Community-Based Practice Variations in Topical Treatment of Actinic Keratoses

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Results | A total of 153 dermatology residents responded Author Contributions: Drs Chapman and Korta had full access to all of the data (Table 1), a 61.2% response rate. A total of 110 residents (71.9%) in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. did not receive any formal education on the hazards of elec- Study concept and design: All authors. trosurgery smoke from their program. One hundred six (69.2%) Acquisition, analysis, or interpretation of data: Chapman, Korta, Linden. reported sometimes or never wearing a surgical mask during Drafting of the manuscript: Chapman, Korta. electrosurgery, and 135 (88.2%) reported never wearing a high- Critical revision of the manuscript for important intellectual content: All authors. Statistical analysis: Chapman, Korta. filtration mask (N95). In terms of smoke management, 69 resi- Administrative, technical, or material support: Chapman, Korta, Linden. dents (45.1%) did not know if a smoke evacuation system was Supervision: Lee, Linden. available in rooms where electrosurgery was performed. Conflict of Interest Disclosures: None reported. Despite the low reported use of protective equipment, 117 resi- 1. Oganesyan G, Eimpunth S, Kim SS, Jiang SI. Surgical smoke in dermatologic dents (76.5%) were concerned about transmission of infec- surgery. Dermatol Surg. 2014;40(12):1373-1377. tious diseases via surgical smoke, and 110 (71.9%) indicated 2. Baggish MS, Poiesz BJ, Joret D, Williamson P, Refai A. Presence of human concern that carcinogens are present in surgical smoke. immunodeficiency virus DNA in laser smoke. Lasers Surg Med. 1991;11(3):197-203. Finally, almost three-fourths of residents (112) reported that 3. Sawchuk WS, Weber PJ, Lowy DR, Dzubow LM. Infectious papillomavirus in the vapor of warts treated with carbon dioxide laser or electrocoagulation: adequate precautions were not being taken to protect them detection and protection. J Am Acad Dermatol. 1989;21(1):41-49. from surgical smoke (Table 2). 4. Lewin JM, Brauer JA, Ostad A. Surgical smoke and the dermatologist. JAm Acad Dermatol. 2011;65(3):636-641. Discussion | Surgical smoke contains toxic organic compounds 5. Facts about benzene. Center for Disease Control and Prevention, 2013. and carcinogens and can transmit live viruses, such as human https://emergency.cdc.gov/agent/benzene/basics/facts.asp. Accessed August papillomavirus.3 Therefore, prevention of smoke inhalation 16, 2016. should be a health consideration for dermatologists. First, a 6. Fan JK, Chan FS, Chu KM. Surgical smoke. Asian J Surg. 2009;32(4):253-257. smoke evacuation system is highly recommended. Our study revealed that almost half of dermatology residents did not know Community-Based Practice Variations if there was a smoke evacuation system available. Second, high- in Topical Treatment of Actinic Keratoses filtration N95 surgical masks are recommended to prevent in- Actinic keratoses (AKs) are precancerous skin lesions afflict- halation of most particulate matter.6 Most dermatology resi- ing nearly 58 million people in the United States per year and dents denied wearing these masks. Notably,the cost of both N95 costing over a billion dollars annually to treat.1,2 Twoofthe grade masks and smoke evacuation systems are obstacles to pro- most widely used topical field-based treatments for AKs are moting surgical smoke safety. For instance, a 3M National fluorouracil and imiquimod.3 Although variations exist in how Institute of Occupational Safety and Health–approved N95 sur- these topical medications are prescribed in terms of fre- gical respirator costs about $1 compared with $0.08 per stan- quency, duration, and strength for AK treatment,4 no studies dard surgical mask, a significant cost difference. Surgical smoke have systematically examined how patient and health care pro- evacuators typically cost more than $1500 per unit plus life- vider factors impact prescribed regimens. Using data from a time maintenance costs, and an assistant might be required to large community-based population, we examined how varia- operate the unit. A dual-purpose hyfrecator/evacuation tub- tions in fluorouracil and imiquimod prescription patterns for ing system allows single-operator use. Finally, reducing the pro- AKs treatment was influenced by patient age, sex, AK ana- duction of intraoperative surgical smoke via knowledge of op- tomic site, and prescriber type. timal time spent to achieve hemostasis should be promoted and taught to residents early in their training. Methods | Kaiser Permanente Northern California (KPNC) is a Our study demonstrates a significant disconnect between large, integrated health care delivery system that provides com- awareness of surgical smoke hazards and a clear lack of protec- prehensive health care to a community-based population of over tive measures. These data can serve as a foundation to help in- 3.4 million members. We identified KPNC members 18 years or form safety guidelines in electrosurgery, ensuring the availabil- older diagnosed with an AK (International Statistical Classifica- ity of smoke management devices and N95 masks and requiring tion of Diseases and Related Health Problems, Ninth Revision formal dermatology resident education on the hazards of sur- code 702.0) in 2007 who were prescribed either fluorouracil gical smoke and recommended protective measures. (n = 5062) or imiquimod (n = 638) for AK treatment. The association between age, sex, anatomic AK location, and health care Lance W. Chapman, MD, MBA provider type and each of the 3 outcomes (frequency, duration, Dorota Z. Korta, MD, PhD and strength) was evaluated using linear regression. Strength was Patrick K. Lee, MD defined as “low” (less than 5%) or “high” (5% or greater). Dura- Kenneth G. Linden, PhD, MD tion ranged from 1 week to greater than 6 weeks. Frequency ranged from once weekly to more than twice daily. This study Author Affiliations: Department of Dermatology, University of California–Irvine was approved by the Kaiser Foundation Research Institute insti- Medical Center, Irvine. tutional review board. The Declaration of Helsinki protocols were Corresponding Author: Lance W. Chapman, MD, MBA, Department of Dermatology, University of California-Irvine Medical Center, 118 Med Surge I, followed, and a waiver of informed consent was obtained. Irvine, CA 92697-2400 ([email protected]). Accepted for Publication: December 8, 2016. Results | Characteristics of the study cohort are summarized Published Online: March 1, 2017. doi:10.1001/jamadermatol.2016.5899 in the Table. Mean (SD) age was 66.4 (11.6) years; 3383

