Publications

Cigarette companies increasingly promote novel smokeless tobacco products to smokers, encouraging them to use smokeless tobacco in smoke-free environments. New messages may counteract this promotion. We developed 12 initial anti-smokeless message ideas and tested them in eight online focus groups with 75 US smokers. Those smokers who never tried smokeless tobacco were unaware of health risks of novel smokeless tobacco products, perceived scary messages as effective and acknowledged the addictive nature of nicotine. Smokers who had tried smokeless tobacco shared their personal (mainly negative) experiences with smokeless tobacco, were aware of health risks of novel smokeless tobacco products, but denied personal addiction, and misinterpreted or disregarded more threatening messages. Portraying women as smokeless tobacco users was perceived as unbelievable, and emphasizing the lack of appeal of novel smokeless tobacco products was perceived as encouraging continued smoking. Future ads should educate smokers about risks of novel smokeless tobacco products, but past users and never users may require different message strategies.

BACKGROUND

Abnormal calcium handling plays a crucial role in arrhythmias, sudden cardiac arrest (SCA), and congestive heart failure (CHF). Calsequestrin 2 (CASQ2) mutations affect calcium release and initiate malignant ventricular arrhythmias (VAs) and SCA syndromes. Common single nucleotide polymorphisms (SNPs) in CASQ2 may be associated with SCA in patients with coronary artery disease (CAD).

OBJECTIVE

The purpose of this study was to examine the association of common CASQ2 SNPs with the risk of SCA in patients with CAD.

METHODS

CASQ2 SNPs (n = 14) were genotyped and analyzed in a case control study comparing 114 patients with CAD and SCA due to VA to 311 CAD controls without VA or SCA.

RESULTS

Multivariate logistic regression adjusting for age and CHF status identified an association between rs7521023 with SCA (odds ratio [OR] 2.72, 95% confidence interval [CI] 1.44-5.13, P = .002). The substantial impact of CHF on SCA in the model (OR 26.6, 95% CI 13.40-52.70, P <.001) led us to further examine the relationship between CHF, SCA, and CASQ2 SNPs. We identified 2 CASQ2 variants (rs7521023: OR 0.4, 95% CI 0.25-0.76, P = .003; rs6684209: OR 19.8, 95% CI 3.63-108.2, P <.001) associated with CHF after adjusting for SCA, age, gender, and hypertension.

CONCLUSION

We observed association between a CASQ2 polymorphism and SCA due to VA in patients with CAD adjusting for CHF and independent associations between CASQ2 SNPs and CHF adjusting for SCA. Further investigation in independent cohorts is needed to confirm these findings.

OBJECTIVE

HIV "elite controllers" (ECs) spontaneously control viral load, but some eventually require combination antiretroviral treatment (cART), due to a loss of viral control or a decline in CD4 T-cell counts. Here we studied the CD4 T-cell count dynamics after cART initiation among 34 ECs followed in U.S. and European cohorts, by comparison with chronically viremic patients (VIRs).

METHODS

ECs were defined as patients with at least ≥5 viral load (VL) measurements below 400 copies/mL during at least a 5-year period despite never receiving ART and were selected from the French ANRS CO18 cohort, the U.S. SCOPE cohort, the International HIV Controllers study and the European CASCADE collaboration. VIRs were selected from the ANRS COPANA cohort of recently-diagnosed (<1 year) ART-naïve HIV-1-infected adults. CD4 T-cell count dynamics after cART initiation in both groups were modelled with piecewise mixed linear models.

RESULTS

After cART initiation, CD4 T-cell counts showed a biphasic rise in VIRs with: an initial rapid increase during the first 3 months (+0.63√CD4/month), followed by +0.19√CD4/month. This first rapid phase was not observed in ECs, in whom the CD4Tc count increased steadily, at a rate similar to that of the second phase observed in VIRs. After cART initiation at a CD4 T-cell count of 300/mm(3), the estimated mean CD4 T-cell gain during the first 12 months was 139/mm(3) in VIRs and 80/mm(3) in ECs (p = 0.048).

CONCLUSIONS

cART increases CD4 T-cell counts in elite controllers, albeit less markedly than in other patients.

BACKGROUND

Acute respiratory illness is the leading cause of asthma exacerbations yet the mechanisms underlying this association remain unclear. To address the deficiencies in our understanding of the molecular events characterizing acute respiratory illness-induced asthma exacerbations, we undertook a transcriptional profiling study of the nasal mucosa over the course of acute respiratory illness amongst individuals with a history of asthma, allergic rhinitis and no underlying respiratory disease.

METHODS

Transcriptional profiling experiments were performed using the Agilent Whole Human Genome 4X44K array platform. Time point-based microarray and principal component analyses were conducted to identify and distinguish acute respiratory illness-associated transcriptional profiles over the course of our study. Gene enrichment analysis was conducted to identify biological processes over-represented within each acute respiratory illness-associated profile, and gene expression was subsequently confirmed by quantitative polymerase chain reaction.

RESULTS

We found that acute respiratory illness is characterized by dynamic, time-specific transcriptional profiles whose magnitudes of expression are influenced by underlying respiratory disease and the mucosal repair signature evoked during acute respiratory illness. Most strikingly, we report that people with asthma who experience acute respiratory illness-induced exacerbations are characterized by a reduced but prolonged inflammatory immune response, inadequate activation of mucosal repair, and the expression of a newly described exacerbation-specific transcriptional signature.

CONCLUSION

Findings from our study represent a significant contribution towards clarifying the complex molecular interactions that typify acute respiratory illness-induced asthma exacerbations.

The use of computed tomographic scanning in blunt head trauma has increased dramatically in recent years without an accompanying rise in the prevalence of injury or hospital admission for serious conditions. Because computed tomography is neither harmless nor inexpensive, researchers have attempted to optimize utilization, largely through research that describes which clinical variables predict intracranial injury, and use this information to develop clinical decision instruments. Although such techniques may be useful when the benefits and harms of each strategy (neuroimaging vs observation) are quantifiable and amenable to comparison, the exact magnitude of these benefits and harms remains unknown in this clinical scenario. We believe that most clinical decision instrument development efforts are misguided insofar as they ignore critical, nonclinical factors influencing the decision to image. In this article, we propose a conceptual model to illustrate how clinical and nonclinical factors influence emergency physicians making this decision. We posit that elements unrelated to standard clinical factors, such as personality of the physician, fear of litigation and of missed diagnoses, patient expectations, and compensation method, may have equal or greater impact on actual decision making than traditional clinical factors. We believe that 3 particular factors deserve special consideration for further research: fear of error/malpractice, financial incentives, and patient engagement. Acknowledgement and study of these factors will be essential if we are to understand how emergency physicians truly make these decisions and how test-ordering behavior can be modified.