Long-term Clinical Outcomes of Cervical Disc Arthroplasty: A Prospective, Randomized, Controlled Trial

Sasso, Willa R.; Smucker, Joseph D. MD; Sasso, Maria P.; Sasso, Rick C. MD

Spine:
doi: 10.1097/BRS.0000000000001746
Randomized Trial
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Abstract

Study Design. Prospective, randomized, single-center, clinical trial.

Objective. To prospectively examine the 7- and 10-year outcomes of cervical arthroplasty to anterior cervical discectomy and fusion (ACDF).

Summary of Background Data. Degeneration of the cervical discs causing radiculopathy is a frequent source of surgical intervention, commonly treated with ACDF. Positive clinical outcomes are associated with arthrodesis techniques, yet there remains a long-term concern for adjacent segment change. Cervical disc arthroplasty has been designed to mitigate some of the challenges associated with arthrodesis whereas providing for a similar positive neurological outcome. As data has been collected from numerous prospective US FDA IDE trials, longer term outcomes regarding adjacent segment change may be examined.

Methods. As part of an FDA IDE trial, a single center collected prospective outcomes data on 47 patients randomized in a 1:1 ratio to ACDF or arthroplasty.

Results. Success of both surgical interventions remained high at the 10-year interval. Both arthrodesis and arthroplasty demonstrated statistically significant improvements in neck disability index, visual analog scale neck and arm pain scores at all intervals including 7- and 10-year periods. Arthroplasty demonstrated an advantage in comparison to arthrodesis as measured by final 10-year NDI score (8 vs. 16, P = 0.0485). Patients requiring reoperation were higher in number in the arthrodesis cohort (32%) in comparison with arthroplasty (9%) (P = 0.055).

Conclusion. At 7 and 10 years, cervical arthroplasty compares favorably with ACDF as defined by standard outcomes scores in a highly selected population with radiculopathy.

Level of Evidence: 1

Author Information

*Department of Research, Indiana Spine Group, Carmel, IN

Indiana Spine Group, Carmel, IN.

Address correspondence and reprint requests to Joseph D. Smucker, MD, Indiana Spine Group, 13225 North Meridian Street, Carmel, IN 46032; E-mail: joe@smuckermd.com

Received 13 February, 2016

Revised 10 May, 2016

Accepted 23 May, 2016

The device(s)/drug(s) is/are FDA-approved or approved by corresponding national agency for this indication.

Medtronic Sofamor Danek funds were received in support of this work.

No relevant financial activities outside the submitted work.

Article Outline

The cervical spine is comprised of motion segments that function in load bearing and motion transfer between the seven vertebral bodies. The phenomenon of degeneration of these structures is a frequent source of clinically symptomatic patient concern, and therefore a frequent source of medical intervention. Surgical treatment of pathology primarily involving the cervical discs has frequently involved removal of disc material and adjacent bone pathology to address a neurological or pain concern.

Anterior cervical discectomy and fusion is a common surgical intervention for patients with cervical radiculopathy or myelopathy.1,2 Concerns for limitations inherent in this procedure are well described, given the long-standing performance of this technique. Alternatives to fusion have been proposed to treat neurological and pain concerns whereas also providing for a more favorable biomechanical and kinematic environment at the index surgical level and adjacent segments.

Adjacent segment degeneration has been well described and is known to occur at a rate of 2.9% of patients per year.3 Over a 10-year interval, 25% of patients who have undergone cervical fusion will have the onset of new symptoms. Recurrence of neurological symptoms and adjacent segment degenerative change have been well documented.4,5 Adverse kinematic and biomechanical findings have been noted adjacent to a cervical arthrodesis including increased range-of-motion and an increase in intradiscal pressure.6,7

Index level pseudarthrosis may be associated with anterior cervical arthrodesis. This phenomenon is well described and has a relationship to the number of levels involved in the fusion procedure. Brodke and Zdeblick have reported a 97% fusion success rated in single-level ACDF, with a decrease in that rate to 83% when three levels are included in the procedure.8 Bohlman et al1 reported an 11% pseudarthrosis rate for single level arthrodesis that increased to 27% when multilevel arthrodesis was examined.

