar spinal stenosis. Design/Settings. The study was designed as an evidence-based review of available data. Studies were identified from PubMed, Embase, and the Cochrane Library. Articles were evaluated using the Grading of Recommendations Assessment, Development and Evaluation Working Group system. Results were compiled assessing short- (4 6 weeks), medium- (3 6 months), and long-term (>1 year) outcomes. The primary outcomes evaluated were pain, measured by the visual analog scale (VAS), and function, measured by the Oswestry Disability Index (). Secondary outcomes included pain and patient satisfaction, measured by the Zurich Claudication Questionnaire, adverse effects/ complications, and changes in utilization of co-interventions. Results. The literature search revealed one randomized controlled trial (RCT) and 12 other studies (seven prospective, four retrospective, and one case series) that provided information on the use of mild in patients with degenerative lumbar spinal stenosis. All studies showed statistically significant improvements in VAS and scores at all time frames compared with preprocedure levels; the RCT showed improvement over controls. Categorical data were not provided; thus, the proportion of patients who experienced minimal clinically meaningful outcomes is unknown. Conclusion. The current body of evidence addressing mild is of low quality. High-quality studies that are independent of industry funding and provide categorical data are needed to clarify the proportions of patients who benefit from mild and the degree to which these patients benefit. Additional data at up to 2 years are needed to determine the overall utility of the procedure. Key Words. Percutaneous Decompression; Spinal Stenosis; Lumbar; Neurogenic Claudication; Intermittent Claudication; Interventional Introduction Lumbar spinal stenosis, or narrowing of the central spinal canal, is associated with increasing age. The prevalence of acquired lumbar spinal stenosis is 4% in patients under the age of 40, but increases to 19.4% by the age of [1]. Although narrowing of the spinal canal is not necessarily symptomatic, by the age of 70, approximately 10% of the population develops symptoms related to lumbar stenosis [2]. Narrowing of the canal causes a variable 196

2 clinical syndrome of gluteal pain, lower extremity pain, and fatigue, which may occur with or without back pain. Symptomatic lumbar spinal stenosis most typically is associated with exercise or positionally induced neurogenic claudication, and symptoms are typically relieved with forward flexion, sitting, and/or recumbency [3]. In degenerative lumbar spinal stenosis, the cause of narrowing in the canal is often multifactorial. Anteriorly, disc degeneration leads to disc bulging and disc-osteophyte complexes projecting posteriorly into the canal. Facet arthrosis and hypertrophy of the ligamentum flavum can narrow the lateral recess in the canal, and the canal may be further narrowed by degenerative spondylolisthesis. Surgical and nonsurgical treatment options exist for symptomatic lumbar spinal stenosis. Nonsurgical treatment options include analgesic medications, physical therapy [4], manipulation [5], and epidural steroid injections [6 8]. Of these conservative treatment options, a multiple injection regimen seems to be the most effective [8 10]. The most common surgical option for degenerative lumbar spinal stenosis is the laminectomy procedure. This procedure, first performed by Dr. Victor Alexander Haden Horsley in 1887, is known to be an effective treatment for degenerative lumbar spinal stenosis [11 13]. In 2004, an interspinous spacer, known as the X-STOP (Medtronic, Minneapolis, MN, USA), was described as a new option to treat degenerative lumbar spinal stenosis [14,15], although its true effectiveness has been challenged [16]. Most recently, a new technique named the mild (Minimally Invasive Lumbar Decompression; Vertos Medical) procedure has been described [17] to treat degenerative lumbar spinal stenosis. This procedure involves inserting a cannula through a six-gauge portal and using tissue and bone sculptors to perform a minimal laminotomy and resect the hypertrophied ligamentum flavum in order to decompress the