Breaking News

Breaking News: The Crestor Controversy

April 1, 2010

Devyani Kothari, MD

Patients are already talking about a New York Times front page article highlighting the risks associated with statin use as a preventive measure for cardiovascular events in relatively “healthy” people. The piece examines the newest FDA indications for the use of Crestor along with the controversies surrounding the drug.

Last month, the FDA approved Rosuvastatin Calcium, marketed as Crestor by AstraZeneca for use in a new patient population , based on the JUPITER trial. Crestor now carries the indication for the primary prevention of cardiovascular disease (to reduce the risk of stroke and heart attack) in individuals who have no clinically evident heart disease but are at an increased risk of heart disease due to the combined effect of the following risk factors:

o Age (> 50 years in men; > 60 years in women), and
o An elevated high-sensitivity C-reactive protein level (> 2 mg/L), and
o Presence of at least one additional cardiovascular risk factor (e.g., high blood pressure, low HDL-C, smoking, or a family history of premature heart disease).

Under these new guidelines, an estimated additional 6.5 million people in the United States will be eligible to take statins.
Despite these recommendations, many clinicians are skeptical of this new role of statins as a largely preventive measure. Statins are already known to cause myopathy and increased liver enzymes in some patients. In addition, a meta-analysis of 13 randomized statin trials recently published in The Lancet by Sattar et al. showed that statin therapy was associated with a 9% increased risk of developing Type II Diabetes. The JUPITER trial also noted increased physician-reported diabetes in the rosuvastatin group, although there were no significant elevations of fasting blood glucose and only minimal differences in HgA1C.

Furthermore, the new indication for Crestor is based on the level of C-reactive protein, or CRP, an inflammatory marker that has been linked to an increased risk of adverse cardiovascular events. This marker however has not yet achieved the overall acceptance as a marker of risk that traditional lipid levels have.

Adding fuel to the controversy is the fact that the JUPITER trial was funded by AstraZeneca, the manufacturer of Crestor, and one of the authors of the trial, Dr. Paul M. Ridker, invented the CRP test, and receives “undisclosed royalties” every time a doctor orders the test. Moreover, Crestor has its patent until 2016, while Pfizer will lose patent protection on Lipitor next year, pushing the company to expand indications for its drug.

The debate of the role and safety of statins in primary prevention raises very important issues for practicing clinicians. Should a CRP level be ordered on all older patients? How aggressive should doctors be about prescribing statins to healthy patients? Is the CRP a better predictor of cardiovascular disease than lipid levels? The answers still remain to be decided. What should however remain clear to our patients is the clearly proven role of statins in secondary prevention, in patients with known cardiovascular disease. This message needs to be reinforced especially with our cardiac patients who balk at taking statins because they heard on TV that “they are too dangerous.”

1. Everett BM, Glynn RJ, MacFadyen JG, Ridker PM. Rosuvastatin in the prevention of stroke among men and women with elevated levels of C-reactive protein: Justification for the use of statins in prevention: An intervention trial evaluating rosuvastatin (JUPITER). Circulation. 2010;121(1):143-150.
2. Sattar N, Preiss D, Murray HM, et al. Statins and risk of incident diabetes: A collaborative meta-analysis of randomised statin trials. Lancet. 2010;375(9716):735-742.
3. U.S. Food and Drug Administration: “Rosuvastatin Calcium (marketed as Crestor) Information.”
4. Wilson, Duff. “Risks Seen in Cholesterol Drug Use in Healthy People.” 31 March 2010. The New York Times.

The 6th Annual Medical Blog Awards-The Polls are Open

January 28, 2010

award_lr1.gifWe are honored  to once again be named as a finalist in the categories of Best Medical Weblog and Best Clinical Sciences Weblog in Medgadget’s 6th Annual Medical Blog Awards.  Reviewing the nominations in each award category is a wonderful opportunity to familiarize yourself with the medical blogosphere.  There are so many worthy sites out there that I strongly urge you to spend some time surfing the nominations in each of the categories.  There’s something here for everyone regardless of where your interest in healthcare lies-be it health care policy, ethics, literature or hardcore internal medicine.  Medgadget, an internet journal that focuses on technological innovations in medicine is a terrific blog in it’s own right and definitely worth reviewing after you finish voting.


