Lead and Pulse Generator Migration After Spinal Cord Stimulation Implantation: Insights From an Analysis of 7322 Patients.

OBJECTIVES: Lead migration (LM) after spinal cord stimulation (SCS) implantation surgery is the most common device-related complication. Our study of lead and implantable pulse generator (IPG) migration using a large administrative claims data base aims to understand rates, risk factors, and outcomes after SCS implantation. MATERIALS AND METHODS: This retrospective cohort study used the IBM® MarketScan® (Armonk, NY) Commercial and Medicare Supplemental Databases from 2016 to 2018. Adult patients who underwent SCS surgical procedures with at least 90 days of follow-up were identified using Current Procedural Terminology (CPT®) codes. Patients with LM and IPG migration after SCS surgery were identified using the International Classification of Diseases, 10th Revision, Clinical Modification (ICD-10 CM) codes. Patients who underwent revision surgery after SCS implantation were identified using the CPT codes and ICD-10 CM codes. In addition, patient characteristics associated with LM or IPG migration, the temporal relationship of migration diagnosis, and revision surgery were evaluated in the cohort. Continuous outcomes were compared between groups using the two-sample Student t-test. The Fisher exact test was used to compare categorical outcomes between groups. RESULTS: A total of 7322 patients (64.4% percutaneous SCS) underwent SCS surgery during the study period. A total of 141 patients (1.9%) had LM or IPG migration. Of those, 116 patients (1.6%) had LM only; 18 patients (0.2%) had IPG migration; and seven patients (0.1%) had LM and IPG migration. The mean duration for migration diagnosis after initial SCS implantation was 168 (±163.1) days. The mean duration to revision surgery after the migration diagnosis was 12.3 (±35.2) days only. Most patients with migration (105, 74.5%) underwent revision surgery. Only younger age (p = 0.02) was associated with migration in this study. CONCLUSIONS: LM and pulse generator migration that required revision surgery occurred in a small proportion of patients who underwent SCS surgical procedures.

Procedure-Related Outcomes Including Readmission Following Spinal Cord Stimulator Implant Procedures: A Retrospective Cohort Study.

BACKGROUND: Spinal cord stimulation (SCS) has been shown to reduce opioid consumption, reduce pain, improve quality of life compared to conventional therapy, and be more effective than spine reoperation in carefully selected patients. In this study, we evaluate readmissions after SCS implantation procedures, costs, predictors, and etiologies for readmission following implantation procedures. METHODS: The study was a retrospective cohort using the National Readmissions Database from 2013 to 2017. Administrative billing codes were used to identify patients undergoing SCS implantation procedures. The primary outcome of our study was 30-day readmission following the SCS implantation procedure. Continuous outcomes were compared between groups using the Student t test or Wilcoxon rank sum test. In addition, multivariable predictors of 30-day readmission were assessed by hierarchical logistic regression analysis. RESULTS: A total of 3737 (26.7% open surgical SCS implants [OS-SCS]) individuals admitted to the hospital for SCS implantation were included in the final cohort analysis. The cohort consisted of predominantly female patients (58.71%) and in the 50- to 64-year age group (35.46%). Patients who underwent open surgical SCS implantation had a longer length of stay during the initial admission and a higher 30-day readmission rate (9.4% vs 7% P = .01). OS-SCS, older age, lower socioeconomic status, patients with specific comorbidities (ie, hypertension or chronic obstructive pulmonary disease [COPD]), and home discharge are associated with readmission. CONCLUSIONS: Readmission rates after SCS implantation are around 7.7% in the United States. Infection and postoperative complications remain the top etiologies for readmission. Open surgical SCS implantation is associated with more extended initial hospitalization and a higher rate of readmission when compared to percutaneous SCS implantation procedures.

Postoperative Oral Antibiotic Use and Infection-Related Complications After Spinal Cord Stimulator Surgery.

