Estimating the reduction in US mortality if cigarettes were largely replaced by e-cigarettes.

BACKGROUND: Recent estimates indicated substantially replacing cigarettes by e-cigarettes would, during 2016-2100, reduce US deaths and life-years lost (millions) by 6.6 and 86.7 (Optimistic Scenario) and 1.6 and 20.8 (Pessimistic). To provide additional insight we use alternative modelling based on a shorter period (1991-2040), four main smoking-associated diseases, deaths aged 30-79 years, and a full product history. We consider variations in: assumed effective dose of e-cigarettes versus cigarettes (F); their relative quitting rate (Q); proportions smoking after 10 years (X); and initiation rate (I) of vaping, relative to smoking. METHODS: We set F = 0.05, X = 5%, Q = 1.0 and I = 1.0 (Main Scenario) and F = 0.4, X = 10%, Q = 0.5 and I = 1.5 (Pessimistic Scenario). Sensitivity Analyses varied Main Scenario parameters singly; F from 0 to 0.4, X 0.01% to 15%, and Q and I 0.5 to 1.5. To allow comparison with prior work, individuals cannot be dual users, re-initiate, or switch except from cigarettes to e-cigarettes. RESULTS: Main Scenario reductions were 2.52 and 26.23 million deaths and life-years lost; Pessimistic Scenario reductions were 0.76 and 8.31 million. These were less than previously, due to the more limited age-range and follow-up, and restriction to four diseases. Reductions in deaths (millions) varied most for X, from 3.22 (X = 0.01%) to 1.31 (X = 15%), and F, 2.74 (F = 0) to 1.35 (F = 0.4). Varying Q or I had little effect. CONCLUSIONS: Substantial reductions in deaths and life-years lost were observed even under pessimistic assumptions. Estimates varied most for X and F. These findings supplement literature indicating e-cigarettes can importantly impact health challenges from smoking.

Estimating the public health impact had tobacco-free nicotine pouches been introduced into the US in 2000.

BACKGROUND: For smokers not intending to quit, switching to a reduced-risk nicotine product should be healthier than continuing smoking. We estimate the health impact, over the period 2000-2050, had the nicotine pouch ZYN hypothetically been introduced into the US in 2000. ZYN's toxicant profile and method of use is like that for Swedish snus, a product with known health effects much less than smoking. METHODS: Our modelling approach is similar to others developed for estimating potential effects of new tobacco products. It starts with a simulated cohort of 100,000 individuals in the year 2000 subdivided by age, sex, and smoking status (including years since quitting). They are followed annually accounting for births, net immigrations, deaths and product use changes, with follow-up carried out in the Base Case (ZYN not introduced) and Modified Case (ZYN introduced). Using informed assumptions about initiation, quitting and switching rates, distributions of the population over time are then constructed for each Case, and used to estimate product mortality based on assumptions about the relative risk according to product use. RESULTS: Whereas in both Base and Modified Cases, the prevalence of any current product use is predicted to decline from about 22% to 10% during follow-up, in the Modified Case about 25% of current users use ZYN by 2050, about a quarter being dual users and the rest ZYN-only users. Over the 50 years, deaths at ages 35-84 from product use among the 100,000 are estimated as 249 less in the Modified than the Base Case, equivalent to about 700,000 less in the whole US. Sensitivity analyses varying individual parameter values confirm the benefits of switching to ZYN, which increase as either the switching rate to ZYN increases or the initiation rate of ZYN relative to smoking increases. Even assuming the reduction in excess mortality risk using ZYN use is 20% of that from smoking rather than the 3.5% assumed in the main analyses, the reduction in product-related deaths would still be 213, or about 600,000 in the US. CONCLUSIONS: Although such model-based estimates involve uncertainties, the results suggest that introducing ZYN could substantially reduce product-related deaths.

Multicenter experience with valve-in-valve transcatheter aortic valve replacement compared with primary, native valve transcatheter aortic valve replacement.

