A Comprehensive Framework for Evaluating the Value Created by Real-World Evidence for Diverse Stakeholders: The Case for Coordinated Registry Networks.

OBJECTIVES: This manuscript presents a comprehensive framework for the assessment of the value of real-world evidence (RWE) in healthcare decision-making. While RWE has been proposed to overcome some limitations of traditional, one-off studies, no systematic framework exists to measure if RWE actually lowers the burden. This framework aims to fill that gap by providing conceptual approaches for evaluating the time and cost efficiencies of RWE, thus guiding strategic investments in RWE infrastructure. METHODS: The framework consists of four components: (114th Congress. 21st Century Cures Act.; 2015. https://www.congress.gov/114/plaws/publ255/PLAW-114publ255.pdf .) identification of stakeholders using and producing RWE, (National Health Council. Glossary of Patient Engagement Terms. Published 2019. Accessed May 18. 2021. https://nationalhealthcouncil.org/glossary-of-patient-engagement-terms/ .) understanding value propositions on how RWE can benefit stakeholders, (Center for Drug Evaluation and Research. CDER Patient-Focused Drug Development. U.S. Food & Drug Administration.) defining key performance indicators (KPIs), and (U.S. Department of Health and Human Services - Food and Drug Administration: Center for Devices and Radiological Health and Center for Biologics Evaluation and Research. Use of Real-World Evidence to Support Regulatory Decision-Making for Medical Devices - Guidance for Industry and Food and Drug Administration Staff. 2017. http://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guida .) establishing metrics and case studies to assess value. KPIs are categorized as 'better, faster, or cheaper" as an indicator of value: better focusing on high-quality actionable evidence; 'faster,' denoting time-saving in evidence generation, and 'cheaper,' emphasizing cost-efficiency decision compared to methodologies that do not involve data routinely collected in clinical practice. Metrics and relevant case studies are tailored based on stakeholder value propositions and selected KPIs that can be used to assess what value has been created by using RWE compared to traditional evidence-generation approaches and comparing different RWE sources. RESULTS: Operationalized through metrics and case studies drawn from the literature, the value of RWE is documented as improving treatment effect heterogeneity evaluation, expanding medical product labels, and expediting post-market compliance. RWE is also shown to reduce the cost and time required to produce evidence compared to traditional one-off approaches. An original example of a metric that measures the time saved by RWE methods to detect a signal of a product failure was presented based on analysis of the National Cardiovascular Disease Registry. CONCLUSIONS: The framework presented in this manuscript offers a comprehensive approach for evaluating the value of RWE, applicable to all stakeholders engaged in leveraging RWE for healthcare decision-making. Through the proposed metrics and illustrated case studies, valuable insights are provided into the heightened efficiency, cost-effectiveness, and improved decision-making within clinical and regulatory domains facilitated by RWE. While this framework is primarily focused on medical devices, it could potentially inform the determination of RWE value in other medical products. By discerning the variations in cost, time, and data utility among various evidence-generation methods, stakeholders are empowered to invest strategically in RWE infrastructure and shape future research endeavors.

Data sources and applied methods for paclitaxel safety signal discernment.

Background: Following the identification of a late mortality signal, the Food and Drug Administration (FDA) convened an advisory panel that concluded that additional clinical study data are needed to comprehensively evaluate the late mortality signal observed with the use of drug-coated balloons (DCB) and drug-eluting stent (DES). The objective of this review is to (1) identify and summarize the existing clinical and cohort studies assessing paclitaxel-coated DCBs and DESs, (2) describe and determine the quality of the available data sources for the evaluation of these devices, and (3) present methodologies that can be leveraged for proper signal discernment within available data sources. Methods: Studies and data sources were identified through comprehensive searches. original research studies, clinical trials, comparative studies, multicenter studies, and observational cohort studies written in the English language and published from January 2007 to November 2021, with a follow-up longer than 36 months, were included in the review. Data quality of available data sources identified was assessed in three groupings. Moreover, accepted data-driven methodologies that may help circumvent the limitations of the extracted studies and data sources were extracted and described. Results: There were 39 studies and data sources identified. This included 19 randomized clinical trials, nine single-arm studies, eight registries, three administrative claims, and electronic health records. Methodologies focusing on the use of existing premarket clinical data, the incorporation of all contributed patient time, the use of aggregated data, approaches for individual-level data, machine learning and artificial intelligence approaches, Bayesian approaches, and the combination of various datasets were summarized. Conclusion: Despite the multitude of available studies over the course of eleven years following the first clinical trial, the FDA-convened advisory panel found them insufficient for comprehensively assessing the late-mortality signal. High-quality data sources with the capabilities of employing advanced statistical methodologies are needed to detect potential safety signals in a timely manner and allow regulatory bodies to act quickly when a safety signal is detected.

