High Tobacco Consumption Research Articles

Screening with Low-Dose Computed Tomography Does Not Improve Survival of Small Cell Lung Cancer

IntroductionSmall cell lung cancer (SCLC) constitutes a distinct component of symptomatic or advanced-stage lung cancers in clinical practice and in lung cancer screening trials. The purpose of this study was to describe the outcome of SCLC in lung cancer screening trials and compare the frequency of SCLC in our cohort with that in the major lung cancer screening trials. MethodsSubjects with a diagnosis of SCLC were selected from two lung cancer screening trials by low-dose computed tomography (LDCT), and their demographic characteristics, clinical parameters, tumor stage at diagnosis, therapy, and survival times were recorded. Survival curves were estimated using the Kaplan-Meier method. ResultsTen cases of SCLC were reported in 45,141 person-years (22 in 100,000 person-years), representing the 6% of all lung cancer cases. Cumulative tobacco consumption was 82 pack-years compared with 39 and 46 pack-years for the overall study population and subjects with non-SCLC, respectively. Most of the neoplasms were in an advanced stage (seven in stage IV and one each in stages IIIb, IIIa, and Ia). Two subjects were treated with lobectomy for curative purposes and died of diffuse metastasis within 2 years of diagnosis. The median overall survival time in the LDCT arms was 20.6 months, with no survivors remaining at 3 years. ConclusionsSubjects in whom SCLC develops are a subgroup of smokers with extremely high cumulative tobacco consumption. Consequently, the frequency of SCLC in our population was lower than in other screening populations, with higher cumulative tobacco consumption. Screening for lung cancer by LDCT does not improve survival of SCLC, with no survivors remaining at 3 years after diagnosis.

Associação entre o consumo de bebidas alcoólicas e tabaco e a religiosidade

Resumo Objetivo Verificar a associação entre a religiosidade e o padrão de consumo de álcool e tabaco em população atendida na Atenção Primária à Saúde. Métodos Estudo transversal realizado com 363 indivíduos, maiores de 18 anos. A variável de exposição, religiosidade, foi avaliada segundo o Índice de Religiosidade da Universidade de Duke. O desfecho, consumo de álcool e tabaco, foi avaliado pelo questionário Alcohol, Smoking and Substance Involvement Screening Test (ASSIST). Verificou-se a associação entre exposição e desfecho, com base na análise de regressão logística multivariada. Resultados Foi alta a prevalência no consumo de álcool e tabaco nos grupos mais vulneráveis. As religiosidades organizacional e intrínseca mostraram-se fator de proteção em relação ao consumo moderado/alto de álcool e tabaco. Conclusão Quanto maior o escore para a religiosidade organizacional e intrínseca, menor o consumo para essas substâncias.

Abstract 581: Mutational landscape of PIK3CA gene and its association with oral squamous cell carcinoma in Indian population

Abstract Oral Squamous Cell Carcinoma (OSCC) - the subset of Head and Neck Cancer is the sixth most common cancer worldwide and leading cancer in India. Western part of India (Gujarat) is a prime tobacco growing belt, henceforth, has a high tobacco consumption and increased occurrence of oral cancer. Phosphatidylinositol- 3- kinase (PI3K) is heterodimeric protein kinase composed of catalytic subunit, p110α, and a regulatory subunit, p85α; which regulates cell proliferation, apoptosis, and metastasis. The PIK3CA gene, encodes p110α catalytic subunit, when somatically mutated gets highly deregulated in number of cancers. Canonical mutations E542K, E545K and H1047R in p110α have proven to have higher oncogenic potential, subsequently activating downstream pathways. However, this observation has been reported in limited ethnicity in OSCC. Therefore, we have analyzed mutation profile of exon9 and 20 of PIK3CA gene in 50 OSCC primary tumors and corresponding control samples by direct sequencing in Indian population. We have observed two hot spots mutations E542K and E545K in exon 9, which were earlier reported to activate downstream signaling pathways and two synonymous mutations C3075T and C2985T in exon 20 in fourteen and one OSCC patients, respectively. Patients harboring oncogenic mutations were at advanced stage of OSCC having tobacco chewing history more than ten years. Additionally, we observed two Single Nucleotide Polymorphism rs114587137 (C>T) and rs17849071 (T>G) in intron 9 of PIK3CA gene, which was found germ line mutated in fifteen and three OSCC patients respectively. In summary, we found 4% (2/50) oncogenic mutation frequency of PIK3CA gene, which may play a crucial role through PI3K downstream signaling pathway in oral neoplasia. Our study supports the notion that lower oncogenic mutation frequency of PIK3CA gene has been found in Asian populations but comparable to that seen in western countries. The knowledge of the involvement of PIK3CA mutations in OSCC is of importance, because a specific kinase inhibitor of PIK3CA may potentially serve as an effective therapeutic target against OSCC as a personalized medicine. Citation Format: Sejal Shah, Siddharth Shah, Harish Padh, Kiran Kalia. Mutational landscape of PIK3CA gene and its association with oral squamous cell carcinoma in Indian population. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 581. doi:10.1158/1538-7445.AM2015-581