BACKGROUND: Valve-in-valve (ViV) transcatheter aortic valve replacement (TAVR) offers an alternative to reoperative surgical aortic valve replacement. The short- and intermediate-term outcomes after ViV TAVR in the real world are not entirely clear. PATIENTS AND METHODS: A multicenter, retrospective analysis of a consecutive series of 121 ViV TAVR patients and 2200 patients undergoing primary native valve TAVR from 2012 to 2017 at six medical centers. The main outcome measures were in-hospital mortality, 30-day mortality, stroke, myocardial infarction, acute kidney injury, and pacemaker implantation. RESULTS: ViV patients were more likely male, younger, prior coronary artery bypass graft, "hostile chest," and urgent. 30% of the patients had Society of Thoracic Surgeons risk score <4%, 36.3% were 4%-8% and 33.8% were >8%. In both groups many patients had concomitant coronary artery disease. Median time to prosthetic failure was 9.6 years (interquartile range: 5.5-13.5 years). 82% of failed surgical valves were size 21, 23, or 25 mm. Access was 91% femoral. After ViV, 87% had none or trivial aortic regurgitation. Mean gradients were <20 mmHg in 54.6%, 20-29 mmHg in 30.6%, 30-39 mmHg in 8.3% and ≥40 mmHg in 5.87%. Median length of stay was 4 days. In-hospital mortality was 0%. 30-day mortality was 0% in ViV and 3.7% in native TAVR. There was no difference in in-hospital mortality, postprocedure myocardial infarction, stroke, or acute kidney injury. CONCLUSION: Compared to native TAVR, ViV TAVR has similar peri-procedural morbidity with relatively high postprocedure mean gradients. A multidisciplinary approach will help ensure patients receive the ideal therapy in the setting of structural bioprosthetic valve degeneration.

Estimating the Population Health Impact of Recently Introduced Modified Risk Tobacco Products: A Comparison of Different Approaches.

INTRODUCTION: Various approaches have been used to estimate the population health impact of introducing a Modified Risk Tobacco Product (MRTP). AIMS AND METHODS: We aimed to compare and contrast aspects of models considering effects on mortality that were known to experts attending a meeting on models in 2018. RESULTS: Thirteen models are described, some focussing on e-cigarettes, others more general. Most models are cohort-based, comparing results with or without MRTP introduction. They typically start with a population with known smoking habits and then use transition probabilities either to update smoking habits in the "null scenario" or joint smoking and MRTP habits in an "alternative scenario". The models vary in the tobacco groups and transition probabilities considered. Based on aspects of the tobacco history developed, the models compare mortality risks, and sometimes life-years lost and health costs, between scenarios. Estimating effects on population health depends on frequency of use of the MRTP and smoking, and the extent to which the products expose users to harmful constituents. Strengths and weaknesses of the approaches are summarized. CONCLUSIONS: Despite methodological differences, most modellers have assumed the increase in risk of mortality from MRTP use, relative to that from cigarette smoking, to be very low and have concluded that MRTP introduction is likely to have a beneficial impact. Further model development, supplemented by preliminary results from well-designed epidemiological studies, should enable more precise prediction of the anticipated effects of MRTP introduction. IMPLICATIONS: There is a need to estimate the population health impact of introducing modified risk nicotine-containing products for smokers unwilling or unable to quit. This paper reviews a variety of modeling methodologies proposed to do this, and discusses the implications of the different approaches. It should assist modelers in refining and improving their models, and help toward providing authorities with more reliable estimates.

Methodological steps used by authors of systematic reviews and meta-analyses of clinical trials: a cross-sectional study.

BACKGROUND: The quality of systematic reviews and meta-analyses (SR/MAs) depends on the extent of the methods used. We investigated the methodological steps used by authors of SR/MAs of clinical trials via an author survey. METHODS: We conducted an email-based cross-sectional study by contacting corresponding authors of SR/MAs that were published in 2015 and 2016 and retrieved through the PubMed database. The 27-item questionnaire was developed to study the methodological steps used by authors when conducting a SR/MA and the demographic characteristics of the respondent. Besides the demographic characteristics, methodological questions regarding the source, extraction and synthesis of data were included. RESULTS: From 10,292 emails sent, 384 authors responded and were included in the final analysis. Manual searches were carried out by 69.2% of authors, while 87.3% do updated searches, 49.2% search grey literature, 74.9% use the Cochrane tool for risk of bias assessment, 69.8% assign more than two reviewers for data extraction, 20.5% use digital software to extract data from graphs, 57.9% use raw data in the meta-analysis, and 43.8% meta-analyze both adjusted and non-adjusted data. There was a positive correlation of years of experience in conducting of SR/MAs with both searching grey literature (P = 0.0003) and use of adjusted and non-adjusted data (P = 0.006). CONCLUSIONS: Many authors still do not carry out many of the vital methodological steps to be taken when performing any SR/MA. The experience of the authors in SR/MAs is highly correlated with use of the recommended tips for SR/MA conduct. The optimal methodological approach for researchers conducting a SR/MA should be standardized.