Use of data from the Vascular Quality Initiative registry to support regulatory decisions yielded a high return on investment.

BACKGROUND: Real-world data (RWD) from the Society for Vascular Surgery Vascular Quality Initiative (VQI) registry has been used to support US Food and Drug Administration (FDA) regulatory decisions regarding vascular devices. The variables of cost and time needed for these registry-based studies have not been previously compared to traditional, independent, industry studies that would otherwise have been conducted to support regulatory decisions. OBJECTIVES: To determine the potential value (cost and time saving and return on investment) created by device evaluation studies using the VQI registry infrastructure. METHODS: We compared studies that used data from the VQI registry with estimated costs of independent industry studies (counterfactual studies) using an established model using design specifications determined by FDA reviewers. RESULTS: We analyzed the initial six studies evaluating vascular devices for regulatory decisions using data from the VQI registry that generated evidence for four device manufacturers. Return on investment for these studies was estimated to be 143% and cost saving as 59% based on an actual per patient (with 5-year follow-up) cost of US$11K using VQI data versus US$26K from the counterfactual when averaged across all studies. Significant enrollment time savings (45%-71%) were also realized compared with industry-based estimates. CONCLUSIONS: The use of RWD from the VQI registry in this study and the transcatheter valve treatment coordinated registry network in a prior study indicates that substantial value was added to device evaluation projects by the reuse of registry data, with additional potential savings if linked claims data can be used instead of costly long-term in-person follow-up.

Determining value of Coordinated Registry Networks (CRNs): a case of transcatheter valve therapies.

BACKGROUND: The Transcatheter Valve Therapy (TVT) Coordinated Registry Network (CRN) supported 23 regulatory decisions and ensured evidence-based evaluation of the application of TVT technology. However, there are cost concerns that require value assessment of the TVT CRN compared with traditional study designs. OBJECTIVES: We aimed to determine the value created by the TVT CRN based on (1) Return on investment (ROI), (2) Time saved (TS) in conducting necessary regulatory studies. METHODS: For both ROI and TS analyses, we compared studies that used the TVT CRN with those that would have been required if the registry did not exist (counterfactual studies). To estimate ROI, we accounted for the costs of investment and gain from investment. Both the counterfactual costs and length of studies were projected using design specifications determined by US Food and Drug Administration (FDA) reviewers. RESULTS: We identified 21 studies using the TVT CRN (supporting 23 FDA decisions) that generated evidence on TVT for three device manufacturers. ROI is estimated to be greater than 550%. TS by using the CRN ranged from months to years. CONCLUSIONS: The CRN method to evidence generation creates value for manufacturers and the broader device ecosystem, demonstrated with this example of the TVT CRN. The public health benefits of evidence created by this CRN outweighs the difference in data quality between traditional clinical studies and the CRN method.

Utility and cutoff value of hair nicotine as a biomarker of long-term tobacco smoke exposure, compared to salivary cotinine.

While hair samples are easier to collect and less expensive to store and transport than biological fluids, and hair nicotine characterizes tobacco exposure over a longer time period than blood or urine cotinine, information on its utility, compared with salivary cotinine, is still limited. We conducted a cross-sectional study with 289 participants (107 active smokers, 105 passive smokers with self-reported secondhand smoke (SHS) exposure, and 77 non-smokers with no SHS exposure) in Baltimore (Maryland, USA). A subset of the study participants (n = 52) were followed longitudinally over a two-month interval.  Median baseline hair nicotine concentrations for active, passive and non-smokers were 16.2, 0.36, and 0.23 ng/mg, respectively, while those for salivary cotinine were 181.0, 0.27, and 0.27 ng/mL, respectively. Hair nicotine concentrations for 10% of passive or non-smokers were higher than the 25th percentile value for active smokers while all corresponding salivary cotinine concentrations for them were lower than the value for active smokers. This study showed that hair nicotine concentration values could be used to distinguish active or heavy passive adult smokers from non-SHS exposed non-smokers. Our results indicate that hair nicotine is a useful biomarker for the assessment of long-term exposure to tobacco smoke.

