International Spine Intervention Society Research Articles

The Effectiveness and Risks of Fluoroscopically-Guided Cervical Medial Branch Thermal Radiofrequency Neurotomy: A Systematic Review with Comprehensive Analysis of the Published Data

To determine the effectiveness and risks of fluoroscopically-guided cervical medial branch thermal radiofrequency neurotomy (CMBTRFN) for treating chronic neck pain of zygapophysial joint origin. Systematic review of the literature with comprehensive analysis of the published data. Four reviewers formally trained in evidence-based medicine searched the literature on CMBTRFN. Each assessed the methodologies of studies found and appraised the quality of evidence presented. The primary outcomes assessed were 100% relief of pain 6 and 12 months after treatment. Other outcomes were noted if reported. The evidence was evaluated in accordance with the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) system. The searches yielded eight primary publications on the effectiveness of the procedure. The evidence shows a majority of patients were pain free at 6 months and over a third were pain free at 1 year. The number needed to treat for complete pain relief at 6 months is 2. The evidence of effectiveness is of high quality according to the GRADE system. Twelve papers were found reporting unwanted effects, most of which are minor and temporary. No serious complications have ever been reported from procedures performed according to the published guidelines. The evidence of risks is of low quality according to the GRADE system. If performed as described in the International Spine Intervention Society Guidelines, fluoroscopically-guided CMBTRFN is effective for abolishing zygapophysial joint pain and carries only minor risks.

Adverse Event Rates Associated with Transforaminal and Interlaminar Epidural Steroid Injections: A Multi-Institutional Study.

Transforaminal epidural steroid injections (TFESI) have demonstrated efficacy and effectiveness in treatment of radicular pain. Despite little evidence of efficacy/effectiveness, interlaminar epidural steroid injections (ILESI) are advocated by some as primary therapy for radicular pain due to purported greater safety. To assess immediate and delayed adverse event rates of TFESI and ILESI injections at three academic medical centers utilizing International Spine Intervention Society practice guidelines. Quality assurance databases from a Radiology and two physical medicine and rehabilitation (PM&R) practices were interrogated. Medical records were reviewed, verifying immediate and delayed adverse events. There were no immediate major adverse events of neurologic injury or hemorrhage in 16,638 consecutive procedures in all spine segments (14,956 TFESI; 1,682 ILESI). Vasovagal reactions occurred in 1.2% of procedures, more frequently (P = 0.004) in TFESI (1.3%) than ILESI (0.5%). Dural punctures occurred in 0.06% of procedures, more commonly after ILESI (0.2% vs 0.04%, P = 0.006). Delayed follow up on PM&R patients (92.5% and 78.5, next business day) and radiology patients (63.1%, 2 weeks) identified no major adverse events of neurologic injury, hemorrhage, or infection. There were no significant differences in delayed minor adverse event rates. Central steroid response (sleeplessness, flushing, nonpositional headache) was seen in 2.6% of both TFESI and ILESI patients. 2.1% of TFESI and 1.8% of ILESI patients reported increased pain. No long-term sequelae were seen from any immediate or delayed minor adverse event. Both transforaminal and ILESI are safely performed with low immediate and delayed adverse event rates when informed by evidence-based procedural guidelines. By demonstrating comparable safety, this study suggests that the choice between ILESI and TFESIs can be based on documented efficacy and effectiveness and not driven by safety concerns.

The Potential Contributing Effect of Ketorolac and Fluoxetine to a Spinal Epidural Hematoma following a Cervical Interlaminar Epidural Steroid Injection: A Case Report and Narrative Review

