Risk perception of IQOS™ and cigarettes: Temporal and cross-country comparisons.

Background: Risk perception (RP) is central to smokers' decision to switch to smoke-free tobacco and nicotine products (TNP). This study assessed temporal trends in the health RP of a novel heated tobacco product, IQOS TM , relative to cigarettes, among current IQOS TM users. Methods: The analyses included repeated cross-sectional data from online surveys in Germany (2018-19), Italy (2018-19), and Japan (2016-17, 2017-18, and 2018-19) among a random sample of current adult IQOS TM users from local registers of IQOS TM users. The health RPs of cigarettes and IQOS TM were assessed using the ABOUT™-Perceived Risk instrument, and their difference was described as the relative RP of IQOS TM to cigarettes (RPCig: IQOS TM ). Results: After adjustment for covariates, the relative RPCig: IQOS TM was higher in 2018 than in 2019 (0.93; standard error, 0.33; P = 0.005). This was driven by an increase in the RP of IQOS TM over time in Italy (2018: 42.6 [95% CI, 41.6-43.5]; 2019: 44.4 [43.4-45.4]) and Japan (2017: 44.0 [43.1-44.9); 2018: 45.9 [45.2-46.7]; 2019: 48.6 [47.9-49.4]), while the RP of cigarettes remained stable. Conclusions: The relative RP of IQOS TM decreased over time, driven by an increase in the RP of IQOS TM , in agreement with epidemiological studies indicating a temporal reduction in the relative RP of smoke-free TNPs. Continued surveillance of the RP of novel TNPs is warranted to inform effective TNP risk communication and ensure that adults smokers who would otherwise continue to smoke understand the relative risks of novel TNPs.

Patient assessment and feasibility of treatment in older patients with cancer: results from the IN-GHO® Registry.

PURPOSE: Predicting feasibility of treatment in older patients with cancer is a major clinical task. The Initiative Geriatrische Hämatologie und Onkologie (IN-GHO®) registry prospectively collected data on the comprehensive geriatric assessment (CGA), physician's and patient's-self assessment of fitness for treatment, and the course of treatment in patients within a treatment decision aged ≥ 70 years. PATIENTS AND METHODS: The registry included 3169 patients from 93 centres and evaluated clinical course and treatment outcomes 2-3 and 6 months after initial assessment. Fitness for treatment was classified as fit, compromised and frail according to results of a CGA, and in addition by an experienced physician's and by patient's itself. Feasibility of treatment (termed IN-GHO®-FIT) was defined as a composite endpoint, including willingness to undergo the same treatment again in retrospect, no modification or unplanned termination of treatment, and no early mortality (within 90 days). RESULTS: CGA classified 30.0% as fit, 35.8% as compromised, and 34.2% as frail. Physician's and patient's-self assessment classified 61.8%/52.3% as fit, 34.2%/42.4% as compromised, and 3.9%/5.3%, as frail, respectively. Survival status at day 180 was available in 2072 patients, of which 625 (30.2%) had died. After 2-3 months, feasibility of treatment could be assessed in 1984 patients. 62.8% fulfilled IN-GHO®-FIT criteria. Multivariable analysis identified physician's assessment as the single most important item regarding feasibility of treatment. CONCLUSION: Geriatricians were involved in 2% of patients only. Classification of fitness for treatment by CGA, and physician's or patient's-self assessment showed marked discrepancies. For the prediction of feasibility of treatment no single item was superior to physician's assessment. However CGA was not performed by trained geriatricians.

Potential predictors of adoption of the Tobacco Heating System by U.S. adult smokers: An actual use study.