Cervical disc arthroplasty has been designed to preserve motion, address concerns related to arthrodesis, and provide for a positive neurological outcome. Over the last decade seven arthroplasty devices have gained US FDA approval.9–15 The prospective data collected in these trials not only represents a substantial effort to assess the efficacy and outcomes of this procedure, but has also allowed for a number of additional conclusions regarding surgical treatment of cervical disc disorders. Data beyond the traditional 24-month term is being reported16–19 and has the potential to demonstrate a significant difference in adjacent segment concerns as they relate to arthrodesis, as many of these concerns may be related to longer-term outcomes.3 We examine the 10-year outcomes of a single center experience with cervical arthroplasty prospectively compared with arthrodesis for single level pathology.

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MATERIALS AND METHODS

As part of a multicenter, randomized, controlled FDA IDE trial, patients were enrolled in a 1:1 ratio to receive either a BRYAN cervical arthroplasty device (Medtronic Sofamor Danek, Memphis, TN) or anterior cervical discectomy and fusion with plating. Patients were limited to those with single-level cervical degenerative disc disease with 6 weeks of failed nonoperative treatment for either cervical radiculopathy or myelopathy. Subaxial cervical segments including C3–4 to C6–7 could be included for surgical treatment. Patients had no history of prior cervical spine surgery, a neck disability index (NDI) ≥30, and were at least 21-years old. Exclusion criteria for this trial included: significant cervical anatomic deformity, advanced degenerative changes, prior cervical spine surgery, metabolic bone disease, spinal metastases, infection, diabetes, allergy to implant materials, extreme obesity, or pregnancy.

Institutional Review Board (IRB) approval was obtained for this entire cohort consistent with the protocol for the multicenter trial. Randomization was generated by the study sponsor. Blinding for the site was maintained through the process of confirmation of eligibility and informed consent. The fusion procedure (Figure 1) was standardized to fusion with commercially available allograft and a single anterior cervical plating system (Medtronic Sofamor Danek, Memphis, TN). Patients in both groups followed a routine postoperative course and were allowed activity as tolerated if it was nonstrenuous. Patients treated in the arthroplasty cohort (Figure 2) received 2-post surgical weeks of a nonsteroidal antiinflammatory drug of the patient's choice. Patients were evaluated at routine postsurgical intervals.

Assessments over the 10-year period were prospectively collected and recorded. Outcomes assessments were made over routine postsurgical intervals and included NDI, and numerical rating scales for neck and arm pain. Statistical analysis was performed in two parts. Paired t tests were done between the preoperation standings and the 7- or 10-year standings to be sure that the operations were successful statistically. Unpaired t tests were done to evaluate the differences between the control group and the experimental group to look for significance. The reoperation statistics were completed using a two- proportion z- test to test for significant differences in success. All findings were considered statistically significant if the P value obtained was less than 0.05.

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RESULTS

Sixty-two patients were screened for eligibility in the trail. Of these patients, 15 were ineligible as denied by the sponsor or secondary to inability to participate in follow-up requirements. Of the 47 patients enrolled and randomized at our center, 22 patients received the arthroplasty device and 25 received an ACDF. The randomization protocol intended 24 patients to receive the arthroplasty and 23 receive a fusion. Of the 25 patients in the ACDF as-treated group, three patients received the fusion (conversion) secondary to technical difficulty with implantation of the arthroplasty device. In the arthroplasty group, one patient had been randomized to fusion, but received the arthroplasty secondary to randomization error (Figure 3). At the time of data analysis, three patients were not available for 7-year follow up and five patients were not available for the 120-month follow-up interval. Patients reaching 7- and 10-year follow-up were assessed via visual analog scale (VAS) neck and arm, and NDI.

At 7-year follow up 20 of 22 (90.9%) of patients had data available in the investigational group (Figure 3) and 24 of 25 (96%) of patients had data available from the control group. NDI scores were followed pre-operatively and at routine post-surgical intervals (Figure 4). At 7-year follow-up the NDI for the arthroplasty group was 8.6 and that for the arthrodesis group was 21 (Table 1), a statistically significant difference favoring the arthroplasty cohort (P = 0.0138). Both groups achieved and maintained improvement in comparison to their pre-operative NDI baseline score of 50 (P < 0.0001).

