Background Cigarette smoking is a major risk factor for COPD and COPD severity. Previous genome-wide association studies (GWAS) have identified numerous single nucleotide polymorphisms (SNPs) associated with the number of cigarettes smoked per day (CPD) and a Dopamine Beta-Hydroxylase (DBH) locus associated with smoking cessation in multiple populations. Objective To identify SNPs associated with lifetime average and current CPD, age at smoking initiation, and smoking cessation in COPD subjects. Methods GWAS were conducted in 4 independent cohorts encompassing 3,441 ever-smoking COPD subjects (GOLD stage II or higher). Untyped SNPs were imputed using HapMap (phase II) panel. Results from all cohorts were meta-analyzed. Results Several SNPs near the HLA region on chromosome 6p21 and in an intergenic region on chromosome 2q21 showed associations with age at smoking initiation, both with the lowest p=2×10−7. No SNPs were associated with lifetime average CPD, current CPD or smoking cessation with p<10−6. Nominally significant associations with candidate SNPs within alpha-nicotinic acetylcholine receptors 3/5 (CHRNA3/CHRNA5; e.g. p=0.00011 for SNP rs1051730) and Cytochrome P450 2A6 (CYP2A6; e.g. p=2.78×10−5 for a nonsynonymous SNP rs1801272) regions were observed for lifetime average CPD, however only CYP2A6 showed evidence of significant association with current CPD. A candidate SNP (rs3025343) in the DBH was significantly (p=0.015) associated with smoking cessation. Conclusion We identified two candidate regions associated with age at smoking initiation in COPD subjects. Associations of CHRNA3/CHRNA5 and CYP2A6 loci with CPD and DBH with smoking cessation are also likely of importance in the smoking behaviors of COPD patients.

Cardiac arrest during pregnancy is rare, but it is important to recognize the causes, which may be either unrelated to pregnancy or unique to the pregnant woman. For the most part, the resuscitation protocol is the same as for nonpregnant victims of cardiac arrest, with a few important modifications, including especially the need for relieving aortocaval compression by the gravid uterus, the need for rapid intubation, and the importance of rapid perimortem cesarean delivery when indicated. In those rare cases of brain death occurring in a pregnant patient, continued somatic support of the mother may be possible, even for prolonged periods, to extend the pregnancy and further fetal maturation. The expected physiologic changes after brain death, challenges to successful somatic support, and specific recommendations regarding organ support of the brain-dead pregnant woman are reviewed.

Background:Professional burnout has been widely explored in health care. We conducted this study in our hospital intensive care unit (ICU) in United States to explore the burnout among nurses and respiratory therapists (RT).Materials and Methods:A survey consisting of two parts was used to assess burnout. Part 1 addressed the demographic information and work hours. Part 2 addressed the Maslach Burnout Inventory-Human Service Survey.Results:The analysis included 213 total subjects; Nurses 151 (71%) and RT 62 (29%). On the emotional exhaustion (EE) scale, 54% scored “Moderate” to “High” and 40% scored “Moderate” to “High” on the depersonalization (DP) scale. Notably 40.6% scored “Low” on personal accomplishment (PA) scale.Conclusion:High level of EE, DP and lower PAs were seen among two groups of health care providers in the ICUs.

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Rationale: The demographic, physiological, and computed tomography (CT) features associated with pneumothorax in smokers with and without chronic obstructive pulmonary disease (COPD) are not clearly defined.Objectives: We evaluated the hypothesis that pneumothorax in smokers is associated with male sex, tall and thin stature, airflow obstruction, and increased total and subpleural emphysema. Methods:The study included smokers with and without COPD from the COPDGene Study, with quantitative chest CT analysis. Pleural-based emphysema was assessed on the basis of local histogram measures of emphysema. Pneumothorax history was defined by subject self-report.Measurements and Main Results: Pneumothorax was reported in 286 (3.2%) of 9,062 participants. In all participants, risk of prior pneumothorax was significantly higher in men (odds ratio [OR], 1.55; 95% confidence interval [CI], 1.08-2.22) and non-Hispanic white subjects (OR, 1.90; 95% CI, 1.34-2.69). Risk of prior pneumothorax was associated with increased percent CT emphysema in all participants and participants with COPD (OR, 1.04 for each 1% increase in emphysema; 95% CI, 1.03-1.06). Increased pleural-based emphysema was independently associated with risk of past pneumothorax in all participants (OR, 1.05 for each 1% increase; 95% CI, 1.01-1.10). In smokers with normal spirometry, risk of past pneumothorax was associated with non-Hispanic white race and lifetime smoking intensity (OR, 1.20 for every 10 pack-years; 95% CI, 1.09-1.33).Conclusions: Among smokers, pneumothorax is associated with male sex, non-Hispanic white race, and increased percentage of total and subpleural CT emphysema. Pneumothorax was not independently associated with height or lung function, even in participants with COPD.Clinical trial registered with www.clinicaltrials.gov (NCT00608764).

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With an estimated one-third of the world's population infected with Mycobacterium tuberculosis (MTB) and approximately 1.6 million deaths in 2006 attributed to tuberculosis (TB) world-wide, TB remains a major public health concern today. Considerable advances have been made in the effective treatment of TB, in particular with the adoption of directly observed therapy short course (DOTS), in national TB control programs, but in spite of this the currently available regimens are suboptimal. The long courses of therapy required, together with significant medication side-effects and resulting difficulties with adherence to therapy all contribute to increasing problems with emerging drug resistance. There is thus an urgent need for new antituberculous drug development, especially to enable effective shorter course therapy for drug-susceptible and resistant TB, to find effective drugs for treatment of drug-resistant TB, to shorten therapy for latent TB infection and to reduce drug interactions in combination with antiretroviral therapy, a major issue in the treatment of HIV co-infected patients. This review will attempt to summarize the current recommendations for treatment of TB and then describe the most promising new antimicrobials with activity against MTB, focusing on the ones currently undergoing clinical trials.

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