OBJECTIVES: Spinal cord stimulation (SCS) is considered a minimally invasive and reversible neuromodulation therapy for various chronic pain disorders. The rates of infection following SCS surgery reported in the literature range from 2.8% to 10%. Several studies indicated no potential benefit of postoperative antibiotics (beyond 24 hours) on subsequent device infection. This study aimed to understand the characteristics of postoperative antibiotic prescriptions and subsequent infections following SCS surgery. MATERIALS AND METHODS: The study was a retrospective cohort using the IBM® MarketScan® Commercial and Medicare Supplemental Databases from 2013 to 2018. Adult patients undergoing SCS surgical procedures with at least 90 days of follow-up were identified using Current Procedural Terminology (CPT®) codes. Postprocedural oral antibiotics within 14 days and preprocedural corticosteroid use within seven days were identified using National Drug Codes (NDC). Administrative claims were analyzed to understand the characteristics of prescribed postoperative antibiotics. Infection-related complications within 90 days were identified using administrative codes. RESULTS: A total of 18,105 patients (age 55.5 ± 13.1 years, 40.2% male) underwent SCS surgery during the study period. Postprocedural oral antibiotics and preprocedural steroids were prescribed for 35.3% and 2.6%, respectively, for SCS surgery patients. The most commonly used postprocedural antibiotics were cephalexin (55.4%) and sulfamethoxazole-trimethoprim (10.6%). The most common duration of antibiotic prescriptions was seven, ten, and five days in our study, from most to least common duration. Superficial surgical site infection (SSI), deep SSI, device infection, or any infection within 90 days occurred in 2.9%, 1.0%, 1.8%, and 4%, respectively, of the patients undergoing SCS surgery. CONCLUSIONS: Prospective studies are needed to understand the reasons for noncompliance with expert consensus recommendations on postoperative antibiotic use beyond 24 hours of SCS surgery. Neuromodulation team members should play an important role in antibiotic stewardship.

Industry Payments to Pain Medicine Physicians: An Analysis of the Centers for Medicare and Medicaid Services Open Payments Program.

OBJECTIVE: To analyze industry payments to pain medicine physicians in the United States. DESIGN: Retrospective cohort study using publicly available databases. SUBJECTS: The study includes U.S. pain medicine physicians (PMPs) with reports in the Open Payments program from 2013 to 2018. METHODS: The Centers for Medicare and Medicaid Services Open Payments program was analyzed for general, investment, and ownership payments to PMPs reported from 2013 to 2018. The nature, type, and geographic variation of payments were analyzed. RESULTS: The main findings of the study are as follows: 1) Payments made to PMPs constituted a small proportion of the payments made to all physicians in the United States, and the number of transactions and the total dollar amount seem to have decreased from 2016 to 2018. 2) The median number of payments among physicians with reported payments was around 4 (interquartile range: 18), and the majority of them were under $20. 3) The majority of payments were for in-kind items and services (85%) and were made for food and beverages (91%), travel and lodging (5.5%). 4) Some of the ownership and investment interest payments exceeded $500,000. 5) The top five drugs associated with physician payments included medications with opioids. 6) A very small minority of payments were made for entertainment or gifts. 7) A third of PMPs with reports had payments reported under more than one taxonomy. CONCLUSIONS: Overall payments made to PMPs seem to be decreasing since 2016. The majority of the payments are made for the food, beverage, and travel categories. Public and physician awareness of the Open Payments system reports is essential to promote transparency and to minimize adverse effects of financial relationships on patient care.

Opioid Prescriptions by Pain Medicine Physicians in the Medicare Part D Program: A Cross-Sectional Study.

BACKGROUND: Pain medicine physicians (PMP) are a group of physicians with background training in various primary specialties with interest and expertise in managing chronic pain disorders. Our objective is to analyze prescription drug (PD) claims from the Medicare Part D program associated with PMP to gain insights into patterns, associated costs, and potential cost savings areas. METHODS: The primary data source for Part D claims data is the Centers for Medicare and Medicaid Services (CMS) Chronic Conditions Data Warehouse, which contains Medicare Part D prescription drug events (PDE) records received through the claims submission cutoff date. Only providers with taxonomies of pain management (PM) and interventional pain management (IPM) were included in the study. The analysis of PDE was restricted to drugs with >250 claims. The distribution of claims and costs were analyzed based on drug class and provider specialty. Subsequently, we explored claims and expenses for opioid drug prescriptions in detail. Prescribing characteristics of the top 5% of providers by costs and claims were examined to gain additional insights. The costs and claims were explored for the top 10 drugs prescribed by PMP in 2017. RESULTS: There were a total of unique 3280 PMP-prescribed drugs with an associated expense of 652 million dollars in the 2017 Medicare Part D program. Prescriptions related to PMP account for a tiny fraction of the program's drug expenditure (0.4%). Opioids, anticonvulsants, and gabapentinoids were associated with the largest number of claims and the largest expenses within this fraction. Among opioid drug prescriptions, brand-named drugs account for a small fraction of claims (8%) compared to generic drugs. However, the expenses associated with brand name drugs were higher than generic drugs. Prescribers in the top 5% by PD costs had a higher number of claims, prescribed a higher proportion of branded medications, and had prescriptions associated with longer day supply compared to an average PMP. There were several opioid medications in the top 10 PD list by cost associated with PMP. CONCLUSIONS: Opioids were the most common medications among Medicare part D claims prescribed by PMP. Only 12% of the total opioid PD claims were by PMP. The top 5% of PMP prescribers had 10 times more claims than the average PMP.

