Bisher AKIL, MD

Archive for March, 2009|Monthly archive page

Folic Acid Supplementation Increases the Risk for Prostate Cancer

In Cancer on March 31, 2009 at 11:55 pm

The Aspirin/Folate Polyp Prevention Study (AFPPS) involved two comparisons in patients with recently resected colorectal adenomas — aspirin versus placebo and folic acid versus placebo (JW Mar 19 2009). Previously published results from the folic acid portion of the study indicated that daily supplementation (1 mg) did not prevent recurrent colorectal adenomas; in fact, investigators found a nonsignificant trend toward more high-grade adenomas in the folic acid group (2007). Now, the researchers report on another outcome — prostate cancer — among 643 participating men (mean age at enrollment, 57).
During a median follow-up of 7 years, prostate cancer was diagnosed in 25 folic acid recipients and in 9 placebo recipients. The estimated 10-year probability of prostate cancer was significantly higher in the folic acid group than in the placebo group (9.7% vs. 3.3%).
Comments: So men who took folic acid daily were more likely to develop cancer during 7 years of follow-up, almost 3-to-1. The etiology is unclear _ BA

Abacavir and Risk for Heart Disease

In Heart on March 23, 2009 at 2:04 pm

In February 2008, findings from the Data Collection on Adverse Events of Anti-HIV Drugs (DAD) study indicated that the incidence of myocardial infarction increased nearly two-fold with recent (less than 6 month) use of abacavir. Subsequently, a retrospective analysis from the SMART (The Strategies for Management of Antiretroviral Therapy) study revealed similar results. In the ensuing year, data from various studies fell on both sides of the subject. This year at the 16th Conference on Retroviruses and Opportunistic Infections (CROI), four different studies were presented, adding more to the controversy:
1. An updated analysis from the DAD Study, involving >178,000 person-years of follow-up, confirmed that recent abacavir use was strongly associated with increased risk for myocardial infarction (MI), whereas cumulative exposure was only modestly associated with myocardial infarction.
2. A case-control study from the French Hospital Database group, involving 289 MI cases and 865 controls, showed that recent, short-term use (<1 year) of abacavir was significantly associated with MI risk
3. In the STEAL Study from Australia, 357 patients with viral loads <50 copies/mL who were HLA B5701–negative had the NRTIs in their current regimens switched to either abacavir/3TC (Epzicom) or tenofovir/FTC (Truvada). At week 96, abacavir/3TC was associated with significantly more cases of serious CVD (8 vs. 1)
4. In contrast to these data, a pooled analysis of five ACTG studies, all conducted in patients initiating antiretroviral therapy (ART), showed no evidence of a link between recent abacavir use and cardiovascular outcomes.
The mechanism of this association was also a subject of speculation and more controversy: The manufacturer-sponsored, randomized HEAT Study, 96-week changes in inflammatory markers (C-reactive protein and interleukin-6) and endothelial activation markers (vascular cell adhesion molecule-1) did not differ significantly between patients who started ART with abacavir/3TC and those who started with tenofovir/FTC. Similar null results were seen in biomarker analyses from the Multicenter AIDS Cohort Study and Women’s Interagency HIV Study and also from ACTG 5095. However, two small studies did suggest that abacavir use was associated with impaired brachial dilatation and increased platelet aggregation.
In reviewing the data from the conference, Dr. Peter Reiss (Associate Professor of Medicine, Academic Medical Center at the University of Amsterdam, and a member of the DAD Study Group), he noticed that studies showing a relationship between abacavir and heart disease had patients that tend to be 7-10 years older than other studies and are usually receiving antirotriviral therapy (ART) with viral suppression.
Comments: This association remains unclear. Furthermore there is no clear etiology ( or more likely several etiologies). People with risk for coronary artery disease (smoking, over 45 years of age, male,…etc) need be evaluated carefully for the choice of medications. What is clear: no one treatment fits all, and the risk for heart disease should be assessed carefully in each individual. Treatment for underlying problems (such as hypertension, hyperlipidemia, obesity, smoking,…etc) much be addressed and treated as aggressive as one treats HIV itself_ BA.

