Guselkumab for Pityriasis Rubra Pilaris and Dysregulation of IL-23/IL-17 and NFkB Signaling: A Nonrandomized Trial.

Importance: There is no US Food and Drug Administration-approved treatment for pityriasis rubra pilaris (PRP), and it is common for patients to fail to experience improvement with several systemic options. Involvement of interleukin (IL) 23 suggests a potential therapeutic target. Objective: To determine whether guselkumab, an IL-23p19 inhibitor, provides clinical improvement for participants with PRP and better understand gene and protein dysregulation in PRP. Design, Setting, and Participants: This single-arm, investigator-initiated nonrandomized trial was conducted from October 2019 to August 2022 at a single-center academic university with participants from 8 states in the US. In total, 14 adults with moderate to severe PRP were enrolled; 12 completed the trial. Age-matched and sex-matched healthy controls provided skin and blood for proteomic and transcriptomic studies. The primary outcome was observed at 24 weeks, and additional follow-up occurred at 36 weeks. Intervention: Guselkumab is a fully human immunoglobulin G1 λ monoclonal antibody that selectively binds and inhibits the p19 subunit of IL-23. Subcutaneous injections were given at the US Food and Drug Administration-approved dosing schedule for psoriasis over a 24-week period. Main Outcomes and Measures: The primary outcome was the mean change in the Psoriasis Area Severity Index (PASI) score at week 24. Secondary outcomes included pruritus, Dermatology Life Quality Index score, clinical response at week 36, and association with transcriptomics and proteomics expression. Results: A per-protocol analysis was performed for the cohort of 4 female and 8 male patients who had a mean (SD) age of 56.5 (18.7) years. The mean improvement in PASI score, pruritus, and Dermatology Life Quality Index score was 61.8% (P < .001), 62.3% (P = .001), and 60.2% (P < .001), respectively. Nine participants (75%) achieved a 50% improvement in PASI. Among these clinical responders, at week 36, 8 of 9 achieved PASI75, and 6 of 9 achieved PASI90. No participants had pathogenic CARD14 gene variations. There was 1 serious adverse event that was not associated with the study drug. Proteomics and gene expression profiles identified dysregulation of a predominance of inflammatory pathways (such as T helper 17 and nuclear factor κ B) in participants with PRP who later responded well to treatment with guselkumab and stronger dysregulation of keratinocyte development pathways in individuals who did not respond to guselkumab. Conclusion and Relevance: The results of this nonrandomized trial suggest that guselkumab has efficacy in treating refractory moderate to severe adult PRP. Trial Registration: ClinicalTrials.gov Identifier: NCT03975153.

Reducing no-show visits and disparities in access: The impact of telemedicine.

BACKGROUND: No-show visits have serious consequences for patients, providers, and healthcare systems as they lead to delays in care, increased costs, and reduced access to services. Telemedicine has emerged as a promising alternative to in-person visits by reducing travel barriers, but risks exacerbating the digital divide. The aim of this study was to assess the impact of telemedicine (video and phone) at a tertiary care academic center on no-show visits compared to in-person visits. METHODS: A retrospective cohort analysis of all weekday clinic visits among in-state adult patients at a single tertiary care center in the southeast from January 2020 to April 2023 was performed. Rates of no-show visits for patients who were seen via phone and video were compared with those who were seen in-person. Demographic and clinical characteristics of these groups were also compared, including age, sex, race/ethnicity, socioeconomic status, and visit type. The primary outcome was the rate of no-show visits for each visit type. RESULTS: Our analysis included 3,105,382 scheduled appointments, of which 81.2% were in-person, 13.4% via video, and 5.4% via phone calls. Compared to in-person visits, phone calls and video visits reduced the odds of no-show visits by 50% (aOR 0.5, CI 0.49-0.51) and 15% (aOR 0.85, CI 0.84-0.86), respectively. Older patients, Black patients, patients furthest from clinic, and patients from counties with the greatest degree of vulnerability and disparities in digital access were more likely to use phone visits. No-shows were more common among non-white, male, and younger patients from counties with lower socioeconomic status. CONCLUSION: Telemedicine effectively reduced no-show visits. However, limiting telemedicine to video-based visits only exacerbated disparities in access. Phone calls allow historically underserved patients from lower socioeconomic backgrounds to access healthcare and should be included within the definition of telemedicine.

