Opportunities and Challenges of Kava in Lung Cancer Prevention.

Lung cancer is the leading cause of cancer-related deaths due to its high incidence, late diagnosis, and limited success in clinical treatment. Prevention therefore is critical to help improve lung cancer management. Although tobacco control and tobacco cessation are effective strategies for lung cancer prevention, the numbers of current and former smokers in the USA and globally are not expected to decrease significantly in the near future. Chemoprevention and interception are needed to help high-risk individuals reduce their lung cancer risk or delay lung cancer development. This article will review the epidemiological data, pre-clinical animal data, and limited clinical data that support the potential of kava in reducing human lung cancer risk via its holistic polypharmacological effects. To facilitate its future clinical translation, advanced knowledge is needed with respect to its mechanisms of action and the development of mechanism-based non-invasive biomarkers in addition to safety and efficacy in more clinically relevant animal models.

Reducing tobacco-associated lung cancer risk: a study protocol for a randomized clinical trial of AB-free kava.

BACKGROUND: Tobacco use is the leading cause of many preventable diseases, resulting in premature death or disease. Given that the majority of adult who smoke want to stop, this health burden could be significantly reduced if the success rate of tobacco cessation can be improved. In addition, most adults planning to quit were interested in trying complementary approaches to facilitating tobacco cessation, which is currently lacking. Therefore, there is an unmet and urgent need for novel interventions to improve the success of tobacco cessation. If such an intervention can reduce tobacco-associated lung carcinogenesis, that will be more desirable. The goal of this project is to develop a safe and effective kava-based intervention to enable tobacco cessation and reduce lung cancer risk, which will improve the health of smokers. METHODS: A randomized controlled trial will enroll 80 adults who currently smoke at least 10 cigarettes daily and randomize 1:1 into the placebo and AB-free kava arms, being exposed for 4 weeks, with a total of six visits (weeks 0, 1, 2, 4, 8, and 12) to evaluate the compliance and potential issues of AB-free kava use among the participants, explore the potential effect of the AB-free kava intervention on tobacco dependence, tobacco use, and lung carcinogenesis biomarkers. Participants will be enrolled during their primary care clinic visit. DISCUSSION: Primary care settings play a critical role in tobacco-related disease screening, counseling, and early intervention, as the majority of adults who smoke visit their physicians annually. Building upon our promising pilot human trial results in conjunction with ample compelling lab animal results, and consistent with evidence of kava's benefits from epidemiological data, this trial will evaluate the compliance of AB-free kava among adults who currently smoke with no intention to quit. The other exploratory aims include (1) whether AB-free kava intervention can reduce tobacco use and tobacco dependence; (2) whether AB-free kava use suppresses tobacco-induced carcinogenesis; and (3) the potential of the mechanism-based noninvasive biomarkers in precision AB-free kava intervention. The positive results from this study are expected to provide a great opportunity to effectively reduce smoking rates and tobacco-related diseases. TRIAL REGISTRATION: ClinicalTrials.gov with the identifier: NCT05081882. Registered on October 18, 2021.

Nicotine and cannabis vaping among adolescents in treatment for substance use disorders.

