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Does Pain Score in Response to a Standardized Subcutaneous Local Anesthetic Injection Predict Epidural Steroid Injection Outcomes in Patients with Lumbosacral Radiculopathy? A Prospective Correlational Study

Steven P. Cohen MD, Jianren Mao MD, PhD, To-Nhu Vu MD, Scott A. Strassels PhD, PharmD, Anita Gupta DO, PharmD, Michael A. Erdek MD, Paul J. Christo MD, MBA, Connie Kurihara RN, Scott R. Griffith MD, Chester C. Buckenmaier III MD, Lucy Chen MD
DOI: http://dx.doi.org/10.1111/pme.12027 327-335 First published online: 1 March 2013

Abstract

Objective Epidural steroid injections (ESI) are the most commonly performed pain procedures. Despite numerous studies, controversy continues to surround their effectiveness. The purpose of this study is to determine whether a standard, clinical local anesthetic injection can predict outcomes for ESI.

Study Design In this multicenter study, 103 patients received two ESI 2 weeks apart. Prior to their first injection, subjects rated the pain intensity of a standardized subcutaneous (SQ) injection of lidocaine prior to the full dose. Numerical rating scale pain scores were correlated with leg and back pain relief, and functional improvement, through 3-month follow-up.

Outcome Measures A composite successful outcome was predetermined to be a ≥2-point decrease in leg pain score, coupled with a positive global perceived effect.

Results A small but significant relationship was found between SQ pain score and reduction in leg (r = −0.21, 95% CI −0.38 to −0.04; P = 0.03) and back pain (r = −0.22, 95% CI −0.36 to −0.07; P = 0.03). Subjects with a positive outcome at 1 month had a mean SQ pain score of 2.5 (SD 1.9) vs 4.1 (SD 2.7) in those with a negative outcome (P = 0.04). Subjects with SQ pain scores <4/10 had lower leg and back pain scores than those with pain scores ≥4 at 1-month (mean 3.2, SD 2.6 vs 5.1, SD 2.7 for leg, P < 0.01; mean 3.7, SD 2.6 vs 5.0, SD 3.0 for back, P = 0.02) and 3-month (mean 3.8, SD 2.7 vs 5.2, SD 3.1 for leg, P = 0.01; mean 4.0, SD 2.6 vs 4.9, SD 3.1 for back; P = 0.14) follow-up.

Conclusions The results of this study found a weak positive correlation between SQ pain scores and treatment results. Further research should consider whether pain perception in conjunction with other variables might prove to be a reliable predictor for ESI and other procedural outcomes.

  • Clinical Stimulus
  • Epidural Steroid Injection
  • Lumbosacral Radiculopathy
  • Predictive Value
  • Sciatica
  • Subcutaneous Injection

Introduction

Low back pain represents a major cause of disability in the world, constituting a financial burden approaching $100 million per year in the United States alone . Between 37% and 54% of these cases are predominantly neuropathic in nature, rendering the patients prime candidates for epidural steroid injections (ESI) . But despite their prominence as the most studied, analyzed, and frequently performed pain-alleviating intervention, systematic reviews remain decidedly mixed regarding efficacy . Conflicting findings for back pain treatment strongly suggest the need to better identify factors that can predict results, and/or refine selection criteria . Yet very few studies have sought to analyze factors associated with ESI outcomes .

Previous studies have found psychosocial variables to have the greatest predictive value for poor treatment outcomes for LBP in general , but the use of individual psychological indices, such as coping skills or somatization, or composite indexes, such as Symptom Checklist-90, Short Form-36 (SF-36), and Common Mental Disorder Questionnaire, are hindered by their subjective nature and labor-intensive utilization . Recently, we developed a noninvasive psychophysical test to evaluate the clinical relevance of opioid-induced hyperalgesia . This measuring tool, which involves patient-reported verbal pain scores in response to a standardized, local anesthetic (LA) injection administered immediately before a pain management procedure, blends psychological parameters, such as expectations and somatization, with physical ones, such as nociceptive threshold and tolerance. In an era of increased emphasis on the containment of spiraling medical costs, additional benefits of this test include its simplicity, convenience, and lack of cost. The objective of this pilot study is therefore to determine whether a standardized clinical LA injection performed in the context of reducing the discomfort of a lumbosacral ESI can predict treatment outcome. Our working hypothesis was that higher pain scores in response to the standardized clinical stimulus would be associated with poorer outcomes following ESI.

