Warning Labels as a Public Health Intervention: Effects and Challenges for Tobacco, Cannabis, and Opioid Medications.

Warning labels help consumers understand product risks, enabling informed decisions. Since the 1966 introduction of cigarette warning labels in the United States, research has determined the most effective message content (health effects information) and format (brand-free packaging with pictures). However, new challenges have emerged. This article reviews the current state of tobacco warning labels in the United States, where legal battles have stalled pictorial cigarette warnings and new products such as electronic cigarettes and synthetic nicotine products pose unknown health risks. This article describes the emerging research on cannabis warnings; as more places legalize recreational cannabis, they are adopting lessons from tobacco warnings. However, its uncertain legal status and widespread underestimation of harms impede strict warning standards. The article also reviews opioid medication warning labels, suggesting that lessons from tobacco could help in the development of effective and culturally appropriate FDA-compliant opioid warning labels that promote safe medication use and increased co-dispensing of naloxone.

Should we depend on reference intervals from manufacturer package inserts? Comparing TSH and FT4 reference intervals from four manufacturers with results from modern indirect methods and the direct method.

OBJECTIVES: Correct interpretation of thyroid function tests relies on correct reference intervals (RIs) for thyroid-stimulating hormone (TSH) and free thyroxine (FT4). ISO15189 mandates periodic verification of RIs, but laboratories struggle with cost-effective approaches. We investigated whether indirect methods (utilizing historical laboratory data) could replace the direct approach (utilizing healthy reference individuals) and compared results with manufacturer-provided RIs for TSH and FT4. METHODS: We collected historical data (2008-2022) from 13 Dutch laboratories to re-establish RIs by employing indirect methods, TMC (for TSH) and refineR (for FT4). Laboratories used common automated platforms (Roche, Abbott, Beckman or Siemens). Indirect RIs (IRIs) were determined per laboratory per year and clustered per manufacturer (>1.000.000 data points per manufacturer). Direct RIs (DRIs) were established in 125 healthy individuals per platform. RESULTS: TSH IRIs remained robust over the years for all manufacturers. FT4 IRIs proved robust for three manufacturers (Roche, Beckman and Siemens), but the IRI upper reference limit (URL) of Abbott showed a decrease of 2 pmol/L from 2015. Comparison of the IRIs and DRIs for TSH and FT4 showed close agreement using adequate age-stratification. Manufacturer-provided RIs, notably Abbott, Roche and Beckman exhibited inappropriate URLs (overall difference of 0.5-1.0 µIU/mL) for TSH. For FT4, the URLs provided by Roche, Abbott and Siemens were overestimated by 1.5-3.5 pmol/L. CONCLUSIONS: These results underscore the importance of RI verification as manufacturer-provided RIs are often incorrect and RIs may not be robust. Indirect methods offer cost-effective alternatives for laboratory-specific or platform-specific verification of RIs.

Minimum labelling requirements for dermatology artificial intelligence-based Software as Medical Device (SaMD): A consensus statement.

BACKGROUND/OBJECTIVES: Artificial intelligence (AI) holds remarkable potential to improve care delivery in dermatology. End users (health professionals and general public) of AI-based Software as Medical Devices (SaMD) require relevant labelling information to ensure that these devices can be used appropriately. Currently, there are no clear minimum labelling requirements for dermatology AI-based SaMDs. METHODS: Common labelling recommendations for AI-based SaMD identified in a recent literature review were evaluated by an Australian expert panel in digital health and dermatology via a modified Delphi consensus process. A nine-point Likert scale was used to indicate importance of 10 items, and voting was conducted to determine the specific characteristics to include for some items. Consensus was achieved when more than 75% of the experts agreed that inclusion of information was necessary. RESULTS: There was robust consensus supporting inclusion of all proposed items as minimum labelling requirements; indication for use, intended user, training and test data sets, algorithm design, image processing techniques, clinical validation, performance metrics, limitations, updates and adverse events. Nearly all suggested characteristics of the labelling items received endorsement, except for some characteristics related to performance metrics. Moreover, there was consensus that uniform labelling criteria should apply across all AI categories and risk classes set out by the Therapeutic Goods Administration. CONCLUSIONS: This study provides critical evidence for setting labelling standards by the Therapeutic Goods Administration to safeguard patients, health professionals, consumers, industry, and regulatory bodies from AI-based dermatology SaMDs that do not currently provide adequate information about how they were developed and tested.