Background: This was a pre-market, observational, actual use study with the Tobacco Heating System (THS), a candidate modified risk tobacco product. The main goal of the study was to describe THS adoption within current adult daily smokers by replicating the usage of THS in real-world conditions with participants being able to consume cigarettes, THS, and any other nicotine-containing products (e.g., e-cigarettes, cigars, etc.) ad libitum. Methods: This study assessed self-reported stick-by-stick consumption of THS compared with the use of commercial cigarettes over six weeks. The aim of the analysis was to identify potential predictors for adoption of THS using stepwise logistic regression analysis. Results: By the end of the observational period (in Week 6), 14.6% of participants (n=965) had adopted THS meaning that THS formed 70% or more of their total tobacco consumption. The main predictors of adoption were the liking of the smell, taste, aftertaste, and ease of use of THS. The proportion of adoption was higher in participants aged 44 years and older and in Hispanic or Latino adult smokers. Additionally, adoption of THS was more likely in participants who had never attempted to quit smoking and in participants who smoked up to 10 cigarettes per day. Finally, the adoption of THS was higher in participants who consumed both regular and menthol THS compared with those who consumed only one THS variant. Conclusions: The findings suggest that the introduction of THS in the U.S. has the potential to result in adoption by current adult smokers who would otherwise continue to smoke cigarettes, and that the adoption of THS is unlikely to result in an increase of tobacco consumption. Post-marketing studies will provide further insights on THS adoption and THS use patterns to allow assessment of the impact of the THS at the individual and the overall population level.

Risk factors for unplanned discontinuation of scheduled treatment in elderly patients with castration-resistant prostate cancer: results of the IBuTu study.

PURPOSE: To gain knowledge about the factors associated with discontinuation of scheduled treatment in elderly men with castration-resistant prostate cancer (CRPC). METHODS: Patients ≥ 70 years with CRPC starting a new line of treatment were included in a prospective cohort study. A geriatric assessment (CGA) was performed at baseline, including comorbidity, mobility, functional/mental/nutritional status, as well as depression. Furthermore, pain intensity, quality of life, ECOG-performance status, and physicians' and patients' perception of health were documented. Reasons for and factors associated with discontinuation of scheduled treatment were analysed by univariate and multivariate analysis. RESULTS: After inclusion of 177 of 300 planned patients, the study was closed due to slow recruitment. 160 patients were eligible for final analysis. Median age was 77.5 years. 46% received chemotherapy, and 54% hormonal treatment. Discontinuation of scheduled treatment occurred in 91 patients (57.6%). The main reasons were progressive disease/death in 63%, adverse events/toxicity in 22%, and withdrawal of consent in 8%. In bivariate analyses, factors associated with discontinuation of treatment were age ≥ 80 years, ECOG PS ≥ 2, compromised/poor health status (physicians'/patients' assessment), and compromised functional or nutritional status. In multivariate analysis, the only remaining factor independently associated with discontinuation of scheduled treatment was impairment of activities of daily living (ADL < 100 points) (OR = 4.2 for discontinuation; p < 0.05). CONCLUSION: Despite limitations due to early termination of the study, our results demonstrate that discontinuation of scheduled treatment was common, and that compromised ADL seems to be a significant risk factor for treatment failure in elderly patients with CRPC.

Reduced exposure evaluation of an Electrically Heated Cigarette Smoking System. Part 8: Nicotine bridging--estimating smoke constituent exposure by their relationships to both nicotine levels in mainstream cigarette smoke and in smokers.

A modeling approach termed 'nicotine bridging' is presented to estimate exposure to mainstream smoke constituents. The method is based on: (1) determination of harmful and potentially harmful constituents (HPHC) and in vitro toxicity parameter-to-nicotine regressions obtained using multiple machine-smoking protocols, (2) nicotine uptake distributions determined from 24-h excretion of nicotine metabolites in a clinical study, and (3) modeled HPHC uptake distributions using steps 1 and 2. An example of 'nicotine bridging' is provided, using a subset of the data reported in Part 2 of this supplement (Zenzen et al., 2012) for two conventional lit-end cigarettes (CC) and the Electrically Heated Cigarette Smoking System (EHCSS) series-K6 cigarette. The bridging method provides justified extrapolations of HPHC exposure distributions that cannot be obtained for smoke constituents due to the lack of specific biomarkers of exposure to cigarette smoke constituents in clinical evaluations. Using this modeling approach, exposure reduction is evident when the HPHC exposure distribution curves between the MRTP and the CC users are substantially separated with little or no overlap between the distribution curves.