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Table. KPNC Members With AKs Treated With Fluorouracil and Imiquimod in 2007 (N = 5700)

No. (%) Full Cohort Fluorouracil Imiquimod Characteristic (n = 5700) (n = 5062) (n = 638) P Value Age, (SD), y 66.4 (11.6) 66.4 (11.5) 66.4 (12.2) .97 Age at index date, y .02 18-49 440 (7.7) 392 (7.7) 48 (7.5) 50-65 2249 (39.5) 1984 (39.2) 265 (41.5) 66-80 2320 (40.7) 2091 (41.3) 229 (35.9) >80 691 (12.1) 595 (11.8) 96 (15.1) Sex .001 Male 3383 (59.3) 3042 (60.1) 341 (53.5) Female 2317 (40.7) 2020 (39.9) 297 (46.5) AK anatomic site .13 Head and/or neck only 2355 (41.3) 2102 (41.5) 253 (39.8) Trunk and/or extremities only 766 (13.4) 678 (13.4) 88 (13.8) Head and/or neck and trunk and/or extremities 537 (9.4) 490 (9.7) 47 (7.4) Not specified or missing 2042 (35.8) 1794 (35.4) 248 (39.0) Prescriber type .02 Dermatologist 5386 (94.5) 4770 (94.2) 616 (96.6) Abbreviations: AK, actinic keratoses; KPNC, Kaiser Permanente Northern Nondermatologist 314 (5.5) 292 (5.8) 22 (3.4) California.