NYU in Haiti

January 24, 2010

s_203In response to the devastating earthquake in Haiti, physicians, nurses, and staff at NYU Langone Medical Center came together to form the Haitian Effort and Relief Team (NYULMC HEART). On Friday, January 22, 2010, the first group of HEART volunteers arrived in Haiti to provide surgical services and support at General Hospital in Port-au-Prince.   Fritz Francois, MD, Assistant Dean for Academic Affairs and Diversity at NYU, is sharing his group’s experience in a compelling blog that puts this tragedy into  real perspective.

Read the NYULMC HEART Blog.

If you are interested in donating to a relief fund but are unsure which one, this post from Kevin is a comprehensive overview of the various charitable organziations.

Happy New Year and Happy Birthday to Us

January 1, 2010

time-square-2010-new-year-ballAs we here at Clinical Correlations celebrate the New Year and mark our 3rd anniversary we realize that we have so much to be thankful for.  2009 has been a very productive year for our website.  Our readership has grown over 65% since last year reaching over 200,000 hits this year.  Readers visited us from over 200 countries including a reader from Greenland, the last major holdout.  We were awarded the 2009 Gold eHealthcare Leadership Award our second major award.  Last week Judith Brenner, our associate editor and Clinical Correlations were prominently quoted by Jane Brody in a New York Times article on osteoporosis.  We’re so proud of all these accomplishments

I just wanted to say a special personal thank you to my senior editors-Cara Litvin, Judith Brenner and Michael Tanner without whom none of this would be possible.  Your energy and commitment has kept Clinical Correlations alive and thriving.  And to all the other editors, authors, reviewers and readers, there are too many to name, thank you all so much.  We greatly appreciate all your enthusiasm and feedback.  Your contributions have made Clinical Correlations far better and more credible than we ever could have imagined.  We have big plans and great aspirations for 2010 so stay tuned…Here’s to a safe, happy and healthy New Year for all.

Neil Shapiro, MD  Editor-In-Chief


Breaking News: Begin Cervical Cancer Screening at 21 Says ACOG

November 20, 2009

800px-ca_in_situ2c_cervix_2Joshua Strauss, MD

In the second decision of its kind and magnitude in a matter of days, a major medical group has again recommended cutting back on cancer screening for women.  On the heels of Monday’s USPSTF release on reducing mammography, newly revised evidence-based guidelines regarding cervical cancer screening were issued today by The American College of Obstetricians and Gynecologists (ACOG) and published in the December issue of Obstetrics & Gynecology. 

The new guidelines, “based on good and consistent scientific evidence,” recommend beginning cervical cancer screening at 21 years of age.  ACOG’s previous guidelines published in 2006 had advised yearly screens 3 years after the initiation of sexual intercourse, but no later than 21 years.  The rationale for changing course, according to the group, is the mounting evidence that the vast majority of precancerous cervical lesions in adolescents and young women are likely to spontaneously resolve.  Thus, the bulletin argues, screening this age group leads to “unnecessary and harmful evaluation and treatment in women at very low risk of cancer.”

Another major guideline revision relates to women ages 21 to 29: Recommendations for annual screens have been changed to biennial testing for this population.  However, screening recommendations for women 30 years and older will remain the same: “Women aged 30 years and older who have had three consecutive negative cervical cytology screening test results and who have no history of CIN 2 or CIN 3, are not HIV infected, are not immunocompromised, and were not exposed to diethylstilbestrol in utero may extend the interval between cervical cytology examinations to every 3 years.”

Media and other public reaction to these latest guidelines have been understandably received in the context of the recent revision of the breast cancer screening guidelines earlier this week, as well as the ongoing national healthcare debate.  Skeptics may see these latest recommendations as an effort to reduce healthcare costs by rationing cancer screenings to smaller groups of individuals.  However, others will argue that the medical community is undergoing an appropriate revision of its screening process.  This opinion is most clearly articulated by Dr. H. Gilbert Welch, a professor of medicine at Dartmouth, in an interview in the New York Times.  He notes that “the efforts to detect cancer early can be a two-edged sword. Yes, it helps some people, but it harms others… we’re trying to negotiate that balance,” he said. “There’s no right answer, but I can tell you that the right answer is not always to start earlier, look harder and look more frequently.”

