Differences in Normative Beliefs and Tobacco Product Use by Age Among Adults Who Smoke: Cross-Sectional Analysis of a Nationally Representative Sample.

BACKGROUND: The prevalence of combusted cigarette (CC) smoking among older adults is stagnant, with 0 declines attributable to e-cigarette (EC) use. Given that normative beliefs are associated with quitting and switching to ECs, we assessed cross-sectional associations between age, CC, and EC descriptive and injunctive norms and potential interactions with tobacco use behavior. METHODS: Data are from people with current, established (≥100 lifetime CCs) CC use (n = 8072) at Wave 5 (2018-2019) of the adult Population Assessment of Tobacco and Health Study. We used adjusted multivariable logistic regressions to model social norms as a function of age (18-24, 25-34, 35-44, 45-54, 55-64, ≥65 years). We also dichotomized age (≥55 vs 18-54) to investigate interactions between age and social norms on past 12-month CC quit attempts and past-month EC use. RESULTS: Older age was positively associated with pro- and anti-CC norms and anti-EC norms. Significant interactive effects revealed that being advised to quit smoking by a healthcare provider was more strongly associated with CC quit attempts among adults ≥55 years (adjusted odds ratio [aOR] [95% CI]: 2.12 [1.66, 2.71]) than adults <55 years (aOR: 1.63 [1.34, 2.00]). Reporting people close to you use ECs was also more strongly associated with EC use among adults ≥55 years (aOR: 4.37 [3.35, 5.69]) than among adults <55 years (aOR: 3.43 [2.89, 4.08]). CONCLUSIONS: This study identified modifiable risk factors for tobacco use that may be particularly beneficial for older adults. Behavioral and communication interventions that target normative beliefs may maximize smoking cessation, or harm reduction when cessation is not possible.

A case-control survey study of environmental risk factors for primary hypoadrenocorticism in dogs.

BACKGROUND: Primary hypoadrenocorticism in dogs is thought to be multifactorial with roles for both genetic and environmental factors. The contributions of environmental factors remain unexplored. OBJECTIVE: Identify environmental and lifestyle exposures associated with primary hypoadrenocorticism in 2 dog breeds with high risk of developing the disease. ANIMALS: Animals were not used in this study. Owners of Standard Poodles (STPDs) and Portuguese water dogs (POWDs) participated in a survey. METHODS: Retrospective case-control study. Dog owners were invited to participate in an online survey through convenience sampling. Questions regarded the demographics, health histories, and indoor/outdoor environments in which their dogs live and play. Responses for dogs with primary hypoadrenocorticism were compared to those without the disease using univariate and multivariate logistic regression models. RESULTS: Five thousand forty-seven responses (358 cases, 4689 controls) met initial inclusion criteria. Significant associations with modest effect size were found for community type, ingestion of canned food, and use of lawn fertilizer in some analysis models. Reproductive (spay/neuter) status exhibited the strongest association with high effect size across all models with adjusted odds ratio (OR) 2.5 (95% confidence interval [CI], 1.4-4.5; P = .003) for spayed females and 6.0 (95% CI, 2.6-13.9; P < .001) for neutered males. CONCLUSIONS AND CLINICAL IMPORTANCE: The large effect size for reproductive status reflects its high potential clinical relevance, whereas modest effect sizes for other environmental variables suggest lower potential clinical relevance. These findings are associations and do not necessarily imply causation. Before any actionable recommendations are warranted, additional evidence regarding biological mechanisms is needed.

Illusion of filtration: Evidence from tobacco industry documents.

INTRODUCTION: We compared the design features of popular filtered and non-filtered cigarettes sold in the United States between 1960 and 1990, to assess the relationship between cigarette filter and tobacco weight. METHODS: We analyzed data on the design features of six popular filtered and three non-filtered cigarette brands sold in the US including the weight of tobacco used provided in the Cigarette Information Reports produced by Philip Morris Tobacco Company between 1960 and 1990. We also collected information on other design features such as stick length and circumference, the percentage of reconstituted tobacco in the blend, among other product parameters. We used joinpoint regression to test for trends in outcome variables for each brand assessed between 1960 and 1990. RESULTS: In all years, filtered cigarettes had less tobacco by weight compared to non-filtered cigarettes. The lower average weight of tobacco found in filtered cigarettes appears to be due to a combination of factors including stick and filter length, and the amount of reconstituted tobacco in the blend. The average percentages of total alkaloids and expanded tobacco increased over time but were similar between filtered and non-filtered brands. CONCLUSIONS: While various design features of popular filtered and non-filtered brands changed between 1960 and 1990, the observed reduction in tobacco weight among filtered brands was perhaps the most salient in terms of disease risk. Less tobacco in a filtered cigarette calls into question the presumed exclusive role of cigarette filter tips in the reduced health risks of filtered versus non-filtered cigarette smoking.