Patients and Methods

Permission to conduct this prospective observational study was granted by the internal review boards of Johns Hopkins Medical Institutions, Walter Reed Army Medical Center, University of Pennsylvania, and WellSpan Health, York, PA, as well as all participants who provided informed consent. Criteria for study enrollment were age greater than 18 years; signs (e.g., positive straight leg raising test) and symptoms (e.g., numbness or pain radiating into lower leg) of lumbosacral radiculopathy; leg pain comparable or greater than back pain; MRI within 18 months or more recently for change in symptoms; and scheduled treatment with epidural steroid injections. Exclusion criteria were as follows: failed back surgery syndrome; symptom duration >4 years; ESI within the past 2 years; serious neurological deficit (e.g., cauda equina syndrome); referral from surgery for a diagnostic injection (i.e., selective nerve root block); serious coexisting psychiatric pathology that could preclude an optimal outcome; and uncontrolled coagulopathy.

Epidural Steroid Injections

All ESI were performed by either an attending physician (all institutions), or a trainee under the supervision of a board-certified pain medicine specialist (Penn, Johns Hopkins, and Walter Reed), using fluoroscopic guidance and coaxial needle placement. In compliance with standard practice, patients with unilateral symptoms generally received transforaminal epidural injections, while those with bilateral symptoms underwent interlaminar procedures. Transforaminal injections were accomplished by inserting 22-gauge spinal needles at >45° angles into the superior part of the targeted foramina. Correct position was confirmed in both anteroposterior and lateral views, with contrast spread delineating the targeted nerve root and ≥50% proximal epidural spread. Following satisfactory needle placement, a 3 mL solution containing 60 mg of depomethylprednisolone, 1 mL of 0.25% bupivacaine, and 0.5 mL of saline was slowly injected.

Interlaminar ESI were performed using the loss of resistance to air or saline technique via 18- or 20-gauge Touhy needles. After loss of resistance was attained, epidural placement was confirmed by the injection of contrast in anteroposterior and lateral views. Once the supervising physician was satisfied with the contrast spread, a 4 mL solution containing 60 mg of methylprednisolone, 1 mL of 0.25% bupivacaine and 1.5 mL of saline was administered.

All patients were scheduled to receive a repeat ESI at the same level 2 weeks after the first injection. Allowances were made, however, so that patients who obtained satisfactory relief after the first injection could forego a second injection, and that subjects who experienced worsening symptoms after their first injection and decided not to pursue a second one could exit the study “per protocol” as treatment failures. In between the initial procedure and final follow-up visit, no patient received any additional therapeutic interventions.

Standardized Clinical Stimulus

Using fluoroscopic guidance, the needle entry site was prepped and draped in sterile fashion and marked on the skin. Subjects were then informed that they were going to receive “a little numbing medication.” The standardized subcutaneous LA injection was administered by a trained physician using a 25-gauge needle and 1 mL of 1% lidocaine to raise a small skin wheal. Immediately after the subcutaneous injection, subjects were asked the following question: On a 0–10 pain scale, with 0 being no pain and 10 being the worst pain you can imagine, how would you rate the injection you just received?

Data regarding the standardized subcutaneous stimulus were recorded by either a disinterested research nurse or medical assistant not involved in patient care. Following the standardized LA injection, subjects were given as much LA as deemed necessary to facilitate completion of the scheduled procedure.

Follow-Up Visits and Data Collection

Baseline data were recorded prior to the first injection. In addition to demographic information, clinical data included duration of pain, average numerical rating scale (NRS) leg and back pain scores over the past week, analgesic usage, duration of symptoms, and Oswestry Disability Index (ODI) 2.0 (version 2.0, MODEMS, Des Plaine, IL, USA). The first follow-up visit occurred 1 month after the second or final injection. Along with baseline parameters, additional categories recorded were medication reduction, which was predefined as >20% decrease in opioid use or cessation of a nonopioid analgesic , global perceived effect (GPE) , and adverse effects. A composite successful outcome was predetermined to be a ≥2-point decrease in leg pain score, coupled with a positive GPE such that the patient was able to forego additional interventions for the duration of their participation in the study. A 2-point pain reduction threshold was chosen because it has been shown to represent the minimal decrease in pain that is clinically meaningful on an 11-point scale . All patients who experienced a positive categorical outcome at their 1-month visit returned to the clinic for 3-month follow-ups. Those with a negative outcome exited the study per protocol with their last observed values carried forward for analysis (Figure ).