Cervical interlaminar epidural steroid injections (ESIs) are commonly performed as one part of a multi-modal analgesic regimen in the management of upper extremity radicular pain. Spinal epidural hematoma (SEH) is a rare complication with a reported incidence ranging from 1.38 in 10,000 to 1 in 190,000 epidurals. Current American Society of Regional Anesthesia (ASRA), American Society of Interventional Pain Physicians (ASIPP), and the International Spine Intervention Society (ISIS) recommendations are that non-steroidal anti-inflammatory drugs (NSAIDs) do not need to be withheld prior to epidural anesthesia. We report a case wherein intramuscular ketorolac and oral fluoxetine contributed to a SEH and tetraplegia following a cervical interlaminar (ESI). A 66 year-old woman with chronic renal insufficiency and neck pain radiating into her right upper extremity presented for evaluation and was deemed an appropriate CESI candidate. Cervical magnetic resonance imaging (MRI) revealed multi-level neuroforaminal stenosis and degenerative intervertebral discs. Utilizing a loss of resistance to saline technique, an 18-gauge Tuohy-type needle entered the epidural space at C6-7. After negative aspiration, 4 mL of saline with 80 mg of methyl-prednisolone was injected. Immediately thereafter, the patient reported significant spasmodic-type localized neck pain with no neurologic status changes. A decision was made to administer 30 mg intramuscular ketorolac as treatment for the spasmodictype pain. En route home, she developed a sudden onset of acute tetraplegia. She was brought to the emergency department for evaluation including platelet and coagulation studies which were normal. MRI demonstrated an epidural hematoma extending from C5 to T7. She underwent a bilateral C5-T6 laminectomy with epidural hematoma evacuation and was discharged to an acute inpatient rehabilitation hospital. Chronic renal insufficiency, spinal stenosis, female gender, and increasing age have been identified as risk factors for SEH following epidural anesthesia. In the present case, it is postulated that after the spinal vascular system was penetrated, hemostasis was compromised by the combined antiplatelet effects of ketorolac, fluoxetine, fish oil, and vitamin E. Although generally well tolerated, the role of ketorolac, a potent anti-platelet medication used for pain relief in the peri-neuraxial intervention period, should be seriously scrutinized when other analgesic options are readily available. Although the increased risk of bleeding for the alternative medications are minimal, they are nevertheless well documented. Additionally, their additive impairment on hemostasis has not been well characterized. Withholding NSAIDs, fluoxetine, fish oil, and vitamin E in the peri-procedural period is relatively low risk and should be considered for all patients with multiple risk factors for SEH. Key words: Spontaneous epidural hematoma, ketorolac, cervical interlaminar epidural steroid injection, fluoxetine, anti-platelet, neuraxial injection, perioperative pain

Time- and Dose-dependent Cytotoxicities of Ioxitalamate and Indigocarmine in Human Nucleus Pulposus Cells