Chemical analysis of fresh and aged Australian e-cigarette liquids.

OBJECTIVES: To assess the chemical composition of electronic cigarette liquids (e-liquids) sold in Australia, in both their fresh and aged forms. DESIGN, SETTING: Gas chromatography-mass spectrometry analysis of commercial e-liquids sold in Australia (online and physical stores). MAIN OUTCOME MEASURES: Chemical composition of 65 Australian e-liquids - excipients/solvents, flavouring chemicals, other known e-liquid constituents (including nicotine), and polycyclic aromatic hydrocarbons - before and after an accelerated ageing process that simulated the effects of vaping. RESULTS: The measured levels of propylene glycol and glycerol often diverged from those recorded on the e-liquid label. All e-liquids contained one or more potentially harmful chemicals, including benzaldehyde, menthol, trans-cinnamaldehyde, and polycyclic aromatic hydrocarbons. Nicotine or nicotyrine were detected in a small proportion of e-liquids at extremely low concentrations. CONCLUSIONS: Australian e-liquids contain a wide variety of chemicals for which information on inhalation toxicity is not available. Further analyses are required to assess the potential long term effects of e-cigarette use on health.

A cross-industry collaboration to assess if acute oral toxicity (Q)SAR models are fit-for-purpose for GHS classification and labelling.

This study assesses whether currently available acute oral toxicity (AOT) in silico models, provided by the widely employed Leadscope software, are fit-for-purpose for categorization and labelling of chemicals. As part of this study, a large data set of proprietary and marketed compounds from multiple companies (pharmaceutical, plant protection products, and other chemical industries) was assembled to assess the models' performance. The absolute percentage of correct or more conservative predictions, based on a comparison of experimental and predicted GHS categories, was approximately 95%, after excluding a small percentage of inconclusive (indeterminate or out of domain) predictions. Since the frequency distribution across the experimental categories is skewed towards low toxicity chemicals, a balanced assessment was also performed. Across all compounds which could be assigned to a well-defined experimental category, the average percentage of correct or more conservative predictions was around 80%. These results indicate the potential for reliable and broad application of these models across different industrial sectors. This manuscript describes the evaluation of these models, highlights the importance of an expert review, and provides guidance on the use of AOT models to fulfill testing requirements, GHS classification/labelling, and transportation needs.

Optimizing Warnings on E-Cigarette Advertisements.

INTRODUCTION: We examined the effect of visual optimizations on warning text recall. METHODS: We used Amazon's Mechanical Turk to recruit 1854 young adult (18-34 years) electronic cigarette (e-cigarette) users or susceptible nonusers. We conducted a between-subjects 3 × 2 × 2 experiment to examine the influence of color (black text on white background [BW] vs. black on yellow [BY] vs. yellow on black [YB]), shape (rectangle vs. novel), and signal word (presence vs. absence of the word "warning"). We randomized participants to view one of 12 warnings on a fictional e-cigarette advertisement. We coded open-ended recall responses into three categories: (1) recalled nothing, (2) recalled something, (3) recalled the concept. We examined main effects on warning text recall using multinomial regression. We examined differences in attention, perceived message effectiveness, and appeal. RESULTS: Those exposed to BW or BY warnings were more likely than those exposed to YB to recall something (AOR = 1.6, AOR = 1.5, respectively) or the concept (OR = 1.4, BW). Those exposed to novel shape (44.7% novel vs. 37.9% rectangle; p = .003) or color (44.5% BY vs. 41.9% YB vs. 37.5% BW; p = .04) warnings were more likely to report attention to the warning. In aided recall, those exposed to the signal word were more likely than those not exposed to select the correct response (64.0% vs. 31.3%; p < .0001). We did not find differences for message effectiveness or appeal. CONCLUSIONS: Visual optimizations such as color may influence warning text recall and should be considered for new warnings. Research should continue exploring variations for advertisement warnings to maximize attention to warning text. IMPLICATIONS: This study examines the impact of visual optimizations on recall of the US Food and Drug Administration-mandated e-cigarette advertisement warning text. We found that color might influence warning text recall, but we did not find effects for shape or signal word. It is possible the newly mandated e-cigarette advertisement warnings, which are required to occupy at least 20% of the advertisement, are currently novel enough to attract attention. Future research should examine optimizations following implementation of the new advertisement warnings.