Figure 1

Flowchart showing progression of study subjects.

Statistical Analysis

Statistical analyses were done using Stata 11.1. A power analysis determined that 90 patients would have 80% power to detect a correlation of 0.26 between leg pain and the standard clinical stimulus pain rating score at an alpha of 0.05. Continuous variables were analyzed using t-tests with unequal variances, ANOVA, or Wilcoxon rank sum tests, as appropriate. Categorical variables were assessed using either Chi-square or Fisher's exact tests. Pairwise Pearson's correlation coefficients with confidence intervals and scatter graphs were used to estimate the relationship between leg and back pain scores, and the standard clinical stimulus pain rating score. Multivariable analyses were explored, but no significant associations were identified (data not reported). A P value < 0.05 was considered to be statistically significant.

Results

Baseline Demographic and Clinical Information

A total of 103 patients were enrolled, with 72.8% undergoing transforaminal ESI for predominantly unilateral pain. The average age of the participants was 51.6 years (SD 14.3). Of the participants, 56.3% were women, with the mean duration of pain being 1.3 years (SD 1.2). Baseline leg and back scores were 6.6 (SD 1.9) and 6.1 (SD 2.5), respectively. Preinjection ODI signified moderate-to-severe functional limitations, averaging 44.5 (SD 17.6). Slight differences were noted between institutions, with the Walter Reed patients having a lower mean age (41.3, SD 11.8) and a higher proportion of males (77%), the University of Pennsylvania (mean 0.8 years, SD 0.7) and WellSpan (1.0, SD 1.0) enrolling subjects with shorter durations of pain, University of Pennsylvania having higher baseline mean ODI (64.9, SD 9.7), and Johns Hopkins patients having higher baseline leg (7.1, SD 1.8) and back (6.7, SD 2.7) pain scores (data not shown). One patient was lost to follow-up after their 1-month visit. This patient was excluded from the 3-month analysis (Table ).

View this table:
Table 1

Demographic & clinical data of study subjects (N = 103)

Mean age in years (SD, range)51.6 (14.3, 25–82)
Sex (N, %)
  Male  45 (43.7)
  Female  58 (56.3)
Mean duration of pain in years (SD, range) 1.3 (1.2, 0.1–6)
Active duty (N, %)
  No 96 (93.2)
  Yes   7 (6.8)
Mean baseline ODI score (SD, range)44.5 (17.6, 8–84)
Baseline leg pain intensity (0–10 NRS) 6.6 (1.9, 3–10)
Baseline back pain intensity (0–10 NRS) 6.1 (2.5, 0–10)
Opioid use
  No (N, %) 66 (64.1)
  Yes (N, %) 37 (35.9)
Injection type
  Transforaminal epidural (N, %) 75 (72.8)
  Interlaminar epidural (N, %) 28 (27.2)
Number of epidural injections (N, %)
  One 31 (30.1)
  Two 72 (69.9)
  • NRS = numerical rating scale; ODI = Oswestry Disability Index.

Follow-Up

At 1-month follow-up, mean leg and back pain scores for the entire cohort declined to 4.0 (SD 2.8) and 4.3 (SD 2.9), respectively. ODI fell 22.0% to an average of 34.6 (SD 19.6). Among the 53 patients who obtained a positive categorical outcome at 1 month and were followed at 3 months, leg and back pain scores continued to show sustained improvement, averaging 2.8 (SD 2.8) and 3.3 (SD 2.7), respectively. The mean 3-month ODI was 29.9 (SD 16.0) in these subjects.

When negative values at 1 month were carried over to 3 months (N = 102), the mean leg, back and ODI scores were 4.4 (SD 2.9), 4.4 (SD 2.9), and 35.9 (SD 18.1), respectively. Sixty-four (62.1%) subjects reported a positive GPE at 1 month, with 44 (43.1%) having a sustained positive GPE at 3 months.

