Faculty Peer Reviewed
Fueling concern over the continued dysfunction in Washington, the Republican-led House of Representatives produced a budget on Friday that included defunding of the Affordable Care Act, commonly referred to as Obamacare. This marks the 42nd attempt to repeal Obamacare and will almost certainly be rejected by the Democratic-led Senate, risking a government shut down on Sept. 30th if a budget is not ratified. This political folly in Washington stands in juxtaposition to the admirable example set earlier last week when several government agencies worked in concert to handle and contain the frightful shooting at the Washington Navy Yard. On a lighter note, this past week also included the launch of a new iphone, twitter announcing its initial public offering, Tesla motors entering the race to build a self-driving car, and the excitement of one of the most entertaining baseball wild card races in recent memory (it seems that the MLB got it right when they expanded the wild card from one to two teams per league). In medical news, this week’s journal review includes significant updates related to cardiac catheterization and screening for colon and lung cancer.
The New England Journal of Medicine published the Preventive Angioplasty in Acute Myocardial Infarction (PRAMI) trial, which was a single-blind, randomized study designed to evaluate the benefit of preventative intervention on noninfarct arteries in patients with acute ST-segment elevation myocardial infarction (STEMI).  The trial was limited to patients with STEMI to more easily distinguish the infarct artery (often occluded) from noninfarct coronary arteries (a task which can be difficult in non-STEMI patients). Included in the study were patients of any age with at least 50% stenosis in one or more noninfarct artery deemed amenable to intervention. Exclusion criteria included cardiogenic shock, meeting indications for CABG, or if the noninfarct stenosis was a chronic total occlusion. The authors state that chronic total occlusions were excluded due low success with percutaneous coronary intervention (PCI) in such cases. The primary endpoint was a composite of cardiac death, nonfatal myocardial infarction, or refractory angina. This 465 patient study was stopped early by the data and safety monitoring committee after a mean follow-up period of 23 months. In terms of the primary outcome, there were 9 events per 100 patients in the preventative PCI group vs 23 events per 100 patients in the group without preventative PCI (HR 0.35; 95% CI 0.21-0.58, P<0.001). The risk reduction was evident within 6 months post-PCI by Kaplan-Meier analysis and was maintained thereafter. These findings stand to challenge the current guidelines on STEMI management, which recommend PCI to only the infarct artery in the acute setting regardless of multivessel disease. Future directions for preventative PCI include immediate vs staged PCI, application to non-STEMI patients, and inclusion of fractional flow reserve in the decision model.
The next note-worthy study comes from JAMA and, similar to the PRAMI trial, looked to challenge the status quo. Currently for cases of severe alcoholic hepatitis (defined as a Maddrey discriminant function of 32 or above), guidelines recommend the use of corticosteroids or pentoxyfylline, as each has been shown to improve short-term outcomes.[2, 3] A randomized, double-blind clinical trial published this week by Mathurin et al. was designed to compare 28 day treatment of prednisolone + pentoxifylline vs prednisolone alone.  The study was mainly conducted in France and consisted of 270 patients (age 18 to 70) with severe biopsy-proven alcoholic hepatitis. At 6 months, there was no significant difference in survival between the two groups (69.9% [combination] vs 69.2% [pred alone], P = 0.91). There was also no significant difference found in the incidence of hepatorenal syndrome (8.4% vs 15.3%, P = 0.07), though it must be noted that the study was not adequately powered for this secondary end point. Based on the results of this study, the combined use of prednisolone and pentoxifylline to treat severe alcoholic hepatitis would not be supported.
In the first of the two important screening studies this week, the New England Journal of Medicine included a paper that sought to quantify the benefit of lower endoscopy (colonoscopy and flexible sigmoidoscopy) in relation to colorectal cancer incidence and mortality.  The authors acknowledge that lower endoscopy is widely endorsed amongst experts, but the magnitude of the benefit remains unknown, particularly for cancer of the proximal colon. The study included 88,902 people from two large U.S. cohorts (taken from the Nurses’ Health Study and the Health Professionals Follow-up Study) followed prospectively over a 22-year period. When compared with no endoscopy for the risk of developing colorectal cancer, multivariate analysis showed a negative colonoscopy had the greatest benefit (multivariate HR 0.44), followed by a negative sigmoidoscopy (multivariate HR 0.60). The results were also broken down by distal vs proximal colorectal cancer; both types of lower endoscopy were associated with a statistically significant reduction in the incidence of distal cancer (HR 0.24 for negative colonoscopy, HR 0.44 for negative sigmoidoscopy), however only colonoscopy was significantly associated with a reduced incidence of proximal cancer (HR 0.73). Mortality from colorectal cancer showed the same pattern with both types of lower endoscopy reducing mortality compared to no endoscopy in distal cancer but only colonoscopy reducing mortality from proximal cancer. Of note, the findings related to sigmoidoscopy appear to conflict with the results from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial in which a 14% reduction in proximal colorectal cancer was noted. The current authors postulate that the reduced incidence was likely explained by the 21.9% of sigmoidoscopy patients that also underwent colonoscopy.