At 10-year follow-up 19 of 22 (86.4%) of patients had data available in the investigational group (Figure 3). In the control group all 23 of 25 (92.0%) of patients were available for assessment. NDI scores were followed preoperatively and at routine postsurgical intervals (Figure 4). At the final follow up of 120 months, the NDI for the arthroplasty group was 8 (8.05) and that for the arthrodesis group was 15 (15.48) (Table 2), a statistically significant difference favoring the arthroplasty cohort (P = 0.0485). Both groups achieved and maintained improvement in comparison with their preoperative NDI baseline score of 50 (P < 0.0001).

VAS neck pain scores were similar in the presurgical groups, 7.5 arthrodesis and 7.2 arthroplasty. Both groups demonstrated sustained postsurgical, statistically significant improvement in these scores in comparison with their presurgical state over the follow-up intervals including the 7- and 10-year assessments (Figure 5). At the 7-year follow-up VAS neck was 2.71 for arthrodesis and 0.9 for arthroplasty (Table 1). At this interval, there was a significant difference between the two groups favoring arthroplasty (P = 0.0146). At the final 10-year, these assessments were 1.5 for arthrodesis and 1.3 for arthroplasty (Table 2). There was no-significant difference between these two groups at the final 10-year interval with respect to VAS neck pain (P = 0.6958).

VAS arm pain scores were also similar in the presurgical groups, 7.0 arthrodesis and 7.8 arthroplasty. Both groups demonstrated sustained postsurgical, statistically significant improvement in these scores in comparison with their presurgical state over the follow-up intervals including the 7- and 10-year assessments (Figure 6). At the 7-year follow-up VAS arm was 1.88 for arthrodesis and 0.45 for arthroplasty (Table 1). At this interval, there was a significant difference between the two groups, favoring the arthroplasty cohort (P = 0.0322). At the 10-year assessment, scores were 0.74 arthrodesis and 0.84 arthroplasty (Table 2). There was no-significant difference between these two groups at the final 10-year interval with respect to VAS arm pain (P = 0.8564).

Reoperations were examined at 10 years. In the arthroplasty cohort, two patients (9%) required operative interventions, one patient at an adjacent level, and a second patient at a nonadjacent level. The single patient initially randomized to fusion who received an arthroplasty did not require a reoperation. In the arthrodesis cohort, eight patients (32%) required reoperation. Two patients required multiple reoperations for a total of 11 operative events (11/25 = 44%). Six patients required an operative event at an adjacent level. None of the patients in our center's experience required a reoperation at the index surgical level.

Ten total patients required reoperation in this investigation overall (21%). Two patients in the arthroplasty group (9%) were later treated with additional cervical spine procedures. One patient underwent an ACDF at a nonadjacent level (two levels from the index arthroplasty site). The second patient was treated with an adjacent level arthrodesis. Eight patients in the arthrodesis group (32%) were later treated with additional cervical spine procedures, two patients of whom required multiple reoperations. Four patients required a single-level adjacent fusion. One patient underwent a secondary arthrodesis at a nonadjacent level. One patient underwent a posterior laminectomy at a nonindex and nonadjacent level. Two patients underwent multiple adjacent level fusions (one above and one below the index segment in separate operative and clinical events). One of these multiadjacent segment patients later required a posterior arthrodesis for pseudoarthrosis. Surgical survivorship of the prosthesis as defined by the metric of patient reoperation was 90.90% representing two reoperations in 22 total patients. By this same metric, arthrodesis surgical survivorship was 68.0% represented by the eight reoperations in 25 total patients. This difference was not a statistically significant finding (P = 0.05551).

A chart review was accomplished to assess the extent of our data availability and understand anomalies with data collection and reporting. Five patients were identified who were not available for 10-year follow up. Of these patients, one patient was deceased and four patient had failed to respond for further data collection and analysis and were “lost” to follow up for patient care and data collection. Three patients were converted intraoperatively from the randomized arthroplasty to ACDF. Intraoperative judgments of the operating surgeon appeared to play a substantial role in conversion of these patients to arthrodesis. One patient had enough degeneration of the index operative level that the disc-space could not be properly prepared with the disc preparation and milling tools. A second patient's disc space was anatomically too small to accommodate the smallest arthroplasty size available for implantation. The third patient's intervention was converted to arthrodesis secondary to inadequate visualization of the index operative level at C6-C7 and preparation and insertion of the arthroplasty device was felt to be inappropriate from a safety perspective. None of these patients required a reoperative event at any point during their 10-year follow up.