Carotenoid intake and head and neck cancer: a pooled analysis in the International Head and Neck Cancer Epidemiology Consortium.

Food and nutrition play an important role in head and neck cancer (HNC) etiology; however, the role of carotenoids remains largely undefined. We explored the relation of HNC risk with the intake of carotenoids within the International Head and Neck Cancer Epidemiology Consortium. We pooled individual-level data from 10 case-control studies conducted in Europe, North America, and Japan. The analysis included 18,207 subjects (4414 with oral and pharyngeal cancer, 1545 with laryngeal cancer, and 12,248 controls), categorized by quintiles of carotenoid intake from natural sources. Comparing the highest with the lowest quintile, the risk reduction associated with total carotenoid intake was 39% (95% CI 29-47%) for oral/pharyngeal cancer and 39% (95% CI 24-50%) for laryngeal cancer. Intakes of β-carotene equivalents, β-cryptoxanthin, lycopene, and lutein plus zeaxanthin were associated with at least 18% reduction in the rate of oral and pharyngeal cancer (95% CI 6-29%) and 17% reduction in the rate of laryngeal cancer (95% CI 0-32%). The overall protective effect of carotenoids on HNC was stronger for subjects reporting greater alcohol consumption (p<0.05). The odds ratio for the combined effect of low carotenoid intake and high alcohol or tobacco consumption versus high carotenoid intake and low alcohol or tobacco consumption ranged from 7 (95% CI 5-9) to 33 (95% CI 23-49). A diet rich in carotenoids may protect against HNC. Persons with both low carotenoid intake and high tobacco or alcohol are at substantially higher risk of HNC.

0470 : Serum IF1 concentration as a predictor of mortality in coronary heart disease patients

The ecto-F1-ATPase/P2Y13 pathway plays a key role in reverse cholesterol transport. Exogenous IF1, known as the natural mitochondrial specific inhibitor of F1-ATPase activity, inhibits ecto-F1-ATPase activity and decreases HDL-C uptake by hepatocytes. We previously found that IF1 is present in human serum and is negatively associated with coronary heart disease (CHD). Here, we investigated the relationship between serum IF1 concentration and mortality in CHD patients. Serum IF1 was measured in 624 CHD patients aged 45-74 from the GENES (Genetique et ENvironement en Europe du Sud) study. After 9.1 years follow up, mortality rate was 24.5%. Patients who had died were older at inclusion, were more often treated for dyslipidemia or diabetes mellitus, had higher tobacco consumption, CRP level but lower physical activity. Resting heart rate and the Gensini score of CHD severity were higher while LVEF (Left Ventricular Ejection Fraction) was decreased. They also had lower serum IF1 concentration (0.41 vs 0,44μg/ml, p=0.03). In CHD patients, IF1 concentration was negatively associated with triglycerides, Gensini score and resting heart rate and positively with physical activity, HDL-C and LVEF. HDL-C was correlated with the Gensini score but not with resting heart rate and LVEF. Serum IF1 in the two highest quartiles (≥0,42μg/ml) was associated with significantly reduced mortality risk, even after multivariate adjustments for classical cardiovascular risk factors and Gensini score (HR=0.55, p=0.026 for the highest quartile). Significance was lost after adjustment for LVEF (HR=0.72, p=0.23). High serum IF1 is predictor of reduced mortality in CHD patients. This prognostic value remains significant whatever the value of HDL-C and Gensini score, a marker of atheroma diffusion, but was lost after adjustment for LVEF. Correlation between serum IF1 concentration and LVEF might underlie the relationship between IF1 level and mortality.