patients (59.3%) were men; the most common AK site was Figure. Treatment Variation by Age, Sex, Actinic Keratoses Site, the head and neck (n = 2355 [41.3%]); and the majority of and Prescriber Type prescribers were dermatologists (n = 5386 [94.5%]). Older patients were prescribed less frequent regimens. With Treatment Variation Age respect to sex, male patients were more frequently pre- Duration scribed fluorouracil than imiquimod, and were prescribed Frequency higher strength fluorouracil than female patients. Actinic Strength keratoses arising on the head and neck were treated with Male lower strength agents than other anatomic locations. Der- Duration matologists were more likely to prescribe imiquimod, to Frequency prescribe higher frequency of application regimens, and Strength treat for a shorter duration as compared with nonderma- Head and neck site Duration tologists. These treatment variations are illustrated in the Frequency Figure. Strength Dermatologist prescriber Discussion | We systematically show that patient characteris- Duration tics including age, sex, and AK anatomic site are associated Frequency with variation in topical AK treatment regimens. The differ- Strength ence in prescribing patterns by age and sex of the patient –0.2–0.1 0 0.1 0.2 0.3 may be influenced by physician perception and patient Slope of Linear Regression expectations of tolerability. The variations in prescribing

patterns between dermatologists and nondermatologists The x-axis represents the slope of the linear regression. The binary variables of may be explained by higher AK burden among patients male sex and dermatologist prescriber are assigned positive values along the seeking specialty care and greater comfort in varying the x-axis; therefore a negative value corresponds with female sex and nondermatologist providers, respectively. Increasing values represent a larger regimen to achieve the desired clinical outcome by specialty observed variation, whereas 0 represents no significant variation. Circles 4 health care providers. represent point estimates and horizontal lines represent 95% CIs. Strength was Strengths of this study include the use of an electronic defined as “low” (less than 5%) or “high” (5% or greater). Duration ranged from pharmacy database for exposure measurement, allowing for 1 week to greater than 6 weeks. Frequency ranged from once weekly to more than twice daily. accurate capture of dispensed medication, as well as the ability to comprehensively capture information on patient and provider factors. Limitations include that we may have underpowered to detect associations with imiquimod, the fact that some of the absolute differences within out- because our study period focused on a time when imi- come categories are small and need to be interpreted in an quimod was first being introduced to clinical practice, and appropriate clinical context.