Updating the evidence relating smoking bans to incidence of heart disease.

In our latest update of the evidence on smoking bans and heart disease we summarize 59 studies. We take account of the underlying trends in incidence rates as far as possible by using control data in eight studies, and by adjustment based on observed trends in cases pre- and post-ban in 40 studies, being unable to make an adjustment in the remaining 11 studies. Overall, based on 62 independent estimates from the 59 studies, we estimate that bans reduce incidence by 5.0% (95% CI 3.2-6.8%), though this estimate reduces to 2.9% (0.01-5.6%) when we exclude regional estimates where national estimates are available, and studies where trend adjustment is not possible. For 25 of the studies, quadratic rather than linear adjustment is possible, but this hardly affects the overall estimates. Ban effects are somewhat greater when the pre-ban period studied is relatively short, and in smaller studies. We compare our findings with those in other recent reviews, one of which totally ignored underlying trends and results from control populations. We discuss reasons why we believe there is likely to be a true small effect of smoking bans, and weaknesses in the data which preclude reaching any very confident conclusion.

Tar level of cigarettes smoked and risk of smoking-related diseases.

BACKGROUND: Opinions differ on the relationship between tar level and risk of smoking-related disease. However, except for lung cancer, few reviews have evaluated the epidemiological evidence. Here the relationship of tar level to risk of the four main smoking-related diseases is considered. METHODS: Papers comparing risk of lung cancer, COPD, heart disease or stroke in smokers of lower and higher tar yield cigarettes were identified from reviews and searches, relative risk estimates being extracted comparing the lowest and highest tar groups. Meta-analyses investigated heterogeneity by various study characteristics. RESULTS: Twenty-six studies were identified, nine of prospective design and 17 case-control. Two studies grouped cigarettes by nicotine rather than tar. Seventeen studies gave results for lung cancer, 16 for heart disease, five for stroke and four for COPD. Preferring relative risks adjusted for daily amount smoked, where adjusted and unadjusted estimates were available, combined estimates for lowest versus highest tar (or nicotine) groups were 0.78 (95% confidence interval 0.70-0.88) for lung cancer, 0.86 (0.81-0.91) for heart disease, 0.77 (0.62-0.95) for stroke and 0.81 (0.65-1.02) for COPD. Lower risks were generally evident in subgroups by publication period, gender, study design, location and extent of confounder adjustment. Estimates were similar preferring data unadjusted for amount smoked or excluding nicotine-based estimates. CONCLUSIONS: Despite evidence that smokers substantially compensate for reduced cigarette yields, the results clearly show lower risks in lower tar smokers. Limitations of the evidence are discussed, but seem unlikely to affect this conclusion.

Estimating the population health impact of introducing a reduced-risk tobacco product into Japan. The effect of differing assumptions, and some comparisons with the U.S.

We estimated, using previously described methodology, the population health impact of introducing a reduced-risk tobacco product (RRP) into Japan. Various simulations were carried out to understand the impact on the population in different situations over a 20-year period from 1990. The overall reduction in tobacco-attributable deaths from lung cancer (LC), ischemic heart disease (IHD), stroke, and chronic obstructive pulmonary disease (COPD) for men and women combined was estimated to be 269,916 over the period if tobacco use disappeared completely at baseline. In contrast, reductions ranging from 167,041 to 232,519 deaths were estimated if the RRP totally replaced smoking at baseline (assuming that switching to it had an effect equivalent to 70%-90% of the effect of quitting). If, more plausibly, the RRP were introduced at baseline, with uptake rates consistent with the known uptake of the RRP IQOS®, the reductions would still be substantial (from 65,126 to 86,885 deaths). Expressed as a percentage of attributable deaths, these proportions are larger than those for the U.S., based on likely uptake rates. We discuss various limitations of the approach, though none should affect the conclusion that the introduction of an RRP into Japan will substantially reduce tobacco-related deaths.