High tobacco consumption lowers body weight: a Mendelian randomization study of the Copenhagen General Population Study.

Conflicting evidence has been found regarding the association between high tobacco consumption and body weight among smokers. We tested the hypothesis that high tobacco consumption is causally associated with low body weight. We conducted a Mendelian randomization study with a genetic variant in CHRNA3 (rs1051730) as proxy for high tobacco consumption. The cohort consisted of 80,342 participants from the Copenhagen General Population Study, with details on body weight, smoking habits and CHRNA3 genotype, including 15,220 current smokers. In observational analyses, high tobacco consumption was associated with high body weight, body mass index, waist circumference, hip circumference and waist-hip ratio. In multivariable adjusted models a 1-cigarette/day higher tobacco consumption was associated with 0.05 kg (95% confidence interval 0.02; 0.08) higher body weight, 0.02 kg/m(2) (0.01; 0.02) higher body mass index, 0.10 cm (0.07; 0.12) higher waist circumference and 0.02 cm (0.001; 0.03) higher hip circumference. In contrast, the per-allele increase inCHRNA3 rs1051730 associated with high tobacco consumption was associated with 0.59 kg (0.96; 0.22) lower body weight, 0.23 kg/m(2) (0.33; 0.13) lower body mass index, 0.32 cm (0.74; 0.003) lower waist circumference and 0.45 cm (0.66; 0.24) lower hip circumference. No association was found between tobacco consumption and waist-hip ratio in genetic analysis, or among CHRNA3 genotype and any of the outcome variables in former or never smokers. High tobacco consumption causes lower body weight among current smokers. However, smoking does not seem to affect body shape or fat distribution causally. The lack of association between CHRNA3 genotype and body weight among former smokers and never smokers favours smoking as the causal factor for the observed associations.

Community based intervention for tobacco cessation: a pilot study experience, north East India.

North East India has a high prevalence of tobacco consumption, but only few individualsseek help for tobacco cessation. Impact of community based tobacco cessation intervention in this part needs more research. Retrospective analysis was done on the dataset from a community-based tobacco cessation intervention pilot project conducted in Guwahati metro during 2009-10. Subjects, both male and female tobacco users, age>15 years, permanent residents of these blocks giving consent were included in the study. The sample was 800 tobacco users, of whom 25% visited any health care provider during last 12 months and 3% received tobacco cessation advice. An 18% quit rate was observed at six weeks follow up, more than the National average, with a 47% quit rate at eight months, while 52% of subjects reduced use. Higher tobacco quit rate and reduced tobacco use, no loss to follow up and negligible relapse was observed with this community based intervention design. Such designs should be given more emphasis for implementation in specified communities with very high tobacco consumption rates, cultural acceptance of tobacco and less motivation towards quitting.

Prevalence of risk factors for cardiovascular disease in paramedics.

Occupational stress and obesity are very prevalent in emergency workers. Some studies have also associated high tobacco consumption rates with occupational stress. Each of these factors is known to increase cardiovascular risk. The aim of this study was to evaluate the prevalence of occupational stress, overweight and tobacco consumption in paramedics. This cross-sectional study of paramedics consisted in a self-report survey of 44 questions divided into two sections. The first section collected demographic information and the second evaluated occupational stressors. The questions were designed to determine the prevalence of work-related psychosocial factors, overweight (body mass index ≥ 25 kg/m(2)) and tobacco consumption (cig/day ≥ 1). The demand-control-social support model and the effort-reward model were used to estimate job strain, iso-strain and imbalance in effort and reward. More than 88 % of paramedics reported at least one cardiovascular risk factor, with males reporting more risk factors than females. Ninety percent of male paramedics reported occupational stress, 12 % reported smoking, and 79 % were overweight or obese by self-report. The prevalence of occupational stress and smoking was similar for female paramedics, but with a lower prevalence of overweight (37 %). By self-report, nine out of ten paramedics are at risk of developing cardiovascular disease. Both individual and organizational efforts should be made to educate and support paramedics and their organizations in reducing these workers' cardiovascular risk.

High tobacco consumption is causally associated with increased all-cause mortality in a general population sample of 55,568 individuals, but not with short telomeres: a Mendelian randomization study.