Effectiveness of strategies to increase the validity of findings from association studies: size vs. replication.

BACKGROUND: The capacity of multiple comparisons to produce false positive findings in genetic association studies is abundantly clear. To address this issue, the concept of false positive report probability (FPRP) measures "the probability of no true association between a genetic variant and disease given a statistically significant finding". This concept involves the notion of prior probability of an association between a genetic variant and a disease, making it difficult to achieve acceptable levels for the FPRP when the prior probability is low. Increasing the sample size is of limited efficiency to improve the situation. METHODS: To further clarify this problem, the concept of true report probability (TRP) is introduced by analogy to the positive predictive value (PPV) of diagnostic testing. The approach is extended to consider the effects of replication studies. The formula for the TRP after k replication studies is mathematically derived and shown to be only dependent on prior probability, alpha, power, and number of replication studies. RESULTS: Case-control association studies are used to illustrate the TRP concept for replication strategies. Based on power considerations, a relationship is derived between TRP after k replication studies and sample size of each individual study. That relationship enables study designers optimization of study plans. Further, it is demonstrated that replication is efficient in increasing the TRP even in the case of low prior probability of an association and without requiring very large sample sizes for each individual study. CONCLUSIONS: True report probability is a comprehensive and straightforward concept for assessing the validity of positive statistical testing results in association studies. By its extension to replication strategies it can be demonstrated in a transparent manner that replication is highly effective in distinguishing spurious from true associations. Based on the generalized TRP method for replication designs, optimal research strategy and sample size planning become possible.

Pattern recognition in menstrual bleeding diaries by statistical cluster analysis.

BACKGROUND: The aim of this paper is to empirically identify a treatment-independent statistical method to describe clinically relevant bleeding patterns by using bleeding diaries of clinical studies on various sex hormone containing drugs. METHODS: We used the four cluster analysis methods single, average and complete linkage as well as the method of Ward for the pattern recognition in menstrual bleeding diaries. The optimal number of clusters was determined using the semi-partial R2, the cubic cluster criterion, the pseudo-F- and the pseudo-t2-statistic. Finally, the interpretability of the results from a gynecological point of view was assessed. RESULTS: The method of Ward yielded distinct clusters of the bleeding diaries. The other methods successively chained the observations into one cluster. The optimal number of distinctive bleeding patterns was six. We found two desirable and four undesirable bleeding patterns. Cyclic and non cyclic bleeding patterns were well separated. CONCLUSION: Using this cluster analysis with the method of Ward medications and devices having an impact on bleeding can be easily compared and categorized.

Systematic review of the relation between smokeless tobacco and non-neoplastic oral diseases in Europe and the United States.