A systematic review of possible serious adverse health effects of nicotine replacement therapy.

We conducted a systematic literature review to identify and critically evaluate studies of serious adverse health effects (SAHEs) in humans using nicotine replacement therapy (NRT) products. Serious adverse health effects refer to adverse events, leading to substantial disruption of the ability to conduct normal life functions. Strength of evidence evaluations and conclusions were also determined for the identified SAHEs. We evaluated 34 epidemiological studies and clinical trials, relating NRT use to cancer, reproduction/development, CVD, stroke and/or other SAHEs in patients, and four meta-analyses on effects in healthy populations. The overall evidence suffers from many limitations, the most significant being the short-term exposure (≤12 weeks) and follow-up to NRT product use in most of the studies, the common failure to account for changes in smoking behaviour following NRT use, and the sparse information on SAHEs by type of NRT product used. The only SAHE from NRT exposure we identified was an increase in respiratory congenital abnormalities reported in one study. Limited evidence indicated a lack of effect between NRT exposure and SAHEs for CVD and various reproduction/developmental endpoints. For cancer, stroke and other SAHEs, the evidence was inadequate to demonstrate any association with NRT use. Our conclusions agree with recent statements from authoritative bodies.

The relationship of snus use to diabetes and allied conditions.

A recent meta-analysis reported smoking to be associated with a 37% higher risk of type 2 diabetes in current smokers, rising to a 57% increase in heavy smokers, which declines on quitting. If the increase results from nicotine exposure, it is possible that using Swedish moist snuff ("snus"), which provides at least equivalent nicotine doses, might also increase diabetes risk. Following a recent publication reporting pooled results from five cohorts, we present a detailed meta-analysis of data from 18 studies. Based on covariate-adjusted estimates, no significant increased risk was seen in never smokers with RRs (95% CIs) of 1.08 (0.86-1.34), 0.93 (0.79-1.11) and 1.05 (0.94-1.18) for current, former and ever snus users. Significant increases were also not seen in the whole population, the corresponding RR estimates being 1.18 (0.94-1.48), 0.69 (0.49-0.96) and 0.95 (0.81-1.11). Nor was there an association of snus use with related endpoints, such as impaired glucose tolerance. However, dose-response analyses showed a relationship, with the highest levels of snus exposure associated with a diabetes RR of 1.65 (1.25-2.18) in never smokers. The evidence relating snus to type 2 diabetes is somewhat limited, requiring further studies to confirm any possible relationship.

Investigation into the risk of ultra-low tar cigarettes and lung cancer.

We present analyses relating cigarette type to lung cancer based on a case-control study in five European countries. The analyses involved 3561 cases and 2301 controls with diseases not associated with smoking. Subjects completed a detailed questionnaire, including a lifetime smoking history. Analyses included never smokers, and those who smoked for at least 80% of the "critical period" from 2 to 20 years before diagnosis, ignoring those who ever smoked pipes or cigars, or chewed tobacco. The main analysis compares risk in those who, in the critical period, smoked ultra-low tar (ULT) cigarettes (machine yield ≤3 mg tar/cigarette) for 8 + years, with those who only smoked full flavour (FF) cigarettes (≥10 mg tar/cigarette). After adjustment for sex, age, country, education, age of starting smoking, mean cigarette consumption and mean tar level 21-50 years before interview, the odds ratio (OR) was 0.73 (95% confidence interval (CI) 0.50-1.06). Other analyses showed a modest, not statistically significant, reduction in risk with tar reduction. Risk in ULT smokers for 8 + years was substantially higher than in never smokers (OR 16.27, 95% CI 10.14-26.09). The study was prematurely terminated due to cost overrun, limiting the power to detect an association. More evidence is needed, particularly on lifetime ULT smoking.

Estimating the effect of differing assumptions on the population health impact of introducing a Reduced Risk Tobacco Product in the USA.