Molecularly-imprinted nanoparticles that recognize Naja mossambica cytotoxins: binding studies and biological effects.

We report the development of molecularly imprinted polyacrylamide nanoparticles that bind to and neutralize the activity of cytotoxins present in the venom of the Mozambique Spitting Cobra (Naja mossambica mossambica). The binding activity of these nanoparticles is avid and specific. These findings hold promise for the development of a synthetic antivenom.

Secondhand tobacco smoke: an occupational hazard for smoking and non-smoking bar and nightclub employees.

BACKGROUND: In the absence of comprehensive smoking bans in public places, bars and nightclubs have the highest concentrations of secondhand tobacco smoke, posing a serious health risk for workers in these venues. OBJECTIVE: To assess exposure of bar and nightclub employees to secondhand smoke, including non-smoking and smoking employees. METHODS: Between 2007 and 2009, the authors recruited approximately 10 venues per city and up to five employees per venue in 24 cities in the Americas, Eastern Europe, Asia and Africa. Air nicotine concentrations were measured for 7 days in 238 venues. To evaluate personal exposure to secondhand smoke, hair nicotine concentrations were also measured for 625 non-smoking and 311 smoking employees (N=936). RESULTS: Median (IQR) air nicotine concentrations were 3.5 (1.5-8.5) µg/m(3) and 0.2 (0.1-0.7) µg/m(3) in smoking and smoke-free venues, respectively. Median (IQR) hair nicotine concentrations were 6.0 (1.6-16.0) ng/mg and 1.7 (0.5-5.5) ng/mg in smoking and non-smoking employees, respectively. After adjustment for age, sex, education, living with a smoker, hair treatment and region, a twofold increase in air nicotine concentrations was associated with a 30% (95% CI 23% to 38%) increase in hair nicotine concentrations in non-smoking employees and with a 10% (2% to 19%) increase in smoking employees. CONCLUSIONS: Occupational exposure to secondhand smoke, assessed by air nicotine, resulted in elevated concentrations of hair nicotine among non-smoking and smoking bar and nightclub employees. The high levels of airborne nicotine found in bars and nightclubs and the contribution of this exposure to employee hair nicotine concentrations support the need for legislation measures that ensure complete protection from secondhand smoke in these venues.

Assessing secondhand smoke using biological markers.

Secondhand smoke exposure (SHSe) is a known cause of many adverse health effects in adults and children. Increasingly, SHSe assessment is an element of tobacco control research and implementation worldwide. In spite of decades of development of approaches to assess SHSe, there are still unresolved methodological issues; therefore, a multidisciplinary expert meeting was held to catalogue the approaches to assess SHSe and with the goal of providing a set of uniform methods for future use by investigators and thereby facilitate comparisons of findings across studies. The meeting, held at Johns Hopkins, in Baltimore, Maryland, USA, was supported by the Flight Attendant Medical Research Institute (FAMRI). A series of articles were developed to summarise what is known about self-reported, environmental and biological SHSe measurements. Non-smokers inhale toxicants in SHS, which are mainly products of combustion of organic materials and are not specific to tobacco smoke exposure. Biomarkers specific to SHSe are nicotine and its metabolites (e.g., cotinine), and metabolites of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). Cotinine is the preferred blood, saliva and urine biomarker for SHSe. Cotinine and nicotine can also be measured in hair and toenails. NNAL (4-[methylnitrosamino]-1-[3-pyridyl]-1-butanol), a metabolite of NNK, can be determined in the urine of SHS-exposed non-smokers. The selection of a particular biomarker of SHSe and the analytic biological medium depends on the scientific or public health question of interest, study design and setting, subjects, and funding. This manuscript summarises the scientific evidence on the use of biomarkers to measure SHSe, analytical methods, biological matrices and their interpretation.