Health and Economic Impact of Health Warnings and Plain Tobacco Packaging in Seven Latin American Countries: Results of a Simulation Model.

INTRODUCTION: The burden of disease attributable to tobacco use in Latin America is very high. Our objective was to evaluate the 10-year potential impact of current legislation related to cigarette packaging and warnings and expected effects of moving to a higher level of strategies implementing cigarette plain packaging on health and cost outcomes in Argentina, Bolivia, Brazil, Chile, Colombia, Mexico, and Peru, using a microsimulation model. AIMS AND METHODS: We used a probabilistic state-transition microsimulation model, considering natural history, costs, and quality of life losses associated with main tobacco-related diseases. We followed up individuals in hypothetical cohorts and calculated health outcomes annually to obtain aggregated long-term population health outcomes and costs. We performed a literature review to estimate effects and analyzed studies and information from ministries, relevant organizations, and national surveys. We calibrated the model comparing the predicted disease-specific mortality rates with local statistics. RESULTS: Current graphic warnings already in place in each country could avert, during 10 years, 69 369 deaths and 638 295 disease events, adding 1.2 million years of healthy life and saving USD 5.3 billion in the seven countries. If these countries implemented plain packaging strategies, additional 155 857 premature deaths and 4 133 858 events could be averted, adding 4.1 million healthy years of life and saving USD 13.6 billion in direct health care expenses of diseases attributable to smoking. CONCLUSIONS: Latin American countries should not delay the implementation of this strategy that will alleviate part of the enormous health and financial burden that tobacco poses on their economies and health care systems. IMPLICATIONS: Tobacco smoking is the single most preventable and premature mortality cause in the world. The Framework Convention on Tobacco Control, supported by the World Health Organization, introduced a package of evidence-based measures for tobacco control. This study adds evidence on the potential health effects and savings of implementing cigarette plain packaging in countries representing almost 80% of the Latin American population; findings are valuable resources for policy makers in the region.

An Experimental Study of Nicotine Warning Statements in E-cigarette Tweets.

INTRODUCTION: It is unclear whether warnings on electronic cigarette (e-cigarette) advertisements required by the US Food and Drug Administration (FDA) will apply to social media. Given the key role of social media in marketing e-cigarettes, we seek to inform FDA decision making by exploring how warnings on various tweet content influence perceived healthiness, nicotine harm, likelihood to try e-cigarettes, and warning recall. METHODS: In this 2 × 4 between-subjects experiment participants viewed a tweet from a fictitious e-cigarette brand. Four tweet content versions (e-cigarette product, e-cigarette use, e-cigarette in social context, unrelated content) were crossed with two warning versions (absent, present). Adult e-cigarette users (N = 994) were recruited via social media ads to complete a survey and randomized to view one of eight tweets. Multivariable regressions explored effects of tweet content and warning on perceived healthiness, perceived harm, and likelihood to try e-cigarettes, and tweet content on warning recall. Covariates were tobacco and social media use and demographics. RESULTS: Tweets with warnings elicited more negative health perceptions of the e-cigarette brand than tweets without warnings (p < .05). Tweets featuring e-cigarette products (p < .05) or use (p < .001) elicited higher warning recall than tweets featuring unrelated content. CONCLUSIONS: This is the first study to examine warning effects on perceptions of e-cigarette social media marketing. Warnings led to more negative e-cigarette health perceptions, but no effect on perceived nicotine harm or likelihood to try e-cigarettes. There were differences in warning recall by tweet content. Research should explore how varying warning content (text, size, placement) on tweets from e-cigarette brands influences health risk perceptions. IMPLICATIONS: FDA's 2016 ruling requires warnings on advertisements for nicotine-containing e-cigarettes, but does not specify whether this applies to social media. This study is the first to examine how e-cigarette warnings in tweets influence perceived healthiness and harm of e-cigarettes, which is important because e-cigarette brands are voluntarily including warnings on Twitter and Instagram. Warnings influenced perceived healthiness of the e-cigarette brand, but not perceived nicotine harm or likelihood to try e-cigarettes. We also saw higher recall of warning statements for tweets featuring e-cigarettes. Findings suggest that expanding warning requirements to e-cigarette social media marketing warrants further exploration and FDA consideration.

