Primecuts-This Week in the Journals

October 5, 2009

800px-canoe_trail_8173Rachana Jani MD

Faculty Peer Reviewed

As summer officially leaves us and fall sets in, the headlines understandably continue to focus on preventative medicine.  Hopes of an H1N1 vaccine were finally realized last week when Sanofi Pasteur sent out the first batch of this much anticipated vaccine [1]. This week, according to the CDC, 3.4 million doses will be available in the form of a live attenuated nasal spray, which may or may be supplemented with an injectable vaccine.  However, even with the wide availability of the vaccine, authorities are concerned that there will be a surge of cases and a resultant bed shortage. According to the CDC’s FluSurge model, some states are already over capacity. With packed hospitals, this potentially means more rapid transmission of the virus.

Although vaccines and antivirals have been advocated as the anchor of pandemic interventions, the British Medical Journal reminds us of basic infection control precautions [2].  Jefferson et al performed a systematic review and found a significant decrease in transmission of respiratory viruses with proper hand hygiene and use of masks.  The current recommendations for influenza promote the use of N95 respirators, however, these masks are in short supply and cumbersome to use. JAMA compared the effectiveness of the surgical mask vs the N95 respirator in protecting healthcare workers [3]. Loeb et al found the use of the surgical mask was non-inferior to the N95 respirators.  However, this study had many limitations, including inadequate surveillance of compliance and a strong assessment of exposure risk.  All things considered, it is decidedly agreed upon to wash up, gown up and reach for a mask – an N95 if you can find one.

The H1N1 vaccine is not the only vaccine that has gotten the community excited.  The investigators of the RV-144 study gave us a sneak peak on the first HIV vaccine that may have practical efficacy in a Phase 3 trial. [4]  In this trial, approximately 16,400 volunteers in Thailand were randomized to receive placebo or the “prime-boost” vaccine.  The “prime” vaccine consisted of the ALVAC HIV which is a canary pox vector with engineered versions of 3 HIV genes – env, gag, and pro. The “boost” portion is AIDSVAX B/E, a recombinant gp120, with HIV surface fragments found in subtype B and E.  The study found that 51 of 8197 people who received the vaccine became infected as compared to 74 of 8198;  a statistically significant difference, P=0.039.  Cynics argue that the effect is modest at best and that years of research still lie ahead, echoing the fallen dreams of an HIV vaccine originally targeted to be completed by 1986. Nevertheless, most see this as the first step towards progress after a series of failures.

In the meanwhile, Nature took notice of new technologies being developed to improve HIV protection for women [5].  Currently condoms are the most effective against HIV infection during intercourse, with male condoms being used much more frequently than female condoms.  In Seattle, researchers are developing a user-friendly female condom – a small capsule and absorbent foam that will allow the condom to open within the vaginal canal and adhere to the vaginal wall. Other ideas are using pH changes during intercourse to transform vaginal gel into a nanoscopic mesh with pores small enough to block HIV entry and vaginal rings laced with anti-HIV compounds in addition to spermicidal agents that are effective for up to 28 days.  Hopefully these new methods will decrease transmission rates while we wait for a vaccine to developed.

Not all interventions have shown such promising results.  Prostate Specific Antigen screening remains controversial without clear data showing an improvement in morbidity and mortality.  A Swedish case control study in the BMJ reexamined the validity of the PSA test, by looking at 540 cases and 1034 controls and comparing positive likelihood ratios [6]. No likelihood ratio was acceptable to support PSA as a screening test. The +LRs found were 4.5,5.5, and 6.4 for PSA values of 3,4, and 5 ug/l respectively.  One can quietly argue that it may be safe to rule-out low risk men with a PSA test less than 1ug/l.  The Archives also exhumed this issue recently [7].  Howard et al created a model of outcomes of annual PSA screening for men divided by risk and age with the idea to incorporate these results into a decision making aid.   Unfortunately, this study also found it difficult to provide sufficient guidance on delineating the risks versus benefits of PSA screening. Given the flaws of the PSA test, the standard has been to discuss the benefits and the harms associated with PSA testing which implies a strong initiative towards patient education and informed decision-making.  In the same Archives issue, Hoffman et al surveyed 375 men who had undergone PSA testing [8].  93.9% of patients reported having discussed the benefits of PSA testing, while a mere third discussed the harms.  Surprisingly, although 58% of patients felt well-informed about PSA testing, only 47.8% of the patients were able to correctly answer even one of the three knowledge questions.  Hoffman et al found that the only salient characteristic associated with testing was the physician’s recommendation – which means one thing – physicians need to dedicate more time to patient education to assist in decision making.