Assessing secondhand smoke exposure with reported measures.

Non-smokers are exposed to tobacco smoke from the burning cigarette and the exhaled smoke from smokers. In spite of decades of development of approaches to assess secondhand smoke exposure (SHSe), there are still unresolved methodological issues. This manuscript summarises the scientific evidence on the use of SHSe reported measures and their methods, objectives, strengths and limitations; and discusses best practices for assessing behaviour leading to SHSe for lifetime and immediate or current SHSe. Recommendations for advancing measurement science of SHSe are provided. Behavioural measures of SHSe commonly rely on self-reports from children and adults. Most commonly, the methodology includes self, proxy and interview-based reporting styles using retrospective recall or diary-style reporting formats. The reporting method used will vary based upon the subject of interest, assessment objectives and cultural context. Appropriately implemented, reported measures of SHSe provide an accurate, timely and cost-effective method for assessing exposure time, location and quantity in a wide variety of populations.

Environmental monitoring of secondhand smoke exposure.

The complex composition of secondhand smoke (SHS) provides a range of constituents that can be measured in environmental samples (air, dust and on surfaces) and therefore used to assess non-smokers' exposure to tobacco smoke. Monitoring SHS exposure (SHSe) in indoor environments provides useful information on the extent and consequences of SHSe, implementing and evaluating tobacco control programmes and behavioural interventions, and estimating overall burden of disease caused by SHSe. The most widely used markers have been vapour-phase nicotine and respirable particulate matter (PM). Numerous other environmental analytes of SHS have been measured in the air including carbon monoxide, 3-ethenylpyridine, polycyclic aromatic hydrocarbons, tobacco-specific nitrosamines, nitrogen oxides, aldehydes and volatile organic compounds, as well as nicotine in dust and on surfaces. The measurement of nicotine in the air has the advantage of reflecting the presence of tobacco smoke. While PM measurements are not as specific, they can be taken continuously, allowing for assessment of exposure and its variation over time. In general, when nicotine and PM are measured in the same setting using a common sampling period, an increase in nicotine concentration of 1 µg/m(3) corresponds to an average increase of 10 µg/m3 of PM. This topic assessment presents a comprehensive summary of SHSe monitoring approaches using environmental markers and discusses the strengths and weaknesses of these methods and approaches.

A luminal glycoprotein drives dose-dependent diameter expansion of the Drosophila melanogaster hindgut tube.

An important step in epithelial organ development is size maturation of the organ lumen to attain correct dimensions. Here we show that the regulated expression of Tenectin (Tnc) is critical to shape the Drosophila melanogaster hindgut tube. Tnc is a secreted protein that fills the embryonic hindgut lumen during tube diameter expansion. Inside the lumen, Tnc contributes to detectable O-Glycans and forms a dense striated matrix. Loss of tnc causes a narrow hindgut tube, while Tnc over-expression drives tube dilation in a dose-dependent manner. Cellular analyses show that luminal accumulation of Tnc causes an increase in inner and outer tube diameter, and cell flattening within the tube wall, similar to the effects of a hydrostatic pressure in other systems. When Tnc expression is induced only in cells at one side of the tube wall, Tnc fills the lumen and equally affects all cells at the lumen perimeter, arguing that Tnc acts non-cell-autonomously. Moreover, when Tnc expression is directed to a segment of a tube, its luminal accumulation is restricted to this segment and affects the surrounding cells to promote a corresponding local diameter expansion. These findings suggest that deposition of Tnc into the lumen might contribute to expansion of the lumen volume, and thereby to stretching of the tube wall. Consistent with such an idea, ectopic expression of Tnc in different developing epithelial tubes is sufficient to cause dilation, while epidermal Tnc expression has no effect on morphology. Together, the results show that epithelial tube diameter can be modelled by regulating the levels and pattern of expression of a single luminal glycoprotein.

Impact of tobacco control interventions on smoking initiation, cessation, and prevalence: a systematic review.