affected dural sac or nerve roots. This procedure is performed using fluoroscopic guidance with a contralateral oblique view epidurogram to visualize depth of the instruments to maintain safety. Members of the Standards Division of the International Spine Intervention Society (ISIS) performed a preliminary review of the literature on the mild procedure in The initial motivation was to assist members of the ISIS Health Policy Division in deciding whether or not to recommend mild for a Category I CPT Code. The current systematic review was performed in order to evaluate the state of the evidence on the procedure. Methods Search Strategy We conducted a comprehensive literature search in PubMed, Embase, and the Cochrane Library using the search terms: lumbar stenosis, percutaneous decompression, and mild procedure. Only publications dealing directly with the mild procedure were retrieved. Studies describing other percutaneous decompression systems were excluded. We identified all relevant full-length articles in any language that were published through May The reference lists of the selected articles were searched. Study Selection Inclusion criteria were 1) study participants with symptomatic lower extremity claudication attributed to lumbar spinal stenosis and confirmed with computed tomography or magnetic resonance imaging, 2) subjects older than 18 years, 3) patients assigned to treatment with mild, and 4) assessment of at least one predefined outcome measure. Individual studies may have excluded subjects based on additional criteria. Outcome Measures The primary outcome measure was lower extremity pain relief as measured using the visual analog scale (VAS) or numeric rating scale. Secondary outcomes included functional benefit measured using the Oswestry Disability Index (), pain and patient satisfaction as measured by the Zurich Claudication Questionnaire (), complications and adverse effects, and the utilization of co-interventions. These outcomes were assessed at various intervals including 30 days, 6 weeks, 3 months, 6 months, and 1 year or longer. Analysis The studies were then individually evaluated for quality using an instrument developed by the ISIS Standards Division to facilitate reliable assessment of studies of therapeutic effectiveness. Three authors reviewed all of the articles. Disagreements were resolved through discussion. A Microsoft Excel spreadsheet and the GradePro software (GRADE Working Group) were then used to consolidate the data from the different studies into workable follow-up periods of short (4 6 weeks), medium (3 6 months), and long term (1 year or more). Results The literature search identified a single randomized controlled trial (RCT), seven prospective studies, four retrospective studies, a single case series, and a meta-analysis. For our purposes, the meta-analysis was discarded, but all references were considered for inclusion in this review. The technical and design features of the other studies are described in Table 1. Mekhail et al. stated that patients with symptomatic low back pain were included; however, elsewhere in the study they indicated that patients included experienced symptomatic lower extremity pain [18]. For this reason, we included the study of Mekhail in this review. Pain The mild Procedure: A Systematic Review In this systematic review, we assessed pain with two outcome measures: the VAS score and the overall 197

3 Kreiner et al. Table 1 Article summary Study Design Inclusion Criteria N F/U Outcome Measures Brown [20] Basu [25] Chopko and Caraway [21] Chopko [19] Chopko [29] Deer and Kapural [17] Deer et al. [24] Durkin et al. [23] Mekhail et al. [26] Mekhail et al. [18] Lingreen and Grider [22] Wang et al. [30] Wilkinson and Fourney [27] RCT Cohort DLSS w/ LFH Neurogenic claudication > 20 grade I spondy DLSS w/ LFH Neurogenic claudication LF > 2.55 mm Failure conservative tx 5 mm spondy High risk for open spine surgery LF > 2.55 mm Failure conservative tx 39 6 weeks, 12 weeks (patients allowed to crossover after 6 weeks) VAS 27 6 months VAS 78 6 weeks VAS weeks VAS 58 2-year data from Mekhail VAS [18] SF-12 not reported Retrospective 90 Complications LF > 2.5 mm Failed conservative tx weeks, 6 months, and 1 year