Practical guidance on modeling choices for the virtual twins method.

Individuals can vary drastically in their response to the same treatment, and this heterogeneity has driven the push for more personalized medicine. Accurate and interpretable methods to identify subgroups that respond to the treatment differently from the population average are necessary to achieving this goal. The Virtual Twins (VT) method is a highly cited and implemented method for subgroup identification because of its intuitive framework. However, since its initial publication, many researchers still rely heavily on the authors' initial modeling suggestions without examining newer and more powerful alternatives. This leaves much of the potential of the method untapped. We comprehensively evaluate the performance of VT with different combinations of methods in each of its component steps, under a collection of linear and nonlinear problem settings. Our simulations show that the method choice for Step 1 of VT, in which dense models with high predictive performance are fit for the potential outcomes, is highly influential in the overall accuracy of the method, and Superlearner is a promising choice. We illustrate our findings by using VT to identify subgroups with heterogeneous treatment effects in a randomized, double-blind trial of very low nicotine content cigarettes.

Tribal Tobacco Use Project II: Planning, Implementation, and Dissemination Using Culturally Relevant Data Collection among American Indian Communities.

American Indians have substantially higher commercial tobacco-related cancer rates when compared to the general population. To effectively combat commercial tobacco-related cancer, it is important that tribal nations obtain current and accurate community-specific data on commercial tobacco use and exposure-related attitudes and behaviors. With the goal to collect, synthesize, and disseminate data on tobacco use, including the role traditional tobacco plays among American Indian people, the American Indian Cancer Foundation (AICAF) and various stakeholders developed and implemented the Tribal Tobacco Use Project II (TTUP II) during 2018-2021. Building upon its predecessor, the Tribal Tobacco Use Project I (TTUP I), TTUP II used principles of community-based participatory research and culturally appropriate methods, such as Reality-Based Research, in partnership with tribal nations. We describe the TTUP II rationale, methods for participant recruitment and data collection, emphasizing the importance of using culturally relevant survey items to disentangle commercial tobacco use from traditional tobacco use. American Indian traditional tobacco is viewed as medicine in these communities with a unique socio-cultural context that must be addressed when engaging in commercial tobacco control efforts in American Indian communities. This approach may be useful to other tribal nations who are interested in conducting culturally relevant tobacco surveillance efforts.

Impact of nicotine reduction in cigarettes on smoking behavior and exposure: Are there differences by race/ethnicity, educational attainment, or gender?

BACKGROUND: Lowering nicotine in cigarettes may reduce smoking prevalences; however, it is not known whether an immediate or gradual reduction in nicotine is the optimal approach for all population groups. OBJECTIVES: We examined whether the optimal approach to nicotine reduction depended on the education, gender, or race of people who smoke and whether the optimal approach differentially benefited people who smoke based on their education, gender, or race. METHODS: Secondary analysis was conducted on a randomized clinical trial (N = 1250) comparing (1) immediate reduction from 15.5 to 0.4 mg of nicotine per gram of tobacco(mg/g);(2) gradual reduction to 0.4 mg/g;(3) control group with normal nicotine cigarettes(15.5 mg/g). Outcomes included cigarettes per day(CPD), carbon monoxide(CO), total nicotine equivalents(TNE), 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol and its glucuronides(NNAL), phenanthrene tetraol(PheT), N-Acetyl-S-(2-cyanoethyl)-l-cysteine(CEMA). Data were analyzed as area under the curve(AUC). RESULTS: Results were presented by education (High school[HS] or less n = 505, more than HS n = 745), gender (males n = 701, females n = 549), and race (Black participants n = 373,White participants n = 758). Regardless of education, gender, and race, CPD, CO, TNE, NNAL, PheT, and CEMA were lower in immediate versus gradual nicotine reduction. Comparing immediate versus the control, outcomes were lower for all subgroups; however, the magnitude of the effect for TNE varied by race. Specifically, geometric mean of the AUC of TNE in immediate versus gradual was 49 % lower in Black participants and 61 % lower in White participants (p-value = 0.047). CONCLUSIONS: Immediately reducing nicotine in cigarettes has the potential to benefit people who smoke across lower and higher educational attainment, male and female gender, and Black and White race.

