Smoking and non-neoplastic lung disease in Canadian men and women

MAIN OBJECTIVE: To document and assess the current health impact of non-neoplastic lung disease (NNLD) in Canadian men and women that is attributable to smoking. DESIGN: Comparison of three recent studies providing estimates of smoking-attributable deaths, potential years of life lost, hospital separations and hospital days due to NNLD in Canada. Review of recent epidemiological studies providing relative risk estimates of smoking-attributable mortality and morbidity for chronic obstructive pulmonary disease and pneumonia, including a meta-analysis. MAIN RESULTS: Each year at least 6700 Canadian men and women die from NNLD attributable to smoking. Smoking-attributable NNLD deaths in men outnumber those in women by about 2 to 1. The majority of these deaths are due to chronic obstructive pulmonary disease, which is exceeded in importance as a smoking-attributable cause of death only by lung cancer and ischemic heart disease. NNLD accounts for about 20% of all smokingattributable deaths in Canada, 14% of the potential years of life lost due to smoking, and 22% and 25% of all smokingattributable hospital separations and hospital days, respectively. Long term follow-up assessments of large cohorts suggest that the impact of smoking on health has been underestimated. Recent studies also suggest that women may be more susceptible than men to the adverse effects of smoking on lung function. CONCLUSION: NNLD caused by smoking has an important health impact in Canada. Tobacco control strategies must be enhanced. Key Words: Lung diseases, Morbidity, Mortality, Smoking Le tabagisme et la maladie pulmonaire non cancéreuse chez les Canadiens et Canadiennes OBJECTIF PRINCIPAL : Documenter et évaluer les influences actuelles sur la santé de la maladie pulmonaire non cancéreuse chez des Canadiens et Canadiennes, et qui sont imputables au tabagisme. MODÈLE : Comparaison de trois études récentes fournissant des estimés des décès attribuables au tabagisme, des années potentielles de vie perdues, des congés donnés aux patients hospitalisés et des journées d'hospitalisation dus à la maladie pulmonaire non cancéreuse au Canada. Revue des études épidémiologiques récen-tes fournissant des estimés du risque relatif de la mortalité attribuable au tabagisme et de la morbidité liée à la maladie pulmonaire obstructive chronique et à la pneumonie, incluant une méta-analyse. voir page suivante I t is now well established that smoking is the most important preventable cause of premature mortality and morbidity in Canadian men and women (1,2), as it is in the populations of other developed countries (3,4). At least 33,000 Canadians die each year as a result of tobacco use, which also accounts for more than 200,000 hospital separations, three million hospital days and some $9.5 billion in costs from lost productivity and direct health care expenditures (2). Despite this enormous health toll, smoking remains prevalent. Estimates from the National Population Health Survey conducted in 1994 indicate that 6.9 million Canadians, 31% of the population aged 15 years and over, smoke (5). Further, rates of smoking among young Canadians, after some years of decline, have now plateaued (6) and may actually be increasing in some provinces, notably in Ontario The primary purpose of this paper is to document and assess current estimates of the health impact of smoking in Canada with regard to non-neoplastic lung disease (NNLD) and to point out some limitations of these data. As well, recent reports concerning long term epidemiological studies of the relationship of smoking to NNLD are reviewed, including a meta-analysis of relative risk estimates. Attention is drawn to recent studies that indicate the possibility that the lungs of women may be particularly susceptible to the adverse effects of tobacco smoke. HEALTH IMPACT OF SMOKING DUE TO NNLD Smoking-attributable mortality: Three studies provide estimates of the current mortality impact of tobacco use in Canadian men and women Makomaski Illing and Kaiserman (1), using risk estimates from the same source, concluded that in 1991 there were more than 8100 NNLD deaths among Canadians attributable to smoking, out of a total of 41,408 smoking-attributable deaths. Most recently, Single et al (2) used mortality estimates derived from a meta-analysis of epidemiological studies conducted by English et al (10), discussed further below. They concluded that in 1992 NNLD deaths in Canadians attributable to smoking exceeded 6700, out of a total estimate of more than 33,000 smoking-attributable deaths. In all three estimates shown in Comparability of the mortality estimates: Because the RISKS OF NNLD MORTALITY AND MORBIDITY ASSOCIATED WITH SMOKING Mortality: A study by Canadian investigators was among the first to document the excess risk of mortality from NNLD in smokers compared with nonsmokers (11,12). In the final six-year follow-up study of some 78,000 male veterans, initiated in 1955 by the Department of National Health and Welfare (12), it was found that veterans with a lifetime history of smoking cigarettes had about 11 and eight times the risk of mortality from chronic bronchitis and emphysema, respectively, compared with nonsmokers. A dose-response relationship between the amount smoked daily and the risk of mortality was also observed. For pneumonia and influenza there was a small increase in relative risk (1.4). Since then, a host of epidemiological studies from many countries have confirmed the causal relationship between smoking and COPD in both men and women, as well as a small increase in the risk of mortality from pneumonia (13-17). Doll et al Doll et al Recently, Gold et al (27), in a study of the effects of cigarette smoking on the level and rate of growth of pulmonary function in large cohorts of adolescent boys and girls, demonstrated that the growth of lung function in association with smoking was more severely affected in the girls. This finding is particularly worrisome in the context of the ages at which adolescent girls and boys begin to smoke. In the 1994 Canadian Youth Smoking Survey (6) it was found that although the rates of beginning to smoke were similar in boys and girls ages 10 to 12 years (4% in each), by ages 13 to 14 years this rate was significantly higher than girls (15%) compared with boys (9%). Girls may not only be more susceptible to the adverse effects of smoking, but they appear to be getting a 'head start' on this addiction. While sex differences in susceptibility to the smokinginduced changes in lung function require more study, particularly with regard to underlying biological mechanisms, the primal importance of smoking cessation in reducing the age-related decline in FEV 1 in smokers with mild obstructive pulmonary disease is beyond disput