Outcomes Associated With Infection of Chronic Pain Spinal Implantable Electronic Devices: Insights From a Nationwide Inpatient Sample Study.

OBJECTIVES: Chronic pain spinal implantable electronic devices (CPSIEDs) include devices that provide spinal cord stimulation and intrathecal drug therapy. In this study, we sought to evaluate the trends of CPSIED infections, related complications, and outcomes following the treatment of infection. MATERIALS AND METHODS: The Nationwide Inpatient Sample database contains data from 48 states, and the District of Columbia was used to identify patients with a primary diagnosis of CPSIED infection during the years 2005-2014. Patients with intrathecal pumps for the treatment of spasticity were excluded to limit the study population to patients with chronic pain disorders. Treatments were categorized as: 1) without device removal, 2) pulse generator or pump only removal, 3) intrathecal pump system removal, and 4) spinal cord stimulation system removal. Complications associated with CPSIED infections were identified using administrative billing codes. RESULTS: During the study period 2005-2014, a total of 11,041 patients were admitted to the hospital with CPSIED infections. The majority of the patients were treated without surgical intervention (56%), and a smaller proportion underwent complete system explantation (22.7%). In-hospital mortality or permanent disability due to paralysis after CPSIED infection was around 1.83% and 2.77%, respectively. Infectious complications such as meningitis, abscess formation, and osteomyelitis occurred in 4.93%, 5.08%, and 1.5%, respectively. The median cost of hospitalization was around US $14,118.00, and the median length of stay was approximately six days (interquartile range = 4-13 days). CONCLUSIONS: The complications of CPSIED infection were higher among patients that did not undergo device removal.

Adverse Events and Complications Associated With Intrathecal Drug Delivery Systems: Insights From the Manufacturer and User Facility Device Experience (MAUDE) Database.

BACKGROUND: Modern intrathecal drug delivery systems (IDDS) are technologically advanced to deliver medication through various automated and patient-controlled programs. They also are associated with unique complications ranging from post-operative complications, medication-related adverse events (AE), device malfunction, to refill associated AE. OBJECTIVES: To systematically analyze real-world complications and AE reported on the Food and Drug Administration's Manufacturer and User Facility Device Experience database (MAUDE) associated with IDDS among patients predominantly with chronic pain disorders. MATERIALS AND METHODS: MAUDE database was sampled for a month four times a year during the study period, February 2018 to February 2019. The database was resampled every six months till August 2020 to evaluate for any additional reported cases during the index months. The two FDA approved IDDS, were included. AE were broadly classified into causes related to catheter malfunction, pump malfunction, biologic, and medication-related AE. RESULTS: A total of 1001 reports were included in the final analysis. The top three reasons for adverse report are infection/erosion (15.7%, n = 157), motor stall (12.4%, n = 125) and adverse medication reactions (11.8%, n = 119), respectively. There were five deaths among patients with IDDS. Epidural hematoma (n = 3) after IDDS surgery resulted in a death and residual neurological deficits after surgical evacuation. Programming errors, medication concentration discrepancy, and failure to turn on the pump after reprogramming are various preventable causes of medication-related IDDS AEs. CONCLUSIONS: Analysis of AE associated with IDDS from the MAUDE database provided a real-world perspective different from reported registry complications. Awareness and vigilance of preventable IDDS-related complications is the first step toward mitigating risks to provide safe and effective intrathecal drug delivery for chronic pain management.

Ultrasound-Assisted Versus Fluoroscopic-Guided Lumbar Sympathetic Ganglion Block: A Prospective and Randomized Study.

