Primecuts – This Week In The Journals

September 27, 2010

Lisa Parikh, MD

Faculty Peer Reviewed

This past week, genetics was the theme of the week.  Genetically engineered salmon hit the headlines on several newspapers and magazines such as the New York Times and Time. The so called “AquAdvantage” (or Frankenfish) contains a growth hormone gene from a Pacific salmon species and a gene promoter from the ocean pout, an eel-like fish, that cause it to grow at a rate twice as fast as normal salmon. [1,2] The maker of AquAdvantage, AquaBounty, claims that their research has shown that their product is not harmful to consumers and is safe for the environment.[1] If approved, AquAdvantage would be the first genetically engineered animal available in supermarkets.  However, the major debate right now is whether or not the FDA should approve labeling of the product as genetically engineered. Currently, the FDA cites that it cannot label a food as such unless it is materially or nutritionally different from real salmon.[1] The FDA has determined that this product is not different—not even in taste.

 For years, the American consumer has unknowingly been buying genetically engineered products.  Several foods such as strawberries, corn, and soybeans have been genetically altered and unlabeled in grocery stores for many years. Labeling may adversely affect the market for these foods, but is the economic benefits these products provide more important than consumer awareness?

Another genetics-related ethical debate that has recently been rehashed in the news is the potential benefits of genetic testing. The New England Journal of Medicine reported the potential risks of an over-the-counter genetic testing kit, a product which was announced this year by Pathway Genomics and Walgreens. The plan was to stock Walgreen’s shelves with the kit in May of this year, but was quickly halted when the FDA sent a letter to Pathway Genomics stating that the device may require FDA approval.  The agency is concerned about analytic and clinical validity of such a test to prevent the potential harm to consumers and health care system from inaccurate test results.[3] So far, many of the health conditions that such kits screen for do not have either a well understood natural history or a proven treatment. Annes et al raised the exemplary issue of a young man who tested positive for a genetic test indicating he has an increased risk of developing prostate cancer. With no signs, symptoms, and family history what would be the next logical step in managing such a patient? Possibilities include obtaining a PSA, ultrasound or biopsy, but we have no established course of action for such situations.[3] As genetic testing kits increase the number of conditions they test for, they provide consumers with the opportunity to learn more about their health care risks.  However, the emotional and economic burden that comes with this knowledge may or may not outweigh the benefits.

 The necessity of screening for prostate cancer in healthy patients was an issue also addressed by the British Medical Journal this week.  Djulbegovic et al conducted a meta-analysis involving six studies to determine if screening for prostate cancer has an effect on overall and disease specific mortality. Screening was conducted using prostate-specific antigen, with or without a digital rectal exam.  The group found that although screening caused an increased diagnosis of patients with stage I prostate cancer, screening had no significant relationship with overall mortality and prostate cancer specific mortality.  They found no significant effect of screening on the diagnosis of stage II and stage III prostate cancer. [4] The USPSTF currently cites that there is insufficient evidence to make a recommendation as to whether or not to screen men ages 75 and younger for prostate cancer. It recommends not screening for prostate cancer in men ages 75 and older. [5] Data on age was limited in many of the studies used in this analysis. Therefore, association of these results with the USPSTF guidelines is somewhat limited. However, the study does again raise the ethical issues associated with screening and early diagnosis of prostate cancer. An increased number of diagnosed patients leads to more patients seeking treatment. If more patients seek treatment for a disease for which they possess no signs or symptoms, the chances of iatrogenic harm and to patients may increase. The impact on quality of life is also an issue that should be explored further.

 Screening for subclinical hypothyroidism has also been a topic of controversy recently, as the condition has been associated with hypercholesterolemia and atherosclerosis.  This week,s JAMA included a meta-analysis that reported the association between subclinical hypothyroidism and the risk of coronary heart disease (CHD) and mortality.  Although studies to determine the same relationship have been undertaken in the past, results have been conflicting. [6]  In order to prevent heterogeneity amongst the study group and methods, the authors used a common definition of subclinical hypothyroidism (serum TSH levels between 4.5 mIU/L and 20 mIU/L and a normal T4 concentration) and CHD. Results showed that subclinical hypothyroidism is associated with an increased risk of CHD. Risk is significantly elevated in adults with a TSH greater than or equal to 10 mIU/L.  Adults with minimally elevated TSH were not associated with an increased risk of CHD events or CHD mortality.  Also, age was not correlated with the impact of an increasing TSH level on CHD events.[6]  Results of this study could provide a TSH cut-off for when to treat subclinical hypothyroidism.  However, further studies of subclinical hypothyroidism should be conducted to show the impact that thyroxine replacement at various TSH levels has on CHD.

 Archives of Internal Medicine this week reported that the use of NSAIDs increases the risk for chronic atrial fibrillation (AF). 1035 chronic AF patients and 525 paroxysmal AF patients on varying doses and duration of NSAIDs were included in a study. Results showed a 44% increased risk with the use of NSAIDs.[7] Risk was not found to be associated with dosing of treatment, but did disappear with discontinuation of treatment.  NSAID treatment of more than one year was associated with an increased risk of paroxysmal AF.[7] As for the mechanism of such a relationship, authors argue that it is not actually the NSAIDs themselves that cause AF, but rather an underlying inflammatory condition. They state that atrial fibrosis, the most common pathoanatomical change found in AF patients, may be caused by underlying inflammatory conditions, such as cardiac sarcoidosis and autoimmune disorders.  These inflammatory conditions prompt the use of NSAIDs and may cause AF.  The authors suggest that any condition causing systemic inflammation, such as autoimmune disorders, is an independent risk factor for AF.[7]  A better understanding of this causal relationship is still necessary.  However, with these findings, physicians should recommend NSAID use at any dose with caution.