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DISCUSSION

Anterior cervical discectomy and fusion demonstrates positive patient outcomes and high success rates with respect to fusion at the index surgical site.1 Cervical disc arthroplasty is an alternative to this procedure and data for many of these devices has been collected via US FDA IDE trials over a number of postsurgical intervals.9–15 Beyond the initial 24-month outcomes, longer-term data has also been published demonstrating favorable outcomes with both arthrodesis and arthroplasty.16–20 Our single-site data has been collected as part of the greater experience with the BRYAN device.9

We demonstrate success of cervical arthrodesis and arthroplasty over long-term 7- and 10-year intervals. Both groups demonstrated sustained improvements from presurgical baseline as assessed by NDI, and VAS arm and neck pain scores. The degree of this improvement compares favorably with former nonrandomized European clinical trials of this same device.21 Investigations of alternative arthroplasty devices have also demonstrated improvement with both of these techniques over time with similar outcome measures. At the final 120-month outcome the arthroplasty device did compare favorably with arthrodesis with respect to NDI, suggesting an advantage in the arthroplasty cohort with respect to this clinical outcome measure.

Although a rapid return to work and index safety of arthroplasty provided an early argument for in comparison with arthrodesis,9 the difference in reoperation rates is notable over the longer-term. A 32% reoperation rate in the arthrodesis cohort is inline with the 10-year predicted rate discussed in the landmark adjacent segment data published by Hilibrand el al.3 Their investigation suggested a rate of 2.9% per annum, a figure which mirrors our 10-year data very closely. In contrast, the 9% reoperation rate in the arthroplasty group at 10 years is suggestive of preservation of the adjacent levels to a degree not provided by arthrodesis at this interval. Longer-term investigations, including this cohort have been previously suggested to be critical to understanding the advantages of arthroplasty in this regard secondary to the altered mechanics of arthrodesis6,7 in contrast to arthroplasty. This advantage with respect to reoperation rate appears to be present in 7-year multicenter outcomes as reported in a randomized prospective investigation reported by Janssen et al,20 who noted a statistically significant (P = 0.0201) difference reoperation rate of 7% and 18% (arthroplasty vs. arthrodesis). These mechanical advantages do not appear to be at the expense of baseline outcomes with continued motion at the index surgical segment. This investigation supplements the effectiveness of arthrodesis in longer-term outcomes, and provides additional prospective data for a “gold standard” surgery.

There are weaknesses in this investigation. All patients in our dataset reached 10-year follow-up, yet data from the five patients (three investigational, two control) who were not examined might have altered our conclusions. It may be that subsets of single-center data do not ultimately reflect the longer-term results of the multicenter experience. Finally, the conclusions made with respect to adjacent segment degeneration, though consistent with prior investigations,3 may not be fully reflective of the characteristics of cervical aging.

Investigational trials are not-inclusive of all patients who may be eligible for a surgical intervention, and exclude patients who would either benefit from or have a poor-outcome with either an investigational device or the study control. This trial represents a narrow patient cohort of single-level disc concerns. Our single-center represents a second subset. Finally, of the 62 patients screened as eligible at our center 15 were excluded (15/62 = 24.2%): 10 patients were excluded by the sponsor as being ineligible (10/62 = 16.1%), and five patients withdrew secondary to follow-up requirements (5/62 = 8.1%). It is possible that conclusions reached in this investigation are not representative of the positive and/or negative outcomes that may be achieved in broad clinical. Although it is interesting to draw a parallel to the data collected by Hilibrand et al.3 and our 10-year reoperation rate, the data reflected in the Hilibrand et al. cohort is potentially far more surgically diverse than our dataset.

