Primecuts: This Week In The Journals

June 14, 2010

By Maryann Kwa, MD

Faculty Peer Reviewed

This week, ecstatic soccer fans around the world are gathering to watch the excitement and celebrate the camaraderie that is the World Cup.  As the enthusiasm reaches a fever pitch in South Africa–the first country on the continent to host the games–the competitive spirit amongst players and fans is surely running high.  Speaking of competition, we start this edition of Primecuts with a very interesting piece in The New York Times about testosterone and trust [1].  Trust plays a crucial role in forming and maintaining human relationships.  Recent research has shown that the peptide hormone oxytocin increases trust in humans.  However, the downside is that it also makes us susceptible to betrayal because under the influence of oxytocin, individuals perseverate in giving trust to others that they know are untrustworthy.  Researchers in Holland published this month in the Proceedings of the National Academy of Sciences a study in which they identified testosterone as the antidote [2]. Testosterone is a hormone which has long been associated with social dominance and success in competition.  Interestingly, levels of testosterone in humans correlate positively with financial gain in the stock market and may be a predictor of economic shrewdness.

In a double-blinded “trust” experiment, the researchers sublingually administered either 0.5mg of testosterone or placebo to 24 healthy adult females.  They then asked them to judge the trustworthiness of a series of unfamiliar male faces shown in photographs.  The authors noted that the women were significantly less inclined to trust a face when given testosterone than when administered a placebo.  However this effect was not the same for all subjects.  The women who were least trusting to start, as determined by the placebo test, were hardly affected by the hormone.  It was the trusting women whose attitude was most changed by testosterone, which downregulated their trust.  The study suggested that testosterone adaptively increases social vigilance in trusting humans, presumably to prepare them for competition over resources and to motivate for rational decision-making and social scrutiny.  Interesting, huh?

Moving on in the news, there have been updates in the fight against infectious diseases.  Headlining the media for the last two years has been the influenza A (H1N1) virus which originated in Mexico and rapidly spread worldwide.  This week, the NEJM reported on the efficacy of oseltamivir ring prophylaxis for containment of the 2009 H1N1 influenza outbreak in a semi-closed environment [3].  The study took place in June 2009 during four outbreaks in Singapore military camps. Oseltamivir prophylaxis and other interventions including isolation and treatment of confirmed cases with oseltamivir, surveillance for influenza-like illness among patients receiving prophylaxis, and home quarantine of close military contacts were implemented.  During this time, “ring prophylaxis” was used which meant that oseltamivir prophylaxis was administered more widely than just among close contacts.  The number of cases of H1N1 virus infection among military personal decreased significantly after the interventions were implemented.   The study showed that early case detection and use of antiviral ring prophylaxis can effectively truncate the spread of infection during an epidemic.  Today, the H1N1 vaccine is available; however antiviral prophylaxis may be considered an additional strategy to reduce the pandemic’s effects, especially in areas where the supply of vaccine may be limited.  Of course, practitioners that are contemplating the use of oseltamivir ring prophylaxis for control of outbreaks need to weigh the risk for development of oseltamivir resistance.

Speaking of resistance, the liberal use and overuse of antibiotics have contributed to a significant problem in our hospitals.  In this week’s issue of JAMA, Sánchez García et al. described the first outbreak of linezolid-resistant Staphylococcus aureus (LRSA) in an ICU at a tertiary care university teaching hospital in Madrid, Spain [4].  Laboratory analysis suggested that a molecular evolution of the resistance mechanism occurred.  Twelve patients were affected between April and June 2008; six had ventilator-associated pneumonia and three had bacteremia.  The authors showed that the outbreak was associated with nosocomial transmission and extensive usage of linezolid.  Isolates were susceptible to trimethoprim-sulfamethoxazole, tigecycline, and daptomycin. They described total ICU consumption of linezolid as 202 defined daily doses in April 2008, which was largely due to indiscriminate antibiotic use.  Following their investigation, the use of linezolid declined to 25 defined daily doses in July 2008.  Subsequent reduction and infection-control measures were associated with termination of the outbreak.  To be sure, what we can learn from this study is that quality measures of antibiotic use are of paramount importance.  The use of an antibiotic stewardship program, like the one we have here at NYU, can aid clinicians in selecting the appropriate antibiotic and decreasing the rate of microbial resistance.