BACKGROUND: How smokeless tobacco contributes to non-neoplastic oral diseases is unclear. It certainly increases risk of oral mucosal lesions, but reviewers disagree as to other conditions. In some areas, especially South-East Asia, risk is difficult to quantify due to the many products, compositions (including non-tobacco ingredients), and usage practices involved. This review considers studies from Europe (in practice mainly Scandinavia) and from the USA. METHODS: Experimental and epidemiological studies published in 1963-2007 were identified that related risk of oral lesions to smokeless tobacco use. Data were assessed separately for oral mucosal lesions, periodontal and gingival diseases, dental caries and tooth loss, and oral pain. RESULTS: Oral mucosal lesions: Thirty-three epidemiological studies consistently show a strong dose-related effect of current snuff on oral mucosal lesion prevalence. In Scandinavia, users have a near 100% prevalence of a characteristic "snuff-induced lesion", but prevalence of the varied lesions reported in the USA is lower. Associations with chewing tobacco are weaker. The lack of clear association with former use suggests reversibility following cessation, consistent with experimental studies showing rapid lesion regression on quitting.Periodontal and gingival diseases: Two of four studies report a significant association of snuff with attachment loss and four out of eight with gingival recession. Snuff is not clearly related to gingivitis or periodontal diseases. Limited evidence suggests chewing tobacco is unrelated to periodontal or gingival diseases.Tooth loss: Swedish studies show no association with snuff, but one US study reported an association with snuff, and another with chewing tobacco.Dental caries: Evidence from nine studies suggests a possible relationship with use of smokeless tobacco, particularly chewing tobacco, and the risk of dental caries.Oral pain: Limited evidence precludes any clear conclusion. CONCLUSION: This review confirms the strong association of current use of smokeless tobacco, particularly snuff, with prevalence of oral mucosal lesions. It provides suggestive evidence of an association of snuff use with gingival recession and attachment loss, and of chewing tobacco with dental caries. While smokeless tobacco clearly increases risk of oral mucosal lesions, interpretation for other endpoints is limited by study weaknesses, including poor confounding control.

Predictors of loss to follow-up in young patients with minor trauma after screening and written intervention for alcohol in an urban emergency department.

OBJECTIVE: In health promotion studies, young age, male gender, low education, and substance use have been found to be relevant predictors of loss to follow-up. The purpose of this study was to assess factors of loss to follow-up after screening and tailored brief advice for alcohol problems in an emergency department setting. METHOD: A randomized controlled intervention study was conducted and followed up at 12 months. At baseline (T0), 2,562 consecutive trauma patients (62.1% male) were screened for substance use (smoking, alcohol consumption, and illicit drug use) and for socioeconomic factors (income, relationship status, and education). Patients with five points or more in the Alcohol Use Disorders Identification Test randomly received tailored brief advice on alcohol and were followed up at 3 (T3), 6 (T6), 9 (T9), and 12 months (T12). RESULTS: At baseline, median age was 32 years (range: 18-89). There was a loss of 950 participants (37.1%) from T0 to T12. Loss to follow-up was strongly dependent on social factors. In participants with a high school diploma, only smoking was predictive of loss to follow-up (odds ratio [OR] = 1.81, 95% confidence interval [CI] = 1.43-2.29). In participants with no high school diploma, alcohol problems alone predicted loss to follow-up (medium level of alcohol problems, OR = 1.57, 95% CI = 1.09-2.27; high level of alcohol problems, OR = 1.62, 95% CI = 0.96-2.76; p = .017). Smoking (OR = 1.35, 95% CI = 0.97-1.89) and, for smokers, age 18-31 years (OR = 1.65, 95% CI = 0.98-2.78) showed a tendency toward an increased risk of loss to follow-up. CONCLUSIONS: After screening and a brief intervention in an emergency department, substance use and differences in education level predicted loss to follow-up. Patients with alcohol problems and no high school diploma are at increased risk of becoming lost to follow-up.

Does diabetes mellitus explain the higher hospital mortality of women with acute myocardial infarction? Results from the Berlin Myocardial Infarction Registry.