Three patients required intraoperative conversion from the randomized intervention (arthroplasty) to ACDF. A variety of factors may lead to such a decision such as: difficulty with implant sizing, imaging challenges related to device location or patient soft-tissue artifact, difficulty with implant seating/placement, intraoperative instability or failure of primary device fixation, failure of bone/disc preparation tools, challenges with device centering or anterior-posterior alignment, bone fracture/structural integrity, neurological decompression needs, and a variety of other surgeon, patient, or anesthesia driven factors. It is notable that these conversions were a deviation from the intended randomization and may have intrinsically changed the patient reported outcomes. However, of the three patients in question who were treated with arthrodesis instead of arthroplasty, all were available for 10-year follow up and none went on to reoperation during the course of their 10-year follow up. The single patient initially randomized to fusion who received an arthroplasty was also available for all follow-ups over the entire 10-year interval. This patient also had an excellent clinical outcome and was not one of the two arthroplasty patients who required a reoperation. Although all four of these patients appeared to have similar 10-year outcomes these deviations in treatment could either reflect negatively or positively on the outcome of arthrodesis or arthroplasty, and should be considered in the interpretation of this dataset.

A variety of investigations have been undertaken and described since the initiation of this FDA IDE trial. Data from investigations into arthroplasty at multiple levels is now becoming available.22 In addition, the mechanics and outcomes of arthroplasty adjacent to an arthrodesis are now being investigated.23,24 Facet degenerative change is not addressed with cervical disc arthroplasty and may serve as another opportunity for intervention. Novel bearing surfaces may address imaging artifact issues and may be coupled with simplified implantation techniques to create a more consistent experience for surgeons and patients. It will be important to compare this data with that collected from other arthroplasty trials over time. There may be arthroplasty design characteristics that prove to be more favorable with time. It is encouraging to find that the longer-term examinations of this technique appear to offer distinct advantages in comparison with arthrodesis.

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Key Points

* At 7- and 10-year follow up, both single-level arthrodesis and arthroplasty demonstrate sustained improvement in comparison to presurgical patient baseline outcome metrics.

* Cervical arthroplasty demonstrates greater improvement in NDI at 10-years in comparison with cervical arthrodesis.

* At 10-year follow-up the reoperation rate in the arthroplasty cohort of this investigation is lower but not statistically different (9%) than that observed in the arthrodesis cohort (32%) (P = 0.05551).