This study examined nicotine and cannabis vaping among adolescents in treatment for substance use disorders. Participants were 363 adolescents aged 12-17 (66% male, mean age = 15.5 [SD = 1.3], 46% non-Hispanic white) seen for a specialty addiction intake evaluation between 2017 and 2019 at one of six medical offices of a large, integrated health care system in Northern California. Multivariable logistic regression models tested for associations of sociodemographics, cigarette smoking, and substance use disorders with vaping behaviors. A majority of adolescents reported ever (68%) or current vaping (60%) of nicotine and/or cannabis; current vaping was similar for nicotine (50%) and cannabis (51%); 40% reported current vaping of both. Current smokers (6% of the sample) had higher odds of ever vaping (aOR = 3.95, 95%CI: 1.04-14.95). Black (versus non-Hispanic white) adolescents had lower odds of current nicotine vaping (aOR = 0.08, 95%CI: 0.02-0.37) and current vaping of both nicotine and cannabis (aOR = 0.12, 95%CI: 0.03-0.60). Having an alcohol use disorder was associated with current vaping (aOR = 2.14, 95%CI: 1.06-4.33). Those who endorsed that most friends get drunk/high (aOR = 1.87, 95%CI: 1.02-3.42) or that cannabis was their substance of choice (aOR = 2.36, 95%CI: 1.16-4.81) had higher odds of current cannabis vaping. Higher neighborhood household income ($80,000-$120,000 and >$120,000 vs. <$80,000, aORs = 2.05-9.48), never versus ever blunt use (aORs = 2.47-8.68), and intakes in 2018 and 2019 versus 2017 (aORs = 2.18-5.38) were associated with higher odds of all vaping outcomes. Vaping was common among adolescents in addiction treatment and varied with sociodemographics and substance-related factors. Research should assess how vaping impacts the development of substance use disorders and whether it interferes with addiction treatment.

Scaling-Up Stage 4 Pediatric Obesity Clinics: Identifying Barriers and Future Directions Using Implementation Science.

Nearly one-fifth of the pediatric population in the United States has obesity. Comprehensive behavioral interventions, with at least 26 contact hours, are the recommended treatment for pediatric obesity; however, there are various barriers to implementing treatment. This Perspective applies the Exploration, Preparation, Implementation, and Sustainment (EPIS) framework to address barriers to implementing multidisciplinary pediatric weight management clinics and identify potential solutions and areas for additional research. Lack of insurance coverage and reimbursement, high operating costs, and limited access to stage 4 care clinics with sufficient capacity were among the main barriers identified. Clinicians, researchers, and patient advocates are encouraged to facilitate conversations with insurance companies and hospital and clinic administrators, increase telehealth adoption, request training to improve competency and self-efficacy discussing and implementing obesity care, and advocate for more stage 4 clinics.

Cost-effectiveness of photobiomodulation therapy for the prevention and management of cancer treatment toxicities: a systematic review.

PURPOSE: To identify and summarize the evidence on the cost-effectiveness of photobiomodulation (PBM) therapy for the prevention and treatment of cancer treatment-related toxicities. METHODS: This systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement (PRISMA) and Meta-analysis Of Observational Studies in Epidemiology (MOOSE). Scopus, MEDLINE/PubMed, and Embase were searched electronically. RESULTS: A total of 1490 studies were identified, and after a two-step review, 4 articles met the inclusion criteria. The included studies analyzed the cost-effectiveness of PBM therapy used in the context of lymphedema for breast cancer and oral mucositis (OM) induced by chemotherapy and radiotherapy. Better outcomes were associated with PBM therapy. The incremental cost-effectiveness ratio ranged from 3050.75 USD to 5592.10 USD per grade 3-4 OM case prevented. PBM therapy cost 21.47 USD per percentage point reduction in lymphedema in comparison with 80.51 USD for manual lymph drainage and physical therapy. CONCLUSION: There is limited evidence that PBM therapy is cost-effective in the prevention and treatment of specific cancer treatment-related toxicities, namely, OM and breast cancer-related lymphedema. Studies may have underreported the benefits due to a lack of a comprehensive cost evaluation. This suggests a wider acceptance of PBM therapy at cancer treatment centers, which has thus far been limited by the number of robust clinical studies that demonstrate cost-effectiveness for the prevention and treatment of toxicities.

Kava as a Clinical Nutrient: Promises and Challenges.