IL-2 increases CD4+ count but no clinical improvement

In Immune System on March 22, 2009 at 11:35 pm

Previous studies have suggested that adding Interleukin (IL)-2 will increase CD4+ cell count. The clinical benefit for such increase was inferred but not proven. In February 2009, during the 16th Conference on Retroviruses and Opportunistic Infections (CROI), two studies attempted to show the clinical benefit.
In the SILCAAT trial [Abstract 90bLB], 1695 patients who had CD4 counts <300 cells/mm3 while receiving antiretroviral therapy (ART) were randomized either to continue ART alone or to also receive IL-2 (4.5 million IU, delivered subcutaneously twice daily in at least 6 cycles of 5 days each, separated by 8-week intervals). The median nadir CD4 count was 60 cells/mm3, and the median entry CD4 count was 202 cells/mm3; 81% of patients had viral loads 500 copies/mL. The two treatment groups were well matched at baseline. During follow-up (median, 7.6 years), the IL-2 group averaged 57 more CD4 cells/mm3 than did the ART-alone group, but the rate of opportunistic disease or death was similar between the groups. Adverse event rates were also similar, except in the first year, when the IL-2 group had a higher rate of grade 4 events (mostly psychiatric and gastrointestinal).
The second study, ESPRIT trial, [Abstract 90aLB], had the same study design as SILCAAT, but the 4111 patients had baseline CD4 counts 300 cells/mm3, and the IL-2 was dosed differently (7.5 million IU, delivered subcutaneously twice daily in at least 3 cycles of 5 days each, separated by 8-week intervals). The overall median nadir CD4 count was 197 cells/mm3, and the mean enrollment CD4 count was 457 cells/mm3; 80% of patients had viral loads 500 copies/mL. Results were similar to those of the SILCAAT study: The IL-2 group gained more CD4 cells than did the ART-alone group (average difference, 153 cells/mm3) but did not have a lower rate of opportunistic disease or death. Again, the IL-2 group had an excess of grade 4 adverse events (this time, mostly vascular complications).
Comments: Why? usually more CD4+ cell count means better immune system and less infections, less death…etc. There is no clear answer, but there is no shortage of possibilities: maybe the cells generated are not as good as the cells one gets from ART; maybe IL-2 does something bad, maybe…etc. In the meantime, these were unexpected results _ BA

Treatment Induced Changes in HDL , LDL and Heart Disease

In Heart on March 22, 2009 at 11:06 pm

High-density lipoprotein (HDL) cholesterol level is associated independently and inversely with coronary heart disease risk. However, evidence that treatment-mediated increases in HDL cholesterol levels lower risk for heart disease is lacking. In analysis of 108 randomized trials (Briel M et al. Association between change in high density lipoprotein cholesterol and cardiovascular disease morbidity and mortality: Systematic review and meta-regression analysis. BMJ 2009 Feb 16; 338:b92.), involving nearly 300,000 patients, investigators assessed whether changes in HDL and Low -density lipoprotein (LDL) as a result of medical treatment was associated with changes in the risk for heart disease.
All but five trials involved lipid-modifying drugs. After adjustment for changes in LDL cholesterol levels related to treatment and drug class, no associations were noted between treatment-mediated changes in HDL cholesterol levels and all-cause death. However, changes in LDL cholesterol levels were associated with significant outcomes: For a 10 mg/dL reduction in LDL cholesterol level, relative risks were lowered for all-cause death by 4.4%, for coronary heart disease-related death by 7.2%.
Comments: the good news is that is the LDL is lowered using medications, there is clear and significant benefit; on the other hand, changes in HDL did not seem to make a difference, in this analysis. This analysis may not reveal hidden benefits for increasing HDL, but it makes it clear that the goal of treatment should be lowering LDL _ BA

High BMI & Death Rate

In General Health on March 18, 2009 at 8:07 pm

Body mass index (BMI) is a measure of someone’s weight in relation to height; to calculate one’s BMI, multiply one’s weight in pounds and divide that by the square of one’s height in inches; overweight is a BMI greater than 25; obese is a BMI greater than 30. A collaborative analysis of 57 prospective studies reported in the March 18 Online First issue of Lancet. The investigators analyzed the association of baseline BMI with mortality in 57 prospective studies enrolling a total of 894,576 participants, mostly in western Europe and North America, with median recruitment year 1979. Mean age at recruitment was 46 ± 11 years, 61% were men, and mean BMI was 25 ± 4 kg/m². The analyses were adjusted for age, sex, smoking status, and study, and the first 5 years of follow-up were excluded. Mortality rate was lowest with BMI at approximately 22.5 to 25 kg/m² for both men and women.On average, each 5-kg/m² higher BMI was associated with approximately 30% higher overall mortality rate. BMI less than 22·5 to 25 kg/m² was inversely associated with overall mortality rate, primarily because of strong inverse associations with respiratory disease and lung cancer. Although cigarette consumption per smoker varied little with BMI, these inverse associations were much stronger for smokers vs nonsmokers.”In adult life, it may be easier to avoid substantial weight gain than to lose that weight once it has been gained,” the study authors conclude. “By avoiding a further increase from 28 kg/m² to 32 kg/m², a typical person in early middle age would gain about 2 years of life expectancy. Alternatively, by avoiding an increase from 24 kg/m² to 32 kg/m² (ie, to a third above the apparent optimum), a young adult would on average gain about 3 extra years of life.”

