Global Expert Opinion on Cryolipolysis Treatment Recommendations and Considerations: A Modified Delphi Study.

Background: Cryolipolysis is an increasingly popular nonsurgical fat-reduction procedure. Published treatment guidance and adverse event (AE) management protocols are limited. Objective: A modified Delphi study aimed to establish global expert consensus on the use of CoolSculpting (Allergan Aesthetics, an AbbVie Company, Irvine, CA), a noninvasive cryolipolysis treatment system. Methods: A literature search informed survey topics for an 11-expert Delphi panel. Panelists completed an online 39-question survey. An interim panel discussion, with open-ended questions and yes/no voting, informed a second survey containing 61 statements, for which panelists rated agreement using a 5-point Likert scale. Topics included treatment outcome and responder definitions, patient evaluation and selection, treatment protocols, patient satisfaction, and AEs. Results: Panelists achieved consensus on 38 final guidelines and recommendations. They reached moderate to complete consensus on 4 statements on defining responders (ie, patients with a range of visible improvement) and 6 statements on patient factors contributing to treatment outcomes (eg, how well the applicator conforms to patient body region). Panelists defined minimum numbers of treatment cycles to achieve visible clinical outcomes for 12 body regions, with moderate to complete consensus on 31 statements. They achieved a strong to complete consensus on 7 statements about patient satisfaction (eg, importance of patient expectations, visible improvement, and before-and-after photographs). Panelists defined management strategies for AEs, with moderate to complete consensus on 15 statements. Conclusions: A modified Delphi process yielded multiple guideline recommendations for cryolipolysis, providing a needed resource for the broad range of clinicians who perform this noninvasive fat-reduction procedure.

Clinical Study Demonstrates that Electromagnetic Muscle Stimulation Does Not Cause Injury to Fat Cells.

BACKGROUND AND OBJECTIVES: A previous pre-clinical study on electromagnetic muscle stimulation (EMMS) suggested that fat cell apoptosis occurs following treatment in a porcine model. While EMMS can induce changes in muscle, the effect on fat tissue is not established. This clinical study sought to assess adipose tissue response to EMMS in comparison to cryolipolysis treatment. STUDY DESIGN/MATERIALS AND METHODS: Study subjects were recruited prior to abdominoplasty to receive body contouring treatments and subsequently to obtain tissue for histological analysis. Non-invasive abdominal treatments were delivered using a commercially available (n = 6) or prototype (n = 3) EMMS system or a cryolipolysis system (n = 2). Subjects received a single EMMS treatment (100% intensity for 30 minutes) or a single cryolipolysis treatment (-11°C for 35 minutes) to the abdomen. Superficial and deep (i.e., adjacent to muscle layer) subcutaneous adipose tissue was harvested at set timepoints post-treatment. The presence or absence of an inflammatory response was evaluated using standard hematoxylin and eosin (H&E) staining. As adipocytes that are destined to become apoptotic cannot be distinguished by traditional H&E staining during the early phases of injury, irreversible fat cell injury was assessed using perilipin immunofluorescence. RESULTS: Following H&E histological analysis at 3, 10, 11, and 17 days post-treatment, no EMMS-treated samples showed an inflammatory response in either the superficial or deep subcutaneous adipose tissue. For the cryolipolysis-treated adipose tissue, however, the H&E staining revealed a marked inflammatory response with an influx of neutrophils, lymphocytes, and macrophages at timepoints consistent with previous histological studies. Further, loss of perilipin staining provided clear visual evidence of irreversible fat cell injury in the cryolipolysis-treated adipose tissue. In contrast, the electromagnetic muscle stimulation-treated samples showed persistence of perilipin staining of adipose tissue indicating that all fat cells were viable. CONCLUSION: This study failed to demonstrate either fat cell injury or inflammatory response following EMMS treatment. While electromagnetic muscle stimulation may non-invasively induce muscle changes, this clinical study found no evidence of an impact injurious or otherwise on subcutaneous fat. © 2020 The Authors. Lasers in Surgery and Medicine published by Wiley Periodicals LLC.

The Use of Radiofrequency in Aesthetic Surgery.

The use of radiofrequency for soft tissue tightening has increased over the past 10 years. Both minimally invasive and noninvasive devices are frequently in use. This article describes the different types of radiofrequency technology and the current evidence behind their safety and efficacy.