Kava beverages are typically prepared from the root of Piper methysticum. They have been consumed among Pacific Islanders for centuries. Kava extract preparations were once used as herbal drugs to treat anxiety in Europe. Kava is also marketed as a dietary supplement in the U.S. and is gaining popularity as a recreational drink in Western countries. Recent studies suggest that kava and its key phytochemicals have anti-inflammatory and anticancer effects, in addition to the well-documented neurological benefits. While its beneficial effects are widely recognized, rare hepatotoxicity had been associated with use of certain kava preparations, but there are no validations nor consistent mechanisms. Major challenges lie in the diversity of kava products and the lack of standardization, which has produced an unmet need for quality initiatives. This review aims to provide the scientific community and consumers, as well as regulatory agencies, with a broad overview on kava use and its related research. We first provide a historical background for its different uses and then discuss the current state of the research, including its chemical composition, possible mechanisms of action, and its therapeutic potential in treating inflammatory and neurological conditions, as well as cancer. We then discuss the challenges associated with kava use and research, focusing on the need for the detailed characterization of kava components and associated risks such as its reported hepatotoxicity. Lastly, given its growing popularity in clinical and recreational use, we emphasize the urgent need for quality control and quality assurance of kava products, pharmacokinetics, absorption, distribution, metabolism, excretion, and foundational pharmacology. These are essential in order to inform research into the molecular targets, cellular mechanisms, and creative use of early stage human clinical trials for designer kava modalities to inform and guide the design and execution of future randomized placebo controlled trials to maximize kava's clinical efficacy and to minimize its risks.

The Impact of One-week Dietary Supplementation with Kava on Biomarkers of Tobacco Use and Nitrosamine-based Carcinogenesis Risk among Active Smokers.

Tobacco smoking is the primary risk factor for lung cancer, driven by the addictive nature of nicotine and the indisputable carcinogenicity of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) as well as other compounds. The integration of lung cancer chemoprevention with smoking cessation is one potential approach to reduce this risk and mitigate lung cancer mortality. Experimental data from our group suggest that kava, commonly consumed in the South Pacific Islands as a beverage to promote relaxation, may reduce lung cancer risk by enhancing NNK detoxification and reducing NNK-derived DNA damage. Building upon these observations, we conducted a pilot clinical trial to evaluate the effects of a 7-day course of kava on NNK metabolism in active smokers. The primary objective was to compare urinary total 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL plus its glucuronides, major metabolites of NNK) before and after kava administration as an indicator of NNK detoxification. Secondary objectives included determining kava's safety, its effects on DNA damage, tobacco use, and cortisol (a biomarker of stress). Kava increased urinary excretion of total NNAL and reduced urinary 3-methyladenine in participants, suggestive of its ability to reduce the carcinogenicity of NNK. Kava also reduced urinary total nicotine equivalents, indicative of its potential to facilitate tobacco cessation. Plasma cortisol and urinary total cortisol equivalents were reduced upon kava use, which may contribute to reductions in tobacco use. These results demonstrate the potential of kava intake to reduce lung cancer risk among smokers.

Disparities in knowledge and use of tobacco treatment among smokers in California following healthcare reform.

The Affordable Care Act (ACA) promised to narrow smoking disparities by expanding access to healthcare and mandating comprehensive coverage for tobacco treatment starting in 2014. We examined whether two years after ACA implementation disparities in receiving clinician advice to quit and smokers' knowledge and use of treatment resources remained. We conducted telephone interviews in 2016 with a stratified random sample of self-reported smokers newly enrolled in the Kaiser Permanente Northern California's (KPNC) integrated healthcare delivery system in 2014 (N = 491; 50% female; 53% non-white; 6% Spanish language). We used Poisson regression with robust standard errors to test whether sociodemographics, insurance type, comorbidities, smoking status in 2016 (former, light/nondaily [<5 cigarettes per day], daily), and preferred language (English or Spanish) were associated with receiving clinician advice to quit and knowledge and use of tobacco treatment. We included an interaction between smoking status and language to test whether the relation between smoking status and key outcomes varied with preferred language. Overall, 80% of respondents received clinician advice to quit, 84% knew that KPNC offers cessation counseling, 54% knew that cessation pharmacotherapy is free, 54% used pharmacotherapy, and 6% used counseling. In multivariate models, Spanish-speaking light/nondaily smokers had significantly lower rates of all outcomes, while there was no association with other demographic and clinical characteristics. Following ACA implementation, most smokers newly enrolled in KPNC received clinician advice to quit and over half used pharmacotherapy, yet counseling utilization was low. Spanish-language outreach efforts and treatment services are recommended, particularly for adults who are light/nondaily smokers.

