By Sherif Shoucri, MD
Faculty Peer Reviewed
Extra! Extra! National Parks Reopen! In fact, so did the rest of the federal government, after an 11th hour budget deal brokered by Senate leaders extended federal borrowing powers for three months and reopened Uncle Sam’s doors for business. The House of Representatives quickly passed “big-brother’s” bill and the US narrowly averted a financial default with global economic repercussions. What is the price tag of a 16 day government shutdown? Experts are estimating this will cost the economy upwards of $3 billion dollars, which is to be expected from a governing body that’s currently just a shade less popular than cockroaches (according to Public Policy Polling). On that optimistic note, this week in the journals, there were a number of fascinating articles to be discussed.
This week, the New England Journal of Medicine published a randomized trial of colchicine for acute pericarditis [1]. While colchicine is an effective and studied treatment in recurrent pericarditis [2], there is inconclusive data regarding its role in acute pericarditis. In this multicenter, double-blinded study, eligible adults were randomly assigned to receive colchicine (at 1mg or 0.5mg daily based on patient weight) or placebo in addition to standard anti-inflammatory therapy with either aspirin or ibuprofen. A total of 240 patients were enrolled with 120 in each treatment group. The primary outcome of the study was rate of recurrent or incessant pericarditis, with recurrent defined as a second episode > 6 weeks after initial therapy and incessant as a second episode < 6weeks after initial presentation.
Acute pericarditis was diagnosed in patients with two of the following criteria; typical chest pain (sharp, pleuritic, relieved with leaning forward or sitting up), a pericardial friction rub, new or worsening pericardial effusion, or EKG changes of either diffuse ST elevation or PR depression.
The primary outcome of recurrent or incessant pericarditis occurred in 20 (16.7%) patients in the colchicine group and 45 (37.5%) in the placebo group (RRR 0.56; 95% CI 0.30-0.72, P<0.001). This translates to a number needed to treat of 4, which is indicative of a meaningful and effective clinical intervention. Colchicine also reduced the symptom rate at 72 hours compared to placebo (19% vs 40%, P=0.001). The recurrence rate in the colchicine group was 9.2%, and 20.8% in the placebo group (RRR 0.56, 95% CI 0.13-0.99; P=0.02). The number needed to treat to prevent one episode of recurrent pericarditis was 9.
It remains unclear exactly why colchicine, which disrupts microtubules and concentrates within neutrophils, is effective in acute pericarditis. In developed countries acute pericarditis is commonly caused by viral syndromes, thus it remains to be seen if disrupting white-cell function with colchicine has adverse effects with regards to immune response. For now, however, this study presents compelling evidence for using colchicine in acute pericarditis.
Published in JAMA, a randomized trial in 20 medical and surgical ICUs in U.S. hospitals assessed whether wearing gloves and gowns for all patient contact decreased the acquisition of antibiotic resistant bacteria [3] compared to standard CDC precautions. A total of 26,180 patients were included, and the primary outcome for this study was patient acquisition of MRSA or VRE based on surveillance cultures taken on admission and discharge from the ICU.
ICUs in the intervention group experienced a decrease in the primary outcome of MRSA or VRE from 21.35 acquisitions per 1000 patient-days at baseline to 16.91. Control ICUs had a decrease in MRSA or VRE from 19.02 at baseline to 16.29. This difference, however, was not statistically significant (P=0.57). As a secondary outcome, MRSA acquisition rates when assessed alone did show a statistically significant decrease in intervention ICUs compared to control. Perhaps not surprisingly, there was also a decrease in the mean number of health-care worker patient visits per hour in intervention ICUs compared to control. These results did not show a significant benefit to wearing gloves and gowns for all ICU patient interactions with regards to the primary endpoint, and the decrease in MRSA acquisition will need to be further studied especially given the rising frequency, and associated costs of these infections. Although it is encouraging, any patient benefit incurred by decreasing the rate of MRSA acquisition will have to be compared to the effects of decreasing the frequency of health-care provider interactions.
Also in JAMA this week, a randomized clinical trial evaluated quality of life after PCI vs CABG among patients with diabetes and stable multivessel coronary artery disease [4]. This study is a follow up to the FREEDOM trial [5], which demonstrated that among patients with diabetes and multivessel coronary artery disease CABG was associated with lower mortality and rate of MI, although higher rate of stroke when compared to PCI.
Investigators used the well-validated Seattle Angina Questionnaire (SAQ) as well as the Rose Dyspnea Scale to assess health status before and after randomization to CABG or PCI in a total of 1900 patients. Using an intention-to-treat analysis, at two year follow up there was a small but statistically significant benefit to CABG over PCI with regard to angina frequency, physical limitations, and quality of life domains of the SAQ. This significant difference was only present on subgroup analysis, in patients with intermediate level symptoms. Beyond two years, however, the two study groups had essentially similar patient-reported outcomes. While this study shows that there may be a small quality of life benefit afforded by CABG over PCI initially in some subgroups, beyond two years there were no consistent differences between the two strategies. In addition, this study was limited though by a lack of long-term follow up in over 40 patients in each study group after the 4 year mark. A thorough review of the benefits and risks of each procedure with patients is imperative before selecting a revascularization strategy, as personal goals and expectations should be acknowledged before choosing CABG or PCI.