VAS Retrospective 50 1, 3, and 6 months NRS LF > 2.55 mm Failure conservative tx LF > 4.0 mm Failed conservative tx 58 1 year VAS SF year PDI RMQ Walking Distance VAS Retrospective days VAS Walk > 15 minutes Stand > 15 minutes Retrospective 22 Variable Time spent in specialty care Number of interventional procedures VAS Cohort LF > 2.5 mm 3 mm spondy Failure conservative tx weeks (poststudy monitor to 18 months) Wong [28] Case Series 17 1 year VAS VAS ASG SF-12 ASG = Analgesic Severity Grade; DLSS = degenerative lumbar spinal stenosis; F/U = follow-up; LF = ligamentum flavum; LFH = ligamentum flavum hypertrophy; = Oswestry Disability Index; PDI = pain disability index; RCT = randomized controlled trial; SF-12 = Short Form 12; VAS = visual analog scale;. = Zurich Claudication Questionnaire. 198

4 The mild Procedure: A Systematic Review Table 2 Mean improvements in VAS scores Study Pats Base 4 6 Weeks 12 Weeks 6 Months 1 Year VAS VAS Imp (%) VAS Imp (%) VAS Imp (%) VAS Imp (%) Basu [25] Brown [20] Chopko and Caraway [21] Deer et al. [24] Durkin et al. [23] Lingreen and Grider [22] Mekhail et al. [26] Mekhail et al. [18] Wilkinson and Fourney [27] Wong [28] Weighted mean VAS = visual analog scale. symptom severity score. The scores are divided into time frames for consistency across studies. For this reason, we have opted to omit the study of Chopko [19] from our review because the data reported vary in duration of follow-up from 4 to 72 weeks (Table 2). Short Term Five studies assessed pain at 4 6 weeks using the VAS score and demonstrated a weighted mean improvement of 41% (4.5 points). The strongest data are provided by Brown s RCT of 39 patients [20]. This study showed a statistically significant reduction in the VAS from 6.3 (95% confidence interval [CI] ± 0.7) to 3.8 (95% CI ± 1.3) compared with the control epidural steroid injection group, which had negligible improvement in the VAS over the same follow-up period [20]. Chopko performed a study of 75 patients, which showed a statistically significant decrease in the average VAS score from 7.3 (range 3 10) to 3.7 (range 0 10) [21]. This study also found a statistically significant reduction in the overall symptom severity score from 3.69 (range ) to 2.35 (range ). It is unclear why the author chose to provide a score range instead of a CI or standard deviation (SD). Lingreen and Grider s retrospective study of 42 patients also found a statistically significant improvement [22]. The VAS score decreased from 9.6 ± 0.42 to 5.8 ± 2.5. The authors did not report whether these ranges represent SDs or 95% CIs. Similarly, Durkin s retrospective review of 50 mild cases showed a VAS score change from 7.5 (95% CI ± 0.48) at baseline to 5.18 (95% CI ± 0.75) [23]. This study also reported improvements in the National Institutes of Health Patient Reported Outcomes Measurement Information System pain interference scores from (95% CI ± 2.55) to (95% CI ± 3.36). Medium Term Six studies were included which provided medium-term results: five prospective studies and a single retrospective study. The weighted mean improvement in pain was 46% (4.1 points) at 3 months and 42% (4.4 points) at 6 months. Brown s study started as an RCT, but by 12 weeks all patients had crossed to the mild group, relegating the study to providing data [20]. This study showed that the VAS significantly decreased from 6.3 (95% CI ± 0.7) to an average of 3.4, although no SD or CI was provided for the 12-week data points. Deer s 2012 study of 46 patients showed a statistically significant decrease in the VAS score from 6.9 (95% CI ± 0.6) to 4.2 (95% CI ± 1.0) at 12 weeks and 4.4 (95% CI ± 1.0) at 6 months [24]. Basu studied 27 patients and found that the VAS improved from 9.1 (95% CI ± 0.59) to 3.9 (95% CI ± 2.25) [25]. This study also assessed pain at 3 6 months using the overall symptom severity score. The authors did not provide the quantitative data, but they reported that the pain and neuroischemic domains were significantly improved at P < Mekhail et al. used VAS as a secondary outcome measure and reported scores at multiple time frames in his 2012 study [26]. The study provides graphical data on VAS improvements from 7.1 at baseline to 3.1 at 12-week follow-up and 3.7 at 6-month follow-up, although no SDs or 95% CIs were provided for this data set. Wilkinson et al. studied 10 patients and found that the VAS improved from 7.3 (±SD 1.5) to 4.3 at 12 weeks and to 4.2 (±SD 2.8) at 6 months [27]. Durkin reported VAS improvements from 7.5 (95% CI ± 0.48) at baseline to 5.31 (95% CI ± 0.95) at 3 months and 5.60 (95% CI ± 0.98) at 6 months. Long Term Five studies assessed pain at 12 months or greater using the VAS score. The weighted mean improvement in pain was 49% (3.9 points) at 1 year. 199