We use Population Health Impact Modelling to assess effects on tobacco prevalence and mortality of introducing a Reduced Risk Tobacco Product (RRP). Simulated samples start in 1990 with a US-representative smoking prevalence. Individual tobacco histories are updated annually until 2010 using estimated probabilities of switching between never/current/former smoking where the RRP is not introduced, with current users subdivided into cigarette/RRP/dual users where it is. RRP-related mortality reductions from lung cancer, IHD, stroke and COPD are derived from the histories and the assumed relative risks of the RRP. A basic analysis assumes a hypothetical RRP reduces effective dose 80% in users and 40% in dual users, with an uptake rate generating ∼10% RRP and ∼6% dual users among current users after 10 years. Sensitivity study changes in tobacco prevalence and mortality from varying effective doses, current smoking risks, quitting half-lives and rates of initiation, switching, re-initiation and cessation. They also study extreme situations (e.g. everyone using RRP), and investigate assumptions which might eliminate the RRP-related mortality reduction. The mortality reduction is proportional to the dose reduction, increasing rapidly with time of follow-up. Plausible increases in re-initiation or dual users' consumption, or decreased quitting by smokers would not eliminate the drop.

Environmental Tobacco Smoke Exposure and Risk of Stroke in Never Smokers: An Updated Review with Meta-Analysis.

OBJECTIVES: The study aimed to review the epidemiological evidence relating environmental tobacco smoke exposure to stroke in never smokers. METHODS: The study is similar to our review in 2006, with searches extended to March 2016. RESULTS: Twelve further studies were identified. A total of 28 studies varied considerably in design, exposure indices used, and disease definition. Based on 39 sex-specific estimates and the exposure index current spousal exposure (or nearest equivalent), the meta-analysis gave an overall fixed-effect relative risk estimate of 1.23 (95% confidence interval: 1.16-1.31), with significant (P < .05) heterogeneity. There was no significant heterogeneity by sex, continent, fatality, disease end point, or degree of adjustment for potential confounding factors. Relative risks were less elevated in prospective studies (1.15, 1.06-1.24) than in case-control studies (1.44, 1.22-1.60) or cross-sectional studies (1.40, 1.21-1.61). They also varied by publication year, but with no trend. A significant increase was not seen in studies that excluded smokers of any tobacco (1.07, .97-1.17), but was seen for studies that included pipe- or cigar-only smokers, occasional smokers, or long-term former smokers. No elevation was seen for hemorrhagic stroke. Relative risk estimates were similar using ever rather than current exposure, or total rather than spousal exposure. Eleven studies provided dose-response estimates, the combined relative risk for the highest exposure level being 1.56 (1.37-1.79). Many studies have evident weaknesses, recall bias, and particularly publication bias being major concerns. CONCLUSIONS: Although other reviewers inferred a causal relationship, we consider the evidence does not conclusively demonstrate this. We repeat our call for publication of data from existing large prospective studies.

Fractional flow reserve versus angiography for guidance of PCI in patients with multivessel coronary artery disease (FAME): 5-year follow-up of a randomised controlled trial.

BACKGROUND: In the Fractional Flow Reserve Versus Angiography for Multivessel Evaluation (FAME) study, fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) improved outcome compared with angiography-guided PCI for up to 2 years of follow-up. The aim in this study was to investigate whether the favourable clinical outcome with the FFR-guided PCI in the FAME study persisted over a 5-year follow-up. METHODS: The FAME study was a multicentre trial done in Belgium, Denmark, Germany, the Netherlands, Sweden, the UK, and the USA. Patients (aged ≥ 18 years) with multivessel coronary artery disease were randomly assigned to undergo angiography-guided PCI or FFR-guided PCI. Before randomisation, stenoses requiring PCI were identified on the angiogram. Patients allocated to angiography-guided PCI had revascularisation of all identified stenoses. Patients allocated to FFR-guided PCI had FFR measurements of all stenotic arteries and PCI was done only if FFR was 0·80 or less. No one was masked to treatment assignment. The primary endpoint was major adverse cardiac events at 1 year, and the data for the 5-year follow-up are reported here. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00267774. FINDINGS: After 5 years, major adverse cardiac events occurred in 31% of patients (154 of 496) in the angiography-guided group versus 28% (143 of 509 patients) in the FFR-guided group (relative risk 0·91, 95% CI 0·75-1·10; p=0·31). The number of stents placed per patient was significantly higher in the angiography-guided group than in the FFR-guided group (mean 2·7 [SD 1·2] vs 1·9 [1·3], p<0·0001). INTERPRETATION: The results confirm the long-term safety of FFR-guided PCI in patients with multivessel disease. A strategy of FFR-guided PCI resulted in a significant decrease of major adverse cardiac events for up to 2 years after the index procedure. From 2 years to 5 years, the risks for both groups developed similarly. This clinical outcome in the FFR-guided group was achieved with a lower number of stented arteries and less resource use. These results indicate that FFR guidance of multivessel PCI should be the standard of care in most patients. FUNDING: St Jude Medical, Friends of the Heart Foundation, and Medtronic.