Lastly, a systematic review and meta-analysis of lifestyle interventions for patients with, and at risk for type 2 diabetes can be found in this week’s Annals of Internal Medicine. Based on current literature, the effectiveness of lifestyle interventions on slowing progression to diabetes in high-risk patients, and in those patients with type 2 diabetes, preventing clinical outcomes including overall mortality, is unclear.
The authors reviewed nine randomized, controlled studies of lifestyle interventions in at risk patients for diabetes as well as eleven randomized, controlled studies of patients with diabetes [6]. The authors determined that there is sufficient evidence to suggest that comprehensive lifestyle interventions can decrease the incidence type 2 diabetes in at-risk patients. This effect was long lasting, up to 10 years following the intervention period. In patients with type 2 diabetes, there appears to be no evidence that lifestyle changes reduce all-cause mortality, and insufficient evidence to show a benefit on cardiovascular or microvascular outcomes as well, although many studies included relied on surrogate markers (such as lipid profile and blood pressure) to draw this conclusion. In addition, there was a considerable amount of heterogeneity among studies included with regard to baseline risk factors for diabetes mellitus, and the lifestyle interventions made. Nevertheless, in anything, this meta-analysis reaffirms the importance of lifestyle changes in patients at increased risk for type 2 diabetes.
Other notable articles worth checking out this week:
In the NEJM, Von Hoff et al. showed an increased survival on pancreatic cancer in patients receiving nab-paclitaxel plus gemcitabine [7]. This multicenter, open-label, randomized trial showed a median overall survival of 8.5 months in patients receiving nab-paclitaxel plus gemcitabine compared to 6.7 months in the gemcitabine group (hazard ratio for death, 0.72; P<0.001). Unfortunately, this two-month survival benefit did not come without cost; the paclitaxel group exhibited significantly more myelosuppression and peripheral neuropathy.
In the British Medical Journal a population based cohort study demonstrated a risk of moderate to advanced kidney disease in patients with psoriasis [8] compared to patients without psoriasis, independent of traditional risk factors. This was especially true in patients with moderate to severe psoriasis.
In Lancet online, cognitive behavior therapy was found to be cost-effective and successful in treating health anxiety in medical patients [9].
Finally in upcoming medical news, the results from an initial Phase 3 trial of alirocumab—a PCSK9 inhibitor—illustrated an average drop in LDL of 47.2% with no significant adverse effects. Stay tuned for their full publication in the coming weeks.
Dr. Sherif Shoucri is a 1st year resident at NYU Langone Medical Center
Peer reviewed by Greg Schrank, MD, Contributing Editor, Clinical Correlations
Image courtesy of Wikimedia Commons
References:
1. Imazio et al. A Randomized Trial of Colchicine for Acute Pericarditis. N Engl J Med. 2013 Oct 17:369(16): 1522-8. Epub 2013 Aug 31. http://www.nejm.org/doi/full/10.1056/NEJMoa1208536
2. Imazio et al. Colchicine as First-choice therapy for recurrent pericarditis: results of the CORE trial. Arch Intern Med. 2005;165:1987-91 http://archinte.jamanetwork.com/article.aspx?articleid=486705
3. Harris et al. Universal Gown and Glove Use and the Acquisition of Antibiotic -Resistant Bacteria in the ICU. JAMA. 2013;310(15):1571-1580 http://jama.jamanetwork.com/article.aspx?articleid=1752753
4. Abdallah et al. Quality of Life After PCI vs CABG Among Patients with Diabetes and Multivessel Coronary Artery Disease. JAMA. 2013;310(15):1581-1590. http://jama.jamanetwork.com/article.aspx?articleid=1752756
5. Farkouh et al. FREEDOM Trial Investigators. Strategies for multivessel revascularization in patients with diabetes. N Engl J Med. 2012;367(25):2375-2384. http://www.nejm.org/doi/full/10.1056/NEJMoa1211585
6. Schellenberg eg al. Lifestyle Interventions for Patients With and at Risk for Type 2 Diabetes: A systematic review and meta-analysis. Ann Intern Med. 2013;159(8):543-551. http://annals.org/article.aspx?articleid=1748845
7. Von Hoff et al. Increased Survival in Pancreatic Cancer with nab-Paclitaxel Plus Gemcitabine. New Engl J Med. 2013 Oct 16: E-publication ahead of print. http://www.nejm.org/doi/full/10.1056/NEJMoa1304369?query=featured_home#t=article
8. Wan et al. Risk of Moderate to Advanced Kidney Disease in Patients with Psoriasis: population based cohort study. BMJ. 2013;347:f5961. http://www.bmj.com/content/347/bmj.f5961
9. Tyrer et al. Clinical and Cost-Effectiveness of Cognitive Behaviour Therapy for Health Anxiety in Medical Patients. Lancet. 2013 Oct 18: 10.1016/S0140-6736(13)61905-4. http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(13)61905-4/fulltext