Risk communication for labeling all ingredients in consumer products.

The labeling of all ingredients contained in consumer products has been requested by consumers concerned regarding their safety. Consequently, regulatory agencies have set guidelines for industries on how to provide safety information regarding the ingredients in their products. However, discordant opinions were raised from stakeholders, resulting in the formation of a risk communication forum among industries, regulatory agencies, consumer groups, and academia. There are several methods that might be utilized to provide ingredient information to consumers: (1) listing all ingredients on the label of products, (2) providing major ingredients on the label of products, (3) presenting all ingredients on the websites of each manufacturer, and (4) listing major ingredients on the label of products and the remainder of ingredients (not on the label) on the websites. Each method might have its own advantages and disadvantages with respect to providing the information regarding the names of the ingredients used in consumer products to the consumers. A continuous risk communication forum might be an effective tool to facilitate an improved understanding of chemical information, toxicological science, regulatory guidelines, labeling methods, and consumers' concern. This study suggests that risk communication efforts may be helpful and a good opportunity for stakeholders to exchange opinions and reach a harmonious conclusion on labeling of consumer products ingredients.

Utility of a US Food and Drug Administration (FDA) label indication for condoms for anal sex.

Condoms are highly effective for HIV prevention, yet are not currently indicated by the US Food and Drug Administration (FDA) for anal sex. We surveyed a national sample of men who have sex with men to assess whether FDA label indication could affect anticipated condom use, and to determine levels of perceived condom failure for anal sex. We found that 69% of respondents anticipated that a label indication change would increase their likelihood of condom use. Median perceived failure was 15%. We anticipate that these results may aid the FDA in developing standards for a label indication for anal sex.

Mass-scale red cell genotyping of blood donors: from data visualization to historical antigen labeling and donor recruitment.

Donor red cell genotyping provides efficiencies to identify "in demand" blood donors for transfusion recipients requiring antigen-negative blood. Donor red cell genotype information can be used to label units with historical types and introduced throughout the supply chain from the blood center to the hospital transfusion service and has potential to be used in recruitment strategies.

Patient-Reported Outcomes in Orphan Drug Labels Approved by the US Food and Drug Administration.

OBJECTIVES: In recent years, there has been increasing recognition of the need to assess treatment benefit from the patient's perspective. The extent of patient-reported outcome (PRO) data included in labeling for rare disease treatment is largely unknown. The objective of this study was to review trends over time for PRO-based labeling granted by the US Food and Drug Administration (FDA) for orphan drugs. STUDY DESIGN: Review of FDA package inserts. METHODS: Products included in this analysis were all new molecular entities (NMEs) and biologic license applications (BLAs) with orphan designations approved by the FDA from 2002 through 2017. For identified products, package inserts were reviewed to determine the number and type of PRO claim(s) granted, endpoint status, and PRO measure named. Two trends were analyzed: (1) over all years 2002 to 2017 and (2) 2002 to 2017 stratified into 3 periods (before draft FDA PRO guidance [2006], between draft and final guidance release, and after final guidance [2009] release. RESULTS: A total of 156 NMEs and BLAs with orphan designations were approved between 2002 and 2017. Of these, 13 products (8.3%) had PRO-based labeling, and 7 of 13 were symptom-related. The percent of orphan drugs approved with PRO-based labeling between 2002 and 2005, 2006 and 2008, and 2009 and 2017 was 0, 10.5, and 9.9, respectively. CONCLUSIONS: In FDA-approved labeling for orphan therapies, PRO measures used as primary and secondary endpoints increased after draft FDA PRO guidance release but remained relatively low thereafter. It is important to understand barriers to PRO measure use to ensure that treatments capture perspectives of patients with rare diseases.