Environmental tobacco smoke exposure and risk of breast cancer in nonsmoking women. An updated review and meta-analysis.

CONTEXT: In 2006, we reviewed the evidence on environmental tobacco smoke (ETS) and breast cancer in nonsmoking women. Since then various studies and reviews have been published but opinion remains divided. OBJECTIVE: To provide an updated review. METHODS: We extracted study details, derived relative risk (RR) estimates with confidence intervals (CIs) for various ETS exposure indices, and conducted meta-analyses. RESULTS: The update increased the number of studies from 22 to 47. Using an index for each study most closely equivalent to "spouse ever smoked", a weak but significant association was seen (random-effects RR = 1.15, 95% CI = 1.07-1.23). However, the estimates were heterogeneous: higher for Asian studies than for North American or European studies, higher for studies adjusting for fewer potential confounding variables, and close to 1.0 for prospective studies, regardless of whether or not they asked detailed questions on ETS exposure. The RR for eight prospective studies asking detailed questions was 1.003, 95% CI = 0.96-1.05. Risk was increased in premenopausal women (RR = 1.36, 95% CI = 1.15-1.60), but not postmenopausal women. Dose-response findings were similarly heterogeneous. No significant increase was seen for childhood or workplace exposure, but an increase was seen for total exposure (RR = 1.22, 95% CI = 1.09-1.37). CONCLUSIONS: Increases mainly derived from case-control studies are prone to recall bias. Study weaknesses and possible publication bias limit interpretation. Considering also the weak association of smoking with breast cancer, and the much lower exposures from ETS than from smoking, our analyses do not clearly demonstrate that ETS exposure increases risk of breast cancer in nonsmokers. More research is needed.

The effect of time changes in diagnosing lung cancer type on its recorded distribution, with particular reference to adenocarcinoma.

Among lung cancers, a substantial shift over time has occurred in the recorded frequency of adenocarcinoma (AdC) relative to that of squamous cell carcinoma (SqCC). This is evident in many countries, and also in those who have never smoked. We attempted to address the extent to which this increase is real, or an artefact of changing diagnostic practices. We reviewed studies re-evaluating diagnoses using more up-to-date criteria, and studies applying standard criteria to cases collected over a long period. We also describe changes to classifications, and factors affecting diagnostic accuracy and consistency. While the four main types have long remained essentially unchanged, successive WHO classifications differ in how tumours are ascribed to these types. Despite refinement of classifications and technological advances, the decision is ultimately the pathologist's. In 11 studies, 189/1212(15.6%) originally diagnosed AdCs were reclassified as non-AdC on review, whereas 541/1564(34.6%) of non-AdCs were reclassified as AdC, increasing AdCs by 30%. Studies examining trends in the proportion of AdC were conflicting; three showing a declining trend, seven no trend, and six some increase. Some studies find lepidic (bronchioloalveolar) carcinoma, but not other AdC sub-types, increased. The rising AdC/SqCC ratio results at least partly from diagnostic changes.

Epidemiological evidence on environmental tobacco smoke and cancers other than lung or breast.