Increasing Trainee Engagement in Surgery Societies: The Society of Asian Academic Surgeons Experience.

INTRODUCTION: Surgical societies provide a plethora of resources for trainees; however, these opportunities are often underused due to suboptimal guidance, sponsorship, or mentorship. Here, we present the Society of Asian Academic Surgeons (SAAS) experience in enhancing the trainee experience and engagement in a surgical society focused on professional development. MATERIALS AND METHODS: We conducted an interactive idea-generating session during the 2022 SAAS Conference with all Associate Members (trainees) present in Honolulu, HI. Recurrent themes, concepts, and ideas/suggestions were carefully considered when planning the next SAAS Conference in Baltimore, MD. We employed a more targeted approach to trainee engagement at the 2023 SAAS Conference, with breakout sessions geared toward various levels of trainees, in addition to increased social events and networking opportunities. We obtained feedback from trainees in attendance through an electronic survey and informal conversations with faculty and Associate Members. RESULTS: Opportunities for surgical subspecialty networking was the most well-received portion of our formal Career Development program. The majority of trainees in attendance were medical students or junior residents who valued the exposure to junior faculty and those in leadership positions at academic institutions. The addition of a group text for easy communication among trainees and informal social activities for Associate Member networking among themselves were crucial in improving the overall conference experience. CONCLUSIONS: Opportunities to maximize trainee engagement in surgical societies are heightened during in-person conferences. Targeted session topics, guided networking opportunities, and creating channels for easier communication along with more social events have enhanced the overall experience for aspiring and current surgical trainees.

What Is Health Literacy Among Orthognathic Surgery Patients?

BACKGROUND: Health literacy of orthognathic surgery patients has not been thoroughly evaluated. PURPOSE: The purpose of this study was to estimate health literacy and identify risk factors associated with inadequate health literacy in orthognathic surgery patients. STUDY DESIGN, SETTING, SAMPLE: A cross-sectional study was implemented utilizing patients ages 14-80 years who presented for orthognathic surgery evaluation between September 2021 and December 2022. Subjects were excluded from the study if they did not complete the orthognathic surgery evaluation, were not between the ages of 14-80 years old, or did not complete the Brief Health Literacy Screening Tool (BRIEF) questionnaire during intake. Subjects who have not undergone orthognathic surgery but completed the initial evaluation for orthognathic surgery were included in the study. PREDICTOR VARIABLES: The predictor variables were a set of risk factors for inadequate health literacy: age, sex, primary language, race, estimated household income, and diagnosis. MAIN OUTCOME VARIABLE: The main outcome variable was health literacy assessed using the BRIEF questionnaire. During intake, subjects completed the BRIEF questionnaire consisting of four questions scored on an ordinal scale of 1-5. Inadequate health literacy was defined as a BRIEF score ≤16. COVARIATES: Not applicable. ANALYSES: Bivariate and multivariate analyses were performed. P < .05 was considered statistically significant. RESULTS: Of 150 patients presenting for orthognathic surgery, fifteen percent of patients had inadequate health literacy via the BRIEF test. The mean age of those with adequate health literacy was 27.9 years (standard deviation, ±12.5) compared to 18.5 years (standard deviation, ±5.7) for those with inadequate health literacy (P = <.001). After adjusting for sex, language, race, estimated household income, and diagnosis via multivariate analysis, increasing age was associated with decreased odds of inadequate health literacy (adjusted odds ratio = 0.81; confidence interval, 0.72-0.92; P = <.001). CONCLUSION AND RELEVANCE: In the complex process of orthognathic surgery, it is essential to identify patients with inadequate health literacy that may require additional health literacy interventions. Ultimately, 15% of orthognathic surgery subjects had inadequate health literacy, and younger patients were the most susceptible as the odds of inadequate health literacy decreased with increasing age.

Understanding the Impact of Enhanced Recovery Programs on Social Vulnerability, Race, and Colorectal Surgery Outcomes.