Lightweight Lead Aprons: The Emperor's New Clothes in the Angiography Suite?

OBJECTIVE: The aim was to determine whether lead containing and lead free composite garments in current use provide the level of radiation protection stated by manufacturers. METHODS: Fifteen garments, produced by five different manufacturers using eight different composites, were randomly selected for testing from four hospitals in South Australia. Labelling, material composition, design, and condition of the garments were assessed by direct garment examination, garment label, and product information. Garment attenuation was tested in a simulated angiography suite using a Siemens Ysio Max digital Xray machine. The front and back panels of each garment were tested under direct beam at 100 kVp. A Perspex phantom was used to simulate the density and scatter properties of the human abdomen. The front panels of each garment were tested under scattered radiation at Xray tube voltages of 50 and 70 kVp. RESULTS: Forty-seven per cent of front panels and 90% of back panels provided lower lead equivalence than claimed by the manufacturer. Twenty per cent of front panels and 62% of back panels tested did not meet the minimum International Electrotechnical Commission requirements for angiographic use. There was a 38 fold difference in front panel performance of garments to scatter radiation, which were all labelled 0.5 mm lead equivalence. 56% of garments had differences in scatter transmission of at least 49% when tested at 50 and 70 kVp. CONCLUSION: The results show that lead containing and lead free composite garments probably provide less radiation protection than manufacturer stated lead equivalence. The demonstrated wide variations in attenuation of scatter radiation are greater than previously reported. It was found that most garments failed to comply with labelling standards. The study highlights challenges in radiation shielding and the need to identify composites that consistently provide better attenuation per unit weight than lead.

Temporal Effects of Message Congruency on Attention to and Recall of Pictorial Health Warning Labels on Cigarette Packages.

OBJECTIVES: Recent research has shown that message congruency is beneficial to recall of pictorial health warning label (PWL) content after initial exposure. Despite less attention to the text warning, smokers exposed to congruent PWLs were more likely to recall the text and the message. This study aimed to replicate these findings and to examine whether congruency also affects recall after multiple exposures over time. METHODS: A total of 320 daily smokers (39.7% female; cigarettes/day: M = 15.31, SD = 7.15) were randomized to one congruent or incongruent PWL and attended 4 laboratory sessions over 10 days. During each session, eye movements were recorded while viewing the PWL and open-ended recall of label content was assessed after exposure. RESULTS: Smokers who were exposed to a congruent PWL were more likely to recall the text (p = .01) and the message (p = .02) and less likely to recall the image (p = .003) of the PWL after initial exposure. By day 4, incongruent PWLs were recalled equally well as congruent PWLs. Independent of condition, image recall was initially high and remained high whereas text and message recall was relatively low initially but increased over time. It was not until day 7 that about 80% of text and message recall was observed. CONCLUSIONS: Even when exposed to the same PWL over time, smokers require multiple exposures to recall the text and the message of a PWL. More research on the effects of congruency in the natural environment, where smokers are exposed to multiple PWLs, is needed. IMPLICATIONS: The findings of this study, and of previous work showing that message congruency in PWLs is beneficial to initial recall of PWL content, could potentially help to address legal challenges regarding the implementation of PWLs in the United States. Factually correct text warnings have been uncontested on US cigarettes packages since 1966. Congruent PWLs simply provide a means to visually support the same information as the existing text using a medium that better garners attention to the health information. Investigating and understanding longer-term effects of congruency are important and can empirically inform future warning label development, both in the United States via the Family Smoking Prevention and Tobacco Control Act, and via other governing bodies.

Advancing Tobacco Product Warning Labels Research Methods and Theory: A Summary of a Grantee Meeting Held by the US National Cancer Institute.