Cryolipolysis: Clinical Best Practices and Other Nonclinical Considerations.

Cryolipolysis is a nonsurgical body contouring procedure that involves cooling of fat cells to induce lipolysis while sparing surrounding structures. Plastic surgery practices are increasingly incorporating noninvasive aesthetic procedures (eg, cryolipolysis, fillers, radiofrequency, ultrasound) to offer their patients a wider range of aesthetic treatment options. Here, we report insights from 8 plastic surgeons with regard to cryolipolysis best practices from a clinical perspective and the impact of integrating this noninvasive body contouring procedure into a plastic surgery practice. The authors prefer cryolipolysis over liposuction for patients who are not amenable to surgery or those who desire to avoid downtime, also taking into consideration body mass index, skin laxity, comorbidities, and risk of contour irregularities. Patient counseling is critical for setting realistic expectations regarding outcomes and should focus on the efficacy of cryolipolysis, individual variability in results, potential side effects, time course of treatment response, and the need for multiple treatment cycles. Strategies for reaching new patients and expanding services among current cryolipolysis patients are discussed.

Adjustable Depth Fractional Radiofrequency Combined With Bipolar Radiofrequency: A Minimally Invasive Combination Treatment for Skin Laxity.

Increasingly, patients are seeking minimally invasive methods to tighten skin and remodel adipose tissue. A large treatment gap exists among 3 types of patients: (1) the younger demographic, who increasingly desire soft tissue tightening without traditional operations, scars, and downtime; (2) patients with soft tissue laxity who are not "severe enough" to justify an excisional procedure, but not "mild enough" to rely on liposuction with soft tissue contraction alone; and (3) those with recurrent laxity who already underwent traditional excisional procedures. In these populations, plastic surgeons risk under- or overtreating with traditional methods. The purpose of this supplement is to describe the utility of radiofrequency (RF) microneedling (Fractora modified to Morpheus8 InMode Aesthetic Solutions, Lake Forest, CA) in combination with bipolar RF (FaceTite/BodyTite, InMode Aesthetic Solutions). By combining these procedures, the aforementioned treatment gap can be addressed. The RF microneedling allows for subdermal adipose remodeling and skin tightening. Addition of bipolar RF also tightens the skin by contraction of the underlaying fibroseptal network in addition to induction of neocollagenesis, elastogenesis, and angiogenesis at skin surface temperatures of 40° to 50°C. In our experience, these technologies have been effective and safe in these patient populations. Level of Evidence: 4.

Long-Term Assessment of Perioral Rhytide Correction with Erbium: YAG Laser Resurfacing.

BACKGROUND: Use of nonsurgical skin rejuvenation has grown over the past two decades. This has led to an increase in ablative and nonablative resurfacing devices. Moderate to heavy perioral rhytides require an ablative laser to maximize results. Traditionally, this was performed with carbon dioxide lasers; however, more recently, erbium lasers have been used to target heavy rhytides. The purpose of this study was to assess long-term correction of perioral rhytides with the use of the senior author's (A.J.B.) erbium laser resurfacing technique. METHODS: A retrospective review of all patients who underwent perioral erbium laser resurfacing performed by the senior author from 2009 to 2016 with a minimum of 6-month follow-up was performed. Ten blinded nonphysicians and 10 blinded plastic surgeons evaluated the imaging based on a previously established standardized grading sheet, with gradation improvement from 1 to 8. The absolute and percentage improvement were evaluated, along with complications. RESULTS: Forty-five patients met inclusion criteria, with an average follow-up of 13 months. A statistically significant score improvement of 2.2 gradations was seen, in addition to a significant improvement (from 56 percent to 66 percent). Both the surgeon and nonphysician groups showed improvement, with no differences between the two groups. There were no cases of hypopigmentation at the 6-month postoperative visit. CONCLUSIONS: Erbium laser resurfacing is a powerful and safe tool for correcting perioral rhytides. It is effective in isolation or with other facial rejuvenation procedures. Erbium laser resurfacing is a useful adjunct in facial rejuvenation that can deliver exceptional results with few complications when performed within the proper guidelines. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

A Multicenter Study for Cellulite Treatment Using a 1440-nm Nd:YAG Wavelength Laser with Side-Firing Fiber.