Shifting gears, we turn to another national problem that is extensively portrayed in our media, the difficult problem of prescription drug misuse.  In 2007, according to the Substance Abuse and Mental Health Services Administration, the illicit use of prescription opioids exceeded that of marijuana among individuals 12 years or older [5].  To reduce the risk for prescription opioid misuse, medical societies have published guidelines with specific risk reduction strategies, including written opioid treatment agreements and urine drug testing for patients with chronic pain who are prescribed long-term opioids.  This week, the Annals of Internal Medicine published a comprehensive review of the evidence about the effectiveness of these two common clinical tools [6].  The authors found that a problem with evaluating compliance and efficacy of treatment agreements and urine drug testing is that there was no consistent definition of “treatment agreement.”  There was also a lack of consistency in utilization of these tools.  Despite reviewing more than 4500 abstracts and 102 full text articles, the authors only found 11 studies that met their inclusion criteria.  They concluded that despite the enthusiastic support of treatment agreements and urine drug testing by some clinicians, there is little evidence documenting their effectiveness.  Also, the lack of clear definitions of these interventions makes comparisons of the few studies that exist difficult.  Future research needs to be conducted in the primary care setting using standardized measures of misuse, ideally those associated with clinical outcomes.  The potential harms of these strategies should also be explored such as patients forgoing pain treatment because of a perceived stigma.

Lastly, we end this week with an interesting study about secondhand smoke and mental health.  In a study of 5,560 nonsmoking adults and 2,595 smokers in the Scottish Health Survey, published online in the Archives of General Psychiatry, researchers at the University College of London reported a 50% greater risk of psychological distress in nonsmokers with the highest levels of nicotine in their blood, compared with those with the lowest levels [7].  The authors controlled for potential confounding factors such as socioeconomic status which is independently linked to smoke exposure and higher risk of depression.  A 12-item questionnaire was used to assess mental health, including sleep problems and symptoms of anxiety and depression.  Salivary levels of a nicotine byproduct assessed exposure to secondhand smoke.  The conclusion was: the greater the level of nicotine, the greater the likelihood of exhibiting psychological distress.  Prior data have suggested a link between smoking and mood disorders.  Nicotine exposure has been known to trigger depressive symptoms and anxiety in the animal model.  While this study does not establish that the exposure directly causes a change in mood in humans, it does suggest a reasonable association.

Dr. Kwa is a first year resident at NYU Langone Medical Center

Peer reviewed by Judith Brenner, MD, Associate Editor, Clinical Correlations

References:

1.  Wade N. She doesn’t trust you? Blame the testosterone [Internet]. The New York Times; 2010 Jun 1. http://www.nytimes.com/2010/06/08/health/08hormone.html?ref=research

2.  Bos PA, Terburg D, van Honk J. Testosterone decreases trust in socially naïve humans. Proceedings of the National Academy of Sciences. 2010 June 1;107(22):9991-9995. http://www.pnas.org/content/107/22/9991

3.  Lee VJ, Yap J, Cook AR, et al. Oseltamivir ring prophylaxis for containment of 2009 H1N1 influenza outbreaks. N Engl J Med. 2010 June 10;362(23):2166-2174.  http://content.nejm.org/cgi/content/abstract/362/23/2166

4.  Sánchez García M, Ángeles De la Torre M, Morales G, et al. Clinical outbreak of linezolid-resistant Staphylococcus aureus in an intensive care unit. JAMA. 2010 June 9;303(22):2260-2264. http://jama.ama-assn.org/cgi/content/abstract/303/22/2260

5.  Heit HA, Gourlay DL. Tackling the difficult problem of prescription opioid misuse [editorial]. Annals of Internal Medicine. 2010 June 1;152:747-748. http://www.annals.org/content/152/11/747.extract

6.  Starrels JL, Becker WC, Alford DP, et al. Systematic review: treatment agreements and urine drug testing to reduce opioid misuse in patients with chronic pain. Annals of Internal Medicine. 2010 June 1;152:712-720.  http://www.annals.org/content/152/11/712.abstract

7.  Hamer M, Stamatakis E, Batty GD. Objectively assessed secondhand smoke exposure and mental health in adults: cross-sectional and prospective evidence from the Scottish Health Survey. Arch Gen Psychiatry. 2010 June 7. [Epub ahead of print] http://archpsyc.ama-assn.org/cgi/content/short/2010.76

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