BACKGROUND: The World Health Organization's Framework Convention on Tobacco Control recommends prominent pictorial health warnings on tobacco products. To advance research methods, theory and understanding of how tobacco product warning labels (TPWLs) work, the US National Cancer Institute convened a grantee meeting. Our article describes the key insights that emerged from the meeting, situated within the context of the scientific literature. RESULTS & RECOMMENDATIONS: First, presentations confirmed that large, pictorial TPWLs motivate people to try to quit and encourage smoking cessation. Second, pictorial TPWLs increase attention, knowledge, negative affect, and thinking about the warning. Third, TPWL studies have primarily used brief-exposure laboratory studies and observational studies of sustained exposure through national policy implementation, with a few randomized trials involving several weeks of exposure-with generally consistent results found across study designs. Fourth, novel assessment methods include brain imaging, eye tracking and "best-worst" discrete choice experiments. To make TPWL even more effective, research is needed to confirm the mechanisms of their influence, their impact across vulnerable populations, and their effect on social media posts about tobacco products. Research is also needed on the effect of trial design choices, the predictive validity of new measurement approaches, and warning labels for non-cigarette tobacco products. IMPLICATIONS: To improve scientific understanding of TPWL effects, this grantee meeting summary describes emerging research methods, theory and study results. Directions for future research include examination of the mechanisms of how warning labels work across diverse tobacco products and across different populations and contexts.

Consumer Perceptions of Cigarette Design in France: A Comparison of Regular, Slim, Pink and Plain Cigarettes.

INTRODUCTION: The cigarette, like the cigarette pack, is used by tobacco companies as a promotional tool. We explore how the cigarette could potentially be used as a dissuasive tool. METHODS: An online survey was conducted with 15-30-year-old smokers and nonsmokers (N = 998) in France to explore their perceptions of a plain cigarette (gray with no brand name) and three branded cigarettes (regular, slim, pink). Participants were randomly assigned to view the plain cigarette and either the regular, slim, or pink cigarette. They were asked to rate the cigarettes by Appeal (tastiest, highest quality, and most expensive), Harm (most dangerous and most effective for motivating people to talk about tobacco dangers), and Perceived behavioral impact (most effective to convince teenagers not to start and to motivate smokers to reduce consumption and quit). RESULTS: In comparison to the gray cigarette, each of the branded cigarettes were considered more appealing, less harmful, and more likely to motivate teenagers to start and less likely to motivate smokers to reduce consumption or quit. CONCLUSIONS: The study suggests that altering the appearance of the cigarette may reduce cigarette appeal, increase harm perceptions, and deter both young people and smokers. IMPLICATIONS: Very little research has focused on dissuasive cigarettes whereas the cigarette stick has become very important for tobacco companies for communication purposes. This is the first study to compare the effect of various branded cigarettes (regular, slim, and pink) with a plain gray cigarette on young adult smokers and nonsmokers. The findings suggest that a plain gray cigarette can reduce cigarette appeal, increase perceptions of harm, and may deter use among both smokers and nonsmokers.

Pilot implementation of a monitoring and enforcement system for the International Code of Marketing of Breast-milk Substitutes in Cambodia.

Globally, monitoring and enforcement mechanisms for the World Health Organization's International Code of Marketing of Breast-milk Substitutes are often lacking. The Cambodian government adopted the Code as the national standard in Sub-Decree 133 on Marketing of Products for Infant and Young Child Feeding. Following the formation of a multisectoral Oversight Board and development of detailed guidance documents for the implementation and enforcement of Sub-Decree 133, a 7-month pilot was conducted in 2017 to trial a monitoring system in four urban areas of Cambodia. The pilot included training of monitors from the Ministries of Health and Commerce, screening for violations at retail locations and health facilities, testing reporting mechanisms, and taking actions against violators. During the pilot, 85 national- and subnational-level monitors were trained, 392 site visits were made, 2,377 monitoring checklists were completed, and 11 warning letters were issued to violators. Half of the completed checklists (52.9%) indicated Code violations, yet monitors submitted zero violation reports. The pilot revealed modifications needed to the monitoring system: integrate monitor trainings into existing ministry training curricula for sustainability; enhance targeting of monitors for Sub-Decree training; delineate clear roles and responsibilities for the national and subnational levels; simplify monitoring checklists and violation reports; and improve integration of monitoring activities into routine ministry operations. Before the Sub-Decree 133 monitoring and enforcement system is implemented throughout Cambodia, revisions must be made to ensure the viability of this system. Challenges and lessons learned can also guide Code monitoring efforts being undertaken by other countries.