BACKGROUND: Policymakers need estimates of the impact of tobacco control (TC) policies to set priorities and targets for reducing tobacco use. We systematically reviewed the independent effects of TC policies on smoking behavior. METHODS: We searched MEDLINE (through January 2012) and EMBASE and other databases through February 2009, looking for studies published after 1989 in any language that assessed the effects of each TC intervention on smoking prevalence, initiation, cessation, or price participation elasticity. Paired reviewers extracted data from studies that isolated the impact of a single TC intervention. FINDINGS: We included 84 studies. The strength of evidence quantifying the independent effect on smoking prevalence was high for increasing tobacco prices and moderate for smoking bans in public places and antitobacco mass media campaigns. Limited direct evidence was available to quantify the effects of health warning labels and bans on advertising and sponsorship. Studies were too heterogeneous to pool effect estimates. INTERPRETATIONS: We found evidence of an independent effect for several TC policies on smoking prevalence. However, we could not derive precise estimates of the effects across different settings because of variability in the characteristics of the intervention, level of policy enforcement, and underlying tobacco control environment.

Epidemiology of tobacco use and dependence in adults in a poor peri-urban community in Lima, Peru.

BACKGROUND: Tobacco smoking is an important public health concern worldwide leading to both chronic disease and early death. In Latin America, smoking prevalence is estimated at approximately 30% and prior studies suggest that the prevalence in Peru is 22% to 38%. We sought to determine the prevalence of daily smoking in a poor peri-urban community in Lima, Peru. METHODS: We conducted a cross-sectional survey in a random sample of adults ≥40 years of age living in Pampas de San Juan de Miraflores, Lima, Peru. We asked participants to respond to a survey that included questions on sociodemographics, tobacco use and dependence. RESULTS: We enrolled 316 participants. Average monthly household income was ≤ 400 USD and nearly all homes had running water, sewage, and electricity. Most individuals had not completed high school. Smoking prevalence was 16% overall, yet daily smoking prevalence was 1.9%. Former daily smokers comprised 3.8% of current nonsmokers and 9.1% current occasional smokers. Average scores for the Fagerstrom Test for Nicotine Dependence for daily smokers and occasional smokers were 1.5 and 0, respectively. CONCLUSIONS: Daily use of tobacco is uncommon among adults in peri-urban communities of Lima, Peru, unlike their counterparts in Lima and other Latin American capital cities. Tobacco dependence is also low. Hence, efforts aimed at primary prevention are of utmost importance in these communities. This study provides an accurate baseline using an internationally recognized assessment tool (Global Adult Tobacco Survey), allowing for accurate assessment of tobacco control interventions over time.

Racial differences in hair nicotine concentrations among smokers.

INTRODUCTION: In the United States, race/ethnicity is a strong determinant of tobacco use patterns, biomarkers of tobacco smoke components and metabolites, and likelihood of successful cessation. Although Black smokers tend to smoke fewer cigarettes than White smokers, they have higher cotinine levels and disease risk and lower cessation success. We examined racial differences in hair nicotine concentrations among daily tobacco smokers (n = 103) in Baltimore, Maryland. METHODS: Participants completed a survey, and hair samples were collected and analyzed for nicotine concentration using gas chromatography coupled with mass spectrometry. RESULTS: After adjustment, hair nicotine concentrations among Black smokers were more than 5 times higher than among White smokers (95% CI 3.0, 10.5). Smokers reporting hair treatments other than coloring (bleaching, permanent, or straightening) in the past 12 months had 66% lower (95% CI 32%, 83%) hair nicotine concentrations. Smokers reporting smoking their first cigarette within 30 min of waking had twice the hair nicotine concentrations of those whose time to first cigarette was greater than 30 min after waking (95% CI 1.1, 4.2). For every additional cigarette smoked per day up to 20, mean hair nicotine concentration among all smokers increased by 4% (95% CI -1%, 9%). CONCLUSIONS: This study demonstrates that Black smokers have substantially higher hair nicotine levels than White smokers, after controlling for cigarettes smoked per day and other exposure sources. Time to first cigarette, cigarettes smoked per day, and use of hair treatments other than coloring were also associated with hair nicotine concentrations among smokers.