Recommendations to researchers for aiding in increasing American Indian representation in genetic research and personalized medicine.

Increasing American Indian/Alaska Native (AI/AN) representation in genetic research is critical to ensuring that personalized medicine discoveries do not widen AI/AN health disparities by only benefiting well-represented populations. One reason for the under-representation of AIs/ANs in research is warranted research distrust due to abuse of some AI/AN communities in research. An approach to easing the tension between protecting AI/AN communities and increasing the representation of AI/AN persons in genetic research is community-based participatory research. This approach was used in a collaboration between a tribe and academic researchers in efforts to increase AI/AN participation in genetic research. From the lessons learned, the authors propose recommendations to researchers that may aid in conducting collaborative and respectful research with AI/AN tribes/communities and ultimately assist in increasing representation of AIs/ANs in personalized medicine discoveries.

Impact of Cigarette Filter Ventilation on U.S. Smokers' Perceptions and Biomarkers of Exposure and Potential Harm.

BACKGROUND: Relationships between cigarette filter ventilation levels, biomarkers of exposure (BOE) and potential harm (BOPH), and harm perceptions were examined. METHODS: Filter ventilation levels in cigarette brands were merged with Wave 1 (2013-2014) Population Assessment of Tobacco Use and Health study. Data were restricted to smokers who reported a usual brand and not regular users of other tobacco products. BOEs included nicotine, tobacco-specific nitrosamines, volatile organic compounds (VOC), and polycyclic aromatic hydrocarbons. BOPHs measured inflammation and oxidative stress. Perceived harm was assessed as self-reported risk of one's usual brand compared with other brands. RESULTS: Filter ventilation ranged from 0.2% to 61.1% (n = 1,503). Adjusted relationships between filter ventilation and BOE or BOPH were nonsignificant except for VOC N-acetyl-S-(phenyl)-L-cysteine (PHMA) and high-sensitivity C-reactive protein (hsCRP). In pairwise comparisons, PHMA was higher in quartile (Q) 4 (4.23 vs. 3.36 pmol/mg; P = 0.0103) and Q3 (4.48 vs. 3.36 pmol/mg; P = 0.0038) versus Q1 of filter ventilation and hsCRP comparisons were nonsignificant. Adjusted odds of perceiving one's own brand as less harmful was 26.87 (95% confidence interval: 4.31-167.66), 12.55 (3.01-52.32), and 19.18 (3.87-95.02) times higher in the Q2, Q3, and Q4 of filter ventilation compared with Q1 (P = 0.0037). CONCLUSIONS: Filter ventilation was not associated with BOE or BOPH, yet smokers of higher ventilated cigarettes perceived their brand as less harmful than other brands compared with smokers of lower ventilated cigarettes. IMPACT: Research to understand the impact of this misperception is needed, and remedial strategies, potentially including a ban on filter ventilation, are recommended.

Health Risk Factors in American Indian and Non-Hispanic White Homeless Adults.

Objectives: American Indians (AIs) are over-represented among homeless populations, but are understudied regarding their unique risk and resilience factors relative to non-Hispanic white (NHW) adults experiencing homelessness. In the current study, we aimed to address this gap. Methods: We recruited participants (108 AIs and 307 NHWs) from 6 homeless serving agencies in Oklahoma City, OK. Participants completed standard assessments of health, health behaviors, including alcohol and drug use, readiness to change endorsed health behaviors (eg, unsafe sex, fruit and vegetable intake, happiness with weight, physical activity), sleep location and quality, personal victimization, and discrimination. Results: Compared to NHWs, AIs endorsed greater alcohol use problems and were more likely to report having been arrested/booked for disorderly conduct or public drunkenness; however, AIs were less likely to report smoking cigarettes and reported greater readiness to change unsafe/unprotected sexual behaviors. Furthermore, compared to NHWs, AIs reported experiencing greater discrimination and were more likely to report sleeping outside or on the streets, versus in shelters; however, AIs reported fewer days of inadequate sleep. Conclusions: Findings suggest AI-specific risk and resilience factors for homelessness. This information can aid in treatment, service, and housing planning for this under-studied group who experiences some of the greatest health disparities.