Warning Statements and Safety Practices Among Manufacturers and Distributors of Electronic Cigarette Liquids in the United States.

Introduction: Prior to the US Food and Drug Administration's (FDA) regulation of electronic cigarettes and warning statements related to nicotine addiction, there was no critical examination of manufacturer/distributor voluntary practices that could potentially inform FDA actions aimed to protect consumers. This study examined the content of warning statements and safety characteristics of electronic cigarette liquid bottles using a national sample. Methods: Research staff randomly selected four electronic cigarette liquid manufacturers/distributors from four US geographic regions. Staff documented the characteristics of product packaging and content of warning statements on 147 electronic cigarette liquids (0-30 mg/ml of nicotine) purchased online from 16 manufacturers/distributors in April of 2016. Results: Data showed that 97.9% of the electronic cigarette liquid bottles included a warning statement, most of which focused on nicotine exposure rather than health. Only 22.4% of bottles used a warning statement that indicated the product "contained nicotine." Of bottles that advertised a nicotine-based concentration of 12 mg/ml, 26% had a warning statements stated that the product "contains nicotine." None of the statements that indicated that the product "contained nicotine" stated that nicotine was "addictive." All bottles had a safety cap and 12% were in plastic shrink-wrap. Fifty-six percent of the websites had a minimum age requirement barrier that prevented under-aged persons from entering. Conclusions: Most manufacturers/distributors printed a warning statement on electronic cigarette liquid bottles, but avoided warning consumers about the presence and the addictiveness of nicotine. Studies are needed to examine manufacturer/distributor modifications to product packaging and how packaging affects consumer behaviors. Implications: These data can inform future FDA requirements related to the packaging and advertising of e-cigarette liquids; regulation related to the content of warning statements, including exposure warning statements, which are not currently mandated; and requirements on websites or language on packaging to help manufacturers adhere to the minimum age of purchase regulation. The data can also be used to help FDA develop additional guidance on the framing of statements on packaging that helps consumers make informed decisions about purchasing the product or protecting young people from use or unintentional exposure to the product.

Is the WHO Creating Unnecessary Confusion Over Breast Milk Substitutes?

A recent statement by WHO that "breast milk substitutes should be understood to include any milks …that are specifically marketed for feeding infants and young children up to the age of 3 years" differs significantly from the definition in the International Code which states "a breast milk substitute is any food being marketed or otherwise presented as a partial or total replacement for breast milk, whether or not suitable for that purpose." The new interpretation, which lacks consultation and endorsement, is also ambiguous, with the boundaries between breast milk substitutes and complementary foods being blurred during the first 3 years of life. The logical definitions of breast milk substitutes and complementary foods contained within the Code should be maintained and inappropriate promotion of foods and fluids for infants and young children should be addressed through effective regulation of composition and labelling standards.

Observed smoking and tobacco pack display in Australian outdoor cafés 2 years after implementation of plain packaging.

Background: Implementation of tobacco plain packaging (PP) in Australia in December 2012 was associated with significant reductions in the percentage of patrons at outdoor cafés observed to be displaying tobacco packs and actively smoking, immediately post-implementation and 1 year later. This study examines whether these positive effects were sustained through to 2 years post-PP. Methods: An observational study conducted at cafés, restaurants and bars with outdoor seating in Melbourne, Australia documented the number of: patrons; patrons actively smoking; tobacco packs on display; orientation and type of displayed packs and whether or not children were present. Data were collected pre-PP (2012), early post-PP (2013), 1 year post-PP (2014) and 2 years post-PP (2015). Multilevel Poisson regressions analyzed changes in each outcome, adjusting for important covariates. Results: Overall, positive effects of PP implementation on tobacco pack display and active smoking were not fully sustained through to 2 years post-PP for the total sample. Interactions between phase and the presence of children indicated that pack display and active smoking were lower in all post-implementation phases (compared with pre-PP) at venues where children were present but not at venues where children were not present. Conclusions: Children at outdoor cafés were still being exposed to less tobacco packaging and active smoking, 2 years after implementation of the packaging changes. More regular refreshment of graphic health warnings is likely to be required to sustain these effects, and to reduce pack display behaviour at venues with no children.