High cumulative tobacco consumption is associated with short telomeres and with increased all-cause mortality. We tested the hypothesis that high tobacco consumption is causally associated with short telomeres and with increased all-cause mortality. We studied 55,568 individuals including 32,823 ever smokers from the Danish general population, of whom 3430 died during 10 years of follow-up. All had telomere length measured, detailed information on smoking history, and CHRNA3 rs1051730 genotype, which is associated with tobacco consumption, determined. In a Mendelian randomization study, we conducted observational, genetic, and mediation analyses. First, tobacco consumption was 21.1 pack-years in non-carriers, 22.8 in heterozygotes and 24.8 in homozygotes (P-trend<0.001). Second, the observational multivariable adjusted hazard ratio for all-cause mortality was 1.12 [95% confidence interval (CI): 1.09, 1.15] per doubling in tobacco consumption. In Mendelian randomization analysis, the hazard ratio was 1.08 (1.02, 1.14) per minor CHRNA3 allele in ever smokers. Third, in observational analysis telomeres shortened with -13 base pairs (-18, -8) per doubling in tobacco consumption. In Mendelian randomization analysis, the estimate was +3 base pairs (-10, +15) per minor CHRNA3 allele. Finally, individuals with the shortest vs longest telomeres had a multivariable adjusted hazard ratio of 1.30 (1.13, 1.50) for all-cause mortality; however, in mediation analysis short telomeres explained only +0.4% (-3.5%, +4.3%) of the association between high tobacco consumption and increased all-cause mortality. High tobacco consumption is causally associated with increased all-cause mortality. High cumulative tobacco consumption is associated with short telomeres observationally, but there is no clear genetic association.

Risk factors for oral diseases among workers with and without dental insurance in a national social security scheme in India

The target population for this cross sectional study comprises subjects with and without social security in a national social security scheme. The study aimed to compare and assess the risk factors for oral diseases among insured (organised sector) and non-insured workers (unorganised sector) in New Delhi, India. The sample comprised a total of 2,752 subjects. Of these, 960 workers belonged to the formal or organised sector with a social security and dental health insurance and 1,792 had no social security or dental insurance from the informal or unorganised sector. Significant differences were noted between the two groups for literacy levels, between-meal sugar consumption, tobacco-related habits and utilisation of dental care. Bleeding/calculus and periodontal pockets were present among 25% and 65.4% of insured workers, respectively. Similarly, 13.6% and 84.5% of non-insured workers had bleeding/calculus and periodontal pockets, respectively. The mean DMFT (decayed, missing, filled teeth) value among the insured workers and non-insured workers was 3.27±1.98 and 3.75±1.80, respectively. The association between absence of health insurance and dental caries was evident with an odds ratio (OR) of 1.94. Subjects with below graduate education were more prone to dental caries (OR=1.62). Subjects who cleaned their teeth two or more times a day were less likely to have dental caries (OR=1.47). Utilisation of dental care was inversely related to dental caries (OR=1.25). The major risk factors for oral diseases in both the groups with similar socio-economic status were the lack of social security and health insurance, low literacy levels, high tobacco consumption and low levels of dental care utilisation.

Eating Behaviors, Body Composition and Risk of Relapse among Persons withdrawing from Substance Abuse: A 3-months Follow-up Study

Objective: To describe eating behaviors and body composition before, during and after substance abuse withdrawal, and to assess if these factors were related with withdrawal outcome. Methods: This was a three month follow-up study examining eating behaviors (measured by validated questionnaires and interview), substance use (assessed with Addiction Severity Index) anthropometry (weight, height and bioimpedance for body composition), medical conditions and psycho-social environment (recorded from medical files and Addiction Severity Index) of 117 patients enrolling in a detoxification program at the University Hospitals, Geneva, Switzerland. Characteristics at baseline and after one month were compared according to patients’ outcome. Variables showing a significant association with relapse were entered in a multivariate logistic regression Results: Most patients were men (84, 71%), and detoxified from alcohol (95, 81%). Relapse rates were 27% after 1 month and 45% after 3 months. Eating disorders were rare but 19% scored high on shape concern scale, 35% experienced nibbling, 20% compulsive night eating and 14% binge episodes, 24% displayed lower than normal fat-free mass and 40% had higher than normal fat mass. Bivariate analysis showed that low nutritional status (low BMI, or low fat mass or low fat free mass), was associated with a decreased risk of relapse. Withdrawal from drugs, higher tobacco consumption and higher severity index for legal area were associated with relapse. These determinants showed no effect on outcome in a multivariate analysis. Conclusion: Problematic eating behaviors were common in this group, whereas eating disorders were rare. Relapse rate was high. No variable was related with relapse at multivariate level. As in general population, overweight and high fat mass were common among persons abusing substances. BMI was a poor indicator of their nutritional status. Our study suggests attention should be given to patients’ eating behaviors, weight and shape preoccupation during substance withdrawal and follow-up.