Relationships Between Race, Gender, and Spot Urine Levels of Biomarkers of Tobacco Exposure Vary Based on How Creatinine Is Handled in Analyses.

INTRODUCTION: We illustrate the differential impact of common analysis approaches to handling urinary creatinine, a measure for urine dilution, on relationships between race, gender, and biomarkers of exposure measured in spot urine. METHODS: In smokers, spot urine levels of total nicotine equivalents (TNE, sum of total nicotine, total cotinine, and total 3'-hydroxycotinine) and total 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) overall and per cigarette were examined. Relationships between race (African Americans [AA] n = 373, Whites n = 758) or gender (males n = 629, females n = 502) and TNE or NNAL were examined using the following approaches to handling creatinine: (1) unadjusted/unstandardized; (2) standardization; (3) adjustment as a covariate. Significance was considered at p < .05. RESULTS: Creatinine was higher in AA versus Whites (1.19 vs. 0.96 mg/mL; p < .0001) and in males versus females (1.21 vs. 0.84 mg/mL; p < .0001). Independent of how creatinine was handled, TNE was lower among AA than Whites (TNE ratios AA vs. Whites: 0.67-0.84; p's < .05). Unadjusted TNE per cigarette was higher among AA versus Whites (ratio 1.12; p = .0411); however, the relationship flipped with standardization (ratio 0.90; p = .0360) and adjustment (ratio 0.95; p = .3165). Regarding gender, unadjusted TNE was higher among males versus females (ratio 1.13; p = .0063), but the relationship flipped with standardization (ratio 0.79; p < .0001) or adjustment (ratio 0.89; p = .0018). Unadjusted TNE per cigarette did not differ across gender (ratio 0.98; p = .6591), but lower levels were found in males versus females with standardization (ratio 0.68; p < .0001) and adjustment (ratio 0.74; p < .0001). NNAL displayed similar patterns. CONCLUSIONS: Relationships between race, gender, and spot urine levels of biomarkers of exposure can vary greatly based on how creatinine is handled in analyses. IMPLICATIONS: Lack of appropriate methods can lead to discrepancies across reports on variability of urinary biomarkers by race and gender. We recommend that for any analyses of biomarkers of exposure measure in spot urine samples across race, gender, or other population subgroups that differ in urinary creatinine levels, sensitivity analyses comparing the different methods for handling urinary creatinine should be conducted. If methods result in discrepant findings, this should be clearly noted and discussed.

Tobacco harm reduction: Past history, current controversies and a proposed approach for the future.

Tobacco harm reduction remains a controversial topic in tobacco control. Tobacco harm reduction involves providing tobacco users who are unwilling or unable to quit using nicotine products with less harmful nicotine-containing products for continued use. The skepticism towards harm reduction is based in part on the experience with low-yield tar/nicotine cigarettes, which were presumed to be associated with lower health risks than higher yield cigarettes and marketed as such by cigarette manufacturers. Only later did the field learn that these cigarettes were a deceptive way for cigarette manufacturers to allay the health concerns over cigarette smoking. Since this experience, there has been a proliferation of tobacco products that might potentially serve as a means to reduce tobacco harm. Some members of the tobacco control community believe that these products have great potential to reduce mortality and morbidity among smokers who completely switch to them. Others believe that we will be addicting another generation to tobacco products. This paper reviews the past history, the current tobacco landscape and controversies, and an approach that might rapidly reduce the yearly half-million deaths associated with cigarette smoking in the U.S.

Relationships between the Nicotine Metabolite Ratio and a Panel of Exposure and Effect Biomarkers: Findings from Two Studies of U.S. Commercial Cigarette Smokers.