BACKGROUND: Increasing social vulnerability, measured by the Social Vulnerability Index, has been associated with worse surgical outcomes. However, less is known about the impact of social vulnerability on patients who underwent colorectal surgery under enhanced recovery programs. OBJECTIVE: We hypothesized that increasing social vulnerability is associated with worse outcomes before enhanced recovery implementation, but that after implementation, disparities in outcomes would be reduced. DESIGN: Retrospective cohort study using multivariable logistic regression to identify associations of social vulnerability and enhanced recovery with outcomes. SETTINGS: Institutional American College of Surgeons National Surgical Quality Improvement Program database. PATIENTS: Patients undergoing elective colorectal surgery (2010-2020). Enhanced recovery programs were implemented in 2015. Those adhering to 70% or more of enhanced recovery program components were defined as enhanced recovery and all others as nonenhanced recovery. OUTCOMES: Length of stay, complications, and readmissions. RESULTS: Of 1523 patients, 589 (38.7%) were in the enhanced recovery group, with 625 patients (41%) in the lowest third of the Social Vulnerability Index, 411 (27%) in the highest third. There were no differences in Social Vulnerability Index distribution by the enhanced recovery group. On multivariable modeling, social vulnerability was not associated with increased length of stay, complications, or readmissions in the enhanced recovery group. Black race was associated with increased length of stay in both the nonenhanced recovery (OR 1.2; 95% CI, 1.1-1.3) and enhanced recovery groups (OR 1.2; 95% CI, 1.1-1.4). Enhanced recovery adherence was associated with reductions in racial disparities in complications as the Black race was associated with increased odds of complications in the nonenhanced recovery group (OR 1.9; 95% CI, 1.2-3.0) but not in the enhanced recovery group (OR 0.8; 95% CI, 0.4-1.6). LIMITATIONS: Details of potential factors affecting enhanced recovery program adherence were not assessed and are the subject of current work by this team. CONCLUSION: High social vulnerability was not associated with worse outcomes among both enhanced recovery and nonenhanced recovery colorectal patients. Enhanced recovery program adherence was associated with reductions in racial disparities in complication rates. However, disparities in length of stay remain, and work is needed to understand the underlying mechanisms driving these disparities. See Video Abstract . COMPRENDIENDO EL IMPACTO DE LOS PROGRAMAS DE RECUPERACIN MEJORADA EN LA VULNERABILIDAD SOCIAL, LA RAZA Y LOS RESULTADOS DE LA CIRUGA COLORRECTAL: ANTECEDENTES:El aumento de la vulnerabilidad social medida por el índice de vulnerabilidad social se ha asociado con peores resultados quirúrgicos. Sin embargo, se sabe menos sobre el impacto de la vulnerabilidad social en los pacientes de cirugía colorrectal bajo programas de recuperación mejorados.OBJETIVO:Planteamos la hipótesis de que el aumento de la vulnerabilidad social se asocia con peores resultados antes de la implementación de la recuperación mejorada, pero después de la implementación, las disparidades en los resultados se reducirían.DISEÑO:Estudio de cohorte retrospectivo que utilizó regresión logística multivariable para identificar asociaciones de vulnerabilidad social y recuperación mejorada con los resultados.ESCENARIO:Base de datos institucional del Programa de Mejora Nacional de la Calidad de la Cirugía del American College of Surgeons.PACIENTES:Pacientes sometidos a cirugía colorrectal electiva (2010-2020). Programas de recuperación mejorada implementados en 2015. Aquellos que se adhieren a ≥70% de los componentes del programa de recuperación mejorada definidos como recuperación mejorada y todos los demás como recuperación no mejorada.MEDIDAS DE RESULTADO:Duración de la estancia hospitalaria, complicaciones y reingresos.RESULTADOS:De 1.523 pacientes, 589 (38,7%) estaban en el grupo de recuperación mejorada, con 732 (40,3%) pacientes en el tercio más bajo del índice de vulnerabilidad social, 498 (27,4%) en el tercio más alto, y no hubo diferencias en la distribución del índice vulnerabilidad social por grupo de recuperación mejorada. En el modelo multivariable, la vulnerabilidad social no se asoció con una mayor duración de la estancia hospitalaria, complicaciones o reingresos en ninguno de los grupos de recuperación mejorada. La raza negra se asoció con una mayor duración de la estadía tanto en el grupo de recuperación no mejorada (OR1,2, IC95% 1,1-1,3) como en el grupo de recuperación mejorada (OR1,2, IC95% 1,1-1,4). La adherencia a la recuperación mejorada se asoció con reducciones en las disparidades raciales en las complicaciones, ya que la raza negra se asoció con mayores probabilidades de complicaciones en el grupo de recuperación no mejorada (OR1,9, IC95% 1,2-3,0), pero no en el grupo de recuperación mejorada (OR0,8, IC95% 0,4-1,6).LIMITACIONES:No se evaluaron los detalles de los factores potenciales que afectan la adherencia al programa de recuperación mejorada y son el tema del trabajo actual de este equipo.CONCLUSIÓN:La alta vulnerabilidad social no se asoció con peores resultados entre los pacientes colorrectales con recuperación mejorada y sin recuperación mejorada. Una mayor adherencia al programa de recuperación se asoció con reducciones en las disparidades raciales en las tasas de complicaciones. Sin embargo, persisten disparidades en la duración de la estadía y es necesario trabajar para comprender los mecanismos subyacentes que impulsan estas disparidades. (Traducción-Dr. Felipe Bellolio ).