BACKGROUND: Treatment of cellulite using a 1440-nm YAG wavelength laser with side-firing fiber has proven safe and effective, lasting at least 6 months. OBJECTIVES: The authors evaluate the safety and efficacy of a single, subdermal procedure to treat the underlying structure of cellulite for at least 1 year. METHODS: Fifty-seven patients underwent a 3-step cellulite treatment with a 1440-nm Nd:YAG laser with a side-firing fiber and temperature-sensing cannula. Efficacy was measured by the blinded evaluators to distinguish baseline photos from those taken at 12 months posttreatment, with results on a 5-point, 2-category ordinal photonumeric scale when comparing baseline photos to 12 months posttreatment. Subject and physician satisfaction was assessed based on completion of a satisfaction survey. Adverse events (AE) were recorded throughout the study. Twelve month data were analyzed and compared to 6 month data. RESULTS: Evaluators chose baseline photographs 97% on average from 6 (-1, +2) months and 91% from the 12 (-3, +2) months posttreatment photographs. At 6 (-1, +2) months, the average improvement score was 1.7 for dimples and 1.1 for contour irregularities. At 12 (-3, +2) months, the average improvement score was 1.4 for dimples and 1.0 for contour irregularities. The average satisfaction score for the physician was 5.6 and the patient was 5.3 on a 6-point scale. CONCLUSIONS: A single, 3-step, minimally invasive laser treatment using a 1440-nm Nd:YAG laser, side-firing fiber, and temperature-sensing cannula to treat the underlying structure of cellulite proved to be safe and maintained effectiveness at least 1 year post treatment. LEVEL OF EVIDENCE 2: Therapeutic.

Safety and efficacy of cryolipolysis for non-invasive reduction of submental fat.

BACKGROUND AND OBJECTIVES: Cryolipolysis has previously received FDA clearance for fat reduction in the abdomen, flanks, and thighs. There is also interest in small volume fat reduction for areas such as the chin, knees, and axilla. This article reports the results of a cryolipolysis pivotal IDE study for reduction of submental fullness. STUDY DESIGN/MATERIAL AND METHODS: A prototype small volume vacuum applicator (CoolMini applicator, CoolSculpting System, ZELTIQ Aesthetics) was used to treat 60 subjects in the submental area. At each treatment visit, a single treatment cycle was delivered at -10°C for 60 minutes, the same temperature and duration used in current commercially-available cryolipolysis vacuum applicators. At the investigator's discretion, an optional second treatment was delivered 6 weeks after the initial treatment. The primary efficacy endpoint was 80% correct identification of baseline photographs by independent physician review. The primary safety endpoint was monitoring incidence of device- and/or procedure-related serious adverse events. Secondary endpoints included assessment of fat layer thickness by ultrasound and subject satisfaction surveys administered 12 weeks after final cryolipolysis treatment. RESULTS: Independent photo review from 3 blinded physicians found 91% correct identification of baseline clinical photographs. Ultrasound data indicated mean fat layer reduction of 2.0 mm. Patient questionnaires revealed 83% of subjects were satisfied, 80% would recommend submental cryolipolysis to a friend, 77% reported visible fat reduction, 77% felt that their appearance improved following the treatment, and 76% found the procedure to be comfortable. No device- or procedure-related serious adverse events were reported. CONCLUSION: The results of this clinical evaluation of 60 patients treated in a pivotal IDE study demonstrate that submental fat can be reduced safely and effectively with a small volume cryolipolysis applicator. Patient surveys revealed that submental cryolipolysis was well-tolerated, produced visible improvement in the neck contour, and generated high patient satisfaction. These study results led to FDA clearance of cryolipolysis for submental fat treatment.

A Prospective, Randomized, Multicenter Trial Assessing a Novel Lysine-Derived Urethane Adhesive in a Large Flap Surgical Procedure without Drains.