We reviewed 87 epidemiological studies relating environmental tobacco smoke (ETS) exposure to risk of cancer other than lung or breast in never smoking adults. This updates a 2002 review which also considered breast cancer. Meta-analysis showed no significant relationship with ETS for nasopharynx cancer, head and neck cancer, various digestive cancers (stomach, rectum, colorectal, liver, pancreas), or cancers of endometrium, ovary, bladder and brain. For some cancers (including oesophagus, colon, gall bladder and lymphoma) more limited data did not suggest a relationship. An increased cervix cancer risk (RR 1.58, 95%CI 1.29-1.93, n = 17 independent estimates), reducing to 1.29 (95%CI 1.01-1.65) after restriction to five estimates adjusting for HPV infection or sexual activity suggests a causal relationship, as do associations with nasosinus cancer observed in 2002 (no new studies since), and less so kidney cancer (RR 1.33, 95%CI 1.04-1.70, n = 6). A weaker association with total cancer (RR 1.13, 95%CI 1.03-1.35, n = 19) based on heterogeneous data is inconclusive. Inadequate confounder control, recall bias, publication bias, and occasional reports of implausibly large RRs in individual studies contribute to our conclusion that the epidemiological evidence does not convincingly demonstrate that ETS exposure causes any of the cancers studied.

Time trends in never smokers in the relative frequency of the different histological types of lung cancer, in particular adenocarcinoma.

The increasing proportion of lung cancers classified as adenocarcinoma has been a topic of interest and research. The main objective of the analyses reported here is to summarize how the proportion of adenocarcinoma varies in never smokers by time, sex and region based on published evidence on the distribution of lung cancer types available from epidemiological studies. Based on 219 sex- and period-specific blocks of data drawn from 157 publications, there appears to be a clear time-related increase in the proportion of lung cancers in never smokers that are adenocarcinoma, which is evident in both sexes, and not specific to any region. It is seen whether the denominator of the proportion is made up of adenocarcinoma plus squamous cell carcinoma cases, cases of the four major types combined, or all lung cancer cases. The ratio of adenocarcinoma to squamous cell carcinoma rose continuously from 1950 to 69 to be almost 4 times higher for the data from 2000 onwards. We discuss factors that may have contributed to the observed findings, including changes in lung cancer classification. Our findings argue against the hypothesis that increases in the ratio arise from changes in cigarette design and composition.

Is the shape of the decline in risk following quitting smoking similar for squamous cell carcinoma and adenocarcinoma of the lung? A quantitative review using the negative exponential model.

One possible contributor to the reported rise in the ratio of adenocarcinoma to squamous cell carcinoma of the lung may be differences in the pattern of decline in risk following quitting for the two lung cancer types. Earlier, using data from 85 studies comparing overall lung cancer risks in current smokers, quitters (by time quit) and never smokers, we fitted the negative exponential model, deriving an estimate of 9.93years for the half-life - the time when the excess risk for quitters compared to never smokers becomes half that for continuing smokers. Here we applied the same techniques to data from 16 studies providing RRs specific for lung cancer type. From the 13 studies where the half-life was estimable for each type, we derived estimates of 11.68 (95% CI 10.22-13.34) for squamous cell carcinoma and 14.45 (11.92-17.52) for adenocarcinoma. The ratio of the half-lives was estimated as 1.32 (95% CI 1.20-1.46, p<0.001). The slower decline in quitters for adenocarcinoma, evident in subgroups by sex, age and other factors, may be one of the factors contributing to the reported rise in the ratio of adenocarcinoma to squamous cell carcinoma. Others include changes in the diagnosis and classification of lung cancer.

A novel approach to assess the population health impact of introducing a Modified Risk Tobacco Product.

Based on the Food and Drug Administration's Modified Risk Tobacco Product (MRTP) Application draft guideline, Philip Morris International (PMI) has developed a Population Health Impact Model to estimate the reduction in the number of deaths over a period following the introduction of an MRTP. Such a model is necessary to assess the effect that its introduction would have on population health, given the lack of epidemiological data available prior to marketing authorization on any risks from MRTPs. The model is based on publicly available data on smoking prevalence and on the relationships between smoking-related disease-specific mortality and various aspects of the smoking of conventional cigarettes (CCs), together with an estimate of exposure from the MRTP relative to that from CCs, and allows the exploration of possible scenarios regarding the effect of MRTP introduction on the prevalence of CC and MRTP use, individually and in combination. By comparing mortality attributable in a scenario where the MRTP is introduced with one where it is not, the model can estimate the mortality attributable to CCs and the MRTP, as well as the reduction in the deaths attributable to the introduction of the MRTP.