BACKGROUND: Fluoroscopy (FL)-guided lumbar sympathetic ganglion block (LSGB) is widely performed to diagnose and manage various diseases associated with sympathetically maintained pain. Recently, numerous ultrasound (US)-assisted procedures in pain medicine have been attempted, showing an advantage of low radiation exposure. This randomized, prospective trial compared the procedural outcomes and complications between FL-guided and US-assisted LSGBs. METHODS: Fifty LSGBs were randomly divided into 2 groups: FL-guided (FL group) or US-assisted (US group) LSGB group. Both groups received FL-guided or US-assisted LSGB with 10 mL of 0.25% levobupivacaine. The primary end point was the total procedure time. Secondary outcomes were success rate, imaging time, onset time (based on temperature rise), dosage of radiation exposure, other procedure-related outcomes, and complications. RESULTS: Total procedure time and success rate were not statistically different between the 2 groups, whereas imaging time of the US group was longer than that of the FL group (P = .012). The onset time was faster in the US group (P = .019), and bone touching during the procedure was less frequent in the US group (P = .001). Moreover, radiation exposure was significantly lower in the US group than in the FL group (P < .001). No serious complications were reported in all patients. CONCLUSIONS: US-assisted LSGB appears to be a feasible method with the added benefit of lower radiation exposure. In our study, we did not find an advantage of US-assisted LSGB over FL-guided LSGB in terms of performance time.

Ultrasound-Guided Peristyloid Steroid Injection for Eagle Syndrome.

The styloid process arising from the temporal bone is normally about 2.5 cm in length. For various reasons, including trauma and inflammation, it may become elongated. This elongated styloid process, when symptomatic with clinical signs and symptoms suggestive of local compression or neuropathic pain, is termed Eagle syndrome. Glossopharyngeal neuralgia is characterized by intermittent shooting sharp pain in the jaw, throat, tongue, and ear. Conservative management includes anticonvulsants, tricyclic antidepressants, and anti-inflammatory agents. Interventional and surgical options are pursued when these fail. Fluoroscopy is usually used to position the needle adjacent to the styloid process for injecting steroid and or local anesthetic. We describe a case of a 41-year-old woman with Eagle syndrome who failed conservative management and subsequently underwent an ultrasound-guided peristyloid steroid injection with short-duration pain relief.

Phantom pain in a patient with brachial plexus avulsion injury.

OBJECTIVE: Phantom limb pain is a painful sensation perceived in the absent limb following surgical or traumatic amputation. Phantom limb sensations, which are nonpainful, occur in nearly all amputees. Deafferentation can also produce similar symptoms. Here we report the presence of phantom pain in a deafferented limb. DESIGN: Case report. SETTING: Hospital-based outpatient clinic. PATIENT: A 65-year-old man was referred to the pain clinic for management of upper extremity pain secondary to brachial plexus avulsion (BPA) following a motor vehicle accident. Initially he noticed a feeling of growing and shrinking of his arm. Following this, the pain started gradually from his elbow extending to his fingertips covering all dermatomes. He described the pain as continuous, severe, and sharp. He also described the arm as being separate from his existing insensate arm and felt as though the fist was closed with the thumb pointing out. On physical examination, he had no sensation to fine touch or pressure below the elbow. There were no consistent areas of allodynia. He had diffuse muscle wasting in all the muscle groups of his left upper extremity, besides winging of the scapula. Electrodiagnostic studies showed a left brachial plexopathy consistent with multilevel nerve root avulsion sparing the dorsal rami. CONCLUSION: This is a report of phantom limb sensations and phantom pain following BPA in an intact but flaccid and insensate limb.

Intraoperative neurophysiological monitoring and spinal cord stimulator implantation.