Medical Care Costs Associated With Cancer in Integrated Delivery Systems.

Background: The high economic burden of cancer is projected to continue growing. Cost-of-care estimates are key inputs for comparative effectiveness and economic analyses that aim to inform policies associated with cancer care. Existing estimates are based largely on SEER-Medicare data in the elderly, leaving a knowledge gap regarding costs for patients aged <65 years. Methods: We estimated total and net medical care costs using data on individuals diagnosed with breast, colorectal, lung, or prostate cancer (n=45,522) and noncancer controls (n=314,887) enrolled in 1 of 4 participating health plans. Net costs were defined as the difference in mean total costs between patients with cancer and controls. The phase-of-care approach and Kaplan-Meier Sample Average method were used to estimate mean total and net 1- and 5-year costs (in 2015 US dollars) by cancer site, stage at diagnosis, and age group (<65 and ≥65 years). Results: Total and net costs were consistently highest for lung cancer and lowest for prostate cancer. Net costs were higher across all cancer sites for patients aged <65 years than those aged ≥65 years. Medical care costs for all cancers increased with advanced stage at diagnosis. Conclusions: This study improves understanding of medical care costs for the 4 most common invasive cancers in the United States. Higher costs among patients aged <65 years highlight limitations of relying on SEER-Medicare data alone to understand the national burden of cancer, whereas higher costs for patients with advanced-stage cancer underscore the importance of early detection to curtail high long-term costs. These cost estimates can be used in the development and evaluation of interventions and policies across the cancer care continuum.

Testing Cessation Messages for Cigarette Package Inserts: Findings from a Best/Worst Discrete Choice Experiment.

This study assessed smokers' responses to different smoking cessation topics and imagery for cigarette package inserts. Adult smokers from Canada (n = 1000) participated in three discrete choice experiments (DCEs): DCE 1 assessed five cessation benefit topics and five imagery types; DCE 2 assessed five messages with tips to improve cessation success and five imagery types; DCE 3 assessed four reproductive health benefits of cessation topics and four imagery types. In each DCE, participants evaluated four or five sets of four inserts, selecting the most and least motivating (DCEs 1 & 3) or helpful (DCE 2) for quitting. Linear mixed models regressed choices on insert and smoker characteristics. For DCE 1, the most motivating messages involved novel disease topics and imagery of younger women. For DCE 2, topics of social support, stress reduction and nicotine replacement therapy were selected as most helpful, with no differences by imagery type. For DCE 3, imagery influenced choices more than topic, with imagery of a family or a mom and baby selected as most motivating. Statistically significant interactions for all three experiments indicated that the influence of imagery type on choices depended on the message topic. Messages to promote smoking cessation through cigarette pack inserts should consider specific combinations of message topic and imagery.

Do you vape? Leveraging electronic health records to assess clinician documentation of electronic nicotine delivery system use among adolescents and adults.

Use of electronic nicotine delivery systems (ENDS) has increased substantially over the past decade. However, unlike smoking, which is systematically captured by clinicians through routine screening and discrete documentation fields in the electronic health record (EHR), unknown is the extent to which clinicians are documenting patients' use of ENDS. Data were gathered from medical visits with patients aged 12 and older (N=9,119; 55% male) treated in a large, integrated healthcare system. We used natural language processing to assess the incidence rates of clinician documentation of patients' ENDS use in unstructured tobacco comments in the EHR, and the words most frequently documented in relation to ENDS, from 2006-2015. ENDS documentation in the EHR increased dramatically over time (from 0.01 to 9.5 per 10,000 patients, p<0.0001), particularly among adults aged 18-24 and 25-44. Most prevalent were "e-cig," "electronic cigarettes", and "vape," with much variation in spelling and phrasing of these words. Records of adolescent and young adult patients were more likely to contain the word "vape", and less likely to have "e-cig" and "electronic cigarette" than records of adults (ps<0.0001). The relatively low observed number of patients with ENDS terms in the EHR suggested vast under documentation. While healthcare providers are increasingly documenting patients' use of ENDS in the EHR, overall documentation rates remain low. Discrete EHR fields for standard screening and documentation of ENDS that reflect the language used by patients would provide more complete longitudinal population-level surveillance of ENDS use and its association with short- and long-term health outcomes.