Image of high grade dysplasia (carcinoma in situ) in the uterine cervix courtesy Wikimedia Commons

Cervical cytology screening. ACOG Practice Bulletin No. 109. American College of Obstetricians and Gynecologists. Obstet Gynecol 2009; 114:1409-20.

 Grady, Denise. “Guidelines Push Back Age for Cervical Cancer Tests.” 20 November 2009. The New York Times.

Ho GY, Bierman R, Beardsley L, Chang CJ, Burk RD. Natural history of cervicovaginal papillomavirus infection in young women. N Engl J Med 1998;338:423-8. (Level II-2)

 Primary and preventive care: periodic assessments. ACOG Committee Opinion No. 357. American College of Obstetricians and Gynecologists. Obstet Gynecol 2006;108:1615-22.

 Sack, Kevin. “Screening Debate Reveals Culture Clash in Medicine.” 20 November 2009. The New York Times.

Read more »

Breaking News: Initiate Mammography Screening at 50, not 40, Says USPSTF.

November 17, 2009

mammogram_showing_breast_cancerAalok Turakhia, MD

As the debate over when to begin screening mammography in women rages on, the United States Prevention Service Task Force (USPSTF) added fuel to the fire by releasing a new recommendation statement in the November 17th issue of the Annals of Internal Medicine.  Applying to women aged ≥40 who are not at an increased genetic risk or have had chest irradiation, the USPSTF now recommends biennial screening in women between ages 50-74.  In February 2002, the task force first recommended that annual or biennial screening start at age 40; however, in a revised statement, “The USPSTF recommends against routine screening mammography in women aged 40 to 49 years.”  It adds, “The decision to start regular, biennial screening mammography before the age of 50 years should be an individual one and take into account patient context, including the patient’s values regarding specific benefits and harms.”  Additionally, regarding screening mammography in women 75 years or older, the evidence is lacking and the risk/benefit ratio has not been fully determined.

Predictably, there has been both supporting and dissenting response from the medical community.  In a statement from the American Cancer Society released yesterday, it “continues to recommend annual screening using mammography and clinical breast examination for all women beginning at age 40.”  The chair of the American College of Radiology’s Breast Imaging Commission had a more stern tone in her response.  Dr. Carol Lee stated, “These unfounded USPSTF recommendations ignore the valid scientific data and place a great many women at risk of dying unnecessarily from a disease that we have made significant headway against over the past 20 years.”  However, the National Breast Cancer Coalition, Breast Cancer Action, and the National Women’s Health Network, all supported the newly released USPSTF guidelines.

There is little doubt that the recommendations would result in billions of dollars of savings in medical costs, and though there are always charges of political motivation when guidelines such as these are released, physicians should always use clinical acumen and adequately weigh the pros and cons of what promises to be continuous topic of discussion and debate.

Brawley, OW. American Cancer Society Press Room. 16 11 2009. 17 11 2009

Casey, B. “USPSTF ups mammography screening age to 50.” 16 11 2009. Aunt Minnie. 17 11 2009

Kolata, Gina. “Panel Urges Mammograms at 50, Not 40.” 16 November 2009. The New York Times . 17 November 2009 <>.

U.S. Preventative Services Task Force. “Screening for Breast Cancer: U.S. Preventive Services Task Force Recommendation Statement.” Annals of Internal Medicine (2009): 716-726.

Image Courtesy Wikimedia Commons

Clinical Correlations Awarded Gold eHealthcare Leadership Award

November 11, 2009

We are very excited to announce that Clinical Correlations has been awarded the 2009 Gold eHealthcare Leadership Award.  This awards program, now in it’s tenth year,  is the largest web-oriented awards program that is focused exclusively on healthcare.  The program attracts over 1100 entrants. Clinical Correlations won this award in the Best Health/Healthcare Content-Physician/Clinician Focused Site category.   To win this prestigious award as we celebrate our third anniversary is a tremendous accomplishment.  Thank you to all our editors and authors who have continued to produce such engaging and fascinating educational content.  Thank you to our readers as well as we continue to strive to accomplish our mission of providing you with A Daily Dose of Medicine… Read more »

Breaking News: FDA issues new warning for Exenatide (Byetta®)

November 5, 2009

byettaKanika Ballani, Pharm.D.
Diana Hubulasvili, Pharm.D.