All-cause mortality and risk factors in a cohort of retired military male veterans, Xi'an, China: an 18-year follow up study

<p>Abstract</p> <p>Background</p> <p>Risk factors of all-cause mortality have not been reported in Chinese retired military veterans. The objective of the study was to examine the risk factors and proportional mortality in a Chinese retired military male cohort.</p> <p>Methods</p> <p>A total of 1268 retired military men aged 55 or older were examined physically and interviewed using a standard questionnaire in 1987. The cohort was followed up every two years and the study censored date was June30, 2005 with a follow-up of up to 18 years. Death certificates were obtained from hospitals and verified by two senior doctors. Data were entered (double entry) by Foxbase, and analysis was carried out by SAS for Windows 8.2. Multivariate Cox proportional hazard regression model was used to compute hazard ratio (HR) and 95% confidence interval (CI).</p> <p>Results</p> <p>The total person-years of follow-up was 18766.28. Of the initial cohort of 1268 men, 491 had died, 748 were alive and 29 were lost to follow up. Adjusted mortality (adjusted for age, blood pressure, body mass index, cholesterol, triglycerides, alcohol, exercise, and existing disease) was 2,616 per 100,000 person years. The proportional mortality of cancer, vascular disease and Chronic Obstructive Pulmonary Disease (COPD) were 39.71%, 28.10% and 16.90% respectively. Multivariate analysis showed that age, cigarettes per day, systolic blood pressure, triglyceride, family history of diseases (hypertension, stroke and cancer), existing diseases (stroke, diabetes and cancer), body mass index, and age of starting smoking were associated with all-cause mortality, HR (95%CI) was1.083(1.062–1.104), 1.026(1.013–1.039), 1.009(1.003–1.015), 1.002(1.001–1.003), 1.330(1.005–1.759), 1.330(1.005–1.759), 1.444(1.103–1.890), 2.237(1.244–4.022), 1.462(1.042–2.051), 2.079(1.051–4.115), 0.963(0.931–0.996)and 0.988(0.978–0.999)respectively. Compared with never-smokers, current smokers had increased risks of total mortality [HR 1.369(1.083–1.731)], CHD [HR 1.805 (1.022–3.188)], and lung cancer [HR 2.939 (1.311–6.585)].</p> <p>Conclusion</p> <p>The three leading causes of diseases were cancer, CHD and stroke, and COPD. Aging, cigarette smoking, high systolic blood pressure, high triglyceride, family history of cancer, hypertension and stroke, existing cases recovering from stroke, diabetes and cancer, underweight, younger age of smoking were risk factors for all-cause mortality. Quitting cigarette smoking, maintaining normal blood pressure, triglyceride and weight are effect control strategies to prevent premature mortality in this military cohort.</p