Tobacco sales and promotion in bars, cafes and nightclubs from large cities around the world.

CONTEXT: Little is known about tobacco promotion activities in low and middle-income countries. Information on tobacco sales, advertisement and promotion in bars, cafes and nightclubs is needed to develop interventions to reduce smoking initiation and relapse, particularly among youths and young adults. OBJECTIVE: To evaluate cigarette sales and tobacco advertisement and promotion in bars, cafes and nightclubs using a volunteer survey approach in large cities throughout the world. METHODS: Between 2007 and 2009, we administered an interview-based survey to 231 bar/cafe/nightclub owners/managers in 24 large cities in Africa, the Americas, Asia and eastern Europe. RESULTS: Cigarette sales and tobacco advertisement and promotions were found in bars/cafes/nightclubs in most cities. Examples of promotions included cigarette giveaways and event sponsorship. Establishments that allowed smoking were more likely to sell cigarettes compared to smoke-free establishments (OR 8.67, 95% CI 3.25 to 23.1). Larger establishments (maximum occupancy ≥ 100 vs <100 customers) were more likely to have tobacco advertising (OR 4.35, 95% CI 2.04 to 9.24) and to receive promotional items from tobacco companies (OR 3.18, 95% CI 1.41 to 7.17). CONCLUSIONS: Cigarette sales and tobacco promotions were common in bars, cafes and nightclubs in the majority of cities. Socialising and hospitality venues must be covered by legislation banning tobacco sales and promotions to limit exposure among populations at high risk of tobacco initiation and relapse from quitting.

A systematic review of randomized controlled trials: Web-based interventions for smoking cessation among adolescents, college students, and adults.

INTRODUCTION: Web-based treatments can deliver broad reaching, relatively inexpensive, and clinically tested methods for smoking cessation. We performed a systematic review of randomized controlled trials (RCTs) of smoking cessation to evaluate the efficacy of Web-based interventions in adults, college students, and adolescents. METHODS: MEDLINE, EMBASE, The Cochrane Library, CINAHL, and PsycINFO were searched from January 1, 1990 through February 12, 2010 for RCTs examining the efficacy of Web-based smoking cessation programs. Paired reviewers abstracted data on study design, patient characteristics, and outcomes sequentially and did quality assessments independently. RESULTS: Twenty-one RCTs met eligibility criteria, with 15 conducted among adults. Among adults, 2 RCTs found that a multicomponent intervention with Web and non-Web-based elements was more efficacious than a self-help manual, and one of 2 RCTs found that Web-based interventions may be more effective than no treatment. Three trials provided insufficient evidence to demonstrate whether Web-based interventions were more efficacious than counseling. By contrast, tailored Web sites in 2 RCTs and greater Web site exposure in 6 of 7 RCTs were associated with higher rates of abstinence. Among college students, evidence supporting use of Web-based interventions was insufficient because the one RCT conducted was also a multicomponent intervention. Five RCTs among adolescents demonstrated mixed results, with insufficient evidence supporting their efficacy. CONCLUSIONS: Evidence supporting the use of Web-based interventions for smoking cessation is insufficient to moderate in adults and insufficient in college students and adolescents. These RCTs have, however, elucidated clinical, methodological, and statistical practices that are likely to improve future trial design and treatment delivery.

Workplace smoking restrictions in China: results from a six county survey.

