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We also updated risk estimates for individual diseases caused by ST; however, we kept to the original list of conditions, i.e. cancers of the oral cavity, pharynx and oesophagus, ischemic heart disease and stroke. We only searched for papers published since our last literature search; our updated search strategies can be found in Additional file 1: Appendix 3. As before, all searches and data extraction were independently scrutinised by a second researcher and any discrepancies were arbitrated by a third researcher. All case definitions for diseases and exposure (ST use) used in the retrieved articles were checked for accuracy and consistency and all analyses undertaken in these studies were assessed to see if they controlled for key confounders (mainly smoking and alcohol). We assessed study quality using the Newcastle-Ottawa Scale for assessing non-randomised studies in meta-analysis . For all new studies, we log transformed their risk estimates and 95% confidence intervals to effect sizes and standard errors and added these to the rerun of our random-effects meta-analyses to estimate pooled risk estimates for individual conditions. Where possible, we pooled effect sizes to obtain country-specific risk estimates. For all outcomes in the meta-analyses, we conducted a GRADE assessment to assess the quality of evidence. We also pooled these effect sizes to obtain non-specific global risk estimates. Given that the risk varies from country to country, depending upon which products are locally popular, we used country-specific risk estimates where possible. In countries with no estimates, we used estimates of those countries where similar ST products were consumed. For other countries without estimates that consumed ST products known to contain high levels of TSNAs, we applied non-specific global estimates. Where no information was available on the composition of ST, we did not apply any estimates. Details on how these statistically significant estimates were applied to each WHO sub-region can be found in web Additional file 1: Appendix 4.
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ST consumption was reported in 127 countries (Fig. 1). These estimates were extracted from nationally representative cross-sectional surveys conducted either as part of international (97/127) or national (30/127) health and tobacco surveillance (Additional file 1: Appendix 5a). A variety of age ranges (as young as 15 or as old as 89, including no upper age limit) were used to define adults.
The above risk estimates were included in the mathematical model to estimate the population attributable fraction (PAF), as follows (also see Additional file 1, Appendix 4 for detailed justification): For oral, pharyngeal and oesophageal cancers, Sweden- and US-based country-specific risk estimates were applied to Europe A and America A regions, respectively. Similarly, India-based country-specific risk estimates were applied to Southeast Asia B and D and Western Pacific B regions. No risk estimates were applied to Europe C due to the non-existence of any risk estimates or information about the toxicity of ST products. For all other regions, non-specific country estimates were applied. A few exceptions were made to the above assumptions: a Pakistan-based country-specific estimate was applied for oral cancers for Pakistan and an India-based estimate for the other two cancers; for the UK, India-based country specific estimates were applied due to the predominant use of South Asian products in the country. For ischaemic heart disease, the INTERHEART disease estimates were applied to all WHO regions except two, i.e. Europe A due to the availability of Sweden-based country specific estimates and Europe C due to the non-availability of relevant information. As previously stated, an exception was made for the UK and the INTERHEART estimates were applied.
While we found a few more recent ST prevalence surveys and observational studies on the risks associated with ST use, big evidence gaps still remain. The ST surveillance data for many countries are either absent or outdated. The biggest gap is in the lack of observational studies on the risks associated with various types of ST used both within and between countries. While longitudinal studies take time, global surveillance of ST products, their chemical composition and risk profile can help improve the precision of future estimates. As cancer registries become more established around the globe, their secondary data analysis can also provide opportunities to estimate ST-related risks.
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