ApoE genotype and obstructive sleep apnea syndrome

The obstructive sleep apnea syndrome (OSAS) is frequently associated with obesity, hypertension, diabetes and dyslipidemia and other cardiovascular risk factors. In addition, patients with untreated of OSAS have an increased cardio-vascular mortality and morbidity Apolipoprotein E (ApoE) plays an important role in the metabolism and transport of lipids. The three main isoforms (E2, E3, and E4) are coded by three common alleles ( ε 2, ε 3, and ε 4), resulting in six main genotypes: ε 2/ ε 2, ε 2/ ε 3, ε 2/ ε 4, ε 3/ ε 3, ε 3/ ε 4, and ε 4/ ε 4. Presence of the APOE ε 4 allele is also associated with HDL (High Density Lipoprotein). The aim of this study was to determine what is in our population the prevalence of different alleles of the ApoE gene, if there is an association of allele ε 4 with OSAS and what is their contribution to metabolic syndrome. Cross-sectional study of 440 men patients. Mean age 54 ± 12 years (range 25–79 years), referred to the sleep unit for study.Written informed consent was obtained from all subjects for the extraction of genetic material, with exclusive analysis of the ApoE gene. Each patient has a clinical history reflecting metabolic and cardiovascular risk and medication in use. nthropometric data were recorded: weight, height, waist circumference and neck circumference. Determination of blood pressure (BP) at baseline. The study protocol included polysomnography (PSG) overnight in our sleep unit. Upon awakening, the BP was measure and simultaneously blood samples were collected, one for biochemical and other for the molecular biology laboratory, in order to extract DNA.The recorded variables were studied with the statistical program Statview. Parametric test was applied ANOVA for quantitative variables and chi-square (X2) for qualitative variables. Accepting a degree of significance of p < 0.05. The distribution of genotypes revealed that the prevalence of the ε 3/ 3 allele was the most predominant (73.6% of cases), followed by the ε 4 allele in 16.4, which is heterozygous in 15.4% ( ε 3/ 4) and 1% homozygous ( ε 4/ 4).The ε 2 allele was the 10% off the population of the study. The ApoE ε 4 patients have more severe OSAS with longer arterial oxygen desaturation during sleep, expressed by the T90. This genotype was associated with a statistically significant increase of inflammation markers and decreased melatonin. Also note that these patients has high tobacco consumption. In our population the distribution of the genotype correlates with is in the literature; there is an evidence of a relationship between ApoE ε 4 genotype with moderate to severe sleep beathing disordered. sleep unit, Hospital General de Castellón.

High Prevalence of Left Ventricle Diastolic Dysfunction in Severe COPD Associated with A Low Exercise Capacity: A Cross-Sectional Study

BackgroundA subclinical left ventricle diastolic dysfunction (LVDD) has been described in patients with chronic obstructive pulmonary disease (COPD).ObjectivesTo evaluate the prevalence of LVDD in stable severe COPD patients, to analyze its relationship with exercise capacity and to look for its possible causes (lung hyperinflation, ventricular interdependence or inflammatory mechanisms).MethodsWe evaluated 106 consecutive outpatients with severe COPD (FEV1 between 30–50%). Thirty-three (31%) were excluded because of previous heart disease. A pulmonary function test, a 6-minute walking test (6MWT), a Doppler echocardiography test, including diastolic dysfunction parameters, and an analysis of arterial blood gases, NT-proBNP and serum inflammatory markers (CRP, leucocytes), were performed in all patients.ResultsThe prevalence of LVDD in severe stable COPD patients was 90% (80% type I, n=57, and 10% type II, n=7). A significant association between a lower E/A ratio (higher LVDD type I) and a lower exercise tolerance (6-minute walked distance (6MWD)) was found (r=0.29, p<0.05). The fully adjusted multivariable linear regression model demonstrated that a lower E/A ratio, a DLCO in the quartile 4th and a higher tobacco consumption were associated with a lower 6MWD (76, 57 and 0.7 metres, respectively, p<0.05). A significant correlation between E/A ratio and PaO2 was observed (r=0.26, p<0.05), but not with static lung hyperinflation, inflammation or right ventricle overload parameters.ConclusionIn stable severe COPD patients, the prevalence of LVDD is high and this condition might contribute in their lower exercise tolerance. Hypoxemia could have a concomitant role in their pathogenesis.