Correlation of Subcutaneous Pain Score with Outcomes

Differences in mean subcutaneous pain scores stratified by outcomes are outlined in Table and . Among subjects with a negative outcome (N = 49), the mean subcutaneous pain score was 4.1 (SD 2.7), which was higher than in those patients who had a positive outcome at 1 month (mean 3.4, SD 2.2; P = 0.17). However, only the difference between those with a negative outcome and those with a positive outcome at 1 month only (mean 2.4, SD 1.9) reached statistical significance (P = 0.03).

View this table:
Table 2

Differences in standardized clinical stimulus pain rating stratified by treatment outcomes

Outcome MeasureMean Subcutaneous Pain Score (SD)P Value
Primary outcome measure*0.10
  Negative outcome at 1 month (N = 49)4.1 (2.7)Reference
  Positive outcome at 1 month only (N = 14)2.5 (1.9)0.04
  Positive outcome at 3 months (N = 40)3.7 (2.2)0.53
Percent pain relief at 1 month
  <50% pain relief of back and leg pain (N = 48)4.0 (2.5)Reference
  ≥50% relief of leg pain (N = 45)4.0 (2.6)0.92
  ≥50% relief of back pain (N = 31)4.3 (3.2)0.77
  ≥50% relief of leg and back pain (N = 24)2.8 (1.9)0.048
Percent pain relief at 3 months
  <50% pain relief in back & leg (N = 56)3.8 (2.7)Reference
  ≥50% relief of leg pain (N = 13)3.8 (2.3)0.99
  ≥50% relief of back pain (N = 10)4.2 (3.0)0.68
  ≥50% relief of leg and back pain (N = 20)3.3 (1.8)0.44
Functional improvement
  <10-point decrease at 1 month (N = 60)4.1 (2.7)Reference
  ≥10-point decrease at 1 month (N = 43)3.2 (1.9)0.05
  <10-point decrease at 3 months (N = 62)3.9 (2.6)Reference
  ≥10-point decrease at 3 months (N = 40)3.4 (2.2)0.34
Global perceived effect§0.57
  Negative at 1 month (N = 39)4.0 (2.7)Reference
  Positive at 1 month (N = 64)3.9 (2.5)0.86
  Positive at 3 months (N = 44)3.4 (2.3)0.31
  • P values for category headings (e.g., primary outcome measure) calculated based on differences between all groups (i.e., three-way ANOVA for differences between positive outcome at 3 months, positive outcome at 1 month, and negative outcome).

  • *Positive outcome predefined as ≥2-point decrease in leg pain score coupled with a positive global perceived effect.

  • Based on imputed values of 1-month treatment failures carried over to 3 months.

  • Based on research by Lauridsen et al. defining a clinically significant improvement in function based on Oswestry disability index.

  • §Negative GPE's of treatment failures at 1 month carried over to 3 months.

View this table:
Table 3

Differences in demographic and clinical variables stratified by pain rating to standardized clinical stimulus

VariableSQ Pain < 4 (%, n = 57)SQ Pain ≥ 4 (%, n = 46)P Value
Mean age in years (SD, range)52.7 (15.4, 25–82)50.2 (12.9, 29–81)0.37*
Sex (n, %)N = 57N = 460.005§
  Male (n = 45) 32 (56.1) 13 (28.3)
  Female (n = 58) 25 (43.9) 33 (71.7)
Mean duration of pain in years (SD, range) 1.3 (1.1, 0.1–4) 1.4 (1.3, 0.1–6)0.53
Active duty0.13
  No (n = 96) 51 (89.5) 45 (97.8)
  Yes (n = 7)  6 (10.5)  1 (2.2)
Baseline ODI score41.4 (16.8, 8–84)48.4 (16.8, 10–84)0.04
  1-month ODI29.1 (17.1, 0–72)41.4 (20.5, 4–80)<0.01*
  3-month ODI31.7 (16.3, 2–72)40.9 (19.1, 6–80)0.01*
Baseline leg pain intensity (0–10 NRS) 6.1 (1.8, 3–10) 7.2 (1.8, 4–10)<0.01
  1-month NRS leg pain 3.2 (2.6, 0–9) 5.1 (2.7, 0–10)<0.01
  3-month NRS leg pain 3.8 (2.7, 0–9) 5.2 (3.1, 0–10)0.01
Baseline back pain intensity (0–10 NRS) 5.8 (2.6, 0–10) 6.5 (2.3, 0–10)0.15
  1-month NRS back pain 3.7 (2.6, 0–9) 5.0 (3.0, 0–10)0.02
  3-month NRS back pain 4.0 (2.6, 0–9) 4.9 (3.1, 0–10)0.14
Opioid use0.31§
  No (n, %)  39 (68.4)  27 (58.7)
  Yes (n, %)  18 (31.6)  19 (41.3)
  • *Analyzed with t-test with unequal variances.