OBJECTIVE: To determine the coverage of smoking restriction policies in indoor workplaces in China and to assess the relationships between these restrictive policies and secondhand smoke (SHS) exposure and smoking behaviours. METHODS: A cross-sectional household survey was conducted in six counties in Sichuan, Jiangxi and Henan provinces in 2004. Using a standardised questionnaire, information on demographic characteristics, knowledge, attitudes and behaviours related to smoking and SHS exposure was collected through face-to-face interviews by trained local investigators among 12 036 respondents. Of respondents, 2698 individuals worked mainly indoors and were included in data analysis. RESULTS: Only 28.5% of respondents reported that indoor workplaces had a smoke-free policy. Even when respondents reported smoke-free policies, 41.1% smokers reported that they were non-compliant with policies and smoked at work. In addition, 32.0% of non-smokers reported being exposed to SHS at work despite smoke-free policies. Non-smokers who reported no smoking restriction policies were 3.7 times more likely to be exposed to SHS than those working in smoke-free workplaces (adjusted OR 3.7, 95% CI 1.3 to 10.1). On average, respondents complying with smoke-free policies smoked 3.8 fewer cigarettes than those reporting no policies in their workplaces at a marginally non-significant level (p=0.06) (adjusted mean difference -3.8, 95% CI -8.0 to 0.5). CONCLUSIONS: In China, few workplaces have implemented policies to restrict smoking, and, even in workplaces that have policies, workers report exposure to SHS while at their places of employment. Many workers report a lack of compliance with smoke-free policies. China needs better implementation of SHS policies to promote compliance. Working to improve implementation of smoke-free policies would promote cessation since Chinese smokers who were compliant with these efforts reported smoking fewer cigarettes per day.

Trafficking through COPII stabilises cell polarity and drives secretion during Drosophila epidermal differentiation.

BACKGROUND: The differentiation of an extracellular matrix (ECM) at the apical side of epithelial cells implies massive polarised secretion and membrane trafficking. An epithelial cell is hence engaged in coordinating secretion and cell polarity for a correct and efficient ECM formation. PRINCIPAL FINDINGS: We are studying the molecular mechanisms that Drosophila tracheal and epidermal cells deploy to form their specific apical ECM during differentiation. In this work we demonstrate that the two genetically identified factors haunted and ghost are essential for polarity maintenance, membrane topology as well as for secretion of the tracheal luminal matrix and the cuticle. We show that they code for the Drosophila COPII vesicle-coating components Sec23 and Sec24, respectively, that organise vesicle transport from the ER to the Golgi apparatus. CONCLUSION: Taken together, epithelial differentiation during Drosophila embryogenesis is a concerted action of ECM formation, plasma membrane remodelling and maintenance of cell polarity that all three rely mainly, if not absolutely, on the canonical secretory pathway from the ER over the Golgi apparatus to the plasma membrane. Our results indicate that COPII vesicles constitute a central hub for these processes.

Estimating the risks and benefits of nicotine replacement therapy for smoking cessation in the United States.

OBJECTIVES: To compare potential population-wide benefits and risks, we examined the potential impact of increased nicotine replacement therapy (NRT) use for smoking cessation on future US mortality. METHODS: We developed a simulation model incorporating a Monte Carlo uncertainty analysis, with data from the 2005 National Health Interview Survey and Cancer Prevention Study II. We estimated the number of avoided premature deaths from smoking attributable to increased NRT use, before and after incorporating assumptions about NRT harm. RESULTS: We estimate that a gradual increase in the proportion of NRT-aided quit attempts to 100% by 2025 would lead to 40,000 (95% credible interval=31,000, 50,000) premature deaths avoided over a 20-year period. Most avoided deaths would be attributable to lung cancer and cardiovascular disease. After we incorporated assumptions about potential risk from long-term NRT, the estimate of avoided premature deaths from all causes declined to 32 000. CONCLUSIONS: Even after we assumed some harm from long-term NRT use, the benefits from increased cessation success far outweigh the risks. However, the projected reduction in premature mortality still reflects a small portion of the tobacco-related deaths expected over a 20-year period.

Promoting smoke-free environments in Latin America: a comparison of methods to assess secondhand smoke exposure.

Secondhand smoke (SHS) contains toxicants and carcinogens that are known to cause premature death and disease. Objectively measuring SHS exposure can support and evaluate smoke-free legislation. In Latin America, the most commonly used methods to measure SHS exposure are airborne nicotine and respirable suspended particles (PM2.5). Here we present results from studies conducted in public places and homes across Latin American countries. Airborne nicotine was detected in most locations between 2002-2006, before the implementation of 100% smoke-free legislation in Uruguay, Panama, Guatemala and other large cities within Latin America. Between 2006 and 2008, PM2.5 levels were found to be five times higher in places where smoking was present at the time of sampling compared to those without smoking. Measuring SHS exposure across Latin America has increased our understanding of the magnitude of exposure in this region and results have been used to effectively promote smoke-free legislation.