BACKGROUND: We examined the nicotine metabolite ratio's (NMR) relationship with smoking intensity, nicotine dependence, and a broad array of biomarkers of exposure and biological effect in commercial cigarette smokers. METHODS: Secondary analysis was conducted on two cross-sectional samples of adult, daily smokers from Wave 1 (2013-2014) of the Population Assessment of Tobacco Use and Health (PATH) Study and baseline data from a 2014-2017 randomized clinical trial. Data were restricted to participants of non-Hispanic, white race. The lowest quartile of NMR (<0.26) in the nationally representative PATH Study was used to distinguish slow from normal/fast nicotine metabolizers. NMR was modeled continuously in secondary analysis. RESULTS: Compared with slow metabolizers, normal/fast metabolizers had greater cigarettes per day and higher levels of total nicotine equivalents, tobacco-specific nitrosamines, volatile organic componds, and polycyclic aromatic hydrocarbons. A novel finding was higher levels of inflammatory biomarkers among normal/fast metabolizers versus slow metabolizers. With NMR modeled as a continuous measure, the associations between NMR and biomarkers of inflammation were not significant. CONCLUSIONS: The results are suggestive that normal/fast nicotine metabolizers may be at increased risk for tobacco-related disease due to being heavier smokers, having higher exposure to numerous toxicants and carcinogens, and having higher levels of inflammation when compared with slow metabolizers. IMPACT: This is the first documentation that NMR is not only associated with smoking exposure but also biomarkers of biological effects that are integral in the development of tobacco-related disease. Results provide support for NMR as a biomarker for understanding a smoker's exposure and potential risk for tobacco-related disease.

The Impact of Gradual and Immediate Nicotine Reduction on Subjective Cigarette Ratings.

BACKGROUND: A recent clinical trial showed that an immediate transition to very low nicotine content (VLNC) cigarettes, compared with a gradual transition, produced greater reductions in smoking behavior, smoke exposure, and dependence. However, there was less compliance with the instruction to smoke only VLNC cigarettes in the immediate versus gradual reduction condition. The goal of this study was to test whether nicotine reduction method alters subjective ratings of VLNC cigarettes, and whether subjective ratings mediate effects of nicotine reduction method on smoking behavior, smoke exposure, dependence, and compliance. METHODS: This is a secondary analysis of a randomized trial conducted across 10 sites in the United States. Smokers (n = 1250) were randomized to either a control condition, or to have the nicotine content of their cigarettes reduced immediately or gradually to 0.04 mg nicotine/g of tobacco during a 20-week study period. Participants completed the modified Cigarette Evaluation Questionnaire (mCEQ). RESULTS: After Week 20, the immediate reduction group scored significantly lower than the gradual reduction group on multiple subscales of the mCEQ (ps < .001). The Satisfaction subscale of the mCEQ mediated the impact of nicotine reduction method on smoke exposure, smoking behavior, dependence, compliance, and abstinence. Other subscales also mediated a subset of these outcomes. CONCLUSIONS: An immediate reduction in nicotine content resulted in lower product satisfaction than a gradual reduction, suggesting that immediate reduction further reduces cigarette reward value. This study will provide the Food and Drug Administration with information about the impact of nicotine reduction method on cigarette reward value. IMPLICATIONS: These data suggest that an immediate reduction in nicotine content will result in greater reductions in cigarette satisfaction than a gradual reduction, and this reduction in satisfaction is related to changes in smoking behavior and dependence.

Pro-tobacco marketing and anti-tobacco campaigns aimed at vulnerable populations: A review of the literature.

INTRODUCTION: We reviewed research literature on pro-tobacco marketing and anti-tobacco campaigns targeting eight vulnerable populations to determine key findings and research gaps. Results can inform tobacco policy and control efforts and the design of public education campaigns for these groups. METHODS: Five journal databases in medicine, communication, and science, were used to identify 8875 peer-reviewed, original articles in English, published in the period 2004-2018. There were 144 articles that met inclusion criteria on pro-tobacco marketing or anti-tobacco campaigns aimed at eight US groups: women of reproductive age, racial/ethnic minority groups (African American, Hispanic/Latino, Asian/Pacific Islander and American Indian/Alaska Native), Lesbian/Gay/Bisexual/Transgender (LGBT) populations, groups with low socioeconomic status, rural/inner city residents, military/veterans, and people with mental health or medical co-morbidities. We summarized the number of articles for each population, type of tobacco, and pro-tobacco or anti-tobacco focus. Narrative summaries were organized by population and by pro-tobacco or anti-tobacco focus, with key strategies and gaps by group. RESULTS: There were more studies on pro-tobacco marketing rather than anti-tobacco campaigns, and on cigarettes rather than other tobacco products. Major gaps included studies on Asian Americans, American Indian/Alaska Natives, pregnant women, LGBT populations, and those with mental health or medical co-morbidities. Gaps related to tobacco products were found for hookah, snus, and pipe/roll-your-own tobacco in the pro-tobacco studies, and for all products except cigarettes in anti-tobacco studies. Common tobacco industry methods used were tailoring of product and package design and messages that were used to reach and appeal to different sociodemographic groups. Studies varied by research design making it difficult to compare results. CONCLUSIONS: We found major research gaps for specific groups and tobacco products. Public education campaigns need a stronger foundation in empirical studies focused on these populations. Research and practice would benefit from studies that permit comparisons across studies.