5 Kreiner et al. Mekhail et al. s prospective observational study of 58 patients showed a reduction in the VAS from 7.4 (95% CI ± 0.5) to 4.5 (95% CI ± 0.8) (P < ) [18]. This study also evaluated pain using the overall symptom severity score and found a significant improvement in the score from 4.54 to SDs and CIs for the baseline measures were not provided, but the SD of the change in was given as Mekhail et al. s 2012 study revealed a baseline VAS of 7.1 (95% CI ± 0.8), which improved to 3.6 (95% CI ± 0.9) at 1 year (P < ) [26]. Deer s prospective study also reported a statistically significant improvement in the VAS from 6.9 (95% CI ± 0.6) to 4.0 (95% CI ± 1.0) at 1 year (P < ) [24]. Wong et al. conducted a retrospective case series of 17 patients and found a VAS improvement from 7.6 to 2.3 [28]. SDs and CIs for the baseline measures were not provided, but the SD of the change in VAS was given as 1.5. Chopko s 2013 study [29] reported 2-year data on Mekhail et al. s [18] 58 patients, but 13 of the initial study patients were unavailable: three underwent lumbar spine surgery after 1 year, one died, and the remaining nine did not respond to multiple contacts or withdrew from the study. This author decided to only evaluate the of remaining 45 patients independently. In these patients, there was a statistically significant improvement in the VAS from 7.2 (95% CI ± 0.6) to 4.8 (95% CI ± 0.8) (P < ) at 2-year follow-up, but it was not felt that this study provided valid information about the effectiveness of the procedure because of the exclusion of 22% of the initial patients. Function Ten studies (one RCT, five prospective s, and four retrospective studies) assessed function after the mild procedure. Nine of the 10 studies used the as their primary functional outcome measure, while Mekhail used the Roland-Morris Disability Questionnaire (RMQ), standing time (ST), and walking distance (WD) (Table 3). Table 3 Study Mean improvements in scores Pats Short Term Four studies assessed short-term functional improvement, revealing an early weighted mean improvement in the of Again, the strongest data are provided by Brown s RCT [20]. This study showed an improvement in the from 38.8 to 27.4, an 11.4-point improvement (95% CI ± 8.2), while there was no statistically significant improvement in the control epidural steroid injection group. Chopko and Caraway s 2010 study also reported a statistically significant improvement in the, which improved from 47.4 (range 16 84) to 29.5 (range 0 72) [21]. Durkin reported a baseline of (95% CI ± 4.5), which improved slightly to (95% CI ± 4.7) (P ) [23]. Wilkinson also published early results, with a baseline of 49.4 that improved to roughly 35 at 6 weeks [27]. These data are provided in graphical form with SD tics, but numerical data for all intermediate assessments are not provided. This change in was noted not to be statistically significant (P < 0.05). Medium Term Five studies report functional data at the 3 6-month mark, showing weighted mean improvements in the of 16.2 at 3 months and 15.4 at 6 months. Again, Brown s study started as an RCT, but by 12 weeks all patients had crossed over to the mild group [20]. This study was reported to show a statistically significant improvement in the from 38.8 to 25.5 at week 12, although no SDs or CIs were provided for the 12-week data. Basu reported a statistically significant improvement in the from 55.1 (95% CI ± 6.34) to 31.1 (95% CI ± 9.29) [25]. Deer reported a baseline of 49.4 (95% CI ± 2.5), which improved to 35.1 (95% CI ± 5.6) at 12 weeks and 35.0 (95% CI ± 5.5) at 6 months, both of which were statistically significant (P < 0.01) [24]. Durkin s retrospective review demonstrated a baseline of (95% CI ± 4.5), which improved to (95% CI ± 5.1) (P = ) at 3 months and (95% CI ± 6.8) (P = ) at 6 months [23]. Lastly, Wilkinson reported Base 6 Weeks 12 Weeks 6 Months 1 Year Imp Imp Imp Imp Basu [25] Brown [20] Chopko and Caraway [21] Deer et al. [24] Durkin et al. [23] Lingreen and Grider [22] 42 Mekhail et al. [26] Wilkinson and Fourney [27] Wong [28] Weighted mean = Oswestry Disability Index. 200

