Publications

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.

Human immunodeficiency virus (HIV)-infected patients are disproportionately affected by cardiovascular disease and sudden cardiac death (SCD). Whether left ventricular (LV) dysfunction predicts SCD in those with HIV is unknown. We sought to determine the impact of LV dysfunction on SCD in patients with HIV. We previously characterized all SCDs and acquired immunodeficiency syndrome (AIDS) deaths in 2,860 consecutive patients in a public HIV clinic from 2000 to 2009. Transthoracic echocardiograms (TTEs) performed during the study period were identified. The effect of ejection fraction (EF), diastolic dysfunction, pulmonary artery pressure, and LV mass on SCD and AIDS death were evaluated: 423 patients had at least 1 TTE; 13 SCDs and 55 AIDS deaths had at least 1 TTE. In the propensity-adjusted analysis, EF 30% to 39% and EF<30% predicted SCD (hazard ratio [HR] 9.5, 95% confidence interval [CI] 1.7 to 53.3, p=0.01 and HR 38.5, 95% CI 7.6 to 195.0, p<0.001, respectively) but not AIDS death. Diastolic dysfunction also predicted SCD (HR 14.8, 95% CI 4.0 to 55.4, p<0.001) but not AIDS death, even after adjusting for EF. The association between EF<40% and SCD was greater in subjects with detectable versus undetectable HIV RNA (adjusted HR 11.7, 95% CI 2.9 to 47.2, p=0.001 vs HR 2.7, 95% CI 0.3 to 27.6, p=0.41; p=0.07 for interaction). In conclusion, LV systolic dysfunction and diastolic dysfunction predict SCD but not AIDS death in a large HIV cohort, with greater effect in those with detectable HIV RNA. Further investigation is needed to thoroughly evaluate the effect of low EF and HIV factors on SCD incidence and the potential benefit of implantable cardioverter-defibrillator therapy in this high-risk population.

OBJECTIVE

To examine variation in the open market cost of a radical prostatectomy (RP) procedure in the US hospitals for an uninsured patient, as many proposals for health care reform highlight the importance of individuals actively participating in selecting care. However, reports suggest that obtaining procedure prices remains challenging and highly variable.

MATERIALS AND METHODS

We used 2011-2012 US News and World Report rankings to identify a cohort of 100 hospitals making an effort to include an equal distribution of both academic and private centers, city size, and geographic region. Each hospital was called and the essence of the script included a caller stating he was a healthy, uninsured 55-year-old man recently diagnosed with Gleason 3 + 4 prostatic adenocarcinoma with no metastases. Facility, surgeon, and anesthesia fees were solicited.

RESULTS

Seventy hospitals provided facility prices. Facility estimates averaged $34,720 (±20,335; range, $10,100-$135,000), which was statistically higher at academics centers. No significant differences were seen by region, population, or hospital ranking. Surgeon and anesthesia fees were provided by 10%, averaging $8280 (±$4282; range, $4028-$18,720). Thirty-three hospitals provided discounted fees for prompt payment averaging 34% (±16%; range, 10%-80%).

CONCLUSION

There is wide variation in pricing for RP, with higher rates found in academic centers. Wide variation in facility costs were observed, and nearly all were unable to provide surgeon and/or anesthesia fees. Currently, it appears to be unacceptably difficult for men with prostate cancer without insurance to obtain prices for an RP procedure.

BACKGROUND

The frequency of isoniazid hepatotoxicity is low in children receiving isoniazid therapy for latent tuberculosis infection. However, isoniazid hepatotoxicity may cause liver failure and death. We evaluated children who developed isoniazid hepatotoxicity to determine demographic and clinical characteristics.

METHODS

A retrospective review was performed of medical records of 1582 patients aged <18 years who were evaluated for isoniazid therapy at a public health department and clinic in California.

RESULTS

There were 13 patients who had latent tuberculosis infection and who developed isoniazid hepatotoxicity (0.8% of all 1582 patients who started isoniazid; 1.1% of 1235 patients who completed the 9-month isoniazid therapy). There were 8 girls (62%) and 9 Hispanic children (69%) who had hepatotoxicity. Sex, age, and race were not independently associated with the development of isoniazid hepatotoxicity. Symptoms and signs of hepatotoxicity were present in 11 of the 13 patients, and 2 other patients had alanine aminotransferase >5 times the upper limit of normal and no signs of hepatotoxicity. The most common symptoms included abdominal pain, anorexia, vomiting, and nausea. Most patients developed hepatotoxicity within 6 months of starting isoniazid, but 3 patients developed hepatotoxicity ≥6 months after starting isoniazid. After stopping isoniazid, the alanine aminotransferase levels decreased to normal in all patients.

CONCLUSIONS

In children who have latent tuberculosis infection, isoniazid hepatotoxicity has low frequency and typically is reversible when isoniazid is stopped. Evidence of late drug-induced liver injury indicates the importance of monitoring symptoms and serum transaminases throughout isoniazid therapy.