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References

1. Bohlman HH, Emery SE, Goodfellow DB, et al. Robinson anterior cervical discectomy and arthrodesis for cervical radiculopathy. Long-term follow-up of one hundred and twenty-two patients. J Bone Joint Surg Am 1993; 75:1298–1307.
2. Emery SE, Fisher JR, Bohlman HH. Three-level anterior cervical discectomy and fusion: radiographic and clinical results. Spine 1997; 22:2622–2624.
3. Hilibrand AS, Carlson GD, Palumbo MA, et al. Radiculopathy and myelopathy at segments adjacent to the site of a previous anterior cervical arthrodesis. J Bone Joint Surg Am 1999; 81:519–528.
4. Goffin J, van Loon J, Van Calenbergh F, et al. Long-term results after anterior cervical fusion and osteosynthetic stabilization for fractures and/or dislocations of the cervical spine. J Spinal Disord 1995; 8:500–508.
5. Goffin J, Geusens E, Vantomme N, et al. Long-term follow-up after interbody fusion of the cervical spine. J Spinal Disord Tech 2004; 17:79–85.
6. Eck JC, Humphreys SC, Lim TH, et al. Biomechanical study on the effect of cervical spine fusion on adjacent-level intradiscal pressure and segmental motion. Spine 2002; 27:2431–2434.
7. Fuller DA, Kirkpatrick JS, Emery SE, et al. A kinematic study of the cervical spine before and after segmental arthrodesis. Spine 1998; 23:1649–1656.
8. Brodke DS, Zdeblick TA. Modified Smith-Robinson procedure for anterior cervical discectomy and fusion. Spine 1992; 17:S427–S430.
9. Heller JG, Sasso RC, Papadopoulos SM, et al. Comparison of BRYAN cervical disc arthroplasty with anterior cervical decompression and fusion: clinical and radiographic results of a randomized, controlled, clinical trial. Spine 2009; 34:101–107.
10. Hisey MS, Bae HW, Davis R, et al. Multi-center, prospective, randomized, controlled investigational device exemption clinical trial comparing Mobi-C Cervical Artificial Disc to anterior discectomy and fusion in the treatment of symptomatic degenerative disc disease in the cervical spine. Int J Spine Surg 2014; 8.
11. Phillips FM, Lee JY, Geisler FH, et al. A prospective, randomized, controlled clinical investigation comparing PCM cervical disc arthroplasty with anterior cervical discectomy and fusion. 2-year results from the US FDA IDE clinical trial. Spine (Phila Pa 1976) 2013; 38:E907–E918.
12. Mummaneni PV, Burkus JK, Haid RW, et al. Clinical and radiographic analysis of cervical disc arthroplasty compared with allograft fusion: a randomized controlled clinical trial. J Neurosurg Spine 2007; 6:198–209.
13. Gornet MF, Burkus JK, Shaffrey ME, et al. Cervical disc arthroplasty with PRESTIGE LP disc versus anterior cervical discectomy and fusion: a prospective, multicenter investigational device exemption study. J Neurosurg Spine 2015; Epub ahead of print.
14. Murrey D, Janssen M, Delamarter R, et al. Results of the prospective, randomized, controlled multicenter Food and Drug Administration investigational device exemption study of the ProDisc-C total disc replacement versus anterior discectomy and fusion for the treatment of 1-level symptomatic cervical disc disease. Spine J 2009; 9:275–286.
15. Vaccaro A, Beutler W, Peppelman W, et al. Clinical outcomes with selectively constrained SECURE-C cervical disc arthroplasty: two-year results from a prospective, randomized, controlled, multicenter investigational device exemption study. Spine (Phila Pa 1976) 2013; 38:2227–2239.
16. Hisey MS, Bae HW, Davis RJ, et al. Prospective, Randomized Comparison of Cervical Total Disk Replacement Versus Anterior Cervical Fusion: Results at 48 Months Follow-up. J Spinal Disord Tech 2015; 28:E237–E243.
17. Delamarter RB, Murrey D, Janssen ME, et al. Results at 24 months from the prospective, randomized, multicenter Investigational Device Exemption trial of ProDisc-C versus anterior cervical discectomy and fusion with 4-year follow-up and continued access patients. SAS J 2010; 4:122–128.
18. Zigler JE, Delamarter R, Murrey D, et al. ProDisc-C and anterior cervical discectomy and fusion as surgical treatment for single-level cervical symptomatic degenerative disc disease: five-year results of a Food and Drug Administration study. Spine (Phila Pa 1976) 2013; 38:203–209.
19. Sasso RC, Anderson PA, Riew KD, et al. Results of cervical arthroplasty compared with anterior discectomy and fusion: four-year clinical outcomes in a prospective, randomized controlled trial. J Bone Joint Surg Am 2011; 93:1684–1692.
20. Janssen ME, Zigler JE, Spivak JM, et al. ProDisc-C total disc replacement versus anterior cervical discectomy and fusion for single-level symptomatic cervical disc disease: seven-year follow-up of the prospective randomized U.S. Food and Drug Administration Investigational Device Exemption Study. J Bone Joint Surg Am 2015; 97:1738–1747.
21. Goffin J, Van Calenbergh F, van Loon J, et al. Intermediate follow-up after treatment of degenerative disc disease with the Bryan Cervical Disc Prosthesis: single-level and bi-level. Spine 2003; 28:2673–2678.
22. Davis RJ, Kim KD, Hisey MS, et al. Cervical total disc replacement with the Mobi-C cervical artificial disc compared with anterior discectomy and fusion for treatment of 2-level symptomatic degenerative disc disease: a prospective, randomized, controlled multicenter clinical trial: clinical article. J Neurosurg Spine 2013; 19:532–545.
23. Phillips FM, Allen TR, Regan JJ, et al. Cervical disc replacement in patients with and without previous adjacent level fusion surgery: a prospective study. Spine (Phila Pa 1976) 2009; 34:556–565.
24. Gandhi AA, Kode S, DeVries NA, et al. Biomechanical analysis of cervical disc replacement and fusion using single level, two level and hybrid constructs. Spine (Phila Pa 1976) 2015.
Keywords:

arthrodesis; arthroplasty; cervical; disc; fusion; outcomes; prospective; randomized

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