Alcohol drinking, tobacco smoking and subtypes of haematological malignancy in the UK Million Women Study.

Background:Previous research suggests associations of lower alcohol intake and higher tobacco consumption with increased risks of haematological malignancy. The prospective Million Women Study provides sufficient power for reliable estimates of subtype-specific associations in women.Methods:Approximately 1.3 million middle-aged women were recruited in the United Kingdom during 1996–2001 and followed for death, emigration and cancer registration until 2009 (mean 10.3 years per woman); potential risk factors were assessed by questionnaire. Adjusted relative risks were estimated by Cox regression.Results:During follow-up, 9162 incident cases of haematological malignancy were recorded, including 7047 lymphoid and 2072 myeloid cancers. Among predominantly moderate alcohol drinkers, higher intake was associated with lower risk of lymphoid malignancies, in particular diffuse large B-cell lymphoma (relative risk 0.85 per 10 g alcohol per day (95% confidence interval 0.75–0.96)), follicular lymphoma (0.86 (0.76–0.98)) and plasma cell neoplasms (0.86 (0.77–0.96)). Among never- and current smokers, higher cigarette consumption was associated with increased risk of Hodgkin lymphoma (1.45 per 10 cigarettes per day (1.22–1.72)), mature T-cell malignancies (1.38 (1.10–1.73)) and myeloproliferative/myelodysplastic disease (1.42 (1.31–1.55)).Conclusion:These findings confirm and extend existing evidence for associations of subtypes of haematological malignancy with two common exposures in women.

Smoking and air pollution exposure and lung cancer mortality in Zhaoyuan County

Simultaneous exposure to high levels of air pollution and high tobacco consumption at the same place is rare. The aim of the present study was to evaluate the impact of the two factors on the risk of developing lung cancer. Data on the number of deaths due to lung cancer and on population from 1970 to 2009 were obtained from Zhaoyuan County. Data on the smoking populations were obtained at random sampling survey during the time in Zhaoyuan. Data on the components of atmospheric surveillance were obtained from the local environmental protection offices. Logarithmic linear regression and general log-linear Poisson age-period-cohort (APC) models were used to estimate age, period, cohort, gender, smoking, and air pollution effects on the risk of lung cancer mortality. The standardized mortality rates of lung cancer drastically increased from 8.43 in per 100 000 individuals in the 1970-1974 to 25.67 in per 100 000 individuals in the 2005-2009 death survey. The annual change of lung cancer mortality was 3.20%. In the log linear regression model, the age, proportion of smokers, gender, period, and air pollution are significantly associated with lung cancer mortality. The APC analysis shows that the relative risks (RRs) of gender, smoking, and air pollution are 2.29 (95% confidence interval (CI): 2.16-2.43), 3.05 (95% CI = 2.76-3.36), and 1.42 (95% CI = 1.19-1.69), respectively. Compared with the period 1970-1974, high RRs were found during 1995-2009. Compared with the birth cohort 1950-1954, the RRs increased in the birth cohorts of 1910 to the 1940. Compared the aged 35-59 and 60-84 in the 1980-1984 death survey (not exposed to air pollution) with that in the 2005-2009 death survey (exposed to air pollution), The two age groups exposed to air pollution, 25 years later, had an increased mortality rates for lung cancer by 2.27 and 3.55 times for males and by 1.47 and 3.35 times for females. The mortality rates of lung cancer drastically increased in the past 35 years. The trend of lung cancer mortality may be in a great extent possibly due to the effects of combined smoking and air pollution exposure.