Development of a comprehensive survey to assess key socioecological determinants of health.

BACKGROUND: Although disparities in surgical outcomes are well-documented, our understanding of how socioecological factors drive these disparities remains limited. Comprehensive and efficient assessment tools are needed. This study's objective was to develop and assess the acceptability and feasibility of a comprehensive tool evaluating socioecological determinants of health in patients requiring colorectal surgery. METHODS: In the first phase, a comprehensive socioecological determinant of health assessment tool was developed. A review of validated socioecological health evaluation instruments was conducted, and a 2-step modified Delphi method addressed the length, clarity, appropriateness, and redundancy of each instrument. A comprehensive tool was then finalized. In the second phase, the tool was tested for acceptability and feasibility in adult patients requiring colorectal surgery using a theory-guided framework at 3 Alabama hospitals. Relationships between survey responses and measures of acceptability and feasibility were evaluated using results from initial pilot tests of the survey. RESULTS: In Phase 1, a modified Delphi process led to the development of a comprehensive tool that included 31 socioecological determinants of health (88 questions). Results of acceptability and feasibility were globally positive (>65%) for all domains. Overall, 83% of participants agreed that others would have no trouble completing the survey, 90.4% of respondents reported the survey was not burdensome, 97.6% of patients reported having enough time to complete the survey, and 80.9% agreed the survey was well-integrated into their appointment. CONCLUSION: An 88-item assessment tool measuring 31 socioecological determinants of health was developed with high acceptability and feasibility for patients who required colorectal surgery. This work aids in the development of research needed to understand and address surgical disparities.

The association of social vulnerability with colorectal enhanced recovery program failure.

Background: Enhanced recovery programs (ERPs) improve outcomes, but over 20 % of patients fail ERP and the contribution of social vulnerability is unknown. This study aimed to characterize the association between social vulnerability and ERP adherence and failure. Methods: This was a retrospective cohort study of colorectal surgery patients between 2015 and 2020 utilizing ACS-NSQIP data. Patients who failed ERP (LOS > 6 days) were compared to patients not failing ERP. The CDC's social vulnerability index (SVI) was used to assess social vulnerability. Result: 273 of 1191 patients (22.9 %) failed ERP. SVI was a significant predictor of ERP failure (OR 4.6, 95 % CI 1.3-16.8) among those with >70 % ERP component adherence. SVI scores were significantly higher among patients non-adherent with 3 key ERP components: preoperative block (0.58 vs. 0.51, p < 0.01), early diet (0.57 vs. 0.52, p = 0.04) and early foley removal (0.55 vs. 0.50, p < 0.01). Conclusions: Higher social vulnerability was associated with non-adherence to 3 key ERP components as well as ERP failure among those who were adherent with >70 % of ERP components. Social vulnerability needs to be recognized, addressed, and included in efforts to further improve ERPs. Key message: Social vulnerability is associated with non-adherence to enhanced recovery components and ERP failure among those with high ERP adherence. Social vulnerability needs to be addressed in efforts to improve ERPs.

Racial disparities in postoperative outcomes persist for patients with inflammatory bowel disease under a colorectal enhanced recovery program.

