Primecuts – This Week In The Journals

May 23, 2011

By Vincent Santillo, MD

Faculty Peer Reviewed

The press and the public that devours it thrive on exciting headlines of misfortune and misdeeds. After a week filled with powerful men acting terribly, it was a relief to see the big new positive news stories — “Paralyzed now walk” and “Coffee Protects from Cancer”. Bring on the caffeine and science fiction as we take a look at some of the more interesting articles appearing this week. The New York Times excitedly announces that “a paralyzed man stands” as it discusses the results of a unique experiment presented in this week’s Lancet. The New York Times is also the source of our second article in which the name of the researchers’ institution figures prominently in the headline, one would suppose to lend weight to the promise that coffee prevents prostate cancer. Another topic always being magnified in all media is obesity, and we discuss a study from the Annals of Internal Medicine which shows that among the elderly the mortality risk may not be as great as one would assume and that it may be future disability that we may be preventing by encouraging weight loss. Lastly we have two studies on proton pump inhibitors – once which seems to give some hope to those wanting to avoid gastric surgery for GERD and another which hints at a new cardiac risk in PPIs via their impact on aspirin absorption.

The health section of the New York Times captivated readers with news that an “Electrode experiment shows promise as a paralyzed man stands”. The authors were relating the results of a case report published this week in The Lancet [1] that presented the case of a 23-year-old man who, having been made paraplegic from a motor vehicle accident in 2006 was able to achieve weight-bearing status. The authors hypothesized that tonic epidural spinal cord stimulation could modulate spinal circuitry that would enable sensory input from standing and stepping movements to serve as a source of neural control to undertake these tasks. The patient had no contraction of trunk of leg muscles after his accident and at the time of implantation of the study’s electrodes, 3.4 years after he was struck by a motor vehicle, the patient was “unable to stand or walk independently or to voluntarily move his legs despite standard-of-care rehabilitation and additional intensive locomotor training.” The 16-electrode array was implanted at T11-L1. After epidural stimulation of the caudal segments (L5-S1) of the spinal cord was combined with sensory information related to bilateral extension and loading the patient was able to generate standing without any assistance on his first attempt with 65% bodyweight support, which was progressively reduced to full weight bearing. In addition to the ability to bear weight, the patient has also seen functional gains in bladder and sexual function as well as temperature regulation. The key problem with the study is that it is an experimental situation with one subject and may not be generalizable. However, it provides valuable information and researchers will be able to use their methods and findings to provide hope where there has been only hopelessness.

Under the very impressive headline “Prevention: Coffee Lowers Risk of Prostate Cancer, Harvard Study Says”, The New York Times presented the results of a study published online in The Journal of the National Cancer Institute that described a “strong inverse association between coffee consumption and risk of lethal prostate cancer.” [2]  The data was taken from baseline food frequency questionnaires filled out by 47,911 men in the Health Professionals Follow-up Study. Participants were asked to recall their consumption of various food items over the prior year. This kind of data collection is rife with recall bias. The recall bias may be tempered in this case by the habitual and ritualized use of coffee by most users. In this study, heavy coffee drinkers (>=6 cups/d) had less than half the risk for lethal and advanced prostate cancers as nondrinkers. Confounding provides little explanation as heavy coffee users were also smokers and sedentary, both of which may increase the risk for advanced prostate cancer. The authors present several hypothetical ways in which coffee may modify the course of prostate cancer, however data is limited. While the study is intriguing and may provide worthy avenues for further investigation, it would be premature to encourage increased coffee consumption as a prostate cancer preventative measure.

In this week’s Annals of Internal Medicine [3] a cohort study was published that showed that obesity is not necessarily associated with a higher risk for premature death. In fact, as the article points out, there have been safety concerns surrounding weight control in elderly persons. The authors relied on the secondary analysis of data from the Medicare Current Beneficiary Survey collected from 1994 to 2000 and linked to Medicare enrollment files through 2008. Their analysis showed that “compared with respondents with a BMI of 22.0 to 24.9 kg/m^2, those with a higher BMI did not have a higher hazard for death, except for those with a BMI of 35 kg/m^2 or greater.” There was some racial disparity in the data as a higher BMI did not confer an increased mortality risk for African American men. Outside of mortality, the study also attempted to quantify the impact of obesity on functional decline. The authors evaluated participants at baseline and annually for two years and “asked whether they had any difficulty performing 6 activities of daily living (ADLs) (bathing or showering, dressing, eating, getting in and out of chairs, walking, and toileting) and 6 instrumental activities of daily living (IADLs) (using the telephone, doing light housework, doing heavy housework, making meals, shopping, and managing money).” The authors found that increasing BMI was “significantly associated with the presence of both ADL and IADL disability at baseline.” While the impact on mortality may be minimal, BMI, even just slightly above normal, was “associated with new or progressive ADL and IADL disability in a dose dependent manner in both men and women.” While the mortality benefit of weight control may be tempered in older populations, there appears to be a mortality benefit of having a BMI <35. As well, a reduced BMI may help to reduce the risk of further functional decline.