Chronic use of benzodiazepines and latent cognitive decline in the elderly: Results from the Three-city study

We aimed to examine whether long-term use of benzodiazepines is associated with an accelerated decline of cognitive performances by using a statistical model specifically adapted to multivariate longitudinal bounded quantitative outcomes. The data came from the “Three-city” study, a French population based study. All the subjects were 65 years old or older at inclusion and had been followed-up for 7 years. The use of benzodiazepines and cognitive functioning were assessed at each examination phase (baseline, 2, 4 and 7 years). Cognitive decline was analyzed using a nonlinear multivariate mixed model with a latent process. This model makes it possible to assess change over time of the latent cognitive process underlying several neuropsychological tests: Mini Mental Status Examination, Isaacs Set test, Benton Visual Retention Test, and Trail Making Test (A and B), and to describe and account for their metrological properties. Analyses were adjusted for age, center, gender, education, socio-professional status, depression, insomnia, high blood pressure, hypercholesterolemia, alcohol, tobacco consumption and physical activity. Nine hundred and sixty nine subjects who reported taking benzodiazepines for 2, 4 or 7 consecutive years were compared to 4226 subjects who were non-benzodiazepine users. Chronic use of benzodiazepine was significantly associated with a lower latent cognitive level (β=−1.79 SE=0.25 p=<0.001), but no association was found between chronic use and an acceleration of cognitive decline, neither on the latent cognitive process (β×time=0.010 SE=0.04 p=0.81), nor on specific neuropsychological tests. Our results suggest that chronic benzodiazepine use is associated with poorer cognitive performance but not with accelerated cognitive decline with age.

Dose–response relationship between tobacco or alcohol consumption and the development of diabetes mellitus in Japanese male workers

BackgroundThe aim of this study was to examine the dose–response relationships between tobacco or alcohol consumption and the development of diabetes mellitus. MethodsAn 8-year prospective cohort study was conducted in 8423 male workers who received annual health check-ups between 2002 and 2010 at a Japanese steel company. The endpoints were defined as an HbAlc≥6.1% or taking any anti-diabetic medication. The dose–response relationships of tobacco or alcohol consumption were investigated using a proportional hazards regression with time-dependent covariates selected from baseline age, body mass index, mean arterial pressure, total serum cholesterol, aspartate aminotransferase, creatinine and uric acid, shift work or day work, and habitual exercise by stepwise selection method. ResultsA positive dose–response relationship between tobacco consumption and the development of diabetes mellitus was observed, with a significantly higher hazard ratio (HR) seen with higher tobacco consumption (11–20 cigarettes/day, HR 1.26 [95% confidence interval (CI), 1.00–1.59], ≥21 cigarettes/day, HR 1.54 [95%CI, 1.20–1.97]). In contrast, we observed a negative dose–response relationship between alcohol consumption and the development of diabetes mellitus, with a significantly lower HR with higher weekly alcohol consumption (7.0–13.9gou/week [154–307g/week], HR 0.73 [95% CI, 0.55–0.97], ≥14.0gou/week [308g/week], HR 0.75 [95% CI, 0.57–0.98]). ConclusionsThe results indicated that decreasing tobacco consumption will achieve significant prevention of diabetes mellitus. On the other hand, we observed a significant, negative dose–response relationship between alcohol consumption and the development of diabetes mellitus, in contrast to previous studies that reported a positive relationship in the Japanese population.

ASSOCIATION BETWEEN A URINARY BIOMARKER OF PRENATAL EXPOSURE TO DISINFECTION BY-PRODUCTS AND ADVERSE PREGNANCY OUTCOMES

Background and aims:The microbiological control of drinking water through chlorinated disinfectants produces a large number of disinfection by-products (DBPs) suspected to have adverse reproductive effects. Most epidemiological investigations of the effect of prenatal exposure to DBPs on pregnancy outcomes used indirect measures of exposure combining estimated residential levels of trihalomethanes (THM) or haloacetid acids (HAAs) in tap water and eventually personal uses of water. Urinary trichloroacetic acid (TCAA) (one of the HAAs) has been validated as a biomarker of chronic exposure to DBPs via ingestion of chlorinated drinking water. We used it to study the association of DBP exposure with fetal growth and duration of gestation. Methods:The PELAGIE birth cohort included 3,421 pregnant women in early pregnancy (&lt;19 weeks of gestation) between 2002 and 2006. At inclusion, women were asked to complete a self-administered questionnaire and to provide a urine sample. Maternal urinary levels of trichloroacetic acid (TCAA) were assessed in a nested case-control study comparing 174 cases of fetal growth restriction, 114 preterm births, and 399 controls. Odds ratios were estimated with logistic models adjusted for high blood pressure, tobacco, alcohol, and coffee consumption, marital and employment status. Results:TCAA was detected in 7% of the 611 maternal urine samples tested. The limit of detection was 0.01 mg/L. Women with detected TCAA in their urine had a significantly higher risk than others of fetal growth restriction (adjusted odds ratio=2.07; 95% confidence interval (CI): 1.00, 4.26). No association was found with preterm birth. Conclusions:Prenatal exposure to DBPs as measured by detected urinary TCAA seems to affect fetal growth. This biomarker should however be considered as a marker of the whole mixture of DBPs and the causal agent(s), if any, remain to be identified.