INTRODUCTION: Spinal cord injury (SCI) is one of the most dreaded complications after spinal cord stimulation (SCS) implantation surgery. As a result, intraoperative neurophysiological monitoring (IONM) has been proposed to avoid accidental damage to nervous structures under anesthesia and confirm positioning for optimal stimulation. Our study uses a large administrative claims database to determine the 30-day risk of SCI after SCS implantation. METHODS: This retrospective cohort study used the IBM MarketScan Commercial and Medicare Supplemental Databases from 2016 to 2019. Adult patients undergoing SCS surgical procedures with at least 90 days of follow-up, IONM use, the type of sedation used during the procedure, and subsequent SCI were identified using administrative codes. In addition, logistic regression was used to examine the relationship between various risk factors and subsequent SCI. RESULTS: A total of 9676 patients underwent SCS surgery (64.7% percutaneous implants) during the study period. Nine hundred and forty-four (9.75%) patients underwent SCS implantation with IONM. Conscious sedation, Monitored Anesthesia Care anesthesia, and general anesthesia were used in patients with 0.9%, 60.2%, and 28.6%, respectively. Eighty-one (0.8%) patients developed SCI within 30 days after SCS implant surgery. The SCI rate was higher in the group that underwent IONM (2% vs 0.7%, p value <0.001) during the implantation procedure, reflecting the underlying risk. After adjustment for other factors, the OR of SCI is 2.39 (95% CI: 1.33 to 4.14, p value=0.002) times higher for those with IONM than those without IONM. CONCLUSIONS: Increased SCI risk among patients with IONM likely reflects higher baseline risk, and further research is needed for risk mitigation.

Use of corticosteroids for adult chronic pain interventions: sympathetic and peripheral nerve blocks, trigger point injections - guidelines from the American Society of Regional Anesthesia and Pain Medicine, the American Academy of Pain Medicine, the American Society of Interventional Pain Physicians, the International Pain and Spine Intervention Society, and the North American Spine Society.

BACKGROUND: There is potential for adverse events from corticosteroid injections, including increase in blood glucose, decrease in bone mineral density and suppression of the hypothalamic-pituitary axis. Published studies note that doses lower than those commonly injected provide similar benefit. METHODS: Development of the practice guideline was approved by the Board of Directors of American Society of Regional Anesthesia and Pain Medicine with several other societies agreeing to participate. The scope of guidelines was agreed on to include safety of the injection technique (landmark-guided, ultrasound or radiology-aided injections); effect of the addition of the corticosteroid on the efficacy of the injectate (local anesthetic or saline); and adverse events related to the injection. Based on preliminary discussions, it was decided to structure the topics into three separate guidelines as follows: (1) sympathetic, peripheral nerve blocks and trigger point injections; (2) joints; and (3) neuraxial, facet, sacroiliac joints and related topics (vaccine and anticoagulants). Experts were assigned topics to perform a comprehensive review of the literature and to draft statements and recommendations, which were refined and voted for consensus (≥75% agreement) using a modified Delphi process. The United States Preventive Services Task Force grading of evidence and strength of recommendation was followed. RESULTS: This guideline deals with the use and safety of corticosteroid injections for sympathetic, peripheral nerve blocks and trigger point injections for adult chronic pain conditions. All the statements and recommendations were approved by all participants after four rounds of discussion. The Practice Guidelines Committees and Board of Directors of the participating societies also approved all the statements and recommendations. The safety of some procedures, including stellate blocks, lower extremity peripheral nerve blocks and some sites of trigger point injections, is improved by imaging guidance. The addition of non-particulate corticosteroid to the local anesthetic is beneficial in cluster headaches but not in other types of headaches. Corticosteroid may provide additional benefit in transverse abdominal plane blocks and ilioinguinal/iliohypogastric nerve blocks in postherniorrhaphy pain but there is no evidence for pudendal nerve blocks. There is minimal benefit for the use of corticosteroids in trigger point injections. CONCLUSIONS: In this practice guideline, we provided recommendations on the use of corticosteroids in sympathetic blocks, peripheral nerve blocks, and trigger point injections to assist clinicians in making informed decisions.

Targeting myofascial taut bands by ultrasound.

Myofascial pain syndrome (MPS) is a frequent diagnosis in chronic pain and is characterized by tender, taut bands known as trigger points. The trigger points are painful areas in skeletal muscle that are associated with a palpable nodule within a taut band of muscle fibers. Despite the prevalence of myofascial pain syndrome, diagnosis is based on clinical criteria alone. A growing body of evidence that suggests that taut bands are readily visualized under ultrasound-guided exam, especially when results are correlated with elastography, multidimensional imaging, and physical exam findings such as local twitch response. The actual image characteristic in B mode appears to be controversial. Ultrasonography provides an objective modality to assist with diagnosis and treatment of trigger points in the future.

Ultrasound imaging of embedded shrapnel facilitates diagnosis and management of myofascial pain syndrome.

