PrimeCuts: This Week in the Journals

August 3, 2009

summerMichael Chu MD

Faculty Peer Reviewed

With summer well underway and a new class of interns having gotten their feet wet by now (perhaps it might feel more like drowning for a few), we have a few interesting articles in the news this past week, ranging from black-market organ sales in the US to immunodeficiency viruses in chimpanzees.

This past week the press reported on an FBI probe into corruption charges in New Jersey involving mayors and several rabbis. What stood out amid the allegations of bribery and money laundering was that a rabbi had allegedly attempted to organize the sale of a human kidney. Time magazine reported on the worldwide business of organ sales and how it reflects on the desperate realities of the impoverished.[1] While essentially unheard of in the United States, the real and seedy business of organ trading in other countries highlights the disparities of rich and poor in our world. Kidney trading rings are known to exist in countries with significant numbers of poor citizens such as India, China, Pakistan, and the Philippines. Kidneys are sold for as little as a few hundred American dollars as a means to afford the basics of survival.

The topic reminds us of the severe shortage of donated kidneys in the United States. There is currently a steady increase in the number of people who need a kidney, while the number of donated kidneys has remained relatively unchanged. The shortage portends a growing number of patients who will go on living with the complications of chronic kidney disease. ABC News reported earlier this month on a record-breaking kidney swap involving 16 people in multiple medical centers.[2] The chain began with one donor who was a match for a recipient who had a family member or friend who donated a kidney for another recipient, and so on, going down the line. These chains are relatively uncommon and are extremely complicated to organize. While it would be nearly impossible to organize such chains on a larger scale to fill the gap for needed kidneys, it does represent an alternative means of efficiently utilizing limited resources.

Researchers in this week’s Nature reported on the pathogenicity of simian immunodeficiency viruses (SIVs) on chimpanzees in Tanzania.[3] HIV-1 and HIV-2 are believed to have originated from SIVs when crossing of the species barrier occurred. It was previously thought that SIV was non-pathogenic; however the researchers found that over the nine years of the study there was a 10-to-16-fold higher age-corrected death hazard for chimpanzees infected with SIVcpz, the immediate precursor of HIV-1, compared to non-infected chimpanzees. It was also found that SIVcpz-infected females were less likely to give birth and had higher infant mortality rates than uninfected females. Chimpanzees that had died of the virus exhibited disease manifestations similar to HIV in humans. These findings are troubling, given the dwindling numbers of wild primates in the world and the potentially devastating effects of the virus on their populations. Study of the virus, however, could be used as a model to discover new approaches in HIV treatment.

In more positive news, researchers published findings in the Annals of Internal Medicine that associate HIV susceptibility testing with improved survival of HIV-infected patients.[4] Currently, it is widely considered standard practice to obtain genotypic and phenotypic susceptibility testing (GPT) when selecting optimal antiretroviral therapy regimens for HIV-infected patients; however, it was not known if this practice actually improved survival.

This was a cohort study involving 2699 HIV-infected patients at ten U.S. HIV clinics who were eligible for GPT testing by virtue of having at least one plasma HIV RNA determination of greater than 1000 copies/mL. Of those eligible, 915 (34%) patients underwent GPT, with the remainder serving as the control group. Patients were observed until death or until about 6 years after study initiation, with a median follow-up time of 3.3 years. Patients were then further divided into two mutually exclusive groups: those who were antiretroviral-naive at baseline (termed “therapy-naïve patients who started HAART”) and those who were already treated with HAART at baseline (termed “HAART experienced”). Another subset of HAART-experienced patients who had received at least 180 cumulative days of therapy with antiretroviral drugs in all three major classes, yet remained viremic with a plasma HIV RNA level above 500 copies/mL, were termed “triple class experienced.”