Prophylactic cranial irradiation in non-small cell lung cancer patients: who might be the candidates?

ObjectivesBrain metastases (BMs) often advance the course of non-small cell lung cancer (NSCLC). We performed an observational study in order to investigate the possible correlation of selected clinical and epidemiological factors with BM appearance in patients suffering from different histological subtypes of NSCLC stage I–IV.MethodsThe study included 161 consecutive patients with NSCLC. Analyzed data included patient- and tumor-related characteristics.ResultsThirty-nine patients (24.2%) presented BMs within 12 (0–36) weeks of diagnosis. BMs decreased the mean overall survival significantly (15.6 versus 50.7 weeks, P < 0.001), with hazard ratio (95% confidence interval) 3.60 (2.42–5.35). The age of the patients with BM was significantly lower than that of the patients without BM (60.8 ± 8.9 versus 66.5 ± 8.5, P < 0.001). Patients with BM had significantly higher pack-years consumption (75.9 ± 23.9 versus 58.9 ± 31.9, P = 0.003) and larger tumor size compared with patients without BM (size in mm: 55.1 ± 20.1 versus 45.9 ± 19.3, P = 0.012). The presence of BM was also correlated with the absence of lung (P < 0.001), bone (P = 0.005), and adrenal (P = 0.046) metastases.ConclusionYounger NSCLC patients with high tobacco consumption, large tumor size, and absence of metastases in other organs (lung, bones, adrenal metastases) are at high risk of BM appearance during the course of NSCLC and are candidates for prophylactic cranial irradiation early in the course of the disease.

Prophylactic cranial irradiation in non-small cell lung cancer patients: who might be the candidates?

Prophylactic cranial irradiation in non-small cell lung cancer patients: who might be the candidates? Charalampos Dimitropoulos1, Georgios Hillas2, Sofia Nikolakopoulou2, Ioanna Kostara2, Konstantinos Sagris2, Fotis Vlastos2, Manos Alchanatis319th Respiratory Medicine Department; 2Department of Respiratory and Critical Care Medicine, Research Unit; 3University of Athens, 1st Respiratory Medicine Department, University of Athens Medical School, “Sotiria” Chest Diseases Hospital, Athens, GreeceObjectives: Brain metastases (BMs) often advance the course of non-small cell lung cancer (NSCLC). We performed an observational study in order to investigate the possible correlation of selected clinical and epidemiological factors with BM appearance in patients suffering from different histological subtypes of NSCLC stage I–IV.Methods: The study included 161 consecutive patients with NSCLC. Analyzed data included patient- and tumor-related characteristics.Results: Thirty-nine patients (24.2%) presented BMs within 12 (0–36) weeks of diagnosis. BMs decreased the mean overall survival significantly (15.6 versus 50.7 weeks, P < 0.001), with hazard ratio (95% confidence interval) 3.60 (2.42–5.35). The age of the patients with BM was significantly lower than that of the patients without BM (60.8 ± 8.9 versus 66.5 ± 8.5, P < 0.001). Patients with BM had significantly higher pack-years consumption (75.9 ± 23.9 versus 58.9 ± 31.9, P = 0.003) and larger tumor size compared with patients without BM (size in mm: 55.1 ± 20.1 versus 45.9 ± 19.3, P = 0.012). The presence of BM was also correlated with the absence of lung (P < 0.001), bone (P = 0.005), and adrenal (P = 0.046) metastases.Conclusion: Younger NSCLC patients with high tobacco consumption, large tumor size, and absence of metastases in other organs (lung, bones, adrenal metastases) are at high risk of BM appearance during the course of NSCLC and are candidates for prophylactic cranial irradiation early in the course of the disease.Keywords: NSCLC, brain metastases, clinical and epidemiological factors, PCI