6 that the baseline of 49.4 (95% CI ± 13.9) showed a statistically significant improvement to 29.4 (95% CI ± 19.8) at 26-week follow-up [27]. Long Term Three studies looked at long-term disability improvements, demonstrating a weighted mean improvement in the of 14.0 at 1 year. In Mekhail et al. s study, the baseline average score of 48.6 (95% CI ± 3.8) decreased to a mean of 36.7 (95% CI ± 5.8) at 1-year follow-up, an improvement of 11.9 points (95% CI ± 4.7) [18]. Wong reported that, in his patients, the average baseline of 48.4 improved to 21.7 at 1-year follow-up [28]. The mean decreased 26.6 points from baseline to 1-year follow-up with a 95% CI of ±8.8 ( 17.9 to 35.4). Chopko s [29] 2-year extension of the Mekhail et al. study [18] showed improvements in the with a baseline of 48.4 (95% CI ± 4.4) to 39.8 (95% CI ± 5.6) at 2 years. Again, these data are of questionable validity, as 13 patients were not available for follow-up and at least two proceeded to lumbar surgery after 1 year. Mekhail et al. s 2012 study demonstrated an improvement in the RMQ from 14.3 (95% CI ± 2.1) to 6.6 (95% CI ± 2.0) (P < ) at 1 year [26]. This study also demonstrated an improvement in ST from 8 to 56 minutes (P < ) and an improvement in the WD from a baseline mean of 246 3,956 ft at 12 months (P < ). Complications Nearly every study assessed patients for complications including dural punctures or tears, nerve root injuries, bleeding, infections, and rehospitalization postprocedure. No substantial direct procedure-related complications were identified. The second of Chopko s studies identified two patients with complications [19]. One with known lymphoma experienced a deep venous thrombosis and pulmonary embolism (PE) on post-op day one and a recurrent PE at 7 months. The second patient was obese and had experienced recurrent abdominal issues. This patient developed an incarcerated small bowel within 48 hours of the procedure. This study also reported that two patients died of complications related to systemic malignancies at 4 and 8 weeks postoperatively. Lingreen and Grider s study noted that of the 42 patients, 20 had soreness at the site, four reported gluteal pain, one had bleeding at the puncture site, and one experienced back spasms [22]. Patient Satisfaction A secondary measure in five of the studies, the patient satisfaction subscale of the, showed that scores ranged from 1.86 to 2.20 (95% CI ± 0.26). Scores in patient satisfaction scale range from 1.0 to 4.0, with values of less than 2.5 indicating some degree of satisfaction, although a score of 2.0 or lower is typically considered satisfied. Co-Interventions Chopko s 2011 study evaluated changes in usage of pain medication preprocedure and postprocedure [19]. Of the 12 patients who were using opioid-based pain medication prior to the mild procedure, six had either decreased or completely stopped their usage at a time interval between 4 and 72 weeks. Durkin s retrospective review noted that 30% of patients were using opiate medications prior to the procedure [23]. Following the procedure, 55% of patients remained opioid free. Of the others, 12% no longer required opioids, 6% reduced opioid-usage, 10% used the same amount as before, but one subject (2%) required higher doses, and 10% required initiation of opioid therapy. Wilkinson and Fourney s study also evaluated the use of pain medication [27]. Interestingly, preoperatively no patients were taking opioid-based analgesia. Following the procedure, the use of nonopioid analgesics decreased over the study period, although the use of opioid analgesics was introduced. The usage of opioid-based analgesics peaked at 1-week postprocedure and then decreased at the 6-week, 12-week, and seemingly the 26-week assessments. In addition, the authors continued