This week JAMA published the results of the LOTUS (Long-Term Usage of Esomeprazole vs Surgery for Treatment of Chronic GERD) randomized clinical trial to evaluate the role of continued optimized PPI therapy vs standardized laparoscopic antireflux surgery (LARS) in patients with GERD.[4]  In order to participate in the study, a 3 month run-in period was required to confirm clinical response to esomeprazole 40mg/d. After that, participants were randomized to either undergo LARS or to receive esomeprazole (initially at 20mg/d). At 5 years, most participants in both groups were in remission; in the LARS group 85% remained in remission (sufficient control without PPI therapy) as compared to 92% in the esomeprazole group (sufficient control without esomeprazole greater than 20mg po bid). The authors state that “this study is not designed as a superiority or equivalence trial”. However, on multiple occasions they refer to remission being achieved using either LARS or esomeprazole as if they are equivalent therapies. It is important to keep in mind that while there was no surgical mortality associated with LARS in this study, there were 33 treatment failures in that group (29 patients required other treatment to control reflux symptoms, 1 needed more than 1 dilatation, a 3 had postfundoplication adverse events including 1 gastric perforation and 2 with severe flatulence, bloating, and diarrhea). It is important to remember that all of these surgical issues are being experienced by patients whose symptoms were controlled on esomeprazole alone after their 3 month run-in. In fact, most of the treatment failures in the LARS group found their symptoms controlled with the addition of acid suppressive drugs. While chronic PPI usage has been associated with cardiac events and bone fractures, this study does not make a strong enough case to give a clinician certain guidance on LARS vs long-term PPI therapy. While awaiting further data, the prudent path may be to continue medical management until the patient is refractory before considering LARS.

The issue of chronic PPI therapy has received a lot of press and research attention vis-à-vis the interactions between PPIs and clopidogrel. However, as an article published online by BMJ this week showed, PPIs may also impact the effectiveness of aspirin. [5]  In a manner similar to its effect on clopidogrel, the use of PPIs may increase the gastric pH above the pKa of acetylsalicylic acid which leads to reduced lipophilicity and reduced absorption of the drug. In this retrospective study, 19,925 Danish patients treated with aspirin-only after a first myocardial infarction were followed for one year. During the study period 17% of the aspirin treated patients had a recurrent MI, stroke or CV death (the study’s combined endpoint). The hazard ratio for the combined end point in patients receiving proton pump inhibitors was 1.46 (p<0.001). The authors raise the intriguing question as to whether the “putative interaction between clopidogrel and proton pump inhibitors may be explained, at least in part, by an interaction between aspirin and proton pump inhibitors, as virtually all patients treated with clopidogrel also receive aspirin.” While PPIs are widely used for the prevention of peptic ulcer disease in patients on chronic aspirin therapy, data being gathered on their impact on the efficacy of clopidogrel and, per this new study, aspirin may lead to reconsidering such broad use. Randomized prospective studies are needed to improve clinical decision making.

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

Peer reviewed by Michael Poles, section editor, Clinical Correlations

Image Courtesy of Wikimedia Commons

References:

[1]    Harkema, Susan et al. Effect of epidural stimulation of the lumbosacral spinal cord on voluntary movement, standing, and assisted stepping after motor complete paraplegia: a case study. Lancet. Published online May 20, 2011. http://http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(11)60547-3/fulltext

[2]   Wilson, Kathryn et al. Coffee consumption and prostate cancer risk and progression in the Health Professionals Follow-up Study. J Natl Cancer Inst. 2011;103:1-9. http://jnci.oxfordjournals.org/content/early/2011/05/17/jnci.djr151.abstract

[3]    Wee, Christina et al. Obesity, race, and risk of death or functional decline among Medicare beneficiaries. Ann Intern Med. 2011;154:645-55. http://www.annals.org/content/154/10/645.abstract?aimhp

[4]   Galmiche, Jean-Paul et al. Laparoscopic antireflux surgery vs esomeprazole treatment for chronic GERD. JAMA. 2011;305:1969-77. http://jama.ama-assn.org/content/305/19/1969.short

[5]    Charlot, Mette et al. Proton pump inhibitor use and risk of adverse cardiovascular events in aspirin treated patients with first time myocardial infarction: nationwide propensity score matched study. BMJ. Published online May 2011. http://www.bmj.com/content/342/bmj.d2690.abstract

 

 

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