 Developed by Amylin Pharmaceuticals, Exenatide (Byetta®) is an incretin mimetic that is used as an adjunctive therapy with metformin, a sulfonylurea or a thiazolidinedione to improve glycemic control in type 2 diabetic patients. Mechanistically, Exenatide mimics the actions of endogenous incretin hormone, glucagon-like peptide (GLP-1), causing an increase in insulin secretion which slows gastric emptying and leads to a decrease in food intake. On November 3rd 2009, the FDA issued a safety warning on Exenatide associating it with the incidence of renal failure. This FDA warning was based on 78 postmarketing cases reported between April 2005 and October 2008. The average patient age in the case reports was 60 years. The FDA approved revisions to the drug label for exenatide due to the temporal-causal relationship that was observed with the initiation of exenatide and the occurrence of serious potential consequences of altered kidney function.1

Sixty-two of the cases reported were classified as acute renal failure and the remaining 16 cases were categorized as renal insufficiency. The postmarketing surveillance data of these cases reported that after the initiation of exenatide, hospitalization was required in 91% (71/78) of the patients. Two patients needed kidney transplantation and there were 4 fatalities. Dialysis had to be initiated in eighteen patients, of which, 2 patients had a known prior history of altered kidney function. Upon discontinuation, 39 patients reported improved signs and symptoms after the discontinuation of the drug. Recurrence in kidney dysfunction was reported in one patient who was reinitiated on exenatide.1

Forty-two patients (54%) reported symptoms associated with volume depletion, such as diarrhea, vomiting, and dehydration. These common gastrointestinal manifestations of exenatide are believed to be the risk factors for the development of altered kidney function. Weiss et al. reported the incidence of exenatide induced ischemic renal failure in 4 patients and established a temporal causal relationship between exenatide and the incidence of renal dysfunction. The induction of nausea and vomiting associated with exenatide use contributes to extracellular volume contraction, which when combined with concomitant therapy with diuretics and ACEIs, leads to an exaggerated decline in glomerular filtration rate. GLP-1 has also been proposed to cause natriuresis decreasing renal perfusion; an effect believed to be shared by exenatide as well.2,3

It must be noted that the time frame for the development of acute renal insufficiency was wide, ranging from 3 days to up to 2 years after the initiation of exenatide. Moreover, pre-existing kidney disease or risk factors for developing renal dysfunction such as- cardiac insufficiency, hypertension, pancreatitis, rhabdomyolysis, urinary tract infections and concomitant use of NSAIDs, antiretrovirals, and diuretics, were evident in 95% (74/78) of patient cases reported. It is plausible that the incidence of renal dysfunction noted in these patients could also have precipitated secondary to the independent risk factors initially present in these patients. In addition, 14 of the cases had a prior medical history of chronic kidney disease, and 4 cases with chronic renal failure, despite recommendations against the use of Byetta in these patients in the current prescribing information.1

Interestingly, Exenatide was approved as a first line agent, in conjunction with diet and exercise to improve glycemic control in type 2 diabetes mellitus on the same day this warning regarding the incidence of renal insufficiency was issued. Based on this warning, practitioners must weigh out risks and benefits before prescribing exenatide as monotherapy for the management of diabetes and exert precaution in administering it concomitantly with other nephrotoxic agents.


2. Weiss et al. Exenatide-Associated Ischemic Renal Failure. Diabetes Care. 2009;32(2):e22-23
3. Gutzwiller JP et al. Glucagon-like peptide 1 induces natriuresis in healthy subjects and in insulin-resistant obese men. J Clin Endocrinol Metab. 2004;89:3055-3061

Breaking News: Federal Advisory Panel Recommends Ban on Vicodin and Percocet

July 1, 2009

tylenolAalok Turakhia MD

In an attempt to err on the side of safety, an advisory panel to the Federal Food and Drug Administration narrowly voted yesterday to ban the popular prescription pain medications Percocet and Vicodin, in a 20-17 vote.[1 ]Both medications are a combination of a narcotic and acetaminophen, and according to the New York Times, it was a growing concern over the safety of acetaminophen that prompted the Drug Safety and Risk Management Advisory Committee to assemble in Adelphi, Maryland early this week.[2]

Acetaminophen is one of the most popular pain medications in the world [2], and though highly effective in reducing fevers and treating headaches, there has always been great concern for hepatotoxicity. In fact, between 1998 and 2003, the most common cause of acute liver injury was this medication.[3] In the United States alone, it is estimated that nearly 400 people die and 42,000 patients are hospitalized resulting from overdose.[1] Almost half of these cases are unintentional.[2]