OBJECTIVE: To evaluate the safety and effectiveness of a lysine-derived urethane adhesive as a noninvasive alternative to closed suction drains in a commonly performed large flap surgical procedure. METHODS: One hundred thirty subjects undergoing abdominoplasty at five centers were prospectively randomized to standard flap closure with surgical drains (Control group) or a lysine-derived urethane adhesive (Treatment group) without drains. The primary outcome measured was the number of post-operative procedures, including drain removals (as the event marking the use of a surgical drain) and needle aspirations. Secondary endpoints included total wound drainage, cumulative days of treatment, and days to drain removal. A patient questionnaire evaluating quality of life measures was also administered. RESULTS: Subjects in the Treatment group required significantly fewer post-operative procedures compared to the Control group (1.8 ± 3.8 vs. 2.4 ± 1.2 procedures; p < 0.0001) and fewer cumulative days of treatment (1.6 ± 0.4 vs. 7.3 ± 3.3; p < 0.0001). A procedure to address fluid accumulation was required for only 27.3 % of the subjects in the Treatment group versus 100 % of Control group, which by study design required the use of drains. The mean duration of use of indwelling surgical drains for the Control group was 6.9 ± 3.3 days. All fluid collections treated with percutaneous aspiration were resolved and there were no unanticipated adverse events. CONCLUSION: The results of the study support that the use of a lysine-derived urethane adhesive is a safe and effective alternative to drains in patients undergoing a common large flap surgical procedure.

Cryolipolysis for safe and effective inner thigh fat reduction.

BACKGROUND AND OBJECTIVES: While cryolipolysis initially received FDA clearance for fat reduction in the abdomen and flanks, there was significant interest in non-surgical fat reduction for other sites, such as the inner and outer thighs. This article reports the results of an inner thigh study which contributed to FDA clearance of cryolipolysis for treatment of thighs. STUDY DESIGN/MATERIAL AND METHODS: A flat cup vacuum applicator (CoolFit applicator, CoolSculpting System) was used to treat 45 subjects bilaterally in the inner thighs. Single cycle treatments were delivered at Cooling Intensity Factor (CIF) 41.6 for 60 minutes followed by 2 minutes of manual massage. Follow-up visits were conducted at 8 and 16 weeks. Efficacy was assessed by ultrasound imaging, circumference measurements, and photographs. Safety was assessed by monitoring adverse events. Patient satisfaction was evaluated by questionnaire. RESULTS: Data is presented for n = 42 patients that completed the 16 week study follow-up and maintained their weight within 5 lbs. of baseline. Independent photo review from three blinded physicians found 91% correct identification of baseline clinical photographs. Ultrasound data indicate fat layer reduction of 2.8 mm. Circumferential measurements indicate mean reduction of 0.9 cm. Patient questionnaires reveal 93% were satisfied with the CoolSculpting procedure; 84% noticed visible fat reduction; 89% would recommend to a friend; and 91% were likely to have a second treatment. There were no device- or procedure-related serious adverse events. CONCLUSION: The CoolFit flat cup vacuum applicator was found to deliver safe and effective cryolipolysis treatment to reduce inner thigh fat. Completed 16-week data from 42 subjects show 2.8 mm reduction in fat thickness and 0.9 cm reduction in circumference. Assessment of clinical photographs found 91% correct identification of baseline images. The results of this prospective, multi-center, interventional clinical study contributed to FDA clearance of cryolipolysis for treatment of thighs in April 2014.

High-intensity focused ultrasound for the reduction of subcutaneous adipose tissue using multiple treatment techniques.

BACKGROUND: High-intensity focused ultrasound (HIFU) is a noninvasive alternative to traditional invasive body sculpting procedures. OBJECTIVE: To assess the effectiveness and tolerability of HIFU treatment using high and low fluence settings with 2 treatment techniques, grid repeat (GR) and site repeat (SR). MATERIALS AND METHODS: Two multicenter studies were conducted. Subjects underwent 1 HIFU treatment with 1 of 5 treatment protocols (total fluence, 150-180 J/cm). Primary end point was change from baseline in waist circumference (CBWC) at 12 weeks. Secondary end points included CBWC at 4 and 8 weeks and investigator- and subject-assessed clinical improvement. Adverse events were monitored throughout the study. RESULTS: In the intent-to-treat (ITT) population, all subjects had a statistically significant mean circumferential reduction of -2.3 ± 2.9 cm (p < .0001) from baseline at 12 weeks, with no significant differences among the 5 treatment groups (ITT: p = .153). Analysis of secondary end points in the ITT population demonstrated a significant circumferential reduction starting as early as 4 weeks in all subjects (-1.1 ± 1.9 cm, p < .0001). Most subjects in all treatment groups showed improvements at 12 weeks as rated by the investigators and subjects. CONCLUSION: High-intensity focused ultrasound treatment using either a low or high fluence setting in a GR or SR method is effective for circumferential waist reduction, resulting in statistically significant CBWC in all treatment groups.