Introduction Ioxitalamate (Telebrix 300) is an ionic iodinated contrast medium (CM) commonly used for discography or PELD (percutaneous endoscopic lumbar discectomy), though it has side effects such as anaphylactic shock and renal toxicity. Indigocarmine is an organic compound dye with a distinctive blue color that is commonly used during PELD to stain the acidic, degenerated nucleus pulposus. Although ioxitalamate and indigocarmine are widely used in spinal surgery, there have been no reports on their effects on nucleus pulposus (NP) cells. We studied the toxicity of both ioxitalamate and indigocarmine to NP cells. Materials and Methods NP cells were obtained via discectomy from lumbar disc patients and isolated. NP cells were cultured in three-dimensional (3D) alginate beads with 0.001, 0.1, 10, and 100 mg/mL ioxitalamate, 0.00001, 0.001, 0.1 and 10 mg/mL indigocarmine, or a mixture of both for 1, 2, or 3 days. The living cells were analyzed with trypan blue staining. FACS analysis using Annexin V and propidium iodide (PI) and 3D alginate bead immunostaining was performed to identify live, apoptotic, and necrotic cells. Results Ioxitalamate, indigocarmine, and their combination induced statistically significant NP cell injury that was both time and dose dependent ( p < 0.05). Also, at the same concentration, ioxitalamate was more cytotoxic than was indigocarmine or the combination ( p < 0.05). All three treatments also showed dose-dependent cytotoxicity according to flow cytometry and immunostaining. Conclusion Ioxitalamate and indigocarmine are toxic to human NP cells in vitro in a time- and dose-dependent manner. We assume that ioxitalamate and indigocarmine may have similar effects in patients undergoing discography and PELD. Thus, we suggest that ioxitalamate and indigocarmine should be used carefully at low concentrations. Disclosure of Interest None declared References Stout A. Discography. Phys Med Rehabil Clin N Am 2010;21(4):859–867 Manchikanti L, Glaser SE, Wolfer L, Derby R, Cohen SP. Systematic review of lumbar discography as a diagnostic test for chronic low back pain. Pain Physician 2009;12(3):541–559 Carragee EJ, Tanner CM, Yang B, Brito JL, Truong T. False-positive findings on lumbar discography. Reliability of subjective concordance assessment during provocative disc injection. Spine 1999;24(23):2542–2547 Laslett M, Oberg B, Aprill CN, McDonald B. Centralization as a predictor of provocation discography results in chronic low back pain, and the influence of disability and distress on diagnostic power. Spine J 2005;5(4):370–380 Kim D, Wadley R. Variability in techniques and patient safety protocols in discography: a national multispecialty survey of International Spine Intervention Society members. J Spinal Disord Tech 2010;23(6):431–438 Carragee EJ, Tanner CM, Khurana S, et al. The rates of false-positive lumbar discography in select patients without low back symptoms. Spine 2000;25(11):1373-1380, discussion 1381 Paul MD, Tsou M. Posterolateral percutaneous endoscopic lumbar discectomy. Oper Tech Orthop 2003;13:207-213 Yeung AT. Selective endoscopic discectomy. In: Kambin P, ed. Arthroscopic and Endoscopic Spinal Surgery. Totowa, NJ: Humana Press; 2005:205–225 Mayer HM, Brock M. Percutaneous endoscopic discectomy: surgical technique and preliminary results compared to microsurgical discectomy. J Neurosurg 1993;78(2):216–225 Yeung AT, Tsou PM. Posterolateral endoscopic excision for lumbar disc herniation: Surgical technique, outcome, and complications in 307 consecutive cases. Spine 2002;27(7):722–731 Lee H, Sowa G, Vo N, et al. Effect of bupivacaine on intervertebral disc cell viability. Spine J 2010;10(2):159–166 Hsu SP, Tsai TJ, Chien CT. Ioxitalamate induces renal tubular apoptosis via activation of renal efferent nerve-mediated adrenergic signaling, renin activity, and reactive oxygen species production in rats. Toxicol Sci 2010;114(1):149–158 Lee HC, Chang JG, Yen HW, Liu IH, Lai WT, Sheu SH. Ionic contrast media induced more apoptosis in diabetic kidney than nonionic contrast media. J Nephrol 2011;24(3):376–380 Belhadjali H, Bouzgarrou L, Youssef M, Njim L, Zili J. DRESS syndrome induced by sodium meglumine ioxitalamate. Allergy 2008;63(6):786–787 Lacour B, Lacroix C, Jungers P, Bailly M. [Effects of intravenous urography using sodium and meglumine ioxitalamate (Telebrix 38) on blood creatinine and urinary excretion of N-acetyl-beta-D-glucosaminidase]. Ann Biol Clin (Paris) 1984;42(6):407–411

Cervical Medial Branch Radiofrequency Neurotomy

As a practicing neurosurgeon with special interest in pain therapy and spine surgery, I read with interest the article “Cervical Medial Branch Radiofrequency Neurotomy in New Zealand” by MacVicar et al. [1]. As I published a related article about Radiofrequency Neurotomy after cervical spine operations [2], I would like to invite a discussion about the indication for radiofrequency neurotomy of the medial branch. First of all, I would like to thank the authors for emphasizing the importance of compliance to the guidelines of the International Spine Intervention Society [3]. If these protocols are strictly followed, a complete and enduring relief of pain is achieved in 60% of the patients. Because radiofrequency neurotomy procedures are done all over the world in …

Outcomes of Percutaneous Zygapophysial and Sacroiliac Joint Neurotomy in a Community Setting

To evaluate the analgesic, physical, and psychological outcomes of percutaneous radiofrequency neurotomy for persistent zygapophysial and sacroiliac joint pain in a community setting. A prospective evaluation of 379 consecutive neurotomies in a single specialist practice over an extended period 2001-2010. A provincial community environment in Australia. All patients who had positive responses to diagnostic blocks, performed according to the guidelines of the International Spine Intervention Society by three trained specialists, underwent percutaneous radiofrequency thermal neurotomies performed by the author. Radiofrequency neurotomies to denervate the zygapophysial or sacroiliac joints according to the standards of the International Spine Intervention Society. Numerical Rating Scale for Pain, Functional Rating Index, 4-Activities of Daily Living Scale, General Health Questionnaire, Depression Anxiety Stress Scale, duration of pain relief, "whether they would do it again," and overall amount of pain relief. Of 379 procedures, 272 (72%) were regarded as successful by the patients. Irrespective of region treated. The results were highly significant by t-test, and the effect size was large as determined by the Cohen's d. Adverse events were infrequent and relatively minor. Repetitions of the procedure were highly successful. Neurotomy of the cervical, thoracic, lumbar, and sacroiliac joints were uniformly successful with 72% recipients obtaining an average of 86% reduction in pain for a period of 12 months.