Physicians should also take the time to educate patients about other factors that contribute to morbidity, including the continuously rising numbers of obese patients and diabetics.  Minamino et. al. found that p53 expression in adipose tissue is closely linked to the development of insulin resistance in mice [9].  They found that excessive caloric intake leads to increases in oxidative stress that ultimately result in cellular senescence, which in turn produces proinflammatory molecules, a process regulated by p53. The upregulation of p53 caused an inflammatory response that ended in insulin resistance and cellular aging, a process bound to the pathogenesis of diabetes.  This kind of data can support economic changes that Brownell et al advocated in NEJM online [10].  Brownell proposed a tax on sugar-sweetened beverages.  He argues that not only is there a clear positive association between intake of sugar-sweetened beverages and body weight, diabetes, and other adverse health effects, but the revenue generated from the tax can also be directed towards more public health education programs.  The obvious goal would be to further decrease the incidence of diabetes and other chronic conditions.

The Annals also looked to see if the increased healthcare spending on Type 2 Diabetes was economically prudent [11].  It was, and thankfully so, as more diabetes treatment options are coming to market after the European Association for the Study of Diabetes Meeting [12].  One drug to look out for is Dapagliflozin, a drug that inhibits the uptake of glucose in the kidneys via SGLT2, which showed a significant reduction in serum glucose and body weight in a phase 3 trial. Though A1c reductions were modest, benefits of this new drug are weight loss and a relatively small side effect profile.   Even with new drugs waiting at the forefront, small steps now may make these drugs unnecessary for younger generations as they age. The NYC Education Department banned traditional bake sales and is refilling the vending machines with healthier items in the city’s schools as part of new wellness programs created because 40% of its students are obese [13].  Though a bold move, this aptly mirrors the emphasis on prevention and protection that has been the theme of medicine clinically and politically over the past few weeks.

Dr. Jani is a 3rd year internal medicine resident at NYU Medical Center.

Peer reviewed by Neil Shapiro, MD, Editor-in Chief, Clinical Correlations

1. http://www.cdc.gov/H1N1FLU

2. Jefferson et al. Physical interventions to interrupt or reduce the spread of respiratory viruses:systematic review. BMJ 2009; 339:b3675 (http://www.bmj.com/cgi/content/abstract/339/sep21_1/b3675)

3. Loeb et al. Surgical Mask vs N95 respirator for preventing influenza among health care workers. JAMA 2009; 302 (17) 1466-1476. (http://jama.ama-assn.org/cgi/content/full/2009.1466)

4. www.hivresearch.org/phase3/phase3pressrelease.html

5. May M. New technologies promise safer sex for women. Nature Medicine 2009; 15 (9): 979. (http://www.nature.com/nm/journal/v15/n9/full/nm0909-979a.html)

6. Holmstrom et al. Prostate specific antigen for early detection of prostate cancer: a longitudinal study. BMJ. 2009; 339:b3537. (http://www.bmj.com/cgi/content/abstract/339/sep24_1/b3537)

7. Howard et al. A model of prostate-specific antigen screening outcomes for low- to high-risk men. Arch Intern Med. 2009; 169 (17):1603-1610. (http://archinte.ama-assn.org/cgi/content/short/169/17/1603?home)

8. Hoffman et al. Prostate cancer screening decisions:results from the national survery of medical decisions. Arch Intern Med. 2009; 169 (17) 1611-1618. (http://archinte.ama-assn.org/cgi/content/short/169/17/1611?home)

9. Minamino et al. A crucial role for adipose tissue p53 in the regulation of insulin resistance.  Nature Medicine. 2009; 15(9) 1082-1087. (http://www.nature.com/nm/journal/v15/n9/full/nm.2014.html)

10. Brownell et al. The public health and economic benefits of taxing sugar-sweetened beverages. NEJM.  2009; 1-7. (http://content.nejm.org/cgi/content/full/NEJMhpr0905723)

11. Eggelston et al. The net value of health care for patients with type 2 diabetes, 1997-2005. Ann Intern Med 2009; 151:386-393. (http://www.annals.org/cgi/content/abstract/151/6/386)

12. http://www.pressreleasepoint.com/dapagliflozen-study-demonstrated-significantly-improved-glycemic-control-and-weight-reduction-type-2

13. http://www.nytimes.com/2009/10/03/nyregion/03bakesale.html?ref=health

 

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