INTRODUCTION: Enhanced recovery programs (ERPs) reduce racial disparities in surgical outcomes for general colorectal surgery populations. It is unclear, however, if disparities in IBD populations are impacted by ERPs. METHODS: Retrospective study comparing IBD patients undergoing major elective colorectal operations before (2006-2014) and after (2015-2021) ERP implementation using ACS-NSQIP data. The primary outcome of length of stay (LOS) was analyzed by negative binomial regression, and secondary outcomes (complications and readmissions) by logistic regression. RESULTS: Of 466 IBD patients, 47% were pre-ERP and 53% were ERP patients. In multivariable analysis stratified by ERP period, Black race was associated with increased odds of complications in the pre-ERP (OR 3.6, 95%CI 1.4-9.3) and ERP groups (OR 3.1 95%CI 1.3-7.6). Race was not a predictor of LOS or readmission in either group. High social vulnerability was associated with increased odds of readmission pre-ERP (OR 15.1, 95%CI 2.1-136.3), but this disparity was mitigated under ERPs (OR 1.4, 95%CI 0.4-5.6). CONCLUSION: While ERPs mitigated some disparities by social vulnerability, racial disparities persist in IBD populations even under ERPs. Further work is needed to achieve surgical equity for IBD patients.

A socioecological qualitative analysis of barriers to care in colorectal surgery.

BACKGROUND: Although specific social determinants of health have been associated with disparities in surgical outcomes, there exists a gap in knowledge regarding the mechanisms of these associations. Gaining perspectives from multiple socioecological levels can help elucidate these mechanisms. Our study aims to identify social determinants of health that act as barriers or facilitators to surgical care among colorectal surgery stakeholders. METHODS: We recruited participants representing 5 socioecological levels: patients (individual); caregivers/surgeons (interpersonal); and leaders in hospitals (organizational), communities (community), and government (policy). Patients participated in focus groups, and the remaining participants underwent individual interviews. Semistructured interview guides were used to explore barriers and facilitators to surgical care at each socioecological level. Transcripts were analyzed by 3 coders in an inductive thematic approach with content analyses. The intercoder agreement was 93%. RESULTS: Six patient focus groups (total n = 18) and 12 key stakeholder interviews were conducted. The mean age of patients was 54.7 years, 66% were Black, and 61% were female. The most common diseases were colorectal cancer (28%), inflammatory bowel disease (28%), and diverticulitis (22%). Key social determinants of health impacting surgical care emerged at each level: individual (clear communication, mental stress), interpersonal (provider communication and trust, COVID-related visitation restrictions), organizational (multiple forms of contact, quality educational materials, scheduling systems, discrimination), community (community and family support and transportation), and policy (charity care, patient advocacy organizations, insurance coverage). CONCLUSION: Key social determinants of health-impacting care among colorectal surgery patients emerged at each socioecological level and may provide targets for interventions to reduce surgical disparities.

Disparities in Perioperative Use of Patient Engagement Technologies - Not All Use is Equal.

OBJECTIVE: To determine the association of patient-level characteristics on the use of a patient engagement technology during the perioperative period. SUMMARY OF BACKGROUND DATA: As implementation of patient engagement technologies continues to grow, it remains unclear who uses, and not uses, these technologies. Existing literature suggests significant disparities in usage of other technologies by patient age, race, sex, and geographic location, however, have yet to characterize patient usage of patient engagement technologies. METHODS: This is a retrospective cohort study of patients undergoing elective surgery by a colorectal surgeon between January 2018 and March 2020 who enrolled in a patient engagement technology at a single institution. Patients enrolled received educational content, healthcare reminders, patient reported outcome (PRO) surveys, and health checks preoperatively, in-hospital, and for 30-days postdischarge. The primary outcome was patient activation of the patient engagement technology. Secondary outcomes were completion of at least 1 PRO survey, 1 in-hospital health check, and 1 postdischarge health check. RESULTS: Of 549 patients who enrolled in the patient engagement technology, 473 (86.2%) activated. On multivariable stepwise regression, female patients [odds ratio (OR) 2.4, confidence interval (CI) 1.4-4.0, P = 0.001] and privately insured patients (OR 2.0, CI 1.1-3.8, P = 0.03) were more likely to activate. Black patients were less likely to activate (OR 0.5, CI 0.3-0.9, P = 0.02). Once activated, privately insured patients were more likely to complete PRO surveys (OR 2.3, CI 1.2-4.3, P = 0.01), in-hospital health checks (OR 2.4, CI 1.4-4.1, P = 0.002), and postdischarge health checks (OR 1.9, CI 1.1 -3.3, P < 0.001) than uninsured patients. Black patients were less likely to complete PRO surveys (OR 0.4, CI 0.3-0.7, P = 0.001) and in-hospital health checks (OR 0.6, CI 0.4-0.9, P = 0.03) than White patients. CONCLUSIONS: Use of a patient engagement technology in the perioperative period differs significantly by sex, race/ethnicity, and insurance status. These technologies may not be used equally by all patients, which should be considered during implementation of interventions to improve surgical outcomes.