  • Analyzed by Wilcoxon rank sum test.

  • Analyzed by Fisher's exact test.

  • §Analyzed by chi-square test.

  • SQ = subcutaneous; ODI = Oswestry Disability Index; NRS = numerical rating scale.

The mean subcutaneous pain score in the 48 patients who obtained <50% relief for leg and back pain at 1 month was 4.0 (SD 2.5), which was significantly higher than in the 24 patients who obtained ≥50% relief for both parameters (mean 2.8, SD 1.9, P = 0.05). However, no differences in outcome were noted when those with negative leg and back pain outcomes (mean 4.0, SD 2.5) were compared with those who experienced a ≥50% improvement in either only back (mean 4.3, SD 3.2) or only leg pain (mean 4.0, SD 2.6) at 1 month, or with any pain relief variable at 3 months. On a similar note, whereas subjects who experienced a ≥10-point decrease in ODI at 1 month had lower subcutaneous pain scores than those who reported a <10-point improvement (3.2 vs 4.1, P = 0.05), these differences largely disappeared at 3 months.

Figures and demonstrate the relationship between leg and back pain reduction, and the standardized clinical stimulus pain rating. For both leg (r = −0.21, 95% CI −0.38 to −0.04; P = 0.03) and back pain (r = −0.22, 95% CI −0.36 to −0.07; P = 0.03), small but significant inverse correlations were noted between subcutaneous pain score and the percent reduction in pain. These findings became more pronounced when pain scores were stratified into “high” and “low” categories. Among the 57 patients who rated the standard clinical stimulus as <4, baseline leg (mean 6.1, SD 1.8 vs 7.2, SD 1.8) pain, back pain (5.8, SD 2.6 vs 6.5, SD 2.3) and ODI (41.4, SD 16.8 vs 48.4, SD 16.8) scores were significantly lower than in the 46 subjects who rated their pain as ≥4. Of the people with subcutaneous pain scores <4, 57.9% had a positive 1-month outcome vs 46.7% in those with scores >4. Reductions in pain and improvements in function were also significantly greater across the board in those subjects with subcutaneous pain scores <4. In those subjects who reported their subcutaneous pain as being ≥7 (N = 14), the mean baseline leg, back, and ODI scores were 7.7 (SD 1.4), 6.9 (SD 1.5), and 48.6 (SD 21.7), respectively. At 1 month, these scores had only slightly declined to 5.7 (SD 2.7), 6.5 (SD 2.7), and 46.9 (SD 21.2). Only 36% of these individuals had a positive 1-month outcome.

Figure 2

Scatter plot demonstrating relationship between percentage pain relief of leg pain at 1 month and standardized clinical stimulus pain rating score. Apparent discrepancies between Figures and for SQ pain scores due to duplicate (superimposed) data points.

Figure 3

Scatter plot demonstrating relationship between percentage pain relief of back pain at 1 month and standardized clinical stimulus pain rating score.

Discussion

In this prospective observational study, we examined the hypothesis that pain scores in response to subcutaneous LA (subcutaneous pain score) during ESI could predict treatment outcomes. Our results indicate that higher subcutaneous pain scores were weakly correlated with poorer ESI outcomes in patients with clinically confirmed lumbosacral radiculopathy. The data suggest that a quick and simple assessment of subcutaneous pain score might be used in the future in conjunction with other variables not evaluated in this study (e.g., facial expression, heart rate response, and psychosocial factors) to predict interventional treatment outcomes for patients with sciatica.