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We report significant differences in prescribing patterns found that the median age of initiation of tanning was 17.0 for fluorouracil and imiquimod for AK treatment, which are years among females and 21.5 years among males.2 One lon- associated with patient and prescriber factors. Our findings gitudinal study3 of female teens found that maternal and have implications for future real-world comparative effective- peer attitudes toward tanning influenced tanning initiation. ness studies that examine AK treatments and associated clini- Maternal behaviors and maternal permissiveness toward cal outcomes. and monitoring of their child’s indoor tanning affect adoles- cents’ longer-term tanning patterns.4 Molly Storer, MS Zheng Zhu, MS Methods | To characterize indoor tanning initiation, we used Monika Sokil, MS self-reported data from Porter Novelli’s 2015 Styles data- Margaret Ford, MD base, a web-based panel weighted to be representative of Romain Neugebauer, PhD the US population. The 2015 SummerStyles survey was sent Maryam M. Asgari, MD, MPH to 6172 adults who belong to the GfK’s KnowledgePanel and who had completed a previous survey. The final sample Author Affiliations: Department of Dermatology, Massachusetts General included 4127 adults (response rate, 67%), 984 of whom Hospital, Harvard Medical School, Boston (Storer, Asgari); Division of Research, reported ever indoor tanning. The Centers for Disease Con- Kaiser Permanente Northern California, Oakland (Zhu, Sokil, Ford, Neugebauer, Asgari). trol and Prevention (CDC) licensed the data from Porter Corresponding Author: Maryam M. Asgari, MD, MPH, Department of Novelli. Personal identifiers were not included in the data Dermatology, Massachusetts General Hospital, 50 Staniford St, Ste 230A, file, and institutional review board approval was not needed Boston, Massachusetts 02114 ([email protected]). because the CDC was not engaged in human subjects Published Online: April 5, 2017. doi:10.1001/jamadermatol.2016.6251 research. Author Contributions: Drs Asgari had full access to all of the data in the study Respondents who had ever tanned indoors were asked and takes responsibility for the integrity of the data and the accuracy of the data about age at initiation and companions present (alone, analysis. Concept and design: Asgari. mom, dad, sister, brother, another family member, friend or Acquisition, analysis, or interpretation of data: All authors. friends, someone else not listed, don’t remember). Other Drafting of the manuscript: Storer, Zhu, Ford, Neugebauer, Asgari. variables of interest included sex and age at survey. We did Critical revision of the manuscript for important intellectual content: Storer, Sokil, Neugebauer, Asgari. not report results by race/ethnicity because of small sample Statistical analysis: Zhu, Neugebauer. sizes of black and Hispanic tanners; 90.0% of respondents Obtained funding: Neugebauer, Asgari. were non-Hispanic white. Administrative, technical, or material support: Sokil, Neugebauer. We examined first experience of indoor tanning by age, Supervision: Neugebauer, Asgari. sex, and whether the tanner first went with friends, family, Conflict of Interests Disclosure: Dr Asgari receives grant funding from Pfizer Inc and Valeant Pharmaceuticals. or alone. We used SAS-callable SUDAAN software (RTI Inter- Funding/Support: This work was supported by the National Institute of national) to analyze data, using weighted proportions and Arthritis Musculoskeletal and Skin Diseases (grant No. R03AR064014 to M.A.). 95% CIs. Role of the Funder/Sponsor: The funder/sponsor had no role in the design and conduct of the study; collection, management, analysis, and interpretation of Results | Overall, 977 indoor tanners responded to questions the data; preparation, review, or approval of the manuscript; and decision to about their first tanning experience: 252 males and 725 submit the manuscript for publication. females. Males and females had similar rates of initiating 1. Landis ET, Davis SA, Taheri A, Feldman SR. Top dermatologic diagnoses by age. Dermatol Online J. 2014;20(4):22368. tanning alone (54.7% and 55.2%, respectively), but initiating tanning with a companion (friend or family member) 2. Bickers DR, Lim HW, Margolis D, et al; American Academy of Dermatology Association; Society for Investigative Dermatology. The burden of skin diseases: was somewhat more common among females than males 2004 a joint project of the American Academy of Dermatology Association and (Table, Figure). the Society for Investigative Dermatology. J Am Acad Dermatol. 2006;55(3): Many tanners (52.5%) began tanning before age 21 490-500. years, with about 1 in 3 initiating indoor tanning before age 3. Chetty P, Choi F, Mitchell T. Primary care review of actinic keratosis and its therapeutic options: a global perspective. Dermatol Ther (Heidelb). 2015;5(1): 18 years. Those who began tanning younger than age 16 19-35. often started with a family member (44.5%). Among those 4. Balkrishnan R, Cayce KA, Kulkarni AS, et al. Predictors of treatment choices first tanning with a family member, 49.2% reported first and associated outcomes in actinic keratoses: results from a national physician tanning with their mother (27.5% of males and 54.4% of survey study. J Dermatolog Treat. 2006;17(3):162-166. females). Those ages 16 to 17 years or older often began tanning alone (Figure). However, for tanners beginning at age Indoor Tanning Initiation Among Tanners 16 to 20 years old, tanning with a companion (usually a in the United States friend) was also common. Indoor tanning is associated with increased risk of skin can- cers, including melanoma.1 The US Food and Drug Adminis- Discussion | Tanning at younger ages is associated with more tration has proposed a regulation that would prohibit minors frequent tanning and increased risk of skin cancer.5 Current (<18 years) from tanning.1 and future state and federal regulations that aim to prohibit Little is known about characteristics of indoor tanning indoor tanning by minors younger than 18 years have the initiation. An analysis among whites younger than 40 years potential to delay initiation of indoor tanning until older

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