Primecuts – This Week In The Journals

October 11, 2011

By Matthew Robinson, MD

Faculty Peer Reviewed

Men like their numbers.  Boys compare little league batting averages.  Teens boast their bench press max. Young men pride themselves in digits ill begotten from a cheap pick-up line.   Older men – those over age 40 – know their PSA (prostate specific antigen) better than the date of their wedding anniversary.  The U.S. Preventive Services Task Force (USPSTF) is now taking away this number, and replacing it with a letter, D – the grade they gave to PSA as a screening test for prostate cancer.  The USPSTF has released a draft this week recommending against PSA screening in healthy men of any age.   They base their recommendation on the low accuracy of screening, lack of meaningful mortality benefit from early screening, and significant harms associated with the requisite additional interventions initiated by an elevated PSA.  This recommendation is in stark contrast to that of the American Urologic Association who recommends offering the test to all men over age 40.  Still in the draft phase, a fierce debate has already begun about these new recommendations.  The USPSTF though is familiar with notoriety.  You may remember them as the Grinch who stole mammograms from women aged 40-50. Cancer screening is always an emotional topic.   Many prostate cancer survivors attribute PSA screening to saving their life.  However, based on the data cited by the USPSTF, these men would have likely survived without ever knowing that they had prostate cancer, and without the side effects of impotence and bloody semen.  Any effort to curtail treatment or screening is often viewed with mistrust and anger.  Add to this that the chair of the committee, a female pediatrician, has a clinical practice and expertise unrelated to the affected patients.  However, I do believe that a dispassionate review of the evidence is just what the doctor ordered.  (1)

Though the cost of PSA does not factor into the decisions of the USPSTF, soaring healthcare costs are the focus of considerable attention these days.  This week, authors in JAMA have found that healthcare costs are lower for some patients who have advanced directives.   The authors analyzed Medicare expenditures in the last six months of life from a cohort of 3302 patients originally recruited for another study.  At first glance of the data, there seems to be no difference in expenditure at the end of life between those with advance directives and those without.  However, this misses the important confounder that more patients with advanced directives were found in high expenditure areas.  In the regions of the country with the highest healthcare expenditures, care in the last six months was $5585 (95% CI, -$10,903 to -$267) cheaper for patients who had advanced directives than for those who did not.  Despite this large difference in cost, life-sustaining treatments were just as likely to be given to patients with advance directives as those without them.  Efforts to fund discussions with patients about advance directives however have been called “downright evil” and likened to the creation of a Death Panel.  Now that Sarah Palin, creator of the term Death Panel, has officially left the 2012 presidential race, it may be time to resume a more open  dialogue about systemically encouraging advance directives. (2)

With or without the Death Panel, there is no question that the last few months of life are expensive.  Based on a study published in Lancet, shockingly high rates of surgery in patients approaching death may be partly to blame.   The authors, led by Kwok and including healthcare luminary Atul Gwande, examined ICD9 codes for all 1,802,029 Medicare fee-for-service patients who died in 2008.  They found that 8% of patients had a surgical procedure performed in the last week of life, 18.3% in the last month of life, and 31.9% in the last year of life.  Rates of surgery at the end of life were not consistent across the country.  Regions where more surgeries were performed were also those that had more hospital beds per population.  This suggests that open hospital capacity may lead to the performance of more surgeries and that if we assume medical care was adequate across the county, some surgeries performed in higher intensity areas may be unnecessary.  (3)

While in America we are faced with many examples of excess in medical care, we now shift our attention to Sub-Saharan Africa where basic care is hard to find.  In today’s Sub-Saharan Africa regular access to medical care is limited, so hormonal birth control injections, best known in the U.S. by the trade name of Depo-Provera , have become quite popular.  However, every sexual encounter in Sub-Saharan Africa carries not only the risk of pregnancy but also an increased risk of HIV transmission.   In a study published in Lancet Infectious Diseases, hormonal birth control injections were shown to double the risk of HIV transmission. There has long been a concern based on animal data and smaller studies that the use of hormonal contraceptives may increase the risk of HIV transmission.  To evaluate this, 3790 heterosexual couples in which only one partner was infected with HIV were followed for up to two years.  Comparing couples in whom the woman used injectable hormonal contraception to those who used no hormonal contraception, the authors found a hazard ratio of 1.98, p= 0.03 for male to female transmission and a hazard ratio of 1.97, p = 0.02 for female to male transmission.  Of note, the HIV patients in this trial all had CD4 counts greater than 250, were not receiving ART, and were co-infected with HSV-2.  In this study, genital concentrations of HIV RNA were higher in those women who were receiving injectable hormone contraceptives suggesting a potential mechanism at least for the increased risk of female to male transmission observed.(4)