Trigger points can result from a variety of inciting events including muscle overuse, trauma, mechanical overload, and psychological stress. When the myofascial trigger points occur in cervical musculature, they have been known to cause headaches. Ultrasound imaging is being increasingly used for the diagnosis and interventional management of various painful conditions. A veteran was referred to the pain clinic for management of his severe headache following a gunshot wound to the neck with shrapnel embedded in the neck muscles a few years prior to presentation. He had no other comorbid conditions. Physical examination revealed a taut band in the neck. An ultrasound imaging of the neck over the taut band revealed the deformed shrapnel located within the levator scapulae muscle along with an associated trigger point in the same muscle. Ultrasound guided trigger point injection, followed by physical therapy resolved his symptoms. This is a unique report of embedded shrapnel and coexisting myofascial pain syndrome revealed by ultrasound imaging. The association between shrapnel and myofascial pain syndrome requires further investigation.

Neck Pain Secondary to Post Radiation Fibrosis Managed With Ultrasound-Guided Adhesiolysis.

BACKGROUND: Radiation therapy may result in complications, including fibrosis, which can result in pain and difficulty with movement - especially in the neck. CASE PRESENTATION: A 52-year-old man with right-sided vague neck pain unresponsive to conservative management had a computed tomography scan that showed a vagal paraganglioma in the carotid sheath surrounding the right carotid arteries and internal jugular vein. Following radiation therapy, he noticed a new pain in his right jaw and neck worse with certain movements of the neck. Nonsurgical conservative measures including physical therapy and pharmacological management were unsuccessful. An ultrasound evaluation demonstrated fibrosis beneath the sternocleidomastoid muscle and in proximity to the carotid sheath. After careful trajectory planning using ultrasound imaging, a 25 G needle was introduced real time in proximity to the fibrosis. Using a dexamethasone/saline mixture under real-time ultrasound guidance, adhesions were released. After 3 injections, the patient reported greater than 90% pain relief, which lasted 4 months. Subsequently, he required similar injections approximately every 3 months to achieve greater than 75% pain relief. CONCLUSIONS: This is a successful demonstration of the utility of ultrasound evaluation and guidance for adhesiolysis following radiation therapy.

Two- and three-dimensional ultrasound imaging to facilitate detection and targeting of taut bands in myofascial pain syndrome.

INTRODUCTION: Ultrasound imaging has gained acceptance in pain management interventions. Features of myofascial pain syndrome have been explored using ultrasound imaging and elastography. There is a paucity of reports showing the benefit clinically. This report provides three-dimensional features of taut bands and highlights the advantages of using two-dimensional ultrasound imaging to improve targeting of taut bands in deeper locations. CASE REPORT: Fifty-eight-year-old man with pain and decreased range of motion of the right shoulder was referred for further management of pain above the scapula after having failed conservative management for myofascial pain syndrome. Three-dimensional ultrasound images provided evidence of aberrancy in the architecture of the muscle fascicles around the taut bands compared to the adjacent normal muscle tissue during serial sectioning of the accrued image. On two-dimensional ultrasound imaging over the palpated taut band, areas of hyperechogenicity were visualized in the trapezius and supraspinatus muscles. Subsequently, the patient received ultrasound-guided real-time lidocaine injections to the trigger points with successful resolution of symptoms. CONCLUSIONS: This is a successful demonstration of utility of ultrasound imaging of taut bands in the management of myofascial pain syndrome. Utility of this imaging modality in myofascial pain syndrome requires further clinical validation.

Potential adverse ultrasound-related biological effects: a critical review.

Ultrasound energy exerts important cellular, genetic, thermal, and mechanical effects. Concern about the safety of ultrasound prompted several agencies to devise regulatory limits on the machine output intensities. The visual display of thermal and mechanical indices during ultrasound imaging provides an aid to limit the output of the machine. Despite many animal studies, no human investigations conducted to date have documented major physiologic consequences of ultrasound exposed during imaging. To date, ultrasound imaging appears to be safe for use in regional anesthesia and pain medicine interventions, and adherence to limiting the output of ultrasound machines as outlined by the Food and Drug Administration may avoid complications in the future. This article reviews ultrasound-related biologic effects, the role of the regulatory agencies in ensuring safety with the use of ultrasound, and the limitations and implications of ultrasound use in humans.