Biomarkers of Exposure and Potential Harm among Natural American Spirit Smokers.

OBJECTIVES: We compared biomarkers of exposure and potential harm in smokers of American Spirit (AS) to smokers of Marlboro, Newport, Camel, and Pall Mall. METHODS: We conducted secondary analysis on: (1) data from a randomized clinical trial (RCT); and (2) the Population Assessment of Tobacco Use and Health (PATH) Study. Biomarkers analyzed included: total nicotine equivalents (TNE); 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol and its glucuronides (total NNAL); N'-nitrosonornicotine and its N-glucuronide (total NNN);3-hydroxypropylmercapturic acid(3-HPMA); 2-hydroxypropylmercapturic acid (2-HPMA), 3-hydroxy-1 methylpropylmercapturic acid (HMPMA); S-phenylmercapturic acid(SPMA); 2-cyanoethylmercapturic acid (CEMA); phenanthrene tetraol(PheT);1-hydroxypyrene (1-HOP);8-iso-PGF2α; white blood count(WBC); prostaglandin E metabolite(PGEM); and high sensitivity C-reactive protein(hsCRP). RESULTS: AS smokers did not differ in TNE but had higher TNE per cigarette compared to other brands. Total NNAL, total NNN, CEMA, and 3-HPMA were lower in AS smokers. All other biomarkers were no different in AS smokers compared to all or the majority of the other brands. CONCLUSIONS: Levels of total NNAL, total NNN, acrylonitrile, and acrolein were reduced in AS smokers; however, it is not known whether reductions in exposure to these toxicants contribute to reduced harm. Higher TNE per cigarette smoked in AS smokers suggests a greater addictive potential compared to other brands. Regulatory action to ensure that consumers are not misled about the risks of the AS brand are recommended.

The impact of a brief cessation induction intervention for waterpipe tobacco smoking: A pilot randomized clinical trial.

BACKGROUND: Waterpipe (WP) tobacco smoking delivers many of the same harmful toxicants as cigarette smoking and is on the rise in the US. This study evaluated the feasibility and efficacy of a brief personalized feedback intervention in affecting changes in WP smoking among current WP smokers. METHODS: Participants (N=109) were recruited as they entered WP lounges and completed a questionnaire and exhaled carbon monoxide (eCO) testing before entering the WP lounge. Participants were cluster-randomized to assessment-only control (AOC) or intervention conditions. The intervention condition received health risk information and personalized feedback on pre- and post-WP session eCO levels. Participants completed a survey at the end of the WP session and at 3-month follow-up. RESULTS: Compared to control, the intervention was effective in increasing knowledge of WP-related harms, correcting risk perceptions, increasing importance of quitting WP smoking, and increasing confidence in ability to quit WP smoking at post-WP session (p<0.05). Differences were maintained for knowledge of WP-related harms, risk perceptions, and commitment to quitting WP at 3-month follow-up; however, no significant difference (p>0.05) was observed in WP smoking (i.e., days smoked and number of WPs smoked) at 3-month follow-up between the intervention (M=3.97days, SD=9.83; M=6.45 bowls, SD=19.60) and control conditions (M=3.32days, SD=5.24; M=3.49 bowls, SD=5.10). CONCLUSIONS: The current research supports the use of personalized feedback as a useful intervention method to increase commitment to quit WP, but suggests more intensive interventions may be necessary to achieve WP cessation.