While HIV usually gathers most of the attention for Sub-Saharan African health care, malaria continues to run rampant, particularly affecting children.  In a sophisticated and sometimes bewildering pair of case-control studies, authors in Lancet explored the risk that malaria posed to a population of Kenyan children for developing invasive bacteremia.  For the purposes of answering this question, they took advantage of the known protective effect of sickle cell trait in developing malaria.  They thus used presence of sickle cell trait as a surrogate for patients that did not have malaria.  They then looked at 292 cases of bacteremia in their patient population and found matched controls in the community without bacteremia to whom they could be compared.  They found that sickle cell trait was less common in cases of bacteremia than in healthy controls with an odds ratio of 0.36 (95% CI 0.2-0.65).  This of course poses the question of whether sickle cell trait protects against bacteremia directly, rather than indirectly by protecting against cases of malaria.  The authors then took advantage of a drastic reduction in malaria incidence over time in the community that they were studying.  While the incidence of malaria dropped, sickle cell trait is a genetic mutation that could not change.  They then demonstrated that the protective effect of sickle cell trait against bacteremia disappeared when malaria incidence dropped, thus ruling out sickle cell trait directly being protective against bacteremia.  Relying on multiple surrogates and comparing rates over time, this study has severe limitations.  However, this study does seem to suggest that malaria does increase a child’s risk for bacteremia.  While the direct clinical application of this is unclear, the public health implications are massive.  Malaria control is one of the cornerstones of global public health and plans are being considered for its eradication.  If controlling malaria will also reduce bacteremia, then the cost to benefit ratios of malaria control measures will change drastically. (5)

The findings of these two studies from Sub-Saharan Africa have shed light on some important public health issues, but their findings are generally not well explained by our current understanding of HIV, malaria, bacteremia, and the immune system.  Now may be a good time though to celebrate how far we have come in understanding immunity.  While we discussed this week the hemorrhaging of American healthcare dollars, our friends in Stockholm are releasing Kronors by the millions.  This week the Nobel Assembly announced that the 2011 Nobel Prize in Physiology or Medicine would be rewarded to three pioneers in immunology – Steinmann for his 1973 discovery of the dendritic cell, Hoffman for his discovery of Toll, and Beutler for Toll-like receptor  - inspirations for future work to come.

Dr. Matthew Robinson is a 2nd year resident at NYU School of Medicine

Peer reviewed by Robert Gianotti, MD, Associate Editor, Clinical Correlations

Image courtesy of Wikimedia Commons

References:

1.  USPSTF. Screening for Prostate Cancer: U.S. Preventive Services Task Force Recommendation Statement DRAFT. Available from: http://www.uspreventiveservicestaskforce.org/uspstf12/prostate/prostateart.htm

2.  Nicholas LH, Langa KM, Iwashyna TJ, Weir DR. Regional Variation in the Association Between Advance Directives and End-of-Life Medicare Expenditures. JAMA: The Journal of the American Medical Association2011 October 5, 2011;306(13):1447-53. http://jama.ama-assn.org/content/306/13/1447.abstract.

3.  Kwok AC, Semel ME, Lipsitz SR, Bader AM, Barnato AE, Gawande AA, Jha AK. The intensity and variation of surgical care at the end of life: a retrospective cohort study. The Lancet(in press). http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(11)61268-3/abstract.

4.  Heffron R, Donnell D, Rees H, Celum C, Mugo N, Were E, de Bruyn G, Nakku-Joloba E, Ngure K, Kiarie J, Coombs RW, Baeten JM. Use of hormonal contraceptives and risk of HIV-1 transmission: a prospective cohort study. The Lancet Infectious Diseases(in press). http://www.thelancet.com/journals/laninf/article/PIIS1473-3099(11)70247-X/abstract.

5.  Scott JAG, Berkley JA, Mwangi I, Ochola L, Uyoga S, Macharia A, Ndila C, Lowe BS, Mwarumba S, Bauni E, Marsh K, Williams TN. Relation between falciparum malaria and bacteraemia in Kenyan children: a population-based, case-control study and a longitudinal study. The Lancet;378(9799):1316-23. http://thelancet.it/journals/lancet/article/PIIS0140-6736(11)60888-X/abstract.

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