Primecuts-This Week in the Journals

December 14, 2009

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Sarah Lee, MD

As the national healthcare debate rages on and while winter decides to give us a premature hello,  Primecuts turns its view towards the overuse of antibiotics in the Petri dish we call the intensive care unit, more discussion on the HIV vaccine we discussed last week, the plight of the uninsured and an in depth analysis of the Tiger Woods story… ok now that we have your attention…

Throughout the world today, infection continues to be one of the main contributors to morbidity and mortality in intensive care units (ICU’s).  There have been few studies addressing our ability to control and understand the patterns of infection that occur in ICU’s internationally. This week in  JAMA, Vincent and colleagues look at the global struggle to combat infection and infection-related deaths in the critical care setting.  Their study (known as EPIC II) was a point prevalence investigation that looked at 13,796 patients in over 1200 ICU’s in 75 different countries on  a single day.  This study served as a follow-up to the 1995 EPIC (European Prevalence of Infection in the ICU) conducted 15 years earlier which similarly surveyed ICU’s in western Europe. (1)  Their results revealed a dismal report of news from the battlefront: of the ICU patients surveyed on the given day, 51% were considered infected and 71% of patients were being administered antibiotics (including prophylactically), with the majority receiving multiple antibiotics. This is in stark contrast to the original EPIC study which showed an infection rate of 44.8% with 62.3% of ICU patients receiving antibiotics. Of the infections, gram-negative infections accounted for 63% of infections compared to 39.1 % in the 1995 EPIC study.  There was likewise a marked increase in multi-drug resistant gram-negative organisms such as acinetobacter and pseudomonas. (2) In North America, most of the S. aureus infections were found to be methicillin-resistant and prevalence of fungal infections increased from 17-19%.  Infections among the most critically ill are certainly not declining.  And so, as Opal and Calandra write in an accompanying editorial we should use antimicrobials wisely-limit their use to clear infection over colonization and discontinue antibiotics as early as possible. These are principles we know, but must recall and put into practice.

Research in the field of infectious disease continues to make headway with studies on the development of a safe and effective vaccination against HIV-1.  Last week’s Primecuts touched on the search for the elusive HIV vaccine and here we dig a little deeper into the article found in last week’s New England Journal of Medicine.   Thailand is a country which has seen a dramatic increase in HIV infection prevalence due to its commercial sex-trade and high rates of IV drug use.  It is here that Rerks-Ngarm and colleagues evaluated the efficacy of a potential vaccination in a randomized, multicenter, double-blind, placebo-controlled efficacy trial centered in 2 Thai provinces. Subjects were 16,402 non-HIV infected men and women, primarily heterosexual, volunteer subjects between the age of 18 and 30. (3) Vaccination protocol consisted of four priming injections with a recombinant vector vaccine (ALVAC-HIV vCP1521) followed by 2 booster injections of a recombinant glycoprotein vaccine (AIDSVAX B/E).  This prime-boost concept had been previously established to induce both cellular and humoral responses. (4)  In this intention-to-treat analysis 132 subjects, were diagnosed with HIV during 52,985 person-years of follow-up 56 of whom were vaccinated and 76 of who received placebo. Overall, results of the study demonstrated a modest vaccination efficacy of 31.2%.  Moreover, immunogenicity, determined by the presence of gamma-interferon produced by T cells, measured by ELISASPOT testing was positive in 19.1% of vaccinated subjects 6 months after the completion of the vaccination series. Unfortunately, the vaccination was not shown to demonstrate any reduction in viral load or in CD4+ T-cell count in subsequently infected subjects. The study thus shows that there is indeed potential for possible protection against infection with the virus through vaccination although efficacy and maintenance of efficacy over time in high risk populations have yet to be more convincingly demonstrated. Given the widespread effect of the global epidemic incurred by the HIV-1 virus, the realization of this potential someday would indeed be profound.

Many agree that the most realistic solution to the lack of universal health coverage in the United States may be through steadily increasing the inclusiveness of existing governmental programs such as Medicare and Medicaid. The obvious issue is the cost incurred by increasing the number of uninsured Americans who would be covered by these programs. Is it possible that we could offset some of these costs  by covering uninsured adults so that they are healthier once they reach the age of 65 ?  This week in the Annals of Internal Medicine, McWilliams and colleagues examine the economics of increasing the inclusiveness of Medicare.  They compared Medicare expenditure for previously uninsured adults to that of previously insured adults, all of whom were then enrolled in Medicare at the age of 65. (5)  In particular, they looked at differential costs incurred in clinical subgroups of patients who had cardiovascular disease (hypertension, heart disease, stroke), diabetes, or required joint replacement. Moreover the study categorized annual spending for claims in four general services: hospital stays, outpatient institutional visits, physician office visits, and days in skilled nursing facilities. After controlling for confounding factors such as deteriorating health causing uninsurance (vs. the converse) and geographical variation in spending, the study showed that adjusted annual total Medicare spending was significantly higher for previously uninsured than previously insured adults ($5796 vs. $4773; difference, $1023 [95% CI, $29 to $2016].  Furthermore, it showed that differences in costs were most notable amongst patients in the highest quartile of spending distributions with $26,787 for previously uninsured compared to $21,813 for previously insured patients in the 95th percentile of Medicare spending. For hospitalizations, 66.7% of the adjusted difference in inpatient spending between previously uninsured and insured adults was accounted for by complications due to cardiovascular disease, diabetes, and joint replacement.

Given the current economic climate, and the increasing numbers of uninsured, the policy implications for the study are significant. It has been calculated that providing healthcare coverage to the uninsured between ages of 51-64 for a continuous period of 4 years would increase spending by $197 billion. However, this study suggests that increasing this coverage would ultimately decrease Medicare spending after the age of 65 by at least $98 billions. Thus it appears that the cost of increasing the inclusiveness of Medicare would be significantly offset by the decrease in Medicare spending after the age of 65.  Clearly this concept needs to be factored into the analyses and arguments on both sides of the aisle.

And as for Tiger Woods…well maybe another time…

Sarah Lee is a first year internal medicine resident at New York University Medical Center

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

1. Vincent J. International Study of the Prevalence and Outcomes of Infection in Intensive Care Units. JAMA. 2009;302(21):2323-2329.  http://jama.ama-assn.org/cgi/content/abstract/302/21/2323

2. Opal S, Calandra T. Antibiotic Usage and Resistance: Gaining or Losing Ground on Infections in Critically Ill Patients? JAMA. 2009;302(21):2367-2368.  http://jama.ama-assn.org/cgi/content/extract/302/21/2367

3. Rerks-Ngarm S. Vaccination with ALVAC and AIDSVAX to Prevent HIV-1 Infection in Thailand. NEJM. 2009;361(23):2209-2220.  http://content.nejm.org/cgi/content/full/361/23/2209

4. Belshe R.  Neutralizing antibodies to HIV-1 in seronegative volunteers immunized with recombinant gp120 from the MN strain of HIV-1. JAMA 1994;272:475-480.  http://jama.ama-assn.org/cgi/reprint/272/6/475

5. McWilliams J. Medicare Spending for Previously Uninsured Adults. Ann Intern Med. 2009;151:757-766.  http://www.annals.org/gca?submit=Get+All+Checked+Abstracts&gca=annintmed%3B151%2F11%2F757

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