Use of Evidence-Based Prostate Cancer Imaging in a Nongovernmental Integrated Health Care System.

PURPOSE: The overuse of imaging, particularly for staging of low-risk prostate cancer, is well documented and widespread. The existing literature, which focuses on the elderly in fee-for-service settings, points to financial incentives as a driver of overuse and may not identify factors relevant to policy solutions within integrated health care systems, where physicians are salaried. METHODS: Imaging rates were analyzed among men with incident prostate cancer diagnosed between 2004 and 2011 within the Colorado and Northwest regions of Kaiser Permanente. The sample was stratified according to indication for imaging, ie, high risk for whom imaging was necessary versus low risk for whom imaging was discouraged. Logistic regression was used to model the association between imaging receipt and clinical/demographic patient characteristics by risk strata. RESULTS: Of the men with low-risk prostate cancer, 35% received nonindicated imaging at diagnosis, whereas 42% of men with high-risk prostate cancer did not receive indicated imaging. Compared with men diagnosed in 2004, those diagnosed in subsequent years were less likely to receive imaging across both risk groups. Men with high-risk cancer diagnosed at ≥ 65 years of age and those with clinical stage ≥ T2 were more likely to receive indicated imaging. Men with comorbidities were more likely to receive imaging across both risk groups. Men with low-risk prostate cancer who had higher median household incomes were less likely to receive nonindicated imaging. CONCLUSION: Nonindicated imaging for diagnostic staging of patients with low-risk prostate cancer was common, but has decreased over the past decade. These findings suggest that factors other than financial incentives may be driving overuse of imaging.

Positron emission tomography and stage migration in head and neck cancer.

IMPORTANCE: Since 2001, there has been a rapid adoption of positron emission tomography (PET) for diagnosis and American Joint Committee on Cancer (AJCC) staging of head and neck cancer (HNC) without data describing improved clinical outcomes. OBJECTIVE: To determine the association between increased use of PET and stage and/or survival for patients with HNC in the managed care environment. DESIGN, SETTING, AND PARTICIPANTS: Adult patients diagnosed as having HNC (n = 958) from 2000 to 2008 at 4 integrated health systems were identified via tumor registries linked to administrative data. The AJCC stage distribution, patient and treatment characteristics, and survival between pre-PET era (2000-2004) vs PET era (2005-2008) and use of PET vs no use of PET during the PET era were compared. The AJCC stages were categorized to represent localized (stage I or II), locally advanced (stage III, IVA, or IVB), and metastatic (stage IVC) disease. INTERVENTIONS: Treatments were determined by billing codes for surgery, radiation treatment, and chemotherapy. MAIN OUTCOMES AND MEASURES: The primary outcome for this study was the use of PET. Secondary outcomes included treatment received and 2-year survival. A logit model estimated the effects of PET on diagnosis of locally advanced disease. Kaplan-Meier estimates described overall survival differences between PET and non-PET. Cox regression evaluated the association of PET on survival in patients with locally advanced disease. RESULTS: An association between PET and locally advanced disease was found (odds ratio, 2.86 [95% CI, 1.90-4.29) (P < .001). Two-year overall survival for patients with locally advanced disease with and without PET was 52% and 32%, respectively (P = .004), but there was no difference for all stages (P = .69). On Cox proportional hazard regression, PET had no association with survival in patients with locally advanced disease (hazard ratio, 1.208 [95% CI, 0.778-1.877]) (P = .40). CONCLUSIONS AND RELEVANCE: The increasing use of PET among patients with HNC is associated with a greater number of patients with higher-stage disease and a dilution of the population with higher-stage disease with patients who have a better prognosis. Thus, the improved survival in patients with locally advanced disease likely reflects selection bias and stage migration. Further research on PET use among patients with HNC is necessary to determine if it results in improved treatment for individual patients.