BACKGROUND: Women with acute myocardial infarction (AMI) exhibit greater hospital mortality than do men. In general, diabetes mellitus is one of the major factors influencing the outcome of patients with AMI. The aim of this study was to analyze the interaction between diabetes and gender, specifically with regard to the higher hospital mortality of female AMI patients aged < or = 75 years. METHODS: We prospectively collected data from 3,715 patients aged < or = 75 (2,794 men, 921 women) with acute myocardial infarction who were treated in 25 hospitals in Berlin, Germany, from 1999 to 2002. In a multivariate analysis, we specifically studied the interaction between the factors diabetes mellitus and gender in their effects on hospital mortality. RESULTS: After adjustment in multivariate analysis, the interaction between gender and diabetes was statistically significant, and the estimated odds ratios were as follows: female diabetic patients compared with male diabetic patients, odds ratio (OR) = 2.28 (95% confidence interval [CI] 1.42-3.68); female diabetic patients compared with male nondiabetic patients, OR = 2.90 (95% CI 1.90-4.42); and female diabetic patients compared with female nondiabetic patients, OR = 2.92 (95% CI 1.75-4.87). There was no statistically significant difference between the risk of dying for female nondiabetic patients or for male diabetic patients when compared with male nondiabetic patients. CONCLUSIONS: In AMI patients aged < or = 75 years, female gender alone is not an independent predictor of hospital mortality. Detailed, multivariate analysis reveals that specifically diabetic women demonstrate higher hospital mortality than do men. Special attention should be provided to these female diabetic patients.

Duration of breastfeeding and risk of overweight: a meta-analysis.

Observational studies suggest a longer duration of breastfeeding to be associated dose dependently with a decrease in risk of overweight in later life. The authors performed a comprehensive meta-analysis of the existing studies on duration of breastfeeding and risk of overweight. Studies were included that reported the odds ratio and 95% confidence interval (or the data to calculate them) of overweight associated with breastfeeding and that reported the duration of breastfeeding and used exclusively formula-fed subjects as the referent. Seventeen studies met the inclusion criteria. By meta-regression, the duration of breastfeeding was inversely associated with the risk of overweight (regression coefficient=0.94, 95% confidence interval (CI): 0.89, 0.98). Categorical analysis confirmed this dose-response association (<1 month of breastfeeding: odds ratio (OR)=1.0, 95% CI: 0.65, 1.55; 1-3 months: OR=0.81, 95% CI: 0.74, 0.88; 4-6 months: OR=0.76, 95% CI: 0.67, 0.86; 7-9 months: OR=0.67, 95% CI: 0.55, 0.82; >9 months: OR=0.68, 95% CI: 0.50, 0.91). One month of breastfeeding was associated with a 4% decrease in risk (OR=0.96/month of breastfeeding, 95% CI: 0.94, 0.98). The definitions of overweight and age had no influence. These findings strongly support a dose-dependent association between longer duration of breastfeeding and decrease in risk of overweight.

Disease management programs for depression: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Substantial deficits in the care of depression make the provision of new evidence-based care models a matter of increasing importance. So far, disease management programs (DMPs) have not been systematically assessed. OBJECTIVE: This study was a systematic review and meta-analysis of randomized controlled trials investigating the effectiveness of DMP for depression as compared with usual primary care. METHODS: Criteria for study selection were depression as main diagnosis in adults, the intervention DMP (evidence-based guidelines, patient/provider education, collaborative care, reminder systems, and monitoring), and trial quality A/B (Cochrane Collaboration guidelines) rated by 2 observers. Measurement instruments had to be published in peer-reviewed journals and filled out by the participants, their relations, or independent raters. Meta-analyses were conducted by using dichotomous outcomes within forest plots. Tests of heterogeneity, sensitivity analyses, and funnel plots were performed. Economic evaluations were descriptively summarized. RESULTS: DMP had a significant effect on depression severity, with a relative risk of 0.75 (95% confidence interval 0.70-0.81) in a homogeneous dataset of 10 high-quality trials. It was robust in all sensitivity analyses (evidence level 1A). Funnel plot symmetry indicated a low probability of publication bias. Patient satisfaction and adherence to the treatment regimen improved significantly, but only in heterogeneous models. The costs per quality adjusted life year ranged between US 9,051 dollars and US 49,500 dollars. CONCLUSION: DMP significantly enhance the quality of care for depression. Costs are within the range of other widely accepted public health improvements. Future research should focus on the effect of long-term interventions, and the compatibility with health care systems other than managed-care driven ones.