Becoming a Sustainable Academic Surgeon.

INTRODUCTION: Health care facilities represent a significant source of pollution, contributing to the growing problems associated with global warming. The resulting climate change impacts our health through worsening air and water quality, diminished access to nutritious food, and safe shelter. METHODS: We outline here the not only the role of the surgeon in contributing to climate change, but also ways in which to minimize one's carbon footprint. RESULTS: Surgeons are leaders within healthcare systems. Adopting environmentally conscious practices can reduce solid waste, energy usage, and carbon emissions. Practices outside of the clinical setting can also incorporate sustainability, including the use of virtual recruitment and educational programs, as well as thoughtful and conscientious travel practices. CONCLUSIONS: Academic surgery combines clinical practice with an element of leadership, at all levels. Our recognition and action to reduce wasteful practices can help leave a better earth for generations to come.

Improving surgical patient education materials using informational design with visual elements.

Patient education materials (PEMs) serve as a foundation for educating patients and families across all surgical fields but are often not understandable. The National Institute of Health (NIH) recommends that PEMs be written at a grade 6-7 reading level; however, most current materials exceed that measure.3 Lack of understandable and appropriate surgical PEMs compounds the difficulties that low health literacy patients face with resultant poor surgical outcomes.2,3 The challenge for surgeons is to adequately educate patients pre-operatively and post-operatively on the complexities of surgery. Another challenge is to compact decades of education and training into an easy-to-understand medium for patients. To address this challenge, many physicians have utilized visual aids to improve PEM efficacy. While visual aids are a critical piece of education materials, they must be designed intentionally to be effective. The most important consideration is that the PEM communicates the information clearly to users. With this in mind, we created a framework for productive utilization of visual aids by integrating the C.A.R.P. graphic design technique into an existing surgical PEM to enhance communication and understandability.

Increased Risk of Postoperative Mortality Associated With Prior COVID-19 Infection.

INTRODUCTION: The impact of COVID-19 infection on surgical patients is largely described by small-cohort studies. This study characterized the risk factors for postoperative mortality among patients with preoperative COVID-19 infection. METHODS: Data were abstracted from the electronic medical record for patients who tested positive for COVID-19 before surgery, excluding procedures related to extracorporeal membrane oxygenation (case, March 2020-April 2021). Mortality was compared with that for patients from the American College of Surgeons National Surgical Quality Improvement Program database (control, January 2018‒February 2020) with chi-square, t test, and multivariable regression. RESULTS: There were 5,209 patients in the control cohort. Among 1,072 patients with positive COVID-19 testing before surgery, 589 had surgeries with specialties tracked by the American College of Surgeons National Surgical Quality Improvement Program (General Surgery, Gynecology, Neurosurgery, Orthopedics, Thoracic, Vascular). Patients with previous COVID-19 infection were younger (age 48 vs 59 years, p<0.001), were more likely to be Black (42% vs 28%, p<0.001), and underwent fewer elective surgeries (55% vs 83%, p<0.001). Postoperative mortality was greater among the case cohort (4.4% vs 1%, p<0.001). On multivariable logistic regression, postoperative mortality increased with age (OR=1.02), emergent surgeries (OR=2.6), and previous COVID-19 infection (OR=3.8). Among patients with previous COVID-19 infection, postoperative mortality was associated with male sex (OR=2.7), higher American Society of Anesthesiologists Physical Status Classification Score (OR=4.8), and smoking history (OR=3.7). CONCLUSIONS: Although data abstraction was limited by the electronic medical record, postoperative mortality is nearly 6 times higher for patients infected with COVID-19 within 2 weeks before surgery when adjusting for patient- and procedure-level factors. Among those with previous COVID-19 infection, postoperative mortality is associated with male sex, American Society of Anesthesiologists Physical Status Classification Score, and smoking history.