their study past the original 6 months. They found that by 18 months post-mild, 6 of 10 patients had undergone spine surgery. While the authors felt that surgical intervention represented a failure of the mild procedure, no VAS or measures were provided either before or after the surgery. For this reason, it is difficult to draw any conclusions from this finding. Wang et al. retrospectively reviewed the charts of 22 patients who had undergone the mild procedure [30]. They compared the amount of time spent in specialty care and the number of interventional procedures performed before and after mild. Two patients could not tolerate the mild procedure; one was lost to follow-up. Twelve out of 22 patients (54.5%) including the patient lost to follow-up were discharged from the chronic pain clinic after mild. They continued to be seen in the primary care clinic for residual symptoms. Ten patients continued their care in the chronic pain clinic. Of those 10 patients, seven received additional interventional procedures. Three were referred for surgical decompression. As a group, the patients received an average of pain procedures per month prior to mild, and as a group, they received <0.1 procedures per month after the procedure over the time period during which they were followed. The amount of time spent in specialty care was reduced by 45% from 9.55 to 5.11 months. Discussion The mild Procedure: A Systematic Review Multiple studies, including a fairly well-conducted RCT, consistently demonstrate statistically significant improvement in VAS scores for pain over baseline at all reported time points. Findings are similar for pain subscales, although these data were not consistently supplied in the literature and, therefore, were felt to be less reliable than 201

7 Kreiner et al. the VAS scores. Nevertheless, the two scores correlated well in all studies that reported both. In addition, multiple studies, including the RCT, demonstrated improvement in scores for function at up to 1 year. One study reporting 2-year outcomes was not accepted as providing valid information. In terms of complications, mild appears to be a relatively safe procedure. Nearly all studies reported complications, and of the adverse events that occurred, all seem to be related more directly to the health of the population rather than the procedure performed. It should be noted, however, that this procedure involves using sharp instruments to debulk the ligamentum flavum from a posterior approach, using an epidurogram to maintain a safe distance from the dura. It is certainly possible to damage dura and nerve roots while performing this procedure, and this has been reported in a letter to the editor [31], but not in the selected studies. The is a validated outcome measure and contains a domain for patient satisfaction. In this study, there was substantial variability in satisfaction scores, with moderately large ranges and CIs surrounding scores that in general are near 2.0 (patients satisfied ). This indicates that patient satisfaction with the procedure is certainly not universal, with some patients clearly falling into the not satisfied range while others are likely very satisfied. Three studies assessed medication usage in patients receiving the mild procedure. These low-quality prospective studies found slightly differing outcomes. The study of Chopko showed that half of the patients were able to decrease or stop the usage of pain medications [19]. Wilkinson and Fourney s study reported a small increase in the use of opioid analgesics [27]. The significance of this medication usage is difficult to assess because the Analgesic Severity Grade scale used in this study is not referenced and could not be found using a routine literature search. Because of the small sample size (10 patients), a single patient taking a medication would cause this scale to be elevated over baseline. It is possible that the opioid usage increased, either acutely or chronically, as a result of the mild procedure, or that the improvement in symptoms after the treatment is a result of opioid use rather than the procedure. Wang et al. found that the mild procedure facilitated discharge from specialty clinic care, but the criteria for