Comments: This is an easy index to use. There are several web pages that will calculate BMI. Try this one Although this index has a lot of shortcomings, it is easy to monitor. Please note that the study measured weight in kilograms and height in meters. BA

Vitamin C & E: do they prevent heart disease?

In Heart on March 17, 2009 at 11:59 pm

Data have suggested possible benefit from antioxidants, especially vitamin C &E in preventing cardiovascular events. However, this benefit has never been confirmed. The Physician’s Health Study II (PHS II) trial was designed to answer this question. The data were presented by Dr. J. Michael Gaziano at the American Heart Association Annual Scientific Sessions, New Orleans, November 2008. The study was placebo controlled, randomized, blinded, parallel and factorial. It screened 273,360 and enrolled: 14,641 male US physicians with mean follow-Up of 8 years and mean age: 64.3 years. Patients were randomized in a 2 x 2 x 2 x 2 factorial trial to either vitamin E (400 IU synthetic α-tocopherol) or placebo every other day, vitamin C (500 mg synthetic ascorbic acid) or placebo daily, multivitamin (Centrum Silver) or placebo, and beta-carotene (50 mg of Lurotin) or placebo every other day. A total of 14,641 healthy males were randomized, 3,656 to active vitamins E and C, 3,659 to active vitamin E and placebo vitamin C, 3,673 to placebo vitamin E and active vitamin C, and 3,653 to placebo vitamins C and E. Baseline characteristics were fairly similar between the four groups. About 61% exercised at least once every week, about 44% were past or current smokers, 77.4% were on aspirin, 42% had a history of hypertension, 36% had a history of hypercholesterolemia, 6% had a history of diabetes, and about 5% had a self-reported history of cardiovascular disease. Compliance was about 72% at 8 years.
Vitamin E: There was no difference between patients receiving vitamin E or placebo in the incidence of major cardiovascular events (8.5% vs. 8.5%, hazard ratio [HR] 1.01, 95% confidence interval [CI] 0.90-1.13, p = 0.86). There was also no difference in the incidence of myocardial infarction (MI) (3.3% vs. 3.7%, p = 0.22), stroke (3.2% vs. 3.1%, p = 0.45), congestive heart failure (4.0% vs. 4.0%, p = 0.80), or all-cause mortality (11.5% vs. 11.2%, p = 0.15). However, there was a significant increase in the risk of hemorrhagic stroke in the vitamin E arm (0.53% vs. 0.31%, HR 1.74, 95% CI 1.04-2.91, p = 0.04).

Vitamin C: There was no difference between patients receiving vitamin C or placebo in the incidence of major cardiovascular events (8.4% vs. 8.6%, HR 0.99, 95% CI 0.89-1.11, p = 0.91). There was also no difference in the incidence of MI (3.5% vs. 3.4%, p = 0.65), stroke (3.0% vs. 3.4%, p = 0.21), or all-cause mortality (11.7% vs. 11.0%, p = 0.16).


The results showed  that neither vitamin C nor vitamin E supplementation is associated with a reduction in major cardiovascular outcomes, as compared with placebo, although vitamin E may be associated with a slightly higher incidence of hemorrhagic stroke, compared with placebo.

Comments: No women were enrolled in this study which limits its benefit; questionnaire were used to assess the results. These may make the results a bit weaker, but they are still valid. Next time you decide to buy vitamins, make sure you are buying them for a good reason, otherwise save your money.BA

Neurosyphilis is probably underestimated in HIV

In Brain on March 2, 2009 at 10:07 pm

Asymptomatic neurosyphilis in HIV infected patients is probably grossly underestimated. he most recent CDC guidelines recommend spinal fluid analysis for HIV-infected patients who have late latent syphilis, syphilis of unknown duration, or serologic failure after a course of syphilis treatment. Other authorities suggest that spinal fluid should be obtained in individuals with CD4 counts ≤350 cells/mm3 or rapid plasma reagin (RPR) titers ≥1:32. To determine which nomogram might yield an ANS diagnosis most efficiently, investigators reviewed data from a large cohort of HIV-infected patients at the Johns Hopkins Moore Clinic. In a recent study, the authors discovered that 202 of 231 patients (87%) did not have neurological symptoms. Immediate lumbar puncture was performed on 46 patients and 22% had neurosyphilis without any symptoms! (Journal of Clinical Infectious Diseases, 2009 Mar 15;48(6):816-21) – Comments: Neurosyphilis remains under diagnosed and under treated. Just because there are no symptoms, does not mean there is no disease. Lumbar puncture is a lot easier that neurosyphilis. BA


In SMB & CVM on March 2, 2009 at 9:28 pm

I am a practicing Internist with primary interest in HIV infection. The purpose of this blog is to bring useful medical information in a scientific format to the reader. I usually add comments to give my thoughts. These thoughts are not always acceptable, and I would like to hear from you. Thank you for reading. BA