Diagnostic accuracy of cerebrospinal fluid protein markers for sporadic Creutzfeldt-Jakob disease in Canada: a 6-year prospective study

<p>Abstract</p> <p>Background</p> <p>To better characterize the value of cerebrospinal fluid (CSF) proteins as diagnostic markers in a clinical population of subacute encephalopathy patients with relatively low prevalence of sporadic Creutzfeldt-Jakob disease (sCJD), we studied the diagnostic accuracies of several such markers (14-3-3, tau and S100B) in 1000 prospectively and sequentially recruited Canadian patients with clinically suspected sCJD.</p> <p>Methods</p> <p>The study included 127 patients with autopsy-confirmed sCJD (prevalence = 12.7%) and 873 with probable non-CJD diagnoses. Standard statistical measures of diagnostic accuracy were employed, including sensitivity (Se), specificity (Sp), predictive values (PVs), likelihood ratios (LRs), and Receiver Operating Characteristic (ROC) analysis.</p> <p>Results</p> <p>At optimal cutoff thresholds (empirically selected for 14-3-3, assayed by immunoblot; 976 pg/mL for tau and 2.5 ng/mL for S100B, both assayed by ELISA), Se and Sp respectively were 0.88 (95% CI, 0.81-0.93) and 0.72 (0.69-0.75) for 14-3-3; 0.91 (0.84-0.95) and 0.88 (0.85-0.90) for tau; and 0.87 (0.80-0.92) and 0.87 (0.84-0.89) for S100B. The observed differences in Sp between 14-3-3 and either of the other 2 markers were statistically significant. Positive LRs were 3.1 (2.8-3.6) for 14-3-3; 7.4 (6.9-7.8) for tau; and 6.6 (6.1-7.1) for S100B. Negative LRs were 0.16 (0.10-0.26) for 14-3-3; 0.10 (0.06-0.20) for tau; and 0.15 (0.09-0.20) for S100B. Estimates of areas under ROC curves were 0.947 (0.931-0.961) for tau and 0.908 (0.888-0.926) for S100B. Use of interval LRs (iLRs) significantly enhanced accuracy for patient subsets [<it>e.g</it>., 41/120 (34.2%) of tested sCJD patients displayed tau levels > 10,000 pg/mL, with an iLR of 56.4 (22.8-140.0)], as did combining tau and S100B [<it>e.g</it>., for tau > 976 pg/mL and S100B > 2.5 ng/mL, positive LR = 18.0 (12.9-25.0) and negative LR = 0.02 (0.01-0.09)].</p> <p>Conclusions</p> <p>CSF 14-3-3, tau and S100B proteins are useful diagnostic markers of sCJD even in a low-prevalence clinical population. CSF tau showed better overall diagnostic accuracy than 14-3-3 or S100B. Reporting of quantitative assay results and combining tau with S100B could enhance case definitions used in diagnosis and surveillance of sCJD.</p

Chronic Stress Induces Sex-Specific Alterations in Methylation and Expression of Corticotropin-Releasing Factor Gene in the Rat

Contains fulltext : 91627.pdf (publisher's version ) (Open Access

The First Human Epitope Map of the Alphaviral E1 and E2 Proteins Reveals a New E2 Epitope with Significant Virus Neutralizing Activity