When ingested in large quantities, acetaminophen has the ability to cause severe centrilobular hepatic necrosis. Most of the medication is metabolized by a phase II reaction, but a small percentage is converted to NAPQI, a hepatotoxic metabolite via the cytochrome P450 pathway. Gluatathione is responsible for the detoxification by binding to NAPQI and forming the harmless, water-soluble mercaptopuric acid. However, when gluatathione levels are low, or when the CYP450 pathway is induced via alcohol, or Phenobarbital, or INH, the levels of NAPQI can quickly lead to acute liver injury.[4]

The panel’s recommendations were not limited to only banning the combination medications, however. It also proposes that the FDA reduce the highest allowed dose in over-the-counter pills from 500 milligrams to 325 milligrams, and to reduce to maximum daily dosage to less than 4000 milligrams. Interestingly, the panel voted against reducing the maximum number of pills allowed in each bottle- citing concern that imposing such a limit would ultimately hurt rural and poor consumers.[1]

Tylenol’s maker, Johnson and Johnson, “strongly disagrees” with the panel, and believes that limiting access to one pain medication will “lead to more serious adverse events as consumers shift to other over-the-counter products”.[1]
Starting in the 1990’s, the FDA has sought to reduce the incidence of liver injury resulting from acetaminophen and continues to expand public knowledge about acetaminophen overdose.[2] And though there is no obligation on the part of the federal agency to agree with and accept the panel’s recommendations, it typically does.[1]

Dr. Turakhia is a 1st year resident in internal medicine at NYU Medical Center.
1. Harris, Gardiner. “Ban Is Advised on 2 Top Pills for Pain Relief.” New York Times. 30 June 2009. Newspaper on-line. Available from Accessed 1 July 2009.

2. USA Food and Drug Administration. “Joint Meeting of the Drug Safety and Risk Management Advisory Committee with the Anesthetic and Life Support Drugs Advisory Committee and the Nonprescription Drugs Advisory Committee Meeting Announcement.” Accessed 1 July 2009.

3. Larson, A.M., J. Polson, R.J. Fontana, et al., Acute Liver Failure Study Group (ALFSG), ‘‘Acetaminophen-Induced Acute Liver Failure: Results of a United States Multicenter, Prospective Study,” Hepatology 2005, Dec;42(6):1364-72.

4. Dienstag Jules L, “Chapter 299. Toxic and Drug-Induced Hepatitis” (Chapter). Fauci AS, Braunwald E, Kasper DL, Hauser SL, Longo DL, Jameson JL, Loscalzo J: Harrison’s Principles of Internal Medicine, 17th Edition:


Clinical Correlations Now Indexed in TRIP Database

May 29, 2009

logoWe are excited to formally announce a new feature of Clinical Correlations. A search box (bottom right of the page) now allows our readers to carry out a direct search of the TRIP Database.

The TRIP Database, now in its 12th year, is an excellent search engine with a focus on providing clinicians with the best available evidence to answer their clinical questions, in keeping with the mission of Clinical Correlations. The TRIP Database is continuously updated with resources that use evidence-based medicine to answer clinical questions. The site is comprehensive in coverage and searches over 250 sites including Cochrane, Agency for Healthcare Research and Quality, National Guideline Clearinghouse, Bandolier, NICE, eMedicine, JAMA, NEJM and now Clinical Correlations! The results can be filtered by a number of categories including systematic reviews, clinical guidelines, clinical questions and eTextbooks. Remarkably, the company behind TRIP has formally answered over 10,000 clinical questions over the last ten years.

To best understand the site we recommend you simply give it a try by carrying out a search. We’re sure you’ll find it to be a very useful site and we’re thrilled to be included in this venture.