discharge were not specified [30]. In all of these studies, the improvements in most outcome measures were statistically significant, but the improvements in mean pain scores were only slightly greater than the accepted minimal clinically important change for chronic lower back pain [32,33] and lumbar radicular pain [34] in the majority of the studies. Clinical and statistical significance are not necessarily enough to justify performing the procedure if a potentially more effective therapeutic option exists. The determination that this procedure is clinically effective enough to justify its performance is typically based on the judgment of the physician. In an attempt to use more standardized criteria, the authors looked to Carragee et al. s definitions of minimally acceptable outcomes related to fusion. In one study, they are: final VAS score < 4, final < 30, no narcotic use, and a return to at least some gainful employment or equivalent [35]. In another study, they are: final VAS score < 3, improvement of 20 points, no narcotic use, and at least some occupational activity [36]. We also looked at 4-year Spine Patient Outcomes Research Trial (SPORT) data on patients with stenosis who underwent laminectomy [13]. Data from the as treated laminectomy group showed improvements of 20.3 at 2 years, 18.6 at 3 years, and 18.7 at 4 years. No other outcome measures used in the SPORT trial matched those in the mild studies. Mean VAS scores after treatment were >3 at all time frames, in all studies except for that of Wong [28], and were >4 in half of the studies. Mean final was similarly >30 in the majority of studies, and a mean improvement of >20 was reported in only two studies [25,28]. These figures suggest that minimally acceptable outcomes were not achieved for the average patient in the majority of studies, but the number of patients who benefited to a clinically significant degree from treatment, and the extent to which they might have benefited, is not known because continuous data (mean VAS and scores) were provided before and after treatment, rather than the categorical data. The relevance of the short-term outcome measures is debatable. The mild procedure cannot be repeated regularly like epidural steroid injections. However, it is not as invasive or risk laden as a laminectomy. A procedure that is being compared with a lumbar laminectomy should be effective for at least 6 months. The 6-week and 12-week data that have been collected are not useful in this regard. However, the 6- and 12-week data are useful in demonstrating an expected course of recovery. These data suggest that the mild procedure is more effective than epidural steroid injections in the treatment of symptomatic lumbar stenosis. In the case of the mild procedure, weighted mean VAS scores post treatment are 4.5 at 6 weeks, 4.1 at 12 weeks, 4.4 at 6 months, and 3.9 at 1 year. Mean weighted scores are improved by 16.5 at 6 weeks, 16.2 at 12 weeks, 15.4 at 6 months, and 14.0 at 1 year. These VAS and scores do not meet Carragee s minimum acceptable outcomes. Opioid medication usage is not consistently documented in the available studies, and in the studies available the data are conflicting. In reviewing the body of evidence, the authors felt that there were no significant reasons to justify upgrading or downgrading the body of evidence based upon the Grading of Recommendations Assessment, Development and Evaluation Working Group system. The majority of the evidence is derived from observational studies with only a 202

8 The mild Procedure: A Systematic Review single RCT and, with no justification to either upgrade or downgrade the quality, the current body of evidence addressing the mild procedure is of low quality. Limitations Industry funding of various degrees was received to perform these studies. Most of this industry involvement was well-disclosed; however, the Chopko and Caraway study inaccurately reported that the lead author had no conflicts, but he later acknowledged he was a paid consultant for the manufacturer while the study was being conducted [21]. In addition, the Mekhail et al. article lacks an appropriate disclosure statement so it is unclear whether the author is paid directly by the