A multicenter study for a single, three-step laser treatment for cellulite using a 1440-nm Nd:YAG laser, a novel side-firing fiber, and a temperature-sensing cannula.

BACKGROUND: Historically, treatments for cellulite have not been able to address all of its physiological components and require multiple sessions. OBJECTIVE: The authors evaluate the safety and efficacy of a single, subdermal procedure to treat the underlying structure of cellulite. METHODS: Fifty-seven patients underwent a 3-step cellulite treatment with a 1440-nm Nd:YAG laser with a side-firing fiber and temperature-sensing cannula. Efficacy was measured by the ability of blinded evaluators to distinguish baseline photos from those taken at 3 and 6 months posttreatment, as well as their rating of the results on a 5-point, 2-category ordinal photonumeric scale when comparing baseline photos to those taken at 2, 3, and 6 months posttreatment. Patient and physician satisfaction was assessed based on completion of a satisfaction survey at 2, 3, and 6 months posttreatment. Adverse events (AE) were recorded throughout the study. RESULTS: At 6 months posttreatment, blinded evaluators rated at least a 1-point improvement in the appearance of cellulite in 96% of treated sites. Blinded evaluators were also able to correctly identify baseline versus posttreatment photos in 95% of cases. At least 90% of patients and physicians reported satisfaction with the results of treatment throughout 6 months. AE were mild in intensity and transient to treatment. CONCLUSIONS: A single, 3-step, minimally invasive laser treatment using a 1440-nm Nd:YAG laser, side-firing fiber, and temperature-sensing cannula to treat the underlying structure of cellulite proved to be safe and maintained effectiveness at least 6 months posttreatment. LEVEL OF EVIDENCE: 2.

Consensus recommendations on the use of an erbium-doped 1,550-nm fractionated laser and its applications in dermatologic laser surgery.

BACKGROUND: Nonablative fractional photothermolysis has revolutionized the way we treat a number of common skin conditions with laser technology. OBJECTIVE: A comprehensive guide is needed for clinicians using this technology to treat specific skin conditions in various skin types. MATERIALS AND METHODS: Recommendations were made from a recent round table discussion among experienced physicians and a review of recent literature findings. RESULTS: Optimal laser parameters are dependent on patient skin type and condition. We recommended guidelines for the successful treatment of several common skin conditions on and off the face using nonablative fractional photothermolysis. Specific conditions were dyschromia, rhytides, acne scars, surgical scars, melasma, and striae distensae. CONCLUSIONS: We developed reproducible guidelines to most effectively treat a variety of skin types and conditions using nonablative fractional photothermolysis. Future large, multicenter trials are indicated for further optimization of treatment parameters.

Classification of vascular anomalies and the comprehensive treatment of hemangiomas.

BACKGROUND: The purpose of this article is to review the biological classification system of vascular anomalies and present a comprehensive treatment approach to hemangiomas. METHODS: An extensive literature review was performed for the classification of vascular anomalies. Emphasis was placed on the epidemiology, pathogenesis, diagnosis, and treatment of hemangiomas, including the authors' preferred algorithm. RESULTS: The authors' comprehensive management of vascular anomalies as described in this article has resulted in high patient satisfaction and an excellent outcome in a majority of patients. CONCLUSIONS: The authors believe that knowledge of proper classification is not just their personal preference but a functional necessity to aid in the treatment of these complex and large lesions. Proper use of the biological classification is inherent to understanding and treating these common vascular lesions optimally.

Role of laser therapy in pediatric patients.

BACKGROUND: Laser applications have revolutionized the treatment of many cutaneous vascular anomalies. Because most of these lesions are congenital, the pediatric population has benefited primarily. In this article, the authors focus primarily on laser treatment options, realizing that this modality is but one part of an overall comprehensive plan of management options for these affected children. METHODS: The literature was reviewed and interjected into the authors' 20 years of experience in the use of lasers in the pediatric population. RESULTS: The use of different therapy modalities, such as the neodymium:yttrium-aluminum-garnet laser, pulsed dye laser, erbium:yttrium-aluminum-garnet laser, and intense pulsed light systems, is discussed. Outcomes, risks, benefits, and treatment protocols vary for each entity and for each laser. The authors' results and those of others are presented. CONCLUSIONS: Lasers play a vital role as an adjunctive therapy or definitive therapy in many of the authors' pediatric patients. Anyone treating such patients should be well aware of lasers as a valuable tool.