-the Clinical Correlations Editors

Breaking News: Swine Flu Reaches New York

April 26, 2009

pigEunice Kang, MD

The Centers for Disease Control (CDC) has confirmed eight cases of swine influenza A (A/H1N1) virus infection in New York City, in addition to a dozen cases caused by the same strain scattered throughout California, Texas, Ohio, and Kansas. The eight confirmed cases in New York are in students who just returned from a trip to Mexico, where officials began reporting three separate outbreaks of influenza-like illness beginning March 18th. According to the New York Times there have been 81 deaths and approximately 1,300 illnesses caused by the swine flu in Mexico, the apparent epicenter of the outbreak, prompting President Felipe Calderón to announce that the government would “take all the necessary measures to deal with this epidemic.” While the swine influenza virus has been confirmed in only 20 of the 81 deaths in Mexico, many of the affected were adults who were previously healthy, an epidemiologic trait that distinguishes the swine flu virus from other flu viruses of prior pandemics.
Swine influenza virus, like other animal flu viruses, usually causes a respiratory illness confined to the animal population that serves as its source. The swine flu virus can be spread to humans who are in close contact with pig populations. Modes of human-to-human transmission are similar to those of seasonal flu viruses. Collecting a respiratory specimen and sending it to the CDC can confirm a suspected diagnosis of swine flu.
The virus that has been isolated in Mexico and the US is being described as a new subtype of A/H1N1 not previously detected in pigs or humans. While the cases in the United States have been mild with only one requiring hospitalization, the CDC earlier today declared a public health emergency over concern of a potential swine flu pandemic. Symptoms of swine flu are similar to those of seasonal flu and include fever, malaise, lethargy, cough, anorexia, and in many cases nausea, vomiting, and diarrhea. Prevention of transmission is also similar to seasonal flu. The CDC is recommending oseltamivir (Tamiflu) and zanamavir (Relenza) as treatments for the current swine flu strain given findings of resistance to amantadine and rimantadine.
The New York City Department of Health and Mental Hygiene is currently recommending routine treatment of severe flu-like illness in people associated with the Queens high school (St. Francis Preparatory School) that is at the center of the New York outbreak. Otherwise, treatment of mild cases of flu-like symptoms, in both persons affiliated with the school and the general population, should be given to individuals who are susceptible to severe illness due to an underlying condition. For updated information on the swine flu outbreak as it evolves go to

Eunice Kang is a Third Year Internal Medicine Resident at NYU Medical Center 

Picture Courtesy Wikimedia Commons

BREAKING NEWS: Another Nut that You’d Rather Not…

March 31, 2009


Commentary by Rebecca Hall MD, PGY-1

Growing concerns over Salmonella  contamination of pistachio products sold by Setton Pistachio of Terra Bella Inc in California have lead the manufacturer to voluntarily recall about a million pounds of its pistachio containing products. 1  The recall involves bulk lots o f roasted shelled pistachios and roasted inshell pistachios shipped on or after September 1st 2008. 2 Because pistachios are a component of numerous other products including many baked goods and nut mixes, many additional products may be affected and could be recalled in the near future.Already, nut containing products from Kroger, the “Georgia Nut Company” and  “Back to Nature Foods Company” have been recalled.

Multiple strains of Salmonella have been implicated.  Thus far, several illnesses in consumers which may be related to pistachio consumption have been reported but it has not yet been verified whether these illnesses have been caused by the Salmonella strains found on the implicated pistachio products.   Salmonellosis most often occurs in those most susceptible to food borne illness including the elderly, infants, and those with compromised immune systems.  Twelve to seventy two hours after exposure, persons infected with Salmonella may experience as diarrhea, fever, abdominal cramps.  It occasionally causes life-threatening diarrhea.3

Diagnosis is based on isolation of Salmonellae from stool cultures which takes a minimum of 48-72 hours. 4  However, given the lack of a rapid diagnostic test, symptomatic patients should be treated empirically with fluids and electrolyte replacement.  For mild to moderate illness, antibiotic treatment is not recommended for immunocompetent children over 12 months of age and adults.4  However, treatment with a fluroquinolone, TMP-SMX, or amoxicillin should be considered in immunocompetent patients with severe diarrhea (>9 stools/day), a high fever, or those patients requiring hospitalization.4


1.U.S. Food and Drug Administration, “Pistachio Product Recalls: Salmonella“. Updated 3/31/09.

2.U.S. Food and Drug Administration, “Recall- Firm Press Release, Setton Pistachio of Terra Bella”

3. CDC, Division of Foodborne, Bacterial and Mycotic Diseases.  “Salmonellosis.”  

4. “Approach to the patient with nontyphoidal Salmonella in a stool culture”, accessed 3/31/09.