“Change and Collaboration: The Only Way Forward”

For the medical community, this past year has been marked largely by change. Healthcare reform has commanded the highest profile, but several other important developments with potentially significant impact on medical practices are in various stages of completion. These developments range from the Food and Drug Administration's efforts to set new rules for opioid prescription practices to the pilot program on open medical records to the planned reductions in Medicare fees. As an organization, the American Academy of Pain Medicine (AAPM) is continuing to work for the best possible outcomes for us and for our patients. As we strive for this, we are convinced that collaboration with other medical organizations offers us an effective mechanism for having our voices heard. There is, as the saying goes, strength in numbers. We’ve made great strides in the past year in reaching out to other medical organizations to collaborate on important initiatives. One recent example is AAPM's participation in the Interventional Spine Leadership Summit meeting, hosted by the International Spine Intervention Society (ISIS). We joined other organizations, including the American Society of Anesthesiology (ASA), the American Academy of Physical Medicine and Rehabilitation (AAPM&R), and the North American Spine Society (NASS), to explore consensus in interventional spine care, discuss scope of practice parameters, and develop cooperative multi-society outcome based treatment data. Another example was our participation in Spine Summit 2010 …

International Spine Intervention Society 18thAnnual Scientific Meeting, Maui HI

July 17, 2010 Presidential Address An old Chinese proverb states, “May you live in interesting times.” Ladies and gentlemen, for better or worse, we are indeed living in interesting times. In the US and abroad, healthcare access issues have come to the forefront of political and public interests. The global recession has fundamentally impacted us, and the patients for whom we care; it has also influenced policies of healthcare coverage. Increasingly, it is administrators—not the physicians or specialists taking care of individual patients—who determine what is medically necessary, indicated or effective, and determine which patients shall have access to care. We have witnessed a fundamental shift in how the effectiveness of medical care is adjudicated, and the new landscape is one very different from that which previously existed: where the RCT was held highest upon the altar of evidence. “Comparative effectiveness research,”“health care value,”“physician performance measures” and even claims data devoid of outcome measures may now be utilized to determine coverage. For the majority of the nearly 20 years of our existence, ISIS has worked tirelessly to promote the conscientious delivery of scientifically validated spinal interventions. Our integrity has allowed us to successfully build bridges of understanding between the leadership of other conscientious medical societies …

Reply to Comment on: Penetration of a Cervical Radicular Artery during a Transforaminal Epidural Injection

Dear Editor, In the letter authored by Dr. Milton Landers, I note that he goes to some lengths to imply that the rationale for the intra-arterial injection recorded and presented in our publication is due to inappropriate needle position. I believe that his commentary is flawed on numerous grounds. The International Spine Intervention Society (ISIS) Guidelines are certainly the preeminent reference for interventional spinal procedures at this time. However, both Dr. Landers and the ISIS Guidelines do not provide any proof that the position of the needle in …