manufacturer [18]. These issues raise the suspicion of bias toward the procedure. While it is expected that the manufacturer will provide the equipment gratis to enable the study to be done, the lead investigator in the majority of these studies was a trainer for the procedure and/or a paid investigator or consultant to the manufacturer. This degree of industry-funded involvement brings a substantial risk of bias to the relevant studies. Conclusion The current body of evidence addressing the mild procedure is of low quality. The mild procedure appears to be a relatively safe procedure for the treatment of symptomatic lumbar spinal stenosis. Outcome data suggest that the procedure provides statistically significant reductions in pain intensity and statistically significant improvements in function, but the data, which are continuous rather than categorical, suggest that these improvements do not meet some definitions of a minimally acceptable outcome. Future studies must provide categorical data that will clarify the proportions and characteristics of patients who are most likely to benefit from the mild procedure and the degree to which these patients benefit. Additional studies, independent of industry funding and involvement, are needed. Data at time frames greater than 1 year, which are clearly lacking, and additional data at up to 2 years, would be beneficial in determining the overall utility of the procedure. Ideally, predictive factors could be identified to help differentiate which patients are most likely to have a positive or negative response to this procedure. References 1 Kalichman L, Cole R, Kim DH, et al. Spinal stenosis prevalence and association with symptoms: The Framingham Study. Spine J 2009;9(7): PubMed PMID: Ishimoto Y, Yoshimura N, Muraki S, et al. Prevalence of symptomatic lumbar spinal stenosis and its association with physical performance in a populationbased in Japan: The Wakayama Spine Study. Osteoarthritis Cartilage 2012;20(10): PubMed PMID: Watters WC 3rd, Baisden J, Gilbert TJ, et al. Degenerative lumbar spinal stenosis: An evidence-based clinical guideline for the diagnosis and treatment of degenerative lumbar spinal stenosis. Spine J 2008;8(2): PubMed PMID: Goren A, Yildiz N, Topuz O, Findikoglu G, Ardic F. Efficacy of exercise and ultrasound in patients with lumbar spinal stenosis: A prospective randomized controlled trial. Clin Rehabil 2010;24(7): PubMed PMID: Murphy DR, Hurwitz EL, Gregory AA, Clary R. A nonsurgical approach to the management of lumbar spinal stenosis: A prospective observational study. BMC Musculoskelet Disord 2006;7:16. PubMed PMID: Pubmed Central PMCID: Lee JW, Myung JS, Park KW, et al. Fluoroscopically guided caudal epidural steroid injection for management of degenerative lumbar spinal stenosis: Short-term and long-term results. Skeletal Radiol 2010;39(7): PubMed PMID: Manchikanti L, Cash KA, McManus CD, et al. Lumbar interlaminar epidural injections in central spinal stenosis: Preliminary results of a randomized, double-blind, active control trial. Pain Physician 2012;15(1): PubMed PMID: Manchikanti L, Cash KA, McManus CD, Pampati V, Abdi S. Preliminary results of a randomized, equivalence trial of fluoroscopic caudal epidural injections in managing chronic low back pain: Part 4 Spinal stenosis. Pain Physician 2008;11(6): PubMed PMID: Botwin K, Brown LA, Fishman M, Rao S. Fluoroscopically guided caudal epidural steroid injections in degenerative lumbar spine stenosis. Pain Physician 2007;10(4): PubMed PMID: Riew KD, Yin Y, Gilula L, et al. The effect of nerve-root injections on the need for operative treatment of lumbar radicular pain. A prospective, randomized, controlled, double-blind study. J Bone Joint Surg Am 2000;82-A(11): PubMed PMID: Athiviraham A, Yen D. Is spinal stenosis better treated surgically or nonsurgically? Clin Orthop Relat Res 2007;458:90 3. PubMed PMID: Slatis P, Malmivaara A, Heliovaara M, et al. Long-term results of surgery for lumbar spinal stenosis: A randomised controlled trial. Eur Spine J 2011;20(7): PubMed PMID: Pubmed Central PMCID: Weinstein JN, Tosteson TD, Lurie JD, et al. Surgical versus nonoperative treatment for lumbar spinal 203

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