 A significant risk factor associated with medication was also reported by the British Journal of Medicine this week. A study by Parker et al found that antipsychotics are associated with an increased risk of venous thromboembolism (VTE). The study took 31,612 newly diagnosed cases of VTE and matched them with 125,559 controls. Antipsychotic usage by both groups in the past 24 months was determined. Results showed a 32% increased risk of VTE for patients prescribed an antipsychotic in the past 24 months. The risk increased to 56% for individuals with any antipsychotic usage in the past 3 months, and 97% for individuals who were newly started on an antipsychotic in the pas three months.[8] Risk was higher for atypical antipsychotics than conventional drugs and greater with low potency rather than high potency drugs. Interestingly, most patients with antipsychotic usage enrolled in this study were using the drugs for conditions such as nausea, vomiting, and vertigo. Also, patients in the case group had a higher usage of drugs that increase risk for VTE (such as OCPs, hormone replacement therapy) than the control group.[8]  In a clinical setting, it is often easy to overlook several common risk factors for VTE that many patients possess, such as BMI, smoking, and concurrent drug use.  Perhaps for patients with an existing increased risk for VTE, physicians should consider an alternate therapy for symptoms like nausea and vomiting.

Dr. Parikh is a 1st year resident at NYU Langone Medical Center

Judith Brenner, MD is an associate editor, Clinical Correlations

Image courtesy of Wikimedia Commons

References:

1. Melnick, Meredith. “‘Frankenfish’ May Soon Be Spawning: Is Genetically Modified Salmon Safe?” Time 19 Sept. 2010. Web.  http://healthland.time.com/2010/09/19/frankenfish-may-soon-be-spawning-is-genetically-modified-salmon-safe/

 2. Pollack, Andrew. “Panel Leans in Favor of Engineered Salmon.” The New York Times 21 Sept. 2010, Business sec.: 3. Print.  http://www.nytimes.com/2010/09/21/business/energy-environment/21salmon.html

 3. Annes, Justin P., Monica A. Giovanni, and Michael F. Murray. “Risk of Presymptomatic Direct-to-Consumer Genetic Testing.” The New England Journal of Medicine 363 (2010): 1100-101. Print.  http://www.nejm.org/doi/full/10.1056/NEJMp1006029

 4. Djulbegovic, Mia, Rebecca J. Beyth, and Molly M. Neuberger. “Screening for Prostate Cancer: Systematic Review and Meta-analysis of Randomised Control Trials.” British Medical Journal 341 (2010). Print.  http://www.bmj.com/content/341/bmj.c4543.full

 5. “Screening: Prostate Cancer.” U.S. Preventive Services Task Force. Aug. 2008. Web. 26 Sept. 2010. http://www.uspreventiveservicestaskforce.org/uspstf/uspsprca.htm

 6. Rodandi, Nicolas, Wendy P.J. Den Elzen, and Douglas C. Bauer. “Subclinical Hypothyroidism and the Risk of Coronary Heart Disease and Mortality.” JAMA 304.12 (2010): 1365-374. Print.  http://jama.ama-assn.org/cgi/content/abstract/304/12/1365

 7. De Caterina, Raffaele, Ana Ruigómez, and Luís Alberto García Rodríguez. “Long-term Use of Anti-inflammatory Drugs and Risk of Atrial Fibrillation.” Archives of Internal Medicine 170.16 (2010): 1450-455. Print.  http://archinte.ama-assn.org/cgi/content/abstract/170/16/1450

 8. Parker, Chris, Carol Coupland, and Julia Hippisley-Cox. “Antipsychotic Drugs and Risk of Venous Thromboembolism: Nested Case-control Study.” British Medical Journal 341 (2010). Print.  http://www.bmj.com/content/341/bmj.c4245.full

One Response to Primecuts – This Week In The Journals

  1. [...] Last week in Primecuts, we read about the controversies surrounding screening for prostate cancer. This week, the Annals re-explored the idea of screening for testicular cancer [2].  The authors were searching for new evidence to update the 2004 United States Preventive Services Task Force guidelines that recommended against it (grade D).  Articles that were to be included in this analysis were new high evidence articles, i.e. randomized controlled trials, meta-analyses, sytematic reviews etc.  Unfortunately, none of the identified new studies met all inclusion criteria.  From the three articles that were reviewed  the authors did not find any new direct evidence of harm from screening, but their conclusion was to continue the current guidelines recommending against screening. Interestingly,  the authors did note a correlation between testicular cancer and both testicular microlithiasis and XIST gene methylation. Both of these factors were explored only in symptomatic patients and therefore this is hypothesis generating rather than conclusive evidence that these could be markers of eventual cancer. You can actually comment on the screening guidelines here; I’m agreeing with the USPSTF on this one. [...]

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