Variability in Techniques and Patient Safety Protocols in Discography

National survey. (1) Characterize the way discography is being carried out and by which specialties. (2) Quantify adherence to the International Spine Intervention Society (ISIS) guidelines. (3) To see if there is experience or specialty differences in technique. Discography is a controversial diagnostic tool that attempts to correlate disc morphology to concordant pain. It is increasingly performed by different specialties as a prelude to fusion, disc replacement, and percutaneous intradiscal procedures. A consensus committee of the ISIS has published guidelines for performing discography to increase diagnostic accuracy, standardize technique, and improve patient safety. This survey wishes to see how closely these guidelines are followed. In all, 500 members of the ISIS were randomly selected to receive a 13-item questionnaire. The questions included the following demographic information: specialty, number of discograms in 1 year (<15, 15-50, >50). Patient safety questions included the following: use of preoperative antibiotics, intradiscal antibiotics, postoperative antibiotics, and use of double needle technique. Technical questions included the following: needle entry on the opposite site of symptoms, injecting the control disc first, using manometry to record opening pressure, using manometry to record pressure on pain reproduction, injecting discs adjacent to the painful disc, and using pain assessment forms. Comparison of responses was made between specialties. Responses to the questions were also compared based on the number of procedures performed per year. The response rate to the questionnaire was 34.6%. Of the 173 respondents, the following specialties were represented: 100 (57.8%) Anesthesiology, 53 (30.6%) Physical Medicine and Rehabilitation (PMR), 16 (9.2%) Radiology, 4 (2.3%) Other. Number of procedures carried out was as follows: <15 (22.54%), 15 to 50 (50.86%), >50 (26.58%). The adherence to patient safety guidelines were as follows: preoperative antibiotics (83.81%), intradiscal antibiotics (84.97%), postprocedure antibiotics (9.82%), use of double needle technique (64.16%). The adherence to technical guidelines were as follows: optional use of computed tomography scan (64.78%), pain assessment sheet (66.47%), entering on the side opposite symptoms (48.55%), manometry for opening pressure (65.31%), manometry of pain reproduction pressure (72.25%), injecting a control disc first (78.61%), injecting discs adjacent to the painful disc (56.64%). Significant differences across Anesthesiology, PMR, and Radiology were detected for computed tomography, intradiscal antibiotics, opening pressure, pain assessment form, and pain pressure measurement. There was no effect of volume of procedures done on overall adherence to guidelines. A significant interaction between specialty and number of procedures performed was detected for compliance with intradiscal antibiotics (P=0.092), opening pressure (P=0.027), and pain pressure (P=0.029) for respondents with >50 procedures. Respondents in Radiology were approximately 98% less likely to use intradiscal antibiotics compared with those in Anesthesiology (odds ratio, 0.019; 95% confidence interval, 0.001-0.264). PMR respondents were approximately 83% less likely than Anesthesiologists to use opening pressure (odds ratio, 0.168; 95% confidence interval, 0.035-0.82) when procedures were <15 per year. Discography is being performed by multiple different specialties: Anesthesiology, PMR, Radiology (highest to lowest in number, respectively). Overall adherence to guidelines pertaining to infection control was fair except for double needle technique which was poor. Adherence to guidelines that affect the diagnostic value was poor. There is specialty variation in adherence to guidelines and to a lesser extent volume based effect on compliance.

Occupational Medicine Practice Guidelines, 2nd Edition: Evaluation and Management of Common Health Problems and Functional Recovery in Workers, 2008 Revision

The American College of Occupational and Environmental Medicine (ACOEM) first published its Occupational Medicine Practice Guidelines (ACOEM Practice Guidelines or Guidelines) in 1997 to identify effective treatment strategies for injured workers. The ACOEM Practice Guidelines are evidence-based guidelines that focus on returning acutely injured employees to work within 90 days of injury. Given the rising societal expectations for quality of care in addition to the increasing utilization of standardized medical guidelines by state workers’ compensation systems across the nation, ACOEM has committed itself to updating individual chapters on a 3-year rotating basis. This version of the second edition of the Guidelines includes revisions to the chapters on Elbow Disorders, Low Back Disorders, and Chronic Pain. ACOEM also performs an annual review of the literature to identify recently published studies that would significantly impact clinical practice and necessitate earlier revisions to the book to ensure their recommendations remain state-of-the-art. The textbook is divided into two major sections. Section one reviews the foundations of occupational medicine practice and includes chapters on prevention, initial assessment and documentation, initial treatment strategies, causation and work-relatedness, disability prevention, chronic pain, and independent medical examinations. The chronic pain guidelines are noteworthy in that they include a detailed review of more than 20 medications commonly used to treat patients with chronic pain, recommendations regarding the use of appliances and alternative therapies, and efficacy outcomes regarding various injection therapies. Although expertly written and informative, it is unclear why several chapters in this section of the book fail to include in-text citations for material that corresponds to the reference list at the end of the chapter. The second section of the Guidelines focuses on disorders with the chapters organized by body part, e.g. neck and upper back, lower back, shoulder, elbow and other physical disorders. This section also includes a chapter on stressrelated disorders. Most of the chapters follow the same general format in terms of content, i.e. general approach and basic principles, initial assessment, medical history, physical examination, special studies and diagnostic considerations, work-relatedness, initial care, activity modification, work activities, follow-up visits, medications and surgical considerations, referral to other healthcare professionals, rehabilitation, algorithms, and references. This format allows for easy access of desired information. The ACOEM Practice Guidelines are well written and organized, but not without its short-comings and controversies. It is interesting that the Guidelines are marketed as an authoritative evidence-based document; however, close scrutiny of the book’s analytic methodology suggests that the final product is ultimately that of a consensus document. Not unexpectedly, the ACOEM Practice Guidelines have been scrutinized by several professional organizations. A joint position statement published by the American Academy of Pain Medicine, American Society of Interventional Pain Physicians, International Spine Intervention Society, Neuromodulation Therapy Access Coalition, and North American Neuromodulation cited several serious flaws in the ACOEM Practice Guidelines such as limited expert review of pain-related tests, therapies and interventions, incomplete and outdated evidence, inconsistencies in the application of ACOEM’s evidence-ranking B. A. Barron (&) Division of Occupational and Environmental Medicine, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA e-mail: bruce_barron@urmc.rochester.edu