The study found that overall patients who had GPT had lower mortality rates than those who did not (2.0 vs. 2.7 deaths per 100 person-years). Subgroup analyses showed an association of GPT with improved survival for the 2107 HAART-experienced patients (2.2 vs. 3.2 deaths per 100 person-years; adjusted HR, 0.60 [CI, 0.43 to 0.82]; p = 0.002) and for the 921 triple class experienced patients (2.1 vs. 3.1 deaths per 100 person-years; adjusted HR, 0.61 [CI 0.40 to 0.93]; p = 0.022). The authors note that while they could not confirm an association between use of GPT and improved survival for antiretroviral-naïve patients who began HAART therapy, the study does not rule out such an association. Although AIDS is still a devastating and serious threat to the public health, the amazing achievements in HIV therapy over the last couple of decades have changed perception of the disease from a death sentence to a chronic disease with which patients can lead normal lives. Nevertheless, HIV worldwide is still a growing problem, and means of eradicating the virus continue to elude us.

Syncope in adults is a common reason for hospital admission and its causes range from fairly benign, such as vasovagal syncope, to more serious, such as arrhythmias. Unfortunately, quite often the etiology of syncope is not found, which can be both frustrating for the treating physician and anxiety provoking for the patient. Because of the diagnostic difficulties in determining the etiology of syncope, a whole host of tests are often ordered, ranging from cardiac enzyme tests to CT scans of the head to electroencephalograms (EEGs). These tests increase costs and may be unnecessary. Researchers published findings in the Archives of Internal Medicine this week to help answer some of these questions.[5] Specifically they sought to determine how often diagnostic tests were obtained in evaluating syncope and whether these tests helped establish an etiology. They also calculated the cost per test that affected diagnosis or management.

The authors reviewed records of 2106 consecutive patients 65 years or older who were admitted to an acute care hospital following a syncopal episode. The most frequently obtained tests were electrocardiogram (99% of admissions), telemetry (95%), and cardiac enzyme tests (95%). Only 5% of patients were found to have abnormal cardiac enzymes. Echocardiograms had the highest frequency of abnormal findings (63%); however only 2% yielded findings reported to have contributed to the syncopal episode, most often aortic stenosis. Telemetry helped determine the etiology in 5% of syncopal episodes. Postural BP recording was performed in 38% of patients; however, it had the highest yield with respect to affecting diagnosis (18%) and management (25%) and was the test that was most frequently reported to have helped determine the etiology of the syncopal episode. The tests with the lowest yields were head CT scan, carotid ultrasound, EEG, and cardiac enzymes. Head CT scans affected diagnosis in only 2% of cases. Seventeen of the 20 cases in which MRI results affected diagnosis or management were already suspected on history or physical examination.

Costs per test affecting diagnosis or management were highest for EEG ($32,973), head CT scan ($24,881) and cardiac enzymes ($22,397) and lowest for postural BP recording ($17-20). High costs per test that helped determine the etiology of syncope included head CT scan ($99,525), cardiac enzymes ($77,144), and EEG ($65,946); costs were low for postural BP recording ($23-$33). The San Francisco syncope rule , used to predict serious outcomes, markedly improved yields and lowered costs without compromising identification of persons with life-threatening cardiac conditions. This study suggests that inexpensive postural BP recording is grossly underutilized in the evaluation of patients with syncope and that use of the San Francisco syncope rule may help determine when certain tests are indicated in specific patients, potentially resulting in savings. Some of the limitations of the study were that the study was a retrospective report at a single hospital, and that ICD-9 codes were used to identify syncope admissions, possibly missing other syncope cases coded as another diagnosis.

Dr. Chu is a third year internal medicine resident at NYU Medical Center.

Peer reviewed by Michael Tanner MD, Section Editor, Clinical Correlations,8599,1912880,00.html




3 Keele BF, Jones JH, Terio KA, et al.  Increased mortality and AIDS-like immunopathology in wild chimpanzees infected with SIVcpz.  Nature. 2009 Jul 23;460(7254):515-9


4 Palella FJ Jr, Armon C, Buchacz K, et al; HOPS (HIV Outpatient Study) Investigators.  The association of HIV susceptibility testing with survival among HIV-infected patients receiving antiretroviral therapy: a cohort study.  Ann Intern Med. 2009 Jul 21;151(2):73-84


5 Mendu ML, McAvay G, Lampert R, Stoehr J, Tinetti ME.  Yield of diagnostic tests in evaluating syncopal episodes in older patients.  Arch Intern Med. 2009 Jul 27;169(14):1299-1305.



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