Although the murine immune response to Venezuelan equine encephalitis virus (VEEV) is well-characterized, little is known about the human antibody response to VEEV. In this study we used phage display technology to isolate a panel of 11 VEEV-specfic Fabs from two human donors. Seven E2-specific and four E1-specific Fabs were identified and mapped to five E2 epitopes and three E1 epitopes. Two neutralizing Fabs were isolated, E2-specific F5 and E1-specific L1A7, although the neutralizing capacity of L1A7 was 300-fold lower than F5. F5 Fab was expressed as a complete IgG1 molecule, F5 native (n) IgG. Neutralization-escape VEEV variants for F5 nIgG were isolated and their structural genes were sequenced to determine the theoretical binding site of F5. Based on this sequence analysis as well as the ability of F5 to neutralize four neutralization-escape variants of anti-VEEV murine monoclonal antibodies (mapped to E2 amino acids 182–207), a unique neutralization domain on E2 was identified and mapped to E2 amino acids 115–119

Global patient outcomes after elective surgery: prospective cohort study in 27 low-, middle- and high-income countries.

BACKGROUND: As global initiatives increase patient access to surgical treatments, there remains a need to understand the adverse effects of surgery and define appropriate levels of perioperative care. METHODS: We designed a prospective international 7-day cohort study of outcomes following elective adult inpatient surgery in 27 countries. The primary outcome was in-hospital complications. Secondary outcomes were death following a complication (failure to rescue) and death in hospital. Process measures were admission to critical care immediately after surgery or to treat a complication and duration of hospital stay. A single definition of critical care was used for all countries. RESULTS: A total of 474 hospitals in 19 high-, 7 middle- and 1 low-income country were included in the primary analysis. Data included 44 814 patients with a median hospital stay of 4 (range 2-7) days. A total of 7508 patients (16.8%) developed one or more postoperative complication and 207 died (0.5%). The overall mortality among patients who developed complications was 2.8%. Mortality following complications ranged from 2.4% for pulmonary embolism to 43.9% for cardiac arrest. A total of 4360 (9.7%) patients were admitted to a critical care unit as routine immediately after surgery, of whom 2198 (50.4%) developed a complication, with 105 (2.4%) deaths. A total of 1233 patients (16.4%) were admitted to a critical care unit to treat complications, with 119 (9.7%) deaths. Despite lower baseline risk, outcomes were similar in low- and middle-income compared with high-income countries. CONCLUSIONS: Poor patient outcomes are common after inpatient surgery. Global initiatives to increase access to surgical treatments should also address the need for safe perioperative care. STUDY REGISTRATION: ISRCTN5181700

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field

Smoking and Non-Neoplastic Lung Disease in Canadian Men and Women

MAIN OBJECTIVE: To document and assess the current health impact of non-neoplastic lung disease (NNLD) in Canadian men and women that is attributable to smoking.DESIGN: Comparison of three recent studies providing estimates of smoking-attributable deaths, potential years of life lost, hospital separations and hospital days due to NNLD in Canada. Review of recent epidemiological studies providing relative risk estimates of smoking-attributable mortality and morbidity for chronic obstructive pulmonary disease and pneumonia, including a meta-analysis.MAIN RESULTS: Each year at least 6700 Canadian men and women die from NNLD attributable to smoking. Smoking-attributable NNLD deaths in men outnumber those in women by about 2 to 1. The majority of these deaths are due to chronic obstructive pulmonary disease, which is exceeded in importance as a smoking-attributable cause of death only by lung cancer and ischemic heart disease. NNLD accounts for about 20% of all smoking-attributable deaths in Canada, 14% of the potential years of life lost due to smoking, and 22% and 25% of all smoking-attributable hospital separations and hospital days, respectively. Long term follow-up assessments of large cohorts suggest that the impact of smoking on health has been underestimated. Recent studies also suggest that women may be more susceptible than men to the adverse effects of smoking on lung function.CONCLUSION: NNLD caused by smoking has an important health impact in Canada. Tobacco control strategies must be enhanced.Peer Reviewe

Smoking and Non-Neoplastic Lung Disease in Canadian Men and Women

MAIN OBJECTIVE: To document and assess the current health impact of non-neoplastic lung disease (NNLD) in Canadian men and women that is attributable to smoking