The Science and Practice of Pain Medicine: A Needed Meeting of Our Minds and Skills

The American Academy of Pain Medicine (AAPM) and members of the pain community have a good reason for optimism in 2009. Important developments are occurring simultaneously on many fronts. The success of our annual meeting this year reflects a satisfying confluence of excitement about our rapidly developing translational science and hope about our growing evidence-based practices. We—our specialty, our patients, and our science—are on a roll, and there is much to be accomplished to maintain our momentum. Advances in public understanding of the societal burden of chronic pain and appreciation for the issues affecting pain treatment progressively galvanize public support for better treatment. Resulting legislation will lead to policy changes that ultimately will improve the training of providers and the care of patients. Congressional pain bills recently signed into law are now being implemented in the Veterans Health Administration and the Department of Defense. We anticipate that a strong cooperative effort with our Pain Care Coalition (PCC) partners and organizations, such as the American Pain Foundation, the Pain Care Forum, and the American Cancer Society, will lead to passage of HR 756 in Congress (see below) and increased National Institutes of Health (NIH) funding for pain research and education. The AAPM continues its collaboration with other professional organizations such as the International Spine Intervention Society (ISIS), the North American Spine Society (NASS), and the American Society of Anesthesiologists (ASA) to improve understanding of the value of pain treatments and reimbursements for our treatments. There is growing recognition within and outside medicine that, for our society as a whole, responsibility for improved pain care, presently an orphan of several specialties whose primary interests lie elsewhere, will improve significantly only with the advent and development of pain medicine as a distinct specialty, unencumbered by its parent specialties' primary interests and attention to …

Poster 267: The Incidence of Intravascular Needle Placement While Performing Medial Branch Nerve Blocks in the Lumbar Spine

Objective: To record the incidence of intravascular needle placement during fluoroscopically guided, contrast-enhanced, medial branch nerve blocks performed at the zygapophyseal joints in the lumbar spine. Design: A prospective, observational study. Setting: Ambulatory surgery center. Participants: Private practice patients with a chief complaint of axial low back pain, clinical signs, and radiographic findings suggestive of zygapophyseal joint-mediated pain. Interventions: 361 consecutive fluoroscopic-guided nerve blocks of the L2, L3, and L4 medial branch nerves and the L5 dorsal rami were performed using International Spine Intervention Society practice guidelines protocol. Once proper needle placement was established, the presence or absence of intravascular needle-tip placement was identified by the performing physician while injecting contrast dye through the needle during live fluoroscopy. Main Outcome Measures: The lumbar level and side-specific presence of vascular flow of contrast injected under live fluoroscopy. Results: In 361 lumbar medial branch nerve blocks, the overall rate of intravascular needle placement was 13.6%. The level with the highest incidence was L4 (18.2%). The level with the lowest incidence was L5 (6.0%). There was no significant side-to-side difference at each respective lumbar nerve level. Conclusions: There is a significant incidence of intravascular needle placement using standard medial branch nerve block techniques, especially at the L4 medial branch nerve level. Performing medial branch nerve blocks without fluoroscopic confirmation of contrast flow may lead to intravascular administration of medication and may therefore potentially lead to an increase in false negative results and/or potential health risks to patients undergoing these procedures.