One interesting finding that could help explain our results is that baseline pain and disability scores were also positively associated with subcutaneous pain score. This raises the possibility that patients who respond poorly to treatment may do so because of low intrinsic pain thresholds and/ or high subjective pain responses. A positive correlation between pain sensitivity and pain treatment outcome has previously been demonstrated for whiplash injury and low back pain surgery . However, these studies utilized complex, labor-intensive instruments to measure pain sensitivity, and in the two surgical studies, pain thresholds were examined over the affected dermatomes.

Several issues should be considered in order to place our findings in context. First, in this prospective study we did not randomly assign patients to a predetermined treatment. Instead, the decision to perform an interlaminar or transforlaminar ESI was made by a treating physician in accordance with clinical and radiological (MRI) assessment. Not utilizing a “control” group can potentially reduce the bias of patient selection inherent in conventional randomized clinical studies. Second, performing the LA infiltration at a distinct location remote from the patient's primary radicular pain could minimize the affective response to painful peripheral stimulation, and negate the effects of peripheral sensitization. In a study by Manabat et al. that evaluated the use of subcutaneous lidocaine injections to estimate pain sensitivity before interventional procedures, the authors found a positive association between subcutaneous pain scores and baseline anxiety. However, most of these patients underwent injections overlying their primary pain location. Compared with previous research, the current study may have been more likely to distinguish true pain threshold from the affective component of pain and the physiological sequelae of neuroplasticity.

Despite efforts devoted to developing clinical tools for the objective assessment of pain, pain assessment remains largely subjective and unpredictable. For instance, numerical and visual analog scales have been used to obtain information on pain intensity and pain affect. But a major barrier to correlating pain scores with clinical pain is the lack of any standard, anchoring pain condition that can be compared across the diverse spectrum of pain patients. This deficiency significantly hinders the progress of both clinical pain research and drug trials. Other methods of pain assessment, such as quantitative sensory testing, are valuable, but difficult to administer, time-consuming, and require specific devices. In an era where cost-effectiveness is expected to play an increasingly important role in decision-making, these factors should not be ignored.

The significant psychosocial pathology present in patients with chronic pain and the limitations of the myriad instruments used to measure core domain outcomes, augur strongly for the development of clinical tools that are both relevant to clinical pain conditions and practical to administer in a clinical setting. This need is especially relevant in the context of treating spinal pain with ESI in light of the controversy surrounding their benefit and the rapid rise in their utilization . Recently, the use of phenotyping to categorize patients and predict response to treatment has taken on an increasingly important role in pain medicine . The simplicity and face validity of a subcutaneous pain score in response to a standardized LA injection may make it an ideal tool in the current medicoeconomic climate to use in conjunction with demographic (e.g., age and gender), clinical (e.g., pain quality, radiation referral pattern and neurological deficits), psychological (e.g., depression, anxiety and somatization), patient report (e.g., sensitivity questionnaires), and treatment (e.g., facial expressions and changes in heart rate) variables in order to develop a strong, inexpensive predictive instrument for ESI. Previous studies have demonstrated a positive correlation between pain sensitivity outside of the clinical area of pain and experiment pain ratings, but did not assess the association with treatment outcome [].

There are several limitations to our study that warrant mention. First, our intent in this pilot study was merely to explore the possibility that this test might prove to be a useful tool to predict treatment outcomes. As such, the selection criteria we used may have been too liberal to best determine the efficacy of this test. The use of this test in conjunction with other possible outcome predictors should also be considered in follow-up studies. Second, we evaluated the use of this test in one clinical pain condition, which enabled the administration of the injection at a site remote from the main pain complaint. This method therefore needs to be validated for other pain diagnoses, including those in which injections are performed over the painful areas (e.g., facet blocks, trigger point injections). Third, no distinction was made between the burning sensation associated with lidocaine infiltration and the pain resulting injection itself, which may represent two different pain experiences. A final concern is that we used a single clinical stimulus that can only be practically used prior to injections. Future studies should address whether pressure-pain thresholds (which do not require an injection) could be used to predict treatment outcomes, or whether some refinement on our “standard” clinical stimulus could enhance the predictive value.

Footnotes

  • Disclosures: The authors assert they have no conflicts of interest to disclose.

  • Funding source: Funded in part by a Congressional Grant from the John P. Murtha Neuroscience and Pain Institute, Johnstown, PA (through the Defense and Veterans Center for Integrated Pain Management, Rockville, MD.

  • The opinions or assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the Department of the Army or the Department of Defense.

References

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