Monopolar radiofrequency tissue tightening--how we do it in our practice.

BACKGROUND AND OBJECTIVES: Monopolar radiofrequency has emerged as the standard for non-surgical tissue tightening. However, its role, usefulness, and value remains unclear to many clinicians. Techniques and treatment parameters used by various practitioners can also be highly variable. STUDY DESIGN/MATERIALS AND METHODS: The role of monopolar radiofrequency in our cosmetic plastic surgery practice will be defined and discussed. Our treatment algorithm will also be outlined. RESULTS: Treatment guidelines and reasonable expectations will be offered based on over 5 years of clinical and research experience with monopolar radiofrequency technology. CONCLUSIONS: Monopolar radiofrequency technology plays a unique and well-defined role in our practice. Strict patient selection in conjunction with detailed, honest, informed consent are the keys to successful treatments and patient satisfaction.

Ultrastructural evaluation of multiple pass low energy versus single pass high energy radio-frequency treatment.

BACKGROUND AND OBJECTIVE: The radio-frequency (RF) device is a system capable of volumetric heating of the mid to deep dermis and selective heating of the fibrous septa strands and fascia layer. Clinically, these effects promote dermal collagen production, and tightening of these deep subcutaneous structures. A new technique of using multiple low energy passes has been described which results in lower patient discomfort and fewer side effects. This technique has also been anecdotally described as giving more reproducible and reliable clinical results of tissue tightening and contouring. This study will compare ultrastructural changes in collagen between a single pass high energy versus up to five passes of a multiple pass lower energy treatment. STUDY DESIGN/MATERIALS AND METHODS: Three subjects were consented and treated in the preauricular region with the RF device using single or multiple passes (three or five) in the same 1.5 cm(2) treatment area with a slight delay between passes to allow tissue cooling. Biopsies from each treatment region and a control biopsy were taken immediately, 24 hours or 6 months post treatment for electron microscopic examination of the 0-1 mm and 1-2 mm levels. Sections of tissue 1 mm x 1 mm x 80 nm were examined with an RCA EMU-4 Transmission Electron Microscope. Twenty sections from 6 blocks from each 1 mm depth were examined by 2 blinded observers. The morphology and degree of collagen change in relation to area examined was compared to the control tissue, and estimated using a quantitative scale. RESULTS: Ultrastructural examination of tissue showed that an increased amount of collagen fibril changes with increasing passes at energies of 97 J (three passes) and 122 J (five passes), respectively. The changes seen after five multiple passes were similar to those detected after much more painful single pass high-energy treatments. CONCLUSIONS: This ultrastructural study shows changes in collagen fibril morphology with an increased effect demonstrated at greater depths of the skin with multiple low-fluence passes and at lesser depths with single pass higher fluence settings. Findings suggest that similar collagen fibril alteration can occur with multiple pass low-energy treatments and single pulse high-energy treatments. The lower fluence multiple pass approach is associated with less patient discomfort, less side effects, and more consistent clinical results.

Nonphysician practice of dermatologic surgery: the Texas perspective.

BACKGROUND: Increases in complications resulting from the nonphysician practice of dermatologic procedures have been reported nationally. This investigation was initiated owing to growing concern regarding the nonphysician practice of medicine in Texas. OBJECTIVE: The objective was to survey dermatologists in Texas to determine the number of patients seeking corrective treatment owing to complications from dermatologic procedures performed by nonphysicians. METHODS: A total of 488 dermatologists in Texas were surveyed and seven patients who experienced complications were interviewed by phone. RESULTS: Nearly 53% of responding physicians noted increased complications resulting from nonphysician practice of medicine. Approximately 33% of responding physicians reported that complications were known to have occurred in the absence of an on-site supervising physician. CONCLUSION: The increase in the number of complications owing to nonphysician practice of medicine in Texas mirrors the increases that have been reported nationally. The serious complications reported underscore the need for improved awareness and regulatory changes by state boards of medicine.