The second study from this week involving a screening modality, published in Annals of Internal Medicine, was a systematic review of low-dose computed tomography (LDCT) for lung cancer screening.  This review is intended to update the U.S. Preventive Services Task Force (USPSTF) judgment from 2004 when the evidence for lung cancer screening was deemed insufficient.  Studies were chosen for inclusion based on predefined USPSTF criteria including study size, quality, consistency of results, and directness of evidence. The analysis yielded four trials; one was a large, high quality trial and the three others were small European trials. The high quality trial was the National Lung Screening trial, in which 26,722 people at high risk for lung cancer underwent three annual screenings with LDCT at 33 U.S. medical centers. The trial found a 20% reduction in lung cancer mortality (95% CI 6.8% to 26.7%) and a 6.7% reduction in all-cause mortality (95% CI 1.2% to 13.6%). On the other hand, the three small European trials showed no benefit from screening, though the authors note that these trials were underpowered and of insufficient duration. Overall, there appears to be strong evidence for LDCT screening reducing mortality. However, the USPSTF will have to take into account the potential harm from radiation exposure, false-positives, and incidental findings in a population where the number needed to screen (NNS) was 219 to prevent 1 death.
Other studies worth noting:
In JAMA, Dantes et al. looked at the national incidence of invasive MRSA infections.  The study showed that from 2005 to 2011, the estimated incidence of health care–associated community-onset MRSA infections decreased by 27.7% and hospital-onset infections decreased by 54.2%. Less impressively, there was only a 5.0% decrease in community-associated infections. These findings highlight the efficacy of measures to reduce MRSA infections in the acute care setting and bring attention to the need for new strategies to help reduce community-associated infections.
Also in JAMA, Lalani et al. found that in patients with prosthetic valve endocarditis, early valve replacement (median time from admission to surgery was 8 days) did not improve mortality compared to medical therapy in the overall cohort.  The authors note that further studies are needed in the subgroup of patients with specific indications for surgery to evaluate the potential benefit of early surgery in such a population.
Dr. Gabriel Schneider, Internal Medicine, NYU Langone Medical Center
Peer Reviewed by Brian Greet, associate editor, Clinical Correlations
Image courtesy of Wikimedia Commons
1. Wald, D.S., et al., Randomized Trial of Preventive Angioplasty in Myocardial Infarction. New England Journal of Medicine, 2013. 369(12): p. 1115-1123. http://www.nejm.org/doi/full/10.1056/NEJMoa1305520
2. Carithers, R.L., Jr., et al., Methylprednisolone therapy in patients with severe alcoholic hepatitis. A randomized multicenter trial. Ann Intern Med, 1989. 110(9): p. 685-90. http://www.ncbi.nlm.nih.gov/pubmed/2648927
3. Akriviadis, E., et al., Pentoxifylline improves short-term survival in severe acute alcoholic hepatitis: a double-blind, placebo-controlled trial. Gastroenterology, 2000. 119(6): p. 1637-48.
4. Mathurin, P., et al., Prednisolone with vs without pentoxifylline and survival of patients with severe alcoholic hepatitis: A randomized clinical trial. JAMA, 2013. 310(10): p. 1033-1041. http://jama.jamanetwork.com/article.aspx?articleid=1737041
5. Nishihara, R., et al., Long-Term Colorectal-Cancer Incidence and Mortality after Lower Endoscopy. New England Journal of Medicine, 2013. 369(12): p. 1095-1105. http://www.nejm.org/doi/full/10.1056/NEJMoa1301969
6. Schoen, R.E., et al., Colorectal-cancer incidence and mortality with screening flexible sigmoidoscopy. N Engl J Med, 2012. 366(25): p. 2345-57. http://www.nejm.org/doi/full/10.1056/NEJMoa1114635
7. Humphrey, L.L., et al., Screening for lung cancer with low-dose computed tomography: a systematic review to update the u.s. Preventive services task force recommendation. Ann Intern Med, 2013. 159(6): p. 411-20. http://annals.org/article.aspx?articleid=1721248
8. Force, U.S.P.S.T., Lung cancer screening: recommendation statement. Ann Intern Med, 2004. 140(9): p. 738-9. http://www.uspreventiveservicestaskforce.org/3rduspstf/lungcancer/lungcanrs.htm
9. National Lung Screening Trial Research, T., et al., Reduced lung-cancer mortality with low-dose computed tomographic screening. N Engl J Med, 2011. 365(5): p. 395-409. http://www.ncbi.nlm.nih.gov/pubmed/21714641
10. Dantes, R., et al., NAtional burden of invasive methicillin-resistant staphylococcus aureus infections, united states, 2011. JAMA Internal Medicine, 2013: p. -. http://archinte.jamanetwork.com/article.aspx?articleID=1738718
11. Lalani, T., et al., IN-hospital and 1-year mortality in patients undergoing early surgery for prosthetic valve endocarditis. JAMA Internal Medicine, 2013. 173(16): p. 1495-1504. http://archinte.jamanetwork.com/article.aspx?articleid=1713509